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PMID:16254
Kinetics of drug decomposition. Part 46. Photooxidation and photolysis of some perazine derivatives.
The rate and type of the photochemical degradation of perazine derivatives in acidic aqueous solutions depends upon the nature of the substituent at C2 atom. Free perazine degrades by two parallel reactions, namely a fast reversible first-order photooxidation and a slow zero-order photolysis. An introduction of the substituent in the C2 position results frequently in the elimination of one of these reactions.
Kinetics of drug decomposition. Part 46. Photooxidation and photolysis of some perazine derivatives. The rate and type of the photochemical degradation of perazine derivatives in acidic aqueous solutions depends upon the nature of the substituent at C2 atom. Free perazine degrades by two parallel reactions, namely a fast reversible first-order photooxidation and a slow zero-order photolysis. An introduction of the substituent in the C2 position results frequently in the elimination of one of these reactions.
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PMID:16255
Kinetics of drug decomposition. Part 47. Effect of substituents on photochemical stability of perazine derivatives.
A quantum yield phi of photooxidation of perazine derivatives estimated actinometrically and the pKa, values were used for the correlation with the substituent volumes. The Hammett type plots of phi= f(sigma) and phi= f(pKa10--pKa1) are discussed.
Kinetics of drug decomposition. Part 47. Effect of substituents on photochemical stability of perazine derivatives. A quantum yield phi of photooxidation of perazine derivatives estimated actinometrically and the pKa, values were used for the correlation with the substituent volumes. The Hammett type plots of phi= f(sigma) and phi= f(pKa10--pKa1) are discussed.
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PMID:16259
Nitrogen-15 nuclear magnetic resonance of aliphatic tripeptides.
The 15N chemical shifts of eight aliphatic tripeptides have been measured at the natural-abundance level. For a given tripeptide, the resonances of the COOH-terminal and NH2-terminal amino acids can be identified by measurements at low or high pH. The shifts of the NH2-terminal amino acid nitrogens are essentially independent of the amino acids in the rest of the peptide. The shifts of the other nitrogens are characteristic of the amino acids themselves and of the immediately preceding amino acid toward the NH2 terminus. Non-terminal amide nitrogens have shifts of about 6 ppm upfield of COOH-terminal amide nitrogens at the isoelectric point of measurement. 15N chemical shifts appear to have considerable potential value for peptide sequencing.
Nitrogen-15 nuclear magnetic resonance of aliphatic tripeptides. The 15N chemical shifts of eight aliphatic tripeptides have been measured at the natural-abundance level. For a given tripeptide, the resonances of the COOH-terminal and NH2-terminal amino acids can be identified by measurements at low or high pH. The shifts of the NH2-terminal amino acid nitrogens are essentially independent of the amino acids in the rest of the peptide. The shifts of the other nitrogens are characteristic of the amino acids themselves and of the immediately preceding amino acid toward the NH2 terminus. Non-terminal amide nitrogens have shifts of about 6 ppm upfield of COOH-terminal amide nitrogens at the isoelectric point of measurement. 15N chemical shifts appear to have considerable potential value for peptide sequencing.
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PMID:16260
Regulation of cholesterol synthesis in rat adrenal gland through coordinate control of 3-hydroxy-3-methylglutaryl coenzyme A synthase and reductase activities.
The activities of cytosolic 3-hydroxy-3-methylglutaryl coenzyme A synthase [3-hydroxy-3-methylglutaryl-CoA acetoacetyl-CoA-lyase (CoA-acylating), EC 4.1.3.5] and microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase[mevalonate:NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34], two sequential enzymes in the cholesterol biosynthetic pathway, were shown to be regulated coordinately in the adrenal gland of the rat. When the plasma cholesterol level was lowered by administration of 4-aminopyrazolopyrimidine, a treatment known to enhance cholesterol synthesis in the adrenal, synthase activity in the gland rose by 14- to 29-fold and reductase activity rose by 50- to 100-fold. The subsequent intravenous infusion of low density lipoprotein restored the plasma cholesterol level and suppressed synthase and reductase activities in parallel. The activities of adrenal 3-hydroxy-3-methylglutaryl coenzyme A synthase and reductase were also shown to exhibit a coordinate pattern of diurnal variation with peaks in both enzymes achieved at the mid-point of the dark cycle. The activity of adrenal acetoacetyl coenzyme A thiolase (acetyl CoA acetyltransferase; acetyl-CoA:acetyl-CoA C-acetyltransferase, EC 2.3.1.9), the enzyme preceding the synthase in the cholesterol biosynthetic pathway, and the activity of adrenal mevalonate kinase (ATP:mevalonate 5-phosphotransferase, EC 2.7.1.36), the enzyme following the reductase, were not enhanced by cholesterol deprivation, and neither exhibited a pattern of diurnal variation. The coordinate control of 3-hydroxy-3-methylglutaryl CoA synthase and reductase in rat adrenal gland provides a model system to study the biochemical mechanism for the regulation of cholesterol synthesis in a tissue that uses cholesterol for the synthesis of steroid hormones.
Regulation of cholesterol synthesis in rat adrenal gland through coordinate control of 3-hydroxy-3-methylglutaryl coenzyme A synthase and reductase activities. The activities of cytosolic 3-hydroxy-3-methylglutaryl coenzyme A synthase [3-hydroxy-3-methylglutaryl-CoA acetoacetyl-CoA-lyase (CoA-acylating), EC 4.1.3.5] and microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase[mevalonate:NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34], two sequential enzymes in the cholesterol biosynthetic pathway, were shown to be regulated coordinately in the adrenal gland of the rat. When the plasma cholesterol level was lowered by administration of 4-aminopyrazolopyrimidine, a treatment known to enhance cholesterol synthesis in the adrenal, synthase activity in the gland rose by 14- to 29-fold and reductase activity rose by 50- to 100-fold. The subsequent intravenous infusion of low density lipoprotein restored the plasma cholesterol level and suppressed synthase and reductase activities in parallel. The activities of adrenal 3-hydroxy-3-methylglutaryl coenzyme A synthase and reductase were also shown to exhibit a coordinate pattern of diurnal variation with peaks in both enzymes achieved at the mid-point of the dark cycle. The activity of adrenal acetoacetyl coenzyme A thiolase (acetyl CoA acetyltransferase; acetyl-CoA:acetyl-CoA C-acetyltransferase, EC 2.3.1.9), the enzyme preceding the synthase in the cholesterol biosynthetic pathway, and the activity of adrenal mevalonate kinase (ATP:mevalonate 5-phosphotransferase, EC 2.7.1.36), the enzyme following the reductase, were not enhanced by cholesterol deprivation, and neither exhibited a pattern of diurnal variation. The coordinate control of 3-hydroxy-3-methylglutaryl CoA synthase and reductase in rat adrenal gland provides a model system to study the biochemical mechanism for the regulation of cholesterol synthesis in a tissue that uses cholesterol for the synthesis of steroid hormones.
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PMID:16261
Cell wall extension in Nitella as influenced by acids and ions.
The giant internode cells of Nitella axillaris exhibit acid-induced growth similar to that found in higher plants. The threshold pH is 4.5, with a maximum at 3.5. The acid growth effect is transient, lasting no more than 32 min. Extensibility measurements of isolated cell walls showed a similar pattern of acid enhancement. Prolonged boiling in water (12 hr) only partially inhibited the acid-induced wall extensibility and actually increased the extensibility at pH 6. It was concluded that physical, rather than enzymatic, processes were responsible for acid-enhanced continuous extension ("creep") in Nitella walls. A complex cation-sensitive mechanism that affects extensibility was also characterized. Among the stimulatory (wall-softening) cations, divalents were generally more effective than monovalents, with magnesium being the most stimulatory. The inhibitory (wall-hardening) cations included divalents and trivalents, aluminum being the most inhibitory. Ionic effects on extensibility were even less sensitive to prolonged boiling in water than acid effects.
Cell wall extension in Nitella as influenced by acids and ions. The giant internode cells of Nitella axillaris exhibit acid-induced growth similar to that found in higher plants. The threshold pH is 4.5, with a maximum at 3.5. The acid growth effect is transient, lasting no more than 32 min. Extensibility measurements of isolated cell walls showed a similar pattern of acid enhancement. Prolonged boiling in water (12 hr) only partially inhibited the acid-induced wall extensibility and actually increased the extensibility at pH 6. It was concluded that physical, rather than enzymatic, processes were responsible for acid-enhanced continuous extension ("creep") in Nitella walls. A complex cation-sensitive mechanism that affects extensibility was also characterized. Among the stimulatory (wall-softening) cations, divalents were generally more effective than monovalents, with magnesium being the most stimulatory. The inhibitory (wall-hardening) cations included divalents and trivalents, aluminum being the most inhibitory. Ionic effects on extensibility were even less sensitive to prolonged boiling in water than acid effects.
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PMID:16262
The product of a newly identified gene, gInF, is required for synthesis of glutamine synthetase in Salmonella.
The product of a newly identified gene, glnF, which is distinct from the glutamine synthetase structural gene (glnA), is required for synthesis of glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2[ in Salmonella typhimurium and probably in Escherichia coli. Salmonella strains with ICR (2-chloro-6-methoxy-9-[3-(2-chloroethyl)aminopropylamino]acridine dihyodrochloride)-induced (frameshift) mutations in glnF are glutamine auxotrophs; they have less than 10% oof wild-type glutamine synthetase activity or antigen and are unable to derepress the synthesis of the enzyme. The mutant allele is recessive to the wild-type allele, indicating that the glnF gene encodes a diffusible product. Mutant glnF strains have normal activities of all proteins involved in covalent modification of glutamine synthetase: adenylyltransferase (EC 2.7.7.42), PII, uridylyltransferase, and uridylyl removing enzyme. In addition, they have glutamate synthase (EC 1.4.1.13) and glutamate dehydrogenase (EC 1.4.1.4) activities. Thus, glnF does not encode the structure of any of these proteins. The above evidence suggests that the product of the glnF gene is (or produces) a positive regulatory factor that is required for synthesis of glutamine synthetase; it indicates that auto-regulation cannot account for control of the synthesis of glutamine synthetase in Salmonella.
The product of a newly identified gene, gInF, is required for synthesis of glutamine synthetase in Salmonella. The product of a newly identified gene, glnF, which is distinct from the glutamine synthetase structural gene (glnA), is required for synthesis of glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2[ in Salmonella typhimurium and probably in Escherichia coli. Salmonella strains with ICR (2-chloro-6-methoxy-9-[3-(2-chloroethyl)aminopropylamino]acridine dihyodrochloride)-induced (frameshift) mutations in glnF are glutamine auxotrophs; they have less than 10% oof wild-type glutamine synthetase activity or antigen and are unable to derepress the synthesis of the enzyme. The mutant allele is recessive to the wild-type allele, indicating that the glnF gene encodes a diffusible product. Mutant glnF strains have normal activities of all proteins involved in covalent modification of glutamine synthetase: adenylyltransferase (EC 2.7.7.42), PII, uridylyltransferase, and uridylyl removing enzyme. In addition, they have glutamate synthase (EC 1.4.1.13) and glutamate dehydrogenase (EC 1.4.1.4) activities. Thus, glnF does not encode the structure of any of these proteins. The above evidence suggests that the product of the glnF gene is (or produces) a positive regulatory factor that is required for synthesis of glutamine synthetase; it indicates that auto-regulation cannot account for control of the synthesis of glutamine synthetase in Salmonella.
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PMID:16279
Synthesis of certain benzo- and pyridodiazepines likely to possess tranquilizing effect.
The synthesis of certain 1.5-benzodiazepinediones, some of their oxygen-free analogues and a number of the 7-nitro derivatives is described. Condensation of 3.4-diaminopyridine with diethylmalonate instead of affording the expected pyridodiazepine, yielded an imidazopyridine, the structure of which was inferred from spectral data Nevertheless, the pyridodiazepine was obtained by condensing the diamino-heterocycle with malonyl dichloride.
Synthesis of certain benzo- and pyridodiazepines likely to possess tranquilizing effect. The synthesis of certain 1.5-benzodiazepinediones, some of their oxygen-free analogues and a number of the 7-nitro derivatives is described. Condensation of 3.4-diaminopyridine with diethylmalonate instead of affording the expected pyridodiazepine, yielded an imidazopyridine, the structure of which was inferred from spectral data Nevertheless, the pyridodiazepine was obtained by condensing the diamino-heterocycle with malonyl dichloride.
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PMID:16280
The biological fate of reserpine.
Orally administered reserpine is readily absorbed from the GI tract. During this process at least a portion of the drug is metabolized by the intestinal mucosa and then presumably is acted upon by serum esterases. Methylreserpate and trimethoxybenzoic acid are the primary metabolites which result from the hydrolytic cleavage of reserpine. Since most of the blood leaving the GI tract passes through the liver via the portal vein, hepatic metabolism would also be expected to reduce reserpine levels in the blood. The relative contributions of serum esterases versus hepatic metabolism in the biotransformation of reserpine in vivo are not known. However, very little unmetabolized reserpine is eventually eliminated in the urine. In the liver, it is quite likely that both microsomal oxidative and hydrolytic enzymes contribute to the metabolism of reserpine. It seems that microsomal oxidation (such as the demethylation of the 4-methoxy group on the TMBA moiety) must precede hydrolysis since inhibition of demethylation markedly reduces the rate of hydrolysis. In addition to oxidation and hydrolysis, conjugative reactions also must occur in liver or extrahepatic tissues since both glucuronide and sulfate conjugates of TMBA have been identified. Some reserpine molecules do seem to escape metabolism, however, since significant amounts of intact reserpine have been found in fecal samples taken from both experimental animals and human beings after either oral or parenteral drug administration. Presumably reserpine is transported from the blood via the biliary tree into the small intestine where it is either reabsorbed or eliminated in the feces. Pulmonary elimination of CO2 produced after complete oxidation of the 4-methoxy group of TMBA has also been shown to occur both in vivo and in vitro. The following may serve as a model for the relationship between the subcellular distribution of reserpine and its site of action. After a single intravenous injection most of the reserpine, probably loosely bound to plasma albumin, is distributed to tissues on the basis of their blood flow. Because of its lipophilic properties, reserpine would easily penetrate cell membranes and then bind possibly electrostatically to intracellular membrane components, particularly those rich in phospholipids. Much of the circulating reserpine would then either be metabolized or be taken up by the lipid depots of the body, leading to a rapid redistribution of the reversibly bound reserpine from the tissues. During this time a relatively small fraction of the total reserpine administered by injection would become associated with monoaminergic granular membranes in a more specific and irreversible manner. This would result in a persistent, nonstoichiometric inhibition of monoamine uptake. Such a small specific binding would not be detectable for at least 18 hr after reserpine administration, i.e., until most of the reversibly bound alkaloid had been metabolized and/or excreted...
The biological fate of reserpine. Orally administered reserpine is readily absorbed from the GI tract. During this process at least a portion of the drug is metabolized by the intestinal mucosa and then presumably is acted upon by serum esterases. Methylreserpate and trimethoxybenzoic acid are the primary metabolites which result from the hydrolytic cleavage of reserpine. Since most of the blood leaving the GI tract passes through the liver via the portal vein, hepatic metabolism would also be expected to reduce reserpine levels in the blood. The relative contributions of serum esterases versus hepatic metabolism in the biotransformation of reserpine in vivo are not known. However, very little unmetabolized reserpine is eventually eliminated in the urine. In the liver, it is quite likely that both microsomal oxidative and hydrolytic enzymes contribute to the metabolism of reserpine. It seems that microsomal oxidation (such as the demethylation of the 4-methoxy group on the TMBA moiety) must precede hydrolysis since inhibition of demethylation markedly reduces the rate of hydrolysis. In addition to oxidation and hydrolysis, conjugative reactions also must occur in liver or extrahepatic tissues since both glucuronide and sulfate conjugates of TMBA have been identified. Some reserpine molecules do seem to escape metabolism, however, since significant amounts of intact reserpine have been found in fecal samples taken from both experimental animals and human beings after either oral or parenteral drug administration. Presumably reserpine is transported from the blood via the biliary tree into the small intestine where it is either reabsorbed or eliminated in the feces. Pulmonary elimination of CO2 produced after complete oxidation of the 4-methoxy group of TMBA has also been shown to occur both in vivo and in vitro. The following may serve as a model for the relationship between the subcellular distribution of reserpine and its site of action. After a single intravenous injection most of the reserpine, probably loosely bound to plasma albumin, is distributed to tissues on the basis of their blood flow. Because of its lipophilic properties, reserpine would easily penetrate cell membranes and then bind possibly electrostatically to intracellular membrane components, particularly those rich in phospholipids. Much of the circulating reserpine would then either be metabolized or be taken up by the lipid depots of the body, leading to a rapid redistribution of the reversibly bound reserpine from the tissues. During this time a relatively small fraction of the total reserpine administered by injection would become associated with monoaminergic granular membranes in a more specific and irreversible manner. This would result in a persistent, nonstoichiometric inhibition of monoamine uptake. Such a small specific binding would not be detectable for at least 18 hr after reserpine administration, i.e., until most of the reversibly bound alkaloid had been metabolized and/or excreted...
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PMID:16283
Meiosis in perspective.
Our understanding of meiosis springs from two suggestions made by Weismann in 1887. One was that meiosis would be found to compensate for fertilization in the life cycles of both sexes and all organisms. The other was that the development of sexual reproduction in evolution depended on the value of meiosis in exposing the results of genetic recombination to natural selection. In confirming these propositions we were bound to discover that the properties of meiosis appear both as the causes and the consequences of evolution: it is the hinge on which turns the evolution of breeding method, reproductive habit, life cycle and hereditary structure, that is the genetic system, in all sexually reproducing species of organism. We have had three main fields of attack on our problem. First, there was the natural variation of meiosis including that of two-track hereditary within the species: here, animals took the lead. Secondly, there was the experimental field - both with genetic controls such as polyploidy and the sterilizing mutations of mitosis as well as meiosis, and with physical and chemical controls: here, the higher plants and micro-organisms have given us our great opportunities. Thirdly, we have the widening field where physicochemical knowledge and genetic control converge and collaborate. In all this work we have to be aware that meiosis works with chromosomes which always have the two functions of accomplishing evolution and of implementing its results in heredity. In consequence, the adaptation of meiosis is perpetually imperfect.
Meiosis in perspective. Our understanding of meiosis springs from two suggestions made by Weismann in 1887. One was that meiosis would be found to compensate for fertilization in the life cycles of both sexes and all organisms. The other was that the development of sexual reproduction in evolution depended on the value of meiosis in exposing the results of genetic recombination to natural selection. In confirming these propositions we were bound to discover that the properties of meiosis appear both as the causes and the consequences of evolution: it is the hinge on which turns the evolution of breeding method, reproductive habit, life cycle and hereditary structure, that is the genetic system, in all sexually reproducing species of organism. We have had three main fields of attack on our problem. First, there was the natural variation of meiosis including that of two-track hereditary within the species: here, animals took the lead. Secondly, there was the experimental field - both with genetic controls such as polyploidy and the sterilizing mutations of mitosis as well as meiosis, and with physical and chemical controls: here, the higher plants and micro-organisms have given us our great opportunities. Thirdly, we have the widening field where physicochemical knowledge and genetic control converge and collaborate. In all this work we have to be aware that meiosis works with chromosomes which always have the two functions of accomplishing evolution and of implementing its results in heredity. In consequence, the adaptation of meiosis is perpetually imperfect.
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PMID:16284
A first view of the meiotic process.
In this introductory paper we have highlighted some aspects of the meiotic process which seem important to us and about which some especially interesting features have been discovered. These include the switch from mitosis to meiosis, premeiotic DNA synthesis, association of the chromosomes with the synaptonemal complex, the nature of chromosome homology in relation to chromosome pairing, the process of chromosome pairing, the regulation of meiosis as a developmental process and the process of recombination. We have indulged in speculation in the hope that it will stimulate additional discussion and research into these crucial meiotic cell divisions which link the generations in higher organisms.
A first view of the meiotic process. In this introductory paper we have highlighted some aspects of the meiotic process which seem important to us and about which some especially interesting features have been discovered. These include the switch from mitosis to meiosis, premeiotic DNA synthesis, association of the chromosomes with the synaptonemal complex, the nature of chromosome homology in relation to chromosome pairing, the process of chromosome pairing, the regulation of meiosis as a developmental process and the process of recombination. We have indulged in speculation in the hope that it will stimulate additional discussion and research into these crucial meiotic cell divisions which link the generations in higher organisms.
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PMID:16285
The time and duration of meiosis.
Ever since meiosis was recognized as a process there has been a continuing interest in its temporal aspects. Two main types of meiotic timing experiments have been conducted: first, experiments to estimate the duration of meiosis (and sometimes its stages); second, experiments to locate the sensitive stage(s) when exposure of meiocytes to various treatments can affect meiotic chromosome behaviour (e.g. pairing or recombination). Such experiments have played an important role in increasing our understanding of the meiotic process. The duration of meiosis has been estimated in about 70 organisms, including two prokaryotes (yeast and Chlamydomonas) and the following eukaryotes: 1 Basidiomycete (Coprinus lagopus), 2 Gymnosperms (Larix decidua and Thuja plicata gracilis). at least 39 angiosperms, and at least 26 animal species. The duration of female meiosis has been estimated in far fewer species than male meiosis. However, estimates of the duration of female meiosis are available for 6 angiosperms. Drosophila melanogaster, Xenopus laevis, and several mammals. Comparison of these data shows that the duration of meiosis is one of the most variable aspects of the meiotic process, ranging from less than 6 h in yeast to more than 40 years in the human female. Developmental holds at different stages of meiosis are common in plants and animals, and inevitably prolong the meiotic division. However, even among species without developmental holds, the duration of meiosis is very variable. For instance, in animals it ranges from about 1-2 days in male Drosophila melanogaster to more than 24 days in male Homo sapiens and several Orthopterans. Despite the large variation in the duration of meiosis three generalizations can be made: (i) first prophase is always very long compared with the remaining meiotic stages, (ii) the rate of meiotic development is very slow compared with the rate of development in dividing somatic meristem cells of the same organisms under the same conditions, (iii) the duration of meiosis is characteristic of the genotype and species. Four main factors have been recognized which effect or determine the duration of meiosis, namely (1) environmental factors (e.g. temperature); (2) nuclear DNA content; (3) ploidy level of the organism; and, (4) the genotype. Because nuclear DNA content plays a major role in determining the duration of meiosis, it has been suggested that DNA influences the rate of meiotic development in two ways: first through its informational content (the genotype), and second indirectly by the physical and mechanical effects of its mass independently of its informational content (i.e. the nucleotype). Thus, the observed duration of meiosis is the result of a complex genotype-nucleotype-environment interaction. With the obvious exception of variation caused by developmental holds, changes in the duration of meiosis usually involve proportional changes in the durations of all its stages...
The time and duration of meiosis. Ever since meiosis was recognized as a process there has been a continuing interest in its temporal aspects. Two main types of meiotic timing experiments have been conducted: first, experiments to estimate the duration of meiosis (and sometimes its stages); second, experiments to locate the sensitive stage(s) when exposure of meiocytes to various treatments can affect meiotic chromosome behaviour (e.g. pairing or recombination). Such experiments have played an important role in increasing our understanding of the meiotic process. The duration of meiosis has been estimated in about 70 organisms, including two prokaryotes (yeast and Chlamydomonas) and the following eukaryotes: 1 Basidiomycete (Coprinus lagopus), 2 Gymnosperms (Larix decidua and Thuja plicata gracilis). at least 39 angiosperms, and at least 26 animal species. The duration of female meiosis has been estimated in far fewer species than male meiosis. However, estimates of the duration of female meiosis are available for 6 angiosperms. Drosophila melanogaster, Xenopus laevis, and several mammals. Comparison of these data shows that the duration of meiosis is one of the most variable aspects of the meiotic process, ranging from less than 6 h in yeast to more than 40 years in the human female. Developmental holds at different stages of meiosis are common in plants and animals, and inevitably prolong the meiotic division. However, even among species without developmental holds, the duration of meiosis is very variable. For instance, in animals it ranges from about 1-2 days in male Drosophila melanogaster to more than 24 days in male Homo sapiens and several Orthopterans. Despite the large variation in the duration of meiosis three generalizations can be made: (i) first prophase is always very long compared with the remaining meiotic stages, (ii) the rate of meiotic development is very slow compared with the rate of development in dividing somatic meristem cells of the same organisms under the same conditions, (iii) the duration of meiosis is characteristic of the genotype and species. Four main factors have been recognized which effect or determine the duration of meiosis, namely (1) environmental factors (e.g. temperature); (2) nuclear DNA content; (3) ploidy level of the organism; and, (4) the genotype. Because nuclear DNA content plays a major role in determining the duration of meiosis, it has been suggested that DNA influences the rate of meiotic development in two ways: first through its informational content (the genotype), and second indirectly by the physical and mechanical effects of its mass independently of its informational content (i.e. the nucleotype). Thus, the observed duration of meiosis is the result of a complex genotype-nucleotype-environment interaction. With the obvious exception of variation caused by developmental holds, changes in the duration of meiosis usually involve proportional changes in the durations of all its stages...
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PMID:16286
Recombination in male and female meiocytes contrasted.
For technical reasons studies of chiasma frequency and distribution, and hence of intrachromosomal recombination, have mostly been confined to male meiosis. However, there is now sufficient comparative data on male and female meiosis, in both plants and animals, to show that the extent of intra-chromosomal recombination in some organisms may be much the same on the female as on the male side, whereas other organisms show extreme sexual divergence in this regard. The evolutionary significance of such diversity remains enigmatic.
Recombination in male and female meiocytes contrasted. For technical reasons studies of chiasma frequency and distribution, and hence of intrachromosomal recombination, have mostly been confined to male meiosis. However, there is now sufficient comparative data on male and female meiosis, in both plants and animals, to show that the extent of intra-chromosomal recombination in some organisms may be much the same on the female as on the male side, whereas other organisms show extreme sexual divergence in this regard. The evolutionary significance of such diversity remains enigmatic.
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PMID:16287
The assembly of the synaptinemal complex.
The assembly of the synaptinemal complex in the ascomycete Neottiella was studied by three-dimensional reconstruction of a late zygotene nucleus. A single banded lateral component is formed between the two sister chromatids of each homologous chromosome prior to their pairing. The central regions are pre-assembled in organized form in folds of the granular part of the nucleolus and then converted into an amorphous transport form. The latter appears to move through the nucleoplasm to sites between the lateral components of synapsing homologous chromosomes. The central region material is reorganized into blocks with a recognizable central component and attached to one lateral component. The last step in the completion of the synaptinemal complex is the association of the free surface of the organized central region with the corresponding segment of the homologous lateral component. The findings are discussed in relation to mechanisms of chromosome pairing and chiasma formation.
The assembly of the synaptinemal complex. The assembly of the synaptinemal complex in the ascomycete Neottiella was studied by three-dimensional reconstruction of a late zygotene nucleus. A single banded lateral component is formed between the two sister chromatids of each homologous chromosome prior to their pairing. The central regions are pre-assembled in organized form in folds of the granular part of the nucleolus and then converted into an amorphous transport form. The latter appears to move through the nucleoplasm to sites between the lateral components of synapsing homologous chromosomes. The central region material is reorganized into blocks with a recognizable central component and attached to one lateral component. The last step in the completion of the synaptinemal complex is the association of the free surface of the organized central region with the corresponding segment of the homologous lateral component. The findings are discussed in relation to mechanisms of chromosome pairing and chiasma formation.
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PMID:16288
Homologous chromosome pairing.
Commonly accepted precepts are challenged: (1) that homologous chromosome pairing is normally mediated by nuclear envelope attachment sites; (2) that crossover site establishment awaits synaptic completion; and (3) that it is the function of the synaptonemal complex to hold homologues in register so that equal crossing over can occur, and perhaps to provide machinery for the crossover process. Although these views may eventually be shown to be true, it is felt that currently available evidence does not warrant their full acceptance, and that alternatives should be considered. As examples of alternatives the following ideas, with some supporting evidence, are suggested: (1) homologous chromosome pairing (in non-haplont organisms) may be accomplished by chance meeting of homologue segments (followed by establishment of invisible, elastic connectors) at congression for a mitotic metaphase (in many cases perhaps the premeiotic mitosis); (2) crossover sites may be established before, during, or immediately following initiation of synapsis; and (3) the synaptonemal complex may somehow function in the crossover process at the inception of its formation, but its complete deployment throughout each normal bivalent may serve some other role, such as mediation of the binding of sister chromatids apparently required for chiasma maintenance until anaphase I.
Homologous chromosome pairing. Commonly accepted precepts are challenged: (1) that homologous chromosome pairing is normally mediated by nuclear envelope attachment sites; (2) that crossover site establishment awaits synaptic completion; and (3) that it is the function of the synaptonemal complex to hold homologues in register so that equal crossing over can occur, and perhaps to provide machinery for the crossover process. Although these views may eventually be shown to be true, it is felt that currently available evidence does not warrant their full acceptance, and that alternatives should be considered. As examples of alternatives the following ideas, with some supporting evidence, are suggested: (1) homologous chromosome pairing (in non-haplont organisms) may be accomplished by chance meeting of homologue segments (followed by establishment of invisible, elastic connectors) at congression for a mitotic metaphase (in many cases perhaps the premeiotic mitosis); (2) crossover sites may be established before, during, or immediately following initiation of synapsis; and (3) the synaptonemal complex may somehow function in the crossover process at the inception of its formation, but its complete deployment throughout each normal bivalent may serve some other role, such as mediation of the binding of sister chromatids apparently required for chiasma maintenance until anaphase I.
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PMID:16289
Some morphological aspects of the synaptonemal complex in higher plants.
The synaptonemal complex is illustrated in electron micrographs from pollen mother cells (p.m.cs) of the following plants: Fritillaria lanceolata, Allium fistulosum, Tulbaghia violacea, Luzula purpurea, Phaedranassa viridiflora and the tulip cultivar Keiserkroon. The possibility that the lateral elements in synaptonemal complexes of plants are tubiform structures is discussed in relation to their fine structure and in the light of a deformity seen in them. An assessment of the evidence suggesting that both lateral and central elements in the complex are ribonucleoprotein structures is made. The effect of brief water treatment on the chromatin and synaptonemal complex at zygotene in p.m.cs of the Phaedranassa is discussed, particularly with reference to two precisely oriented axial strands then seen running between the lateral elements. Examination of stages of premeiotic interphase and early leptotene in p.m.cs of the Fritillaria, revealed that the axial cores laid down at leptotene are formed first in heterochromatic regions, which in this species are locked in chromocentres that persist until pachytene. Further, at leptotene the chromatin in these parts was singularly more decondensed (diffuse) than at any other period, including the premeiotic interphase, subsequent stages of meiosis and mitotic cycle in meristems. It is suggested that the diffuse state of the chromatin in chromocentres at the onset of leptotene, allows the necessary freedom of movement required to promote homologous pairing of the heterochromatic segments. Evidence of such a movement was indicated by a change in position of the nucleoli, which moved from a more central position at early premeiotic interphase to a peripheral one at the onset of leptotene, when they are seen adpressed to the nuclear envelope.
Some morphological aspects of the synaptonemal complex in higher plants. The synaptonemal complex is illustrated in electron micrographs from pollen mother cells (p.m.cs) of the following plants: Fritillaria lanceolata, Allium fistulosum, Tulbaghia violacea, Luzula purpurea, Phaedranassa viridiflora and the tulip cultivar Keiserkroon. The possibility that the lateral elements in synaptonemal complexes of plants are tubiform structures is discussed in relation to their fine structure and in the light of a deformity seen in them. An assessment of the evidence suggesting that both lateral and central elements in the complex are ribonucleoprotein structures is made. The effect of brief water treatment on the chromatin and synaptonemal complex at zygotene in p.m.cs of the Phaedranassa is discussed, particularly with reference to two precisely oriented axial strands then seen running between the lateral elements. Examination of stages of premeiotic interphase and early leptotene in p.m.cs of the Fritillaria, revealed that the axial cores laid down at leptotene are formed first in heterochromatic regions, which in this species are locked in chromocentres that persist until pachytene. Further, at leptotene the chromatin in these parts was singularly more decondensed (diffuse) than at any other period, including the premeiotic interphase, subsequent stages of meiosis and mitotic cycle in meristems. It is suggested that the diffuse state of the chromatin in chromocentres at the onset of leptotene, allows the necessary freedom of movement required to promote homologous pairing of the heterochromatic segments. Evidence of such a movement was indicated by a change in position of the nucleoli, which moved from a more central position at early premeiotic interphase to a peripheral one at the onset of leptotene, when they are seen adpressed to the nuclear envelope.
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PMID:16290
Chromosome distribution: experiments on cell hybrids and in vitro.
Ostergren (1951) provided a simple explanation for both chromosome distribution in mitosis and chromosome segregation in meiosis, and more recently a molecular extension of his hypothesis has been possible. This report focuses on experimental tests of these ideas. Micromanipulation experiments on cell hybrids containing both meiotic and mitotic spindles demonstrate that differences in meiotic and mitotic chromosome behavior are determined by something intrinsic to the chromosome: meiotic chromosomes transferred to a mitotic spindle (or vice versa) behave just as they normally would. The molecular explanation postulates polarized growth or binding of microtubules at kinetochores. This has just been tested in vitro by McGill & Brinkley (1975) and by Telzer, Moses & Rosenbaum (1975), and their results are reviewed. In addition, a novel method for in vitro studies is described - mechanical demembranation of cells which is compatible with quite normal chromosome movement in anaphase. After addition of microtubule subunits to a demembranated prophase cell, chromosome orientation and movement toward an aster was observed for the first time in vitro. It is concluded that important aspects of chromosome distribution are probably understood at both the cellular and molecular levels, but final tests are still required. The outlook is hopeful indeed because the gaps in our knowledge are well known - the necessity of observations on prophase is a recurrent theme - and the means of filling the gaps are in hand.
Chromosome distribution: experiments on cell hybrids and in vitro. Ostergren (1951) provided a simple explanation for both chromosome distribution in mitosis and chromosome segregation in meiosis, and more recently a molecular extension of his hypothesis has been possible. This report focuses on experimental tests of these ideas. Micromanipulation experiments on cell hybrids containing both meiotic and mitotic spindles demonstrate that differences in meiotic and mitotic chromosome behavior are determined by something intrinsic to the chromosome: meiotic chromosomes transferred to a mitotic spindle (or vice versa) behave just as they normally would. The molecular explanation postulates polarized growth or binding of microtubules at kinetochores. This has just been tested in vitro by McGill & Brinkley (1975) and by Telzer, Moses & Rosenbaum (1975), and their results are reviewed. In addition, a novel method for in vitro studies is described - mechanical demembranation of cells which is compatible with quite normal chromosome movement in anaphase. After addition of microtubule subunits to a demembranated prophase cell, chromosome orientation and movement toward an aster was observed for the first time in vitro. It is concluded that important aspects of chromosome distribution are probably understood at both the cellular and molecular levels, but final tests are still required. The outlook is hopeful indeed because the gaps in our knowledge are well known - the necessity of observations on prophase is a recurrent theme - and the means of filling the gaps are in hand.
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PMID:16291
Biochemistry of meiosis.
The process of meiosis in Lilium falls into four physiological stages - prezygotene, zygotene, pachytene, and post-pachytene. Each of these stages has distinctive metabolic characteristics. Commitment to meiosis occurs during the prezygotene interval at about the time when S-phase replication is completed. The activities following commitment are essential to synapsis inasmuch as perturbations of cells during that interval have subsequent effects on synapsis and crossing over. Just before the initiation of synapsis, a distinctive lipoprotein complex appears in the nucleus. The complex most probably functions in the process of pairing. Zygotene is marked by the delayed replication of specific intercalary segments of chromosomal DNA (Z-DNA), the replication being a necessary condition for ongoing synapsis. The replication occurs in the lipoprotein complex in the presence of a reassociation protein (r-protein). Z-DNA segments would appear to have other meiotic functions inasmuch as the replicated segments remain unligated to the body of chromosomal DNA until the beginning of chromosome disjunction. The pachytene interval is marked by an activation of endonucleolytic activity. The enzyme produces single-stranded nicks in the DNA at specific loci. These loci consist of moderately repeated segments; about 100-200 base pairs long. Extracellular agents, such as radiation, cause random nicking regardless of the meiotic stage at which they are applied. Localized nicking and repair are thus unique features of meiosis. The temporal segregation of metabolic activities concerned with pairing and crossing over and their operation in special chromosome regions constitute the most prominent features of the biochemical events associated with meiosis.
Biochemistry of meiosis. The process of meiosis in Lilium falls into four physiological stages - prezygotene, zygotene, pachytene, and post-pachytene. Each of these stages has distinctive metabolic characteristics. Commitment to meiosis occurs during the prezygotene interval at about the time when S-phase replication is completed. The activities following commitment are essential to synapsis inasmuch as perturbations of cells during that interval have subsequent effects on synapsis and crossing over. Just before the initiation of synapsis, a distinctive lipoprotein complex appears in the nucleus. The complex most probably functions in the process of pairing. Zygotene is marked by the delayed replication of specific intercalary segments of chromosomal DNA (Z-DNA), the replication being a necessary condition for ongoing synapsis. The replication occurs in the lipoprotein complex in the presence of a reassociation protein (r-protein). Z-DNA segments would appear to have other meiotic functions inasmuch as the replicated segments remain unligated to the body of chromosomal DNA until the beginning of chromosome disjunction. The pachytene interval is marked by an activation of endonucleolytic activity. The enzyme produces single-stranded nicks in the DNA at specific loci. These loci consist of moderately repeated segments; about 100-200 base pairs long. Extracellular agents, such as radiation, cause random nicking regardless of the meiotic stage at which they are applied. Localized nicking and repair are thus unique features of meiosis. The temporal segregation of metabolic activities concerned with pairing and crossing over and their operation in special chromosome regions constitute the most prominent features of the biochemical events associated with meiosis.
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PMID:16292
The genetic analysis of meiosis in female Drosophila melanogaster.
The three major features of meiosis are first synapsis, then exchange, and finally, disjunction of homologous chromosomes; these phenomena occur before pachytene, during pachytene, and after pachytene respectively. The effects of meiotic mutants, or other perturbations, either endogenous or exogenous, on the meiotic process may be assigned tentatively to one of these intervals, based on the earliest discernible abnormality. Thus mutants exhibiting abnormal disjunction and normal exchange affect post-pachytene functions; mutants exhibiting abnormal disjunction and exchange but with ultrastructurally normal appearing synaptonemal complex affect pachytene functions; and mutants with abnormal disjunction, exchange, and synaptonemal complex affect prepachytene functions. This rationale is applied to the temporal seriation of effects of meiotic mutants and chromosomal abnormalities on the meiotic programme.
The genetic analysis of meiosis in female Drosophila melanogaster. The three major features of meiosis are first synapsis, then exchange, and finally, disjunction of homologous chromosomes; these phenomena occur before pachytene, during pachytene, and after pachytene respectively. The effects of meiotic mutants, or other perturbations, either endogenous or exogenous, on the meiotic process may be assigned tentatively to one of these intervals, based on the earliest discernible abnormality. Thus mutants exhibiting abnormal disjunction and normal exchange affect post-pachytene functions; mutants exhibiting abnormal disjunction and exchange but with ultrastructurally normal appearing synaptonemal complex affect pachytene functions; and mutants with abnormal disjunction, exchange, and synaptonemal complex affect prepachytene functions. This rationale is applied to the temporal seriation of effects of meiotic mutants and chromosomal abnormalities on the meiotic programme.
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PMID:16293
Inferences from genetical evidence on the course of meiotic chromosome pairing in plants.
Meiotic chromosome pairing is a process that is amenable to genetic and experimental analysis. The combined use of these two approaches allows for the process to be dissected into several finite periods of time in which the developmental stages of pairing can be precisely located. Evidence is now available, in particular in plants, that shows that the pairing of homologous chromosomes, as observed at metaphase I, is affected by events occurring as early as the last premeiotic mitosis; and that the maintenance of this early determined state is subsequently maintained by constituents (presumably proteins) that are sensitive to either colchicine, temperature or gene control. A critical assessment of this evidence in wheat and a comparison of the process of pairing in wheat with the course of meiotic pairing in other plants and animals is presented.
Inferences from genetical evidence on the course of meiotic chromosome pairing in plants. Meiotic chromosome pairing is a process that is amenable to genetic and experimental analysis. The combined use of these two approaches allows for the process to be dissected into several finite periods of time in which the developmental stages of pairing can be precisely located. Evidence is now available, in particular in plants, that shows that the pairing of homologous chromosomes, as observed at metaphase I, is affected by events occurring as early as the last premeiotic mitosis; and that the maintenance of this early determined state is subsequently maintained by constituents (presumably proteins) that are sensitive to either colchicine, temperature or gene control. A critical assessment of this evidence in wheat and a comparison of the process of pairing in wheat with the course of meiotic pairing in other plants and animals is presented.
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PMID:16294
Ribosomes, membranes and organelles during meiosis in angiosperms.
Evidence is presented from both observational and analytical techniques indicating profound changes to take place in the ribosome population during male and female meiosis in some flowering plants. During microsporogenesis these appear to involve the elimination of the major part of the ribosome complement early in the meiotic prophase, and its subsequent restoration by the disintegration in the tetrad cytoplasm of 'nucleoloids', themselves synthesized in the nucleus during late prophase. In female tissue the process is essentially similar except for differences in the restoration of the ribosome population. Immediately before the eradication of the ribosomes in both sexes, a sizeable proportion of the meiocyte cytoplasm is encapsulated by double, or multiple unit membrane profiles. Significantly this cytoplasm remains unaffected by the agents responsible for the degredation of the ribosome population. These events are also reflected in the organelle populations where cycles of dedifferentiation and redifferentiation take place. In view of evidence from other organisms, it is considered unlikely that these cycles are in any way a prerequisite of meiosis, but more a characteristic of cells undergoing major changes of phase, where a cytoplasmic 'clean-up' is required before the next stage of growth may begin.
Ribosomes, membranes and organelles during meiosis in angiosperms. Evidence is presented from both observational and analytical techniques indicating profound changes to take place in the ribosome population during male and female meiosis in some flowering plants. During microsporogenesis these appear to involve the elimination of the major part of the ribosome complement early in the meiotic prophase, and its subsequent restoration by the disintegration in the tetrad cytoplasm of 'nucleoloids', themselves synthesized in the nucleus during late prophase. In female tissue the process is essentially similar except for differences in the restoration of the ribosome population. Immediately before the eradication of the ribosomes in both sexes, a sizeable proportion of the meiocyte cytoplasm is encapsulated by double, or multiple unit membrane profiles. Significantly this cytoplasm remains unaffected by the agents responsible for the degredation of the ribosome population. These events are also reflected in the organelle populations where cycles of dedifferentiation and redifferentiation take place. In view of evidence from other organisms, it is considered unlikely that these cycles are in any way a prerequisite of meiosis, but more a characteristic of cells undergoing major changes of phase, where a cytoplasmic 'clean-up' is required before the next stage of growth may begin.
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PMID:16295
Meiosis in Bombyx mori females.
Crossing over is absent in oocytes of the silkworm, Bombyx mori. Synaptonemal complexes are present during pachytene between the paired chromosomes. At leptotene, lateral components of the synaptonemal complex are attached in a bouquet to a limited region of the nuclear envelope. Before completion of lateral components, synaptonemal complex formation begins at the nuclear envelope. With synaptonemal complex formation proceeding from both ends bivalents occasionally become interlocked. After pairing is completed, the bouquet arrangement is dissolved possibly as a result of a flow of the inner membrane of the nuclear envelope thereby separating the telomeres. After the telomeres are released from the nuclear envelope, material is deposited onto the lateral components of the synaptonemal complex. The modified synaptonemal complexes are retained by the bivalents until metaphase I. It is suggested that these modified synaptonemal complexes substitute for chiasmata in order to ensure regular disjunction of homologous chromosomes in the absence of crossing over.
Meiosis in Bombyx mori females. Crossing over is absent in oocytes of the silkworm, Bombyx mori. Synaptonemal complexes are present during pachytene between the paired chromosomes. At leptotene, lateral components of the synaptonemal complex are attached in a bouquet to a limited region of the nuclear envelope. Before completion of lateral components, synaptonemal complex formation begins at the nuclear envelope. With synaptonemal complex formation proceeding from both ends bivalents occasionally become interlocked. After pairing is completed, the bouquet arrangement is dissolved possibly as a result of a flow of the inner membrane of the nuclear envelope thereby separating the telomeres. After the telomeres are released from the nuclear envelope, material is deposited onto the lateral components of the synaptonemal complex. The modified synaptonemal complexes are retained by the bivalents until metaphase I. It is suggested that these modified synaptonemal complexes substitute for chiasmata in order to ensure regular disjunction of homologous chromosomes in the absence of crossing over.
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PMID:16296
Meiosis in a temperature-sensitive DNA-synthesis mutant and in an apomictic yeast strain (Saccharomyces cerevisiae).
It is shown that in the temperature-sensitive yeast mutant (Saccharomyces cerevisiae) spo 11 at the restrictive temperature of 34 degrees C. (1) premeiotic DNA synthesis is nearly completely blocked; (2) the nucleus enters meiotic prophase indicated by the formation of axial cores and polysynaptonemal complexes; (3) the kinetic apparatus functions normally at meiosis I and II; (4) early spore formation occurs in nearly all cells but it is variable and all spores eventually degenerate. It is concluded that chromosome replication is not a prerequisite for the functions listed above. The apomictic yeast strain 4117 produces 2 diploid spores. It is shown that a diploid which produces 2-spored asci, synthesized from 4117, no. 5, and an adenine requiring strain (1) has a normal meiotic prophase with abundant synaptonemal complexes; (2) has only one meiotic spindle; (3) has spores which form red clones more frequently than normal or u.v.-treated vegetative cells form ade/ade red sectors through mitotic recombination. It is concluded that this apomictic yeast has maintained meiotic prophase, but that one of the two meiotic divisions is suppressed.
Meiosis in a temperature-sensitive DNA-synthesis mutant and in an apomictic yeast strain (Saccharomyces cerevisiae). It is shown that in the temperature-sensitive yeast mutant (Saccharomyces cerevisiae) spo 11 at the restrictive temperature of 34 degrees C. (1) premeiotic DNA synthesis is nearly completely blocked; (2) the nucleus enters meiotic prophase indicated by the formation of axial cores and polysynaptonemal complexes; (3) the kinetic apparatus functions normally at meiosis I and II; (4) early spore formation occurs in nearly all cells but it is variable and all spores eventually degenerate. It is concluded that chromosome replication is not a prerequisite for the functions listed above. The apomictic yeast strain 4117 produces 2 diploid spores. It is shown that a diploid which produces 2-spored asci, synthesized from 4117, no. 5, and an adenine requiring strain (1) has a normal meiotic prophase with abundant synaptonemal complexes; (2) has only one meiotic spindle; (3) has spores which form red clones more frequently than normal or u.v.-treated vegetative cells form ade/ade red sectors through mitotic recombination. It is concluded that this apomictic yeast has maintained meiotic prophase, but that one of the two meiotic divisions is suppressed.
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PMID:16297
Recombination and meiosis.
Although exchanges between sister chromatids are common in mitotic cells, those involving homologous chromosomes are rare. Since recombination between homologues is one of the functions of meiosis, it follows that one aspect of the differentiation of the meiocyte involves the synthesis of proteins or enzymes which facilitate synapsis and exchange. Mutants are known which seem to have constitutive levels of mitotic recombination between homologues, and these may be defective in the mechanism which normally represses mitotic recombination. It has been proposed that one component of the synaptonemal complex (s.c.) is a filamentous pairing protein with DNA binding sites which are base sequence specific. Synapsis occurs because the distribution of these sequences is the same in homologues. When only non-homologous chromosomes are present, as in haploid meiosis, only weak pairing can occur, since the base sequences are largely out of register. Although certain features of recombination at the molecular level are known, none of the models so far proposed suggest an explanation for interference between crossovers. It is suggested that interference may depend on the presence of a limited amount of another DNA binding protein which is specifically located within the s.c. A crossover between naked DNA molecules is initially a weak structure, which must be later converted into a visible and mechanically strong chiasma. It is assumed that this stabilization of a crossover is achieved by the DNA binding protein, which can diffuse freely within the s.c. and bind cooperatively to any recombinant DNA molecules within it. Depletion of the binding protein within the vicinity of a crossover makes it unlikely that the second crossover can be formed nearby.
Recombination and meiosis. Although exchanges between sister chromatids are common in mitotic cells, those involving homologous chromosomes are rare. Since recombination between homologues is one of the functions of meiosis, it follows that one aspect of the differentiation of the meiocyte involves the synthesis of proteins or enzymes which facilitate synapsis and exchange. Mutants are known which seem to have constitutive levels of mitotic recombination between homologues, and these may be defective in the mechanism which normally represses mitotic recombination. It has been proposed that one component of the synaptonemal complex (s.c.) is a filamentous pairing protein with DNA binding sites which are base sequence specific. Synapsis occurs because the distribution of these sequences is the same in homologues. When only non-homologous chromosomes are present, as in haploid meiosis, only weak pairing can occur, since the base sequences are largely out of register. Although certain features of recombination at the molecular level are known, none of the models so far proposed suggest an explanation for interference between crossovers. It is suggested that interference may depend on the presence of a limited amount of another DNA binding protein which is specifically located within the s.c. A crossover between naked DNA molecules is initially a weak structure, which must be later converted into a visible and mechanically strong chiasma. It is assumed that this stabilization of a crossover is achieved by the DNA binding protein, which can diffuse freely within the s.c. and bind cooperatively to any recombinant DNA molecules within it. Depletion of the binding protein within the vicinity of a crossover makes it unlikely that the second crossover can be formed nearby.
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PMID:16299
Variation in the spire index of some coiled gastropod shells, and its evolutionary significance.
The spire index (height/maximum diameter of shell) is a fairly adequate measure of the shape of the coiled shell of most terrestrial and freshwater gastropod shells but less so in complex marine shells with thorns, flanges and spouts. In this study, only adult free-crawling forms with several whorls, able to retract completely into the shell, are considered. In the Stylommatophora of the Western European terrestrial fauna the distribution of the spire index is markedly bimodal, the modes, with values of about 3 and about 0.5, corresponding respectively to shells with a high to very high spire (and small spire angle) and those varying from more or less globular or trochoid to very flattened and disk-like (spire angle from 60 degrees to 180 degrees). The same two modes are found in the taxonomically different terrestrial stylommatophorans of the U.S.A., and in the faunas of Puerto Rico (Caribbean) and New Caledonia (southwest Pacific). Basommatophorans also show two, rather different, modes. North American marine archaeogastropods are mainly equidimensional but with a few disk-like forms and a very few high-spired ones, marine mesogastropods are mainly high-spired but with disk-like forms, neogastropods high-spired, and relevant euthyneurans sharply bimodal, like the stylommatophorans. Fossil archaeogastropods of the Palaeozoic were much more various at first than modern forms. There is some indication that they became restricted in variety as caenogastropods became abundant, but also that the proportion of marine disk-like shells has decreased markedly since the Palaeozoic. Modes of h/d are characteristic of large taxonomic groups but not taxonomically restricted since given values may appear as specific, generic or subfamilial variants from a mode, and appear sporadically in unrelated forms. There is also no broad association between modal value and broad ecological characters. Since nearly all values do occur in some group or other, no mechanical requirement can be invoked to explain such variation. In the land Stylommatophora enough is known of the broad ecology to suggest that in extreme habitats species with very different size or shell-shape may occur together, and that generalized feeders with similar shells may show separation, ecological or geographical (but in that case, also ecological). Since different shapes of shell will have different mechanical characteristics when considered as burdens to be carried, it is suggested tentatively that they may be related to the positions in which different species normally walk and hence to their preferred feeding places. This would explain an apparent tendency for different taxonomic groups to occupy the same part of the scatter of h/d in different regions of the world, for many groups in the same region to occupy different portions of the scatter, and perhaps the apparent exclusion by caenogastropods of archaeogastropods from part of the scatter since the Palaeozoic. It is argued that the distributions discovered are explicable only by natural selection.
Variation in the spire index of some coiled gastropod shells, and its evolutionary significance. The spire index (height/maximum diameter of shell) is a fairly adequate measure of the shape of the coiled shell of most terrestrial and freshwater gastropod shells but less so in complex marine shells with thorns, flanges and spouts. In this study, only adult free-crawling forms with several whorls, able to retract completely into the shell, are considered. In the Stylommatophora of the Western European terrestrial fauna the distribution of the spire index is markedly bimodal, the modes, with values of about 3 and about 0.5, corresponding respectively to shells with a high to very high spire (and small spire angle) and those varying from more or less globular or trochoid to very flattened and disk-like (spire angle from 60 degrees to 180 degrees). The same two modes are found in the taxonomically different terrestrial stylommatophorans of the U.S.A., and in the faunas of Puerto Rico (Caribbean) and New Caledonia (southwest Pacific). Basommatophorans also show two, rather different, modes. North American marine archaeogastropods are mainly equidimensional but with a few disk-like forms and a very few high-spired ones, marine mesogastropods are mainly high-spired but with disk-like forms, neogastropods high-spired, and relevant euthyneurans sharply bimodal, like the stylommatophorans. Fossil archaeogastropods of the Palaeozoic were much more various at first than modern forms. There is some indication that they became restricted in variety as caenogastropods became abundant, but also that the proportion of marine disk-like shells has decreased markedly since the Palaeozoic. Modes of h/d are characteristic of large taxonomic groups but not taxonomically restricted since given values may appear as specific, generic or subfamilial variants from a mode, and appear sporadically in unrelated forms. There is also no broad association between modal value and broad ecological characters. Since nearly all values do occur in some group or other, no mechanical requirement can be invoked to explain such variation. In the land Stylommatophora enough is known of the broad ecology to suggest that in extreme habitats species with very different size or shell-shape may occur together, and that generalized feeders with similar shells may show separation, ecological or geographical (but in that case, also ecological). Since different shapes of shell will have different mechanical characteristics when considered as burdens to be carried, it is suggested tentatively that they may be related to the positions in which different species normally walk and hence to their preferred feeding places. This would explain an apparent tendency for different taxonomic groups to occupy the same part of the scatter of h/d in different regions of the world, for many groups in the same region to occupy different portions of the scatter, and perhaps the apparent exclusion by caenogastropods of archaeogastropods from part of the scatter since the Palaeozoic. It is argued that the distributions discovered are explicable only by natural selection.
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PMID:16301
Pigment epithelial ensheathment and phagocytosis of extrafoveal cones in human retina.
The association between extrafoveal cone outer segments and pigment epithelial cells was studied by transmission electron microscopy in three human retinas; ages 5,45 and 60. The pigment epithelial apical surface from a fourth human retina, age 38,was viewed in the scanning electron microscope. Multiple villous-like apical processes protrude from the pigment epithelium into the space above each cone. Sometimes one or more of these processes is sheet-like in form and contains a wealth of intracellular organelles, including mitochondria. One or more of the villous-like procesess reaches the cone and expands to ensheath the upper one-third of the outer segment. Llike vertebrate rods, extrafoveal human cones shed their terminal disks in packets and these packets are phagocytosed by the ensheathing apical processes. The phagosomes then ascend in the processes toward the pigment epithelia soma. Digestion of phagosomes appears to begin in the apical processes.
Pigment epithelial ensheathment and phagocytosis of extrafoveal cones in human retina. The association between extrafoveal cone outer segments and pigment epithelial cells was studied by transmission electron microscopy in three human retinas; ages 5,45 and 60. The pigment epithelial apical surface from a fourth human retina, age 38,was viewed in the scanning electron microscope. Multiple villous-like apical processes protrude from the pigment epithelium into the space above each cone. Sometimes one or more of these processes is sheet-like in form and contains a wealth of intracellular organelles, including mitochondria. One or more of the villous-like procesess reaches the cone and expands to ensheath the upper one-third of the outer segment. Llike vertebrate rods, extrafoveal human cones shed their terminal disks in packets and these packets are phagocytosed by the ensheathing apical processes. The phagosomes then ascend in the processes toward the pigment epithelia soma. Digestion of phagosomes appears to begin in the apical processes.
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PMID:16303
Relationship between neurotransmitters and atherosclerosis.
Dyslipemia and finally the producing of atherosclerosis signal some modulation disturbances in neurotransmitters by the onset of a permanent incapacity of the organism to coordinate the adapting mechanism against the over-high activity of stress factors. Neurotransmitters and related substances facilitate and modulate energy and information in biosystems, assigning an important role to central control as noradrenaline, serotonin and other biogenic amines mediate emotional stress.
Relationship between neurotransmitters and atherosclerosis. Dyslipemia and finally the producing of atherosclerosis signal some modulation disturbances in neurotransmitters by the onset of a permanent incapacity of the organism to coordinate the adapting mechanism against the over-high activity of stress factors. Neurotransmitters and related substances facilitate and modulate energy and information in biosystems, assigning an important role to central control as noradrenaline, serotonin and other biogenic amines mediate emotional stress.
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PMID:16313
[New views referred to gamma-glutamyl-transpeptidase (author's transl].
The AA. have observed some patients suffering from persistent chronic hepatitis, aggressive chronic hepatitis, severe virus hepatitis, hepatic cirrhosis, hepatic metastasis, cholecystolithiasis, hepatic abscess, congestic heart disorder, alcoholism also patients treated with barbiturics and benzodiazepine, comparising in the meanwhile gamma-glutamyl-transaminase. They would suggest a new interpretation: the observed enzyme was higher in the obstructive diseases, gamma-GT also notable higher in the cellular hepatic diseases (hepatitis, cirrhosis and so on). In their opinion gamma-GT should be a regular enzymatic screening for liver diseases, but should not anyway eliminate the till now used enzymes.
[New views referred to gamma-glutamyl-transpeptidase (author's transl]. The AA. have observed some patients suffering from persistent chronic hepatitis, aggressive chronic hepatitis, severe virus hepatitis, hepatic cirrhosis, hepatic metastasis, cholecystolithiasis, hepatic abscess, congestic heart disorder, alcoholism also patients treated with barbiturics and benzodiazepine, comparising in the meanwhile gamma-glutamyl-transaminase. They would suggest a new interpretation: the observed enzyme was higher in the obstructive diseases, gamma-GT also notable higher in the cellular hepatic diseases (hepatitis, cirrhosis and so on). In their opinion gamma-GT should be a regular enzymatic screening for liver diseases, but should not anyway eliminate the till now used enzymes.
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PMID:16319
Alpha-adrenergic blockers on ventricular automatism in rat heart.
The role of the alpha-adrenergic receptors in the genesis of cardiac arrhythmias induced in the isolated rat right ventricle has been studied. The administration of six alpha-adrenergic blocking agents (phenoxybenzamine, dibenamine, phentolamine, tolazoline, azapetine and SY-28) did not alter the automatism induced. Even when can not be excluded the existance of alpha-adrenergic receptors in the rat ventricle, it is clear that alpha-blocking drugs are ineffective to abolish the arrhythmias induced by an increase in the activity of the Purkinje fibers.
Alpha-adrenergic blockers on ventricular automatism in rat heart. The role of the alpha-adrenergic receptors in the genesis of cardiac arrhythmias induced in the isolated rat right ventricle has been studied. The administration of six alpha-adrenergic blocking agents (phenoxybenzamine, dibenamine, phentolamine, tolazoline, azapetine and SY-28) did not alter the automatism induced. Even when can not be excluded the existance of alpha-adrenergic receptors in the rat ventricle, it is clear that alpha-blocking drugs are ineffective to abolish the arrhythmias induced by an increase in the activity of the Purkinje fibers.
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PMID:16321
Cardiorespiratory and behavioral reactions to the lidocaine-induced convulsions in the dog.
Central nervous system (CNS) reactions to intermittently infused lidocaine HCl (i.v.) were evaluated from cardiorespiratory and behavioral responses in 33 mongrel dogs. Threshold convulsive doses were established for each of three distinct and predictable seizure patterns. The first seizure activity observed was tonic extension (TE) which occurred at an infused lidocaine dose of 12.2+/-0.6 mg/kg followed by running activity after 22.7+/-0.9 mg/kg lidocaine was given. The threshold for intermittent tonic-clonic seizures (ICS) occurred at an infused lidocaine dose of 33.3+/-1.5 mg/kg. Mean blood pressure and pulse pressure increased at the onset of TE and ICS, with a decline in arterial pH and PCO2 during the ICS. No relationship was found between the animals' acid-base status and the ICS threshold. Toxicity to lidocaine in the dog is expressed by distinct behavioral responses suggesting lidocaine may affect various parts of the CNS. The mongrel dog appears to be a satisfactory and simple model system to evaluate lidocaine toxicity from behavioral and cardiorespiratory responses.
Cardiorespiratory and behavioral reactions to the lidocaine-induced convulsions in the dog. Central nervous system (CNS) reactions to intermittently infused lidocaine HCl (i.v.) were evaluated from cardiorespiratory and behavioral responses in 33 mongrel dogs. Threshold convulsive doses were established for each of three distinct and predictable seizure patterns. The first seizure activity observed was tonic extension (TE) which occurred at an infused lidocaine dose of 12.2+/-0.6 mg/kg followed by running activity after 22.7+/-0.9 mg/kg lidocaine was given. The threshold for intermittent tonic-clonic seizures (ICS) occurred at an infused lidocaine dose of 33.3+/-1.5 mg/kg. Mean blood pressure and pulse pressure increased at the onset of TE and ICS, with a decline in arterial pH and PCO2 during the ICS. No relationship was found between the animals' acid-base status and the ICS threshold. Toxicity to lidocaine in the dog is expressed by distinct behavioral responses suggesting lidocaine may affect various parts of the CNS. The mongrel dog appears to be a satisfactory and simple model system to evaluate lidocaine toxicity from behavioral and cardiorespiratory responses.
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PMID:16322
Inhibition by naloxone of tolerance and dependence in mice treated acutely and chronically with morphine.
The inhibition by naloxone of tolerance and dependence in morphinized mice is dose- and time-dependent. In animals receiving a single, large dose of morphine, partial inhibition by naloxone of the analgesic effect results in partial development of tolerance and dependence. This relationship appears to be true for animals which have been treated with morphine chronically. Complete and sustained blockage of morphine receptors by naloxone is required for complete inhibition of the development of tolerance and dependence.
Inhibition by naloxone of tolerance and dependence in mice treated acutely and chronically with morphine. The inhibition by naloxone of tolerance and dependence in morphinized mice is dose- and time-dependent. In animals receiving a single, large dose of morphine, partial inhibition by naloxone of the analgesic effect results in partial development of tolerance and dependence. This relationship appears to be true for animals which have been treated with morphine chronically. Complete and sustained blockage of morphine receptors by naloxone is required for complete inhibition of the development of tolerance and dependence.
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PMID:16323
Exercise-induced bronchoconstriction in patients with bronchial asthma. Its prevention with an antihistaminic agent.
14 asthmatic patients developing regularly exercise-induced bronchoconstriction were subjected to a submaximal exercise on a bicycle ergometer. On the first day the exercise was not preceded by any medication; on the second, 50 mg thiazinamium was given, and on the third day 2 mg atropine was given before the exercise. The changes in the calibre of the bronchi were assessed with a Wright peak flow meter. With thiazinamium a complete protection against the bronchoconstriction was observed in 12 patients, in one the protection was partial and in an other no beneficial effect of the drug was found. It seems that protection given by thiazinamium was due to its antihistaminic property and not to the anticholinergic one, as among 10 patients protected by thiazinamium, only 2 were also protected by the atropine.
Exercise-induced bronchoconstriction in patients with bronchial asthma. Its prevention with an antihistaminic agent. 14 asthmatic patients developing regularly exercise-induced bronchoconstriction were subjected to a submaximal exercise on a bicycle ergometer. On the first day the exercise was not preceded by any medication; on the second, 50 mg thiazinamium was given, and on the third day 2 mg atropine was given before the exercise. The changes in the calibre of the bronchi were assessed with a Wright peak flow meter. With thiazinamium a complete protection against the bronchoconstriction was observed in 12 patients, in one the protection was partial and in an other no beneficial effect of the drug was found. It seems that protection given by thiazinamium was due to its antihistaminic property and not to the anticholinergic one, as among 10 patients protected by thiazinamium, only 2 were also protected by the atropine.
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PMID:16337
[Beta blocking agents in the treatment of algo-neuro-dystrophies. Apropos of 34 cases].
The authors report results of a series of thirty four cases of algo-neuro-dystrophy treated with beta blockers. This treatment produced favorable results in thirty out of the thirty four cases and the mode of action is discussed.
[Beta blocking agents in the treatment of algo-neuro-dystrophies. Apropos of 34 cases]. The authors report results of a series of thirty four cases of algo-neuro-dystrophy treated with beta blockers. This treatment produced favorable results in thirty out of the thirty four cases and the mode of action is discussed.
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PMID:16339
Comparison of rimiterol and terbutaline, given by aerosol, in a long-term study.
In a double-blind long-term study, regular inhalations of a short-acting selective beta2-stimulator, rimiterol, was compared with a long-acting one, terbutaline. The trial comprised 60 patients with chronic obstructive lung disease, all patients were on a small dose of an oral beta2-stimulator. Both drugs were regularly given in aerosol form with a minimum dose of three inhalations three times daily. The main purpose was to study subjective and objective side effects. Haematological, hepatic and renal functions were screened for toxicity. Consumption of spray was recorded. No side effects occurred. There was no evidence of development of isoprenaline resistance. The consumption of spray was the same in both groups. In this study, regular inhalation treatment of rimiterol seemed to be as effective as terbutaline in long-term bronchodilator therapy.
Comparison of rimiterol and terbutaline, given by aerosol, in a long-term study. In a double-blind long-term study, regular inhalations of a short-acting selective beta2-stimulator, rimiterol, was compared with a long-acting one, terbutaline. The trial comprised 60 patients with chronic obstructive lung disease, all patients were on a small dose of an oral beta2-stimulator. Both drugs were regularly given in aerosol form with a minimum dose of three inhalations three times daily. The main purpose was to study subjective and objective side effects. Haematological, hepatic and renal functions were screened for toxicity. Consumption of spray was recorded. No side effects occurred. There was no evidence of development of isoprenaline resistance. The consumption of spray was the same in both groups. In this study, regular inhalation treatment of rimiterol seemed to be as effective as terbutaline in long-term bronchodilator therapy.
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PMID:16340
[Vasculitis in hepatitis B infection].
Personal observations have confirmed the frequent association of HB-infection with certain forms of vasculitis. 4 of 11 patients with polyarteritis nodosa were repeatedly found to be HBs-Ag positive and had chronic hepatitis of varying severity. In patients with giant cell arteritis (polymyalgia rheumatica and temporal arteritis) anti-HBs was found more frequently than in controls, especially when examined within 6 months after onset of symptoms (7 of 20 equal 35% had anti-HBs, versus 6% of controls). Several lines of evidence point to the important role played by circulating HBs-Ag/anti-HBs complexes in the development of HB-associated vasculitis.
[Vasculitis in hepatitis B infection]. Personal observations have confirmed the frequent association of HB-infection with certain forms of vasculitis. 4 of 11 patients with polyarteritis nodosa were repeatedly found to be HBs-Ag positive and had chronic hepatitis of varying severity. In patients with giant cell arteritis (polymyalgia rheumatica and temporal arteritis) anti-HBs was found more frequently than in controls, especially when examined within 6 months after onset of symptoms (7 of 20 equal 35% had anti-HBs, versus 6% of controls). Several lines of evidence point to the important role played by circulating HBs-Ag/anti-HBs complexes in the development of HB-associated vasculitis.
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PMID:16336
[Role of neuropsychiatric pathology and pharmacology in neuroendocrinologic research].
Experimental, pharmacological and clinical data are presented suggesting that neurotransmitters, neurohormones and adenohypophyseal hormones have effects respectively on aterior pituitary and on the CNS. The related functional hypothesis are proposed and discussed.
[Role of neuropsychiatric pathology and pharmacology in neuroendocrinologic research]. Experimental, pharmacological and clinical data are presented suggesting that neurotransmitters, neurohormones and adenohypophyseal hormones have effects respectively on aterior pituitary and on the CNS. The related functional hypothesis are proposed and discussed.
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PMID:16343
Direct resorption of bone by human monocytes.
Cultured human peripheral blood monocytes stimulate the release of bone mineral and matrix from killed long bones of fetal rats. These effects were inhibited by cortisol but were not altered by hormones that normally stimulate osteoclastic bone resorption. There was no evidence of morphologic differentiation of the monocytes into osteoclasts during bone resorption.
Direct resorption of bone by human monocytes. Cultured human peripheral blood monocytes stimulate the release of bone mineral and matrix from killed long bones of fetal rats. These effects were inhibited by cortisol but were not altered by hormones that normally stimulate osteoclastic bone resorption. There was no evidence of morphologic differentiation of the monocytes into osteoclasts during bone resorption.
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PMID:16344
Prelytic damage of red cells in filtrates from peroxidizing microsomes.
When liver microsomes are incubated in the presence of reduced nicotinamide adenine dinucleotide phosphate (NADPH), their constituent lipids undergo peroxidative degeneration. If erythrocytes are present in such a peroxidizing system, they hemolyze. Filtrates obtained by ultrafiltration of peroxidizing microsomal systems were found to have the capacity to produce prelytic damage in red cells. Filtrates obtained from microsomes that had not undergone peroxidative lipid decomposition were inert. The toxic activity in the active filtrates was not due to continuing oxidation of NADPH nor to continuing liver microsomal lipid peroxidation. Neither the chemical identity of the toxic product or products in active filtrates nor the mechanisms involved in the erythrocyte damage are known at this time.
Prelytic damage of red cells in filtrates from peroxidizing microsomes. When liver microsomes are incubated in the presence of reduced nicotinamide adenine dinucleotide phosphate (NADPH), their constituent lipids undergo peroxidative degeneration. If erythrocytes are present in such a peroxidizing system, they hemolyze. Filtrates obtained by ultrafiltration of peroxidizing microsomal systems were found to have the capacity to produce prelytic damage in red cells. Filtrates obtained from microsomes that had not undergone peroxidative lipid decomposition were inert. The toxic activity in the active filtrates was not due to continuing oxidation of NADPH nor to continuing liver microsomal lipid peroxidation. Neither the chemical identity of the toxic product or products in active filtrates nor the mechanisms involved in the erythrocyte damage are known at this time.
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PMID:16348
Acute erosive gastritis induced by aspirin, ketoprofen, ibuprofen, and naproxen: its prevention by metiamide and cimetidine.
Aspirin, ketoprofen, ibuprofen, and naproxen all produced acute gastric erosions in rats. Aspirin produced significantly more erosions than ketoprofen, ibuprofen, or naproxen. There was no significant difference between the effects of ketoprofen, ibuprofen, and naproxen. Aspirin and naproxen produced a synergistic effect at higher dosage. Metiamide and cimetidine were effective in preventing this type of experimental acute erosive gastritis.
Acute erosive gastritis induced by aspirin, ketoprofen, ibuprofen, and naproxen: its prevention by metiamide and cimetidine. Aspirin, ketoprofen, ibuprofen, and naproxen all produced acute gastric erosions in rats. Aspirin produced significantly more erosions than ketoprofen, ibuprofen, or naproxen. There was no significant difference between the effects of ketoprofen, ibuprofen, and naproxen. Aspirin and naproxen produced a synergistic effect at higher dosage. Metiamide and cimetidine were effective in preventing this type of experimental acute erosive gastritis.
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PMID:16349
Human intestinal helminthiases in East Timor.
In a study of 210 people from all age groups in the Venilale District of East Timor, 49% had Ascaris lumbricoides, 1% Trichuris trichiura and 67% hookworm infection. There were high Ascaris infection rates among some of the children, but the Trichuris and hookworm rates were almost uniformly low. The factors responsible for these rates are enumerated, and the complex interaction of the factors is discussed. The relative lack of shade and the well-drained limestone soil are probably in large measure responsible for the generally low helminth prevalence. Ascaris was the principal cause of eosinophilia. It was not possible to relate any other haematological or serological findings to the helminths. Apart from the high Ascaris infections in young children, it is not thought that these helminths constitute a heatlh problem.
Human intestinal helminthiases in East Timor. In a study of 210 people from all age groups in the Venilale District of East Timor, 49% had Ascaris lumbricoides, 1% Trichuris trichiura and 67% hookworm infection. There were high Ascaris infection rates among some of the children, but the Trichuris and hookworm rates were almost uniformly low. The factors responsible for these rates are enumerated, and the complex interaction of the factors is discussed. The relative lack of shade and the well-drained limestone soil are probably in large measure responsible for the generally low helminth prevalence. Ascaris was the principal cause of eosinophilia. It was not possible to relate any other haematological or serological findings to the helminths. Apart from the high Ascaris infections in young children, it is not thought that these helminths constitute a heatlh problem.
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PMID:16352
The influence of coronary arterial pH on myocardial oxygen demand.
The purpose of this study was to examine the magnitude of the influence of coronary arterial pH (pHa) on myocardial oxygen uptake (MV 02). In order to isolate and control the recognized determinants of MV02, a perfused heart preparation was developed which permitted control of heart rate and pressure and flow work. A perfusion system was used which allowed independent regulation of O2 N2 and CO2 flow to a membrane lung and precise control of coronary blood flow. Myocardial oxygen delivery (Ca02 x flow) could be held constant (+/- 1%) during 4 hours of perfusion. Catheter decompression of both ventricles prevented any external pressure or flow work. Blood temperature was maintained at 37.27 +/- 0.07degrees C. Perfusing blood pH was related initially to spontaneous heart rate in five dogs: pulse = 82 pH - 487. In 12 subsequent animals heart rate was fixed. MV02 was directly and significantly related to coronary arterial pH in all animals studied: MVO2% = 109 pH - 143 (r = 0.823). An increase in pHa of 0.1 will increase MV02 by 10.9%. This study isolates pH as a determinant of myocardial oxygen uptake and indicates that progressive alkalosis induces increased myocardial oxygen uptake. This must be recognized in the treatment of patients with compromised myocardial function and rerional areas of ischemia.
The influence of coronary arterial pH on myocardial oxygen demand. The purpose of this study was to examine the magnitude of the influence of coronary arterial pH (pHa) on myocardial oxygen uptake (MV 02). In order to isolate and control the recognized determinants of MV02, a perfused heart preparation was developed which permitted control of heart rate and pressure and flow work. A perfusion system was used which allowed independent regulation of O2 N2 and CO2 flow to a membrane lung and precise control of coronary blood flow. Myocardial oxygen delivery (Ca02 x flow) could be held constant (+/- 1%) during 4 hours of perfusion. Catheter decompression of both ventricles prevented any external pressure or flow work. Blood temperature was maintained at 37.27 +/- 0.07degrees C. Perfusing blood pH was related initially to spontaneous heart rate in five dogs: pulse = 82 pH - 487. In 12 subsequent animals heart rate was fixed. MV02 was directly and significantly related to coronary arterial pH in all animals studied: MVO2% = 109 pH - 143 (r = 0.823). An increase in pHa of 0.1 will increase MV02 by 10.9%. This study isolates pH as a determinant of myocardial oxygen uptake and indicates that progressive alkalosis induces increased myocardial oxygen uptake. This must be recognized in the treatment of patients with compromised myocardial function and rerional areas of ischemia.
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PMID:16368
Distribution of acid phosphatase activity in the larval stages of Wuchereria bancrofti, Brugia malayi, B. pahangi and Dirofilaria immitis in the mosquito.
The histochemical distribution of acid phosphatase in microfilariae and in the larval stages of four mosquito-borne filariae: Wuchereria bancrofti, Brugia malayi, B. pahangi and Dirofilaria immitis was studied using naphthol AS-TR-hexazonium technique and light microscopy. Accurate differentiation between microfilariae of the four species could be made on the basis of their patterns of acid phosphatase activity. In contrast to microfilariae in the blood, the larval stages in the mosquito exhibited different patterns of acid phosphatase activity which were characteristic for each developmental stage. In the first-stage larva, maximum acid phosphatase activity was found in the anal vesicle, the growing anal membrane (anal plug), buccal cavity, forming intestine and rectum. In the second-stage larva, acid phosphatase activity was present throughout the alimentary canal, particularly in the section of the intestine and rectum. In the infective third-stage larva, the whole body stained densely red. The reaction for acid phosphatase in the excretory cell complex of W. bancrofti and of both species of Brugia gradually decreased in intensity and disappeared completely towards the end of the first-larval stage, whereas in D. immitis a strong reaction in this area persisted throughout the larval life in the mosquito. The presence or absence of enzymic activity in the excretory cell complex and in the Mundgebilde (amphids) of the developing larvae can be used as an adjunctive diagnostic method.
Distribution of acid phosphatase activity in the larval stages of Wuchereria bancrofti, Brugia malayi, B. pahangi and Dirofilaria immitis in the mosquito. The histochemical distribution of acid phosphatase in microfilariae and in the larval stages of four mosquito-borne filariae: Wuchereria bancrofti, Brugia malayi, B. pahangi and Dirofilaria immitis was studied using naphthol AS-TR-hexazonium technique and light microscopy. Accurate differentiation between microfilariae of the four species could be made on the basis of their patterns of acid phosphatase activity. In contrast to microfilariae in the blood, the larval stages in the mosquito exhibited different patterns of acid phosphatase activity which were characteristic for each developmental stage. In the first-stage larva, maximum acid phosphatase activity was found in the anal vesicle, the growing anal membrane (anal plug), buccal cavity, forming intestine and rectum. In the second-stage larva, acid phosphatase activity was present throughout the alimentary canal, particularly in the section of the intestine and rectum. In the infective third-stage larva, the whole body stained densely red. The reaction for acid phosphatase in the excretory cell complex of W. bancrofti and of both species of Brugia gradually decreased in intensity and disappeared completely towards the end of the first-larval stage, whereas in D. immitis a strong reaction in this area persisted throughout the larval life in the mosquito. The presence or absence of enzymic activity in the excretory cell complex and in the Mundgebilde (amphids) of the developing larvae can be used as an adjunctive diagnostic method.
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PMID:16363
Analysis of vasoactivity of local pH, PCO2 and bicarbonate on pial vessels.
The mechanism by which the local effect of CO2ON pial arterioles is exerted was examined in anesthetized cats equipped with a cranial window for the direct observation of the microcirculation of the parietal cortex. The dilation of pial arterioles in response to application of artificial cerebrospinal fluid with low pH was the same whether or not the PCO2 of the solution was maintained in the normal range or markedly increased. The constriction of pial arterioles in response to application of artificial cerebrospinal fluid with high pH was the same whether or not the PCO2 of the solution was maintained in the normal range or markedly decreased. Finally, pial arterioles did not change their caliber in response to application of cerebrospinal fluid with unchanged pH but markedly increased or decreased Pco, or bicarbonate ion concentration. These results show that the action of CO2 on cerebral vessels is exerted via changes in extracellular fluid pH and that molecular CO2 and bicarbonate ions do not have independent vasoactivity on these vessels.
Analysis of vasoactivity of local pH, PCO2 and bicarbonate on pial vessels. The mechanism by which the local effect of CO2ON pial arterioles is exerted was examined in anesthetized cats equipped with a cranial window for the direct observation of the microcirculation of the parietal cortex. The dilation of pial arterioles in response to application of artificial cerebrospinal fluid with low pH was the same whether or not the PCO2 of the solution was maintained in the normal range or markedly increased. The constriction of pial arterioles in response to application of artificial cerebrospinal fluid with high pH was the same whether or not the PCO2 of the solution was maintained in the normal range or markedly decreased. Finally, pial arterioles did not change their caliber in response to application of cerebrospinal fluid with unchanged pH but markedly increased or decreased Pco, or bicarbonate ion concentration. These results show that the action of CO2 on cerebral vessels is exerted via changes in extracellular fluid pH and that molecular CO2 and bicarbonate ions do not have independent vasoactivity on these vessels.
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PMID:16364
Effect of carotid artery ligation on regional cerebral blood flow in normotensive and spontaneously hypertensive rats.
Regional cerebral blood flow (rCBF) was measured in normotensive rate (NTR) and spontaneously hypertensive rats (SHR), in a lightly anesthetized state and with control of PaCO2 by artificial ventilation. Without carotid artery ligation, NTR and SHR showed almost identical rCBF values and distribution, despite significantly elevated levels of blood pressure in SHR. Bilateral carotid artery ligation, however, caused much more pronounced decreases of rCBF (ischemia) in SHR than NTR, in regions supplied by the carotid artery. The reduction of rCBF in SHR was rather homogenous and symmetrical. Mechanisms causing the differences between NTR and SHR are discussed.
Effect of carotid artery ligation on regional cerebral blood flow in normotensive and spontaneously hypertensive rats. Regional cerebral blood flow (rCBF) was measured in normotensive rate (NTR) and spontaneously hypertensive rats (SHR), in a lightly anesthetized state and with control of PaCO2 by artificial ventilation. Without carotid artery ligation, NTR and SHR showed almost identical rCBF values and distribution, despite significantly elevated levels of blood pressure in SHR. Bilateral carotid artery ligation, however, caused much more pronounced decreases of rCBF (ischemia) in SHR than NTR, in regions supplied by the carotid artery. The reduction of rCBF in SHR was rather homogenous and symmetrical. Mechanisms causing the differences between NTR and SHR are discussed.
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PMID:16372
Aggregation of calcium oxalate crystals: effect of urine and various inhibitors.
The influence of various factors on aggregation of calcium oxalate crystals in vitro was determined. Aggregation was assessed by filtering the crystal suspension and measuring the flow rate through a filter. 10% urine completely inhibited aggregation. Orthophosphate and magnesium at concentrations occuring in urine had no effect. Citrate had no effect at 10(-4) M ,but did inhibit at 10(-3) M. The latter effect is probably due to calcium binding. Pyrophosphate and disodium dichioromethylene diphosphonate (C12MDP) inhibited strongly at 10(-4) M, disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) at 10(-5) M, whereas pentanemonophosphonate had no effect. Uromucoid also did not show any inhibitory activity. Studies by means of heat inactivation, ultrafiltration and fractionation on DEAE-cellulose and gel-filtration indicated that the inhibitory activity was heterogenous and that the major part was larger than 10 000 daltons.
Aggregation of calcium oxalate crystals: effect of urine and various inhibitors. The influence of various factors on aggregation of calcium oxalate crystals in vitro was determined. Aggregation was assessed by filtering the crystal suspension and measuring the flow rate through a filter. 10% urine completely inhibited aggregation. Orthophosphate and magnesium at concentrations occuring in urine had no effect. Citrate had no effect at 10(-4) M ,but did inhibit at 10(-3) M. The latter effect is probably due to calcium binding. Pyrophosphate and disodium dichioromethylene diphosphonate (C12MDP) inhibited strongly at 10(-4) M, disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) at 10(-5) M, whereas pentanemonophosphonate had no effect. Uromucoid also did not show any inhibitory activity. Studies by means of heat inactivation, ultrafiltration and fractionation on DEAE-cellulose and gel-filtration indicated that the inhibitory activity was heterogenous and that the major part was larger than 10 000 daltons.
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PMID:16375
[Use of preparations with sympatholytic activity for prevention and treatment of postoperative intestinal paresis].
For prophylaxis and treatment of postoperative intestinal paresis the authors employed in 1059 patients gangliolytics and drugs of sympatholytic action -- benzohexonium, aminazine, pyrroxane. An early sympathetic blockade after abdominal surgery was found to be effective both with respect to the prophylaxis of intestinal paresis and in treatment of grave functional disturbances of enteric motility, that develop in different abdominal complications.
[Use of preparations with sympatholytic activity for prevention and treatment of postoperative intestinal paresis]. For prophylaxis and treatment of postoperative intestinal paresis the authors employed in 1059 patients gangliolytics and drugs of sympatholytic action -- benzohexonium, aminazine, pyrroxane. An early sympathetic blockade after abdominal surgery was found to be effective both with respect to the prophylaxis of intestinal paresis and in treatment of grave functional disturbances of enteric motility, that develop in different abdominal complications.
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PMID:16377
[Determination of the effective concentration of Jodonal a for the disinfection of the skin and teats after milking].
The bactericidal effectivity of Jodonal A in 1:10, 1:5, and 1:3 solutions was tested on human skin and on the teats of cow mammary glands. The 1:3 dilution ratio proved best for three-minute exposure. Jodonal A used in this concentration in 522 cows for the post-milking disinfection of teats for 10 months exerted no harmful effect on the skin of the mammary glands.
[Determination of the effective concentration of Jodonal a for the disinfection of the skin and teats after milking]. The bactericidal effectivity of Jodonal A in 1:10, 1:5, and 1:3 solutions was tested on human skin and on the teats of cow mammary glands. The 1:3 dilution ratio proved best for three-minute exposure. Jodonal A used in this concentration in 522 cows for the post-milking disinfection of teats for 10 months exerted no harmful effect on the skin of the mammary glands.
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PMID:16378
[Devitalizing effect of Jodonal A in vitro on bacteria subject to a short-term exposure].
In a three-minute exposure in vitro Jodonal A devitalized a culture of serological group B streptococci in a 2% concentration, Staphylococcus aureus in a 16% concentration, Pneumococcus in a 4.5% concentration, Corynebacterium pyogenes in a 2.5% concentration, Pseudomonas aeruginosa in a 3% concentration, and Klebsiella pneumoniae in a 2% concentration. Hence Jodonal A concentrations higher than 16% should be tested for udder teat disinfection after the removal of teat cups.
[Devitalizing effect of Jodonal A in vitro on bacteria subject to a short-term exposure]. In a three-minute exposure in vitro Jodonal A devitalized a culture of serological group B streptococci in a 2% concentration, Staphylococcus aureus in a 16% concentration, Pneumococcus in a 4.5% concentration, Corynebacterium pyogenes in a 2.5% concentration, Pseudomonas aeruginosa in a 3% concentration, and Klebsiella pneumoniae in a 2% concentration. Hence Jodonal A concentrations higher than 16% should be tested for udder teat disinfection after the removal of teat cups.
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PMID:16385
[Acid gamma-amylase of rabbit and human brain].
Preparations of acidic gamma-amylase, which cleaved glycogen and maltose, were isolated from human and rabbit brain tissues. The specific activity of the gamma-amylase preparations from human brain was approximately twice higher than the activity of the enzyme from rabbit brain. In degradation of glycogen gamma-amylases from human and rabbit brain had the pH optima at pH 4.9 and 4.6 and with maltose as a substrate- at pH 4.3 and 4.1, respectively. gamma-Amylases from both sources possessed the high stability in presence of monovalent cations. K+ distinctly increased the cleavage of glycogen by gamma-amylase from human and rabbit brain. alpha, alpha-Trehalose and alpha-menthyl glucoside proved to be inhibitors of the glucoamylase activity of the enzymes from both sources. Km values of the gamma-amylases for glycogen were equal to 19.3 mM 19.8 and for maltose -5.54 mM and 5.78 mM, respectively. The data obtained suggest that acidic gamma-amylases from human and rabbit brain are similar to acidic gamma-amylases from other sources.
[Acid gamma-amylase of rabbit and human brain]. Preparations of acidic gamma-amylase, which cleaved glycogen and maltose, were isolated from human and rabbit brain tissues. The specific activity of the gamma-amylase preparations from human brain was approximately twice higher than the activity of the enzyme from rabbit brain. In degradation of glycogen gamma-amylases from human and rabbit brain had the pH optima at pH 4.9 and 4.6 and with maltose as a substrate- at pH 4.3 and 4.1, respectively. gamma-Amylases from both sources possessed the high stability in presence of monovalent cations. K+ distinctly increased the cleavage of glycogen by gamma-amylase from human and rabbit brain. alpha, alpha-Trehalose and alpha-menthyl glucoside proved to be inhibitors of the glucoamylase activity of the enzymes from both sources. Km values of the gamma-amylases for glycogen were equal to 19.3 mM 19.8 and for maltose -5.54 mM and 5.78 mM, respectively. The data obtained suggest that acidic gamma-amylases from human and rabbit brain are similar to acidic gamma-amylases from other sources.
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PMID:16388
[Intracellular localization of the processes of biosynthesis and degradation of NADP in skeletal muscle].
In studies on intracellular NADP localization the process of NADP biosynthesis was observed in mitochondria and hyaloplasm of rabbit sceletal muscle cells. This synthesis was not found in microsomal and nuclear fractions. The seasonal alterations in the NAD-kinase activity were established: in autumn and winter months NADP synthesis proceeded at the maximal rate in hyaloplasm; in sping months the higher specific activity was observed in mitochondrial fraction. The rate of NADP synthesis was 2-5 times lower in initial and reconstructed (hyaloplasm+cell organelles) homogenate then in hyaloplasm, among the enzymes, degrading the NADP molecule in sceletal muscle, the highest activity was exhibitel by nucleosidase, which was localized mainly in mitochondria and microsomes. Mechanisms for regulation of the rate of NADP synthesis and degradation in cytostructures of rabbit sceletal muscles are discussed.
[Intracellular localization of the processes of biosynthesis and degradation of NADP in skeletal muscle]. In studies on intracellular NADP localization the process of NADP biosynthesis was observed in mitochondria and hyaloplasm of rabbit sceletal muscle cells. This synthesis was not found in microsomal and nuclear fractions. The seasonal alterations in the NAD-kinase activity were established: in autumn and winter months NADP synthesis proceeded at the maximal rate in hyaloplasm; in sping months the higher specific activity was observed in mitochondrial fraction. The rate of NADP synthesis was 2-5 times lower in initial and reconstructed (hyaloplasm+cell organelles) homogenate then in hyaloplasm, among the enzymes, degrading the NADP molecule in sceletal muscle, the highest activity was exhibitel by nucleosidase, which was localized mainly in mitochondria and microsomes. Mechanisms for regulation of the rate of NADP synthesis and degradation in cytostructures of rabbit sceletal muscles are discussed.
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PMID:16389
[Isolation of the islands of Langerhans from rat pancreas and determination of proteolytic activity in them].
A modified method for isolation of Langerhans islands from rat pancreas is described. The islands obtained were free from acinous tissue as shown by means of an amylase test and by microscopy. In homogenates of the islands proteolytic activities were observed (pH optimum at 5.3--5.5 and 6.9--7.2).
[Isolation of the islands of Langerhans from rat pancreas and determination of proteolytic activity in them]. A modified method for isolation of Langerhans islands from rat pancreas is described. The islands obtained were free from acinous tissue as shown by means of an amylase test and by microscopy. In homogenates of the islands proteolytic activities were observed (pH optimum at 5.3--5.5 and 6.9--7.2).
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PMID:16390
[Pyridine nucleotide content in the brain and myocardium of rats under combined effect of hypercapnia, hypoxia and cooling].
In experiments with rats, subjected to single and repeated simultaneous effect of hypercapnia, hypoxia and cooling, contents of pyridine nucleotides (NAD, NADP, NAD-H2 and NADP-H2) and macroergic substances were studied and also the activity of dehydrogenases of the pentose pathway was determined in brain and myocardium. In brain NADP was not practically determined and in heart its content was increased after the first and the second treatments. Content of NADP-H2 was distinctly decreased in both tissues after the single treatment. NAD was not altered in the tissues in all the periods studied. The amount of NAD-H2 was decreased in brain after the single treatment and it was increased in myocardium after the repeated one. In the activity of dehydrogenases marked alterations were not observed. Total macroergic substances were not altered in brain after the single treatment and after the repeated one they were increased mainly due to the ATP increase. In myocardium total macroergic substances were decreased after the both treatments.
[Pyridine nucleotide content in the brain and myocardium of rats under combined effect of hypercapnia, hypoxia and cooling]. In experiments with rats, subjected to single and repeated simultaneous effect of hypercapnia, hypoxia and cooling, contents of pyridine nucleotides (NAD, NADP, NAD-H2 and NADP-H2) and macroergic substances were studied and also the activity of dehydrogenases of the pentose pathway was determined in brain and myocardium. In brain NADP was not practically determined and in heart its content was increased after the first and the second treatments. Content of NADP-H2 was distinctly decreased in both tissues after the single treatment. NAD was not altered in the tissues in all the periods studied. The amount of NAD-H2 was decreased in brain after the single treatment and it was increased in myocardium after the repeated one. In the activity of dehydrogenases marked alterations were not observed. Total macroergic substances were not altered in brain after the single treatment and after the repeated one they were increased mainly due to the ATP increase. In myocardium total macroergic substances were decreased after the both treatments.
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PMID:16391
[Adenyl cyclase and adenosine-3',5'-monophosphate phosphodiesteraze: their nature, properties and regulation].
Modern data on the nature, properties and pathways of regulation enzymes, participated metabolism of cyclic, adenosine-3',5'-monophosphate, are described. Much consideration is being given to the problem of regulation of the phosphodiesterase activity due to the effect of Ca2+-binding proteins.
[Adenyl cyclase and adenosine-3',5'-monophosphate phosphodiesteraze: their nature, properties and regulation]. Modern data on the nature, properties and pathways of regulation enzymes, participated metabolism of cyclic, adenosine-3',5'-monophosphate, are described. Much consideration is being given to the problem of regulation of the phosphodiesterase activity due to the effect of Ca2+-binding proteins.
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PMID:16392
[Chemiluminescence of the blood serum in the presence of divalent iron salts].
On incubation of diluted blood serum with ferrous ions kinetics of chemiluminescence, typical for lipid containing systems, was observed. It comprised several sequental steps: quick flash, inhibition of the chemiluminescence, slow flash with subsequent steady-state luminescence. At each step of the phenomenon a correlation was found between the intensity of chemiluminescence, the rate of accumulation of products of lipid peroxidation (malone dialdehyde) and concentration of Fe2+ in the mixture. The data obtained suggest that chemiluminescence of blood serum in presence of Fe2+ is due to lipid peroxidation in the serum. Kinetics of the reaction and shape of the chemiluminiscence curve depended upon a number of factors: dilution of blood serum, concentration of Fe2+ added, temperature, pH and (if blood plasma was used) type of an anticoagulant use. Only in blood lipoproteins, mainly in beta-lipoproteins, the distinctive pattern of peroxidation was developed with simultaneous accumulation of malone dialdehyde, oxidation of ferrous ions and ultralow chemiluminescence. In protein fraction of blood serum addition of Fe2+ caused only the quick splash of chemiluminescence without the malone dialdehyde production.
[Chemiluminescence of the blood serum in the presence of divalent iron salts]. On incubation of diluted blood serum with ferrous ions kinetics of chemiluminescence, typical for lipid containing systems, was observed. It comprised several sequental steps: quick flash, inhibition of the chemiluminescence, slow flash with subsequent steady-state luminescence. At each step of the phenomenon a correlation was found between the intensity of chemiluminescence, the rate of accumulation of products of lipid peroxidation (malone dialdehyde) and concentration of Fe2+ in the mixture. The data obtained suggest that chemiluminescence of blood serum in presence of Fe2+ is due to lipid peroxidation in the serum. Kinetics of the reaction and shape of the chemiluminiscence curve depended upon a number of factors: dilution of blood serum, concentration of Fe2+ added, temperature, pH and (if blood plasma was used) type of an anticoagulant use. Only in blood lipoproteins, mainly in beta-lipoproteins, the distinctive pattern of peroxidation was developed with simultaneous accumulation of malone dialdehyde, oxidation of ferrous ions and ultralow chemiluminescence. In protein fraction of blood serum addition of Fe2+ caused only the quick splash of chemiluminescence without the malone dialdehyde production.
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PMID:16393
[Androgen participation in realizing the action of hydrocortisone and insulin on tyrosine-alpha-ketoglutarate transaminase synthesis in rat liver mitochondria].
Castration of adult rats did not distinctly alter the tyrosine alpha-ketoglutarate transaminase activity in liver tissue mitochondria. Administration of hydrocortisone caused the more pronounced increased of the tyrosine alpha-ketoglutarate transaminae activity in liver tissue mitochondria of young males as compared with the adult intact rats. Castration of adult rats did no alter stimulating effect of the glucocorticoid. Insulin decreased the stimulating effect of hydrocortisone on the synthesis of the synthesis of the enzyme in liver tissue mitochondria of young and adult castrated males. Insulin decreased the effect of hydrocortisone in adult castrated rats, provided with excess of testosterone propionate and did not change the effect in adul intact animals.
[Androgen participation in realizing the action of hydrocortisone and insulin on tyrosine-alpha-ketoglutarate transaminase synthesis in rat liver mitochondria]. Castration of adult rats did not distinctly alter the tyrosine alpha-ketoglutarate transaminase activity in liver tissue mitochondria. Administration of hydrocortisone caused the more pronounced increased of the tyrosine alpha-ketoglutarate transaminae activity in liver tissue mitochondria of young males as compared with the adult intact rats. Castration of adult rats did no alter stimulating effect of the glucocorticoid. Insulin decreased the stimulating effect of hydrocortisone on the synthesis of the synthesis of the enzyme in liver tissue mitochondria of young and adult castrated males. Insulin decreased the effect of hydrocortisone in adult castrated rats, provided with excess of testosterone propionate and did not change the effect in adul intact animals.
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PMID:16394
[Purification and properties of the serotonin-stimulated adenylate deaminase from the mitochondrial fraction of rat liver].
A method is described for partial purification of structurally bound adenilate desaminase from rat liver tissue mitochondria; the enzyme was stimulated by parenteral administration of serotonine. The enzymatic preparations obtained desaminated AMP, 2',3'-AMP and adenosine, but they did not effect on ATP, 2',3'-cycloAMP or 3',5'-cycloAMP. The maximal rate of desaminating of these substances by AMP-desaminase, stimulated with serotonine, exceeded approximately 1.4-fold the same values, which were obtained for the enzymatic preparations from liver tissue mitochondria of rats, administered with physiological solution. Mitochondrial serotomine-stimulated adenilate desaminase was differentiated from the other soluble adenilate desaminases by some properties; the enzyme was likely to participate also in the regulation of nucleotides balance in the organism.
[Purification and properties of the serotonin-stimulated adenylate deaminase from the mitochondrial fraction of rat liver]. A method is described for partial purification of structurally bound adenilate desaminase from rat liver tissue mitochondria; the enzyme was stimulated by parenteral administration of serotonine. The enzymatic preparations obtained desaminated AMP, 2',3'-AMP and adenosine, but they did not effect on ATP, 2',3'-cycloAMP or 3',5'-cycloAMP. The maximal rate of desaminating of these substances by AMP-desaminase, stimulated with serotonine, exceeded approximately 1.4-fold the same values, which were obtained for the enzymatic preparations from liver tissue mitochondria of rats, administered with physiological solution. Mitochondrial serotomine-stimulated adenilate desaminase was differentiated from the other soluble adenilate desaminases by some properties; the enzyme was likely to participate also in the regulation of nucleotides balance in the organism.
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PMID:16395
[Methylmalonic acid excretion in experimental B2-avitaminosis in rats].
Providing of rats with a diet, deficient in vitamin B2 within 2 and 5 weeks, was not shown to be accompanied by an increase in excretion of methylmalonic acid. In the animals some tendency to the increased excretion of methylmalonic acid was observed within 8 weeks of the diet. The data obtained suggest that the test for excretion of methylmalonic acid was the highly specific as a pattern of supply with vitamin B12. The possible role of vitamin B2 and flavoproteins in biosynthesis of coenzyme forms of vitamin B12 is discussed.
[Methylmalonic acid excretion in experimental B2-avitaminosis in rats]. Providing of rats with a diet, deficient in vitamin B2 within 2 and 5 weeks, was not shown to be accompanied by an increase in excretion of methylmalonic acid. In the animals some tendency to the increased excretion of methylmalonic acid was observed within 8 weeks of the diet. The data obtained suggest that the test for excretion of methylmalonic acid was the highly specific as a pattern of supply with vitamin B12. The possible role of vitamin B2 and flavoproteins in biosynthesis of coenzyme forms of vitamin B12 is discussed.
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PMID:16397
[Isoelectric focusing in a boroborate buffer-mannitol system (BBM)].
The data of the following study of isoelectric focusing in the system 'buffer--nonelectrolyte' are described. The method was shown to be employed for study of proteins, when human serum albumin was used as a model. A standard method and an apparatus device are proposed for the analytical isoelectric focusing of proteins both in the wide (pH 4.00-8.50) and in the limit (PH 4.50-6.00) PH regions. Advantages and limitations of the method are discussed as compared with the method of isoelectric focusing in ampholines.
[Isoelectric focusing in a boroborate buffer-mannitol system (BBM)]. The data of the following study of isoelectric focusing in the system 'buffer--nonelectrolyte' are described. The method was shown to be employed for study of proteins, when human serum albumin was used as a model. A standard method and an apparatus device are proposed for the analytical isoelectric focusing of proteins both in the wide (pH 4.00-8.50) and in the limit (PH 4.50-6.00) PH regions. Advantages and limitations of the method are discussed as compared with the method of isoelectric focusing in ampholines.
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PMID:16402
[Acid-base and water-electrolyte status in animals with experimental tumors].
It is noted that rats with Heren carcinoma show alkalization of blood, decreased pH levels of the urine, hypokalemia, hypocalcemia, hypomagnesiemia, sodium and water retention, increased kalium level in the liver. Analogous changes are observed in rabbits with Brown-Pearce carcinoma. The organism of tumor-bearing rats responds to stress effects otherwise than the organism of normal animals.
[Acid-base and water-electrolyte status in animals with experimental tumors]. It is noted that rats with Heren carcinoma show alkalization of blood, decreased pH levels of the urine, hypokalemia, hypocalcemia, hypomagnesiemia, sodium and water retention, increased kalium level in the liver. Analogous changes are observed in rabbits with Brown-Pearce carcinoma. The organism of tumor-bearing rats responds to stress effects otherwise than the organism of normal animals.
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PMID:16398
[Kinetic properties of partially purified glucosephosphate dehydrogenase of human erythrocytes].
Partially purified glucose-6-phosphate dehydrogenase was isolated from small amounts of human erythrocytes (15-20 ml). The Km value for glucose-6-phosphate was 35.0 +/- 3.0 micronM, the Km for NADP was 4.27 +/- 0.3 micronM. The optimal activity of the enzyme was at pH 9.0. Glucose-6-phosphate dehydrogenase, dialyzed in presence of 1-10(-5) M NADP, had critical temperature about 52 degrees within 10 min of incubation; without NADP it was at 45 degrees. The method for isolation and purification of the enzyme was modified.
[Kinetic properties of partially purified glucosephosphate dehydrogenase of human erythrocytes]. Partially purified glucose-6-phosphate dehydrogenase was isolated from small amounts of human erythrocytes (15-20 ml). The Km value for glucose-6-phosphate was 35.0 +/- 3.0 micronM, the Km for NADP was 4.27 +/- 0.3 micronM. The optimal activity of the enzyme was at pH 9.0. Glucose-6-phosphate dehydrogenase, dialyzed in presence of 1-10(-5) M NADP, had critical temperature about 52 degrees within 10 min of incubation; without NADP it was at 45 degrees. The method for isolation and purification of the enzyme was modified.
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PMID:16396
[Method for the direct spectrophotometric determination of the rate of the tyrosine hydroxylase reaction].
A rate of the tyrosine hydroxylase reaction was estimated by an increase in absorption at 335 nm, which was caused by oxidation of pterin cofactor 6,7-dimethyl-5, 6, 7, 8-tetrahydroxypterin (DMPH) coupled with the convertion of the substrate 1-tyrosine into dihydroxyphenylalanine. At pH 6.2 the ratios of molar extinction were as follows: in trisacetate ADMPH4-1370, ADMPH2-5350; in tris-malate tadmph4-1250, admph25300. the enzyme, associated with membranes, had the Km value for Tyr-0.045 mM, the Km for DMPH4 was 0.18 mM; the soluble enzyme had Km for Tyr-0,050 mM, the Km for DMPH4 was 0.74 mM. The stoichiometry of the reaction was 1:1 (I mole DOPA per I mole of DMPH2 formed).
[Method for the direct spectrophotometric determination of the rate of the tyrosine hydroxylase reaction]. A rate of the tyrosine hydroxylase reaction was estimated by an increase in absorption at 335 nm, which was caused by oxidation of pterin cofactor 6,7-dimethyl-5, 6, 7, 8-tetrahydroxypterin (DMPH) coupled with the convertion of the substrate 1-tyrosine into dihydroxyphenylalanine. At pH 6.2 the ratios of molar extinction were as follows: in trisacetate ADMPH4-1370, ADMPH2-5350; in tris-malate tadmph4-1250, admph25300. the enzyme, associated with membranes, had the Km value for Tyr-0.045 mM, the Km for DMPH4 was 0.18 mM; the soluble enzyme had Km for Tyr-0,050 mM, the Km for DMPH4 was 0.74 mM. The stoichiometry of the reaction was 1:1 (I mole DOPA per I mole of DMPH2 formed).
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PMID:16405
[Neurohumoral influences of steroid hormones on sexual responsiveness in women (author's transl)].
An analysis has been carried out on the basis of endocrinological and psychosomatic studies of the influence of steroid hormones, acting via probable transmitter substances, on the sexual response in women. From a review in the literature it can be concluded that among other factors the endocrine state of the women determines her sexual response and behaviour. However, the present lack of specific psychological tests is pointed out, as well as the absence of relevant hormonal data to the sexual sphere, both normal and pathological.
[Neurohumoral influences of steroid hormones on sexual responsiveness in women (author's transl)]. An analysis has been carried out on the basis of endocrinological and psychosomatic studies of the influence of steroid hormones, acting via probable transmitter substances, on the sexual response in women. From a review in the literature it can be concluded that among other factors the endocrine state of the women determines her sexual response and behaviour. However, the present lack of specific psychological tests is pointed out, as well as the absence of relevant hormonal data to the sexual sphere, both normal and pathological.
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PMID:16406
[The influence of socio-economic factors on the results of a prematury-Dysmaturity prevention programme (author's transl)].
All high-risk gravidae with regard to prematurity and dysmaturity (PDP programme) were collected over a time-limited period. More than two thirds (n = 72) of these women were submitted to intensive care (PDP group); one third (n = 33) (control group) refused intensive care. Furthermore, socio-economic factors were taken into consideration in this study and appropriate classification into 4 groups was undertaken. Gravidae of a higher social class were more often willing to undergo intensive care than gravidae of a lower class. In the PDP group 75% of the gravidae were delivered after the end of the 36th gestational week and 51% of the gravidae in the control group. A similar relationship was found in regard to the birth weight of the newborn infants: in the PDP group 74.4% of the babies weighed over 2500 g at birth in contrast to the respective figure of 42.9% in the control group. However, this socio-economic study shows that the results of intensive care are much more successful in women from a lower social stata than in women from a higher social class.
[The influence of socio-economic factors on the results of a prematury-Dysmaturity prevention programme (author's transl)]. All high-risk gravidae with regard to prematurity and dysmaturity (PDP programme) were collected over a time-limited period. More than two thirds (n = 72) of these women were submitted to intensive care (PDP group); one third (n = 33) (control group) refused intensive care. Furthermore, socio-economic factors were taken into consideration in this study and appropriate classification into 4 groups was undertaken. Gravidae of a higher social class were more often willing to undergo intensive care than gravidae of a lower class. In the PDP group 75% of the gravidae were delivered after the end of the 36th gestational week and 51% of the gravidae in the control group. A similar relationship was found in regard to the birth weight of the newborn infants: in the PDP group 74.4% of the babies weighed over 2500 g at birth in contrast to the respective figure of 42.9% in the control group. However, this socio-economic study shows that the results of intensive care are much more successful in women from a lower social stata than in women from a higher social class.
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PMID:16399
[Role of lipid peroxides in the pathogenesis of arteriosclerosis. Detoxication of lipid peroxides by the glutathione-peroxidase system in the aorta].
In aorta of intact rabbits the high activity of glutathione-peroxidase, which detoxicates lipoperoxides, was observed. In aorta of animals with pronounced experimental atheromatosis the enzyme activity did not distinctly differ from the control values. The animals with high initial content of glutathione-peroxidase in aorta were shown to be less subjected to the impairment in alimentary atherosclerosis.
[Role of lipid peroxides in the pathogenesis of arteriosclerosis. Detoxication of lipid peroxides by the glutathione-peroxidase system in the aorta]. In aorta of intact rabbits the high activity of glutathione-peroxidase, which detoxicates lipoperoxides, was observed. In aorta of animals with pronounced experimental atheromatosis the enzyme activity did not distinctly differ from the control values. The animals with high initial content of glutathione-peroxidase in aorta were shown to be less subjected to the impairment in alimentary atherosclerosis.
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PMID:16407
[New aspects in diagnosis and therapy of placental insufficiency. Placental perfusion measurements; placental perfusion test (PPT) and betamimetic long term treatment (clinical and experimental data (authors transl)].
The rate of utero-placental blood flow depends on functional components (perfusion pressure and flow resistance within the area of the vascular bed of the placenta), as well as on morphological factors (regressive changes in the placenta). Different primary maternal conditions and diseases may lower the rate of placental flow, leading to placental insufficiency; the highest percentage, by far, of placental dysfunction is found in patients suffering from gestosis. Hypocirculation initially present in cases of EPH gestosis and caused by arteriolar spasms triggers off a vicious circle involving placental infarction and severe reduction in the utero-placental perfusion rate. This in turn leads to fetal hypotrophy, a high rate of premature births and perinatal mortality. Verification of HPL, HCG, alpha-Fetoprotein or E3 in maternal serum and amniotic fluid or urine greatly improved the recording of partial placental functions. Along with ultrasonic biometry, cardiotocography and amnioscopy, these hormonal parameters allow only indirect assessment of the placental function. On the other hand, measurements of the utero-placental flow offers a direct approach. In order to evaluate the placental flow measurements it is imperative to obtain a curve indicating the course over the last third of the pregnancy-in addition to establishing a general normal range. In case of placental insufficiency, it is necessary to determine whether this is due to functional disorders alone, or to more extenisve morphological changes. A placental perfusion test (PPT) was developed in order to make this distinction. Beta2-mimetic treatment is indicated if functional factors predominate, whereby it appears essential to obtain the requisite experimental data for precise quantification of beta-mimetic action.
[New aspects in diagnosis and therapy of placental insufficiency. Placental perfusion measurements; placental perfusion test (PPT) and betamimetic long term treatment (clinical and experimental data (authors transl)]. The rate of utero-placental blood flow depends on functional components (perfusion pressure and flow resistance within the area of the vascular bed of the placenta), as well as on morphological factors (regressive changes in the placenta). Different primary maternal conditions and diseases may lower the rate of placental flow, leading to placental insufficiency; the highest percentage, by far, of placental dysfunction is found in patients suffering from gestosis. Hypocirculation initially present in cases of EPH gestosis and caused by arteriolar spasms triggers off a vicious circle involving placental infarction and severe reduction in the utero-placental perfusion rate. This in turn leads to fetal hypotrophy, a high rate of premature births and perinatal mortality. Verification of HPL, HCG, alpha-Fetoprotein or E3 in maternal serum and amniotic fluid or urine greatly improved the recording of partial placental functions. Along with ultrasonic biometry, cardiotocography and amnioscopy, these hormonal parameters allow only indirect assessment of the placental function. On the other hand, measurements of the utero-placental flow offers a direct approach. In order to evaluate the placental flow measurements it is imperative to obtain a curve indicating the course over the last third of the pregnancy-in addition to establishing a general normal range. In case of placental insufficiency, it is necessary to determine whether this is due to functional disorders alone, or to more extenisve morphological changes. A placental perfusion test (PPT) was developed in order to make this distinction. Beta2-mimetic treatment is indicated if functional factors predominate, whereby it appears essential to obtain the requisite experimental data for precise quantification of beta-mimetic action.
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PMID:16409
[Physiology and biochemistry of streptomycetes. VIII. Esterase activity and production of turimycin in cultures of Streptomyces hygroscopicus JA 6599].
Esterase in cell-free extracts of Streptomyces hygroscopicus JA 6599 has a temperature-optimum of 35 degrees C, a pH-optimum with p-nitrophenylacetate as substrate at pH 7.7--8.1, with alpha-naphthylacetate at pH 7--9. Michaelis constants in cell-free extracts: with alpha-naphthylacetate Km = = 0.71 mM, with p-nitrophenylacetate Km = 0.21 mM. Phenylesters were better hydrolyzed than naphthylesters, phenylacetate was best hydrolyzed; beta-naphthylacetate was better hydrolyzed than alpha-naphthylacetate. Among the naphthylesters the ester of propionic acid was hydrolyzed best. Caprylate, stearate, and 0,0-diethyl-0-(p-nitrophenyl)-phosphate inhibit the splitting of alpha-naphthylacetate. A comparison with esterases of other biological origin shows that the enzyme studied can be a carboxylesterase (E.C.3.1.1.1.). In cultures of JA 6599 V13 and JA 6599-6 the change of esterase activity during the fermentation was determined. We found a carrelation between the enzymatic activity and the antibiotic-concentration in the culture medium.
[Physiology and biochemistry of streptomycetes. VIII. Esterase activity and production of turimycin in cultures of Streptomyces hygroscopicus JA 6599]. Esterase in cell-free extracts of Streptomyces hygroscopicus JA 6599 has a temperature-optimum of 35 degrees C, a pH-optimum with p-nitrophenylacetate as substrate at pH 7.7--8.1, with alpha-naphthylacetate at pH 7--9. Michaelis constants in cell-free extracts: with alpha-naphthylacetate Km = = 0.71 mM, with p-nitrophenylacetate Km = 0.21 mM. Phenylesters were better hydrolyzed than naphthylesters, phenylacetate was best hydrolyzed; beta-naphthylacetate was better hydrolyzed than alpha-naphthylacetate. Among the naphthylesters the ester of propionic acid was hydrolyzed best. Caprylate, stearate, and 0,0-diethyl-0-(p-nitrophenyl)-phosphate inhibit the splitting of alpha-naphthylacetate. A comparison with esterases of other biological origin shows that the enzyme studied can be a carboxylesterase (E.C.3.1.1.1.). In cultures of JA 6599 V13 and JA 6599-6 the change of esterase activity during the fermentation was determined. We found a carrelation between the enzymatic activity and the antibiotic-concentration in the culture medium.
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PMID:16400
[Effect of psychotropic preparations on the activity of Ca- and Mg-dependent ATPase of the sarcoplasmic reticulum].
In sarcoplasmic reticulum of rabbit skeletal muscles the activity of Ca2+, Mg2+- dependent ATPase was distinctly inhibited under effect of neuroleptic drugs - derivatives of phenothiazine and butyrophenone. The effect of tricyclic antidepressants was less pronounced. Tranquilizers (derivatives of 1,4-benzodiazepine) inhibited the enzyme, but trioxazin was only slightly active. High concentrations of lithium salts and of psychostimulants caffeine and corasole were found to stimulate the Ca2+, Mg2+-ATPase activity; low concentrations of the substances slightly inhibited the enzyme. The blocking effect of psychotropic drugs was more distinct, if the enzyme preparations were previously treated with ATP.
[Effect of psychotropic preparations on the activity of Ca- and Mg-dependent ATPase of the sarcoplasmic reticulum]. In sarcoplasmic reticulum of rabbit skeletal muscles the activity of Ca2+, Mg2+- dependent ATPase was distinctly inhibited under effect of neuroleptic drugs - derivatives of phenothiazine and butyrophenone. The effect of tricyclic antidepressants was less pronounced. Tranquilizers (derivatives of 1,4-benzodiazepine) inhibited the enzyme, but trioxazin was only slightly active. High concentrations of lithium salts and of psychostimulants caffeine and corasole were found to stimulate the Ca2+, Mg2+-ATPase activity; low concentrations of the substances slightly inhibited the enzyme. The blocking effect of psychotropic drugs was more distinct, if the enzyme preparations were previously treated with ATP.
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PMID:16401
[Use of potentiometric titration at constant pH for determination of the activity of lipoprotein lipase].
A method is developed for determination of the lipoprotein lipase activity. The method is based on the steady state potentiometric titration at constant pH value of higher fatty acids, liberated during the hydrolysis. An oil emulsion intralipid, activated by human blood serum, was used as a substrate. The sensitivity of the method was equal to 0.004-0.010 micronM of fatty acids per min. The reproducibility of the results was 2-5%. This simple and rapid method enabled to study kinetic of reactions, catalyzed by lipoprotein lipases.
[Use of potentiometric titration at constant pH for determination of the activity of lipoprotein lipase]. A method is developed for determination of the lipoprotein lipase activity. The method is based on the steady state potentiometric titration at constant pH value of higher fatty acids, liberated during the hydrolysis. An oil emulsion intralipid, activated by human blood serum, was used as a substrate. The sensitivity of the method was equal to 0.004-0.010 micronM of fatty acids per min. The reproducibility of the results was 2-5%. This simple and rapid method enabled to study kinetic of reactions, catalyzed by lipoprotein lipases.
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PMID:16410
NAD(P)H utilization in the reduction of pyruvate to lactate in a glycogen-containing subline of Ehrlich ascites tumour cells.
The possible pathways of utilization of glucose-6-phosphate (G-6-P) produced from glycogen breakdown have been investigated in a glycogen-containing subline of Ehrlich ascites tumour cells. Addition of either mitochondrial inhibitors or pyruvate to ascites cells metabolizing endogenous substrates enhances the rate of lactate production. However, only in the former condition such effect is abolished by iodoacetate (IAA). In pyruvate-supplemented cells mitochondrial inhibitors cause a further increase in lactate production which becomes insensitive to IAA when the cells are depleted of endogenous substrates. Measurements of the glycogen content show that either in the presence of mitochondrial inhibitors or pyruvate there is a stimulation of glycogenolysis. Significant changes (about 10--20 fold increase) of the G-6-P level are observed only in the presence of both mitochondrial inhibitors and IAA, irrespective of pyruvate addition. However, with pyruvate the accumulation of G-6-P becomes lower if the cells are starved. The results obtained indicate that in our conditions G-6-P which is produced during glycogenolysis may be oxidized either through the Embden-Meyerhof pathway or the phosphogluconate pathway. Indeed, whereas mitochondrial inhibitors promote the utilization of this metabolite through the first route by enhancing the activity of phosphofructokinase, added pyruvate favours the other route by lowering the cytosolic NADPH/NADP+ ratio.
NAD(P)H utilization in the reduction of pyruvate to lactate in a glycogen-containing subline of Ehrlich ascites tumour cells. The possible pathways of utilization of glucose-6-phosphate (G-6-P) produced from glycogen breakdown have been investigated in a glycogen-containing subline of Ehrlich ascites tumour cells. Addition of either mitochondrial inhibitors or pyruvate to ascites cells metabolizing endogenous substrates enhances the rate of lactate production. However, only in the former condition such effect is abolished by iodoacetate (IAA). In pyruvate-supplemented cells mitochondrial inhibitors cause a further increase in lactate production which becomes insensitive to IAA when the cells are depleted of endogenous substrates. Measurements of the glycogen content show that either in the presence of mitochondrial inhibitors or pyruvate there is a stimulation of glycogenolysis. Significant changes (about 10--20 fold increase) of the G-6-P level are observed only in the presence of both mitochondrial inhibitors and IAA, irrespective of pyruvate addition. However, with pyruvate the accumulation of G-6-P becomes lower if the cells are starved. The results obtained indicate that in our conditions G-6-P which is produced during glycogenolysis may be oxidized either through the Embden-Meyerhof pathway or the phosphogluconate pathway. Indeed, whereas mitochondrial inhibitors promote the utilization of this metabolite through the first route by enhancing the activity of phosphofructokinase, added pyruvate favours the other route by lowering the cytosolic NADPH/NADP+ ratio.
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PMID:16411
The effect of iron, tin, aluminium, and chromium on fading, discoloration, and precipitation in berry and red beet juices.
The effect of iron(II), tin(II), aluminium(III), and chromium(III) on the properties of red whortleberry, blackcurrant, and red beet juices was followed during storage for 10 months at 5 degrees C. The colour and pH changes were studied, and the precipitates formed were weighed and their metal contents assayed. Of the metals tested, only tin caused bluish discoloration in the berry juices. In the case of iron, aluminium, and chromium the low pH prevented this type of discoloration. In berry juices, some increases in colour intensity took place with the lowering of pH value, whereas in red beet juice the opposite change occurred. The colour changes due to storage appear to take place irrespective of the metals. Precipitation is enhanced in red whortleberry juice only by tin, and in blackcurrant juice by tin and iron. In red beet juice, precipitation is increased by the lowering of pH resulting from metal salt addition. In general, increase in the amount of metal added increased the metal content of the precipitate. Iron showed the greatest tendency to become bound in the precipitate, particularly in blackcurrant and red beet juice. The suitabilities of the metals for canning purposes are considered. Chromium, in particular, has interesting possibilities in view of the low degree of colour change associated with it.
The effect of iron, tin, aluminium, and chromium on fading, discoloration, and precipitation in berry and red beet juices. The effect of iron(II), tin(II), aluminium(III), and chromium(III) on the properties of red whortleberry, blackcurrant, and red beet juices was followed during storage for 10 months at 5 degrees C. The colour and pH changes were studied, and the precipitates formed were weighed and their metal contents assayed. Of the metals tested, only tin caused bluish discoloration in the berry juices. In the case of iron, aluminium, and chromium the low pH prevented this type of discoloration. In berry juices, some increases in colour intensity took place with the lowering of pH value, whereas in red beet juice the opposite change occurred. The colour changes due to storage appear to take place irrespective of the metals. Precipitation is enhanced in red whortleberry juice only by tin, and in blackcurrant juice by tin and iron. In red beet juice, precipitation is increased by the lowering of pH resulting from metal salt addition. In general, increase in the amount of metal added increased the metal content of the precipitate. Iron showed the greatest tendency to become bound in the precipitate, particularly in blackcurrant and red beet juice. The suitabilities of the metals for canning purposes are considered. Chromium, in particular, has interesting possibilities in view of the low degree of colour change associated with it.
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PMID:16412
[On the enzymatic breakdown of tripolyphosphate and diphosphate in minced meat. V. Change in the diphosphatase activity of muscle post mortem (author's transl)].
The diphosphatase (DPase) activity of minced bovine muscle decreased during storage of the intact muscle post mortem (p.m.) but there was only little change after development of rigor mortis. The drop in pH p.m. seems to be not the only reason for the decrease in DPase activity. In the postrigor muscle the DPase activity, measured at pH greater than 6, increased during the breakdown of DP. The rise of activity was the slower the longer the muscle was stored. The result of a mathematical regression analysis, developed for the kinetic study of this anomaly in the breakdown of DP, indicates that a certain mechanism of activation of the initially inactive DPase in muscle exists.
[On the enzymatic breakdown of tripolyphosphate and diphosphate in minced meat. V. Change in the diphosphatase activity of muscle post mortem (author's transl)]. The diphosphatase (DPase) activity of minced bovine muscle decreased during storage of the intact muscle post mortem (p.m.) but there was only little change after development of rigor mortis. The drop in pH p.m. seems to be not the only reason for the decrease in DPase activity. In the postrigor muscle the DPase activity, measured at pH greater than 6, increased during the breakdown of DP. The rise of activity was the slower the longer the muscle was stored. The result of a mathematical regression analysis, developed for the kinetic study of this anomaly in the breakdown of DP, indicates that a certain mechanism of activation of the initially inactive DPase in muscle exists.
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PMID:16413
[On the enzymatic breakdown of tripolyphosphate and diphosphate in minced meat. VI. Influence of pH on the tripolyphosphatase and diphosphatase activities in bovine muscle (author's transl)].
The pH optimum of the tripolyphosphatase activity of minced bovine muscle post rigor was 5.6. The pH optimum of the diphosphatase activity was in the range between pH 6.7 and 6.8. The prolonged influence of pH values around 7 caused an additional increase in the diphosphatase activity.
[On the enzymatic breakdown of tripolyphosphate and diphosphate in minced meat. VI. Influence of pH on the tripolyphosphatase and diphosphatase activities in bovine muscle (author's transl)]. The pH optimum of the tripolyphosphatase activity of minced bovine muscle post rigor was 5.6. The pH optimum of the diphosphatase activity was in the range between pH 6.7 and 6.8. The prolonged influence of pH values around 7 caused an additional increase in the diphosphatase activity.
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PMID:16416
[Gluconic acid forming enzymes in Aspergillus niger (author's transl)].
At least three gluconic acid forming enzymes were identified in cell-free extracts of Aspergillus niger: glucose oxidase (EC 1.1.3.4), a glucose dehydrogenase (EC 1.1.99.10), and an enzyme or a mixture of enzymes catalyzing the cleavage of 6-phosphogluconate into gluconate and inorganic phosphate. 2,6-dichlorphenolindophenol was one of the hydrogen acceptors in vitro of the glucose dehydrogenase. Some properties of this enzyme (Km values, pH-dependence, substrate and hydrogen acceptor specificity), as determined in cell-free extracts, were found to be in good agreement with properties described in literature for a glucose dehydrogenase which has been purified from Aspergillus oryzae. The formation of Pi from 6-phosphogluconate and other phosphate esters was found to have an optimum between pH 7 and 8 , and another below pH 4. This suggests that it is catalyzed by an alkaline and an acid phosphomonoesterase (EC 3.1.3.1, 3.1.3.2), both enzymes exhibiting only low substrate specificity. The influence of extraction and assay buffers on the activity of gluconate forming enzymes was investigated. Loss of activity during preparation of cell-free extracts, as calculated from loss of activity storage of cell-free extracts at 4 degrees C, was found to be lower than 4%. Purified glucose oxidase added before homogenization was found in the extract almost quantitatively.
[Gluconic acid forming enzymes in Aspergillus niger (author's transl)]. At least three gluconic acid forming enzymes were identified in cell-free extracts of Aspergillus niger: glucose oxidase (EC 1.1.3.4), a glucose dehydrogenase (EC 1.1.99.10), and an enzyme or a mixture of enzymes catalyzing the cleavage of 6-phosphogluconate into gluconate and inorganic phosphate. 2,6-dichlorphenolindophenol was one of the hydrogen acceptors in vitro of the glucose dehydrogenase. Some properties of this enzyme (Km values, pH-dependence, substrate and hydrogen acceptor specificity), as determined in cell-free extracts, were found to be in good agreement with properties described in literature for a glucose dehydrogenase which has been purified from Aspergillus oryzae. The formation of Pi from 6-phosphogluconate and other phosphate esters was found to have an optimum between pH 7 and 8 , and another below pH 4. This suggests that it is catalyzed by an alkaline and an acid phosphomonoesterase (EC 3.1.3.1, 3.1.3.2), both enzymes exhibiting only low substrate specificity. The influence of extraction and assay buffers on the activity of gluconate forming enzymes was investigated. Loss of activity during preparation of cell-free extracts, as calculated from loss of activity storage of cell-free extracts at 4 degrees C, was found to be lower than 4%. Purified glucose oxidase added before homogenization was found in the extract almost quantitatively.
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PMID:16418
The fermentative production of acetone-butanol by Clostridium acetobutylicum.
Fourteen different media were used in the fermentative production of acetone-butanol. The highest total yields were achieved in medium I. Potato starch and soluble starch were suitable as carbon sources. The best concentrations of potato starch and soluble starch were 500.0 and 10.0 g/l, respectively. Peptone was the most favourable nitrogen source. The best concentration of peptone was 4.0 g/l. Calcium carbonate in 3.6 g/l acted as buffering agent in the fermentation process. The best initial pH value of the fermentation medium was 6.0. The optimum temperature was 32--33degreesC. The fermentation process required 120 h to obtain maximum yields of acetone-butanol.
The fermentative production of acetone-butanol by Clostridium acetobutylicum. Fourteen different media were used in the fermentative production of acetone-butanol. The highest total yields were achieved in medium I. Potato starch and soluble starch were suitable as carbon sources. The best concentrations of potato starch and soluble starch were 500.0 and 10.0 g/l, respectively. Peptone was the most favourable nitrogen source. The best concentration of peptone was 4.0 g/l. Calcium carbonate in 3.6 g/l acted as buffering agent in the fermentation process. The best initial pH value of the fermentation medium was 6.0. The optimum temperature was 32--33degreesC. The fermentation process required 120 h to obtain maximum yields of acetone-butanol.
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PMID:16419
Histomorphology and proteolytic activity in the gastric apparatus of frugivorous, carnivorous and omnivorous species of birds.
The histomorphology of the gastric apparatus, the pepsin level and the optimum pH for pepsin were investigated in Psittacula krameri (frugivore), Lanius schach (carnivore) and Acridotheres tristis (omnivore) species of birds. The proventricular glands were found to be made up of oxynticopeptic cells. The lobules of the oxynticopeptic cells are polyhedral; they are the largest in P. krameri, and the smallest in A. tristis. However, their greater number in A. tristis enables a higher secretion of hydrochloric acid and pepsin. The villi are more developed in A. tristis than in L. schach and P. krameri. The gizzard is larger in A. tristis than in P. krameri and A. tritis than in the carnivore L. schach. Koilin lining is beset with horny cones, which were well developed in A. tristis, moderately developed in P. krameri and absent in L. schach. The pepsin activity is higher in the proventriculus of the carnivorous L. schach and the omnivorous A. tristis than in the frugivorous P. krameri. Slight pepsin activity was also observed in gizzard tissue extracts in all the three species. The optimum pH for pepsin was found to be 1.5 for P. krameri and 1.8 for both L. schach and A. tristis.
Histomorphology and proteolytic activity in the gastric apparatus of frugivorous, carnivorous and omnivorous species of birds. The histomorphology of the gastric apparatus, the pepsin level and the optimum pH for pepsin were investigated in Psittacula krameri (frugivore), Lanius schach (carnivore) and Acridotheres tristis (omnivore) species of birds. The proventricular glands were found to be made up of oxynticopeptic cells. The lobules of the oxynticopeptic cells are polyhedral; they are the largest in P. krameri, and the smallest in A. tristis. However, their greater number in A. tristis enables a higher secretion of hydrochloric acid and pepsin. The villi are more developed in A. tristis than in L. schach and P. krameri. The gizzard is larger in A. tristis than in P. krameri and A. tritis than in the carnivore L. schach. Koilin lining is beset with horny cones, which were well developed in A. tristis, moderately developed in P. krameri and absent in L. schach. The pepsin activity is higher in the proventriculus of the carnivorous L. schach and the omnivorous A. tristis than in the frugivorous P. krameri. Slight pepsin activity was also observed in gizzard tissue extracts in all the three species. The optimum pH for pepsin was found to be 1.5 for P. krameri and 1.8 for both L. schach and A. tristis.
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PMID:16420
Phospholipase C from Bacillus cereus. Action on some artificial lecithins.
The hydrolysis by phospholipase C from B. cereus of several lecithins of different fatty acyl chain length was examined. The enzyme showed significant activity towards mono-molecularly dispersed short chain lecithins and the reaction obeyed normal Michaelis-Menten kinetics. Rate vs. substrate concentration curves obtained with dihexanoyl-, diheptanoyl- and dioctanoyllecithins showed marked discontinuities in the region of the known critical micelle concentrations for these substrates and distinctly higher rates were obtained just above these levels. Using these three lecithins at levels below their respective critical micelle concentrations, rate increases were noted if the reactions were allowed to proceed to a sufficiently great extent. The presence of deoxycholate in the reaction system had little or no effect on the rate of enzyme-catalysed hydrolysis of lecithins of fatty acyl chain length less than or equal to Cbeta, but for fatty acyl chain lengths greater than C10, significant rate increases occurred. The pH profile for the enzyme activity was also examined.
Phospholipase C from Bacillus cereus. Action on some artificial lecithins. The hydrolysis by phospholipase C from B. cereus of several lecithins of different fatty acyl chain length was examined. The enzyme showed significant activity towards mono-molecularly dispersed short chain lecithins and the reaction obeyed normal Michaelis-Menten kinetics. Rate vs. substrate concentration curves obtained with dihexanoyl-, diheptanoyl- and dioctanoyllecithins showed marked discontinuities in the region of the known critical micelle concentrations for these substrates and distinctly higher rates were obtained just above these levels. Using these three lecithins at levels below their respective critical micelle concentrations, rate increases were noted if the reactions were allowed to proceed to a sufficiently great extent. The presence of deoxycholate in the reaction system had little or no effect on the rate of enzyme-catalysed hydrolysis of lecithins of fatty acyl chain length less than or equal to Cbeta, but for fatty acyl chain lengths greater than C10, significant rate increases occurred. The pH profile for the enzyme activity was also examined.
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PMID:16423
Inactivation of somatostatin by peptidases in different areas of the rat brain.
With the availability of a sensitive and specific radioimmunoassay for growth hormone-release-inhibiting hormone (somatostatin or GH-RIH), it has been possible to investigate the presence of peptidase enzymes capable of inactivating this hypothalamic hormone in the hypothalamus and other brain areas of the rat. It was found that both supernatant and particulate fractions from male rat hypothalami rapidly inactivated somatostatin and that the enzymes involved have an optimum pH of 7.3. Peptidase activity was significantly higher in the supernatant than in the particulate fraction from the hypothalamus, thalamus, cortex and cerebellum. Besides confirming the presence of peptidases inactivating the release-inhibiting hormone in the hypothalamus (the site of somatostatin synthesis and release), the results may indicate that somatostatin has a functional significance outside the hypothalamus-anterior pituitary axis but within the central nervous system.
Inactivation of somatostatin by peptidases in different areas of the rat brain. With the availability of a sensitive and specific radioimmunoassay for growth hormone-release-inhibiting hormone (somatostatin or GH-RIH), it has been possible to investigate the presence of peptidase enzymes capable of inactivating this hypothalamic hormone in the hypothalamus and other brain areas of the rat. It was found that both supernatant and particulate fractions from male rat hypothalami rapidly inactivated somatostatin and that the enzymes involved have an optimum pH of 7.3. Peptidase activity was significantly higher in the supernatant than in the particulate fraction from the hypothalamus, thalamus, cortex and cerebellum. Besides confirming the presence of peptidases inactivating the release-inhibiting hormone in the hypothalamus (the site of somatostatin synthesis and release), the results may indicate that somatostatin has a functional significance outside the hypothalamus-anterior pituitary axis but within the central nervous system.
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PMID:16424
Corticotrophic and melanotrophic functions in congenital adrenal hyperplasia.
In 15 patients with congenital adrenal hyperplasia, the corticotrophic and melanotrophic functions were evaluated by plasma ACTH and beta-MSH radioimmunoassay. Evaluation of the corticotrophic and melanotrophic functions was also performed in 3 subjects after provocative tests (insulin-induced hypoglycaemia, metyrapone) and in 5 subjects after infusion of synthetic MIF (MSH-release inhibiting factor). The results indicate a significant increase in plasma ACTH and beta-MSH in CAH. In addition, we found that although in most cases there was a significant positive correlation between the plasma ACTH and beta-MSH levels, in some only the plasma ACTH values were high and beta-MSH values normal. No other anomalies of the corticotrophic and melanotrophic functions occurred in CAH as shown by the results of the provcative tests. Lastly, it must be emphasized that no modifications of plasma beta-MSH after synthetic MIF infusion were found in subject with normal or high plasma beta-MSH. These findings induce us to consider it unlikely that synthetic MIF is active in man.
Corticotrophic and melanotrophic functions in congenital adrenal hyperplasia. In 15 patients with congenital adrenal hyperplasia, the corticotrophic and melanotrophic functions were evaluated by plasma ACTH and beta-MSH radioimmunoassay. Evaluation of the corticotrophic and melanotrophic functions was also performed in 3 subjects after provocative tests (insulin-induced hypoglycaemia, metyrapone) and in 5 subjects after infusion of synthetic MIF (MSH-release inhibiting factor). The results indicate a significant increase in plasma ACTH and beta-MSH in CAH. In addition, we found that although in most cases there was a significant positive correlation between the plasma ACTH and beta-MSH levels, in some only the plasma ACTH values were high and beta-MSH values normal. No other anomalies of the corticotrophic and melanotrophic functions occurred in CAH as shown by the results of the provcative tests. Lastly, it must be emphasized that no modifications of plasma beta-MSH after synthetic MIF infusion were found in subject with normal or high plasma beta-MSH. These findings induce us to consider it unlikely that synthetic MIF is active in man.
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PMID:16425
Complex of D-glyceraldehyde-3-phosphate dehydrogenase with Cu2+ ion. The properties of ternary Cu-enzyme-coenzyme complex.
The formation of ternary Cu-enzyme-coenzyme complex from cupric ion and D-glyceraldehyde-3-phosphate dehydrogenase holoenzyme results in similar spectral changes as the formation of binary Cu-apoenzyme complex, which indicates that the complex bonds between cupric ion and the holoenzyme, and cupric ion and the apoenzyme are similar. Spectrophotometric titration, chemical modification experiments and inhibition studies with cupric ion gave evidence that cupric ion is selectively bound on Cys-149 residue also in the Cu-GAPD-NAD complex. The charge transfer interaction between the coenzyme and Cu-GAPD, i.e. the difference spectrum of the combination of NAD with Cu-GAPD complex, is different from that of the enzyme-coenzyme complex in the absence of cupric ion. The shape of this "modified enzyme-coenzyme charge transfer spectrum" is influenced by various anions. The difference absorption does not depend on the pH in the range of 5.5 to 9. This indicates that the bound cupric ion abolishes the effect of deprotonation of a functional group in the protein on the charge transfer interaction. It is suggested that this functional group is a histidine imidazole, which activates the Cys-149 thiol group in the native enzyme and binds the metal ion in the cupric complex in a Cys-Cu-His chelate structure.
Complex of D-glyceraldehyde-3-phosphate dehydrogenase with Cu2+ ion. The properties of ternary Cu-enzyme-coenzyme complex. The formation of ternary Cu-enzyme-coenzyme complex from cupric ion and D-glyceraldehyde-3-phosphate dehydrogenase holoenzyme results in similar spectral changes as the formation of binary Cu-apoenzyme complex, which indicates that the complex bonds between cupric ion and the holoenzyme, and cupric ion and the apoenzyme are similar. Spectrophotometric titration, chemical modification experiments and inhibition studies with cupric ion gave evidence that cupric ion is selectively bound on Cys-149 residue also in the Cu-GAPD-NAD complex. The charge transfer interaction between the coenzyme and Cu-GAPD, i.e. the difference spectrum of the combination of NAD with Cu-GAPD complex, is different from that of the enzyme-coenzyme complex in the absence of cupric ion. The shape of this "modified enzyme-coenzyme charge transfer spectrum" is influenced by various anions. The difference absorption does not depend on the pH in the range of 5.5 to 9. This indicates that the bound cupric ion abolishes the effect of deprotonation of a functional group in the protein on the charge transfer interaction. It is suggested that this functional group is a histidine imidazole, which activates the Cys-149 thiol group in the native enzyme and binds the metal ion in the cupric complex in a Cys-Cu-His chelate structure.
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PMID:16428
The testing of the antibiotic sensitivity of bacteria on an agar medium: The problem of a double zone of inhibition.
When the sensitivity of Micrococcus luteus ATTC9341 to streptomycin, erythromycin, oleandomycin and spiramycin was tested by an agar diffusion method using antibiotic impregnated filter paper disks on unbuffered Penassay Seed Agar two zones of inhibition were observed around the disks after an incubation period of 24 hours at 30 degrees C. The pH of the M. luteus seeded Penassay Seed Agar was measured before and after 24 hours incubation at 30 degrees C and found to be 6.6 and 8.7, respectively. When the Penassay Seed Agar was buffered to pH 6.1 and the sensitivity of the microbe to the antibiotics was tested as before no double zones of inhibition could be observed. The phenomenon of the double zones of inhibition may possibly be due to the pH increase of the medium from a relatively low level to the optimum range of activities of the antibiotics during the incubation period.
The testing of the antibiotic sensitivity of bacteria on an agar medium: The problem of a double zone of inhibition. When the sensitivity of Micrococcus luteus ATTC9341 to streptomycin, erythromycin, oleandomycin and spiramycin was tested by an agar diffusion method using antibiotic impregnated filter paper disks on unbuffered Penassay Seed Agar two zones of inhibition were observed around the disks after an incubation period of 24 hours at 30 degrees C. The pH of the M. luteus seeded Penassay Seed Agar was measured before and after 24 hours incubation at 30 degrees C and found to be 6.6 and 8.7, respectively. When the Penassay Seed Agar was buffered to pH 6.1 and the sensitivity of the microbe to the antibiotics was tested as before no double zones of inhibition could be observed. The phenomenon of the double zones of inhibition may possibly be due to the pH increase of the medium from a relatively low level to the optimum range of activities of the antibiotics during the incubation period.
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PMID:16429
Effect of propranolol and related drugs on transmembraneous pH differences in liposomes.
Propranolol (1-isopropylamino-3-(1-naphtoloxy)-propan-2-ol) a beta-adrenergic receptor blocking agent was found to cause changes of transmembraneous pH in liposomes prepared from Soy-lecithin and cardiolipin. When the external pH was neutral and the internum of the liposomes acidic, the drug decreased the pH gradient. When the externum was acidic and the internum neutral, the gradient was increased by the drug. The effect of butacaine was similar to that of propranolol, while procaine, timolol and practolol were ineffective. It is suggested that the charged form of propranolol is bound to the membrane and dislocates protons from binding sites in the membrane and that the uncharged form of propranolol penetrates the membrane. After penetration it could associate with protons in the intraliposomal compartment and hence increase the pH of the interior. Depending on the direction of the pre-existing proton gradient propranolol would thus be able to increase or decrease the pH difference across the liposomal membrane.
Effect of propranolol and related drugs on transmembraneous pH differences in liposomes. Propranolol (1-isopropylamino-3-(1-naphtoloxy)-propan-2-ol) a beta-adrenergic receptor blocking agent was found to cause changes of transmembraneous pH in liposomes prepared from Soy-lecithin and cardiolipin. When the external pH was neutral and the internum of the liposomes acidic, the drug decreased the pH gradient. When the externum was acidic and the internum neutral, the gradient was increased by the drug. The effect of butacaine was similar to that of propranolol, while procaine, timolol and practolol were ineffective. It is suggested that the charged form of propranolol is bound to the membrane and dislocates protons from binding sites in the membrane and that the uncharged form of propranolol penetrates the membrane. After penetration it could associate with protons in the intraliposomal compartment and hence increase the pH of the interior. Depending on the direction of the pre-existing proton gradient propranolol would thus be able to increase or decrease the pH difference across the liposomal membrane.
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PMID:16430
On the aromatic hydroxylation of amphetamine in rat liver microsomes and perfused liver preparations: effects of long-term administration.
The liver microsomal p-hydroxylation of amphetamine to parahydroxyamphetamine (pOHA) was dependent on NADP and inhibited by carbon monoxide indicating the involvement of cytochrome P-450, SKF 525-A, fenfluramine and desmethylimipramine were the most effective inhibitors of this pathway of amphetamine metabolism. Repeated administraion of phenobarbital resulted in reduced p-hydroxylation of amphetamine in vitro. Chronic administration of amphetamine reduced the microsomal p-hydroxylation of amphetamine without apparent changes in the cytochrome P-450 levels or in the activity of NADPH-cytochrome c reductase. The aromatic hydroxylation of aniline and the demethylation of ethylmorphine was not affected by this treatment. However, the 455 nm complex formed during the microsomal metabolism of N-hydroxy-amphetamine was increased by the long-term administration of amphetamine. These results indicate some pecularities of the in vitro hydroxylation of amphetamine by rat liver microsomes. Amphetamine disappeared from the perfusate of the perfused liver at the same rate in rats given a single dose of amphetamine and in rats given amphetamine orally for four weeks. The excretion of pOHA and its conjugate increased at 60 and 90 min. and 30, 60 and 90 min. respectively in the perfusate of the same experiment as compared to the controls. The total excretion of radioactive amphetamine metabolites at the end of the perfusion was increased in the perfusate and reduced in the bile compared to the control experiment.
On the aromatic hydroxylation of amphetamine in rat liver microsomes and perfused liver preparations: effects of long-term administration. The liver microsomal p-hydroxylation of amphetamine to parahydroxyamphetamine (pOHA) was dependent on NADP and inhibited by carbon monoxide indicating the involvement of cytochrome P-450, SKF 525-A, fenfluramine and desmethylimipramine were the most effective inhibitors of this pathway of amphetamine metabolism. Repeated administraion of phenobarbital resulted in reduced p-hydroxylation of amphetamine in vitro. Chronic administration of amphetamine reduced the microsomal p-hydroxylation of amphetamine without apparent changes in the cytochrome P-450 levels or in the activity of NADPH-cytochrome c reductase. The aromatic hydroxylation of aniline and the demethylation of ethylmorphine was not affected by this treatment. However, the 455 nm complex formed during the microsomal metabolism of N-hydroxy-amphetamine was increased by the long-term administration of amphetamine. These results indicate some pecularities of the in vitro hydroxylation of amphetamine by rat liver microsomes. Amphetamine disappeared from the perfusate of the perfused liver at the same rate in rats given a single dose of amphetamine and in rats given amphetamine orally for four weeks. The excretion of pOHA and its conjugate increased at 60 and 90 min. and 30, 60 and 90 min. respectively in the perfusate of the same experiment as compared to the controls. The total excretion of radioactive amphetamine metabolites at the end of the perfusion was increased in the perfusate and reduced in the bile compared to the control experiment.
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0.03579334542155266, 0.0180578101426363, -0.07831654697656631, 0.0730205774307251, 0.09501044452190399, -0.23892773687839508, -0.03723215311765671, -0.021529261022806168, -0.02251281403005123, -0.010955413803458214, 0.015396393835544586, 0.025869974866509438, -0.012675258331000805, -0.044472984969615936, 0.04435858502984047, 0.04675891622900963, 0.06197807565331459, 0.06654909253120422, 0.07230480760335922, 0.0352514311671257, -0.042168207466602325, 0.024953771382570267, 0.04163658991456032, -0.009084446355700493, -0.02730134315788746, 0.015957757830619812, -0.04760320484638214, 0.08917375653982162, -0.00855186302214861, -0.016862906515598297, 0.0065191080793738365, 0.029013434424996376, 0.04499349743127823, -0.0160067081451416, 0.01192578487098217, -0.057868778705596924, 0.016811653971672058, 0.11938510835170746, -0.0304036233574152, 0.08815529197454453, -0.048027947545051575, -0.0825929120182991, 0.004833867307752371, -0.00012040927686030045, 0.012623699381947517, 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PMID:16426
[Measurement of transport in mucous membrane in the human nose with Cr-51-labeled resin beads].
The mucociliary transport of the human nasal mucosa was studied by using very small resin beads tagged with 51Cr. Several modifications of previous methods were introduced, e.g. kind of nuclide, particle size, pH, mode of application, measuring technique and reduction of local irradiation. Finally arrangements implying exact measurements of transport not only horizontally but also vertically or obliquely were obtained. No mucociliary transport was demonstrated in five of nine subjects with a common cold 10 days before or one week after the investigation. Xylometazolin as a nasal spray diminished the mucociliary transport significantly. In addition, the effects on mucociliary transport caused by homolateral or contralateral experimental nasal obstruction as well as by tobacco smoking were studied in healthy subjects. Finally, patients with various diseases: pollen allergy in free intervals, chronic rhinitis, septal deviation or perforation, and condition after laryngectomy were also investigated.
[Measurement of transport in mucous membrane in the human nose with Cr-51-labeled resin beads]. The mucociliary transport of the human nasal mucosa was studied by using very small resin beads tagged with 51Cr. Several modifications of previous methods were introduced, e.g. kind of nuclide, particle size, pH, mode of application, measuring technique and reduction of local irradiation. Finally arrangements implying exact measurements of transport not only horizontally but also vertically or obliquely were obtained. No mucociliary transport was demonstrated in five of nine subjects with a common cold 10 days before or one week after the investigation. Xylometazolin as a nasal spray diminished the mucociliary transport significantly. In addition, the effects on mucociliary transport caused by homolateral or contralateral experimental nasal obstruction as well as by tobacco smoking were studied in healthy subjects. Finally, patients with various diseases: pollen allergy in free intervals, chronic rhinitis, septal deviation or perforation, and condition after laryngectomy were also investigated.
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PMID:16436
Distribution of coronary blood flow in the left ventricular wall of dogs evaluated by the uptake of Xe-133.
The distribution of coronary blood flow was estimated in anesthetized dogs by counting the activity in tissue blocks of the left ventricular free wall immediately after bolus injection of Xe-133 into the aortic root. No differences in the uptake of isotope were observed between the apex and the base of the heart; between areas supplied by the anterior descending and circumflex branches of the left coronary artery; or between the endo- and epicardial halves of the wall. In most experiments a bolus injection of the isotope into the left coronary artery was followed by a difference in activity between areas supplied by the left anterior descending and left circumflex branches. This indicated inadequate mixing of blood and isotope in the main stem of the artery. The uneven distribution did not result in differences between the epi- and endocardial activity concentrations. The results from one normal, anesthetized dog in which tissue activities were measured after constant rate infusion of Xe-133 into the left coronary artery for 8 min were in accordance with the general assumption of equal epi- and endocardial volumes of distribution (values of lambda).
Distribution of coronary blood flow in the left ventricular wall of dogs evaluated by the uptake of Xe-133. The distribution of coronary blood flow was estimated in anesthetized dogs by counting the activity in tissue blocks of the left ventricular free wall immediately after bolus injection of Xe-133 into the aortic root. No differences in the uptake of isotope were observed between the apex and the base of the heart; between areas supplied by the anterior descending and circumflex branches of the left coronary artery; or between the endo- and epicardial halves of the wall. In most experiments a bolus injection of the isotope into the left coronary artery was followed by a difference in activity between areas supplied by the left anterior descending and left circumflex branches. This indicated inadequate mixing of blood and isotope in the main stem of the artery. The uneven distribution did not result in differences between the epi- and endocardial activity concentrations. The results from one normal, anesthetized dog in which tissue activities were measured after constant rate infusion of Xe-133 into the left coronary artery for 8 min were in accordance with the general assumption of equal epi- and endocardial volumes of distribution (values of lambda).
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PMID:16437
The ability of ATP-free granule material from bovine adrenal medulla to bind inorganic cations and biogenic amines.
Bovine adrenal medullary granules isolated by millipore filtration were depleted of CA and ATP by dialysis. The resulting material showed an ability to bind inorganic cations and biogenic amines in a concentration-dependent manner. The similarity of the uptake curves, the identical uptake maxima and the narrow pH range (between 4-7) over which the uptake of the inorganic and organic cations took place indicated a binding of these ions to common sites. In addition, the fact that all the uptake curves fitted the Rothmund-Kornfeld equation for cation exchangers corroborated the cation exchanger properties of the dialyzed granule material. The CA binding capacity corresponded to 20-30% of the normal CA content of bovine medullary granules.
The ability of ATP-free granule material from bovine adrenal medulla to bind inorganic cations and biogenic amines. Bovine adrenal medullary granules isolated by millipore filtration were depleted of CA and ATP by dialysis. The resulting material showed an ability to bind inorganic cations and biogenic amines in a concentration-dependent manner. The similarity of the uptake curves, the identical uptake maxima and the narrow pH range (between 4-7) over which the uptake of the inorganic and organic cations took place indicated a binding of these ions to common sites. In addition, the fact that all the uptake curves fitted the Rothmund-Kornfeld equation for cation exchangers corroborated the cation exchanger properties of the dialyzed granule material. The CA binding capacity corresponded to 20-30% of the normal CA content of bovine medullary granules.
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PMID:16438
Effect of hypercapnia and hypocapnia on tryptophan and tyrosine hydroxylation in rat brain.
The effects of induced hypo- and hypercapnia upon the rate of hydroxylation of tryptophan and tyrosine in the rat brain were studied by measuring the accumulation of 5-HTP and DOPA following administration of the aromatic L-aminoacid decarboxylase inhibitor 3-hydroxybenzylhydrazine HCl (NSD 1015). The results suggest that the hydroxylation of tryptophan varies directly with the tissue Po2. On the other hand, the hydroxylation of tyrosine did not show a simple relationship to Po2 but appeared to be influenced by pH changes.
Effect of hypercapnia and hypocapnia on tryptophan and tyrosine hydroxylation in rat brain. The effects of induced hypo- and hypercapnia upon the rate of hydroxylation of tryptophan and tyrosine in the rat brain were studied by measuring the accumulation of 5-HTP and DOPA following administration of the aromatic L-aminoacid decarboxylase inhibitor 3-hydroxybenzylhydrazine HCl (NSD 1015). The results suggest that the hydroxylation of tryptophan varies directly with the tissue Po2. On the other hand, the hydroxylation of tyrosine did not show a simple relationship to Po2 but appeared to be influenced by pH changes.
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PMID:16439
Angiography of the testicular artery. II. Cryptorchism and testicular agenesis.
A selective angiography of the testicular artery was performed in 7 boys and 7 men without a palpable testicle in order to localize cryptorchid testes or to establish testicular agenesis. The examination could be carried out in all cases, and the angiographic diagnosis was confirmed at operation and at a subsequent microscopy in the 12 cases hitherto operated upon. The width of the artery and its branches are also presented.
Angiography of the testicular artery. II. Cryptorchism and testicular agenesis. A selective angiography of the testicular artery was performed in 7 boys and 7 men without a palpable testicle in order to localize cryptorchid testes or to establish testicular agenesis. The examination could be carried out in all cases, and the angiographic diagnosis was confirmed at operation and at a subsequent microscopy in the 12 cases hitherto operated upon. The width of the artery and its branches are also presented.
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PMID:16453
Factors affecting urate reabsorption in the rat kidney.
1. Urate transport in the rat appears to be saturable. However, affinity of the transport system for urate is very low and transport far from saturated at physiological plasma concentrations. 2. Since increase of the nonionized fraction of uric acid by a factor of five failed to increase urate reabsorption, transport cannot be due to nonionic diffusion but rather involves ionized urate. 3. Increases in luminal flow rate markedly depress urate reabsorption in the loop of Henle, which results in wash out of medullary urate.
Factors affecting urate reabsorption in the rat kidney. 1. Urate transport in the rat appears to be saturable. However, affinity of the transport system for urate is very low and transport far from saturated at physiological plasma concentrations. 2. Since increase of the nonionized fraction of uric acid by a factor of five failed to increase urate reabsorption, transport cannot be due to nonionic diffusion but rather involves ionized urate. 3. Increases in luminal flow rate markedly depress urate reabsorption in the loop of Henle, which results in wash out of medullary urate.
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PMID:16456
Uric acid transport characteristics in human erythrocytes.
Taken all together the results show that the RBC transport of U.A. seems to be partly of passive nature, closely similar to others mineral or organic anions, and partly of active nature related to compound of the membrane playing a role in cellular metabolism. It remains to be precised the role of the membrane itself and to characterize the membrane site which could be responsible of a part of the transport of U.A. through erythrocyte membrane.
Uric acid transport characteristics in human erythrocytes. Taken all together the results show that the RBC transport of U.A. seems to be partly of passive nature, closely similar to others mineral or organic anions, and partly of active nature related to compound of the membrane playing a role in cellular metabolism. It remains to be precised the role of the membrane itself and to characterize the membrane site which could be responsible of a part of the transport of U.A. through erythrocyte membrane.
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PMID:16463
The pressor activity of burimamide: a relationship between chemical constitution and pressor activity of burimamide and related histamine H2-receptor antagonists.
Burimamide, a histamine H2-receptor antagonist, has been shown to cause pressor responses in pithed rats. The response can be prevented by prior removal of the adrenal glands or by pretreatment with the alpha-adrenoceptor antagonist, phentolamine, 5 mg/kg, suggesting that the pressor response to burimamide is due to release of catecholamines from the adrenal glands. The pressor activity of burimamide has been compared with that of metiamide and two close chemical analogues, methylburimamide and thiaburimamide, in order to identify which chemical features of the compounds are necessary for this activity. Methylburimamide was the most potent pressor agent, followed by burimamide, metiamide and thiaburimamide. The pressor effects (and presumably catecholamine-releasing activities) appear to be related to the basicities of the compounds. We conclude that the release of catecholamines by these histamine H2-receptor antagonists is probably due to their cationic (imidazolium) forms.
The pressor activity of burimamide: a relationship between chemical constitution and pressor activity of burimamide and related histamine H2-receptor antagonists. Burimamide, a histamine H2-receptor antagonist, has been shown to cause pressor responses in pithed rats. The response can be prevented by prior removal of the adrenal glands or by pretreatment with the alpha-adrenoceptor antagonist, phentolamine, 5 mg/kg, suggesting that the pressor response to burimamide is due to release of catecholamines from the adrenal glands. The pressor activity of burimamide has been compared with that of metiamide and two close chemical analogues, methylburimamide and thiaburimamide, in order to identify which chemical features of the compounds are necessary for this activity. Methylburimamide was the most potent pressor agent, followed by burimamide, metiamide and thiaburimamide. The pressor effects (and presumably catecholamine-releasing activities) appear to be related to the basicities of the compounds. We conclude that the release of catecholamines by these histamine H2-receptor antagonists is probably due to their cationic (imidazolium) forms.
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PMID:16465
A new semi-defined medium for Trypanosoma brucei sspp.
A new, easy to prepare semi-defined medium for the cultivation of trypanosomes of the T. brucei complex is introduced. Containing the two commercially available media MEM (Minimum Essential Medium) and Medium 199 TC45 as well as 10% inactivated foetal calf serum (fcs), the medium supports optimum growth and direct adaptation of bloodstream forms. Growth characteristics, glucose uptake, amino acid utilization and the ultrastructure of trypanosomes grown in this medium are described briefly.
A new semi-defined medium for Trypanosoma brucei sspp. A new, easy to prepare semi-defined medium for the cultivation of trypanosomes of the T. brucei complex is introduced. Containing the two commercially available media MEM (Minimum Essential Medium) and Medium 199 TC45 as well as 10% inactivated foetal calf serum (fcs), the medium supports optimum growth and direct adaptation of bloodstream forms. Growth characteristics, glucose uptake, amino acid utilization and the ultrastructure of trypanosomes grown in this medium are described briefly.
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PMID:16466
Anaemia in trypanosomiasis: mechanisms of erythrocyte destruction in mice infected with Trypanosoma congolense or T. brucei.
Studies in mice infected with T. brucei or T. congolense showed that increased red cell destruction in the spleen occurred as from the third day of patent parasitaemia and this resulted in a marked reduction of the half-life of transfused syngeneic 51Cr labelled cells. There was a progressive increase in the osmotic fragility of the red cells, especially in T. congolense infected mice which also showed a more severe anaemia. The antiglobulin test was only rarely positive in the late stages of T. brucei infection. Incubation of normal red cells with plasma from infected mice in vitro did not result in haemolysis, but in the case of plasma from T. brucei infected mice, it caused an appreciable reduction in the half-life of the cells when transfused into normal mice. It is suggested that mechanisms of red cell destruction in trypanosome infections are complex and may vary with the species of trypanosomes, the host and the stage of infection.
Anaemia in trypanosomiasis: mechanisms of erythrocyte destruction in mice infected with Trypanosoma congolense or T. brucei. Studies in mice infected with T. brucei or T. congolense showed that increased red cell destruction in the spleen occurred as from the third day of patent parasitaemia and this resulted in a marked reduction of the half-life of transfused syngeneic 51Cr labelled cells. There was a progressive increase in the osmotic fragility of the red cells, especially in T. congolense infected mice which also showed a more severe anaemia. The antiglobulin test was only rarely positive in the late stages of T. brucei infection. Incubation of normal red cells with plasma from infected mice in vitro did not result in haemolysis, but in the case of plasma from T. brucei infected mice, it caused an appreciable reduction in the half-life of the cells when transfused into normal mice. It is suggested that mechanisms of red cell destruction in trypanosome infections are complex and may vary with the species of trypanosomes, the host and the stage of infection.
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PMID:16467
Susceptibility of a rodent-adapted strain of Trypanosoma vivax to Berenil, Samorin and Novidium.
The susceptibility of a rodent-adapted strain of Trypanosoma vivax (Leeflant strain Y58) to Berenil, Samorin and Novidium was tested in mice. When infected mice were treated on the second day of detectable parasitaemia, there was complete cure with Berenil at 10 mg/kg, Novidium at 4 mg/kg and Samorin at 0.2 mg/kg body weight respectively. Berenil and Novodium at lower doses rendered the mice aparasitaemic for a few days followed by heavy parasitaemia (relapse) and death. Lower doses of Samorin, on the other hand, were curative for none or only some of the mice but without relapses. These observations are related to the accepted modes of action of these drugs and their use in the field.
Susceptibility of a rodent-adapted strain of Trypanosoma vivax to Berenil, Samorin and Novidium. The susceptibility of a rodent-adapted strain of Trypanosoma vivax (Leeflant strain Y58) to Berenil, Samorin and Novidium was tested in mice. When infected mice were treated on the second day of detectable parasitaemia, there was complete cure with Berenil at 10 mg/kg, Novidium at 4 mg/kg and Samorin at 0.2 mg/kg body weight respectively. Berenil and Novodium at lower doses rendered the mice aparasitaemic for a few days followed by heavy parasitaemia (relapse) and death. Lower doses of Samorin, on the other hand, were curative for none or only some of the mice but without relapses. These observations are related to the accepted modes of action of these drugs and their use in the field.
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PMID:16468
Observations on the feeding and defecation patterns of three triatomine species (Hemiptera: Reduviidae).
A comparative laboratory study of feeding and defecation behavior of three species of tritomines (Rhodnius prolixus, Triatoma infestans and T. dimidiata) indicated evident differences among the species and among the different stages of same species. Time required for a full blood meal was related to the size of the specimen. Insects required an average of 11-28 min for engorgement although some finished within 10 min. T. dimidata frequently interrupted the act of feeding, a probable explanation of the higher number of defecations before finishing a blood meal observed in the species. R. prolixus was superior to the other two species in number of defecating insects and in rapidity and frequency of defecations within a given time. T. dimidiata was inferior in all three parameters and T. infestans was intermediate. Males of all species tended to be less effective. A "defecation index" is proposed for comparing this different behavior in triatomine specimens under standard conditions. Effectivity of the insects according to the measured parameters is discussed in relation to the prevalence of Chagas' disease in those areas where they are principal vectors.
Observations on the feeding and defecation patterns of three triatomine species (Hemiptera: Reduviidae). A comparative laboratory study of feeding and defecation behavior of three species of tritomines (Rhodnius prolixus, Triatoma infestans and T. dimidiata) indicated evident differences among the species and among the different stages of same species. Time required for a full blood meal was related to the size of the specimen. Insects required an average of 11-28 min for engorgement although some finished within 10 min. T. dimidata frequently interrupted the act of feeding, a probable explanation of the higher number of defecations before finishing a blood meal observed in the species. R. prolixus was superior to the other two species in number of defecating insects and in rapidity and frequency of defecations within a given time. T. dimidiata was inferior in all three parameters and T. infestans was intermediate. Males of all species tended to be less effective. A "defecation index" is proposed for comparing this different behavior in triatomine specimens under standard conditions. Effectivity of the insects according to the measured parameters is discussed in relation to the prevalence of Chagas' disease in those areas where they are principal vectors.
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PMID:16470
Comparison of infectivity of Trypanosoma cruzi blood stream trypomastigotes and metacyclic trypomastigotes from Rhodnius prolixus.
Four strains of Trypanosoma cruzi (Y, BG, M and Peru) retain their ability to infect Rhodnius prolixus and to produce virulent infections in mice for from 12 to 39 years. About 60 or more metacyclic trypomastigotes were consistently lethal to mice. The mean number of metacyclics per bug ranged from 1.2 to 17.3 x 10(3). Comparative studies of virulence of metacyclics and blood trypomastigotes showed the blood forms to be slightly more virulent. The route of injection was shown to be more significant in varying the host response to infection, subcutaneous inoculation being the preferred route.
Comparison of infectivity of Trypanosoma cruzi blood stream trypomastigotes and metacyclic trypomastigotes from Rhodnius prolixus. Four strains of Trypanosoma cruzi (Y, BG, M and Peru) retain their ability to infect Rhodnius prolixus and to produce virulent infections in mice for from 12 to 39 years. About 60 or more metacyclic trypomastigotes were consistently lethal to mice. The mean number of metacyclics per bug ranged from 1.2 to 17.3 x 10(3). Comparative studies of virulence of metacyclics and blood trypomastigotes showed the blood forms to be slightly more virulent. The route of injection was shown to be more significant in varying the host response to infection, subcutaneous inoculation being the preferred route.
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PMID:16471
Immunization against Trypanosoma cruzi using killed antigens and with saponin as adjuvant.
The immunization of mice with killed epimastigotes or trypomastigotes with saponin SPL as adjuvant was challenged by inoculation of blood or metacyclic trypomastigotes of T. cruzi. Immunogenic preparations were obtained by freeze-thawing of formalin treatment. The protection was effective against homologous and heterologous challenge, and lasted up to 12 weeks after the last immunization. The immunization was also effective against metacyclic trypomastigote challenge. The immunogenicity of the killed T. cruzi suspension was retained after freeze-drying.
Immunization against Trypanosoma cruzi using killed antigens and with saponin as adjuvant. The immunization of mice with killed epimastigotes or trypomastigotes with saponin SPL as adjuvant was challenged by inoculation of blood or metacyclic trypomastigotes of T. cruzi. Immunogenic preparations were obtained by freeze-thawing of formalin treatment. The protection was effective against homologous and heterologous challenge, and lasted up to 12 weeks after the last immunization. The immunization was also effective against metacyclic trypomastigote challenge. The immunogenicity of the killed T. cruzi suspension was retained after freeze-drying.
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PMID:16475
Worms: transmission from animals to man.
It is useful to know that household pets are not involved in the life cycles of some worms, for example, pinworms. Some worms require a household pet in their cycles: the dog and cat roundworms, heartworms, and the dog and cat hookworms, the larvae of which are responsible for cutaneous larva migrans. Strongyloides (threadworm) infestation is sometimes difficult to diagnose and may be traced directly to the family dog.
Worms: transmission from animals to man. It is useful to know that household pets are not involved in the life cycles of some worms, for example, pinworms. Some worms require a household pet in their cycles: the dog and cat roundworms, heartworms, and the dog and cat hookworms, the larvae of which are responsible for cutaneous larva migrans. Strongyloides (threadworm) infestation is sometimes difficult to diagnose and may be traced directly to the family dog.
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PMID:16476
Sudden infant death syndrome (crib death).
Sudden infant death syndrome (SIDS) is diagnosed by the absence of lethal autopsy findings, or in a resuscitatable, "near miss" form with cyanosis, apnea, and bradycardia. The event is unexpected, although a minor respiratory infection is common, and occurs during sleep, between 1 and 6 months of age. There is growing evidence that the victims have had previous hypoxic episodes. Although suffocation is no longer considered a tenable explanation, other forms of airway obstruction are still postulated by many; the evidence, however, favors hypoxia as the common feature. A lethal arrhythmia had been proposed by several groups, based on inappropriate reflex activity, "pathology" of the conduction system, and the long QT syndrome, but the evidence is against arrhythmia as the primary event in most cases of SIDS. Based on the reversible "near miss," apnea is likely as the primary event in SIDS. Several reflexes have the ability to produce apnea, in addition to the relatively common sleep apnea; the crucial aspect, rather, appears to be thefailure of the immature infant to resume respiration. The possibility exists that the infant, who did not have to breather for 9 months of fetal life, literally is not alarmed and aroused by the persistance of apnea. In human and animal studies, respiratory infections and sleep deprivation have been proved to increase the likelihood and duration of sleep apnea. If primary apnea continues for long (45 seconds or more), a dangerous positive feedback develops into hypoxic apnea. Hhis will persist until circulatory failure occurs, or until gasping occurs. The gasp is a highly effective mechanism at birth, but will occur too late for autoresuscitation after the anerobic capacity of fetal life dimineshes; we believe this capacity lasts for approximately 1 month, accounting for the hiatus of crib death, sparing the first month. The "near-miss" infant, after resuscitation, should be monitored at home, if practical, until 6 months of age. A simple cardiac monitor for bradycardia has definite advantage over an apnea monitor alone.
Sudden infant death syndrome (crib death). Sudden infant death syndrome (SIDS) is diagnosed by the absence of lethal autopsy findings, or in a resuscitatable, "near miss" form with cyanosis, apnea, and bradycardia. The event is unexpected, although a minor respiratory infection is common, and occurs during sleep, between 1 and 6 months of age. There is growing evidence that the victims have had previous hypoxic episodes. Although suffocation is no longer considered a tenable explanation, other forms of airway obstruction are still postulated by many; the evidence, however, favors hypoxia as the common feature. A lethal arrhythmia had been proposed by several groups, based on inappropriate reflex activity, "pathology" of the conduction system, and the long QT syndrome, but the evidence is against arrhythmia as the primary event in most cases of SIDS. Based on the reversible "near miss," apnea is likely as the primary event in SIDS. Several reflexes have the ability to produce apnea, in addition to the relatively common sleep apnea; the crucial aspect, rather, appears to be thefailure of the immature infant to resume respiration. The possibility exists that the infant, who did not have to breather for 9 months of fetal life, literally is not alarmed and aroused by the persistance of apnea. In human and animal studies, respiratory infections and sleep deprivation have been proved to increase the likelihood and duration of sleep apnea. If primary apnea continues for long (45 seconds or more), a dangerous positive feedback develops into hypoxic apnea. Hhis will persist until circulatory failure occurs, or until gasping occurs. The gasp is a highly effective mechanism at birth, but will occur too late for autoresuscitation after the anerobic capacity of fetal life dimineshes; we believe this capacity lasts for approximately 1 month, accounting for the hiatus of crib death, sparing the first month. The "near-miss" infant, after resuscitation, should be monitored at home, if practical, until 6 months of age. A simple cardiac monitor for bradycardia has definite advantage over an apnea monitor alone.
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PMID:16478
Coronary arterial narrowing in Takayasu's aortitis.
A patient with Takayasu's aortitis and angina pectoris due to severe narrowing of the right and left coronary arterial ostia is described. Takayasu's arteritis produces a panaortitis, with thickening of the adventitia predominating, and an inflammatory cell infiltrate involving the adventitia, outer media and vasa vasorum. Narrowing of the coronary arteries in this disease is due to extension into these arteries of the processes of proliferation of the intima and contraction of the fibrotic media and adventitia that occur in the aorta. The distal coronary arteries usually do not manifest arteritis and are normal in caliber. Angina pectoris may be the first symptom of the disease if the coronary arteries are the initial site of severe arterial narrowing. The coronary arterial bypass graft operation is effective therapy for treating coronary arterial narrowing due to Takayasu's arteritis.
Coronary arterial narrowing in Takayasu's aortitis. A patient with Takayasu's aortitis and angina pectoris due to severe narrowing of the right and left coronary arterial ostia is described. Takayasu's arteritis produces a panaortitis, with thickening of the adventitia predominating, and an inflammatory cell infiltrate involving the adventitia, outer media and vasa vasorum. Narrowing of the coronary arteries in this disease is due to extension into these arteries of the processes of proliferation of the intima and contraction of the fibrotic media and adventitia that occur in the aorta. The distal coronary arteries usually do not manifest arteritis and are normal in caliber. Angina pectoris may be the first symptom of the disease if the coronary arteries are the initial site of severe arterial narrowing. The coronary arterial bypass graft operation is effective therapy for treating coronary arterial narrowing due to Takayasu's arteritis.
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PMID:16479
Derangements of myocardial metabolism preceding onset of ventricular fibrilliation after coronary occlusion.
To determine alterations in myocardial metabolism and and hemodynamics that occur within the first 30 minutes after coronary arterial occlusion, before the onset of ventricular fibrillation, measurements were compared in two series of dogs. Series A, 90 dogs that did not manifest ventricular fibrillation after coronary occlusion, were considered a control group. Series B consisted of 28 dogs that had ventricular fibrillation within 30 minutes after occlusion. All had similar comprehensive measurements completed preceding the onset of ventricular fibrillation. The animals in series B (subseuqnt fibrillation) had significantly higher heart rates before and after coronary occlusion. In this series cardiac metabolism of the occluded segment judged by transmyocardial lactate extraction, potassium balance, sodium/potassium ratio and blood pH because grossly more abnormal after coronary occlusion than in series A. In 5 animals whose measurements were obtained within 5 minutes of the onset of ventricular fibrillation, a sudden massive lactate production, potassium loss and increased acidosis of the occluded portion supervened minutes before the onset of the fatal arrhythmia. Animals with ventricular fibrillation had higher intracoronary S-T segment elevation that persisted until the onset of ventricular fibrillation. Measurements of abnormal hemodynamic function (left ventricular end-diastolic pressure, peak systolic pressure and first derivative of left ventricular pressure [DP/dt]) were not associated with an increased incidence of ventricular fibrillation. The study indicates that animals that manifest ventricular fibrillation within 30 minutes after coronary occlusion have higher preocclusion heart rates, a more severe metabolic disorder of the coronary occluded segment and more persistent intracoronary S-T segment elevation compared with animals that do not manifest ventricular fibrillation.
Derangements of myocardial metabolism preceding onset of ventricular fibrilliation after coronary occlusion. To determine alterations in myocardial metabolism and and hemodynamics that occur within the first 30 minutes after coronary arterial occlusion, before the onset of ventricular fibrillation, measurements were compared in two series of dogs. Series A, 90 dogs that did not manifest ventricular fibrillation after coronary occlusion, were considered a control group. Series B consisted of 28 dogs that had ventricular fibrillation within 30 minutes after occlusion. All had similar comprehensive measurements completed preceding the onset of ventricular fibrillation. The animals in series B (subseuqnt fibrillation) had significantly higher heart rates before and after coronary occlusion. In this series cardiac metabolism of the occluded segment judged by transmyocardial lactate extraction, potassium balance, sodium/potassium ratio and blood pH because grossly more abnormal after coronary occlusion than in series A. In 5 animals whose measurements were obtained within 5 minutes of the onset of ventricular fibrillation, a sudden massive lactate production, potassium loss and increased acidosis of the occluded portion supervened minutes before the onset of the fatal arrhythmia. Animals with ventricular fibrillation had higher intracoronary S-T segment elevation that persisted until the onset of ventricular fibrillation. Measurements of abnormal hemodynamic function (left ventricular end-diastolic pressure, peak systolic pressure and first derivative of left ventricular pressure [DP/dt]) were not associated with an increased incidence of ventricular fibrillation. The study indicates that animals that manifest ventricular fibrillation within 30 minutes after coronary occlusion have higher preocclusion heart rates, a more severe metabolic disorder of the coronary occluded segment and more persistent intracoronary S-T segment elevation compared with animals that do not manifest ventricular fibrillation.
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PMID:16480
Effect of gallstone-dissolution therapy on human liver structure.
To assess potential toxic effects liver biopsies were performed before and after 6-8 months therapy with chenodeoxycholic acid (CDCA), 750 mg daily, in 6 patients with gallbladder stones. Minor fatty change and lipofuscin were seen prior to therapy, which tended to increase afterwards. Otherwise there was no consistent change on light microscopy. Electron microscopy showed parallel changes in the hepatocytes with no marked damage. There was a patchy loss of microvilli in the biliary epithelium. However, there was a significant increase in sinusoidal lipocytes or Ito cells, which was seen in every case. These 6 patients were representative of a group of 20 patients in whom serum liver function tests have been followed monthly for at least 6 months. During this period aspartate aminotransferase levels rose slightly but significantly, the mean remaining within the normal range. There was a trend to a decline in alpha-glutamyl transpeptidase levels, but this was less impressive and not statistically significant.
Effect of gallstone-dissolution therapy on human liver structure. To assess potential toxic effects liver biopsies were performed before and after 6-8 months therapy with chenodeoxycholic acid (CDCA), 750 mg daily, in 6 patients with gallbladder stones. Minor fatty change and lipofuscin were seen prior to therapy, which tended to increase afterwards. Otherwise there was no consistent change on light microscopy. Electron microscopy showed parallel changes in the hepatocytes with no marked damage. There was a patchy loss of microvilli in the biliary epithelium. However, there was a significant increase in sinusoidal lipocytes or Ito cells, which was seen in every case. These 6 patients were representative of a group of 20 patients in whom serum liver function tests have been followed monthly for at least 6 months. During this period aspartate aminotransferase levels rose slightly but significantly, the mean remaining within the normal range. There was a trend to a decline in alpha-glutamyl transpeptidase levels, but this was less impressive and not statistically significant.
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