Haruhisa Nakao

Immunohistochemical study of autoimmune pancreatitis using anti-IgG4 antibody and patients' sera

Aims : Autoimmune pancreatitis (AIP), characterized by raised serum IgG4 levels, is frequently complicated by disorders of extrapancreatic organs. The aim of the present study was to examine immunohistochemically which extrapancreatic organs are affected, and whether an autoantibody to such organs is present in the serum of AIP patients.

Advantages of endoscopic submucosal dissection over conventional endoscopic mucosal resection

Background:  Endoscopic mucosal resection is an established method for treating intramucosal gastric neoplasms. Conventional endoscopic mucosal resection has predominantly been performed using strip biopsy, but local recurrence sometimes occurs due to such piecemeal resection. Endoscopic submucosal dissection has recently been performed in Japan using new devices such as an insulation‐tip diathermic knife. The efficacy and problems associated with endoscopic submucosal dissection were evaluated by comparison with conventional endoscopic mucosal resection.

Infection with GB virus C (GBV-C) in patients with fulminant hepatitis

BACKGROUND/METHODS There appear to be hepatitis viruses other than hepatitis A, B, C, D and E. One of these has been proposed with a designation of GB virus C. Sera from 44 patients with fulminant hepatitis were tested for RNA of GB virus C by reverse-transcription polymerase chain reaction with nested primers deduced from the putative non-structural 3 (helicase) region. RESULTS RNA of GB virus C was detected in three (20%) of 15 patients with hepatitis B virus infection and three (12%) of 25 patients without markers of hepatitis A-E virus infection. Overall, GB virus C RNA was detected in six (14%) of the 44 patients with fulminant hepatitis, at a frequency significantly higher (p < 0.001) than that in three (0.9%) of 326 blood donors matched for age with the patients. CONCLUSIONS These results indicate a role of GB virus C in inducing fulminant hepatitis either by itself or in concert with the other hepatitis viruses.

Prevalence of hepatitis B, hepatitis C, and GB virus C/hepatitis G virus infections in liver disease patients and inhabitants in Ho Chi Minh, Vietnam

The prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), and GB virus C or hepatitis G virus (GBV‐C/HGV) infections was determined in 289 patients with liver disease in Ho Chi Minh City and 890 healthy inhabitants of its rural area, Dalat City, Vietnam, respectively. Serum HCV RNA and GBV‐C/HGV RNA were detected by reverse transcription–polymerase chain reaction (RT‐PCR). HBsAg, HCV antibodies, and GBV‐C/HGV RNA were detected in 139 (47%), 69 (23%), and ten (3%) subjects, respectively, often accompanied by elevated serum levels of alanine aminotransferase. HBsAg and HCV antibodies or HCV antibodies and GBV‐C/HGV RNA were detectable simultaneously in 8% and 2% of the patients, respectively. In the inhabitants, HBsAg, HCV antibodies, and GBV‐C/HGV RNA were found in 51 (5.7%), nine (1.0%), and 11 (1.2%) subjects, respectively. Thus, the prevalence of HBsAg, HCV antibodies, and GBV‐C/HGV RNA was significantly higher in liver disease patients than those in the general population. In the samples from 69 patients and nine inhabitants who were seropositive for HCV antibodies, HCV RNA was detectable in 42 (61%) and 4 (44%), respectively. In patients with liver disease, ten belonged to HCV genotype 1a, ten to HCV 1b, three to HCV 2a, four to HCV 2b, and two to HCV 3a by PCR with genotype‐specific primers. Nine patients had mixed genotypes, and the remaining four were not classified. Of the GBV‐C/HGV RNA‐positive individuals, two patients and two inhabitants were positive for HBsAg, while none of the residents had HCV antibodies, although six HCV antibodies (60%) and four HCV RNA (40%) were found in patients. When a phylogenetic tree of GBV‐C/HGV was constructed based on the nucleotide sequences, the 21 isolates were classified into at least two genotypes; four isolates belonged to G2, and 17 to G3. The results indicate that in Ho Chi Minh HCV infection prevails with broad distribution of genotypes together with HBV infection among patients with liver disease. This study suggests that GBV‐C/HGV infection occurs independently in the two different districts in association with HCV infection. J. Med. Virol. 54:243–248, 1998.

Full-length genomic sequence of a hepatitis C virus genotype 2c isolate (BEBE1) and the 2c-specific PCR primers

SummaryWe sequenced the entire genome of an Italian isolate of hepatitis C virus: the first full-length sequence for the genotype 2c. We report hereby its characteristics and differential detection of 2c isolates using PCR.

Infection with GB virus C in leprous patients in Japan.

The detection of hepatitis C virus (HCV) in blood donors and patients with acute and chronic hepatitis has brought to the fore another virus or viruses which can be transmitted parenterally and induce liver disease. The RNA of a candidate virus designated GB virus C (GBV‐C) was determined by the polymerase chain reaction with primers deduced from a helicase‐like region in 229 leprous patients in Japan. GBV‐C RNA was detected in 12 (5.2%) patients, and HCV RNA in 41 (18%). Three patients were coinfected with GBV‐C and HCV. The nine patients infected with GBV‐C alone had aminotransferase levels lower than the three patients with the mixed infection or the 38 patients infected with HCV only (P < 0.001). Sequence comparison within 100 base pairs in the helicase‐like region suggested that two, three and three patients, respectively, would have been infected with three distinct strains of GBV‐C. These results indicate that patients with leprosy are at increased risk for infection not only with HCV, but also with GBV‐C, and that the infection with GBV‐C alone would not induce hepatic injuries as severe as HCV infection.

Helicobacter pylori-Stimulated Interleukin-8 (IL-8) Promotes Cell Proliferation Through Transactivation of Epidermal Growth Factor Receptor (EGFR) by Disintegrin and Metalloproteinase (ADAM) Activation

Helicobacter pylori infection increases the risk of hyperplastic polyps and gastric cancer, but the mechanisms remain to be elucidated. H. pylori was recently shown to transactivate epidermal growth factor receptor (EGFR) through metalloprotease stimulation. The present study was designed to investigate the effect of interleukin-8 (IL-8) induced by H. pylori infection on EGFR transactivation and epithelial cell growth. H. pylori Sydney strain 1 (SS1) having wild-type cag+A was used. Phospho-EGFR assay was performed by immunoprecipitation using anti-human EGFR and anti-phosphotyrosine antibodies. DNA synthesis was evaluated by [3H]thymidine uptake using the human gastric cancer cell line, KATO III. H. pylori induced EGFR phosphorylation, and a disintegrin and metalloproteinase (ADAM) inhibitor, KB-R7785, completely suppressed EGFR phosphorylation. IL-8 also induced EGFR phosphorylation, while anti-IL-8 and anti-IL-8 receptor (CXCR1) neutralizing antibodies suppressed EGFR phosphorylation. [3H]Thymidine uptake analysis demonstrated that H. pylori increased DNA synthesis in gastric epithelial cells, and tyrosine kinase inhibitor, MEK inhibitor, and ADAM inhibitor suppressed the DNA synthesis induced by H. pylori. H. pylori-stimulated IL-8 accelerates processing of EGFR ligands through ADAM activation, and cleaved EGFR ligands bind and stimulate EGFR in paracrine and autocrine manners to induce cell proliferation. This may be one of the mechanisms of hyperplastic polyp and gastric cancer development in H. pylori-infected gastric mucosa.

Infection with hepatitis G virus and its strain variant, the GB agent (GBV-C), among blood donors in Japan

BACKGROUND: The purpose of the study was to survey the epidemiology of recently reported non‐A through ‐E hepatitis virus designated hepatitis G virus (HGV) and its strain variant, the GB agent (GBV‐C). STUDY DESIGN AND METHODS: Pilot samples from 2461 blood donors in Japan, randomly selected to form cohorts with different levels of alanine aminotransferase (ALT) and markers of hepatitis B virus or hepatitis C virus (HCV) infection, were tested for RNA of HGV/GBV‐C by reverse transcription‐polymerase chain reaction with nested primers deduced from the 5′‐noncoding region. RESULTS: HGV/GBV‐C RNA was detected in 23 (7.4%) of the 361 donors with anti‐HCV and HCV RNA. This detection is more frequent than that in donors without elevated ALT levels (< or = 45 U/L) or markers of HCV or hepatitis B virus infection (15/1303; 1.2%) (p < 0.001), donors with ALT values between 46 and 99 U per L (0/108) (p < 0.002), donors with ALT values > or = 100 U per L (5/361; 1.4%), and donors with anti‐HCV but without detectable HCV RNA (1/93; 1.1%) (p < 0.05). CONCLUSION: More than 1 percent of Japanese blood donors were infected with HGV/GBV‐C, and the prevalence was much higher in those with HCV RNA. Should persistent infection with HGV/GBV‐C induce any hepatotoxic sequelae, either alone or in concert with the other hepatitis viruses, screening of blood units for HGV/GBV‐C would deserve consideration.

Percutaneous radio-frequency ablation therapy using a clustered electrode for malignant liver tumors.

Goals To examine the safety and effectiveness of percutaneous radio-frequency ablation therapy (PRAT) for malignant liver tumors, using a needle with cluster radio-frequency (RF) electrodes. Study The subjects were 13 patients with solitary malignant liver tumors: 10 had hepatocellular carcinoma and 3 had metastatic liver tumors. One session of PRAT with cluster RF electrodes was performed until roll-off occurred two times. Dynamic computed tomography (CT) and fine needle tumor biopsy under ultrasonographic guidance were conducted to assess the therapeutic efficacy. Aspartate aminotransferase, alanine aminotransferase, lactic dehydrogenase, and total bilirubin were evaluated before and 1, 3, and 7 days after PRAT. Results There were no serious complications. Aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase levels peaked 1 day after PRAT and decreased thereafter. No icterus occurred. Of the 13 tumors, 12 showed complete necrosis on dynamic CT; however, one of them showed histologically incomplete necrosis in the tumor biopsy. In both of the ineffective cases, the tumors were located near relatively large vessels. There was no recurrence in the liver in all cases of PRAT that were effective (observation periods: 6–14 months; mean, 10 months). Conclusions Percutaneous radio-frequency ablation therapy using a clustered electrode is a safe and effective treatment of malignant liver tumors, if the tumor is not located near the large vessels.

Location on the evolutionary trees of the non-structural protein (NS) and neuraminidase (NA) genes of late human influenza A (H2N2) viruses: parental viruses of the NS and NA genes of Hong Kong influenza A (H3N2) viruses

The nucleotide sequences of the non-structural protein (NS) and neuraminidase (NA) genes of human influenza A (H2N2) viruses isolated in 1967 and 1968 in Europe, Asia and North and South America were located on evolutionary trees in order to identify the parental virus of Hong Kong influenza A (H3N2) viruses, which appeared in the human population in 1968. From the evolutionary trees, the H2N2 viruses isolated during the 1967 to 1968 period were divided into two groups. Group I includes that A/Tokyo/3/67, A/Hachioji/1/67, A/Perg/1/68, A/Cordoba/522/67, A/Texas/2/68 and A/Berkeley/1/68 viruses, whereas group II includes the A/Georgia/1/67, A/England/10/67 and A/Poland/6/67 viruses. The NS and NA genes of Hong Kong H3N2 viruses isolated in 1968 were genetically closer to those of group II viruses and closest to those of A/Poland/6/67.