Liver‐specific inactivation of Notch2, but not Notch1, compromises intrahepatic bile duct development in mice

Fabian Geisler, Florian Nagl, Pawel K. Mazur, Marcel Lee, Ursula Zimber‐Strobl, Lothar J. Strobl, Freddy Radtke, Roland M. Schmid, Jens T. Siveke – 18 April 2008 – The Notch pathway is an evolutionary conserved, intercellular signaling pathway that plays an important role in cell fate specification and the embryonic development of many organs, including the liver. In humans, mutations in the Notch receptor ligand Jagged1 gene result in defective intrahepatic bile duct (IHBD) development in Alagille syndrome.

Single‐nucleotide polymorphism analysis of the multidrug resistance protein 3 gene for the detection of clinical progression in Japanese patients with primary biliary cirrhosis

Yuki Ohishi, Minoru Nakamura, Naomi Iio, Shingo Higa, Mao Inayoshi, Yoshihiro Aiba, Atsumasa Komori, Katsuhisa Omagari, Hiromi Ishibashi, Kazuhiro Tsukamoto – 18 April 2008 – Primary biliary cirrhosis (PBC) is a multifactorial disease in which genetic factors rather than environmental factors may predominantly contribute to the pathogenesis.

Accuracy and reproducibility of transient elastography for the diagnosis of fibrosis in pediatric nonalcoholic steatohepatitis

Valerio Nobili, Francesco Vizzutti, Umberto Arena, Juan G. Abraldes, Fabio Marra, Andrea Pietrobattista, Rodolfo Fruhwirth, Matilde Marcellini, Massimo Pinzani – 18 April 2008 – Transient elastography (TE) has received increasing attention as a means to evaluate disease progression in chronic liver disease patients. In this study, we assessed the value of TE for the prediction of fibrosis stage in a cohort of pediatric patients with nonalcoholic steatohepatitis. Furthermore, TE interobserver agreement was evaluated.

Selection of high‐avidity CD8 T cells correlates with control of hepatitis C virus infection

Bérangère Neveu, Emilie Debeaupuis, Klara Echasserieau, Béatrice le Moullac‐Vaidye, Michelle Gassin, Loïg Jegou, Jérémie Decalf, Matthew Albert, Nicolas Ferry, Jérôme Gournay, Elisabeth Houssaint, Marc Bonneville, Xavier Saulquin – 18 April 2008 – Both strong antigenic avidity and acquisition of proper effector functions contribute to the efficacy of antiviral T cell responses.

Nuclear receptor cofactor receptor interacting protein 140 controls hepatic triglyceride metabolism during wasting in mice

Mauricio Berriel Diaz, Anja Krones‐Herzig, Dagmar Metzger, Anja Ziegler, Alexandros Vegiopoulos, Martin Klingenspor, Karin Müller‐Decker, Stephan Herzig – 18 April 2008 – In mammals, triglycerides (TG) represent the most concentrated form of energy. Aberrant TG storage and availability are intimately linked to the negative energy balance under severe clinical conditions, such as starvation, sepsis, or cancer cachexia. Despite its crucial role for energy homeostasis, molecular key determinants of TG metabolism remain enigmatic.

Cognitive impairment in primary biliary cirrhosis: Symptom impact and potential etiology

Julia L. Newton, Kieren G. Hollingsworth, Roy Taylor, Ahmed M. El‐Sharkawy, Zia Uda Khan, Ruth Pearce, Kathryn Sutcliffe, Oke Okonkwo, Adrian Davidson, Jennifer Burt, Andrew M. Blamire, David Jones – 16 April 2008 – Qualitative studies suggest that patients with primary biliary cirrhosis (PBC) experience significant problems with memory and concentration. Studies of nonhepatic disease have linked hypotension and cognitive impairment.

Genetic control of resistance to hepatocarcinogenesis by the mouse Hpcr3 locus

Giacomo Manenti, Antonella Galvan, F. Stefania Falvella, Rosa M. Pascale, Elena Spada, Silvano Milani, Anna Gonzalez Neira, Francesco Feo, Tommaso A. Dragani – 16 April 2008 – The genome of the BALB/c mouse strain provides alleles that dominantly inhibit hepatocellular tumor development in F1 crosses with the highly hepatocarcinogenesis‐susceptible C3H/He strain.

Glutathione S‐transferase m1 and t1 null genotypes increase susceptibility to idiosyncratic drug‐induced liver injury

M. Isabel Lucena, Raúl J. Andrade, Carmen Martínez, Eugenia Ulzurrun, Elena García‐Martín, Yolanda Borraz, M. Carmen Fernández, Manuel Romero‐Gomez, Agustin Castiella, Ramón Planas, Joan Costa, Sandra Anzola, José A. G. Agúndez – 16 April 2008 – Individual vulnerability to drug‐induced liver injury (DILI) might result from deficiencies in the detoxification process, which determines the level of exposure to the reactive metabolite.

Dietary cholesterol, rather than liver steatosis, leads to hepatic inflammation in hyperlipidemic mouse models of nonalcoholic steatohepatitis

Kristiaan Wouters, Patrick J. van Gorp, Veerle Bieghs, Marion J. Gijbels, Hans Duimel, Dieter Lütjohann, Anja Kerksiek, Roger van Kruchten, Nobuyo Maeda, Bart Staels, Marc van Bilsen, Ronit Shiri‐Sverdlov, Marten H. Hofker – 15 April 2008 – Nonalcoholic steatohepatitis (NASH) involves liver lipid accumulation (steatosis) combined with hepatic inflammation. The transition towards hepatic inflammation represents a key step in pathogenesis, because it will set the stage for further liver damage, culminating in hepatic fibrosis, cirrhosis, and liver cancer.

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