Embryoid‐body cells derived from a mouse embryonic stem cell line show differentiation into functional hepatocytes

Ryoko Chinzei, Yujiro Tanaka, Keiko Shimizu‐Saito, Yuzuru Hara, Sei Kakinuma, Mamoru Watanabe, Kenichi Teramoto, Shigeki Arii, Kozo Takase, Chifumi Sato, Naohiro Terada, Hirobumi Teraoka – 30 December 2003 – Embryonic stem (ES) cells have a potential to differentiate into various progenitor cells. Here we investigated the differentiation capacity of mouse ES cells into hepatocytes both in vitro and in vivo.

Intracellular pathways mediating estrogen‐induced cholangiocyte proliferation in the rat

Domenico Alvaro, Paolo Onori, Veronica Drudi Metalli, Gianluca Svegliati‐Baroni, Franco Folli, Antonio Franchitto, Gianfranco Alpini, Maria Grazia Mancino, Adolfo Francesco Attili, Eugenio Gaudio – 30 December 2003 – The aim of this study was to explore the intracellular signaling pathways involved in the stimulatory effects of estrogens on cholangiocyte proliferation.

Noninvasive monitoring of patients with chronic hepatitis C

Robert J. Fontana, Anna S. F. Lok – 30 December 2003 – Hepatic fibrosis is the main determinant of clinical outcomes of chronic hepatitis C. Liver histology is frequently considered the gold standard for assessing hepatic fibrosis. However, liver biopsy is associated with sampling error, interobserver variability, and potential complications. Thus, there is a need for simple, inexpensive, and reliable noninvasive means to assess disease severity in patients with chronic hepatitis C. Clinical examination is unreliable in differentiating different stages of compensated liver disease.

Side effects of therapy of hepatitis C and their management

Michael W. Fried – 30 December 2003 – Interferon and ribavirin combination therapy for chronic hepatitis C produces a number of well‐described side effects that are dominated by fatigue, influenza‐like symptoms, hematologic abnormalities, and neuropsychiatric symptoms. Combination therapy with pegylated interferons (peginterferon alfa‐2a and alfa‐2b) yields an adverse event profile similar to standard interferon, although the frequency of certain adverse events may vary by preparation.

Deletion of the Ron receptor tyrosine kinase domain in mice provides protection from endotoxin‐induced acute liver failure

Mike A. Leonis, Kenya Toney‐Earley, Sandra J. F. Degen, Susan E. Waltz – 30 December 2003 – The targeted deletion of the cytoplasmic domain of the Ron receptor tyrosine kinase (TK) in mice leads to exaggerated responses to injury in several murine models of inflammation as well as increased lethality in response to endotoxin (lipopolysaccharide [LPS]). Using a well‐characterized model of LPS‐induced acute liver failure (ALF) in galactosamine (GalN)‐sensitized mice, we show that Ron TK−/− mice display marked protection compared with control Ron TK+/+ mice.

Fibrosis and disease progression in hepatitis C

Patrick Marcellin, Tarik Asselah, Nathalie Boyer – 30 December 2003 – The progression of fibrosis in chronic hepatitis C determines the ultimate prognosis and thus the need and urgency of therapy. Fibrogenesis is a complex dynamic process, which is mediated by necroinflammation and activation of stellate cells. The liver biopsy remains the gold standard to assess fibrosis. Scoring systems allow a semiquantitative assessment and are useful for cross‐sectional and cohort studies and in treatment trials. The rate at which fibrosis progresses varies markedly between patients.

Hepatitis C virus–like particles combined with novel adjuvant systems enhance virus‐specific immune responses

Ming Qiao, Kazumoto Murata, Anthony R. Davis, Sook‐Hyang Jeong, T. Jake Liang – 30 December 2003 – We have previously described the generation of hepatitis C virus–like particles (HCV‐LPs) in insect cells and shown that immunization with HCV‐LPs elicited both humoral and cellular immune responses in mice. To further characterize the HCV‐LPs as a vaccine candidate, we evaluated the effects of adjuvant AS01B (monophosphoryl lipid A [MPL] and QS21), CpG 10105, and the combination of the 2 adjuvants on the immunogenicity of HCV‐LPs in AAD mice (transgenic for HLA‐A2.1).

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