Hepatitis C vaccines: Inducing and challenging memory T cells

Masaaki Shiina, Barbara Rehermann – 25 May 2006 – Three percent of the world's population is chronically infected with the hepatitis C virus (HCV) and at risk of developing liver cancer. Effective cellular immune responses are deemed essential for spontaneous resolution of acute hepatitis C and long‐term protection. Here we describe a new T‐cell HCV genetic vaccine capable of protecting chimpanzees from acute hepatitis induced by challenge with heterologous virus.

Cytotoxic T cell responses to human telomerase reverse transcriptase in patients with hepatocellular carcinoma

Eishiro Mizukoshi, Yasunari Nakamoto, Yohei Marukawa, Kuniaki Arai, Tatsuya Yamashita, Hirokazu Tsuji, Kiyotaka Kuzushima, Masafumi Takiguchi, Shuichi Kaneko – 25 May 2006 – Human telomerase reverse transcriptase, hTERT, has been identified as the catalytic enzyme required for telomere elongation. hTERT is expressed in most tumor cells but seldom expressed in most human adult cells. It has been reported that 80% to 90% of hepatocellular carcinomas (HCCs) express hTERT, making the enzyme a potential target in immunotherapy for HCC.

Step‐by‐step progress toward understanding the hepatitis C virus RNA helicase

David N. Frick – 25 May 2006 – Helicases are a ubiquitous class of enzymes involved in nearly all aspects of DNA and RNA metabolism. Despite recent progress in understanding their mechanism of action, limited resolution has left inaccessible the detailed mechanisms by which these enzymes couple the rearrangement of nucleic acid structures to the binding and hydrolysis of ATP. Observing individual mechanistic cycles of these motor proteins is central to understanding their cellular functions.

Interferon‐inducible expression of APOBEC3 editing enzymes in human hepatocytes and inhibition of hepatitis B virus replication

Marianne Bonvin, François Achermann, Isabell Greeve, Deborah Stroka, Adrian Keogh, Daniel Inderbitzin, Daniel Candinas, Peter Sommer, Simon Wain‐Hobson, Jean‐Pierre Vartanian, Jobst Greeve – 25 May 2006 – Hypermutations in hepatitis B virus (HBV) DNA by APOBEC3 cytidine deaminases have been detected in vitro and in vivo, and APOBEC3G (A3G) and APOBEC3F (A3F) have been shown to inhibit the replication of HBV in vitro, but the presumably low or even absent hepatic expression of these enzymes has raised the question as to their physiological impact on HBV replication.

Renal damage in experimentally‐induced cirrhosis in rats: Role of oxygen free radicals

Sathish Kumar Natarajan, Jayasree Basivireddy, Anup Ramachandran, Simmy Thomas, Prabhu Ramamoorthy, Anna B. Pulimood, Molly Jacob, Kunissery A. Balasubramanian – 25 May 2006 – Cirrhosis with ascites is associated with impaired renal function accompanied by sodium and water retention. Although it has been suggested that mediators such as nitric oxide play a role in the development of renal failure in this situation, other mechanisms underlying the process are not well understood.

Ursodeoxycholic acid exerts no beneficial effect in patients with symptomatic gallstones awaiting cholecystectomy

Niels G. Venneman, Marc G.H. Besselink, Yolande C.A. Keulemans, Gerard P. vanBerge‐Henegouwen, Marja A. Boermeester, Ivo A.M.J. Broeders, Peter M.N.Y.H. Go, Karel J. van Erpecum – 25 May 2006 – Ursodeoxycholic acid (UDCA) and impaired gallbladder motility purportedly reduce biliary pain and acute cholecystitis in patients with gallstones. However, the effect of UDCA in this setting has not been studied prospectively. This issue is important, as in several countries (including the Netherlands) scheduling problems result in long waiting periods for elective cholecystectomy.

Neutrophil depletion protects against murine acetaminophen hepatotoxicity

Zhang‐Xu Liu, Derick Han, Basuki Gunawan, Neil Kaplowitz – 25 May 2006 – We previously reported that liver natural killer (NK) and NKT cells play a critical role in mouse model of acetaminophen (APAP)‐induced liver injury by producing interferon gamma (IFN‐γ) and modulating chemokine production and subsequent recruitment of neutrophils into the liver. In this report, we examined the role of neutrophils in the progression of APAP hepatotoxicity.

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