Tadayuki Oshima

An Open-Label Prospective Randomized Multicenter Study Shows Very Rapid Remission of Ulcerative Colitis by Intensive Granulocyte and Monocyte Adsorptive Apheresis as Compared With Routine Weekly Treatment

OBJECTIVES:Granulocyte and monocyte adsorptive apheresis (GMA) has shown efficacy in patients with active ulcerative colitis (UC). However, with routine weekly treatment, it may take several weeks to achieve remission, and to date, the efficacy of a more frequent treatment schedule remains unknown. The aim of this study was to assess the clinical efficacy and safety of intensive GMA treatment in patients with active UC.METHODS:This was an open-label, prospective, randomized multicenter study to compare an intensive, two GMA sessions per week, with the routine, one GMA session per week. A total of 163 patients with mild-to-moderately active UC were randomly assigned to routine weekly treatment or intensive treatment. The maximum number of sessions of GMA permitted was 10. However, when patients achieved remission, GMA was discontinued. Remission rate at the end of the study, time to remission, and adverse events were assessed in both groups.RESULTS:Of the 163 patients, 149 were available for efficacy analysis as per protocol, 76 were in weekly GMA, and 73 were in intensive GMA. At the end of the study period, clinical remission was achieved in 41 of 76 patients (54.0%) in weekly GMA and in 52 of 73 patients (71.2%) in intensive GMA (P=0.029). The mean time to remission was 28.1±16.9 days in the weekly GMA treatment group and 14.9±9.5 days in the intensive GMA group (P<0.0001). Intensive GMA was well tolerated without GMA-related serious adverse side effects.CONCLUSIONS:Intensive GMA in patients with active UC seems to be more efficacious than weekly treatment, and significantly reduced the patients morbidity time without increasing the incidence of side effects.

Changes in the expression of claudins in active ulcerative colitis

Background and Aim:u2002 Epithelial barrier function is impaired in ulcerative colitis (UC), but the pathophysiological mechanisms leading to this barrier defect are still far from clear. Because epithelial barrier function is primarily regulated by the most apical intercellular junction, referred to as the tight junction (TJ), we investigated the expression of TJ proteins on rectal epithelial mucosa in UC.

Advantages of endoscopic submucosal dissection over conventional endoscopic mucosal resection

Background:u2002 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.

Wip1 protects hydrogen peroxide-induced colonic epithelial barrier dysfunction

Abstract.Tight junctions (TJs) create a paracellular permeability barrier. Although reactive oxygen species have been implicated as mediators of inflammation in inflammatory bowel diseases, their influence on the function of colonic epithelial TJs remains unknown. Oxidative stress-mediated colonic epithelial permeability was significantly attenuated by a p38 mitogen-activated protein (MAP) kinase inhibitor, SB203580. Although the amount of TJ proteins was not altered, hydrogen peroxide (H2O2) changed the localization of claudin-4 protein from an NP-40 insoluble fraction to a soluble fraction and from an apical TJ to lateral membrane. The p38 MAP kinase inactivator Wip1 significantly attenuated phosphorylation of p38 MAP kinase, and oxidative stress mediated permeability. H2O2-induced changes in claudin-4 localization were abolished by SB203580 pretreatment as well as Wip1-expressing adenovirus infection. This is the first study to demonstrate that exogenous Wip1 functions to protect oxidative stress-mediated colonic mucosal permeability and that H2O2-induced claudin-4 dislocalization is abolished by Wip1.

Subcellular localization of ATBF1 regulates MUC5AC transcription in gastric cancer

Human gastric epithelium has a unique mucin gene expression pattern, which becomes markedly altered in gastrointestinal disorder. This alteration in mucin expression, including the mucin MUC5AC, may be related to the development and prognosis of gastric cancers, and MUC5AC‐positive gastric cancer has been reported to be poor prognosis. However, the molecular mechanism of MUC5AC transcriptional regulation has not been fully elucidated. AT motif‐binding factor 1 (ATBF1) is a homeotic transcriptional regulatory factor recently identified as a tumor suppressor gene, and its subcellular localization suggests a link to cell proliferation and differentiation. We investigated the mechanism of MUC5AC transcriptional regulation by ATBF1. In 123 gastric cancer lesions, ATBF1 expressed in the nucleus significantly suppressed MUC5AC expression, as determined by immunohistochemistry. In addition, analysis of the MUC5AC promoter region revealed an AT motif‐like element. This element was found to be essential for ATBF1 suppression of MUC5AC promoter activity as shown in a dual luciferase‐reporter assay. Over‐expressed ATBF1 also significantly suppressed endogenous MUC5AC protein expression in gastric cancer cells. Chromatin immunoprecipitation demonstrated that ATBF1 binds to the AT motif‐like element in the MUC5AC promoter. These results indicate that ATBF1 in the nucleus negatively regulates the MUC5AC gene in gastric cancer by binding to an AT motif‐like element in the MUC5AC promoter.

The protective effect of rebamipide on paracellular permeability of rat gastric epithelial cells

Background :u2002Barrier function in gastric epithelial cells is essential for the gastric defence mechanism against acid back‐diffusion into the mucosal layer. Our previous study indicated that trans‐epithelial resistance (TER) of rat gastric epithelial cells was rapidly increased when the cells were exposed to acid. This response to acid was diminished by indometacin.

Efficacy of famotidine and omeprazole in healing symptoms of non-erosive gastro-oesophageal reflux disease: randomized-controlled study of gastro-oesophageal reflux disease

Background :u2002The epidemiology and pathophysiology of non‐erosive gastro‐oesophageal reflux disease differs from erosive gastro‐oesophageal reflux disease. There is a possibility that non‐erosive gastro‐oesophageal reflux disease treatment requires a different regimen/approach but it is not yet acknowledged.

A Novel Strategy in Production of Oligosaccharides in Digestive Tract: Prevention of Postprandial Hyperglycemia and Hyperinsulinemia

The aim of this study was to evaluate the effects of oral administration of transglucosidase (TG) on postprandial glucose concentrations in healthy subjects. A randomized placebo-controlled three-way crossover trial was separated by a washout period of more than 3 days. Twenty-one normal healthy volunteers, aged 30–61 years old (17 males and 4 females) were selected for this study. The subjects’ health was assessed as normal by prestudy screening. All subjects received 3 types of test meals (3 rice balls: protein, 14.4 g; fat, 2.1 g; and carbohydrate, 111 g: total energy, 522 kcal) with 200 ml water in which 0 mg, 150 mg, or 300 mg of TG was dissolved. Blood samples for estimating plasma glucose and insulin concentrations were collected before and every 30 min after the experiment. As compared to no TG treatment, TG administration tended to prevent a postprandial increase in plasma glucose (p = 0.069: 150 mg of TG vs control) but there were no significant difference among three groups. With regard to the 17 subjects who were suggested to have impaired glucose tolerance, TG significantly decreased the postprandial blood glucose (p<0.05: 150 mg and 300 mg of TG vs control) and marginally decreased insulin concentrations (p = 0.099: 300 mg of TG vs control). These results suggest that TG may be useful for preventing the progression of type 2 diabetes mellitus.

Bone morphogenetic protein 2 induced differentiation toward superficial epithelial cells in the gastric mucosa

BackgroundEpithelial–mesenchymal interactions are important for maintenance of the gastrointestinal tract mucosa. Moreover, diffusible factors from the underlying mesenchyme control the proliferation and differentiation of the epithelial cells. However, the details of the associated signaling remain unknown.MethodsTwo novel cell lines, designated MSE1 (mouse stomach epithelium) and MSMF1 (mouse stomach myofibroblast) cells, were established from mouse glandular stomach and cocultured in three-dimensional collagen gels in vitro.ResultsMSE1 cells formed dramatic branching tubular structures upon coculture with MSMF1 cells. In contrast, they formed spherical cyst structures in the absence of fibroblast support or the presence of Swiss 3T3 cells. Since bone morphogenetic protein 2 (BMP2) was expressed by MSMF1 cells but not Swiss 3T3 cells, we investigated whether it induced the morphological differentiation. Addition of BMP2 to MSE1 cells induced the formation of branching tubular structures, even in the absence of MSMF1 cells. Noggin, a BMP2 antagonist, blocked the MSMF1-induced tubular branch formation by MSE1 cells. MSE1 cells were induced to express mRNA of MUC5AC, an important marker for gastric superficial epithelium in the upper part of pits, upon branching tubule formation after BMP2 addition. Coculture with MSMF1 cells or BMP2 addition induced Smad1 phosphorylation in MSE1 cells. Furthermore, BMP2 inhibited MSE1 cell proliferation in MTS assays and suppressed AKT phosphorylation.ConclusionsBMP2 stimulated MSE1 cells to form branching duct-like structures and differentiate toward superficial epithelium in three-dimensional cocultures in vitro, suggesting that it may act as a morphogen and differentiation inducer in epithelial–mesenchymal interactions of gastric mucosa.

Helicobacter pylori eradication decreases blood neutrophil and monocyte counts.

Background :u2002The effect of Helicobacter pylori infection on systemic disorders is not well understood.