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Hajime Isomoto

Publications and source records attributed to Hajime Isomoto.

At least 37 records · Page 2Linked to original sources
PubMed2005

Helicobacter pylori strain-specific modulation of gastric inflammation in Mongolian gerbils.

AIM: The cag pathogenicity island (PAI) is one of potential virulence determinants of Helicobacter pylori. The Mongolian gerbil is a suitable experimental animal for the screening of virulence factors of H pylori. METHODS: Five-week-old Mongolian gerbils were inoculated with a standard H pylori strain (ATCC 43504) possessing the cag PAI or a clinical isolate lacking the genes' cluster (OHPC-0002). The animals were killed at 2, 4, 8, 24 and 48 wk after inoculation (n = 5 each), and macroscopic and histopathological findings in the stomachs were compared. RESULTS: In gerbils infected with ATCC 43504, a more severe degree of infiltration of polynuclear and mononuclear cells and lymphoid follicles was observed from 4 wk after inoculation compared to gerbils infected with OHPC-0002 especially in the antrum and transitional zone from the fundic to pyloric gland area. In addition, glandular atrophy, intestinal metaplasia, gastric ulcer and hyperplastic polyps were noted in gerbils infected with ATCC 43504, whereas only mild gastric erosions occurred in those infected with OHPC-0002. CONCLUSION: Our results indicate that the cag PAI could be directly involved in gastric immune and inflammatory responses in the Mongolian gerbils, leading to a more advanced gastric disease.

Animals↗
PubMed2005

Effect of Helicobacter pylori eradication on gastric hyperplastic polyposis in Cowden's disease.

A 21-year-old woman with complaints of hematochezia was diagnosed as having Cowden's disease (CD), an autosomal dominant condition characterized by multiple hamartomas, since facial papules and gingival papillomas were identified. On endoscopy, multiple hyperplastic polyps were seen in the rectum and left-side colon. There were also esophageal glycogenic acanthosis and hyperplastic polyposis in the antrum accompanied by Helicobacter pylori-related gastritis. Although gastric hyperplastic polyposis had by no means regressed with unsuccessful first-line eradication therapy for H pylori, following cure of the infection with salvage therapy consisting of rabeprazole, amoxicillin and metronidazole, the polyposis lesions almost disappeared. Follow-up gastroscopy 2 and 3 years after cessation of the second-line eradication therapy revealed almost complete regression of the polyposis lesions with no evidence of H pylori infection. We recommend eradication treatment for CD patients with gastric hyperplastic polyps and the infection, as the occurrence of gastric carcinoma among hyperplastic polyps has been described.

Adult↗
PubMed2005

Enhanced production of leptin in gastric fundic mucosa with Helicobacter pylori infection.

AIM: To determine the concentrations of leptin in plasma and gastric fundic mucosa in humans, with reference to Helicobacter pylori (H pylori) infection, and their association with gastric mucosal levels of interleukin (IL)-1beta, IL-6 and IL-8. METHODS: Plasma leptin concentrations were determined in 135 outpatients with non-ulcer dyspepsia, consisting of 95 H pylori-infected and 40 uninfected subjects, and 13 patients before and after cure of the infection with anti-H pylori regimen. Using biopsy samples that were endoscopically obtained from the middle corpus along the greater curvature, gastric leptin contents were measured by radioimmunoassay and the mucosal concentrations of IL-1beta, IL-6 and IL-8 were measured by enzyme linked immunosorbent assay. We also analysed the expression of leptin in the fundic mucosa by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS: The mucosal levels of leptin in the fundic mucosa of H pylori-infected patients were significantly higher than those of uninfected patients. The amount of gastric leptin correlated positively with the mucosal levels of IL-1beta and IL-6, but not IL-8. Circulating leptin correlated with body mass index, but not with H pylori status, and there was no change in plasma leptin levels following cure of the infection. Leptin immunoreactive cells were noted in the lower half of the fundic glands, and its expression of messenger ribonucleic acid in the oxyntic mucosa was detected by RT-PCR. CONCLUSION: Leptin production is enhanced in H pylori-infected gastric mucosa. Gastric leptin may be involved in immune and inflammatory response during H pylori infection, through interaction with proinflammatory cytokines.

Adult↗
PubMed2005

Concentrations of alpha- and beta-defensins in gastric juice of patients with various gastroduodenal diseases.

AIM: To determine the concentration of alpha- and beta-defensins in gastric juice of patients with various gastroduodenal diseases. METHODS: Concentrations of human neutrophil peptides (HNPs) 1-3, the major forms of alpha-defensins, and human beta-defensin (HBD)-1 and HBD-2 were measured by radioimmunoassay in plasma and gastric juice of 84 subjects, consisting of 54 Helicobacter pylori-infected and 30 uninfected subjects. They included 33 patients with chronic gastritis (CG), 12 with gastric ulcer (GU), 11 with duodenal ulcer (DU), 11 with benign gastric polyp (BGP) and 16 with normal mucosa (N group) on upper endoscopy. Plasma pepsinogen I and II levels, biomarkers for gastric mucosal inflammation and atrophy, were also measured. RESULTS: Gastric juice HNPs 1-3 levels in patients with CG, GU and BGP were significantly higher than those in patients with DU and N. Gastric juice HBD-2 concentrations in patients with CG and GU were significantly higher than those in the N group, but were significantly lower in DU patients than in GU patients. Gastric juice HBD-1 levels and plasma levels of these peptides were similar in the patient groups. Concentrations of gastric juice HNPs 1-3 and HBD-2 of in H pylori-infected patients were significantly different from those in uninfected subjects. HNPs 1-3 concentrations in gastric juice correlated negatively with plasma pepsinogen I levels and I/II ratios. HBD-2 levels in gastric juice correlated positively and negatively with plasma pepsinogen II concentrations and I/II ratios, respectively. CONCLUSION: HNPs 1-3 and HBD-2 levels in gastric juice are diverse among various gastrointestinal diseases, reflecting the inflammatory and atrophic events of the background gastric mucosa affected by H pylori.

Duodenal Diseases↗
PubMed2005

Interleukin 6 upregulates myeloid cell leukemia-1 expression through a STAT3 pathway in cholangiocarcinoma cells.

Interleukin 6 (IL-6) contributes to the pathogenesis of cholangiocarcinoma by upregulating myeloid cell leukemia-1 (Mcl-1), a key antiapoptotic Bcl-2 family member protein. IL-6 can alter gene transcription via Janus kinases (JAK) and signal transducer and activator of transcription (STAT) signal cascade. We examined this cascade in IL-6 regulation of Mcl-1 transcription in human cholangiocarcinoma cell lines. STAT3 was constitutively activated (i.e., tyrosine-phosphorylated) in cholangiocarcinoma cells but not in nonmalignant cholangiocytes. Treatment with anti-IL-6 antisera or the JAK inhibitor AG490 or transfection with dominant negative STAT3 diminished Mcl-1 messenger RNA and protein levels. Likewise, these attempts to interrupt the STAT3 cascade also reduced Mcl-1 promoter activity. Site-directed mutagenesis of a putative STAT3 consensus binding sequence decreased Mcl-1 promoter activity. Chromatin immunoprecipitation analysis demonstrated a direct binding of STAT3 to the putative STAT3 binding sequences in the Mcl-1 promoter. Downregulation of Mcl-1 by AG490 sensitized the cells to apoptosis mediated by tumor necrosis factor-related apoptosis-inducing ligand. In conclusion, we have directly demonstrated a STAT3 regulatory element in the Mcl-1 promoter. Downregulation of Mcl-1 transcription by inhibiting this cascade is a potential strategy for the treatment of this cancer.

Apoptosis↗
PubMed2005

Circulating ghrelin levels in patients with various upper gastrointestinal diseases.

The stomach is the main source of circulating ghrelin. Plasma concentrations of this hormone in patients with various upper gastrointestinal diseases remain undetermined. Thus we measured plasma ghrelin levels by radioimmunoassay in 225 subjects, including 134 Helicobacter pylori-infected and 91 uninfected subjects. They included 67 patients with chronic gastritis (CG), 26 with benign gastric polyp (BGP), 24 with gastric ulcer (GU), 24 with reflux esophagitis (RE), 18 with duodenal ulcer (DU), 28 with acute gastritis (AG), 23 with gastric cancer (GC), and 39 who had normal mucosa on upper endoscopy (N). Plasma pepsinogen I and II levels were also measured. The extent of gastritis was assessed endoscopically. Ghrelin levels differed significantly among the different disease groups. Plasma ghrelin concentrations were lowest in the CG group, followed by the GU group, and highest in the AG patients. There was a significant difference in the levels between differentiated and undifferentiated GC. Ghrelin concentrations in BGP, RE, and DU patients were comparable to those in the N group. Ghrelin circulating levels were lower in H. pylori-positive than -negative individuals, but the significant differences among disease groups were still observed in H. pylori-infected and uninfected populations. Ghrelin concentrations correlated positively with plasma pepsinogen I levels and I/II ratios and inversely with the extent of H. pylori-related gastritis. Plasma ghrelin levels varied widely in diverse conditions of the upper digestive tract, reflecting the inflammatory and atrophic events of the background gastric mucosa. Further investigation is warranted to unravel the mechanisms of the high circulating ghrelin levels in certain upper gastrointestinal diseases.

Adult↗
PubMed2005

Placental and intestinal alkaline phosphatases are receptors for Aeromonas sobria hemolysin.

The Aeromonas sobria hemolysin causes diarrhea following infection by this enteropathogenic bacterium. We previously identified the putative receptor for A. sobria hemolysin as a p66 protein on Intestine 407 cells (Microb. Pathog. 27 (1999) 215-221). Here, we have partially purified and obtained a peptide mass fingerprint of p66 which revealed its identity with placental alkaline phosphatase (PLAP). Recombinant PLAP expressed in 293T cells was also found to bind to hemolysin and the binding was found not to be dependent on the N-linked glycosylation of PLAP. By immunohistochemical analysis, PLAP expression was detected in human intestinal mucosa, the target tissue in disease. In addition to PLAP, hemolysin also binds to intestinal alkaline phosphatase (IAP), an enzyme that is also abundantly expressed in intestine. Thus, both PLAP and IAP are very likely involved in the pathogenesis of diarrhea caused by this bacterial toxin.

Aeromonas↗
PubMed2005

Impact of Helicobacter pylori infection on gastric and plasma ghrelin dynamics in humans.

OBJECTIVES: There are contradictory reports on the relationship between Helicobacter pylori and circulating ghrelin. We sought to clarify the influence of H. pylori infection on gastric and plasma ghrelin dynamics in humans. METHODS: Using endoscopic biopsies from the corpus of 56 H. pylori-infected patients and 25 uninfected subjects, ghrelin mRNA expression levels and gastric ghrelin peptide contents were measured by real-time polymerase chain reaction and radioimmunoassay, respectively. We also measured plasma ghrelin concentrations and analyzed the numbers of ghrelin immunoreactive cells in the fundic gland area. Fifty-one patients with H. pylori infection were treated with a 7-day triple therapy consisting of lansoprazole, clarithromycin, and amoxicillin. RESULTS: The gastric ghrelin mRNA expression level of H. pylori-positive patients (1.64 +/- 1.27 in arbitrary units) was significantly lower than in H. pylori-negative subjects (4.87 +/- 4.1, p < 0.0001). A similar trend was noted for ghrelin peptide contents (31.2 +/- 27.5 vs 81.2 +/- 64.1 ng/mg protein, respectively, p < 0.0001). There was no significant difference in the number of ghrelin immunoreactive cells/mm(2) in terms of H. plyori status. Plasma ghrelin concentrations in H. pylori-infected patients (144.6 +/- 7.8.8 fmol/ml) were significantly lower than in uninfected subjects (196.1 +/- 97.2, p < 0.05) and increased following cure of the infection. Plasma ghrelin levels correlated positively with the expression levels of ghrelin mRNA (r = 0.583, p < 0.0001) and peptide products (r = 0.574, p < 0.0001). There was a significant stepwise decrease in gastric ghrelin mRNA expression (p < 0.05), peptide contents (p < 0.01) and density of ghrelin immunoreactive cells (p < 0.05) with progression of histological severity of glandular atrophy in the corpus. The histological severity of chronic inflammation also negatively influenced the ghrelin mRNA expression (p < 0.001) and peptide production (p < 0.005). CONCLUSIONS: H. pylori infection has a negative impact on gastric and plasma ghrelin dynamics. Chronic inflammatory and atrophic changes associated with the infection may affect gastric ghrelin biosynthesis and contribute to the low circulating levels.

Adult↗
PubMed2004

Endoscopic identification of Peyer's patches of the terminal ileum in a patient with Crohn's disease.

We presented a 20-year-old patient with Crohn's disease (CD). Colonoscopy revealed longitudinal ulceration in the terminal ileum and rectal aphtoid ulcers. After treatment with mesalamine and total parenteral nutrition, repeat colonoscopy revealed a granular elevated area in the terminal ileum, which appeared as an irregular dome-like elevation with irregularly arranged villi on magnifying endoscopy. Biopsy specimens taken from the region showed microgranulomas and lymphoid hyperplasia. Scanning electron microscopy revealed the presence of M cells, confirming that the area corresponded to Peyer's patches. Peyer's patches by magnifying endoscopy and electron microscopy may provide insights into the pathogenesis of CD.

Adult↗
PubMed2004

Chronic visceral hypersensitivity renders defecation more susceptible to stress via a serotonergic pathway in rats.

Visceral hypersensitivity, intestinal dysmotility, and stress play major roles in irritable bowel syndrome. However, the significance of visceral hypersensitivity in stress-induced changes of colorectal motor function is not conclusive. A rat model of chronic visceral hypersensitivity was induced by mechanical colorectal irritation during postnatal development. Defecation and colonic transit time were not different between the visceral hypersensitivity and the control groups at baseline. Stress and a 5-hydroxytryptamine (5-HT) agonist both resulted in a significant increase in defecation in the visceral hypersensitivity group compared with the controls. Prior administration of granisetron, a 5-HT3 receptor antagonist, inhibited stress-induced changes in defecation in the visceral hypersensitivity group as well as the controls. Stress-induced acceleration of colonic transit was not significantly different between the two groups. Our results indicate that chronic visceral hypersensitivity can modulate the effect of stress on defecation via a serotonergic pathway and suggest that visceral hypersensitivity may be related to the susceptibility of the defecative response to stressful events in patients with irritable bowel syndrome.

Animals↗