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PMID:16655 | Possible regulation of thiamine diphosphatase activity in rat brain microsomes by lipids. | The effects of various treatments, which affect membrane structure, on microsomal thiamine diphosphatase and thiamine triphosphatase activities of rat brain, were examined. The treatment of micorosomes at alkaline pH caused a 2-fold activation of the thiamine diphosphatase, this being related to a change in membrane structure which was evidenced by a decrease of the turbidity of the microsomal suspension. Repeated freezing and thawing after hypo-osmotic treatment also increased the activity of microsomal thiamine diphosphatase. In addition, the thiamine diphosphatase activity was enhanced by treatment of the microsomes with phospholipase C or acetone. This lipid depletion resulted in a marked reduction in the apparent Km value of the thiamine diphosphatase with a corresponding loss in heat stability of the enzyme. We found further that brain thiamine diphosphatase was solubilized by Triton X-100. This decreased the phospholipid content in the preparation, but did not affect the apparent Km value and heat stability of the enzyme. In contrast with thiamine diphosphatase, thiamine triphosphatase was inactivated by treatment at alkaline pH or with acetone. However, treatment with phospholipase C did not affect the activity of thiamine triphosphatase. | Possible regulation of thiamine diphosphatase activity in rat brain microsomes by lipids. The effects of various treatments, which affect membrane structure, on microsomal thiamine diphosphatase and thiamine triphosphatase activities of rat brain, were examined. The treatment of micorosomes at alkaline pH caused a 2-fold activation of the thiamine diphosphatase, this being related to a change in membrane structure which was evidenced by a decrease of the turbidity of the microsomal suspension. Repeated freezing and thawing after hypo-osmotic treatment also increased the activity of microsomal thiamine diphosphatase. In addition, the thiamine diphosphatase activity was enhanced by treatment of the microsomes with phospholipase C or acetone. This lipid depletion resulted in a marked reduction in the apparent Km value of the thiamine diphosphatase with a corresponding loss in heat stability of the enzyme. We found further that brain thiamine diphosphatase was solubilized by Triton X-100. This decreased the phospholipid content in the preparation, but did not affect the apparent Km value and heat stability of the enzyme. In contrast with thiamine diphosphatase, thiamine triphosphatase was inactivated by treatment at alkaline pH or with acetone. However, treatment with phospholipase C did not affect the activity of thiamine triphosphatase. | [
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PMID:16656 | Inhibition of alkaline phosphatase by sialic acid. | The interaction of human organ alkaline phosphatases (orthophosphoric-monoester phosphohydrolases (alkaline optimum), EC 3.1.3.1) with sugars was studied. Hexosamines, N-acetylneuraminic acid (NANA or sialic acid), N-acetylmuramic acid and N-acetylglycolylneuraminic acid inhibited human organ alkaline phosphatase activities. Of these, sialic acid was the most effective inhibitor. The pH profiles for the enzymes in the absence and presence of sialic acid were similar. The sialic acid - enzyme complex was more heat stable than the free enzyme between 20 and 45 degrees C. Lineweaver-Burk plots of 1/v versus 1/S at various concentrations of sialic acid showed intersecting straight lines indicating that the mechanism of inhibition was a mixed type. The Ki value obtained from the plots of 1/v versus the square of sialic acid concentration was 0.07 mM for the hepatic, sialidase-treated hepatic, and intestinal alkaline phosphatases. The respective Hill coefficients varied somewhat with the alkaline phosphatase isoenzyme. Hyperbolic curves were obtained when the percentage of remaining activity was plotted against the substrate concentration at different concentrations of sialic acid. The Hill coefficient was lowered in the presence of sialic acid. The sialidase-treated hepatic enzymes used gave the most effective conversion. Partial denaturation of the enzyme with urea, or pronase digestion had a little if any effect on the sialic acid inhibition with constant time. | Inhibition of alkaline phosphatase by sialic acid. The interaction of human organ alkaline phosphatases (orthophosphoric-monoester phosphohydrolases (alkaline optimum), EC 3.1.3.1) with sugars was studied. Hexosamines, N-acetylneuraminic acid (NANA or sialic acid), N-acetylmuramic acid and N-acetylglycolylneuraminic acid inhibited human organ alkaline phosphatase activities. Of these, sialic acid was the most effective inhibitor. The pH profiles for the enzymes in the absence and presence of sialic acid were similar. The sialic acid - enzyme complex was more heat stable than the free enzyme between 20 and 45 degrees C. Lineweaver-Burk plots of 1/v versus 1/S at various concentrations of sialic acid showed intersecting straight lines indicating that the mechanism of inhibition was a mixed type. The Ki value obtained from the plots of 1/v versus the square of sialic acid concentration was 0.07 mM for the hepatic, sialidase-treated hepatic, and intestinal alkaline phosphatases. The respective Hill coefficients varied somewhat with the alkaline phosphatase isoenzyme. Hyperbolic curves were obtained when the percentage of remaining activity was plotted against the substrate concentration at different concentrations of sialic acid. The Hill coefficient was lowered in the presence of sialic acid. The sialidase-treated hepatic enzymes used gave the most effective conversion. Partial denaturation of the enzyme with urea, or pronase digestion had a little if any effect on the sialic acid inhibition with constant time. | [
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|
PMID:16657 | Some properties of human liver acid alpha-glucosidase. | 1. Albumin activates human liver acid alpha-glucosidase (alpha-D-glucoside hydrolase, EC 3.2.1.20). From the Arrhenius plot, pH-dependence and Lineweaver-Burk plots it can be concluded that this activation is not only due to stabilisation of the enzyme, but also influences the enzymatic activity. It is proposed that for optimal functioning human liver acid alpha-glucosidase needs a protein environment. 2. Glycogen has a competitive inhibitory effect on the hydrolysis of 4-methylumbelliferyl-alpha-D-glucopyranoside, in contrast to maltose which exhibits a non-competitive type of inhibition. It is concluded that two catalytic sites exist, one for glycogen and one for maltose, while both sites influence each other. With glycogen as substrate a break in the Arrhenius plot is found. This is not the case when maltose is used as substrate. 3. The effect of antibody raised against human liver acid alpha-glucosidase on the activity of human liver acid alpha-glucosidase is studied. No corss-reacting material could be demonstrated in the liver of a patient with glycogen storage disease Type II (M. Pompe, acid alpha-glucosidase deficiency). | Some properties of human liver acid alpha-glucosidase. 1. Albumin activates human liver acid alpha-glucosidase (alpha-D-glucoside hydrolase, EC 3.2.1.20). From the Arrhenius plot, pH-dependence and Lineweaver-Burk plots it can be concluded that this activation is not only due to stabilisation of the enzyme, but also influences the enzymatic activity. It is proposed that for optimal functioning human liver acid alpha-glucosidase needs a protein environment. 2. Glycogen has a competitive inhibitory effect on the hydrolysis of 4-methylumbelliferyl-alpha-D-glucopyranoside, in contrast to maltose which exhibits a non-competitive type of inhibition. It is concluded that two catalytic sites exist, one for glycogen and one for maltose, while both sites influence each other. With glycogen as substrate a break in the Arrhenius plot is found. This is not the case when maltose is used as substrate. 3. The effect of antibody raised against human liver acid alpha-glucosidase on the activity of human liver acid alpha-glucosidase is studied. No corss-reacting material could be demonstrated in the liver of a patient with glycogen storage disease Type II (M. Pompe, acid alpha-glucosidase deficiency). | [
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|
PMID:16658 | Lysosomal phospholipase A activities of rat ovarian tissue. | 1.1. Lysosome-enriched fractions were prepared by differential centrifugation of homogenates of luteinized rats ovaries. Acid phospholipase A activities were characterized with [U-14C]diacyl-sn-glycero-3-phosphocholine and 1-palmitoyl-2-[9,10-3H]- or [1-14C]oleoyl-sn-glycero-3-phosphocholine as substrates. Acid phospholipase A1 activity had properties similar to other hydrolases of lysosomal origin; subcellular distribution, latency and acidic pH optimum. Acid phospholipase A2 activity with similar characteristics was also tentatively identified. We were unable to exclude the possibility that the combined action of phospholipase A1 and lysophospholipase contributed to the release of acyl moieties from the 2-position of the synthetic substrates. 2. Lysophospholipase activity was present in the lysosome-enriched fractions. This activity had an alkaline pH optimum. 3. Phospholipase A1 and A2 activities solubilized from lysosome fractions by freeze-thawing were inhibited by Ca2+ and slightly activated by EDTA. A Ca2+- stimulated phospholipase A2 activity, with an alkaline pH optimum, remained in the particulate residue of freeze-thawed lysosome preparations. This activity is believed to represent mitochondrial contamination. 4. Activities of acid phospholipase A, as well as other acid hydrolases, increased approx. 1.5-fold between 1 and 4 days following induction of luteinizatin, suggesting a hormonal influence on lysosomal enzyme activities. | Lysosomal phospholipase A activities of rat ovarian tissue. 1.1. Lysosome-enriched fractions were prepared by differential centrifugation of homogenates of luteinized rats ovaries. Acid phospholipase A activities were characterized with [U-14C]diacyl-sn-glycero-3-phosphocholine and 1-palmitoyl-2-[9,10-3H]- or [1-14C]oleoyl-sn-glycero-3-phosphocholine as substrates. Acid phospholipase A1 activity had properties similar to other hydrolases of lysosomal origin; subcellular distribution, latency and acidic pH optimum. Acid phospholipase A2 activity with similar characteristics was also tentatively identified. We were unable to exclude the possibility that the combined action of phospholipase A1 and lysophospholipase contributed to the release of acyl moieties from the 2-position of the synthetic substrates. 2. Lysophospholipase activity was present in the lysosome-enriched fractions. This activity had an alkaline pH optimum. 3. Phospholipase A1 and A2 activities solubilized from lysosome fractions by freeze-thawing were inhibited by Ca2+ and slightly activated by EDTA. A Ca2+- stimulated phospholipase A2 activity, with an alkaline pH optimum, remained in the particulate residue of freeze-thawed lysosome preparations. This activity is believed to represent mitochondrial contamination. 4. Activities of acid phospholipase A, as well as other acid hydrolases, increased approx. 1.5-fold between 1 and 4 days following induction of luteinizatin, suggesting a hormonal influence on lysosomal enzyme activities. | [
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|
PMID:16659 | Phospholipase A in pulmonary secretions of patients with alveolar proteinosis. | This report presents evidence for the presence of phospholipase A2 (EC 3.1.1.4) activity in the insoluble pulmonary secretions of patients with alveolar proteinosis. The enzyme activity has a pH optimum between 7.5 and 8.5 and is stimulated by deoxycholate and Ca2+. | Phospholipase A in pulmonary secretions of patients with alveolar proteinosis. This report presents evidence for the presence of phospholipase A2 (EC 3.1.1.4) activity in the insoluble pulmonary secretions of patients with alveolar proteinosis. The enzyme activity has a pH optimum between 7.5 and 8.5 and is stimulated by deoxycholate and Ca2+. | [
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|
PMID:16660 | Specific phospholipid requirement for activity of the purified respiratory chain NADH dehydrogenase of Escherichia coli. | The highly purified respiratory chain NADH dehydrogenase (EC 1.6.99.3) of Escherichia coli is inactive in the absence of detergent or phospholipid. Triton X-100 is the detergent that gives optimal activity, but the Triton X-100-activated enzyme is stimulated an additional 2-fold by E. coli phospholipids. Phosphatidylglycerol and diphosphatidylglycerol are the most effective lipid activators. The activated complex prepared with diphosphatidylglycerol is stable, whereas that with phosphatidylglycerol loses activity rapidly. Maximum activation by phospholipids occurs after preincubation at 0 degrees C and at pH 7. Triton X-100 is required at low concentrations for lipid activation, but high concentrations interfere with the activation. When the enzyme is optimally activated by phospholipids, it may be additionally activated 2-fold by spermidine, but not by magnesium. In contrast, the Triton X-100-activated form of the enzyme is stimulated by several divalent cations, without specificity. Thus, the most stable, active form of the purified NADH dehydrogenase is generated in the presence of diphosphatidylglycerol and spermidine. | Specific phospholipid requirement for activity of the purified respiratory chain NADH dehydrogenase of Escherichia coli. The highly purified respiratory chain NADH dehydrogenase (EC 1.6.99.3) of Escherichia coli is inactive in the absence of detergent or phospholipid. Triton X-100 is the detergent that gives optimal activity, but the Triton X-100-activated enzyme is stimulated an additional 2-fold by E. coli phospholipids. Phosphatidylglycerol and diphosphatidylglycerol are the most effective lipid activators. The activated complex prepared with diphosphatidylglycerol is stable, whereas that with phosphatidylglycerol loses activity rapidly. Maximum activation by phospholipids occurs after preincubation at 0 degrees C and at pH 7. Triton X-100 is required at low concentrations for lipid activation, but high concentrations interfere with the activation. When the enzyme is optimally activated by phospholipids, it may be additionally activated 2-fold by spermidine, but not by magnesium. In contrast, the Triton X-100-activated form of the enzyme is stimulated by several divalent cations, without specificity. Thus, the most stable, active form of the purified NADH dehydrogenase is generated in the presence of diphosphatidylglycerol and spermidine. | [
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|
PMID:16661 | Effect of hydrophobic probes on the higher structure of D-amino acid oxidase. | 1. The holoenzyme of D-amino acid oxidase [D-amino acid: O2 oxidoreductase (deaminating), EC 1.4.3.3] was found to combine with 1-anilinonaphthalene-8-sulfonate without liberation of its coenzyme, FAD. No energy transfer interaction was found to occur between the bound dye and FAD of the holoenzyme. On the other hand, when the apoenzyme was bound to the dye and then to FAD, energy transfer interaction between the bound dye and bound FAD was observed. In both cases, the dye competes with the substrate, D-alanine. It is concluded that the dye bound to the holoenzyme is oriented in such a special manner that the mutual orientation factor between the dye and FAD becomes very small in magnitude. 2. When the apoenzyme combined with the dye, the monomer-dimer equilibrium of the apoenzyme shifted towards the dimer. On the other hand, 4-monobenzoylamido-4'-aminostilbene-2,2'-disulfonate combined with the apoenzyme to induce monomerization. | Effect of hydrophobic probes on the higher structure of D-amino acid oxidase. 1. The holoenzyme of D-amino acid oxidase [D-amino acid: O2 oxidoreductase (deaminating), EC 1.4.3.3] was found to combine with 1-anilinonaphthalene-8-sulfonate without liberation of its coenzyme, FAD. No energy transfer interaction was found to occur between the bound dye and FAD of the holoenzyme. On the other hand, when the apoenzyme was bound to the dye and then to FAD, energy transfer interaction between the bound dye and bound FAD was observed. In both cases, the dye competes with the substrate, D-alanine. It is concluded that the dye bound to the holoenzyme is oriented in such a special manner that the mutual orientation factor between the dye and FAD becomes very small in magnitude. 2. When the apoenzyme combined with the dye, the monomer-dimer equilibrium of the apoenzyme shifted towards the dimer. On the other hand, 4-monobenzoylamido-4'-aminostilbene-2,2'-disulfonate combined with the apoenzyme to induce monomerization. | [
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|
PMID:16662 | The interaction of histone H3 with histone H4 and with other histones studied by 19F nuclear magnetic resonance. | The behaviour, upon variations in ionic strength, pH and temperature of 19F nuclear nuclear magnetic resonance signals of the trifluoroacetonylated derivative of histone H3 is compared with those of the H3-H4 complex and of the Hv fraction (an equimolar mixture of H2A, H2B, H3 and h4). The line width of the 19F-labelled histone H3 signals increases with ionic strength or pH, an effect consistent with aggregation of the protein. In the case of H3-H4 complex or Hv the line width decreases at intermediate ionic strengths (0.1-0.25 M NaCl). This effect is interpreted as the consequence of the formation of a well defined structure with ionic strength. At high salt concentrations the line width increases as a consequence of the final rigid quaternary structure or of the formation of higher aggregates. | The interaction of histone H3 with histone H4 and with other histones studied by 19F nuclear magnetic resonance. The behaviour, upon variations in ionic strength, pH and temperature of 19F nuclear nuclear magnetic resonance signals of the trifluoroacetonylated derivative of histone H3 is compared with those of the H3-H4 complex and of the Hv fraction (an equimolar mixture of H2A, H2B, H3 and h4). The line width of the 19F-labelled histone H3 signals increases with ionic strength or pH, an effect consistent with aggregation of the protein. In the case of H3-H4 complex or Hv the line width decreases at intermediate ionic strengths (0.1-0.25 M NaCl). This effect is interpreted as the consequence of the formation of a well defined structure with ionic strength. At high salt concentrations the line width increases as a consequence of the final rigid quaternary structure or of the formation of higher aggregates. | [
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|
PMID:16664 | The denaturation of beta-lactoglobulin-A at pH 2. | The denaturation of beta-lactoglobulin-A by heat and guanidine hydrochloride at pH 2 has been investigated. The effect of ethylene glycol on the thermal denaturation at this pH has also been studied. The conditions of the experiments have been chosen so as to eliminate complications arising out of disulfide interchange, changes in the degree of association of the protein during denaturation, and intermolecular aggregation. The physical parameters characterizing the denatured states of the protein which are produced by heat and guanidine hydrochloride have been determined. The thermodynamic parameters for these transitions have been estimated using a two-state hypothesis in each case. Both the physical and thermodynamic parameters indicate that the heat-denatured state of beta-lactoglobulin-A retains about 15-20% of residual structure which is destroyed on adding guanidine hydrochloride. | The denaturation of beta-lactoglobulin-A at pH 2. The denaturation of beta-lactoglobulin-A by heat and guanidine hydrochloride at pH 2 has been investigated. The effect of ethylene glycol on the thermal denaturation at this pH has also been studied. The conditions of the experiments have been chosen so as to eliminate complications arising out of disulfide interchange, changes in the degree of association of the protein during denaturation, and intermolecular aggregation. The physical parameters characterizing the denatured states of the protein which are produced by heat and guanidine hydrochloride have been determined. The thermodynamic parameters for these transitions have been estimated using a two-state hypothesis in each case. Both the physical and thermodynamic parameters indicate that the heat-denatured state of beta-lactoglobulin-A retains about 15-20% of residual structure which is destroyed on adding guanidine hydrochloride. | [
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|
PMID:16667 | [Influence of pH on the steady state kinetics of electron transfer through the cytochrome chain of submitochondrial particles. Kinetic model for regulating the activity of carriers by the local concentration of hydrogen ions in the membrane]. | The kinetic parameters of the submitochondrial particles cytochrome chain obtained from steady-state kinetics were studied for pH dependence. The life-times of the activated states (tau) for cytochrome pairs b leads to c1 and a leads to a3 are shown to bear dissimilar dependence on pH of the medium, while for cytochrome pairs c1 leads to c and c leads to a they display practically no pH dependence at all. The rate constants of the non-activated state (alphai-kiCo) decreased for the pair b leads to c1 and increased for a leads to a3 with the increase of pH from 6.5 to 8.5. The apparent pK values obtained therefrom were 7.2 and 8.9, respectively. A kinetic model is proposed suggesting that local pH in the mitochondrial membrane, dependent on the rate of electron transfer, may be a controlling factor for the ratio of activated and non-activated carrier states. The model is in good consistence with the experimental dependences of k'i on V and the pH dependences of alpha2 for b leads to c1 and a leads to a3. It also gives a qualitative prediction for the pH dependences of the ordinate intercepts of the straight lines in l/(k'i--alphai) vs. l/V plots. The rate constants for the diffusion of hydrogen and hydroxyl ions in the membrane are estimated on the basis of our kinetic data to be 10(4)--10(5) s-1 and 10(2)--10(3) s-i, respectively. | [Influence of pH on the steady state kinetics of electron transfer through the cytochrome chain of submitochondrial particles. Kinetic model for regulating the activity of carriers by the local concentration of hydrogen ions in the membrane]. The kinetic parameters of the submitochondrial particles cytochrome chain obtained from steady-state kinetics were studied for pH dependence. The life-times of the activated states (tau) for cytochrome pairs b leads to c1 and a leads to a3 are shown to bear dissimilar dependence on pH of the medium, while for cytochrome pairs c1 leads to c and c leads to a they display practically no pH dependence at all. The rate constants of the non-activated state (alphai-kiCo) decreased for the pair b leads to c1 and increased for a leads to a3 with the increase of pH from 6.5 to 8.5. The apparent pK values obtained therefrom were 7.2 and 8.9, respectively. A kinetic model is proposed suggesting that local pH in the mitochondrial membrane, dependent on the rate of electron transfer, may be a controlling factor for the ratio of activated and non-activated carrier states. The model is in good consistence with the experimental dependences of k'i on V and the pH dependences of alpha2 for b leads to c1 and a leads to a3. It also gives a qualitative prediction for the pH dependences of the ordinate intercepts of the straight lines in l/(k'i--alphai) vs. l/V plots. The rate constants for the diffusion of hydrogen and hydroxyl ions in the membrane are estimated on the basis of our kinetic data to be 10(4)--10(5) s-1 and 10(2)--10(3) s-i, respectively. | [
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|
PMID:16668 | [Properties of alpha-chymotrypsin and cis-cinnamoylchymotrypsin in free, covalently bound to a carrier and microcapsulated states]. | alpha-Chymotrypsin and its light-sensitive derivative, cis-cinnamoylchymotrypsin, free and immobilysed (by means of microcapsulation, covalent binding with sepharose 4B and p-aminobenzyl cellulose) are studied. Effect of pH on the hydrolysis rate of N-alpha-acetyl-L-tyrosine ethyl ester by different immobilized enzyme preparations, their acylation with isomeric mixture of cis- and trans-cinnamoylimidazole, reactivation of stable cis-derivatives of different enzyme samples and thermal stability of native and microcapsulated enzyme preparations are investigated. | [Properties of alpha-chymotrypsin and cis-cinnamoylchymotrypsin in free, covalently bound to a carrier and microcapsulated states]. alpha-Chymotrypsin and its light-sensitive derivative, cis-cinnamoylchymotrypsin, free and immobilysed (by means of microcapsulation, covalent binding with sepharose 4B and p-aminobenzyl cellulose) are studied. Effect of pH on the hydrolysis rate of N-alpha-acetyl-L-tyrosine ethyl ester by different immobilized enzyme preparations, their acylation with isomeric mixture of cis- and trans-cinnamoylimidazole, reactivation of stable cis-derivatives of different enzyme samples and thermal stability of native and microcapsulated enzyme preparations are investigated. | [
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PMID:16669 | [Role of low-molecular weight factors isolated from Methanobacillus kuzneceovii in the activating effect of visible light on methane formation and reduction of pyridine nucleotides]. | Four low molecular weight fluorescent factors are isolated from thermophylic methaneproducing facteria Methanobacterium kuzneceovii. These factors are: the factor 340; the factor 420 (both reduced and oxidized); and a flavine derivative, comprising together with proteins a biochemical system, which reduces pyridine nucleotides in dark (at 55degrees C) and in the light (at 21degrees C). | [Role of low-molecular weight factors isolated from Methanobacillus kuzneceovii in the activating effect of visible light on methane formation and reduction of pyridine nucleotides]. Four low molecular weight fluorescent factors are isolated from thermophylic methaneproducing facteria Methanobacterium kuzneceovii. These factors are: the factor 340; the factor 420 (both reduced and oxidized); and a flavine derivative, comprising together with proteins a biochemical system, which reduces pyridine nucleotides in dark (at 55degrees C) and in the light (at 21degrees C). | [
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|
PMID:16670 | The effect of birth on the maturation of hepatic cytochrome(s) P-450 mono-oxygenase and tyrosine aminotransferase activities in the guinea pig. | Mixed coat guinea pigs delivered by Cesarian section 5 days before term were compared to spontaneously delivered full-term animals with respect to the postnatal maturation of hepatic mono-oxygenase activity in vitro toward aniline and p-chloro-N-methylaniline. Tyrosine aminotransferase acitivity was studied in the same preparations as a positive control for birth-related phenomena. Mono-oxygenase activities toward both sustrates increased significantly in both premature and full-term animals during the first 3 postnatal days and approached adult values 72 h after birth. The maturation of tyrosine aminotransferase activity occured in a qualitatively similar fashion. The mechanism through which birth initiates the maturation of drug oxidative capacity is unresolved; the gestational age at which competence to respond to the event of birth is acquired, remains undefined. | The effect of birth on the maturation of hepatic cytochrome(s) P-450 mono-oxygenase and tyrosine aminotransferase activities in the guinea pig. Mixed coat guinea pigs delivered by Cesarian section 5 days before term were compared to spontaneously delivered full-term animals with respect to the postnatal maturation of hepatic mono-oxygenase activity in vitro toward aniline and p-chloro-N-methylaniline. Tyrosine aminotransferase acitivity was studied in the same preparations as a positive control for birth-related phenomena. Mono-oxygenase activities toward both sustrates increased significantly in both premature and full-term animals during the first 3 postnatal days and approached adult values 72 h after birth. The maturation of tyrosine aminotransferase activity occured in a qualitatively similar fashion. The mechanism through which birth initiates the maturation of drug oxidative capacity is unresolved; the gestational age at which competence to respond to the event of birth is acquired, remains undefined. | [
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|
PMID:16671 | Human cytomegalovirus. A review of developments between 1970 and 1976. I. Clinical developments. | Cytomegalovirus (CMV), like other members of the herpesviruses, is widely distributed in human populations where the frequency of seropositive individuals is influenced by such factors as age, sex and socio-economic conditions. While this virus causes such diseases as mononucleosis, it is also implicated in autoimmune phenomena and plays an adverse role renal and bone marrow transplantation. Perhaps the most menacing aspect of CMV is the role which it play in congenital malformations resulting from in utero or neo-natal infection. Indeed, this virus is one of the few which can be transmitted vertically. The above mentioned clinical aspects of CMV are discussed here in light of recent clinically studies. The second part of this review will be devoted to the great mass of information recently acquired through experimentation. | Human cytomegalovirus. A review of developments between 1970 and 1976. I. Clinical developments. Cytomegalovirus (CMV), like other members of the herpesviruses, is widely distributed in human populations where the frequency of seropositive individuals is influenced by such factors as age, sex and socio-economic conditions. While this virus causes such diseases as mononucleosis, it is also implicated in autoimmune phenomena and plays an adverse role renal and bone marrow transplantation. Perhaps the most menacing aspect of CMV is the role which it play in congenital malformations resulting from in utero or neo-natal infection. Indeed, this virus is one of the few which can be transmitted vertically. The above mentioned clinical aspects of CMV are discussed here in light of recent clinically studies. The second part of this review will be devoted to the great mass of information recently acquired through experimentation. | [
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|
PMID:16672 | The effects of adrenergic agonists and blockers on antigen-induced DNA synthesis in vitro. | The effects of both alpha and beta adrenergic agonists and blockers on antigen-stimulated DNA synthesis in human lymphocyte cultures were studied. Results show that antigen-induced responses were enhanced by the presence of the beta blockers, propranolol and dichloroisoproterenol, and that this effect appeared to be specific blocking of the lymphocyte beta receptor since D (+) propranolol, a compound devoid of such acitvity, has no effect. Similarly, and alpha adrenergic agonist such as norepinephrine enhanced lymphocyte responsiveness. | The effects of adrenergic agonists and blockers on antigen-induced DNA synthesis in vitro. The effects of both alpha and beta adrenergic agonists and blockers on antigen-stimulated DNA synthesis in human lymphocyte cultures were studied. Results show that antigen-induced responses were enhanced by the presence of the beta blockers, propranolol and dichloroisoproterenol, and that this effect appeared to be specific blocking of the lymphocyte beta receptor since D (+) propranolol, a compound devoid of such acitvity, has no effect. Similarly, and alpha adrenergic agonist such as norepinephrine enhanced lymphocyte responsiveness. | [
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|
PMID:16674 | [Lactic acid as a factor in altering vascular reactivity]. | It was shown that the constrictor responses to the electrostimulation of the isolated vessel segments were replaced by dilatation when the drugs were contained in the lactic acid solution. The capacity to constrictor effects was not lost completely, but these effects appeared in repsonse to the intensive stimulation. Changes in the character of these reactions to the electrostimulation were connected with the changes in the pH of the solution, as well as with the specific action of lactic acid. | [Lactic acid as a factor in altering vascular reactivity]. It was shown that the constrictor responses to the electrostimulation of the isolated vessel segments were replaced by dilatation when the drugs were contained in the lactic acid solution. The capacity to constrictor effects was not lost completely, but these effects appeared in repsonse to the intensive stimulation. Changes in the character of these reactions to the electrostimulation were connected with the changes in the pH of the solution, as well as with the specific action of lactic acid. | [
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|
PMID:16675 | [Graft vs host reaction in reciprocal combinations of mouse strains differing by the H-2 complex of histocompatibility]. | Intraperitoneal transplantation of 0.5 x 10(7), 1 x 10(7) or 2 x 10(7) spleen cells from the C57BL mice to newborn CBA recipients induced an acute form or runt disease which resulted in the death of 43%, 86% or 95% of the recipient mice, respectively, in the course of 2--3 weeks after the cell transfer. Preliminary immunization of C57BL donors with CBA isoantigens led to a marked enhancement, and immunization with foreign antigens (sheep red blood cells)--to weakening the reaction. In reverse combination of mouse strains the runt disease was 4--5 times less severe and no "preimmunization effect" occurred. In C57BL leads to CBA combination the reaction was accompanied by proliferation of pyroninophilic mononuclears and follicular destruction, while in the CBA leads to C57BL combination-by the retardation of their growth. | [Graft vs host reaction in reciprocal combinations of mouse strains differing by the H-2 complex of histocompatibility]. Intraperitoneal transplantation of 0.5 x 10(7), 1 x 10(7) or 2 x 10(7) spleen cells from the C57BL mice to newborn CBA recipients induced an acute form or runt disease which resulted in the death of 43%, 86% or 95% of the recipient mice, respectively, in the course of 2--3 weeks after the cell transfer. Preliminary immunization of C57BL donors with CBA isoantigens led to a marked enhancement, and immunization with foreign antigens (sheep red blood cells)--to weakening the reaction. In reverse combination of mouse strains the runt disease was 4--5 times less severe and no "preimmunization effect" occurred. In C57BL leads to CBA combination the reaction was accompanied by proliferation of pyroninophilic mononuclears and follicular destruction, while in the CBA leads to C57BL combination-by the retardation of their growth. | [
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|
PMID:16681 | Blood pressure and heart rate and withdrawal of antihypertensive drugs. | The immediate effects on heart rate and blood pressure of withdrawing antihypertensive drugs were studied over three-day periods in 26 patients. Four groups of drugs were studied. After withdrawal all patients taking clonidine showed a considerable increase in heart rate and blood pressure with intense ectopic activity. Patients taking postganglionic neurone-blocking drugs showed a similar but less pronounced reaction with increased ventricular ectopic activity. No alarming reactions were seen after withdrawal of methyldopa or beta-blocking drugs. Methyldopa and, especially, beta-blocking drugs are less likely to produce withdrawal reactions than clonidine or the postganglionic neurone-blocking drugs, and patients taking these drugs are therefore less likely to suffer violent reactions if they forget to take their tablets. | Blood pressure and heart rate and withdrawal of antihypertensive drugs. The immediate effects on heart rate and blood pressure of withdrawing antihypertensive drugs were studied over three-day periods in 26 patients. Four groups of drugs were studied. After withdrawal all patients taking clonidine showed a considerable increase in heart rate and blood pressure with intense ectopic activity. Patients taking postganglionic neurone-blocking drugs showed a similar but less pronounced reaction with increased ventricular ectopic activity. No alarming reactions were seen after withdrawal of methyldopa or beta-blocking drugs. Methyldopa and, especially, beta-blocking drugs are less likely to produce withdrawal reactions than clonidine or the postganglionic neurone-blocking drugs, and patients taking these drugs are therefore less likely to suffer violent reactions if they forget to take their tablets. | [
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|
PMID:16678 | [Blood gas measurements and automatization (author's transl)]. | The Corning 175, a fully automatic new blood-gas analyzer, was tested and compared with manual analyzers (Eschweiler-Radiometer). The precision was evaluated by means of tonometered bloods and precision gas mixtures. With the Corning 175 four parameters are measured: pH, PCO2, PO2, barometric pressure, and four computed: HCO3-, BE, oxygen content, oxygen saturation. These are automatically corrected for patient hemoglobin and temperature. A microprocessor controls the sequencing of all operations during the calibrations and the measurements and continuously checks the performances of the electrodes and the entire system. The operator part is limited to the introduction of blood. The advantages and the fiability of the automatism in clinical routine are described. | [Blood gas measurements and automatization (author's transl)]. The Corning 175, a fully automatic new blood-gas analyzer, was tested and compared with manual analyzers (Eschweiler-Radiometer). The precision was evaluated by means of tonometered bloods and precision gas mixtures. With the Corning 175 four parameters are measured: pH, PCO2, PO2, barometric pressure, and four computed: HCO3-, BE, oxygen content, oxygen saturation. These are automatically corrected for patient hemoglobin and temperature. A microprocessor controls the sequencing of all operations during the calibrations and the measurements and continuously checks the performances of the electrodes and the entire system. The operator part is limited to the introduction of blood. The advantages and the fiability of the automatism in clinical routine are described. | [
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|
PMID:16685 | Transmitter histochemistry of the rat olfactory bulb. I. Immunohistochemical localization of monoamine synthesizing enzymes. Support for intrabulbar, periglomerular dopamine neurons. | The rat olfactory bulb was studied at the light and electron microscopic level with the indirect immunofluorescence technique and the unlabelled antibody enzyme method (PAP-technique), respectively. Antibodies to all 4 enzymes in the catecholamine synthesis were used. In the principal bulb the first two enzymes, tyrosine hydroxylase (TH) and DOPA decarboxylase (DDC), but not dopamine-beta-hydroxylase (DBH), were present in a proportion of periglomerular cell bodies and dendrites indicating that these neurons synthesize dopamine (DA). This amine may therefore be released as a transmitter substance at some of the intraglomerular dendrodendritic synapses which periglomerular cells form with the mitral cells. There is evidence to suggest that some periglomerular cells use GABA as their transmitter. Thus, a morphologically and physiologically homogenous population of neurons can be subdivided on the basis of transmitter histochemical criteria. There was an impression of more DDC-positive than TH-positive fibers in the glomeruli. Such presumably DDC-positive, but TH-negative processes may represent 5-hydroxytryptamine (5-HT) nerve terminals. DBH-positive fibers were seen in the granular, external plexiform, and very rarely, in the glomerular layers, probably representing noradrenaline (NA) nerve terminals ascending from the lower brain stem. Weakly fluorescent DDC-positive fibers may represent nerve terminals of ascending 5-HT neurons. No phenylethanolamine-N-methyltransferase (PNMT)-positive neurons were observed. | Transmitter histochemistry of the rat olfactory bulb. I. Immunohistochemical localization of monoamine synthesizing enzymes. Support for intrabulbar, periglomerular dopamine neurons. The rat olfactory bulb was studied at the light and electron microscopic level with the indirect immunofluorescence technique and the unlabelled antibody enzyme method (PAP-technique), respectively. Antibodies to all 4 enzymes in the catecholamine synthesis were used. In the principal bulb the first two enzymes, tyrosine hydroxylase (TH) and DOPA decarboxylase (DDC), but not dopamine-beta-hydroxylase (DBH), were present in a proportion of periglomerular cell bodies and dendrites indicating that these neurons synthesize dopamine (DA). This amine may therefore be released as a transmitter substance at some of the intraglomerular dendrodendritic synapses which periglomerular cells form with the mitral cells. There is evidence to suggest that some periglomerular cells use GABA as their transmitter. Thus, a morphologically and physiologically homogenous population of neurons can be subdivided on the basis of transmitter histochemical criteria. There was an impression of more DDC-positive than TH-positive fibers in the glomeruli. Such presumably DDC-positive, but TH-negative processes may represent 5-hydroxytryptamine (5-HT) nerve terminals. DBH-positive fibers were seen in the granular, external plexiform, and very rarely, in the glomerular layers, probably representing noradrenaline (NA) nerve terminals ascending from the lower brain stem. Weakly fluorescent DDC-positive fibers may represent nerve terminals of ascending 5-HT neurons. No phenylethanolamine-N-methyltransferase (PNMT)-positive neurons were observed. | [
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|
PMID:16686 | Striatal lesions with kainic acid: neurochemical characteristics. | Stereotaxic injection of 2.5 microng of kainic acid, a rigid analogue of glutamate into the rat striatum caused a 70% reduction in the striatum of the cholinergic parameters, choline acetyltransferase, acetylcholine and synaptosomal uptake of choline and a similar reduction in the GABAergic parameters, glutamic acid decarboxylase, psi-aminobutyric acid (GABA) and synaptosomal uptake of GABA. In contrast, the striatal content of dopamine and the synaptosomal uptake of dopamine were unchanged, and the activity of tyrosine hydroxylase was significantly increased. Significant changes in the activity of neurotransmitter synthesizing enzymes were demonstrable within 6h after injection of 2.5 microng of kainic acid and maximal effects occurred at 48h; the activities of choline acetyltransferase and glutamic acid decarboxylase remained depressed up to 21 days after injection. The kinetic characteristics of striatal tyrosine hydroxylase were altered 48h after injection with a two-fold increase in the Vmax for tyrosine and a three-fold reduction in Km for the pteridine cofactor. In contrast to the effects of kainic acid, the injection of copper sulfate, a non-specific toxin, caused a proportionate reduction in the dopaminergic as well as the cholinergic and GABAergic presynaptic markers. The kainate lesion caused an 85% decrement in the activity of dopamine-sensitive adenylate cyclase, a 40% reduction in the specific binding of [3H]quinuclidinyl benzilate and a 195% increase in the specific binding of [3H]GABA in the striatum. The morphology of the kainate injected striatum was markedly altered with nearly a complete loss of intrinsic neurons, increased number of glial cells but intact internal capsule fibers. Intracerebral injection of nanomolar quantities of kainic acid appears to cause degeneration of neurons with cell bodies near the injection site while sparing axons terminating in or passing through the region. | Striatal lesions with kainic acid: neurochemical characteristics. Stereotaxic injection of 2.5 microng of kainic acid, a rigid analogue of glutamate into the rat striatum caused a 70% reduction in the striatum of the cholinergic parameters, choline acetyltransferase, acetylcholine and synaptosomal uptake of choline and a similar reduction in the GABAergic parameters, glutamic acid decarboxylase, psi-aminobutyric acid (GABA) and synaptosomal uptake of GABA. In contrast, the striatal content of dopamine and the synaptosomal uptake of dopamine were unchanged, and the activity of tyrosine hydroxylase was significantly increased. Significant changes in the activity of neurotransmitter synthesizing enzymes were demonstrable within 6h after injection of 2.5 microng of kainic acid and maximal effects occurred at 48h; the activities of choline acetyltransferase and glutamic acid decarboxylase remained depressed up to 21 days after injection. The kinetic characteristics of striatal tyrosine hydroxylase were altered 48h after injection with a two-fold increase in the Vmax for tyrosine and a three-fold reduction in Km for the pteridine cofactor. In contrast to the effects of kainic acid, the injection of copper sulfate, a non-specific toxin, caused a proportionate reduction in the dopaminergic as well as the cholinergic and GABAergic presynaptic markers. The kainate lesion caused an 85% decrement in the activity of dopamine-sensitive adenylate cyclase, a 40% reduction in the specific binding of [3H]quinuclidinyl benzilate and a 195% increase in the specific binding of [3H]GABA in the striatum. The morphology of the kainate injected striatum was markedly altered with nearly a complete loss of intrinsic neurons, increased number of glial cells but intact internal capsule fibers. Intracerebral injection of nanomolar quantities of kainic acid appears to cause degeneration of neurons with cell bodies near the injection site while sparing axons terminating in or passing through the region. | [
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|
PMID:16690 | Methylamine dehydrogenase from the obligate methylotroph Methylomonas methylovora. | An obligate methyltroph Methylomonas methylovora oxidized methylamine, formaldehyde, and formate. Enzymes oxidizing these substrates were detected in a cell-free system. Phenazine methosulfate-linked methylamine dehydrogenase was purified 21-fold. The enzyme had optimum activity at pH 7.5 and was stable at 60 degrees C for 5 min. The enzyme activity was inhibited by parachloromercuric benzoate, isonicotinic acid hydrazide, mercuric chloride, and sodium borate. | Methylamine dehydrogenase from the obligate methylotroph Methylomonas methylovora. An obligate methyltroph Methylomonas methylovora oxidized methylamine, formaldehyde, and formate. Enzymes oxidizing these substrates were detected in a cell-free system. Phenazine methosulfate-linked methylamine dehydrogenase was purified 21-fold. The enzyme had optimum activity at pH 7.5 and was stable at 60 degrees C for 5 min. The enzyme activity was inhibited by parachloromercuric benzoate, isonicotinic acid hydrazide, mercuric chloride, and sodium borate. | [
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|
PMID:16691 | Partial purification and some properties of a neutral sulfhydryl and an acid proteinase from Entamoeba histolytica. | The partial purification of two intracellular proteinases from the protozoan parasite Entamoeba histolytica is reported. One of these enzymes is an acid proteinase exhibiting maximum activity at pH 3.5 (hemoglobin substrate), is little affected by a range of inhibitors or activators, and is presumed to be similar to cathepsin D. Also present is a neutral proteinase exhibiting optimum activity at pH 6.0 (azocasein) but only poorly hydrolyzing either hemoglobin or serum albumen. This latter enzyme displayed no metal ion requirement, but was markedly inhibited by thiol-blocking agents and activated by free sulhydryl-containing compounds. | Partial purification and some properties of a neutral sulfhydryl and an acid proteinase from Entamoeba histolytica. The partial purification of two intracellular proteinases from the protozoan parasite Entamoeba histolytica is reported. One of these enzymes is an acid proteinase exhibiting maximum activity at pH 3.5 (hemoglobin substrate), is little affected by a range of inhibitors or activators, and is presumed to be similar to cathepsin D. Also present is a neutral proteinase exhibiting optimum activity at pH 6.0 (azocasein) but only poorly hydrolyzing either hemoglobin or serum albumen. This latter enzyme displayed no metal ion requirement, but was markedly inhibited by thiol-blocking agents and activated by free sulhydryl-containing compounds. | [
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|
PMID:16692 | Lawnmower injuries in children. | Over an 8-year period 31 children in the Winnipeg area were admitted to hospital with lawnmower injuries. The accidents were always preventable and were caused by patient or parent carelessness. The wounds were severe, often resulting in amputation of a portion of an extremity. Infection was common; prophylaxis with a broad-spectrum antibiotic and human antitetanus globulin is recommended. Radiography, débridement of the wound with thorough exploration under general anesthesia, and defatting and reapplication of degloved skin should be done initially, then the wound should be reinspected and redressed at 2 to 3 days, and finally closed or skin grafted at 6 to 8 days. Children must be educated about the dangers of lawnmowers and prevented from riding on tractor mowers. The grass catcher should be used and the path cleared of missiles. Hand controls should be mounted on the mower's handle and the blade should be kept sharp so that the machine's speed can be reduced. | Lawnmower injuries in children. Over an 8-year period 31 children in the Winnipeg area were admitted to hospital with lawnmower injuries. The accidents were always preventable and were caused by patient or parent carelessness. The wounds were severe, often resulting in amputation of a portion of an extremity. Infection was common; prophylaxis with a broad-spectrum antibiotic and human antitetanus globulin is recommended. Radiography, débridement of the wound with thorough exploration under general anesthesia, and defatting and reapplication of degloved skin should be done initially, then the wound should be reinspected and redressed at 2 to 3 days, and finally closed or skin grafted at 6 to 8 days. Children must be educated about the dangers of lawnmowers and prevented from riding on tractor mowers. The grass catcher should be used and the path cleared of missiles. Hand controls should be mounted on the mower's handle and the blade should be kept sharp so that the machine's speed can be reduced. | [
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|
PMID:16694 | An endo-(1 leads to 3)-beta-D-glucanase from Mucor hiemalis. | An endo-(1 leads to 3)-beta-D-glucanase (EC 3.2.1.6), isolated from the culture filtrate of the fungus Mucor hiemalis, was purified by ammonium sulfate fractionation, gel filtration, and column chromatography on O-(carboxymethyl)cellulose. The optimum pH, optimum temperature, and Km value of the enzyme were pH 5.0, 50 degrees, and 0.048%, respectively. The enzyme was strongly inactivated by Pb2+, Cu2+, and Hg2+ ions and also inhibited by Zn2+ and Fe3+ ions. The enzyme was specific for laminaran and the action pattern of the enzyme was of the endo-type. The molecular weight of the enzyme, as determined by gel filtration, was 30,000. | An endo-(1 leads to 3)-beta-D-glucanase from Mucor hiemalis. An endo-(1 leads to 3)-beta-D-glucanase (EC 3.2.1.6), isolated from the culture filtrate of the fungus Mucor hiemalis, was purified by ammonium sulfate fractionation, gel filtration, and column chromatography on O-(carboxymethyl)cellulose. The optimum pH, optimum temperature, and Km value of the enzyme were pH 5.0, 50 degrees, and 0.048%, respectively. The enzyme was strongly inactivated by Pb2+, Cu2+, and Hg2+ ions and also inhibited by Zn2+ and Fe3+ ions. The enzyme was specific for laminaran and the action pattern of the enzyme was of the endo-type. The molecular weight of the enzyme, as determined by gel filtration, was 30,000. | [
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|
PMID:16701 | Effect of streptovaricin on the incorporation of uridine into cellular and viral RNA. | Poxvirus replication is inhibited by streptovaricin. The most readily observed effect is the inhibition of incorporation of [3H]uridine into viral mRNA, suggesting an inhibition of RNA synthesis. Streptovaricin also inhibits the incorporation of [3H]uridine into cellular RNA but not as severely as viral RNA. On the other hand, [3H]uridine incorporation into the RNA of Semliki Forest virus (SFV), which contains a positive strand RNA genome, does not seem to be inhibited by streptovaricin. The inhibitory effect of streptovaricin is completely reversible after removal of the inhibitor. In addition to inhibiting RNA synthesis, streptovaricin also may inhibit the methylation of cellular RNA. Viral RNA is stable in the presence of streptovaricin. | Effect of streptovaricin on the incorporation of uridine into cellular and viral RNA. Poxvirus replication is inhibited by streptovaricin. The most readily observed effect is the inhibition of incorporation of [3H]uridine into viral mRNA, suggesting an inhibition of RNA synthesis. Streptovaricin also inhibits the incorporation of [3H]uridine into cellular RNA but not as severely as viral RNA. On the other hand, [3H]uridine incorporation into the RNA of Semliki Forest virus (SFV), which contains a positive strand RNA genome, does not seem to be inhibited by streptovaricin. The inhibitory effect of streptovaricin is completely reversible after removal of the inhibitor. In addition to inhibiting RNA synthesis, streptovaricin also may inhibit the methylation of cellular RNA. Viral RNA is stable in the presence of streptovaricin. | [
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|
PMID:16704 | [Control of pituitary secretion of melanotropin in an anuran amphibian by thyrotropin releasing factor (TRH). Study in vitro]. | Intermediate lobes from Rana esculenta pituitary glands were continuously superfused for 7 hrs at 28 degrees C with amphibian culture medium. alpha-MSH release was measured by use of a sensitive double antibody radio-immunoassay system. alpha-MSH secretion was inhibited by low temperatures. A large increase in alpha-MSH release was observed when Thyrotropin Releasing Hormone (TRH) at doses ranging from 10(-9) to 10(-7) molar was added to the superfusion medium. Since large amounts of TRH are to be found in the hypothalamus of amphibians but have no effect over pituitary TSH secretion, the action of TRH over alpha-MSH release may have a physiological significance. | [Control of pituitary secretion of melanotropin in an anuran amphibian by thyrotropin releasing factor (TRH). Study in vitro]. Intermediate lobes from Rana esculenta pituitary glands were continuously superfused for 7 hrs at 28 degrees C with amphibian culture medium. alpha-MSH release was measured by use of a sensitive double antibody radio-immunoassay system. alpha-MSH secretion was inhibited by low temperatures. A large increase in alpha-MSH release was observed when Thyrotropin Releasing Hormone (TRH) at doses ranging from 10(-9) to 10(-7) molar was added to the superfusion medium. Since large amounts of TRH are to be found in the hypothalamus of amphibians but have no effect over pituitary TSH secretion, the action of TRH over alpha-MSH release may have a physiological significance. | [
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|
PMID:16705 | [Spontaneous phospholipase A activity of rat pancreatic homogenates]. | Rat pancreas presents a spontaneous phospholipase A activity which appears before trypsin activation at optimal pH 6.5. The responsible enzyme is independent of pancreatic prophospholipase A, as can be seen through experiments done in the presence of trypsin inhibitors. On the other hand, this enzyme is distinct from excretory phospholipase which is more active and whose optimal pH is 8.8. Thermostability and insensibility of spontaneously active phospholipase A to DFP differentiate it from lipase, carboxyl-esterhydrolase and lysophospholipase, respectively. | [Spontaneous phospholipase A activity of rat pancreatic homogenates]. Rat pancreas presents a spontaneous phospholipase A activity which appears before trypsin activation at optimal pH 6.5. The responsible enzyme is independent of pancreatic prophospholipase A, as can be seen through experiments done in the presence of trypsin inhibitors. On the other hand, this enzyme is distinct from excretory phospholipase which is more active and whose optimal pH is 8.8. Thermostability and insensibility of spontaneously active phospholipase A to DFP differentiate it from lipase, carboxyl-esterhydrolase and lysophospholipase, respectively. | [
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|
PMID:16707 | Studies on alkaline phosphatase isoenzymes. Relation to gamma-glutamyltransferase and lactate dehydrogenase isoenzymes. | Gamma-Glutamyltransferase (GT) and isoenzymes of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) have been studied in 282 cases with increased S-ALP and in 18 chronic alcoholics with normal routine liver tests. There was a high degree of correlation between S-GT and the bile (alpha 1) and liver (alpha 2) fractions of S-ALP. Fractionation of alkaline phosphatases sometimes yielded clinical information, which could not be obtained by determinations of S-ALP and S-GT only. The presence of alpha 1-ALP and increased S-GT appeared to be more sensitive indicators of ethanol-induced liver involvement than other liver tests, including LDH-5/LDH-4 ratios. | Studies on alkaline phosphatase isoenzymes. Relation to gamma-glutamyltransferase and lactate dehydrogenase isoenzymes. Gamma-Glutamyltransferase (GT) and isoenzymes of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) have been studied in 282 cases with increased S-ALP and in 18 chronic alcoholics with normal routine liver tests. There was a high degree of correlation between S-GT and the bile (alpha 1) and liver (alpha 2) fractions of S-ALP. Fractionation of alkaline phosphatases sometimes yielded clinical information, which could not be obtained by determinations of S-ALP and S-GT only. The presence of alpha 1-ALP and increased S-GT appeared to be more sensitive indicators of ethanol-induced liver involvement than other liver tests, including LDH-5/LDH-4 ratios. | [
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|
PMID:16703 | [Incidence of Arbovirus isolated from mosquitoes in the forest region of South Cameroun, region of Yaoundé ]. | The authors give results of a survey of arboviruses isolated from mosquitoes in the neighborhood of Yaoundé, Southern Cameroon, from 1964 to 1972. During this period of nine years 127.520 female mosquitoes including at least 72 species were collected and processed for attempt of virus isolation. 55 strains belonging to 12 viral types were recovered from at least 19 species of mosquitoes. The appearance of different viruses over the years was quite intermittent. A possible reason for this is the need for viruses to move in search of susceptible vertebrate hosts. There was not definite evidence of vector host specificity except likely for Anopheles gambiae s. l. as a vector of Tataguine. However, among the more infected species, some ones show by their host preferences they could be true vectors of the viruses isolated from them. | [Incidence of Arbovirus isolated from mosquitoes in the forest region of South Cameroun, region of Yaoundé ]. The authors give results of a survey of arboviruses isolated from mosquitoes in the neighborhood of Yaoundé, Southern Cameroon, from 1964 to 1972. During this period of nine years 127.520 female mosquitoes including at least 72 species were collected and processed for attempt of virus isolation. 55 strains belonging to 12 viral types were recovered from at least 19 species of mosquitoes. The appearance of different viruses over the years was quite intermittent. A possible reason for this is the need for viruses to move in search of susceptible vertebrate hosts. There was not definite evidence of vector host specificity except likely for Anopheles gambiae s. l. as a vector of Tataguine. However, among the more infected species, some ones show by their host preferences they could be true vectors of the viruses isolated from them. | [
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|
PMID:16708 | Comparison of human membrane-bound neutral arylamidases from small intestine, lung, kidney, liver and placenta. | Human membrane-bound neutral arylamidases were solubilized from small intestinal mucosa, lung, kidney, liver and placenta with trypsin. These five membrane-bound neutral arylamidases were identified by polyacrylamide gel-disc electrophoresis. The heat sensitivity of each enzyme was in the order, liver and placenta greater than kidney greater than lung greater than small intestine. This order correlates with that of electrophoretic mobility, except for the placental membrane-bound neutral arylamidase. Five membrane-bound neutral arylamidases have the same molecular weight, 240 000, as estimated by Sephadex G-200 gel filtration. The five membrane-bound neutral arylamidase have very similar KM values (8.7 x 10(-5) M towards L-alanyl-beta-naphthylamide), optimal pH values, hydrolysis ratios towards L-alanyl-beta-naphthylamide and L-leucyl-beta-naphthylamide, and sensitivities of inhibition by chelators or amino acids. These results suggest that the multiple forms of membrane-bound neutral arylamidase found in five different human organs are organ-specific isoenzymes. | Comparison of human membrane-bound neutral arylamidases from small intestine, lung, kidney, liver and placenta. Human membrane-bound neutral arylamidases were solubilized from small intestinal mucosa, lung, kidney, liver and placenta with trypsin. These five membrane-bound neutral arylamidases were identified by polyacrylamide gel-disc electrophoresis. The heat sensitivity of each enzyme was in the order, liver and placenta greater than kidney greater than lung greater than small intestine. This order correlates with that of electrophoretic mobility, except for the placental membrane-bound neutral arylamidase. Five membrane-bound neutral arylamidases have the same molecular weight, 240 000, as estimated by Sephadex G-200 gel filtration. The five membrane-bound neutral arylamidase have very similar KM values (8.7 x 10(-5) M towards L-alanyl-beta-naphthylamide), optimal pH values, hydrolysis ratios towards L-alanyl-beta-naphthylamide and L-leucyl-beta-naphthylamide, and sensitivities of inhibition by chelators or amino acids. These results suggest that the multiple forms of membrane-bound neutral arylamidase found in five different human organs are organ-specific isoenzymes. | [
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|
PMID:16711 | Anti-tumour immunity by normal allogeneic blood transfusion in rat. | Growth of transplantable KMT-17 tumour in syngeneic WKA/MK rats was inhibited by i.v. preimmunization with whole blood from normal rats of allogeneic strains. The inhibitory effect was also observed in rats immunized with allogeneic white blood cells alone. The strength of the inhibitory effect mainly depended on the the strain of donor rat used; blood from Donryu and Kyoto strain rats produced the strongest inhibition, blood from Tokyo and Fischer strain rats produced moderate inhibition to the syngeneic tumour growth. Blood from ACI/N strain rats did not produce the inhibition. The mechanism of blood transfusion in inhibiting tumour growth is not yet clear. However, it seems that GVH reaction does not play an important role in the mechanism of the inhibition effect, because the effect was obtained by immunization with mitomycin C-treated allogeneic white blood cells and also by the immunization effect may be due to nonspecific active immunization. Significance of blood transfusion with special reference to clinical immunogtherapy of cancer is discussed. | Anti-tumour immunity by normal allogeneic blood transfusion in rat. Growth of transplantable KMT-17 tumour in syngeneic WKA/MK rats was inhibited by i.v. preimmunization with whole blood from normal rats of allogeneic strains. The inhibitory effect was also observed in rats immunized with allogeneic white blood cells alone. The strength of the inhibitory effect mainly depended on the the strain of donor rat used; blood from Donryu and Kyoto strain rats produced the strongest inhibition, blood from Tokyo and Fischer strain rats produced moderate inhibition to the syngeneic tumour growth. Blood from ACI/N strain rats did not produce the inhibition. The mechanism of blood transfusion in inhibiting tumour growth is not yet clear. However, it seems that GVH reaction does not play an important role in the mechanism of the inhibition effect, because the effect was obtained by immunization with mitomycin C-treated allogeneic white blood cells and also by the immunization effect may be due to nonspecific active immunization. Significance of blood transfusion with special reference to clinical immunogtherapy of cancer is discussed. | [
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|
PMID:16712 | The immune reponse to type III pneumococcal polysaccharide in mice with malaria. | The immune response of BALB/c mice to type III pneumococcal polysaccharide (SIII), as measured by splenic PFC, was abolished at the height of an acute self-limiting attack of malaria caused by the murine plasmodium P. yoelii, over a wide range of antigen doses. The response to antigen, given at various times after clinical recovery, gradually reappeared, but did not reach normal levels until 12 weeks after the injection of the parasite. A second injection of P. yoelii given 1 hr before SIII caused a moderate degree of depression, although in this case the plasmodium does not multiply. In chronic malaria the response to SIII was also very poor. Short term under-nourishment was found to reduce only slightly the response to SIII. | The immune reponse to type III pneumococcal polysaccharide in mice with malaria. The immune response of BALB/c mice to type III pneumococcal polysaccharide (SIII), as measured by splenic PFC, was abolished at the height of an acute self-limiting attack of malaria caused by the murine plasmodium P. yoelii, over a wide range of antigen doses. The response to antigen, given at various times after clinical recovery, gradually reappeared, but did not reach normal levels until 12 weeks after the injection of the parasite. A second injection of P. yoelii given 1 hr before SIII caused a moderate degree of depression, although in this case the plasmodium does not multiply. In chronic malaria the response to SIII was also very poor. Short term under-nourishment was found to reduce only slightly the response to SIII. | [
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|
PMID:16716 | Beta-2 adrenoceptor blocking activity of penbutolol and propranolol at very low doses. | The relative potency of penbutolol, a new beta adrenergic receptor blocking agent, was compared with propranolol by a four-point assay on healthy male subjects. A dose-response relationship to intravenous doses of propranolol in the microgram range was obtained during a steady state of infusion of epinephrine. Two subjects underwent the entire assay according to the Latin square design and four others each underwent one schedule of design on different days. The potency of penbutolol thus assessed was consistent with reported results. This study emphasizes the importance of intersubject variation and differential receptor sensitivity in individuals. The use of epinephrine as a beta receptor adrenergic agonist for evaluation of selective beta adrenergic receptor blocking activities is discussed. | Beta-2 adrenoceptor blocking activity of penbutolol and propranolol at very low doses. The relative potency of penbutolol, a new beta adrenergic receptor blocking agent, was compared with propranolol by a four-point assay on healthy male subjects. A dose-response relationship to intravenous doses of propranolol in the microgram range was obtained during a steady state of infusion of epinephrine. Two subjects underwent the entire assay according to the Latin square design and four others each underwent one schedule of design on different days. The potency of penbutolol thus assessed was consistent with reported results. This study emphasizes the importance of intersubject variation and differential receptor sensitivity in individuals. The use of epinephrine as a beta receptor adrenergic agonist for evaluation of selective beta adrenergic receptor blocking activities is discussed. | [
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|
PMID:16717 | Cardiovascular effects of total hip placement in man. With observations on the effects of methylmethacrylate on the isolated rabbit heart. | The cardiovascular effects of total hip placement were evaluated in 10 surgical patients, aged 55 to 82, while receiving fluroxene-N2O-O2 anesthesia. The anesthetic regimen caused mild cardiovascular depression. The placement of the acrylic cement into the acetabulum and femoral shaft also induced mild cardiovascular depression, but these changes were not significant at p less than 0.05. In one 67-yr-old woman, there were significant reductions of cardiac output and stroke volume 2 min after the insertion of acrylic into the femoral shaft, despite careful replacement of intravascular loss and careful anesthetic management. Methylmethacrylate (1 X 10(-6) to 1 X 10(-4), v/v) was administered to 24 isolated perfused rabbits hearts. These concentrations of methylmetacrylate are of the same order as measurable blood levels in surgical patients. There was a dose-dependent depression of left ventricular dP/dt correlated with a depression of the spontaneous heart rate. When the bradycardia was prevented by electrically pacing the hearts or the administration of atropine, the depressed dP/dt rose to control levels. Reduction in myocardial temperature and heart rate by means of reduction in perfusate temperature of the isolated hearts reduced the myocardial depressant effect of methylmethacrylate. | Cardiovascular effects of total hip placement in man. With observations on the effects of methylmethacrylate on the isolated rabbit heart. The cardiovascular effects of total hip placement were evaluated in 10 surgical patients, aged 55 to 82, while receiving fluroxene-N2O-O2 anesthesia. The anesthetic regimen caused mild cardiovascular depression. The placement of the acrylic cement into the acetabulum and femoral shaft also induced mild cardiovascular depression, but these changes were not significant at p less than 0.05. In one 67-yr-old woman, there were significant reductions of cardiac output and stroke volume 2 min after the insertion of acrylic into the femoral shaft, despite careful replacement of intravascular loss and careful anesthetic management. Methylmethacrylate (1 X 10(-6) to 1 X 10(-4), v/v) was administered to 24 isolated perfused rabbits hearts. These concentrations of methylmetacrylate are of the same order as measurable blood levels in surgical patients. There was a dose-dependent depression of left ventricular dP/dt correlated with a depression of the spontaneous heart rate. When the bradycardia was prevented by electrically pacing the hearts or the administration of atropine, the depressed dP/dt rose to control levels. Reduction in myocardial temperature and heart rate by means of reduction in perfusate temperature of the isolated hearts reduced the myocardial depressant effect of methylmethacrylate. | [
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|
PMID:16718 | Erythrocyte adenosine triphosphate and 2,3-diphosphoglycerate after human renal transplantation: dissociation from hypophosphataemia. | 1. Erythrocyte 2,3-diphosphoglycerate (2,3-DPG) and adenosine triphosphate (ATP) were determined in normal individuals, uraemic patients on chronic haemodialysis and patients who underwent renal transplantation, and correlated with plasma phosphate and arterial blood pH. 2. Significant increases in the 2,3-DPG and ATP content were found in the uraemic patients and these persisted after transplantation in spite of marked hypophosphataemia. 3. No correlation was established with plasma phosphate for either of the compounds but 2,3-DPG had a significant correlation with arterial blood pH. 4. Normal values for ATP and 2,3-DPG were observed in post-transplant patients with normal haematological values. The high amounts of erythrocyte 2,3-DPG and ATP in the early post-transplant period are independent of the circulating concentration of inorganic phosphate, and might represent the response of erythrocyte glycolysis to changing arterial blood pH. | Erythrocyte adenosine triphosphate and 2,3-diphosphoglycerate after human renal transplantation: dissociation from hypophosphataemia. 1. Erythrocyte 2,3-diphosphoglycerate (2,3-DPG) and adenosine triphosphate (ATP) were determined in normal individuals, uraemic patients on chronic haemodialysis and patients who underwent renal transplantation, and correlated with plasma phosphate and arterial blood pH. 2. Significant increases in the 2,3-DPG and ATP content were found in the uraemic patients and these persisted after transplantation in spite of marked hypophosphataemia. 3. No correlation was established with plasma phosphate for either of the compounds but 2,3-DPG had a significant correlation with arterial blood pH. 4. Normal values for ATP and 2,3-DPG were observed in post-transplant patients with normal haematological values. The high amounts of erythrocyte 2,3-DPG and ATP in the early post-transplant period are independent of the circulating concentration of inorganic phosphate, and might represent the response of erythrocyte glycolysis to changing arterial blood pH. | [
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|
PMID:16731 | A study of the in vitro and in vivo interaction of barium sulphate particles with gastro-intestinal mucus. | The in vivo interaction of various radiopaques with mucus was investigated by a determination of the pH-mobility curves of the treated particles. It was found that mucus covered the radiopaque particles both in vivo and in vitro. This interaction was not affected by the nature of the radiopaque or by the state of the mucous membrane. The changed state of the mucus was modified by the diet of the rat from which it was derived. The results are discussed with reference to the technique used in the administration of radiopaques. | A study of the in vitro and in vivo interaction of barium sulphate particles with gastro-intestinal mucus. The in vivo interaction of various radiopaques with mucus was investigated by a determination of the pH-mobility curves of the treated particles. It was found that mucus covered the radiopaque particles both in vivo and in vitro. This interaction was not affected by the nature of the radiopaque or by the state of the mucous membrane. The changed state of the mucus was modified by the diet of the rat from which it was derived. The results are discussed with reference to the technique used in the administration of radiopaques. | [
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|
PMID:16732 | In vitro efficacy of some drugs on promastigotes of Leishmania donovani. | Sodium stibogluconate, metronidazole and dehydroemetine Roche were tested for their in vitro action on the mobility, morphology and survival of promastigotes of Leishmania donovani. At low concentrations, sodium stibogluconate, the drug of choice for kala azar treatment in Iraq proved to be poorly effective in the prevention of promastigotes growth in vitro. On the other hand, both metronidazole and dehydroemetine Roche at low concentrations were highly effective in the prevention of promastigotes of L. donovani growth in vitro. 3.51 X 10(2), 9.34 and 3.13 mmol of sodium stibogluconate, metronidazole and dehydroemetine, respectively, were required to show the same effect in vitro. | In vitro efficacy of some drugs on promastigotes of Leishmania donovani. Sodium stibogluconate, metronidazole and dehydroemetine Roche were tested for their in vitro action on the mobility, morphology and survival of promastigotes of Leishmania donovani. At low concentrations, sodium stibogluconate, the drug of choice for kala azar treatment in Iraq proved to be poorly effective in the prevention of promastigotes growth in vitro. On the other hand, both metronidazole and dehydroemetine Roche at low concentrations were highly effective in the prevention of promastigotes of L. donovani growth in vitro. 3.51 X 10(2), 9.34 and 3.13 mmol of sodium stibogluconate, metronidazole and dehydroemetine, respectively, were required to show the same effect in vitro. | [
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|
PMID:16733 | [The influence of surgery on serum enzyme changes]. | Gamma-GT, which appears as a sensitive indicator in the enzyme pattern during postoperative examination, is especially recommended (besides the GOT and GPT enzymes) in detecting and watching the course of hepatocellular lesions. Distinction between parenchymatous and obstructive icterus can in some cases be made at an early stage by comparison with AP. Distinction between increases in biliary and ossal AP activity is possible with the help of Gamma-GT. Where liver metastases are suspected clinically, increased Gamma-GT activity makes metastization into the liver appear likely. | [The influence of surgery on serum enzyme changes]. Gamma-GT, which appears as a sensitive indicator in the enzyme pattern during postoperative examination, is especially recommended (besides the GOT and GPT enzymes) in detecting and watching the course of hepatocellular lesions. Distinction between parenchymatous and obstructive icterus can in some cases be made at an early stage by comparison with AP. Distinction between increases in biliary and ossal AP activity is possible with the help of Gamma-GT. Where liver metastases are suspected clinically, increased Gamma-GT activity makes metastization into the liver appear likely. | [
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|
PMID:16729 | Spontaneous variability of the hemoglobin affinity for oxygen. | In order to evaluate the accuracy of our method of P50 determination, we measured P50 and 2,3-DPG on different days on several members of our laboratory staff and were surprised to find significant variation. Initially, we indicted our methodology but subsequent data suggest that significant P50 variability occurs, not correlated to alterations in 2,3-DPG or red cell pH. The largest variability on different days. 8.5 torr, occurred in a laboratory staff member studied 7 days apart. The P50 determinations were made by fixing PO2 by tonometry and determining oxyhemoglobin saturation by Van Slyke analysis. In contrast to our in vivo data, serial studies over 5-20 days performed upon 3 samples of stored CPD bank blood demonstrated the expected progressive decline in both 2,3-DPG and P50. | Spontaneous variability of the hemoglobin affinity for oxygen. In order to evaluate the accuracy of our method of P50 determination, we measured P50 and 2,3-DPG on different days on several members of our laboratory staff and were surprised to find significant variation. Initially, we indicted our methodology but subsequent data suggest that significant P50 variability occurs, not correlated to alterations in 2,3-DPG or red cell pH. The largest variability on different days. 8.5 torr, occurred in a laboratory staff member studied 7 days apart. The P50 determinations were made by fixing PO2 by tonometry and determining oxyhemoglobin saturation by Van Slyke analysis. In contrast to our in vivo data, serial studies over 5-20 days performed upon 3 samples of stored CPD bank blood demonstrated the expected progressive decline in both 2,3-DPG and P50. | [
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PMID:16734 | Tardive dyskinesia: relationship with a primary affective disorder. | We reviewed all Mayo Clinic case histories in which a diagnosis of tardive dyskinesia or dyskinesia might have been recorded during the years 1965 through 1973 and interviewed 18 consecutive patients in the Department of Psychiatry and Psychology. Among the histories and patients, we found a high incidence of primary affective disorders. Four of the five men had a history of chronic alcohol abuse and symptoms of depression. We recommend that people who have primary affective disorders and chronic alcohol abuse with depression should be given antipsychotic medication, stimulants, or diazepam only after extremely careful consideration. | Tardive dyskinesia: relationship with a primary affective disorder. We reviewed all Mayo Clinic case histories in which a diagnosis of tardive dyskinesia or dyskinesia might have been recorded during the years 1965 through 1973 and interviewed 18 consecutive patients in the Department of Psychiatry and Psychology. Among the histories and patients, we found a high incidence of primary affective disorders. Four of the five men had a history of chronic alcohol abuse and symptoms of depression. We recommend that people who have primary affective disorders and chronic alcohol abuse with depression should be given antipsychotic medication, stimulants, or diazepam only after extremely careful consideration. | [
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PMID:16730 | Oxygen availability during hypothermic cardiopulmonary bypass. | Oxygen availability during cardiopulmonary bypass was assessed in 22 patients under hypothermic and relatively normothermic conditions. The patients were divided into two groups, 17 of whom received ACD blood and 5, CPD blood. The mean P50 for all patients fell from a preoperative value of 25.9 +/- 2.4 (SD) to 15.6 +/- 2.1 during hypothermia confirming a leftward shift of the oxyhemoglobin dissociation curve. Oxygen uptake, calculated from a-v oxygen content differences (avDO2) and flow, was significantly lower during hypothermic bypass (65 +/- 27 ml/min) than during rewarming (121 +/- 41 ml/min). The increase in oxygen affinity during hypothermia was influenced also by changes in acid base and 2,3-DPG concentrations, the changes being similar in both the ACD and CPD groups of patients. During rewarming, however, oxygen availability was increased in the CPD group presumably from significantly increased 2,3-DPG concentrations. A "functional" value of hemoglobin, based upon the effects of the shift of the oxyhemoglobin dissociation curve and, therefore, reflecting the true capacity of hemoglobin to unload oxygen at the tissue level, was calculated. During the hypothermic phase of bypass, this functional hemoglobin was only 4.2 g/100 ml blood, suggesting that, in spite of reduced metabolic demands, oxygenation reserves are minimal. | Oxygen availability during hypothermic cardiopulmonary bypass. Oxygen availability during cardiopulmonary bypass was assessed in 22 patients under hypothermic and relatively normothermic conditions. The patients were divided into two groups, 17 of whom received ACD blood and 5, CPD blood. The mean P50 for all patients fell from a preoperative value of 25.9 +/- 2.4 (SD) to 15.6 +/- 2.1 during hypothermia confirming a leftward shift of the oxyhemoglobin dissociation curve. Oxygen uptake, calculated from a-v oxygen content differences (avDO2) and flow, was significantly lower during hypothermic bypass (65 +/- 27 ml/min) than during rewarming (121 +/- 41 ml/min). The increase in oxygen affinity during hypothermia was influenced also by changes in acid base and 2,3-DPG concentrations, the changes being similar in both the ACD and CPD groups of patients. During rewarming, however, oxygen availability was increased in the CPD group presumably from significantly increased 2,3-DPG concentrations. A "functional" value of hemoglobin, based upon the effects of the shift of the oxyhemoglobin dissociation curve and, therefore, reflecting the true capacity of hemoglobin to unload oxygen at the tissue level, was calculated. During the hypothermic phase of bypass, this functional hemoglobin was only 4.2 g/100 ml blood, suggesting that, in spite of reduced metabolic demands, oxygenation reserves are minimal. | [
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PMID:16735 | Multi-clinic cross-over comparison of triazolam (Halcion) and placebo in the treatment of co-existing insomnia and anxiety in anxious out-patients. | In this multi-clinic double-blind cross-over designed study, forty-five anxious and insomniac out-patients received either triazolam (Halcion) 0.25 mg or placebo at bedtime. After seven days the medications were crossed over. The dosage was doubled after nights 2 and 9 if good sleep was not produced. Three patients dropped out, two on placebo (one for side effects and one for lack of efficacy) and one on triazolam (due to misunderstanding instructions). Analysis of sleep questionnaire data showed superiority of triazolam to placebo (p less .001) in all parameters. The incidence of dreams was not affected. Analysis of antianxiety efficacy showed that triazolam was superior to placebo (p less than .001) in all parameters, both physician's and self ratings. Thus, either triazolam or a good night's sleep significantly relieved the patient's anxiety. No side effects or abnormal laboratory values of significance were attributable to triazolam. | Multi-clinic cross-over comparison of triazolam (Halcion) and placebo in the treatment of co-existing insomnia and anxiety in anxious out-patients. In this multi-clinic double-blind cross-over designed study, forty-five anxious and insomniac out-patients received either triazolam (Halcion) 0.25 mg or placebo at bedtime. After seven days the medications were crossed over. The dosage was doubled after nights 2 and 9 if good sleep was not produced. Three patients dropped out, two on placebo (one for side effects and one for lack of efficacy) and one on triazolam (due to misunderstanding instructions). Analysis of sleep questionnaire data showed superiority of triazolam to placebo (p less .001) in all parameters. The incidence of dreams was not affected. Analysis of antianxiety efficacy showed that triazolam was superior to placebo (p less than .001) in all parameters, both physician's and self ratings. Thus, either triazolam or a good night's sleep significantly relieved the patient's anxiety. No side effects or abnormal laboratory values of significance were attributable to triazolam. | [
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PMID:16736 | Interactions with antiepileptic drugs. | Most of the currently available antiepileptic drugs have a low therapeutic ratio and therefore a drug interaction causing elevation of the serum level of one of these compounds can readily lead to drug intoxication. Phenytoin, in particular, is vulnerable because its metabolism is dose-related and at therapeutic serum levels the enzyme system involved in its degradation is easily inhibited by concurrent drug administration. As multiple drug therapy has traditionally been practised in the management of epilepsy, clinically important interactions are common. Furthermore, most of the drugs used in the treatment of major epilepsies are potent inducers of hepatic microsomal enzymes and can therefore stimulate the metabolism of concurrently-administered drugs to such an extent that they may be rendered ineffective. The use of one drug alone is recommended, where possible, in the management of epilepsy. | Interactions with antiepileptic drugs. Most of the currently available antiepileptic drugs have a low therapeutic ratio and therefore a drug interaction causing elevation of the serum level of one of these compounds can readily lead to drug intoxication. Phenytoin, in particular, is vulnerable because its metabolism is dose-related and at therapeutic serum levels the enzyme system involved in its degradation is easily inhibited by concurrent drug administration. As multiple drug therapy has traditionally been practised in the management of epilepsy, clinically important interactions are common. Furthermore, most of the drugs used in the treatment of major epilepsies are potent inducers of hepatic microsomal enzymes and can therefore stimulate the metabolism of concurrently-administered drugs to such an extent that they may be rendered ineffective. The use of one drug alone is recommended, where possible, in the management of epilepsy. | [
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PMID:16740 | [Sugar studies at Turku]. | This survey concerns the essential findings in two clinical trials. The first study involved almost complete substitution of sucrose (S) by fructose (F) or xylitol (X). After 2 years the mean DMFS-increment was 7.2 in the S-group, 3.8 in the F-group, and 0.0 in the X-group. The second study comprised partial substitution, the effects of a S- or X-containing chewing gum being compared during 1 year. The subjects consumed 4.0 chewing gums per day in the S-group and correspondingly 4.5 in the X-group. In the S-group the caries incidence assessed independently by clinical and radiographical means was significantly higher than in the X-group. It is concluded that the metabolic studies indicate the relative safety of perorally administered xylitol at the present dosage levels. In view on the findings in the chewing gum study it is suggested that the non- and anti-cariogenic properties of xylitol principally depend on its lack of suitability for microbial metabolism and the physico-chemical effects in plaque and saliva brought about through low and repeated dosage. | [Sugar studies at Turku]. This survey concerns the essential findings in two clinical trials. The first study involved almost complete substitution of sucrose (S) by fructose (F) or xylitol (X). After 2 years the mean DMFS-increment was 7.2 in the S-group, 3.8 in the F-group, and 0.0 in the X-group. The second study comprised partial substitution, the effects of a S- or X-containing chewing gum being compared during 1 year. The subjects consumed 4.0 chewing gums per day in the S-group and correspondingly 4.5 in the X-group. In the S-group the caries incidence assessed independently by clinical and radiographical means was significantly higher than in the X-group. It is concluded that the metabolic studies indicate the relative safety of perorally administered xylitol at the present dosage levels. In view on the findings in the chewing gum study it is suggested that the non- and anti-cariogenic properties of xylitol principally depend on its lack of suitability for microbial metabolism and the physico-chemical effects in plaque and saliva brought about through low and repeated dosage. | [
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PMID:16742 | The effects of dopamine on renin release in vitro. | To examine the direct effects of dopamine on renin release, the in vitro rat kidney slice system, devoid of hemodynamic and humoral effects, was chosen. In the presence of an antioxidant, ascorbic acid (6 X 10(-4)M), a significant dose-related stimulation of renin release was observed with addition of 10(-5)M and higher concentrations of dopamine. When the monoamine oxidase inhibitor, pheniprazine (1 X 10(-5)M) was added, significant, dose-related stimulation of renin release was observed with 10(-8)M and higher concentrations of dopamine. Dopamine-induced renin release was not inhibited by the presence of the alpha-adrenergic antagonist, phentolamine (9 X 10(-4)M), the dopaminergic antagonist, haloperidol (5 X 10(-5)M) or the neural uptake inhibitor, cocaine (1 X 10(-5)M). However, the presence of the beta-adrenergic antagonist, propranolol (2 X 10(-4)M) completely inhibited dopamine-induced renin release. These studies indicate that dopamine can directly stimulate renin release in the absence of effects of hemodynamic factors, alterations in sodium metabolism or release of endogenous adrenergic agents. Further, this direct effect of dopamine on renin release appears to be mediated by an agonistic effect on the juxtaglomerular beta receptor rather than by the presence of a specific dopaminergic receptor for renin release. | The effects of dopamine on renin release in vitro. To examine the direct effects of dopamine on renin release, the in vitro rat kidney slice system, devoid of hemodynamic and humoral effects, was chosen. In the presence of an antioxidant, ascorbic acid (6 X 10(-4)M), a significant dose-related stimulation of renin release was observed with addition of 10(-5)M and higher concentrations of dopamine. When the monoamine oxidase inhibitor, pheniprazine (1 X 10(-5)M) was added, significant, dose-related stimulation of renin release was observed with 10(-8)M and higher concentrations of dopamine. Dopamine-induced renin release was not inhibited by the presence of the alpha-adrenergic antagonist, phentolamine (9 X 10(-4)M), the dopaminergic antagonist, haloperidol (5 X 10(-5)M) or the neural uptake inhibitor, cocaine (1 X 10(-5)M). However, the presence of the beta-adrenergic antagonist, propranolol (2 X 10(-4)M) completely inhibited dopamine-induced renin release. These studies indicate that dopamine can directly stimulate renin release in the absence of effects of hemodynamic factors, alterations in sodium metabolism or release of endogenous adrenergic agents. Further, this direct effect of dopamine on renin release appears to be mediated by an agonistic effect on the juxtaglomerular beta receptor rather than by the presence of a specific dopaminergic receptor for renin release. | [
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|
PMID:16743 | Diagnosis of bilateral abdominal cryptorchidism by laparoscopy. | The authors report a case of abdominal retention of both testes, where the exact diagnosis was made by laparoscopy. They suggest the usefulness of laparoscopy also in urology. | Diagnosis of bilateral abdominal cryptorchidism by laparoscopy. The authors report a case of abdominal retention of both testes, where the exact diagnosis was made by laparoscopy. They suggest the usefulness of laparoscopy also in urology. | [
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PMID:16744 | An approach to the toxicology of combustion products of materials. | Physiological and behavioral (conditioned avoidance) responses of male Long-Evans rats were determined during exposure to combustion products produced on thermal degradation of three different polymeric materials. Arterial blood samples were obtained for determination of carboxyhemoglobin (COHb) and acid/base status. Material A produced a syndrome of carbon monoxide (CO)-induced anoxia, the severity of which was a function of the mass of material degraded. Material B produced grand mal seizures despite COHb levels of less than 10%. Material C produced metabolic acidosis and a mild degree of CO-induced anoxia. Loss of avoidance responses occurred at significantly lower COHb levels for materials B and C in comparison to CO alone. Using responses to COHb as a reference, it was possible to detect the presence of other toxicants present in combustion products. Compounds found in smoke in very low concentrations may have a high degree of biological activity and be responsible for impairment of survival responses. We have labeled these compounds "limiting" toxicants. They constitute a significant hazard, which is added to that of CO and anoxia. | An approach to the toxicology of combustion products of materials. Physiological and behavioral (conditioned avoidance) responses of male Long-Evans rats were determined during exposure to combustion products produced on thermal degradation of three different polymeric materials. Arterial blood samples were obtained for determination of carboxyhemoglobin (COHb) and acid/base status. Material A produced a syndrome of carbon monoxide (CO)-induced anoxia, the severity of which was a function of the mass of material degraded. Material B produced grand mal seizures despite COHb levels of less than 10%. Material C produced metabolic acidosis and a mild degree of CO-induced anoxia. Loss of avoidance responses occurred at significantly lower COHb levels for materials B and C in comparison to CO alone. Using responses to COHb as a reference, it was possible to detect the presence of other toxicants present in combustion products. Compounds found in smoke in very low concentrations may have a high degree of biological activity and be responsible for impairment of survival responses. We have labeled these compounds "limiting" toxicants. They constitute a significant hazard, which is added to that of CO and anoxia. | [
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PMID:16745 | Development of hepatic acetyl coenzyme A carboxylase in hormone-treated chicks. | It has been suggested that the carbohydrate-rich diet of chicks after hatching is responsible for the emergence of hepatic enzymes involved in lipogenesis; the injection of glucose to newly hatched chicks gives rise to an appreciable elvation on the activities of acetyl coenzyme A carboxylase and fatty acid synthetase. The present study shows that during the first hours after hatching, there is a natural elevation of glycemia which parallels the increase in acetyl coenzyme A carboxylase activity. However, the administration of hormones which alter the blood glucose levels considerably (insulin, tolbutamide, glucagon and hydrocortisone) did not influence the enzyme activity. The administration of thyroxine, estradiol and cyclic AMP, was also without effect. These results do not support the theory that the increased amount of blood glucose is the natural effector of the induction acetyl coenzyme A carboxylase. They also show that different lipogenic enzymes are not regulated via the same 'operon' since thyroxine or glucagon which alter the level of some enzymes on this pathway did not modify that of the acetyl coenzyme A carboxylase. | Development of hepatic acetyl coenzyme A carboxylase in hormone-treated chicks. It has been suggested that the carbohydrate-rich diet of chicks after hatching is responsible for the emergence of hepatic enzymes involved in lipogenesis; the injection of glucose to newly hatched chicks gives rise to an appreciable elvation on the activities of acetyl coenzyme A carboxylase and fatty acid synthetase. The present study shows that during the first hours after hatching, there is a natural elevation of glycemia which parallels the increase in acetyl coenzyme A carboxylase activity. However, the administration of hormones which alter the blood glucose levels considerably (insulin, tolbutamide, glucagon and hydrocortisone) did not influence the enzyme activity. The administration of thyroxine, estradiol and cyclic AMP, was also without effect. These results do not support the theory that the increased amount of blood glucose is the natural effector of the induction acetyl coenzyme A carboxylase. They also show that different lipogenic enzymes are not regulated via the same 'operon' since thyroxine or glucagon which alter the level of some enzymes on this pathway did not modify that of the acetyl coenzyme A carboxylase. | [
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PMID:16747 | The energy metabolism of the leukocyte. IX. Changes in the concentration of the coenzymes NAD, NADH, NADP, and NADPH in polymorphonuclear leukocytes during phagocytosis of Staphylococcus albus and due to the action of phospholipase C. | The determination of the coenzymes NAD+, NADH, NADP+ and NADPH, by the use of a method of enzymatic cycling, demonstrates that the enzymes responsible for the stimulations found during the phagocytosis of Staphylococcus albus are NADH and NADPH oxidase of human leukocytes and NADPH oxidase in the case of guinea pig leukocytes. The effects of serum, of the bacterial strain used and of phospholipase C are also discussed. | The energy metabolism of the leukocyte. IX. Changes in the concentration of the coenzymes NAD, NADH, NADP, and NADPH in polymorphonuclear leukocytes during phagocytosis of Staphylococcus albus and due to the action of phospholipase C. The determination of the coenzymes NAD+, NADH, NADP+ and NADPH, by the use of a method of enzymatic cycling, demonstrates that the enzymes responsible for the stimulations found during the phagocytosis of Staphylococcus albus are NADH and NADPH oxidase of human leukocytes and NADPH oxidase in the case of guinea pig leukocytes. The effects of serum, of the bacterial strain used and of phospholipase C are also discussed. | [
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|
PMID:16748 | Tissue distribution and blood levels of gamma-glutamyl transferase in the horse. | In the horse, gamma-glutamyl transferase (GGT) was found to be mainly located in the kidneys, liver and pancreas. As renal lesions are followed by a urinary escape of enzyme, it can be assumed that if there are raised serum enzyme levels then the source will be chiefly from the liver and pancreas. In the blood, GGT can be measured either in plasma or serum. Its mean level in 58 horses was 12 U/L. This level was not affected by moderate dilution or slight haemolysis and its activity was only slightly decreased by storage at--30 degrees C. The relative hepatic specificity of this enzyme and its easy measurement make it a potentially very useful measure of liver dysfunction in the horse. | Tissue distribution and blood levels of gamma-glutamyl transferase in the horse. In the horse, gamma-glutamyl transferase (GGT) was found to be mainly located in the kidneys, liver and pancreas. As renal lesions are followed by a urinary escape of enzyme, it can be assumed that if there are raised serum enzyme levels then the source will be chiefly from the liver and pancreas. In the blood, GGT can be measured either in plasma or serum. Its mean level in 58 horses was 12 U/L. This level was not affected by moderate dilution or slight haemolysis and its activity was only slightly decreased by storage at--30 degrees C. The relative hepatic specificity of this enzyme and its easy measurement make it a potentially very useful measure of liver dysfunction in the horse. | [
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|
PMID:16750 | An isolation procedure for the native alpha chain of bovine hemoglobin. A study of the functional properties of this chain and its hybrid with the human beta chain. | In this paper we present a procedure for the isolation of the native bovine alpha chain. The method is based on affinity chromatography. The results show that the ligand-binding properties of the bovine alpha chain are almost identical to those of the human alpha chain. The hybrid alphaB2 betaH2 prepared by mixing bovine alpha chains and human beta chains shows ligand binding properties similar to those of human hemoglobin and different from those of bovine hemoglobin. | An isolation procedure for the native alpha chain of bovine hemoglobin. A study of the functional properties of this chain and its hybrid with the human beta chain. In this paper we present a procedure for the isolation of the native bovine alpha chain. The method is based on affinity chromatography. The results show that the ligand-binding properties of the bovine alpha chain are almost identical to those of the human alpha chain. The hybrid alphaB2 betaH2 prepared by mixing bovine alpha chains and human beta chains shows ligand binding properties similar to those of human hemoglobin and different from those of bovine hemoglobin. | [
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|
PMID:16751 | Uridine phosphorylase from Escherichia coli. Physical and chemical characterization. | Uridine phosphorylase from Escherichia coli has been purified to homogeneity. The enzyme was found to have a molecular weight of 176000 and to consist of 8 probably identical subunits with molecular weights of 22000. These numbers were determined from equilibrium centrifugations in the analytical ultracentrifuge, from dodecylsulphate gel electrophoresis and from amino acid analysis. Moreover the following physico-chemical constants were determined: s020,w = 8.2 x 10(-13) s, upsilon2 = 0.751 cm3/g, A1%280 (1 cm) = 6.73 and a specific activity of 183 units/mg towards uridine. The enzyme shows some activity towards deoxyuridine and thymidine. The activity is not impaired through substitution by bromo, fluoro or methyl groups in the 5-position of the uracil base, but no enzymatic activity is observed when cytosine base is used in the nucleoside substrate. | Uridine phosphorylase from Escherichia coli. Physical and chemical characterization. Uridine phosphorylase from Escherichia coli has been purified to homogeneity. The enzyme was found to have a molecular weight of 176000 and to consist of 8 probably identical subunits with molecular weights of 22000. These numbers were determined from equilibrium centrifugations in the analytical ultracentrifuge, from dodecylsulphate gel electrophoresis and from amino acid analysis. Moreover the following physico-chemical constants were determined: s020,w = 8.2 x 10(-13) s, upsilon2 = 0.751 cm3/g, A1%280 (1 cm) = 6.73 and a specific activity of 183 units/mg towards uridine. The enzyme shows some activity towards deoxyuridine and thymidine. The activity is not impaired through substitution by bromo, fluoro or methyl groups in the 5-position of the uracil base, but no enzymatic activity is observed when cytosine base is used in the nucleoside substrate. | [
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|
PMID:16752 | The exchange reaction of peptides R-D-alanyl-D-alanine with D-[14C]alanine to R-D-alanyl-D-[14C]alanine and D-alanine, catalysed by the membranes of Streptococcus faecalis ATCC 9790. | Under alkaline conditions, the membrane-bound DD-carboxypeptidase of Streptococcus faecalis ATCC 9790 catalyses exchange reactions in which the X-L-R3-D-Ala moiety of peptides of the type X-L-R3-D-Ala-D-Ala is transferred to simple amino compounds such as D-alanine, glycine and glycyl-glycine. The enzyme system is unable, however, to catalyse complex reactions that would simulate the natural transpeptidation reaction. | The exchange reaction of peptides R-D-alanyl-D-alanine with D-[14C]alanine to R-D-alanyl-D-[14C]alanine and D-alanine, catalysed by the membranes of Streptococcus faecalis ATCC 9790. Under alkaline conditions, the membrane-bound DD-carboxypeptidase of Streptococcus faecalis ATCC 9790 catalyses exchange reactions in which the X-L-R3-D-Ala moiety of peptides of the type X-L-R3-D-Ala-D-Ala is transferred to simple amino compounds such as D-alanine, glycine and glycyl-glycine. The enzyme system is unable, however, to catalyse complex reactions that would simulate the natural transpeptidation reaction. | [
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|
PMID:16753 | The phosphoenolpyruvate-dependent phosphotransferase system of Staphylococcus aureus. 3. 1H and 31P nuclear-magnetic-resonance studies on the phosphocarrier protein HPr; tyrosine titration and denaturation studies. | The phosphocarrier protein HPr has been investigated by proton nuclear magnetic resonance (NMR) at 270 MHz in order to evaluate structural properties of the whole molecule and its active site. The titration behaviour of the three tyrosines of the HPr protein was analysed by monitoring the chemical shifts of the aromatic proton resonances of these residues as a function of pH. It was found that the HPr protein contains a lot of slowly exchanging NH backbone protons which suggested a relatively rigid secondary structure of the protein molecule itself although it contains no disulfide bridges. The HPr protein shows a sharp reversible denaturation behaviour at alkaline pH values. Between pH 10.8 and 11.1 two C-2 proton resonance peaks for the single histidine residue could be observed together with abrupt changes in the aromatic and aliphatic absorption region of the HPr protein which are due to chemical exchange processes. The NMR spectrum of the HPr protein is only changed a little upon raising the temperature from 14 degrees C to 70 degrees C. At 76 degrees C all resonances in the spectrum broaden and almost disappear. This process is irreversible. | The phosphoenolpyruvate-dependent phosphotransferase system of Staphylococcus aureus. 3. 1H and 31P nuclear-magnetic-resonance studies on the phosphocarrier protein HPr; tyrosine titration and denaturation studies. The phosphocarrier protein HPr has been investigated by proton nuclear magnetic resonance (NMR) at 270 MHz in order to evaluate structural properties of the whole molecule and its active site. The titration behaviour of the three tyrosines of the HPr protein was analysed by monitoring the chemical shifts of the aromatic proton resonances of these residues as a function of pH. It was found that the HPr protein contains a lot of slowly exchanging NH backbone protons which suggested a relatively rigid secondary structure of the protein molecule itself although it contains no disulfide bridges. The HPr protein shows a sharp reversible denaturation behaviour at alkaline pH values. Between pH 10.8 and 11.1 two C-2 proton resonance peaks for the single histidine residue could be observed together with abrupt changes in the aromatic and aliphatic absorption region of the HPr protein which are due to chemical exchange processes. The NMR spectrum of the HPr protein is only changed a little upon raising the temperature from 14 degrees C to 70 degrees C. At 76 degrees C all resonances in the spectrum broaden and almost disappear. This process is irreversible. | [
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|
PMID:16755 | Stability in vitro of methylproscillaridin. | The in vitro stability of methylproscillaridin has been compared with that of proscillaridin, the activities of the glycosides being assayed by the 86Rb-technique. After incubation in gastric juice at pH 1,2, and 3, the activity half life of each glycoside was proportional to pH and was approximately 0.25 h, 2.5 h, and 25 h, respectively. The inactivation rate in pure hydrochloric acid at pH 2 did not differ from that in gastric juice of the same pH. The glycosides were stable in bile and enteric juice. In faeces, methylproscillaridin was stable and proscillaridin was inactivated with a half life of 32 h. It is concluded that the difference in biological availability between the two glycosides cannot be explained by differences in gastrointestinal stability. | Stability in vitro of methylproscillaridin. The in vitro stability of methylproscillaridin has been compared with that of proscillaridin, the activities of the glycosides being assayed by the 86Rb-technique. After incubation in gastric juice at pH 1,2, and 3, the activity half life of each glycoside was proportional to pH and was approximately 0.25 h, 2.5 h, and 25 h, respectively. The inactivation rate in pure hydrochloric acid at pH 2 did not differ from that in gastric juice of the same pH. The glycosides were stable in bile and enteric juice. In faeces, methylproscillaridin was stable and proscillaridin was inactivated with a half life of 32 h. It is concluded that the difference in biological availability between the two glycosides cannot be explained by differences in gastrointestinal stability. | [
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|
PMID:16756 | The effect of LSD and 2-bromo LSD on the striatal DOPA accumulation after decarboxylase inhibition in rats. | LSD and BOL (0.125-0.5 mg/kg) were equipotent in increasing the in vivo tyrosine hydroxylation in the striatum as measured by the accumulation of DOPA after inhibition of neuronal decarboxylase. However, with 2--4 mg/kg doses, the maximum effect of BOL was larger than that of LSD. LSD and BOL antagonized the apomorphine-induced decrease of DOPA accumulation, without affecting the haloperidol-induced increase. LSD like apomorphine inhibited the increase of DOPA accumulation seen after reserpine, cerebral hemisection and after gamma-butyrolactone (GBL). The effect of apomorphine in rats given GBL was blocked by haloperidol, but not by BOL and promethazine, whereas that of LSD was inhibited by haloperidol, BOL, and promethazine. These findings suggest that LSD and BOL directly affect nigro-neostriatal dopamine neurons. LSD therefore appears to be a partial agonist and BOL a pure antagonist at dopamine autoreceptors. It is proposed in addition that LSD activates and BOL blocks 5-HT receptors that control DOPA formation. | The effect of LSD and 2-bromo LSD on the striatal DOPA accumulation after decarboxylase inhibition in rats. LSD and BOL (0.125-0.5 mg/kg) were equipotent in increasing the in vivo tyrosine hydroxylation in the striatum as measured by the accumulation of DOPA after inhibition of neuronal decarboxylase. However, with 2--4 mg/kg doses, the maximum effect of BOL was larger than that of LSD. LSD and BOL antagonized the apomorphine-induced decrease of DOPA accumulation, without affecting the haloperidol-induced increase. LSD like apomorphine inhibited the increase of DOPA accumulation seen after reserpine, cerebral hemisection and after gamma-butyrolactone (GBL). The effect of apomorphine in rats given GBL was blocked by haloperidol, but not by BOL and promethazine, whereas that of LSD was inhibited by haloperidol, BOL, and promethazine. These findings suggest that LSD and BOL directly affect nigro-neostriatal dopamine neurons. LSD therefore appears to be a partial agonist and BOL a pure antagonist at dopamine autoreceptors. It is proposed in addition that LSD activates and BOL blocks 5-HT receptors that control DOPA formation. | [
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|
PMID:16757 | Vascular beta-adrenoceptor stimulating properties of phenylephrine. | In pithed rats pretreated with propranolol changes occurred in the slopes of dose--pressor response curves to i.v. phenylephrine and noradrenaline but not to LD 3098, a pure alpha-adrenoceptor stimulant. In dogs, cats, and spontaneously hypertensive rats pretreated with an alpha-adrenoceptor blocker, i.v. phenylephrine induced vasodilatory responses which were antagonised by propranolol. These results indicate that phenylephrine, in addition to its known beta1-agonistic properties, stimulates the vascular beta2-adrenoceptors. | Vascular beta-adrenoceptor stimulating properties of phenylephrine. In pithed rats pretreated with propranolol changes occurred in the slopes of dose--pressor response curves to i.v. phenylephrine and noradrenaline but not to LD 3098, a pure alpha-adrenoceptor stimulant. In dogs, cats, and spontaneously hypertensive rats pretreated with an alpha-adrenoceptor blocker, i.v. phenylephrine induced vasodilatory responses which were antagonised by propranolol. These results indicate that phenylephrine, in addition to its known beta1-agonistic properties, stimulates the vascular beta2-adrenoceptors. | [
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|
PMID:16767 | Subpopulations of T-lymphocytes in Peyer's patches: sensitivity to antilymphocyte serum and adult thymectomy. | Anti-lymphocyte (ALS) treatment or adult thymectomy of the donor have been shown to depress respectively the cell proliferation and the cytotoxicity in the graft-versus-host (GVH) reaction. A quantitative assay and the histological criteria of the GVH reaction have been used to demonstrate that all the known subpopulations of T-lymphocytes involved in the GVH reaction are present in the Peyer's patches as well as in the spleen and mesenteric lymph nodes in the rat. | Subpopulations of T-lymphocytes in Peyer's patches: sensitivity to antilymphocyte serum and adult thymectomy. Anti-lymphocyte (ALS) treatment or adult thymectomy of the donor have been shown to depress respectively the cell proliferation and the cytotoxicity in the graft-versus-host (GVH) reaction. A quantitative assay and the histological criteria of the GVH reaction have been used to demonstrate that all the known subpopulations of T-lymphocytes involved in the GVH reaction are present in the Peyer's patches as well as in the spleen and mesenteric lymph nodes in the rat. | [
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|
PMID:16769 | Correlation between serum dopamine-beta-hydroxylase activity and dopamine-beta-hydroxylase and tyrosine hydroxylase activities in central and peripheral adrenergic neurons and adrenal glands. | Serum dopamine-beta-hydroxylase activity in spontaneously hypertensive rats and Wistar-Kyoto rats had a positive correlation with dopamine-beta-hydroxylase and tyrosine hydroxylase activities in mesenteric vessels, vas deferens, and adrenal glands at 14-16 weeks of age, a negative correlation with dopamine-beta-hydroxylase activity in locus coeruleus at 3 weeks and 14-16 weeks of age, and a positive correlation with tyrosine hydroxylase activity only at 3 weeks of age, but not at 14-16 weeks of age. | Correlation between serum dopamine-beta-hydroxylase activity and dopamine-beta-hydroxylase and tyrosine hydroxylase activities in central and peripheral adrenergic neurons and adrenal glands. Serum dopamine-beta-hydroxylase activity in spontaneously hypertensive rats and Wistar-Kyoto rats had a positive correlation with dopamine-beta-hydroxylase and tyrosine hydroxylase activities in mesenteric vessels, vas deferens, and adrenal glands at 14-16 weeks of age, a negative correlation with dopamine-beta-hydroxylase activity in locus coeruleus at 3 weeks and 14-16 weeks of age, and a positive correlation with tyrosine hydroxylase activity only at 3 weeks of age, but not at 14-16 weeks of age. | [
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|
PMID:16776 | Specific metabolic pathway in vitro of pinazepam and diazepam by liver microsomal enzymes of different animal species. | The metabolic pathway of Pinazepam and Diazepam in vitro was studied with rat, guinea pig and dog liver microsomes using a chromatographic and spectrophotometric technique. Two main pathways were observed, N1-dealkylation and C3-hydroxylation. N1-dealkylation was shown to be the predominant reaction for Pinazepam in all the animal species studied, while C3-hydroxylation was the major metabolic pathway for Diazepam in the rat. No oxazepam was found when Pinazepam and Diazepam were incubated with liver microsomes. | Specific metabolic pathway in vitro of pinazepam and diazepam by liver microsomal enzymes of different animal species. The metabolic pathway of Pinazepam and Diazepam in vitro was studied with rat, guinea pig and dog liver microsomes using a chromatographic and spectrophotometric technique. Two main pathways were observed, N1-dealkylation and C3-hydroxylation. N1-dealkylation was shown to be the predominant reaction for Pinazepam in all the animal species studied, while C3-hydroxylation was the major metabolic pathway for Diazepam in the rat. No oxazepam was found when Pinazepam and Diazepam were incubated with liver microsomes. | [
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|
PMID:16774 | [Mechanism of the action of apressin under conditions of high temperature and physical exertion]. | In experiments on rats subject to study were regularities governing the metabolism of glycogen, milk, pyruvic acid, phosphocreatine in the liver tissues, cortex, musculus gastrocnemius and in the myocardium, as well as of acids in the peripheral blood at 40 degrees C of outside temperature, 95 per cent humidity and during swimming. Investigations also covered preventive application of apressin in rats. The influence of stress was found to produce metabolic changes in the organism of rats. In hypoxia apressin tended to prolong the life-span of the test animals by as much as 30 per cent, to keep intact metabolism in the musculus gastrocnemius and in the myocardium, but, when used in a dose of 0.05 mg/kg, it failed to avert disorders in the cortex tissues. | [Mechanism of the action of apressin under conditions of high temperature and physical exertion]. In experiments on rats subject to study were regularities governing the metabolism of glycogen, milk, pyruvic acid, phosphocreatine in the liver tissues, cortex, musculus gastrocnemius and in the myocardium, as well as of acids in the peripheral blood at 40 degrees C of outside temperature, 95 per cent humidity and during swimming. Investigations also covered preventive application of apressin in rats. The influence of stress was found to produce metabolic changes in the organism of rats. In hypoxia apressin tended to prolong the life-span of the test animals by as much as 30 per cent, to keep intact metabolism in the musculus gastrocnemius and in the myocardium, but, when used in a dose of 0.05 mg/kg, it failed to avert disorders in the cortex tissues. | [
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|
PMID:16775 | [Sulfaphenazole binding by p-450 cytochrome of liver microsomes of rats and its effect of cytochrome-p-450-reductase]. | Tests set up "in vitro" on the rats' liver microsomes showed that sulfaphenazol, which in an inhibitor of the mixed type N-and O-demethylation, is bound as a substrate of the II type (aniline type). It attenuates spectral changes caused by aniline and vice versa. Sulfaphenazol inhibits the activity of the ADPH cytochrome-P-450-reductase. | [Sulfaphenazole binding by p-450 cytochrome of liver microsomes of rats and its effect of cytochrome-p-450-reductase]. Tests set up "in vitro" on the rats' liver microsomes showed that sulfaphenazol, which in an inhibitor of the mixed type N-and O-demethylation, is bound as a substrate of the II type (aniline type). It attenuates spectral changes caused by aniline and vice versa. Sulfaphenazol inhibits the activity of the ADPH cytochrome-P-450-reductase. | [
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|
PMID:16782 | Regulation of gastric acid secretion. | The advent of the H2-histamine-receptor antagonists has given new life to the old hypothesis that histamine might be the final common chemical mediator of acid secretion. The available evidence, however, does not prove this hypothesis but does confer on histamine a role in the regulation of acid secretion in normal physiology. Evidence is mounting that, in addition to its stimulatory action, the vagus may play an inhibitory role in acid secretion and gastrin release. Our concepts of the gastric phase of acid secretion have been extended by the discovery of cross distension reflexes in the stomach: the pyloro-oxyntic reflex for acid secretion and the oxyntopyloric reflex for gastrin release. In addition, digested protein has been shown to stimulate directly the oxyntic gland mucosa, but the evidence is against a role for this mechanism in the intact stomach. The hormone(s) responsible for the intestinal phase have not been isolated but the physiological characteristics of entero-oxyntin (a nongastrin, enteric substance that acts on the oxyntic cell) have been defined. Gastric inhibitory polypeptide is an excellent candidate for the entero-gastrone released by fat, but whether it is the sole enterogastrone released is yet to be determined. | Regulation of gastric acid secretion. The advent of the H2-histamine-receptor antagonists has given new life to the old hypothesis that histamine might be the final common chemical mediator of acid secretion. The available evidence, however, does not prove this hypothesis but does confer on histamine a role in the regulation of acid secretion in normal physiology. Evidence is mounting that, in addition to its stimulatory action, the vagus may play an inhibitory role in acid secretion and gastrin release. Our concepts of the gastric phase of acid secretion have been extended by the discovery of cross distension reflexes in the stomach: the pyloro-oxyntic reflex for acid secretion and the oxyntopyloric reflex for gastrin release. In addition, digested protein has been shown to stimulate directly the oxyntic gland mucosa, but the evidence is against a role for this mechanism in the intact stomach. The hormone(s) responsible for the intestinal phase have not been isolated but the physiological characteristics of entero-oxyntin (a nongastrin, enteric substance that acts on the oxyntic cell) have been defined. Gastric inhibitory polypeptide is an excellent candidate for the entero-gastrone released by fat, but whether it is the sole enterogastrone released is yet to be determined. | [
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|
PMID:16783 | Localization of hypophysiotropic neurohormones by assay of sections from various brain areas. | The results of studies of the localization of the hypothalamic hypophysiotropic factors based on their direct determination in sections or nuclear punches are described. Luteinizing hormone-releasing hormone was found in high concentrations in the median eminence-arcuate nucleus complex, in lower concentrations in the mediobasal zone of the preoptic area. In addition to these hypothalamic sites, it is present in all four periventricular organs, especially in the organum vasculosum laminae terminalis. Thyrotropin releasing hormone has a widespread distribution. High concentrations are in the median eminence, arcuate nucleus, dorsomedial nucleus, and anterior part of the ventromedial nucleus. Lower concentrations are in several other structures of the hypothalamus, preoptic area and septum, and low but measurable quantities are found in most of the structures of the brain. Somatostatin is also present in most structures of the central nervous system, with highest concentrations in the median eminence, arcuate nucleus, ventromedial nucleus and periventricular nucleus. There are indications that the ventromedial nucleus or its immediate vicinity contains growth hormone releasing factor. Prolactin releasing activity was present in the median eminence and mediobasal parts of the anterior hypothalamus, whereas prolactin inhibitory activity was in the dorsolateral parts of the anterior hypothalamus and/or preoptic area. | Localization of hypophysiotropic neurohormones by assay of sections from various brain areas. The results of studies of the localization of the hypothalamic hypophysiotropic factors based on their direct determination in sections or nuclear punches are described. Luteinizing hormone-releasing hormone was found in high concentrations in the median eminence-arcuate nucleus complex, in lower concentrations in the mediobasal zone of the preoptic area. In addition to these hypothalamic sites, it is present in all four periventricular organs, especially in the organum vasculosum laminae terminalis. Thyrotropin releasing hormone has a widespread distribution. High concentrations are in the median eminence, arcuate nucleus, dorsomedial nucleus, and anterior part of the ventromedial nucleus. Lower concentrations are in several other structures of the hypothalamus, preoptic area and septum, and low but measurable quantities are found in most of the structures of the brain. Somatostatin is also present in most structures of the central nervous system, with highest concentrations in the median eminence, arcuate nucleus, ventromedial nucleus and periventricular nucleus. There are indications that the ventromedial nucleus or its immediate vicinity contains growth hormone releasing factor. Prolactin releasing activity was present in the median eminence and mediobasal parts of the anterior hypothalamus, whereas prolactin inhibitory activity was in the dorsolateral parts of the anterior hypothalamus and/or preoptic area. | [
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|
PMID:16787 | Lysis of periadnexal adhesions for correction of infertility. | A series of patients is presented in whom lysis of periadnexal adhesions was carried out for correction of infertility. These 35 couples had been infertile for at least 1 year prior to surgery. Seventy-seven per cent had been trying to conceive for more than 18 months. Following diagnostic evaluation, periadnexal adhesions were found to be the sole cause of infertility in 83% of cases. Subsequent to surgery, 63% of the patients conceived, 82% within 18 months, and 57% gave birth to at least one viable child. There can be no doubt that periadnexal adhesions represent true pathology. Although often seemingly insignificant in character, at the macroscopic level, they appear to play a major role at the microscopic level in impairing ovum pickup by the fallopian tube. Gynecologists should recognize the importance of these structures as mediators of a condition of relative sterility. Thus, despite the demonstration of tubal patency, the function of the rather delicate fimbria may be compromised by periadnexal adhesions, conglutinations, and hydatids so that only a fraction of those eggs that leave the ovary at ovulation reach the interior of the fallopian tube. | Lysis of periadnexal adhesions for correction of infertility. A series of patients is presented in whom lysis of periadnexal adhesions was carried out for correction of infertility. These 35 couples had been infertile for at least 1 year prior to surgery. Seventy-seven per cent had been trying to conceive for more than 18 months. Following diagnostic evaluation, periadnexal adhesions were found to be the sole cause of infertility in 83% of cases. Subsequent to surgery, 63% of the patients conceived, 82% within 18 months, and 57% gave birth to at least one viable child. There can be no doubt that periadnexal adhesions represent true pathology. Although often seemingly insignificant in character, at the macroscopic level, they appear to play a major role at the microscopic level in impairing ovum pickup by the fallopian tube. Gynecologists should recognize the importance of these structures as mediators of a condition of relative sterility. Thus, despite the demonstration of tubal patency, the function of the rather delicate fimbria may be compromised by periadnexal adhesions, conglutinations, and hydatids so that only a fraction of those eggs that leave the ovary at ovulation reach the interior of the fallopian tube. | [
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|
PMID:16791 | Double-blind placebo-controlled efficacy study of ketazolam (U-28,774). | The safety and efficacy of ketazolam (15 mg capsules) was compared to placebo in seventy-nine out-patients suffering from psychoneurotic anxiety, moderate or worse in severity. A flexible dosage range of 15-75 mg was used in this double-blind study lasting twenty-eight days. The average optimum therapeutic dose of ketazolam was 46-9 mg administered as a once-day dose at bedtime. Ketazolam was found to be significantly better than placebo in alleviating anxiety and its concomitant symptomatology as measured by the Hamilton Anxiety Rating Scale, three Physician's Global Impressions, two Patient's Global Impressions, and three Target Symptoms. Fifteen patients dropped from the placebo group before completion of the study, and two withdrew from the ketazolam group. The patients receiving ketazolam experienced a greater reduction in symptomatology throughout the study when compared to the placebo group. Side-effects experienced by the ketazolam patients were less than, or equal to, the placebo patients. No deleterious side-effects occurred. No differences between the two groups were found for vital signs, EKG's, laboratory tests, or physical examinations. | Double-blind placebo-controlled efficacy study of ketazolam (U-28,774). The safety and efficacy of ketazolam (15 mg capsules) was compared to placebo in seventy-nine out-patients suffering from psychoneurotic anxiety, moderate or worse in severity. A flexible dosage range of 15-75 mg was used in this double-blind study lasting twenty-eight days. The average optimum therapeutic dose of ketazolam was 46-9 mg administered as a once-day dose at bedtime. Ketazolam was found to be significantly better than placebo in alleviating anxiety and its concomitant symptomatology as measured by the Hamilton Anxiety Rating Scale, three Physician's Global Impressions, two Patient's Global Impressions, and three Target Symptoms. Fifteen patients dropped from the placebo group before completion of the study, and two withdrew from the ketazolam group. The patients receiving ketazolam experienced a greater reduction in symptomatology throughout the study when compared to the placebo group. Side-effects experienced by the ketazolam patients were less than, or equal to, the placebo patients. No deleterious side-effects occurred. No differences between the two groups were found for vital signs, EKG's, laboratory tests, or physical examinations. | [
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|
PMID:16792 | Hypnotic efficacy of triazolam and methyprylon ininsomniac in-patients. | The hypnotic effects of a new triazolobenzodiazepine, triazolam (Halcion) 0-5 mg and methyprylon 300 mg was compared in twenty oncologic in-patient volunteers with insomnia using the preference technique. On the first night of the two-night trial, or methyprylon was given on a double-blind basis and on the second night the patients received the alternate medication. Following each trial night the patients were interviewed in regard to their sleep. Of the seventeen patients who completed the study, eleven patients preferred triazolam, three preferred methyprylon and three had no preference (p=0-057). Analysis of the various sleep parameters showed that triazolam helped the patients sleep more than methyprylon (p=0-13), induced more rapid sleep onset (p=0-003), gave a longer duration of sleep (p=0-013). The treatment was considered a success if the patient went to sleep in thirty minutes or less and slept for at least six hours. Triazolam was more successful than methyprylon in this respect (p=0-012). There were no side-effects reported on either of the drugs. | Hypnotic efficacy of triazolam and methyprylon ininsomniac in-patients. The hypnotic effects of a new triazolobenzodiazepine, triazolam (Halcion) 0-5 mg and methyprylon 300 mg was compared in twenty oncologic in-patient volunteers with insomnia using the preference technique. On the first night of the two-night trial, or methyprylon was given on a double-blind basis and on the second night the patients received the alternate medication. Following each trial night the patients were interviewed in regard to their sleep. Of the seventeen patients who completed the study, eleven patients preferred triazolam, three preferred methyprylon and three had no preference (p=0-057). Analysis of the various sleep parameters showed that triazolam helped the patients sleep more than methyprylon (p=0-13), induced more rapid sleep onset (p=0-003), gave a longer duration of sleep (p=0-013). The treatment was considered a success if the patient went to sleep in thirty minutes or less and slept for at least six hours. Triazolam was more successful than methyprylon in this respect (p=0-012). There were no side-effects reported on either of the drugs. | [
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|
PMID:16793 | Intermediate use of triazolam: a sleep laboratory study. | The present study was undertaken to evaluate the intermediate effects of triazolam 0-5 mg on the sleep of insomniac patients. The results showed that triazolam is effective in inducing and maintaining sleep without producing any major effects on sleep staging. Triazolam did not lead to significant subjective complaints or any deterioration in the physical condition of the patients. The effectiveness of traizolam did not vary over a two-week period. | Intermediate use of triazolam: a sleep laboratory study. The present study was undertaken to evaluate the intermediate effects of triazolam 0-5 mg on the sleep of insomniac patients. The results showed that triazolam is effective in inducing and maintaining sleep without producing any major effects on sleep staging. Triazolam did not lead to significant subjective complaints or any deterioration in the physical condition of the patients. The effectiveness of traizolam did not vary over a two-week period. | [
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|
PMID:16794 | Psychometric assessment of the therapeutic efficiency of antidepressant agents. | A clinical trial of four weeks duration was conducted involving a total of thirty depressed patients, of both sexes, aged between twenty and thirty-four years. The total number of patients was divided into three groups of ten patients each. One group received amitriptyline, the second group was administered noxiptyline and the third group was given dibenzepine. All drugs were administered orally. Patients were submitted to psychometric testing before and after drug administration. The tests used included the 'Hamilton Rating Scale for depression', the 'Hildreth Feeling Scale' and the 'D Scale' and the 'Trail Making Test' for the evaluation of psychomotor retardation. It was concluded that the Hamilton Rating Scale was the most relatively sensitive test utilized in assessing the depressive state and its improvement. Amitriptyline was found to be mostly anxiolytic; noxiptyline controlled both depression and anxiety to approximately the same extent; and dibenzepine was found to be a mood-elevating drug with an energizing action. | Psychometric assessment of the therapeutic efficiency of antidepressant agents. A clinical trial of four weeks duration was conducted involving a total of thirty depressed patients, of both sexes, aged between twenty and thirty-four years. The total number of patients was divided into three groups of ten patients each. One group received amitriptyline, the second group was administered noxiptyline and the third group was given dibenzepine. All drugs were administered orally. Patients were submitted to psychometric testing before and after drug administration. The tests used included the 'Hamilton Rating Scale for depression', the 'Hildreth Feeling Scale' and the 'D Scale' and the 'Trail Making Test' for the evaluation of psychomotor retardation. It was concluded that the Hamilton Rating Scale was the most relatively sensitive test utilized in assessing the depressive state and its improvement. Amitriptyline was found to be mostly anxiolytic; noxiptyline controlled both depression and anxiety to approximately the same extent; and dibenzepine was found to be a mood-elevating drug with an energizing action. | [
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|
PMID:16795 | Some aspects of the pharmacology of analgesia. | This paper makes comparisons of some of the pharmacological properties of the opiate analgesics and the tricyclic antidepressants in order to justify the clinical examination of the tricyclics as potential analgesic or proanalgesic agents in man. Preliminary animal data suggest that the tricyclic agent clomipramine (Anafranil, Geigy) will potentiate the effects of morphine, pentazocine and cyclazocine. | Some aspects of the pharmacology of analgesia. This paper makes comparisons of some of the pharmacological properties of the opiate analgesics and the tricyclic antidepressants in order to justify the clinical examination of the tricyclics as potential analgesic or proanalgesic agents in man. Preliminary animal data suggest that the tricyclic agent clomipramine (Anafranil, Geigy) will potentiate the effects of morphine, pentazocine and cyclazocine. | [
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|
PMID:16796 | The use of psychotropic drugs in rheumatology. | The possible role of various psychotropic drugs in the management of rheumatic diseases is considered--tranquillizers, sedatives, tricyclic antidepressants and monoamine oxidase inhibitors. The dilemma of which anti-depressant for which patient is considered. The possible association between rheumatoid disease and disorders of the brain, brain-stem and autonomic nervous system is discussed. Psychotropic drugs may effect the disease itself as well as the patient's mood. The author is opposed, however, to the idea that rheumatoid arthritis may be regarded as a psychosomatic disease. | The use of psychotropic drugs in rheumatology. The possible role of various psychotropic drugs in the management of rheumatic diseases is considered--tranquillizers, sedatives, tricyclic antidepressants and monoamine oxidase inhibitors. The dilemma of which anti-depressant for which patient is considered. The possible association between rheumatoid disease and disorders of the brain, brain-stem and autonomic nervous system is discussed. Psychotropic drugs may effect the disease itself as well as the patient's mood. The author is opposed, however, to the idea that rheumatoid arthritis may be regarded as a psychosomatic disease. | [
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|
PMID:16797 | The use of psychotropic drugs in a pain clinic. | The paper is based on experiences gained at a hospital pain clinic. Patients attending such a pain clinic can be divided into three categories: (1) Those with chronic organic lesions in whom the mental state was little affected. (2) Those with organic lesions who had mental changes which influenced their experience of the pain. (3) Patients who had primary mental changes in whom the complaint of pain was a symptom of their mental state. The importance of full history taking, ab initio, is stressed. Much can be learned from patients' ideas of causation and these should be considered. Phychiatric diagnoses should be reached positively and not by a process of exclusion. Distinction must be made between depression and normal sadness and it is important to establish the relationship between the onset of depression and the painful symptoms. When psychopathology is evident a variety of treatments are available. There is, however, a 'hard core' of patients who display no depression and little anxiety. In such cases the manipulative value of pain should be considered. | The use of psychotropic drugs in a pain clinic. The paper is based on experiences gained at a hospital pain clinic. Patients attending such a pain clinic can be divided into three categories: (1) Those with chronic organic lesions in whom the mental state was little affected. (2) Those with organic lesions who had mental changes which influenced their experience of the pain. (3) Patients who had primary mental changes in whom the complaint of pain was a symptom of their mental state. The importance of full history taking, ab initio, is stressed. Much can be learned from patients' ideas of causation and these should be considered. Phychiatric diagnoses should be reached positively and not by a process of exclusion. Distinction must be made between depression and normal sadness and it is important to establish the relationship between the onset of depression and the painful symptoms. When psychopathology is evident a variety of treatments are available. There is, however, a 'hard core' of patients who display no depression and little anxiety. In such cases the manipulative value of pain should be considered. | [
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|
PMID:16799 | Nefopam HCl interaction study with eight other drugs. | A controlled clinical trial was undertaken to determine potential for drug interaction of nefopam HCl, a new analgesic, with eight other widely used compounds. Nefopam HCl was administered in combination with these drugs and placebo to forty-five healthy volunteer subjects in nine groups of five subjects each. Possible drug interactions were detected by the occurrence of side-effects and interference with bioavailability of the new analgesic, also by changes in vital signs or in various laboratory tests. Results indicated no statistically significant differences in these parameters between the nefopam HCl-placebo regimen and the other eight combinations. Despite this, there were substantial clinical differences in the intensity and incidence of side-effects with combinations of codeine, pentazocine and propoxyphene. These differences warrant further study. Serum nefopam HCl levels were significantly higher on Day 3 than on Day 1, indicating no defect in bioavailability due to drug interaction. Overall, results of this study support the feasibility of concomitant use of these eight drugs with nefopam HCl for short treatment periods. | Nefopam HCl interaction study with eight other drugs. A controlled clinical trial was undertaken to determine potential for drug interaction of nefopam HCl, a new analgesic, with eight other widely used compounds. Nefopam HCl was administered in combination with these drugs and placebo to forty-five healthy volunteer subjects in nine groups of five subjects each. Possible drug interactions were detected by the occurrence of side-effects and interference with bioavailability of the new analgesic, also by changes in vital signs or in various laboratory tests. Results indicated no statistically significant differences in these parameters between the nefopam HCl-placebo regimen and the other eight combinations. Despite this, there were substantial clinical differences in the intensity and incidence of side-effects with combinations of codeine, pentazocine and propoxyphene. These differences warrant further study. Serum nefopam HCl levels were significantly higher on Day 3 than on Day 1, indicating no defect in bioavailability due to drug interaction. Overall, results of this study support the feasibility of concomitant use of these eight drugs with nefopam HCl for short treatment periods. | [
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|
PMID:16800 | A comparative study of antidepressants in the treatment of depressive states. | The effect of six antidepressants has been investigated in six groups of twenty patients suffering from depressive states. The over-all response of the six groups, as well as the response of the individual target symptoms of depression according to the Hamilton Rating Scale are reported. | A comparative study of antidepressants in the treatment of depressive states. The effect of six antidepressants has been investigated in six groups of twenty patients suffering from depressive states. The over-all response of the six groups, as well as the response of the individual target symptoms of depression according to the Hamilton Rating Scale are reported. | [
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PMID:16801 | Preference studies of triazolam with standard hypnotics in out-patients with insomnia. | One hundred and four patients suffering from insomnia took part in four different two-night double-blind crossover trials of triazolam. In three separate studies, triazolam 0-5 mg was compared to placebo, flurazepam 30 mg and chloral hydrate 500 mg. Triazolam 0-5 mg was found to be preferred and to be superior to placebo, flurazepam and chloral hydrate in the treatment of insomnia. Analysis of sleep questionnaire data showed triazolam to be superior to the other treatments on the following: How much did the medication help you sleep, onset of sleep, duration of sleep and number of awakenings. Additionally, triazolam was superior to chloral hydrate on the feeling in the morning parameter. In another comparison of triazolam 0-25 mg to flurazepan 15 mg, triazolam was not significantly better than flurazepam on any of the efficacy parameters except that the patients felt more alert the morning following triazolam that following flurazepam. On all efficacy endpoints, trends for all parameters favoured triazolam 0-25 mg over flurazepam 15 mg. Untoward side-effects in these four studies were minimal. | Preference studies of triazolam with standard hypnotics in out-patients with insomnia. One hundred and four patients suffering from insomnia took part in four different two-night double-blind crossover trials of triazolam. In three separate studies, triazolam 0-5 mg was compared to placebo, flurazepam 30 mg and chloral hydrate 500 mg. Triazolam 0-5 mg was found to be preferred and to be superior to placebo, flurazepam and chloral hydrate in the treatment of insomnia. Analysis of sleep questionnaire data showed triazolam to be superior to the other treatments on the following: How much did the medication help you sleep, onset of sleep, duration of sleep and number of awakenings. Additionally, triazolam was superior to chloral hydrate on the feeling in the morning parameter. In another comparison of triazolam 0-25 mg to flurazepan 15 mg, triazolam was not significantly better than flurazepam on any of the efficacy parameters except that the patients felt more alert the morning following triazolam that following flurazepam. On all efficacy endpoints, trends for all parameters favoured triazolam 0-25 mg over flurazepam 15 mg. Untoward side-effects in these four studies were minimal. | [
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|
PMID:16803 | The nocturnal intragastric pH in EEG sleep stages in peptic ulcer patients. | In 10 peptic ulcer patients, 5 duodenal ulcer and 5 gastric ulcer patients, the relation of nocturnal intragastric pH to EEG sleep stages was examined. The nocturnal intragastric pH was monitored by pH-measuring telemeter and sleep stages were recorded simultaneously by electroencephalography throughout the night. The EEG sleep stages were classified after the criteria of Dement and Kleitman. The average of intragastric pH level at each sleep stage was higher in gastric ulcer than the duodenal ulcer. The intragastric pH level became low as the patients' sleep advanced to deep stage. This tendency was more likely in duodenal ulcer patients than the gastric ulcer patients, which indicated that the cephalic phase might play an important role in the pathogenesis of hyperacidity in duodenal ulcer. | The nocturnal intragastric pH in EEG sleep stages in peptic ulcer patients. In 10 peptic ulcer patients, 5 duodenal ulcer and 5 gastric ulcer patients, the relation of nocturnal intragastric pH to EEG sleep stages was examined. The nocturnal intragastric pH was monitored by pH-measuring telemeter and sleep stages were recorded simultaneously by electroencephalography throughout the night. The EEG sleep stages were classified after the criteria of Dement and Kleitman. The average of intragastric pH level at each sleep stage was higher in gastric ulcer than the duodenal ulcer. The intragastric pH level became low as the patients' sleep advanced to deep stage. This tendency was more likely in duodenal ulcer patients than the gastric ulcer patients, which indicated that the cephalic phase might play an important role in the pathogenesis of hyperacidity in duodenal ulcer. | [
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PMID:16806 | Comparison of an H2 receptor antagonist and a neutralizing antacid on postprandial acid delivery into the duodenum in patients with duodenal ulcer. | Measurement of the postprandial rate of acid delivery into the duodenum directly assessed the efficacy of two radically different acid-reducing therapies for duodenal ulcer disease. Cimetidine, 400 mg, with an ordinary solid meal decreased the 4-hr delivery of titratable acid and hydrogen ion into the duodenum by 63 and 86%, respectively (P less than 0.01 versus control). Liquid Maalox, 30 ml, 1 and 3 hr after an identical meal reduced 4-hr delivery of acid by 47 and 74%, respectively (P less than 0.01 versus control). During the study period, the H2 receptor antagonist effected a continuous reduction in gastric acidity and the delivery of acid into the duodenum. The liquid neutralizing antacid produced a more fluctuating decrease in these parameters. However, given in these dosages, the magnitude and duration of the acid-reducing effect were similar for both treatments. | Comparison of an H2 receptor antagonist and a neutralizing antacid on postprandial acid delivery into the duodenum in patients with duodenal ulcer. Measurement of the postprandial rate of acid delivery into the duodenum directly assessed the efficacy of two radically different acid-reducing therapies for duodenal ulcer disease. Cimetidine, 400 mg, with an ordinary solid meal decreased the 4-hr delivery of titratable acid and hydrogen ion into the duodenum by 63 and 86%, respectively (P less than 0.01 versus control). Liquid Maalox, 30 ml, 1 and 3 hr after an identical meal reduced 4-hr delivery of acid by 47 and 74%, respectively (P less than 0.01 versus control). During the study period, the H2 receptor antagonist effected a continuous reduction in gastric acidity and the delivery of acid into the duodenum. The liquid neutralizing antacid produced a more fluctuating decrease in these parameters. However, given in these dosages, the magnitude and duration of the acid-reducing effect were similar for both treatments. | [
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PMID:16807 | Aspirin esterase of gastric mucosal origin. | The enzyme, aspirin esterase, which converts acetylsalicyclic acid to the less toxic salicyclic acid, was found to be present in gastric mucosal specimens obtained from surgically resected tissue. The enzyme was found to be stable to storage and active at two pH optima. Alcohol in the reaction mixture produced a net effect of slowing the rate of aspirin hydrolysis; this was attributable to a marked inhibitory effect on aspirin esterase activity which was not completely counteracted by the increased rate of spontaneous breakdown of aspirin by alcohol. Age, sex, or gastric disease state of the patient from whom the tissue was obtained, did not significantly alter the level of enzyme activity measured, nor were different levels obtained from body or antral mucosa. In patients with gastric ulcer, those with a previous history of regular aspirin consumption did not show significantly different levels from those without such a history. It is concluded that aspirin esterase activity of gastric mucosa is not alone a significant factor in any role acetylsalicyclic acid may play in the etiology and natural history of chronic peptic ulcer. | Aspirin esterase of gastric mucosal origin. The enzyme, aspirin esterase, which converts acetylsalicyclic acid to the less toxic salicyclic acid, was found to be present in gastric mucosal specimens obtained from surgically resected tissue. The enzyme was found to be stable to storage and active at two pH optima. Alcohol in the reaction mixture produced a net effect of slowing the rate of aspirin hydrolysis; this was attributable to a marked inhibitory effect on aspirin esterase activity which was not completely counteracted by the increased rate of spontaneous breakdown of aspirin by alcohol. Age, sex, or gastric disease state of the patient from whom the tissue was obtained, did not significantly alter the level of enzyme activity measured, nor were different levels obtained from body or antral mucosa. In patients with gastric ulcer, those with a previous history of regular aspirin consumption did not show significantly different levels from those without such a history. It is concluded that aspirin esterase activity of gastric mucosa is not alone a significant factor in any role acetylsalicyclic acid may play in the etiology and natural history of chronic peptic ulcer. | [
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|
PMID:16812 | Ditazole and platelets. I. Effect of ditazole on human platelet function in vitro. | Ditazole (4,5-diphenyl-2-bis-(2-hydroxyethyl)-aminoxazol) has been shown to be a strong in vitro inhibitor of human platelet aggregation brought about by release reaction inducers; in contrast, it did not significantly affect primary ADP-induced aggregation. Ditazole strongly inhibited the release of platelet-bound 14C-serotonin under the influence of Thrombofax, whereas it did not interfere with the transport and storage of serotonin in nonstimulated platelets. The effect of ditazole was not potentiated by acetylsalicylic acid. Ditazole also inhibited ADP-reptilase clot retraction and modified thrombin-induced clot formation. The inhibition of platelet aggregation exerted by ditazole in plasma could be removed following gel filtration of platelets on Sepharose 2-B gel. This would indicate that ditazole does not act on platelets by a 'hit and run' mechanism. | Ditazole and platelets. I. Effect of ditazole on human platelet function in vitro. Ditazole (4,5-diphenyl-2-bis-(2-hydroxyethyl)-aminoxazol) has been shown to be a strong in vitro inhibitor of human platelet aggregation brought about by release reaction inducers; in contrast, it did not significantly affect primary ADP-induced aggregation. Ditazole strongly inhibited the release of platelet-bound 14C-serotonin under the influence of Thrombofax, whereas it did not interfere with the transport and storage of serotonin in nonstimulated platelets. The effect of ditazole was not potentiated by acetylsalicylic acid. Ditazole also inhibited ADP-reptilase clot retraction and modified thrombin-induced clot formation. The inhibition of platelet aggregation exerted by ditazole in plasma could be removed following gel filtration of platelets on Sepharose 2-B gel. This would indicate that ditazole does not act on platelets by a 'hit and run' mechanism. | [
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|
PMID:16809 | [Histamine 2 receptor antagonists in the treatment of gastric ulcer]. | Eight patients with a clinical, radiology and endoscopic diagnosis of benign peptic ulcer were studied in a prospective fashion using Cimetidine (H2-Receptor antagonist). With this outgoing form of therapy the need for antiacid diminished greatly and pain totally disappeared. We discuss the possible etiological pathways of gastric ulcer and finally propose the simultaneous use of H2-Receptor antagonist and colesteramine with the goal of eliminating the two predominant factors that cause the lesion. | [Histamine 2 receptor antagonists in the treatment of gastric ulcer]. Eight patients with a clinical, radiology and endoscopic diagnosis of benign peptic ulcer were studied in a prospective fashion using Cimetidine (H2-Receptor antagonist). With this outgoing form of therapy the need for antiacid diminished greatly and pain totally disappeared. We discuss the possible etiological pathways of gastric ulcer and finally propose the simultaneous use of H2-Receptor antagonist and colesteramine with the goal of eliminating the two predominant factors that cause the lesion. | [
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PMID:16814 | [Glucocorticoid action of beclomethasone and its propionate ester derivatives]. | In the present pharmacokinetic studies on beclomethasone dipropionate in rats, it was suggested that most of the beclomethasone-17, 21dipropionate is transformed rapidly into beclomethasone-17-monopropionate or beclomethasone in the blood or tissues and exerts the glucocorticoid effect in the form of beclomethasone. Glucocorticoid activity of beclomethasone was revealed to be 1-10% that of dexamethasone both in the hypothalamopituitaryadrenocortical suppressive effect and liver tyrosine amino transferase inducing efect in rats. Beclomethasone and its propionate derivatives were shown to have higher binding affinity to glucocorticoid receptors in rat liver, thymus and hypophysis than that of dexamethasone. The experimental results herein may serve to explain why beclomethasone and its propionate derivatives showed such a weak glucocorticoid action in comparison with that of dexamethasone. The amounts of receptor-beclomethasone (or its propionate derivatives) complexes which bound specifically to liver nuclei were only 10% or less than those of receptordexamethasone complexes and the in vivo metabolism of beclomethasone and beclomethasone-dipropionate was more rapid than that of dexamethasone. | [Glucocorticoid action of beclomethasone and its propionate ester derivatives]. In the present pharmacokinetic studies on beclomethasone dipropionate in rats, it was suggested that most of the beclomethasone-17, 21dipropionate is transformed rapidly into beclomethasone-17-monopropionate or beclomethasone in the blood or tissues and exerts the glucocorticoid effect in the form of beclomethasone. Glucocorticoid activity of beclomethasone was revealed to be 1-10% that of dexamethasone both in the hypothalamopituitaryadrenocortical suppressive effect and liver tyrosine amino transferase inducing efect in rats. Beclomethasone and its propionate derivatives were shown to have higher binding affinity to glucocorticoid receptors in rat liver, thymus and hypophysis than that of dexamethasone. The experimental results herein may serve to explain why beclomethasone and its propionate derivatives showed such a weak glucocorticoid action in comparison with that of dexamethasone. The amounts of receptor-beclomethasone (or its propionate derivatives) complexes which bound specifically to liver nuclei were only 10% or less than those of receptordexamethasone complexes and the in vivo metabolism of beclomethasone and beclomethasone-dipropionate was more rapid than that of dexamethasone. | [
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|
PMID:16815 | A comparative clinical study for the evaluation of antianxiety agents, (lorazepam, diazepam and placebo), in neurosis. | To evaluate the clinical effects of lorazepam on neurosis, a double-blind controlled trial by group comparison procedure was carried out using diazepam and placebo as control drugs. The clinical improvement and aggravation rates by means of a variety of assessment of change were compared between each of the two active drugs and placebo. The superiority, characteristics of therapeutic effects and minor side effects of lorazepam which is similar to those of diazepam, a standard benzodiazepine anxiolytic for the treatment of neurosis, were demonstrated. From this study, many important problems which might be influenced upon the outcome of the pharmacotherapy on neurotics, such as positive and negative placebo effects, aggravation and drop-out during the trial, were also evaluated. | A comparative clinical study for the evaluation of antianxiety agents, (lorazepam, diazepam and placebo), in neurosis. To evaluate the clinical effects of lorazepam on neurosis, a double-blind controlled trial by group comparison procedure was carried out using diazepam and placebo as control drugs. The clinical improvement and aggravation rates by means of a variety of assessment of change were compared between each of the two active drugs and placebo. The superiority, characteristics of therapeutic effects and minor side effects of lorazepam which is similar to those of diazepam, a standard benzodiazepine anxiolytic for the treatment of neurosis, were demonstrated. From this study, many important problems which might be influenced upon the outcome of the pharmacotherapy on neurotics, such as positive and negative placebo effects, aggravation and drop-out during the trial, were also evaluated. | [
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|
PMID:16816 | [The regulation of FSH release by the testis. Studies on inhibin]. | The FSH release from the hypophysis is suggested to be particularly regulated by a testicular hormone called inhibin. Origin, structure and target organs of inhibin are unknown. Experiments to test some hypotheses in this field are described. Adult male rats, prenatally treated with busulfan, show only Sertoli cells in the semiferous tubules. Experimental cryptorchidism and orchidectomy, however, leads to an increase in FSH levels as observed in normal animals. This indicates the role of Sertoli cells in FSH regulation. Ligation of efferent ducts of testes leads to an increase of FSH levels, too, indicating that an FSH-inhibiting principle cannot be absorbed. Interstitial testis fluid (ITF) of normal rats was applicated to immature female rats. Their FSH release is inhibited, visible in the lower ovarian weight gain following additional hCG-administration. Orchidectomized animals react with a decrease of FSH levels to the application of ITF. Therefore ITF seems to contain a FSH-inhibiting factor. Androgen binding protein-content of epididymes, however, is increased after repeated injections of ITF. It is concluded that testis (probably the Sertoli cells) produces a FSH-inhibiting factor, but ITF contains only small amounts of inhibin. | [The regulation of FSH release by the testis. Studies on inhibin]. The FSH release from the hypophysis is suggested to be particularly regulated by a testicular hormone called inhibin. Origin, structure and target organs of inhibin are unknown. Experiments to test some hypotheses in this field are described. Adult male rats, prenatally treated with busulfan, show only Sertoli cells in the semiferous tubules. Experimental cryptorchidism and orchidectomy, however, leads to an increase in FSH levels as observed in normal animals. This indicates the role of Sertoli cells in FSH regulation. Ligation of efferent ducts of testes leads to an increase of FSH levels, too, indicating that an FSH-inhibiting principle cannot be absorbed. Interstitial testis fluid (ITF) of normal rats was applicated to immature female rats. Their FSH release is inhibited, visible in the lower ovarian weight gain following additional hCG-administration. Orchidectomized animals react with a decrease of FSH levels to the application of ITF. Therefore ITF seems to contain a FSH-inhibiting factor. Androgen binding protein-content of epididymes, however, is increased after repeated injections of ITF. It is concluded that testis (probably the Sertoli cells) produces a FSH-inhibiting factor, but ITF contains only small amounts of inhibin. | [
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PMID:16818 | Suppression of ACTH secretion by synthetic MSH-release inhibiting factor Pro-Leu-Gly-NH2 in Addison's disease. | The regulation of release of MSH and ACTH seems to be closely related. The effect of Pro-Leu-Gly-NH2, the most active MSH-release inhibiting factor (MIF), was investigated on ACTH-hypersecretion in six patients suffering from primary adrenocortical insufficiency. MIF was infused at constant rates with stepwise increase in concentration (0.25 mg, 2.5 mg, 25.0 mg/30 min). Plasma ACTH-levels were measured radioimmunologically at 10 minutes intervals. In four cases there was a remarkable decrease (P less than 0.005) in the ACTH plasma level of more than 50% as compared to the elevated starting levels of 800 to 1400 pg/ml. It is concluded that under certain circumstances MIF could play a role in the regulation of ACTH-secretion. | Suppression of ACTH secretion by synthetic MSH-release inhibiting factor Pro-Leu-Gly-NH2 in Addison's disease. The regulation of release of MSH and ACTH seems to be closely related. The effect of Pro-Leu-Gly-NH2, the most active MSH-release inhibiting factor (MIF), was investigated on ACTH-hypersecretion in six patients suffering from primary adrenocortical insufficiency. MIF was infused at constant rates with stepwise increase in concentration (0.25 mg, 2.5 mg, 25.0 mg/30 min). Plasma ACTH-levels were measured radioimmunologically at 10 minutes intervals. In four cases there was a remarkable decrease (P less than 0.005) in the ACTH plasma level of more than 50% as compared to the elevated starting levels of 800 to 1400 pg/ml. It is concluded that under certain circumstances MIF could play a role in the regulation of ACTH-secretion. | [
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|
PMID:16827 | Isolation and partial characterization of plasma membranes from the livers of control and Streptococcus pneumoniae-infected rats. | Plasma membranes were isolated from the livers of control and Streptococcus pneumoniae-infected rats. This work, therefore, represents the first isolation of plasma membranes from infected actron microscopy and by the use of enzyme markers for microsomes (glucose-6-phosphatase), mitochondria (glutamate and malate dehydrogenases), and lysosomes (acid phosphatase). Plasma membranes from infected cells banded at the same sucrose density as plasma membranes from uninfected cells. Moreover, equivalent amounts of plasma membranes could be isolated from control and infected rat livers. There were, however, significant alterations in the enzyme complement of the plasma membrane after infection. 5'-Nucleotidase activity was significantly decreased, whereas alkaline phosphatase activity was significantly increased. Kinetic analysis demonstrated that only the Vmax and not the Km of these two enzymes was changed, suggesting that the altered affinity of the enzymes for substrate was not the mechanism responsible for the observed alterations. No change in the mitochondrial enzyme markers was observed after infection, but the specific activity of microsomal glucose-6-phosphatase decreased significantly. Possible explanations for the observed alterations are discussed. | Isolation and partial characterization of plasma membranes from the livers of control and Streptococcus pneumoniae-infected rats. Plasma membranes were isolated from the livers of control and Streptococcus pneumoniae-infected rats. This work, therefore, represents the first isolation of plasma membranes from infected actron microscopy and by the use of enzyme markers for microsomes (glucose-6-phosphatase), mitochondria (glutamate and malate dehydrogenases), and lysosomes (acid phosphatase). Plasma membranes from infected cells banded at the same sucrose density as plasma membranes from uninfected cells. Moreover, equivalent amounts of plasma membranes could be isolated from control and infected rat livers. There were, however, significant alterations in the enzyme complement of the plasma membrane after infection. 5'-Nucleotidase activity was significantly decreased, whereas alkaline phosphatase activity was significantly increased. Kinetic analysis demonstrated that only the Vmax and not the Km of these two enzymes was changed, suggesting that the altered affinity of the enzymes for substrate was not the mechanism responsible for the observed alterations. No change in the mitochondrial enzyme markers was observed after infection, but the specific activity of microsomal glucose-6-phosphatase decreased significantly. Possible explanations for the observed alterations are discussed. | [
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|
PMID:16828 | Gamma-irradiated chymotrypsin-like proteins. II. Connection between inactivation and structural changes. | The radiation yeilds of unfolding (Gconf) determined by the method of tryptophan fluorescence coincide with the radiation yields of proteolytic inactivation (Gin) for chymotrypsin-like (CT-like) enzymes on irradiation in air, both in solution and in the dry state with futher dissolution at pH7. It can be supposed that the unfolding is the main process determining the proteolytic gamma-inactivation of CT-like enzymes. It was also shown that the transition of chymotrypsin and trypsin gamma-irradiated at acid pH to neutral pH is an additional action, leading to unfolding of part of the molecules. | Gamma-irradiated chymotrypsin-like proteins. II. Connection between inactivation and structural changes. The radiation yeilds of unfolding (Gconf) determined by the method of tryptophan fluorescence coincide with the radiation yields of proteolytic inactivation (Gin) for chymotrypsin-like (CT-like) enzymes on irradiation in air, both in solution and in the dry state with futher dissolution at pH7. It can be supposed that the unfolding is the main process determining the proteolytic gamma-inactivation of CT-like enzymes. It was also shown that the transition of chymotrypsin and trypsin gamma-irradiated at acid pH to neutral pH is an additional action, leading to unfolding of part of the molecules. | [
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|
PMID:16831 | Effect of changes in Pco2 on intraocular tension. | Elevated levels of inspired CO2 and blood Pco2 resulted in moderate elevation of IOT. A marked rapid decrease in IOT to a level less than baseline value was noted when inspired CO2 was suddenly decreased to ambient levels. Decrease in IOT was more pronounced than the decrease in Pco2 and increase in blood pH. Changes in IOT appeared related to the rate of change of Pco2 rather than the actual level of Pco2. Increased ventilatory excursions with constant inspired CO2 levels did not cause any elevation of IOT, but a minimal compensatory drop in IOT below resting values occurred when increased ventilatory excursions were discontinued. It is postulated that the changes in IOT noted are the result of sudden changes in aqueous production or ocular blood volume. | Effect of changes in Pco2 on intraocular tension. Elevated levels of inspired CO2 and blood Pco2 resulted in moderate elevation of IOT. A marked rapid decrease in IOT to a level less than baseline value was noted when inspired CO2 was suddenly decreased to ambient levels. Decrease in IOT was more pronounced than the decrease in Pco2 and increase in blood pH. Changes in IOT appeared related to the rate of change of Pco2 rather than the actual level of Pco2. Increased ventilatory excursions with constant inspired CO2 levels did not cause any elevation of IOT, but a minimal compensatory drop in IOT below resting values occurred when increased ventilatory excursions were discontinued. It is postulated that the changes in IOT noted are the result of sudden changes in aqueous production or ocular blood volume. | [
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|
PMID:16834 | Loss of histochemically demonstrable catecholamines in the glomus cells of the carotid body after alpha-methyl-para-tyrosine treatment. | A statistically significant decrease in the intensity of catecholamine fluorescence of some carotid body glomus cells was observed after inhibition of the enzyme tyrosine hydroxylase by injection of 80 mg/kg alpha-methyl-paratyrosine. The intensity of the formaldehyde-induced fluorescence was measured in individual glomus cells. The maximum decrease in the intensity was observed 4 to 6 hr after the alpha-methyltyrosine injection. This suggests a rapid turnover in the catecholamines of the carotid body. | Loss of histochemically demonstrable catecholamines in the glomus cells of the carotid body after alpha-methyl-para-tyrosine treatment. A statistically significant decrease in the intensity of catecholamine fluorescence of some carotid body glomus cells was observed after inhibition of the enzyme tyrosine hydroxylase by injection of 80 mg/kg alpha-methyl-paratyrosine. The intensity of the formaldehyde-induced fluorescence was measured in individual glomus cells. The maximum decrease in the intensity was observed 4 to 6 hr after the alpha-methyltyrosine injection. This suggests a rapid turnover in the catecholamines of the carotid body. | [
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|
PMID:16832 | A new glucose 6-phosphate dehydrogenase variant (GDTrinacria) in two unrelated families of Sicilian ancestry. | A new G6PD variant in two unrelated families of Sicilian extraction is described. It is characterized by an enzyme activity amounting to 20% of normal, by a slow electrophoretic mobility, decreased Km values for both TPN and G6P, increased utilization of substrates analogues, thermolability and biphasic pH curve. It has been named G6PD Trinacria. | A new glucose 6-phosphate dehydrogenase variant (GDTrinacria) in two unrelated families of Sicilian ancestry. A new G6PD variant in two unrelated families of Sicilian extraction is described. It is characterized by an enzyme activity amounting to 20% of normal, by a slow electrophoretic mobility, decreased Km values for both TPN and G6P, increased utilization of substrates analogues, thermolability and biphasic pH curve. It has been named G6PD Trinacria. | [
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|
PMID:16833 | Endopolygalacturonase, an extracellular pectic enzyme of Rhizoctonia fragariae. | A pectolytic enzyme from culture filtrates of Rhizoctonia fragariae was purified approx. 29-fold. The enzyme exhibited maximal depolymerizing activity on Na-polypectate rather than pectin at pH 5.0 and was inhibited at different extent by divalent cations Mg++, Mn++, Ca++. The analysis by paper chromatography of the products of enzyme hydrolysis suggested that the enzyme attacks the substrate by a random mechanism. The absorption spectrum of the chromogen formed by the hydrolysis products and thiobarbituric acid suggested that the enzyme is a hydrolytic enzyme. On the basis of these results the enzyme is classifiable as endo-polygalacturonase (poly alpha-1,4-galacturonide glycanohydrolase E.C. 3.2.1.15). | Endopolygalacturonase, an extracellular pectic enzyme of Rhizoctonia fragariae. A pectolytic enzyme from culture filtrates of Rhizoctonia fragariae was purified approx. 29-fold. The enzyme exhibited maximal depolymerizing activity on Na-polypectate rather than pectin at pH 5.0 and was inhibited at different extent by divalent cations Mg++, Mn++, Ca++. The analysis by paper chromatography of the products of enzyme hydrolysis suggested that the enzyme attacks the substrate by a random mechanism. The absorption spectrum of the chromogen formed by the hydrolysis products and thiobarbituric acid suggested that the enzyme is a hydrolytic enzyme. On the basis of these results the enzyme is classifiable as endo-polygalacturonase (poly alpha-1,4-galacturonide glycanohydrolase E.C. 3.2.1.15). | [
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|
PMID:16859 | Volume characteristics of extra- and intraparenchymal segments of the canine pulmonary artery. | The volumes of the extraparenchymal segment (VpaEP) and intraparenchymal segment (VpaIP) of the pulmonary arterial tree were determined in intact anesthetized dogs during room air breathing and acute hypoxia. Total pulmonary arterial blood volume (Vpatotal) was calculated as the product of pulmonary blood flow and pulmonary arterial circulation time. An angiographic technique was used to estimate VpEP. VpaIP was calculated by subtracting VpaEP from Vpatotal. During room air breathing at functional residual capacity, mean +/- SD of VpaEP was 17.1 +/- 5.1 ml and of VpaIP was 31.7 +/- 20.8 ml, representing 40% and 60%, respectively, of Vpatotal. Vpatotal increased 22.2 +/- 10.5 ml during lung inflation, with proportional increases in VpaIP and VpaEP. VpaEP was found to be influenced equally by changes in transmural pulmonary arterial and transpulmonary pressures. Acute hypoxia was accompanied by an increase in pulmonary vascular resistance and a decrease in volume distensibility of the extraparenchymal segment. Vpatotal increased 76% without changes in the relative volume distribution of VpaEP and VpaIP. These findings can be best explained by active vasomotion with an increase in down-stream pulmonary vascular resistance. | Volume characteristics of extra- and intraparenchymal segments of the canine pulmonary artery. The volumes of the extraparenchymal segment (VpaEP) and intraparenchymal segment (VpaIP) of the pulmonary arterial tree were determined in intact anesthetized dogs during room air breathing and acute hypoxia. Total pulmonary arterial blood volume (Vpatotal) was calculated as the product of pulmonary blood flow and pulmonary arterial circulation time. An angiographic technique was used to estimate VpEP. VpaIP was calculated by subtracting VpaEP from Vpatotal. During room air breathing at functional residual capacity, mean +/- SD of VpaEP was 17.1 +/- 5.1 ml and of VpaIP was 31.7 +/- 20.8 ml, representing 40% and 60%, respectively, of Vpatotal. Vpatotal increased 22.2 +/- 10.5 ml during lung inflation, with proportional increases in VpaIP and VpaEP. VpaEP was found to be influenced equally by changes in transmural pulmonary arterial and transpulmonary pressures. Acute hypoxia was accompanied by an increase in pulmonary vascular resistance and a decrease in volume distensibility of the extraparenchymal segment. Vpatotal increased 76% without changes in the relative volume distribution of VpaEP and VpaIP. These findings can be best explained by active vasomotion with an increase in down-stream pulmonary vascular resistance. | [
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|
PMID:16860 | Comparison of arm versus leg work in induction of acute episodes of asthma. | The severity of exercise-induced asthma varies with the type of exercise performed. To determine whether such variation could be attributed to the use of different muscle groups, we exercised arms separately from legs using a bicycle ergometer. First, arms were exercised to exhaustion, then legs were exercised at the same load for the same duration. Arm work resulted in greater ventilation, heart rate, hydrogen ion concentration, and airway obstruction than did leg work. Later, legs were exercised to exhaustion using a load more than twice that of the arm work. Both the exhausting leg work and exhausting arm work resulted in significant bronchospasm and acidosis, whereas the nonexhausting leg work did not. These data suggest that, in arm and/or leg exercise, the relationship of work load to muscle mass is a determinant of airway obstruction. | Comparison of arm versus leg work in induction of acute episodes of asthma. The severity of exercise-induced asthma varies with the type of exercise performed. To determine whether such variation could be attributed to the use of different muscle groups, we exercised arms separately from legs using a bicycle ergometer. First, arms were exercised to exhaustion, then legs were exercised at the same load for the same duration. Arm work resulted in greater ventilation, heart rate, hydrogen ion concentration, and airway obstruction than did leg work. Later, legs were exercised to exhaustion using a load more than twice that of the arm work. Both the exhausting leg work and exhausting arm work resulted in significant bronchospasm and acidosis, whereas the nonexhausting leg work did not. These data suggest that, in arm and/or leg exercise, the relationship of work load to muscle mass is a determinant of airway obstruction. | [
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|
PMID:16861 | Ventilatory response in the fetal lamb following peripheral chemodenervation. | Carotid infusions of sodium cyanide solution and perfusions of hypoxemic or hypercapnic fetal blood were done before and after peripheral chemoreceptor denervation. Step changes in PaO2 ranged from -11 to -22 Torr; step changes in PaCO2 ranged from +17 to +42 Torr. The cyanide dose was 0.2 mg/kg per loop system. Control perfusions consisted of 25 ml of fetal blood without changes in pH and blood gases. A ventilatory response occurred in the majority of all experimental perfusions regardless of innervation status of the peripheral chemoreceptors. No response occurred with control perfusions. There was a marked variability in the time of onset of ventilatory activity with a delay of greater than 10 s occurring following most perfusions. These studies demonstrate that the fetus has an attenuated ventilatory response to chemical stimuli and that hypoxia stimulates ventilation in the absence of peripheral chemoreceptors. | Ventilatory response in the fetal lamb following peripheral chemodenervation. Carotid infusions of sodium cyanide solution and perfusions of hypoxemic or hypercapnic fetal blood were done before and after peripheral chemoreceptor denervation. Step changes in PaO2 ranged from -11 to -22 Torr; step changes in PaCO2 ranged from +17 to +42 Torr. The cyanide dose was 0.2 mg/kg per loop system. Control perfusions consisted of 25 ml of fetal blood without changes in pH and blood gases. A ventilatory response occurred in the majority of all experimental perfusions regardless of innervation status of the peripheral chemoreceptors. No response occurred with control perfusions. There was a marked variability in the time of onset of ventilatory activity with a delay of greater than 10 s occurring following most perfusions. These studies demonstrate that the fetus has an attenuated ventilatory response to chemical stimuli and that hypoxia stimulates ventilation in the absence of peripheral chemoreceptors. | [
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|
PMID:16862 | H+ transport from CNS in hypercapnia and regulation of CSF [HCO3-]. | CSF HCO3- increases more than plasma HCO3- in hypercapnia, and there are at least two sources for the CSF HCO3- increase--one derived from the simultaneous increase in plasma HCO3-, and the other, HCO3-formed from hydration of CO2 in the choroid plexus and glia and susceptible to inhibition by acetazolamide (J. Appl. Physiol. 38: 504-512, 1975). It was proposed that the H+ formed in the CNS in CO2 hydration is actively exchanged for plasma Na+ utilizing the Na-K ATPase pump. H+ transport from the CNS was therefore studied in four groups of dogs breathing 5% CO2 at constant VA for 4 h with repeated injections of saline, acetazolamide 5 mg/ml, ouabain 0.1 mg/ml, and acetazolamide and ouabain together into lateral cerebral ventricles. Arterial HCO3-increased 2.5 meq/l at 4 h of hypercapnia in all groups. CSF HCO3-increased 5.8 meq/l in the saline-injected animals, but it increased only about 2 meq/l and equaled plasma HCO3- rise in the other three groups. Therefore CNS HCO3- formation in hypercapnia can be blocked by inhibiting the CO2 hydration reaction with acetazolamide or by blocking H+ removal by inhibiting Na-K ATPase with ouabain. The data support the thesis of active H+ removal from the CNS in exchange for plasma Na+ in hypercapnia. | H+ transport from CNS in hypercapnia and regulation of CSF [HCO3-]. CSF HCO3- increases more than plasma HCO3- in hypercapnia, and there are at least two sources for the CSF HCO3- increase--one derived from the simultaneous increase in plasma HCO3-, and the other, HCO3-formed from hydration of CO2 in the choroid plexus and glia and susceptible to inhibition by acetazolamide (J. Appl. Physiol. 38: 504-512, 1975). It was proposed that the H+ formed in the CNS in CO2 hydration is actively exchanged for plasma Na+ utilizing the Na-K ATPase pump. H+ transport from the CNS was therefore studied in four groups of dogs breathing 5% CO2 at constant VA for 4 h with repeated injections of saline, acetazolamide 5 mg/ml, ouabain 0.1 mg/ml, and acetazolamide and ouabain together into lateral cerebral ventricles. Arterial HCO3-increased 2.5 meq/l at 4 h of hypercapnia in all groups. CSF HCO3-increased 5.8 meq/l in the saline-injected animals, but it increased only about 2 meq/l and equaled plasma HCO3- rise in the other three groups. Therefore CNS HCO3- formation in hypercapnia can be blocked by inhibiting the CO2 hydration reaction with acetazolamide or by blocking H+ removal by inhibiting Na-K ATPase with ouabain. The data support the thesis of active H+ removal from the CNS in exchange for plasma Na+ in hypercapnia. | [
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|
PMID:16863 | Hematology, viscosity, and respiratory functions of whole blood of the lesser mouse deer, Tragulus javanicus. | Blood samples from the lesser mouse deer were examined for hematology, viscosity, oxygen dissociation curve, and magnitude of the Bohr effect. Red corpuscle dimensions, determined under oil immersion with an ocular micrometer, averaged 2.2 micron while the cell counts averaged 53 million/micronl blood, and the packed cell volume averaged 31.2%. Blood hemoglobin concentration averaged 11.2 g/100 ml and the calculated mean cell hemoglobin concentration was 38 g/100 ml. The relative viscosity of the mouse deer plasma was 1.97 and increased in a nonlinear manner with hematocrit to 100 at 80% packed cell volume. Oxygen-hemoglobin equilibrium curves, determined with a mixing technique at 37 degrees C and 10, 36 and 71 Torr PCO2, have the same configuration observed in blood from mammals in general. The P50 of the mouse deer blood at pH = 7.40 is 34 Torr and the Bohr effect (deltalog P50/deltapH) is -0.483. The mouse deer have blood hematocrits which are well below the hematocrits observed in mammals with larger erythrocytes, but similar to the blood hematocrits observed in other mammals with small erythrocytes. We suggest that the low hematocrit is an adaptation which circumvents the hemodynamic problems associated with a high blood viscosity and that, in the mouse deer, the expected concomitantly low total blood hemoglobin concentration is compensated by a higher than average mean cell hemoglobin concentration. | Hematology, viscosity, and respiratory functions of whole blood of the lesser mouse deer, Tragulus javanicus. Blood samples from the lesser mouse deer were examined for hematology, viscosity, oxygen dissociation curve, and magnitude of the Bohr effect. Red corpuscle dimensions, determined under oil immersion with an ocular micrometer, averaged 2.2 micron while the cell counts averaged 53 million/micronl blood, and the packed cell volume averaged 31.2%. Blood hemoglobin concentration averaged 11.2 g/100 ml and the calculated mean cell hemoglobin concentration was 38 g/100 ml. The relative viscosity of the mouse deer plasma was 1.97 and increased in a nonlinear manner with hematocrit to 100 at 80% packed cell volume. Oxygen-hemoglobin equilibrium curves, determined with a mixing technique at 37 degrees C and 10, 36 and 71 Torr PCO2, have the same configuration observed in blood from mammals in general. The P50 of the mouse deer blood at pH = 7.40 is 34 Torr and the Bohr effect (deltalog P50/deltapH) is -0.483. The mouse deer have blood hematocrits which are well below the hematocrits observed in mammals with larger erythrocytes, but similar to the blood hematocrits observed in other mammals with small erythrocytes. We suggest that the low hematocrit is an adaptation which circumvents the hemodynamic problems associated with a high blood viscosity and that, in the mouse deer, the expected concomitantly low total blood hemoglobin concentration is compensated by a higher than average mean cell hemoglobin concentration. | [
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|
PMID:16864 | Effects of potassium ions on the electrical and pH gradients across the membrane of Streptococcus lactis cells. | Bacteria transduce and conserve energy at the plasma membrane in the form of an electrochemical gradient of hydrogen ions (deltap). Energized cells of Streptococcus lactis accumulate K+ ions presumably in exchange for H+. We reasoned that if the movement of H+ is limited, then an increase in H+ efflux, effected by potassium transport inward, should result in changes in the steady-state deltap. We determined the electrical gradient (deltapsi) from the fluorescence of a membrane potential-sensitive cyanine dye, and the chemical H+ gradient (deltapH) from the distribution of a weak acid. The deltap was also determined independently from the accumulation levels of the non-metabolizable sugar thiomethyl-beta-galactoside. KCl addition to cells fermenting glucose or arginine at pH 5 changed the deltap very little, but lowered the deltapsi, while increasing the deltapH. At pH 7, the deltapH only increased slightly; thus, the decrease in deltapsi, effected by addition of potassium ions, resulted in a lowered steady-state deltap. These effects were shown not to be due to swelling or shrinking of the cells. Thus, in these nongrowing cells, under conditions of energy utilization for the active transport of K+, the components of deltap can vary depending on the limitations on the net movement of protons. | Effects of potassium ions on the electrical and pH gradients across the membrane of Streptococcus lactis cells. Bacteria transduce and conserve energy at the plasma membrane in the form of an electrochemical gradient of hydrogen ions (deltap). Energized cells of Streptococcus lactis accumulate K+ ions presumably in exchange for H+. We reasoned that if the movement of H+ is limited, then an increase in H+ efflux, effected by potassium transport inward, should result in changes in the steady-state deltap. We determined the electrical gradient (deltapsi) from the fluorescence of a membrane potential-sensitive cyanine dye, and the chemical H+ gradient (deltapH) from the distribution of a weak acid. The deltap was also determined independently from the accumulation levels of the non-metabolizable sugar thiomethyl-beta-galactoside. KCl addition to cells fermenting glucose or arginine at pH 5 changed the deltap very little, but lowered the deltapsi, while increasing the deltapH. At pH 7, the deltapH only increased slightly; thus, the decrease in deltapsi, effected by addition of potassium ions, resulted in a lowered steady-state deltap. These effects were shown not to be due to swelling or shrinking of the cells. Thus, in these nongrowing cells, under conditions of energy utilization for the active transport of K+, the components of deltap can vary depending on the limitations on the net movement of protons. | [
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|
PMID:16865 | Purification and properties of cis-toluene dihydrodiol dehydrogenase from Pseudomonas putida. | The purification of (+)-cis-1(S),2(R)-dihydroxy-3-methylcyclohexa-3,5-diene dehydrogenase from cells of Pseudomonas putida grown with toluene as the sole source of carbon and energy is reported. The molecular weight of the enzyme is 104,000 at pH 9.7. The enzyme is composed of four apparently identical subunits with molecular weights of 27,000. The enzyme is specific for nicotinamide adenine dinucleotide and oxidizes a number of cis-dihydrodiols. Both enantiomers of a racemic mixture of cis-1,2-dihydroxyl-1,2-dihydronaphthalene dihydrodiol are oxidized by the enzyme. No enzymatic activity is observed with trans-1,2-dihydroxyl-1,2-dihydronaphthalene dihydrodiol. | Purification and properties of cis-toluene dihydrodiol dehydrogenase from Pseudomonas putida. The purification of (+)-cis-1(S),2(R)-dihydroxy-3-methylcyclohexa-3,5-diene dehydrogenase from cells of Pseudomonas putida grown with toluene as the sole source of carbon and energy is reported. The molecular weight of the enzyme is 104,000 at pH 9.7. The enzyme is composed of four apparently identical subunits with molecular weights of 27,000. The enzyme is specific for nicotinamide adenine dinucleotide and oxidizes a number of cis-dihydrodiols. Both enantiomers of a racemic mixture of cis-1,2-dihydroxyl-1,2-dihydronaphthalene dihydrodiol are oxidized by the enzyme. No enzymatic activity is observed with trans-1,2-dihydroxyl-1,2-dihydronaphthalene dihydrodiol. | [
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|
PMID:16866 | Purification and characterization of a neutral protease from Saccharomycopsis lipolytica. | Saccharomycopsis lipolytica 37-1 produced two inducible extracellular proteases, one under neutral or alkaline growth conditions and the second under acid conditions. Secretion of the neutral protease was repressed in the presence of glycerol or glucose, both of which supported rapid growth of the organism. Ammonium ions also repressed the secretion of the enzyme. The neutral protease activity copurified with esterase activity during ammonium sulfate fractionation, chromatography on diethylaminoethyl-cellulose, and gel filtration on Sephadex G-150. The molecular weight of the enzyme was estimated to be 42,000 by sucrose density gradient centrifugation and 38,500 by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The purified enzyme had a pH optimum of 6.8. Phenylmethylsulfonylfluoride inhibited both protease and esterase activities, indicating the presence of a serine residue in the active center. Protease, but not esterase, activity was sensitive to ethylenediaminetetraacetate and was significantly activated by divalent ions. Dithiothreitol inhibited both protease and esterase activities, indicating the presence of a critical disulfide bridge. The enzyme hydrolyzed casein (K(m) = 25.6 muM) and hemoglobin as well as the nitrophenyl esters of tyrosine (K(m) = 2.4 mM), glycine, tryptophan, and phenylalanine. | Purification and characterization of a neutral protease from Saccharomycopsis lipolytica. Saccharomycopsis lipolytica 37-1 produced two inducible extracellular proteases, one under neutral or alkaline growth conditions and the second under acid conditions. Secretion of the neutral protease was repressed in the presence of glycerol or glucose, both of which supported rapid growth of the organism. Ammonium ions also repressed the secretion of the enzyme. The neutral protease activity copurified with esterase activity during ammonium sulfate fractionation, chromatography on diethylaminoethyl-cellulose, and gel filtration on Sephadex G-150. The molecular weight of the enzyme was estimated to be 42,000 by sucrose density gradient centrifugation and 38,500 by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The purified enzyme had a pH optimum of 6.8. Phenylmethylsulfonylfluoride inhibited both protease and esterase activities, indicating the presence of a serine residue in the active center. Protease, but not esterase, activity was sensitive to ethylenediaminetetraacetate and was significantly activated by divalent ions. Dithiothreitol inhibited both protease and esterase activities, indicating the presence of a critical disulfide bridge. The enzyme hydrolyzed casein (K(m) = 25.6 muM) and hemoglobin as well as the nitrophenyl esters of tyrosine (K(m) = 2.4 mM), glycine, tryptophan, and phenylalanine. | [
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|
PMID:16867 | 6-Phospho-D-gluconate:NAD+ 2-oxidoreductase (decarboxylating) from slow-growing Rhizobia. | 6-Phospho-D-gluconate:NAD+ 2-oxidoreductase (decarboxylating) (NAD+-6PGD) was detected in several slow-growing strains of rhizobia, and no activity involving NADP+ was found in the same extracts. By contrast, fast-growing strains of rhizobia had NADP+-6PGD activity; most of them also had NAD+-6PGD activity. NAD+-6PGD was partially purified from the slow-growing strain Rhizobium japonicum 5006. The reaction was shown to be an oxidative decarboxylation. | 6-Phospho-D-gluconate:NAD+ 2-oxidoreductase (decarboxylating) from slow-growing Rhizobia. 6-Phospho-D-gluconate:NAD+ 2-oxidoreductase (decarboxylating) (NAD+-6PGD) was detected in several slow-growing strains of rhizobia, and no activity involving NADP+ was found in the same extracts. By contrast, fast-growing strains of rhizobia had NADP+-6PGD activity; most of them also had NAD+-6PGD activity. NAD+-6PGD was partially purified from the slow-growing strain Rhizobium japonicum 5006. The reaction was shown to be an oxidative decarboxylation. | [
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|
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