Resistance to fulminant hepatitis and carcinogenesis conferred by overexpression of retinoblastoma protein in mouse liver

Toshiaki Ichihara, Yoshinori Komagata, Xiao‐Li Yang, Tadayoshi Uezato, Katsuhiko Enomoto, Kenji Koyama, Jun‐ichi Miyazaki, Toshihiro Sugiyama, Naoyuki Miura – 30 December 2003 – Previously, retinoblastoma (Rb) transgenic mice were produced under the control of the Rb gene promoter and showed dwarf characteristics. Here, we created transgenic mice, in which the human Rb gene was controlled by the hepatocyte nuclear factor‐1 gene promoter/enhancer and was expressed primarily in the liver. The liver of these novel transgenic mice was normally developed.

Repopulation of mouse liver with human hepatocytes and in vivo infection with hepatitis B virus

Maura Dandri, Martin R. Burda, Eva Török, Joerg M. Pollok, Alicja Iwanska, Gunhild Sommer, Xavier Rogiers, Charles E. Rogler, Sanjeev Gupta, Hans Will, Heiner Greten, Joerg Petersen – 30 December 2003 – Mice containing livers repopulated with human hepatocytes would provide excellent in vivo models for studies on human liver diseases and hepatotropic viruses, for which no permissive cell lines exist.

Central venulitis in pediatric liver allografts

Alyssa M. Krasinskas, Eduardo D. Ruchelli, Elizabeth B. Rand, Jesse L. Chittams, Emma E. Furth – 30 December 2003 – Central venulitis (CV), a distinct histologic lesion described in adult liver transplants, can occur with acute portal tract rejection or in isolation (ICV). Possible etiologies include immunosuppressive drug toxicity, acute cellular rejection, viral hepatitis, ischemic injury, and recurrent disease.

Tauroursodeoxycholic acid inserts the apical conjugate export pump, Mrp2, into canalicular membranes and stimulates organic anion secretion by protein kinase C–dependent mechanisms in cholestatic rat liver

Ulrich Beuers, Manfred Bilzer, Anila Chittattu, Gerd A. Kullak‐Ublick, Dietrich Keppler, Gustav Paumgartner, Frank Dombrowski – 30 December 2003 – Ursodeoxycholic acid (UDCA) exerts anticholestatic effects by undefined mechanisms. Previous work suggested that UDCA stimulates biliary exocytosis via Ca++‐ and protein kinase C (PKC)‐dependent mechanisms.

Zinc mesoporphyrin represses induced hepatic 5‐aminolevulinic acid synthase and reduces heme oxygenase activity in a mouse model of acute hepatic porphyria

Macé M. Schuurmans, Francine Hoffmann, Raija L. Lindberg, Urs A. Meyer – 30 December 2003 – Zinc mesoporphyrin (ZnMP) is a potent inhibitor of heme oxygenase (HO) and represses 5‐aminolevulinic acid synthase (ALAS). These properties make it a potential candidate for treatment of inducible acute hepatic porphyrias, diseases characterized by neurovisceral symptoms, and massive ALAS induction.

The phenobarbital response enhancer module in the human bilirubin UDP‐glucuronosyltransferase UGT1A1 gene and regulation by the nuclear receptor CAR

Junko Sugatani, Hiroyuki Kojima, Akiko Ueda, Satoru Kakizaki, Kouichi Yoshinari, Qi‐Hui Gong, Ida S. Owens, Masahiko Negishi, Tatsuya Sueyoshi – 30 December 2003 – The UDP‐glucuronosyltransferase, UGT1A1, is the critical enzyme responsible for detoxification of the potentially neurotoxic bilirubin by conjugating it with glucuronic acid. For decades, phenobarbital (PB) treatment for hyperbilirubinemia has been known to increase expression of the UGT1A1 gene in liver. We have now delineated the PB response activity to a 290‐bp distal enhancer sequence (−3483/−3194) of the UGT1A1 gene.

Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity

Luigi E. Adinolfi, Michele Gambardella, Augusto Andreana, Marie‐françoise Tripodi, Riccardo Utili, Giuseppe Ruggiero – 30 December 2003 – The role of steatosis in the progression of liver damage in chronic hepatitis C (CHC) was studied. Enrolled were 180 consecutive liver biopsy‐proven CHC patients and 41 additional subjects with a known duration of infection. We evaluated the histological activity index (HAI), grade of fibrosis and steatosis, body mass index (BMI; kg/m2), distribution of body fat, HCV genotype, and levels of HCV RNA.

Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States

Tushar Patel – 30 December 2003 – Clinical observations suggest a recent increase in intrahepatic biliary tract malignancies. Thus, our aim was to determine recent trends in the epidemiology of intrahepatic cholangiocarcinoma in the United States. Reported data from the Surveillance, Epidemiology, and End Results (SEER) program and the United States Vital Statistics databases were analyzed to determine the incidence, mortality, and survival rates of primary intrahepatic cholangiocarcinoma.

Differential effects of microsomal enzyme–inducing chemicals on the hepatic expression of rat organic anion transporters, OATP1 and OATP2

Lesley C. Rausch‐Derra, Dylan P. Hartley, Peter J. Meier, Curtis D. Klaassen – 30 December 2003 – The organic anion transporting polypeptides, Oatp1 (Slc21a1) and Oatp2 (Slc21a5), mediate hepatic uptake of cardiac glycosides. Previously, we demonstrated that chemicals that increase cytochrome P450s differentially affect hepatic uptake of cardiac glycosides. We postulated that increased uptake of cardiac glycosides observed after pretreatment of animals with phenobarbital (PB) and pregnenolone‐16α‐carbonitrile (PCN) occurs via increased hepatic expression of Oatp1 and/or Oatp2.

Subscribe to