Metabolome, transcriptome, and bioinformatic cis-element analyses point to HNF-4 as a central regulator of gene expression during enterocyte differentiation.

DNA-binding transcription factors bind to promoters that carry their binding sites. Transcription factors therefore function as nodes in gene regulatory networks. In the present work we used a bioinformatic approach to search for transcription factors that might function as nodes in gene regulatory networks during the differentiation of the small intestinal epithelial cell. In addition we have searched for connections between transcription factors and the villus metabolome. Transcriptome data were generated from mouse small intestinal villus, crypt, and fetal intestinal epithelial cells. Metabolome data were generated from crypt and villus cells. Our results show that genes that are upregulated during fetal to adult and crypt to villus differentiation have an overrepresentation of potential hepatocyte nuclear factor (HNF)-4 binding sites in their promoters. Moreover, metabolome analyses by magic angle spinning (1)H nuclear magnetic resonance spectroscopy showed that the villus epithelial cells contain higher concentrations of lipid carbon chains than the crypt cells. These findings suggest a model where the HNF-4 transcription factor influences the villus metabolome by regulating genes that are involved in lipid metabolism. Our approach also identifies transcription factors of importance for crypt functions such as DNA replication (E2F) and stem cell maintenance (c-Myc).

[Right ventricle myocardial infarction from personal observations]. / Zawal prawej komory serca w obserwacjach wlasnych.

In 2514 patients with myocardial infarction (1961 male and 823 female) hospitalized between 1991 and 1997 right ventricle myocardial infarction was diagnosed based on of V3R-V5R electrocardiographic leads tracing in 147 patients aged 35-86 (105 male and 42 female), which means 5.4% of treated patients. Only one case of isolated right ventricle infarction was observed. In other cases it coexisted with left ventricle infarction--most often with inferior myocardial infarction (118 cases, which means 10.7% cases with this localization). Streptokinase was administered to 64 patients with right ventricle infarction, which means 43.5% treated. 10 patients, including 5 female, deceased during the hospitalization, hospital mortality was 6.8%. Cardiogenic shock was the reason of death in all cases. The frequency of concomitant chronic diseases (hypertension, congestive heart failure, diabetes mellitus) and hyperlipidaemia (hypercholesterolaemia and/or hypertriglyceridaemia), as well as arrhythmia and conduction disturbances, in patients with right ventricle myocardial infarction did not differ from the ones estimated in people with left ventricle infarction. According to the analysis of our own material (the most numerous group of patients as juxtaposed to ones observed by other authors) inferior myocardial infarction is most commonly accompanied by right ventricle infarction. Low hospital mortality in these patients is connected with fibrinolytic therapy. The performance of V3R-V5R electrocardiographic leads tracing is indispensable in patients with acute myocardial infarction. The diagnosis of right ventricle infarction is highly important because of the specific treatment of these patients.