Ohmic contacts to an n-type GaN layer using an electron cyclotron resonance (ECR)-sputtered AlN (thickness of 3 nm)/Ti/Pt/Au electrode without an Al metal layer were investigated. Ohmic ...characteristics were achieved when annealed at a temperature of 400°C or more. Contact resistance reached a minimum (7.67 × 10−1 Ω-mm) at an annealing temperature of 500°C.
Background: Involvement of peroxisome proliferator activated receptor γ (PPARγ) in the growth response of colon cancer cells has been suggested. Aims: To investigate the characteristics of PPARγ ...induced apoptosis in colon cancer cells. Methods: The effects of ligands for each of the PPAR subtypes (α, δ, and γ) on DNA synthesis and cell viability were examined in HT-29 colon cancer cells. Modulation of apoptosis related gene expression by PPARγ ligands was screened with cDNA arrays, and the results were confirmed by quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis. Results: PPARα, PPARδ, and PPARγ were all expressed in HT-29 cells. PPARγ ligands, 15-deoxy-δ12,14-prostaglandin J2 (15d-PGJ2) and troglitazone (TGZ), suppressed DNA synthesis of HT-29 cells whereas ligands for PPARα and PPARδ had no significant effects. Both 15d-PGJ2 and TGZ induced HT-29 cell death in a dose dependent manner which was associated with an increase in fragmented DNA and was sensitive to a caspase inhibitor. Among several genes selected by cDNA array screening, quantitative RT-PCR analysis confirmed downregulation of c-myc expression and upregulation of c-jun and gadd153 expression by 15d-PGJ2 and TGZ. PPARγ induced apoptosis was antagonised by the presence of serum in the culture medium, and interaction between PPARγ signalling and cell survival signalling through the phosphatidylinositol 3-kinase pathway was suggested. Conclusions: As c-myc is an important target gene of the adenomatous polyposis coli (APC)/β-catenin and/or APC/γ-catenin pathway, activation of PPARγ signalling appears to compensate for deregulated c-myc expression caused by mutated APC. The present results suggest the potential usefulness of PPARγ ligands for chemoprevention and treatment of colon cancers.
Recent evidence suggests that peripheral blood granulocytes and monocytes/macrophages have a major role in the exacerbation of ulcerative colitis.
Our objective was to investigate if selective ...granulocyte and monocyte adsorptive apheresis with Adacolumn promotes remission of active ulcerative colitis and spares corticosteroid.
Sixty patients with active ulcerative colitis were studied, of whom 39 had relapsing-remitting ulcerative colitis, 15 had chronic continuous and 6 had their first episode of ulcerative colitis.
Granulocytapheresis was done with an Adacolumn filled with cellulose acetate beads as apheresis carriers that adsorb FcγR and complement receptors bearing leucocytes (granulocytes, monocytes and a small fraction of lymphocytes). Patients received up to 10 Adacolumn sessions over 12 weeks, one session was 60–90
min at 30
mL/min. No additional medication was given. Efficacy was assessed with Seo's activity index (AI) Seo M, Okada M, Yao T. An index of disease activity in patients with ulcerative colitis. Am J Gastroenterol 1992;87:971–6. The mean AI was 197.5 and range 154.4–277.7. AI < 150 was considered significant improvement and AI < 100 was considered clinical remission.
Of 60 patients, 50 (83.3%) improved, 14 achieved remission, granulocytapheresis was most effective in steroid-dependent patients. At entry, the mean dose of prednisolone was 15.3
mg/day per patient and was reduced to 3.6
mg/day after 10 sessions. Granulocytapheresis was well tolerated and no serious side-effects were observed.
Based on our experience in patients with diverse ulcerative colitis disease expression and long-term exposure to conventional drug therapy, we believe that granulocytapheresis is an effective adjunct to conventional medication for promoting remission and sparing steroids in patients with active ulcerative colitis.
Summary
Background : The majority of gastro‐oesophageal reflux disease (GERD) seems to be non‐erosive reflux disease. Nonerosive reflux disease includes minimal change oesophagitis (whitish or ...reddish, oedematous change and erosion that is not regarded as mucosal break) and no endoscopic abnormalities.
Aim : To investigate the accurate proportion of those with minimal change oesophagitis and to clarify its characteristics. In addition, we evaluated the effect of famotidine (40 mg/ day) in those with minimal change.
Methods : Prospective endoscopic assessment was performed for consecutive 606 out‐patients. Of the 582 patients suitable for analysis, 347 were non‐treated. The latter were divided into those with erosive GERD or minimal change, and their endoscopic findings and characteristics were compared.
Results : Among 347 non‐treated patients, 88 (25%) had erosive GERD and 249 (72%) had minimal change. Compared with patients who have erosive GERD and those with minimal change, the latter were less likely to have hiatal hernia or bile reflux, but more likely to have gastric atrophy. Symptomatic patients (n = 55) with minimal change oesophagitis were more likely to have hiatal hernia than those who were asymptomatic (n= 194). Most patients preferred taking famotidine on‐demand, during a 4‐week follow‐up period.
Conclusions : Most non‐erosive reflux disease can be classified as minimal change oesophagitis, and that have different characteristics from erosive GERD. On‐demand famotidine may be a suitable alternative treatment for patients with minimal change disease.
Sonographically guided percutaneous ethanol injection therapy has been used widely in the treatment of hepatocellular carcinoma. However, few reports have been published on the results of this ...treatment in large numbers of patients. Accordingly, we describe our experience with 146 patients who had this treatment. The study is an update of our previous reports on this subject.
We used ethanol injection, with or without transcatheter arterial embolization, 1048 times in 146 patients who had 242 lesions of hepatocellular carcinoma. In 98 patients, ethanol injection was used to attempt a cure of the disease. In the remaining 48 patients, ethanol injection was used palliatively only to reduce the tumor burden. In most cases, 2-8 ml of absolute ethanol was injected in one treatment session. Patients were given the injections two or three times each week until ethanol was injected throughout the lesion. When tumors were greater than 2 cm in diameter, ethanol was injected into the edges of the lesion.
Histopathologic examination after treatment in 21 cases showed that the lesion was completely necrotic in 15 cases, 90% necrotic in five cases, and 70% necrotic in the remaining case. Follow-up angiography performed in 69 cases showed no contrast stains in the treated tumors in 60 cases. Elevated serum levels of alpha-fetoprotein decreased in 39 of 43 cases. The 1-, 2-, 3-, 4-, and 5-year survival rates of all 146 patients were 79%, 64%, 46%, 38%, and 38%, respectively. Among 98 patients in whom ethanol injection was used as a potentially curative therapy, these rates were 85%, 70%, 62%, 52%, and 52%, respectively. After ethanol injection, the cancer recurred frequently; the 1-, 2-, 3-, 4-, and 5-year recurrence rates in the potentially curative group were 26%, 38%, 51%, 60%, and 60%, respectively. However, 84% of recurrences were new lesions in different portions of the liver; recurrence of lesions treated by ethanol injection was rare. Major complications of the treatment were peritoneal bleeding in two cases and pleural effusion in one case.
Histopathologic examination, angiography, and serum levels of alpha-fetoprotein showed that percutaneous ethanol injection is a valuable treatment of hepatocellular carcinoma. The therapy increased the long-term survival of patients who have this disease.
Background: This study attempted to determine the indication for endoscopic mucosal resection with a ligating device (EMRL) and to assess the efficacy of radical (complete) resection of early gastric ...carcinoma and adenoma.
Methods: Sixteen patients with early gastric carcinoma (17 lesions) and 21 patients with gastric adenoma (23 lesions) underwent EMRL with an endoscope with a ligating device. After epinephrine solution was injected into the submucosa, the lesions were aspirated, ligated, and resected.
Results: Twelve of 17 early carcinomas (70.6%) and 18 of 23 adenomas (78.3%) were radically resected by EMRL. The average size of the resected specimens was 12.8 × 11.0 mm. The rate of successful radical resection by EMRL, including piecemeal resection, was 100% (15/15) for lesions located in the antrum, 80% (4/5) in the angle, 61.1% (11/18) in the body, and 0% (0/2) for lesions at the cardia. Repeat EMRL was performed successfully in cases of partial resection (n = 3). No serious complication was encountered. No recurrence of the tumors was identified in cases of radical resection during a median follow-up period of 22.8 months.
Conclusion: EMRL is suitable for the treatment of gastric tumorous lesions. For the treatment of early carcinoma, well-differentiated mucosal carcinomas smaller than 10 mm located in the distal stomach represent the best indication for EMRL. (Gastrointest Endosc 1999;49:192-8)
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.
Summary
Background : Trefoil factor family peptides are expressed in gastrointestinal epithelial cells and play a critical role in maintaining mucosal integrity. Although non‐steroidal ...anti‐inflammatory drugs (NSAIDs) are important causative agents of gastric mucosal lesions, few data are available about the effect of NSAIDs on trefoil family peptides in gastric mucosa.
Aim : To examine whether indometacin, a widely used NSAID, affects trefoil factor family expression in gastric epithelial cells.
Methods : MKN45, a cell line derived from human gastric cancer, was used. TFF1, TFF2, and TFF3 mRNA expression was assessed by real‐time quantitative reverse transcription‐polymerase chain reaction (RT‐PCR). TFF2 gene transcription was also examined by luciferase reporter gene assay.
Results : Relative expression level of TFF1, TFF2, TFF3 mRNA was 616: 12: 1 in unstimulated MKN45 cells. Although indometacin (1–250 µmol/L) had no significant effect on the expression of TFF1 and TFF3 mRNA, it up‐regulated TFF2 mRNA expression in a dose‐ and time‐dependent manner. Luciferase reporter gene assay confirmed the up‐regulation of TFF2 gene transcription by indometacin. Indometacin‐induced up‐regulation of TFF2 expression was not antagonized by externally applied prostaglandin E2.
Conclusion : These results suggest that indometacin up‐regulates gastric epithelial cell TFF2 expression through a COX‐independent mechanism. Since TFF peptides play an important role in gastric mucosal protection, indometacin‐induced TFF2 may reduce the degree of gastric mucosal damage induced by indometacin.
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.
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