Involvement of integrin‐linked kinase in carbon tetrachloride–induced hepatic fibrosis in rats

Yining Zhang, Tadashi Ikegami, Akira Honda, Teruo Miyazaki, Bernard Bouscarel, Marcos Rojkind, Ichinosuke Hyodo, Yasushi Matsuzaki – 29 August 2006 – Integrin‐linked kinase (ILK) is a multidomain focal adhesion protein implicated in signal transduction between integrins and growth factor receptors. Although its expression is upregulated in pulmonary and renal fibrosis, its role in the development of hepatic fibrosis remains to be determined.

Hypercholesterolemia in rats with hepatomas: Increased oxysterols accelerate efflux but do not inhibit biosynthesis of cholesterol

Takeshi Hirayama, Akira Honda, Yasushi Matsuzaki, Teruo Miyazaki, Tadashi Ikegami, Mikio Doy, Guorong Xu, Michael Lea, Gerald Salen – 29 August 2006 – Hypercholesterolemia is an important paraneoplastic syndrome in patients with hepatoma, but the nature of this defect has not yet been identified. We investigated the molecular mechanisms of hypercholesterolemia in a hepatoma‐bearing rat model. Buffalo rats were implanted in both flanks with Morris hepatoma 7777 (McA‐RH7777) cells. After 4 weeks, tumor weight was 5.5 ± 1.7 g, and serum cholesterol level increased from 60 ± 2 to 90 ± 2 mg/dL.

Disruption of the Arnt gene in endothelial cells causes hepatic vascular defects and partial embryonic lethality in mice

Sun Hee Yim, Yatrik Shah, Shuhei Tomita, H. Douglas Morris, Oksana Gavrilova, Gilles Lambert, Jerrold M. Ward, Frank J. Gonzalez – 29 August 2006 – Vascular endothelial cells (ECs) play a critical role in angiogenesis and organogenesis, especially in embryonic liver development. Hypoxia‐inducible transcription factors (Hifs) are a key trigger of hypoxic signals, a primary stimulus of angiogenesis. The aryl hydrocarbon receptor nuclear translocator (Arnt), also called Hif‐1β, serves as an obligate heterodimerization partner of Hif‐1α and Hif‐2α.

HLA class II alleles, genotypes, haplotypes, and amino acids in primary biliary cirrhosis: A large‐scale study

Peter T. Donaldson, Anna Baragiotta, Michael A. Heneghan, Annarosa Floreani, Carla Venturi, James A. Underhill, David E.J. Jones, Oliver F.W. James, Margaret F. Bassendine – 29 August 2006 – Twin and family studies suggest there is a significant genetic component to primary biliary cirrhosis (PBC). However, the inability to replicate reported associations has been a recurring problem, with the only consistently reported genetic association that between PBC and HLA‐DRB1*0801. However, recently even this has been questioned, and a number of novel associations have also been reported.

Matrix metalloproteinase‐9 is an important factor in hepatic regeneration after partial hepatectomy in mice

Eric W. Olle, Xiaodan Ren, Shannon D. McClintock, Roscoe L. Warner, Michael P. Deogracias, Kent J. Johnson, Lisa M. Colletti – 29 August 2006 – Partial hepatectomy triggers hepatocyte proliferation, hepatic matrix remodeling, and hepatocyte apoptosis, all of which are important processes in the regenerating liver. Previous studies have shown an increase in the levels of matrix metalloproteinases gelatinase A (MMP‐2) and gelatinase B (MMP‐9) after partial hepatectomy. The goal of this study was to investigate the role of MMP‐9 in liver regeneration after partial hepatectomy.

Patterns of viral decline during PEG‐interferon alpha‐2b therapy in HBeAg‐positive chronic hepatitis B: Relation to treatment response

Martijn J. ter Borg, Monika van Zonneveld, Stefan Zeuzem, Hakan Senturk, Ulus S. Akarca, Christopher Simon, Bettina E. Hansen, Bart L. Haagmans, Robert A. de Man, Solko W. Schalm, Harry L.A. Janssen, HBV 99‐01 Study Group – 29 August 2006 – In chronic hepatitis B, it is difficult to predict an early therapeutic response. We investigated the viral decline during therapy with pegylated interferon alpha‐2b (PEG‐IFN) with or without lamivudine in 266 HBeAg‐positive chronic hepatitis B patients.

Pegylated interferon alpha‐2b as monotherapy or in combination with ribavirin in chronic hepatitis delta

Grazia Anna Niro, Alessia Ciancio, Giovanni Battista Gaeta, Antonina Smedile, Aldo Marrone, Antonella Olivero, Maria Stanzione, Ezio David, Giuseppina Brancaccio, Rosanna Fontana, Francesco Perri, Angelo Andriulli, Mario Rizzetto – 29 August 2006 – Therapy of chronic hepatitis delta with standard interferon therapy has met with limited efficacy. This study was designed to examine the efficacy and safety of peginterferon with or without ribavirin.

The effect of single oral low‐dose losartan on posture‐related sodium handling in post‐TIPS ascites‐free cirrhosis

George Therapondos, Lieke Hol, Fabiana Benjaminov, Florence Wong – 29 August 2006 – Post‐TIPS ascites‐free patients with cirrhosis and previous refractory ascites demonstrate subtle sodium retention when challenged with a high sodium load. This is also observed in pre‐ascitic patients with cirrhosis. This phenomenon is dependent on an intrarenal angiotensin II (ANG II) mechanism related to the assumption of erect posture. We investigated whether similar mechanisms were involved in post‐TIPS ascites‐free patients, by studying 10 patients with functioning TIPS and no ascites.

Intrahepatic levels and replicative activity of covalently closed circular hepatitis B virus DNA in chronically infected patients

Andreas Laras, John Koskinas, Evangelini Dimou, Ageliki Kostamena, Stephanos J. Hadziyannis – 29 August 2006 – Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is responsible for viral persistence in the natural course of chronic HBV infection and during prolonged antiviral therapy and serves as the template for the production of HBV pregenomic RNA (pgRNA), the primary step in HBV replication.

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