Search PubMed⌕ Search

Biomedical subjects

J Ross

Publications and source records attributed to J Ross.

At least 433 records · Page 24Linked to original sources
PubMed1989

Regulation of c-myc mRNA stability in vitro by a labile destabilizer with an essential nucleic acid component.

The turnover rates of some mRNAs vary by an order of magnitude or more when cells change their growth pattern or differentiate. To identify regulatory factors that might be responsible for this variability, we investigated how cytosolic fractions affect mRNA decay in an in vitro system. A 130,000 X g supernatant (S130) from the cytosol of exponentially growing erythroleukemia cells contains a destabilizer that accelerates the decay of polysome-bound c-myc mRNA by eightfold or more compared with reactions lacking S130. The destabilizer is deficient in or absent from the S130 of cycloheximide-treated cells, indicating that it is labile or is repressed when translation is blocked. It is not a generic RNase, because it does not affect the turnover of delta-globin, gamma-globin, or histone mRNA and does not destabilize a major portion of polysomal polyadenylated mRNA. The destabilizer accelerates the turnover of the c-myc mRNA 3' region, as well as subsequent 3'-to-5' degradation of the mRNA body. It is inactivated in vitro by mild heating and by micrococcal nuclease, suggesting that it contains a nucleic acid component. c-myb mRNA is also destabilized in S130-supplemented in vitro reactions. These results imply that the stability of some mRNAs is regulated by cytosolic factors that are not associated with polysomes.

Cytosol↗
PubMed1989

Characteristics of regional myocardial stunning after exercise in dogs with chronic coronary stenosis.

Persistent impairment of regional contraction of the left ventricle after restoration of blood flow following transient coronary occlusion has been termed "stunning," and reversible regional dysfunction has also been observed during recovery from exercise-induced regional ischemia. To determine whether limitation of subendocardial blood flow after exercise is a determinant of such dysfunction in the presence of chronic coronary stenosis, nine conscious chronically instrumented dogs having an Ameroid constrictor were studied before, during, and after treadmill runs that induced regional ischemia. During exercise, systolic wall thickening (%WTh, sonomicrometers) in the ischemic region decreased from a normal level of 22.1 +/- 9.1% at rest to 8.8 +/- 5.2% (+/- SD, P less than 0.01), whereas subendocardial blood flow (microspheres) in the ischemic region decreased from 0.75 +/- 0.25 to 0.45 +/- 0.27 ml.min-1.g-1 (P less than 0.05). %WTh in the ischemic region gradually improved after exercise but remained depressed (75% of control) at 30 min after the run (P less than 0.05). Postexercise dysfunction was not related to simultaneous regional hypoperfusion, since at 5 and 10 min after running there was a tendency toward subendocardial hyperemia (control 0.75 vs. 1.33 and 1.30 ml.min-1.g-1, NS) with a return to control by 30 min. Thus persistent regional dysfunction after exercise-induced regional ischemia in the conscious dog is not due to sustained subendocardial ischemia in the presence of chronic coronary stenosis and represents an example of myocardial stunning.

Animals↗
PubMed1989

A decision scheme for coronary angiography after acute myocardial infarction.

It is important to select patients in the convalescent phase of acute myocardial infarction in whom knowledge of coronary anatomy may identify those potentially suitable for intervention aimed at improving prognosis. However, differing guidelines have been proposed, and by applying some of these guidelines to our large database of patients after acute myocardial infarction, several problem areas were identified. These include lack of considering patients with resting ischemia beyond day 5 of hospitalization, management of patients with reduced ventricular function or patients not exercise tested, and the role of coronary angiography in the elderly. Based on this experience and further analysis in 1,848 patients surviving beyond day 5 of hospitalization, a modified decision scheme for coronary angiography was developed and then tested in a second population (n = 780). In the new scheme, patients over 75 years of age are considered individually. Those under 75 years of age with severe resting ischemia in the hospital at any time beyond the first 24 hours (18% mortality between day 6 and year 1), and hospital survivors with a history of previous myocardial infarction and clinical or radiographic signs of left ventricular failure in the hospital (25% 1-year mortality after discharge), are recommended for coronary angiography. Among the remaining patients, some will perform an exercise test, and those with an ischemic response or poor workload (11% 1-year mortality) are also assigned to coronary angiography. When an exercise test is not performed, a resting radionuclide left ventricular ejection fraction is recommended, and coronary angiography is considered if the value lies between 0.20 and 0.44 (12% 1-year mortality). This relatively simple scheme does not make general recommendations in the elderly, considers patients with in-hospital left ventricular failure or reduced left ventricular function or both, and approaches the problem of patients who do not perform an exercise test. This general approach would avoid early coronary angiography in patients with an average 1-year mortality risk after discharge of 3% and recommend coronary angiography in those at increased risk (average mortality rate, 16%) who make up about 55% of this population under 75 years of age.

Aged↗
PubMed1989

Short- and long-term clinical outcome after Q wave and non-Q wave myocardial infarction in a large patient population.

Prognosis for patients with non-Q wave myocardial infarction is controversial although a number of studies have shown a less favorable outlook after hospital discharge for patients with non-Q wave than for those with Q wave infarction. Therefore, the in-hospital and 1-year prognosis was investigated in a sufficiently large patient population (n = 2,024) to allow stratification by subgroups, in particular by age and previous myocardial infarction. Patients with non-Q wave infarction (n = 444; 22% of the total study population) were somewhat older (65 vs. 63 years, p less than 0.001) and had an increased incidence of previous myocardial infarction (46% vs. 24%, p less than 0.001) and congestive heart failure (21% vs. 8%, p less than 0.001) than patients with Q wave infarction. In-hospital mortality of patients with non-Q wave infarction was lower (8.1% vs. 11.5%; p less than 0.06), whereas their 1-year mortality after hospital discharge was significantly higher (13.7% vs. 9.2%, p less than 0.05) than for patients with Q wave infarction. However, total mortalities at 1 year were nearly equal. When patients were subgrouped by presence or absence of a previous myocardial infarction, patients in both subgroups exhibited mortality patterns typical of the entire population with Q wave or non-Q wave infarction. However, when stratified by age and previous infarction, in-hospital mortality for patients with non-Q wave infarction was significantly lower only in patients older than 70 years of age. Similarly, the higher mortality after hospital discharge in patients with non-Q wave infarction occurred only in patients older than 70 years of age without previous myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1989

Differing circadian patterns of symptom onset in subgroups of patients with acute myocardial infarction.

Circadian variation of the onset of acute myocardial infarction has been noted in many studies and may carry important pathophysiologic implications. However, only a few previous studies have attempted subgroup analyses. In 4,796 patients with documented acute myocardial infarction, the time of symptom onset was recorded. As in other studies, the peak of onset occurred in the morning from 6:01 AM to 12:00 noon, and 28% of the population (1.16 times the average percentage for the other time periods) experienced symptom onset in that period (p less than 0.001). There was a second, lower peak (25%) in the evening between 6:01 PM and 12:00 midnight, which was also observed in some previous studies. We sought to determine whether or not the presence of subgroups with specific clinical characteristics would exhibit different patterns and thereby contribute to these peaks in the overall population. In patients with a history of congestive heart failure (n = 606) or with non-Q wave infarction (n = 832), a pronounced peak (29%) occurred only in the evening. Two nearly equal peaks were observed in patients older than 70 years of age (n = 1,422), smokers (n = 2,057), diabetics (n = 767), women (n = 1,213), and patients taking beta-blocking drugs (n = 847). Finally, in patients with a previous myocardial infarction (n = 1,104), no peaks were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1989

Mechanisms of improved ischemic regional dysfunction by bradycardia. Studies on UL-FS 49 in swine.

In anesthetized swine, the left anterior descending coronary artery was cannulated and perfused at constant blood flow levels during two grades of ischemia. In one group (n = 10), moderate ischemia reduced percent systolic wall thickening (by sonomicrometry) from 25 +/- 7% to 6 +/- 2%, whereas in the other group (n = 7), severe ischemia reduced percent wall thickening from 24 +/- 6% to -0.5 +/- 4%. Heart rate was paced in both groups at 91 beats/min. After reperfusion and complete return to control conditions, administration of the bradycardic agent UL-FS 49 (0.37 mg/kg i.v.) decreased the heart rate to 55 +/- 5 beats/min. During subsequent ischemia at the same coronary inflow as before bradycardia, percent wall thickening in the ischemic zone during moderate ischemia was increased from 6 +/- 2% to 25 +/- 6% (p less than 0.01) (not significantly different from control without ischemia), and during severe ischemia, percent wall thickening increased from -0.5 +/- 4% to 13 +/- 7% (p less than 0.01). During moderate ischemia, bradycardia caused an increase in the subendocardial blood flow from 0.24 +/- 0.60 to 0.42 +/- 0.17 (ml/min)/g (p less than 0.009) and during severe ischemia, bradycardia caused an increase from 0.14 +/- 0.08 to 0.2 +/- 0.1 (ml/min)/g (p less than 0.001). At each level of ischemia, a more marked improvement occurred in subendocardial blood flow per beat ([(ml/min)/g]/heart rate). The relation between myocardial blood flow and wall function at a heart rate of 55 beats/min (n = 14) was plotted and compared with that studied at a heart rate of 122 beats/min in another group of pigs (n = 14). The increase in subendocardial blood flow per minute during bradycardia was not sufficient to explain the striking increase in function; thus, an independent relation (p less than 0.05) between blood flow per minute and contractile function (percent wall thickening) was found for for each heart rate. In contrast, when myocardial blood flow was normalized for heart rate and expressed per beat, data from both heart rate groups could be described by a single relation. Thus, the subendocardial blood flow per beat predicted wall function independently of heart rate and accounted for changes in both oxygen supply and demand.

Animals↗
PubMed1989

Consequences of regional inotropic stimulation of ischemic myocardium on regional myocardial blood flow and function in anesthetized swine.

Determination of the effect of inotropic stimulation on regionally ischemic and hypokinetic myocardium is complicated when intravenous administration of the inotropic agent also causes stimulation of nonischemic adjacent and distant regions, thereby altering global ventricular hemodynamics. To obviate such events, 16 anesthetized swine were studied during regional inotropic stimulation by infusion of dobutamine hydrochloride (2.5 +/- 1 microgram/min) into the cannulated left anterior descending coronary artery. Coronary inflow was controlled by a pump in an extracorporeal circuit. Two groups of swine with different degrees of ischemia were studied. In the first group of animals (n = 8), reduction in coronary inflow to produce a fall in coronary artery pressure (CAP) from 114 +/- 7 mm Hg to 62 +/- 2 mm Hg caused a decrease in percent systolic wall thickening (%WTh) from 34.6 +/- 8.1% to 25.4 +/- 5.8% (p less than 0.005). In the second group of animals (n = 8), CAP was decreased to 46 +/- 5 mm Hg (control: 115 +/- 8 mm Hg) and % WTh decreased from 34.1 +/- 16.4% to 10.4 +/- 6.9% (p less than 0.001). Subendocardial blood flow was reduced from 1.41 +/- 0.38 ml/min/g to 0.65 +/- 0.13 ml/min/g (group 1, p less than 0.001) and from 1.08 +/- 0.22 ml/min/g to 0.24 +/- 0.08 ml/min/g (group 2, p less than 0.001). Regional infusion of dobutamine caused asynchronous ventricular contraction with early systolic augmentation in wall thickening followed by late systolic thinning. Therefore, during hypoperfusion regional myocardial function assessed by %WTh remained unchanged (26.2 +/- 5.8%, p = NS) in group 1 and decreased significantly to 1.6 +/- 5.1% (p less than 0.041) in group 2. Subendocardial blood flow decreased to 0.44 +/- 0.15 ml/min/g in group 1 (p less than 0.005) and to 0.15 +/- 0.07 ml/min/g in group 2 (p less than 0.012). To account for the augmented early systolic thickening that occurred during asynchronous contraction, a myocardial work index was developed in which the sum of the instantaneous left ventricular pressure-wall thickness product was calculated for estimation of regional myocardial work. Increases in this work index were apparent with the addition of dobutamine at both levels of hypoperfusion. This significant enhancement in regional myocardial function in group 2 caused a significant increase of 16% (p less than 0.009) in overall left ventricular power during ejection. Thus, regional inotropic stimulation with dobutamine caused enhancement of maximum work of the ischemic myocardium in the steady state despite a further decrease in subendocardial blood flow.

Animals↗
PubMed1989

Pitch motion with random chord sequences.

Perception of global pitch motion was studied through psychoacoustic experiments with random chord sequences. Chords contained either six or eight (fixed) tone elements, being sinusoidal, sawtooth-like, or Shepard tones, which were either on or off according to a probability controlled by the experimenter. Sequences of 2, 4, 5, or 8 chords were used. Identification by subjects of the perceived direction of overall pitch motion (up or down) was found to be well accounted for by a model in which the ultimate pitch motion percept is given by a sum of contributions from selected element transitions--that is, transitions between adjoining tone elements in successive time frames only. In its simplest form, this dipole contribution model has only one free parameter, the perceptual noise for an element transition, which was estimated for various acoustic tone representations and chord arrangements. Results of two experiments, which were carried out independently in two different laboratories, are reported.

Adult↗
PubMed1989

Exonuclease activity that degrades histone mRNA is stable when DNA or protein synthesis is inhibited.

The induction and repression of histone synthesis during the cell cycle are regulated, in part, by modulating histone mRNA stability. When DNA synthesis stops, histone mRNA seems to be destabilized, perhaps via an autoregulatory circuit triggered by cytoplasmic histones. We have used an in vitro mRNA decay system to determine whether differential histone mRNA turnover is linked to changes in the basal activity of cytoplasmic mRNA-degrading enzymes. The basal level of the polysome-associated exonuclease enzyme or enzymes that degrade histone mRNA was similar in untreated cells and in cells exposed to DNA or protein synthesis inhibitors. Histone mRNA decay was accelerated in reactions supplemented with histones and soluble cytoplasmic factor(s) (S130), but S130s from control and inhibitor-treated cells were indistinguishable in these assays. The data indicate that basal exonuclease activity is stable or constitutive. The putative factor(s) required for autoregulating histone mRNA decay also do not change appreciably when DNA or protein synthesis is inhibited. The implications of these results with regard to the autoregulation of histone mRNA turnover are discussed.

Cycloheximide↗
PubMed1989

Benign metastasizing giant-cell tumor of bone. Report of three cases and review of the literature.

Three cases of benign giant-cell tumor (GCT) of bone with pulmonary metastasis are reported. In addition, 28 cases from the literature are reviewed. The patients were followed for a mean of 7.8 years (range from two to 29 years). The interval to metastasis ranged from zero to ten years with a mean of 3.2 years. Metastasis was not related to the number of previous operations. The local recurrence rate in the tumors that metastasized was 63%, suggesting that GCTs that metastasize may be an aggressive form of the tumor. The overall mortality rate was 16%. Persistent pulmonary disease does not carry a poor prognosis; surgical resection of accessible pulmonary nodules is recommended to provide histologic confirmation of the diagnosis, and prevent future complications secondary to local growth of the implants, as well as provide a potential cure. Chemotherapy has not improved survival and is associated with significant morbidity and is thus not recommended. Adjuvant radiation is recommended only for control of surgically unresectable lesions because of its potential association with sarcomatous degeneration in GCT.

Adult↗
PubMed1989

Non-Q-wave myocardial infarction: incidence, pathophysiology, and clinical course compared with Q-wave infarction.

Acute myocardial infarction can be stratified into electrocardiographic subsets based on the presence or absence of new Q waves. This stratification has important clinical and prognostic utility. Coronary angiography during acute non-Q-wave compared with Q-wave infarction shows much higher infarct-related artery patency rates (about 75 vs. 10%) and increased coronary collateralization. Culprit legion morphology in non-Q-wave infarction commonly is complex. The frequent demonstration of recurrent clinical ischemia, or residual thallium-201 uptake abnormalities, and metabolic activity on persistent emission tomography suggest the presence of viable myocardium in the distribution of the non-Q-wave infarction usually represents 20-25% of acute myocardial infarctions. The University of California San Diego Collaborative Postinfarction Database and other large studies have found non-Q-wave infarctions to be more common in patients with a history of previous infarction and congestive heart failure, although their mortality during acute hospitalization is lower. However, in long-term followup to one year and beyond, non-Q-wave infarct mortality rates equal those of Q-wave infarction. Patients at low early and late risk of mortality include those with a first infarction who are under age 70, whereas patients with evidence of residual ischemia postinfarction are at increased risk of events. It is interesting to speculate that the settings of unstable angina pectoris, non-Q-wave infarction, and perhaps the picture after thrombolysis for acute myocardial infarction, have pathophysiologic similarities which may carry implications for future research and therapy.

Electrocardiography↗
PubMed1989

Improving the validity of clinical exercise testing: the relationship between practice and performance.

Many studies involving exercise testing fail to address the issue of practice. Those that do vary considerably with respect to the parameters of practice used. We evaluated the effect of two standardized practices on a horizontal submaximal exercise test performed on a treadmill. Healthy men (n = 20) with no previous treadmill exposure were alternately assigned to the experimental (practice) or control (no practice) group. Heart rate (HR), systolic blood pressure (SBP), rate pressure product (RPP), step cadence (CAD) and perceived exertion (PE) were recorded at the end of each work load of the practices and/or tests. We observed no significant differences in these variables over the common work loads for the first practice session in the experimental group and the exercise test in the control group (p greater than 0.05). The two groups were homogeneous with respect to fitness and magnitude of arousal on initial exposure to the treadmill. During the submaximal test, HR, SBP, RPP, CAD, and PE were systematically lower for the experimental group than for the control group. The SBP and RPP were significantly lower in the experimental group (p less than 0.01). The CAD tended toward statistical significance (p less than 0.07), whereas HR and PE were not significantly different for the two groups (p greater than 0.05). When the four common work loads were compared over the two practices and the exercise test for the experimental group, SBP and CAD were significantly higher for practice 1 than for practice 2 and the test (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Acute myocardial infarction in women: influence of gender on mortality and prognostic variables.

The contention that mortality after acute myocardial infarction (AMI) is increased in women compared with men has been controversial, with findings in a recent multicenter study suggesting that gender plays an important prognostic role. To assess whether or not early and late mortality after AMI is greater in women, 2,089 patients (1,551 men, 538 women) were followed for 1 year after AMI. In the hospital, women had an increased mortality compared to men (17.5 vs 12.3%, p less than 0.003) and were on average 7 years older, whereas after hospital discharge and up to 1 year no difference in mortality was observed. Multivariate analyses of historical, clinical and laboratory features demonstrated that gender had no independent predictive value when variables that included age, congestive heart failure in the hospital, history of congestive failure, prior AMI and diabetes mellitus were considered. Moreover, when age stratification was performed, the significant difference of in-hospital mortality between genders was no longer present. Causes of death in the hospital and during 1 year after hospital discharge were similar between men and women, whether or not age stratification was performed. Several baseline clinical characteristics were different between men and women; a history of systemic hypertension and congestive heart failure occurred more frequently in women and previous AMI and smoking occurred more commonly in men. Also, the value of several other important prognostic indicators after AMI, such as the ejection fraction, was found to differ between men and women.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

Influence on prognosis and morbidity of left ventricular ejection fraction with and without signs of left ventricular failure after acute myocardial infarction.

The left ventricular (LV) ejection fraction (EF) is known to be an independent predictor of late prognosis after acute myocardial infarction. Despite a previous report that early heart failure (evidenced only by advanced pulmonary rales in the hospital) can predict prognosis in the absence of severe depression of the LVEF at hospital discharge, the potentially strong influence of various measures of in-hospital heart failure on the predictive ability of LVEF has not been generally appreciated. Accordingly, in 972 patients with acute myocardial infarction the effect on late mortality of the presence or absence in-hospital of both clinical and radiographic signs of LV failure in subgroups of patients with normal, moderately or severely depressed LVEF was examined and measured close to hospital discharge. Patients were divided into 3 groups according to LVEF: group I LVEF less than or equal to 40, n = 265; group II LVEF 0.41 to 0.50, n = 241 and group III LVEF greater than or equal to 0.51, n = 466. When clinical signs of LV failure were present at any time during the coronary care unit period, the 1-year mortality rate after hospital discharge in groups I, II and III was 26, 19 and 8%, compared with 12% (p less than 0.01), 6% (p less than 0.01) and 3% (p less than 0.02), respectively, when signs of LV failure were absent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Role of calcium channel blockers in experimental exercise-induced ischemia.

Calcium channel blockers, which induce vasodilation by relaxing vascular smooth muscle cells, have proven effective in the treatment of angina pectoris. To study mechanisms of calcium blockade in ischemic heart disease, conscious chronically instrumented dogs with a single coronary artery ameroid constrictor were studied during steady-state treadmill runs which induced regional myocardial ischemia. During exercise-induced ischemia, regional systolic wall thickening and subendocardial blood flow were both significantly reduced in the ischemic zone. Calcium channel blockade with verapamil, diltiazem, or nifedipine enhanced regional systolic wall thickening. Regional subendocardial blood flow in the ischemic region, measured during diltiazem and nifedipine experiments, improved during exercise. Reduced coronary artery resistance in the native vessels and/or recruitment of collaterals appears to largely explain the increased total myocardial blood supply in the jeopardized area and the increased function. However, after diltiazem, reduced exercise heart rates as well as reduced left ventricular end-diastolic pressure also contributed to the improvement in the oxygen-supply imbalance in the ischemic myocardium. These data provide a basis for understanding the efficacy of calcium channel blocker treatment in patients with coronary artery disease.

Animals↗
PubMed1988

First myocardial infarction: age and ejection fraction identify a low-risk group.

This study examines patients with a first myocardial infarction (MI) (about 70% of the population, n = 2089), and identifies factors associated with 1-year cardiac mortality in patients discharged alive. With the use of multivarate analysis of variables observed at hospital discharge in patients with a first MI, age was the most important predictor, followed by left ventricular ejection fraction (LVEF) (determined in 56%) and other variables. Based on this finding, age subsets (less than or equal to 50, 51 to 70, greater than 70 years) were related to LVEF groups (less than or equal to 0.40, 0.41 to 0.50, greater than 0.50). Patients with a first MI who were less than 50 years of age with LVEF greater than 0.40 and patients between 51 and 70 years of age with LVEF greater than 0.50 had a very low risk for 1-year cardiac death, 1.2 +/- 1.1% (95% confidence interval). Such patients comprised 47% of individuals with a first MI having an LVEF determination. Mortality in the remaining patients less than 70 years was 7.4 +/- 3.5%. Mortality for patients greater than 70 years was high, 22.2 +/- 6.6%. Thus with LVEF as the only predischarge test, a sizable low risk group can be identified among patients with a first MI.

Age Factors↗
PubMed1988

Mutational spectrum and recombinogenic effects induced by aminofluorene adducts in bacteriophage M13.

Double-stranded replicative form (RFI) DNA of bacteriophage M13 strain M13mp10 which carries partial lacZ gene has been modified in vitro to various extents with N-hydroxy-2-amino-fluorene (N-OH-AF) and then transfected into E. coli cells. High-performance liquid chromatography (HPLC) analysis results demonstrate that the sole adduct (95%) formed in modified DNA is N-(deoxyguanosine-8-yl)-2-aminofluorene (dG-C8-AF). Approximately 20 adducts per RFI molecule constitute 1 lethal event when plaque-forming ability is assayed on E. coli cells which have received no prior SOS induction. The mutagenicity of dG-C8-AF adducts was assayed by measuring loss of beta-galactosidase activity as a function of adducts per molecule. A dose-dependent increase in Lac- mutants was observed, with a 4-fold increase in mutants per survivor at 30 adducts/molecule. The mutations produced, characterized by DNA sequencing, occur predominantly at either G or C positions different from those observed in the spontaneous mutant spectrum. Restriction-mapping results show that in our assay system, dG-C8-AF adducts induce a previously unreported recombinogenic activity.

Bacteriophages↗