Th1 cytokine–induced downregulation of PPARγ in human biliary cells relates to cholangitis in primary biliary cirrhosis

Kenichi Harada, Kumiko Isse, Takashi Kamihira, Shinji Shimoda, Yasuni Nakanuma – 23 May 2005 – Peroxisome proliferator‐activated receptor‐γ (PPARγ) is known to inhibit the production of proinflammatory cytokines. In Th1‐predominant diseases, PPARγ ligands can ameliorate clinical severity by downregulating the expression of proinflammatory cytokines. Primary biliary cirrhosis (PBC) is characterized by chronic destructive cholangitis with a Th1‐predominant cytokine milieu. Unusual immune responses to infectious agents are suspected to underlie its etiopathogenesis.

Genome‐wide analysis of gene expression in human intrahepatic cholangiocarcinoma

Kazutaka Obama, Katsuaki Ura, Meihua Li, Toyomasa Katagiri, Tatsuhiko Tsunoda, Akinari Nomura, Seiji Satoh, Yusuke Nakamura, Yoichi Furukawa – 23 May 2005 – Intrahepatic cholangiocarcinoma is a neoplasm arising in the liver, and its incidence is increasing in Japan as well as in Western countries. Prognosis of patients with this type of tumor remains unsatisfactory because no effective chemotherapeutic drugs are available, we have no sensitive tumor markers to detect this tumor in its early stage, and it is difficult to identify a high‐risk group for the disease.

An inhibitor of cyclin‐dependent kinase, stress‐induced p21Waf‐1/Cip‐1, mediates hepatocyte mito‐inhibition during the evolution of cirrhosis

John G. Lunz, Hirokazu Tsuji, Isao Nozaki, Noriko Murase, Anthony J. Demetris – 23 May 2005 – During the evolution of cirrhosis, there is a relative decrease in volume percentage of hepatocytes and a relative increase in biliary epithelial cells and myofibroblasts. This is recognized histopathologically as a ductular reaction and leads to gradual distortion of the normal hepatic architecture.

MELD score and clinical type predict prognosis in hepatorenal syndrome: Relevance to liver transplantation

Carlo Alessandria, Osman Ozdogan, Mónica Guevara, Tea Restuccia, Wladimiro Jiménez, Vicente Arroyo, Juan Rodés, Pere Ginès – 23 May 2005 – Important progress has been made recently regarding the pathogenesis and treatment of hepatorenal syndrome (HRS). However, scant information exists about factors predicting outcome in patients with cirrhosis and HRS. Moreover, the prognostic value of the model of end‐stage liver disease (MELD) score has not been validated in the setting of HRS.

Dose‐ and time‐dependent oval cell reaction in acetaminophen‐induced murine liver injury

Alexander V. Kofman, Glyn Morgan, Adam Kirschenbaum, Jon Osbeck, Mehboob Hussain, Scott Swenson, Neil D. Theise – 23 May 2005 – We examined the response of murine oval cells, that is, the putative liver progenitor cells, to acetaminophen. Female C57BL/6J mice were injected intraperitoneally with varying doses of N‐acetyl‐paraaminophen (APAP) (250, 500, 750, and 1,000 mg/kg of weight) and sacrificed at 3, 6, 9, 24, and 48 hours. In preliminary studies, we showed that anticytokeratin antibodies detected A6‐positive cells with a sensitivity and specificity of greater than 99%.

Activation of CREB by tauroursodeoxycholic acid protects cholangiocytes from apoptosis induced by mTOR inhibition

LiFu Wang, Anne‐Christine Piguet, Karin Schmidt, Thierry Tordjmann, Jean‐François Dufour – 23 May 2005 – Tauroursodeoxycholic acid (TUDCA) is a cytoprotective bile acid frequently prescribed to patients with cholestatic diseases. Several mechanisms of action have been investigated, but the possibility that cyclic adenosine monophosphate responsive element binding protein (CREB), a transcription factor promoting cell survival, mediates TUDCA's protective effects has not been considered.

An intronic silencer element is responsible for specific zonal expression of glutamine synthetase in the rat liver

Frank Gaunitz, Danilo Deichsel, Kerstin Heise, Max Werth, Ulf Anderegg, Rolf Gebhardt – 23 May 2005 – The most striking phenomenon of glutamine synthetase (GS) expression in the liver is its unique restriction to cells surrounding the terminal hepatic venules. Expression is positively regulated by elements located in the 5′‐upstream region and in the first intron of the gene. It was long believed that transcription factors present in GS‐positive cells and absent in GS‐negative cells are responsible for the phenomenon of zonal expression.

Long‐term follow‐up of peginterferon and lamivudine combination treatment in HBeAg‐positive chronic hepatitis B

Henry Lik‐Yuen Chan, Alex Yui Hui, Vincent Wai‐Sun Wong, Angel Mei‐Ling Chim, May‐Ling Wong, Joseph Jao‐Yiu Sung – 23 May 2005 – We have previously demonstrated that combination peginterferon and lamivudine treatment has superior antiviral efficacy to lamivudine monotherapy in chronic hepatitis B. In this study, we investigated the long‐term posttreatment virological response to this combination treatment.

Purification and characterization of mouse fetal liver epithelial cells with high in vivo repopulation capacity

Dirk Nierhoff, Atsushi Ogawa, Michael Oertel, Yuan‐Qing Chen, David A. Shafritz – 13 May 2005 – Epithelial cells in embryonic day (ED) 12.5 murine fetal liver were separated from hematopoietic cell populations using fluorescence‐activated cell sorting (FACS) and were characterized by immunocytochemistry using a broad set of antibodies specific for epithelial cells (α‐fetoprotein [AFP], albumin [ALB], pancytokeratin [PanCK], Liv2, E‐cadherin, Dlk), hematopoietic/endothelial cells (Ter119, CD45, CD31), and stem/progenitor cells (c‐Kit, CD34, Sca‐1).

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