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Function of contractile and cytoskeletal proteins in smooth muscle: Effects of hypertrophy and age and desmin removal in a transgenic animal.

In man, the urinary bladder responds to an urinary outflow obstruction with a pronounced dilatation and growth of the bladder wall. This clinical situation can be mimicked in rat by creation of a partial urinary outflow obstruction and the papers included in the present thesis use this animal model to address questions regarding the adaptive changes in the smooth muscle of the growing bladder. In

Pro- and anticoagulant activities of factor V

Coagulation factor V (FV) is activated by thrombin through proteolytic cleavage at Arg-709, Arg-1018 and Arg-1545. Upon thrombin activation, the active form of factor V (FVa) is formed. FVa functions as a cofactor to factor Xa in the conversion of prothrombin to thrombin during coagulation. Recently, it was shown that in addition to being a precursor form of the procoagulant FVa, FV functions as a

Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease.

Monogenic causes of autoimmunity provide key insights into the complex regulation of the immune system. We report a new monogenic cause of autoimmunity resulting from de novo germline activating STAT3 mutations in five individuals with a spectrum of early-onset autoimmune disease, including type 1 diabetes. These findings emphasize the critical role of STAT3 in autoimmune disease and contrast with

Genetic vasopressin 1b receptor variance in overweight and diabetes mellitus.

Recently, imbalance in the vasopressin (AVP) system, measured as elevated levels of copeptin (the c-terminal part of the AVP pro-hormone) in plasma, was linked to development of abdominal obesity and diabetes mellitus (DM). Here, we aim to investigate if genetic variation of the human AVP receptor 1b gene (AVPR1B) is associated with measures of obesity and DM.

Reduced risk of death with warfarin - results of an observational nationwide study of 20 442 patients with atrial fibrillation and ischaemic stroke

BackgroundWarfarin is demonstrated to be superior in efficacy over antiplatelet agents for the prevention of stroke, but the relationship between warfarin and mortality is less clear. Our aim was to investigate this relationship in a large cohort of unselected patients with atrial fibrillation and ischaemic stroke. MethodsThis observational study was based on patients who were discharged alive and

Inhibition of HIV-1 disease progression by contemporaneous HIV-2 infection.

BACKGROUND: Progressive immune dysfunction and the acquired immunodeficiency syndrome (AIDS) develop in most persons with untreated infection with human immunodeficiency virus type 1 (HIV-1) but in only approximately 20 to 30% of persons infected with HIV type 2 (HIV-2); among persons infected with both types, the natural history of disease progression is poorly understood. METHODS: We analyzed d

Collagen and related extracellular matrix proteins in atherosclerotic plaque development.

The structure, composition and turnover of the extracellular matrix (ECM) as well as cell-matrix interactions are crucial in the developing atherosclerotic plaque. There is a need for further insight into specific proteins in the ECM and their functions in the developing plaque, and during the last few years a number of publications have highlighted this very important field of research. These nov

Polymorphisms in inflammation associated genes ALOX15 and IL-6 are associated with bone properties in young women and fracture in elderly.

ALOX12 and ALOX15 encode arachidonate lipoxygenases which produce lipid metabolites involved in inflammatory processes. Metabolites generated by ALOX12 and ALOX15 can activate the expression of the potent pro-inflammatory cytokine IL-6, and produce endogenous ligands for PPARG. In this study, polymorphisms in ALOX12, ALOX15, IL6 and PPARG were investigated for association with bone properties in y

Exome Sequencing and Directed Clinical Phenotyping Diagnose Cholesterol Ester Storage Disease Presenting as Autosomal Recessive Hypercholesterolemia.

Autosomal recessive hypercholesterolemia is a rare inherited disorder, characterized by extremely high total and low-density lipoprotein cholesterol levels, that has been previously linked to mutations in LDLRAP1. We identified a family with autosomal recessive hypercholesterolemia not explained by mutations in LDLRAP1 or other genes known to cause monogenic hypercholesterolemia. The aim of this s

Gene-Lifestyle Interaction and Type 2 Diabetes: The EPIC InterAct Case-Cohort Study.

Understanding of the genetic basis of type 2 diabetes (T2D) has progressed rapidly, but the interactions between common genetic variants and lifestyle risk factors have not been systematically investigated in studies with adequate statistical power. Therefore, we aimed to quantify the combined effects of genetic and lifestyle factors on risk of T2D in order to inform strategies for prevention.

Thrombus Aspiration during ST-Segment Elevation Myocardial Infarction.

Background The clinical effect of routine intracoronary thrombus aspiration before primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) is uncertain. We aimed to evaluate whether thrombus aspiration reduces mortality. Methods We conducted a multicenter, prospective, randomized, controlled, open-label clinical trial, with enrollment of

Epigenetic alterations in human liver from subjects with type 2 diabetes in parallel with reduced folate levels.

Epigenetic variation may contribute to the development of complex metabolic diseases such as type 2 diabetes (T2D). Hepatic insulin resistance is a hallmark of T2D. However, it remains unknown if epigenetic alterations take place in the liver from diabetic subjects. Therefore, we investigated the genome-wide DNA methylation pattern in the liver from subjects with T2D and non-diabetic controls and

Plasma S100A8/A9 Correlates With Blood Neutrophil Counts, Traditional Risk Factors, and Cardiovascular Disease in Middle-Aged Healthy Individuals.

The S100 alarmins A8, A9, and A8/A9, secreted by activated neutrophils and monocytes/macrophages, are involved in the pathogenesis of various inflammatory diseases. S100A8/A9 has previously been linked to atherogenesis and cardiovascular (CV) disease. We investigated whether S100A8, A9, and A8/A9 correlate with carotid artery disease and CV risk in apparently healthy individuals.

Type 2 diabetes susceptibility gene variants predispose to adult-onset autoimmune diabetes

Aims/hypothesis Latent autoimmune diabetes in adults (LADA) is phenotypically a hybrid of type 1 and type 2 diabetes. Genetically LADA is poorly characterised but does share genetic predisposition with type 1 diabetes. We aimed to improve the genetic characterisation of LADA and hypothesised that type 2 diabetes-associated gene variants also predispose to LADA, and that the associations would be s

Mucosal glucagon-like peptide-1 and gastric inhibitory polypeptide cell numbers in the super-obese human foregut after gastric bypass.

Super-obesity, a body mass index>50 kg/m(2), is difficult to treat. Many studies have focused on the anatomic changes of the intestines; the physiologic background is not clearly identified. It is established that Roux-en-Y gastric bypass (RYGB) augments secretion of glucagon-like peptide-1 (GLP-1), peptide tyrosine tyrosine (PYY), and insulin, but other aspects of gut hormone cell function in the