Asymmetric assessments in valuing pharmaceutical risks.
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Drug Approval↗
Biomedical subjects
R Scharff
Publications and source records attributed to R Scharff.
Doppler sonographic pulse curve analysis for estimation of the haemodynamic function.
Experience with Doppler sonographic pulse curve analysis is given from 40 glaucoma patients (examination of the temporal posterior ciliary artery), and from premature babies (blood flow in the anterior cerebral artery). In the latter group the reaction to pain and stress connected with blood sampling was studied. In the glaucoma patients focus was on the influence of IOP level on vascular autoregulation, and the possible response to therapy with beta-blockers. Describing an averaging technique, methodological problems are discussed as relevant for the detection of changes in flow and velocity in small blood vessels.
Adrenergic beta-Antagonists↗
A cellular factor involved in the formation of a DNA-synthesizing complex from DNA polymerase I in Escherichia coli.
A factor ('E') has been identified which stabilizes an endogenous DNA-synthesizing complex involving DNA polymerase I. The complex is separated from free DNA polymerase by polyacrylamide gel electrophoresis. The factor will reform the complex after it has been dissociated and will convert a preparation of DNA polymerase I to complex. The factor and the DNA-synthesizing complex both appear to be localized at the cell membrane.
DNA Polymerase I↗
DNA synthesis involving a complexes form of DNA polymerase I in extracts of Escherichia coli.
DNA polymerase I (EC 2.7.7.7; deoxynucleosidetriphosphate:DNA deoxynucleotidyltransferase) has been recovered as a complex of about 390,000 molecular weight. The complex displays an ATP-stimulated DNA-synthesizing activity that prefers native to heat-denatured DNA. Genetic evidence indicates that the recBC enzyme is associated with the polymerase in the complex. Preliminary evidence for complexes involving DNA polymerases II and III is also presented.
Adenosine Triphosphate↗
Respiration and protein synthesis in Escherichia coli membrane-envelope fragments. IV. Chemical and cytological characterization and biosynthetic capabilities of fragments obtained by mild procedures.
Membrane-envelope fragments have been isolated from Escherichia coli by comparatively mild techniques. The use of DNAase, RNAase, detergents, sonication, lysozyme, and ethylenediaminetetraacetate were avoided in the belief that rather delicate, but metabolically important, associations may exist between the plasma membrane and various cytoplasmic components. The membrane-envelope fragments have been characterized in terms of their content of major chemical components as well as their electron microscope appearance. Fractions containing membrane-envelope fragments were found to possess appreciable DNA- and protein-synthesizing activities. The fragments were rich in membrane content as determined by reduced nicotinamide adenine dinucleotide (NADH) oxidase activity and deficient in soluble components as measured by NADH dehydrogenase activity. The particulate fraction obtained between 20,000 g and 105,000 g and usually considered a ribosomal fraction was rich in membrane content and had a relatively high capacity for DNA synthesis. Envelope fragments sedimenting at 20,000 g attained very high levels of incorporation of amino acids into protein.
Amino Acids↗
Respiration and protein synthesis in Escherichia coli membrane-envelope fragments. II. Effects of fatty acids and albumin on respiration.
Fatty acids inhibited the ability of Escherichia coli membrane-envelope fragments to catalyze the oxidation of succinate and nicotinamide adenine dinucleotide, reduced form (NADH) and also inhibited the response of the Clark oxygen electrode to nonenzymatic oxygen uptake. In all cases, unsaturated fatty acids were much more inhibitory than saturated fatty acids. Albumin afforded complete protection from inhibition in the nonenzymatic oxygen-uptake experiments but only partial protection for the respiratory activities of the membrane fragments. The succinoxidase activity was totally inhibited by bovine serum albumin at concentrations that inhibited succinate dehydrogenase only slightly and NADH oxidase not at all. The E. coli acellular preparation showed no dehydrogenase or oxidase activity for any of the fatty acids under a variety of conditions. These conditions included variations of pH, concentration of fatty acids, and the presence or absence of albumin, CoA, ATP, NAD, cysteine, succinate, and carnitine. It thus appears that E. coli grown in the absence of fatty acid can not use fatty acids as an energy source.
Adenosine Triphosphate↗
Respiration and protein synthesis in Escherichia coli membrane-envelope fragments. I. Oxidative activities with soluble substrates.
This paper describes experiments conducted with membranous and soluble fractions obtained from Escherichia coli that had been grown on succinate, malate, or enriched glucose media. Oxidase and dehydrogenase activities were studied with the following substrates: nicotinamide adenine dinucleotide, reduced form (NADH), nicotinamide adenine dinucleotide phosphate, reduced form (NADPH), succinate, malate, isocitrate, glutamate, pyruvate, and alpha-ketoglutarate. Respiration was virtually insensitive to poisons that are commonly used to inhibit mitochondrial systems, namely, rotenone, antimycin, and azide. Succinate dehydrogenase and NADH, NADPH, and succinate oxidases were primarily membrane-bound whereas malate, isocitrate, and NADH dehydrogenases were predominantly soluble. It was observed that E. coli malate dehydrogenase could be assayed with the dye 2,6-dichlorophenol indophenol, but that porcine malate dehydrogenase activity could not be assayed, even in the presence of E. coli extracts. The characteristics of E. coli NADH dehydrogenase were shown to be markedly different from those of a mammalian enzyme. The enzyme activities for oxidation of Krebs cycle intermediates (malate, succinate, isocitrate) did not appear to be under coordinate genetic control.
Bacterial Proteins↗
Effect of diabetes on the concentration of amino acids in plasma and heart muscle of rats.
1. The effect of three types of diabetes (alloxan, partial pancreatectomy and anti-insulin serum) on the concentrations of individual amino acids in the plasma and heart muscle of rats was studied. 2. Insulin deficiency produced complex alterations in the concentrations of amino acids in plasma and heart muscle; the concentrations of some (alanine, valine, leucine and isoleucine) increased, others decreased and a small number were unchanged. The complexity of the results may in part be attributed to the diverse hormonal and metabolic changes that accompany diabetes.
Amino Acids↗
Accumulation of amino acids in muscle of perfused rat heart. Effect of insulin.
1. Rat heart perfused with Krebs-Henseleit bicarbonate buffer released material containing ninhydrin-positive nitrogen, but the amount was less than that reported to be released by diaphragm; glucose, but not insulin, decreased the release of ninhydrin-positive nitrogen and increased the concentration of the same material in the intracellular water of heart. 2. When heart was perfused with a mixture of amino acids and glucose, there was actually a net uptake, and an increase in intracellular concentration, of ninhydrin-positive nitrogen. Changes in the concentration of ninhydrin-positive nitrogen did not accurately reflect changes in concentration of amino acids. 3. The effect of insulin on the actual concentration of individual amino acids in heart muscle was examined by perfusing the heart with a mixture of amino acids and other ninhydrin-positive substances in the same concentration as they are found in plasma. 4. The effect of insulin on the concentrations of amino acids in the medium and in the intracellular water of the heart was determined after perfusion for different periods of time. No clear or meaningful effect of insulin was observed, despite the fact that insulin significantly increased the accumulation, in each of the same hearts, of radioactivity from amino[(14)C]isobutyric acid.
Journal Article↗
Accumulation of amino acids in muscle of perfused rat heart. Effect of insulin in the presence of puromycin.
1. Rat heart was perfused with a mixture of amino acids and other ninhydrin-positive substances in the same concentrations as they are found in plasma, and with or without sufficient puromycin to suppress protein synthesis all but completely. 2. In the presence of puromycin, but not in its absence, insulin increased the concentrations of most of the individual amino acids in the intracellular water of heart. 3. The results accord with the conclusion that insulin increases the entry of most, if not all, amino acids into muscle.
Journal Article↗