Severe left ventricular hypertrophy in Anderson-Fabry disease.
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Biomedical subjects
Publications and source records attributed to D L Connolly.
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The recent discovery of aquaporins, a family of highly conserved water channel proteins, which are expressed in both eukaryotes and prokaryotes, has provoked a re-evaluation of the physiology of water transport in all organisms. So far, seven distinct aquaporins have been characterised in mammals, but highly homologous family members have also been found in amphibians, insects, plants and bacteria. These transmembrane proteins serve to facilitate water transport down osmotic gradients with low activation energy. Alterations in channel expression, cellular targeting and perhaps channel permeability regulate membrane water transport. Naturally occurring and experimentally produced mutations in aquaporins cause a variety of perturbations of water homeostasis. Manipulation of aquaporin expression may have a therapeutic role in several disease processes including cardiac failure and the ascites associated with liver disease.
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The in vivo diagnosis of right atrial thrombus is difficult by transthoracic echocardiography and it is likely that small thrombi are underdiagnosed using this approach. Transoesophageal echocardiography provides an unobstructed view of cardiac structures and the great vessels. In this report we describe the findings in five patients with right atrial thrombi that illustrate the potential usefulness of transoesophageal echocardiography for both the initial diagnosis and the subsequent management of these patients.
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Bacterial endocarditis may present with acute chest pain due to coronary embolization and mimics acute myocardial infarction secondary to coronary atherosclerosis. We present the first case report of coronary embolization secondary to aortic valve endocarditis treated with standard doses of streptokinase and aspirin. The patient survived but sustained a large myocardial infarction and a major gastrointestinal bleed. Infective endocarditis should be considered in all patients presenting with acute chest pain. When myocardial infarction is due to coronary embolism from endocarditic valves standard thrombolysis regimes should be avoided.
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The aquaporins are a rapidly expanding family of highly conserved proteins which function as transmembrane water channels. We have previously shown that the gene for aquaporin-1 (AQP-1) is expressed in rat, aortic vascular smooth muscle cells (VSMCs) implying a specific role for AQP-1 in vascular function. In this study we set out to document the expression of AQP-1 in human arteries and found mRNA and protein in normal endothelial and VSMCs of human arteries and capillaries and in a subset of VSMCs in human atherosclerotic plaques. Secondly, we examined the regulation of AQP-1 gene expression during vascular development and following vascular injury. Studies in the rat demonstrated that AQP-1 mRNA is induced in the neonatal aorta at week 2 of postnatal development and that the protein is present in neointimal VSMCs following balloon injury. Finally, by measuring the rate of change in cell size induced by changes in external osmolarity and demonstrating that water transport can be inhibited with mercuric chloride, we show that AQP-1 is responsible for water transport across human VSMC membranes. Thus, this study provides evidence for a hitherto unrecognised role for aquaporins in mediating rapid water transport across human VSMC membranes. By analogy with other tissues, these data argue for an important role for AQP-1 in regulating transcellular fluid flow and tissue hydration.