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Background: Primary biliary cirrhosis (PBC) is regarded as an autoimmune liver disease and familial clustering of PBC could represent some genetic predisposition to the disease.Aims: To elucidate the genetic background of PBC by investigating familial cases of PBC.Methods: Familial cases were picked out from 171 PBC patients who enrolled in this study. We analyzed them and their family members, and compared them clinically and immunogenetically to non-familial cases.Results: Out of 171 PBC patients, ten (5.8%) were identified as familial PBC in five families. The clinical features of familial PBC were almost comparable to those of non-familial PBC. The distribution of human leukocyte antigens (HLA)-A, -B and -DR in familial PBC showed no specificity. Two new PBC patients were identified in one family in addition to the two originally enrolled PBC patients, resulting in four patients with PBC within the same family. The two new PBC patients had an identical HLA haplotype. On the other hand, one HLA-identical sister of a PBC patient in another family did not develop PBC.Conclusions: Primary biliary cirrhosis can exhibit familial clustering without any HLA predisposition, however, a survey of families for PBC could be useful for identifying new patients with PBC in the asymptomatic stage for earlier diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children, yet molecular events associated with the genesis and progression of this potentially fatal disease are largely unknown. For the molecules and pathways that have been implicated, genetic validation has been impeded by lack of a mouse model of RMS. Here we show that simultaneous loss of Ink4a/Arf function and disruption of c-Met signaling in Ink4a/Arf[sup -/-] mice transgenic for hepatocyte growth factor/scatter factor (HGF/SF) induces RMS with extremely high penetrance and short latency. In cultured myoblasts, c-Met activation and Ink4a/Arf loss suppress myogenesis in an additive fashion. Our data indicate that human c-MET and INK4a/ARF, situated at the nexus of pathways regulating myogenic growth and differentiation, represent critical targets in RMS pathogenesis. The marked synergism in mice between aberrant c-Met signaling and Ink 4a/Arf inactivation, lesions individually implicated in human RMS, suggests a therapeutic combination to combat this devastating childhood cancer. [ABSTRACT FROM AUTHOR]

Background: The incidence of acute hepatitis A infection in Japan peaked 10 years ago and has been decreasing since then. However, an increase in severe cases of the disease has been documented recently. We experienced an outbreak in 1998–1999, and compared the clinical features of the disease in 1998–1999 (recent outbreak) and in 1987–1988 (past outbreak) in our prefecture (Gunma). Methods: Forty patients with acute hepatitis A were admitted to nine Gunma hospitals from October 1998 to September 1999. Their clinical features were compared with those of 100 patients with acute hepatitis A admitted to the same hospitals in 1987–1988. Results: Both outbreaks occurred mostly during the winter-spring season. Secondary familial infection was significantly decreased in the recent outbreak. Patients in the recent outbreak were 7 years older than those in the past outbreak. Laboratory findings, such as serum aspartatate aminotransferase (AST) and alanine aminotransferase (ALT) levels and prothrombin time, were worse in the recent than in the past outbreak. Severe-type hepatitis and fulminant hepatitis occurred in 5 patients (12.5%) in the recent outbreak but in only 2 patients (2.0%) in the past outbreak. Conclusions: Clinical data and manifestations were more severe in the recent outbreak than in the past outbreak of acute hepatitis A. It is important to be aware of hepatitis A virus infection and to take into account the available vaccination against hepatitis A virus in Japan. [ABSTRACT FROM AUTHOR]

Presents a study which investigated the promoting effect of hepatocyte growth factor on diethylnitrosamine-induced hepatocarcinogenesis. Review of related literature; Materials and methods used; Results.