Motofusa Hasegawa

Confocal endomicroscopy in patients with ulcerative colitis

Background:  Confocal endomicroscopy is a new technology that provides microscopic images of cellular morphology in the gastrointestinal tract in vivo. In particular, confocal microendoscopy allows histological diagnosis during the endoscopic examination. We examined patients with ulcerative colitis (UC) using confocal endoscopy and investigated the features of confocal endomicroscopic images of inflamed and non‐inflamed rectal mucosa.

Helicobacter pylori infection upregulates interleukin-18 production from gastric epithelial cells.

Background Helicobacter pylori infection induces a biased T helper type 1 (Th1) response that produces IFN-&ggr; and Fas ligand (FasL). Th1 cytokines are associated with apoptosis in the gastric epithelial cells. Aim We aimed to define the role of the recently cloned IL-18, a IFN-&ggr; inducing factor, in gastric mucosal injury induced by H. pylori infection. Methods Twenty-seven gastric ulcer (GU) patients and 20 functional dyspepsia (FD) patients were enrolled in this study. Mucosal biopsy samples were obtained from the gastric antrum and GU site during endoscopy. Samples were used for histological examination, H. pylori culture and in-situ stimulation for 48 h in the presence of 10 μg/ml phytohemagglutinin-P. IL-18, IFN-&ggr;, and soluble FasL (sFasL) levels in culture supernatants were assayed by the enzyme-linked immunosorbent assay method. IL-18, IL-1&bgr;-converting enzyme (ICE) and caspase-3 were evaluated by western blotting in gastric cancer cell lines (MKN45) cocultured with H. pylori. Results All 27 GU patients and ten out of 20 FD patients were found to be H. pylori-positive, whereas ten FD patients were H. pylori-negative. Antral mucosal tissues from H. pylori-positive FD patients contained (P<0.01) higher levels of IL-18, IFN-&ggr;, and sFasL than those from uninfected FD patients. IL-18, IFN-&ggr;, and sFasL levels at the ulcer site were significantly (P<0.01) higher than those at distant sites in the antrum. A significant relationship was seen between IL-18 and IFN-&ggr; levels at the ulcer site (r=0.7, P<0.01). H. pylori eradication led to a significant decrease in the levels of IL-18, IFN-&ggr;, and sFasL at the ulcer site. Western blotting showed that IL-18, ICE, and caspase-3 were activated in gastric cancer cell lines cocultured with H. pylori. Conclusion This study suggests that H. pylori infection enhanced mucosal injury by stimulating a Th1 response, which was mediated by IL-18 upregulation as well as activation of ICE and caspase-3.

Potential Role for Matrix Metallo- proteinase-3 in Gastric Ulcer Healing

Background/Aims: Matrix metalloproteinases (MMPs) are endopeptidases which perform important functions in extracellular matrix remodeling, cell proliferation, and inflammatory processes. Here, we compared MMP-3 levels with those of tissue inhibitor of metalloproteinases (TIMP)-1 and several inflammatory cytokines in gastric ulcer (GU) patients. Methods: This study enrolled 50 patients with GU and 6 with functional dyspepsia (FD). Samples of gastric mucosa from the antrum and the ulcer site were harvested from GU patients and of antral mucosa alone from FD patients during upper gastrointestinal endoscopy. Mucosal biopsy tissues were cultured for 24 h, and the culture supernatant was measured for levels of MMP-3, TIMP-1, IL-1β, IL-6, and IL-8. Results: All GU patients were positive for Helicobacter pylori, while all FD patients were negative. Antral levels of TIMP-1, IL-1β, IL-6, and IL-8 were significantly higher in GU than FD patients. Further, MMP-3 levels were significantly higher in GU patients at the ulcer site than in the antrum, and had a significantly positive correlation with TIMP-1, IL-1β, IL-6, and IL-8. Conclusion: MMP-3 levels were significantly higher at the ulcer site than in the antrum, suggesting that MMP-3 may perform an important function in gastric ulcer healing.

Relationships between Helicobacter pylori infection status, endoscopic, histopathological findings, and cytokine production in the duodenum of Crohn's disease patients.

Background:  The chronic inflammatory process in patients with Crohns disease (CD) may affect any part of the gastrointestinal (GI) tract. The pathogenesis of CD involves immunological abnormalities, including deficient or excessive expression of cytokines. We examined Helicobacter pylori infection status, endoscopic and histopathological findings, and cytokine production in the duodenum of CD patients in comparison with controls.

Role of endoscopic ultrasonography in predicting the response to cyclosporin A in ulcerative colitis refractory to steroids

BACKGROUND AND AIMS Although cyclosporin A has been reported to be effective in the treatment of severe ulcerative colitis, factors predicting its therapeutic efficacy remain unclear. Technical progress in endoscopic ultrasonography has improved visualisation of the structure of the colon wall. Here, to assess the value of endoscopic ultrasonography in predicting the response to cyclosporin A treatment, we evaluated the therapeutic effect of cyclosporin A by determining the pre- and post-cyclosporin A thickness of the mucosal layer in the rectum using endoscopic ultrasonography with an ultrasonic catheter probe. PATIENTS AND METHODS Fifteen ulcerative colitis patients who did not respond to high-doses of corticosteroids were treated with cyclosporin A by continuous intravenous infusion at 4mg/kg/day for 20 days. Before and 20 days after cyclosporin A therapy, clinical disease activity was assessed using clinical activity index scores. Colonoscopy and endoscopic ultrasonography were undertaken before and 20 days after cyclosporin A therapy. RESULTS Following treatment with cyclosporin A, nine patients showed a decrease in clinical activity index score by six points or more and were defined as responders, while the other six were defined as non-responders. Endoscopic ultrasonography measurement using an ultrasonic catheter probe showed that thickness of the rectal mucosal layer before cyclosporin A was significantly greater in responders than in non-responders (p<0.05). Further, thickness after cyclosporin A was statistically decreased (p<0.01) in the responders but not in the non-responders. CONCLUSIONS The ultrasonic catheter probe may represent a useful means of predicting and evaluating the efficacy of cyclosporin A treatment in severely ill ulcerative colitis patients.

Immunological Status of the Stomach in Inflammatory Bowel Disease – Comparison between Ulcerative Colitis and Crohn’s Disease

Background/Aims: Ulcerative colitis (UC) mainly affects the colon and rectum, whereas the chronic inflammatory process in Crohn’s disease (CD) can affect any part of the gastrointestinal tract. Recently, however, upper gastrointestinal lesions have been reported in UC patients. In this study, we investigated the immunological status of the stomach in UC or CD patients. Methods: 26 patients each with UC, CD or functional dyspepsia (FD) underwent diagnostic upper gastrointestinal endoscopy, and biopsy specimens were obtained from the gastric antrum.The contents of interleukin (IL)-6 and IL-8 in the organ culture supernatants of antral mucosal tissues were measured with enzyme-linked immunosorbent assay. Results: Endoscopically abnormal findings in the stomach were more frequent in CD than in UC or FD patients. Mononuclear cell infiltration and IL-6 production in the gastric antrum did not significantly differ between UC and FD patients, but were higher in those with CD. There was no significant difference in neutrophil infiltration or IL-8 production between UC, CD, and FD patients. Conclusions: UC patients did not show the immunological abnormalities in the stomach seen in CD patients.