Shin'ichi Takahashi

Guidelines for the Management of Helicobacter pylori Infection in Japan: 2009 Revised Edition

Background:  Over the past few years, the profile of Helicobacter pylori infection has changed in Japan. In particular, the relationship between H. pylori and gastric cancer has been demonstrated more clearly. Accordingly, the committee of the Japanese Society for Helicobacter Research has revised the guidelines for diagnosis and treatment of H. pylori infection in Japan.

Guidelines in the Management of Helicobacter pylori Infection in Japan

In preparation of the approval of Helicobacter pylori therapy by the Japanese national health system, the board of directors of the Japanese Society for Helicobacter Research decided to prepare guidelines on the diagnosis and treatment of H. pylori infection for physicians in routine medical practice.

“Candidatus Helicobacter heilmannii” from a Cynomolgus Monkey Induces Gastric Mucosa-Associated Lymphoid Tissue Lymphomas in C57BL/6 Mice

ABSTRACT Both Helicobacter pylori and “Candidatus Helicobacter heilmannii” infections are associated with peptic ulcers, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue (MALT) lymphomas. However, good animal models of H. pylori clinical diseases are rare. In this study, we aimed to establish an animal model of “Candidatus Helicobacter heilmannii” gastric MALT lymphoma. We used a urease-positive gastric mucosal and mucus homogenate from a cynomolgus monkey maintained in C57BL/6 mouse stomachs. The bacterium in the homogenate was identified as “Candidatus Helicobacter heilmannii” based on a DNA sequence analysis of the 16S rRNA and urease genes. Mucosal and mucus homogenates were used to inoculate C57BL/6 mice, which were then examined for 24 months. We observed a gradual increase in the surface area of protrusive lesions in almost all infected C57BL/6 mouse fundic stomachs 6 months after infection. Light microscopic observations revealed an accumulation of B lymphocytes along with destruction of glandular elements and the presence of lymphoepithelial lesions consistent with low-grade MALT lymphomas. Electron microscopic observation revealed numerous “Candidatus Helicobacter heilmannii” bacilli in the fundic glandular lumen, the intracellular canaliculi, and the cytoplasm of intact cells, as well as damaged parietal cells. In conclusion, “Candidatus Helicobacter heilmannii” induced gastric MALT lymphomas in almost 100% of infected C57BL/6 mice after a 6-month period associated with the destruction of parietal cells.

A prospective randomized trial of either famotidine or omeprazole for the prevention of bleeding after endoscopic mucosal resection and the healing of endoscopic mucosal resection‐induced ulceration

Background : It has been reported that inhibitors of gastric acid secretion prevent bleeding after endoscopic mucosal resection for mucosal gastric neoplasm. However, uncertain whether an histamine2‐receptor antagonist or proton‐pump inhibitor is more effective.

Preliminary results of multicenter questionnaire study on long-term outcomes of curative endoscopic submucosal dissection for early gastric cancer.

There are a number of published reports on long‐term outcomes of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC), but most reports are from single centers with median follow‐up periods shorter than 5 years. This questionnaire study investigated long‐term outcomes of curative ESD for EGC at six Japanese institutions with follow‐up rates of at least 90% over a minimum 5‐year period.

Efficacy of Clostridium butyricum preparation concomitantly with Helicobacter pylori eradication therapy in relation to changes in the intestinal microbiota

Antibiotic associated diarrhea due to human intestinal microbiota abnormalities is a side effect of H. pylori eradication therapy. We examined intestinal microbiota changes during H. pylori eradication therapy and the preventive effect of CBM588 as a probiotic agent. Nineteen patients with gastro‐duodenal ulcer were randomly divided into three groups: group A (without probiotics), group B (with regular doses of CBM588) and group C (with double doses of CBM588). The incidence of diarrhea and soft stools during H. pylori eradication therapy was 43% in group A and 14% in group B, while none of the patients in group C reported diarrhea or soft stools. Both bacterial counts and detection rates of bifidobacteria and/or obligate anaerobe were decreased by eradication therapy. However, bacterial counts of obligate anaerobes in group C were significantly higher than in group A (P < 0.05). Additionally, during eradication therapy C. difficile toxin A was detected in both group A and group B but not in group C.

Presence of antimitochondrial autoantibodies in patients with autoimmune hepatitis

Background and Aim:  Antimitochondrial autoantibodies (AMA) are known to be a hallmark of primary biliary cirrhosis, and it has been suggested that AMA play a crucial role in generating biliary changes. Biliary tract lesions are not uncommon in patients with autoimmune hepatitis (AIH) and previous works have demonstrated that AMA are occasionally detectable in sera of patients with AIH. Therefore, the role of AMA as a cause of bile duct lesions in AIH livers should be addressed. The aim of the present study was to determine whether the presence of AMA is associated with clinical features, especially the occurrence of bile duct lesions, in patients with AIH.

Quantitative detection of hepatitis C virus RNA by multicyclic RT-PCR

Abstract We have developed a method to quantitate hepatitis C virus (HCV)-RNA from serum by using ‘multicylic’ RT-PCR. This method requires 100 μl of sera and synthetic HCV-RNA with a known copy number to be used as a standard. HCV RNA in serum are amplified by the RT-PCR technique and quantitated by comparing the darkness of the spot on the film with the standards after dot blot hybridization. Accuracy of this technique was comparable to the competitive RT PCR method (CRT-PCR) when compared using the same sample. Also, this technique uses one-tenth of the sample volume required in CRT-PCR with the additional advantages of low cost, faster assay time, and ability to run a larger number of samples. We analyzed the amount of HCV-RNA in 71 patients with chronic liver disease due to HCV subclassified into chronic inactive hepatitis (CIH), chronic active hepatitis (CAH), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Seventy-five percent of the patients contained 106 to 108 copies/ml of HCV-RNA. The number of samples which contained over 106 copies/ml in the four groups were CIH,5/8 (62.5%); CAH,15/20 (75.0%); LC,25/27 (92.6%); and HCC,14/16 (87.5%).

Randomised clinical trial: rabeprazole improves symptoms in patients with functional dyspepsia in Japan

The efficacy of proton pump inhibitors (PPIs) for treating functional dyspepsia (FD) is not well established.

Neonatal Fc receptor for IgG (FcRn) expressed in the gastric epithelium regulates bacterial infection in mice

Neonatal Fc receptors for immunoglobulin (Ig)G (FcRn) assume a central role in regulating host IgG levels and IgG transport across polarized epithelial barriers. We have attempted to elucidate the contribution of FcRn in controlling Helicobacter infection in the stomach. C57BL/6J wild-type or FcRn−/− mice were infected with Helicobacter heilmannii, and gastric lesions, bacterial load and the levels of antigen-specific IgG in serum and gastric juice were analyzed. The elevated levels of anti-H. heimannii IgG in gastric juice were observed exclusively in wild-type mice but not in FcRn−/− mice. In contrast, an increase in lymphoid follicles and bacterial loads along with deeper gastric epithelium invasion were noted in FcRn−/− mice. C57BL/6J wild-type or FcRn−/− mice were also infected with Helicobacter pylori SS1, and the results of the bacterial load in stomachs of these mice and the anti-H. pylori IgG levels in serum and gastric juice were similar to those from H. heilmannii infection. Our data suggest that FcRn can be functionally expressed in the stomach, which is involved in transcytosis of IgG, and prevent colonization by H. heilmannii and the associated pathological consequences of infection.