Single nucleotide polymorphism–mediated translational suppression of endoplasmic reticulum mannosidase I modifies the onset of end‐stage liver disease in alpha1‐antitrypsin deficiency

Shujuan Pan, Lu Huang, John McPherson, Donna Muzny, Farshid Rouhani, Mark Brantly, Richard Gibbs, Richard N. Sifers – 23 June 2009 – Inappropriate accumulation of the misfolded Z variant of alpha1‐antitrypsin in the hepatocyte endoplasmic reticulum (ER) is a risk factor for the development of end‐stage liver disease. However, the genetic and environmental factors that contribute to its etiology are poorly understood. ER mannosidase I (ERManI) is a quality control factor that plays a critical role in the sorting and targeting of misfolded glycoproteins for proteasome‐mediated degradation.

The etiology of liver damage imparts cytokines transforming growth factor β1 or interleukin‐13 as driving forces in fibrogenesis

Hong‐Lei Weng, Yan Liu, Jia‐Lin Chen, Tong Huang, Li‐Jun Xu, Patricio Godoy, Jun‐Hua Hu, Cheng Zhou, Felix Stickel, Alexander Marx, Rainer M. Bohle, Vincent Zimmer, Frank Lammert, Sebastian Mueller, Michelle Gigou, Didier Samuel, Peter R. Mertens, Manfred V. Singer, Helmut K.

Statins potentiate the in vitro anti‐hepatitis C virus activity of selective hepatitis C virus inhibitors and delay or prevent resistance development

Leen Delang, Jan Paeshuyse, Inge Vliegen, Pieter Leyssen, Susan Obeid, David Durantel, Fabien Zoulim, Anne Op de Beeck, Johan Neyts – 23 June 2009 – Statins are 3‐hydroxyl‐3‐methylglutaryl coenzyme A (HMG CoA) reductase inhibitors used for the treatment of hypercholesterolemia. It was recently reported that statins inhibit in vitro hepatitis C virus (HCV) RNA replication.

Vigorous activation of monocytes in juvenile autoimmune liver disease escapes the control of regulatory T‐cells

Maria Serena Longhi, Ragai R. Mitry, Marianne Samyn, Astrid Scalori, Munther J. Hussain, Alberto Quaglia, Giorgina Mieli‐Vergani, Yun Ma, Diego Vergani – 23 June 2009 – Interface hepatitis, the histological lesion typical of autoimmune hepatitis (AIH), is composed of CD4 and CD8 T lymphocytes and of innate immunity cells, particularly monocytes. Studies in AIH have focused on autoreactive CD4 and CD8 T cells and impairment of CD4+CD25+ regulatory T cells (T‐regs), whereas little is known about the role of monocytes and their relationship with T‐regs.

Association between dietary nutrient composition and the incidence of cirrhosis or liver cancer in the united states population

George N. Ioannou, Olivia B. Morrow, Marah L. Connole, Sum P. Lee – 23 June 2009 – Little is known about the impact of dietary factors on the progression of liver disease. Our aim was to determine whether dietary intake was associated with the risk of cirrhosis‐related or liver cancer–related death or hospitalization in the U.S. population.

Independent effects of physical activity in patients with nonalcoholic fatty liver disease

Alexis St. George, Adrian Bauman, Amanda Johnston, Geoffrey Farrell, Tien Chey, Jacob George – 23 June 2009 – Nonalcoholic fatty liver disease, characterized by elevated liver enzymes, central obesity, and insulin resistance, is becoming increasingly prevalent. The effects of changes in physical activity on the metabolic profile of this group have not been reported. We assessed at 3 months the impact of a behavior change‐based lifestyle intervention on physical activity and the effects of this change on the metabolic profile of people with fatty liver disease.

Diferentially expressed adenylyl cyclase isoforms mediate secretory functions in cholangiocyte subpopulation

Mario Strazzabosco, Romina Fiorotto, Saida Melero, Shannon Glaser, Heather Francis, Carlo Spirli, Gianfranco Alpini – 23 June 2009 – Cyclic adenosine monophosphate (cAMP) is generated by adenylyl cyclases (ACs), a group of enzymes with different tissue specificity and regulation. We hypothesized that AC isoforms are heterogeneously expressed along the biliary tree, are associated with specific secretory stimuli, and are differentially modulated in cholestasis.

L‐ornithine and phenylacetate synergistically produce sustained reduction in ammonia and brain water in cirrhotic rats

Nathan A. Davies, Gavin Wright, Lars M. Ytrebø, Vanessa Stadlbauer, Ole‐Martin Fuskevåg, Claudia Zwingmann, D. Ceri Davies, Abeba Habtesion, Stephen J. Hodges, Rajiv Jalan – 23 June 2009 – Treatment of hyperammonemia and hepatic encephalopathy in cirrhosis is an unmet clinical need.

Hepatic recruitment of the inflammatory Gr1+ monocyte subset upon liver injury promotes hepatic fibrosis

Karlin Raja Karlmark, Ralf Weiskirchen, Henning W. Zimmermann, Nikolaus Gassler, Florent Ginhoux, Christian Weber, Miriam Merad, Tom Luedde, Christian Trautwein, Frank Tacke – 23 June 2009 – In addition to liver‐resident Kupffer cells, infiltrating immune cells have recently been linked to the development of liver fibrosis. Blood monocytes are circulating precursors of tissue macrophages and can be divided into two functionally distinct subpopulations in mice: Gr1hi (Ly6Chi) and Gr1lo (Ly6Clo) monocytes.

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