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PMID:17947 | A physician extender training program based on clinical algorithms. | The ability of physician extenders to provide patient care in a variety of settings has been reported widely. Less attention has been paid to training programs, especially those of short duration, for physician extenders. A three-month training program for physician extenders at a large teaching hospital was based on teaching the skills needed to run 39 clinical algorithms. The course content and the methods used to test the students during the three months may prove of value to those preparing similar programs. | A physician extender training program based on clinical algorithms. The ability of physician extenders to provide patient care in a variety of settings has been reported widely. Less attention has been paid to training programs, especially those of short duration, for physician extenders. A three-month training program for physician extenders at a large teaching hospital was based on teaching the skills needed to run 39 clinical algorithms. The course content and the methods used to test the students during the three months may prove of value to those preparing similar programs. | [
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PMID:17948 | [Aspartate transfer across the blood-retina barrier (author's transl)]. | Permeability of the blood-brain barrier is restricted with respect to amino acids involved in neurotransmission. This finding is well-documented in the case of gamma-amino-butyric acid (GABA) and glycine. Aspartic acid, which is also considered to be a transmitter, equally does not cross the blood-brain barrier in the rat with ease. This amino acid is also thought to be a transmitter in the retina. In order to examine the permeability of the blood-retina barrier with respect to aspartic acid, and investigation was undertaken of the effect of asparate on the light-induced sum potential of the retina in the isolated, perfused cat eyeball, a preparation which guarantees intact retinal circulation. The findings were compared with findings in the isolated retina where the substance was brought into direct contact with the retinal neurons. It was found that aspartate crossed the vascular barrier only to a limited extent and with delay. These results support the hypothesis that aspartic acid is involved in the retinal information processing. | [Aspartate transfer across the blood-retina barrier (author's transl)]. Permeability of the blood-brain barrier is restricted with respect to amino acids involved in neurotransmission. This finding is well-documented in the case of gamma-amino-butyric acid (GABA) and glycine. Aspartic acid, which is also considered to be a transmitter, equally does not cross the blood-brain barrier in the rat with ease. This amino acid is also thought to be a transmitter in the retina. In order to examine the permeability of the blood-retina barrier with respect to aspartic acid, and investigation was undertaken of the effect of asparate on the light-induced sum potential of the retina in the isolated, perfused cat eyeball, a preparation which guarantees intact retinal circulation. The findings were compared with findings in the isolated retina where the substance was brought into direct contact with the retinal neurons. It was found that aspartate crossed the vascular barrier only to a limited extent and with delay. These results support the hypothesis that aspartic acid is involved in the retinal information processing. | [
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PMID:17949 | [Recent concepts of respiratory regulation (author's transl)]. | There are two functional aspects of the respiratory control system, the one being adaptation of ventilation to metabolic needs and the other acid-base homeostasis of the extracellular fluid of the brain. These two functions are perfectly compatible with one another under normal conditions. During hypoxia or hyperthermia, however, a compromise has to be reaches by the system between securing oxygen availability or homeothermy, respectively and acid-base homeostasis of the brain. The control system works with tonic chemosensitive and non-chemosensitive neural input of action potentials to the centres. The centres, either by indigenous mechanisms or by phasic reflex input from the stretch receptors of the lungs or phasic feedback mechanisms from the pontine pneumotaxic centre, modulate the tonic impulse input into the rhythmic output to the respiratory muscles. Recent observations on this "inspiratory off switch mechanism" are discussed. Chemosensitive sensors are found in the carotid and aortic glomera responding to low pO2 and, additionally, to pH and pCO2 and in central chemosensitive structures on the ventral side of the medulla oblongata, responding mainly to changes in local hydrogen ion concentration. The proprioceptive reflexes in the sense of a gamma loop improve the performance of the system if additional flow resistance must be overcome. In metabolic and respiratory acidosis-alkalosis the kidney either plays a compensatory role or serves to restore normal conditions. The maternal hormones in pregnancy effect air improvement in CO2 output of the fetus. | [Recent concepts of respiratory regulation (author's transl)]. There are two functional aspects of the respiratory control system, the one being adaptation of ventilation to metabolic needs and the other acid-base homeostasis of the extracellular fluid of the brain. These two functions are perfectly compatible with one another under normal conditions. During hypoxia or hyperthermia, however, a compromise has to be reaches by the system between securing oxygen availability or homeothermy, respectively and acid-base homeostasis of the brain. The control system works with tonic chemosensitive and non-chemosensitive neural input of action potentials to the centres. The centres, either by indigenous mechanisms or by phasic reflex input from the stretch receptors of the lungs or phasic feedback mechanisms from the pontine pneumotaxic centre, modulate the tonic impulse input into the rhythmic output to the respiratory muscles. Recent observations on this "inspiratory off switch mechanism" are discussed. Chemosensitive sensors are found in the carotid and aortic glomera responding to low pO2 and, additionally, to pH and pCO2 and in central chemosensitive structures on the ventral side of the medulla oblongata, responding mainly to changes in local hydrogen ion concentration. The proprioceptive reflexes in the sense of a gamma loop improve the performance of the system if additional flow resistance must be overcome. In metabolic and respiratory acidosis-alkalosis the kidney either plays a compensatory role or serves to restore normal conditions. The maternal hormones in pregnancy effect air improvement in CO2 output of the fetus. | [
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|
PMID:17951 | [Bistability in the activity of glutamine synthetase in ammonium-limiting chemostat cultures of Escherichia coli ML 30]. | The approximative estimation of the function micron([NH+4]) in cultures of E. coli ML 30 had shown that bistability of the ammonium concentration in ammonium limited continuous cultures could be possible (BERGTER et al. 1977). This phenomenon suggested a bistability in the regulation of ammonia assimilation. Therefore, the activity of one key enzyme of the two ammonia assimilation systems was measured. The distribution of the activity of glutamine synthetase in ammonia limited continuous cultures after different transition states confirmed this suggestion. | [Bistability in the activity of glutamine synthetase in ammonium-limiting chemostat cultures of Escherichia coli ML 30]. The approximative estimation of the function micron([NH+4]) in cultures of E. coli ML 30 had shown that bistability of the ammonium concentration in ammonium limited continuous cultures could be possible (BERGTER et al. 1977). This phenomenon suggested a bistability in the regulation of ammonia assimilation. Therefore, the activity of one key enzyme of the two ammonia assimilation systems was measured. The distribution of the activity of glutamine synthetase in ammonia limited continuous cultures after different transition states confirmed this suggestion. | [
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|
PMID:17957 | [The problems of adverse effects to the liver of alpha-methyldopa]. | In 20 patients who were treated with alpha-methyldopa since at least one year the bilirubin content, the activities of aspartate and alanine-aminotransferase, alkaline phosphatase and gamma-glutamyl transpeptidase as well as the retention of bromsulphalein were determined. In altogether 10 patients pathological findings of laboratory examinations were the result. The gamma-glutamyl transpeptidase activity proved to be particularly sensitive. By means of biopsy in 3 of these patients a fatty degeneration of the liver in stage I and in 4 of them a fatty degeneration of the parenchyma cell of minor degree were proved. A connection between duration and dosage of the treatment with alpha-methyldopa and these hepatological findings could not be ascertained statistically. | [The problems of adverse effects to the liver of alpha-methyldopa]. In 20 patients who were treated with alpha-methyldopa since at least one year the bilirubin content, the activities of aspartate and alanine-aminotransferase, alkaline phosphatase and gamma-glutamyl transpeptidase as well as the retention of bromsulphalein were determined. In altogether 10 patients pathological findings of laboratory examinations were the result. The gamma-glutamyl transpeptidase activity proved to be particularly sensitive. By means of biopsy in 3 of these patients a fatty degeneration of the liver in stage I and in 4 of them a fatty degeneration of the parenchyma cell of minor degree were proved. A connection between duration and dosage of the treatment with alpha-methyldopa and these hepatological findings could not be ascertained statistically. | [
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|
PMID:17963 | [Relationship between thermal treatment of milk and hysteresis of the milk protein system. II. Studies on casein micelles (author's transl)]. | The association of colloidal calcium phosphate with the casein micelles is the principal reason for hysteresis of the milk protein system. Because of this association the secondary calcium phosphate cannot be titrated at its pK = 7.2, but only at lower pH values depending on the previous thermal treatment of the milk. However after overcoming certain energy barriers it can be titrated (between pH 5.8 and 5.2), but then calcium phosphate is separated irreversibly from the micelles. Therefore in the subsequent base titration other molecular conditions are passed through than in acid titration. The consequence is a hysteresislike titration curve. By heating, the surface of the micelles are covered successively with serum proteins. Due to this coating additional diffusion barriers are constructed. The diffusion of the protons into the interior of the micelles is measurably retarded. The expansion of the hysteresis loop can be determined quantitatively. | [Relationship between thermal treatment of milk and hysteresis of the milk protein system. II. Studies on casein micelles (author's transl)]. The association of colloidal calcium phosphate with the casein micelles is the principal reason for hysteresis of the milk protein system. Because of this association the secondary calcium phosphate cannot be titrated at its pK = 7.2, but only at lower pH values depending on the previous thermal treatment of the milk. However after overcoming certain energy barriers it can be titrated (between pH 5.8 and 5.2), but then calcium phosphate is separated irreversibly from the micelles. Therefore in the subsequent base titration other molecular conditions are passed through than in acid titration. The consequence is a hysteresislike titration curve. By heating, the surface of the micelles are covered successively with serum proteins. Due to this coating additional diffusion barriers are constructed. The diffusion of the protons into the interior of the micelles is measurably retarded. The expansion of the hysteresis loop can be determined quantitatively. | [
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|
PMID:17958 | Regulation and characterization of L-serine: pyruvate aminotransferase in rat liver cytosol and mitochondria. | Distribution of rat liver serine: pyruvate aminotransferase between cytosol and mitochondria varies considerably with the dietary and hormonal state of animals. Feeding a high-protein diet or fasting the animals results in an increase in the enzyme activity of both fractions but more marked in the mitochondrial fraction. A low-protein diet exerts the reverse effect. A single administration of dibutyryl cyclic AMP causes a rapid elevation of the enzyme activity in both fractions, which is effectively prevented by cycloheximide, actinomycin D and cortisone. The activity in mitochondria increases with a lag of 2 h following injection of the nucleotide inducer, in contrast to the cytosol enzyme, which increases without any lag. Gel filtration and DEAE cellulose chromatography of the enzyme from both fractions revealed the similar pattern and some kinetic constants of these two types of the enzyme were not significantly different from each other. These results indicate that rat liver serine: pyruvate aminotransferase is synthesized in the extra-mitochondrial site and transfered to mitochondria. | Regulation and characterization of L-serine: pyruvate aminotransferase in rat liver cytosol and mitochondria. Distribution of rat liver serine: pyruvate aminotransferase between cytosol and mitochondria varies considerably with the dietary and hormonal state of animals. Feeding a high-protein diet or fasting the animals results in an increase in the enzyme activity of both fractions but more marked in the mitochondrial fraction. A low-protein diet exerts the reverse effect. A single administration of dibutyryl cyclic AMP causes a rapid elevation of the enzyme activity in both fractions, which is effectively prevented by cycloheximide, actinomycin D and cortisone. The activity in mitochondria increases with a lag of 2 h following injection of the nucleotide inducer, in contrast to the cytosol enzyme, which increases without any lag. Gel filtration and DEAE cellulose chromatography of the enzyme from both fractions revealed the similar pattern and some kinetic constants of these two types of the enzyme were not significantly different from each other. These results indicate that rat liver serine: pyruvate aminotransferase is synthesized in the extra-mitochondrial site and transfered to mitochondria. | [
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|
PMID:17959 | Identification of essential histidine residues of aminoacylase by photooxidation and by reaction with diethylpyrocarbonate. | State and function of the histidine residues of aminoacylase were investigated by photoxidation in the presence of methylene blue and by chemical modification with diethylpyrocarbonate. Complete inactivation of the enzyme was observed after oxidation of 4 histidine residues. From the pH dependence of the photooxidation it becomes evident that the inactivation of the enzyme is not a consequence of the simultaneous oxidation of tryptophan residues. The enzyme is also inactivated by chemical modification of histidine residues with diethylpyrocarbonate. Activity is restored by treatment with hydroxylamine. Zn2+-ions which are essential for the activity of aminoacylase protect the available histidine molecules against photooxidation and attack by diethylpyrocarbonate. It is suggested that histidine is involved in the binding of the essential Zn2+-ions. | Identification of essential histidine residues of aminoacylase by photooxidation and by reaction with diethylpyrocarbonate. State and function of the histidine residues of aminoacylase were investigated by photoxidation in the presence of methylene blue and by chemical modification with diethylpyrocarbonate. Complete inactivation of the enzyme was observed after oxidation of 4 histidine residues. From the pH dependence of the photooxidation it becomes evident that the inactivation of the enzyme is not a consequence of the simultaneous oxidation of tryptophan residues. The enzyme is also inactivated by chemical modification of histidine residues with diethylpyrocarbonate. Activity is restored by treatment with hydroxylamine. Zn2+-ions which are essential for the activity of aminoacylase protect the available histidine molecules against photooxidation and attack by diethylpyrocarbonate. It is suggested that histidine is involved in the binding of the essential Zn2+-ions. | [
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|
PMID:17964 | [On the enzymatic breakdown of tripolyphosphate and diphosphate in comminuted meat. VII. Influence of sodium chloride on the tripolyphosphatase and diphosphatase activity in bovine muscle (author's transl)]. | Sodium chloride activates the tripolyphosphatase of the muscle tissue. Optimum activity occurs at 4--5 percent NaC1. The increase in activity seems to be due to the effect of C1-ions. NaC1 inhibits the tripolyphosphatase activity of muscle press juice. NaC1 decreases the total diphosphatase activity of muscle tissue as well as the diphosphatase activity of muscle press juice. Addition of NaC1 to pre-rigor muscle increases the ultimate pH value (post-rigor-muscle) and, consequently, causes a lower tripolyphosphatase activity and a higher diphosphatase activity than is observed, when NaC1 is added to the post-rigor muscle. | [On the enzymatic breakdown of tripolyphosphate and diphosphate in comminuted meat. VII. Influence of sodium chloride on the tripolyphosphatase and diphosphatase activity in bovine muscle (author's transl)]. Sodium chloride activates the tripolyphosphatase of the muscle tissue. Optimum activity occurs at 4--5 percent NaC1. The increase in activity seems to be due to the effect of C1-ions. NaC1 inhibits the tripolyphosphatase activity of muscle press juice. NaC1 decreases the total diphosphatase activity of muscle tissue as well as the diphosphatase activity of muscle press juice. Addition of NaC1 to pre-rigor muscle increases the ultimate pH value (post-rigor-muscle) and, consequently, causes a lower tripolyphosphatase activity and a higher diphosphatase activity than is observed, when NaC1 is added to the post-rigor muscle. | [
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|
PMID:17965 | [On the enzymatic breakdown of tripolyphosphate and diphosphate in comminuted meat. VIII. Influence of divalent cations on the tripolyphosphatase activity of muscle tissue (author's transl)]. | The tripolyphosphatase of comminuted muscle tissue is activated by MgC1(2) and ethylenediamine tetraacetate and inhibited by CaC1(2) and diphosphate. These results are discussed with reference to the formation of an inactive enzyme-substrate complex. | [On the enzymatic breakdown of tripolyphosphate and diphosphate in comminuted meat. VIII. Influence of divalent cations on the tripolyphosphatase activity of muscle tissue (author's transl)]. The tripolyphosphatase of comminuted muscle tissue is activated by MgC1(2) and ethylenediamine tetraacetate and inhibited by CaC1(2) and diphosphate. These results are discussed with reference to the formation of an inactive enzyme-substrate complex. | [
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|
PMID:17983 | Factors influencing L-asparaginase production by staphylococci. | Cultural and nutritional requirements for a maximum synthesis of 1-asparaginase by staphylococci were determined. The best production of the enzyme was found in the stationary phase of growth of a batch culture. The highest 1-asparaginase yield was obtained when the culture were aerated during an exponential phase of growth and further incubated in the stationary phase. Optimum pH for the enzyme production was 7.5. Glucose inhibited the enzyme formation. Maximum yield of 1-asparaginase was obtained when casein hydrolysate and yeast extract were supplied as carbon and nitrogen sources. Repression by 1-asparagine and 1-aspartic acid was absent. | Factors influencing L-asparaginase production by staphylococci. Cultural and nutritional requirements for a maximum synthesis of 1-asparaginase by staphylococci were determined. The best production of the enzyme was found in the stationary phase of growth of a batch culture. The highest 1-asparaginase yield was obtained when the culture were aerated during an exponential phase of growth and further incubated in the stationary phase. Optimum pH for the enzyme production was 7.5. Glucose inhibited the enzyme formation. Maximum yield of 1-asparaginase was obtained when casein hydrolysate and yeast extract were supplied as carbon and nitrogen sources. Repression by 1-asparagine and 1-aspartic acid was absent. | [
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|
PMID:17984 | Subcellular distribution and properties of alkaline inorganic pyrophosphatase of maize leaves. | 1. Studies on the distribution of alkaline inorganic pyrophosphatase (pyrophosphate phosphohydrolase, EC 3.6.1.1) in the subcellular fractions of maize leaves showed that the enzyme is present in cytoplasm, chloroplasts and mitochondria. The activity observed in nuclei and microsomes may result from contamination with the mitochondrial fraction. 2. Alkaline pyrophosphatases from three subcellular fractions were purified by fractionation with (NH4)2SO4, followed by ion-exchange and gel-filtration chromatography, and by isoelectric focusing. Highly purified enzyme preparations, with specific activities ranging from 55 to 188 micronmoles/min/mg protein, were obtained. 3. All the enzymes exhibited the maximum activity at pH 8.5 and the Mg2+/PPi ratio of 5. They differed in electrophoretic mobility, pI, and susceptibility to urea and thermal denaturation. This indicates that they represent isoenzymes compartmentized in particular subcellular fractions. | Subcellular distribution and properties of alkaline inorganic pyrophosphatase of maize leaves. 1. Studies on the distribution of alkaline inorganic pyrophosphatase (pyrophosphate phosphohydrolase, EC 3.6.1.1) in the subcellular fractions of maize leaves showed that the enzyme is present in cytoplasm, chloroplasts and mitochondria. The activity observed in nuclei and microsomes may result from contamination with the mitochondrial fraction. 2. Alkaline pyrophosphatases from three subcellular fractions were purified by fractionation with (NH4)2SO4, followed by ion-exchange and gel-filtration chromatography, and by isoelectric focusing. Highly purified enzyme preparations, with specific activities ranging from 55 to 188 micronmoles/min/mg protein, were obtained. 3. All the enzymes exhibited the maximum activity at pH 8.5 and the Mg2+/PPi ratio of 5. They differed in electrophoretic mobility, pI, and susceptibility to urea and thermal denaturation. This indicates that they represent isoenzymes compartmentized in particular subcellular fractions. | [
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|
PMID:17985 | Acid phosphatase of the yeast Rhodotorula rubra. Purification and properties of the enzyme. | 1. Acid phosphatase from the yeast Rhodotorula rubra was purified 44-fold. The purification procedure involved mechanical disruption of cells, precipitation with ethanol, chromatography on DEAE- and CM-cellulose. 2. The purified enzyme is homogeneous in polyacrylamide gels at pH 4.5, 9.5 and 8.4. Carbohydrate content accounts for 57% of the total weight. The optimum pH is at 4.0-4.6, and the enzyme is stable over pH range from 2.6 to 6.0. Full activity was retained on 60-min incubation at 50 degrees C, but it was reduced by half on 60-min incubation at 65 degrees C. 3. Specificity of the enzyme is fairly broad; monoesters of carbohydrates, and nucleosides and inorganic pyrophosphate can serve as substrates. Km was found to be 1 X 10(-4) M for p-nitrophenyl phosphate as a substrate. The enzyme is inhibited by molybdate, phosphate, arsenate and fluoride ions. | Acid phosphatase of the yeast Rhodotorula rubra. Purification and properties of the enzyme. 1. Acid phosphatase from the yeast Rhodotorula rubra was purified 44-fold. The purification procedure involved mechanical disruption of cells, precipitation with ethanol, chromatography on DEAE- and CM-cellulose. 2. The purified enzyme is homogeneous in polyacrylamide gels at pH 4.5, 9.5 and 8.4. Carbohydrate content accounts for 57% of the total weight. The optimum pH is at 4.0-4.6, and the enzyme is stable over pH range from 2.6 to 6.0. Full activity was retained on 60-min incubation at 50 degrees C, but it was reduced by half on 60-min incubation at 65 degrees C. 3. Specificity of the enzyme is fairly broad; monoesters of carbohydrates, and nucleosides and inorganic pyrophosphate can serve as substrates. Km was found to be 1 X 10(-4) M for p-nitrophenyl phosphate as a substrate. The enzyme is inhibited by molybdate, phosphate, arsenate and fluoride ions. | [
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|
PMID:17986 | [Proof of guanylate cyclase activity in the coronary artery of cattle]. | Guanylate cyclase activities were identified in a soluble fraction and a particular fraction obtained from the Arteria coronaria of cattle. The Km-value was 1.0 +/- 0.7 - 10(-4) M for the enzyme substrate complex of the guanylate cyclase of the soluble fraction and 9.2 +/- 1.5 - 10(-4) M for the particular fraction. For the enzyme activity of the soluble fraction Mn++ cannot be replaced by Ca++ or Mg++, whereas for the enzyme activity of the particulate fraction Mn++ can be replaced by Mg++ but not by Ca++. The guanylate cyclase of the particulate fraction can be activated by acetylcholine. This activation can be cancelled by atropine. Acetylcholine exerts no influence on the guanylate cyclase activity of the soluble fraction. ATP inhibits the enzyme activities of both fractions whereas cAMP shows no influence on the guanylate cyclase activity. | [Proof of guanylate cyclase activity in the coronary artery of cattle]. Guanylate cyclase activities were identified in a soluble fraction and a particular fraction obtained from the Arteria coronaria of cattle. The Km-value was 1.0 +/- 0.7 - 10(-4) M for the enzyme substrate complex of the guanylate cyclase of the soluble fraction and 9.2 +/- 1.5 - 10(-4) M for the particular fraction. For the enzyme activity of the soluble fraction Mn++ cannot be replaced by Ca++ or Mg++, whereas for the enzyme activity of the particulate fraction Mn++ can be replaced by Mg++ but not by Ca++. The guanylate cyclase of the particulate fraction can be activated by acetylcholine. This activation can be cancelled by atropine. Acetylcholine exerts no influence on the guanylate cyclase activity of the soluble fraction. ATP inhibits the enzyme activities of both fractions whereas cAMP shows no influence on the guanylate cyclase activity. | [
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|
PMID:17987 | [Demonstration of protein kinase activities in the coronary artery of cattle]. | Protein kinase activities were identified in a soluble and a particulate fraction from the A. coronaria of cattle. For both protein kinase activities Mg++ is essential. Protamine was used as a substrate of the protein kinase activity of the soluble fraction. The pH optimum of the protein kinase activity of the soluble fraction is around 6.5. The Km-value of the protein kinase for ATP is 1.9 +/- 0.4 - 10(-5) M. cAMP stimulates the protein kinase activity more effectively than cGMP. Ca++ cannot replace Mg++; monovalent cations (Na+ and K+) show no influence. The protein kinase activity of the fraction was determined via endogenous phosphorylation. By means of the cAMP-dependent particulate protein kinase 72 to 80 percent of the serine residues are phosphorylated. The pH optimum of the protein kinase activity of the particulate fraction lies around 7.0. The Km-value of the enzyme for ATP is 6.6 +/- 0.8 - 10(-5) M. cGMP stimulates the protein kinase of the particulate fraction better than cAMP. For the protein kinase activity of this fraction Ca++ replaces Mg++ in the endogenous phosphorylation but not in the exogenous phosphorylation (protamine). In the presence of Mg++ and in the additional presence of Na+ or K+, the protein kinase activity is suppressed in the endogenous phosphorylation whereas it is stimulated in the exogenous phosphorylation. | [Demonstration of protein kinase activities in the coronary artery of cattle]. Protein kinase activities were identified in a soluble and a particulate fraction from the A. coronaria of cattle. For both protein kinase activities Mg++ is essential. Protamine was used as a substrate of the protein kinase activity of the soluble fraction. The pH optimum of the protein kinase activity of the soluble fraction is around 6.5. The Km-value of the protein kinase for ATP is 1.9 +/- 0.4 - 10(-5) M. cAMP stimulates the protein kinase activity more effectively than cGMP. Ca++ cannot replace Mg++; monovalent cations (Na+ and K+) show no influence. The protein kinase activity of the fraction was determined via endogenous phosphorylation. By means of the cAMP-dependent particulate protein kinase 72 to 80 percent of the serine residues are phosphorylated. The pH optimum of the protein kinase activity of the particulate fraction lies around 7.0. The Km-value of the enzyme for ATP is 6.6 +/- 0.8 - 10(-5) M. cGMP stimulates the protein kinase of the particulate fraction better than cAMP. For the protein kinase activity of this fraction Ca++ replaces Mg++ in the endogenous phosphorylation but not in the exogenous phosphorylation (protamine). In the presence of Mg++ and in the additional presence of Na+ or K+, the protein kinase activity is suppressed in the endogenous phosphorylation whereas it is stimulated in the exogenous phosphorylation. | [
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|
PMID:17988 | Effect of tilorone hydrochloride on graft-versus-host (GvH) reaction in mice. | The effects of tilorone hydrochloride (TH), a powerful interferonogenic agent exhibiting also immune modulatory properties, on GvH reaction was studied, using the popliteal lymph node assay in mice. Administration of TH at ten days 0 or +2 relative to cell transfer to recipient mice led to a significant dose-dependent reduction of GvH reaction, whereas treatment of prospective donor mice at day -4 or -2 induced an enhanced GvH re activity of donor spleen cells. This effect was found not to be due to an altered proportion in the spleen cell inoculum of B and T lymphocytes, which latter are responsible for induction for GvH reaction. However, since normal parental lymphocytes are prepared for an enhanced GvH reactivity by addition of TH-treated macrophages, a stimulatory effect of the latter cells via macrophage-derived mediators, induced by TH, is suggested. | Effect of tilorone hydrochloride on graft-versus-host (GvH) reaction in mice. The effects of tilorone hydrochloride (TH), a powerful interferonogenic agent exhibiting also immune modulatory properties, on GvH reaction was studied, using the popliteal lymph node assay in mice. Administration of TH at ten days 0 or +2 relative to cell transfer to recipient mice led to a significant dose-dependent reduction of GvH reaction, whereas treatment of prospective donor mice at day -4 or -2 induced an enhanced GvH re activity of donor spleen cells. This effect was found not to be due to an altered proportion in the spleen cell inoculum of B and T lymphocytes, which latter are responsible for induction for GvH reaction. However, since normal parental lymphocytes are prepared for an enhanced GvH reactivity by addition of TH-treated macrophages, a stimulatory effect of the latter cells via macrophage-derived mediators, induced by TH, is suggested. | [
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|
PMID:17989 | [An ion exchange method to determine free metal concentrations, adapted for use in biological fluids: methods and determination of (Mg2+)]. | An ion exchange method for measuring concentrations of free (ionized) metal ions and its application to the determination of [Mg2+] is described. A surface sulfonated polystyrene material is used as the "twodimensional" cation exchanger. The sample-volume is 1 ml. About 50 determinations can be performed within 1 hr having a standard error of +/- (2-4)% in the optimal range of measurement. Advantages and disadvantages of the method compared with other ones are demonstrated and discussed. Free Mg2+ ion concentrations were measured in solutions containing pyrophosphate as well as haemoglobin and compared with those which were determined by equilibrium calculation or ultrafiltration. | [An ion exchange method to determine free metal concentrations, adapted for use in biological fluids: methods and determination of (Mg2+)]. An ion exchange method for measuring concentrations of free (ionized) metal ions and its application to the determination of [Mg2+] is described. A surface sulfonated polystyrene material is used as the "twodimensional" cation exchanger. The sample-volume is 1 ml. About 50 determinations can be performed within 1 hr having a standard error of +/- (2-4)% in the optimal range of measurement. Advantages and disadvantages of the method compared with other ones are demonstrated and discussed. Free Mg2+ ion concentrations were measured in solutions containing pyrophosphate as well as haemoglobin and compared with those which were determined by equilibrium calculation or ultrafiltration. | [
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|
PMID:17990 | Pulmonary complications, ventilation and blood gases after upper abdominal surgery. | Forty patients who underwent elective cholecystectomy were examined preoperatively and during the first postoperative week by physical examination, measurement of FVC and FEV1, arterial pH and blood gas analyses, and chest x-ray. Postoperative pulmonary complications (p.p.c.) were detected in 30 (75%) of the patients. Simple auscultation was the most sensitive tool in discovering p.p.c., but 18 of the 30 patients with complications also had a pathological chest x-ray. Obesity, smoking postoperative naso-gastric tube and postoperative wound infection were predisposing factors for p.p.c. Six patients with preoperative pulmonary disease all had a progress in their lung pathology. There was no definite relationship of duration of anaesthesia or drainage of the abdominal wound to development of p.p.c. The patients with p.p.c. showed a deeper and more prolonged fall in Pao2 postoperatively than the normal group. None of the normals showed an arterial Po2 below 70 mmHg in the postoperative course, while 63% of the p.p.c. group did. FVC and FEV1 showed marked reductions from preoperative values on the first postoperative day, and then gradually increased to near preoperative values after 1 week. Arterial pH and Pco2 showed no definite changes during the postoperative course. | Pulmonary complications, ventilation and blood gases after upper abdominal surgery. Forty patients who underwent elective cholecystectomy were examined preoperatively and during the first postoperative week by physical examination, measurement of FVC and FEV1, arterial pH and blood gas analyses, and chest x-ray. Postoperative pulmonary complications (p.p.c.) were detected in 30 (75%) of the patients. Simple auscultation was the most sensitive tool in discovering p.p.c., but 18 of the 30 patients with complications also had a pathological chest x-ray. Obesity, smoking postoperative naso-gastric tube and postoperative wound infection were predisposing factors for p.p.c. Six patients with preoperative pulmonary disease all had a progress in their lung pathology. There was no definite relationship of duration of anaesthesia or drainage of the abdominal wound to development of p.p.c. The patients with p.p.c. showed a deeper and more prolonged fall in Pao2 postoperatively than the normal group. None of the normals showed an arterial Po2 below 70 mmHg in the postoperative course, while 63% of the p.p.c. group did. FVC and FEV1 showed marked reductions from preoperative values on the first postoperative day, and then gradually increased to near preoperative values after 1 week. Arterial pH and Pco2 showed no definite changes during the postoperative course. | [
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|
PMID:17991 | The cerebrovascular CO2 reactivity during the acute phase of brain injury. | Using the intra-arterial 133xenon (133Xe) method, the cerebrovascular response to acute Paco2 reduction was studied in 26 unconscious, brain-injured patients subjected to controlled ventilation. The CO2 reactivity was calculated as delta in CBF/delta Paco2. The perfusion pressure was defined as the difference between mean arterial pressure and mean intraventricular pressure. Although the CO2 reactivities did not differ significantly from that in awake, normocapnic subjects, it was low in the acute phase of injury, especially in those patients with severe outcome in whom the brain-stem reflexes were often affected. An increase of the CO2 reactivity with time was observed, indicating normal response after 1-2 weeks. Chronic hypocapnia in six unconscious patients resulted in sustained CSF pH adaptation. The question whether a delay in CSF pH adapation exerts an influence on the CO2 reactivity, and the influence of cerebral lactacidosis on the CO2 response are discussed. | The cerebrovascular CO2 reactivity during the acute phase of brain injury. Using the intra-arterial 133xenon (133Xe) method, the cerebrovascular response to acute Paco2 reduction was studied in 26 unconscious, brain-injured patients subjected to controlled ventilation. The CO2 reactivity was calculated as delta in CBF/delta Paco2. The perfusion pressure was defined as the difference between mean arterial pressure and mean intraventricular pressure. Although the CO2 reactivities did not differ significantly from that in awake, normocapnic subjects, it was low in the acute phase of injury, especially in those patients with severe outcome in whom the brain-stem reflexes were often affected. An increase of the CO2 reactivity with time was observed, indicating normal response after 1-2 weeks. Chronic hypocapnia in six unconscious patients resulted in sustained CSF pH adaptation. The question whether a delay in CSF pH adapation exerts an influence on the CO2 reactivity, and the influence of cerebral lactacidosis on the CO2 response are discussed. | [
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|
PMID:17992 | The pressure-flow relations of the canine brain in acute mechanically induced arterial hypertension at different levels of cerebral blood flow. | Cerebral pressure-flow relations were studied in anaesthetized dogs during acute arterial hypertension, induced by compression of the thoracic aorta. In one group of animals steady state measurements were made with the radioactive gas elimination method. In another group the immediate changes of blood flow at a blood pressure change, as indicated by variations in the cerebral venous oxygen saturation, were studied with continuous oximetric analyses of the superior sagittal sinus blood. The initial blood flow was varied by variations of the arterial carbon dioxide tension of injections of papaverine. At low or normal blood flows autoregulation was efficient up to pressures around 180-200 mmHg, while at higher flows the upper autoregulatory pressure limit was found at lower blood pressures. Above the autoregulatory limit-irrespective of the control flow level-there was a rise in blood flow and a decrease in cerebrovascular resistance. | The pressure-flow relations of the canine brain in acute mechanically induced arterial hypertension at different levels of cerebral blood flow. Cerebral pressure-flow relations were studied in anaesthetized dogs during acute arterial hypertension, induced by compression of the thoracic aorta. In one group of animals steady state measurements were made with the radioactive gas elimination method. In another group the immediate changes of blood flow at a blood pressure change, as indicated by variations in the cerebral venous oxygen saturation, were studied with continuous oximetric analyses of the superior sagittal sinus blood. The initial blood flow was varied by variations of the arterial carbon dioxide tension of injections of papaverine. At low or normal blood flows autoregulation was efficient up to pressures around 180-200 mmHg, while at higher flows the upper autoregulatory pressure limit was found at lower blood pressures. Above the autoregulatory limit-irrespective of the control flow level-there was a rise in blood flow and a decrease in cerebrovascular resistance. | [
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|
PMID:17993 | Peroperative arterial blood pressure control in ophthalmological anaesthesia. | The effects were studied of a standardised general anaesthesia on mean arterial blood pressure, central venous pressure, blood gas values and the course of cataract operations. The material consisted of 20 unselected senile cataract operations, the mean age of the patients being 71.3 years. The arterial blood pressure was continuously checked, using an intra-arterial cannula. In order to avoid vitreous loss, the blood pressure was successfully kept optimally low during the extraction of the lens. No vitreous problems were noted. The oxygenation and ventilation of the patients were sufficient during anaesthesia and immediately postoperatively. | Peroperative arterial blood pressure control in ophthalmological anaesthesia. The effects were studied of a standardised general anaesthesia on mean arterial blood pressure, central venous pressure, blood gas values and the course of cataract operations. The material consisted of 20 unselected senile cataract operations, the mean age of the patients being 71.3 years. The arterial blood pressure was continuously checked, using an intra-arterial cannula. In order to avoid vitreous loss, the blood pressure was successfully kept optimally low during the extraction of the lens. No vitreous problems were noted. The oxygenation and ventilation of the patients were sufficient during anaesthesia and immediately postoperatively. | [
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|
PMID:17994 | Effects upon the fetus of oxygen administration to the mother. A study in monkey. | Catheters were placed into assorted arteries and veins of 8 anaesthetized pregnant monkeys and their fetuses. Oxygen-sensitive electrodes were also inserted subcutaneously into 3 of the 8 fetuses. Periodic samples of maternal and fetal blood were analyzed for PO2, PCO2 and pH. Oxygen administration to the mothers reliably increased the PO2 of blood taken from the fetal carotid artery and less constantly augmented the PO2 of blood withdrawn from the femoral artery and vein. During 5-6 hours of study the oxygen tension of fetal blood samples of all animals progressively declined. However, the most marked declines in PO2 values at all fetal sites were regularly observed at those times as--or after--the mothers emerged from anaesthesia. At these times also the magnitudes of the increases in fetal blood PO2 brought about by administering oxygen to the mothers diminished markedly and in parallel at all sample sites. The closely similar magnitudes of these various reductions at all fetal sample sties indicate that the basic mechanisms leading to decreased oxygen delivery lie outside the fetuses and are most likely due to decreased maternal blood flow to the uterus because of increased maternal sympathetic stimulation. These reductions in oxygen delivery to the fetus are all regularly reversed by reanasthetizing the mothers. The studies carried out with oxygen-sensitive electrodes demonstrate that administering oxygen to the mothers regularly increases oxygen tension of fetal tissues but after a 50 sec delay. | Effects upon the fetus of oxygen administration to the mother. A study in monkey. Catheters were placed into assorted arteries and veins of 8 anaesthetized pregnant monkeys and their fetuses. Oxygen-sensitive electrodes were also inserted subcutaneously into 3 of the 8 fetuses. Periodic samples of maternal and fetal blood were analyzed for PO2, PCO2 and pH. Oxygen administration to the mothers reliably increased the PO2 of blood taken from the fetal carotid artery and less constantly augmented the PO2 of blood withdrawn from the femoral artery and vein. During 5-6 hours of study the oxygen tension of fetal blood samples of all animals progressively declined. However, the most marked declines in PO2 values at all fetal sites were regularly observed at those times as--or after--the mothers emerged from anaesthesia. At these times also the magnitudes of the increases in fetal blood PO2 brought about by administering oxygen to the mothers diminished markedly and in parallel at all sample sites. The closely similar magnitudes of these various reductions at all fetal sample sties indicate that the basic mechanisms leading to decreased oxygen delivery lie outside the fetuses and are most likely due to decreased maternal blood flow to the uterus because of increased maternal sympathetic stimulation. These reductions in oxygen delivery to the fetus are all regularly reversed by reanasthetizing the mothers. The studies carried out with oxygen-sensitive electrodes demonstrate that administering oxygen to the mothers regularly increases oxygen tension of fetal tissues but after a 50 sec delay. | [
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|
PMID:17995 | The finding that secretory component is not associated with gamma-glutamyltranspeptidase activity. | The gamma-glutamyltranspeptidase activity of human milk was concentrated by ammonium sulphate precipitation. On gel chromatography of the dissolved precipitate, the activity was eluted in the high-molecular-weight fraction containing secretory IgA, while no activity appeared in the eluate at the position of free secretory component. Various antisera were added to portions of the pool of active fractions. No change of gamma-glutamyltranspeptidase activity appearedse activity was obtained with antisera against either IgA, secretory IgA or secretory component, while a large reduction of activity was seen with anti-human colostrum. Finally, purified free secretory component, secretory IgA and in vitro complexes between secretory component and IgA dimers were shown to be inactive in the gamma-glutamltranspeptidase assay, both in the absence and presence of zinc ions. Thus secretory component, either when free or bound to IgA, does not exhibit gamma-glutamyltranspeptidase activity, and therefore cannot function as such an enzyme in the transport of IgA across mucous membranes, as has been suggested previously. | The finding that secretory component is not associated with gamma-glutamyltranspeptidase activity. The gamma-glutamyltranspeptidase activity of human milk was concentrated by ammonium sulphate precipitation. On gel chromatography of the dissolved precipitate, the activity was eluted in the high-molecular-weight fraction containing secretory IgA, while no activity appeared in the eluate at the position of free secretory component. Various antisera were added to portions of the pool of active fractions. No change of gamma-glutamyltranspeptidase activity appearedse activity was obtained with antisera against either IgA, secretory IgA or secretory component, while a large reduction of activity was seen with anti-human colostrum. Finally, purified free secretory component, secretory IgA and in vitro complexes between secretory component and IgA dimers were shown to be inactive in the gamma-glutamltranspeptidase assay, both in the absence and presence of zinc ions. Thus secretory component, either when free or bound to IgA, does not exhibit gamma-glutamyltranspeptidase activity, and therefore cannot function as such an enzyme in the transport of IgA across mucous membranes, as has been suggested previously. | [
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|
PMID:17996 | Atenolol in the treatment of angina pectoris. | Nineteen men, aged 41-64 years, with stable angina pectoris have completed a random double-blind study of atenolol, 50 mg b.i.d., atenolol, 100 mg b.i.d., and placebo. Fifteen patients had subjective improvement on atenolol, two were unchanged and two felt worse (because of asthenia/leg fatigue). No significant placebo effect was found. On both atenolol dosages there were highly significant reductions in heart rate at rest and during exercise and in BP. Only the maximal heart rate decreased significantly more on 100 mg atenolol than on 50 mg (p less than 0.01). Fourteen patients had the same or a better physical performance on the 50 mg b.i.d. regimen than on the 100 mg b.i.d. regimen, although this difference was not significant. Sixteen patients had higher bicycle exercise performance on atenolol than on placebo. Disregarding the three non-responders, a mean increase of 44% in bicycle performance was found. No serious side-effects were seen. Most individuals reported an increased feeling of well-being on atenolol. | Atenolol in the treatment of angina pectoris. Nineteen men, aged 41-64 years, with stable angina pectoris have completed a random double-blind study of atenolol, 50 mg b.i.d., atenolol, 100 mg b.i.d., and placebo. Fifteen patients had subjective improvement on atenolol, two were unchanged and two felt worse (because of asthenia/leg fatigue). No significant placebo effect was found. On both atenolol dosages there were highly significant reductions in heart rate at rest and during exercise and in BP. Only the maximal heart rate decreased significantly more on 100 mg atenolol than on 50 mg (p less than 0.01). Fourteen patients had the same or a better physical performance on the 50 mg b.i.d. regimen than on the 100 mg b.i.d. regimen, although this difference was not significant. Sixteen patients had higher bicycle exercise performance on atenolol than on placebo. Disregarding the three non-responders, a mean increase of 44% in bicycle performance was found. No serious side-effects were seen. Most individuals reported an increased feeling of well-being on atenolol. | [
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|
PMID:18002 | Acute myocardial infarction and ischemic injury during surgery for coronary artery disease. | The incidence of myocardial infarction, acute ischemic injury, and associated serum enzyme abnormalities has been evaluated in four operations involving the coronary circulation. The highest incidence of infarction was associated with internal mammary implantation (Vineberg procedure). There was no significant difference in the incidence of infarction, ischemic injury, or abnormal enzyme levels between patients with stable angina and those with unstable angina who had vein bypass surgery. In operations involving combined vein bypass grafting and valve replacement surgery, the incidence of abnormal serum enzyme elevations was higher than in any other procedure. The incidence of infarction and acute ischemic injury in combined operations was similar to that in other procedures but this may have been due to the difficulty in the ECG diagnosis of infarction in this group of patients, most of whom had abnormal preoperative ECGs. | Acute myocardial infarction and ischemic injury during surgery for coronary artery disease. The incidence of myocardial infarction, acute ischemic injury, and associated serum enzyme abnormalities has been evaluated in four operations involving the coronary circulation. The highest incidence of infarction was associated with internal mammary implantation (Vineberg procedure). There was no significant difference in the incidence of infarction, ischemic injury, or abnormal enzyme levels between patients with stable angina and those with unstable angina who had vein bypass surgery. In operations involving combined vein bypass grafting and valve replacement surgery, the incidence of abnormal serum enzyme elevations was higher than in any other procedure. The incidence of infarction and acute ischemic injury in combined operations was similar to that in other procedures but this may have been due to the difficulty in the ECG diagnosis of infarction in this group of patients, most of whom had abnormal preoperative ECGs. | [
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|
PMID:18003 | Isolated coronary periarteritis: report of a case of unexpected death in a young pregnant woman. | A case of sudden unexpected death in a 23 year old woman in her 8th month of pregnancy is reported. Death occurred from isolated coronary periarteritis with thrombosis. It is believed that the thrombosis was secondary to the adventitial infiltrate, which was of a type suggesting a hypersensitivity factor. It is proposed that pathogenetically this case is identical to reported cases of dissecting hemorrhage or aneurysm of the coronary artery and represents an entity different from other forms of inflammatory coronary disease. | Isolated coronary periarteritis: report of a case of unexpected death in a young pregnant woman. A case of sudden unexpected death in a 23 year old woman in her 8th month of pregnancy is reported. Death occurred from isolated coronary periarteritis with thrombosis. It is believed that the thrombosis was secondary to the adventitial infiltrate, which was of a type suggesting a hypersensitivity factor. It is proposed that pathogenetically this case is identical to reported cases of dissecting hemorrhage or aneurysm of the coronary artery and represents an entity different from other forms of inflammatory coronary disease. | [
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|
PMID:18004 | An isozyme of erythrocyte pyruvate kinase (PK-Los Angeles) with impaired kinetics corrected by fructose-1, 6-diphosphate. | A mutant isozyme of erythrocyte pyruvate kinase was found in a family of French-Canadian ancestry in association with hemolytic anemia. The isozyme was characterized by normal maximal activity, pH optimum, heat stability, and fructosediphosphate activation constants, but had markedly reduced affinity for the substrate, phosphoenolpyruvate. This kinetic defect was corrected almost entirely in vitro by low concentrations of fructosediphosphate. | An isozyme of erythrocyte pyruvate kinase (PK-Los Angeles) with impaired kinetics corrected by fructose-1, 6-diphosphate. A mutant isozyme of erythrocyte pyruvate kinase was found in a family of French-Canadian ancestry in association with hemolytic anemia. The isozyme was characterized by normal maximal activity, pH optimum, heat stability, and fructosediphosphate activation constants, but had markedly reduced affinity for the substrate, phosphoenolpyruvate. This kinetic defect was corrected almost entirely in vitro by low concentrations of fructosediphosphate. | [
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|
PMID:18005 | Bacteremia in hospitalized children. | The results of 6,951 blood cultures taken from hospitalized children are reviewed. One or more organisms grew from 6% (399) of the cultures, of which 189 (two thirds) were considered to represent confirmed bacteremia. The most common organisms associated with bacteremia were Haemophilus influenzae, Streptococcus pneumoniae, enterobacteriaceae, and Staphylococcus aureus. Patients with deficient host defenses (newborns, oncology patients) with bacteremia had a higher mortality than normal children. Laboratory techniques allowing more rapid detection of positive blood cultures resulted in major alterations in therapy in almost one half of all bacteremic patients. | Bacteremia in hospitalized children. The results of 6,951 blood cultures taken from hospitalized children are reviewed. One or more organisms grew from 6% (399) of the cultures, of which 189 (two thirds) were considered to represent confirmed bacteremia. The most common organisms associated with bacteremia were Haemophilus influenzae, Streptococcus pneumoniae, enterobacteriaceae, and Staphylococcus aureus. Patients with deficient host defenses (newborns, oncology patients) with bacteremia had a higher mortality than normal children. Laboratory techniques allowing more rapid detection of positive blood cultures resulted in major alterations in therapy in almost one half of all bacteremic patients. | [
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|
PMID:18007 | Effects of cimetidine, a histamine H2-receptor antagonist, on various experimental gastric and duodenal ulcers. | The effects of cimetidine, a new histamine H2-receptor antagonist, on the development of experimental gastric and duodenal ulcers were studied. It was found that either by the oral, intraduodenal, or intraperitoneal route this agent had a marked inhibitory activity on stress-, aspirin-, indomethacin-, or histamine-induced gastric ulcers in rats and guinea pigs. The effects of cimetidine on stress-, aspirin-, and indomethacin-induced gastric ulcers were dose-dependent in many cases. Pylorus-ligation uclers, reserpine- or serotonin-induced gastric ulcers were little influenced by cimetidine. Duodenal ulcers induced by continuous infusion of carbachol-histamine were significantly inhibited by a simultaneous infusion of cimetidine. An analysis of gastric contents in pylorus-ligated rats after stressing indicated a decreased volume and acid output as the result of intraduodenal cimetidine treatment. In contrast, cimetidine exerted little influence on gastric secretion in rats treated with aspirin or in guinea pigs treated with histamine. Thus, the mechanism of action of cimetidine in preventing gastric or duodenal ulcers is likely to occur by suppression of gastric secretory function in a duodenal ulcer model but by suppression of other unknown ulcerogenic factors in gastric ulcer models. | Effects of cimetidine, a histamine H2-receptor antagonist, on various experimental gastric and duodenal ulcers. The effects of cimetidine, a new histamine H2-receptor antagonist, on the development of experimental gastric and duodenal ulcers were studied. It was found that either by the oral, intraduodenal, or intraperitoneal route this agent had a marked inhibitory activity on stress-, aspirin-, indomethacin-, or histamine-induced gastric ulcers in rats and guinea pigs. The effects of cimetidine on stress-, aspirin-, and indomethacin-induced gastric ulcers were dose-dependent in many cases. Pylorus-ligation uclers, reserpine- or serotonin-induced gastric ulcers were little influenced by cimetidine. Duodenal ulcers induced by continuous infusion of carbachol-histamine were significantly inhibited by a simultaneous infusion of cimetidine. An analysis of gastric contents in pylorus-ligated rats after stressing indicated a decreased volume and acid output as the result of intraduodenal cimetidine treatment. In contrast, cimetidine exerted little influence on gastric secretion in rats treated with aspirin or in guinea pigs treated with histamine. Thus, the mechanism of action of cimetidine in preventing gastric or duodenal ulcers is likely to occur by suppression of gastric secretory function in a duodenal ulcer model but by suppression of other unknown ulcerogenic factors in gastric ulcer models. | [
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|
PMID:18008 | Quantitative determination of four antihistamines in combination by high-pressure liquid chromatography. | A procedure used to assay four antihistamines--brompheniramine maleate, chlorpheniramine maleate, pheniramine maleate and pyrilamine maleate in combination--is discussed. The method requires a high-pressure liquid chromatograph and an intermediate polarity column. The method is accurate and appears to be stability-indicating. The four antihistamines can be separated and assayed accurately. There is no interference from the two commonly used decongestants, phenylephrine hydrochloride and phenylpropanolamine hydrochloride, from the expectorant potassium guaiacolsulfonate, from the preservative propyl paraben or from two other antihistamines, diphenhydramine hydrochloride and bromdiphenhydramine hydrochloride. Guaifenesin, methylparaben and sodium benzoate interfere only with pheniramine maleate. Methapyrilene hydrochloride interferes only with pyrilamine maleate. | Quantitative determination of four antihistamines in combination by high-pressure liquid chromatography. A procedure used to assay four antihistamines--brompheniramine maleate, chlorpheniramine maleate, pheniramine maleate and pyrilamine maleate in combination--is discussed. The method requires a high-pressure liquid chromatograph and an intermediate polarity column. The method is accurate and appears to be stability-indicating. The four antihistamines can be separated and assayed accurately. There is no interference from the two commonly used decongestants, phenylephrine hydrochloride and phenylpropanolamine hydrochloride, from the expectorant potassium guaiacolsulfonate, from the preservative propyl paraben or from two other antihistamines, diphenhydramine hydrochloride and bromdiphenhydramine hydrochloride. Guaifenesin, methylparaben and sodium benzoate interfere only with pheniramine maleate. Methapyrilene hydrochloride interferes only with pyrilamine maleate. | [
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|
PMID:18009 | Bladder dysfunction after radical abdominal hysterectomy. | Bladder dysfunction is a common occurrence following radical hysterectomy. We studied bladder function prospectively in 10 patients before and after radical hysterectomy. Results suggest that the hypertonic phase observed immediately postoperatively is the result of an increase in myogenic tonicity of the detrusor muscle secondary to the trauma of operation and prolonged catheter drainage. The inability of patients to urinate effectively is due to partial detrusor denervation. Combined cystometry and electromyography confirmed the presence of normal sphincter function and the absence of detrusor sphincter dyssynergia. Prevention of postoperative bladder atony includes a careful preoperative urologic evaluation, including cystometry. Postoperative bladder care should emphasize the prevention of overdistention. Inability to empty the bladder after operation may be managed effectively by intermittent self-catheterization, Urecholine, or prolonged catheter drainage. Patients should be evaluated periodically to uncover delayed bladder decompensation. | Bladder dysfunction after radical abdominal hysterectomy. Bladder dysfunction is a common occurrence following radical hysterectomy. We studied bladder function prospectively in 10 patients before and after radical hysterectomy. Results suggest that the hypertonic phase observed immediately postoperatively is the result of an increase in myogenic tonicity of the detrusor muscle secondary to the trauma of operation and prolonged catheter drainage. The inability of patients to urinate effectively is due to partial detrusor denervation. Combined cystometry and electromyography confirmed the presence of normal sphincter function and the absence of detrusor sphincter dyssynergia. Prevention of postoperative bladder atony includes a careful preoperative urologic evaluation, including cystometry. Postoperative bladder care should emphasize the prevention of overdistention. Inability to empty the bladder after operation may be managed effectively by intermittent self-catheterization, Urecholine, or prolonged catheter drainage. Patients should be evaluated periodically to uncover delayed bladder decompensation. | [
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|
PMID:18010 | Effects of prolonged infusion of beta-adrenergic agonists on uterine and umbilical blood flow in pregnant sheep. | We have extended our evaluation of the effects of three beta-adrenergic agents in near-term pregnant sheep to include a period of infusion three times longer than previously studied. This extension has provided the following information: (1) Initial depression of uterine blood flow and mean arterial pressure associated with administration of ritodrine or salbutamol abate with time despite continued drug infusion; (2) the uterine hyperemia associated with salbutamol and fenoterol are drug-related rather than postinfusion-related phenomena; (3) increased uterine vascular resistance is found with ritodrine, and decreased uterine vascular resistance occurs with salbutamol and fenoterol. | Effects of prolonged infusion of beta-adrenergic agonists on uterine and umbilical blood flow in pregnant sheep. We have extended our evaluation of the effects of three beta-adrenergic agents in near-term pregnant sheep to include a period of infusion three times longer than previously studied. This extension has provided the following information: (1) Initial depression of uterine blood flow and mean arterial pressure associated with administration of ritodrine or salbutamol abate with time despite continued drug infusion; (2) the uterine hyperemia associated with salbutamol and fenoterol are drug-related rather than postinfusion-related phenomena; (3) increased uterine vascular resistance is found with ritodrine, and decreased uterine vascular resistance occurs with salbutamol and fenoterol. | [
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|
PMID:18011 | Thymic involution in murine graft-versus-host reaction. Epithelial injury mimicking human thymic dysplasia. | Mild, moderate, and severe graft-versus-host (GVH) reactions were induced in four series of experiments in 71 CBA X A and C57BL/6 X A F1 hybrid mice. At regular intervals post-GVH reaction induction (Days 4-42), the animals were sacrificed, autopsied, and histologically studied. Visceral alterations of GVH reaction were recorded in the spleen, lymph nodes, liver, kidney, gut, and thymus. A spectrum of thymic changes was documented, ranging from obliteration of a definable cortex and medulla with loss of Hassall's corpuscles to marked involution with complete disappearance of the gland. Ultrastructural studies revealed damage to both lymphocytes and epithelial cells along with lymphocyte emperipolesis of epithelial cells, lymphocytolysis within epithelial cells, and accumulation of numerous autophagic vacuoles containing fragments of cellular debris within epithelial cells and histiocytes. The resemblance of these alterations to human thymic dysplasia as observed in primary immunodeficient conditions was striking. The theoretical implications of these studies for the pathogenesis of human congenital immunodeficiency states are considered. | Thymic involution in murine graft-versus-host reaction. Epithelial injury mimicking human thymic dysplasia. Mild, moderate, and severe graft-versus-host (GVH) reactions were induced in four series of experiments in 71 CBA X A and C57BL/6 X A F1 hybrid mice. At regular intervals post-GVH reaction induction (Days 4-42), the animals were sacrificed, autopsied, and histologically studied. Visceral alterations of GVH reaction were recorded in the spleen, lymph nodes, liver, kidney, gut, and thymus. A spectrum of thymic changes was documented, ranging from obliteration of a definable cortex and medulla with loss of Hassall's corpuscles to marked involution with complete disappearance of the gland. Ultrastructural studies revealed damage to both lymphocytes and epithelial cells along with lymphocyte emperipolesis of epithelial cells, lymphocytolysis within epithelial cells, and accumulation of numerous autophagic vacuoles containing fragments of cellular debris within epithelial cells and histiocytes. The resemblance of these alterations to human thymic dysplasia as observed in primary immunodeficient conditions was striking. The theoretical implications of these studies for the pathogenesis of human congenital immunodeficiency states are considered. | [
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|
PMID:18013 | Thyroid cold acclimation influences on norepinephrine metabolism in brown fat. | Norepinephrine turnover rates and tyrosine hydroxylase activities were determined in the interscapular brown fat pad of the rat during cold acclimation, hyperthyroxinism, and after thyroidectomy. Rats were cold acclimated by placement in a cold room, one rat to a cage, for a period of 6 wk. Hyperthyroxinism was induced by daily subcutaneous injections of L-thyroxine (1 mg/kg) for 6 days. Norepinephrine turnover rate and enzyme activity were determined at the end of each experimental period and at 8 wk after thyroidectomy. The rate of norepinephrine turnover increased during cold acclimation and hyperthyroxinism and decreased after thyroidectomy. Cold acclimation resulted in a significant increase in tyrosine hydroxylase activity, whereas no significant effect on enzyme activity was observed in hyperthyroxinism or after thyroidectomy. None of the conditions produced a change compared to controls in the apparent Km of tyrosine hydroxylase for L-tyrosine. Cold acclimation resulted in a significant decrease in the apparent Km of tyrosine hydroxylase for pterin cofactor, whereas thyroxine treatment and thyroidectomy had no effect. | Thyroid cold acclimation influences on norepinephrine metabolism in brown fat. Norepinephrine turnover rates and tyrosine hydroxylase activities were determined in the interscapular brown fat pad of the rat during cold acclimation, hyperthyroxinism, and after thyroidectomy. Rats were cold acclimated by placement in a cold room, one rat to a cage, for a period of 6 wk. Hyperthyroxinism was induced by daily subcutaneous injections of L-thyroxine (1 mg/kg) for 6 days. Norepinephrine turnover rate and enzyme activity were determined at the end of each experimental period and at 8 wk after thyroidectomy. The rate of norepinephrine turnover increased during cold acclimation and hyperthyroxinism and decreased after thyroidectomy. Cold acclimation resulted in a significant increase in tyrosine hydroxylase activity, whereas no significant effect on enzyme activity was observed in hyperthyroxinism or after thyroidectomy. None of the conditions produced a change compared to controls in the apparent Km of tyrosine hydroxylase for L-tyrosine. Cold acclimation resulted in a significant decrease in the apparent Km of tyrosine hydroxylase for pterin cofactor, whereas thyroxine treatment and thyroidectomy had no effect. | [
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|
PMID:18014 | Hexose monophosphate shunt in isolated cardiac myocytes from normal rats. | The activity of the hexose monophosphate shunt was studied in myocytes obtained from the ventricles of normal, adult, male rats. When myocytes were incubated in buffer containing either 1-14C- or 6-14C-labeled glucose the ratio of C-1/C-6 14CO2 evolved was essentially unity. The addition of plasma levels of amino acids did not alter this finding. If, however, a competitive substrate (pyruvate, octanoate, acetate, or lactate) was present, in sufficient quantity to lower the oxidation of glucose to approximately 20% of the control, the C-1/C-6 14CO2 ratio rose to values between 1.3 and 2.1. This ratio was dependent on the concentration of the competitive substrate, which was dependent on the buffer system. The data indicates that the hexose monophosphate shunt is active in the heart because it can be demonstrated when a substrate, which competes with glucose for oxidation, is present. The presence of competing substrates parallels the situation occuring in vivo. | Hexose monophosphate shunt in isolated cardiac myocytes from normal rats. The activity of the hexose monophosphate shunt was studied in myocytes obtained from the ventricles of normal, adult, male rats. When myocytes were incubated in buffer containing either 1-14C- or 6-14C-labeled glucose the ratio of C-1/C-6 14CO2 evolved was essentially unity. The addition of plasma levels of amino acids did not alter this finding. If, however, a competitive substrate (pyruvate, octanoate, acetate, or lactate) was present, in sufficient quantity to lower the oxidation of glucose to approximately 20% of the control, the C-1/C-6 14CO2 ratio rose to values between 1.3 and 2.1. This ratio was dependent on the concentration of the competitive substrate, which was dependent on the buffer system. The data indicates that the hexose monophosphate shunt is active in the heart because it can be demonstrated when a substrate, which competes with glucose for oxidation, is present. The presence of competing substrates parallels the situation occuring in vivo. | [
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|
PMID:18015 | HCO3- and H+ secretion in rat ileum in vivo. | Replacing Cl- in the perfusion fluids decreased the luminal pH of rat ileum perfused in vivo. Varying the initial pH in Cl- depletion studies indicated an equilibrium pH near 6.6. Na+ depletion in Cl- deleted fluids partially inhibited luminal acidification. Addition of HCO3- accelerated Na+ absorption and decreased Cl- absorption. Luminal PCO2 was increased using fluids buffered to initial pH 6.6, suggesting secretion of HCO3- rather than OH-. The decreased HCO3- secretion using Cl- depleted fluids was not due to an acclerated rate of H+ secretion. Reaffirmed and expanded in this study is an ileal H+ secretory process that is partially related to Na+ absorption and direct HCO3- secretion that is related to Cl- and Na+ absorption. | HCO3- and H+ secretion in rat ileum in vivo. Replacing Cl- in the perfusion fluids decreased the luminal pH of rat ileum perfused in vivo. Varying the initial pH in Cl- depletion studies indicated an equilibrium pH near 6.6. Na+ depletion in Cl- deleted fluids partially inhibited luminal acidification. Addition of HCO3- accelerated Na+ absorption and decreased Cl- absorption. Luminal PCO2 was increased using fluids buffered to initial pH 6.6, suggesting secretion of HCO3- rather than OH-. The decreased HCO3- secretion using Cl- depleted fluids was not due to an acclerated rate of H+ secretion. Reaffirmed and expanded in this study is an ileal H+ secretory process that is partially related to Na+ absorption and direct HCO3- secretion that is related to Cl- and Na+ absorption. | [
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|
PMID:18016 | Neural control of glycogen content and its diurnal rhythm in mouse pineal cell. | In adult male dd mice, possible mechanisms regulating the glycogen content in the pineal cell were investigated by a semiquantitative histochemical method, with particular reference to the role of the sympathetic innervation. Reserpine, superior cervical ganglionectomy (SCGX), or decentralization of the ganglia (DC), as well as continuous light, prevented the nocturnal decrease in the glycogen content, causing a marked increase, and caused a gradual decrease in the size of the pineal cell. In the SCGX or DC group, the glycogen content reached a peak at 2 days and then decreased gradually. The nocturnal decrease was also prevented by propranolol. Noradrenaline caused a marked decrease in the glycogen content. These findings support the hypothesis that the glycogen metabolism and its diurnal rhythm in the pineal cell are regulated by the sympathetic nerve terminals innervating the pineal gland, presumably by the release of noradrenaline. In addition, the nature of the internal mechanism in the organism generating the pineal glycogen rhythm was examined. Light was considered to induce a phase shift in such a mechanism, but reserpine was not. | Neural control of glycogen content and its diurnal rhythm in mouse pineal cell. In adult male dd mice, possible mechanisms regulating the glycogen content in the pineal cell were investigated by a semiquantitative histochemical method, with particular reference to the role of the sympathetic innervation. Reserpine, superior cervical ganglionectomy (SCGX), or decentralization of the ganglia (DC), as well as continuous light, prevented the nocturnal decrease in the glycogen content, causing a marked increase, and caused a gradual decrease in the size of the pineal cell. In the SCGX or DC group, the glycogen content reached a peak at 2 days and then decreased gradually. The nocturnal decrease was also prevented by propranolol. Noradrenaline caused a marked decrease in the glycogen content. These findings support the hypothesis that the glycogen metabolism and its diurnal rhythm in the pineal cell are regulated by the sympathetic nerve terminals innervating the pineal gland, presumably by the release of noradrenaline. In addition, the nature of the internal mechanism in the organism generating the pineal glycogen rhythm was examined. Light was considered to induce a phase shift in such a mechanism, but reserpine was not. | [
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|
PMID:18017 | Function of human platelets during extracorporeal circulation. | The interaction between human platelets and nonbiologic surfaces was studied during in vitro recirculation of 500 ml of fresh, heparinized human blood in four different perfusion circuits. Circuits differed in surface area (0.1 m2 or 0.9 m2) and in surface composition. No important differences were observed between standard silicone-rubber and filler-free, silicone-rubber surfaces. Platelet counts decreased to 85% of control in 0.1- m2 circuits, but retained normal sensitivity to aggregating agents and released only small amounts of platelet factor 4 (PF4). In contrast, platelet counts in 0.9-m2 circuits decreased to 20% of control within 2 min and platelet sensitivity was depressed out of proportion to the fall in platelet count. Plasma PF4 progressively increased and platelet PF4 content progressively decreased during 6 h of recirculation. The results indicate that human platelets may exist in three conditions during extracorporeal circulation. Some platelets are unaltered, some are less sensitive to aggregating agents, and others have undergone extensive release. The ratio of blood volume to surface area appears to be an important determinant of platelet-surface interaction. | Function of human platelets during extracorporeal circulation. The interaction between human platelets and nonbiologic surfaces was studied during in vitro recirculation of 500 ml of fresh, heparinized human blood in four different perfusion circuits. Circuits differed in surface area (0.1 m2 or 0.9 m2) and in surface composition. No important differences were observed between standard silicone-rubber and filler-free, silicone-rubber surfaces. Platelet counts decreased to 85% of control in 0.1- m2 circuits, but retained normal sensitivity to aggregating agents and released only small amounts of platelet factor 4 (PF4). In contrast, platelet counts in 0.9-m2 circuits decreased to 20% of control within 2 min and platelet sensitivity was depressed out of proportion to the fall in platelet count. Plasma PF4 progressively increased and platelet PF4 content progressively decreased during 6 h of recirculation. The results indicate that human platelets may exist in three conditions during extracorporeal circulation. Some platelets are unaltered, some are less sensitive to aggregating agents, and others have undergone extensive release. The ratio of blood volume to surface area appears to be an important determinant of platelet-surface interaction. | [
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|
PMID:18018 | Development of SHR hypertension and cardiac hypertrophy during prolonged beta blockade. | Spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were treated with beta-adrenergic receptor inhibiting drugs (either propranolol or timolol) from conception until 12 weeks of age to determine if this therapy would alter the development of systemic hypertension or left ventricular hypertrophy. Therapy (propranolol or timolol, 500 mg/liter drinking water) was initiated with breeding parents and continued throughout the pregnancy, nursing, and postweaning periods. Although the heart rates of beta-adrenergic receptor inhibited WKY and SHR rats were consistently reduced with respect to their respective tap-water controls, this therapy did not alter body growth. Hemodynamic studies demonstrated reduced central venous pressure, cardiac index, and maximum acceleration of aortic flow in the beta-adrenergic inhibited rats. In spite of these findings, the arterial pressure of the treated rats and the degree of left ventricular hypertrophy of the SHR were unaltered by treatment. Thus, administration of the beta-adrenergic receptor blocking agents, propranolol or timolol, from conception through the developmental stage of SHR hypertension, failed to alter either the progressive rise in arterial pressure or the development of hypertensive vascular disease and left ventricular hypertrophy. | Development of SHR hypertension and cardiac hypertrophy during prolonged beta blockade. Spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were treated with beta-adrenergic receptor inhibiting drugs (either propranolol or timolol) from conception until 12 weeks of age to determine if this therapy would alter the development of systemic hypertension or left ventricular hypertrophy. Therapy (propranolol or timolol, 500 mg/liter drinking water) was initiated with breeding parents and continued throughout the pregnancy, nursing, and postweaning periods. Although the heart rates of beta-adrenergic receptor inhibited WKY and SHR rats were consistently reduced with respect to their respective tap-water controls, this therapy did not alter body growth. Hemodynamic studies demonstrated reduced central venous pressure, cardiac index, and maximum acceleration of aortic flow in the beta-adrenergic inhibited rats. In spite of these findings, the arterial pressure of the treated rats and the degree of left ventricular hypertrophy of the SHR were unaltered by treatment. Thus, administration of the beta-adrenergic receptor blocking agents, propranolol or timolol, from conception through the developmental stage of SHR hypertension, failed to alter either the progressive rise in arterial pressure or the development of hypertensive vascular disease and left ventricular hypertrophy. | [
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|
PMID:18019 | Effects of increased intracranial pressure on pulmonary vascular resistance of fetal and neonatal goats. | The effects of increased intracranial pressure on the pulmonary circulation were investigated in fetal and neonatal goats. Pulmonary vascular resistance and systemic arterial pressure increased with elevation of intracranial pressure in neonatal animals. Alpha-adrenergic blockade completely eliminated both of these responses. The response of the fetal pulmonary circulation was unlike that seen in the postnatal animal. Although there was a slight elevation of pulmonary vascular resistance initially, the predominant response was a decrease in resistance. The decrease in fetal pulmonary vascular resistance was unaffected by phenoxybenzamine, but reversed by propranolol. After the beta-adrenergic blockade, increased intracranial pressure produced an increase in pulmonary vascular resistance. Similarly, ventilation of fetal lungs resulted in an increase in pulmonary vascular resistance after increased intracranial pressure. These results demonstrate for the first time that pulmonary vascular resistance may be altered in fetal and neonatal animals by increasing intracranial pressure. The elevation of pulmonary vascular resistance after elevated intracranial pressure must be due to an active pulmonary vascular constriction. | Effects of increased intracranial pressure on pulmonary vascular resistance of fetal and neonatal goats. The effects of increased intracranial pressure on the pulmonary circulation were investigated in fetal and neonatal goats. Pulmonary vascular resistance and systemic arterial pressure increased with elevation of intracranial pressure in neonatal animals. Alpha-adrenergic blockade completely eliminated both of these responses. The response of the fetal pulmonary circulation was unlike that seen in the postnatal animal. Although there was a slight elevation of pulmonary vascular resistance initially, the predominant response was a decrease in resistance. The decrease in fetal pulmonary vascular resistance was unaffected by phenoxybenzamine, but reversed by propranolol. After the beta-adrenergic blockade, increased intracranial pressure produced an increase in pulmonary vascular resistance. Similarly, ventilation of fetal lungs resulted in an increase in pulmonary vascular resistance after increased intracranial pressure. These results demonstrate for the first time that pulmonary vascular resistance may be altered in fetal and neonatal animals by increasing intracranial pressure. The elevation of pulmonary vascular resistance after elevated intracranial pressure must be due to an active pulmonary vascular constriction. | [
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|
PMID:18020 | Active alkalinization by amphibian gastric fundic mucosa in vitro. | Gastric fundic mucosae in vitro from four species of frog and Necturus secrete HCO-3 at a steady-state rate of 0.25-0.55 microneq-cm-2-h-1 which corresponds to 5-10% of maximal H+ secretion. Net alkalinization was quantitated in mucosae with spontaneously resting H+ secretion or in mucosae inhibited by histamine H2-receptor antagonists or SNC-. HCO-3 secretion was inhibited by DNP (10(-4) M), CN- (10(-2) M), or anoxia. Acetazolamide inhibited alkalinization at 10(-2) M when added to the nutrient side and at 10(-4) M on the luminal side. Carbachol (10(-4) M) and DBcGMP (10(-4) M) stimulated alkalinization and caused a transient rise in the transmucosal PD; DBcAMP (10(-3) M) was without effect. An almost identical secretion occurred spontaneously in antral mucosae and was insensitive to histamine (10(-5) M). Occurrence in both antral and fundic mucosa suggests that active alkalinization is a property of gastric surface epithelial cells. Gastric alkalinization may protect the luminal surface of the mucosa from the damaging effects of acid and contribute to the continuous removal of H+ ions from gastric contents. | Active alkalinization by amphibian gastric fundic mucosa in vitro. Gastric fundic mucosae in vitro from four species of frog and Necturus secrete HCO-3 at a steady-state rate of 0.25-0.55 microneq-cm-2-h-1 which corresponds to 5-10% of maximal H+ secretion. Net alkalinization was quantitated in mucosae with spontaneously resting H+ secretion or in mucosae inhibited by histamine H2-receptor antagonists or SNC-. HCO-3 secretion was inhibited by DNP (10(-4) M), CN- (10(-2) M), or anoxia. Acetazolamide inhibited alkalinization at 10(-2) M when added to the nutrient side and at 10(-4) M on the luminal side. Carbachol (10(-4) M) and DBcGMP (10(-4) M) stimulated alkalinization and caused a transient rise in the transmucosal PD; DBcAMP (10(-3) M) was without effect. An almost identical secretion occurred spontaneously in antral mucosae and was insensitive to histamine (10(-5) M). Occurrence in both antral and fundic mucosa suggests that active alkalinization is a property of gastric surface epithelial cells. Gastric alkalinization may protect the luminal surface of the mucosa from the damaging effects of acid and contribute to the continuous removal of H+ ions from gastric contents. | [
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|
PMID:18021 | Pancreatic bicarbonate, serum gastrin, and secretin responses to meals varying in pH. | The role of secretin in the postprandial bicarbonate response by the pancreas is not clear. This study reports secretin and bicarbonate secretion after exogenous and endogenous acidification of meal. In dogs with gastric and pancreatic fistulas, a liver extract meal at various pH levels was introduced into the stomach and kept at the preselected pH by intragastric titration. Gastric acid, pancreatic bicarbonate, serum gastrin, and plasma secretin were measured. The meal at pH 7 produced an increase of gastrin levels of 230% above basal and a gastric acid output from a basal of 0.8-16.9 meq/30 min. Acidification of the meal evoked a pH-dependent reduction of gastrin and gastric acid secretion, a pH-dependent elevation of pancreatic bicarbonate, and significant elevation of secretin at pH 3 (43% above basal) and at pH 2 (80% above basal). Postprandial endogenous acidification of a meal, without intragastric titration, also provoked significant release of secretin. Maximal pancreatic bicarbonate secretion in response to exogenous secretin was augmented 30% by the addition of a liver extract meal at pH7. It is concluded that in dogs with pancreatic fistulas, a meal exogenously or endogenously (postprandial) acidified is capable of the release of secretin in immunoassayable amounts. The normal pancreatic bicarbonate response to food may depend partially upon potentiation of the secretin effect by other neurohumoral stimuli. | Pancreatic bicarbonate, serum gastrin, and secretin responses to meals varying in pH. The role of secretin in the postprandial bicarbonate response by the pancreas is not clear. This study reports secretin and bicarbonate secretion after exogenous and endogenous acidification of meal. In dogs with gastric and pancreatic fistulas, a liver extract meal at various pH levels was introduced into the stomach and kept at the preselected pH by intragastric titration. Gastric acid, pancreatic bicarbonate, serum gastrin, and plasma secretin were measured. The meal at pH 7 produced an increase of gastrin levels of 230% above basal and a gastric acid output from a basal of 0.8-16.9 meq/30 min. Acidification of the meal evoked a pH-dependent reduction of gastrin and gastric acid secretion, a pH-dependent elevation of pancreatic bicarbonate, and significant elevation of secretin at pH 3 (43% above basal) and at pH 2 (80% above basal). Postprandial endogenous acidification of a meal, without intragastric titration, also provoked significant release of secretin. Maximal pancreatic bicarbonate secretion in response to exogenous secretin was augmented 30% by the addition of a liver extract meal at pH7. It is concluded that in dogs with pancreatic fistulas, a meal exogenously or endogenously (postprandial) acidified is capable of the release of secretin in immunoassayable amounts. The normal pancreatic bicarbonate response to food may depend partially upon potentiation of the secretin effect by other neurohumoral stimuli. | [
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|
PMID:18022 | Influence of aldosterone on renal ammonia production. | Administering D-aldosterone, 7 microgram 100 g-1, to rats results in a marked rise in ammonium excretion and metabolic alkalosis. Increased ammonium excretion is not related to either a significant elevation in potassium excretion nor to hypokalemia. Consequently, potassium depletion does not appear to be the causative factor in the aldosterone-stimulated ammonium excretion. Isolated kidneys from aldosterone-treated rats, perfused with 1 mM L-glutamine, produced twice as much ammonia from glutamine as did controls. Ammonia production per glutamine extracted increased from 1.33 +/- 0.07 in control to 1.79 +/- 0.08 in kidneys from hormone-treated rats, suggesting stimulation of the mitochondrial glutaminase I-glutamate dehydrogenase pathway; this was supported by a proportional rise in production of glucose and CO2, end products of glutamine's carbon skeleton. Consequently, aldosterone-stimulated renal ammonia production, by specifically activating the mitochondrial pathway, leads to the elimination of hydrogen ions in the form of urinary ammonium excretion and an ensuing metabolic alkalosis. | Influence of aldosterone on renal ammonia production. Administering D-aldosterone, 7 microgram 100 g-1, to rats results in a marked rise in ammonium excretion and metabolic alkalosis. Increased ammonium excretion is not related to either a significant elevation in potassium excretion nor to hypokalemia. Consequently, potassium depletion does not appear to be the causative factor in the aldosterone-stimulated ammonium excretion. Isolated kidneys from aldosterone-treated rats, perfused with 1 mM L-glutamine, produced twice as much ammonia from glutamine as did controls. Ammonia production per glutamine extracted increased from 1.33 +/- 0.07 in control to 1.79 +/- 0.08 in kidneys from hormone-treated rats, suggesting stimulation of the mitochondrial glutaminase I-glutamate dehydrogenase pathway; this was supported by a proportional rise in production of glucose and CO2, end products of glutamine's carbon skeleton. Consequently, aldosterone-stimulated renal ammonia production, by specifically activating the mitochondrial pathway, leads to the elimination of hydrogen ions in the form of urinary ammonium excretion and an ensuing metabolic alkalosis. | [
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|
PMID:18023 | Solute permeability of the alveolar epithelium in acute hemodynamic pulmonary edema in dogs. | Ten anesthetized dogs, 48 h postintravenous 131I-albumin injection, had a segment of lung airspace isolated by a balloon-tipped catheter lodged in a bronchus. An isotonic saline solution containing trace amounts of Blue Dextran, 125I-albumin, and 57Co-cyanocobalamin was instilled into the lung segment. During control periods, lung saline was absorbed at a rate of 0.133% per minute as measured by indicator dilution of Blue Dextran. Only 57Co-cyanocobalamin crossed the epithelium. Acute hemodynamic pulmonary edema was produced by aortic constriction plus saline overload. In pulmonary edema the fluid volume in the airspace increased at the rate of 0.96% per minute, and there was a significant influx of 131I-albumin into the lung saline from the blood in all animals. However, neither 125I-albumin nor Blue Dextran diffused from the airspace into blood during edema; both were merely diluted by fluid influx. The rate of diffusion of 57Co-cyanocobalamin increased fivefold during edema. A small number of discrete breaks in the lung epithelium allowing bulk flow of interstitial fluid is proposed to account for the one-way movement of albumin in hemodynamic alveolar edema. | Solute permeability of the alveolar epithelium in acute hemodynamic pulmonary edema in dogs. Ten anesthetized dogs, 48 h postintravenous 131I-albumin injection, had a segment of lung airspace isolated by a balloon-tipped catheter lodged in a bronchus. An isotonic saline solution containing trace amounts of Blue Dextran, 125I-albumin, and 57Co-cyanocobalamin was instilled into the lung segment. During control periods, lung saline was absorbed at a rate of 0.133% per minute as measured by indicator dilution of Blue Dextran. Only 57Co-cyanocobalamin crossed the epithelium. Acute hemodynamic pulmonary edema was produced by aortic constriction plus saline overload. In pulmonary edema the fluid volume in the airspace increased at the rate of 0.96% per minute, and there was a significant influx of 131I-albumin into the lung saline from the blood in all animals. However, neither 125I-albumin nor Blue Dextran diffused from the airspace into blood during edema; both were merely diluted by fluid influx. The rate of diffusion of 57Co-cyanocobalamin increased fivefold during edema. A small number of discrete breaks in the lung epithelium allowing bulk flow of interstitial fluid is proposed to account for the one-way movement of albumin in hemodynamic alveolar edema. | [
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|
PMID:18024 | Prostaglandin metabolism in the kidneys of spontaneously hypertensive rats. | Renal prostaglandins have been implicated in the regulation of blood pressure. We have therefore compared prostaglandin metabolism in the kidneys of spontaneously hypertensive rats (SHR's) of the Aoki-Okamoto strain and normotensive Wistar-Kyoto (WKY) controls. The microsomal fraction of the renal medulla contained most of the prostaglandin synthetase activity in both groups; SHR's had significantly higher enzymatic activity than their normotensive controls at age 10 wk and thereafter; furthermore, synthetase activity in SHR's increased with age. Two forms of 15-hydroxyprostaglandin dehydrogenases were demonstrated: an NAD+-dependent form which was localized mainly in the cortex and an NADP+-dependent form, higher in the medulla. The activities of these enzymes were lower in the hypertensive animals at all ages studied; this depression was more pronounced for the NAD+-dependent dehydrogenase. The results indicate that, in hypertension, renal prostaglandin metabolism is altered so that enhanced synthesis is accompanied by decreased degradation rate. | Prostaglandin metabolism in the kidneys of spontaneously hypertensive rats. Renal prostaglandins have been implicated in the regulation of blood pressure. We have therefore compared prostaglandin metabolism in the kidneys of spontaneously hypertensive rats (SHR's) of the Aoki-Okamoto strain and normotensive Wistar-Kyoto (WKY) controls. The microsomal fraction of the renal medulla contained most of the prostaglandin synthetase activity in both groups; SHR's had significantly higher enzymatic activity than their normotensive controls at age 10 wk and thereafter; furthermore, synthetase activity in SHR's increased with age. Two forms of 15-hydroxyprostaglandin dehydrogenases were demonstrated: an NAD+-dependent form which was localized mainly in the cortex and an NADP+-dependent form, higher in the medulla. The activities of these enzymes were lower in the hypertensive animals at all ages studied; this depression was more pronounced for the NAD+-dependent dehydrogenase. The results indicate that, in hypertension, renal prostaglandin metabolism is altered so that enhanced synthesis is accompanied by decreased degradation rate. | [
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|
PMID:18025 | Properties of the laryngeal chemoreflex in neonatal piglets. | Cardiorespiratory reflex responses to laryngeal chemoreceptor stimulation were studied in 62 piglets of both sexes varying in age from 1 to 79 days. The distal trachea was cannulated to provide a free airway and the proximal end used to introduce fluids into the laryngeal area. Introduction of either water or milk produced apnea, bradycardia, and hypertension. Swab application of test fluids to the laryngeal epithelium produced similar responses. The reflex could be interrupted by flushing the laryngeal region with saline, by cutting the superior laryngeal nerves (SLN) or by anesthetizing the laryngeal epithelium with lidocaine. Electrical stimulation of SLN elicited identical responses. Respiratory inhibition by the reflex was enhanced following central depression with chloralose and overridden by administration of the respiratory stimulant, aminophylline. The relative potency of the laryngeal reflex was estimated to be equivalent to about 40% of the dose of chloralose which produced permanent respiratory arrest. It is concluded that in circumstances where respiratory drive is reduced the laryngeal inhibitory reflex is capable of caused persistent apnea and asphyxial death in the young piglet. | Properties of the laryngeal chemoreflex in neonatal piglets. Cardiorespiratory reflex responses to laryngeal chemoreceptor stimulation were studied in 62 piglets of both sexes varying in age from 1 to 79 days. The distal trachea was cannulated to provide a free airway and the proximal end used to introduce fluids into the laryngeal area. Introduction of either water or milk produced apnea, bradycardia, and hypertension. Swab application of test fluids to the laryngeal epithelium produced similar responses. The reflex could be interrupted by flushing the laryngeal region with saline, by cutting the superior laryngeal nerves (SLN) or by anesthetizing the laryngeal epithelium with lidocaine. Electrical stimulation of SLN elicited identical responses. Respiratory inhibition by the reflex was enhanced following central depression with chloralose and overridden by administration of the respiratory stimulant, aminophylline. The relative potency of the laryngeal reflex was estimated to be equivalent to about 40% of the dose of chloralose which produced permanent respiratory arrest. It is concluded that in circumstances where respiratory drive is reduced the laryngeal inhibitory reflex is capable of caused persistent apnea and asphyxial death in the young piglet. | [
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|
PMID:18027 | [The aging alimentary tract (author's transl)]. | The physiological process of aging causes changes in volumen and composition of saliva, gastric and pancreatic juice and bile flow, a diminished absorption and an altered bacterial flora. However, these changes are compensated and do not cause symptoms. Besides of an increased disposition to develop carcinoma of the gut the alimentary tract in contrast to the cardiovascular system has no specific symptomatology as signs of wear. In old age, too, functional disorders rank first in clinical symptomatology. | [The aging alimentary tract (author's transl)]. The physiological process of aging causes changes in volumen and composition of saliva, gastric and pancreatic juice and bile flow, a diminished absorption and an altered bacterial flora. However, these changes are compensated and do not cause symptoms. Besides of an increased disposition to develop carcinoma of the gut the alimentary tract in contrast to the cardiovascular system has no specific symptomatology as signs of wear. In old age, too, functional disorders rank first in clinical symptomatology. | [
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|
PMID:18028 | [Differentiation of the aging intestinal epithelium by morphology, histochemistry and discelectrophoresis (author's transl)]. | The intestinal epithelium of the small and large intestine of fetal rats (19th, 20th and 21st day of pregnancy) newborn and juvenile rats (1st to 50th day of life) adult rats (3rd to 4th month) and senile rats (18th to 30th month) was investigated by means of morphology, enzyme histochemistry and discelectrophoresis. The results obtained permit division of the development and aging of the rat intestinal epithelium into five periods: 1. The period of prenatal development. 2. The period of postnatal development. 3. The period of adaptation. 4. The stage of adult maturity. 5. The senile atrophy of the intestinal mucosa. | [Differentiation of the aging intestinal epithelium by morphology, histochemistry and discelectrophoresis (author's transl)]. The intestinal epithelium of the small and large intestine of fetal rats (19th, 20th and 21st day of pregnancy) newborn and juvenile rats (1st to 50th day of life) adult rats (3rd to 4th month) and senile rats (18th to 30th month) was investigated by means of morphology, enzyme histochemistry and discelectrophoresis. The results obtained permit division of the development and aging of the rat intestinal epithelium into five periods: 1. The period of prenatal development. 2. The period of postnatal development. 3. The period of adaptation. 4. The stage of adult maturity. 5. The senile atrophy of the intestinal mucosa. | [
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|
PMID:18029 | [Gastroscopic findings in aged patients (author's transl)]. | Endoscopic findings in a group of 169 aged patients are shown to be concentrated in the stomach, whereas pathologic findings in the duodenal bulb are less frequent. In comparison to a group of young patients gastric mucosal atrophy, gastric ulcer, carcinoma of the operated and unoperated stomach, polyps are predominant in the aged patients. Approximately one half of carcinomas were seen in patients operated by the Billroth II technique. On behalf of this fact it is necessary to review patients endoscopically from the fifteenth year after operation on with regularity in order to detect growth of carcinoma in the early stage. | [Gastroscopic findings in aged patients (author's transl)]. Endoscopic findings in a group of 169 aged patients are shown to be concentrated in the stomach, whereas pathologic findings in the duodenal bulb are less frequent. In comparison to a group of young patients gastric mucosal atrophy, gastric ulcer, carcinoma of the operated and unoperated stomach, polyps are predominant in the aged patients. Approximately one half of carcinomas were seen in patients operated by the Billroth II technique. On behalf of this fact it is necessary to review patients endoscopically from the fifteenth year after operation on with regularity in order to detect growth of carcinoma in the early stage. | [
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PMID:18030 | [Gastroduodenal ulcers in patients of a geriatric hospital (author's transl)]. | Among 3646 patients of a geriatric hospital we we found 7,82% = 285 patients who suffered once in their life from a gastroduodenal ulcer. We noted: 1. gastroduodenal scars in 3,3% = 121 cases, 2. anamnestic proved gastroduodenal ulcer disease in 1,5% = 57 cases, 3. clinical and/or pathological proved gastroduodenal ulcers in 3% = 107 cases. Additional findings were put down as there are aortal arteriosclerosis, pulmonary heart and complications like perforation, penetration, bleeding and death. | [Gastroduodenal ulcers in patients of a geriatric hospital (author's transl)]. Among 3646 patients of a geriatric hospital we we found 7,82% = 285 patients who suffered once in their life from a gastroduodenal ulcer. We noted: 1. gastroduodenal scars in 3,3% = 121 cases, 2. anamnestic proved gastroduodenal ulcer disease in 1,5% = 57 cases, 3. clinical and/or pathological proved gastroduodenal ulcers in 3% = 107 cases. Additional findings were put down as there are aortal arteriosclerosis, pulmonary heart and complications like perforation, penetration, bleeding and death. | [
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|
PMID:18031 | [Ischemic bowel disease (author's transl)]. | Geriatric patients are preferentially involved in ischemic bowel disease. The sudden occlusion of the large mesenteric arteries (a. mesenterica superior (more frequently) and inferior) is followed by intestinal gangrene and peritonitis with a poor prognosis and a high letality (greater than 90%). In chronic intestinal ischemia the leading clinical symptom is postprandial pain ('claudicatio intestinalis'). In some cases of acute mesenteric artery occlusion no embolus or thrombus will be found. In these cases the circulation in the arteriosclerotic vessels falls below a critical value due to cardiac insufficiency, shock, digitalis overdose and others. In less severe ischemia the mucosa is involved being most sensitive to O2 deprivation. It usually regenerates within a few days. This form is found more frequently in the colon than in other parts of the gut (about 40%): ischemic colitis. The therapy - if possible in acute, fulminant ischemia or if necessary in chronic intestinal ischemia - is surgical consisting in reconstructive procedures of the mesenteric circulation. | [Ischemic bowel disease (author's transl)]. Geriatric patients are preferentially involved in ischemic bowel disease. The sudden occlusion of the large mesenteric arteries (a. mesenterica superior (more frequently) and inferior) is followed by intestinal gangrene and peritonitis with a poor prognosis and a high letality (greater than 90%). In chronic intestinal ischemia the leading clinical symptom is postprandial pain ('claudicatio intestinalis'). In some cases of acute mesenteric artery occlusion no embolus or thrombus will be found. In these cases the circulation in the arteriosclerotic vessels falls below a critical value due to cardiac insufficiency, shock, digitalis overdose and others. In less severe ischemia the mucosa is involved being most sensitive to O2 deprivation. It usually regenerates within a few days. This form is found more frequently in the colon than in other parts of the gut (about 40%): ischemic colitis. The therapy - if possible in acute, fulminant ischemia or if necessary in chronic intestinal ischemia - is surgical consisting in reconstructive procedures of the mesenteric circulation. | [
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|
PMID:18032 | [Dependence of diverticulosis on age (author's transl)]. | The diverticulosis of the gastrointestinal tract is a widespread senile disease. The dependence of the diverticulosis on age is investigated on the basis of 1 000 proven cases of this disease. The importance of the anatomicomorphological lesions of the organs at old age as its cause is pointed out. The males seem to be affected by the diverticulosis somewhat more than the females, whereas its percental manifestation in the different organs is about equal for both sexes. It prevails in the colon with 48.4% and in the duodenum with 35.4% of all cases of organ diverticulosis. The existence of constitutional associations with other diseases, such as diabetes mellitus, is discussed. Finally, the therapeutic problems of the diverticulitis and their dependence on age are examined. | [Dependence of diverticulosis on age (author's transl)]. The diverticulosis of the gastrointestinal tract is a widespread senile disease. The dependence of the diverticulosis on age is investigated on the basis of 1 000 proven cases of this disease. The importance of the anatomicomorphological lesions of the organs at old age as its cause is pointed out. The males seem to be affected by the diverticulosis somewhat more than the females, whereas its percental manifestation in the different organs is about equal for both sexes. It prevails in the colon with 48.4% and in the duodenum with 35.4% of all cases of organ diverticulosis. The existence of constitutional associations with other diseases, such as diabetes mellitus, is discussed. Finally, the therapeutic problems of the diverticulitis and their dependence on age are examined. | [
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PMID:18033 | [Functional digestive troubles in old age (author's transl)]. | Functional disorders are frequent in elderly patients. However the high incidence of organic lesions in advanced age demands a most careful examination. Each diagnosis of functional disorders made by exclusion of organic lesions has to be revised, if symptoms persist or symptomatic treatment remains inefficient. Gastroenterological diagnostic should not be restricted to an endoscopic or radiologic glance to the gastrointestinal tract. It includes the less spectacular but more human trial to get an insight to the soul of the patient. This may be more helpful than any treatment with the newest double blind tested medication. | [Functional digestive troubles in old age (author's transl)]. Functional disorders are frequent in elderly patients. However the high incidence of organic lesions in advanced age demands a most careful examination. Each diagnosis of functional disorders made by exclusion of organic lesions has to be revised, if symptoms persist or symptomatic treatment remains inefficient. Gastroenterological diagnostic should not be restricted to an endoscopic or radiologic glance to the gastrointestinal tract. It includes the less spectacular but more human trial to get an insight to the soul of the patient. This may be more helpful than any treatment with the newest double blind tested medication. | [
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|
PMID:18035 | Age-dependent alterations of the rate of RNA synthesis in rat brain cell nuclei. | Endogenous Mn2+ and Mg2+ activated RNA polymerase activity was measured in isolated cell nuclei of brain from rats of different age-groups. It was established that the activity of the nucleoplasmic RNA polymerase is maintained at the level of young animals up to an age of 16 months but is decreased after 24 months. The nucleolar RNA polymerase activity decreases already at 16 months and a higher ratio of the Mn2+:Mg2+ activated RNA polymerase activities has been found to be characteristic for the older animals. By means of stepwise sucrose density gradient centrifugation fractions were obtained from the nuclear preparations highly enriched in cell nuclei of neuronal and glial origin respectively. By measuring the activity of the nucleoplasmic and nucleolar RNA polymerases in these fractions it was found that the elevated ratio of the nucleoplasmic to nucleolar RNA polymerase activity at 16 months of age is a characteristic of the neuronal nuclei while the glial nuclei behave by the opposite manner. A parallelism existing between the age-dependent change of the endogenous RNA polymerase activity and that of perichromatic granules of rat brain cortical cells is discussed. | Age-dependent alterations of the rate of RNA synthesis in rat brain cell nuclei. Endogenous Mn2+ and Mg2+ activated RNA polymerase activity was measured in isolated cell nuclei of brain from rats of different age-groups. It was established that the activity of the nucleoplasmic RNA polymerase is maintained at the level of young animals up to an age of 16 months but is decreased after 24 months. The nucleolar RNA polymerase activity decreases already at 16 months and a higher ratio of the Mn2+:Mg2+ activated RNA polymerase activities has been found to be characteristic for the older animals. By means of stepwise sucrose density gradient centrifugation fractions were obtained from the nuclear preparations highly enriched in cell nuclei of neuronal and glial origin respectively. By measuring the activity of the nucleoplasmic and nucleolar RNA polymerases in these fractions it was found that the elevated ratio of the nucleoplasmic to nucleolar RNA polymerase activity at 16 months of age is a characteristic of the neuronal nuclei while the glial nuclei behave by the opposite manner. A parallelism existing between the age-dependent change of the endogenous RNA polymerase activity and that of perichromatic granules of rat brain cortical cells is discussed. | [
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|
PMID:18034 | [Nutritional problems in old age (author's transl)]. | While age is increasing involutiones specific to age can be proofed at the gastrointestinal tract, which lead to a deceleration but quantitative unchanged adsorption. Wrong nutrition concerning to the take up of fat, carbohydrates, proteins and trace elements can be found in greater age very often. By watching a collective of healthy persons beyond the age of 90 years however it turns out that this group keeps a nearly faultless nutrition. The requirements of lysin, methionin and calcium is a little higher in old age than in younger. By intermitting starvation or addition of antioxidants life can be prolonged in experiments on animals, when this therapy starts already in younger age. Starvation in higher age, however, leads to a shortening of life in experiments on animals. | [Nutritional problems in old age (author's transl)]. While age is increasing involutiones specific to age can be proofed at the gastrointestinal tract, which lead to a deceleration but quantitative unchanged adsorption. Wrong nutrition concerning to the take up of fat, carbohydrates, proteins and trace elements can be found in greater age very often. By watching a collective of healthy persons beyond the age of 90 years however it turns out that this group keeps a nearly faultless nutrition. The requirements of lysin, methionin and calcium is a little higher in old age than in younger. By intermitting starvation or addition of antioxidants life can be prolonged in experiments on animals, when this therapy starts already in younger age. Starvation in higher age, however, leads to a shortening of life in experiments on animals. | [
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PMID:18036 | [In vitro-phosphorylation of histones in chromatin of various tissues in relation to age (author's transl)]. | The influence of age on the structure of chromatin of various mammalian cells with modest or terminated mitotic activity has been examined. For this purpose chromatin from dog skeletal muscle, and human neuronal and glial cells, has been incubated together with an exogenous histone phosphokinase and ATP-gamma32P, and the phosphate incorporated into the histones determined. For comparison, also free histone has been phosphorylated. The amount of phosphate incorporated into total histone is 16-18 nmol Pi per mg histone in the case of free histone, and about equal for all cell types and ages. Into chromatin-bound histones only 5.5-8.2 nmol Pi per mg histone are incorporated. The differences between the various cell types and age groups are not significant. The relative phosphate incorporation into the single histone fractions depends on the histone as being free or chromatin-bound. In addition, relative phosphate incorporation into the single fractions of chromatin-bound histones is also cell type- and age-specific. The results permit the conclusion that the chromatin is subject to structural changes in the course of aging. | [In vitro-phosphorylation of histones in chromatin of various tissues in relation to age (author's transl)]. The influence of age on the structure of chromatin of various mammalian cells with modest or terminated mitotic activity has been examined. For this purpose chromatin from dog skeletal muscle, and human neuronal and glial cells, has been incubated together with an exogenous histone phosphokinase and ATP-gamma32P, and the phosphate incorporated into the histones determined. For comparison, also free histone has been phosphorylated. The amount of phosphate incorporated into total histone is 16-18 nmol Pi per mg histone in the case of free histone, and about equal for all cell types and ages. Into chromatin-bound histones only 5.5-8.2 nmol Pi per mg histone are incorporated. The differences between the various cell types and age groups are not significant. The relative phosphate incorporation into the single histone fractions depends on the histone as being free or chromatin-bound. In addition, relative phosphate incorporation into the single fractions of chromatin-bound histones is also cell type- and age-specific. The results permit the conclusion that the chromatin is subject to structural changes in the course of aging. | [
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|
PMID:18037 | [RNA metabolism and ageing (author's transl)]. | The labelling behaviour of RNA fractions in rat liver after application of 32P-orthophosphate and 14C-orotate in vivo in young (3-5 months) and old animals (20 months) was presented. Whereas the tracer incorporation in old animals 60 minutes after 32P-application seems to be decreased we observed increased specific activities of nuclear RNA 30 and 60 minutes after application of 14C-orotate i.p. - Measuring of RNA synthesis in isolated cell nuclei after in vivo stimulation by cortisol (2 mg/100 g body weight) showed a stronger and longer continued stimulation in young animals as in old both in the Mn++ system and in the Mg++ system. When we compared the young with the old controls the rate of synthesis was increased in the old controls. The results support observations on changed regulations of the transcription of genetic informations in the age. | [RNA metabolism and ageing (author's transl)]. The labelling behaviour of RNA fractions in rat liver after application of 32P-orthophosphate and 14C-orotate in vivo in young (3-5 months) and old animals (20 months) was presented. Whereas the tracer incorporation in old animals 60 minutes after 32P-application seems to be decreased we observed increased specific activities of nuclear RNA 30 and 60 minutes after application of 14C-orotate i.p. - Measuring of RNA synthesis in isolated cell nuclei after in vivo stimulation by cortisol (2 mg/100 g body weight) showed a stronger and longer continued stimulation in young animals as in old both in the Mn++ system and in the Mg++ system. When we compared the young with the old controls the rate of synthesis was increased in the old controls. The results support observations on changed regulations of the transcription of genetic informations in the age. | [
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|
PMID:18038 | [The vascularisation of the granulation tissue in different ages. - Its importance for wound healing (author's transl)]. | The part of capillaries of a plastic sponge granuloma was determined in rats of different ages. It was found that granulation tissue of older rats contains significantly fewer capillaries than that of young animals. The diminished vascularisation of granulation tissue may be responsible for the deterioration of wound healing in aged individuals. | [The vascularisation of the granulation tissue in different ages. - Its importance for wound healing (author's transl)]. The part of capillaries of a plastic sponge granuloma was determined in rats of different ages. It was found that granulation tissue of older rats contains significantly fewer capillaries than that of young animals. The diminished vascularisation of granulation tissue may be responsible for the deterioration of wound healing in aged individuals. | [
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|
PMID:18039 | [Histone phosphorylation of human lymphocytes after PHA stimulation in relation to age (author's transl)]. | Lymphocytes of young and old donors are stimulated by phytohemagglutinin (PHA). The 32P-incorporation into the histones which occurs in the early phase after PHA-stimulation is determined. In lymphocytes of old persons the 32P-incorporation in the histones is diminished by about 50% with respect to the cells of young donors. Furthermore, it could be shown that in the histones prepared from old cells the amount of H1 is much increased. It is postulated that, in old age, the other 4 histones are poorly extractable. | [Histone phosphorylation of human lymphocytes after PHA stimulation in relation to age (author's transl)]. Lymphocytes of young and old donors are stimulated by phytohemagglutinin (PHA). The 32P-incorporation into the histones which occurs in the early phase after PHA-stimulation is determined. In lymphocytes of old persons the 32P-incorporation in the histones is diminished by about 50% with respect to the cells of young donors. Furthermore, it could be shown that in the histones prepared from old cells the amount of H1 is much increased. It is postulated that, in old age, the other 4 histones are poorly extractable. | [
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|
PMID:18040 | [Hydroxylation of skin collagen in relation to age: analyses of the human skin]. | The results of human skin analysis are demonstrated. It has been pointed out, that the content of hydroxyproline and hydroxylysine, in addition to the usual variation as the other aminoacids varies extensively. The extent of hydroxylation was estimated from the relation of OH-aminoacids to (not hydroxylated) each other. The determined variation of the results is most probably due to a different collagen hydroxylation within the biological dispersion. An age-related degree of hydroxylation could not be detected. | [Hydroxylation of skin collagen in relation to age: analyses of the human skin]. The results of human skin analysis are demonstrated. It has been pointed out, that the content of hydroxyproline and hydroxylysine, in addition to the usual variation as the other aminoacids varies extensively. The extent of hydroxylation was estimated from the relation of OH-aminoacids to (not hydroxylated) each other. The determined variation of the results is most probably due to a different collagen hydroxylation within the biological dispersion. An age-related degree of hydroxylation could not be detected. | [
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|
PMID:18041 | [Investigations about the effect of run-training and run-stress on glucose tolerance and insulin secretion with ageing streptozotocin-diabetic rats (author's transl)]. | Untrained grown-up and old rats with a mild Streptozotocin-diabetes show in i.v. glucose tolerance test a pathological glucose assimilation and diminished insulin secretion in comparison to control rats of the same age after a maximal run-stress. Trained rats show a different behaviour in glucose tolerance test depending on their age and seriousness of diabetes: Glucose tolerance is improved in grown-up rats with a mild diabetes and unchanged in old rats. Six-week run-training causes a significant deterioration of glucose tolerance in rats with a medium seriously Streptozotocin-diabetes and even leads to death of old rats because of decompensated metabolism. Grown-up rats with a mild diabetes stand run-stress after run-training better than the old ones. No animal with a medium seriously diabetes survives maximal run-stress, old rats don't even survive the slowly increasing run-training. - These results confirm the dualistic effect of muscular work. Metabolism of mild diabetes becomes better through muscular exertion the one of medium diabetes gets worse. Therefore a good effect of run-training is measurable only in grown-up rats not in old ones. | [Investigations about the effect of run-training and run-stress on glucose tolerance and insulin secretion with ageing streptozotocin-diabetic rats (author's transl)]. Untrained grown-up and old rats with a mild Streptozotocin-diabetes show in i.v. glucose tolerance test a pathological glucose assimilation and diminished insulin secretion in comparison to control rats of the same age after a maximal run-stress. Trained rats show a different behaviour in glucose tolerance test depending on their age and seriousness of diabetes: Glucose tolerance is improved in grown-up rats with a mild diabetes and unchanged in old rats. Six-week run-training causes a significant deterioration of glucose tolerance in rats with a medium seriously Streptozotocin-diabetes and even leads to death of old rats because of decompensated metabolism. Grown-up rats with a mild diabetes stand run-stress after run-training better than the old ones. No animal with a medium seriously diabetes survives maximal run-stress, old rats don't even survive the slowly increasing run-training. - These results confirm the dualistic effect of muscular work. Metabolism of mild diabetes becomes better through muscular exertion the one of medium diabetes gets worse. Therefore a good effect of run-training is measurable only in grown-up rats not in old ones. | [
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|
PMID:18042 | [Determination of neurophysiological parameters of the aging CNS. I. Evoked potentials (author's transl)]. | Somatosensory (SEP) and visual (VEP) evoked potentials were studied in 65 healthy subjects who ranged in age from 62-91 years and in 48 normal persons aged 18-38 years. The amplitudes and latencies of the different components of the evoked potentials were measured. The transmission of evoked potentials from the specific response area into different regions of the ipsi- and contralateral hemisphere were studied. The findings can be summarized as follows: The latencies of the SEP and VEP of aged subjects are significantly prolonged. The increase in latency is relatively slight for the first components, progressively higher for the following components. The amplitudes of the different components of the SEP and VEP are significantly increased in aged subjects. The modifications of the SEP-latencies and of the VEP-amplitudes are more important over the dominant hemisphere. In young subjects the SE are confirmed to the centro-parietal region. In aged persons the SEP spreads over the whole hemisphere. The hypothesis that the aging process involves the synaptic transmitter mechanisms at the cortical level is discussed in relation to the involvement of the latencies. The increase in amplitude of the evoked potentials could be explained by assuming that the inhibition - an essential property of the cortex - decreases during the aging process. | [Determination of neurophysiological parameters of the aging CNS. I. Evoked potentials (author's transl)]. Somatosensory (SEP) and visual (VEP) evoked potentials were studied in 65 healthy subjects who ranged in age from 62-91 years and in 48 normal persons aged 18-38 years. The amplitudes and latencies of the different components of the evoked potentials were measured. The transmission of evoked potentials from the specific response area into different regions of the ipsi- and contralateral hemisphere were studied. The findings can be summarized as follows: The latencies of the SEP and VEP of aged subjects are significantly prolonged. The increase in latency is relatively slight for the first components, progressively higher for the following components. The amplitudes of the different components of the SEP and VEP are significantly increased in aged subjects. The modifications of the SEP-latencies and of the VEP-amplitudes are more important over the dominant hemisphere. In young subjects the SE are confirmed to the centro-parietal region. In aged persons the SEP spreads over the whole hemisphere. The hypothesis that the aging process involves the synaptic transmitter mechanisms at the cortical level is discussed in relation to the involvement of the latencies. The increase in amplitude of the evoked potentials could be explained by assuming that the inhibition - an essential property of the cortex - decreases during the aging process. | [
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|
PMID:18065 | [Lens changes occuring as a result of lowered pH (acidosis) (author's transl)]. | In the lens, disorders of the metabolism occur, and, with them, active permeability (the cation pump with uptake of K and release of Na) changes to passive permeability and consequently Na ions enter with water. As a result, the lens increases in weight and a subcapsular (permeability) cataract develops. It is shown that the cattle lens in vitro increases in weight the lower the pH (6.5 greater than 7.5 greater than 8.5) of the surrounding fluid becomes. In a further experiment, 1 ml of buffered liquids with different pH were injected into the anterior chamber of the eyes of freshly slaughtered cattle. Here, too, the mechanically undamaged, untouched lens increased in weight more greatly as the pH (5.5 greater than 6.5 greater than 7.5 greater than 8.5) of the injected fluid was lowered. The significance of the lowering of the pH, e.g., in local inflammation (iritis, cyclitis, retinitis, etc.) or general acidoses (diabetes mellitus, galactosemia, hunger, extracorporeal circulation for atrophic kidney. Albright-, Love-, Fanconi-syndrome) for the appearance of incipient subcapsular clouding of the lens is pointed out. | [Lens changes occuring as a result of lowered pH (acidosis) (author's transl)]. In the lens, disorders of the metabolism occur, and, with them, active permeability (the cation pump with uptake of K and release of Na) changes to passive permeability and consequently Na ions enter with water. As a result, the lens increases in weight and a subcapsular (permeability) cataract develops. It is shown that the cattle lens in vitro increases in weight the lower the pH (6.5 greater than 7.5 greater than 8.5) of the surrounding fluid becomes. In a further experiment, 1 ml of buffered liquids with different pH were injected into the anterior chamber of the eyes of freshly slaughtered cattle. Here, too, the mechanically undamaged, untouched lens increased in weight more greatly as the pH (5.5 greater than 6.5 greater than 7.5 greater than 8.5) of the injected fluid was lowered. The significance of the lowering of the pH, e.g., in local inflammation (iritis, cyclitis, retinitis, etc.) or general acidoses (diabetes mellitus, galactosemia, hunger, extracorporeal circulation for atrophic kidney. Albright-, Love-, Fanconi-syndrome) for the appearance of incipient subcapsular clouding of the lens is pointed out. | [
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|
PMID:18069 | [The present state of hypotension (author's transl)]. | The study was made of the recent literature on controlled hypotension and its place in modern anaesthetic practice. The effects of the different techniques and drugs are outlined in this paper. The results of investigation revealed that the circulation of heart, brain, liver, and kidneys is able to tolerate a wide range of deviation of blood pressure. Hypotension induced by high doses of halothane alone, which used to be considered as an adequate measure, has recently been shown to cause such serious side-effects that it can no longer be recommended. Halothane lowers blood pressure almost exclusively by means of a reduction of the contractility of the heart muscle. Ganglionic blocking agents alone should not be used either because of their depressing effect on the heart; moreover their hypotensive effects are hard to control. The sole exception is trimetaphan but it produces other severe side-effects such as liberation of histamine. On the other hand ganglionic blocking agents combined with halothane can be recommended. The combined administration of these drugs allow an easy control of hypotension and the side effects are minimal. Only sodium-nitroprusside meets all the requirements of a hypotensive drug. It operates selectively in a peripheral vasoplegic manner without effecting the cerebral centres. Regarding the heart, no side-effect is known apart from tachycardia; cardiac output is not altered. The metabolism of sodium-nitroprusside requires precaution in dosage, as degradation takes place via the toxic compounds of cyanide. Therefore liver disease and disturbances in vitamin B12 utilisation are regarded as contraindications for the use of nitroprusside. That is also the reason why a maximum allowable dose of 10-15 gamma/kg body weight and minute should not be exceeded. Prophylactic administration of vitamin B 12a (hydroxocobalamin) should be considered in every case when nitroprusside is used. | [The present state of hypotension (author's transl)]. The study was made of the recent literature on controlled hypotension and its place in modern anaesthetic practice. The effects of the different techniques and drugs are outlined in this paper. The results of investigation revealed that the circulation of heart, brain, liver, and kidneys is able to tolerate a wide range of deviation of blood pressure. Hypotension induced by high doses of halothane alone, which used to be considered as an adequate measure, has recently been shown to cause such serious side-effects that it can no longer be recommended. Halothane lowers blood pressure almost exclusively by means of a reduction of the contractility of the heart muscle. Ganglionic blocking agents alone should not be used either because of their depressing effect on the heart; moreover their hypotensive effects are hard to control. The sole exception is trimetaphan but it produces other severe side-effects such as liberation of histamine. On the other hand ganglionic blocking agents combined with halothane can be recommended. The combined administration of these drugs allow an easy control of hypotension and the side effects are minimal. Only sodium-nitroprusside meets all the requirements of a hypotensive drug. It operates selectively in a peripheral vasoplegic manner without effecting the cerebral centres. Regarding the heart, no side-effect is known apart from tachycardia; cardiac output is not altered. The metabolism of sodium-nitroprusside requires precaution in dosage, as degradation takes place via the toxic compounds of cyanide. Therefore liver disease and disturbances in vitamin B12 utilisation are regarded as contraindications for the use of nitroprusside. That is also the reason why a maximum allowable dose of 10-15 gamma/kg body weight and minute should not be exceeded. Prophylactic administration of vitamin B 12a (hydroxocobalamin) should be considered in every case when nitroprusside is used. | [
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|
PMID:18070 | [Cardiovascular effects of flunitrazepam (rohypnol, RO-5-4200) (author's transl)]. | We reported on the haemodynamic effects of 0.03 mg/kg flunitrazepam during surgical procedures in neuroleptanalgesia in 39 patients with congenital or acquired heart diseases, functional class II-IV. The benzodiazepine derivative did not cause any relevant effect on the inotropic state of the myocardium. There were only minor changes in cardiac index, stroke index, right and left atrial pressure. Changes in arterial pressure and left ventricular pressure during and immediately after surgical procedures, and in arterial perfusion pressure during extracorporeal circulation, as well as an only short lasting increase in heart rate were demonstrative a peripheral vasodilator effect. The decrease in ventricular work and myocardial oxygen consumption are of value in patients with coronary heart disease, especially immediately after surgical procedures. Flunitrazepam is considered an additional drug during neuroleptanalgesia, when hypertension is causing some problems. | [Cardiovascular effects of flunitrazepam (rohypnol, RO-5-4200) (author's transl)]. We reported on the haemodynamic effects of 0.03 mg/kg flunitrazepam during surgical procedures in neuroleptanalgesia in 39 patients with congenital or acquired heart diseases, functional class II-IV. The benzodiazepine derivative did not cause any relevant effect on the inotropic state of the myocardium. There were only minor changes in cardiac index, stroke index, right and left atrial pressure. Changes in arterial pressure and left ventricular pressure during and immediately after surgical procedures, and in arterial perfusion pressure during extracorporeal circulation, as well as an only short lasting increase in heart rate were demonstrative a peripheral vasodilator effect. The decrease in ventricular work and myocardial oxygen consumption are of value in patients with coronary heart disease, especially immediately after surgical procedures. Flunitrazepam is considered an additional drug during neuroleptanalgesia, when hypertension is causing some problems. | [
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|
PMID:18071 | Intramuscular lorazepam versus pentobarbital premedication: a comparison of patient sedation, anxiolysis, and recall. | In a double-blind, controlled study in 40 veterans, IM lorazepam was significantly superior to IM pentobarbital as a preoperative sedative and in ability to suppress the memory of events of the operative day. A trend was noted (not statistically in this small series) toward greater patient acceptance of lorazepam. No important adverse effects or changes in vital signs occurred with either agent. | Intramuscular lorazepam versus pentobarbital premedication: a comparison of patient sedation, anxiolysis, and recall. In a double-blind, controlled study in 40 veterans, IM lorazepam was significantly superior to IM pentobarbital as a preoperative sedative and in ability to suppress the memory of events of the operative day. A trend was noted (not statistically in this small series) toward greater patient acceptance of lorazepam. No important adverse effects or changes in vital signs occurred with either agent. | [
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|
PMID:18075 | New techniques to measure blood cholinesterase activity in domesticated animals. | A macromethod and a semimicromethod were developed to measure erythrocyte acetylcholinesterase activity in cattle, sheep, goats, horses, dogs, and swine, and to measure plasma cholinesterase activity in horses, dogs, and swine. Comparison of the 2 methods with erythrocytes of sheep, cattle, goats, and horses indicated both methods gave similar results. They can be done in a shorter time and are more sensitive than Michel's method. Normal deltapH values per minutes, with standard deviations for blood cholinesterase activity of animals of different ages, sexes, breeds, and species, were: 0.76 +/- 0.12/30; 0.65 +/- 0.10/15; 0.69 +/- 0.19/45; 0.78 +/- 0.11/45; 0.63 +/- 0.11/45; and 0.71 +/- 0.06/25 for sheep, cattle, goats, horses, dogs, and swine erythrocyte acetylcholinesterase, respectively; and 0.66 +/- 0.18/20; 0.67 +/- 0.20/30, and 0.46 +/- 0.05/60 for horses, dogs, and swine plasma cholinesterase, respectively. It was shown that either the chloride or the iodide salt of acetylcholine can be used as the enzyme substrate. tin blood samples stored at 5 C for 24 hours, there was no significant change of the enzymatic activity. | New techniques to measure blood cholinesterase activity in domesticated animals. A macromethod and a semimicromethod were developed to measure erythrocyte acetylcholinesterase activity in cattle, sheep, goats, horses, dogs, and swine, and to measure plasma cholinesterase activity in horses, dogs, and swine. Comparison of the 2 methods with erythrocytes of sheep, cattle, goats, and horses indicated both methods gave similar results. They can be done in a shorter time and are more sensitive than Michel's method. Normal deltapH values per minutes, with standard deviations for blood cholinesterase activity of animals of different ages, sexes, breeds, and species, were: 0.76 +/- 0.12/30; 0.65 +/- 0.10/15; 0.69 +/- 0.19/45; 0.78 +/- 0.11/45; 0.63 +/- 0.11/45; and 0.71 +/- 0.06/25 for sheep, cattle, goats, horses, dogs, and swine erythrocyte acetylcholinesterase, respectively; and 0.66 +/- 0.18/20; 0.67 +/- 0.20/30, and 0.46 +/- 0.05/60 for horses, dogs, and swine plasma cholinesterase, respectively. It was shown that either the chloride or the iodide salt of acetylcholine can be used as the enzyme substrate. tin blood samples stored at 5 C for 24 hours, there was no significant change of the enzymatic activity. | [
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|
PMID:18072 | Selection of the source of mixed venous blood samples in severely traumatized patients. | The technic of balloon flotation catheterization represents a significant advance in providing an additional aid to diagnosis, clinical assessment, and management of the critically ill. The fact that such patients are admitted to an intensive care unit (ICU) invariably presumes that their management will include close and accurate monitoring of the cardiovascular and respiratory systems. In a prospective study of 51 patients, not in clinical shock, in an ICU, the authors demonstrated that superior vena cava samples are not a reliable index of mixed venous blood saturation in the critically injured patient, and that a pulmonary arterial catheter is essential for obtaining true mixed venous samples for valid estimations of intrapulmonary shunts and arteriovenous O2 content differences. | Selection of the source of mixed venous blood samples in severely traumatized patients. The technic of balloon flotation catheterization represents a significant advance in providing an additional aid to diagnosis, clinical assessment, and management of the critically ill. The fact that such patients are admitted to an intensive care unit (ICU) invariably presumes that their management will include close and accurate monitoring of the cardiovascular and respiratory systems. In a prospective study of 51 patients, not in clinical shock, in an ICU, the authors demonstrated that superior vena cava samples are not a reliable index of mixed venous blood saturation in the critically injured patient, and that a pulmonary arterial catheter is essential for obtaining true mixed venous samples for valid estimations of intrapulmonary shunts and arteriovenous O2 content differences. | [
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|
PMID:18078 | Drug therapy in the management of asthma. | In the past decade there has been substantial improvement in the quality of drug therapy for asthma. In part, this reflects the greater sophistication and confidence in the use of bronchodilator drugs, after their role in modifying the intracellular concentration of cyclic nucleotides was discovered. Another advance has come from the appearance of adequate information on theophylline blood levels and half-lives and their variability in man. The increasing availability of theophylline blood levels has aided not only in the selection of therapeutic doses but also in determining the effectiveness of newer products that, for example, promise to have a more sustained effect when given by mouth. The plight of asthmatic patients dependent on oral glucosteroid therapy has been substantially eased with the development of new steroid-sparing drugs that are effective by inhalation. | Drug therapy in the management of asthma. In the past decade there has been substantial improvement in the quality of drug therapy for asthma. In part, this reflects the greater sophistication and confidence in the use of bronchodilator drugs, after their role in modifying the intracellular concentration of cyclic nucleotides was discovered. Another advance has come from the appearance of adequate information on theophylline blood levels and half-lives and their variability in man. The increasing availability of theophylline blood levels has aided not only in the selection of therapeutic doses but also in determining the effectiveness of newer products that, for example, promise to have a more sustained effect when given by mouth. The plight of asthmatic patients dependent on oral glucosteroid therapy has been substantially eased with the development of new steroid-sparing drugs that are effective by inhalation. | [
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|
PMID:18079 | [Behavior therapy in disorders of dietary behavior]. | Behaviour therapies using conditioning principles have been successful in the treatment of some psychopatological eating behaviours. Such have been the cases for anorexia nervosae in adolescents and adults, refusal to eat in the young child and difficulties of swallowing. Some of these cases are described. Research has been done in different countries on the applications of these methods to the treatment of obesity caused by overeating which appears very frequently in our societies. Systematic and covert desensitization and operant conditioning using positive reinforcements are more frequently used in these behaviour modification procedures than aversive methods. More recently, researches on self-control (self-reward and self-punishment) have shown it as a very efficient tool for inducing weight loss. These methods using self-control have been applied to large populations: after a first, careful examination of the patient's eating behaviour, the program of reinforcement is established. It can be partially controlled by written instructions and letters. Results are already encouraging although they need to be followed up. But more research should be done on overeating behaviours, the way they appear and are maintained and on different programs of reinforcement for weight loss. | [Behavior therapy in disorders of dietary behavior]. Behaviour therapies using conditioning principles have been successful in the treatment of some psychopatological eating behaviours. Such have been the cases for anorexia nervosae in adolescents and adults, refusal to eat in the young child and difficulties of swallowing. Some of these cases are described. Research has been done in different countries on the applications of these methods to the treatment of obesity caused by overeating which appears very frequently in our societies. Systematic and covert desensitization and operant conditioning using positive reinforcements are more frequently used in these behaviour modification procedures than aversive methods. More recently, researches on self-control (self-reward and self-punishment) have shown it as a very efficient tool for inducing weight loss. These methods using self-control have been applied to large populations: after a first, careful examination of the patient's eating behaviour, the program of reinforcement is established. It can be partially controlled by written instructions and letters. Results are already encouraging although they need to be followed up. But more research should be done on overeating behaviours, the way they appear and are maintained and on different programs of reinforcement for weight loss. | [
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|
PMID:18081 | Isoelectric focusing of hog cholera virus. | The isoelectric point of Hog Cholera virus (Alfort strain) has been determined (pHi = 4.8). A clear stimulation of its infectivity can be recorded at this pH. The isoelectrophoretic profiles of strains isolated in the field show no significant differences. | Isoelectric focusing of hog cholera virus. The isoelectric point of Hog Cholera virus (Alfort strain) has been determined (pHi = 4.8). A clear stimulation of its infectivity can be recorded at this pH. The isoelectrophoretic profiles of strains isolated in the field show no significant differences. | [
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|
PMID:18082 | [Spectrophotometric determination of rifampicin S in the presence of rifampicin O]. | The limits of the use of the methods of direct photometric and differential spectrophotometric determination of rifamycin S containing rifamycin O as an admixture were discussed. The method of direct photometry did not provide determination of rifamycin S in the presence of rifamycin O since instability of the latter under the analysis conditions. A possibility of using the differential-spectrophotometric method for determination of rifamycin S in the presence of not more than 5 per cent of rifamycin O was shown. | [Spectrophotometric determination of rifampicin S in the presence of rifampicin O]. The limits of the use of the methods of direct photometric and differential spectrophotometric determination of rifamycin S containing rifamycin O as an admixture were discussed. The method of direct photometry did not provide determination of rifamycin S in the presence of rifamycin O since instability of the latter under the analysis conditions. A possibility of using the differential-spectrophotometric method for determination of rifamycin S in the presence of not more than 5 per cent of rifamycin O was shown. | [
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|
PMID:18083 | Azlocillin: in vitro studies of a new semisynthetic penicillin. | The activity of azlocillin, a new semisynthetic penicillin, was determined against 582 clinical isolates of gram-negative bacilli and gram-positive cocci. Over 75% of the isolates of Pseudomonas aeruginosa were inhibited at a concentration of 12.5 mug or less per ml. Azlocillin is also active against indole-negative and -positive Proteus spp., inhibiting 98 and 71%, respectively, at a concentration of 12.5 mug or less per ml. Isolates of Klebsiella spp. and Enterobacter spp. showed less susceptibility than isolates of Escherichia coli and Serratia spp. Gram-positive cocci except penicillin G-resistant Staphylococcus aureus were susceptible to azlocillin. Azlocillin failed to inhibit the growth of gram-negative bacilli when large inocula were used. It was more active in alkaline pH, but the type of medium used had little effect on its activity. Azlocillin was more active than mezlocillin, ticarcillin, and carbenicillin and as active as BLP-1654 against isolates of P. aeruginosa. It was not as active as mezlocillin against the majority of the other gram-negative bacilli. | Azlocillin: in vitro studies of a new semisynthetic penicillin. The activity of azlocillin, a new semisynthetic penicillin, was determined against 582 clinical isolates of gram-negative bacilli and gram-positive cocci. Over 75% of the isolates of Pseudomonas aeruginosa were inhibited at a concentration of 12.5 mug or less per ml. Azlocillin is also active against indole-negative and -positive Proteus spp., inhibiting 98 and 71%, respectively, at a concentration of 12.5 mug or less per ml. Isolates of Klebsiella spp. and Enterobacter spp. showed less susceptibility than isolates of Escherichia coli and Serratia spp. Gram-positive cocci except penicillin G-resistant Staphylococcus aureus were susceptible to azlocillin. Azlocillin failed to inhibit the growth of gram-negative bacilli when large inocula were used. It was more active in alkaline pH, but the type of medium used had little effect on its activity. Azlocillin was more active than mezlocillin, ticarcillin, and carbenicillin and as active as BLP-1654 against isolates of P. aeruginosa. It was not as active as mezlocillin against the majority of the other gram-negative bacilli. | [
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|
PMID:18084 | Phosphate inhibition of secondary metabolism in Serratia marcescens. | The synthesis of prodigiosin by non-proliferating cells of Serratia marcescens was examined in the presence of a wide range of concentrations of inorganic phosphate (Pi). A high elevation of pigment formation was obtained at less than or equal to 0.3 mM, and a broader but much lower elevation was obtained at 10 to 250 mM Pi. The synthesis of two immediate precursors of the pitment also was inhibited by Pi. The mechanism of action of Pi did not involve changes in pH or accumulation of the trace metal nutrient iron or zinc. Inhibition was most pronounced when Pi was added to the induction system before the onset of pigment formation. The inhibitor also diminished the burst of alkaline phosphatase activity that occurred in the period between the start of induction and appearance of prodigiosin. | Phosphate inhibition of secondary metabolism in Serratia marcescens. The synthesis of prodigiosin by non-proliferating cells of Serratia marcescens was examined in the presence of a wide range of concentrations of inorganic phosphate (Pi). A high elevation of pigment formation was obtained at less than or equal to 0.3 mM, and a broader but much lower elevation was obtained at 10 to 250 mM Pi. The synthesis of two immediate precursors of the pitment also was inhibited by Pi. The mechanism of action of Pi did not involve changes in pH or accumulation of the trace metal nutrient iron or zinc. Inhibition was most pronounced when Pi was added to the induction system before the onset of pigment formation. The inhibitor also diminished the burst of alkaline phosphatase activity that occurred in the period between the start of induction and appearance of prodigiosin. | [
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|
PMID:18085 | Effect of cadmium on fungi and on interactions between fungi and bacteria in soil: influence of clay minerals and pH. | Fungi (Rhizopus stolonifer, Trichoderma viride, Fusarium oxysporum f. sp. conglutinans, Cunninghamella echinulata, and several species of Aspergillus and Penicillium) tolerated higher concentrations of cadmium (Cd) when grown in soil than when grown on laboratory media, indicating that soil mitigated the toxic effects of Cd. In soil amended with clay minerals, montmorillonite provided partial or total protection against fungistatic effects of Cd, whereas additions of kaolinite provided little or no protection. Growth rates of Aspergillus niger were inhibited to a greater extent by 100 or 250 mug of Cd per g in soil adjusted to pH 7.2 than in the same soil at its natural pH of 5.1. However, there were no differences in the growth rates of Aspergillus fischeri with 100 or 250 mug of Cd per g in the same soil, whether at pH 5.1 or adjusted to pH 7.2. Growth of A. niger and A. fischeri in a soil contaminated with a low concentration of Cd (i.e., 28 mug/g), obtained from a site near a Japanese smelter, did not differ significantly from growth in a soil collected some distance away and containing 4 mug of Cd per g. Growth of A. niger in sterile soil amended with 100 mug of Cd per g and inoculated with Bacillus cereus or Agrobacterium tumefaciens was reduced to a greater extent than in the same soil containing 100 mug of Cd per g but no bacteria. The inhibitory effects of Agrobacterium radiobacter to A. niger were slightly reduced in the presence of 100 mug of Cd per g, whereas the inhibitory effects of Serratia marcescens were enhanced. | Effect of cadmium on fungi and on interactions between fungi and bacteria in soil: influence of clay minerals and pH. Fungi (Rhizopus stolonifer, Trichoderma viride, Fusarium oxysporum f. sp. conglutinans, Cunninghamella echinulata, and several species of Aspergillus and Penicillium) tolerated higher concentrations of cadmium (Cd) when grown in soil than when grown on laboratory media, indicating that soil mitigated the toxic effects of Cd. In soil amended with clay minerals, montmorillonite provided partial or total protection against fungistatic effects of Cd, whereas additions of kaolinite provided little or no protection. Growth rates of Aspergillus niger were inhibited to a greater extent by 100 or 250 mug of Cd per g in soil adjusted to pH 7.2 than in the same soil at its natural pH of 5.1. However, there were no differences in the growth rates of Aspergillus fischeri with 100 or 250 mug of Cd per g in the same soil, whether at pH 5.1 or adjusted to pH 7.2. Growth of A. niger and A. fischeri in a soil contaminated with a low concentration of Cd (i.e., 28 mug/g), obtained from a site near a Japanese smelter, did not differ significantly from growth in a soil collected some distance away and containing 4 mug of Cd per g. Growth of A. niger in sterile soil amended with 100 mug of Cd per g and inoculated with Bacillus cereus or Agrobacterium tumefaciens was reduced to a greater extent than in the same soil containing 100 mug of Cd per g but no bacteria. The inhibitory effects of Agrobacterium radiobacter to A. niger were slightly reduced in the presence of 100 mug of Cd per g, whereas the inhibitory effects of Serratia marcescens were enhanced. | [
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|
PMID:18086 | Significance of fecal coliform-positive Klebsiella. | A total of 191 Klebsiella pneumoniae isolates of human clinical, bovine mastitis, and a wide variety of environmental sources were tested for fecal coliform (FC) response with the membrane filtration and most probable number techniques. Twenty-seven Escherichia coli cultures of human clinical and environmental origins were also tested. Eighty-five percent (49/58) of known pathogenic K. pneumoniae were FC positive, compared with 16% (19/120) of the environmental strains. E. coli results indicated 93% (13/14) of the clinical and 85% (11/13) of the environmental strains as FC positive. There was no significant difference in the incidence of FC-positive cultures between pathogenic Klebsiella and E. coli. pH measurements of K. pneumoniae and E. coli cultures growing in m-FC broth at 44.5 degrees C revealed three distinct pH ranges correlating with colony morphology. beta-Galactosidase assays of Klebsiella and E. coli cultures at 44.5 degrees C indicated all were able to hydrolyze lactose, even if they were FC negative by the membrane filtration or most probable number techniques. The FC response pattern appears stable in K. pneumoniae. Three pathogenic cultures showed no change in FC responses after 270 generations of growth in sterile pulp mill effluent. Since K. pneumoniae is carried in the gastrointestinal tract of humans and animals and 85% of the tested pathogenic strains were FC positive, the isolation of FC-positive Klebsiella organisms from the environment would indicate their fecal or clinical origin or both. The added fact that K. pneumoniae is an opportunistic pathogen of increasing importance makes the occurrence of FC-positive environmental Klebsiella, particularly in large numbers, a potential human and animal health hazard. | Significance of fecal coliform-positive Klebsiella. A total of 191 Klebsiella pneumoniae isolates of human clinical, bovine mastitis, and a wide variety of environmental sources were tested for fecal coliform (FC) response with the membrane filtration and most probable number techniques. Twenty-seven Escherichia coli cultures of human clinical and environmental origins were also tested. Eighty-five percent (49/58) of known pathogenic K. pneumoniae were FC positive, compared with 16% (19/120) of the environmental strains. E. coli results indicated 93% (13/14) of the clinical and 85% (11/13) of the environmental strains as FC positive. There was no significant difference in the incidence of FC-positive cultures between pathogenic Klebsiella and E. coli. pH measurements of K. pneumoniae and E. coli cultures growing in m-FC broth at 44.5 degrees C revealed three distinct pH ranges correlating with colony morphology. beta-Galactosidase assays of Klebsiella and E. coli cultures at 44.5 degrees C indicated all were able to hydrolyze lactose, even if they were FC negative by the membrane filtration or most probable number techniques. The FC response pattern appears stable in K. pneumoniae. Three pathogenic cultures showed no change in FC responses after 270 generations of growth in sterile pulp mill effluent. Since K. pneumoniae is carried in the gastrointestinal tract of humans and animals and 85% of the tested pathogenic strains were FC positive, the isolation of FC-positive Klebsiella organisms from the environment would indicate their fecal or clinical origin or both. The added fact that K. pneumoniae is an opportunistic pathogen of increasing importance makes the occurrence of FC-positive environmental Klebsiella, particularly in large numbers, a potential human and animal health hazard. | [
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|
PMID:18087 | Purification and characteristics of an alginase from Alginovibrio aquatilis. | An exocellular inducible alginase from a strain of Alginovibrio aquatilis was purified 61-fold by ammonium sulfate precipitation and column chromatography on Sephadex G-150 and diethylaminoethyl-cellulose. The purified enzyme was more resistant than the crude enzyme to elevated temperatures. The monovalent cations Cs+, Rb+, K+, Na+, and Li+, in order of decreasing enzyme activation, were required for activity. The pH optimum of the purified alginase was 8.0 and its molecular weight from exclusion chromatography on Sephadex G-150 was 110,000. | Purification and characteristics of an alginase from Alginovibrio aquatilis. An exocellular inducible alginase from a strain of Alginovibrio aquatilis was purified 61-fold by ammonium sulfate precipitation and column chromatography on Sephadex G-150 and diethylaminoethyl-cellulose. The purified enzyme was more resistant than the crude enzyme to elevated temperatures. The monovalent cations Cs+, Rb+, K+, Na+, and Li+, in order of decreasing enzyme activation, were required for activity. The pH optimum of the purified alginase was 8.0 and its molecular weight from exclusion chromatography on Sephadex G-150 was 110,000. | [
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|
PMID:18088 | Concentration of enteroviruses from estuarine water. | Pleated cartridge filters readily adsorb viruses in estuarine water at low pH containing aluminum chloride. Adsorbed viruses are efficiently recovered by treating filters with glycine buffer at high pH. By using these procedures, it was possible to recover approximately 70% of the poliovirus added to 400 liters of estuarine water in 3 liters of filter eluate. Reconcentration of virus in the filter eluate in small volumes that are convenient for viral assays was more difficult. Reconcentration methods described previously for eluates from filters that process tap water or treated wastewater were inadequate when applied to eluates from filters used to process estuarine water containing large amounts of organic compounds. Two methods were found to permit efficient concentration of virus in filter eluates in small volumes. In both methods, virus in 3 liters of filter eluate was adsorbed to aluminum hydroxide flocs and then recovered in approximately 150 ml of buffered fetal calf serum. Additional reductions in volume were achieved by ultrafiltration or hydroextraction. By using these procedures 60 to 80% of the virus in 3 liters of filter eluate could be recovered in a final volume of 10 to 40 ml. | Concentration of enteroviruses from estuarine water. Pleated cartridge filters readily adsorb viruses in estuarine water at low pH containing aluminum chloride. Adsorbed viruses are efficiently recovered by treating filters with glycine buffer at high pH. By using these procedures, it was possible to recover approximately 70% of the poliovirus added to 400 liters of estuarine water in 3 liters of filter eluate. Reconcentration of virus in the filter eluate in small volumes that are convenient for viral assays was more difficult. Reconcentration methods described previously for eluates from filters that process tap water or treated wastewater were inadequate when applied to eluates from filters used to process estuarine water containing large amounts of organic compounds. Two methods were found to permit efficient concentration of virus in filter eluates in small volumes. In both methods, virus in 3 liters of filter eluate was adsorbed to aluminum hydroxide flocs and then recovered in approximately 150 ml of buffered fetal calf serum. Additional reductions in volume were achieved by ultrafiltration or hydroextraction. By using these procedures 60 to 80% of the virus in 3 liters of filter eluate could be recovered in a final volume of 10 to 40 ml. | [
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|
PMID:18116 | Bucolome in prevention of hyperbilirubinaemia in preterm infants. | Fifty preterm babies were randomly assigned to a group given oral bucolome (30 mg/kg per day for 5 days) and a control group. Serum bilirubin levels of the treated infants from day 4 onwards were consistently lower than those of the control infants. 3 of the 25 control infants (but none of the 25 treated infants) had bilirubin levels greater than 18 mg/100 ml (308 mumol/l) and required exchange transfusion. No sedation or drowsiness was observed in the infants given bucolome, and though the drug caused some vomiting, weight gains were unaffected. | Bucolome in prevention of hyperbilirubinaemia in preterm infants. Fifty preterm babies were randomly assigned to a group given oral bucolome (30 mg/kg per day for 5 days) and a control group. Serum bilirubin levels of the treated infants from day 4 onwards were consistently lower than those of the control infants. 3 of the 25 control infants (but none of the 25 treated infants) had bilirubin levels greater than 18 mg/100 ml (308 mumol/l) and required exchange transfusion. No sedation or drowsiness was observed in the infants given bucolome, and though the drug caused some vomiting, weight gains were unaffected. | [
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|
PMID:18119 | Prospective study of the Robertshaw endobronchial catheter in thoracic surgery. | One hundred three men undergoing thoracotomy on a general thoracic surgery service received endobronchial anesthesia with 100% oxygen using the Robertshaw tube. Bronchial intubation was accomplished in all. However, cross-leak or difficulty with deflation necessitated discontinuance in 8, while Pao2 values of 41 and 45 mm Hg caused abandonment in 2. There were no operative deaths. Surprisingly, hypoxemia in these patients related more to insufficient alveolar ventilation than to the venoarterial shunt. | Prospective study of the Robertshaw endobronchial catheter in thoracic surgery. One hundred three men undergoing thoracotomy on a general thoracic surgery service received endobronchial anesthesia with 100% oxygen using the Robertshaw tube. Bronchial intubation was accomplished in all. However, cross-leak or difficulty with deflation necessitated discontinuance in 8, while Pao2 values of 41 and 45 mm Hg caused abandonment in 2. There were no operative deaths. Surprisingly, hypoxemia in these patients related more to insufficient alveolar ventilation than to the venoarterial shunt. | [
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|
PMID:18125 | [The cellulase enzyme system during growth and development of Acanthamoeba castellanii (author's transl)]. | It could be shown that extracts of growing cultures of Acanthamoeba castellanii contained a cellulose degrading system. Reducing sugars are split off by one component of this system at an optimum of pH 4, another enzyme changes the viscosity at an optimum of pH 6, and a third component is a beta-glucosidase with an optimum at pH 3.5. At pH 4 the cellulose degradation products are cellobiose and glucose; at pH 6 higher molecular weight oligosaccharides are produced. During the development from trophozoites to cysts in a nutrient-free medium, the activities of both cellulases decline: Prior to the start of cellulose synthesis only 30%, and in cysts only 10% of the original existing activities are detectable. The biological function of the cellulase enzyme system is discussed together with a consideration of the fact that excystment takes place without digestion of the cyst wall in which the cellulose is deposited. | [The cellulase enzyme system during growth and development of Acanthamoeba castellanii (author's transl)]. It could be shown that extracts of growing cultures of Acanthamoeba castellanii contained a cellulose degrading system. Reducing sugars are split off by one component of this system at an optimum of pH 4, another enzyme changes the viscosity at an optimum of pH 6, and a third component is a beta-glucosidase with an optimum at pH 3.5. At pH 4 the cellulose degradation products are cellobiose and glucose; at pH 6 higher molecular weight oligosaccharides are produced. During the development from trophozoites to cysts in a nutrient-free medium, the activities of both cellulases decline: Prior to the start of cellulose synthesis only 30%, and in cysts only 10% of the original existing activities are detectable. The biological function of the cellulase enzyme system is discussed together with a consideration of the fact that excystment takes place without digestion of the cyst wall in which the cellulose is deposited. | [
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|
PMID:18126 | Gamma glutamyl transpeptidase in colon cancer induced by 1,2-dimethylhydrazine. | The study of the gamma-glutamyl transpeptidase (GTase) in colon of adult rats showed that in the sequence: duodenum, jejunum, ileum, cecum and colon, the colon has the lowest activity. There are, on the other hand, relatively small differences between GTase activities in the ascending, transverse and descending portions of the large intestine. GTase activity in the colon of neonatal rat is several times higher than in the colon of adult rats. Colon adenocarcinoma induced by 1,2-dimethylhydrazine were found to have a much higher GTase activity than the homologous normal tissue. Because these tumors resemble human colonic adenocarcinomas, it is suggested that the assay of GTase levels of human colon mucosa might be of potential value in the diagnosis of neoplastic changes. | Gamma glutamyl transpeptidase in colon cancer induced by 1,2-dimethylhydrazine. The study of the gamma-glutamyl transpeptidase (GTase) in colon of adult rats showed that in the sequence: duodenum, jejunum, ileum, cecum and colon, the colon has the lowest activity. There are, on the other hand, relatively small differences between GTase activities in the ascending, transverse and descending portions of the large intestine. GTase activity in the colon of neonatal rat is several times higher than in the colon of adult rats. Colon adenocarcinoma induced by 1,2-dimethylhydrazine were found to have a much higher GTase activity than the homologous normal tissue. Because these tumors resemble human colonic adenocarcinomas, it is suggested that the assay of GTase levels of human colon mucosa might be of potential value in the diagnosis of neoplastic changes. | [
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|
PMID:18117 | [A study on the behaviour of 7 serological parameters in many subjects affected by acute viral hepatitis (author's transl)]. | The AA. have studied the behaviour of 7 serological parameters in 32 subjects affected by acute viral hapatitis, by means of 4 samples of blood performes at the distance of 12 days for the first and of 15 days for the others. The results are alike to these formerly knows, exception made for alkaline phosphatase, gamma Gt and immunoglobulines G and M. | [A study on the behaviour of 7 serological parameters in many subjects affected by acute viral hepatitis (author's transl)]. The AA. have studied the behaviour of 7 serological parameters in 32 subjects affected by acute viral hapatitis, by means of 4 samples of blood performes at the distance of 12 days for the first and of 15 days for the others. The results are alike to these formerly knows, exception made for alkaline phosphatase, gamma Gt and immunoglobulines G and M. | [
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|
PMID:18118 | [Quantitative study and typization of aerobic bacteria in the conjunctival sacs of healthy eyes]. | We carried out a qualitative and quantitative bacteriological research into the conjunctives of 220 subjects in good health mostly women (180) exempt from recent or previous eyes diseases. In order to gather conjunctival bacteria we employed with a few variations Hadley's et al. (1973 [12]) method. Among the calculated bacterial flora we found as the most numerous ones Staphylococcus epidermidis (mean valor 1960/ml), then Streptococci (480/ml), Micrococci (465/ml), Diphteroides (360/ml), Enterococci (77/ml) and numerous (700/ml) Gram-positives Cocci like Sarcina, Micrococcus tetragenes, Diplococcus, and very rarely bacterial genera Gram-negatives or Iphomycetes, also numerically inferior as regards the researches of other Authors, because owen study is carried by into eyes exempt from diseases. | [Quantitative study and typization of aerobic bacteria in the conjunctival sacs of healthy eyes]. We carried out a qualitative and quantitative bacteriological research into the conjunctives of 220 subjects in good health mostly women (180) exempt from recent or previous eyes diseases. In order to gather conjunctival bacteria we employed with a few variations Hadley's et al. (1973 [12]) method. Among the calculated bacterial flora we found as the most numerous ones Staphylococcus epidermidis (mean valor 1960/ml), then Streptococci (480/ml), Micrococci (465/ml), Diphteroides (360/ml), Enterococci (77/ml) and numerous (700/ml) Gram-positives Cocci like Sarcina, Micrococcus tetragenes, Diplococcus, and very rarely bacterial genera Gram-negatives or Iphomycetes, also numerically inferior as regards the researches of other Authors, because owen study is carried by into eyes exempt from diseases. | [
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|
PMID:18127 | Isolation and properties of muscular glucose dehydrogenase (E.C. 1.1.1.47) from the stomachs of geese and ducks. | A method which purified 30-fold perparations of muscular glucose dehydrogenase from the stomachs of geese and ducks was elaborated. Activity of this enzyme was found to be dependent on presence of free-SH groups, NAD or NADP as coenzymes, and had an optimum at about pH 7-8. The enzyme's activity against 17 different monosaccharides and their derivatives was tested. The best substrate was beta-D-glucose, followed by D-glucose, D-glucosamine and D-xylose. Other compounds such as D-glucose-6-phosphate, D-fructose, D-mannose and 2-deoxyglucose were not oxidized. The enzyme preparation showed presence of enzymes which conduct gluconic acid metabolism. | Isolation and properties of muscular glucose dehydrogenase (E.C. 1.1.1.47) from the stomachs of geese and ducks. A method which purified 30-fold perparations of muscular glucose dehydrogenase from the stomachs of geese and ducks was elaborated. Activity of this enzyme was found to be dependent on presence of free-SH groups, NAD or NADP as coenzymes, and had an optimum at about pH 7-8. The enzyme's activity against 17 different monosaccharides and their derivatives was tested. The best substrate was beta-D-glucose, followed by D-glucose, D-glucosamine and D-xylose. Other compounds such as D-glucose-6-phosphate, D-fructose, D-mannose and 2-deoxyglucose were not oxidized. The enzyme preparation showed presence of enzymes which conduct gluconic acid metabolism. | [
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|
PMID:18128 | Analgesic drugs in the management of pain. | The use of potent narcotics to control severe pain should be of short duration and limited to patients with acute diseases or inoperable or metastatic cancer who require long-term relief. Continued and prolonged use of narcotics in patients with chronic benign pain is not recommended because of serious behavioral consequences, the development of tolerance, and addiction liability. Long-term use of analgesic drugs in chronic pain usually produces negative behavioral complications that are more difficult to manage than the pain it was desired to eliminate. The use of antidepressant drugs in the pain regimen has been found to provide increased relief of pain and often allows the dose of narcotic analgesic to be reduced or totally eliminated. | Analgesic drugs in the management of pain. The use of potent narcotics to control severe pain should be of short duration and limited to patients with acute diseases or inoperable or metastatic cancer who require long-term relief. Continued and prolonged use of narcotics in patients with chronic benign pain is not recommended because of serious behavioral consequences, the development of tolerance, and addiction liability. Long-term use of analgesic drugs in chronic pain usually produces negative behavioral complications that are more difficult to manage than the pain it was desired to eliminate. The use of antidepressant drugs in the pain regimen has been found to provide increased relief of pain and often allows the dose of narcotic analgesic to be reduced or totally eliminated. | [
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|
PMID:18129 | A sensitive method for gas-chromatographic assay of barbiturates in body fluids. | The Authors present a gas-chromatographic method which allows for the rapid identification and assay of barbiturates and antiepileptics in body fluids. The Kupferberger procedure for extraction is used. The identification is obtained on two different columns: 10% Dexil 300 GC on Chromosorb W-HP and 3% OV 17 on Chromosorb G AW-DMCS (80-100 mesh). A considerable and interesting reduction of the barbiturates adsorption in the columns is obtained by preliminary conditioning with tetraethylorthosilicate. In this way, phenobarbital and cyclobarbital may also be assayed up to 1 microgram/ml in blood. For the simultaneous assay of therapeutic levels of phenobarbital and hydrantoins methylderivates are better employed: blood concentrations as low as 0.1 microgram/ml are easily detected. | A sensitive method for gas-chromatographic assay of barbiturates in body fluids. The Authors present a gas-chromatographic method which allows for the rapid identification and assay of barbiturates and antiepileptics in body fluids. The Kupferberger procedure for extraction is used. The identification is obtained on two different columns: 10% Dexil 300 GC on Chromosorb W-HP and 3% OV 17 on Chromosorb G AW-DMCS (80-100 mesh). A considerable and interesting reduction of the barbiturates adsorption in the columns is obtained by preliminary conditioning with tetraethylorthosilicate. In this way, phenobarbital and cyclobarbital may also be assayed up to 1 microgram/ml in blood. For the simultaneous assay of therapeutic levels of phenobarbital and hydrantoins methylderivates are better employed: blood concentrations as low as 0.1 microgram/ml are easily detected. | [
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|
PMID:18130 | Spectral evidence for 2,2,3-trichloro-oxirane formation during microsomal trichloroethylene oxidation. | During aerobic incubation of trichloroethylene with rabbit liver microsomes and NADPH a difference absorption peak appears at 451-452 nm. Trichloroethylene does not form a ligand absorption spectrum with hepatic microsomes reduced by dithionite, or in anaerobic incubates in the presence of NADPH. Addition of trichloroethylene epoxide (2,2,3-trichloro-oxirane) to reduced suspensions of rabbit liver microsomes produces high difference absorption at 452 nm, the optical Ks being approximately 2 mM. Of all possible metabolites of trichloroethylene only trichloroethanol forms absorption in the vicinity of 480 nm, and the broad absorption band reveals relatively low absorption near 450 nm. Dichloroacetyl chloride is the main thermal rearrangement product of trichloroethylene epoxide, and also produces 452 nm absorption in reduced microsomes. However, the difference absorption is 5 times smaller than the absorption produced by the intermediate formed during incubation of trichloroethylene in metabolising liver microsomes. These observations include strong evidence for epoxide formation during microsomal oxidation of trichloroethylene. 14C-labelled trichloroethylene binds irreversibly to hepatic macromolecules in vivo and in vitro. Possible rearrangement pathways of 2,2,3-trichloro-oxirane and reactive intermediates are presented. | Spectral evidence for 2,2,3-trichloro-oxirane formation during microsomal trichloroethylene oxidation. During aerobic incubation of trichloroethylene with rabbit liver microsomes and NADPH a difference absorption peak appears at 451-452 nm. Trichloroethylene does not form a ligand absorption spectrum with hepatic microsomes reduced by dithionite, or in anaerobic incubates in the presence of NADPH. Addition of trichloroethylene epoxide (2,2,3-trichloro-oxirane) to reduced suspensions of rabbit liver microsomes produces high difference absorption at 452 nm, the optical Ks being approximately 2 mM. Of all possible metabolites of trichloroethylene only trichloroethanol forms absorption in the vicinity of 480 nm, and the broad absorption band reveals relatively low absorption near 450 nm. Dichloroacetyl chloride is the main thermal rearrangement product of trichloroethylene epoxide, and also produces 452 nm absorption in reduced microsomes. However, the difference absorption is 5 times smaller than the absorption produced by the intermediate formed during incubation of trichloroethylene in metabolising liver microsomes. These observations include strong evidence for epoxide formation during microsomal oxidation of trichloroethylene. 14C-labelled trichloroethylene binds irreversibly to hepatic macromolecules in vivo and in vitro. Possible rearrangement pathways of 2,2,3-trichloro-oxirane and reactive intermediates are presented. | [
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|
PMID:18132 | Inheritance of muscle and liver types of supernatant NADP-dependent isocitrate dehydrogenase in rainbow trout (Salmo gairdneri). | The genetics of allelic variation for NADP-dependent isocitrate dehydrogenase (IDH-s) found in the supernatant of liver and white muscle extracts of rainbow trout (Salmo gairdneri) was examined. Twenty progeny from each of 50 controlled matings were examined for IDH phenotypes. Progeny data clearly indicated that the IDH-s variation in the muscle is controlled by two loci--one fixed and one with two alleles producing molecules of different electrophoretic mobilities. IDH-s variation in the liver is controlled by two disomic loci which code for four alleles. No linkage between the loci controlling IDH-s in the liver and the loci controlling it in the muscle was detected. | Inheritance of muscle and liver types of supernatant NADP-dependent isocitrate dehydrogenase in rainbow trout (Salmo gairdneri). The genetics of allelic variation for NADP-dependent isocitrate dehydrogenase (IDH-s) found in the supernatant of liver and white muscle extracts of rainbow trout (Salmo gairdneri) was examined. Twenty progeny from each of 50 controlled matings were examined for IDH phenotypes. Progeny data clearly indicated that the IDH-s variation in the muscle is controlled by two loci--one fixed and one with two alleles producing molecules of different electrophoretic mobilities. IDH-s variation in the liver is controlled by two disomic loci which code for four alleles. No linkage between the loci controlling IDH-s in the liver and the loci controlling it in the muscle was detected. | [
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PMID:18133 | Purification and properties of a new testosterone 17beta-dehydrogenase (NADP+) from guinea-pig liver. | As a result of studies of guinea-pig live testosterone 17beta-dehydrogenase (NADP+) (EC 1.1.1.64), a new testosterone 17beta-dehydrogenase was discovered. The new enzyme was purified to a single homogeneous protein from the 105 000 g-supernatant fraction of guinea-pig liver by (NH4)2SO4 fractional precipitation and two gel-filtration stages, DEAE-cellulose column chromatography and hydroxyapatite column chromatography. It was characterized by many properties. The enzyme has almost the same properties as the classical testosterone 17beta-dehydrogenase (NADP+) (EC 1.1.1.64), with respect to cofactor requirement, pH optima for dehydrogenation, effect of phosphate ion on the NAD+-dependent reaction and molecular weight, but characteristic differences were observed in substrate-specificity between the two dehydrogenases. With various androstane derivatives, the configuration of the A/B-ring junction was closely connected with enzyme activity. 5alpha-Androstanes, such as 5alpha-androstane-3alpha,17beta-diol, 5alpha-androstane-3beta,17beta-diol and 17beta-hydroxy-5alpha-androstan-3-one, and 5beta-congeners, such as 5beta-androstane-3alpha,17beta-diol, 5beta-androstane-3beta,17beta-diol and 17beta-hydroxy-5beta-androstan-3-one, served as substrates for both the EC 1.1.1.64 enzyme and the new enzyme. The EC 1.1.1.64 enzyme oxidized testosterone more rapidly than did the new enzyme. These comparisons were based on the relative activities, apparent Km values and apparent Vmax values. | Purification and properties of a new testosterone 17beta-dehydrogenase (NADP+) from guinea-pig liver. As a result of studies of guinea-pig live testosterone 17beta-dehydrogenase (NADP+) (EC 1.1.1.64), a new testosterone 17beta-dehydrogenase was discovered. The new enzyme was purified to a single homogeneous protein from the 105 000 g-supernatant fraction of guinea-pig liver by (NH4)2SO4 fractional precipitation and two gel-filtration stages, DEAE-cellulose column chromatography and hydroxyapatite column chromatography. It was characterized by many properties. The enzyme has almost the same properties as the classical testosterone 17beta-dehydrogenase (NADP+) (EC 1.1.1.64), with respect to cofactor requirement, pH optima for dehydrogenation, effect of phosphate ion on the NAD+-dependent reaction and molecular weight, but characteristic differences were observed in substrate-specificity between the two dehydrogenases. With various androstane derivatives, the configuration of the A/B-ring junction was closely connected with enzyme activity. 5alpha-Androstanes, such as 5alpha-androstane-3alpha,17beta-diol, 5alpha-androstane-3beta,17beta-diol and 17beta-hydroxy-5alpha-androstan-3-one, and 5beta-congeners, such as 5beta-androstane-3alpha,17beta-diol, 5beta-androstane-3beta,17beta-diol and 17beta-hydroxy-5beta-androstan-3-one, served as substrates for both the EC 1.1.1.64 enzyme and the new enzyme. The EC 1.1.1.64 enzyme oxidized testosterone more rapidly than did the new enzyme. These comparisons were based on the relative activities, apparent Km values and apparent Vmax values. | [
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|
PMID:18134 | Partial purification and properties of frog liver tyrosine aminotransferase. | Hepatic tyrosine aminotransferase of the frog Rana temporaria was partially purified by (NH4)2SO4 fractionation and successive chromatography on DEAE-cellulose DE-52, Ultrogel AcA-34, DEAE-cellulose DE-52 again and, finally, hydroxyapatite. During the last step, the enzyme activity separated into two fractions; traces of a third fraction were also found. The major form was purified 6000-fold to a specific activity of 200 units/mg of protein; it was about 50% pure by electrophoretic criteria. It had mol.wt. about 85 000 as determined by gel filtration on a Sephadex G-100 column. It was not activated by added pyridoxal 5'-phosphate. The enzyme was, however, inactivated by the pyridoxal phosphate reactants canaline and amino-oxyacetate. The enzyme was specific for 2-oxoglutarate as the amino group acceptor. Homogentisate inhibited the enzyme and adrenaline was an activator; both effects were seen at low concentrations of the effectors. The relationship between initial rate and tyrosine or 2-oxoglutarate concentration was abnormal and complex. Form-2 enzyme had similar or identical molecular weight, cofactor requirements, oxo acid specificity and kinetics. | Partial purification and properties of frog liver tyrosine aminotransferase. Hepatic tyrosine aminotransferase of the frog Rana temporaria was partially purified by (NH4)2SO4 fractionation and successive chromatography on DEAE-cellulose DE-52, Ultrogel AcA-34, DEAE-cellulose DE-52 again and, finally, hydroxyapatite. During the last step, the enzyme activity separated into two fractions; traces of a third fraction were also found. The major form was purified 6000-fold to a specific activity of 200 units/mg of protein; it was about 50% pure by electrophoretic criteria. It had mol.wt. about 85 000 as determined by gel filtration on a Sephadex G-100 column. It was not activated by added pyridoxal 5'-phosphate. The enzyme was, however, inactivated by the pyridoxal phosphate reactants canaline and amino-oxyacetate. The enzyme was specific for 2-oxoglutarate as the amino group acceptor. Homogentisate inhibited the enzyme and adrenaline was an activator; both effects were seen at low concentrations of the effectors. The relationship between initial rate and tyrosine or 2-oxoglutarate concentration was abnormal and complex. Form-2 enzyme had similar or identical molecular weight, cofactor requirements, oxo acid specificity and kinetics. | [
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PMID:18135 | Characterization of an adenosine 3':5'-cyclic monophosphate phosphodiesterase from baker's yeast. Its binding to subcellular particles, catalytic properties and gel-filtration behaviour. | 1. The 3':5'-cyclic AMP phosphodiesterase in the microsomal fraction of baker's yeast is highly specific for cyclic AMP, and not inhibited by cyclic GMP, cyclic IMP or cyclic UMP. Catalytic activity is abolished by 30 micrometer-EDTA. At 30 degrees C and pH8.1, the Km is 0.17 micrometer, and theophylline is a simple competitive inhibitor with Ki 0.7 micrometer. The pH optimum is about 7.8 at 0.25 micrometer-cyclic AMP, so that over the physiological range of pH in yeast the activity changes in the opposite direction to that of adenylate cyclase [PH optimum about 6.2; Londesborough & Nurminen (1972) Acta Chem. Scand. 26, 3396-3398].2. At pH 7.2, dissociation of the enzyme from dilute microsomal suspensions increased with ionic strength and was almost complete at 0.3 M-KCl. MgCl2 caused more dissociation than did KCl or NaCl at the same ionic strength, but at low KCl concentrations binding required small amounts of free bivalent metal ions. In 0.1 M-KCl the binding decreased between pH 4.7 and 9.3. At pH 7.2 the binding was independent of temperature between 5 and 20 degrees C. These observations suggest that the binding is electrostatic rather than hydrophobic. 3. The proportion of bound activity increased with the concentration of the microsomal fraction, and at 22 mg of protein/ml and pH 7.2 was 70% at I0.18, and 35% at I0.26. Presumably a substantial amount of the enzyme is particle-bound in vivo. 4. At 5 degrees C in 10 mM-potassium phosphate, pH 7.2, the apparent molecular weight of KCl-solubilized enzyme decreased with enzyme concentration from about 200 000 to 40 000. In the presence of 0.5M-KCl, a constant mol.wt. of about 55 000 was observed over a 20-fold range of enzyme concentrations. | Characterization of an adenosine 3':5'-cyclic monophosphate phosphodiesterase from baker's yeast. Its binding to subcellular particles, catalytic properties and gel-filtration behaviour. 1. The 3':5'-cyclic AMP phosphodiesterase in the microsomal fraction of baker's yeast is highly specific for cyclic AMP, and not inhibited by cyclic GMP, cyclic IMP or cyclic UMP. Catalytic activity is abolished by 30 micrometer-EDTA. At 30 degrees C and pH8.1, the Km is 0.17 micrometer, and theophylline is a simple competitive inhibitor with Ki 0.7 micrometer. The pH optimum is about 7.8 at 0.25 micrometer-cyclic AMP, so that over the physiological range of pH in yeast the activity changes in the opposite direction to that of adenylate cyclase [PH optimum about 6.2; Londesborough & Nurminen (1972) Acta Chem. Scand. 26, 3396-3398].2. At pH 7.2, dissociation of the enzyme from dilute microsomal suspensions increased with ionic strength and was almost complete at 0.3 M-KCl. MgCl2 caused more dissociation than did KCl or NaCl at the same ionic strength, but at low KCl concentrations binding required small amounts of free bivalent metal ions. In 0.1 M-KCl the binding decreased between pH 4.7 and 9.3. At pH 7.2 the binding was independent of temperature between 5 and 20 degrees C. These observations suggest that the binding is electrostatic rather than hydrophobic. 3. The proportion of bound activity increased with the concentration of the microsomal fraction, and at 22 mg of protein/ml and pH 7.2 was 70% at I0.18, and 35% at I0.26. Presumably a substantial amount of the enzyme is particle-bound in vivo. 4. At 5 degrees C in 10 mM-potassium phosphate, pH 7.2, the apparent molecular weight of KCl-solubilized enzyme decreased with enzyme concentration from about 200 000 to 40 000. In the presence of 0.5M-KCl, a constant mol.wt. of about 55 000 was observed over a 20-fold range of enzyme concentrations. | [
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PMID:18136 | Physical and binding properties of large fragments of human serum albumin. | Three large fragments of human serum albumin were produced by peptic digestion of the native protein [Geisow & Beaven (1977) Biochem. J. 161, 619-625]. Fragment P44 represents residues 1-386 and fragments P29 and P31 represent residues 49-307 and residues 308-584 respectively of the albumin molecule. The large N-terminal fragment P44 has a similar percentage of alpha-helix to stored defatted albumin, although the alpha-helix content of all the fragments is significantly less than that of freshly prepared albumin. The fragment P44 appears to account for all the binding of the hydrophobic probe 8-anilinonaphthalene-1-sulphonate to albumin. N-Acetyl-L-tryptophan binds to this fragment and displaces one of the bound molecules of 8-anilinonaphthalene-1-sulphonate. Bilirubin binds to fragments P44 and P29, and the complexes show similar circular-dichroism spectra to that of the complex between bilirubin and whole albumin. These results are in agreement with affinity-labeling work on albumin with reactive ligands where substitution occurs in the N-terminal region of the molecule. The sharp conformational transitional transition in albumin which is observed between pH4 and 3.5 was absent from the fragments. This isomerization, usually called the N-F transition, probably occurs in intact albumin as a result of the unfolding or separation of the C-terminal third of the protein from the remainder of the molecule. | Physical and binding properties of large fragments of human serum albumin. Three large fragments of human serum albumin were produced by peptic digestion of the native protein [Geisow & Beaven (1977) Biochem. J. 161, 619-625]. Fragment P44 represents residues 1-386 and fragments P29 and P31 represent residues 49-307 and residues 308-584 respectively of the albumin molecule. The large N-terminal fragment P44 has a similar percentage of alpha-helix to stored defatted albumin, although the alpha-helix content of all the fragments is significantly less than that of freshly prepared albumin. The fragment P44 appears to account for all the binding of the hydrophobic probe 8-anilinonaphthalene-1-sulphonate to albumin. N-Acetyl-L-tryptophan binds to this fragment and displaces one of the bound molecules of 8-anilinonaphthalene-1-sulphonate. Bilirubin binds to fragments P44 and P29, and the complexes show similar circular-dichroism spectra to that of the complex between bilirubin and whole albumin. These results are in agreement with affinity-labeling work on albumin with reactive ligands where substitution occurs in the N-terminal region of the molecule. The sharp conformational transitional transition in albumin which is observed between pH4 and 3.5 was absent from the fragments. This isomerization, usually called the N-F transition, probably occurs in intact albumin as a result of the unfolding or separation of the C-terminal third of the protein from the remainder of the molecule. | [
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|
PMID:18137 | Purification and properties of urease from bovine rumen. | Urease (urea amidohydrolase, EC 3.5.1.5) was extracted from the mixed rumen bacterial fraction of bovine rumen contents and purified 60-fold by (NH4)2SO4 precipitation, calcium phosphate-gel adsorption and chromatography on hydroxyapatite. The purified enzyme had maximum activity at pH 8.0. The molecular weight was estimated to be 120000-130000. The Km for urea was 8.3 X 10(-4) M+/-1.7 X 10(-4) M. The maximum velocity was 3.2+/-0.25 mmol of urea hydrolysed/h per mg of protein. The enzyme was stabilized by 50 mM-dithiothreitol. The enzyme was not inhibited by high concentrations of EDTA or phosphate but was inhibited by Mn2+, Mg2+, Ba2+, Hg2+, Cu2+, Zn2+, Cd2+, Ni2+ and Co2+. p-Chloromercuribenzenesulfphonate and N-ethylmaleimide inhibited the enzyme almost completely at 0.1 mM. Hydroxyurea and acetohydroxamate reversibly inhibited the enzyme. Polyacrylamide-gel electrophoresis showed that the mixed rumen bacteria produce ureases which have identical molecular weights and electrophoretic mobility. No multiple forms of urease were detected. | Purification and properties of urease from bovine rumen. Urease (urea amidohydrolase, EC 3.5.1.5) was extracted from the mixed rumen bacterial fraction of bovine rumen contents and purified 60-fold by (NH4)2SO4 precipitation, calcium phosphate-gel adsorption and chromatography on hydroxyapatite. The purified enzyme had maximum activity at pH 8.0. The molecular weight was estimated to be 120000-130000. The Km for urea was 8.3 X 10(-4) M+/-1.7 X 10(-4) M. The maximum velocity was 3.2+/-0.25 mmol of urea hydrolysed/h per mg of protein. The enzyme was stabilized by 50 mM-dithiothreitol. The enzyme was not inhibited by high concentrations of EDTA or phosphate but was inhibited by Mn2+, Mg2+, Ba2+, Hg2+, Cu2+, Zn2+, Cd2+, Ni2+ and Co2+. p-Chloromercuribenzenesulfphonate and N-ethylmaleimide inhibited the enzyme almost completely at 0.1 mM. Hydroxyurea and acetohydroxamate reversibly inhibited the enzyme. Polyacrylamide-gel electrophoresis showed that the mixed rumen bacteria produce ureases which have identical molecular weights and electrophoretic mobility. No multiple forms of urease were detected. | [
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|
PMID:18138 | Adenosine triphosphate-activated adenylate deaminase from marine invertebrate animals. Properties of the enzyme from lugworm (Arenicola cristata) body-wall muscle. | Adenylate deaminase (AMP aminohydrolase, EC 3.5.4.6) from lugworm (Arenicola cristata) body-wall muscle was partially purified by extraction in KCl solutions and chromatography on phosphocellulose. Enzyme activity was eluted from the column at two salt concentrations. Both forms show co-operative binding of AMP (Hill coefficient, h, 2.85) with s0.5 values of 20 mM and 15.6 mM. ATP and ADP act as positive effectors lowering h to 1.07 and s0.5 to 2mM. The apparent Ka (activation) for ATP was 1.5mM. GTP is an inhibitor with an apparent Ki of 0.12 mM. In vivo the ATP-activated adenylate deaminase is in the active form and may be regulated by changes in GTP concentrations. Adenylate deaminase may act as a primary ammonia-forming enzyme in ammonotelic marine invertebrates with the purine nucleotide cycle. | Adenosine triphosphate-activated adenylate deaminase from marine invertebrate animals. Properties of the enzyme from lugworm (Arenicola cristata) body-wall muscle. Adenylate deaminase (AMP aminohydrolase, EC 3.5.4.6) from lugworm (Arenicola cristata) body-wall muscle was partially purified by extraction in KCl solutions and chromatography on phosphocellulose. Enzyme activity was eluted from the column at two salt concentrations. Both forms show co-operative binding of AMP (Hill coefficient, h, 2.85) with s0.5 values of 20 mM and 15.6 mM. ATP and ADP act as positive effectors lowering h to 1.07 and s0.5 to 2mM. The apparent Ka (activation) for ATP was 1.5mM. GTP is an inhibitor with an apparent Ki of 0.12 mM. In vivo the ATP-activated adenylate deaminase is in the active form and may be regulated by changes in GTP concentrations. Adenylate deaminase may act as a primary ammonia-forming enzyme in ammonotelic marine invertebrates with the purine nucleotide cycle. | [
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|
PMID:18139 | Multiple alpha-mannosidase activities in mammalian tissues as shown by metal-ion activation. | 1. Four different types of alpha-mannosidase activity were shown to occur in several tissues from the rat. There is the Zn2+-dependent enzyme, active at acidic pH, and three enzymes that are active near to neutral pH. 2. The 'neutral' enzymes are activated by Fe2+, Co2+ or Mn2+. 3. Optimum activities for these three enzymes are shown at pH values of 5.2, 6.5 and 7.3. The activity at pH6.5 is the only one evident without metal-ion activation, but activity is enhanced by all three metal ions. The activity at pH 5.2 is seen only in the presence of Fe2+ or Co2+, and the activity at pH7.3 is seen only in the presence of Co2+ or Mn2+ and in a non-chelating buffer medium. 4. The pH6.5-active enzyme is inactivated by EDTA, but activity is restored by excess of metal ion. 5. The enzymes differ markedly in their stability. The pH6.5-active enzyme is very labile and the pH7.3-active enzyme is the most stable. 6. Tissue preparations vary widely in their activity at pH6.5, but where activity is low it can be increased by incubation with one of the activating metal cations. 7. All the enzymes active at neutral pH are inhibited by heavy-metal ions and stabilized to some extent by thiol groups. | Multiple alpha-mannosidase activities in mammalian tissues as shown by metal-ion activation. 1. Four different types of alpha-mannosidase activity were shown to occur in several tissues from the rat. There is the Zn2+-dependent enzyme, active at acidic pH, and three enzymes that are active near to neutral pH. 2. The 'neutral' enzymes are activated by Fe2+, Co2+ or Mn2+. 3. Optimum activities for these three enzymes are shown at pH values of 5.2, 6.5 and 7.3. The activity at pH6.5 is the only one evident without metal-ion activation, but activity is enhanced by all three metal ions. The activity at pH 5.2 is seen only in the presence of Fe2+ or Co2+, and the activity at pH7.3 is seen only in the presence of Co2+ or Mn2+ and in a non-chelating buffer medium. 4. The pH6.5-active enzyme is inactivated by EDTA, but activity is restored by excess of metal ion. 5. The enzymes differ markedly in their stability. The pH6.5-active enzyme is very labile and the pH7.3-active enzyme is the most stable. 6. Tissue preparations vary widely in their activity at pH6.5, but where activity is low it can be increased by incubation with one of the activating metal cations. 7. All the enzymes active at neutral pH are inhibited by heavy-metal ions and stabilized to some extent by thiol groups. | [
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|
PMID:18140 | Specific labelling of a constituent polypeptide of bovine heart mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone reductase by the inhibitor diphenyleneiodonium. | 1. NADH-ubiquinone-1 and NADH-menadione reductase activities of Complex I were inhibited by diphenyleneiodonium (apparent Ki 23 and 30 nmol/mg of protein respectively). Reduction of K3Fe(CN)6 and juglone was relatively unaffected. 2. Iodoniumdiphenyl and derivatives were much less effective inhibitors. Compounds with similar ring structures to diphenyleneiodonium, in particular dibenzofuran, were inhibitors of NADH-ubiquinone-1 oxidoreductase. 3. Diphenylene[125I]iodonium specifically labelled a polypeptide of mol.wt. 23500. Maximum incorporation was 1 mol/mol of Complex-I flavin or 1 mol/mol of the 23500-mol.wt. polypeptide. 4. The label associated with this polypeptide was of limited stability, especially at lower pH. 5. Complete inhibition of ubiquinone reduction was achieved when 1 mol of inhibitor was incorporated/mol of Complex-I flavin, but the relationship between inhibition and labelling was not linear. 6. No evidence for covalent interaction between diphenyleneiodonium and the phospholipids of Complex I was obtained. 7. Rotenone increased the apparent affinity of diphenyleneiodonium for the 23500-mol.wt. polypeptide without affecting the maximum incorporation. 8. The 23500-mol.wt. polypeptide was not solubilized by chaotropic agents. Prior treatment of Complex I with chaotropic agents or sodium dodecyl sulphate prevented incorporation of diphenyleneiodonium into this polypeptide. | Specific labelling of a constituent polypeptide of bovine heart mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone reductase by the inhibitor diphenyleneiodonium. 1. NADH-ubiquinone-1 and NADH-menadione reductase activities of Complex I were inhibited by diphenyleneiodonium (apparent Ki 23 and 30 nmol/mg of protein respectively). Reduction of K3Fe(CN)6 and juglone was relatively unaffected. 2. Iodoniumdiphenyl and derivatives were much less effective inhibitors. Compounds with similar ring structures to diphenyleneiodonium, in particular dibenzofuran, were inhibitors of NADH-ubiquinone-1 oxidoreductase. 3. Diphenylene[125I]iodonium specifically labelled a polypeptide of mol.wt. 23500. Maximum incorporation was 1 mol/mol of Complex-I flavin or 1 mol/mol of the 23500-mol.wt. polypeptide. 4. The label associated with this polypeptide was of limited stability, especially at lower pH. 5. Complete inhibition of ubiquinone reduction was achieved when 1 mol of inhibitor was incorporated/mol of Complex-I flavin, but the relationship between inhibition and labelling was not linear. 6. No evidence for covalent interaction between diphenyleneiodonium and the phospholipids of Complex I was obtained. 7. Rotenone increased the apparent affinity of diphenyleneiodonium for the 23500-mol.wt. polypeptide without affecting the maximum incorporation. 8. The 23500-mol.wt. polypeptide was not solubilized by chaotropic agents. Prior treatment of Complex I with chaotropic agents or sodium dodecyl sulphate prevented incorporation of diphenyleneiodonium into this polypeptide. | [
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|
PMID:18141 | Changes in the kinetic behaviour of threonine transport into Trypanosoma brucei elicited by variation in hydrogen ion concentration. | 1. The dependence of V and V/K(m) for threonine transport into Trypanosoma brucei upon the external concentration of H(+) was studied. 2. Two ionizing groups, the alpha-amino group of the substrate and a group at the substrate-binding site of the carrier, were found to influence the observed kinetic behaviour of transport. 3. The pK of the group at the substrate-binding site on the free carrier was found to be 6.95 at 30 degrees C and to be temperature-dependent; its heat of ionization was -63.8kJ, which is outside the range for most proton dissociations and suggests a significant contribution from some other source, possibly the remainder of the carrier or the membrane environment. 4. Binding of substrate caused the pK of its alpha-amino group to shift to a higher value, whereas that of the carrier group shifted to a lower value (6.65 at 30 degrees C). 5. The ionic interaction between substrate and carrier appeared to be involved in the stabilizing of the protonated substrate and the species of the carrier-substrate complex required for the membrane-translocation step. 6. The same ionic species of carrier-substrate complex is required for both substrate dissociation and translocation of the substrate through the membrane. 7. H(+) symport or antiport did not occur during threonine uptake. | Changes in the kinetic behaviour of threonine transport into Trypanosoma brucei elicited by variation in hydrogen ion concentration. 1. The dependence of V and V/K(m) for threonine transport into Trypanosoma brucei upon the external concentration of H(+) was studied. 2. Two ionizing groups, the alpha-amino group of the substrate and a group at the substrate-binding site of the carrier, were found to influence the observed kinetic behaviour of transport. 3. The pK of the group at the substrate-binding site on the free carrier was found to be 6.95 at 30 degrees C and to be temperature-dependent; its heat of ionization was -63.8kJ, which is outside the range for most proton dissociations and suggests a significant contribution from some other source, possibly the remainder of the carrier or the membrane environment. 4. Binding of substrate caused the pK of its alpha-amino group to shift to a higher value, whereas that of the carrier group shifted to a lower value (6.65 at 30 degrees C). 5. The ionic interaction between substrate and carrier appeared to be involved in the stabilizing of the protonated substrate and the species of the carrier-substrate complex required for the membrane-translocation step. 6. The same ionic species of carrier-substrate complex is required for both substrate dissociation and translocation of the substrate through the membrane. 7. H(+) symport or antiport did not occur during threonine uptake. | [
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|
PMID:18142 | Effect of prolonged ethanol ingestion on hepatic lipogenesis and related enzyme activities. | 1. Hepatic lipogenesis in vivo and the activities of enzymes associated with fatty acid synthesis in the liver were studied in rats fed for 21 days on liquid diets containing ethanol. 2. The ethanol-fed rats developed a moderate hepatic triacylglycerol accumulation during this period. When carbohydrate was replaced by ethanol in the diet, the rate of fatty acid synthesis was slower in the ethanol-fed rats on low-, medium- and high-fat diets than in the appropriate controls. However, when the fat/carbohydrate ratio was kept the same in the ethanol-fed and control rats, ethanol had no influence on the rate of fatty acid synthesis. 3. Glucose 6-phosphate dehydrogenase activity was lower in the ethanol-fed group. ;Malic' enzyme activity did not change during the ethanol treatment when the fat/carbohydrate ratio was kept unchanged. 4. The ATP citrate lyase activity was lower in the ethanol-fed rats on all diets, whereas acetyl-CoA synthetase activity was independent of the composition of the control diet, but was lower in the ethanol-fed rats, in which the concentration of the active form of pyruvate dehydrogenase was also lower. 5. It is concluded that hepatic fatty acid synthesis does not play any major role in ethanol-induced triacylglycerol accumulation. Careful design of the diets is necessary to reveal the specific effects of ethanol on the enzymes associated with lipogenesis. | Effect of prolonged ethanol ingestion on hepatic lipogenesis and related enzyme activities. 1. Hepatic lipogenesis in vivo and the activities of enzymes associated with fatty acid synthesis in the liver were studied in rats fed for 21 days on liquid diets containing ethanol. 2. The ethanol-fed rats developed a moderate hepatic triacylglycerol accumulation during this period. When carbohydrate was replaced by ethanol in the diet, the rate of fatty acid synthesis was slower in the ethanol-fed rats on low-, medium- and high-fat diets than in the appropriate controls. However, when the fat/carbohydrate ratio was kept the same in the ethanol-fed and control rats, ethanol had no influence on the rate of fatty acid synthesis. 3. Glucose 6-phosphate dehydrogenase activity was lower in the ethanol-fed group. ;Malic' enzyme activity did not change during the ethanol treatment when the fat/carbohydrate ratio was kept unchanged. 4. The ATP citrate lyase activity was lower in the ethanol-fed rats on all diets, whereas acetyl-CoA synthetase activity was independent of the composition of the control diet, but was lower in the ethanol-fed rats, in which the concentration of the active form of pyruvate dehydrogenase was also lower. 5. It is concluded that hepatic fatty acid synthesis does not play any major role in ethanol-induced triacylglycerol accumulation. Careful design of the diets is necessary to reveal the specific effects of ethanol on the enzymes associated with lipogenesis. | [
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|
PMID:18143 | The mechanism of inhibition by acidosis of gluconeogenesis from lactate in rat liver. | 1. Gluconeogenesis from lactate or pyruvate was studied in perfused livers from starved rats at perfusate pH7.4 or under conditions simulating uncompensated metabolic acidosis (perfusate pH6.7-6.8). 2. In 'acidotic' perfusions gluconeogenesis and uptake of lactate or pyruvate were decreased. 3. Measurement of hepatic intermediate metabolites suggested that the effect of acidosis was exerted at a stage preceding phosphoenolpyruvate. 4. Total intracellular oxaloacetate concentration was significantly decreased in the acidotic livers perfused with lactate. 5. It is suggested that decreased gluconeogenesis in acidosis is due to substrate limitation of phosphoenolypyruvate carboxykinase. 6. The possible reasons for the fall in oxaloacetate concentration in acidotic livers are discussed; two of the more likely mechanisms are inhibition of the pyruvate carboxylase system and a change in the [malate]/[oxaloacetate] ratio due to the fall in intracellular pH. | The mechanism of inhibition by acidosis of gluconeogenesis from lactate in rat liver. 1. Gluconeogenesis from lactate or pyruvate was studied in perfused livers from starved rats at perfusate pH7.4 or under conditions simulating uncompensated metabolic acidosis (perfusate pH6.7-6.8). 2. In 'acidotic' perfusions gluconeogenesis and uptake of lactate or pyruvate were decreased. 3. Measurement of hepatic intermediate metabolites suggested that the effect of acidosis was exerted at a stage preceding phosphoenolpyruvate. 4. Total intracellular oxaloacetate concentration was significantly decreased in the acidotic livers perfused with lactate. 5. It is suggested that decreased gluconeogenesis in acidosis is due to substrate limitation of phosphoenolypyruvate carboxykinase. 6. The possible reasons for the fall in oxaloacetate concentration in acidotic livers are discussed; two of the more likely mechanisms are inhibition of the pyruvate carboxylase system and a change in the [malate]/[oxaloacetate] ratio due to the fall in intracellular pH. | [
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|
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