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Biomedical subjects

A Terano

Publications and source records attributed to A Terano.

At least 55 records · Page 3Linked to original sources
PubMed1999

Monochloramine-induced cytolysis to cultured rat gastric mucosal cells: role of glutathione and iron in protection and injury.

Helicobacter pylori (H. pylori) infection plays a role in the pathogenesis of peptic ulceration as well as active chronic gastritis. Possible mechanisms of H. pylori-induced mucosal injury include the generation of toxic monochloramine (NH2Cl) from oxidant (HOCl)--which is a product of activated neutrophils-and ammonia (NH3), which is a metabolite of H. pylori urease. To clarify mechanisms by which NH2Cl induces cytolysis, we determined the effects of glutathione (GSH) alteration and iron chelation on NH2Cl-induced damage in cultured rat gastric mucosal cells, because these are involved in oxidant injury. Cytotoxicity was quantified by chromium 51 release from prelabeled cells that were exposed to NH2Cl or hydrogen peroxide (H2O2). Although both NH2Cl and H2O2 caused a time-related and dose-dependent increase in 51Cr release, NH2Cl was more cytotoxic than H2O2. Pretreatment with extracellular GSH caused a right shift of the dose-response curve for NH2Cl, whereas pretreatment with diethyl maleate (a depletor of cellular GSH) rendered cells less resistant to NH2Cl. Iron chelation with 1,10-phenanthroline or deferoxamine failed to influence NH2Cl injury, whereas such treatment was protective against H2O2. Intracellular GSH seems to play an important role as a potent defense system against NH2Cl, as observed in H2O2-induced damage. However, the mechanisms of NH2Cl-induced damage seem to be distinctly different from cytolysis by H2O2 in terms of the mediation of cellular iron.

Animals↗
PubMed1999

Redox regulation of interleukin-8 expression in MKN28 cells.

Recent evidence suggests a role of reactive oxygen intermediates (ROI) in intracellular signaling and regulation of gene expression. We examined whether expression of interleukin-8 (IL-8), a key cytokine in the inflammatory responses of gastric epithelial cells, is sensitive to antioxidants and oxidative stress. IL-8 secretion was quantified by IL-8 enzyme-linked immunosorbent assay, and IL-8 mRNA expression was determined by northern blot analysis. Electrophoretic mobility shift assay was performed to detect the transcription factor, nuclear factor kappaB (NF-kappaB). N-Acetylcysteine (NAC) or dimethylsulfoxide inhibited IL-8 expression induced by tumor necrosis factor-alpha (TNF-alpha) or interleukin-1beta (IL-1beta). Externally applied H2O2 significantly up-regulated IL-8 expression. TNF-alpha-induced activation of NF-kappaB activity was suppressed by NAC, and H2O2 caused significant activation of NF-kappaB. Since ROI production is increased in the inflamed gastric mucosa, for example, in H. pylori-associated gastritis, the present results suggest that ROI may be an important modulator of IL-8 expression in gastric mucosal cells.

Acetylcysteine↗
PubMed1999

Polaprezinc protects gastric mucosal cells from noxious agents through antioxidant properties in vitro.

BACKGROUND: Polaprezinc has been shown to exert an anti-oxidant property in a tube experiment, protect gastric mucosa from experimental ulcerations in vivo, and accelerate the healing of gastric ulcer in humans. AIM: To examine a possible protective effect of polaprezinc on oxidant-mediated injury in primary monolayer cultures of rat gastric fundic mucosa. METHODS: Cytotoxicity was quantified by measuring 51Cr release. Whether or not polaprezinc exerts an antioxidant property was investigated by determining the effect of this agent on hydrogen peroxide (H2O2)-induced injury. The effects of polaprezinc on superoxide (O2-. ) generation as well as on ethanol (EtOH)-induced injury were also examined. Generation of O2-. was assessed by the reduction in cytochrome c. RESULTS: H2O2 caused a time- and dose-dependent increase in 51Cr release. The dose-response curve of 51Cr release by H2O2 shifted to the right in the presence of polaprezinc. Polaprezinc, at submillimolar concentrations, prevented H2O2-induced 51Cr release. EtOH also caused a dose-dependent increase in 51Cr release, which was prevented by the addition of polaprezinc. The incubation of cells with EtOH caused an increase in cytochrome c reduction, as the concentrations of EtOH increased. Polaprezinc inhibited EtOH-induced cytochrome c reduction. Protection by polaprezinc was microscopically associated with the prevention of monolayer disruption. CONCLUSIONS: Polaprezinc is antioxidative and directly protects gastric mucosal cells from noxious agents through its antioxidant properties in vitro. This finding may provide the theoretical basis for the usage of an antiulcer drug with antioxidant properties for the treatment of gastric inflammation, such as that induced by ethanol.

Animals↗
PubMed1999

Immunolocalisation of PIVKA-II in paraffin-embedded specimens of hepatocellular carcinoma.

AIMS/BACKGROUND: Although serum PIVKA-II has been widely used as a tumor marker for hepatocellular carcinoma (HCC), little information is available concerning tissue PIVKA-II, and detection of tissue PIVKA-II in paraffin-embedded tissue specimens of HCC is also considered difficult. METHODS: Paraffin-embedded HCC tissues obtained at autopsy from 22 patients were subjected to immunohistochemical staining using the antibody MU-3 (Eisai Co., Ltd.) after microwave antigen retrieval. RESULTS: PIVKA-II was mainly detected in the cytoplasm of HCC cells. The intensity of tissue PIVKA-II staining was not correlated with serum PIVKA-II levels or with the histotogical differentiation of HCC. However PIVKA-II staining tended to be more intense in tissue from patients with portal tumor thrombus, distant metastases, or a longer duration of HCC. CONCLUSION: This method of immunohistochemical staining is easy and simple to use and may be helpful for detecting tissue PIVKA-II in paraffin-embedded HCC specimens.

Adult↗
PubMed1999

Massive gastrointestinal hemorrhage in systemic lupus erythematosus: successful treatment with corticosteroid pulse therapy.

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.

Anti-Inflammatory Agents↗
PubMed1999

[Effect of Helicobacter pylori eradication from patients with gastritis evaluated by the pathological grading and cell proliferation related factors].

We used Image Analysis Processor to clarify the relation ship between cell proliferation, apoptosis and inflammation before and after eradication in H. pylori gastritis. Fifty-two patients with H. pylori gastritis were diagnosed using the Rapid Urease Test under endoscopical and histological examination. The grading of gastritis was determined by the Updated Sydney System. While the effects of Ki-67 on epithelial cell proliferation were examined by immunohistochemistry using Image Analysis Processor, and apoptosis in epithelial cells was counted after staining by in situ TDT. H. pylori density, the number of neutrophils, mononuclear cell, and number of lymphoid follicles had significantly decreased after eradication. Ki-67 labeling index significantly decreased from 11.74 percent to 0.98 percent after eradication (p < 0.0001). The apoptotic index had also decreased after eradication, but with a lack of significant difference (p < 0.06). These data suggest that H. pylori gastritis was remarkably ameliorated by eradication, have led to being capable of improving epithelial cell damage, and activity of proliferative cells and apoptotic cells were becoming normalization.

Apoptosis↗
PubMed1999

Role of antioxidant defenses against ethanol-induced damage in cultured rat gastric epithelial cells.

Reactive oxygen species appears to be involved in the pathogenesis of ethanol-induced gastric mucosal injury in vivo. Because ingested ethanol diffuses into the gastric mucosa, targeting both epithelium and endothelium, in the present study we examined the possible protective effect of antioxidants on ethanol damage in gastric epithelial cells and endothelial cells in vitro. Cytotoxicity by ethanol was quantified by measuring 51Cr release. The effects of impairment of the glutathione redox cycle and of inhibition of cellular catalase were examined. The generation of superoxide was assessed by the reduction in cytochrome c. Ethanol caused a time- and dose-dependent increase in 51Cr release from epithelial cells. Incubation of cells with DL-buthionine-(S,R)-sulfoximine, while reducing glutathione production, dose dependently enhanced ethanol-induced injury. 1,3-Bis(chloroethyl)-nitrosourea, while inhibiting glutathione reductase activity, also sensitized cells to ethanol. In contrast, the inhibition of catalase with 3-amino-1,2, 4-triazole did not alter the susceptibility of epithelial cells to ethanol. Ethanol induced damage to endothelial cells in a similar fashion. In endothelial cells, however, neither impairment of the glutathione cycle nor inhibition of catalase influenced ethanol-induced damage. Epithelial cells, when exposed to ethanol, increased superoxide production as a function of ethanol concentration, whereas endothelial cells did not. The glutathione redox cycle, but not cellular catalase, plays a critical role in protecting epithelial cells against ethanol damage, whereas neither antioxidant seems to play a role in protection of endothelial cells. The distinct difference in antioxidant protection against ethanol appears to depend on the capability of each cell to produce cytotoxic oxygen species in response to ethanol exposure.

Amitrole↗
PubMed1999

[Positivity rate of TTV-DNA in patients with acute liver injury of undetermined etiology].

To elucidate a role of TTV infection in patients with acute liver injury, TTV-DNA in the sera from 97 patients with acute liver injury of various etiology were determined according to Okamoto's method. Out of 77 patients with acute liver injury of determined etiology, 31 patients(40.3%) showed TTV-DNA positive, and out of 15 patients with acute liver injury of undetermined etiology, 8 patients(53.3%) showed TTV-DNA positive. These results suggested no evident role of TTV in patients with acute liver injury was shown. Further study including genotype and quantitative determination of TTV-DNA and antibody assay is needed.

Acute Disease↗
PubMed1999

Polaprezinc down-regulates proinflammatory cytokine-induced nuclear factor-kappaB activiation and interleukin-8 expression in gastric epithelial cells.

Gastric epithelial chemokine response is a primary factor in the induction of gastric inflammation associated with Helicobacter pylori infection. Because sustained inflammation is a risk for gastric mucosal damage, agents that down-regulate inflammatory responses may be of therapeutic significance. We examined the effect of polaprezinc, a potent antiulcer agent, on proinflammatory cytokine-induced interleukin (IL)-8 expression in gastric epithelial cells. Because IL-8 expression is regulated by the transcription factor nuclear factor-kappaB (NF-kappaB), we also examined the effect of polaprezinc on NF-kappaB activity. MKN28 cells were used as a model of gastric epithelial cells. Secreted IL-8 was quantified by IL-8 specific enzyme-linked immunosorbent assay, and IL-8 mRNA expression was examined by Northern blot analysis. NF-kappaB activity was analyzed by electrophoretic mobility shift assay. Western blot analysis with anti-phospho-IkappaB-alpha antibody was performed to assess IkappaB-alpha phosphorylation. Polaprezinc-suppressed IL-8 secretion induced by tumor necrosis factor alpha (TNF-alpha) or IL-1beta in a dose-dependent manner. IL-8 mRNA expression also was inhibited by polaprezinc. NF-kappaB activation in response to TNF-alpha, IL-1beta, phorbol ester, and H(2)O(2) was down-regulated by polaprezinc. Western blot analysis showed inhibition of TNF-alpha-induced IkappaB-alpha phosphorylation in the presence of polaprezinc. Collectively, these results suggest that polaprezinc is a novel type of anti-inflammatory agent that down-regulates inflammatory responses of gastric mucosal cells.

Anti-Ulcer Agents↗
PubMed1998

Chemokine expression in Helicobacter pylori-infected gastric mucosa.

Inflammatory response to Helicobacter pylori is characterized by infiltration of neutrophils, monocytes, and lymphocytes into the gastric mucosa. Interleukin-8 (IL-8), a prototype of the CXC-chemokine subfamily, may be a key modulator in inducing neutrophil migration and activation in H. pylori-infected gastric mucosa. IL-8 is produced by gastric epithelial cells in response to H. pylori infection, and IL-8 expression is induced by local production of proinflammatory cytokines and attachment of H. pylori organisms to the gastric epithelial cell surface. Multiple genes in the H. pylori cag pathogenicity island seem to be involved in inducing the epithelial IL-8 response to H. pylori attachment. Activation of the transcription factor, nuclear factor kappaB (NF-kappaB), is associated with this IL-8 response. Reactive oxygen intermediates whose production is increased in H. pylori-infected gastric mucosa may also modulate IL-8 expression in the gastric mucosa. Recent reports also suggest that the local production of CC-chemokines, another chemokine subfamily, is important in H. pylori-associated gastritis.

Antigens, Bacterial↗
PubMed1998

Human platelet activation by thrombolytic agents: effects of tissue-type plasminogen activator and urokinase on platelet surface P-selectin expression.

The mechanisms that underlie reocclusion during thrombolytic therapy have not yet been clarified. The purpose of this study was to investigate the activating effects of tissue-type plasminogen activator and urokinase and the inhibitory effects of acetylsalicylic acid by measuring platelet surface P-selectin as a marker of platelet activation. After addition of urokinase (final concentration 192 U/ml, 1920 U/ml, or 19,200 U/ml) or tissue-type plasminogen activator (final concentration 120 U/ml, 1200 U/ml, or 12,000 U/ml) to platelet-rich plasma from 12 healthy persons, platelet surface P-selectin expression was measured by means of flow cytometry with an anti-CD62 monoclonal antibody. The presence of urokinase and tissue-type plasminogen activator increased platelet surface P-selectin expression in a concentration-dependent manner. In the next step, either 160 mg/day (n = 6) or 660 mg/day (n = 6) acetylsalicylic acid was administered to the 12 healthy persons, and venous blood samples were collected after 7 days of treatment. Platelet surface P-selectin expression was measured with the method used earlier and after addition of tissue-type plasminogen activator or urokinase. Although the effect of acetylsalicylic acid at 160 mg/day on P-selectin expression was minimal, a dose of 660 mg/day suppressed platelet P-selectin expression and inhibited the platelet activating effects of tissue-type plasminogen activator and urokinase in a statistically significant way. Platelets were activated by tissue-type plasminogen activator or urokinase, and this platelet activation was suppressed with administration of acetylsalicylic acid at 660 mg/day.

Aspirin↗