Leptin is required for fibrogenic responses induced by thioacetamide in the murine liver

Hajime Honda, Kenichi Ikejima, Miyoko Hirose, Mutsuko Yoshikawa, Tie Lang, Nobuyuki Enomoto, Tsuneo Kitamura, Yoshiyuki Takei, Nobuhiro Sato – 30 December 2003 – In this study, we investigated hepatic fibrogenesis caused by long‐term thioacetamide (TAA) administration in ob/ob mice, a naturally occurring leptin deficient animal. In the lean littermates, prominent hepatic fibrosis, as well as positive staining for α smooth muscle actin (α‐SMA), was induced by treatment with TAA (200 μg/g, IP, 3 times per week) for 4 to 8 weeks as expected.

Bilirubin induces apoptosis via the mitochondrial pathway in developing rat brain neurons

Cecília M. P. Rodrigues, Susana Solá, Dora Brites – 30 December 2003 – Increased levels of unconjugated bilirubin, the end‐product of heme catabolism, are detrimental to the central nervous system. To examine the role of apoptosis in bilirubin‐induced toxicity and to characterize the biochemical pathway of cell death, we exposed developing rat brain neurons to purified unconjugated bilirubin at concentrations below and above saturation of human serum albumin. Isolated neurons treated with bilirubin showed increased levels of apoptosis.

Dose‐dependent inhibition of hepatic fibrosis in mice by a TGF‐β soluble receptor: Implications for antifibrotic therapy

Yutaka Yata, Philip Gotwals, Victor Koteliansky, Don C. Rockey – 30 December 2003 – Transforming growth factor (TGF) β isoforms (in particular, TGF‐β1) play a central role in the fibrogenic response to injury in many organs, including the liver. Although TGF‐β is clearly important in fibrogenesis, a number of issues related to therapeutic antagonism have emerged. For example, the long‐term effect of TGF‐β antagonism is unknown; furthermore, controversy exists as to appropriate levels of TGF‐β inhibition.

Relationship between acetaldehyde levels and cell survival in ethanol‐metabolizing hepatoma cells

Dahn L. Clemens, Andrew Forman, Thomas R. Jerrells, Michael F. Sorrell, Dean J. Tuma – 30 December 2003 – We have created a number of recombinant Hep G2 cell lines, designated VA cells, that constitutively express alcohol dehydrogenase. Oxidation of ethanol by the VA cells results in the production and accumulation of acetaldehyde, and a dramatic increase in the nicotinamide adenine dinucleotide, reduced (NADH)/nicotinamide adenine dinucleotide (NAD+) ratio (redox‐state).

Liver transplantation as definitive therapy for complications after arterial embolization for hepatic manifestations of hereditary hemorrhagic telangiectasia

Jon S. Odorico,, M. Nawar Hakim, Yolanda T. Becker, Willem Van der Werf, Alexandru Musat, Stuart J. Knechtle, Anthony M. D'Alessandro, Munci Kalayoglu – 30 December 2003 – Experience with hepatic artery embolization for the treatment of symptomatic hepatic arteriovenous malformations (AVMs) in Rendu‐Osler‐Weber disease is limited. We report 2 cases of hepatic AVMs that caused mesenteric angina‐like symptoms that were treated with embolization.

Relationship of the genomic complexity of hepatitis C virus with liver disease severity and response to interferon in patients with chronic HCV genotype 1b interferon

Francesc‐Xavier López‐Labrador, Sergi Ampurdanès, Mireia Giménez‐Barcons, Magdalena Guilera, Josep Costa, María Teresa Jiménez de Anta, Jose M. Sánchez‐Tapias, Juan Rodés, Juan‐Carlos Sáiz – 30 December 2003 – In patients with chronic hepatitis C, the influence of the genetic heterogeneity of the hepatitis C virus (HCV) on the progression of liver disease and on the responsiveness to interferon therapy is a matter of controversy.

Role of C‐kitreceptor tyrosine kinase in development of oval cells in the rat 2‐acetylaminofluorene/partial hepatectomy model

Satoshi Matsusaka, Tohru Tsujimura, Akihiro Toyosaka, Keiji Nakasho, Ayako Sugihara, Eizo Okamoto, Kunio Uematsu, Nobuyuki Terada – 30 December 2003 – Oval cells that develop in the rat 2‐acetylaminofluorene/partial hepatectomy (AAF/PH) model express the c‐kit receptor tyrosine kinase (KIT) and its ligand, stem cell factor (SCF). We investigated the role of the SCF/KIT system in the development of oval cells usingWs/Ws rats, whose c‐kitkinase activity was severely impaired owing to a small deletion in the kinase domain.

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