Captopril and central nervous system effects.
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Biomedical subjects
Publications and source records attributed to S Rapoport.
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The formation of O2- radicals as primary products of O2 reduction by human erythrocytes is demonstrated. O2- radicals react directly with GSH and OxyHb as 1e-donors forming GSSG and MetHb. After exhaustion of the glutathione system MetHb increases greatly and secondary radicals formation ensues with breakdown of Hb. The toxicity of O2- radicals is caused mainly by secondary radicals.
The V/Q scintigram is the mainstay of pulmonary embolism diagnosis, but there are limitations, such as the need for sophisticated interpretation, the production of indeterminate readings, and the lack of specificity. The authors discuss these problems and the emerging techniques that may be more of a help to the radiologist faced with diagnosing pulmonary embolism.
Purified lipoxygenase from rabbit reticulocytes contains 1 g atom iron per molecule. The amino acid composition shows that the enzyme contains 11 cysteine residues but no disulfide bridges and contains a relatively high content of hydrophobic amino acids. The enzyme shows heterogeneity in the C-terminus. With the tritium labeling method the amino acids His, Asn and Ile were found in the C-terminal region. The absorption co-efficient was found to be 1.68 (E0.1% 280 1 cm) in the native state and 1.77 in the unfolded state.
The rate of oxidation of exogenous arachidonate by homogenous samples of lipoxygenase from rabbit reticulocyte cytosol is significantly increased in the presence of various biological membranes (mitochondria, microsomes, erythrocyte ghosts, etc.). Unlike reticulocyte lipoxygenase, the rate of arachidonate oxidation by soybean lipoxygenase I in the presence of biomembranes is considerably reduced. The rate of arachidonate oxidation by reticulocyte lipoxygenase is also strongly increased in the presence of artificial membranes, e. g. liposomes from various phospholipids.
The sum-total of ATP produced amounts to 135 mmoles X 1 reticulocytes-1 X hour-1. About 70% of the ATP consumption has been accounted for by specific processes. The main contributing processes are: the globin synthesis with about 28%; the Na+/K+-ATPase with 23%, and the ATP-dependent share of proteolysis with more than 15%. 30% of ATP consumption has not been accounted for. Cycloheximide (20 X 10(-6) M) leads to a dissociation between synthesis and degradation of proteins, which argues against any obligatory connection between these processes. About 90% of the lysine liberated from mitochondria by proteolysis were reutilized for the globin synthesis demonstrating the high nitrogen economy of reticulocytes. Each of the ATP consuming processes studied appears to control ATP production in an independent manner without competition with each other.
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For the past several years, observation of flow direction in non-parenchymal renal artery branches, particularly during pharmacoangiography, has proved to be extremely reliable in the preoperative evaluation of the hemodynamic significance of renal artery stenoses. The advent of percutaneous transluminal angioplasty (PTA) has expanded the applications for these methods. Their value in PTA is demonstrated through five illustrative cases. In four stenoses shown to be significant before PTA, clinical responses were favorable. In one case undergoing PTA of an anatomically severe, but hemodynamically insignificant stenosis, blood pressure was unchanged after PTA. After PTA, observation of orthograde flow in the pararenal arteries confirms the adequacy of the procedure, and predicates a favorable clinical response.
Metrizamide was employed in six patients who, during angiography, had had severe anaphylactoid reactions to conventional ionic contrast media. Five of these patients had received corticoid premedication before injection of both conventional contrast medium and metrizamide; anaphylaxis occurred only after administration of conventional contrast media. Four patients had no detectable reaction whatsoever after metrizamide; a fifth had only transient tachycardia. In the sixth patient, delayed edema developed in the region of his cerebral arteriovenous malformation. These observations suggest a marked decrease in the incidence and severity of anaphylactoid reactions when metrizamide is substituted in patients who have reacted to ionic contrast media. Metrizamide, or a comparable nonionic contrast agent, should be strongly considered in patients who have had a severe reaction to conventional contrast medium.
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The ATP production of human erythrocytes in the steady state (approximately 2 mmoles . 1 cells-1 . h-1, 37 degrees C, pHi 7.2) is maintained by glycolysis and the ATP consumption is essentially limited to the cell membrane. About 25% of the ATP consumption is used for ion transport ATPases. The bulk of the ATP consuming processes in intact erythrocytes remains poorly understood. "Isotonic" erythrocyte membranes prepared under approximate intracellular conditions after freeze-thaw hemolysis have high (Ca2+, Mg2+)-ATPase activities (80% of the total membrane ATPase activity). There is a great discrepancy between the high capacity of the (Ca2+, Mg2+)-ATPase in isotonic membranes and the actual activity in the intact cell. The (Ca2+, Mg2+)-ATPase of isotonic membranes has a "high" Ca2+-affinity (Ka less than 0.5 microM) and a "low" Mg-ATP affinity (Km approximately 760 microM). This state of (Ca2+, Mg2+)-ATPase is caused by the association of calmodulin and 30000 Dalton polypeptides (ATP affinity modulator protein). Hypotonic washings of isotonic membranes result in a loss of the 30 kD polypeptides. EGTA (0.5 mM) extracts derived from isotonic membranes contain the 30 kD modulator protein and restore the properties of the (Ca2+, Mg2+)-ATPase of hypotonic membrane preparations to the isotonic characteristics. The Mg-ATP affinity modulator protein is assumed to form a complex with calmodulin and (Ca2+, Mg2+)-ATPase.
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Addition of pyruvate to human red cells incubated in vitro at alkaline pH values inhibits the accumulation of phosphate esters otherwise observed as well as the decrease of ATP and the corresponding increase of ADP and AMP. The increase of glycolysis at alkaline pH values is only partly due to a pH effect per se. About one-half of it is caused by a partial release of the inhibition of phosphofructokinase by a lowering of the ATP concentration and particularly by the increase of AMP. Only in the presence of pyruvate there occurs an increase of 2,3-bisphosphoglycerate, such as is observed in vivo, which is balanced by the consumption of pyruvate. At alkaline pH values in the absence of pyruvate there is a low movement from the fructose-1,6-bisphosphate + triosephosphates pool to the components of the pentose phosphate pathway, mostly by way of recombination from glyceraldehyde-phosphate.
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In this work it is demonstrated the NH3 potentially available from the oxidation of amino acids by the reticulocyte is utilized for the new-synthesis of serine via transamination reactions with hydroxypyruvate and phosphohydroxypyruvate. These compounds are derived from glucose, which furnishes in this manner the carbon skeleton of serine. It was shown that serine is mainly degraded via glycine, while glycine is in the main formed from serine. Furthermore it was found that serine synthesis is localized in the cytosol, while the reversible transformation of serine to glycine takes place in the mitochondria. A transfer of methylenetetrahydrofolate occurs in both directions across the mitochondrial membrane. A concentrative uptake of serine by the mitochondria was found, while glycine is transported slowly in both directions. On the basis of the data an overall balance is given of the quantitative relations between protein breakdown and hemoglobin synthesis as well as for the new-formation and utilization of serine and glycine. The new-formation of serine may amount to about one tenth of the glucose utilized by the reticulocyte and furnishes about one-half of the serine and glycine moieties required for the synthesis of heme and globin. The remainder is provided by the energy-dependent protein breakdown.
1. A method is reported, based on the isotopic dilution of lysine, which is suitable for the measurement of the degradation of stroma proteins of reticulocytes. 2. Proteolysis is extensive and time-limited. It may reach 50% of the stroma in 2 h at pH 7.6 and 37 degrees C. It is strongly dependent on pH and temperature, being small at low pH and temperatures. Proteolysis is largely ATP-dependent. The extent of proteolysis is nearly proportional to the degree of reticulocytosis. 3. The proteolytic system may be reconstructed in hemolysates if ATP is produced or supplied. It is assumed that the system is identical and that studied by Goldberg et al. and Hershko et al. on abnormal or denatured proteins as substrates. The main significance of the proteolytic system appears to be the degradation of mitochondria during maturation of the red cell.
Infusion of 25% mannitol into the internal carotid artery of the dog results in a reversible disruption of the blood-brain barrier (BBB). This osmotic BBB disruption enhances the penetratin of systemically administered methotrexate (MTX) into the ipsilateral cerebral hemisphere. Brain methotexate levels were maximized by giving this chemotherapeutic drug by the intracarotid rather than the intravenous route after osmotic BBB disruption. Assays of MTX levels in cerebrospinal fluid were found to be a very unreliable and inconsistent monitor of brain MTX levels after osmotic BBB disruption.