Studies to localize and characterize the isoform specific functional differences between cardiac and skeletal troponin C

Thin filament regulation of muscle contraction is a calcium dependent process mediated by the Tn complex. Calcium is released into the sarcomere and is bound by TnC. The subsequent conformation change in TnC is thought to begin a cascade of events that result in the activation of the actin-myosin ATPase. While the general events of this cascade are known, the molecular mechanisms of this signal transduction event are not. Recombinant DNA techniques, physiological and biochemical studies have been used to localize and characterize the structural domains of TnC that play a role in the calcium dependent signal transduction event that serves to trigger muscle contraction. The strategy exploited the observed functional differences between the isoforms of TnC to map regions of functional significance to the proteins. Chimeric cardiac-skeletal TnC proteins were generated to localize the domains of TnC that are required for maximal function in the myofibrilar ATPase assay. Characterization of these regions has yielded information concerning the molecular mechanism of muscle contraction. ^

Pathways linking socioeconomic position and diabetes: The role of psychosocial factors

Despite increasing interest in the relationship between socioeconomic position (SEP) and health, there remains little understanding of the mechanisms through which SEP is related to chronic disease. This dissertation utilized data from 2,592 U.S. households in the 1995 telephone survey of the Aging, Status, and the Sense of Control study to: (1) investigate potential mediating factors in the association between educational level and prevalence of diabetes and (2) to investigate the association between the three major measures of SEP—income, education, and occupation—and the prevalence of diabetes. Regression analyses were conducted to examine the degree to which sense of personal control and social support mediate the association between level of educational attainment and diabetes and to examine the contribution of each of the SEP measures to diabetes. After adjusting for age, obesity, sex, and race, respondents with less than a high school education had greater odds of having diabetes than those with a college degree or higher level of educational attainment, although the corresponding confidence interval contained the null value (OR = 1.2, 95% CI: 0.7, 2.0). Neither sense of control nor social support significantly mediated the association between education and diabetes. However, sense of control was associated with diabetes status (OR = 0.7, 95% CI: 0.5, 1.0). Compared with income and education, employment status was the most strongly associated measure of SEP with diabetes prevalence. After adjusting for age, obesity, sex, and race, respondents who were unable to work due to disability had fourfold greater odds of having diabetes than those who were employed full time (OR = 4.0; 95% CI: 1.9, 8.3). Adding income and/or education to the model did not improve the fit. Understanding the impact of socioeconomic factors on diabetes requires consideration of multiple measures of SEP as well as the psychosocial pathways through which SEP may influence diabetes. ^

Thrombolytic therapy for acute myocardial infarction: A cohort study to evaluate a selective approach to invasive diagnosis and therapy. The Corpus Christi Heart Project

Coronary perfusion with thrombolytic therapy and selective reperfusion by percutaneous transluminal coronary angioplasty (PTCA) were examined in the Corpus Christi Heart Project, a population-based surveillance program for hospitalized acute myocardial infarction (MI) patients in a biethnic community of Mexican-Americans (MAs) and non-Hispanic whites (NHWs). Results were based on 250 (12.4%) patients who received thromobolytic therapy in a cohort of 2011 acute MI cases. Out of these 107 (42.8%) underwent PTCA with a mean follow-up of 25 months. There were 186 (74.4%) men and 64 (25.6%) women; 148 (59.2%) were NHWs, 86 (34.4%) were MAs. Thrombolysis and PTCA were performed less frequently in women than in men, and less frequently in MAs than in NHWs.^ According to the coronary reperfusion interventions used, patients were divided in two groups, those that received no-PTCA (57.2%) and the other that underwent PTCA (42.8%) after thrombolysis. The case-fatality rate was higher in no-PTCA patients than in the PTCA (7.7% versus 5.6%), as was mortality at one year (16.2% versus 10.5%). Reperfusion was successful in 48.0% in the entire cohort and (51.4% versus 45.6%) in the PTCA and no-PTCA groups. Mortality in the successful reperfusion patients was 5.0% compared to 22.3% in the unsuccessful reperfusion group (p = 0.00016, 95% CI: 1.98-11.6).^ Cardiac catheterization was performed in 86.4% thrombolytic patients. Severe stenosis ($>$75%) obstruction was present most commonly in the left descending artery (52.8%) and in the right coronary artery (52.8%). The occurrence of adverse in-hospital clinical events was higher in the no-PTCA as compared to the PTCA and catheterized patients with the exception of reperfusion arrythmias (p = 0.140; Fisher's exact test p = 0.129).^ Cox regression analysis was used to study the relationship between selected variables and mortality. Apart from successful reperfusion, age group (p = 0.028, 95% CI: 2.1-12.42), site of acute MI index (p = 0.050) and ejection-fraction (p = 0.052) were predictors of long-term survival. The ejection-fraction in the PTCA group was higher than (median 78% versus 53%) in the no-PTCA group. Assessed by logistic regression analysis history of high cholesterol ($>$200mg/dl) and diabetes mellites did have significant prognostic value (p = 0.0233; p = 0.0318) in long-term survival irrespective of treatment status.^ In conclusion, the results of this study support the idea that the use of PTCA as a selective intervention following thrombolysis improves survival of patients with acute MI. The use of PTCA in this setting appears to be safe. However, we can not exclude the possibility that some of these results may have occurred due to the exclusion from PTCA of high risk patients (selection bias). ^