Norio Koide

Hepatitis C virus genotype distribution in Myanmar : predominance of genotype 6 and existence of new genotype 6 subtype

Aim:u2002 This study was performed to determine the prevalence and distribution of hepatitis C virus (HCV) genotypes in Myanmar.

Functional promoter upstream p53 regulatory sequence of IGFBP3 that is silenced by tumor specific methylation

BackgroundInsulin-like growth factor binding protein (IGFBP)-3 functions as a carrier of insulin-like growth factors (IGFs) in circulation and a mediator of the growth suppression signal in cells. There are two reported p53 regulatory regions in the IGFBP3 gene; one upstream of the promoter and one intronic. We previously reported a hot spot of promoter hypermethylation of IGFBP-3 in human hepatocellular carcinomas and derivative cell lines. As the hot spot locates at the putative upstream p53 consensus sequences, these p53 consensus sequences are really functional is a question to be answered.MethodsIn this study, we examined the p53 consensus sequences upstream of the IGFBP-3 promoter for the p53 induced expression of IGFBP-3. Deletion, mutagenesis, and methylation constructs of IGFBP-3 promoter were assessed in the human hepatoblastoma cell line HepG2 for promoter activity.ResultsDeletions and mutations of these sequences completely abolished the expression of IGFBP-3 in the presence of p53 overexpression. In vitro methylation of these p53 consensus sequences also suppressed IGFBP-3 expression. In contrast, the expression of IGFBP-3 was not affected in the absence of p53 overexpression. Further, we observed by electrophoresis mobility shift assay that p53 binding to the promoter region was diminished when methylated.ConclusionFrom these observations, we conclude that four out of eleven p53 consensus sequences upstream of the IGFBP-3 promoter are essential for the p53 induced expression of IGFBP-3, and hypermethylation of these sequences selectively suppresses p53 induced IGFBP-3 expression in HepG2 cells.

Camostat, an oral trypsin inhibitor, reduces pancreatic fibrosis induced by repeated administration of a superoxide dismutase inhibitor in rats

Background and Aim:u2002 An oral trypsin inhibitor, camostat (CM), has a beneficial effect on chronic pancreatitis, but its mechanism is not yet fully understood. Recently, pancreatic stellate cells (PSC) have been reported to play an essential role in pancreatic fibrosis. An experimental model of pancreatic fibrosis induced by a superoxide dismutase (SOD) inhibitor (diethyldithiocarbamate [DDC]) was developed in rats. Thus, the effect of an oral trypsin inhibitor on pancreatic fibrosis and PSC was investigated.

Hepatitis B virus DNA in liver tissue and risk for hepatocarcinogenesis in patients with hepatitis C virus-related chronic liver disease

Aims: To prospectively study whether occult hepatitis B virus (HBV) infection can promote the development of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related chronic liver disease. In addition, to evaluate the difference among HBV DNA-negative patients and patients with high and low HBV copy numbers. Methods: A total of 167 patients with HCV-related chronic liver disease without HBV surface antigen (HBsAg) were studied. HBV DNA in liver tissue was determined using polymerase chain reaction (PCR). Results: HBV DNA was detected in 9 of 167 patients (5.4%) by single PCR and in 25 patients (15.0%) by nested PCR. HCC developed in 12 of 167 patients (7.2%). Ten of 142 HBV DNA-negative patients (7.0%) and 2 of 9 patients with a high HBV copy number (22.2%) developed HCC, whereas none of 16 patients with a low HBV copy number developed HCC. The incidence rate of HCC in patients with a high HBV copy number was significantly higher than in HBV DNA-negative patients and patients with low HBV copy number. Conclusion: A high amount of HBV DNA in liver tissue of HBsAg-negative patients with HCV-related liver disease might be associated with HCC development.

Xanthine oxidase-derived free radicals directly activate rat pancreatic stellate cells.

Background and Aim:u2002 Free radicals are reported to be associated with fibrosis in the pancreas. It is generally accepted that pancreatic stellate cells (PSC) play an important role in pancreatic fibrosis. However, the exact role of free radicals in activation of PSC has not been fully elucidated. In the present study, using a superoxide dismutase (SOD) inhibitor, diethyldithiocarbamate (DDC) with cultured PSC, we investigated how free radicals act on the activation of PSC.

Intrahepatic mRNA levels of type I interferon receptor and interferon-stimulated genes in genotype 1b chronic hepatitis C. Association between IFNAR1 mRNA level and sustained response to interferon therapy.

Objective: The aim of this study was to determine the association between pretreatment intrahepatic mRNA levels of interferon receptor and interferon-stimulated genes and response to interferon therapy for genotype 1b chronic hepatitis C. Methods: Forty-four patients with genotype 1b chronic hepatitis C who underwent liver biopsy and then received interferon therapy participated in this study. Pretreatment intrahepatic mRNA levels of interferon receptor genes (IFNAR1, IFNAR2b, and IFNAR2c) and interferon-stimulated genes (OAS1 and PKR) were quantified by competitive polymerase chain reaction. Results: In the genes examined, only IFNAR1 mRNA level was significantly higher in patients with sustained virological and biochemical response to interferon therapy versus those with nonsustained response (p < 0.01). Moreover, mRNA expression ratios of IFNAR1 to IFNAR2 were also significantly higher in patients with sustained virological and biochemical response to IFN therapy (p < 0.01 and p < 0.05, respectively). On the other hand, mRNA levels of IFNAR2b, IFNAR2c, and PKR were significantly higher in patients with histologically active or advanced liver rather than patients with mild or less advanced liver. Conclusions: High intrahepatic mRNA levels of IFNAR1 and mRNA ratio of IFNAR1 to IFNAR2 before treatment may be associated with a favorable response to interferon therapy.

Oral administration of taurine improves experimental pancreatic fibrosis

Background and Aim:u2002 The mechanism of pancreatic fibrosis is unclear. Taurine is used in the clinical treatment of a wide variety of diseases, but its effect on improving pancreatic fibrosis is unknown. We examined whether a diet with added taurine improves pancreatic fibrosis induced by dibutyltin dichloride (DBTC) in an experimental chronic pancreatitis rat model. In addition, we examined the influence of taurine on pancreatic stellate cells.

A CASE OF SIALADENOMA PAPILLIFERUM OF THE ESOPHAGUS

Sialadenoma papilliferum of the esophagus is an extremely rare benign tumor that derives from the submucosal gland duct of the minor salivary gland. A 45‐year‐old man underwent upper gastrointestinal series. A 13u2003mm diameter esophageal polyp was suspected in the mid esophagus. Endoscopy examination revealed a pedunculated polyp arising from the posterior wall of the esophagus. The head of the polyp was covered with exudate and was slightly nodular but the pedicle had normal mucosa. We performed endoscopic mucosal resection (EMR) and the histological examination of the polyp showed that it was compatible with sialadenoma papilliferum of the esophagus.