Familial intrahepatic cholestasis 1: Studies of localization and function

Peter Ujhazy, Daniel Ortiz, Suniti Misra, Shohua Li, James Moseley, Hugh Jones, Irwin M. Arias – 30 December 2003 – Mutations in the FIC1 gene constitute the molecular defect in familial intrahepatic cholestasis I (Fic1 [Byler's disease]) and benign recurrent intrahepatic cholestasis. This report describes the localization of Fic1 in rat liver and intestine, as well as biochemical and transfection studies that support its function as an energy‐dependent aminophospholipid translocase.

Prevalence of naturally occurring surface gene variants of hepatitis B virus in nonimmunized surface antigen–negative Chinese carriers

Jinlin Hou, Zhanghui Wang, Jinjun Cheng, Yulong Lin, George K. K. Lau, Jian Sun, Fuyuan Zhou, Jenny Waters, Peter Karayiannis, Kangxian Luo – 30 December 2003 – Previous studies have suggested that hepatitis B virus (HBV) variants may account for the presence of HBV DNA in hepatitis B surface antigen (HBsAg)‐negative patients (occult HBV infection). However, it is not known how widespread these variants are and how they influence the course of liver disease.

Bile acid feeding increased proliferative activity and apical bile acid transporter expression in both small and large rat cholangiocytes

Gianfranco Alpini, Yoshiyuki Ueno, Shannon S. Glaser, Marco Marzioni, Jo Lynne Phinizy, Heather Francis, Gene LeSage – 30 December 2003 – Bile acids (BA) enter cholangiocytes by the Na+‐dependent apical BA transporter (ABAT). By this mechanism, taurocholate (TC) and taurolithocholate (TLC) increase cholangiocyte proliferation. No in vivo studies exist regarding the anatomical sites involved in BA‐regulation of cholangiocyte growth. Specific cholangiocyte subpopulations participate in BA‐regulated proliferation.

Hepatitis B virus X protein increases expression of p21Cip‐1/WAF1/MDA6 and p27Kip‐1 in primary mouse hepatocytes, leading to reduced cell cycle progression

Liang Qiao, Kevin Leach, Robert McKinstry, Donna Gilfor, Adly Yacoub, Jong Sung Park, Steven Grant, Philip B. Hylemon, Paul B. Fisher, Paul Dent – 30 December 2003 – Previously, we have linked prolonged intense mitogen‐activated protein kinase (MAP kinase; MAPK) signaling in hepatocytes to increased expression of p21Cip‐1/WAF1/MDA6 (p21) and p16INK4a (p16), that leads to a p21‐dependent growth arrest. In this study, we investigated the impact of hepatitis B virus X protein (pX) expression on MAPK‐modulated cell cycle progression in primary mouse hepatocytes.

High rates of hepatocellular carcinoma in cirrhotic patients with high liver cell proliferative activity

Maria Francesca Donato, Eliana Arosio, Ersilio Del Ninno, Guido Ronchi, Pietro Lampertico, Alberto Morabito, Maria Rita Balestrieri, Massimo Colombo – 30 December 2003 – The prevalence, risk factors, and clinical significance of high liver cell proliferative activity were investigated in 208 well‐compensated cirrhotic patients (150 men; 50 years; 135 with chronic hepatitis C) who had been under prospective surveillance for hepatocellular carcinoma (HCC) with annual abdominal ultrasound (US) and serum α‐fetoprotein (AFP) determination.

Increased production of vascular endothelial growth factor in peritoneal macrophages of cirrhotic patients with spontaneous bacterial peritonitis

Pilar Cejudo‐Martín, Josefa Ros, Miguel Navasa, Javier Fernández, Guillermo Fernádez‐Varo, Luis Ruiz‐del‐Arbol, Francisca Rivera, Vicente Arroyo, Juan Rodés, Wladimiro Jiménez – 30 December 2003 – Spontaneous bacterial peritonitis (SBP) is a common complication of cirrhotic patients with ascites that usually results in renal failure and death despite the efficacy of the current antibiotic therapy. The pathogenesis of these phenomena is poorly known but it has been related to the production of vasoactive cell mediators locally acting on the splanchnic vasculature.

Factors associated with hepatitis B virus DNA breakthrough in patients receiving prolonged lamivudine therapy

Man‐Fung Yuen, Erwin Sablon, Chee‐Kin Hui, He‐Jun Yuan, Hilde Decraemer, Ching‐Lung Lai – 30 December 2003 – Factors associated with hepatitis B virus (HBV) DNA breakthrough and the significance of YMDD variants without the presence of wild‐type YMDD during prolonged lamivudine treatment are unknown. We studied the amino acid sequence of codon 552 (YMDD motif) and codon 528 by means of a line probe assay in 159 chronic HBV patients (median follow‐up 29.6 months).

Chronic ethanol consumption stimulates hepatitis B virus gene expression and replication in transgenic mice

Jonathan Larkin, Marcia M. Clayton, Jie Liu, Mark A. Feitelson – 30 December 2003 – Epidemiologic observations show a higher frequency of hepatitis B virus (HBV) serologic markers in chronic alcoholics compared with the general population. This may be the result of an increased susceptibility of alcoholics to infection and/or to an ethanol‐mediated stimulation of HBV gene expression and replication. To test the latter hypothesis, HBV transgenic SCID mice, which support consistent levels of virus replication, were fed with a standard Lieber‐DiCarli or isocaloric diet for 5 weeks.

Oxidized low‐density lipoproteins bind to the scavenger receptor, CD36, of hepatic stellate cells and stimulate extracellular matrix synthesis

Wilhelm Schneiderhan, Alexandra Schmid‐Kotsas, Jinshun Zhao, Adolf Grünert, Andreas Nüssler, Hans Weidenbach, Andre Menke, Roland M. Schmid, Guido Adler, Max G. Bachem – 30 December 2003 – Cumulating evidence suggests that oxidative stress resulting in lipid peroxidation and protein modification is involved in the pathogenesis of chronic liver injury and fibrogenesis. We investigated the effects of oxidized low‐density lipoproteins (oxLDL) on collagen and fibronectin synthesis of cultured human and rat hepatic stellate cells (HSC).

High glucose and hyperinsulinemia stimulate connective tissue growth factor expression: A potential mechanism involved in progression to fibrosis in nonalcoholic steatohepatitis

Valerie Paradis, Gabriel Perlemuter, Franck Bonvoust, Delphine Dargere, Beatrice Parfait, Michel Vidaud, Marc Conti, Stephane Huet, Nathalie Ba, Catherine Buffet, Pierre Bedossa – 30 December 2003 – Nonalcoholic steatohepatitis (NASH) may progress to liver fibrosis and cirrhosis. Mechanisms directly involved in the development of fibrosis have been poorly investigated.

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