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PMID:21849
|
Opsonic requirements for phagocytosis of Streptococcus pneumoniae types VI, XVIII, XXIII, and XXV.
|
An assay system employing radiolabeled, heat-killed Streptococcus pneumoniae and human polymorphonuclear leukocytes was utilized to study serum pneumococcal opsonic requirements. Comparing the kinetics of phagocytosis in normal serum, heat-inactivated serum, immunoglobulin G (IgG)-deficient serum, C2-deficient serum, and magnesium dichloride ethyleneglycol-tetraacetic acid (MgEGTA)-chelated serum allowed definition of the opsonic requirements for four pneumococcal serotypes: VI XVIII, XXIII, and XXV. All four serotypes were efficiently opsonized in 10% normal serum. Only type XVIII was opsonized in heat-inactivated serum. All four were also opsonized in IgG-deficient serum but not as efficiently as in normal serum. Opsonization via the alternative pathway was diminished for all four serotypes in 10% MgEGTA-chelated and C2-deficient serum. Furthermore, by varying the concentration of MgEGTA-chelated serum, it was found that type XXV was least efficiently opsonized via the alternative pathway. The quantitative nature of this assay system will permit measurement of bacterial and host factors that may contribute to host susceptibility to pneumococcal infection.
|
Opsonic requirements for phagocytosis of Streptococcus pneumoniae types VI, XVIII, XXIII, and XXV. An assay system employing radiolabeled, heat-killed Streptococcus pneumoniae and human polymorphonuclear leukocytes was utilized to study serum pneumococcal opsonic requirements. Comparing the kinetics of phagocytosis in normal serum, heat-inactivated serum, immunoglobulin G (IgG)-deficient serum, C2-deficient serum, and magnesium dichloride ethyleneglycol-tetraacetic acid (MgEGTA)-chelated serum allowed definition of the opsonic requirements for four pneumococcal serotypes: VI XVIII, XXIII, and XXV. All four serotypes were efficiently opsonized in 10% normal serum. Only type XVIII was opsonized in heat-inactivated serum. All four were also opsonized in IgG-deficient serum but not as efficiently as in normal serum. Opsonization via the alternative pathway was diminished for all four serotypes in 10% MgEGTA-chelated and C2-deficient serum. Furthermore, by varying the concentration of MgEGTA-chelated serum, it was found that type XXV was least efficiently opsonized via the alternative pathway. The quantitative nature of this assay system will permit measurement of bacterial and host factors that may contribute to host susceptibility to pneumococcal infection.
|
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] |
PMID:21850
|
Rabbit intestinal fluid stimulation by an enterotoxigenic factor of Staphylococcus aureus.
|
An exoprotein of Staphylococcus aureus 100 that elicited a positive ileal loop response in the rabbit model was investigated in this study. The protein, as it occurred in the culture supernatant fluid, could be detected initially in the late log phase of growth under aerobic and anaerobic conditions. It was stable under acidic conditions to pH 2.0 after 24 h at 4 degrees C. Thirty-minute treatments at 80 degrees C destroyed the ileal loop activity whereas similar trials at 70 degrees C had no effect. Although preparations of staphylococcal enterotoxins purified by other investigators did not produce positive ileal loops, the enterotoxigenic activity of the S. aureus 100 supernatant fluid could be neutralized by antisera prepared against enterotoxins A and B. Throughout purification studies, the active moiety reacted serologically with antiserum A. Polyacrylamide gel electrophoresis of the partially purified protein produced migration patterns nearly identical to those of enterotoxin A.
|
Rabbit intestinal fluid stimulation by an enterotoxigenic factor of Staphylococcus aureus. An exoprotein of Staphylococcus aureus 100 that elicited a positive ileal loop response in the rabbit model was investigated in this study. The protein, as it occurred in the culture supernatant fluid, could be detected initially in the late log phase of growth under aerobic and anaerobic conditions. It was stable under acidic conditions to pH 2.0 after 24 h at 4 degrees C. Thirty-minute treatments at 80 degrees C destroyed the ileal loop activity whereas similar trials at 70 degrees C had no effect. Although preparations of staphylococcal enterotoxins purified by other investigators did not produce positive ileal loops, the enterotoxigenic activity of the S. aureus 100 supernatant fluid could be neutralized by antisera prepared against enterotoxins A and B. Throughout purification studies, the active moiety reacted serologically with antiserum A. Polyacrylamide gel electrophoresis of the partially purified protein produced migration patterns nearly identical to those of enterotoxin A.
|
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] |
PMID:21851
|
Factors affecting germination of Trichophyton mentagrophytes arthrospores.
|
Nutritional and environmental factors affecting germination of Trichophyton mentagrophytes arthrospores were investigated. Germination of dormant arthrospores occurred only in rich complex media such as Sabouraud dextrose broth or vitamin-free Casamino Acids. However, once activated, arthrospores were able to germinate under wide ranges of pH (5.5 to 8.0, optimal 6.5) and temperature (20 to 39 degrees C, optimal 37 degrees C) in the presence of certain single amino acids or oligopeptides known to be present in the human cutaneous tissues. Dormant arthrospores could be activated by incubation in distilled water at 25 degrees C for 24 h or by brief exposure to sublethal doses of heat (45 degrees C for 10 to 20 min). Approximately 20% of activated arthrospores underwent spontaneous germination at 37 degrees C during an additional 18 h of incubation in distilled water. All monosaccharides, purines, pyrimidines, and nucleosides tested failed to induce germination of T. mentagrophytes arthrospores. Germination rate was affected by the concentration of germination inducers as well as that of arthrospores. The germination process of T. mentagrophytes arthrospores was found to be oxygen dependent and was relatively tolerant to NaCl, clotrimazole, cycloheximide, griseofulvin, and tolnaftate.
|
Factors affecting germination of Trichophyton mentagrophytes arthrospores. Nutritional and environmental factors affecting germination of Trichophyton mentagrophytes arthrospores were investigated. Germination of dormant arthrospores occurred only in rich complex media such as Sabouraud dextrose broth or vitamin-free Casamino Acids. However, once activated, arthrospores were able to germinate under wide ranges of pH (5.5 to 8.0, optimal 6.5) and temperature (20 to 39 degrees C, optimal 37 degrees C) in the presence of certain single amino acids or oligopeptides known to be present in the human cutaneous tissues. Dormant arthrospores could be activated by incubation in distilled water at 25 degrees C for 24 h or by brief exposure to sublethal doses of heat (45 degrees C for 10 to 20 min). Approximately 20% of activated arthrospores underwent spontaneous germination at 37 degrees C during an additional 18 h of incubation in distilled water. All monosaccharides, purines, pyrimidines, and nucleosides tested failed to induce germination of T. mentagrophytes arthrospores. Germination rate was affected by the concentration of germination inducers as well as that of arthrospores. The germination process of T. mentagrophytes arthrospores was found to be oxygen dependent and was relatively tolerant to NaCl, clotrimazole, cycloheximide, griseofulvin, and tolnaftate.
|
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0.038725510239601135,
0.004368154797703028
] |
PMID:21852
|
International aspects of oral microbiology.
|
It appears that the bacteria of the mouth are remarkably similar throughout the world. There are differences, but they are mostly of a quantitative rather than a qualitative nature. Although much is yet to be learned on the regulation of the oral ecosystems, these quantitative fluctuations to a large extent seem to be induced by different dietary patterns: the food exerting a strong selective pressure on the oral microbiota.
|
International aspects of oral microbiology. It appears that the bacteria of the mouth are remarkably similar throughout the world. There are differences, but they are mostly of a quantitative rather than a qualitative nature. Although much is yet to be learned on the regulation of the oral ecosystems, these quantitative fluctuations to a large extent seem to be induced by different dietary patterns: the food exerting a strong selective pressure on the oral microbiota.
|
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] |
PMID:21853
|
Classification and determination of cerebral biovailability of psychotropic drugs by quantitative "pharmaco-EEG" and psychometric investigations (studies with AX-A411-BS).
|
Utilizing computerized quantitative analysis of the human scalp recorded electroencephalogram (EEG), it is possible to classify psychotropic drugs. While neuroleptic compounds produce an increase of slow and decrease of fast activities, anxiolytic substances induce an augmentation of fast waves, decrease of alpha waves and--according to the sedative properties of the drug--an increase or decrease of slow waves. Antidepressants produce a concomitant augmentation of slow and fast activities as well as an attenuation of alpha waves. Nootropic substances attenuate slow activities, augment alpha and slow beta waves and decrease fast beta waves. The latter alterations are quite opposite to age-related changes. Since the main psychopharmacological classes seem to have characteristic pharmaco-EEG profiles, the method proved to be useful for determination of psychoactivity and cerebral bioavailability of newly developed substances as for instance AX-A411-BS, a new benzodiazepine. The latter substance was found to be CNS-active and was classified as anxiolytic. It induced dosedependent changes, which were barely visible in the 2nd hour post-drug, became quite obvious in the 4th hour and increased until the 8th hour after oral administration of one single dose. In the higher dosage range, slow activities came to the fore, indicating aoditional sedative properties. Psychometric tests measuring attention, psychomotor activity. mood, vigilance, extroversion, concentration aith a long-lasting effect. The implications of these methods are discussed.
|
Classification and determination of cerebral biovailability of psychotropic drugs by quantitative "pharmaco-EEG" and psychometric investigations (studies with AX-A411-BS). Utilizing computerized quantitative analysis of the human scalp recorded electroencephalogram (EEG), it is possible to classify psychotropic drugs. While neuroleptic compounds produce an increase of slow and decrease of fast activities, anxiolytic substances induce an augmentation of fast waves, decrease of alpha waves and--according to the sedative properties of the drug--an increase or decrease of slow waves. Antidepressants produce a concomitant augmentation of slow and fast activities as well as an attenuation of alpha waves. Nootropic substances attenuate slow activities, augment alpha and slow beta waves and decrease fast beta waves. The latter alterations are quite opposite to age-related changes. Since the main psychopharmacological classes seem to have characteristic pharmaco-EEG profiles, the method proved to be useful for determination of psychoactivity and cerebral bioavailability of newly developed substances as for instance AX-A411-BS, a new benzodiazepine. The latter substance was found to be CNS-active and was classified as anxiolytic. It induced dosedependent changes, which were barely visible in the 2nd hour post-drug, became quite obvious in the 4th hour and increased until the 8th hour after oral administration of one single dose. In the higher dosage range, slow activities came to the fore, indicating aoditional sedative properties. Psychometric tests measuring attention, psychomotor activity. mood, vigilance, extroversion, concentration aith a long-lasting effect. The implications of these methods are discussed.
|
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] |
PMID:21854
|
On the distribution of drugs in saliva and blood plasma.
|
The equilibration of drug concentrations between blood plasma (unbound part) and saliva was studied for selected drugs with different physicochemical properties: Quinidine, sulfamerazine, paracetamol, diazepam and ethanol. From these and other experimental results it is suggested: 1. The concentration ratio between saliva and blood plasma (unbound) can only equal one for basic drugs with a pK a lower than 5.5 and acid drugs with a pK a higher than 8.5 and for pH indifferent drugs. 2. The drug must have a sufficient permeation ability through lipid membranes, valuable by the lipid water partition coefficient.
|
On the distribution of drugs in saliva and blood plasma. The equilibration of drug concentrations between blood plasma (unbound part) and saliva was studied for selected drugs with different physicochemical properties: Quinidine, sulfamerazine, paracetamol, diazepam and ethanol. From these and other experimental results it is suggested: 1. The concentration ratio between saliva and blood plasma (unbound) can only equal one for basic drugs with a pK a lower than 5.5 and acid drugs with a pK a higher than 8.5 and for pH indifferent drugs. 2. The drug must have a sufficient permeation ability through lipid membranes, valuable by the lipid water partition coefficient.
|
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] |
PMID:21866
|
Consumer survey: an approach to teaching consumer participation in community health.
|
This consumer survey conducted by senior baccalaureate students in a family and community nursing course developed as a result of student recognition of the need for direct consumer input in identification of community health needs. The format was developed, pretested and revised by faculty. The door-to-door survey was carried out by pairs of students during clinical time over a six-week period. Through a written summary of the experience and class discussion students indicated an increased awareness of the community as a dynamic reality and a heightened awareness of their caseload families' relationships to the community. Students also demonstrated an appreciation for consumer representation in health planning and for some of the strengths and weaknesses of surveying as a method for consumer involvement.
|
Consumer survey: an approach to teaching consumer participation in community health. This consumer survey conducted by senior baccalaureate students in a family and community nursing course developed as a result of student recognition of the need for direct consumer input in identification of community health needs. The format was developed, pretested and revised by faculty. The door-to-door survey was carried out by pairs of students during clinical time over a six-week period. Through a written summary of the experience and class discussion students indicated an increased awareness of the community as a dynamic reality and a heightened awareness of their caseload families' relationships to the community. Students also demonstrated an appreciation for consumer representation in health planning and for some of the strengths and weaknesses of surveying as a method for consumer involvement.
|
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] |
PMID:21867
|
An evalutive study of a nursing center for community health nursing student experiences.
|
The findings from the evaluation study indicated that nursing students were able to accomplish the community health nursing course objectives through a non-traditional entry point. The study also demonstrated that a School of Nursing can successfully initiate and carry out health care (the service program was also evaluated) and that students, challenged and integrated into such efforts can become extremely useful as a resource to the community while simultaneously contributing to their own learning and professional development. The Nursing Services Center approach (nursing clinic that also offers home care) has been able to serve some of the preventive health needs of a population while at the same time providing students with educational experience in the field.
|
An evalutive study of a nursing center for community health nursing student experiences. The findings from the evaluation study indicated that nursing students were able to accomplish the community health nursing course objectives through a non-traditional entry point. The study also demonstrated that a School of Nursing can successfully initiate and carry out health care (the service program was also evaluated) and that students, challenged and integrated into such efforts can become extremely useful as a resource to the community while simultaneously contributing to their own learning and professional development. The Nursing Services Center approach (nursing clinic that also offers home care) has been able to serve some of the preventive health needs of a population while at the same time providing students with educational experience in the field.
|
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] |
PMID:21868
|
Physiologic measures of nonhuman primates during physical restraint and chemical immobilization.
|
The arterial acid-base balance and other selected physiologic measures of physically restrained and chemically immobilized nonhuman primates from the families Callithricidae, Cebidae, Cercopithecidae, and Pongidae were compared. The physically restrained primates had significantly lower pH, pCO2, and base excess values, but they had significantly higher pO2 values, rectal temperatures, and pulse and respiration rates. Of 56 physically restrained primates, 30 (54%) experienced severe metabolic acidosis, with pH values less than 7.2; 15 (27% of total) had pH values less than 7.1. Two types of behavior were observed during the physical restraint of golden marmosets. Some of the marmosets were excited during restraint, with a great deal of struggling and vocalizing. The other marmosets were quiet and calm, with minimal struggling. The excited group had significantly lower pH, pCO2, and base excess values, but significantly higher pO2 values, rectal temperatures, and pulse and respiration rates. Primates immobilized with ketamine or tiletaminezolazepam had a near normal acid-base balance and were handled more easily than the physically restrained animals.
|
Physiologic measures of nonhuman primates during physical restraint and chemical immobilization. The arterial acid-base balance and other selected physiologic measures of physically restrained and chemically immobilized nonhuman primates from the families Callithricidae, Cebidae, Cercopithecidae, and Pongidae were compared. The physically restrained primates had significantly lower pH, pCO2, and base excess values, but they had significantly higher pO2 values, rectal temperatures, and pulse and respiration rates. Of 56 physically restrained primates, 30 (54%) experienced severe metabolic acidosis, with pH values less than 7.2; 15 (27% of total) had pH values less than 7.1. Two types of behavior were observed during the physical restraint of golden marmosets. Some of the marmosets were excited during restraint, with a great deal of struggling and vocalizing. The other marmosets were quiet and calm, with minimal struggling. The excited group had significantly lower pH, pCO2, and base excess values, but significantly higher pO2 values, rectal temperatures, and pulse and respiration rates. Primates immobilized with ketamine or tiletaminezolazepam had a near normal acid-base balance and were handled more easily than the physically restrained animals.
|
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] |
PMID:21872
|
Isolation and preliminary characterization of two forms of ribulose 1,5-bisphosphate carboxylase from Rhodopseudomonas capsulata.
|
The presence of two distinct forms of ribulose 1,5-bisphosphate carboxylase has been demonstrated in extracts of Rhodopseudomonas capsulata, similar to the form I (peak I) and form II (peak II) carboxylases previously described from R. sphaeroides (J. Gibson and F. R. Tabita, J. Biol. Chem 252:943-949, 1977). The two activities, separated by diethylaminoethyl-cellulose chromatography, were shown to be of different molecular size after assay on polyacrylamide gels. The higher-molecular-weight carboxylase from R. capsulata was designated form I-C, whereas the smaller enzyme was designated form II-C. Catalytic studies revealed significant differences between the two enzymes in response to pH and the effector 6-phosphogluconate. Immunological studies with antisera directed against the carboxylases from R. sphaeroides demonstrated antigenic differences between the two R. capsulata enzymes; cross-reactivity was observed only between R. sphaeroides anti-form II serum and the corresponding R. capsulata enzyme, form II-C.
|
Isolation and preliminary characterization of two forms of ribulose 1,5-bisphosphate carboxylase from Rhodopseudomonas capsulata. The presence of two distinct forms of ribulose 1,5-bisphosphate carboxylase has been demonstrated in extracts of Rhodopseudomonas capsulata, similar to the form I (peak I) and form II (peak II) carboxylases previously described from R. sphaeroides (J. Gibson and F. R. Tabita, J. Biol. Chem 252:943-949, 1977). The two activities, separated by diethylaminoethyl-cellulose chromatography, were shown to be of different molecular size after assay on polyacrylamide gels. The higher-molecular-weight carboxylase from R. capsulata was designated form I-C, whereas the smaller enzyme was designated form II-C. Catalytic studies revealed significant differences between the two enzymes in response to pH and the effector 6-phosphogluconate. Immunological studies with antisera directed against the carboxylases from R. sphaeroides demonstrated antigenic differences between the two R. capsulata enzymes; cross-reactivity was observed only between R. sphaeroides anti-form II serum and the corresponding R. capsulata enzyme, form II-C.
|
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] |
PMID:21873
|
Thermodynamics of the electrochemical proton gradient in bovine heart submitochondrial particles.
|
The electrical and chemical components of the electrochemical proton gradient of submitochondrial particles can be monitored simultaneously by continuously recording optical signals from the probes oxonol-VI and 9-aminoacridine. Either respiration or ATP hydrolysis causes a red shift in the absorption spectrum of oxonol-VI indicative of a membrane potential and a decrease of the fluorescence of 9-aminoacridine indicative of a pH gradient. The magnitude of the membrane potential and pH gradient formed by respiring submitochondrial particles can be modulated 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. Increasing values of deltaGp cause an increase in the steady state magnitudes of both the membrane potential and pH gradient. Thermodynamic phosphorylation potential titration experiments indicate that the electrochemical proton gradient normally maintained by respiring submitochondrial particles has an energy equivalent to 10.5 to 10.9 kcal/mol.
|
Thermodynamics of the electrochemical proton gradient in bovine heart submitochondrial particles. The electrical and chemical components of the electrochemical proton gradient of submitochondrial particles can be monitored simultaneously by continuously recording optical signals from the probes oxonol-VI and 9-aminoacridine. Either respiration or ATP hydrolysis causes a red shift in the absorption spectrum of oxonol-VI indicative of a membrane potential and a decrease of the fluorescence of 9-aminoacridine indicative of a pH gradient. The magnitude of the membrane potential and pH gradient formed by respiring submitochondrial particles can be modulated 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. Increasing values of deltaGp cause an increase in the steady state magnitudes of both the membrane potential and pH gradient. Thermodynamic phosphorylation potential titration experiments indicate that the electrochemical proton gradient normally maintained by respiring submitochondrial particles has an energy equivalent to 10.5 to 10.9 kcal/mol.
|
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] |
PMID:21874
|
Singlet oxygen as a mediator in the hematoporphyrin-catalyzed photooxidation of NADPH to NADP+ in deuterium oxide.
|
The oxygen-dependent photooxidation of NADPH in the presence of hematoporphyrin in D2O results in the production of enzymatically active NADP+. The reaction is not inhibited by benzoate, mannitol, superoxide dismutase, or catalase. Moreover, addition of either potassium superoxide or H2O2 does not potentiate the reaction. This suggests OH-, H2O2, and O-2 are not likely to be the reactive oxygen species in this system. The oxidation is inhibited by various singlet oxygen quenchers and inhibitors such as 1,4-diazabicyclo[2.2.2]octane, 2,5-dimethylfuran plus methanol, histidine, and methionine. In addition, the rate of oxidation in H2O is less than one-fifth of that in D2O. The results suggest a singlet oxygen-mediated process. During the oxidation, no superoxide radical production could be detected with either ferricytochrome c or nitroblue tetrazolium. However, H2O2 has been found as one of the products. These observations are consistent with an oxidation-reduction reaction between singlet oxygen and NADPH to form H2O2 and NADP+, catalyzed by the light-activated photosensitizer hematoporphyrin.
|
Singlet oxygen as a mediator in the hematoporphyrin-catalyzed photooxidation of NADPH to NADP+ in deuterium oxide. The oxygen-dependent photooxidation of NADPH in the presence of hematoporphyrin in D2O results in the production of enzymatically active NADP+. The reaction is not inhibited by benzoate, mannitol, superoxide dismutase, or catalase. Moreover, addition of either potassium superoxide or H2O2 does not potentiate the reaction. This suggests OH-, H2O2, and O-2 are not likely to be the reactive oxygen species in this system. The oxidation is inhibited by various singlet oxygen quenchers and inhibitors such as 1,4-diazabicyclo[2.2.2]octane, 2,5-dimethylfuran plus methanol, histidine, and methionine. In addition, the rate of oxidation in H2O is less than one-fifth of that in D2O. The results suggest a singlet oxygen-mediated process. During the oxidation, no superoxide radical production could be detected with either ferricytochrome c or nitroblue tetrazolium. However, H2O2 has been found as one of the products. These observations are consistent with an oxidation-reduction reaction between singlet oxygen and NADPH to form H2O2 and NADP+, catalyzed by the light-activated photosensitizer hematoporphyrin.
|
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0.010524286888539791,
0.11715807765722275,
0.08560466766357422,
0.03859430551528931,
0.009678729809820652,
-0.02484247088432312,
0.01681818999350071,
0.04118028283119202,
0.036199185997247696,
0.012540972791612148,
0.03683849424123764,
-0.06393785029649734,
0.08328763395547867,
0.10089357942342758
] |
PMID:21875
|
Metabolism of dog gastric mucosa. Levels of glycolytic, citric acid cycle and other intermediates.
|
Several metabolites, including those of glycolysis, the citric acid cycle, the hexose monophosphate shunt, glutamate, aspartate, and Coenzyme A were measured in defined parietal cell-enriched freeze-dried sections of dog gastric biopsies derived from nonsecreting and secreting tissue. In addition, NH3, ribulose 5-phosphate, glycerol, and succinate were measured in perchloric acid extracts of biopsies. The onset of secretion increased the level of glycolytic intermediates including pyruvate and lactate with the most marked increase being in fructose 1,6-diphosphate levels. The level of 6-phosphogluconate and ribulose 5-phosphate also increased, in spite of a constant NADP+/NADPH ratio. The levels of all the citric acid cycle intermediates measured also rose, the most marked rise being in malate and fumarate. The levels of glycerol, acetyl-CoA, and CoA increased, but the ratio of the latter intermediates remained constant. Calculation of the ratio of the oxidized to reduced form of diphosphopyridine nucleotide indicated a fall of the ratio in the cytoplasm and a rise in the mitochondria. From these data, it is concluded that the major energy source for acid secretion is due to an increase in citric acid cycle activity and that glycolysis, and probably also fatty acid oxidation, is stimulated to provide mitochondrial substrate.
|
Metabolism of dog gastric mucosa. Levels of glycolytic, citric acid cycle and other intermediates. Several metabolites, including those of glycolysis, the citric acid cycle, the hexose monophosphate shunt, glutamate, aspartate, and Coenzyme A were measured in defined parietal cell-enriched freeze-dried sections of dog gastric biopsies derived from nonsecreting and secreting tissue. In addition, NH3, ribulose 5-phosphate, glycerol, and succinate were measured in perchloric acid extracts of biopsies. The onset of secretion increased the level of glycolytic intermediates including pyruvate and lactate with the most marked increase being in fructose 1,6-diphosphate levels. The level of 6-phosphogluconate and ribulose 5-phosphate also increased, in spite of a constant NADP+/NADPH ratio. The levels of all the citric acid cycle intermediates measured also rose, the most marked rise being in malate and fumarate. The levels of glycerol, acetyl-CoA, and CoA increased, but the ratio of the latter intermediates remained constant. Calculation of the ratio of the oxidized to reduced form of diphosphopyridine nucleotide indicated a fall of the ratio in the cytoplasm and a rise in the mitochondria. From these data, it is concluded that the major energy source for acid secretion is due to an increase in citric acid cycle activity and that glycolysis, and probably also fatty acid oxidation, is stimulated to provide mitochondrial substrate.
|
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] |
PMID:21877
|
Purification and properties of an endo-alpha-N-acetyl-D-galactosaminidase from Diplococcus pneumoniae.
|
An enzyme that hydrolyzes the O-glycosidic linkage between alpha-N-acetyl-D-galactosamine and serine or threonine in mucins and mucin-type glycoproteins was purified by chromatography on an Affi-Gel 202 column or isoelectric focusing from filtrates of Diplococcus pneumoniae cultures. The final preparations were free of protease and a wide range of other glycosidase activities. The preparation obtained by isoelectric focusing was shown to consist of a single protein by gel filtration and sodium dodecyl sulfate-gel electrophoresis. This preparation had an apparent molecular weight of about 160,000, determined by gel filtration, an optimum pH of 7.6, and an isoelectric point in the range pH 8 to 9. The enzyme releases the disaccharide Gal-GalNAc from a variety of glycopeptide and glycoprotein substrates and appears to have a specific requirement for an unsubstituted galactose in the nonreducing terminus and an alpha linkage between N-acetylgalactosamine and the aglycone. This is the only endoenzyme known capable of cleaving the linkage between a carbohydrate and serine or threonine residues in glycoproteins. The ability of this enzyme to act on macromolecular substrates and its pH optimum makes it ideally suited to explore the distribution and function of mucin-type glycoproteins on normal and cancer cell surfaces.
|
Purification and properties of an endo-alpha-N-acetyl-D-galactosaminidase from Diplococcus pneumoniae. An enzyme that hydrolyzes the O-glycosidic linkage between alpha-N-acetyl-D-galactosamine and serine or threonine in mucins and mucin-type glycoproteins was purified by chromatography on an Affi-Gel 202 column or isoelectric focusing from filtrates of Diplococcus pneumoniae cultures. The final preparations were free of protease and a wide range of other glycosidase activities. The preparation obtained by isoelectric focusing was shown to consist of a single protein by gel filtration and sodium dodecyl sulfate-gel electrophoresis. This preparation had an apparent molecular weight of about 160,000, determined by gel filtration, an optimum pH of 7.6, and an isoelectric point in the range pH 8 to 9. The enzyme releases the disaccharide Gal-GalNAc from a variety of glycopeptide and glycoprotein substrates and appears to have a specific requirement for an unsubstituted galactose in the nonreducing terminus and an alpha linkage between N-acetylgalactosamine and the aglycone. This is the only endoenzyme known capable of cleaving the linkage between a carbohydrate and serine or threonine residues in glycoproteins. The ability of this enzyme to act on macromolecular substrates and its pH optimum makes it ideally suited to explore the distribution and function of mucin-type glycoproteins on normal and cancer cell surfaces.
|
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] |
PMID:21881
|
Characterization of human thyroxine-binding globulin. Evidence for a single polypeptide chain.
|
Thyroxine-binding globulin (TBG) was purified from fresh human plasma by affinity, anion exchange, and gel filtration chromatography. The protein gave a single band in overloaded analytical disc gel electrophoresis. The molecular weight was 54,000 and E1%/1 cm at 280 nm, corrected for thyroxine (T4) absorbance, was 6.17. Six preparations of TBG contained from 0.09 to 0.64 mol of T4/mol; the TBG used in this study contained 0.19 mol of T4 and was able to bind an additional 0.85 mol. The carbohydrate composition was determined and accounted for 23% of the molecular weight. Four lines of chemical and physical evidence failed to demonstrate subunits. These included quantitative COOH-terminal amino acid analysis, peptide mapping and amino acid composition, treatment with sodium dodecyl sulfate, and denaturation of the reduced, alkylated protein with guanidine. From these data, we conclude that TBG is a single polypeptide chain.
|
Characterization of human thyroxine-binding globulin. Evidence for a single polypeptide chain. Thyroxine-binding globulin (TBG) was purified from fresh human plasma by affinity, anion exchange, and gel filtration chromatography. The protein gave a single band in overloaded analytical disc gel electrophoresis. The molecular weight was 54,000 and E1%/1 cm at 280 nm, corrected for thyroxine (T4) absorbance, was 6.17. Six preparations of TBG contained from 0.09 to 0.64 mol of T4/mol; the TBG used in this study contained 0.19 mol of T4 and was able to bind an additional 0.85 mol. The carbohydrate composition was determined and accounted for 23% of the molecular weight. Four lines of chemical and physical evidence failed to demonstrate subunits. These included quantitative COOH-terminal amino acid analysis, peptide mapping and amino acid composition, treatment with sodium dodecyl sulfate, and denaturation of the reduced, alkylated protein with guanidine. From these data, we conclude that TBG is a single polypeptide chain.
|
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] |
PMID:21882
|
Structure and stability of human thyroxine-binding globulin.
|
The secondary and tertiary structure of human plasma thyroxine-binding globulin (TBG) was investigated by circular dichroism and fluorescence properties. The relaxation time of TBG indicated that it is a compact, symmetric molecule. It was calculated from the far ultraviolet CD spectrum that about one-half of the peptide groups are equally distributed in alpha helical and beta structures. In the near ultraviolet, the CD spectrum of TBG was modified when thyroxine was bound. TBG was stable at temperatures below 50 degrees at pH 9 and below 35 degrees at pH 10.5. Below pH 5 tryptophanyl fluorescence revealed a molecular transition which followed first order kinetics. The transition resulted in an irreversible loss of binding of the hormone. Acidification to pH 3.4 produced only a minor change in the CD spectrum, in which some of the alpha helical peptides were converted to beta structure.
|
Structure and stability of human thyroxine-binding globulin. The secondary and tertiary structure of human plasma thyroxine-binding globulin (TBG) was investigated by circular dichroism and fluorescence properties. The relaxation time of TBG indicated that it is a compact, symmetric molecule. It was calculated from the far ultraviolet CD spectrum that about one-half of the peptide groups are equally distributed in alpha helical and beta structures. In the near ultraviolet, the CD spectrum of TBG was modified when thyroxine was bound. TBG was stable at temperatures below 50 degrees at pH 9 and below 35 degrees at pH 10.5. Below pH 5 tryptophanyl fluorescence revealed a molecular transition which followed first order kinetics. The transition resulted in an irreversible loss of binding of the hormone. Acidification to pH 3.4 produced only a minor change in the CD spectrum, in which some of the alpha helical peptides were converted to beta structure.
|
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] |
PMID:21883
|
Neurospora crassa glutamine synthetase. Role of enzyme synthesis and degradation on the regulation of enzyme concentration during exponential growth.
|
The specific activity of Neurospora crassa glutamine synthetase varies according to the nitrogen source in which the organism is grown. In a poor nitrogen source such as glutamate, the specific activity of the enzyme is higher than that found in good nitrogen sources such as ammonium or glutamine. These differences in specific enzyme activity correspond to differences in enzyme concentration. The relative rates of glutamine synthetase synthesis and degradation were measured in exponential cultures grown in different nitrogen sources. The differences in enzyme concentration are explained by differences in the relative rate of enzyme synthesis.
|
Neurospora crassa glutamine synthetase. Role of enzyme synthesis and degradation on the regulation of enzyme concentration during exponential growth. The specific activity of Neurospora crassa glutamine synthetase varies according to the nitrogen source in which the organism is grown. In a poor nitrogen source such as glutamate, the specific activity of the enzyme is higher than that found in good nitrogen sources such as ammonium or glutamine. These differences in specific enzyme activity correspond to differences in enzyme concentration. The relative rates of glutamine synthetase synthesis and degradation were measured in exponential cultures grown in different nitrogen sources. The differences in enzyme concentration are explained by differences in the relative rate of enzyme synthesis.
|
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] |
PMID:21887
|
Studies of the human testis. VIII. Product activation of 17beta-hydroxysteroid oxidoreductase for testosterone.
|
Cell-free homogenates prepared from human testis tissue were incubated with either 1.3 x 10(-5)M[4-14C]testosterone and 2 x 10(-4)M NADP or 1.3 x 10(-5) [4-14C]nadrostenedione and 2 x 10(-4)M NADPH. Addition of non-radioactive androstenedione and testosterone to the incubation medium increased the formation of [14C]androstenedione from [4-14C]testosterone and [14C]testosterone from [4-14C]androstenedione, respectively, while addition of product nucleotide NADPH or NADP, respectively, decreased the conversions. The addition of androstenedione to the incubation medium changed the apparent optimal pH of 17beta-hydroxysteroid oxidoreductase for testosterone from 8.6 to 8.0. It appears likely that in a cell-free system human testicular 17beta-hydroxysteroid oxidoreductase not solubilized and still attached to membrane is activated by the product of the reaction catalyzed by the enzyme.
|
Studies of the human testis. VIII. Product activation of 17beta-hydroxysteroid oxidoreductase for testosterone. Cell-free homogenates prepared from human testis tissue were incubated with either 1.3 x 10(-5)M[4-14C]testosterone and 2 x 10(-4)M NADP or 1.3 x 10(-5) [4-14C]nadrostenedione and 2 x 10(-4)M NADPH. Addition of non-radioactive androstenedione and testosterone to the incubation medium increased the formation of [14C]androstenedione from [4-14C]testosterone and [14C]testosterone from [4-14C]androstenedione, respectively, while addition of product nucleotide NADPH or NADP, respectively, decreased the conversions. The addition of androstenedione to the incubation medium changed the apparent optimal pH of 17beta-hydroxysteroid oxidoreductase for testosterone from 8.6 to 8.0. It appears likely that in a cell-free system human testicular 17beta-hydroxysteroid oxidoreductase not solubilized and still attached to membrane is activated by the product of the reaction catalyzed by the enzyme.
|
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0.07594163715839386,
-0.010072307661175728,
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0.0815025046467781,
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] |
PMID:21888
|
Rapid measurement of an index of testosterone binding to serum binding globulin using ion exchange columns.
|
DEAE cellulose "mini" columns at pH 7.4 retain testosterone (T) bound to testosterone binding globulin (TeBG), which can be eluted at pH 2. Small 1:2 diluted serum or plasma samples are incubated with a tracer dose of tritiated T in pH 7.4 Tris buffer at 37 C then chilled and placed on columns at 4 C. Free and albumin bound T are washed off columns with pH 7.4 Tris buffer and columns are eluted with pH 2 Tris into vials for scintillation counting. After a simple mathematical correction for the small residual fraction of albumin bound T eluted at pH 2, we obtain a measure of TeBG binding of T which is highly correlated (r = .945) with that determined by dialysis. The method is quick, reproducible and applicable to serum or plasma volumes of 50 to 200 microliter. A single operator can process 100 samples in approximately 4 h.
|
Rapid measurement of an index of testosterone binding to serum binding globulin using ion exchange columns. DEAE cellulose "mini" columns at pH 7.4 retain testosterone (T) bound to testosterone binding globulin (TeBG), which can be eluted at pH 2. Small 1:2 diluted serum or plasma samples are incubated with a tracer dose of tritiated T in pH 7.4 Tris buffer at 37 C then chilled and placed on columns at 4 C. Free and albumin bound T are washed off columns with pH 7.4 Tris buffer and columns are eluted with pH 2 Tris into vials for scintillation counting. After a simple mathematical correction for the small residual fraction of albumin bound T eluted at pH 2, we obtain a measure of TeBG binding of T which is highly correlated (r = .945) with that determined by dialysis. The method is quick, reproducible and applicable to serum or plasma volumes of 50 to 200 microliter. A single operator can process 100 samples in approximately 4 h.
|
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] |
PMID:21889
|
Identification of Neisseria by electron capture gas-liquid chromatography of metabolites in a chemically defined growth medium.
|
A dual-purpose study was carried out in an attempt to develop a rapid, sensitive method to identify Neisseria species by gas chromatography and to learn more about the metabolism of these organisms. Sixty-nine isolates of Neisseria were grown in a chemically defined fluid medium; the spent medium was extracted sequentially at pH 2 with diethyl ether and at pH 10 with chloroform. The pH 10 extracts were derivatized with heptafluorobutyric anhydride and analyzed by electron capture gas-liquid chromatography. The resulting spent culture medium electron capture gas-liquid chromatography profiles showed several qualitative and significant quantitative differences among the Neisseria species potentially useful in separating and identifying these organisms. Putrescine and cadaverine which were present in the spent culture medium of some Neisseria, including N. gonorrhoeae, were tentatively identified. Substituting carbohydrates for the chemically defined medium containing glucose in the base medium produced altered profiles with increased quantitative and qualitative differences.
|
Identification of Neisseria by electron capture gas-liquid chromatography of metabolites in a chemically defined growth medium. A dual-purpose study was carried out in an attempt to develop a rapid, sensitive method to identify Neisseria species by gas chromatography and to learn more about the metabolism of these organisms. Sixty-nine isolates of Neisseria were grown in a chemically defined fluid medium; the spent medium was extracted sequentially at pH 2 with diethyl ether and at pH 10 with chloroform. The pH 10 extracts were derivatized with heptafluorobutyric anhydride and analyzed by electron capture gas-liquid chromatography. The resulting spent culture medium electron capture gas-liquid chromatography profiles showed several qualitative and significant quantitative differences among the Neisseria species potentially useful in separating and identifying these organisms. Putrescine and cadaverine which were present in the spent culture medium of some Neisseria, including N. gonorrhoeae, were tentatively identified. Substituting carbohydrates for the chemically defined medium containing glucose in the base medium produced altered profiles with increased quantitative and qualitative differences.
|
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] |
PMID:21890
|
Auditory word discrimination in male children diagnosed as having minimal brain dysfunction.
|
Investigated auditory word discrimination skill in children diagnosed as having minimal brain dysfunction (MBD), a heretofore unexplored topic in the study of MBD. A lack of auditory discrimination skill seems relevant to learning deficiency in language acquisition, a typical sign of MBD. The present study tested the hypothesis that phonemic aural discriminations would be difficult to make for boys diagnosed as having MBD. Errors and nonresponses made while Ss performed an extended auditory word discrimination task were compared between a group of 26 boys diagnosed as having MBD and a matched normal group. As expected, the MBD group had a significantly higher error rate than the normal group even when Ss were discriminating easy word pairs composed of dissimilar items (e.g., reading, math). These and other results suggested that the MBD group was very susceptible to fatigue even while motivated to perform well and while able to improve with practice. The relatively inferior performance of the MBD group was interpreted as resulting directly from a lack of auditory discrimination skill and indirectly from fatigue and its accompanying attention loss.
|
Auditory word discrimination in male children diagnosed as having minimal brain dysfunction. Investigated auditory word discrimination skill in children diagnosed as having minimal brain dysfunction (MBD), a heretofore unexplored topic in the study of MBD. A lack of auditory discrimination skill seems relevant to learning deficiency in language acquisition, a typical sign of MBD. The present study tested the hypothesis that phonemic aural discriminations would be difficult to make for boys diagnosed as having MBD. Errors and nonresponses made while Ss performed an extended auditory word discrimination task were compared between a group of 26 boys diagnosed as having MBD and a matched normal group. As expected, the MBD group had a significantly higher error rate than the normal group even when Ss were discriminating easy word pairs composed of dissimilar items (e.g., reading, math). These and other results suggested that the MBD group was very susceptible to fatigue even while motivated to perform well and while able to improve with practice. The relatively inferior performance of the MBD group was interpreted as resulting directly from a lack of auditory discrimination skill and indirectly from fatigue and its accompanying attention loss.
|
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-0.008563880808651447,
0.053797341883182526,
-0.02035922184586525
] |
PMID:21891
|
Patient characteristics and expectancy measures as factors that influence the expectancy-improvement relationship.
|
A recent study found factored measures of patient's expectancies for therapeutic gain significantly correlated with 1 of 15 objective measures of treatment outcome for the hospitalized patients. A subsequent study of the same relationship that used unfactored expectancy measured with a diagnostically homogenous sample of patients found the patients' expectancies significantly correlated with 10 of the same 15 measures of improvement. This study reexamined the initial expectancy-improvement data using unfactored measures of expectancy. The overall results showed that characteristics of samples of Ss and the adequacy of expectancy measures both significantly influence the results of tests of the expectancy-improvement relationship.
|
Patient characteristics and expectancy measures as factors that influence the expectancy-improvement relationship. A recent study found factored measures of patient's expectancies for therapeutic gain significantly correlated with 1 of 15 objective measures of treatment outcome for the hospitalized patients. A subsequent study of the same relationship that used unfactored expectancy measured with a diagnostically homogenous sample of patients found the patients' expectancies significantly correlated with 10 of the same 15 measures of improvement. This study reexamined the initial expectancy-improvement data using unfactored measures of expectancy. The overall results showed that characteristics of samples of Ss and the adequacy of expectancy measures both significantly influence the results of tests of the expectancy-improvement relationship.
|
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] |
PMID:21892
|
An application of actuarial methods in psychiatric diagnosis.
|
An actuarial program for psychiatric diagnosis is evaluated for agreement with final clinical diagnosis in a series of 288 patients. The acturial program provides a probability differential diagnosis based on an analysis of history and background data, symptom rating profiles, and MMPI clinical scale profiles. The observed agreement with final clinical diagnosis is approximately 50% higher than previously reported for psychological testing in this same setting. The results emphasize the importance for psychologists of clinical interview and observation skills.
|
An application of actuarial methods in psychiatric diagnosis. An actuarial program for psychiatric diagnosis is evaluated for agreement with final clinical diagnosis in a series of 288 patients. The acturial program provides a probability differential diagnosis based on an analysis of history and background data, symptom rating profiles, and MMPI clinical scale profiles. The observed agreement with final clinical diagnosis is approximately 50% higher than previously reported for psychological testing in this same setting. The results emphasize the importance for psychologists of clinical interview and observation skills.
|
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] |
PMID:21893
|
Pretty patient - healthy patient? A study of physical attractiveness and psychopathology.
|
Recent research has shown that physically attractive persons are viewed by others, and by themselves, as "better" in many ways than less attractive persons. The trend in research findings is pervasive, and a stereotype has been proposed: "what is beautiful is good." This study explored the relationship between physical attractiveness and emotional adjustment of hospitalized schizophrenic patients. It was hypothesized (1) that judges would consider attractive patients better adjusted than unattractive patients; and (2) that attractive patients would appear healthier or better adjusted than unattractive patients on standard diagnostic measures. The results of multivariate analyses supported the first hypothesis, but consistently failed to support the second. Limitations of the present findings and of the "beautiful is good" stereotype are discussed.
|
Pretty patient - healthy patient? A study of physical attractiveness and psychopathology. Recent research has shown that physically attractive persons are viewed by others, and by themselves, as "better" in many ways than less attractive persons. The trend in research findings is pervasive, and a stereotype has been proposed: "what is beautiful is good." This study explored the relationship between physical attractiveness and emotional adjustment of hospitalized schizophrenic patients. It was hypothesized (1) that judges would consider attractive patients better adjusted than unattractive patients; and (2) that attractive patients would appear healthier or better adjusted than unattractive patients on standard diagnostic measures. The results of multivariate analyses supported the first hypothesis, but consistently failed to support the second. Limitations of the present findings and of the "beautiful is good" stereotype are discussed.
|
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] |
PMID:21898
|
Chronic eosinophilic pneumonia followed by polyarteritis nodosa complicating the course of bronchial asthma. Report of a case.
|
The syndrome of pulmonary infiltrates with eosinophilia (PIE) occurs rarely in the asthmatic patient. An unusual case is presented in which progressive bronchoconstriction and exaggerated blood eosinophilia preceded the recognition of two seemingly unrelated diseases, each of which can independently result in hypereosinophilia and the PIE syndrome. In the male patient studied, the first illness, biopsy-proved chronic eosinophilic pneumonia, was responsive to corticosteroid therapy. Four uneventful years later, polyarteritis nodosa with eventual pulmonary involvement developed. A careful search for specific underlying pulmonary and systemic disease is in order when hypereosinophilia occurs in the clinically unstable asthmatic patient.
|
Chronic eosinophilic pneumonia followed by polyarteritis nodosa complicating the course of bronchial asthma. Report of a case. The syndrome of pulmonary infiltrates with eosinophilia (PIE) occurs rarely in the asthmatic patient. An unusual case is presented in which progressive bronchoconstriction and exaggerated blood eosinophilia preceded the recognition of two seemingly unrelated diseases, each of which can independently result in hypereosinophilia and the PIE syndrome. In the male patient studied, the first illness, biopsy-proved chronic eosinophilic pneumonia, was responsive to corticosteroid therapy. Four uneventful years later, polyarteritis nodosa with eventual pulmonary involvement developed. A careful search for specific underlying pulmonary and systemic disease is in order when hypereosinophilia occurs in the clinically unstable asthmatic patient.
|
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] |
PMID:21899
|
Tardive dyskinesia in psychogeriatric patients: a five-year follow-up.
|
The neurologic side effects of antipsychotic drugs in the treatment of major psychiatric disorders are causing great concern. The status of tardive dyskinesia in 13 elderly psychiatric patients at the 5-year follow-up point, is reported. In 11 of the 13, tardive dyskinesia persisted. tamong these 11 patients, the severity was reduced in 2, increased in 2, and unchanged in 7. Only in 2 of the total 13 subjects had the tardive dyskinesia disappeared. However, both of these patients were receiving neuroleptic drugs and had parkinsonism, a syndrome that might have masked the dyskinesia. Recommendations are made for prophylaxis and for good clinical judgment in the use of antipsychotic drugs.
|
Tardive dyskinesia in psychogeriatric patients: a five-year follow-up. The neurologic side effects of antipsychotic drugs in the treatment of major psychiatric disorders are causing great concern. The status of tardive dyskinesia in 13 elderly psychiatric patients at the 5-year follow-up point, is reported. In 11 of the 13, tardive dyskinesia persisted. tamong these 11 patients, the severity was reduced in 2, increased in 2, and unchanged in 7. Only in 2 of the total 13 subjects had the tardive dyskinesia disappeared. However, both of these patients were receiving neuroleptic drugs and had parkinsonism, a syndrome that might have masked the dyskinesia. Recommendations are made for prophylaxis and for good clinical judgment in the use of antipsychotic drugs.
|
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] |
PMID:21931
|
A prospective analysis interstitial pneumonia and opportunistic viral infection among recipients of allogeneic bone marrow grafts.
|
A prospective study of 80 bone marrow transplant recipients with acute leukemia and aplastic anemia employed serial viral cultures, determination of complement-fixing antibody to cytomegalovirus (CMV), and study of material obtained from open lung biopsy and autopsy. There were 43 episodes of interstitial pneumonia, 28 of which were fatal. About 40% of the cases were idiopathic. CMV was the most common candidate pathogen, present in 47% of affected lungs. By a median of 53 days following transplantation, 46% of the recipients were shedding CMV from some site. This event was three times more frequent among recipients who had positive titers of antibody to CMV before transplantation than among seronegative recipients. Failure to respond werologically to CMV infection markedly increased the hazard of dying of interstitial pneumonia. Graft-vs-host disease significantly increased the incidence and lethality of interstitial pneumonia. The presence of leukemia (rather than aplastic anemia) and/or certain factors in the technique of preparation for engraftment may have been significant.
|
A prospective analysis interstitial pneumonia and opportunistic viral infection among recipients of allogeneic bone marrow grafts. A prospective study of 80 bone marrow transplant recipients with acute leukemia and aplastic anemia employed serial viral cultures, determination of complement-fixing antibody to cytomegalovirus (CMV), and study of material obtained from open lung biopsy and autopsy. There were 43 episodes of interstitial pneumonia, 28 of which were fatal. About 40% of the cases were idiopathic. CMV was the most common candidate pathogen, present in 47% of affected lungs. By a median of 53 days following transplantation, 46% of the recipients were shedding CMV from some site. This event was three times more frequent among recipients who had positive titers of antibody to CMV before transplantation than among seronegative recipients. Failure to respond werologically to CMV infection markedly increased the hazard of dying of interstitial pneumonia. Graft-vs-host disease significantly increased the incidence and lethality of interstitial pneumonia. The presence of leukemia (rather than aplastic anemia) and/or certain factors in the technique of preparation for engraftment may have been significant.
|
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] |
PMID:21932
|
pH as an indicator of free fatty acid release from adipocytes.
|
A convenient method of measuring initial rates of free fatty acid efflux from isolated adipocytes during triglyceride breakdown by hormone-sensitive lipase is described. The procedure is based on the dissociation of protons from carboxyl groups of free fatty acids. A recording pH meter is used to monitor H+ concentration in the medium continuously as an index of free fatty acid release. A stoichiometric relationship was demonstrated between proton release and extracellular free fatty acid concentration as determined by the 63Ni radioassay method of Ho (1970. Anal. Biochem. 36: 105-113). An acid pH (6.8) caused a reduction in proton release, which was immediately and completely reversed by raising the pH to 7.4.
|
pH as an indicator of free fatty acid release from adipocytes. A convenient method of measuring initial rates of free fatty acid efflux from isolated adipocytes during triglyceride breakdown by hormone-sensitive lipase is described. The procedure is based on the dissociation of protons from carboxyl groups of free fatty acids. A recording pH meter is used to monitor H+ concentration in the medium continuously as an index of free fatty acid release. A stoichiometric relationship was demonstrated between proton release and extracellular free fatty acid concentration as determined by the 63Ni radioassay method of Ho (1970. Anal. Biochem. 36: 105-113). An acid pH (6.8) caused a reduction in proton release, which was immediately and completely reversed by raising the pH to 7.4.
|
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] |
PMID:21933
|
Type I Escherichia coli pili: characterization of binding to monkey kidney cells.
|
We have demonstrated binding of purified pili from a strain of Escherichia coli to Vero cell monolayers as a model of prokaryotic-eukaryotic cell adherence. Pili bound to the tissue culture in a rapid reaction that did not require enzymatic activation. Attachment occurred optimally at pH 4-5 and could be inhibited by analogues of D-mannose, anti-pili antibodies, or by preincubation of tissue cells with mannose-specific plant lectins. Binding remained after treatment of the monolayer with glycosidases, trypsin, or a protease mixture but was enhanced after neuraminidase treatment. These results indicate that bacterial binding can occur via pili which act like lectins and presumably bind to mannose-containing glycoproteins on mammalian cell surfaces.
|
Type I Escherichia coli pili: characterization of binding to monkey kidney cells. We have demonstrated binding of purified pili from a strain of Escherichia coli to Vero cell monolayers as a model of prokaryotic-eukaryotic cell adherence. Pili bound to the tissue culture in a rapid reaction that did not require enzymatic activation. Attachment occurred optimally at pH 4-5 and could be inhibited by analogues of D-mannose, anti-pili antibodies, or by preincubation of tissue cells with mannose-specific plant lectins. Binding remained after treatment of the monolayer with glycosidases, trypsin, or a protease mixture but was enhanced after neuraminidase treatment. These results indicate that bacterial binding can occur via pili which act like lectins and presumably bind to mannose-containing glycoproteins on mammalian cell surfaces.
|
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] |
PMID:21934
|
Isolation of pH-optima and apparent Michaelis constants of highly purified enzymes from human and animal sources. Comparison of enzymes of human and animal origin, I.
|
Enzymes from animal sources are frequently used for quality control of enzyme activity determination in clinical chemistry. For this purpose they should be very similar to human enzymes. It is shown that preparations of enzymes of diagnostic interest from human and porcine organs, purified in exactly the same way, have very similar pH-optima and apparent Michaelis constants for their substrates.
|
Isolation of pH-optima and apparent Michaelis constants of highly purified enzymes from human and animal sources. Comparison of enzymes of human and animal origin, I. Enzymes from animal sources are frequently used for quality control of enzyme activity determination in clinical chemistry. For this purpose they should be very similar to human enzymes. It is shown that preparations of enzymes of diagnostic interest from human and porcine organs, purified in exactly the same way, have very similar pH-optima and apparent Michaelis constants for their substrates.
|
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] |
PMID:21935
|
A nurse practitioner in a family practice residency: role description and impact on continuity of the practitioner-patient relationship.
|
The nurse practitioner and physician's assistant are new health practitioners providing primary health care. When teamed with family physicians, these new health practitioners can extend patient services. Family physicians should be trained to work with new health practitioners effectively. Presented is a model where a nurse practitioner and family practice residents work as co-practitioners in a family practice unit. A nurse practitioner in this role can improve the continuity of the relationship between patient and provider in a family practice residency.
|
A nurse practitioner in a family practice residency: role description and impact on continuity of the practitioner-patient relationship. The nurse practitioner and physician's assistant are new health practitioners providing primary health care. When teamed with family physicians, these new health practitioners can extend patient services. Family physicians should be trained to work with new health practitioners effectively. Presented is a model where a nurse practitioner and family practice residents work as co-practitioners in a family practice unit. A nurse practitioner in this role can improve the continuity of the relationship between patient and provider in a family practice residency.
|
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] |
PMID:21936
|
Regulation of the bacterial microflora of the vagina in cyclic female rats.
|
The bacterial microflora was examined in the vagina of cyclic female rats kept under normal laboratory conditions. Large variations occurred during the cycle with high numbers of bacteria (10(5)-10(8) per vagina) during proestrus and estrus and low numbers (10(1)-10(4) per vagina) during the diestrus period. Histological analysis of in situ vaginal tissue and transplanted vaginal tissue revealed an association of high bacterial numbers with the presence of large amounts of cellular debris in the vaginal lumen during the period of epithelial keratinization. Absence of phagocytosis in leucocytes at mestestrus suggested that leucocytes did not play an active role in reduction of bacterial numbers between estrus and metestrus. Accurate measurement of the pH in the vaginal lumen failed to reveal differences which could explain the reduction in bacterial numbers between estrus and metestrus. The cyclic changes in the bacterial population-consisting of species which are normally present in the intestinal flora-- seem to be controlled by cyclic changes in the amounts of cellular debris in the vaginal lumen.
|
Regulation of the bacterial microflora of the vagina in cyclic female rats. The bacterial microflora was examined in the vagina of cyclic female rats kept under normal laboratory conditions. Large variations occurred during the cycle with high numbers of bacteria (10(5)-10(8) per vagina) during proestrus and estrus and low numbers (10(1)-10(4) per vagina) during the diestrus period. Histological analysis of in situ vaginal tissue and transplanted vaginal tissue revealed an association of high bacterial numbers with the presence of large amounts of cellular debris in the vaginal lumen during the period of epithelial keratinization. Absence of phagocytosis in leucocytes at mestestrus suggested that leucocytes did not play an active role in reduction of bacterial numbers between estrus and metestrus. Accurate measurement of the pH in the vaginal lumen failed to reveal differences which could explain the reduction in bacterial numbers between estrus and metestrus. The cyclic changes in the bacterial population-consisting of species which are normally present in the intestinal flora-- seem to be controlled by cyclic changes in the amounts of cellular debris in the vaginal lumen.
|
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] |
PMID:21937
|
Effects of neurotransmitters upon the discharge of secretory product from the cutaneous glands of the red-spotted newt.
|
The effects of sympathetic and parasympathetic agonists and antagonists on discharge of secretory product by the granular and mucous glands were examined in the red-spotted newt, Notopthalmus viridescens viridescens. Observations were made also on the South African clawed toad. Xenopus laevis, the grass frog, Rana pipiens, and the crested newt, Triturus cristatus. In contrast to the granular glands of the South African clawed toad and the grass frog, which were stimulated by alpha-adrenergic agents, those of the red-spotted newt discharge in response to acetylcholine, either in vitro when added to the Holtfreter's solution in which explants were incubated, or in vivo when injected subcutaneously. Granular glands of the crested newt were also dischared in response to subcutaneous injection of acetylcholine. Stimulation of the granular glands by acetylcholine was blocked by atopine but not by tubocurarie, indicating that the cholinergic receptors are muscarinic rather than nicotinic. The mucous glands of the red-spotted newt, on the other hand, did not discharge in response to either acetylcholine or to adrenergic agents.
|
Effects of neurotransmitters upon the discharge of secretory product from the cutaneous glands of the red-spotted newt. The effects of sympathetic and parasympathetic agonists and antagonists on discharge of secretory product by the granular and mucous glands were examined in the red-spotted newt, Notopthalmus viridescens viridescens. Observations were made also on the South African clawed toad. Xenopus laevis, the grass frog, Rana pipiens, and the crested newt, Triturus cristatus. In contrast to the granular glands of the South African clawed toad and the grass frog, which were stimulated by alpha-adrenergic agents, those of the red-spotted newt discharge in response to acetylcholine, either in vitro when added to the Holtfreter's solution in which explants were incubated, or in vivo when injected subcutaneously. Granular glands of the crested newt were also dischared in response to subcutaneous injection of acetylcholine. Stimulation of the granular glands by acetylcholine was blocked by atopine but not by tubocurarie, indicating that the cholinergic receptors are muscarinic rather than nicotinic. The mucous glands of the red-spotted newt, on the other hand, did not discharge in response to either acetylcholine or to adrenergic agents.
|
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] |
PMID:21938
|
Glutamate dehydrogenases from tissues of the ribbed mussel Modiolus demissus: ADP activation and possible physiological significance.
|
Glutamate dehydrogenase (E.C. 14.1.3) was localized in the mitochondria from heart, gill, mantle and hepatopancreas of this euryhaline bivalve mollusc. Activity levels were low (0.1-0.4 mumoles/min/g wet weight) in all tissues when assayed in the glutamate forming direction. Partially purified gill mitochondrial GDH was most active at pH 8.5. The rate in the glutamate deaminating direction was 10-20% of the rate in the glutamate forming direction. ADP at apparent Ka concentrations of micrometer (glutamate formation) and 170 micrometer (glutamate deamination) enhanced GDH activity, 8- and 4-fold respectively. GDH, in vivo, is probably in the activated form and appears to function in glutamate synthesis rather than ammonia formation. However, based on the low activities obtained, the role of GDH in salinity induced amino acid synthesis seems minimal.
|
Glutamate dehydrogenases from tissues of the ribbed mussel Modiolus demissus: ADP activation and possible physiological significance. Glutamate dehydrogenase (E.C. 14.1.3) was localized in the mitochondria from heart, gill, mantle and hepatopancreas of this euryhaline bivalve mollusc. Activity levels were low (0.1-0.4 mumoles/min/g wet weight) in all tissues when assayed in the glutamate forming direction. Partially purified gill mitochondrial GDH was most active at pH 8.5. The rate in the glutamate deaminating direction was 10-20% of the rate in the glutamate forming direction. ADP at apparent Ka concentrations of micrometer (glutamate formation) and 170 micrometer (glutamate deamination) enhanced GDH activity, 8- and 4-fold respectively. GDH, in vivo, is probably in the activated form and appears to function in glutamate synthesis rather than ammonia formation. However, based on the low activities obtained, the role of GDH in salinity induced amino acid synthesis seems minimal.
|
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] |
PMID:21939
|
On the induction of zoosporogenesis in the rumen phycomycetes Neocallimastix frontalis, Piromonas communis and Sphaeromonas communis.
|
The plant components inducing zoosporogenesis in the rumen phycomycetes Neocallimastix frontalis, Sphaeromonas communis and Piromonas communis were widely distributed in the plant kingdom with no apparent taxonomic relationship. In Lolium perenne L. (perennial rye-grass) and Hordeum distichon (barley), the components were principally present in the leaves and aerial tissues. Sufficient inducer was present in the normal diet of the host animal to trigger the differentiation and release of the zoospores from all the sporangia of each phycomycete species present in the rumen fluid tested. The inducers were unstable to oxygen, especially at elevated temperatures, and were destroyed by rumen micro-organisms. They may be similar compounds for each species.
|
On the induction of zoosporogenesis in the rumen phycomycetes Neocallimastix frontalis, Piromonas communis and Sphaeromonas communis. The plant components inducing zoosporogenesis in the rumen phycomycetes Neocallimastix frontalis, Sphaeromonas communis and Piromonas communis were widely distributed in the plant kingdom with no apparent taxonomic relationship. In Lolium perenne L. (perennial rye-grass) and Hordeum distichon (barley), the components were principally present in the leaves and aerial tissues. Sufficient inducer was present in the normal diet of the host animal to trigger the differentiation and release of the zoospores from all the sporangia of each phycomycete species present in the rumen fluid tested. The inducers were unstable to oxygen, especially at elevated temperatures, and were destroyed by rumen micro-organisms. They may be similar compounds for each species.
|
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0.08167669177055359,
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] |
PMID:21940
|
Studies on the mechanism of action of oxygen-labile haemolysins.
|
The sensitivities of the binding step and the lytic step of haemolysis by pneumolysin to the action of various inhibitors and to variations in the assay conditions were studied. Binding was inhibited by HgCl2 and N-ethylmaleimide. Lysis by previously fixed lysin was insensitive to HgCl2 and only slightly sensitive to N-ethylmaleimide. Binding of pneumolysin was independent of ionic strength. Binding of pneumolysin and streptolysin O decreased above pH 8-0 and 8-4 respectively. These results suggest that binding requires a non-ionized unsubstituted sulphydryl group. Incubation of erythrocytes with NaF caused inhibition of pneumolysin, indicating that some metabolic function of the cell may be involved in lysis. The action of streptolysin O was not affected by NaF.
|
Studies on the mechanism of action of oxygen-labile haemolysins. The sensitivities of the binding step and the lytic step of haemolysis by pneumolysin to the action of various inhibitors and to variations in the assay conditions were studied. Binding was inhibited by HgCl2 and N-ethylmaleimide. Lysis by previously fixed lysin was insensitive to HgCl2 and only slightly sensitive to N-ethylmaleimide. Binding of pneumolysin was independent of ionic strength. Binding of pneumolysin and streptolysin O decreased above pH 8-0 and 8-4 respectively. These results suggest that binding requires a non-ionized unsubstituted sulphydryl group. Incubation of erythrocytes with NaF caused inhibition of pneumolysin, indicating that some metabolic function of the cell may be involved in lysis. The action of streptolysin O was not affected by NaF.
|
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] |
PMID:21941
|
The enzymic interconversion of acetate and acetyl-coenzyme A in Escherichia coli.
|
Mutants of Escherichia coli K12 have been isolated that grow on media containing pyruvate of proline as sole carbon sources despite the presence of 10 or 50 mM-sodium fluoroacetate. Such mutants lack either acetate kinase [ATP: acetate phosphotransferase; EC 2.7.2.1] or phosphotransacetylase [acetyl-CoA: orthophosphate acetyltransferase; EC 2.3.1.8] activity. Unlike wild-type E. coli, phosphotransacetylase mutants do not excrete acetate when growing aerobically or anaerobically on glucose; their anaerobic growth on this sugar is slow. The genes that specify acetate kinase (ack) and phosphotransacetylase (pta) activities are cotransducible with each other and with purF and are thus located at about min 50 on the E. coli linkage map. Although Pta- and Ack- mutants are greatly impaired in their growth on acetate, they incorporate [2-14C]acetate added to cultures growing on glycerol, but not on glucose. An inducible acetyl-CoA synthetase [acetate: CoA ligase (AMP-forming); EC 6.2.1.1] effects this uptake of acetate.
|
The enzymic interconversion of acetate and acetyl-coenzyme A in Escherichia coli. Mutants of Escherichia coli K12 have been isolated that grow on media containing pyruvate of proline as sole carbon sources despite the presence of 10 or 50 mM-sodium fluoroacetate. Such mutants lack either acetate kinase [ATP: acetate phosphotransferase; EC 2.7.2.1] or phosphotransacetylase [acetyl-CoA: orthophosphate acetyltransferase; EC 2.3.1.8] activity. Unlike wild-type E. coli, phosphotransacetylase mutants do not excrete acetate when growing aerobically or anaerobically on glucose; their anaerobic growth on this sugar is slow. The genes that specify acetate kinase (ack) and phosphotransacetylase (pta) activities are cotransducible with each other and with purF and are thus located at about min 50 on the E. coli linkage map. Although Pta- and Ack- mutants are greatly impaired in their growth on acetate, they incorporate [2-14C]acetate added to cultures growing on glycerol, but not on glucose. An inducible acetyl-CoA synthetase [acetate: CoA ligase (AMP-forming); EC 6.2.1.1] effects this uptake of acetate.
|
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] |
PMID:21942
|
Adsorption of a phage tail-like bacteriocin to isolated lipopolysaccharide of Rhizobium.
|
Purified lipopolysaccharide (LPS) from the bacteriocin sensitive strain Rhizobium lupini i6-2 was shown to neutralize the killing activity of the bacteriocin. In the electron microscopical preparation the phage tail-like bacteriocin appears to be adsorbed to the LPS; the tail sheath is contracted and the fibres are oriented towards the LPS ribbon. In contrast, no interaction was observed between the bacteriocin and the LPS of two resistant strains of Rhizobium (16-2/Ii and 16-3). The inactivation of the bacteriocin by LPS depends on salt concentration, pH, and temperature. The receptor activity of LPS was destroyed by mild acid hydrolysis and by treatment with deoxycholate, which indicates that the micellar structure of the LPS is necessary for bacteriocin adsorption. The chemical composition of the 16-2 LPS was compared to that of the LPS of two resistant strains. In the case of 16-2/ii LPS minor modifications suffice to confer resistance against the bacteriocin.
|
Adsorption of a phage tail-like bacteriocin to isolated lipopolysaccharide of Rhizobium. Purified lipopolysaccharide (LPS) from the bacteriocin sensitive strain Rhizobium lupini i6-2 was shown to neutralize the killing activity of the bacteriocin. In the electron microscopical preparation the phage tail-like bacteriocin appears to be adsorbed to the LPS; the tail sheath is contracted and the fibres are oriented towards the LPS ribbon. In contrast, no interaction was observed between the bacteriocin and the LPS of two resistant strains of Rhizobium (16-2/Ii and 16-3). The inactivation of the bacteriocin by LPS depends on salt concentration, pH, and temperature. The receptor activity of LPS was destroyed by mild acid hydrolysis and by treatment with deoxycholate, which indicates that the micellar structure of the LPS is necessary for bacteriocin adsorption. The chemical composition of the 16-2 LPS was compared to that of the LPS of two resistant strains. In the case of 16-2/ii LPS minor modifications suffice to confer resistance against the bacteriocin.
|
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] |
PMID:21943
|
Alertness and clear thinking as characteristics of high naturally occurring autonomic nervous system arousal.
|
Studies of the effect of induced mood on the autonomic nervous system (ANS) suggested that naturally occurring mood might also covary with the ANS. Ss were 13 men and women aged 20 to 70. Fatigue, confusion, and depression were measured on the Profile of Mood States, while barometric pressure and the ANS indices of heart rate and body temperature were also recorded. Fatigue and confusion each showed negative relationships to both heart rate and body temperature. Barometric pressure showed a suggestively positive relationship to the mood of depression. Hypothalamic serotonin concentration was suggested as a central factor producing the covariations between the mood indices (alertness and clear thinking) and the ANS measures.
|
Alertness and clear thinking as characteristics of high naturally occurring autonomic nervous system arousal. Studies of the effect of induced mood on the autonomic nervous system (ANS) suggested that naturally occurring mood might also covary with the ANS. Ss were 13 men and women aged 20 to 70. Fatigue, confusion, and depression were measured on the Profile of Mood States, while barometric pressure and the ANS indices of heart rate and body temperature were also recorded. Fatigue and confusion each showed negative relationships to both heart rate and body temperature. Barometric pressure showed a suggestively positive relationship to the mood of depression. Hypothalamic serotonin concentration was suggested as a central factor producing the covariations between the mood indices (alertness and clear thinking) and the ANS measures.
|
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] |
PMID:21944
|
Effects of denervation on the neuraminidase activity of slow and fast muscles of rabbits.
|
The presence in skeletal muscles of rabbits of neuraminidase activity on sialyl lactose was demonstrated. By comparing the specific activity of this enzyme in different control muscles, it was shown that it was 2.3 times higher in the slow than in the fast muscles. Seven days after denervation, we observed a significant increase of activity in fast muscle and a significant decrease of activity in slow muscle. These results, together with previous data, are in favour of the hypothesis that turnover of muscle glycoconjugates is under a type-specific neural control.
|
Effects of denervation on the neuraminidase activity of slow and fast muscles of rabbits. The presence in skeletal muscles of rabbits of neuraminidase activity on sialyl lactose was demonstrated. By comparing the specific activity of this enzyme in different control muscles, it was shown that it was 2.3 times higher in the slow than in the fast muscles. Seven days after denervation, we observed a significant increase of activity in fast muscle and a significant decrease of activity in slow muscle. These results, together with previous data, are in favour of the hypothesis that turnover of muscle glycoconjugates is under a type-specific neural control.
|
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] |
PMID:21945
|
Influence of zinc deficiency on retinal reductase and oxidase activities in rat liver and testes.
|
The influence of zinc deficiency on vitamin A metabolism in rats was investigated by assessing two specific enzymes involved in its metabolism viz retinal reductase and retinal oxidase in the liver as well as in the testes. The activity of retinal reductase in the liver was not altered in zinc deficiency. Retinal oxidase activity on the other hand, was increased approximately 1.5 fold over the pair-fed controls. In contrast, both retinal reductase and oxidase in the testes were decreased during zinc deficiency. The effects of zinic deficiency on vitamin A metabolism in the liver could be partly attributed to the secondary effect of reduced food intake and growth. However, the effects seen in the testes on the metabolic enzymes of vitamin A appear to be due to zinc deficiency per se. The liver concentration of vitamin A (microgram/g) as well as total vitamin A (microgram/liver) were higher in the zinc-deficient rats when compared to the zinc-sufficient rats although not significantly different from the pair-fed controls. In aggreement with previous reports, the plasma vitamin A in zinc-deficient rats were found to be markedly lowered compared to zinc sufficient ad libitum controls.
|
Influence of zinc deficiency on retinal reductase and oxidase activities in rat liver and testes. The influence of zinc deficiency on vitamin A metabolism in rats was investigated by assessing two specific enzymes involved in its metabolism viz retinal reductase and retinal oxidase in the liver as well as in the testes. The activity of retinal reductase in the liver was not altered in zinc deficiency. Retinal oxidase activity on the other hand, was increased approximately 1.5 fold over the pair-fed controls. In contrast, both retinal reductase and oxidase in the testes were decreased during zinc deficiency. The effects of zinic deficiency on vitamin A metabolism in the liver could be partly attributed to the secondary effect of reduced food intake and growth. However, the effects seen in the testes on the metabolic enzymes of vitamin A appear to be due to zinc deficiency per se. The liver concentration of vitamin A (microgram/g) as well as total vitamin A (microgram/liver) were higher in the zinc-deficient rats when compared to the zinc-sufficient rats although not significantly different from the pair-fed controls. In aggreement with previous reports, the plasma vitamin A in zinc-deficient rats were found to be markedly lowered compared to zinc sufficient ad libitum controls.
|
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] |
PMID:21948
|
Oxidation kinetics of phenothiazine and 10-methylphenothiazine in acidic medium.
|
The rate of phenothiazine degradation in an acidic oxygen-saturated medium was studied. 3H-Phenothiazine-3-one and phenothiazine 5-oxide are produced by parallel reactions, and 7-(10'-phenothiazinyl)-3H-phenothiazine-3-one is produced in a more complex manner. The overall phenothiazine degradation rate appears to be pH independent up to pH 7.0. The degradation kinetics of 10-methylphenothiazine were studied after isolation and identification of its degradation products, 10-methylphenothiazine 5-oxide and 3H-phenothiazine-3-one. The main degradation product is 10-methylphenothiazine 5-oxide; but at low pH values and high temperatures, more 3H-phenothiazine-3-one is formed. The degradation rate of 10-methylphenothiazine is pH independent up to pH 7.
|
Oxidation kinetics of phenothiazine and 10-methylphenothiazine in acidic medium. The rate of phenothiazine degradation in an acidic oxygen-saturated medium was studied. 3H-Phenothiazine-3-one and phenothiazine 5-oxide are produced by parallel reactions, and 7-(10'-phenothiazinyl)-3H-phenothiazine-3-one is produced in a more complex manner. The overall phenothiazine degradation rate appears to be pH independent up to pH 7.0. The degradation kinetics of 10-methylphenothiazine were studied after isolation and identification of its degradation products, 10-methylphenothiazine 5-oxide and 3H-phenothiazine-3-one. The main degradation product is 10-methylphenothiazine 5-oxide; but at low pH values and high temperatures, more 3H-phenothiazine-3-one is formed. The degradation rate of 10-methylphenothiazine is pH independent up to pH 7.
|
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] |
PMID:21949
|
Mechanism for phenothiazine oxidation.
|
The mechanism of phenothiazine degradation was studied by following the degradation of 3,10'-diphenothiazine in ethanol-water mixtures as well as the electrochemical oxidation of phenothiazine. A mechanism, including the formation of an oxidized dimer and some polymers, is suggested.
|
Mechanism for phenothiazine oxidation. The mechanism of phenothiazine degradation was studied by following the degradation of 3,10'-diphenothiazine in ethanol-water mixtures as well as the electrochemical oxidation of phenothiazine. A mechanism, including the formation of an oxidized dimer and some polymers, is suggested.
|
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] |
PMID:21950
|
Synthesis, physicochemical properties, and antitumor activities of analogs of 1-phenyl-3-benzyl-3-methyltriazenes.
|
To study the effect of substituents on the antitumor activities of analogs of 1-phenyl-3-benzyl-3-methyltriazenes, a series of compounds was designed and synthesized in which the substituent on the 1-phenyl was an electron-withdrawing group and the substituent on the 3-benzyl had a broad range of physicochemical properties. Of the 13 analogs prepared and tested against Sarcoma-180 in the mouse, five showed significant activity. The results were submitted to discriminant analysis to determine structure-activity relationships.
|
Synthesis, physicochemical properties, and antitumor activities of analogs of 1-phenyl-3-benzyl-3-methyltriazenes. To study the effect of substituents on the antitumor activities of analogs of 1-phenyl-3-benzyl-3-methyltriazenes, a series of compounds was designed and synthesized in which the substituent on the 1-phenyl was an electron-withdrawing group and the substituent on the 3-benzyl had a broad range of physicochemical properties. Of the 13 analogs prepared and tested against Sarcoma-180 in the mouse, five showed significant activity. The results were submitted to discriminant analysis to determine structure-activity relationships.
|
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-0.0178604144603014,
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-0.01915009319782257,
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0.018930189311504364,
0.008244913071393967,
0.09869006276130676,
0.025889607146382332
] |
PMID:21951
|
Biopharmaceutic factors that influence effects of anticholinergic drugs: comparison of propantheline, hexocyclium, and isopropamide.
|
The antisecretory (determined from salivary flow rates) and antimotility (determined from riboflavin absorption) effects of usually recommended doses of propantheline, hexocyclium, and isopropamide were compared in four adult volunteers. Both propantheline and hexocyclium significantly decreased salivary flow and increased riboflavin absorption. Although the usual dose of propantheline was about twice as effective as the usual dose of hexocyclium in suppressing salivary flow, these doses produced comparable effects on riboflavin absorption. Isopropamide had little or no effect on either the salivary flow rate or riboflavin absorption. Propantheline and hexocyclium elicited little effect on salivary flow when administered after a meal. Prolonged-release dosage forms of these drugs produced effects comparable to those produced by much smaller doses in conventional tablets and gave no indication of providing prolonged anticholinergic effects.
|
Biopharmaceutic factors that influence effects of anticholinergic drugs: comparison of propantheline, hexocyclium, and isopropamide. The antisecretory (determined from salivary flow rates) and antimotility (determined from riboflavin absorption) effects of usually recommended doses of propantheline, hexocyclium, and isopropamide were compared in four adult volunteers. Both propantheline and hexocyclium significantly decreased salivary flow and increased riboflavin absorption. Although the usual dose of propantheline was about twice as effective as the usual dose of hexocyclium in suppressing salivary flow, these doses produced comparable effects on riboflavin absorption. Isopropamide had little or no effect on either the salivary flow rate or riboflavin absorption. Propantheline and hexocyclium elicited little effect on salivary flow when administered after a meal. Prolonged-release dosage forms of these drugs produced effects comparable to those produced by much smaller doses in conventional tablets and gave no indication of providing prolonged anticholinergic effects.
|
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] |
PMID:21952
|
Nature of acid-induced fluorescence of 17alpha-methyltestosterone.
|
The fluorescence of the 17alpha-methyltestosterone-trichloroacetic acid reaction product, 1,2,10,15,16,17-hexahydro-10,17,17-trimethylcyclopenta[alpha]phenanthren-3-one, in strong acid was investigated. Structural requirements for fluorescence were derived from absorption and fluorescence studies of related phenanthrenones and cinnamylidene compounds possessing a similar chromophore. All compounds showed fluorescence intensity that was structure and pH dependent. Fluorescence is attributed to both enol and protonated species.
|
Nature of acid-induced fluorescence of 17alpha-methyltestosterone. The fluorescence of the 17alpha-methyltestosterone-trichloroacetic acid reaction product, 1,2,10,15,16,17-hexahydro-10,17,17-trimethylcyclopenta[alpha]phenanthren-3-one, in strong acid was investigated. Structural requirements for fluorescence were derived from absorption and fluorescence studies of related phenanthrenones and cinnamylidene compounds possessing a similar chromophore. All compounds showed fluorescence intensity that was structure and pH dependent. Fluorescence is attributed to both enol and protonated species.
|
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] |
PMID:21953
|
Indolizine derivativatives with biological activity III: 3-(3-Aminopropyl)-2-methylindolizine, 3-(3-Aminopropyl)-2-methyl-5,6,7,8-tetrahydroindolizine, and their N -alkyl derivatives.
|
The syntheses and a preliminary pharmacological evaluation of some aminopropylindolizines and aminopropyltetrahydroindolizines are reported. All compounds showed anti-5-hydroxytryptamine, anti-histamine, and antiacetylcholine activities. Some also exhibited weak CNS activity.
|
Indolizine derivativatives with biological activity III: 3-(3-Aminopropyl)-2-methylindolizine, 3-(3-Aminopropyl)-2-methyl-5,6,7,8-tetrahydroindolizine, and their N -alkyl derivatives. The syntheses and a preliminary pharmacological evaluation of some aminopropylindolizines and aminopropyltetrahydroindolizines are reported. All compounds showed anti-5-hydroxytryptamine, anti-histamine, and antiacetylcholine activities. Some also exhibited weak CNS activity.
|
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] |
PMID:21954
|
Fluorescence properties of glafenine.
|
The fluorescence properties of glafenine are partly caused by the anthranilic acid nucleus of the molecule. Correlations are made between fluorescence capacities and UV absorbance. Analytical determinations can be carried out in different solvents, e.g., ether, benzene, and ethanol. Linearity of the emission intensity with the concentration, limiting detectable sample concentrations, and Stokes shifts are reported.
|
Fluorescence properties of glafenine. The fluorescence properties of glafenine are partly caused by the anthranilic acid nucleus of the molecule. Correlations are made between fluorescence capacities and UV absorbance. Analytical determinations can be carried out in different solvents, e.g., ether, benzene, and ethanol. Linearity of the emission intensity with the concentration, limiting detectable sample concentrations, and Stokes shifts are reported.
|
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] |
PMID:21957
|
Effects of 4-aminopyridine at the frog neuromuscular junction.
|
Micromolar concentrations of 4-aminopyridine (4-AP) were able to increase the amplitude of the end-plate current in frog neuromuscular junction blocked either by d-tubocurarine or by low Ca++ high Mg++ medium. The end-plate potential was also increased. These effects were reversible. The changes in the end-plate current amplitude observed after 4-AP treatment had no effect on the end-plate current time course. There was no significant difference in the resting membrane potential or mean amplitude and frequency of spontaneous miniature end-plate potentials in the presence of 4-AP. The quantal content of the end-plate potential was increased in every preparation tested and the minimal synpatic delay was lengthened in a dose-related way. 4-AP did not modify the dependence of the amplitude of the end-plate current on membrane potential. In the presence of 4-AP, the time constant of the falling phase of the end-plate current remained an exponential function of the membrane potential. The end-plate current equilibrium potential was unaffected by 4-AP. The increase in the amount of acetylcholine released by nerve impulse induced by 4-AP occurs without modification in the calcium cooperativity. The authors suggest that 4-AP, by prolonging the presynaptic action potential, could increase calcium concentration in the nerve terminal and, thus, the transmitter release.
|
Effects of 4-aminopyridine at the frog neuromuscular junction. Micromolar concentrations of 4-aminopyridine (4-AP) were able to increase the amplitude of the end-plate current in frog neuromuscular junction blocked either by d-tubocurarine or by low Ca++ high Mg++ medium. The end-plate potential was also increased. These effects were reversible. The changes in the end-plate current amplitude observed after 4-AP treatment had no effect on the end-plate current time course. There was no significant difference in the resting membrane potential or mean amplitude and frequency of spontaneous miniature end-plate potentials in the presence of 4-AP. The quantal content of the end-plate potential was increased in every preparation tested and the minimal synpatic delay was lengthened in a dose-related way. 4-AP did not modify the dependence of the amplitude of the end-plate current on membrane potential. In the presence of 4-AP, the time constant of the falling phase of the end-plate current remained an exponential function of the membrane potential. The end-plate current equilibrium potential was unaffected by 4-AP. The increase in the amount of acetylcholine released by nerve impulse induced by 4-AP occurs without modification in the calcium cooperativity. The authors suggest that 4-AP, by prolonging the presynaptic action potential, could increase calcium concentration in the nerve terminal and, thus, the transmitter release.
|
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] |
PMID:21958
|
Pharmacologic studies on W10,294A, a new bronchodilator.
|
W10,294A (1,2,3,4-tetrahydro-8,9-dimethoxy-3(2-piperidinoethyl)-5H-[1] benzopyrano [3,4-c] pyridin-5-one dihydrochloride) is a potent antagonist of the bronchoconstriction induced by histamine, methacholine or acetylcholine. In vitro evaluation on guinea pig trachea indicated that W10,294A had both direct smooth muscle relaxant activity and modest antihistaminic properties. Resistance and dynamic compliance measurements in anesthetized dogs indicated that W10,294A prevented or reversed bronchoconstriction due to histamine or pilocapine. Bronchodilator activity of long duration was observed in dogs after oral administration. W10,294A was compared with aminophylline in several tests. W10,294A was 6 times more potent than aminophylline in relaxing isolated guinea-pig trachea. In the anesthetized dog W10,294A was more potent and longer acting than aminophylline in reversing pilocarpine-induced bronchospasm. The bronchodilator activity of W10,294A was not blocked by the beta adrenoceptor antagonist bunolol. Comparative studies in dogs and guinea pigs, using identical doses, showed that W10,294A had considerably less effect on the cardiovascular system than did aminophylline.
|
Pharmacologic studies on W10,294A, a new bronchodilator. W10,294A (1,2,3,4-tetrahydro-8,9-dimethoxy-3(2-piperidinoethyl)-5H-[1] benzopyrano [3,4-c] pyridin-5-one dihydrochloride) is a potent antagonist of the bronchoconstriction induced by histamine, methacholine or acetylcholine. In vitro evaluation on guinea pig trachea indicated that W10,294A had both direct smooth muscle relaxant activity and modest antihistaminic properties. Resistance and dynamic compliance measurements in anesthetized dogs indicated that W10,294A prevented or reversed bronchoconstriction due to histamine or pilocapine. Bronchodilator activity of long duration was observed in dogs after oral administration. W10,294A was compared with aminophylline in several tests. W10,294A was 6 times more potent than aminophylline in relaxing isolated guinea-pig trachea. In the anesthetized dog W10,294A was more potent and longer acting than aminophylline in reversing pilocarpine-induced bronchospasm. The bronchodilator activity of W10,294A was not blocked by the beta adrenoceptor antagonist bunolol. Comparative studies in dogs and guinea pigs, using identical doses, showed that W10,294A had considerably less effect on the cardiovascular system than did aminophylline.
|
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] |
PMID:21962
|
Combining therapeutic approaches.
|
It would seem on the surface that psychotherapeutic approaches as different as psychoanalysis and behavioral therapy have little in common. In fact, they seem to be similar in terms of expectation of help, nonconfirming experiences, informational learning, changes in self-concept, reinforcement/influence, paradox, and problem solving. Therapists who work with clients who present life-threatening symptoms, self-reinforcing cycles, and/or therapeutic engagement difficulties may do well to consider ways to combine therapeutic approaches in order to deal with these sticky therapeutic problems.
|
Combining therapeutic approaches. It would seem on the surface that psychotherapeutic approaches as different as psychoanalysis and behavioral therapy have little in common. In fact, they seem to be similar in terms of expectation of help, nonconfirming experiences, informational learning, changes in self-concept, reinforcement/influence, paradox, and problem solving. Therapists who work with clients who present life-threatening symptoms, self-reinforcing cycles, and/or therapeutic engagement difficulties may do well to consider ways to combine therapeutic approaches in order to deal with these sticky therapeutic problems.
|
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] |
PMID:21963
|
Orally active esters of cephalosporin antibiotics. Synthesis and biological properties of acyloxymethyl esters of 7-(D-2-amino-2-phenylacetamido)-3-[5-methyl-(1,3,4-thiadiazol-2-yl)thiomethyl]-3-cephem-4-carboxylic acid.
|
The synthesis of the acetoxymethyl (AOM), pivaloloxymethyl (POM), and phthalidyl (PHTH) esters of 7-[D-(-)-2-amino-2-phenylacetamido]-3-[5-methyl-(1,3,4-thiadiazol-2-yl)thiomethyl]-3-cephem-4-carboxylic acid (1a), a broad-spectrum semisynthetic cephalosporin antibiotic, is described. These esters were examined as potential orally active antibiotic prodrugs. The superior oral absorption of the three esters relative to the unesterified parent, 1a, is demonstrated by differential blood levels as well as measurement of the rate at which doses of the ester leave the gastrointestinal tract and appear in the urine. A study of the decreased stability of the three esters relative to 1a at pH 4.5, 6.5, and 7.5 is also presented.
|
Orally active esters of cephalosporin antibiotics. Synthesis and biological properties of acyloxymethyl esters of 7-(D-2-amino-2-phenylacetamido)-3-[5-methyl-(1,3,4-thiadiazol-2-yl)thiomethyl]-3-cephem-4-carboxylic acid. The synthesis of the acetoxymethyl (AOM), pivaloloxymethyl (POM), and phthalidyl (PHTH) esters of 7-[D-(-)-2-amino-2-phenylacetamido]-3-[5-methyl-(1,3,4-thiadiazol-2-yl)thiomethyl]-3-cephem-4-carboxylic acid (1a), a broad-spectrum semisynthetic cephalosporin antibiotic, is described. These esters were examined as potential orally active antibiotic prodrugs. The superior oral absorption of the three esters relative to the unesterified parent, 1a, is demonstrated by differential blood levels as well as measurement of the rate at which doses of the ester leave the gastrointestinal tract and appear in the urine. A study of the decreased stability of the three esters relative to 1a at pH 4.5, 6.5, and 7.5 is also presented.
|
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] |
PMID:21964
|
Some practical results of the London Medical Group conference on iatrogenic disease.
|
Although many conferences stimulate a great deal of discussion and practical interest at the time, not so many are followed up to try and estimate what, if any, practical results followed the meeting. This the authors of this study have done. (In Britain the 'medical groups' are voluntary groupings of students at medical schools who meet to discuss ethical problems related to their profession). Sixty-five participants (not all of them students) in the conference on iatrogenic disease replied to the questionnaire, and from the answers it was clear that not only the attitudes of those responding had in some cases been changed but in some positive action had resulted, for example, in the matter of prescribing. This analysis may provide an answer to those who criticize conferences as being a waste of time and money, because much more than could be evaluated from the responses to this survey must have affected all the participants.
|
Some practical results of the London Medical Group conference on iatrogenic disease. Although many conferences stimulate a great deal of discussion and practical interest at the time, not so many are followed up to try and estimate what, if any, practical results followed the meeting. This the authors of this study have done. (In Britain the 'medical groups' are voluntary groupings of students at medical schools who meet to discuss ethical problems related to their profession). Sixty-five participants (not all of them students) in the conference on iatrogenic disease replied to the questionnaire, and from the answers it was clear that not only the attitudes of those responding had in some cases been changed but in some positive action had resulted, for example, in the matter of prescribing. This analysis may provide an answer to those who criticize conferences as being a waste of time and money, because much more than could be evaluated from the responses to this survey must have affected all the participants.
|
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] |
PMID:21966
|
Glucose-6-phosphate dehydrogenase (G6PD) activity of human sperm.
|
Sperm from normal human donors and a G6PD-A- individual were examined for x-linked glucose-6-phosphate dehydrogenase activity and autosomally linked 6-phosphogluconate dehydrogenase activity. With the use of fluorescence microscopy, we divised a procedure to visualise in individual sperm cells the fluorescence of reduced coenzyme NADPH formed by each of the two enzymes in the presence of appropriate substrates. We found significant differences in the population distribution of sperm expressing each of the two activities, and the ratio of the two activities in sperm homogenate is very different from the one found in erythrocyte lysates. The possibility of haploid gene expression has been considered in interpreting these results.
|
Glucose-6-phosphate dehydrogenase (G6PD) activity of human sperm. Sperm from normal human donors and a G6PD-A- individual were examined for x-linked glucose-6-phosphate dehydrogenase activity and autosomally linked 6-phosphogluconate dehydrogenase activity. With the use of fluorescence microscopy, we divised a procedure to visualise in individual sperm cells the fluorescence of reduced coenzyme NADPH formed by each of the two enzymes in the presence of appropriate substrates. We found significant differences in the population distribution of sperm expressing each of the two activities, and the ratio of the two activities in sperm homogenate is very different from the one found in erythrocyte lysates. The possibility of haploid gene expression has been considered in interpreting these results.
|
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] |
PMID:21967
|
Primary care education trends in U.S. medical schools and teaching hospitals.
|
In 1973 Schroeder and colleagues conducted a survey of U.S. Medical schools in order to ascertain the nature of change in primary care education which had occurred by that date. In 1976 the authors of the present paper utilized the same survey instrument to document trend data over the three-year period. While conclusions from the 1973 survey pictured primary care education in a transitional state, the 1976 data suggest movement toward a general consolidation of efforts. The 1976 data indicate a continued emphasis on education in the ambulatory care area with no well-defined locus for coordinating institutionwide primary care training efforts, a leveling off of interest in health maintenance organizations (HMO) affiliations, no significant change in the number of affiliated programs for training nurse practitioners or physician's assistants, and a marked increase in the number of schools with affiliated generalist residency programs in internal medicine and pediatrics.
|
Primary care education trends in U.S. medical schools and teaching hospitals. In 1973 Schroeder and colleagues conducted a survey of U.S. Medical schools in order to ascertain the nature of change in primary care education which had occurred by that date. In 1976 the authors of the present paper utilized the same survey instrument to document trend data over the three-year period. While conclusions from the 1973 survey pictured primary care education in a transitional state, the 1976 data suggest movement toward a general consolidation of efforts. The 1976 data indicate a continued emphasis on education in the ambulatory care area with no well-defined locus for coordinating institutionwide primary care training efforts, a leveling off of interest in health maintenance organizations (HMO) affiliations, no significant change in the number of affiliated programs for training nurse practitioners or physician's assistants, and a marked increase in the number of schools with affiliated generalist residency programs in internal medicine and pediatrics.
|
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] |
PMID:21968
|
Orientation effects on microwave-induced hyperthermia and neurochemical correlates.
|
This paper describes the effect of field orientation on the hyperthermia produced by microwave irradiation. Rats exposed in the E-orientation (long-axis of animal parallel to E-field) to 1600 tmhz radiation become significantly hotter than those exposed in the H-field at the same power density. Norepinephrine and dopamine, but not serotonin content of the basal hypothalamus is reduced as a concomitant of microwave-induced brain hyperthermia.
|
Orientation effects on microwave-induced hyperthermia and neurochemical correlates. This paper describes the effect of field orientation on the hyperthermia produced by microwave irradiation. Rats exposed in the E-orientation (long-axis of animal parallel to E-field) to 1600 tmhz radiation become significantly hotter than those exposed in the H-field at the same power density. Norepinephrine and dopamine, but not serotonin content of the basal hypothalamus is reduced as a concomitant of microwave-induced brain hyperthermia.
|
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] |
PMID:21970
|
An electron microscopic study of early developmental stages, myogenesis, oogenesis and cnidogenesis in the anthomedusa, Podocoryne carnea M. Sars.
|
This descriptive electron microscopic study of the blastogenetic medusa development of Podocoryne carnea focuses on the earliest stages of primordium formation, myogenesis, oogenesis and cnidogenesis. The events which take place at the cellular level prior to the formation of stage 1 (Frey, '68), which are characterized by ecto- and entodermal accumulations of undifferentiated I-cells and the beginning of transdifferentiation of epithelial cells, have been subdivided into four distinct stages (U1-U4). The genealogy of cells participating in medusa differentiation indicates that some cell types of the medusa are derived by transdifferentiation from the polyp's epithelial cells, while others originate by differentiation from I-cells. The myogenesis of the subumbrellar muscle cells resembles vertebrate myocardiac differentiation in many respects.
|
An electron microscopic study of early developmental stages, myogenesis, oogenesis and cnidogenesis in the anthomedusa, Podocoryne carnea M. Sars. This descriptive electron microscopic study of the blastogenetic medusa development of Podocoryne carnea focuses on the earliest stages of primordium formation, myogenesis, oogenesis and cnidogenesis. The events which take place at the cellular level prior to the formation of stage 1 (Frey, '68), which are characterized by ecto- and entodermal accumulations of undifferentiated I-cells and the beginning of transdifferentiation of epithelial cells, have been subdivided into four distinct stages (U1-U4). The genealogy of cells participating in medusa differentiation indicates that some cell types of the medusa are derived by transdifferentiation from the polyp's epithelial cells, while others originate by differentiation from I-cells. The myogenesis of the subumbrellar muscle cells resembles vertebrate myocardiac differentiation in many respects.
|
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] |
PMID:21972
|
Hormonal regulation of testicular descent: experimental and clinical observations.
|
Hormonal regulation of testicular descent has been investigated. Based on experimental studies using the rat and on a review of clinical material it has been determined that testicular descent is an androgen-mediated event directly under the regulation of pituitary gonadotropin. Furthermore, the active androgenic metabolite involved in this process appears to be dihydrotestosterone, which is synthesized by the testis and must be present in high local concentrations to be effective. In addition to these hormonal requirements the anatomy of the inguinal canal must provide unimpeded migration of the testis into the scrotum. Any imbalance or anomaly of these prerequisites may lead to cryptorchidism.
|
Hormonal regulation of testicular descent: experimental and clinical observations. Hormonal regulation of testicular descent has been investigated. Based on experimental studies using the rat and on a review of clinical material it has been determined that testicular descent is an androgen-mediated event directly under the regulation of pituitary gonadotropin. Furthermore, the active androgenic metabolite involved in this process appears to be dihydrotestosterone, which is synthesized by the testis and must be present in high local concentrations to be effective. In addition to these hormonal requirements the anatomy of the inguinal canal must provide unimpeded migration of the testis into the scrotum. Any imbalance or anomaly of these prerequisites may lead to cryptorchidism.
|
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] |
PMID:21973
|
Protective efficacy of pneumococcal polysaccharide vaccines.
|
Clinical studies of 6- and 12-valent pneumococcal capsular polysaccharide vaccines were carried out in controlled studies among novice gold miners in South Africa. In the studies 1,523 persons received pneumococcal vaccine, and 3,171 were included as controls. In the great majority of subjects given pneumococcal vaccine, antibodies developed against the capsular types included in the vaccine. The 6-valent vaccine afforded 76% reduction in cases of laboratory-verified pneumococcal pneumonia caused by the homologous types, and there was 92% reduction in the cases afforded by the 12-valent vaccine. The vaccines were well tolerated and offer great promise for effective control of illnesses caused by pneumococci.
|
Protective efficacy of pneumococcal polysaccharide vaccines. Clinical studies of 6- and 12-valent pneumococcal capsular polysaccharide vaccines were carried out in controlled studies among novice gold miners in South Africa. In the studies 1,523 persons received pneumococcal vaccine, and 3,171 were included as controls. In the great majority of subjects given pneumococcal vaccine, antibodies developed against the capsular types included in the vaccine. The 6-valent vaccine afforded 76% reduction in cases of laboratory-verified pneumococcal pneumonia caused by the homologous types, and there was 92% reduction in the cases afforded by the 12-valent vaccine. The vaccines were well tolerated and offer great promise for effective control of illnesses caused by pneumococci.
|
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] |
PMID:21974
|
Management of diabetic patients with low blood pH.
|
In metabolic acidosis, where blood pH is less than 7.20, loss of respiratory centre response to lowered carbon dioxide content and increased hydrogen ion concentration may result. The use of sodium bicarbonate for management of diabetic ketosis and lactic acidosis has been controversial (Kaye 1975) in the past, but it is now the treatment of choice.
|
Management of diabetic patients with low blood pH. In metabolic acidosis, where blood pH is less than 7.20, loss of respiratory centre response to lowered carbon dioxide content and increased hydrogen ion concentration may result. The use of sodium bicarbonate for management of diabetic ketosis and lactic acidosis has been controversial (Kaye 1975) in the past, but it is now the treatment of choice.
|
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] |
PMID:21981
|
Cause of decrease of ethylmorphine N-demethylase activity of lipid peroxidation in microsomes from the rat, guinea pig and rabbit.
|
There were marked differences among animal species between NADPH-dependent and ascorbic acid-Fe++-dependent lipid peroxidation. In NADPH-dependent lipid peroxidation, this activity occurred to the greatest extent in rats followed by guinea pigs and rabbits and such was much lower in rabbits than in guinea pigs. On the other hand, rabbit microsomes exhibited higher lipid peroxidation activity than guinea pigs in ascorbic acid plus Fe++ or Fe++-dependent lipid peroxidation although the activity was still lower than in rats. The ascorbic acid plus Fe++-stimulated lipid peroxidation produced a decrease in ethylmorphine N-demethylase activity which was closely related to ethylmorphine-enhanced NADPH-cytochrome P-450 reductase activity but was not related to the change of the apparent content of cytochrome P-450 in all animal species. These results indicate that decrease of NADPH-cytochrome P-450 reductase activity induces a decrease in ethylmorphine N-demethylase activity by lipid peroxidation.
|
Cause of decrease of ethylmorphine N-demethylase activity of lipid peroxidation in microsomes from the rat, guinea pig and rabbit. There were marked differences among animal species between NADPH-dependent and ascorbic acid-Fe++-dependent lipid peroxidation. In NADPH-dependent lipid peroxidation, this activity occurred to the greatest extent in rats followed by guinea pigs and rabbits and such was much lower in rabbits than in guinea pigs. On the other hand, rabbit microsomes exhibited higher lipid peroxidation activity than guinea pigs in ascorbic acid plus Fe++ or Fe++-dependent lipid peroxidation although the activity was still lower than in rats. The ascorbic acid plus Fe++-stimulated lipid peroxidation produced a decrease in ethylmorphine N-demethylase activity which was closely related to ethylmorphine-enhanced NADPH-cytochrome P-450 reductase activity but was not related to the change of the apparent content of cytochrome P-450 in all animal species. These results indicate that decrease of NADPH-cytochrome P-450 reductase activity induces a decrease in ethylmorphine N-demethylase activity by lipid peroxidation.
|
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] |
PMID:21982
|
Dualist or pseudo-dualist interactions of mepyramine, diphenhydramine and eprozinol with histamine at H1-receptors.
|
The types of interaction of mepyramine (M), diphenhydramin: (D) and eprozinol (E), with histamine H1-receptors of guinea pig ileal and tracheal smooth muscle, were comparatively studied in vitro. According to the concentrations used, all three substances showed an apparent dualist mechanism of action on both preparations when histamine (dihydrochloride) was used as the agonist. The competitive component of this mechanism (at low concentrations) was characterized by the following pA2 values: 9.01 (M), 7.80 (D) and 5.64 (E) with the ileum; 8.06 (M), 7.00 (D) and 6.02 (E) with the trachea. The so called non specific component (at high concentrations) was of comparable intensity in the two organs. The pD'2 values were 5.54-5.66 (M), 4.65-4.38 (D) and 3.82-3.55 (E) with ileal and tracheal muscle, respectively. At low concentrations the equi-active dose-ratio for N/D/E (1/16/2300 on the ileum) became 1/12/110 when the trachea was used as the effector. This is surprising since histaminergic receptors of the two preparations are of the same H1-type. It is suggested that only diphenhydramine and eprozinol are really dualistic, and that the non-specific mechanism of activity differs for each drug with that of eprozinol being effective on tracheal muscle.
|
Dualist or pseudo-dualist interactions of mepyramine, diphenhydramine and eprozinol with histamine at H1-receptors. The types of interaction of mepyramine (M), diphenhydramin: (D) and eprozinol (E), with histamine H1-receptors of guinea pig ileal and tracheal smooth muscle, were comparatively studied in vitro. According to the concentrations used, all three substances showed an apparent dualist mechanism of action on both preparations when histamine (dihydrochloride) was used as the agonist. The competitive component of this mechanism (at low concentrations) was characterized by the following pA2 values: 9.01 (M), 7.80 (D) and 5.64 (E) with the ileum; 8.06 (M), 7.00 (D) and 6.02 (E) with the trachea. The so called non specific component (at high concentrations) was of comparable intensity in the two organs. The pD'2 values were 5.54-5.66 (M), 4.65-4.38 (D) and 3.82-3.55 (E) with ileal and tracheal muscle, respectively. At low concentrations the equi-active dose-ratio for N/D/E (1/16/2300 on the ileum) became 1/12/110 when the trachea was used as the effector. This is surprising since histaminergic receptors of the two preparations are of the same H1-type. It is suggested that only diphenhydramine and eprozinol are really dualistic, and that the non-specific mechanism of activity differs for each drug with that of eprozinol being effective on tracheal muscle.
|
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] |
PMID:21983
|
Norepinephrine-synthesizing enzymes in brain, adrenals and peripheral sympathetic nerves of spontaneously hypertensive rats.
|
Dopamine-beta-hydroxylase (DBH) activity in serum, DBH and tyrosine hydroxylase (TH) activities in mesenteric vessels, and DBH and TH activities in locus coeruleus and hypothalamus of brain did not differ significantly between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKR) at 16 weeks of age when hypertension of SHR was fixed. In contrast, DBH and TH activities in vas deferens and adrenal glands were significantly higher in SHR than in WKR. These changes in SHR at 16 weeks of age after establishment of hypertension are directly opposite those reported previously in SHR at 3 weeks of age before the onset of hypertension.
|
Norepinephrine-synthesizing enzymes in brain, adrenals and peripheral sympathetic nerves of spontaneously hypertensive rats. Dopamine-beta-hydroxylase (DBH) activity in serum, DBH and tyrosine hydroxylase (TH) activities in mesenteric vessels, and DBH and TH activities in locus coeruleus and hypothalamus of brain did not differ significantly between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKR) at 16 weeks of age when hypertension of SHR was fixed. In contrast, DBH and TH activities in vas deferens and adrenal glands were significantly higher in SHR than in WKR. These changes in SHR at 16 weeks of age after establishment of hypertension are directly opposite those reported previously in SHR at 3 weeks of age before the onset of hypertension.
|
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] |
PMID:21992
|
The action of antacids on serum gastrin concentrations in man.
|
The effects of two doses of NaCl and NaHCO3 as well as of Al(OH3) and AlCl3 respectively, on serum gastrin concentrations and intragastric pH were compared in duodenal ulcer patients. Also the effect of one dose of an AlPO4 containing commercial antacid on serum gastrin concentration and intragastric pH was studied in duodenal ulcer patients and in a control group. Care was taken to induce swallowing at the times the substances were given through an orogastric tube. The study showed that antacids elicited significantly greater gastrin responses than their non-buffering chloride compounds and that the rise of gastrin after a single dose of antacid was small but significant in duodenal ulcer patients and insignificant in non-ulcer controls. Several factors as rising intragastric pH, individual responsiveness, duodenal ulcer state, vagal influences, the participating ions and their amount contribute to the rise of gastrin after antacids.
|
The action of antacids on serum gastrin concentrations in man. The effects of two doses of NaCl and NaHCO3 as well as of Al(OH3) and AlCl3 respectively, on serum gastrin concentrations and intragastric pH were compared in duodenal ulcer patients. Also the effect of one dose of an AlPO4 containing commercial antacid on serum gastrin concentration and intragastric pH was studied in duodenal ulcer patients and in a control group. Care was taken to induce swallowing at the times the substances were given through an orogastric tube. The study showed that antacids elicited significantly greater gastrin responses than their non-buffering chloride compounds and that the rise of gastrin after a single dose of antacid was small but significant in duodenal ulcer patients and insignificant in non-ulcer controls. Several factors as rising intragastric pH, individual responsiveness, duodenal ulcer state, vagal influences, the participating ions and their amount contribute to the rise of gastrin after antacids.
|
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] |
PMID:21999
|
Pleural effusions.
|
Many different conditions result in the accumulation of pleural fluid. A diagnostic thoracentesis should be performed on all patients with pleural effusion from whom pleural fluid can be easily obtained. Empirically we have found that when the pleural effusion is more than 10 mm thick on the lateral decubitus roentgenogram, pleural fluid is easily obtained. At least 30 cc fluid should be obtained and distributed to the various laboratories as outlined in Table 2. The results of these tests will show whether the fluid is a transudate or an exudate. If the fluid is a transudate, no further diagnostic procedures need be directed towards the pleura. If the fluid is an exudate, the diagnosis will frequently be made by these original tests and therapy for the pleural disease can be instituted. If the diagnosis has not been made, the results of these tests should lead to a rational diagnostic attack.
|
Pleural effusions. Many different conditions result in the accumulation of pleural fluid. A diagnostic thoracentesis should be performed on all patients with pleural effusion from whom pleural fluid can be easily obtained. Empirically we have found that when the pleural effusion is more than 10 mm thick on the lateral decubitus roentgenogram, pleural fluid is easily obtained. At least 30 cc fluid should be obtained and distributed to the various laboratories as outlined in Table 2. The results of these tests will show whether the fluid is a transudate or an exudate. If the fluid is a transudate, no further diagnostic procedures need be directed towards the pleura. If the fluid is an exudate, the diagnosis will frequently be made by these original tests and therapy for the pleural disease can be instituted. If the diagnosis has not been made, the results of these tests should lead to a rational diagnostic attack.
|
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] |
PMID:21998
|
Alterations in tyrosine aminotransferase isoenzymes of liver of rats as a function of age.
|
The specific activities (units/mg protein) of tyrosine aminotransferase (TAT) and its isoenzymes, cytoplasmic (c-), mitochondrial (m-) and nuclear (n-TAT), of the liver of 6-, 35- and 76-week old male albino rats were determined. The activities of all the isoenzymes are highest at 6 weeks and are significantly lower at 35 weeks. Total TAT and c-TAT remain unchanged, m-TAT decreases and n-TAT increases significantly after 35 weeks. c-TAT was partially purified from the liver of rats of the three ages to study its kinetic and molecular properties. These properties apparently do not change as a function of age.
|
Alterations in tyrosine aminotransferase isoenzymes of liver of rats as a function of age. The specific activities (units/mg protein) of tyrosine aminotransferase (TAT) and its isoenzymes, cytoplasmic (c-), mitochondrial (m-) and nuclear (n-TAT), of the liver of 6-, 35- and 76-week old male albino rats were determined. The activities of all the isoenzymes are highest at 6 weeks and are significantly lower at 35 weeks. Total TAT and c-TAT remain unchanged, m-TAT decreases and n-TAT increases significantly after 35 weeks. c-TAT was partially purified from the liver of rats of the three ages to study its kinetic and molecular properties. These properties apparently do not change as a function of age.
|
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] |
PMID:22033
|
Effectors of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase of rat liver.
|
The lower Vmax of 6PGDH with respect to G6PDH and its higher sensitivity to inhibition by NADPH, suggest the existence of an imbalance between the two dehydrogenases of the pentose phosphate pathway in rat liver. Possible modulators of these activities, particularly in relation with the inhibition by NADPH in physiological conditions, have been investigated. The results suggest that in both cases the inhibition by NADPH is strictly isosteric and that the relative affinities for the reduced and oxidized forms of the pyridine nucleotide are unaffected by glutathion, the intermediates of the pentose phosphate shunt or some divalent ions.
|
Effectors of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase of rat liver. The lower Vmax of 6PGDH with respect to G6PDH and its higher sensitivity to inhibition by NADPH, suggest the existence of an imbalance between the two dehydrogenases of the pentose phosphate pathway in rat liver. Possible modulators of these activities, particularly in relation with the inhibition by NADPH in physiological conditions, have been investigated. The results suggest that in both cases the inhibition by NADPH is strictly isosteric and that the relative affinities for the reduced and oxidized forms of the pyridine nucleotide are unaffected by glutathion, the intermediates of the pentose phosphate shunt or some divalent ions.
|
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] |
PMID:22034
|
Isocitrate dehydrogenase of Tetrahymena pyriformis.
|
We have studied the isocitrate dehydrogenase of Tetrahymena pyriformis. This enzyme is able to utilize both NAD and NADP, but kinetic studies suggest that the enzymatic activity with NAD is not of physiological signifance. Some of the factors that might regualte the NADP-dependent isocitrate dehydrogenase were also studied. This enzyme has an absolute requirement for divalent cations; Mg,+ and Mn2+ will serve as cofactors but the latter is more effective than the former. It is known that this enzyme is subject to a concerted inhibition by oxaloacetate and glyoxylate. Either glyoxylate or oxaloacetate alone also are capable of inhibiting the enzyme although higher concentrations are required. We have found concerted inhibition also for the NAD-dependent isocitrate dehydrogenase from rat liver and yeast. The activity of the Tetrahymena pyriformis enzyme is inhibited by NADPH. This inhibition is competitive with NADP. The Ki and Km values are, respectively, 20 micrometers and 18 micrometers.
|
Isocitrate dehydrogenase of Tetrahymena pyriformis. We have studied the isocitrate dehydrogenase of Tetrahymena pyriformis. This enzyme is able to utilize both NAD and NADP, but kinetic studies suggest that the enzymatic activity with NAD is not of physiological signifance. Some of the factors that might regualte the NADP-dependent isocitrate dehydrogenase were also studied. This enzyme has an absolute requirement for divalent cations; Mg,+ and Mn2+ will serve as cofactors but the latter is more effective than the former. It is known that this enzyme is subject to a concerted inhibition by oxaloacetate and glyoxylate. Either glyoxylate or oxaloacetate alone also are capable of inhibiting the enzyme although higher concentrations are required. We have found concerted inhibition also for the NAD-dependent isocitrate dehydrogenase from rat liver and yeast. The activity of the Tetrahymena pyriformis enzyme is inhibited by NADPH. This inhibition is competitive with NADP. The Ki and Km values are, respectively, 20 micrometers and 18 micrometers.
|
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] |
PMID:22035
|
[The legal status of medical students during practical training in hospitals (author's transl)].
|
The most important change in the qualification regulations in force at the present time is the provision for the practical training of medical students, which occurs not only in university hospitals but also in "teaching hospitals" outside the university. The realization of the practical year is problematic according to the actual conditions because of the difficulties and financial investment necessarily associated with it. Furthermore, the legal status of the students during the practical activities differes from that of earlier medical assistants, because according to the present law the legal provisions for employment and social insurance such as the determination of division of labour, working hours and remuneration and also for third party and accident insurance do not apply.
|
[The legal status of medical students during practical training in hospitals (author's transl)]. The most important change in the qualification regulations in force at the present time is the provision for the practical training of medical students, which occurs not only in university hospitals but also in "teaching hospitals" outside the university. The realization of the practical year is problematic according to the actual conditions because of the difficulties and financial investment necessarily associated with it. Furthermore, the legal status of the students during the practical activities differes from that of earlier medical assistants, because according to the present law the legal provisions for employment and social insurance such as the determination of division of labour, working hours and remuneration and also for third party and accident insurance do not apply.
|
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] |
PMID:22036
|
[Hyperergic collagenoses. Clinical aspects, differential diagnosis and therapy (author's transl)].
|
On the basis of inpatient and outpatient observations of the longterm course in 44 patients with erythematodes disseminatus, 8 with periarteritis nodosa, 4 with Wegener's granulomatosis, 5 with dermatomyositis, 3 with giant cell arteritis and 9 with scleroderma the pathogenesis, differential diagnosis and therapy of these diseases is discussed. The differential diagnosis and longterm supervision being dealt with particularly thoroughly. Early recognition of the disease episodes and appropriate therapeutic action in the shape of increased doses of prednisolone are important. Additional cytostatics were given if the kidney was involved.
|
[Hyperergic collagenoses. Clinical aspects, differential diagnosis and therapy (author's transl)]. On the basis of inpatient and outpatient observations of the longterm course in 44 patients with erythematodes disseminatus, 8 with periarteritis nodosa, 4 with Wegener's granulomatosis, 5 with dermatomyositis, 3 with giant cell arteritis and 9 with scleroderma the pathogenesis, differential diagnosis and therapy of these diseases is discussed. The differential diagnosis and longterm supervision being dealt with particularly thoroughly. Early recognition of the disease episodes and appropriate therapeutic action in the shape of increased doses of prednisolone are important. Additional cytostatics were given if the kidney was involved.
|
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] |
PMID:22042
|
Factors influencing germ tube production in Candida albicans.
|
The capacity of Candida albicans to produce germ tubes in a simple medium is analysed as a function of the pH variation, the bacterial supernatant and the addition of differing concentrations of various species of bacteria.
|
Factors influencing germ tube production in Candida albicans. The capacity of Candida albicans to produce germ tubes in a simple medium is analysed as a function of the pH variation, the bacterial supernatant and the addition of differing concentrations of various species of bacteria.
|
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] |
PMID:22043
|
Determinations of pH, moisture, carbohydrates and ash of Egyptian buffalo meat.
|
A total of 128 samples of Egyptian buffalo meat was analysed for its pH value, moisture, carbohydrates and ash contents. Statistical analysis of the data obtained shows significant difference at 0.01 level for moisture in relation to sex and cut (abdomen and thigh, respectively). There is also significant difference at 0.05 level for moisture in dry season in relation to sex and for ash in relation to cut. At 0.1 level moisture shows a significant difference in relation to season, female in relation to season and green season in relation to sex. Ash also shows a significant difference at 0.1 level in female in relation to season.
|
Determinations of pH, moisture, carbohydrates and ash of Egyptian buffalo meat. A total of 128 samples of Egyptian buffalo meat was analysed for its pH value, moisture, carbohydrates and ash contents. Statistical analysis of the data obtained shows significant difference at 0.01 level for moisture in relation to sex and cut (abdomen and thigh, respectively). There is also significant difference at 0.05 level for moisture in dry season in relation to sex and for ash in relation to cut. At 0.1 level moisture shows a significant difference in relation to season, female in relation to season and green season in relation to sex. Ash also shows a significant difference at 0.1 level in female in relation to season.
|
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] |
PMID:22044
|
[Alkali treatment of proteins. I. Behavior of sulfhydryl and disulfide groups in alkali-treated beta-lactoglobulin and alpha-lactalbumin].
|
The alkali treatment of beta-lactoglobulin and alpha-lactalbumin results in the splitting of disulphide bonds in the protein molecules. When a 0.8-10(4) M beta-lactoglobulin solution in a 0.022 N sodium hydroxide solution (pH = 12) is heated at 90 degrees C for 30 min, 0-4 M disulphide groups, 2.2 M sulfhydryl groups and 1.8 M sulphide ions/M dimeric beta-lactoglobulin are detectable of the total of 4 M disulphide groups and 2 M sulfhydryl groups/M dimeric beta-lactoglobulin. The sulphide ions can be determined directly in the form of hydrogen sulphide or by calculating the difference between the values from the amperometric-argentometric titration and those from the method of ELLMAN (reaction with DTNB). The disulphide groups are determined with the aid of DTNB after reduction with sodium borohydride. The sulfhydryl groups obtained by reduction with sodium borohydride re-oxidize, the reaction velocity being of the second order. If the disulphide groups are reduced with sodium borohydride, the argentometric-amperometric determination of the sulfhydryl groups by means of the platinum rotating-disk electrode is disturbed by the presence of boric acid.
|
[Alkali treatment of proteins. I. Behavior of sulfhydryl and disulfide groups in alkali-treated beta-lactoglobulin and alpha-lactalbumin]. The alkali treatment of beta-lactoglobulin and alpha-lactalbumin results in the splitting of disulphide bonds in the protein molecules. When a 0.8-10(4) M beta-lactoglobulin solution in a 0.022 N sodium hydroxide solution (pH = 12) is heated at 90 degrees C for 30 min, 0-4 M disulphide groups, 2.2 M sulfhydryl groups and 1.8 M sulphide ions/M dimeric beta-lactoglobulin are detectable of the total of 4 M disulphide groups and 2 M sulfhydryl groups/M dimeric beta-lactoglobulin. The sulphide ions can be determined directly in the form of hydrogen sulphide or by calculating the difference between the values from the amperometric-argentometric titration and those from the method of ELLMAN (reaction with DTNB). The disulphide groups are determined with the aid of DTNB after reduction with sodium borohydride. The sulfhydryl groups obtained by reduction with sodium borohydride re-oxidize, the reaction velocity being of the second order. If the disulphide groups are reduced with sodium borohydride, the argentometric-amperometric determination of the sulfhydryl groups by means of the platinum rotating-disk electrode is disturbed by the presence of boric acid.
|
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] |
PMID:22049
|
Neurotransmitter synthesis and uptake by isolated sympathetic neurones in microcultures.
|
Assays of isolated single sympathetic neurones show that their transmitter functions can be either adrenergic or cholinergic depending on growth conditions. The data suggest that the number of transmitters made by most mature individual neurones is restricted.
|
Neurotransmitter synthesis and uptake by isolated sympathetic neurones in microcultures. Assays of isolated single sympathetic neurones show that their transmitter functions can be either adrenergic or cholinergic depending on growth conditions. The data suggest that the number of transmitters made by most mature individual neurones is restricted.
|
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] |
PMID:22051
|
The influence of pH on the excision of UV-photoproducts from HeLa cells.
|
Excision of pyrimidine dimers with pH decreasing in UV irradiated HeLa cells can be depressed. This depression is independent of the UV dose within the investigated range. The excision capacity of HeLa repair system from absolute amount of excised dimers is shown.
|
The influence of pH on the excision of UV-photoproducts from HeLa cells. Excision of pyrimidine dimers with pH decreasing in UV irradiated HeLa cells can be depressed. This depression is independent of the UV dose within the investigated range. The excision capacity of HeLa repair system from absolute amount of excised dimers is shown.
|
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] |
PMID:22053
|
Local glucose utilization in acute focal cerebral ischemia: local dysmetabolism and diaschisis.
|
By means of an autoradiographic technique employing 14C-2-deoxyglucose, abnormalities of local brain glucose utilization were studied 90 minutes following occlusion of the left middle cerebral and common carotid arteries in a series of pentobarbital-anesthetized cats. Sham-insulted control animals exhibited a normal pattern of regional glucose utilization. In animals with vascular occlusion, a zone of greatly suppressed glucose utilization occupied the caudate nucleus of the ischemic hemisphere, with variable extension, and was surrounded by a narrow rim of increased local brain glucose utilization, suggesting the occurrence of enhanced anaerobic glycolysis in the latter zones. The cerebral cortex, which was less constantly affected, showed alternating regions of increased and decreased glucose utilization. Quantitation of local brain glucose utilization values from the contralateral nonischemic hemisphere revealed a mild suppression of cortical glucose utilization relative to the control animals. This may be the metabolic equivalent of diaschisis.
|
Local glucose utilization in acute focal cerebral ischemia: local dysmetabolism and diaschisis. By means of an autoradiographic technique employing 14C-2-deoxyglucose, abnormalities of local brain glucose utilization were studied 90 minutes following occlusion of the left middle cerebral and common carotid arteries in a series of pentobarbital-anesthetized cats. Sham-insulted control animals exhibited a normal pattern of regional glucose utilization. In animals with vascular occlusion, a zone of greatly suppressed glucose utilization occupied the caudate nucleus of the ischemic hemisphere, with variable extension, and was surrounded by a narrow rim of increased local brain glucose utilization, suggesting the occurrence of enhanced anaerobic glycolysis in the latter zones. The cerebral cortex, which was less constantly affected, showed alternating regions of increased and decreased glucose utilization. Quantitation of local brain glucose utilization values from the contralateral nonischemic hemisphere revealed a mild suppression of cortical glucose utilization relative to the control animals. This may be the metabolic equivalent of diaschisis.
|
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] |
PMID:22057
|
Significance of oscillation frequency in intrapartum fetal monitoring.
|
Until now, no statistical data have been available on the significance of the frequency of FHR oscillations. In order to evaluate the relation between oscillation frequency and neonatal outcome, the last 30 minutes of 812 FHR records were analyzed with respect to the number of 812 FHR records were analyzed with respect to the number of oscillations per minute only. Close correlations were found between slow oscillations below 2 per minute and the arterial cord pH as well as the Apgar scores after 1 and 5 minutes, respectively. No relation could be established between any oscillation frequency above 2 per minute and the measures of the neonatal outcome. In discussing the results, slow oscillations are suggested to be identical with the sinusoidal FHR. Emphasis is made that for an appropriate pattern recognition, true beat-to-beat recording is required, avoiding any averaging procedure.
|
Significance of oscillation frequency in intrapartum fetal monitoring. Until now, no statistical data have been available on the significance of the frequency of FHR oscillations. In order to evaluate the relation between oscillation frequency and neonatal outcome, the last 30 minutes of 812 FHR records were analyzed with respect to the number of 812 FHR records were analyzed with respect to the number of oscillations per minute only. Close correlations were found between slow oscillations below 2 per minute and the arterial cord pH as well as the Apgar scores after 1 and 5 minutes, respectively. No relation could be established between any oscillation frequency above 2 per minute and the measures of the neonatal outcome. In discussing the results, slow oscillations are suggested to be identical with the sinusoidal FHR. Emphasis is made that for an appropriate pattern recognition, true beat-to-beat recording is required, avoiding any averaging procedure.
|
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] |
PMID:22058
|
Hyaline membrane disease and acidosis at birth in twins.
|
To test the hypothesis that the increased incidence of hyaline membrane disease in second-born twins is related to acidosis at birth, umbilical arterial [H+] was measured in 26 sets of premature twins. Although overall Twin B had a lower Apgar score than Twin A, there was no difference in their [H+]. If the delivery interval was prolonged over 8 minutes then Twin B infants were more acidemic and had lower Apgar scores. Infants with hyaline membrane disease had lower Apgar scores, but were not more acidemic than infants without respiratory distress. Our data suggest that acidosis at birth is not an important factor in the development of hyaline membrane disease.
|
Hyaline membrane disease and acidosis at birth in twins. To test the hypothesis that the increased incidence of hyaline membrane disease in second-born twins is related to acidosis at birth, umbilical arterial [H+] was measured in 26 sets of premature twins. Although overall Twin B had a lower Apgar score than Twin A, there was no difference in their [H+]. If the delivery interval was prolonged over 8 minutes then Twin B infants were more acidemic and had lower Apgar scores. Infants with hyaline membrane disease had lower Apgar scores, but were not more acidemic than infants without respiratory distress. Our data suggest that acidosis at birth is not an important factor in the development of hyaline membrane disease.
|
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] |
PMID:22060
|
Serotonin-containing neurons: their possible role in pain and analgesia.
|
Experimental evidence is reviewed showing that brain and spinal cord serotonergic neurons are involved in nociceptive responses, as well as in the analgesic effects of opiate narcotics. This evidence, based on studies employing pharmacological, surgical, electrophysiological, and dietary manipulations of central nervous system serotonergic neurotransmission, suggests that increases in the activity of brain and spinal cord serotonin neurons are associated with analgesia and enhanced antinociceptive drug potency, whereas decreases in the activities of these neurons correlate with hyperalgesia and diminished analgesic drug potency.
|
Serotonin-containing neurons: their possible role in pain and analgesia. Experimental evidence is reviewed showing that brain and spinal cord serotonergic neurons are involved in nociceptive responses, as well as in the analgesic effects of opiate narcotics. This evidence, based on studies employing pharmacological, surgical, electrophysiological, and dietary manipulations of central nervous system serotonergic neurotransmission, suggests that increases in the activity of brain and spinal cord serotonin neurons are associated with analgesia and enhanced antinociceptive drug potency, whereas decreases in the activities of these neurons correlate with hyperalgesia and diminished analgesic drug potency.
|
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] |
PMID:22063
|
Bicarbonate-induced phosphaturia: Dependence upon the magnitude of phosphate reabsorption.
|
The acute effect of bicarbonate infusion on inorganic phsophate (Pi) reabsorption was determined in thyroparathyroidectomized (TPTX) rats stabilized on a high phsophorus diet. In the normophosphatemic state, bicarbonate did not affect Pi reabsorption significantly. On the other hand, after hyperphosphatemia was induced by phosphate loading, bicarbonate inhibited Pi reabsorption. In order to determin if eht aboslute level of plasma or filtered Pi was an improtant determinant of this phosphaturic action of bicarbonate during hyperphosphatemia, equivalent rates of Pi reabsorption were achieved after phosphate infusion in TPTX rats previously stabilized on a low dietary phosphorus intake, but at significantly lower plasma Pi concentrations and filtered Pi loads than in their high dietary phosphorus counterparts. Bicarbonate inhibited Pi reabsorption equivalently in both hyperphosphatemic groups, indicating that the magnitude of Pi transport itself was of importance in determining the inhibitory response to bicarbonate. In addition, the results suggest that transport mechanisms for bicarbonate and Pi may interact competitively.
|
Bicarbonate-induced phosphaturia: Dependence upon the magnitude of phosphate reabsorption. The acute effect of bicarbonate infusion on inorganic phsophate (Pi) reabsorption was determined in thyroparathyroidectomized (TPTX) rats stabilized on a high phsophorus diet. In the normophosphatemic state, bicarbonate did not affect Pi reabsorption significantly. On the other hand, after hyperphosphatemia was induced by phosphate loading, bicarbonate inhibited Pi reabsorption. In order to determin if eht aboslute level of plasma or filtered Pi was an improtant determinant of this phosphaturic action of bicarbonate during hyperphosphatemia, equivalent rates of Pi reabsorption were achieved after phosphate infusion in TPTX rats previously stabilized on a low dietary phosphorus intake, but at significantly lower plasma Pi concentrations and filtered Pi loads than in their high dietary phosphorus counterparts. Bicarbonate inhibited Pi reabsorption equivalently in both hyperphosphatemic groups, indicating that the magnitude of Pi transport itself was of importance in determining the inhibitory response to bicarbonate. In addition, the results suggest that transport mechanisms for bicarbonate and Pi may interact competitively.
|
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] |
PMID:22069
|
Reversible lactic acidosis associated with repeated intravenous infusions of sorbitol and ethanol.
|
Infusions of fructose or sorbitol are used commonly in parenteral nutrition and may cause lactic acidosis. A case is reported in whom blood lactate concentration was monitored frequently over a 5-day period during intravenous feeding with a sorbitol-ethanol-amino acid mixture. During the first five infusions blood lactate rose only moderately, but with the final infusion lactate rose to 11-1 mmol/l and the patient had a severe metabolic acidosis. In retrospect the patient had shown deterioration in renal and hepatic function tests during the preceding 24 hr. On terminating the infusions the blood lactate concentration fell rapidly. It is suggested that great care should be exercised when using such infusions in ill patients and acid base status and renal and hepatic function should be monitored frequently.
|
Reversible lactic acidosis associated with repeated intravenous infusions of sorbitol and ethanol. Infusions of fructose or sorbitol are used commonly in parenteral nutrition and may cause lactic acidosis. A case is reported in whom blood lactate concentration was monitored frequently over a 5-day period during intravenous feeding with a sorbitol-ethanol-amino acid mixture. During the first five infusions blood lactate rose only moderately, but with the final infusion lactate rose to 11-1 mmol/l and the patient had a severe metabolic acidosis. In retrospect the patient had shown deterioration in renal and hepatic function tests during the preceding 24 hr. On terminating the infusions the blood lactate concentration fell rapidly. It is suggested that great care should be exercised when using such infusions in ill patients and acid base status and renal and hepatic function should be monitored frequently.
|
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] |
PMID:22075
|
Unfolding and refolding occur much faster for a proline-free proteins than for most proline-containing proteins.
|
The kinetics for unfolding and refolding of a parvalbumin (band 5) have been examined as a function of pH near the transition region, using stopped-flow techniques. This protein is rather unusual in that it has no proline residues, and therefore serves as a good example to test the hypothesis that the rate-limiting step seen in denaturation reactions is due to the cis-trans isomerization of proline peptide bonds in the denatured state. The kinetics for parvalbumin unfolding and refolding are complex, with the data being resolvable into two fast phases at 25 degrees. The slower of the two phases seen for the parvalbumin is about 100 to 500 times faster than the slow phase seen for proline-containing proteins under the same conditions! These results argue strongly in support of the proline isomerization hypothesis. It is also suggested that the slower phase seen for parvalbumin and the second-slowest phase seen for proline-containing proteins might be due to the cis-trans isomerization of peptide bonds of non-proline residues.
|
Unfolding and refolding occur much faster for a proline-free proteins than for most proline-containing proteins. The kinetics for unfolding and refolding of a parvalbumin (band 5) have been examined as a function of pH near the transition region, using stopped-flow techniques. This protein is rather unusual in that it has no proline residues, and therefore serves as a good example to test the hypothesis that the rate-limiting step seen in denaturation reactions is due to the cis-trans isomerization of proline peptide bonds in the denatured state. The kinetics for parvalbumin unfolding and refolding are complex, with the data being resolvable into two fast phases at 25 degrees. The slower of the two phases seen for the parvalbumin is about 100 to 500 times faster than the slow phase seen for proline-containing proteins under the same conditions! These results argue strongly in support of the proline isomerization hypothesis. It is also suggested that the slower phase seen for parvalbumin and the second-slowest phase seen for proline-containing proteins might be due to the cis-trans isomerization of peptide bonds of non-proline residues.
|
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] |
PMID:22076
|
Dopaminergic stimulation of cyclic AMP accumulation and parathyroid hormone release from dispersed bovine parathyroid cells.
|
The effects of dopaminergic agonists and antagonists have been studied in dispersed bovine parathyroid cells. Dopaminergic agonists caused a transient 20- to 40-fold increase in cellular cyclic AMP and a 2- to 3-fold increase in parathyroid hormone release. Dose-response relationships were similar for cyclic AMP accumulation and hormone release, whether studied by increasing agonist concentration or by increasing concentration of antagonist with constant agonist. The effects on the dopamine receptor could be differentiated from those of the previously characterized beta-adrenergic receptor by specific inhibitors. These results appear to represent proof with a homogeneous cell population that dopaminergic receptors linked to adenylate cyclase can regulate a secretory process mediated by cyclic AMP. This system should be useful in further studies on dopamine receptors and should provide a valid tool for determining interactions of radiolabeled ligands with such receptors.
|
Dopaminergic stimulation of cyclic AMP accumulation and parathyroid hormone release from dispersed bovine parathyroid cells. The effects of dopaminergic agonists and antagonists have been studied in dispersed bovine parathyroid cells. Dopaminergic agonists caused a transient 20- to 40-fold increase in cellular cyclic AMP and a 2- to 3-fold increase in parathyroid hormone release. Dose-response relationships were similar for cyclic AMP accumulation and hormone release, whether studied by increasing agonist concentration or by increasing concentration of antagonist with constant agonist. The effects on the dopamine receptor could be differentiated from those of the previously characterized beta-adrenergic receptor by specific inhibitors. These results appear to represent proof with a homogeneous cell population that dopaminergic receptors linked to adenylate cyclase can regulate a secretory process mediated by cyclic AMP. This system should be useful in further studies on dopamine receptors and should provide a valid tool for determining interactions of radiolabeled ligands with such receptors.
|
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] |
PMID:22074
|
[Comparative evaluation of the effect of serotonin, melatonin and methoxytryptamine on the content of biogenic amines in the hypothalamus and gonadotropic hormones in the pituitary gland depending on the periodicity of phases of the estrous cycle in rats].
|
This work is experimental and devoted to the study of functional activity of the pineal gland. The influence of the main biologically active substances (serotonin, melatonin, mexamin) produced by the epiphysis, on the hypothalamo-hypophysial structures was studied; results pointed to the significant role played by the epiphysis in the neuroendocrine regulation system.
|
[Comparative evaluation of the effect of serotonin, melatonin and methoxytryptamine on the content of biogenic amines in the hypothalamus and gonadotropic hormones in the pituitary gland depending on the periodicity of phases of the estrous cycle in rats]. This work is experimental and devoted to the study of functional activity of the pineal gland. The influence of the main biologically active substances (serotonin, melatonin, mexamin) produced by the epiphysis, on the hypothalamo-hypophysial structures was studied; results pointed to the significant role played by the epiphysis in the neuroendocrine regulation system.
|
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] |
PMID:22077
|
Activation of guanylate cyclase by superoxide dismutase and hydroxyl radical: a physiological regulator of guanosine 3',5'-monophosphate formation.
|
Partially purified soluble rat liver guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] was activated by superoxide dismutase (superoxide: superoxide oxidoreductase, EC 1.15.1.1). This activation was prevented with KCN or glutathione, inhibitors of superoxide dismutase. Guanylate cyclase preparations formed superoxide ion. Activation by superoxide dismutase was further enhanced by the addition of nitrate reductase. Although guanylate cyclase activity was much greater with Mn2+ than with Mg2+ as sole cation cofactor, activation with superoxide dismutase was not observed when Mn2+ was included in incubations. Catalase also decreased the activation induced with superoxide dismutase. Thus, activation required the formation of both superoxide ion and H2O2 in incubations. Activation of guanylate cyclase could not be achieved by the addition of H2O2 alone. Scavengers of hydroxyl radicals prevented the activation. It is proposed that superoxide ion and hydrogen peroxide can lead to the formation of hydroxyl radicals that activate guanylate cyclase. This mechanism of activation can explain numerous observations of altered guanylate cyclase activity and cyclic GMP accumulation in tissues with oxidizing and reducing agents. This mechanism will also permit physiological regulation of guanylate cyclase and cyclic GMP formation when there is altered redox or free radical formation in tissues in response to hormones, other agents, and processes.
|
Activation of guanylate cyclase by superoxide dismutase and hydroxyl radical: a physiological regulator of guanosine 3',5'-monophosphate formation. Partially purified soluble rat liver guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] was activated by superoxide dismutase (superoxide: superoxide oxidoreductase, EC 1.15.1.1). This activation was prevented with KCN or glutathione, inhibitors of superoxide dismutase. Guanylate cyclase preparations formed superoxide ion. Activation by superoxide dismutase was further enhanced by the addition of nitrate reductase. Although guanylate cyclase activity was much greater with Mn2+ than with Mg2+ as sole cation cofactor, activation with superoxide dismutase was not observed when Mn2+ was included in incubations. Catalase also decreased the activation induced with superoxide dismutase. Thus, activation required the formation of both superoxide ion and H2O2 in incubations. Activation of guanylate cyclase could not be achieved by the addition of H2O2 alone. Scavengers of hydroxyl radicals prevented the activation. It is proposed that superoxide ion and hydrogen peroxide can lead to the formation of hydroxyl radicals that activate guanylate cyclase. This mechanism of activation can explain numerous observations of altered guanylate cyclase activity and cyclic GMP accumulation in tissues with oxidizing and reducing agents. This mechanism will also permit physiological regulation of guanylate cyclase and cyclic GMP formation when there is altered redox or free radical formation in tissues in response to hormones, other agents, and processes.
|
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] |
PMID:22078
|
Precursor role of arachidonic acid in release of slow reacting substance from rat basophilic leukemia cells.
|
The release of slow reacting substance (SRS) from rat basophilic leukemia cells (RBL-1) by the ionophore A23187 (5-10 mug/ml) was stimulated 5-fold by arachidonate and inhibited 78% by 5,8,11,14-eicosatetraynoate (an inhibitor of both fatty acid cyclooxygenase and lipoxygenase). Linoleic acid and linolenic acid both inhibited SRS formation, whereas indomethacin (a cyclooxygenase inhibitor) had no effect. Radiolabel from [14C]- or [3H]arachidonate was incorporated into SRS as indicated by comigration of radioactivity and bioreactivity in several chromatographic systems after purification to apparent radiochemical homogeneity. The radiolabeled SRS was clearly separated chromatographically from other known arachidonate metabolites. Thus, SRS appears to be a previously undescribed product of arachidonic acid metabolism, probably formed through the lipoxygenase pathway. The ability to prepare purified, biosynthetically labeled, SRS should be of considerable help in further studies of its structure, biologic function, and catabolism.
|
Precursor role of arachidonic acid in release of slow reacting substance from rat basophilic leukemia cells. The release of slow reacting substance (SRS) from rat basophilic leukemia cells (RBL-1) by the ionophore A23187 (5-10 mug/ml) was stimulated 5-fold by arachidonate and inhibited 78% by 5,8,11,14-eicosatetraynoate (an inhibitor of both fatty acid cyclooxygenase and lipoxygenase). Linoleic acid and linolenic acid both inhibited SRS formation, whereas indomethacin (a cyclooxygenase inhibitor) had no effect. Radiolabel from [14C]- or [3H]arachidonate was incorporated into SRS as indicated by comigration of radioactivity and bioreactivity in several chromatographic systems after purification to apparent radiochemical homogeneity. The radiolabeled SRS was clearly separated chromatographically from other known arachidonate metabolites. Thus, SRS appears to be a previously undescribed product of arachidonic acid metabolism, probably formed through the lipoxygenase pathway. The ability to prepare purified, biosynthetically labeled, SRS should be of considerable help in further studies of its structure, biologic function, and catabolism.
|
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] |
PMID:22079
|
Human leukocytic pyrogen: purification and development of a radioimmunoassay.
|
Leukocytic pyrogen is a small endogenous protein that mediates fever. Because of the limitations of bioassays, circulating leukocytic pyrogen has not been demonstrated during fever in humans. The pyrogen was produced in vitro after phagocytosis of staphylococci by blood monocytes. Antibody against the pyrogen was obtained from rabbits immunized with leukocytic pyrogen and the antiserum was purified by solid-phase immunoadsorbants. Purified antibody to the pyrogen was attached to activated Sepharose 4B and used in conjunction with gel filtration to purify the pyrogen. The pyrogen was labeled with 125I and further purified by gel filtration and ion-exchange chromatography. The final preparation of 125I-labeled pyrogen demonstrated a homogeneous band during isoelectric focusing and other separation procedures. With antibody to pyrogen attached to Sepharose, less than 0.1 of a rabbit pyrogenic dose of human leukocytic pyrogen inhibited the binding of 125I-labeled pyrogen to this immunoadsorbant, and this inhibition was not affected by the presence of human serum. Thus, a radioimmunoassay for human leukocytic pyrogen has been developed that may be used to detect circulating pyrogen during fever in humans.
|
Human leukocytic pyrogen: purification and development of a radioimmunoassay. Leukocytic pyrogen is a small endogenous protein that mediates fever. Because of the limitations of bioassays, circulating leukocytic pyrogen has not been demonstrated during fever in humans. The pyrogen was produced in vitro after phagocytosis of staphylococci by blood monocytes. Antibody against the pyrogen was obtained from rabbits immunized with leukocytic pyrogen and the antiserum was purified by solid-phase immunoadsorbants. Purified antibody to the pyrogen was attached to activated Sepharose 4B and used in conjunction with gel filtration to purify the pyrogen. The pyrogen was labeled with 125I and further purified by gel filtration and ion-exchange chromatography. The final preparation of 125I-labeled pyrogen demonstrated a homogeneous band during isoelectric focusing and other separation procedures. With antibody to pyrogen attached to Sepharose, less than 0.1 of a rabbit pyrogenic dose of human leukocytic pyrogen inhibited the binding of 125I-labeled pyrogen to this immunoadsorbant, and this inhibition was not affected by the presence of human serum. Thus, a radioimmunoassay for human leukocytic pyrogen has been developed that may be used to detect circulating pyrogen during fever in humans.
|
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] |
PMID:22080
|
Oxygen intermediates and mixed valence states of cytochrome oxidase: infrared absorption difference spectra of compounds A, B, and C of cytochrome oxidase and oxygen.
|
A study of the near-infrared absorption spectra of three oxygen compounds of membrane-bound cytochrome oxidase (ferrocytochrome c:oxygen oxidoreductase; EC 1.9.3.1) shows that the formation of compound A (oxycytochrome oxidase) causes no significant infrared absorbance changes at -103 degrees. At -64 degrees, the formation of compound C from the mixed-valence state of the oxidase leads to increased absorption at 740-750 nm. The formation of compound B at -84 degrees from the fully reduced state of the oxidase causes increased absorption at 790-800 nm. Further oxidation of cytochrome oxidase results in increased infrared absorption at 820-830 nm at -60 degrees. The position of the infrared absorption band in compound C thus depends at least upon the oxidation-reduction state of heme a and its associated copper atom. Compound C contains two types of oxidized (cupric) copper; that associated with heme a is initially oxidized, and that associated with heme a3 is oxidized as a second step in the reaction with oxygen. Compound C exhibits a unique intense absorption band at 606-609 nm that is tentatively assigned to a charge transfer interaction between heme a3 in the reduced state and its associated copper in the oxidized state, with heme a and its associated copper in the oxidized state.
|
Oxygen intermediates and mixed valence states of cytochrome oxidase: infrared absorption difference spectra of compounds A, B, and C of cytochrome oxidase and oxygen. A study of the near-infrared absorption spectra of three oxygen compounds of membrane-bound cytochrome oxidase (ferrocytochrome c:oxygen oxidoreductase; EC 1.9.3.1) shows that the formation of compound A (oxycytochrome oxidase) causes no significant infrared absorbance changes at -103 degrees. At -64 degrees, the formation of compound C from the mixed-valence state of the oxidase leads to increased absorption at 740-750 nm. The formation of compound B at -84 degrees from the fully reduced state of the oxidase causes increased absorption at 790-800 nm. Further oxidation of cytochrome oxidase results in increased infrared absorption at 820-830 nm at -60 degrees. The position of the infrared absorption band in compound C thus depends at least upon the oxidation-reduction state of heme a and its associated copper atom. Compound C contains two types of oxidized (cupric) copper; that associated with heme a is initially oxidized, and that associated with heme a3 is oxidized as a second step in the reaction with oxygen. Compound C exhibits a unique intense absorption band at 606-609 nm that is tentatively assigned to a charge transfer interaction between heme a3 in the reduced state and its associated copper in the oxidized state, with heme a and its associated copper in the oxidized state.
|
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] |
PMID:22084
|
Regulation of release from isolated adrenergic secretory vesicles by ATP-mediated changes in transmembrane potential and anion permeability.
|
Isolated chromaffin granules release their contents when exposed to calcium, magnesium, ATP, and high levels of chloride ions. The mechanism of release is not well-understood, but changes in anion permeability may be involved. We found that another anion, thiocyanate (SCN-), also activated release in a fashion similar to chloride, while isethionate (HO-CH2-CH2SO3-) an impermeant anion, was inactive. Mg++-ATP was found to activate the uptake of 36Cl and 14C-SCN, leading us to conclude that activation of anion uptake might be involved in the release process. The 36Cl and the 14C-SCN compartments were then compared by studying displacement of the trace anions by excess cold mass. Chloride and SCN displaced large amounts of both 36Cl and 14C-SCN, while isethionate displaced little of either tracer anion. We suggest, on the basis of these data, that ATP-mediated anion uptake may be the basis for the release mechanism. Release may occur as a consequence of anion and subsequent water uptake into granules, resulting in osmotic imbalance and osmotic shock. This may also be of physiologic importance, and we propose a cellular model for secretion based on the biochemical properties of the isolated chromaffin granule.
|
Regulation of release from isolated adrenergic secretory vesicles by ATP-mediated changes in transmembrane potential and anion permeability. Isolated chromaffin granules release their contents when exposed to calcium, magnesium, ATP, and high levels of chloride ions. The mechanism of release is not well-understood, but changes in anion permeability may be involved. We found that another anion, thiocyanate (SCN-), also activated release in a fashion similar to chloride, while isethionate (HO-CH2-CH2SO3-) an impermeant anion, was inactive. Mg++-ATP was found to activate the uptake of 36Cl and 14C-SCN, leading us to conclude that activation of anion uptake might be involved in the release process. The 36Cl and the 14C-SCN compartments were then compared by studying displacement of the trace anions by excess cold mass. Chloride and SCN displaced large amounts of both 36Cl and 14C-SCN, while isethionate displaced little of either tracer anion. We suggest, on the basis of these data, that ATP-mediated anion uptake may be the basis for the release mechanism. Release may occur as a consequence of anion and subsequent water uptake into granules, resulting in osmotic imbalance and osmotic shock. This may also be of physiologic importance, and we propose a cellular model for secretion based on the biochemical properties of the isolated chromaffin granule.
|
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] |
PMID:22085
|
Regulation of the growth and development of sympathetic neurons in vivo.
|
The superior cervical ganglion (SCG) in the neonatal mouse and rat has been employed as a model system to study the regulation of ontogeny of presynaptic cholinergic nerves and postsynaptic adrenergic neurons. During postnatal development presynaptic choline acetyltransferase (ChAc) activity increases 30- to 40-fold, whereas postsynaptic tyrosine hydroxylase (T-OH) activity rises 6- to 8-fold. Transection of the presynaptic cholinergic nerves innervating the SCG prevents the normal development of T-OH activity and the normal accumulation of T-OH enzyme molecules in each postsynaptic neuron. The trans-synaptic regulation of T-OH development is apparently mediated by acetylcholine and postsynaptic depolarization, since pharmacologic ganglionic blockade also prevents normal maturation. Ganglion decentralization also prevents the normal maturation of adrenergic nerve terminals, and the development of end-organ innervation by SCG. Consequently, trans-synaptic factors regulate the ontogeny of adrenergic terminals as well as perikarya. Moreover, normal efferent as well as afferent connections are apparently required for sympathetic development, since removal of salivary glands and orbital contents, target organs of the SCG, in neonates also prevents T-OH development in the ganglia. The postsynaptic neuron contributes to the development of presynaptic cholinergic fibers in SCG. Selective destruction of adrenergic neurons in neonatal mice with either 6-hydroxydopamine or antiserum to nerve growth factor prevents the normal maturation of ChAc activity in presynaptic terminals of SCG. Thus, presynaptic and postsynaptic cells appear to exert reciprocal regulatory influences during ontogeny.
|
Regulation of the growth and development of sympathetic neurons in vivo. The superior cervical ganglion (SCG) in the neonatal mouse and rat has been employed as a model system to study the regulation of ontogeny of presynaptic cholinergic nerves and postsynaptic adrenergic neurons. During postnatal development presynaptic choline acetyltransferase (ChAc) activity increases 30- to 40-fold, whereas postsynaptic tyrosine hydroxylase (T-OH) activity rises 6- to 8-fold. Transection of the presynaptic cholinergic nerves innervating the SCG prevents the normal development of T-OH activity and the normal accumulation of T-OH enzyme molecules in each postsynaptic neuron. The trans-synaptic regulation of T-OH development is apparently mediated by acetylcholine and postsynaptic depolarization, since pharmacologic ganglionic blockade also prevents normal maturation. Ganglion decentralization also prevents the normal maturation of adrenergic nerve terminals, and the development of end-organ innervation by SCG. Consequently, trans-synaptic factors regulate the ontogeny of adrenergic terminals as well as perikarya. Moreover, normal efferent as well as afferent connections are apparently required for sympathetic development, since removal of salivary glands and orbital contents, target organs of the SCG, in neonates also prevents T-OH development in the ganglia. The postsynaptic neuron contributes to the development of presynaptic cholinergic fibers in SCG. Selective destruction of adrenergic neurons in neonatal mice with either 6-hydroxydopamine or antiserum to nerve growth factor prevents the normal maturation of ChAc activity in presynaptic terminals of SCG. Thus, presynaptic and postsynaptic cells appear to exert reciprocal regulatory influences during ontogeny.
|
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] |
PMID:22086
|
Intramembrane particle aggregation in erythrocyte membranes and band 3-lipid recombinants.
|
The low pH-induced aggregation of intramembrane particles in human erythrocyte membranes was studied in native membranes and in a reconstituted model system. A significant difference in such aggregation was found when samples of freshly prepared ghosts were compared to ghosts receiving pretreatments that removed most of spectrin-actin from underneath the membrane. All conditions effective in aggregating particles are equally effective in precipitating extracted mixtures of spectrin and actin. In Band 3-lipid recombinants, the pH-induced aggregation of particles was duplicated only in samples containing spectrin-actin that equilibrated with these recombinants in sucrose gradients. Therefore, it was proposed that spectrin-actin components, through their associations with the underlying intramembrane particles, could impede particle lateral mobility and also determine particle redistribution in erythrocyte membrane.
|
Intramembrane particle aggregation in erythrocyte membranes and band 3-lipid recombinants. The low pH-induced aggregation of intramembrane particles in human erythrocyte membranes was studied in native membranes and in a reconstituted model system. A significant difference in such aggregation was found when samples of freshly prepared ghosts were compared to ghosts receiving pretreatments that removed most of spectrin-actin from underneath the membrane. All conditions effective in aggregating particles are equally effective in precipitating extracted mixtures of spectrin and actin. In Band 3-lipid recombinants, the pH-induced aggregation of particles was duplicated only in samples containing spectrin-actin that equilibrated with these recombinants in sucrose gradients. Therefore, it was proposed that spectrin-actin components, through their associations with the underlying intramembrane particles, could impede particle lateral mobility and also determine particle redistribution in erythrocyte membrane.
|
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] |
PMID:22087
|
The contractile basis of amoeboid movement III. Structure and dynamics of motile extracts and membrane fragments from Dictyostelium discoideum and Amoeba proteus.
|
Motile extracts from D, discoideum and A. proteus have been characterized in order to compare the structural dynamics and chemical regulation of movement in 2 different types of amoeboid cells. The structural dynamics of both extracts involve the formation of a nonmotile cytoskeleton followed by the contraction of actin and myosin to generate both direct contractile force and cytoplasmic streaming. The contractions are regulated by calcium ions and a threshold of ca. 1.0 X 10(-6) M calcium induces a transformation of actin to the free F-actin state which is capable of interacting with myosin. Furthermore, 3 low molecular weight proteins are concentrated along with actin and myosin during contraction and might play a regulatory role in movement. Several common characteristics of amoeba cytoplasm have been exhibited by these two types of amoeboid cells. The major contractile and "associated" proteins are similar, actin and associated proteins are structurally dynamic, and movement is regulated by calcium. The different modes of movement observed in different types of amoeboid cells could result from the site, rate, and extent of actin transformation followed in some regions by contractions.
|
The contractile basis of amoeboid movement III. Structure and dynamics of motile extracts and membrane fragments from Dictyostelium discoideum and Amoeba proteus. Motile extracts from D, discoideum and A. proteus have been characterized in order to compare the structural dynamics and chemical regulation of movement in 2 different types of amoeboid cells. The structural dynamics of both extracts involve the formation of a nonmotile cytoskeleton followed by the contraction of actin and myosin to generate both direct contractile force and cytoplasmic streaming. The contractions are regulated by calcium ions and a threshold of ca. 1.0 X 10(-6) M calcium induces a transformation of actin to the free F-actin state which is capable of interacting with myosin. Furthermore, 3 low molecular weight proteins are concentrated along with actin and myosin during contraction and might play a regulatory role in movement. Several common characteristics of amoeba cytoplasm have been exhibited by these two types of amoeboid cells. The major contractile and "associated" proteins are similar, actin and associated proteins are structurally dynamic, and movement is regulated by calcium. The different modes of movement observed in different types of amoeboid cells could result from the site, rate, and extent of actin transformation followed in some regions by contractions.
|
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] |
PMID:22091
|
Factors affecting the urinary excretion of endogenously formed dimethyltryptamine in normal human subjects.
|
The hallucinogenic substance N',N'-dimethyltryptamine and its precursor N-methyltryptamine were found in 24-h specimens of urine from 19 normal human subjects; the mean excretion rates were 386 ng 24 h(-1) and 856 ng 24 h(-1) respectively. The urinary excretion of both compounds was unrelated to age, sex, urinary volume, or creatinine, nor was any consistent diurnal pattern observed. Rates for the mono and dimethylated compounds were not correlated. Diet and the intestinal flora were excluded as a source of urinary dimethyltryptamine. Administration to 4 subjects of sufficient ammonium chloride to increase the H ion concentration of the urine caused a transient increase in dimethyltryptamine excretion but no consistent increase in the rate for N-methyltryptamine. Acidification of the urine did not appear to be the determining factor in this result since in one subject the same drop in urinary pH was achieved by feeding methionine without any increase in dimethyltryptamine excretion.
|
Factors affecting the urinary excretion of endogenously formed dimethyltryptamine in normal human subjects. The hallucinogenic substance N',N'-dimethyltryptamine and its precursor N-methyltryptamine were found in 24-h specimens of urine from 19 normal human subjects; the mean excretion rates were 386 ng 24 h(-1) and 856 ng 24 h(-1) respectively. The urinary excretion of both compounds was unrelated to age, sex, urinary volume, or creatinine, nor was any consistent diurnal pattern observed. Rates for the mono and dimethylated compounds were not correlated. Diet and the intestinal flora were excluded as a source of urinary dimethyltryptamine. Administration to 4 subjects of sufficient ammonium chloride to increase the H ion concentration of the urine caused a transient increase in dimethyltryptamine excretion but no consistent increase in the rate for N-methyltryptamine. Acidification of the urine did not appear to be the determining factor in this result since in one subject the same drop in urinary pH was achieved by feeding methionine without any increase in dimethyltryptamine excretion.
|
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] |
PMID:22105
|
Properties of four temperate bacteriophages active on Clostridium perfringens type A.
|
Four temperature bacteriophages (designated as PF1, PF2, PF3 and PF4) were isolated from lysogenic strains of Clostridium perfringens type A. On the basis of plaque morphology, pH stability, DNase and RNase resistance, buoyant density, one-step growth parameters and electron microscope phage dimensions, it seems that these phages are different and unrelated. Calcium was required for better phage replication. Bacterial strain S107 appears to be the only UV-inducible strain as compared with the other three lysogenic strains. PF2 has a unique pattern of pH stability showing two optima values: one at pH 5 and the second at pH 8-9. Generally, all four phages have a better resistance in acid than in alkaline pH values. The CsC1 equilibrium centrifugation patterns reveal low figures for phage PF1, PF2 and PF3 and show off the fact that PF4 lysates contain two viral particules different with respect to their densities, a property which other determinations failed to demonstrate. Each phage, except PF4, is well characterized by the parameters of the one-step growth cycle.
|
Properties of four temperate bacteriophages active on Clostridium perfringens type A. Four temperature bacteriophages (designated as PF1, PF2, PF3 and PF4) were isolated from lysogenic strains of Clostridium perfringens type A. On the basis of plaque morphology, pH stability, DNase and RNase resistance, buoyant density, one-step growth parameters and electron microscope phage dimensions, it seems that these phages are different and unrelated. Calcium was required for better phage replication. Bacterial strain S107 appears to be the only UV-inducible strain as compared with the other three lysogenic strains. PF2 has a unique pattern of pH stability showing two optima values: one at pH 5 and the second at pH 8-9. Generally, all four phages have a better resistance in acid than in alkaline pH values. The CsC1 equilibrium centrifugation patterns reveal low figures for phage PF1, PF2 and PF3 and show off the fact that PF4 lysates contain two viral particules different with respect to their densities, a property which other determinations failed to demonstrate. Each phage, except PF4, is well characterized by the parameters of the one-step growth cycle.
|
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] |
PMID:22110
|
Hemolytic activity of a lipid material obtained from peroxidized microsomes.
|
Lipid peroxidation was induced in rat liver microsomes by the addition of NADPH. When mixed with red cells in the presence of EDTA, these peroxidized microsomes caused hemolysis. All of the hemolytic activity of peroxidized microsomes could be extracted with lipid solvents and recovered as an aqueous lipid emulsion.
|
Hemolytic activity of a lipid material obtained from peroxidized microsomes. Lipid peroxidation was induced in rat liver microsomes by the addition of NADPH. When mixed with red cells in the presence of EDTA, these peroxidized microsomes caused hemolysis. All of the hemolytic activity of peroxidized microsomes could be extracted with lipid solvents and recovered as an aqueous lipid emulsion.
|
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] |
PMID:22111
|
Fungal proteases and the mammalian kinin system: I. Brinolase-catalyzed kinin formation and S2160 hydrolysis.
|
Brinolase, a fungal protease advocated for thrombolytic therapy, released kinin peptides from semi-purified kininogens of the human, rabbit, guinea pig, and mouse, and moreover cleaved an arginyl bond of the chromogenic peptide S2160. Its kinetics demonstrated marked differences from the mammalian protease trypsin. Whereas trypsin liberated 100% of the available kinin in 30 min at pH 8, brinolase generated a maximum of only 22% under optimal conditions, viz. incubation of 5 microgram/ml enzyme at pH 4.7 for 5 min. Longer incubations yielded less detectable kinin. This maximal release at acidic pH was not due to increased kininogen consumption, nor was it inhibited by the acid protease inhibitor pepstatin. Evidence is presented that brinolase, unlike trypsin, might both release and destroy kinins.
|
Fungal proteases and the mammalian kinin system: I. Brinolase-catalyzed kinin formation and S2160 hydrolysis. Brinolase, a fungal protease advocated for thrombolytic therapy, released kinin peptides from semi-purified kininogens of the human, rabbit, guinea pig, and mouse, and moreover cleaved an arginyl bond of the chromogenic peptide S2160. Its kinetics demonstrated marked differences from the mammalian protease trypsin. Whereas trypsin liberated 100% of the available kinin in 30 min at pH 8, brinolase generated a maximum of only 22% under optimal conditions, viz. incubation of 5 microgram/ml enzyme at pH 4.7 for 5 min. Longer incubations yielded less detectable kinin. This maximal release at acidic pH was not due to increased kininogen consumption, nor was it inhibited by the acid protease inhibitor pepstatin. Evidence is presented that brinolase, unlike trypsin, might both release and destroy kinins.
|
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] |
PMID:22112
|
III. Covalent coupling of rat liver phenylalanine hydroxylase.
|
Optimal conditions have been determined for the coupling of rat liver phenylalanine hydroxylase (PheH) to activated CH-Sepharose-4B. When 12 mg of ligand was reacted with 100 mg of matrix, 20% of the initial enzyme activity was covalently bound along with 55% of the protein. The coupled enzyme showed greater thermal stability from 50 degrees to 60 degrees after heating for 15 min, a lower optimum pH, 5.8, slightly less inhibition by Ag+, Cu+2, and Hg+2, and greater resistance to hydrolysis by alpha-chymotrypsin and protease. The uncoupled enzyme, however, exhibited greater storage stability than the covalently linked enzyme at 25 degrees after 24 hrs and at 0 degrees after 21 days. Alteration of the microenvironment by the introduction of sulfhydryl groups and positive and negative charged carriers during coupling of the enzyme either had no effect or markedly reduced hydroxylase activity.
|
III. Covalent coupling of rat liver phenylalanine hydroxylase. Optimal conditions have been determined for the coupling of rat liver phenylalanine hydroxylase (PheH) to activated CH-Sepharose-4B. When 12 mg of ligand was reacted with 100 mg of matrix, 20% of the initial enzyme activity was covalently bound along with 55% of the protein. The coupled enzyme showed greater thermal stability from 50 degrees to 60 degrees after heating for 15 min, a lower optimum pH, 5.8, slightly less inhibition by Ag+, Cu+2, and Hg+2, and greater resistance to hydrolysis by alpha-chymotrypsin and protease. The uncoupled enzyme, however, exhibited greater storage stability than the covalently linked enzyme at 25 degrees after 24 hrs and at 0 degrees after 21 days. Alteration of the microenvironment by the introduction of sulfhydryl groups and positive and negative charged carriers during coupling of the enzyme either had no effect or markedly reduced hydroxylase activity.
|
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] |
PMID:22113
|
[An experimental study on the pathogenesis of the acute pulmonary insufficiency (author's transl)].
|
Parameters of the lungs as Compliance PaCO2, PaO2, have been measured in connection with experimental, pathophysiological insults like hematoma, bone marrow intravasation and hemorrhage, in rabbits. Concerning the compliance quotient, a statistically proved decrease was found within the groups, which have had a hematoma. Moreover, the histological picture of the lungs from rabbits with a hematom showed perivascular and intersitial edema and considerable atelectases. Serum of animals, which have had a hematom for at least 24 h has been fractionated by gel chromatography; low molecular weight substances of the fractionated serum were injected into healthy recipients. Thereafter, measurement of the centralvenous pressure suggests the appearance of substances, pharmacodynamic similar to 5-Hydroxytryptamin, in blood of rabbits with hematom.
|
[An experimental study on the pathogenesis of the acute pulmonary insufficiency (author's transl)]. Parameters of the lungs as Compliance PaCO2, PaO2, have been measured in connection with experimental, pathophysiological insults like hematoma, bone marrow intravasation and hemorrhage, in rabbits. Concerning the compliance quotient, a statistically proved decrease was found within the groups, which have had a hematoma. Moreover, the histological picture of the lungs from rabbits with a hematom showed perivascular and intersitial edema and considerable atelectases. Serum of animals, which have had a hematom for at least 24 h has been fractionated by gel chromatography; low molecular weight substances of the fractionated serum were injected into healthy recipients. Thereafter, measurement of the centralvenous pressure suggests the appearance of substances, pharmacodynamic similar to 5-Hydroxytryptamin, in blood of rabbits with hematom.
|
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] |
PMID:22114
|
[Calculation of the pH profile in the intercapillary regions of tumour tissues before and after long-term glucose infusion into the blood stream (author's transl)].
|
The pH profile in the intercapillary region of tumor tissue is calculated for normal (Case I) and enhanced glucose concentration in blood (Case II) which was increased by a factor of 4 for an extended period of time. The statement used, which takes into account the reduced lactic acid formation in the unsaturated region of cancer cell glycolysis, and the resulting solution of the lactic acid diffusion field equation are given. For Case II (conditions of cancer multistep therapy) and a capillary radius of 4 micrometer this yields the following pH values: Wall at venous end of the capillary 6.7 (or 6.5); at R greater than 12 micrometer, i.e. still in the vicinity of the capillary less than 6.3: at R approximately 60 micrometer a minimum of 5.9. This rather good pH homogeneity is the prerequisite that all lytic actions and activation mechanism induced by a temporary extreme hyperacidification of the tumor tissue can take place in the major portion of the intercapillary region with a strength of adequate uniformity. Conclusions were drawn from these results with respect to the further planning of cancer therapy. This refers to the utilization of processes serving to increase primary damage to tumor tissue through body defense mechanisms, inhibition of cell proliferation as well as the applicability of new anticancer drugs (CMT Selectines) that are rendered active only in strongly hyperacidified foci of cancer. Moreover, this includes the possible use for increasing the secondary damage to tumor tissue by way of the lysosomal cytolysis, by drastic decrease of microcirculation and the damage of the capillaries in tumor tissue.
|
[Calculation of the pH profile in the intercapillary regions of tumour tissues before and after long-term glucose infusion into the blood stream (author's transl)]. The pH profile in the intercapillary region of tumor tissue is calculated for normal (Case I) and enhanced glucose concentration in blood (Case II) which was increased by a factor of 4 for an extended period of time. The statement used, which takes into account the reduced lactic acid formation in the unsaturated region of cancer cell glycolysis, and the resulting solution of the lactic acid diffusion field equation are given. For Case II (conditions of cancer multistep therapy) and a capillary radius of 4 micrometer this yields the following pH values: Wall at venous end of the capillary 6.7 (or 6.5); at R greater than 12 micrometer, i.e. still in the vicinity of the capillary less than 6.3: at R approximately 60 micrometer a minimum of 5.9. This rather good pH homogeneity is the prerequisite that all lytic actions and activation mechanism induced by a temporary extreme hyperacidification of the tumor tissue can take place in the major portion of the intercapillary region with a strength of adequate uniformity. Conclusions were drawn from these results with respect to the further planning of cancer therapy. This refers to the utilization of processes serving to increase primary damage to tumor tissue through body defense mechanisms, inhibition of cell proliferation as well as the applicability of new anticancer drugs (CMT Selectines) that are rendered active only in strongly hyperacidified foci of cancer. Moreover, this includes the possible use for increasing the secondary damage to tumor tissue by way of the lysosomal cytolysis, by drastic decrease of microcirculation and the damage of the capillaries in tumor tissue.
|
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] |
PMID:22115
|
Phenylalanine inhibited p-nitrophenyl phosphatase activity in the serum as an indication of intestinal cellular disruption in the horse.
|
Examination of tissues obtained from thoroughbred horses showed that the 'intestinal' phosphatase activity could be differentiated from other phosphatases by analysis at a pH of 9-5 and inhibition with 15 mM L-phenylalanine. A simple method for the measurement of 'intestinal' phosphatase in heparinised plasma or serum is described. Application of the technique to serum or plasma from normal and diseased horses indicates that the increase in the activity of 'intestinal' phosphatase is associated with cases showing clinical, biochemical and haematological evidence of intestinal damage.
|
Phenylalanine inhibited p-nitrophenyl phosphatase activity in the serum as an indication of intestinal cellular disruption in the horse. Examination of tissues obtained from thoroughbred horses showed that the 'intestinal' phosphatase activity could be differentiated from other phosphatases by analysis at a pH of 9-5 and inhibition with 15 mM L-phenylalanine. A simple method for the measurement of 'intestinal' phosphatase in heparinised plasma or serum is described. Application of the technique to serum or plasma from normal and diseased horses indicates that the increase in the activity of 'intestinal' phosphatase is associated with cases showing clinical, biochemical and haematological evidence of intestinal damage.
|
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] |
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