Mesenteric Th1 polarization and monocyte TNF‐α production: First steps to systemic inflammation in rats with cirrhosis

Leticia Muñoz, Agustín Albillos, Mónica Nieto, Eduardo Reyes, Lourdes Lledó, Jorge Monserrat, Eva Sanz, Antonio de la Hera, Melchor Alvarez‐Mon – 15 July 2005 – A systemic inflammatory state with increased circulating tumor necrosis factor alpha (TNF‐α) has been related to the bacterial infection susceptibility and hemodynamic derangement of patients with cirrhosis.

Induction of cytochrome P450 2E1 increases hepatotoxicity caused by Fas agonistic Jo2 antibody in mice

Xiaodong Wang, Yongke Lu, Arthur I. Cederbaum – 15 July 2005 – Cytochrome P450 2E1 (CYP2E1) may be a central pathway in generating oxidative stress, reactive oxygen species, and causing hepatotoxic injury by alcohol and various hepatotoxins. This study evaluated the ability of CYP2E1 to potentiate or synergize the hepatotoxicity of Fas in vivo. C57BL/6 mice were injected intraperitoneally with pyrazole (Pyr) to induce CYP2E1. Then, 16‐hour fasted mice were administered agonistic Jo2 anti‐Fas antibody ip. Other mice were treated with Pyr or Jo2 alone.

Hepatic steatosis in HIV/hepatitis C coinfection: Prevalence and significance compared with hepatitis C monoinfection

Alexander Monto, Lorna M. Dove, Alan Bostrom, Sanjay Kakar, Phyllis C. Tien, Teresa L. Wright – 15 July 2005 – Liver disease in patients coinfected with HIV and hepatitis C virus (HCV) has received increasing attention in recent years. Steatosis is accepted as an important contributor to liver disease in patients with HCV, but despite coinfected patients having several reasons to have steatosis, the prevalence and significance of such changes has received scant attention.

The role of hepatic type 1 plasminogen activator inhibitor (PAI‐1) during murine hemorrhagic shock

Claudio E. Lagoa, Yoram Vodovotz, Donna B. Stolz, Franck Lhuillier, Carol McCloskey, David Gallo, Runkuan Yang, Elena Ustinova, Mitchell P. Fink, Timothy R. Billiar, Wendy M. Mars – 15 July 2005 – Hemorrhagic shock (HS) followed by resuscitation (HS‐R) is characterized by profound physiological changes. Even if the patient survives the initial blood loss, these poorly understood changes can lead to morbidity. One of the tissues most often affected is liver. We sought to recognize specific hepatic changes induced by this stressor to identify targets for therapeutic intervention.

CD154–CD40 interactions drive hepatocyte apoptosis in murine fulminant hepatitis

Feng Zhou, Maureen N. Ajuebor, Paul L. Beck, Tai Le, Cory M. Hogaboam, Mark G. Swain – 15 July 2005 – The CD154–CD40 interaction is a critical costimulatory pathway modulating the cellular immune response. Moreover, fulminant hepatitis of various etiologies is characterized by a hepatic influx of CD154‐expressing T cells and an upregulation of CD40 expression on Kupffer cells and hepatocytes, implicating this pathway in the pathogenesis of fulminant hepatitis.

Conventional liver CD4 T cells are functionally distinct and suppressed by environmental factors

Steven C. Katz, Venu G. Pillarisetty, Joshua I. Bleier, T. Peter Kingham, Umer I. Chaudhry, Alaap B. Shah, Ronald P. DeMatteo – 15 July 2005 – The contribution of intrahepatic conventional T cells to the unique immunologic properties of the liver has not been clearly defined. We isolated bulk and CD4 T cells from mouse liver and compared their functions with each other and with their splenic counterparts. Unlike bulk spleen T cells, bulk liver T cells reacted minimally to allogeneic or antigen‐loaded syngeneic dendritic cells.

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