Topoisomerase inhibitor camptothecin sensitizes mouse hepatocytes in vitro and in vivo to TNF‐mediated apoptosis

Hannes Hentze, Markus Latta, Gerald Künstle, Saravanakumar Dhakshinamoorthy, Poh Yong Ng, Alan G. Porter, Albrecht Wendel – 26 April 2004 – Topoisomerases are nuclear enzymes that maintain and modulate DNA structure. Inhibitors of topoisomerases like camptothecin (CPT), etoposide, and others are widely used antitumor drugs that interfere with transcription, induce DNA strand breaks, and trigger apoptosis preferentially in dividing cells.

Improved prediction of fibrosis in chronic hepatitis C using measures of insulin resistance in a probability index

Archana Sud, Jason M. Hui, Geoffrey C. Farrell, Priyanka Bandara, James G. Kench, Carolyn Fung, Rita Lin, Dev Samarasinghe, Christopher Liddle, Geoffrey W. McCaughan, Jacob George – 26 April 2004 – We sought to develop a clinically useful index comprising standard and physiologically relevant variables to predict the probability of significant hepatic fibrosis in subjects with chronic hepatitis C virus (HCV) infection. Fibrosis was graded as mild (stages F0 or F1) or significant (stages F2–F4).

Short‐term interferon‐alfa therapy for acute hepatitis C: A randomized controlled trial

Hideyuki Nomura, Suketo Sou, Hironori Tanimoto, Takashi Nagahama, Yoichi Kimura, Jun Hayashi, Hiromi Ishibashi, Seizaburo Kashiwagi – 26 April 2004 – Acute hepatitis C often progresses to chronic infection. We undertook a randomized controlled trial to determine whether short‐term therapy with interferon (IFN) during acute hepatitis C is effective in preventing the development of chronic hepatitis. Thirty patients with acute hepatitis C were randomized into 1 of 2 treatment groups.

Thy1‐positive mesenchymal cells promote the maturation of CD49f‐positive hepatic progenitor cells in the mouse fetal liver

Toshitaka Hoppo, Hideaki Fujii, Tetsuro Hirose, Kentaro Yasuchika, Hisaya Azuma, Shinji Baba, Masato Naito, Takafumi Machimoto, Iwao Ikai – 26 April 2004 – Previously, we reported a system to enrich mouse fetal hepatic progenitor cells (HPCs) by forming cell aggregates. In this study, we sorted two cell populations, CD49f+Thy1−CD45− cells (CD49f‐postive cells) and CD49f±Thy1+CD45− cells (Thy1‐positive cells), from the cell aggregates using a flow cytometer.

Administration of the potent PPARα agonist, Wy‐14,643, reverses nutritional fibrosis and steatohepatitis in mice

Emilia Ip, Geoff Farrell, Pauline Hall, Graham Robertson, Isabelle Leclercq – 26 April 2004 – Administration of a methionine and choline deficient (MCD) diet to rodents causes progressive fibrosing steatohepatitis pathologically similar to human metabolic steatohepatitis. We have previously shown that the peroxisome proliferator‐activated receptor‐α (PPARα) agonist, Wy‐14,643, prevented the development of MCD diet‐induced steatohepatitis. We have now tested whether Wy‐14,643 ameliorates established steatohepatitis and fibrosis.

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