Pathogenesis of chronic hepatitis C: Immunological features of hepatic injury and viral persistence

Andreas Cerny, Francis V. Chisari – 30 December 2003 – The immune response to viral antigens is thought to be responsible for viral clearance and disease pathogenesis during hepatitis C virus (HCV) infection. In chronically infected patients, the T‐cell response to the HCV is polyclonal and multispecific, although it is not as strong as the response in acutely infected patients who display a more vigorous T‐cell response. Importantly, viral clearance in acutely infected patients is associated with a strong CD4+ helper T‐cell response.

Glucose intolerance and insulin resistance in cirrhosis are normalized after liver transplantation

Manuela Merli, Frida Leonetti, Oliviero Riggio, Valentina Valeriano, Mária Cristina Ribaudo, Fabio Sprati, Giuseppe Tisone, Carlo Umberto Casciani, Livio Capocaccia – 30 December 2003 – Cirrhosis is often associated with insulin resistance and glucose intolerance. We evaluated if these alterations are restored by liver transplantation (LT).

Inhibition of 11β‐hydroxysteroid dehydrogenase by bile acids in rats with cirrhosis

Daniel Ackermann, Bruno Vogt, Geneviève Escher, Bernhard Dick, Jürg Reichen, Brigitte M. Frey, Felix J. Frey – 30 December 2003 – Renal sodium retention and potassium loss occur early, in many instances in the preascitic state of cirrhosis, an observation that cannot be fully explained by increased aldosterone concentrations. We therefore hypothesize that 11β‐hydroxysteroid dehydrogenase 2 (11β‐HSD2), which protects mineralocorticoid receptors (MR) from glucocorticosteroids, is down‐regulated in cirrhosis. Cirrhosis was induced by bile duct ligation in rats.

Targeting of aminopeptidase n to bile canaliculi correlates with secretory activities of the developing canalicular domain

Wei‐Nan Lian, Jin‐Wu Tsai, Pang‐Mien Yu, Tzu‐Wei Wu, Shun‐Chun Yang, Yat‐Pang Chau, Chi‐Hung Lin – 30 December 2003 – We have used human hepatoma cell lines as an in vitro model to study the development of hepatic bile canaliculi (BC). Well‐differentiated hepatoma cells cultured for 72 hours could develop characteristic spheroid structures at sites of cell‐cell contact that contained tight junctions and various membrane protein markers, resembling BC found in vivo. Intact cytoskeleton was essential for this differentiation process.

The alteration of fas receptor and ligand system in hepatocellular carcinomas: How do hepatoma cells escape from the host immune surveillance in vivo?

Mitsuo Nagao, Yoshiyuki Nakajima, Michiyoshi Hisanaga, Nobuhiko Kayagaki, Hiromichi Kanehiro, Yukio Aomatsu, Saiho Ko, Hideo Yagita, Takatsugu Yamada, Ko Okumura, Hiroshige Nakano – 30 December 2003 – Escape from the immune surveillance may play an important role in tumor outgrowth and metastasis. Alteration of the Fas receptor (Fas)/ligand (FasL) system including soluble forms is regarded as one of the mechanisms preventing the immune system from rejecting the tumor cells. However, less attention has been paid to the role of Fas/FasL interaction in vivo.

B7‐1 (CD80)‐gene transfer combined with interleukin‐12 administration elicits protective and therapeutic immunity against mouse hepatocellular carcinoma

Tomohide Tatsumi, Tetsuo Takehara, Tatsuya Kanto, Noriyoshi Kuzushita, Akihiko Ito, Akinori Kasahara, Yutaka Sasaki, Masatsugu Hori, Norio Hayashi – 30 December 2003 – Human hepatocellular carcinoma (HCC) frequently recurs after primary therapy, resulting in poor prognosis. To try to find a way to prevent this, we examined the combined effectiveness of B7‐1 (CD80)‐gene transfer and interleukin‐12 (IL‐12) on the induction of protective antitumor immunity against poorly immunogenic BNL1ME A.7R.1 (BNL) mouse HCC cells. We introduced mouse B7‐1 gene into BNL1ME A.7R.1 cells.

Liver and bile duct pathology following Cryptosporidium parvum infection of immunodeficient mice

Janet Stephens, Mary Cosyns, Michelle Jones, Anthony Hayward – 30 December 2003 – Patients with acquired immune deficiency syndrome (AIDS) and boys with mutations of the CD154 gene (causing congenital X‐linked immunodeficiency with hyper‐IgM [XHIM]) are susceptible to chronic infections of the biliary tract with Cryptosporidium parvum (CP) that may lead to biliary sclerosis and ultimately to cholangiocarcinoma.

Short‐term regulation of bile acid uptake by microfilament‐dependent translocation of rat ntcp to the plasma membrane

Jonathan A. Dranoff, Mitchell McClure, Angela D. Burgstahler, Lee A. Denson, Aleta R. Crawford, James M. Crawford, Saul J. Karpen, Michael H. Nathanson – 30 December 2003 – The Na+‐taurocholate cotransport polypeptide (ntcp) is the primary transporter for the uptake of bile acids in the liver. The second messenger adenosine 3′:5′‐cyclic monophosphate (cAMP) rapidly increases ntcp protein concentration in the plasma membrane, yet the mechanism is unknown.

Complex feedback regulation of bile acid synthesis in the hamster: The role of newly synthesized cholesterol

Jürgen Scheibner, Michael Fuchs, Erwin Hörmann, Eduard F. Stange – 30 December 2003 – Hepatic bile acid synthesis is regulated by recirculating bile acids, possibly by modulating the availability of newly synthesized and preformed cholesterol. Because data in the hamster on this mechanism are lacking, we fitted these animals with an extracorporeal bile duct and administered tritiated water intraperitoneally to label newly formed cholesterol.

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