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Biomedical subjects

A Terano

Publications and source records attributed to A Terano.

At least 73 records · Page 4Linked to original sources
PubMed1998

Role of cyclooxygenase 2 in hepatocyte growth factor-mediated gastric epithelial restitution.

Migration of epithelial cells (restitution) is an essential step in the repair of gastric mucosal lesions. Although a variety of growth factors are reported to facilitate gastric epithelial restitution, the intracellular mechanisms of this process are not fully understood. In this study we investigated the effects of hepatocyte growth factor (HGF) on restitution of normal rat gastric epithelial RGM-1 cell monolayers after injury and examined whether cyclooxygenase-2 (COX-2) is involved in HGF-mediated epithelial restitution. Restitution of RGM-1 monolayers was assessed using a round wound restitution model. Application of HGF (5 ng/ml) significantly facilitated the restitution of RGM-1 monolayers after artificial wounding. HGF also induced expression of COX-2 protein in RGM-1 cells, and wounding itself induced COX-2 expression in the cells located at the edge of the wound. Inhibition of COX-2 activity by NS-398, a specific COX-2 inhibitor, significantly delayed the HGF-mediated restitution. These results suggest the involvement of COX-2 in the action of HGF on gastric epithelial restitution.

Animals↗
PubMed1998

The possible role of vascular endothelial growth factor (VEGF) in gastric ulcer healing: effect of sofalcone on VEGF release in vitro.

Angiogenesis plays an important role in gastric ulcer repair. Several growth factors are involved in angiogenesis and, of these, vascular endothelial growth factor (VEGF) has received considerable attention because it is the only factor that acts specifically on endothelial cells and, unlike other angiogenic growth factors, has the hydrophobic signal peptide required for extracellular transport according to classical secretory pathways. We have lately demonstrated the role of VEGF in gastric ulcer repair. Previous reports confirmed that sofalcone has remarkable effects on gastric ulcer healing, which may be mediated by its stimulatory effect on prostaglandin (PG) release in gastric cells. Our data indicate that PGs stimulate VEGF expression in gastric fibroblasts. In this report we hypothesize that the clinical effect of sofalcone is mediated by VEGF expression and we demonstrate that sofalcone stimulates VEGF release by gastric fibroblasts in primary culture.

Anti-Ulcer Agents↗
PubMed1998

Treatment of chronic post-radiation proctitis with oral administration of sucralfate.

Several nonsurgical approaches to the treatment of postradiation proctitis have been described, but no effective conservative treatment has yet been established. As an alternative to the usual treatment, three cases of chronic postradiation proctitis with hemorrhage were successfully treated with oral administration of sucralfate, with resultant decreased bleeding in long term follow-up period. Oral sucralfate may provide a novel approach to the treatment of intractable postradiation proctitis.

Administration, Oral↗
PubMed1998

A case of late onset primary hyperoxaluria type I (PH-I) presented with black liver.

A 63-year-old woman who had received hemodialysis therapy since she fell acute on chronic renal failure 4 years ago presented with multiple joint pain. Nephrocalcinosis was not detected by abdominal X-ray when hemodialysis therapy was initiated. Laboratory testing showed azotemia, anemia, hypoproteinemia and mild liver dysfunction but no liver cirrhosis. Biopsied bone tissue demonstrated numerous calcium oxalate crystal depositions. Laparoscopy revealed black liver in macroscopic view. Histological studies showed numerous lipofuscin-like dark brown granules were deposited in hepatocytes. The activity of alanine : glyoxylate aminotransferase (AGT) was less than 0.1 U/g in biopsied patient's liver tissue. Generally, clinical symptoms demonstrated by Japanese primary hyperoxaluria type I (PH-I) patients are milder than those of European patients. Some PH-I patients may successfully avoid urinary tract calcification unless they fall into oliguria by some other causes. The lipofuscin granules are most likely the source of the dark color. Massive deposition of the lipofuscin granules indicated that the duration of the liver metabolic abnormality had lasted for long time. Thus, black liver may be related to a mild form of PH-I.

Biopsy↗
PubMed1998

[Cytokines and gut].

Cytokines are soluble proteins or glycoproteins produced by a wide variety of cell types. Cytokines are local regulatory factors which are involved in cell growth, cell differentiation, inflammation, and immune responses. In the gastrointestinal mucosa, not only inflammatory cells but also epithelial and mesenchymal cells secrete cytokines in response to various stimuli. Inflammatory cytokines are playing critical roles in the inflammation associated with gastrointestinal infections, including Helicobacter pylori infection in the gastric mucosa. Animal studies have shown that abnormal cytokine response may be risk for developing inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease. Cytokines will be important therapeutic targets in these diseases.

Animals↗
PubMed1997

Promoters of epithelialization induce expression of vascular endothelial growth factor in human gastric epithelial cells in primary culture.

Both epithelialization and angiogenesis are indispensable processes in gastric ulcer healing. Coordination between these processes has not been well studied. In the present study, we have established a new primary culture system of human gastric epithelial cells and investigated the effect of epithelialization stimulants on a specific angiogenic factor, vascular endothelial growth characterized as epithelial cells. Both epithelialization stimulants, hepatocyte growth factor (HGF) and epidermal growth factor (EGF), significantly stimulated vascular EGF expression in gastric epithelial cells. HGF and EGF receptors were expressed by the cells, suggesting that regulation may be mediated through specific receptors.

Adult↗
PubMed1997

Expression of vascular endothelial growth factor at the human gastric ulcer margin and in cultured gastric fibroblasts: a new angiogenic factor for gastric ulcer healing.

Angiogenesis plays a pivotal role in gastric ulcer repair. Several growth factors are involved in angiogenesis, and of these, vascular endothelial growth factor (VEGF) has received considerable attention, since it is the only factor that specifically acts on endothelial cells. However, the role of VEGF in gastric ulcer repair is not known. In the present study, we demonstrate the specific expression of VEGF at the gastric ulcer margin, using immunohistochemistry and RT-PCR. The specific receptors of VEGF, flt-1 and KDR were also detected in gastric mucosa. We further demonstrate the expression of VEGF by cultured human gastric fibroblasts which is enhanced by tumor necrosis factor-alpha. These data suggest that VEGF may play a role in angiogenesis in the process of gastric ulcer healing.

Base Sequence↗
PubMed1997

Antioxidant defenses of cultured colonic epithelial cells against reactive oxygen metabolites.

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.

Animals↗
PubMed1997

Hydrogen peroxide-mediated cytotoxicity to cultured colonic epithelial cells.

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.

Animals↗
PubMed1997

Effect of sofalcone on the expression of hepatocyte growth factor (HGF) and a brief review of HGF in the stomach.

Previous studies of hepatocyte growth factor (HGF) in the stomach are briefly reviewed. Exogenous HGF has a strong effect on proliferation and migration of gastric epithelial cells. These effects of HGF are mediated by the specific receptor c-MET. Our previous immunohistochemical study revealed that the main source of endogenous HGF in human gastric ulcer is gastric fibroblasts. These findings suggest that HGF may play an important role in the repair of gastric ulcers through a paracrine mechanism. Therefore, regulation of HGF expression by gastric fibroblasts may be important. We have demonstrated that prostaglandins (PGs) E1 and E2 strongly stimulate HGF expression by gastric fibroblasts, indicating that the clinical efficacy of PGs is mediated by HGF, PGE1 actually facilitates restitution in an in vitro gastric mucosal model consisting of gastric epithelial cells and fibroblasts, which was completely inhibited by anti-HGF antibody. In this study we investigated the effect of an anti-ulcer drug, sofalcone, on PGE2 release and HGF expression by human gastric fibroblasts in primary culture. Sofalcone induced PGE2 release by human gastric fibroblasts in a dose-dependent manner. It also stimulated HGF expression by gastric fibroblasts, indicating that PGs induced by sofalcone increased HGF expression. These findings suggest that clinical efficacy of PGs and sofalcone might be mediated, at least in part, by HGF.

Anti-Ulcer Agents↗
PubMed1997

Proinflammatory cytokines and Helicobacter pylori stimulate CC-chemokine expression in gastric epithelial cells.

Helicobacter pylori (H. pylori) has been shown to stimulate secretion of IL-8, a CXC-chemokine, from gastric epithelial cells, and this process is important in the induction of gastric mucosal inflammation associated with H. pylori infection. However, considering the biological effects and target cells, CC-chemokines may also be playing an important role in H. pylori-associated gastritis. In the present study, we investigated the expression of IL-8 (CXC-chemokine), MCP-1 (CC-chemokine), and RANTES (CC-chemokine) in human gastric mucosa by RT-PCR analysis. The positive rates of IL-8, MCP-1, and RANTES in 35 patients were 68.5%, 80%, and 80% respectively, suggesting the possible importance of CC-chemokines. We next examined the production of MCP-1 by MKN28 gastric epithelial cells. MKN28 cells were found to secrete MCP-1 in response to IL-1 beta or TNFalpha in a dose- and time-dependent manner. Quantitative RT-PCR analysis showed the induction of MCP-1 mRNA by these proinflammatory cytokines. Co-culture with H. pylori also induced the expression of MCP-1 mRNA. These results suggest that gastric epithelial cells secrete CC chemokine MCP-1 in response to proinflammatory cytokines and H. pylori, and this process may also be important in the chronic gastric inflammation associated with H. pylori infection.

Adult↗
PubMed1997

Helicobacter pylori infection in early gastric adenocarcinoma: relationship between histologic subtypes and ulcer-formation.

Early stage of gastric cancers were divided into two subtypes; differentiated and undifferentiated adenocarcinomas, histologically. We examined the involvement of Helicobacter pylori (Hp) infection in the development and progression of cancer, and presence or absence of peptic ulcer (UL+/UL-). From the results, these findings obtained as follows; 1) Hp positive rate of UL+ group was significantly higher than that of UL-group. 2) Neither of gross features nor depth of the tumor did not correlate with Hp positive rates. 3) Hp positive rate of undifferentiated type carcinoma was significantly higher than that of differentiated type, contrarily to our expectation. These findings suggested that Hp infection might relate with ulcer formation in the cancerous lesion. The hypothesis which is "gastritis-intestinal metaplasia-differentiated type carcinoma sequence" was not supported by present study. Hence, Hp infection was suggested as an important factor of the gastric cancer development and progression, not only in differentiated type but also in undifferentiated type.

Adenocarcinoma↗
PubMed1997

[Recent topics in the medical treatment of reflux esophagitis].

Reflux esophagitis is one of the most common disorders of the upper gastrointestinal tract. It can lead to obstruction through stricture formation, in more severe form to bleeding through ulceration, and to cancer development through the association of Barrett's esophagus. The vast majority of esophagitis can be managed medically. Medical management is separated into two categories: (1) life style modification and (2) drug therapy. Drug therapy includes antacids, prokinetics, sucralfate, H2 receptor antagonists (H2-RAs) and proton pump inhibitors (PPIs). Among these, antisecretory therapy is the mainstay for the treatment. PPIs are shown to be superior to H2-RAs in healing of esophagitis and symptom relief. Recurrence, particularly of erosive esophagitis, is common without maintenance therapy. PPIs are also consistently superior to H2-RAs in maintenance of esophagitis healing. Interestingly, a recent report has suggested that curing Helicobacter pylori infection may provoke reflux esophagitis, raising the possibility that the gastroesophageal reflux diseases become more common in the future. Therefore, treatment strategy for reflux esophagitis needs to be re-established in terms of the future cost-effectiveness evaluation and quality-of-life assessments.

Antacids↗
PubMed1996

Hepatocyte growth factor as a key to modulate anti-ulcer action of prostaglandins in stomach.

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.

Adult↗