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Biomedical subjects

E Rapaport

Publications and source records attributed to E Rapaport.

At least 73 records · Page 4Linked to original sources
PubMed1985

Creatine kinase: purification, characterization, and tissue distribution of the MM subtypes.

The MM isozyme of creatine kinase can be separated into four subtypes by isoelectric focusing: MM3 (pI 6.90), MM2 (pI 6.70), MM1 (pI 6.45), and MMx (pI 6.25). Individual subtypes were produced and purified from canine heart and then separated by chromatofocusing. Subtypes could not be distinguished by relative molecular mass or kinetic properties. They differed slightly in amino acid composition. Canine and human necropsy tissues were studied to determine subtype distribution. Heart and skeletal muscle contained the most MM isozyme of creatine kinase and it was predominantly of the MM3 subtype.

Amino Acids↗
PubMed1985

Covalent modification of phenylalanyl-tRNA synthetase with phenylalanine during the amino acid activation reaction catalyzed by the enzyme.

Yeast phenylalanyl-tRNA synthetase (PRS) is shown to undergo autoaminoacylation with phenylalanine under in vitro amino acid activation conditions. Phenylalanyl adenylate enzyme complex yields a covalent phenylalanyl isopeptide exclusively with the beta subunit of the alpha 2 beta 2 enzyme. Contrary to previously reported cases of autoaminoacylation of aspartyl-tRNA synthetase and tryptophanyl-tRNA synthetase, the autoaminoacylation of PRS occurs under a specific set of conditions and results in the identification of only one labeled tryptic peptide on two types of high pressure liquid chromatography columns. The ability of PRS to undergo this covalent modification directly correlates with its ability to catalyze the synthesis of diadenosine 5',5"'-P1,P4-tetraphosphate from enzyme-bound phenylalanyl adenylate. Both reactions require the presence of low levels of zinc or cadmium and are inhibited by tRNAPhe or by low levels of low molecular weight thiols. Since diadenosine 5',5"'-P1,P4-tetraphosphate synthesis is known to be catalyzed in vivo in response to oxidation stress, it is also likely that the autoaminoacylation of phenylalanyl-tRNA synthetase may occur in vivo under a similar set of conditions. These reactions are thus not simply the result of accumulation of phenylalanyl adenylate and probably reflect conformational changes in the protein which are brought about by its interaction with zinc or cadmium.

Amino Acyl-tRNA Synthetases↗
PubMed1985

Influence of long-acting nitrate therapy on the risk of reinfarction, sudden death, and total mortality in survivors of acute myocardial infarction.

The effects of 20 variables that might influence postmyocardial infarction prognosis were assessed retrospectively in 139 patients followed up for an average of 11 months after discharge from San Francisco General Hospital following an acute myocardial infarction. When these variables were analyzed with the use of multivariate techniques, the presence of complex ventricular ectopy was the variable most highly predictive of the mortality rate, followed by age and failure to receive long-acting nitrates, principally isosorbide dinitrate (ISDN). Whereas 23 of 90 patients (25.6%) not receiving ISDN died, only 5 of the 49 patients (10%) receiving ISDN died (p less than 0.05). Although total mortality was statistically significantly greater among patients receiving antiarrhythmic drugs or digitalis than among patients not receiving these agents, these relationships did not persist when subjected to multivariate analysis.

Age Factors↗
PubMed1985

Effect of venous retroperfusion on experimental myocardial ischemia in the open-chest pig.

Venous retroperfusion, by arterialization of the coronary sinus or the vein accompanying an ischemic artery, has been suggested as an alternative method of myocardial revascularization in patients with severe coronary disease in whom direct revascularization would be an unacceptable risk or technically impossible. This study was carried out to assess whether or not venous retroperfusion can increase myocardial blood flow in the area of ischemia after sudden occlusion of a normal coronary artery in an animal, the pig, with a coronary vasculature similar to that of humans. It was found that net flow measured with an electromagnetic flowmeter through either an aorta-to-coronary sinus shunt or an aorta-to-left anterior descending coronary vein shunt after occlusion of the left anterior descending artery was at first high but rapidly decreased toward zero flow within 1 hr. Blood flow in the ischemic region measured by the microsphere method 20 min after coronary occlusion did not increase. This disparity between electromagnetic flow and regional flow suggests that there are venous-to-thebesian or venous-to-venous shunts into the systemic and pulmonary circulation through vessels greater than 14 micron. It is unlikely that effective oxygen or metabolite exchange would occur in vessels this size.

Animals↗
PubMed1985

Intracardiac shunts.

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Cardiac Catheterization↗
PubMed1984

Adenosine(5')tetraphospho(5')adenosine-binding protein of calf thymus.

An adenosine(5')tetraphospho(5')adenosine (Ap4A) binding protein has been purified from calf thymus. The protein is comprised of a single polypeptide of Mr 54000 and is capable of high-affinity (Kd = 13 microM) binding of Ap4A with great substrate specificity. The Ap4A binding protein has been isolated in two forms: a 'free', or non-polymerase-bound, form which predominates, and a similar form which copurifies with DNA polymerase alpha, but which can be resolved from it. The free form of Ap4A binding protein contains associated adenosine(5')tetraphospho(5')adenosine phosphohydrolase (Ap4Aase) activity, while the form resolved from DNA polymerase alpha contains no such activity. The Ap4Aase activity, which catalyzes the phosphohydrolysis of Ap4A to ATP and AMP, is strongly inhibited by low levels (50-100 microM) of Zn2+ without any effect on the Ap4A binding protein activity. This difference in associated Ap4Aase activity between free and polymerase-bound forms of the protein, plus the copurification mentioned above, indicate a specific association between Ap4A binding protein and DNA polymerase alpha.

Animals↗
PubMed1984

Retinoic acid alters subcellular compartmentalization of ATP pools in 3T3 cells but not in HeLa cells.

Retinoic acid (RA; beta-all-trans) inhibits the proliferation of both murine 3T3 cells and human HeLa cells. Flow cytometric analyses of exponentially growing cultures show that 3T3 cells are inhibited during the S phase of their cell cycle, while HeLa cells show only a small increase in G1 phase cells. RA (10 microM) causes a 50% increase in total cellular adenosine triphosphate (ATP) pools of 3T3 cells, but not of HeLa cells. We have previously demonstrated that the effects of RA on cellular ATP pools of 3T3 cells are directly related to its inhibition of cellular growth, and now report data which provide a biochemical basis for this process. Established procedures were utilized to investigate the effects of RA on the functional compartmentalization of the nuclear ATP pool which serves as a precursor for RNA synthesis in these cells, and which is shown to be a small pool in comparison with cytoplasmic ATP pools. Expansion of total cellular ATP pools by 1 mM of exogenously supplied unlabeled adenosine is ineffective in reducing the subsequent incorporation of [3H]adenosine into RNA of 3T3 cells. Similar treatment of HeLa cells yields a modest reduction in the incorporation of [3H]adenosine into RNA. RA treatment of HeLa cells does not affect the preferential uptake of exogenous [3H] adenosine into the immediate precursor ATP pool for RNA synthesis. RA treatment of 3T3 cells markedly reduces the incorporation of [3H] adenosine into RNA, indicating a lesser degree of functional compartmentalization of the nuclear ATP pool. Similar conclusions are drawn from correlations of the specific radioactivities of total cellular [3H] ATP pools and the levels of incorporation of radioactive label into cellular RNA. In addition, pulse-chase experiments show that RA-treated 3T3 cells continue to incorporate radioactive label from pools prelabeled with [3H]adenosine despite the presence of a large excess of unlabeled adenosine in the chase medium. Control 3T3 and both control and RA-treated HeLa cells cease to incorporate label immediately upon the start of the chase, suggesting that the functional precursor ATP pool for RNA synthesis is small and readily diluted. These data suggest that RA decreases the degree of functional compartmentalization for 3T3, but not HeLa cell ATP pools, and provides a probable mechanism for expansion of nuclear ATP pools of 3T3 cells. The expanded nuclear ATP pools may provide the biochemical mechanism for the inhibition of DNA synthesis during the S phase of the 3T3 cell cycle.

Adenosine↗
PubMed1984

99mTc-labeled nucleotides as tumor-seeking radiodiagnostic agents.

Several lines of human tumor cells in monolayer and soft agar cultures allow permeation of low levels of adenine nucleotides through their plasma membranes, while, in general, untransformed cells do not incorporate adenine nucleotides into their cellular pools without prior degradation of the nucleotides to adenosine. This study determined the uptake of 99mTc-radiolabeled chelated forms of adenine nucleotides, 99mTc-Ap4A (diadenosine 5',5"',P1,P4-tetraphosphate) and 99mTc-ATP chelates as radiodiagnostic agents suitable for the in vivo detection of tumors by radionuclide imaging. Biodistribution studies revealed that Ap4A accumulated preferentially in RT-24 tumors implanted in rats and that V2 carcinoma implanted in rabbits could be readily visualized by in vivo imaging. The biodistribution at various time points showed increased tumor-to-muscle ratios after 99mTc-Ap4A or 99mTc-ATP injections when compared with a nonspecific marker of the extracellular fluid space, 99mTc-labeled diethylenetriaminepentaacetic acid and with an agent known to localize in some tumors, 67Ga-labeled citrate. Studies of ectoenzymatic activities of virus-transformed animal cells and their untransformed counterparts in monolayer cultures showed marked decreases in the ectoenzymatic activities that degrade Ap4A in the transformed cells. Incorporation of en bloc [3H, 32P]Ap4A into cellular acid-soluble nucleotide pools of certain transformed cells was observed. Normal untransformed cells incorporated the radioactive label only by prior degradation to [3H]adenosine and 32Pi.

Adenine Nucleotides↗
PubMed1984

Imbalance of total cellular nucleotide pools and mechanism of the colchicine-induced cell activation.

Treatment with colchicine or vinblastine, both inhibitors of microtubule assembly, renders quiescent 3T3 cells in an "activated state" as evidenced by induction of DNA synthesis and other criteria. Microtubule disassembly caused by colchicine or vinblastine brings about a dramatic expansion of total cellular UTP pools with a concomitant diminution in total cellular ATP pools, thus resulting in a marked imbalance in total cellular nucleotide pools. Colchicine and vinblastine also stimulate total cellular RNA synthesis without enhancing uridine phosphorylation, suggesting that these drugs affect the G1 phase of the cell cycle at a point beyond the enhancement of uridine phosphorylation that usually accompanies mitogenic stimulation of quiescent mammalian cells. The markedly expanded cellular UTP pools appear to be necessary for initiation of the colchicine-stimulated DNA synthesis because decreasing cellular UTP pools by addition of D-glucosamine results in a selective inhibition of DNA synthesis in the colchicine-stimulated, but not control, cells. Furthermore, D-glucosamine exerts its inhibitory effect only when it is present in the cultures within the first 14 hr after colchicine treatment. When added at 21 hr, D-glucosamine still decreases cellular UTP pools, but it is no longer inhibitory for DNA synthesis, which commences 14-16 hr after colchicine stimulation. Taxol, an antitumor drug, prevents microtubule disassembly and also blocks such events as expansion of total cellular UTP pools and stimulation of RNA and DNA synthesis, indicating that microtubule depolymerization acts as a primary event initiating the process of cell activation induced by colchicine.

Adenosine Triphosphate↗
PubMed1984

Creatine kinase MM isoenzyme subforms in myocardium, cardiac lymph and blood after coronary artery occlusion in dogs.

A time-varying pattern of creatine kinase MM (CK-MM) isoenzyme subforms has been found in the blood of patients after acute myocardial infarction, but the site of enzyme modification has not been identified. Therefore, we studied the CK-MM subform patterns in myocardium, cardiac lymph and blood of dogs after coronary artery occlusion. In five conscious dogs, serial blood samples were taken for 72 h after occlusion of the left anterior descending coronary artery. Samples of non-infarcted and infarcted myocardium were taken after 72 h. In five other anaesthetised, open-chest dogs, cardiac lymph and blood samples were taken for 6 h after coronary artery occlusion. CK-MM subforms were quantitated by an isoelectric focusing method. Before coronary occlusion, 64% of the total CK activity in blood appeared as the anodal subform CK-MM 1 (pI 6.3); 20% and 9% as the cathodal subforms CK-MM 2 (pI 6.6) and CK-MM 3 (pI 6.9), respectively. However, after 2 h of coronary occlusion CK-MM 2 and CK-MM 3 were increased (38% and 17% of total activity respectively) compared with CK-MM 1. Between 4 h and 10 h, CK-MM 2 and CK-MM 3 decreased as CK-MM 1 increased restoring the control relative activities of subforms. In contrast to the subform changes in blood, CK-MM 3 was the predominant subform in both non-infarcted and infarcted myocardium after 72 h of coronary occlusion and in cardiac lymph during 6 h of coronary occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Postextrasystolic pulsus alternans and heart rate.

Postextrasystolic (PES) pulsus alternans, an alternation in systolic blood pressure above and then below base line for several beats after a premature ventricular depolarization was noted many years ago in patients with heart failure. We noted in acute animals studies that the occurrence of PES alternans was related to heart rate. We studied five open-chest dogs suppressing intrinsic heart rate by vagal stimulation and pacing the right ventricle over a range of 100-200 beats/min introducing an extrastimulus at 50% of the paced rate. We found that the pressure of the second PES beat was augmented up to 120 beats/min and then began to decrease approximately 10 Torr for each 10-beats/min increase in rate. The physiological variables most closely related to the occurrence of PES alternans were the duration of systole of the first PES (strong) beat and the rate of rapid diastolic filling of the second PES (weak) beat. Postextrasystolic and possibly sustained pulsus alternans is an inevitable consequence of heart rate and of the relationship between ejection and diastolic filling. The details of that relationship and the effects of various diseases determine whether alternans is observed or not.

Animals↗
PubMed1984

High-speed eight-channel thermocouple amplifier.

An eight-channel thermocouple amplifier system was constructed to measure rapid changes in temperature of only 1 or 2 degrees C simultaneously from many sites within the heart. The system has a response time of less than 5 ms, a resolution of less than 0.025 degrees C, and a voltage gain of approximately 2,500.

Animals↗
PubMed1983

The high risk patient after recovery from myocardial infarction: recognition and management.

Patients at high risk for recurrent myocardial infarction or death can be identified after recovery from an acute myocardial infarction. Predictors of high risk at the time of initial hospital discharge may vary in different localities depending on the underlying baseline characteristics of the patient cohort. The medical records were analyzed of 139 patients discharged from San Francisco General Hospital after recovery from an acute myocardial infarction between July 1978 and September 1981. Multivariate stepwise discriminant analysis of 20 variables contributing to sudden and total death identified complex ventricular ectopic rhythm as the most important variable, followed by age. Failure to receive chronic long-acting nitrates was an independent variable contributing to total mortality but not to sudden death, while the presence of an initial anterior myocardial infarction and impaired left ventricular function were independent variables contributing to sudden death but not to total mortality. Routine 24 hour ambulatory monitoring, radionuclide ventriculography and submaximal stress tests performed during the second week after recovery from an acute myocardial infarction provide identification of a high risk cohort for subsequent recurrent myocardial infarction or death and permit appropriate interventions designed to lessen risk to be undertaken.

Aged↗
PubMed1983

Serum creatine kinase MM isoenzyme sub-bands after acute myocardial infarction in man.

Using an isoelectric-focusing (IEF) method developed to quantitate MM isoenzyme-creatine kinase (CK) sub-band activity, we identified a reproducible time-varying pattern of these sub-bands in the serum of eight patients with acute myocardial infarction (MI). Our observations are consistent with the view that MM3-CK (the M2-CK dimer, the pure gene product) is converted intravascularly to MM2-CK, and then to MM1-CK (the M1-CK dimer, the pure postsynthetic sub-band). The MM3-CK reaches a peak first, 16 hours after infarction, followed by MM2-CK, and then by MM1-CK. The MM3-CK is the dominant sub-band in normal myocardium; there is much less MM2-CK and virtually no MM1-CK. The MM3-CK sub-band peak may indicate the time at which enzyme ceases to be released from the injured myocardium. The ratio MM3-CK:MM1-CK rises within 6 hours after onset of chest pain from a baseline of 0.38 and peaks 10 hours after MI. The peak ratio was between 1.1 and 4.2, and the value correlated with the time when total CK activity peaked after MI. The 10-fold change in the MM3:MM1 ratio after MI, as well as the early period at which this ratio peaks (10 hours), makes this an earlier and more sensitive indicator of enzyme release.

Aged↗