Takayoshi Ito, Kotaro Yasui, Jun Mukaigawa, Asao Katsume, Michinori Kohara, Keiji Mitamura – 30 December 2003 – Hepatitis C virus (HCV) replicates in human and chimpanzee hepatocytes. To characterize the nature of HCV and evaluate antiviral agents, the development of an HCV replication system in a cell culture is essential. We developed a cell line derived from human hepatocytes by fusing them with a hepatoblastoma cell line, HepG2, and obtained several clones.

Monica G. Chiaramonte, Allen W. Cheever, James D. Malley, Debra D. Donaldson, Thomas A. Wynn – 30 December 2003 – In several allergic, autoimmune, and infectious diseases, fibrosis is a major cause of morbidity and mortality. Here, using a model of infection‐induced liver fibrosis, we show that interleukin (IL)‐13 is required at all stages of Schistosomiasis mansoni infection to induce fibrosis. IL‐4 production was preserved in IL‐13–deficient mice, yet failed to significantly contribute to the fibrotic response in either acute or chronic infection.

Amedeo Columbano, Giovanna M. Ledda‐Columbano, Monica Pibiri, Danilo Concas, Janardan K. Reddy, M. Sambasiva Rao – 30 December 2003 – Previously, we have suggested that liver cell proliferation induced by certain mitogens is dependent on their binding and activation of nuclear receptors of the steroid/thyroid superfamily.

Mireia Giménez‐Barcons, Sandra Franco, Yanette Suárez, Xavier Forns, Sergi Ampurdanès, Francesc Puig‐Basagoiti, Alberto Sánchez‐Fueyo, Josep‐Maria Barrera, Josep‐Maria Llovet, Jordi Bruix, José‐María Sánchez‐Tapias, Juan Rodés, Juan‐Carlos Saiz – 30 December 2003 – Interferon therapy may decrease the risk of hepatocellular carcinoma in patients with hepatitis C virus (HCV)‐related liver cirrhosis. Interaction of the cellular protein kinase PKR with the PKR‐binding domain (PKR‐bd) of HCV‐NS5A protein may affect cellular growth control and viral resistance to interferon therapy.

Takehiko Uesugi, Matthias Froh, Gavin E. Arteel, Blair U. Bradford, Ronald G. Thurman – 30 December 2003 – Chronic alcohol administration increases gut‐derived endotoxin in the portal blood, which activates Kupffer cells and causes liver injury. Mice (C3H/HeJ) with mutations in toll‐like receptor 4 (TLR4) are hyporesponsive to endotoxin. To test the hypothesis that TLR4 is involved in early alcohol‐induced liver injury, the long‐term intragastric ethanol feeding protocol developed by Tsukamoto and French for rats was adapted to mice.

Valentina Factor, Aundrea L. Oliver, Ganesh R. Panta, Snorri S. Thorgeirsson, Gail E. Sonenshein, Marcello Arsura – 30 December 2003 – NF‐κB regulates liver cell death during development, regeneration, and neoplastic transformation. For example, we showed that oncogenic Ras‐ or Raf‐mediated transformation of rat liver epithelial cells (RLEs) led to altered NF‐κB regulation through IKK complex activation, which rendered these cells more resistant to TGF‐β1‐induced apoptosis.

Shotaro Sakisaka, Takumi Kawaguchi, Eitaro Taniguchi, Shinichiro Hanada, Kurumi Sasatomi, Hironori Koga, Masaru Harada, Rina Kimura, Michio Sata, Norimasa Sawada, Michio Mori, Satoru Todo, Toshihiko Kurohiji – 30 December 2003 – Tight junctions (TJ) of biliary epithelial cells (BEC) and hepatocytes prevent bile regurgitation from the biliary tract. Alterations in these TJs may participate in chronic cholestatic liver diseases such as primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). We examined the localization of 2 TJ proteins, ZO‐1 and 7H6, in these diseases.

Jenny E. Ros, John D. Schuetz, Mariska Geuken, Konrad Streetz, Han Moshage, Folkert Kuipers, Michael P. Manns, Peter L. M. Jansen, Christian Trautwein, Michael Müller – 30 December 2003 – The multidrug resistance protein Mdr1b in rats is up‐regulated during liver regeneration after partial hepatectomy or after endotoxin treatment. We hypothesize that up‐regulation of Mdr1b in these models is TNF‐α–dependent.

Xinhe Wang, Nai‐Jung Hung, Robert H. Costa – 30 December 2003 – Partial hepatectomy (PH) or toxic liver injury induces the proliferation of terminally differentiated hepatic cells to regenerate the original size of the adult liver. Previous PH liver regeneration studies showed that premature transgenic expression of the Forkhead Box M1b (FoxM1b, HFH‐11B) transcription factor accelerated hepatocyte entry into DNA replication (S‐phase).

Harri A. Järveläinen, Arto Orpana, Markus Perola, Vesa T. Savolainen, Pekka J. Karhunen, Kai O. Lindros – 30 December 2003 – Twin concordance studies indicate that genetic factors influence the individual susceptibility for alcoholic liver disease (ALD). Both clinical and experimental data suggest that Kupffer cell activation by gut‐derived endotoxins and other bacterial products is an important pathogenic factor. Activated Kupffer cells release proinflammatory cytokines, a process that is regulated by the CD14 endotoxin receptor (CD14).