Alterations in tight junctions differ between primary biliary cirrhosis and primary sclerosing cholangitis

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.

Induction of Mdr1b expression by tumor necrosis factor‐α in rat liver cells is independent of p53 but requires NF‐κB signaling

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.

Earlier expression of the transcription factor HFH‐11B diminishes induction of p21CIP1/WAF1 levels and accelerates mouse hepatocyte entry into S‐phase following carbon tetrachloride liver injury

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).

Promoter polymorphism of the CD14 endotoxin receptor gene as a risk factor for alcoholic liver disease

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).

Endothelin‐1 induces vasoconstriction on portal‐systemic collaterals of portal hypertensive rats

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.

Immunolocalization of a novel cholesteryl ester hydrolase in the endoplasmic reticulum of murine and human hepatocytes

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.

Pseudocapillarization and associated energy limitation in the aged rat liver

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.

Mechanism of retarded liver regeneration in plasminogen activator‐deficient mice: Impaired activation of hepatocyte growth factor after Fas‐mediated massive hepatic apoptosis

Masahito Shimizu, Akira Hara, Masataka Okuno, Hiroyuki Matsuno, Kiyotaka Okada, Shigeru Ueshima, Osamu Matsuo, Masayuki Niwa, Kuniharu Akita, Yasuhiro Yamada, Naoki Yoshimi, Toshihiko Uematsu, Soichi Kojima, Scott L. Friedman, Hisataka Moriwaki, Hideki Mori – 30 December 2003 – Urokinase‐type plasminogen activator (uPA) is implicated in the regulation of hepatic regeneration by activating hepatocyte growth factor (HGF).

Bile acid transport and regulating functions in the human biliary epithelium

Nicolas Chignard, Martine Mergey, Danielle Veissière, Rolland Parc, Jacqueline Capeau, Raoul Poupon, Annick Paul, Chantal Housset – 30 December 2003 – Whether bile acids regulate biliary epithelial cell (BEC) secretory functions in human is poorly known. The purpose of the study was to determine if human gallbladder‐derived BEC exhibit bile acid transport activity that affect their secretory functions and to evaluate the influence of bile acid hydrophobicity in this response by comparing the effects of tauroursodeoxycholate (TUDC) and of taurochenodeoxycholate (TCDC).

Visual demonstration of hepatitis C virus‐specific memory CD8+ T‐cell expansion in patients with acute hepatitis C

Yuji Sobao, Hiroko Tomiyama, Saburo Nakamura, Hisahiko Sekihara, Katsuaki Tanaka, Masafumi Takiguchi – 30 December 2003 – Hepatitis C virus (HCV)‐specific CD8+ T cells in peripheral blood mononuclear cells (PBMCs) from patients infected with HCV were quantitatively analyzed by flow cytometry using an HLA‐B*3501‐HCV epitope tetrameric complex. In chronic hepatitis C, tetramer+CD8+ T cells were detected at frequencies ranging from 0.05% to 0.12% of total CD8+ T cells.

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