Hepatic cytochrome P450 down‐regulation during aseptic inflammation in the mouse is interleukin 6 dependent

Elmar Siewert, Roque Bort, Reinhart Kluge, Peter C. Heinrich, José Castell, Ramiro Jover – 30 December 2003 – Expression of cytochromes P450 (CYP) is markedly reduced during inflammatory processes. In vitro studies with hepatocytes have shown that cytokines generated during these processes down‐regulate CYP. However, it is not clear to what extent each individual cytokine contributes to the overall reduced expression of the various CYP isoenzymes in vivo.

Reversion of hepatobiliary alterations by bone marrow transplantation in a murine model of erythropoietic protoporphyria

Antonio Fontanellas, Frèdèric Mazurier, Marc Landry, Laurence Taine, Carine Morel, Monique Larou, Jean‐Yves Daniel, Xavier Montagutelli, Rafael Enriquez de Salamanca, Hubert de Verneuil – 30 December 2003 – Erythropoietic protoporphyria (EPP) is characterized clinically by cutaneous photosensitivity and biochemically by the accumulation of excessive amounts of protoporphyrin in erythrocytes, plasma, feces, and other tissues, such as the liver. The condition is inherited as an autosomal dominant or recessive trait, with a deficiency of ferrochelatase activity.

Hepatitis C–related cirrhosis: A predictor of diabetes after liver transplantation

Dave L. Bigam, Jason J. Pennington, Andre Carpentier, Ian R. Wanless, Alan W. Hemming, Ruth Croxford, Paul D. Greig, Leslie B. Lilly, Jenny E. Heathcote, Gary A. Levy, Mark S. Cattral – 30 December 2003 – Hepatitis C virus (HCV) infection has recently been suggested to be a risk factor for the development of diabetes mellitus. The aim of our study was to investigate whether the prevalence of diabetes is increased among liver transplant recipients infected with HCV.

Clearance of the original hepatitis B virus YMDD‐motif mutants with emergence of distinct lamivudine‐resistant mutants during prolonged lamivudine therapy

Chau‐Ting Yeh, Rong‐Nan Chien, Chia‐Ming Chu, Yun‐Fan Liaw – 30 December 2003 – Tyrosine‐methionine‐aspartate‐aspartate (YMDD)‐motif mutants may emerge and elicit immune clearance during prolonged lamivudine treatment. The aim of this study was to investigate the virological events following development of the original mutants. Twenty‐three patients who developed YMDD‐motif mutants during the Asian lamivudine trial were included. Serial serum samples from these patients were subjected to sequence analysis to identify new mutants.

Bioelectrical impedance analysis is a useful bedside technique to assess malnutrition in cirrhotic patients with and without ascites

Matthias Pirlich, Tatjana Schütz, Theo Spachos, Siegfried Ertl, Marie‐Luise Weiß, Herbert Lochs, Mathias Plauth – 30 December 2003 – Protein‐calorie malnutrition is associated with poor prognosis in chronic liver disease, but reliable assessment is hampered by changes in body water. We prospectively evaluated the effect of fluid retention on bioelectrical impedance analysis (BIA) as a simple method for the estimation of body cell mass (BCMBIA) in 41 patients with cirrhosis (n = 20 with ascites; n = 21 without ascites) using total body potassium counting (BCMTBP) as a reference method.

Tissue inhibitor of metalloproteinases‐1 promotes liver fibrosis development in a transgenic mouse model

Hitoshi Yoshiji, Shigeki Kuriyama, Yoji Miyamoto, Unnur P. Thorgeirsson, Daniel E. Gomez, Mitsuhiro Kawata, Junichi Yoshii, Yasuhide Ikenaka, Ryuichi Noguchi, Hirohisa Tsujinoue, Toshiya Nakatani, Snorri S. Thorgeirsson, Hiroshi Fukui – 30 December 2003 – Tissue inhibitor of metalloproteinases‐1 (TIMP‐1) has been shown to be increased in liver fibrosis development both in murine experimental models and human samples. However, the direct role of TIMP‐1 during liver fibrosis development has not been defined.

Control by signaling modulators of the sorting of canalicular transporters in rat hepatocyte couplets: Role of the cytoskeleton

Marcelo G. Roma, Piotr Milkiewicz, Elwyn Elias, Roger Coleman – 30 December 2003 – Hormonal control of the restoration of hepatocanalicular polarity in short‐term cultured hepatocyte couplets was analyzed. One hour following isolation, couplets were unable to accumulate the fluorescent bile acid analogue, cholyl‐lysyl‐fluorescein (CLF), and showed a nonpolarized distribution of F‐actin and mrp2 over the cell body. A progressive, time‐dependent restoration of couplet‐polarized function and morphology was reached after 4 hours of culture.

Fibrous obliterative lesions of veins contribute to progressive fibrosis in chronic liver allograft rejection

Yuichi Nakazawa, Julie R. Jonsson, Neal I. Walker, Paul Kerlin, Charles Steadman, Stephen V. Lynch, Russell W. Strong, Andrew D. Clouston – 30 December 2003 – Fibrosis in liver allografts undergoing chronic rejection (CR) is variable and poorly understood. The temporal and spatial relationships of venous, arterial, and biliary lesions were studied to clarify their potential contributions to graft fibrosis. The severity, prevalence, and morphology of intimal lesions of vessels were analyzed and compared with the fibrosis stage.

Induction of bile acid synthesis by cholesterol and cholestyramine feeding is unimpaired in mice deficient in apolipoprotein AI

Christopher D. Jolley, John M. Dietschy, Stephen D. Turley – 30 December 2003 – High density lipoprotein (HDL) cholesterol is believed to be preferentially utilized for bile acid synthesis and biliary secretion. In mice, the deletion of apolipoprotein AI (apo AI), the major apolipoprotein in HDL, results in very low plasma HDL‐cholesterol levels. This article describes bile acid metabolism in apo AI‐deficient (Apo AI−/−) mice and their C57BL/6 (Apo AI+/+) controls fed either a basal rodent diet alone or containing cholesterol or cholestyramine.

Effect of cholera toxin and cyclic adenosine monophosphate on fluid‐phase endocytosis, distribution, and trafficking of endosomes in rat liver

Rebecca W. Van Dyke – 30 December 2003 – In prior studies, we showed that cholera (CTX) and pertussis toxins (PTX) increase rat liver endosome acidification. This study was performed to characterize the effects of these toxins and cyclic adenosine monophosphate (cAMP) on endosome ion transport, fluid‐phase endocytosis (FPE), and endosome trafficking in liver. In control liver, more mature populations of endosomes acidified progressively more slowly, but both toxins and cAMP caused retention of an early endosome acidification profile in maturing endosomes.

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