S Ota

Dokkyo Medical University, Tochigi, Tochigi-ken, Japan

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Publications (69)318.97 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: In 1979, a new mechanism of gastric defense named cytoprotection was followed by numerous reports elucidating this interesting and important phenomenon. During this decade, however, the concept and definition of gastric cytoprotection have been modified from the morphological and ultrastructural viewpoints. This review attempts to describe the concept and mechanisms of cytoprotection as well as its pathophysiological features. Specifically, in vitro studies using isolated cells or monolayer cultured cells as well as molecular investigations of signal transduction system have been documented.
    Acta pathologica japonica 01/2008; 43(1-2):2-10.
  • Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 08/2002; 99(7):760-8.
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    ABSTRACT: Although mesenteric vasculitis due to systemic lupus erythematosus (SLE) is relatively uncommon, it is the most dangerous manifestation associated with high mortality. We describe the case of a SLE patient with life-threatening gastrointestinal hemorrhage due to mesenteric vasculitis in whom methylprednisolone pulse therapy was quite effective in controlling the hemorrhage and resulted in a satisfactory long term outcome. A 47-yr-old woman presenting with high fever, rash, and melena was diagnosed with SLE from positive antinuclear antibodies, anti-dsDNA, and low complement titers. Although fever and rash subsided with administration of prednisolone, massive hematemesis appeared with melena. Endoscopy demonstrated bleeding ulceration of the antrum, which was intractable despite intensive antiulcer therapy and transfusion. Surgical exploration revealed ileal penetration, and multiple bleeding ulcerations were observed over the resected ileum as well as the antral ulceration. However, bleeding persisted after surgery and surgical findings prompted us to select methylprednisolone pulse. Hemorrhage responded promptly to the therapy, and the patient has remained well since then for >10 yr. Our report indicates that corticosteroid pulse may serve as one of the therapeutic options for SLE with massive hemorrhage due to widespread mesenteric vasculitis.
    The American Journal of Gastroenterology 11/1999; 94(11):3349-53. · 7.55 Impact Factor
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    ABSTRACT: Endoscopic variceal ligation (EVL) is a recently developed alternative to endoscopic injection sclerotherapy (EIS) for the treatment of oesophageal varices. Endoscopic variceal ligation and EIS were compared in an attempt to clarify the efficacy and safety of EVL for patients with cirrhosis due to hepatitis C. Endoscopic variceal ligation was performed in 60 patients and EIS in 30. Varices were eradicated in all patients by EVL and 87% (26 out of 30) by EIS. There was no significant difference between EVL and EIS in relation to the incidence of bleeding and the 5 year survival rate after treatment. There were no severe complications except mild substernal pain after EVL, while pulmonary embolism occurred in one patient receiving EIS. Endoscopic variceal ligation is a safe and effective technique for eradicating oesophageal varices in patients with hepatitis C cirrhosis.
    Journal of Gastroenterology and Hepatology 04/1999; 14(3):236-40. · 3.33 Impact Factor
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    ABSTRACT: Many cytokines are involved in the repair of damaged tissue, and one of these, hepatocyte growth factor (HGF), is involved not only with liver regeneration but also in the repair of other tissues. To investigate the importance of HGF in the repair of the small intestine, we evaluated its effect and that of other growth factors in IEC-6 cells, an intestinal epithelial cell line derived from normal rat small intestine. Round "wounds" were made in confluent monolayers of IEC-6 by silicon rubber-tipped steel rods and various cytokines; transforming growth factor alpha (TGF-alpha), transforming growth factor beta1 (TGF-beta1), keratinocyte growth factor (KGF), and HGF, were added. We photographed the repaired monolayers every 24 h and calculated the ratios of areas not covered by cells to initial areas. Cell proliferation with TGF-alpha, TGF-beta, KGF, or HGF was examined in terms of [3H]-thymidine uptake. Finally, we determined c-met (the HGF receptor) mRNA in the IEC-6 cells by Northern blot hybridization. HGF was the most potent of the cytokines in accelerating repair of the damaged monolayer of IEC-6. HGF was also 1.34 times more effective than control the medium for inducing cell proliferation of IEC-6. By Northern blot hybridization, three bands of mRNA bound to c-met cDNA. These results suggest that HGF is important in the repair of the small intestine.
    Journal of Gastroenterology 05/1998; 33(2):172-8. · 3.79 Impact Factor
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    ABSTRACT: Caffeine is known to stimulate gastric acid secretion, but, the effects of caffeine on gastric mucus secretion have not been clarified. To elucidate the action of caffeine on gastric mucin-producing cells and its underlying mechanism, the effects of caffeine on mucus glycoprotein secretion and agonist-induced [Ca2+]i mobilization were examined in human gastric mucin secreting cells (JR-I cells). The measurement of [Ca2+]i using Indo-1 and the whole cell voltage clamp technique were applied. Mucus glycoprotein secretion was assessed by release of [3H]glucosamine. Caffeine by itself failed to increase [Ca2+]i and affect membrane currents, while it dose-dependently inhibited agonist (acetylcholine (ACh) or histamine)-induced [Ca2+]i rise, resulting in inhibiting activation of Ca2+-dependent K+ current (I(K.Ca)) evoked by agonists. The effect of caffeine was reversible, and the half maximal inhibitory concentration was about 0.5 mM. But, caffeine did not suppress [Ca2+]i rise and activation of I(K.Ca) induced by A23187 or inositol trisphosphate (IP3). Theophylline or 3-isobutyl-1-methyl-xanthine (IBMX) did not mimic the effect of caffeine. Caffeine failed to stimulate mucus secretion, while it significantly decreased ACh-induced mucus secretion. These results indicate that caffeine selectively inhibits agonist-mediated [Ca2+]i rise in human gastric epithelial cells, probably through the blockade of receptor-IP3 signaling pathway, which may affect the mucin secretion.
    Biochimica et Biophysica Acta 05/1997; 1356(2):198-206. · 4.66 Impact Factor
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    ABSTRACT: Reactive oxygen metabolites produce colonic epithelial cellular injury. The present study evaluated the protective role of cellular superoxide dismutase, catalase, and glutathione (GSH) redox cycle in cultured rabbit colonic cells. Cultured rabbit colonic epithelial cells were exposed to reactive oxygen metabolites generated by hypoxanthine (1 mM) and xanthine oxidase (1 mU/ml) for up to 5 h. Cytotoxicity was quantified by measuring 51Cr release from prelabeled cells. Pretreatment with diethyldithiocarbamate (inhibitor of superoxide dismutase) reduced activity of cellular superoxide dismutase and increased 51Cr release caused by hypoxanthine/xanthine oxidase from colonic cells. Pretreatment with diethyl maleate (covalently binds GSH as catalyzed by GSH transferase), or buthionine sulfoximine (inhibitor of gamma-glutamylcysteine synthetase) decreased cellular GSH and enhanced reactive oxygen metabolites induced injury. Pretreatment with bis(chloroethyl)-nitrosourea (inhibitor of GSH reductase) inhibited activity of GSH reductase and increased 51Cr release from colonic cells. Preincubation with aminotriazole (inhibitor of catalase) reduced cellular catalase, but did not affect cellular injury. Therefore, we concluded that both cellular superoxide dismutase and the GSH redox cycle appeared to play a role in detoxifying reactive oxygen metabolites and that cellular catalase may be less important in rabbit colonic epithelial cells.
    European Journal of Pharmacology 03/1997; 321(1):113-9. · 2.59 Impact Factor
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    ABSTRACT: Reactive oxygen metabolites (ROM) contribute to colonic cellular injury, in certain pathophysiological conditions. We investigated the role of iron and individual metabolites in their cytotoxicity to cultured colonic epithelial cells from adult white rabbits. Reactive oxygen metabolites, enzymatically generated by hypoxanthine/xanthine oxidase, have a direct cytotoxic effect on cultured colonic epithelial cells. This cellular injury was inhibited by catalase but not SOD. Damage was not aggravated by ferrous iron or EDTA-chelated iron. Such damage was prevented by chelating intracellular iron, but not extracellular iron. These results suggest that H2O2 is more toxic to colonic epithelial cells than 02.- and OH. in the extracellular space. H2O2 enter the intracellular space and is converted to the more reactive and harmful OH. leading to cellular injury in the presence of intracellular iron.
    Life Sciences 02/1997; 60(24):2221-30. · 2.56 Impact Factor
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    ABSTRACT: Although the clinical efficacy of prostaglandins (PGs), especially on gastric mucosal injuries induced by nonsteroidal antiinflammatory drugs, is widely appreciated, their mechanism of action, apart from acid suppression, is quite unclear. In this study, we have established a primary culture system of human gastric fibroblasts and clearly demonstrated that PGs strongly induce the expression of hepatocyte growth factor (HGF) in the fibroblasts, which is mediated by PGE specific receptor, EP2 or EP4. Since HGF facilitates repair and protection of gastric epithelial cells in a paracrine manner, it is assumed that some of the beneficial effects of PGs may be mediated by HGF. To confirm this assumption, we established a simplified in vitro culture gastric mucosal model which consists of gastric epithelial cells and gastric fibroblasts. Using the model, we performed a round wound restitution assay. PGE1 remarkably accelerated restitution which was completely inhibited by anti-HGF antibody, indicating that the action was mediated by HGF. To confirm these in vitro data, we further demonstrated that HGF mRNA expression is downregulated at the edges of nonsteroidal antiinflammatory drug-induced gastric ulcers where PGs should be depleted. In summary, we proposed that gastric fibroblasts are newly recognized targets of PGs, and HGF produced by human gastric fibroblasts may be a key factor for anti-ulcer action of PGs in the stomach.
    Journal of Clinical Investigation 01/1997; 98(11):2604-11. · 12.81 Impact Factor
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    ABSTRACT: Mesenchymal-epithelial interactions are important in the gastric mucosal repair. However, specific factors responsible for such interactions have not been established. In the present study, keratinocyte growth factor (KGF) significantly stimulated proliferation of gastric epithelial cells dose dependently and synergistically with hepatocyte growth factor (HGF), epidermal growth factor (EGF) and insulin. Restitution of gastric epithelial monolayers was also assessed, using a round wound restitution model. Keratinocyte growth factor facilitated the restitution of gastric epithelial cells significantly but did not have any effects on gastric fibroblasts. Keratinocyte growth factor receptor mRNA was expressed by gastric epithelial cells, indicating that these effects were elicited by the specific receptor mediated pathway. Northern blot analysis revealed the expression of KGF mRNA in gastric fibroblasts but not in gastric epithelial cells, indicating the production of KGF. These results suggest that KGF might be involved in gastric mucosal repair, through mesenchymal-epithelial interaction.
    Journal of Gastroenterology and Hepatology 12/1996; 11(11):1089-96. · 3.33 Impact Factor
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    ABSTRACT: While NO has been reported to act as a protective factor to gastric mucosa, it has been shown to be cytotoxic to various cells. NO also has been demonstrated to stimulate prostaglandin (PG) release and mucous glycoprotein secretion which could result in the activation of gastric defensive mechanisms. We examined the effect of NO on cytotoxicity induced by hydrogen peroxide, and mucous glycoprotein secretion and PGE2 release from cultured rabbit gastric mucosal cells. NO enhanced cytotoxicity induced by hydrogen peroxide. Defensive prostaglandin E2 release and mucous glycoprotein secretion were not altered by NO. Under certain circumstances, NO might behave as an aggressive factor in gastric mucosal injury.
    Biochimica et Biophysica Acta 09/1996; 1290(3):257-60. · 4.66 Impact Factor
  • The Lancet 06/1996; 347(9011):1342-3. · 39.06 Impact Factor
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    ABSTRACT: We have recently established an in vitro primary culture system for esophageal epithelial cells, which enabled us to investigate the effect of hepatocyte growth factor (HGF) and other factors on esophageal restitution. HGF remarkably stimulated restitution of these cells. So did epidermal growth factor (EGF), though moderately. Restitution velocity of esophageal cells was remarkably higher than that of gastric epithelial cells. The expression of c-met, specific HGF receptor was demonstrated by the esophageal cells, suggesting that the effect of HGF was mediated by its specific receptor. The expression level of c-met mRNA was the same as that of gastric epithelial cells, as assessed by competitive RT-PCR technique. These results suggest that HGF might be involved in the repair process of esophageal mucosal damage.
    Biochemical and Biophysical Research Communications 12/1995; 216(1):298-305. · 2.41 Impact Factor
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    ABSTRACT: Various growth factors are suggested to be involved in gastric mucosal repair. Our previous studies have shown that exogenous hepatocyte growth factor (HGF) has a proliferative effect on gastric epithelial cells. In the present study, comparison of the maximum proliferative effects and the optimum concentrations of several growth factors revealed that HGF was the most potent mitogen for gastric epithelial cells, as is the case for hepatocytes. Restitution of gastric epithelial cell monolayers was assessed using a round wound restitution model. HGF was the most effective agent for facilitating gastric epithelial restitution among those tested. A binding assay revealed specific binding of HGF to its receptor on gastric epithelial cells. Northern blot analysis confirmed the expression of specific HGF receptor mRNA (c-met) by gastric epithelial cells but not by gastric fibroblasts. To investigate endogenous HGF production, we determined the effect of gastric fibroblast-conditioned medium on epithelial proliferation and restitution. The conditioned medium produced similar effects to HGF and its activity was neutralized by an anti-HGF antibody. In addition, expression of HGF mRNA was detected in gastric fibroblasts but not in gastric epithelial cells. Our immunohistochemical study confirmed these in vitro data by means of demonstrating the existence and localization of HGF at human native gastric mucosa. HGF was localized at fibroblasts under the epithelial cell layer around gastric ulcers. These results suggest that HGF may be a potent endogenous promotor of gastric epithelial cell proliferation and migration, and may contribute to gastric mucosal repair through a paracrine mechanism.
    Journal of Clinical Investigation 06/1995; 95(5):1994-2003. · 12.81 Impact Factor
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    ABSTRACT: The clinical efficacy of lansoprazole plus amoxicillin treatment in eradicating Helicobacter pylori was examined in peptic ulcer patients. H. pylori eradication was assessed by the polymerase chain reaction (PCR) method in addition to conventional methods. Fifteen H. pylori-positive patients with active peptic ulcers (10 duodenal ulcer patients and 5 gastric ulcer patients) were given lansoprazole 30 mg/day from day 1 to day 56 and amoxicillin 1,500 mg/day from day 15 to day 28. Four weeks after the end of treatment, no H. pylori organisms were detected in 9 of 15 patients (60%) as assessed by the rapid urease test and in 10 of 15 patients (67%) as assessed by bacterial culture. However, only three patients were negative for H. pylori when evaluated by the PCR method. Therefore, although lansoprazole plus amoxicillin treatment appears to be promising, a very small number of H. pylori organisms are apparently able to survive such treatment, which may result in the recurrence of H. pylori colonization in some patients.
    Journal of Clinical Gastroenterology 02/1995; 20 Suppl 2:S100-3. · 3.20 Impact Factor
  • Gastroenterology 01/1995; 108(4). · 12.82 Impact Factor
  • Gastroenterology 01/1995; 108(4). · 12.82 Impact Factor
  • International Hepatology Communications - INT HEPTAOL COMM. 01/1995; 3.
  • Gastroenterology 01/1995; 108(4). · 12.82 Impact Factor
  • Gastroenterology 01/1995; 108(4). · 12.82 Impact Factor

Publication Stats

804 Citations
318.97 Total Impact Points

Institutions

  • 1994–1999
    • Dokkyo Medical University
      • Department of Gastroenterology (Hospital)
      Tochigi, Tochigi-ken, Japan
  • 1989–1999
    • The University of Tokyo
      • • Department of Internal Medicine
      • • Division of Internal Medicine
      • • Faculty & Graduate School of Medicine
      Tokyo, Tokyo-to, Japan
  • 1997
    • California State University, Long Beach
      Long Beach, California, United States
  • 1988–1997
    • Long Beach Memorial Medical Center
      Long Beach, California, United States