Mitsuki Miyata

Immune responses in mice to intranasal and intracutaneous administration of a DNA vaccine encoding Helicobacter pylori-catalase

We previously reported that the intracutaneous injection of DNA vaccines encoding Helicobacter pylori heat shock proteins elicited specific immune responses, and led to reduced infection in mice. In this study, we constructed DNA vaccine encoding H. pylori-catalase (pcDNA3.1-kat) and investigated the immune responses to intranasal and intracutaneous administration of pcDNA3.1-kat. C57/BL6 mice were immunized intracutaneously with 10 microg of pcDNA3.1-kat or intranasally with 50 microg of pcDNA3.1-kat. Catalase-specific IgG antibody was detected in the sera of intranasal and intracutaneous immunized mice. Both intranasal and intracutaneous immunized mice were significantly protected from colonization by H. pylori and had significantly reduced degrees of gastritis. These results demonstrate that DNA vaccine encoding H. pylori-catalase can induce an immune response against H. pylori, and that intranasal immunization works as well as intracutaneous immunization.

Therapeutic Efficacy of Infliximab on Patients with Short Duration of Crohn’s Disease: A Japanese Multicenter Survey

PurposeThis study was designed to evaluate the efficacy of infliximab in patients with Crohn’s disease of durations less than one year.MethodsTwo nationwide surveys of 35 Japanese institutions majoring in inflammatory bowel disease identified 41 patients with active Crohn’s disease who were treated by infliximab within 12 months after the diagnosis (E-group) and 97 patients treated later during their clinical course (L-group). Clinical features, responses to infliximab, and accompanying medications were compared between the two groups. A decrease in Crohn’s disease activity index ≥70 or the index <150 two weeks after infliximab was regarded to be efficacious.ResultsThe age was younger (24 vs. 33 years, median, P < 0.0001) and intestinal stricture (12 vs. 49 percent, P < 0.0001), internal fistula (0 vs. 26 percent, P = 0.0003), and previous intestinal resection (7 vs. 57 percent, P < 0.0001) were less frequent in the E-group than in the L-group. The efficacy of infliximab was different between the two groups with a significantly higher value in the E-group than in the L-group (90 vs. 61 percent, P = 0.0012). A multivariate logistic regression analysis revealed nonstricturing intestinal lesion to be a significant factor related to the efficacy of infliximab.ConclusionInfliximab is more efficacious in Crohn’s disease with short duration, probably because of less frequent stenosis.

Rebamipide Enemas–New Effective Treatment for Patients with Corticosteroid Dependent or Resistant Ulcerative Colitis

In this study we investigated the effect of rebamipide enema in patients with steroid-resistant and/or dependent ulcerative colitis. Rebamipide enemas were administered twice daily for a 12-week period; this treatment was further continued longer in patients who requested this. Disease activity index as reflecting the clinical condition and endoscopic index with histological grading were determined before and after the treatment period. Nine of 11 (81.8%) patients on 12-week treatment with rebamipide approved and were classified as colitis in remission. Moreover, seven of 11 patients requested long-term medication, the longest medication term being 80 weeks. These results medicated that rebamipide enemas may be effective in patients with steroid-resistant and/or dependent ulcerative colitis.

ASSESSMENT OF MISS AND INCIDENCE RATES OF NEOPLASTIC POLYPS AT COLONOSCOPY

Background:  The incidence rate after a colonoscopic polypectomy includes the true incidence rate of new polyp formation and miss rate of polyps at the initial colonoscopy. It is therefore important to assess accurate incidence rates of polyps as well as those of missing polyps with colocoscopy.

Acid stimulates E-cadherin surface expression on gastric epithelial cells to stabilize barrier functions via influx of calcium

Background and aims E-cadherin, which is a [Ca21]-dependent, homotypic cell–cell adhesion molecule, is expressed in gastrointestinal epithelial cells. Much has been learned about the down-regulation of E-cadherin expression in gastrointestinal tumours, Barretts oesophageal dysplasia, and Crohns disease, but the functions of this molecule in normal gastrointestinal mucosa are less known. Methods In this study, we investigated the relationship between E-cadherin expression and permeability using rat cultured gastric and intestinal epithelial cells following a 30-min exposure to various pH solutions. We also investigated the participation of [Ca21] in these events. Results E-cadherin expression increased under acid (pH 4) but not alkali (pH 10 or 11) exposure only for gastric epithelial cells. Gastric epithelial permeability was maintained only against acid exposure while intestinal permeability increased under both conditions. Transient influx of [Ca21] was only observed for gastric epithelial cells just after acid exposure. Conclusions These findings suggest that E-cadherin expression on gastric epithelium stabilizes the epithelial barrier against acid, probably through influx of [Ca21]. This event is thought to be one of the protective mechanisms in gastric mucosa against acid back-diffusion, which is one of the causes of peptic ulcer formation.

Protective actions of rat gastric epithelial E-cadherin expression against epithelial barrier dysfunctions induced by chemical hypoxia-reoxygenation in vitro

Background and aim E-cadherin expressed on gastric epithelium is reported to form adherence junctions and stabilize barrier functions. While hypoxia–reoxygenation is well known to cause gastric mucosal injury during reoxygenation, gastric E-cadherin actions against this stress remain unclear. In this study, using the oxygen depleting agent thioglycolic acid we examined whether E-cadherin expressed on rat cultured gastric epithelial cells has protective actions against epithelial barrier dysfunction induced by chemical hypoxia–reoxygenation. Methods Chemical hypoxia was induced by incubating cells with 5 mm thioglycolic acid in glucose free medium for 60 min. Cells were then reoxygenated for 240 min by changing to normal medium. The expression of E-cadherin on the cell surface was measured with an enzyme immunoassay, and epithelial permeability was determined by the diffusion rate of FITC–dextran through the cell layer. Results E-cadherin expression increased during the 60 min hypoxic period, accompanied by activation of protein kinase C, protein kinase G and protein kinase A. The increased expression significantly diminished, but was considerably higher than the control values during reoxygenation for 180 min, which was partially due to generation of reactive oxygen species but not to activation of protein kinase. Conversely, epithelial permeability was stabilized during hypoxia, but increased only for 30 min of reoxygenation, probably due to generation of reactive oxygen species. Epithelial permeability during hypoxia was elevated by a combination of all the protein kinase inhibitors. Conclusion An increase in the expression of E-cadherin during hypoxia through the activation of the kinases is likely to stabilize epithelial barrier functions. The reactive oxygen species generated during 30 min reoxygenation increased the molecular expression of E-cadherin less than during hypoxic stress. The transient break in the barrier functions caused by reactive oxygen species during reoxygenation appears to overcome the reactive oxygen species mediated cytoprotective action increasing E-cadherin expression.