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Biomedical subjects

E Rapaport

Publications and source records attributed to E Rapaport.

At least 55 records · Page 3Linked to original sources

Sudden cardiac death.

Most sudden deaths in industrial nations are the result of underlying coronary artery disease. Longitudinal studies have demonstrated that the percent of all coronary events presenting as sudden death increases with age in both men and women. Relative weight is another important risk factor; the age-adjusted rate of sudden cardiac death for the upper weight tercile in the Framingham study was over 2 times higher for men and 3 times higher for women than the rate for the lower weight tercile. Most patients who die suddenly initially experience ventricular tachycardia that subsequently degenerates into ventricular fibrillation. Patients with a high risk of sudden cardiac death include: survivors of myocardial infarction with left ventricular dysfunction or complex ventricular ectopy, or both; survivors of out-of-hospital cardiac arrest, particularly when the event is not associated with an acute myocardial infarction; patients with recurrent ventricular tachycardia; and patients with dilated congestive cardiomyopathy, particularly when associated with ventricular ectopy. Reducing the risk of sudden death in these patients remains a major challenge.

Arrhythmias, Cardiac↗

Epoprostenol (prostacyclin) in unstable angina.

The purpose of this randomized, double-blind multicenter trial was to investigate the potential therapeutic effect of epoprostenol (prostacyclin, PGI2) in patients with unstable angina, as compared with placebo, and to investigate the safety of this agent. Of the 184 patients enrolled, 28 did not fit the study criteria; of the remaining 156 patients, 30 received prostacyclin in an open-label fashion. In the double-blind portion of the study, 63 patients each received prostacyclin or placebo. The drug or its vehicle was infused intravenously up to 5 ng/kg/min dose for 72 hours with a tapering off period for the last 12 hours. Both treatment groups from the double-blind portion were comparable in regard to the demographic data, length of infusion, and total dose received. There were no significant differences between the placebo and prostacyclin group in the following clinical endpoints: levels of cardiac enzymes throughout hospitalization period (with the exception of lower SGOT level in the prostacyclin group at day 2), and severity of angina (throughout the study), and at the end of the study (day 30). The number of patients who had congestive heart failure, new myocardial infarction, balloon pump insertion, coronary artery bypass grafting, or percutaneous coronary angioplasty was similar in both groups. Similar results in regard to the efficacy endpoints were also apparent in the prostacyclin group that was treated under open-label fashion. There was also no difference in the New York Heart Association (NYHA) functional status at the end of the double-blind study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Experimental cancer therapy in mice by adenine nucleotides.

Adenosine 5'-monophosphate (AMP), adenosine 5'-diphosphate (ADP) and adenosine 5'-triphosphate (ATP), injected intraperitoneally into tumor-bearing (s.c. implanted footpad tumors) mice, exhibited significant anticancer activity. Daily treatments (for 10 days) inhibited the growth of the fast-growing, aggressive CT 26 colon adenocarcinoma in CB6F1 mice. The growth-inhibitory activity of adenine nucleotides was also observed against a human pancreatic adenocarcinoma, CAPAN-1, xenografts in athymic nude mice. With low tumor burdens some 'cures' were obtained in both model systems. No inherent toxicity, as determined by changes in host weight, were observed during and after the period of treatment. Intraperitoneal injections of 1 ml of 50 mM AMP, ADP or ATP in saline, yielded elevated blood and plasma levels of ATP which lasted for several hours in both strains of mice. The growth-inhibitory activities of adenine nucleotides against tumor cells in vitro, have previously been demonstrated.

Adenine Nucleotides↗

Stress- and Growth Phase-Associated Proteins of Clostridium acetobutylicum.

The response of Clostridium acetobutylicum ATCC 4259 to the stresses produced by a temperature upshift from 28 degrees C to 45 degrees C and by exposure of the organisms to 0.1% n-butanol or to air was examined by analysis of pulse-labeled proteins. The stress response was the induction of the synthesis of a number of proteins, some of which were elicited by the three forms of stress. Eleven heat shock proteins were identified by two-dimensional electrophoresis, as were two proteins whose synthesis was heat sensitive. In the absence of applied stress, the synthesis of four proteins was found to be associated with the growth phase in batch culture; three of these proteins had a higher rate of de novo synthesis when the cells entered the solvent production phase. One of the stress-induced proteins, hsp74, was partially purified an found to be immunologically related to Escherichia coli heat shock protein Dnak. The similarities of the proteins induced at the onset of solventogenesis and by stress suggest a relationship between the two processes.

Journal Article↗

Metabolism of adenylylated nucleotides in Clostridium acetobutylicum.

In response to the stresses imposed by temperature upshift or addition of butanol, Clostridium acetobutylicum cultures accumulated diadenosine-5',5'''-P1,P4-tetraphosphate (Ap4A) and adenosine 5'-P1,P4-tetraphospho-5'-guanosine (Ap4G) to high levels. The two adenylylated nucleotides were also accumulated in batch culture in the absence of imposed stresses when the clostridia switched from the acidogenic phase of growth to the solventogenic phase. Most of the adenylylated nucleotides were extracellular. The intracellular concentrations of these compounds were low throughout batch growth and in cells stressed by added butanol. In contrast to other procaryotes, these clostridia did not possess enzymes to degrade the dinucleotides, as shown with both intact cells and cell-free preparations. Our findings are consistent with the hypothesis that endogenously produced solvents are stressful to the cells, stimulating the synthesis of adenylylated nucleotides. The nucleotides accumulate extracellularly because they cannot be degraded and because the cell membranes are permeabilized by the solvents produced.

1-Butanol↗

Aminoacyl-tRNA synthetases catalyze AMP----ADP----ATP exchange reactions, indicating labile covalent enzyme-amino-acid intermediates.

Aminoacyl-tRNA synthetases (amino acid-tRNA ligases, EC 6.1.1.-) catalyze the aminoacylation of specific amino acids onto their cognate tRNAs with extraordinary accuracy. Recent reports, however, indicate that this class of enzymes may play other roles in cellular metabolism. Several aminoacyl-tRNA synthetases are herein shown to catalyze the AMP----ADP and ADP----ATP exchange reactions (in the absence of tRNAs) by utilizing a transfer of the gamma-phosphate of ATP to reactive AMP and ADP intermediates that are probably the mixed anhydrides of the nucleotide and the corresponding amino acid. AMP and ADP produce active intermediates with amino acids by entering the back-reaction of amino acid activation, reacting with labile covalent amino acid-enzyme intermediates. Gramicidin synthetases 1 and 2, which are known to activate certain amino acids through the formation of intermediate thiol-esters of the amino acids and the enzymes, catalyze the same set of reactions with similar characteristics. Several lines of evidence suggest that these activities are an inherent part of the enzymatic reactions catalyzed by the aminoacyl-tRNA synthetases and gramicidin synthetases and are not due to impurities of adenylate kinase, NDP kinase, or low levels of tRNAs bound to the enzymes. The covalent amino acid-enzyme adducts are likely intermediates in the aminoacylation of their cognate tRNAs. The use of gramicidin synthetases has thus helped to illuminate mechanistic details of amino acid activation catalyzed by the aminoacyl-tRNA synthetases.

Adenine Nucleotides↗

MM-CK subtypes diagnose reperfusion early after myocardial infarction.

Isoelectric focusing (IEF) was used to analyze the serum MM-CK isoenzyme subtypes in 16 patients receiving streptokinase (SK) for attempted coronary thrombolysis early after acute myocardial infarction. Twelve patients had revascularization documented by serial coronary angiograms (Group I); in four patients, angiography documented no such reperfusion (Group II). The data also were compared with a previously reported group of 8 patients who did not receive streptokinase (Group III). Total and MB-CK activity, as well as the MM-CK isoenzyme subtypes MM3-CK, MM2-CK, and MM1-CK tended to rise earlier and peak earlier in Group I compared with Group II; serum MM3-CK, the predominant subtype in myocardium, however, definitely peaked earlier in Group I (8.65 +/- 2.07 hr) compared with Group II (18.50 +/- 6.67 hr) (p less than 0.001). Soon after its release from myocardium, MM3-CK is converted in the serum to MM2-CK and eventually to MM1-CK; thus, the MM3-CK:MM1-CK ratio amplifies the time course of subtype conversion. The MM3-CK:MM1-CK activity ratio peaked earlier in Group I (5.51 +/- 0.97 H) compared to Group II (10.74 +/- 3.28 hr) (p less than 0.01), and peaked even earlier than MM3-CK (p less than 0.007) in both Groups I and II. Thus, the time course of the MM3-CK:MM1-CK ratio separates those patients who reperfuse when early SK is used after acute myocardial infarction from those who do not, and does it significantly earlier than the other enzymatic parameters of cellular necrosis, total CK, and MB-CK.

Adult↗

Streptokinase alters myocardial creatine kinase depletion after ischaemia and reperfusion in rabbits.

The efficacy of streptokinase as an intracoronary thrombolytic agent is well-recognized. The effect of streptokinase, distinct from its thrombolytic action, on ischaemic myocardium distal to an area of coronary artery occlusion when reperfusion occurs has not been well-defined. In order to do this, myocardial creatine kinase depletion and the histopathology of infarctions produced in rabbits after 1 h of circumflex coronary artery occlusion and mechanical release of the occlusion were assessed. Streptokinase or saline was infused intravenously for 1 h beginning 0.5 h after occlusion. Rabbits were divided into two time intervals: early (less than 10 h) and late (24 h) after release of coronary artery occlusion. When streptokinase was infused in early infarctions, haemorrhage did not correlate with infarction cross-sectional area or myocardial creatine kinase depletion. However, myocardial creatine kinase depletion was 40% less when streptokinase was infused than when saline was infused, suggesting that streptokinase might limit infarct size. In late infarctions, the degree of haemorrhage, infarction cross-sectional area, and myocardial creatine kinase depletion were similar after reperfusion with streptokinase or saline. By 24 h, the beneficial effect of a single dose of streptokinase given early in the course of occlusion-reperfusion myocardial injury was no longer evident in limiting infarct size.

Animals↗

Thermal dilution assessment of proximal aortic and left ventricular mixing chambers in dogs.

The adequacy of left ventricular mixing and the effect of mixing in the left ventricle and aorta on the measurement of the residual fraction by thermal dilution were assessed in open-chest dogs. Temperature was recorded at seven ventricular and two aortic sites during ventricular injections of iced saline at heart rates of 100, 150 and 200 bpm. The residual fraction, K, was calculated for each beat from the inscribed dilution curves and compared with the actual temperature at each measurement site and heart rate. Temperature was non-uniform throughout the ventricle after saline injections indicating incomplete tracer mixing. Thermal equilibration was slowest at the apex and decreased as heart rate increased. K, however, was similar for all sites in the ventricle and aorta at each heart rate by the third beat after saline injection. Thus, in spite of incomplete mixing, the beat-to-beat washout of indicator quickly stabilized which suggests that a reproducible measurement of functional volume can be obtained by this technique.

Animals↗