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R S Blumenthal

Publications and source records attributed to R S Blumenthal.

45 records · Page 3Linked to original sources

Effects of chronic ethanol exposure on cardiac receptor-adenylyl cyclase coupling: studies in cultured embryonic chick myocytes and ethanol fed rats.

Ethanol effects in the brain appear to be mediated at least in part by an alteration in receptor-effector coupling via guanine nucleotide-binding regulatory proteins (G proteins). To test the hypothesis that a similar pathway participates in the cardiotoxic effects of ethanol, we assessed the effects of chronic ethanol on two commonly used experimental models: embryonic chick myocytes in culture and ventricular myocardium from chronically fed rats. Ethanol had no effect on either the function or quantity of G proteins as assessed by effector-stimulated adenylyl cyclase activity and the levels of ADP-ribosylation substrates. In contrast, effector-stimulated adenylyl cyclase activity was significantly altered in the liver of ethanol-fed rats. These results suggest that receptor-effector coupling via G proteins in our two cardiac models is insensitive to ethanol and that ethanol effects may be species or organ specific.

ADP-Ribosylation Factors↗

Diminished beta-adrenergic receptor responsiveness and cardiac dilation in hearts of myopathic Syrian hamsters (BIO 53.58) are associated with a functional abnormality of the G stimulatory protein.

Previous studies have demonstrated a diminution in the bioactivity of the guanine nucleotide-binding regulatory protein that stimulates adenylyl cyclase (Gs) in hearts of the hypertrophic BIO 14.6 Syrian hamster. In this study, we measured functional activity and immunodetectable levels of Gs in a mutant strain of hamsters (BIO 53.58) that develop a dilated cardiomyopathy. Pathological studies demonstrated that 100-day-old BIO 53.58 hamsters had substantial ventricular dilation when compared with age-matched F1B controls. Additionally, these 100-day-old hamsters demonstrated diminished contractile response to beta-adrenergic receptor stimulation. The pathological and hemodynamic changes were associated with defective coupling of Gs to adenylyl cyclase as adenylyl cyclase activation was distinctly decreased in the presence of isoproterenol, fluoride ion, guanine nucleotides, and forskolin. Additionally, the ability of the alpha-subunit of Gs to reconstitute isoproterenol-stimulated adenylyl cyclase activity in S49 cyc- membranes was reduced approximately 65%. By contrast, cyc- complementation assays did not reveal a difference between the functional activity of Gs in hearts from 30-day-old BIO 53.58 hamsters and F1B controls. Furthermore, beta-adrenergic receptor stimulation of adenylyl cyclase in the membranes of the young BIO 53.58 hamsters was not significantly different from controls. The substantial alterations in Gs bioactivity in hearts of the 100-day-old BIO 53.58 hamsters was not associated with alterations in the immunodetectable levels of either alpha Gs or alpha Gi on Western Blots. These results suggest that G protein changes are associated with ventricular dilation in BIO 53.58 hamsters and that G protein levels are not always reflective of G protein bioactivity.

Adenylyl Cyclases↗

Antagonistic behavior, dominance, hostility, and coronary heart disease.

PURPOSE: This study investigated the relationship between antagonistic behavior, dominance, attitudinal hostility, and coronary heart disease (CHD). METHODS: One hundred one men and 95 women referred for thallium stress testing were administered the Structured Interview and the Cook-Medley Hostility Scale. The Hostile Behavior Index, derived from the Structured Interview and developed by Haney et al., served as an index of antagonism, and the frequency with which interviewees interrupted their interviewer served as a measure of dominance. On the basis of their medical history and thallium stress test results, patients were classified as having (N = 44) or not having (N = 99) CHD. RESULTS AND CONCLUSIONS: Multivariate logistic regressions (with age, gender, disease, and lifestyle risk factors in the model) revealed that both the Hostile Behavior Index and dominance were significant independent risk factors for CHD (relative risk [RR] = 1.22 and 1.47, p < .03). Of the two Hostile Behavior Index component scores, indirect challenge and irritability, only the latter correlated significantly with CHD (RR = 1.27, p < .03). Separate logistic regressions for men and women suggest that subtle, indirect manifestations of antagonism confer CHD risk in women and that more overt expressions of anger confer risk in men. A significant univariate correlation between hostility scale scores and CHD became not significant when we adjusted for socioeconomic status.

Aged↗

ABCs of cardiovascular disease risk management.

The past 20 years have witnessed a marked decline in morbidity and mortality from cardiovascular disease. This decline has been due in large part to advances in coronary risk factor modification and a better understanding of the atherosclerotic process. Compelling scientific and clinical trial evidence proves that comprehensive risk factor modification extends patient survival and reduces cardiovascular and cerebrovascular events. This article reviews the ABCs of optimal medical and lifestyle management in patients with documented atherosclerotic vascular disease as well as in those adults who are at increased risk for the development of cardiovascular disease, based on contemporary clinical trial evidence.

Adrenergic beta-Antagonists↗

Optimal management of dyslipidemia in women and men.

Relatively few studies have examined the clinical effectiveness of cholesterol-lowering drugs in women as compared with men. Most clinical trials do indicate that cholesterol lowering reduces clinical events equally effectively in both genders. However, high-density lipoprotein cholesterol and triglyceride levels may have more prognostic significance in women. The recent finding of a higher risk of death in younger women as compared with younger men who sustain a heart attack, combined with the high proportion of morbidity and mortality due to CHD in older women, emphasizes the need for a better understanding of heart disease in women. This review explores the similarities and differences between women and men regarding the management of dyslipidemia.

Aged↗

Racial differences in low-density lipoprotein particle size in families at high risk for premature coronary heart disease.

OBJECTIVE: Although small, dense low-density lipoprotein (LDL) has been implicated in atherogenesis and coronary heart disease (CHD) events, little is known about possible racial differences in LDL particle size. This study was designed to examine racial differences in the prevalence of small, dense LDL among 159 African-American and 477 White siblings of persons with premature (<60 years of age) CHD. METHODS AND RESULTS: This study examined fasting levels of total cholesterol, LDL cholesterol, high-density lipoprotein cholesterol, apolipoprotein B (ApoB), apolipoprotein A-1, and triglycerides, as well as factors known to be associated with small, dense LDL, including age, sex, obesity, hypertension, and diabetes. Relative LDL particle size was defined by the LDL cholesterol to ApoB ratio. Direct measurement of LDL particle size was obtained by proton NMR spectroscopy in a subset of 64 siblings. Despite similar levels of total and LDL cholesterol, White siblings were more likely to have low LDL cholesterol to ApoB ratios, indicative of atherogenic small, dense LDL, compared with African-American siblings. Multiple logistic regression analysis predicting the presence of LDL cholesterol/ApoB < or = 1.0 demonstrated that race (P = .009), triglyceride level (P = .0001), and diabetes (P = .02) were independent predictors, controlling for age and all other variables. Direct measurement of LDL particle size by NMR spectroscopy supported these findings. CONCLUSION: These findings provide the first known evidence that White individuals from a population at high risk for premature CHD have a greater probability of having a preponderance of small, dense LDL particles than do African Americans, independent of triglyceride levels, and despite comparable levels of total and LDL cholesterol.

Adult↗

Prevalence of hypercholesterolemia among siblings of persons with premature coronary heart disease. Application of the Second Adult Treatment Panel guidelines.

BACKGROUND: Increased blood cholesterol, specifically high low-density lipoprotein cholesterol, increases risk for coronary heart disease (CHD). Persons with a positive family history of premature CHD also are at markedly increased risk. OBJECTIVE: To examine the prevalence of hypercholesterolemia based on the second report of the National Cholesterol Educational Program Adult Treatment Panel (ATP II) guidelines in the asymptomatic healthy siblings of people with premature CHD. METHODS: A total of 668 asymptomatic healthy siblings (354 men and 314 women) underwent screening for risk factors for CHD. Siblings were categorized into treatment categories for primary prevention defined by ATP II. The percentage who were candidates for intervention were compared with the published national estimates for those without CHD from the third National Health and Nutrition Examination Survey (NHANES III). RESULTS: Based on ATP II guidelines, 65% of the asymptomatic adult siblings required fasting lipoprotein analysis compared with 33% of adults without CHD in the national reference population. Of the siblings who met the criteria for fasting lipoprotein analysis, most (56%) were candidates for dietary therapy, more than twice the proportion of adults from NHANES III. The percentage of the siblings who qualified for drug intervention and dietary therapy was 3 times greater than the national sample, 33% vs 11%, respectively. Assuming a 10% hypothetical reduction in low-density lipoprotein cholesterol levels as the result of dietary modification, the proportion of the sibling sample who were possible candidates for drug therapy was 20%, still 4 times that predicted for the national sample. CONCLUSIONS: These results underscore the need for aggressive detection and treatment of hypercholesterolemia in this easily identifiable high-risk population of siblings of people with premature CHD.

Adult↗