Contribution to antimitochondrial antibody production: Cleavage of pyruvate dehydrogenase complex‐E2 by apoptosis‐related proteases

Shuji Matsumura, Judy Van De Water, Hiroto Kita, Ross L. Coppel, Takao Tsuji, Kazuhide Yamamoto, Aftab A. Ansari, M. Eric Gershwin – 30 December 2003 – Patients with PBC produce a directed, specific response to a single immunodominant autoepitope of PDC‐E2 within the inner lipoyl domain. In contrast, immunized animals react to multiple epitopes and rarely recognize the inner lipoyl domain. In other autoimmune diseases, apoptosis plays a critical role in antigen presentation; the caspases and granzyme B are the key proteases in the generation of autoepitopes.

α‐Fetoprotein mRNA in the circulation as a predictor of postsurgical recurrence of hepatocellular carcinoma: A prospective study

Masayoshi Ijichi, Tadatoshi Takayama, Masayuki Matsumura, Yasushi Shiratori, Masao Omata, Masatoshi Makuuchi – 30 December 2003 – α‐fetoprotein (AFP) messenger RNA (mRNA) has been proposed as a marker of hepatocellular carcinoma (HCC) cells disseminated into the circulation, but its clinical significance remains controversial. We prospectively assessed the prognostic value of AFP mRNA in patients undergoing curative hepatic resection for HCC.

Time‐dependent Cox regression model is superior in prediction of prognosis in primary sclerosing cholangitis

Kirsten Muri Boberg, Giuseppe Rocca, Thore Egeland, Annika Bergquist, Ulrika Broomé, Llorenc Caballeria, Roger Chapman, Rolf Hultcrantz, Stephen Mitchell, Albert Pares, Floriano Rosina, Erik Schrumpf – 30 December 2003 – More precise prognostic models are needed for prediction of survival in patients with primary sclerosing cholangitis (PSC), particularly for the selection of candidates for liver transplantation. The aim of this study was to develop a time‐dependent prognostic model for the calculation of updated short‐term survival probability in PSC.

COX‐2 inhibits Fas‐mediated apoptosis in cholangiocarcinoma cells

Ugochukwu C. Nzeako, Maria Eugenia Guicciardi, Jung‐Hwan Yoon, Steven F. Bronk, Gregory J. Gores – 30 December 2003 – Fas expression has been shown to negatively regulate the progression of cholangiocarcinoma cells in xenografts. However, many human cholangiocarcinomas express Fas, suggesting these cancers have developed mechanisms to inhibit Fas‐mediated apoptosis. Cyclooxygenase‐2 (COX‐2), which generates prostanoids, is expressed by many cholangiocarcinomas.

Recombinant factor VIIa improves clot formation but not fibrolytic potential in patients with cirrhosis and during liver transplantation

Ton Lisman, Frank W.G. Leebeek, Karina Meijer, Jan Van Der Meer, H. Karel Nieuwenhuis, Philip G. De Groot – 30 December 2003 – Cirrhosis is associated with a bleeding tendency, which is particularly pronounced during orthotopic liver transplantation (OLT). A novel approach to treating the bleeding diathesis of patients with cirrhosis is administration of recombinant factor VIIa (rFVIIa). This study examined whether the efficacy of rFVIIa in cirrhosis might be explained in part by enhanced down‐regulation of fibrinolysis by thrombin‐activatable fibrinolysis inhibitor (TAFI).

γ‐Glutamyl transpeptidase overexpression increases metastatic growth of B16 melanoma cells in the mouse liver

Elena Obrador, Julian Carretero, Angel Ortega, Ignacio Medina, Vicente Rodilla, José A. Pellicer, José M. Estrela – 30 December 2003 – B16 melanoma (B16M) cells with high glutathione (GSH) content show rapid proliferation in vitro and high metastatic activity in the liver in vivo. γ‐Glutamyl transpeptidase (GGT)‐mediated extracellular GSH cleavage and intracellular GSH synthesis were studied in vitro in B16M cells with high (F10) and low (F1) metastatic potential. GGT activity was modified by transfection with the human GGT gene (B16MF1/Tet‐GGT cells) or by acivicin‐induced inhibition.

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