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Kazuhide Higuchi

Publications and source records attributed to Kazuhide Higuchi.

At least 55 records · Page 3Linked to original sources
PubMed2003

Increased expression of cytokines and adhesion molecules in rat chronic esophagitis.

BACKGROUND/AIMS: Cytokines and adhesion molecules regulate many inflammatory processes in several gastrointestinal diseases. The dynamics of cytokines and adhesion molecules in reflux esophagitis are unknown in detail. We examined the expression and dynamics of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-2, GRO/cytokine-induced neutrophil chemoattractant-2alpha (CINC-2alpha), intercellular adhesion molecule-1 (ICAM-1), leukocyte function-associated antigen 1 (LFA-1; CD11a/CD18), and Mac-1 (CD11b/CD18) in rat chronic reflux esophagitis. METHODS: Chronic acid reflux esophagitis was induced in Wistar rats by ligating the transitional region between the forestomach and the glandular portion and wrapping the duodenum near the pylorus with a small piece of an 18-Fr Nélaton catheter. Rats were killed 3 or 21 days after operation. The levels of mRNA expression of cytokines and ICAM-1 were determined by real-time quantitative RT-PCR. Localization of adhesion molecules and cytokines was investigated by immunohistochemical staining, and numbers of LFA-1- or Mac-1-positive cells were quantified. RESULTS: IL-1beta, TNF-alpha, MCP-1, MIP-1alpha, MIP-2, CINC-2alpha, and ICAM-1 mRNA expression was significantly increased in esophageal lesions compared with normal esophagus. There were few these cytokines- or adhesion molecule-positive cells in normal esophagus. In regions of esophagitis, numerous inflammatory leukocytes in lamina propria and the submucosal layer exhibited positive reactions for these cytokines and endothelial cells were intensely stained for ICAM-1. Numbers of LFA-1- and Mac-1-positive cells were significantly increased in rat chronic esophagitis. Treatment with rabeprazole almost completely inhibited development of chronic acid reflux esophagitis and significantly decreased expression of cytokines and ICAM-1 mRNA in esophageal tissue compared with control. CONCLUSION: Cytokines and adhesion molecules play important roles in the pathogenesis of chronic reflux esophagitis in this rat model.

Animals↗
PubMed2003

Anti-inflammatory effect of two isoforms of COX in H. pylori-induced gastritis in mice: possible involvement of PGE2.

Neutrophil infiltration mediated by TNF-alpha is associated with various types of gastric injury, whereas PGs play a crucial role in gastric defense. We examined roles of two isoforms of cyclooxygenase (COX) and PGE2 in Helicobacter pylori-induced gastritis in mice. Mice infected with H. pylori were given selective COX-1 inhibitor SC-560 (10 mg/kg), selective COX-2 inhibitor NS-398 (10 mg/kg), or nonselective COX inhibitor indomethacin (2 mg/kg) with or without 16,16-dimethyl PGE2 for 1 wk. H. pylori infection increased levels of mRNA for COX-1 and -2 in gastric tissue by 1.2-fold and 3.3-fold, respectively, accompanied by a significant increase in PGE2 production by gastric tissue. H. pylori infection significantly elevated MPO activity, a marker of neutrophil infiltration, and epithelial cell apoptosis in the stomach. SC-560 augmented MPO activity and epithelial cell apoptosis with associated reduction in PGE2 production, whereas NS-398 had the same effects without affecting PGE2 production. Inhibition of both COX-1 and -2 by indomethacin or concurrent treatment with SC-560 and NS-398 resulted in a stronger increase in MPO activity and apoptosis than inhibition of either COX-1 or -2 alone. H. pylori infection elevated TNF-alpha mRNA expression in the stomach, which was further increased by indomethacin. Effects of COX inhibitors on neutrophil infiltration, apoptosis, and TNF-alpha expression in H. pylori-infected mice were abolished by exogenous 16,16-dimethyl PGE2. In conclusion, PGE2 derived from either COX-1 or -2 is involved in regulation of gastric mucosal inflammation and contributes to maintenance of mucosal integrity during H. pylori infection via inhibition of TNF-alpha expression.

Animals↗
PubMed2003

Cross-reactivity of yeast antigens in human colon and peripheral leukocytes.

Elevation of the serum anti-Saccharomyces cerevisiae antibody (ASCA) level has been reported in patients with Crohn's disease. This study investigated the antigenic distribution of S. cerevisiae in human colon and peripheral leukocytes. ASCA was isolated from sera from patients with Crohn's disease using immuno-affinity chromatography and then biotinylated and assayed immunohistologically and immunocytologically to determine the distribution of antigens recognized by ASCA in human colon and peripheral leukocytes. Immunoblot analysis of yeast extract and human peripheral leukocytes was performed. Immunohistological study using biotinylated ASCA revealed the presence of yeast-like particles in the granulation tissue of inflamed colonic mucosa. Biotinylated ASCA also stained lymphocytes and polymorphonuclear cells infiltrating inflamed intestine. Monocytes in epithelioid granulomas of colon with Crohn's disease were also stained. Polymorphonuclear leukocytes in peripheral blood were also stained with biotinylated ASCA. The antigens reactive to ASCA among heat-extracted, non-heat-extracted yeast antigens, and human leukocyte extract differed. The findings of cross-reactivity of polymorphonuclear leukocytes with S. cerevisiae antigen and the presence of S. cerevisiae antigen in Crohn's disease granulomas suggest the possibility of involvement of S. cerevisiae in the pathogenesis of Crohn's disease.

Adult↗
PubMed2003

Association between gastroesophageal flap valve, reflux esophagitis, Barrett's epithelium, and atrophic gastritis assessed by endoscopy in Japanese patients.

BACKGROUND: Endoscopic grading of the gastroesophageal flap valve (GEFV) is a useful predictor of gastroesophageal reflux status; abnormal GEFV was associated with reflux esophagitis. Atrophic gastritis is often found in Japanese patients and is inversely related to reflux esophagitis. The aim of this study was to examine the association between GEFV, reflux esophagitis, Barrett's epithelium, and atrophic gastritis in Japanese patients by prospective endoscopic assessment. METHODS: We enrolled 548 Japanese patients (296 men and 252 women; mean age, 57.3 years). GEFV was assessed by the classification of Hill and colleagues, reflux esophagitis was assessed by the Los Angeles classification, and the degree of atrophic gastritis was scored as: none, mild, moderate, or severe. Barrett's epithelium was recognized by the endoscopic detection of an upward shift in the columnar lining. RESULTS: Reflux esophagitis and Barrett's epithelium were found in 42 (7.7%) and 67 (12.2%) patients, respectively. An increased prevalence of reflux esophagitis and Barrett's epithelium was correlated with an increased grade of GEFV. Abnormal GEFV (grades III and IV) was a risk for reflux esophagitis (adjusted odds ratio [OR]), 13.33 (95% confidence interval [CI], 6.08-29.25) and Barrett's epithelium (OR, 3.55 [95% CI, 2.04-6.20]), while the presence of atrophic gastritis was inversely associated with reflux esophagitis (OR, 0.15 [95% CI, 0.07-0.36]), but it was not associated with the prevalence of Barrett's epithelium (OR, 1.16 [95% CI, 0.67-2.01]). The prevalence of Barrett's epithelium and the severity of atrophic gastritis increased with age, while that of reflux esophagitis and abnormal GEFV did not change. CONCLUSIONS: Reflux esophagitis and Barrett's epithelium are associated with abnormal GEFV in Japanese patients. The presence of atrophic gastritis is inversely related to reflux esophagitis, but it is not related to Barrett's epithelium in Japanese patients.

Age Factors↗
PubMed2003

Crohn's disease complicated by adult-onset Still's disease.

A 31-year-old man with Crohn's disease developed arthritis, spiking fever, and skin rash indistinguishable from that of adult-onset Still's disease. He was admitted to our hospital because of a periumbilical intestinal skin fistula. Crohn's disease had been diagnosed in 1991, and had required intestinal resection twice, and schizophrenia had been diagnosed in 1993. He developed polyarthritis and spiking fever, accompanied by a macular skin rash on both forearms. Marked hepatosplenomegaly and bilateral pleural effusion were detected on computed tomography examination. These findings are indistinguishable from those of adult-onset Still's disease. Because his mental status had deteriorated following high-dose prednisolone on a previous admission, he was treated with an immunosuppressive agent on this occasion, with the treatment being successful. This is the first report of adult-onset Still's disease complicating Crohn's disease. In patients with Crohn's disease, polyarthritis and skin rash can easily be misdiagnosed as enteropathic arthritis with erythema nodosum associated with the Crohn's disease. Although adult-onset Still's disease may not be fatal, early diagnosis is important because it can, in rare cases, result in life-threatening complications.

Adult↗
PubMed2003

No additive effect between Helicobacter pylori infection and portal hypertensive gastropathy on inducible nitric oxide synthase expression in gastric mucosa of cirrhotic patients.

Increased expression of inducible nitric oxide synthase (iNOS) has been reported in gastric mucosa of patients with Helicobacter pylori infection or portal hypertensive gastropathy (PHG) but whether there is an additive or synergistic impact between H. pylori and PHG on iNOS expression was unknown. Sixty cirrhotic patients and 21 age-matched control subjects without liver disease were included. Biopsies from the gastric antrum and body were obtained for quantitative histological assessment and immunohistochemical staining for iNOS. iNOS staining was detected in endothelial cells and macrophages. In the absence of PHG, H. pylori significantly induced iNOS expression in cirrhotic patients. PHG also significantly induced iNOS expression in H. pylori-negative patients. However, there was no synergistic or additive effect between H. pylori and PHG on this expression. Furthermore, expression of iNOS was significantly higher in patients with severe PHG than in those with mild PHG and without PHG.

Case-Control Studies↗
PubMed2003

Outpatient treatment of moderately severe active ulcerative colitis with pulsed steroid therapy and conventional steroid therapy.

Pulsed steroid therapy may induce rapid remission in patients with moderately severe ulcerative colitis in outpatient clinics. A total of 19 patients with moderately severe active ulcerative colitis who refused hospitalization were treated between October 1999 and September 2001 in the outpatient clinic. Patients were treated with either conventional oral steroid therapy or intravenous pulsed steroid therapy followed by conventional oral steroid therapy. Eight patients received conventional steroid therapy and 11 patients received pulsed steroid therapy followed by conventional steroid therapy. The efficacies of the two types of steroid therapy were equal, but patients with active colitis responded more quickly to pulsed steroid therapy than to conventional steroid therapy. No serious adverse effects were observed. Moderately severe colitis can be safely treated with either conventional or pulsed steroid therapy in the outpatient clinic, but pulsed steroid therapy may induce clinical remission more quickly than conventional steroid therapy.

Administration, Oral↗
PubMed2003

Esophagogastric varices due to arterioportal shunt in a serous cystadenoma of the pancreas in von Hippel-Lindau disease.

Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited disorder characterized by extensively vascularized tumors and cysts in specific organs. Angiogenesis is a striking future of VHL disease with its characteristic cysts and well-vascularized tumors. The hypervascular nature of VHL lesions has been linked to the overproduciton of vascular endothelial growth factor (VEGF) through increased expression of hypoxia inducible factor-1alpha (HIF-1alpha). Here we describe a rare case of VHL disease with esophageal and gastric varices due to arterioportal shunt in a serous cystadenoma of the pancreas, which, upon immunohistochemical examination, exhibited HIF-1alpha and VEGF expression. Rupture of esophageal varices was successfully treated with endoscopic injection sclerotherapy.

Angiography↗
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

Food/nutrient intake and risk of atrophic gastritis among the Helicobacter pylori-infected population of northeastern Japan.

Although Helicobacter pylori (H. pylori ) infection is considered a key risk factor for atrophic gastritis, along with other environmental factors, it is still unclear which factor is involved in the development of atrophic gastritis among H. pylori-infected subjects. In the present cross-sectional study, therefore, we analyzed various dietary factors in relation to the presence of atrophic gastritis among H. pylori-infected subjects who participated in a health check-up program in a town in northeastern Japan. One thousand and seventy-one subjects (362 males and 709 females) who provided both self-administered validated food frequency questionnaires and blood samples were the basis for the study, and all of them were serologically positive for H. pylori immunoglobulin G (IgG) antibody. Among them, 663 (223 males and 440 females) were diagnosed as having atrophic gastritis on the basis of serum pepsinogen levels. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated based on tertile categories of subjects without atrophic gastritis, using logistic regression analysis. Among females, high consumptions of rice (OR = 1.6, 95% CI: 1.1-2.3), cod roe (OR = 1.5, 95% CI: 1.0-2.2) and cuttlefish (OR = 1.5, 95% CI: 1.0-2.3) were associated with a moderately increased risk of atrophic gastritis after adjustment for age (P for trend = 0.02 for these items). Among males, high consumptions of rice and miso soup showed a tendency toward an increased risk (P for trend = 0.12 and 0.13, respectively). Vegetables and fruits showed no association among either males or females. From these results, it is suggested that the dietary habits of consumers of traditional Japanese foods may play a role in the development of atrophic gastritis after H. pylori infection.

Cross-Sectional Studies↗
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

A case of gastric duplication evaluated by gastric emptying scintigraphy.

Gastric duplications are relatively rare, and communication with the gastric lumen is extremely rare. A 67-year-old man was referred to our hospital because of recurrence of epigastric pain and fullness. An upper gastrointestinal contrast study revealed a double compartment stomach, with gastric duplication starting at the esophagogastric junction outside the greater curvature. Computed tomography of the stomach with gastrografin as contrast demonstrated complete communication of the gastric duplication and primary stomach. The patient was diagnosed with complete gastric duplication. Gastric emptying scintigraphy with Tc-99m diethyltriamine pentaacetic acid was performed. Test meal entered the primary stomach and duplication cyst simultaneously, and radioactivity in the primary stomach decreased linearly and gastric emptying was not delayed. In the duplication cyst, about 70% of the food that entered the cyst once was immediately evacuated from it, but the remaining 30% remained in the cyst for a long time. Gastric emptying of the primary stomach was not affected by formation of the duplication cyst.

Aged↗
PubMed2002

Rebamipide prevents delay of acetic acid-induced gastric ulcer healing caused by Helicobacter pylori infection in Mongolian gerbils.

In this study, we examined the effect of rebamipide, a mucoprotective drug, on gastric ulcer healing in Mongolian gerbils infected with H. pylori. Male Mongolian gerbils were inoculated with H. pylori or vehicle alone 12 hr after the production of an acetic acid-induced gastric ulcer. On day 5, the gerbils inoculated with H. pylori were divided into three groups and fed rebamipide-containing diet (0.038%, 60 mg/kg, or 0.0038%, 6 mg/kg), or standard laboratory chow. The gerbils inoculated with the vehicle were fed standard laboratory chow throughout the experiment. The gerbils were killed on day 5, 15, or 30 after ulcer production, and removed stomachs were subjected to calculation of ulcer size, culture for H. pylori, and measurement of myeloperoxidase activity, a marker for neutrophil infiltration, in ulcerated tissue. Apoptotic and proliferating cells of gastric epithelium in ulcer margins were detected by the in situ DNA nick end-labeling method and immunohistochemical staining for 5-bromo-2'-deoxyuridine (BrdU), respectively. Rebamipide did not affect colonization levels of H. pylori. Infection with H. pylori did not affect ulcer size by day 5 but significantly delayed ulcer healing by days 15 and 30, accompanied by an increase in the number of apoptotic cells, a decrease in the number of BrdU-positive cells, and an increase in myeloperoxydase activity. Rebamipide prevented delay of ulcer healing and abolished these effects of H. pylori on cell kinetics and neutrophil infiltration. In conclusion, rebamipide may prevent the delay of acetic acid-induced gastric ulcer healing caused by H. pylori through modulating cell kinetics and inhibiting neutrophil infiltration.

Acetic Acid↗