Cell culture–produced hepatitis C virus does not infect peripheral blood mononuclear cells

Svetlana Marukian, Christopher T. Jones, Linda Andrus, Matthew J. Evans, Kimberly D. Ritola, Edgar D. Charles, Charles M. Rice, Lynn B. Dustin – 24 November 2008 – Hepatitis C virus (HCV) replicates primarily in the liver, but HCV RNA has been observed in association with other tissues and cells including B and T lymphocytes, monocytes, and dendritic cells. We have taken advantage of a recently described, robust system that fully recapitulates HCV entry, replication and virus production in vitro to re‐examine the issue of HCV infection of blood cell subsets.

Transplantation‐mediated alloimmune thrombocytopenia: Guidelines for utilization of thrombocytopenic donors

Geraldine C. Diaz, Joan Prowda, Irene J. Lo, Gowthami M. Arepally, Neal Evans, Yvonne Wheeless, Benjamin Samstein, James V. Guarrera, John F. Renz – 24 November 2008 – Transplantation‐mediated alloimmune thrombocytopenia (TMAT) is donor‐derived thrombocytopenia following solid‐organ transplantation. To date, no clear consensus on the appropriateness of organ utilization from cadaver donors with a history of idiopathic thrombocytopenia purpura (ITP) has emerged.

Local accumulation and activation of regulatory Foxp3+ CD4 TR cells accompanies the appearance of activated CD8 T cells in the liver

Petra Bochtler, Petra Riedl, Ivan Gomez, Reinhold Schirmbeck, Jörg Reimann – 24 November 2008 – Only small populations of nonactivated, nonproliferating Foxp3+ CD4 regulatory T cell (TR) cells are found in the nonparenchymal cell compartment of the mouse liver while liver‐draining celiac nodes contain expanded, activated TR cell populations (similar to other lymph nodes). Liver Foxp3+ CD4 TR cells suppress activation of T cell responses.

Selenoprotein P expression is controlled through interaction of the coactivator PGC‐1α with FoxO1a and hepatocyte nuclear factor 4α transcription factors

Bodo Speckmann, Philippe L. Walter, Lirija Alili, Roland Reinehr, Helmut Sies, Lars‐Oliver Klotz, Holger Steinbrenner – 24 November 2008 – Selenoprotein P (SeP), the major selenoprotein in plasma, is produced mainly by the liver, although SeP expression is detected in many organs. Recently, we reported stimulation of SeP promoter activity by the forkhead box transcription factor FoxO1a in hepatoma cells and its attenuation by insulin. Here, we demonstrate that this translates into fine‐tuning of SeP production and secretion by insulin.

The membrane protein ATPase class I type 8B member 1 signals through protein kinase C zeta to activate the farnesoid X receptor

Tamara Frankenberg, Tamir Miloh, Frank Y. Chen, Meena Ananthanarayanan, An‐Qiang Sun, Natarajan Balasubramaniyan, Irwin Arias, Kenneth D. R. Setchell, Frederick J. Suchy, Benjamin L. Shneider – 24 November 2008 – Prior loss‐of‐function analyses revealed that ATPase class I type 8B member 1 [familial intrahepatic cholestasis 1 (FIC1)] posttranslationally activated the farnesoid X receptor (FXR). Mechanisms underlying this regulation were examined by gain‐of‐function studies in UPS cells, which lack endogenous FIC1 expression.

Hepatitis C virus therapy in liver transplant recipients: Response predictors, effect on fibrosis progression, and importance of the initial stage of fibrosis

Bruno Roche, Mylene Sebagh, Maria Laura Canfora, Teresa Antonini, Anne‐Marie Roque‐Afonso, Valerie Delvart, Faouzi Saliba, Jean‐Charles Duclos‐Vallee, Denis Castaing, Didier Samuel – 24 November 2008 – Antiviral therapy after liver transplantation (LT) using interferon (IFN) and ribavirin (RBV) can achieve a sustained virological response (SVR) rate ranging from 20% to 45%. The aims of our study were to assess efficacy and tolerability of therapy, effect on fibrosis progression and the importance of the initial fibrosis stage to outcome.

Decline in native kidney function in liver transplant recipients is not associated with BK virus infection

Muna Salama, Neil Boudville, David Speers, Garry P. Jeffrey, Paolo Ferrari – 24 November 2008 – BK virus (BKV) infection is an established cause of allograft dysfunction in renal transplant recipients. The relationship between BKV infection and chronic kidney disease (CKD) post–orthotopic liver transplantation (OLT) is not well understood. This study aimed to determine the prevalence of BKV infection, its relationship to CKD and renal function loss over time in patients receiving OLT.

Genotype‐dependent sensitivity of hepatitis C virus to inhibitors of the p7 ion channel

Stephen Griffin, Corine StGelais, Ania M. Owsianka, Arvind H. Patel, David Rowlands, Mark Harris – 24 November 2008 – The hepatitis C virus (HCV) p7 protein plays a critical role during particle formation in cell culture and is required for virus replication in chimpanzees. The discovery that it displayed cation channel activity in vitro led to its classification within the “viroporin” family of virus‐coded ion channel proteins, which includes the influenza A virus (IAV) M2 protein.

Switch from type II to I Fas/CD95 death signaling on in vitro culturing of primary hepatocytes

Dorothée Walter, Kathrin Schmich, Sandra Vogel, Robert Pick, Thomas Kaufmann, Florian Christoph Hochmuth, Angelika Haber, Karin Neubert, Sabine McNelly, Fritz von Weizsäcker, Irmgard Merfort, Ulrich Maurer, Andreas Strasser, Christoph Borner – 24 November 2008 – Fas/CD95‐induced apoptosis of hepatocytes in vivo proceeds through the so‐called type II pathway, requiring the proapoptotic BH3‐only Bcl‐2 family member Bid for mitochondrial death signaling. Consequently, Bid‐deficient mice are protected from anti‐Fas antibody injection induced fatal hepatitis.

Liver‐specific ablation of integrin‐linked kinase in mice results in abnormal histology, enhanced cell proliferation, and hepatomegaly

Vasiliki Gkretsi, Udayan Apte, Wendy M. Mars, William C. Bowen, Jian‐Hua Luo, Yu Yang, Yan P. Yu, Ann Orr, René St.‐Arnaud, Shoukat Dedhar, Klaus H. Kaestner, Chuanyue Wu, George K. Michalopoulos – 24 November 2008 – Hepatocyte differentiation and proliferation are greatly affected by extracellular matrix (ECM). Primary hepatocytes cultured without matrix dedifferentiate over time, but matrix overlay quickly restores differentiation. ECM also is critical in liver regeneration where ECM degradation and reconstitution are steps in the regenerative process.

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