Search

Helicobacter (H.) suis is capable of infecting various animals including humans, and H. suis infections can lead to gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Recently, we reported that interferon-γ (IFN-γ) was highly expressed in the stomachs of H. suis-infected mice, but the direct relationship between the upregulation of IFN-γ expression and the formation of gastric lymphoid follicles after H. suis infection remains unclear. Here, we demonstrated that the IFN-γ produced by B cells plays an important role in the formation of gastric lymphoid follicles after H. suis infection. In addition, IFN-γ-producing B cells evoked gastric lymphoid follicle formation independent of T-cell help, suggesting that they are crucial for the development of gastric MALT induced by Helicobacter infection.

Helicobacter suis infects the stomachs of both animals and humans, and can induce gastric mucosa-associated lymphoid tissue (MALT) lymphomas. It is known that CXC chemokine ligand 13 (CXCL13) is highly expressed in the Helicobacter-infected mice and gastric MALT lymphoma patients, but the pathway that links the activation of CXCL13 and the formation of gastric MALT lymphomas remains unclear. In this study, we examined whether CXCL13 neutralization would interfere with the formation of gastric lymphoid follicles including B cells, CD4+T cells, dendritic cells (DCs), and follicular DCs (FDCs) in germinal centers to determine the role of CXCL13 in the formation of B-cell aggregates after H. suis infection. Moreover, the expression of genes associated with the lymphoid follicle formation was also effectively suppressed by anti-CXCL13 antibody treatment. These results suggest that the upregulation of CXCL13 has an important role in the development of gastric MALT lymphomas and highlight the potential of anti-CXCL13 antibody for protection against Helicobacter-induced gastric diseases.

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.

Background: Dieulafoy's lesion is an important cause of GI bleeding. The results of hemoclip application as the first treatment of choice for Dieulafoy's lesions have not been reported. This study prospectively examined the short- and long-term outcomes of hemoclip application for Dieulafoy's lesions. Methods: The study was conducted over a 7-year period beginning in January 1995 during which hemoclip application was used as the first-choice hemostatic treatment for Dieulafoy's lesions. Clinical data, endoscopic findings, and outcome of treatment were evaluated. Long-term outcome for patients was also investigated. Results: A Dieulafoy's lesion was diagnosed in 34 patients (27 men, 7 women; mean age, 54 years, range 21-81 years) after a mean of 1.2 endoscopies; 79.4% of the patients had active bleeding. Initial hemostasis was attained by hemoclip placement in 94.1%. The rate of recurrent bleeding was 9.3%. No patient required additional treatment such as surgery. The 30-day mortality rate was 2.9% (1 death, unrelated). For the remaining 33 patients, median follow-up was 53.8 months (range 19 to 90 months). Another Dieulafoy's lesion developed in one patient during follow-up, but in a different location compared with the index lesion. Conclusions: Endoscopic hemoclip application for Dieulafoy's lesions was effective and safe with short- and long-term benefits. (Gastrointest Endosc 2003;57:653-6.)

Background: Endoscopic hemoclipping is known to be highly effective as hemostatic treatment for upper gastrointestinal bleeding. However, the efficacy and safety of hemoclipping for Mallory-Weiss syndrome (MWS) have not been reported. Thus, the aim of the present study was to assess prospectively the usefulness of endoscopic hemoclipping for MWS bleeding. Methods: This study was conducted from January 1994 to August 1999. Hemoclipping was performed when active bleeding (spurting, streaming or oozing), visible vessels or fresh adhesive clots were found on endoscopic examination. Patients who did not have any of these findings were conservatively treated. Follow-up endoscopy was performed within 24 hours, after 5 days and between 1 and 2 months after the procedure. Results: MWS was diagnosed in a total of 58 patients during the study. Hemoclipping was performed in 26 patients and was technically successful in all cases. The average number of hemoclips used was 2.8 ± 1.6 (range 1 to 8). The number of hemoclips required for hemostasis depended on the nature of the bleeding. No complications, recurrent bleeding, or deaths resulted. Follow-up endoscopy showed no evidence of hemoclip-induced tissue injury and no impairment of Mallory-Weiss tears. Conclusion: Endoscopic hemoclipping provided an effective and safe modality for obtaining hemostasis when bleeding is due to MWS. (Gastrointest Endosc 2001;53:427-30.)

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%).

Background/Aim: One of the features of gastroesophageal reflux disease (GERD) in Japan is that its frequency and severity tend to increase in elderly women. In addition, elderly patients (≥65 years) with non-erosive reflux disease (NERD) present with typical symptoms more frequently than do non-elderly patients with NERD. Rikkunshito (RKT), a traditional Japanese medicine, acts as a prokinetic agent and enhances gastric emptying and improves gastric accommodation. Our previous prospective randomized multicenter placebo-controlled study, the G-GRIDE study, showed that RKT combined with a standard-dose of rabeprazole (RPZ) therapy significantly improved the acid-related dysmotility (ARD) symptoms in elderly patients with PPI-refractory NERD. The aim of this study was to evaluate clinical characteristics of elderly PPI-refractory NERD patients with ARD symptoms who responded to RKT. Methods: Two hundred forty-two patients with PPI-refractory NERD were enrolled from August 2011 to July 2012 at 71 hospitals in Japan. Patients were randomly assigned to 8 weeks of either RPZ (10 mg/q.d.) plus rikkunshito (7.5 g/t.i.d.) (RKT group) or RPZ plus placebo (PL group) therapy. Of the 242 patients, 95 were elderly patients (≥65 years) with ARD (RKT group: n=52, PL group: n=43). We analyzed the changes using the 12 subscale score of the frequency scale for the symptoms of GERD (FSSG) at 4 and 8 weeks and compared the therapeutic efficacy between the 2 groups. Results: No significant differences were seen between the 2 groups in terms of subject background. The FSSG score (mean±SD; at 0, 4, and 8 weeks) in both the RKT [16.0±7.0; 9.9±8.4; 7.0±6.4] and PL [15.1±6.4; 10.9±6.7, 11.1±8.5] groups significantly decreased after the treatment. However, the degree of improvement of total and ARD scores of FSSG after 8 weeks of treatment was significantly greater in the RKT group than in the PL group. Combination therapy with RKT for 8 weeks showed significant improvement in 3 subscale scores (abdominal bloating, heavy feeling in stomach after meals, and sick feeling after meals) of the ARD domain and 1 subscale score (heartburn after meals) of the reflux symptom domain. Conclusion: RKT may be useful for improving GERD symptoms in elderly PPI-refractory NERD patients with ARD. RKT was especially effective for resolving postprandial GERD symptoms (heavy feeling in stomach after meals, sick feeling after meals, and heartburn after meals).

as well as a reduced expression of CD80/CD86. Co-cultivation of allogenic T cells with H. pylori challenged MoDC results in an Interferon-γ secretion by T cells. However, the T cell response was modified when TLR-2 was neutralized. Conclusion: For the recognition of H. pylori by MoDC, TLR-2 plays an important role. When neutralized, MoDC induce stronger H. pylori specific T cell responses, although co-stimulatory activation markers on MoDC and secreted cytokines were reduced. The role of TLR subtypes therefore appears to have an important impact on regulation of T cell activation, andmechanisms are being investigated. Similar mechanism may account for other autoimmune diseases, which is of considerable clinical impact.

The Most Effectible Dose of Mosapride Citrate on the Examination for Small Bowel Capsule Endoscopy in Healthy Subjects: A Prospective Double-Blind Cross-Over Study Mari Hayashida*, Shin’Ichi Takahashi Kyorin University School of Internal Medicine, Tokyo, Japan Aims: The aim of this study was to evaluate the efficacy dose of mosapride citrate on the intestinal-transit time. Methods: We reported the 10mg mosapride citrate efficacy on intestinal-transit time and diagnostic yield of CE. 10mg mosapride citrate markedly shortened the gastric transit time but without statistical significance (16.2min. in mosapride citrate group vs 44.4 min. in the placebo group). No significant difference was found in the small bowel transit time (193 min. in mosapride citrate group vs 196 min. in the placebo group). The study was performed in 10 healthy male volunteers, aged 31-44 yrs (mean age: 38 yrs). They were given informed consent before the study. This was a prospective, and double-blind cross-over study. After overnight fasting, they were given a single dose of 20mg mosapride (group 20mgM) or placebo (group P) one hour before CE examination. The intestinal-transit time and the number of reaching the cecum within 8 hours were evaluated for each group. After then the gastric transit time and small bowel transit time were evaluated between mosapride citrate 10mg group and 20mg group. Results: All subjects had a complete examination with capsule reaching the cecum in time. The gastric transit time in the group 20mgM was statistical significant shortened (11.8 min in group 20mgM vs 42.2 min in group P. p 0.05). The small bowel transit time in the group 20mgM was also statistical significant shortened (113 min in group 20mgM vs 236 min in group P. p 0.05). No significant difference was found in the gastric transit time between 10mg and 20mg mosapride citrate group (16.2 min vs 11.8 min). But the small bowel transit time between 10mg and 20mg mosapride citrate group was statistical significant shortened in group 20mgM (193min vs 113 min). Conclusion: We suggested that 20mg mosapride citrate is the most efficacy dose on the examination of small bowel CE.

liver. Twelve and eighteen months after the infection, approximately 100% of infected mice had liver and pulmonary lesions. Some of the MALT lymphomas were defined as belonging to the high-grade group by the PCNA positivity. Eradication of the bacteria induced shrinkage of the tumor in the liver and the lung with apoptotic cells as well as in the stomach. Conclusion: Long-term infection with Helicobacter heilmannii in C57BL/6 mouse induced lowand high-grade hepatic and pulmonary MALT lymphoma as well as gastric lymphoma. Eradication of the bacteria brought about shrinkage of the hepatic and pulmonary lesions as well as gastric MALT lymphoma.

liver. Twelve and eighteen months after the infection, approximately 100% of infected mice had liver and pulmonary lesions. Some of the MALT lymphomas were defined as belonging to the high-grade group by the PCNA positivity. Eradication of the bacteria induced shrinkage of the tumor in the liver and the lung with apoptotic cells as well as in the stomach. Conclusion: Long-term infection with Helicobacter heilmannii in C57BL/6 mouse induced lowand high-grade hepatic and pulmonary MALT lymphoma as well as gastric lymphoma. Eradication of the bacteria brought about shrinkage of the hepatic and pulmonary lesions as well as gastric MALT lymphoma.

G A A b st ra ct s located either in the proximal third of the corpus or in the fundus. Cardia tumors were classified according to the AEG-classification by Siewert and colleagues (AEG = adenocarcinoma of the esophagogastric junction; Siewert Br J Surg 1998). Included were tumors with their main tumor mass located directly at the cardia or subcardial with involvement of the cardia (AEG 2 and 3). Barrett carcinomas and supracardial cancers (AEG1) have been excluded. Patients were compared concerning the influence of H. pylori infection and the presence of histopathological changes. The chi-square test and consecutively Fisher's exact test were used for statistical analysis. RESULTS: There was no difference in the prevalence of H. pylori in proximal versus distal GC. The histological differentiation between intestinal versus diffuse type cancers revealed significantly more intestinal type tumors at proximal location compared to distal GC (65 vs 46%; P = 0.022). Individual parameters of the proximal versus distal GC are reported in the table. Subanalysis of adenocarcinomas at the esophagogastric junction revealed no significant difference of H. pylori prevalence between cardial (AEG2) and subcardial (AEG3) tumors. CONCLUSION: There is no difference in the prevalence of H. pylori infection in proximal as compared to distal gastric cancer provided the allocation of the tumor is correctly assessed. To obtain correct prevalence data it is essential to exclude Barrett's carcinomas (AEG1) from other adenocarcinomas at the esophagogastric junction. There was no distinct association of H. pylori with any of the histological types according to Lauren. Prevalence for H. pylori, CagA, IM and glandular atrophy by histolgical type and tumor location.

Study On Japanese Patients with Obscure Gastrointestinal Bleeding Based On the Combined Use of Capsule Endoscopy and Double-Ballon Endoscopy Mari Hirata, Kyoto Imase, Yuji Yamada, Yoko Ikei, Genichi Koyama, Shin-Ichi Takahashi Background: Recently, the development of capsule endoscopy (CE) and doubleballon endoscopy (DBE) has made diagnosis and treatment on the disease of small-intestinal disorders more effective. Aim: The aim of this study was to evaluate the utility of CE and DBE for obscure gastrointestinal bleeding (OGIB). Patients & Method: The subjects were 46 patients (mean age: 54 G 17 yrs., 22 males and 24 females) with OGIB who underwent treatment in our hospital between March 2004 and October 2005. In principle, we performed CE at first and then DBE on the basis of the diagnosis of CE. CE was performed in all patients. DBE examinations were performed in 15 patients. As the approach method of DBE, we choosed ‘oral approach’ or ‘anal approach’ which depend upon the presumable source of the abnormal small bowel located by CE. Results: The rate of concomitant disease of the case of OGIB at our hospital was 26.2%. The details of concomitant disease are as follows: liver cirrhosi (6 cases), Chronic renal failure (3 cases), heart disease (3 cases), no concomitant disease (34 cases). Median hemoglobin was 9.9 G 2.0 g/dl, 41% of patients had required transfusion, 15% took NSAID or anticoagulant drugs. CE detected significant diagnosis in the OGIB to 26 patients (60%) out of 46 patients: 5 cases of Angiodysplasia, 5 cases of Ulcer, 10 cases of erosion, 6 cases of active bleeding, one case of esophageal varix. The rate of significant diagnosis by DBE was 73.3%. The significant diagnosis were Angiodysplasia (6 cases), Ulcer (4 cases), Crohn’s disease (1 case). With regard to treatment, endoscopic treatment was performed in 6 patients (argon plasma coagulation and clipping: 1case, argon plasma coagulation: 1case, clipping: 4cases) for Angiodysplasia. Conclusion: Performing CE before DBE was useful not only for getting the information of small bowel disease, but also for choosing approach method of DBE as well as for diagnosis and treatment of OGIB.

Background: Gastric mucosa has two types of mucous cells: surface mucous cells (SMCs) and gland mucous cells (GMCs). Hdicobacter pylori (li. pyIori) do not attach to GMCs and mucins from GMCs inhibit the movement of li, pylori in the gastric mucous gel layer. H. pylon increase the cell kinetics ot gastric epithelial cells. AIM: To examine the effect of li. IEvlori intection on gastric epithelial cell kinetics from the viewpoint of the phenotype of gastric mucous ceils. Methods: Gastric mucosal biopsy specimens obtained from 10 nonintectad volunteers and 20 H, pylori infected patients before and after eradication were used. Formalin-fixed and paraffin-embedded tissue sections were examined by a sequential staining consisting ot immunoalkaline phosphatase method for Ki67, immunopemxidase method with monoclonal antibody HIK1083, and histochemical staining for SMCs (periodic acid oxidation-thionine Schiff reaction: PA-TS), Ki-67 labeling indices (Lls) and phenotype of proliferating gastric mucous cells were analyzed. Results: SMCs, GMCs and proliferating cells were simultaneously visualized in histological specimens; SMCs were stained blue with PA-TS, GMCs were stained red with liIK1083, and nuclei of proliferating cells stained brown with Ki-67. Proliferating SMCs were distributed in lower part of gastric foveola and proliferating GMCs were localized in the lower part ot gastric lm, eola around the generating zone. Ki-67 LIs were higher in H. pylori infected patmnts (0.15 in the corpus and 0,21 in the antrum) than in vohinteers (0.06 and 0.11) (p

Background: Hemorrhagic gastric ulcer is a more serious disorder in elderly patients than in young patients. Emergency surgery in elderly patients carries high risk. Thus, less invasive treatment by endoscopy may be advantageous. This study aimed to evaluate the efficacy of endoscopic treatment for hemorrhagic gastric ulcer in patients aged 80 or more. Methodology: A total of 269 patients underwent endoscopic hemostatic treatment for hemorrhagic gastric ulcer over a four year period. As hemostatic measures, hemoclipping and pure ethanol injection, either alone or in combination, were employed. These patients were divided into two groups: elderly (≥80 years old, n=26) and younger (

Aim: Endoscopic treatment with sclerotherapy or thermal methods has been widely used for upper gastrointestinal (UGI ) bleeding due to Mallory-Weiss syndrome (MWS). However, the potential drawback of thermal methods and the injection of sclerosing agents is that these may cause excessive tissue injury leading to necrosis and perforation. Recently, endoscopic hemoclipping was shown to be highly effective for as a hemostatic treatment for UGI bleeding. Hemoclipping causes less damage to the surrounding area than sclerotherapy or thermal methods. However, the efficacy and safety of hemoclipping for MWS bleeding has not been reported. The aim of the present study was to assess prospectively the usefulness of endoscopic hemoclipping for MWS bleeding. Methods: This prospective study was performed over a 5 year period beginning in January 1994. When patients were diagnosed with MWS by endoscopy , hemoclipping was performed for patients with active bleeding , visible vessel and/or red clots (Group H). The remaining patients with old clots and linear tears in the Esophagogastric junctional (EGJ) mucosa as the only possible origin of bleeding were conservatively treated (Group C). The clinical data and outcome of endoscopic treatment were compared between these two groups. Results: A total of 58 patients underwent emergency endoscopy for UGI bleeding due to MWS from January 1994 to August 1999. During endoscopic examination, active bleeding was found in 17 patients (29%), a visible vessel in one patient (2%) and red clots in 8 patients (14%); Hemoclipping was performed on all 26 patients. Of the remaining 32 patients, 12 patients (21%) had old clots, and 20 (34%) had linear tears without stigmata of recent hemorrhage in the EGJ; these patients did not receive hemoclipping. Significantly more patients in Group H had shock and trasfusional requirements over 800ml than in Group C [the former 4 (17%) vs 0, the latter 4 (17%) vs 0]. The mean hemoglobin level on admission was significantly lower in Group H (10.6±2.9g/dl)than in Group C (12.2±3.0g/dl). Significantly more patients in Group H had critical concomitant diseases than in Group C [14 (54%) vs 8 (25%)]. However, all patients in Group H successfully underwent endoscopic hemostasis with no rebleeding. No patients in Conservative group had rebleeding. No complications related to the endoscopic procedures and no hospital deaths were found in either group. Conclusion : Endoscopic hemoclipping provided an effective and safe modality for securing hemostasis for MWS bleeding.