Presence of distinct AP‐1 dimers in normal and transformed rat hepatocytes under basal conditions and after epidermal growth factor stimulation

F Nadori, B Lardeux, M Rahmani, A Bringuier, A Durand‐Schneider, D Bernuau – 30 December 2003 – Activation of the transcriptional regulator AP‐1, a dimeric complex formed of various combinations of Fos and Jun proteins, is a key step in the cellular response to mitogens. Because different dimers are believed to display different regulatory functions, we hypothesized that transformed cells that lack normal growth constraints might display AP‐1 dimers that are different from those of normal cells.

Transient selection of a hepatitis B virus polymerase gene mutant associated with a decreased replication capacity and famciclovir resistance

Christian Pichoud, Béatrice Seignères, Zhirui Wang, Christian Trépo, Fabien Zoulim – 30 December 2003 – Prolonged therapy for chronic hepatitis B (HBV) with nucleoside analogs may result in the emergence of HBV mutants resistant to antivirals. Here, we describe the transient selection of an HBV polymerase gene mutant that was associated with viral persistence in an immune competent patient treated with famciclovir. Viral polymerase gene sequence was analyzed directly on polymerase chain reaction (PCR) products and also after cloning.

Clinical significance of serum bilirubin levels under ursodeoxycholic acid therapy in patients with primary biliary cirrhosis

Anne‐Marie Bonnand, E. Jenny Heathcote, Keith D. Lindor, Renée Eugénie Poupon – 30 December 2003 – We determined whether the normalization of serum bilirubin level (SBL) induced by ursodeoxycholic acid (UDCA) therapy was associated with an improved clinical outcome in patients with primary biliary cirrhosis (PBC). We estimated the prognostic values of SBL measured after 6 months of UDCA treatment for survival free of orthotopic liver transplantation (OLT). We used a database of 548 patients with PBC followed in three trials of UDCA.

Natural history of untreated nonsurgical hepatocellular carcinoma: Rationale for the design and evaluation of therapeutic trials

Josep M. Llovet, Javier Bustamante, Antoni Castells, Ramon Vilana, Maria Del Carmen Ayuso, Margarita Sala, Concepció Brú, Joan Rodés, Jordi Bruix – 30 December 2003 – This study analyzed the natural history and prognostic factors of patients with nonsurgical hepatocellular carcinoma (HCC). Twenty variables from 102 cirrhotic patients with HCC who were not treated within prospective randomized controlled trials (RCT) were investigated through uni‐ and multivariate analyses.

Quality of life before and after liver transplantation for cholestatic liver disease

Cynthia R. Gross, Michael Malinchoc, W. Ray Kim, Roger W. Evans, Russell H. Wiesner, Janice L. Petz, Jeffrey S. Crippin, Goran B. Klintmalm, Marlon F. Levy, Paola Ricci, Terry M. Therneau, E. Rolland Dickson – 30 December 2003 – Liver transplantation (LT) is an established therapy for patients with end‐stage primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC). In this report, we describe the health status and quality of life (QOL) in patients with these cholestatic liver diseases before and after LT.

Expression of vascular endothelial growth factor promotes colonization, vascularization, and growth of transplanted hepatic tissues in the mouse

Itsuki Ajioka, Toshihiro Akaike, Yoshifumi Watanabe – 30 December 2003 – A complex vascular network forms an important component of the liver architecture. This network is essential for the supply of oxygen and nutrients to cells and delivery of molecules for metabolic exchange. In this study, we attempted to construct a vascular network in transplanted hepatic tissues and examined the effect of such network on tissue formation.

Association of diabetes mellitus and chronic hepatitis C virus infection

Andrew L. Mason, Johnson Y. Lau, Nicole Hoang, KePing Qian, Graeme J. Alexander, Lizhe Xu, Linsheng Guo, Sheraj Jacob, Fredric G. Regenstein, Robert Zimmerman, James E. Everhart, Clive Wasserfall, Noel K. Maclaren, Robert P. Perrillo – 30 December 2003 – While patients with liver disease are known to have a higher prevalence of glucose intolerance, preliminary studies suggest that hepatitis C virus (HCV) infection may be an additional risk factor for the development of diabetes mellitus.

Reduced C‐terminal Src kinase (Csk) activities in hepatocellular carcinoma

Tsutomu Masaki, Masato Okada, Masaki Tokuda, Yasushi Shiratori, Osamu Hatase, Mutsunori Shirai, Mikio Nishioka, Masao Omata – 30 December 2003 – The proto‐oncogene product pp60c‐src is the cellular homologue of the Rous sarcoma transforming gene, and it is a non–receptor‐linked and membrane‐associated tyrosine kinase. There is a close correlation between elevated pp60c‐src activity and cell transformation. We have recently reported that pp60c‐src was activated in hepatocellular carcinoma (HCC) of human and Long‐Evans cinnamon (LEC) rats.

Mutations in the basic core promotor and the precore region of hepatitis b virus and their selection in children with fulminant and chronic hepatitis B

Michael Friedt, Patrick Gerner, Ekkehart Lausch, Hubert Trübel, Bernhard Zabel, Stefan Wirth – 30 December 2003 – The involvement of precore stop codon 1896‐A and base exchanges in the AT‐rich region at positions 1762 and 1764 of the hepatitis B core promotor has been controversely discussed in adults with fulminant hepatitis B. Because no data are currently available on children, we analyzed the basic core promotor (BCP) and precore region in children with chronic and fulminant hepatitis B. The BCP and precore region were sequenced directly and after cloning from mothers and infants.

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