New ways of interfering with HCV replication

Peter Hasselblatt, Hubert E. Blum, Wolf‐Bernhard Offensperger – 30 December 2003 – RNA interference is a cellular process of gene silencing in which small duplexes of RNA specifically target a homologous sequence for cleavage by cellular ribonucleases. The introduction of approximately 22‐nt small interfering RNAs (siRNAs) into mammalian cells can specifically silence cellular mRNAs without induction of the nonspecific IFN responses that are activated by longer RNA duplexes.

Expression of MUC1 and MUC2 mucin antigens in intrahepatic bile duct tumors: Its relationship with a new morphological classification of cholangiocarcinoma

Michiyo Higashi, Suguru Yonezawa, Jenny J. L. Ho, Sadao Tanaka, Tatsuro Irimura, Young S. Kim, Eiichi Sato – 30 December 2003 – Our previous immunohistochemical study on intrahepatic bile duct tumors showed that invasive cholangiocarcinoma (ICC) with a poor outcome expressed MUC1 mucin but was negative for MUC2 mucin, whereas bile duct cystadenocarcinoma (BDCC) with a favorable outcome was MUC1 negative and MUC2 positive. In the present study, ICC was further subdivided into 2 subtypes: intraductal growth type and/or periductal infiltrating type (ICC‐IP) and mass forming type (ICC‐M).

Phase I and Phase II drug‐metabolizing enzymes are expressed and heterogeneously distributed in the biliary epithelium

Fatima Lakehal, Dominique Wendum, Véronique Barbu, Laurent Becquemont, Raoul Poupon, Pierre Balladur, Laurent Hannoun, François Ballet, Philippe H. Beaune, Chantal Housset – 30 December 2003 – Tissue expression of drug‐metabolizing enzymes influences susceptibility to drugs and carcinogens. Because the biliary epithelium, exposed to bile‐borne chemicals, may give rise to drug‐induced cholangiopathies and to cholangiocarcinomas, we determined the pattern of expression of drug‐metabolizing enzymes in this epithelium.

Living‐related liver transplantation for patients with fulminant and subfulminant hepatic failure

Shiro Miwa, Yasuhiko Hashikura, Atsuyoshi Mita, Tatsuya Kubota, Hisanao Chisuwa, Yuichi Nakazawa, Toshihiko Ikegami, Masaru Terada, Shinichi Miyagawa, Seiji Kawasaki – 30 December 2003 – The prognosis for patients with fulminant (FHF) or subfulminant hepatic failure (SFHF) has improved since the introduction of liver transplantation. However, the death rate of patients awaiting liver transplantation is high, possibly because of the difficulty in obtaining grafts in a timely manner, given the relative shortage of cadaveric donors.

Support of sinusoidal endothelial cell glutathione prevents hepatic veno‐occlusive disease in the rat

Xiangdong Wang, Gary C. Kanel, Laurie D. DeLeve – 30 December 2003 – Depletion of sinusoidal endothelial cell glutathione (GSH) has been proposed as a common mechanism leading to hepatic veno‐occlusive disease (HVOD). This study examines whether intraportal infusion of GSH can prevent HVOD in the monocrotaline rat model. HVOD was induced in rats with monocrotaline 160 mg/kg i.g. on day 0. GSH was infused intraportally by mini‐osmotic pump. Monocrotaline decreased GSH in sinusoidal endothelial cells, but not in liver homogenate.

Phosphatidylinositol 3–kinase and protein kinase C contribute to the inhibition by interleukin 6 of phosphoenolpyruvate carboxykinase gene expression in cultured rat hepatocytes

Bruno Christ, Emine Yazici, Annegret Nath – 30 December 2003 – The participation of phosphatidylinositol 3–kinase (PI3‐kinase), protein kinase C, and mitogen‐activated protein kinase (MAP‐kinase) in the inhibition by interleukin 6 (IL‐6) and insulin of phosphoenolpyruvate carboxykinase (PCK) gene expression was investigated in cultured rat hepatocytes. IL‐6 or insulin inhibited the glucagon‐stimulated increase in PCK messenger RNA (mRNA) by about 70%.

Latent hepatitis B virus infection in healthy individuals with antibodies to hepatitis B core antigen

Hiroyuki Marusawa, Shinji Uemoto, Makoto Hijikata, Yoshihide Ueda, Koichi Tanaka, Kunitada Shimotohno, Tsutomu Chiba – 30 December 2003 – Several recent reports have shown that hepatitis B virus (HBV) could be frequently transmitted to the recipients from donors who have antibodies to hepatitis B core antigen (anti‐HBc) through liver transplantation. We provide here the molecular evidence of latent HBV infection accompanied with ongoing viral replication in the liver tissue of anti‐HBc–positive healthy individuals.

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