Annals of medicine
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Hypertrophic cardiomyopathy (HCM) is a genetically and clinically heterogeneous myocardial disease caused by mutations in genes encoding sarcomeric proteins. To assess the genetic background and phenotypic expression of HCM in eastern Finland, we screened 35 unrelated patients with HCM from the Kuopio University Hospital area for variants in 9 genes encoding sarcomeric proteins with the PCR-SSCP method. We herewith describe our previous findings in five sarcomeric genes and also report hitherto unpublished data on four additional sarcomeric genes. ⋯ Altogether, the aforementioned 6 mutations found in MYBPC3, TPM1, and MYH7 accounted for 61% of familial and 40% of all HCM cases. The mutations were associated mostly with benign or intermediary phenotypes with only few HCM-related deaths. We conclude that the genetic profile of HCM in eastern Finland is unique, characterized by few founder mutations with benign or intermediary phenotypes.
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Patients with the 3243A > G mutation in mitochondrial DNA (mtDNA) have an increased risk for cardiovascular morbidity and mortality. The function of the autonomic nervous system has not been evaluated in these patients. ⋯ Patients with the 3243A > G mutation in mtDNA have abnormalities in the spectral and fractal characteristics of HRV suggesting altered cardiac autonomic regulation. The abnormalities are not clearly associated with clinical manifestations related to 3243A > G suggesting that mitochondrial dysfunction may affect the autonomic regulatory systems more directly.
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Review
DISC1 and DISC2: discovering and dissecting molecular mechanisms underlying psychiatric illness.
A balanced (1;11)(q42;q14) translocation co-segregates with schizophrenia and major affective disorders in a large Scottish family. The translocation breakpoint on chromosome 1 is located within the Disrupted in Schizophrenia 1 and 2 genes (DISC1 and DISC2). Consequently loss of normal function of these genes is likely to underlie the susceptibility to developing psychiatric disorders that is conferred by inheritance of the translocation. ⋯ Intriguingly, all data obtained to date point towards an involvement in processes critical to neurodevelopment and function. DISC2 has not been studied in detail, but is likely to modulate DISC1 expression. Overall, it is clear from the combination of genetic and functional data that DISC1 and/or DISC2 are emerging as important factors in the molecular genetics of psychiatric illness.
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Leptin is best known as a regulator of energy homeostasis, but it also interacts with sleep and breathing. Leptin secretion increases at night and decreases during the day. The circadian secretory profile of leptin is determined both by the hypothalamic circadian pacemaker and sleep-wake cycle. ⋯ Serum leptin levels are higher in obstructive sleep apnoea syndrome but lower during extended sleep deprivation in healthy subjects or in narcolepsy. Abnormalities in serum leptin concentrations have recently been linked with deleterious effects on weight control, cardiovascular health and glucose regulation. Since sleep curtailment and sleep-disordered breathing are epidemics of the modern society, better understanding of leptin pathophysiology could open new perspectives to pathophysiology of major public diseases, including obesity and metabolic syndrome.
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The pathophysiology of tobacco-related diseases is complex and multifactorial. Among the approximately 4,000 compounds in tobacco smoke are carcinogens such as nitrosamines, irritants such as a variety of phenolic compounds, volatiles such as carbon monoxide, and of course nicotine. ⋯ This review discusses the mechanisms by which nicotine contributes to tobacco-related disease, with a focus on the surprising new finding that nicotine is a potent angiogenic agent. Nicotine hijacks an endogenous nicotinic cholinergic pathway present in endothelial cells that is involved in physiological, as well as pathological angiogenesis.