Targeted induction of interferon-λ in humanized chimeric mouse liver abrogates hepatotropic virus infection.

Background & Aims: The interferon (IFN) system plays a critical role in innate antiviral response. We presume that targeted induction of IFN in human liver shows robust antiviral effects on hepatitis C virus (HCV) and hepatitis B virus (HBV).

Methods: This study used chimeric mice harboring humanized livers and infected with HCV or HBV.

Impairment of interferon regulatory factor-3 activation by hepatitis C virus core protein basic amino acid region 1.

Interferon regulatory factor-3 (IRF-3), a key transcriptional factor in the type I interferon system, is frequently impaired by hepatitis C virus (HCV), in order to establish persistent infection. However, the exact mechanism by which the virus establishes persistent infection has not been fully understood yet. The present study aimed to investigate the effects of various HCV proteins on IRF-3 activation, and elucidate the underlying mechanisms.

Upper gastrointestinal bleeding in patients receiving dual antiplatelet therapy after coronary stenting.

Objective: We investigated the risk of upper gastrointestinal (UGI) bleeding and the protective effect of concomitant anti-secretory drugs during dual antiplatelet therapy administered following implantation of drug-eluting stents (DES) for coronary heart disease. Because proton pump inhibitors (PPIs) are reported to decrease the platelet inhibitory effects of clopidogrel, we also assessed cardiovascular outcomes in patients taking thienopyridine derivatives with or without anti-secretory drug.

Methods: We retrospectively analyzed 243 patients, who underwent DES implantation between January 2006 and December 2007 and were receiving dual anti-platelet therapy post-surgery.

Plasma exchange in combination with online-hemodiafiltration as a promising method for purifying the blood of fulminant hepatitis patients.

Background: Fulminant hepatitis is an intractable disease caused by various etiological agents. Artificial liver support (ALS) is a symptomatic treatment used to control serious symptoms, such as bleeding tendency, hepatic coma, and brain edema.

Methods: The present study involved four patients with fulminant hepatitis who were admitted to Showa University Fujigaoka Hospital between January 2007 and June 2007.

Predicting the success of endoscopic transpapillary gallbladder drainage for patients with acute cholecystitis during pretreatment evaluation.

Introduction: Although endoscopic transpapillary gallbladder drainage (ETGBD) has been reported to be an effective treatment for acute cholecystitis, technical difficulties have precluded more widespread use of this technique. Case evaluations that can predict the occurrence of such difficulties should increase the acceptance of ETGBD for acute cholecystitis treatment.

Objective: To establish a pretreatment evaluation protocol for patients with acute cholecystitis.

Liver target delivery of small interfering RNA to the HCV gene by lactosylated cationic liposome.

Background/aims: RNA interference has considerable therapeutic potential, particularly for anti-viral therapy. We previously reported that hepatitis C virus (HCV)-directed small interfering RNA (siRNA; siE) efficiently inhibits HCV replication, using HCV replicon cells. To employ the siRNA as a therapeutic strategy, we attempted in vivo silencing of intrahepatic HCV gene expression by siE using a novel cationic liposome.

Evaluation of a cyclophilin inhibitor in hepatitis C virus-infected chimeric mice in vivo.

Unlabelled: Cyclosporin A (CsA) inhibits replication of the HCV subgenomic replicon, and this effect is believed to not be mediated by its immunosuppressive action. We found that DEBIO-025, a novel non-immunosuppressive cyclophilin inhibitor derived from CsA, inhibited HCV replication in vitro more potently than CsA. We also examined the inhibitory effect of DEBIO-025 on naive HCV genotypes 1a or 1b in vivo using chimeric mice with human hepatocytes.

Involvement of membrane-type bile acid receptor M-BAR/TGR5 in bile acid-induced activation of epidermal growth factor receptor and mitogen-activated protein kinases in gastric carcinoma cells.

Bile acids, which have been implicated in gastrointestinal-tract cell carcinogenesis, share properties with tumor promoters in that both affect signal transduction pathways responsible for cell proliferation and apoptosis. In the present study, we demonstrate that EGFR-ERK1/2 is activated following treatment of AGS human gastric carcinoma cells with bile acids. EGFR phosphoactivation is ligand-dependent, since treatment of cells with HB-EGF antisera or CM197 (a selective inhibitor of HB-EGF) markedly inhibits deoxycholate (DC)-promoted activation.

Possible association of vigorous hepatitis B virus replication with the development of fulminant hepatitis.

A 49 year-old man was referred to our hospital for fear of developing fulminant hepatic failure. There had been an outbreak of fulminant hepatitis B in a dialysis clinic in the western part of Honshu, Japan, that resulted in four deaths among six patients. After the sixth patient contracted severe hepatitis, all patients in the unit were screened biweekly for hepatitis B surface antigen (HBsAg) to detect newly infected patients as soon as possible.

Acute necrotizing esophagitis: role of nonsteroidal anti-inflammatory drugs.

Background: Acute necrotizing esophagitis (ANE) is a rarely described entity that is thought to be a cause of upper gastrointestinal (UGI) bleeding, The present study examined the incidence of ANE among patients with UGI bleeding, as well as the clinical features of ANE, and the coexisting illnesses and medication histories of ANE patients.

Methods: A retrospective analysis of clinical and endoscopic findings and the clinical course in 16 patients with ANE was carried out over a 3-year period.

Results: We observed 16 patients (6%) of ANE in 239 patients with UGI bleeding during the 3-year period.

Elevated cyclooxygenase-2 expression in patients with early gastric cancer in the gastric pylorus.

Background: Duodenogastric reflux after surgery increases the risk of gastric carcinoma. To determine whether bile reflux influences the development of gastric cancer in patients who have not had surgery, we compared cyclooxygenase-2 (COX-2) immunoreactivity in early gastric cancer originating from the gastric pylorus and that originating from other locations. We also examined the effects of bile acids on the expression and activity of COX-2 in gastric cells in vitro.

Intraductal tubular neoplasms of the pancreas: histogenesis and differentiation.

Objectives: Intraductal neoplasms of the pancreas are generally referred to as intraductal papillary mucin-producing neoplasms (IPMNs), according to the WHO classification system. Herein, we report that morphologic and immunohistochemical features of intraductal tubular carcinoma (ITC) are quite different from those of intraductal papillary mucinous carcinoma (IPMC).

Methods: We analyzed histogenesis and differentiation of ITC by light microscopy and immunohistochemistry.

Osteopontin expression in proliferated bile ductules: the correlation with liver damage in fulminant hepatitis.

There have been many reports about the severity of hepatic necrosis caused by fulminant hepatitis; however, the relation between proliferated bile ductules and osteopontin (OPN) expression in inflamed areas in each of the clinical forms of fulminant hepatitis has not been described. To analyze the mechanism in the onset of fulminant hepatitis, we classified not only 16 autopsy cases of fulminant hepatitis into two clinical forms--acute and subacute--but also 3 autopsy cases of late-onset hepatic failure (LOHF) associated with fulminant hepatitis, and examined liver specimens by light microscopy and immunohistochemistry and also serum transaminase levels. Histopathologic study revealed that some of the proliferated bile ductules were associated directly with deteriorating hepatocytes and that bile plugs were present in the proliferated bile ductules.

Histologic and immunohistochemical comparison of intraductal tubular carcinoma, intraductal papillary-mucinous carcinoma, and ductal adenocarcinoma of the pancreas.

Objective: To analyze the differences between intraductal tubular carcinoma (ITC) and intraductal papillary-mucinous carcinoma (IPMC), we performed light microscopic and immunohistochemical analysis of 4 cases of ITC, 6 cases of IPMC, and 9 cases of ductal adenocarcinoma of the pancreas.

Methods And Results: Light microscopic examination showed no hyperplasia or adenoma around the carcinoma in ITC, and immunohistochemical analysis showed that the apical side of the cell membrane was positive for MUC-1 in almost all ITC cells. In contrast to ITC cells, all IPMC cells were negative for MUC-1 and ductal adenocarcinoma cells were strongly positive for MUC-1 in the cytoplasm and cell membrane.

[Allogeneic peripheral blood stem cell transplantation for a hepatitis B virus carrier with Epstein-Barr virus associated with hemophagocytic syndrome].

We report herein a 21-year-old hepatitis B virus (HBV) female carrier who developed persistent fever, lymphadenopathy and pancytopenia in September of 2000. Hemophagocytes were found in the bone marrow smears. Epstein-Barr virus (EBV) serology showed positive for VCA-IgG, IgM and EB-ER and negative for EBNA.

Mucinous cystadenoma of the pancreas 17 years after excision of gallbladder because of a choledochal cyst.

A 56-year-old woman who had undergone excision of the gallbladder because of a choledochal cyst had a tumorous lesion of the pancreas identified by upper abdominal ultrasonography, but an operation was not carried out, because there was no apparent increase in the cystic mass and no elevation of serum tumor markers. In October 2001, she was admitted to our hospital to check for malignancy because of elevated levels of the tumor marker Dupan-2. Abdominal enhanced computed tomography and upper abdominal ultrasonography revealed a large multilocular cystic mass in the body to tail of the pancreas.

Virological significance of low-level hepatitis B virus infection in patients with hepatitis C virus associated liver disease.

The clinical and virological significance of low-level viremia by hepatitis B virus (HBV) in hepatitis C virus (HCV)-infected patients remains unclear. HBV-DNA and HCV-RNA were, therefore, quantitatively analyzed in livers and sera from co-infected patients. HBV-DNA and HCV-RNA were quantitated using real-time detection of polymerase chain reaction (RTD-PCR), based on Taq-Man chemistry, in 220 non-HCV-infected healthy volunteers and 93 HCV-infected patients without detectable HBsAg.

Combined interferon alpha2b and cyclosporin A in the treatment of chronic hepatitis C: controlled trial.

Background: Only 15% to 20% of patients with chronic hepatitis C have a sustained virological response to interferon monotherapy. The aim of the present study was to compare the efficacy and safety of interferon, in combination with oral cyclosporin A, with interferon monotherapy in the treatment of chronic hepatitis C.

Methods: We assigned 120 patients with chronic hepatitis C to receive the standard Japanese dose of interferon alpha2b alone for 24 weeks or that dose of interferon alpha2b in combination with cyclosporin A, at doses of 200 mg daily for the first 4 weeks and 100 mg daily for the following 20 weeks.