Hepatology : official journal of the American Association for the Study of Liver Diseases
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Cystic fibrosis transmembrane conductance regulator (CFTR), the cystic fibrosis (CF) gene product, functions as an adenosine 3', 5'-cyclic monophosphate (cAMP)-regulated chloride channel in the apical membrane of biliary epithelial cells, including gallbladder epithelial cells. It has been shown that triangle upF508, the most common CF mutation, impedes CFTR trafficking to the apical surface of epithelial cells. To elucidate the mechanisms of CF biliary disease, we examined structural features, CFTR expression, and chloride transport properties in gallbladder epithelial cells from nine triangle upF508 homozygous liver transplant recipients. ⋯ The CF cells exhibited a residual cAMP-dependent chloride secretion that was inversely correlated with ATP-induced chloride secretion, and almost completely blunted in the cells derived from microgallbladders. Our results suggest that epithelial structural alterations aggravate triangle upF508 CFTR mislocalization in the gallbladder epithelium. The associated decrease in residual cAMP-dependent chloride secretion may contribute to biliary damage despite the up-regulation of alternative chloride transport pathways.
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The health care system in the United States is at a turning point. We are experiencing a shift in focus from structure and process to outcomes, and from specific clinical outcomes to generic outcomes. ⋯ Rather, payers, employers, and patients themselves demand evidence that the health care system produces patients who feel better, can do more, and are confident about their health. These concepts, collectively referred to as Health-Related Quality of Life (HQL), are an important aspect of the natural history of liver diseases and an important means of assessing the results of therapeutic interventions.