David G. Le Couteur, Victoria C. Cogger, Astrid M.A. Markus, Peta J. Harvey, Zhan‐Li Yin, Annick D. Ansselin, Allan J. McLean – 30 December 2003 – Age‐related impairment of drug metabolism by the liver is consistent with hepatocyte hypoxia, suggestive of the development of a diffusional barrier to oxygen supply. Because the effects of aging on the diffusional pathway (sinusoidal endothelium and space of Disse) have not been described, we performed comparative studies on the livers of Fischer F344 rats aged 4 to 7, 12 to 15, and 24 to 27 months.

Olatz Fresnedo, Miguel López De Heredia, María José Martínez, Susana Cristóbal, María Teresa Rejas, José M. Cuezva, Begoña Ochoa – 30 December 2003 – We have recently purified a cholesteryl ester hydrolase (CEH) from rat liver microsomes. Antibodies raised against the purified protein specifically reacted with a 106‐kd protein and neutralized 90% of the CEH activity of rat liver microsomes (J Lipid Res 1999;40:715‐725). In this work we have used the anti‐CEH antibody to study both the subcellular distribution of the protein in hepatocytes as well as its tissue‐specific expression in rat.

Che‐Chang Chan, Sun‐Sang Wang, Fa‐Yauh Lee, Full‐Young Chang, Han‐Chieh Lin, Chi‐Jen Chu, Chien‐Ting Chen, Hui‐Chun Huang, Shou‐Dong Lee – 30 December 2003 – Portal hypertension is associated with increased hepatic and collateral resistance to an increased portal blood flow. Endothelin‐1 (ET‐1) can induce intrahepatic vasoconstriction and consequently increase portal pressure. It is unknown if ET‐1 also modulates portal pressure by a direct vasoconstrictive effect on collaterals.

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).

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).

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.

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.

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.

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.

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.