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Biomedical subjects

J Ross

Publications and source records attributed to J Ross.

At least 469 records · Page 26Linked to original sources

Substrate specificity of the exonuclease activity that degrades H4 histone mRNA.

We have investigated the substrate specificity of an exonuclease that degrades human H4 histone mRNA, using synthetic RNA templates incubated in a cell-free mRNA decay system (Ross, J., and Kobs, G. (1986) J. Mol. Biol. 188, 579-593). Five RNAs that lacked poly(A), including histone, were degraded rapidly in vitro. Polyadenylated histone mRNA was degraded at least 10-fold more slowly than unmodified histone mRNA. Double-stranded RNA and DNA were very stable. Single-stranded DNA was degraded approximately 20-fold more slowly than single-stranded, non-polyadenylated RNA, and RNA with a 3' phosphoryl group was degraded more slowly than RNA with a 3'-hydroxyl group. Uncapped RNAs were degraded rapidly in the unfractionated system but were stable in reactions containing a ribosomal high salt wash extract. Therefore, the exonuclease activity released from ribosomes by high salt extraction was separated from the enzyme(s) that degraded uncapped RNAs.

DNA↗

Ischemic myocardial dysfunction assessed by temporal Fourier transform of regional myocardial wall thickening.

A Fourier analysis including the first 20 harmonics was performed on sonomicrometric measurements of regional myocardial wall thickness in eight conscious dogs under control conditions and at four levels of ischemia produced by a hydraulic occluder on the left circumflex coronary artery. Systolic wall thickening was reduced from 26.47 +/- 6.20% (S.D.) (control) to 22.05 +/- 5.73% (mild stenosis), 17.00 +/- 5.86% (moderate stenosis), 11.46 +/- 3.56% (severe stenosis), and 3.69 +/- 2.57% (30-second occlusion), values significantly different from each other (p less than 0.01). The amplitude of the first harmonic decreased stepwise from 1.35 +/- 0.31 to 1.08 +/- 0.29 mm, 0.90 +/- 0.27 mm, 0.69 +/- 0.24 mm, and 0.43 +/- 0.12 mm, all significantly different from each other (p less than 0.05). These amplitude values correlated to percent systolic wall thickening (r = 0.894, p = 0.001). A phase shift of the first harmonic from 137 +/- 11 to 139 +/- 14 degrees, 150 +/- 15 degrees (p less than 0.05 vs control), 161 +/- 21 degrees (p less than 0.01 vs control), and 191 +/- 21 degrees (p less than 0.01 vs control and severe stenosis) correlated with the increase in time from end diastole to the point of maximum wall excursion (r = 0.662, p less than 0.001). These data indicate that the extent of ischemic regional myocardial hypokinesis can be adequately described by the amplitude of the first harmonic, and that the asynchrony of ventricular contraction and relaxation can be detected from the phase of the first harmonic.

Animals↗

Influence of obesity on morbidity and mortality after acute myocardial infarction.

The influence of being overweight or obese on hospital and late (1 year) mortality and reinfarction was studied in 1760 patients with acute myocardial infarction. Body mass index (BMI) was used to categorize patients as normal weight (BMI less than 25), overweight (BMI 25 to 30), and obese (BMI greater than 30). Clinical features and prognosis were compared in 658 normal weight patients, 884 overweight patients, and 218 obese patients. Complications during hospitalization and 1-year reinfarction rates following discharge were similar among the weight subsets. Hospital mortality was 13% in obese patients, similar to the 14% hospital mortality in normal weight patients, but significantly more than that in overweight patients (9%, p less than 0.05). When stratified according to age, 30% of obese patients greater than or equal to 65 years died in the hospital, compared to 13% of overweight patients (p less than 0.001), and 17% of normal weight patients (p less than 0.01). In patients less than 65 years, the obese group had a 6% mortality compared to a hospital mortality of 5% in overweight and 8% in normal weight groups (NS). In a multivariate analysis, obesity was an independent predictor of hospital death in the older, but not in the younger patient subset. One-year mortality for patients discharged from the hospital was significantly less in obese than in normal weight patients (7% vs 13%, p less than 0.05), but not different from the 11% mortality rate in overweight patients. Differences in mortality disappeared when patients were age stratified.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Application of end-systolic pressure-volume and pressure-wall thickness relations in conscious dogs.

The usefulness of end-systolic measures of ventricular function was compared with that of standard contractility indexes in conscious dogs. End-systolic relations between left ventricular pressure and volume and between pressure and wall thickness were analyzed in dogs previously instrumented with ultrasonic crystals. Progressive angiotensin infusions were used to generate computer-averaged pressure-volume and pressure-wall thickness loops. Both relations were linear in every study and highly reproducible. With low and high dose dobutamine, the end-systolic pressure-volume relations were significantly displaced, with increased slope and inconsistent changes in intercept. This relation was more useful than the ejection fraction for detecting contractility increases at different afterloads, but it showed no advantage over maximal left ventricular dP/dt at all ranges of preload and afterload. The end-systolic pressure-volume relations were insensitive for detecting mild decreases in inotropic state produced by propranolol, and maximal dP/dt was superior for detecting such mild acutely reduced contractility. The end-systolic pressure-wall thickness relations showed displacement with dobutamine, although slope and intercept changes were not significant; these relations did not detect mild decreases in contractility produced by propranolol. It is concluded that the end-systolic pressure-volume relation and a simplified end-systolic measure using pressure and wall thickness provide sensitive, load-independent and reproducible approaches for defining acute increases in left ventricular contractility in conscious animals. Maximal dP/dt was equally effective for defining these increases in contractility and more sensitive for detecting slight acute decreases in contractility.

Angiotensin II↗

Regional myocardial blood flow, function and metabolism using phosphorus-31 nuclear magnetic resonance spectroscopy during ischemia and reperfusion in dogs.

Postreperfusion regional myocardial dysfunction may be associated with depletion of high energy phosphate compounds during ischemia and with their relatively slow repletion during reperfusion. However, few studies have correlated relatively rapid changes in regional myocardial function (sonomicrometers) and blood flow (microspheres) with high energy phosphate concentrations measured using phosphorus-31 nuclear magnetic resonance spectroscopy in intact large animal models of regional myocardial ischemia. The left anterior descending coronary artery of mongrel dogs was abruptly occluded for 17.1 +/- 1.9 minutes and then completely released; measurements were made for an additional 22 minutes. Transmural blood flow decreased from 1.07 +/- 0.25 to 0.25 +/- 0.10 ml/(min X g) and holosystolic expansion was observed in all dogs (segmental systolic shortening decreased from 9.3 +/- 3.7 to -6.3 +/- 6.0%). Phosphocreatine (PCr) measured during 4.4 minute sampling intervals decreased to steady state within the first sampling period after occlusion and was 45.9 +/- 17.0% of control at the end of the occlusion, whereas beta-adenosine triphosphate (beta-ATP) reached its lowest level early after reperfusion (72.7 +/- 13.3% of control). The ratio of PCr to inorganic phosphate (Pi) decreased during the occlusion (3.34 +/- 0.75 versus 1.01 +/- 0.61) but returned to control level early during reperfusion. The ratio of PCr to beta-ATP also decreased during coronary occlusion (2.16 +/- 0.39 versus 1.29 +/- 0.39) but did not return to control level during reperfusion. Significant correlations were observed between the intensity of ischemia (reduced blood flow) and reductions in regional contractile function, PCr, beta-ATP, myocardial pH and the increase in Pi during the coronary occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Dissociation between regional myocardial dysfunction and subendocardial ST segment elevation during and after exercise-induced ischemia in dogs.

The onset and resolution of electrical and functional measures of regional myocardial ischemia were examined in nine conscious dogs during control exercise and exercise after beta-receptor blockade. The dogs had been instrumented with an ameroid constrictor and were studied when no regional dysfunction was evident at rest, although severe coronary stenosis or coronary occlusion with collateral circulation development was present. ST segment elevation was measured on subendocardial electrograms, and regional wall motion was studied by sonomicrometry. During control exercise, subendocardial myocardial blood flow in the ischemic zone, normalized to blood flow in the nonischemic zone, decreased. Subendocardial ST elevation increased slowly, was significantly different from control standing values by 2.5 minutes of exercise and returned quickly to control values within 5 minutes after exercise. Percent systolic wall thickening decreased rapidly, was significantly depressed by 1 minute of exercise and did not return to control values until 30 minutes after exercise. A second, identical exercise stress was performed on the same day after a single oral dose (1 mg/kg body weight) of atenolol. In the ischemic zone during exercise after atenolol compared with control exercise, normalized subendocardial myocardial blood flow was improved and significantly less ST elevation occurred, but the onset and resolution of ST elevation were not altered. Systolic wall dysfunction during exercise was significantly less after atenolol, and function returned toward preexercise values by 1 minute after exercise, even more rapidly than ST segment resolution.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Changes in the virulence of myxoma virus strains in Britain.

National surveys of the virulence of field strains of myxoma virus were carried out in 1975 (128 virus strains) and in 1981 (123 strains), using the virulence testing method employed in a similar survey in 1962. Results showed that the virulence of field strains had increased between 1962 and 1975, and again between 1975 and 1981. The increases in virulence are thought to be a result of the development of resistance to myxomatosis in wild rabbit populations. The effects of the changes in virulence and resistance are discussed.

Animals↗

Dependence of thermodynamic efficiency of proton pumps on frequency of oscillatory concentration of ATP.

In order to evaluate the utilization of variable ATP concentration produced by an oscillatory reaction (as in anaerobic glycolysis), we analyze the thermodynamic efficiency of power output of a cyclic, ATP-driven proton pump found in the plasma membrane of plant cells. The model used includes the coupling of potassium and calcium ion transport. Oscillations in the concentration of ATP can lead to either increases or decreases in efficiency compared to that at constant ATP concentration, with corresponding decreases and increases in dissipation in the irreversible processes of the proton pump, depending on the frequency of the oscillations. Variations of imposed frequencies induce, in the periodic response, variations of phase shifts between the components of the total membrane current, which consist of the pump's proton current and the currents of potassium and calcium ions. Increases in efficiency are attained when the phase shifts are such that maxima (or minima) in the proton pump current and membrane potential occur simultaneously.

Adenosine Diphosphate↗

Role of heart rate reduction in the treatment of exercise-induced myocardial ischaemia.

The role of bradycardia in reducing exercise-induced ischaemia and wall dysfunction was examined in dogs with single vessel chronic coronary artery stenosis created using an ameroid constrictor. Treadmill exercise produced significant regional myocardial ischaemia (blood flow measured using microspheres) and contractile dysfunction (systolic wall thickening measured with sonomicrometers). Dogs were initially studied during a control run before and during a second identical run after administration of the cardioselective beta-adrenergic blocker atenolol, which improved regional ischaemic function from 4.4 +/- 3.7% to 8.5 +/- 2.8% and subendocardial perfusion from 0.43 +/- 0.23 to 0.55 +/- 0.29 ml min-1 g-1. In another group of dogs during a run with atenolol, the heart rate was paced to match the rate observed in the control run. During the atenolol run with pacing, all beneficial effects of atenolol observed at the reduced exercise heart rate were lost. A third group of dogs received the bradycardic agent UL-FS 49 (1.0 mg kg-1, i.v.) prior to exercise. UL-FS 49 produced a heart rate reduction during exercise from 230 +/- 19 to 139 +/- 10 beats min-1; this was associated with an increase in systolic wall thickening from 9.3 +/- 5.0% (during the control run) to 21.5 +/- 8.4%, thereby eliminating the exercise-induced contractile dysfunction. Transmural myocardial blood flow per beat to the poststenotic myocardium was improved significantly from 4.8 X 10(-3) +/- 1.9 X 10(-3) ml beat-1 to 9.8 X 10(-3) +/- 1.7 X 10(-3). Atrial pacing to match heart rate to the control exercise rate during the UL-FS 49 run did not eliminate all of the improvement in systolic wall thickening.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Autogenous regulation of histone mRNA decay by histone proteins in a cell-free system.

We tested the hypothesis that histone mRNA turnover is accelerated in the presence of free histone proteins. In an in vitro mRNA decay system, histone mRNA was degraded four- to sixfold faster in reaction mixtures containing core histones and a cytoplasmic S130 fraction than in reaction mixtures lacking these components. The decay rate did not change significantly when histones or S130 was added separately, suggesting either that the histones were modified and thereby activated by S130 or that additional factors besides histones were required. RecA, SSB (single-stranded binding), and histone proteins all formed complexes with histone mRNA, but only histones induced accelerated histone mRNA turnover. Therefore, the effect was not the result of random RNA-protein interactions. Moreover, histone proteins did not induce increased degradation of gamma globin mRNA, c-myc mRNA, or total poly(A)- or poly(A)+ polysomal mRNAs. This autoregulatory mechanism is consistent with the observed accumulation of cytoplasmic histone proteins in cells after DNA synthesis stops, and it can account, in part, for the rapid disappearance of histone mRNA at the end of S phase.

Cell-Free System↗

Effect of experimental pancreatic growth on the content of xenobiotic-metabolising enzymes in the pancreas.

The concentration in pancreatic tissue and the total pancreatic content of three xenobiotic metabolising enzymes has been determined in two models of experimental pancreatic growth namely, cholecystokinin-octapeptide injections and soy flour feeding. No significant change in pancreatic concentrations of benzo(a)pyrene hydroxylase or glucuronyl transferase was detected. In both models of pancreatic growth, however, the concentration of glutathione-S-transferase was significantly reduced. It is possible that the reduction in this enzyme may be of some importance in determining the susceptibility of the pancreas to carcinogenesis observed with long term soy flour feeding.

Animals↗

Contractile responses to sympathetic activation after coronary instrumentation.

The consequences of acute coronary dissection and chronic coronary instrumentation on contractile responses to sympathetic activation were examined in dogs. Stimulation of the left ventrolateral cervical cardiac nerve in seven anesthetized dogs after acute dissection of the left circumflex coronary artery (CX) did not change the increase in systolic shortening velocity. After acute dissection of the left anterior descending coronary artery (LAD), nerve stimulation increased shortening velocity of the posterior wall in all dogs but enhanced that of the anterior wall in only five dogs. In six conscious dogs with chronic instrumentation of the CX, reflex sympathetic activation induced by occlusion of the inferior vena cava comparably increased thickening velocities of both the anterior wall and posterior walls both at 1 and 3 wk after instrumentation. In six other dogs with chronic instrumentation of the LAD, responses to caval occlusion were nonuniform and correlated to the morphological degree of sympathetic denervation. Therefore, acute dissection and chronic instrumentation of the LAD may produce sympathetic denervation but do not cause functionally significant sympathetic denervation of the CX region.

Animals↗

Attenuation of exercise-induced myocardial ischemia in dogs with recruitment of coronary vasodilator reserve by nifedipine.

There is now evidence that under resting conditions coronary vasodilator reserve exists even in the presence of myocardial ischemia. Therefore, we tested the hypothesis that a vasodilator reserve may exist during exercise so that during exercise-induced ischemia a reduction in coronary constrictor tone can be produced that attenuates the decreases in regional myocardial blood flow and function distal to a severe coronary stenosis without changing the determinants of myocardial oxygen demand. Nine dogs were instrumented with an ameroid constrictor on the left circumflex coronary artery and were studied 2 to 3 weeks later. During a control treadmill run, heart rate increased from 119 +/- 20 to 225 +/- 20 beats/min and peak left ventricular pressure increased from 144 +/- 17 to 163 +/- 28 mm Hg. Poststenotic subendocardial blood flow (measured by a microsphere technique) fell from 1.19 +/- 0.36 to 0.51 +/- 0.30 ml/min X g and systolic wall thickening (by sonomicrometry) decreased from 24.3 +/- 5.8% to 6.0 +/- 6.1%. During an identical run after nifedipine (10 micrograms/kg iv), systemic hemodynamics were not significantly altered. However, subendocardial blood flow was increased to 0.85 +/- 0.51 ml/min X g (p less than .05) and systolic wall thickening to 11.4 +/- 7.8% (p less than .01). We conclude that in this study the amelioration of exercise-induced myocardial ischemia was due to the recruitment by nifedipine of coronary vasodilator reserve.

Animals↗

Elimination of exercise-induced regional myocardial dysfunction by a bradycardiac agent in dogs with chronic coronary stenosis.

We have previously demonstrated that the beneficial effect of cardioselective beta-blockade on exercise-induced ischemia is due entirely to negative chronotropism. Therefore we studied the effect of a new bradycardiac agent (UL-FS 49) in 10 dogs with chronic coronary artery stenosis produced by an ameroid constrictor. Regional myocardial function (sonomicrometers, wall thickness) and blood flow (microspheres) were measured during a control treadmill exercise bout and an identical run 3 hr later after the administration of UL-FS 49 (1.0 mg/kg iv). In the control run, heart rate increased from 114 +/- 20 to 230 +/- 19 beats/min and systolic wall thickening (%WT) in the poststenotic myocardium decreased from 23.3 +/- 5.2% at rest to 9.3 +/- 5.0%, a 60% reduction. Subendocardial blood flow in the ischemic area decreased from 1.04 +/- 0.30 to 0.55 +/- 0.40 ml/min/g, blood flow per beat decreased from 9.1 X 10(-3) to 2.5 X 10(-3) ml/g, and mean transmural flow failed to increase (1.06 +/- 0.30 vs 1.08 +/- 0.39 ml/min/g). During exercise with UL-FS 49, heart rate increased from 89 +/- 10 to only 139 +/- 10 beats/min. End-diastolic left ventricular pressure was increased compared with that during the control run (35.7 +/- 3.0 vs 28.9 +/- 5.5 mm Hg) but left ventricular peak systolic pressure and dP/dt were unchanged. %WT in the ischemic zone did not change significantly during exercise with UL-FS 49 (23.3 +/- 7.9% at rest, 21.5 +/- 8.4% during the run), and in the nonischemic zone it increased to the same extent as during the control run.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Mechanism of beneficial effect of beta-adrenergic blockade on exercise-induced myocardial ischemia in conscious dogs.

We examined the importance of decreased heart rate in the beneficial effect of beta-adrenergic blockade on exercise-induced regional myocardial ischemia and contractile dysfunction in conscious dogs with single vessel coronary stenosis (ameroid constrictor). Studies were performed during control treadmill exercise, which produced regional myocardial ischemia (blood flow measured with microspheres) and wall dysfunction (measured using sonomicrometers). A second run was performed after the administration of atenolol (0.3-1.0 mg/kg i.v.), and the reduced heart rate caused by atenolol during early steady-state running was then prevented by atrial pacing during the latter portion of the run. Atenolol reduced the exercise heart rate from 217 +/- 25 beats per minute (SD, n = 9) to 166 +/- 15, and ischemic zone wall thickening during systole improved from 27 +/- 22% of the resting value in the control run to 50 +/- 25% of the resting value in the atenolol run (p less than 0.01). Atrial pacing then increased heart rate to 217 +/- 23 beats per minute, and regional wall thickening deteriorated to 15 +/- 25% of the resting value. Regional subendocardial blood flow in the ischemic zone during atrial pacing with atenolol was slightly less than that observed in the control run, in both ischemic and control zones, indicating no remaining beneficial effect of atenolol when heart rate reduction was eliminated. We conclude that the only significant mechanism for the improvement in exercise-induced ischemia and wall motion produced by atenolol is a reduction in the exercise heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Positive correlations between temporal lobe signs and hypnosis induction profiles: a replication.

48 university students were tested singly. Each student was first asked to complete an inventory that determined the frequency of temporal lobe signs. The subject was then taken into an acoustic chamber and evaluated on the hypnosis induction procedure (HIP) of Spiegel. Positive correlations obtained between the intensity of the sensations of floating and the total induction score and also the number of responses on clusters of items considered as temporal lobe signs. There were no significant correlations between scores on the hypnotic measures and responses for two control clusters of items or a lie scale. The results support the hypothesis that temporal lobe "experiences" and hypnotic susceptibility may share a common factor.

Adult↗