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Nobuhide Oshitani

Publications and source records attributed to Nobuhide Oshitani.

51 records · Page 3Linked to original sources
PubMed2003

COX-2 is essential for EGF induction of cell proliferation in gastric RGM1 cells.

Growth factors upregulate cyclooxygenase-2 (COX-2) expression and extracellular signal-regulated kinase (ERK) activity, yet little is known regarding the interaction between COX-2 and ERK in terms of mitogenic signal transduction pathways in gastric epithelial cells. Therefore, we examined the role of COX-2 in EGF-induced proliferation of gastric epithelial RGM1 cells. EGF treatment significantly induced ERK activity (peaked at 30 min) and significantly increased COX-2 protein (peaked at 6 hr), production of prostaglandin E2 (PGE2), and cell proliferation. MEK inhibitor (PD98059) decreased ERK activity and cell proliferation induced by EGF. The selective COX-2 inhibitor (NS-398) significantly reduced EGF-induced cell proliferation. Exogenous PGE2 partly reversed the NS-398-induced inhibitory action on cell proliferation, clearly indicating the importance of PGE2 in mitogenic pathway. The induction of COX-2 protein by EGF was completely blocked by preincubation with MEK inhibitor. These results suggest that the ERK-COX-2 pathway is critical for EGF-induced proliferation of gastric epithelial cells.

Animals↗
PubMed2003

Dietary fat attenuates the benefits of an elemental diet in active Crohn's disease: a randomized, controlled trial.

OBJECTIVES: Although an elemental diet has been established as the primary treatment for patients with Crohn's disease, the influence of dietary fat on the elemental diet remains unclear. We have designed the first randomized, controlled trial for elemental diets containing different fat percentages in patients with active Crohn's disease. METHODS: Each patient was randomized to receive one of three dose levels of fat in an elemental diet (Elental) for 4 weeks: 10 patients received low fat (3.06 g/day), 10 patients received medium fat (16.56 g/day) and eight patients received high fat (30.06 g/day). The additional fat was composed of long-chain fatty acids. All patients were evaluated using the International Organization of Inflammatory Bowel Disease rating, plus C-reactive protein level and erythrocyte sedimentation rate, which were measured at weekly intervals. RESULTS: Although the International Organization of Inflammatory Bowel Disease rating, C-reactive protein level and erythrocyte sedimentation rate in the low-fat group decreased, the values in the medium- and high-fat groups fluctuated during the study. The remission rate after 4 weeks in each group was 80%, 40% and 25% for patients in the low-, medium- and high-fat groups, respectively. CONCLUSIONS: When the fat consisted of long-chain triglycerides, a high amount of this fat in the elemental diet formula decreased its therapeutic effect against active Crohn's disease.

Adult↗
PubMed2003

Distinct elevation of levels of anti-Caenorhabditis elegans antibody in sera of patients with inflammatory bowel disease.

Dysregulation of immune responses to intestinal exogenous antigens contributes to the pathogenesis of inflammatory bowel disease, but the specific antigen responsible for the pathogenesis of inflammatory bowel disease is unknown. We measured serum antibody titers against Caenorhabditis elegans antigens. Immunoglobulin G (IgG) and IgG subclass anti-C. elegans antibodies in serum samples from 29 patients with ulcerative colitis, 30 patients with Crohn's disease, 7 patients with intestinal Behçet's disease, and 11 healthy controls were measured by enzyme-linked immunosorbent assay. Serum IgG and IgG2 antibody titers against C. elegans were significantly higher in patients with inflammatory bowel disease than in controls. Antibody levels were not affected by age, gender, disease activity, extent of disease, or small bowel involvement. The anti-C. elegans antibody titer was significantly lower in patients with Crohn's disease taking mesalazine or sulfasalazine than in patients not taking these drugs. The increased immune responses to C. elegans found in patients with inflammatory bowel disease reflect dysregulated immune responses to enteric antigens, which might play a role in the pathogenesis of inflammatory bowel disease.

Adult↗
PubMed2003

Analysis of intestinal HLA-DR bound peptides and dysregulated immune responses to enteric flora in the pathogenesis of inflammatory bowel disease.

Isolation of antigenic peptides from the MHC-groove has contributed to the understanding of T cell responses. However, these MHC-associated peptides have been isolated from various murine and human cell lines. The specific antigen responsible for the pathogenesis of inflammatory bowel disease is unknown. We examined antigenic peptides bound to the class II major histocompatibility complex (MHC) groove in human intestine by ion-trap tandem mass spectrometry equipped with online reverse-phase high performance liquid chromatography. We detected 55 parent proteins from 4 controls, 9 patients with ulcerative colitis, and 9 patients with Crohn's disease. The calculated molecular masses (m/z) of these peptides ranged from 874.4 to 2727.4, representing 10-26 amino acid residues. Fifty-one of these 55 parent proteins were exogenous proteins. Escherichia coli-, Saccharomyces cerevisiae-, and Caenorhabditis elegans-derived peptides were found frequently in patients with inflammatory bowel disease. The present results suggest that in vivo antigen processing by antigen-presenting cells and T lymphocytes in human intestine participate with exogenous antigen presentation. Increased immune responses against E. coli, S. cerevisiae and C. elegans found in patients with inflammatory bowel may participate as dysregulated immune responses to enteric flora in the pathogenesis of inflammatory bowel disease.

Adolescent↗
PubMed2003

Comprehensive analysis of intestinal cytokine messenger RNA profile by real-time quantitative polymerase chain reaction in patients with inflammatory bowel disease.

Although the cytokine network plays a key role in the inflammatory responses in inflammatory bowel disease, no comprehensive analysis of the intestinal cytokine network has been reported. We analyzed messenger RNA levels for various cytokines in human intestine by real-time quantitative polymerase chain reaction to clarify the cytokine profiles involved in the pathogenesis of inflammatory bowel disease. Biopsy specimens were obtained from 23 patients with ulcerative colitis (15 men, 8 women, mean age of 44.1 years), 17 patients with Crohn's disease (15 men, 2 women, mean age of 21.6 years), and 8 normal controls (6 men, 2 women, mean age of 62.7 years) who underwent colonoscopy for suspected colonic disease. Messenger RNA was isolated from two biopsy samples and reverse-transcribed to obtain cDNA. Mucosal mRNA levels for IL-1beta, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p35, IL-12p40, IL-15, IFN-gamma and TNF-alpha were simultaneously analyzed by real-time quantitative polymerase chain reaction. In patients with active ulcerative colitis, IL-1beta, IL-4, IL-5, IL-8, IL-12p40, IFN-gamma and TNF-alpha mRNA levels were significantly higher than those in controls. In patients with active Crohn's disease, IL-1beta, IL-8, and IL-12p40 mRNA levels were significantly higher than those in controls. Mucosal level of IL-12p40 mRNA was significantly higher in patients with inactive Crohn's disease than in controls. Both Th1 and Th2 cytokine mRNA levels were increased in colonic mucosa of patients with ulcerative colitis suggesting the possibility that cellular and humoral immunity play roles in the pathogenesis of this disease. In patients with Crohn's disease, Th1 cytokine mRNA levels were increased in colonic mucosa, suggesting predominance of cellular immunity in the pathogenesis of this disease.

Colon↗
PubMed2003

Differential expression of homing receptor CD103 on lamina propria lymphocytes and association of CD103 with epithelial adhesion molecules in inflammatory bowel disease.

Intraepithelial lymphocytes play an important role in mucosal immunology, and are involved in the pathogenesis of inflammatory bowel disease. We studied expression of CD103 on mucosal lymphocytes with epithelial adhesion molecules in patients with inflammatory bowel disease. Surgical specimens of human colon were obtained from 12 patients with ulcerative colitis, 12 patients with Crohn's disease, and 5 controls. Frozen sections were cut and expression of CD103 on lymphocytes, E-cadherin, CD44V3, and CD44v6 on intestinal epithelium was studied. Frequency of CD103-positive intraepithelial lymphocytes did not differ among controls, patients with ulcerative colitis, and patients with Crohn's disease. The frequency of CD103-positive lamina propria lymphocytes was significantly higher in patients with Crohn's disease than in controls and patients with ulcerative colitis. The frequency of CD103-positive intraepithelial lymphocytes was significantly correlated with that of lamina propria lymphocytes in patients with ulcerative colitis. The frequency of CD103-positive intraepithelial lymphocytes was significantly correlated with epithelial E-cadherin expression but that of lamina propria lymphocytes was not. Differential up-regulation of CD103 expression on lamina propria lymphocytes in Crohn's disease may indicate differential humoral or cellular regulation in inducing CD103 molecules on lymphocytes in patients with this disease.

Antigens, CD↗
PubMed2002

Expression of 4C8 antigen, a novel transendothelial migration-associated molecule on activated T lymphocytes, in inflammatory bowel disease.

Recruitment of peripheral leukocytes to intestine is an essential process for intestinal inflammation. This study examined the localization of a novel molecule, 4C8 antigen, in inflammatory bowel disease; this molecule is involved in the transendothelial migration of T lymphocytes. Surgical specimens of human intestine were obtained from nine patients with ulcerative colitis, 13 with Crohn's disease, and eight controls. Immunohistological staining was performed using antibodies against 4C8 antigen, and CD3, CD4, CD8, CD20, CD68, CD45RA, CD45RO, CD11a, and CD62 (E- and P-selectin) by the peroxidase method. Immunological double staining was subsequently performed for the same specimens stained with anti-4C8 antibody using the alkaline phosphatase method. In normal controls, 4C8-positive cells were mainly found in lamina propria. 4C8-positive cells were increased in lamina propria and submucosa of specimens with Crohn's disease. Accumulation of 4C8-positive cells surrounding CD62-positive vessels was found in the submucosa of specimens with inflammatory bowel disease, but not in controls. Immunohistological double staining revealed that the major subsets of 4C8-positive cells were positive for CD3, CD4, CD45RO, and CD11a. 4C8-positive cells in human intestine belong to the subset of helper/inducer memory T cells newly recruited from the peripheral pool. Inhibition of the 4C8-ligand system could have potentially uses in the treatment of inflammatory bowel disease.

Adult↗
PubMed2002

Heterogeneity of HPLC profiles of human class II MHC-bound peptides isolated from intestine with inflammatory bowel disease.

Studies of the T-cell-receptor repertoire and oligoclonal expansion of lamina propria T cells in patients with Crohn's disease suggest restricted antigen processing in this disease. We examined HPLC elution profiles of HLA-DR-bound peptides isolated from human intestine. Surgical samples of colon and ileum were obtained from patients with ulcerative colitis, patients with Crohn's disease, and normal colon from patients undergoing colon carcinoma treatment as controls. Specimens were homogenized and HLA-DR molecules were isolated using anti-HLA-DR antibody-coupled immunoaffinity chromatography. HLA-DR-bound peptides were dissociated from the HLA-DR groove by acid treatment, isolated, and analyzed by reversed-phase HPLC. HPLC elution profiles of HLA-DR-bound peptides were similar in patients with ulcerative colitis and controls. Large peaks were found in patients with Crohn's disease, but the retention times of these peaks differed among individuals. Elution profiles of HLA-DR bound peptides suggest that specific antigen presentation might occur in patients with Crohn's disease, although the specific antigens appear to differ between patients.

Adult↗
PubMed2002

Asymptomatic chronic intestinal ischemia caused by idiopathic phlebosclerosis of mesenteric vein.

Phlebosclerosis of the mesenteric vein is a rare condition causing chronic intestinal ischemia, it has only been reported in Japan. A 56-year-old man with liver cirrhosis and hepatic tumor presented with phlebosclerosis of mesenteric vein without any abdominal symptoms. He was admitted for examination of suspected hepatic tumor. Abdominal plain x-ray films and computed tomography revealed calcification of the mesenteric vein. Barium enema revealed narrowing and thumbprinting from the cecum to transverse colon. On colonoscopic examination, blue-black vessels were visible in the terminal ileum, and hyperemic nodular mucosa with small irregular ulcers surrounded by dark purple mucosa was found from the cecum to transverse colon. The etiology of mesenteric vein phlebosclerosis is unknown, although a physical mechanism rather than inflammatory changes appear to be involved in this rare and usually progressive condition of chronic intestinal ischemia.

Calcinosis↗
PubMedDate not supplied

Mycobacterial trehalose 6,6'-dimycolate preferentially induces type 1 helper T cell responses through signal transducer and activator of transcription 4 protein.

Mycobacterium tuberculosis is an intracellular pathogen of tuberculosis and its pathogenicity is related to the ability to escape killing by ingested macrophages and induce delayed-type hypersensitivity (DTH). A major component of the cell wall of M. tuberculosis is trehalose 6,6'-dimycolate (TDM), which has been implicated as a pathogenetic factor. The expression of DTH and cell-mediated immunity is dependent on the macrophage-cytokine-type 1 helper T (Th1) lymphocyte axis. Cytokines, interleukin-12 (IL-12) and interferon-gamma (IFN-gamma), play a critical role in the process and IL-12-activated signal transducer and activator of transcription (STAT) 4 is required for the development of fully functional Th1 cells. To clarify host responses to mycobacterial TDM, we have analyzed footpad reaction, histopathology and cytokine profile of experimental granulomatous lesions using STAT4-deficient mice. In the present study, we have demonstrated that mycobacterial TDM selectively induces the Th1 response through the STAT4 signaling pathway, because mice lacking STAT4 protein significantly reduced to develop DTH, hypersensitivity granulomas, and Th1 cytokine responses, when compared to BALB/c mice. These results shed light on the molecular pathogenesis of mycobacterial disease. Taken together with previous studies, TDM is a pleiotropic molecule against the host and participates in the pathogenesis.

Animals↗
PubMedDate not supplied

Three cases of primary sclerosing cholangitis associated with ulcerative colitis; diagnostic usefulness of magnetic resonance cholangiopancreatography.

BACKGROUND/AIMS: Primary sclerosing cholangitis is often accompanied by inflammatory bowel disease in western countries. However, the incidence of primary sclerosing cholangitis in patients with ulcerative colitis appears to be much lower in Japan. METHODOLOGY: Between 1980 and 1998, a total of 402 patients with ulcerative colitis were seen in our department. The patients were evaluated by abdominal ultrasonography, endoscopic retrograde cholangiopancreatography, and/or magnetic resonance cholangiopancreatography when persisting abnormalities of biochemical findings suggested the presence of hepatobiliary diseases. RESULTS: Of the 402 patients with ulcerative colitis, 3 patients with primary sclerosing cholangitis were found. There were 2 men and 1 woman. One patient had left-sided colitis while 2 had total colitis. Magnetic resonance cholangiopancreatography was done in 2 of these 3 patients and demonstrated diagnostic features of primary sclerosing cholangitis. All 3 patients had intra- and extrahepatic involvement by primary sclerosing cholangitis. One male patient died due to progressive hepatic failure. The other male patient was treated with ursodeoxycholic acid, but serum alkaline phosphatase level remained above the normal range. The female patient maintained normal serum alkaline phosphatase levels without specific medication. CONCLUSIONS: Magnetic resonance cholangiopancreatography is the most safe and convincing tool for the diagnosis of coexistent primary sclerosing cholangitis in the patients with ulcerative colitis.

Adult↗
PubMedDate not supplied

Does colitis associated with primary sclerosing cholangitis represent an actual subset of ulcerative colitis?

BACKGROUND/AIMS: The clinical course and endoscopic features of colitis associated with primary sclerosing cholangitis have not been well documented. METHODOLOGY: Since 1980, a total of 485 patients with ulcerative colitis have been seen in our departments. During this period, we experienced 6 patients with primary sclerosing cholangitis, 4 of whom had ulcerative colitis concomitantly. RESULTS: Colitis preceded primary sclerosing cholangitis in 3 of the 4 patients. There were 2 males and 2 females. One patient had left-sided colitis while 3 had total colitis, 1 with a first attack and 3 with relapsing-remitting type. Two of the 4 patients had colonoscopically dominant inflammation in the proximal colon with continuous histological inflammation from the rectum to the proximal colon. Three colitic patients have been well controlled with oral sulfasalzine or mesalazine administration. Only 1 female patient had been hospitalized twice for moderately severe attacks of ulcerative colitis that required systemic prednisolone administration, however, this patient quickly responded to this treatment for each admission. CONCLUSIONS: Colitis associated with primary sclerosing cholangitis exhibited atypical colonoscopic findings and exhibited milder disease activity than ulcerative colitis without primary sclerosing cholangitis.

Adult↗