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Affective values continue to attract attention as a new evaluation axis of commercial value. Our research emphasizes the affective value of contents based on the physical attributes of containers/packages. We previously performed affective evaluation experiments on the tactile material perception of bead-coated resin surfaces with different surface textures generated by such physical attributes as resin materials, bead diameters, and bead densities. Our results clarified the affective relationship between bead-coated resin surfaces and related adjectives. In our new affective evaluation experiment, we added hues, which is one of the three elements of color, and performed two preliminary experiments to select appropriate adjective pairs for the affective evaluation of the effect of hues and to select hue candidates. With 21 adjective pairs and seven hues, we experimentally clarified the combined effect of tactile sensations and hues on affective evaluations using combinations of actual bead-coated resin and 3D models with both male and female participants in their 20's or 40's/50's. Our analysis results suggest that hue and bead diameter have stronger effects than gender and age-generation, suggesting that the influences of physical attributes are stronger than customer gender and age, which is useful from the viewpoint of container/package manufacturing and can be applied to web services with visual and tactile information.

We previously performed affective evaluation experiments on tactile material perception of bead-coated resin surfaces with different surface textures generated by such various physical attributes as resin materials, bead diameters and bead densities. Our results clarified the affective relation between beads-coated resin surfaces and related adjectives. In our new affective evaluation experiment, we added hues, which is one of the three elements of color, and performed two preliminary experiments to select appropriate adjective pairs for affective evaluation of the effect of hues and to select the hue candidates. With 21 adjective pairs (ex. masculine-feminine and relaxed-anxious), and seven hues (ex. yellow-red and blue-purple), we clarified the combined effect of the tactile sensation and the hues on the affective evaluations using combinations of actual bead-coated resin and 3D models. Our analysis results suggest that hue, bead diameter, and gender are important for affective evaluation.

Amorphous carbon (a-C) based semiconductor materials with variable optical gap and high semiconductor properties could be successfully fabricated by radio frequency plasma enhanced chemical vapor deposition (RF-PeCVD) method using a mixed solution of tetramethylsilane (TES) and 1,1,1,3,3,3-hexamethyldisilazane (HMDS) as a liquid source. The optical gap could be controlled by varying sizes and number of sp 2 clusters included in multi-phase structure of a-C by incorporating Si atoms. The resulting Si-doped a-C with 10 six-membered rings in sp 2 clusters shows 1.76 eV of optical gap and Si-doped a-C with 4 six-membered rings in sp 2 clusters shows 2.76 eV. From photocurrent measurement under UV exposure, it was clarified that these films functioned as high performance n-type semiconductors with ca. 4 % of quantum yield, which was on the same level as that obtained at anatase-type titanium oxide prepared by the sol-gel method.

The possibility of a high sensitive amperometric detection of glucose using electrochemically-generated hydroxyl radicals at N-doped DLC was examined. Flow injection analytical system using N-doped DLC as an electrode of electrochemical detector showed higher performance of glucose detection in a potential region of oxygen evolution (>3.6 V vs. Ag|AgCl). Linear dynamic range was 5 orders of magnitude (1 μM to 10 mM) and theoretical detection limit (S/N = 3) was 1.37 mM at 3.6 V vs. Ag|AgCl. In addition to glucose, linear relations between values of response current and of sample concentration were observed in molecules easily oxidized by OH radicals (ascorbic acid, 2-propanol, ethyl acetate and ethyl acetoacetate). The oxidation of glucose mediated by OH radicals generated at N-doped DLC in higher potential region is included in the mechanism of amperometric glucose detection at N-doped DLC.

Kansei/affective values are attracting attention as a new evaluation axis of commercial value. We performed affective evaluation experiments on the tactile material perception of bead-coated resin surfaces and found that physical attributes change affective evaluations. Then, we planned to perform new affective evaluation experiment by adding hues, one of the three elements of color, as an important attribute of surfaces as the next step of our research. For the experiment, we performed two preliminary experiments: the experiment to select appropriate adjective pairs, and the experiment to select the hue candidates. This report describes the first preliminary experiment. We performed an experiment to reduce the number of adjective pairs for affective evaluations. The experimental results were analyzed by correlation analysis and hierarchical clustering analyses. From the results of those analyses, we selected 21 adjective pairs.

Humans can manipulate objects with grasp forces maintained slightly above the minimum required force to prevent slipping. When humans grasp and lift an object, they use fast acting receptors in their skin. These receptors respond to local slips that occur before the gross slip. The estimation of the coefficient of friction and the detection of the incipient slip play a key role in human grasp stability. However, it is not easy to strictly measure the coefficient of friction between the skin and the object’s surface during object manipulations because the shape and dryness of an individual’s skin vary widely. To quantitatively and continuously evaluate the slip condition during a sliding motion, we propose ‘eccentricity’ in the contact area as a measure, which is determined based on the changes in the contact area before and after the sliding motion. In this paper, we employ eccentricity-based slip condition measurement and evaluate the slip condition between a human’s skin and various surface textures. Then, we compare the results with the affective evaluation experiments to assess the subjective feeling of the surface texture and discuss the influence of the slip condition on the subjective feeling.

The electrochemical activity of the surface of Nitrogen-doped hydrogenated amorphous carbon thin films (a-CNH, N-doped DLC) toward the inner sphere redox species is controllable by modifying the surface termination. At the oxygen plasma treated N-doped DLC surface (O-DLC), the surface functional groups containing carbon doubly bonded to oxygen (C=O), which improves adsorption of polar molecules, were generated. By oxidative treatment, the electron-transfer rate for dopamine (DA) positively charged inner-sphere redox analyte could be improved at the N-doped DLC surface. For redox reaction of 2,4-dichlorophenol, which induces an inevitable fouling of the anode surface by forming passivating films, the DLC surfaces exhibited remarkably higher stability and reproducibility of the electrode performance. This is due to the electrochemical decomposition of the passive films without the interference of oxygen evolution by applying higher potential. The N-doped DLC film can offer benefits as the polarizable electrode surface with the higher reactivity and higher stability toward inner-sphere redox species. By making use of these controllable electrochemical reactivity at the O-DLC surface, the selective detection of DA in the mixed solution of DA and uric acid could be achieved.

Real surface structures of the high-index planes of Pt with three atomic rows of terraces (Pt(331) = 3(111)-(111) and Pt(511) = 3(100)-(111)) have been determined in 0.1 M HClO(4) at 0.1 and 0.5 V(RHE) with the use of surface X-ray scattering (SXS). The surfaces with two atomic rows of terraces, Pt(110) = 2(111)-(111) and Pt(311) = 2(100)-(111) = 2(111)-(100), are reconstructed to a (1 × 2) structure according to previous studies. However, the surfaces with three atomic rows of terraces have pseudo-(1 × 1) structures. The interlayer spacing between the first and the second layers, d(12), is expanded 13% on Pt(331) compared to that of the bulk, whereas it is contracted 37% on Pt(511). The surface structures do not depend on the applied potential on either surface.

To evaluate the efficacy and safety of proton-beam therapy for locoregionally advanced esophageal cancer. The subjects were 51 patients with esophageal cancer who were treated between 1985 and 2005 using proton beams with or without X-rays. All but one had squamous cell carcinoma. Of the 51 patients, 33 received combinations of X-rays (median 46 Gy) and protons (median 36 GyE) as a boost. The median total dose of combined X-rays and proton radiation for these 33 patients was 80 GyE (range 70–90 GyE). The other 18 patients received proton-beam therapy alone (median 79 GyE, range 62–98 GyE). Treatment interruption due to radiation-induced esophagitis or hematologic toxicity was not required for any patient. The overall 5-year actuarial survival rate for the 51 patients was 21.1% and the median survival time was 20.5 months (95% confidence interval 10.9–30.2). Of the 51 patients, 40 (78%) showed a complete response within 4 months after completing treatment and seven (14%) showed a partial response, giving a response rate of 92% (47/51). The 5-year local control rate for all 51 patients was 38.0% and the median local control time was 25.5 months (95% confidence interval 14.6–36.3). The results suggest that proton-beam therapy is an effective treatment for patients with locally advanced esophageal cancer. Further studies are required to determine the optimal total dose, fractionation schedules, and best combination of proton therapy with chemotherapy.

Human cystathionine β-synthase (CBS) is a pyridoxal 5-phosphate (PLP) dependent hemoprotein, which catalyzes the condensation of serine and homocysteine. Our mutagenesis studies suggest that Arg-266 is important to sense structural changes in heme-binding site, and that Gln-222 as well as Tyr-223 are involved in interactions with substrates.

経管栄養で嚥下性肺炎を繰り返す患者に対して大建中湯を投与し良好な結果を認めた。症例1は94歳男性，心不全と脳梗塞で入院したが，肺炎を繰り返していた。経皮内視鏡的胃瘻造設術（Percutaneous endoscopic gastrostomy, PEG）後も肺炎を発症したが，大建中湯投与後は肺炎を発症せず，全身状態が安定した。症例2は80歳男性，PEG施行後，重症肺炎で入院した。治療後も嚥下性肺炎を繰り返したが，大建中湯投与で口腔内逆流が消失し，症状の安定を認めた。症例3は85歳男性，心不全と脳梗塞で入院したが，嚥下性肺炎を発症した。経鼻胃管で栄養摂取したが，肺炎を繰り返した。大建中湯を開始後は肺炎を発症せず，状態が安定し転院した。症例4は81歳男性，肺炎と心不全で入院した。食欲不振が強く，経口摂取が困難だったため，PEGを施行した。肺炎を頻回繰り返していたため，予防的に大建中湯を投与した。その後は殆ど発熱を認めず転院した。大建中湯は経管栄養下での後期高齢者の嚥下性肺炎予防に有用と思われた。

薯蕷丸は金匱要略収載の方剤で治験例は殆どない。今回，末期肺癌で食欲と全身状態の維持に有用であった一例を報告した。62歳女性。主腫瘍は左下葉にあり，両側胸膜，縦隔に浸潤していた。転移は骨折した左大腿骨を始め，腸骨，胸腰椎，肝臓に及んだ。発症後5カ月の時点で薯蕷丸を開始した。すでにステロイド剤・麻薬を用いており，全身状態は極めて不良であった。服薬開始後，食欲回復，栄養状態の改善を認め，QOLの維持にも貢献し，その後2カ月生存した。経過中，胸水細胞診にて腺癌が診断された。薯蕷丸は作成に手間のかかる方剤であるが，厥陰病期の患者の全身状態を改善できる薬であり，より使われて良いと考え報告した。

Surface structure of Pt(3 1 0) = 3(1 0 0)–(1 1 0), which contains kink atoms in the step, has been determined with the use of in situ surface X-ray scattering (SXS) in the double layer region (0.50 V(RHE)) in 0.1 M HClO 4 . Clean Pt(3 1 0) surface has pseudo (1 × 1) structure on which lateral displacements of 2–9% and 0.3–1% are found along a and b directions, respectively, whereas the surfaces of Pt(1 1 0) = 2(1 1 1)–(1 1 1) and Pt(3 1 1) = 2(1 0 0)–(1 1 1) are reconstructed to (1 × 2) according to previous reports. Interlayer spacing between the first and the second layers d 12 is contracted about 5% compared with the bulk spacing, whereas those between underlying layers are expanded down to fourth layer. Fully adsorbed CO has no effect on the surface structure of Pt(3 1 0). This result differs from that on Pt(1 1 1), where d 12 is expanded after CO adsorption.

Background/Aim: Geranylgeranylacetone (GGA) enhances gastric mucosal protection against nonsteroidal anti-inflammatory drugs by upregulating mucosal heat shock proteins (HSP), but the effects of GGA on the human gastric mucosa have not been well examined. This study was conducted to determine whether a clinical dose of GGA protects the human gastric mucosa from diclofenac (DIC)-induced gastric mucosal injury. Methods: The study group comprised 40 healthy volunteers: 20 subjects were randomly assigned to take either placebo (lactose 1.5 g/day) or GGA (150 mg/day) for 2 weeks (study 1), and 20 subjects were assigned to take DIC (75 mg/day) plus placebo (lactose 1.5 g/day) or DIC (75 mg/day) plus GGA (150 mg/day) for 2 weeks (study 2). In both studies, gastroscopic biopsy specimens were obtained before and after treatment. Mucosal HSP70 expression and DNA damage were analyzed by measuring the levels of HSP70 and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-OHdG), respectively. Results: In study 1, GGA increased the mucosal HSP70 expression without increasing the 8-OHdG production. In study 2, DIC treatment increased the 8-OHdG production, whereas the combination of GGA and DIC enhanced the HSP70 expression and attenuated the increase in 8-OHdG induced by DIC. Conclusion: The clinical dose of GGA enhanced the gastric mucosal HSP70 expression and inhibited the DIC-induced gastric mucosal damage in humans.

Background and aim Gastric cancer is associated not only with Helicobacter pylori (H. pylori) infection, but also with the intake of a high salt diet. Interleukin-1beta (IL-1beta) is highly expressed in H. pylori-infected gastric mucosa. The aim of the present study was to determine if hyperosmotic stress induces IL-1beta expression in gastric epithelial cells in vitro. Method Murine gastric epithelial cells, GSM06, were cultured with or without H. pylori (Sydney strain-1) at different osmolarities in the range of 300-450 mOsM. Expressions of IL-1beta mRNA and mature IL-1beta protein were evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and an IL-1beta enzyme-linked immunosorbent assay (ELISA), respectively. IL-1beta converting enzyme (ICE) activity was measured by an ICE colorimetric assay. Apoptosis was evaluated by a single stranded-DNA assay. Results Addition of H. pylori at 300 mosM caused significant increases in IL-1beta mRNA, IL-1beta protein, ICE activity and apoptosis. Hyperosmotic stress alone also caused upregulation of IL-1beta mRNA and IL-1beta protein, enhanced ICE activity and accelerated apoptosis. Hyperosmotic stress accentuated the increases in IL-1beta mRNA, IL-1beta protein, ICE activity and apoptosis induced by H. pylori alone. Enhancement of IL-1beta protein release induced by hyperosmotic stress was significantly attenuated by an ICE inhibitor, Z-YVAD-FMK. Conclusions Hyperosmotic stress enhances the release of bioactive mature IL-1beta protein in H. pylori-infected gastric epithelial cells, in part by upregulating IL-1beta mRNA expression, and in part by enhancing ICE activity. These results may explain the mechanisms by which chronic intake of a high salt diet increases the risk of gastric cancer among H. pylori-infected human subjects.

Several studies have demonstrated that intratumoral expression of catabolizing and anabolizing enzymes for 5-fluorouracil (5-FU) is important in the response of cancers to 5-FU-based chemotherapy. We investigated the influence of other chemotherapeutic agents or cytokines, which are often administered for enhancing the efficacy of 5-FU, on the tumoral expression of 5-FU-associated enzymes, i.e., dihydropyrimidine dehydrogenase (DPD), thymidylate synthase (TS), orotate phosphoribosyl transferase (OPRT), and thymidine phosphorylase (TP). Human colon cancer cell lines (HT-29, Caco-2, and DLD-1) were incubated with 5-FU and with 5-FU combined with cisplatin, camptothecin, paclitaxel, mitomycin C, interferon, or TNF-related apoptosis-inducing ligand. mRNA expression of 5-FU-associated enzymes was assessed by real-time PCR. Activity of each enzyme and intracellular 5-FU accumulation after incubation with such agents were also evaluated. Each agent had a synergistic effect on the cytotoxicity of 5-FU. All chemotherapeutic agents other than cytokines induced marked alteration of the mRNA expression profile of 5-FU-associated enzymes; depression of DPD, elevation of TS, and slight suppression of OPRT and TP. In accordance with mRNA expression, enzyme activity of DPD was significantly depressed by such agents. Furthermore, although 5-FU itself increased DPD mRNA expression, a mechanism considered to be related to the acquisition of 5-FU resistance, the addition of cisplatin or camptothecin significantly inhibited the 5-FU-induced elevation of DPD. 5-FU-associated enzymes in colon cancer cells were greatly influenced by various chemotherapeutic agents; in particular, DPD expression was depressed. These results appear important in planning chemotherapy and also in understanding the development of adverse effects of 5-FU.

Nonsteroidal antiinflammatory drugs (NSAIDs) cause complications such as gastrointestinal injury. NSAIDs were recently reported to cause mitochondrial injury: to dissipate the mitochondrial transmembrane potential (MTP), and to induce mitochondrial permeability transition pore (PTP), which liberates cytochrome c. This enzyme generates reactive oxygen species (ROS) thereby triggers caspase cascade and cellular lipid peroxidation, resulting in cellular apoptosis. However, the mechanism of this NSAID-induced MTP's role in cellular apoptosis remains unknown. Rebamipide, an antiulcer drug, is reported to scavenge ROS and to show the protective effects on indomethacin-induced tissue peroxidations. Since cytochrome c and its generation of ROS are involved in indomethacin-induced cellular apoptosis, rebamipide may attenuate mitochondrial damage. The aim of this study was to elucidate whether indomethacin induces both the MTP decrease and cellular apoptosis, and the effect of rebamipide on these phenomena. We examined the effect of rebamipide on 1) MTP change, 2) lipid peroxidation, 3) apoptosis, and 4) caspase activation using gastric mucosal epithelial cell-line treated with indomethacin. With a specially designed fluorescence analyzing microscope system, MTP change, cellular lipid peroxidation, and cellular apoptosis were investigated with the small star, filled following fluorescent dyes, MitoRed, DPPP, and Hoechst 33,258, respectively. Indomethacin treatment decreased MTP but increased both cellular lipid peroxidation and cellular apoptosis via caspase 3 and 9 activation. Rebamipide clearly inhibited these phenomena {in vitro}. We demonstrated that fluorescent dyes such as MitoRed, DPPP, and Hoechst 33,258 are useful indicators for detecting oxidative cellular injuries in living cells. Rebamipide exerts a protective effect on mitochondrial membrane stability in gastric epithelial cells.

OBJECTIVE Endoscopic papillary balloon dilatation (EPBD) has been reported to increase the risk of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (4%-11%). Based on the hypothesis that performing endoscopic nasobiliary drainage (ENBD) could prevent this complication, we performed EPBD combined with ENBD (EPBD/ENBD) and analyzed the risk of pancreatitis. METHODS Thirty-four patients underwent EPBD followed by ENBD for common bile duct stone(s). Serum amylase levels the following morning and incidence of pancreatitis were compared with those previously reported and with complications of simple diagnostic ERCP performed in our institution. RESULTS After EPBD/ENBD, amylase levels the following morning were 214.5 +/- 152.9 U/L, and no cases developed pancreatitis or hyperamylasemia (>3 times normal). These outcomes were favorable compared with previous EPBD reports. Furthermore, despite the stress of EPBD/ENBD after ERCP, these outcomes were better, even compared with simple ERCP performed at our institution [amylase levels: 318.7 +/- 475.2 U/L; hyperamylasemia: 16.5% (P = 0.006); pancreatitis: 7.1%]. CONCLUSION Although EPBD has been regarded as a risk factor for post-ERCP pancreatitis, our results suggest the possibility that application of ENBD after EPBD decreases the incidence of pancreatitis and should be studied further. We speculate that ENBD itself prevents pancreatic duct obstruction by residual stones or papillary edema.

Purpose To present the results of proton beam therapy for patients with esophageal cancer. Methods and materials This study reviewed 46 patients with esophageal cancer who were treated between 1985 and 1998 using proton beams with or without X-rays. All patients had locoregionally confined disease; all but one had squamous cell carcinoma. Of the 46 patients, 40 received combinations of X-rays (median, 48 Gy) and protons (median, 31.7 Gy) as a boost. The median total dose of combined X-ray and proton radiation for the 40 patients was 76.0 Gy (range, 69.1–87.4 Gy). The remaining 6 patients received only proton beam therapy (median, 82.0 Gy; range, 75–89.5 Gy). Results The 5-year actuarial survival rate for the 46 patients, patients with T1 ( n = 23), and those with T2–T4 ( n = 23) was 34%, 55%, and 13%, respectively. The 5-year disease-specific survival rate for the 46 patients, those with T1, and those with T2–T4 was 67%, 95%, and 33%, respectively. The 5-year local control rate for patients with T1 and T2–T4 lesions was 83% and 29%, respectively. The site of the first relapse was locoregional for 16 patients and distant organs for 2 patients. Conclusion The results suggest that proton beam therapy is an effective treatment for patients with locally confined esophageal cancer. Additional studies are required to determine the optimal total dose, fractionation schedule, and best combinations of protons and conventional X-rays with or without chemotherapy.

Background: Various types of classification of gastritis have been proposed, but no plausible classification has been available until now. The Research Society for Gastritis performed a pilot study to establish an endoscopic classification, taking into consideration the following: (i) ease of use; (ii) permitting everyone the common image; and (iii) presence of histopathological evidence. Methods: One hundred and fifty-five patients were enrolled and underwent gastroscopy. Eight basic endoscopic and histological types of gastritis (superficial, hemorrhagic, erosive, verrucous, atrophic, metaplastic, hyperplastic and special types) were defined. Gastritis was endoscopically diagnosed according to the definition of the endoscopic types of gastritis. Four or more biopsy specimens were obtained from the lesser and the greater curvatures of the antrum and the corpus of each patient, and the histological findings of gastritis and Helicobacter pylori infection were assessed. The histological diagnosis of gastritis was made according to the definition of histology types of gastritis. The endoscopic and the histological diagnoses were then compared in a blinded fashion. Results: Endoscopic diagnosis was 62% as sensitive as histological diagnosis for erosive gastritis, 67% for verrucous gastritis and 84% for atrophic gastritis in the antrum. In superficial gastritis, sensitivity was approximately 25% in the corpus, but only 8% in the antrum. Metaplastic and hyperplastic gastritis were correctly diagnosed only in severe cases. Conclusion: Five basic types of gastritis (superficial, erosive, verrucous, atrophic and special types) should be employed for the new endoscopic gastritis classification. Metaplastic and hyperplastic gastritis are considered to be subtypes of atrophic gastritis and they should be excluded from the basic endoscopic classification. A new definition of gastritis in the antrum accompanied by redness still remains to be investigated.

Telomerase, the ribonucleoprotein enzyme that synthesizes telomeric DNA, is thought to be necessary for cellular immortality and carcinogenesis. Telomerase activity is associated with the majority of malignant human cancers. The mRNA that encodes the telomerase catalytic subunit (human telomerase repeat transcriptase; hTERT) has recently been identified, and the expression of the hTERT gene is thought to regulate the activation of telomerase. However, the expression of hTERT mRNA in esophageal tissues has not been reported. We investigated hTERT gene expression in cancerous and noncancerous esophageal tissues, and determined the relationship between hTERT mRNA expression and telomerase activity.Tissues from esophageal carcinomas in 14 patients, reflux esophagitis in 12 patients, esophageal acanthosis in 2 patients, esophageal papilloma in 1 patient, radiation esophagitis in 1 patient, and normal esophageal epithelium in 11 patients (including 3 specimens of normal epithelium from patients with esophageal carcinoma) were examined. All specimens were taken endoscopically. hTERT gene expression was investigated using reverse transcription-polymerase chain reaction (RT-PCR). Quantitative analysis of telomerase activity was analyzed by fluorescence telomeric repeat amplification protocol (F-TRAP) assay.Thirteen of the 14 (93%) esophageal carcinoma specimens expressed hTERT mRNA and revealed detectable telomerase activity. Noncancerous esophageal lesions had not only hTERT mRNA expression with a high frequency (14 of 16 cases; 88%) but also detectable telomerase activity (12 of 13 cases; 92%). Normal esophageal epithelium also highly expressed hTERT mRNA (10 of 11 cases; 91%) and revealed detectable telomerase activity (all 9 cases; 100%). In 32 of the 35 specimens analyzed for both hTERT mRNA and telomerase activity (91%), the expression of hTERT mRNA was consistent with detectable telomerase activity.The expression of hTERT mRNA was detected not only in cancerous but also in noncancerous esophageal tissues at a high frequency. This result was different from that reported for other gastrointestinal epithelium. Moreover, telomerase activity in esophageal carcinoma was significantly stronger than that in reflux esophagitis and normal epithelium. In addition, there was a strong relation ship between the detection of telomerase activity and the expression of hTERT mRNA in cancerous and noncancerous esophageal tissues. Thus, the qualitative analysis of hTERT mRNA expression may not be useful as a biomarker of carcinoma in esophageal tissues. Nevertheless, the quantitative analysis of telomerase activity may be somewhat useful.

Background and study aims The present authors have already reported that mucosal autofluorescence intensity was increased in gastric lesions induced by nonsteroidal anti-inflammatory drugs. The aim of this study was to clarify whether the observation of mucosal autofluorescence with a newly established endoscopic fluorescence analyzing system could help us to recognize indomethacin-induced gastric lesion formation in vivo. Materials and methods Gastric mucosal fluorescence intensity was measured time-sequentially after indomethacin treatment in rats, using a fluorescence endoscope system. The concentration of thiobarbituric acid-reactive substances in gastric mucosa was measured as an indicator of tissue lipid peroxidation. Fluorescent substances from rat stomachs were analyzed using high performance liquid chromatography. Results Treatment with indomethacin induced a time-dependent increase of fluorescence intensity. The concentration of thiobarbituric acid-reactive substances was also increased after the treatment. Pretreatment with radical scavenging reagent constrained the increase of both the fluorescence intensity and the concentration of thiobarbituric acid-reactive substances. The fluorescence products were coproporphyrin, protoporphyrin and mesoporphyrin. Conclusions These findings indicate that the intensity of porphyrin fluorescence increased in gastric mucosal lesions induced by oxygen radicals. Endoscopic observation of mucosal fluorescence was shown to aid the sensitive and objective diagnosis of gastric injuries.

Collagenous gastritis (CG) is a rare disorder characterized by the thick collagenous subepithelial bands associated with mucosal inflammation. There have been approximately fifty reports in the literature since it was first described in 1989. According to previous reports, CG is heterogeneous and classified into two groups—(1) cases limited to the gastric mucosa in children or young adults, and (2) CG associated with collagenous colitis in elderly adults presenting with chronic watery diarrhea. In Japan, only nine previous cases were reported, and all of them were young adults. We report a case of CG with collagenous duodenitis in a 22-year-old female. She had repeated upper gastrointestinal bleeding from a Dieulafoy lesion of the fornix, but had no symptoms of malabsorption or diarrhea. Endoscopic findings revealed striking nodularity with a smooth islet-shaped normal area in the antrum and the body. The pathological findings of nodular mucosa showed the deposition of collagen bands just under the mucoepithelial lesion. In addition, she had collagenous duodenitis in part of the bulbs, and a colonoscopy showed no abnormalities. We provide a literature review of CG and collagenous gastroduodenitis without colonic involvement.

We investigated the role of xanthine oxidase-derived oxygen radicals in the development of endothelin-1-induced gastric ulcer. Mucosal lipid peroxidation showed a peak 24 h after injection, while gastric mucosal haemodynamics were fully restored 26 h after endothelin-1 injection. Allopurinol and oxypurinol, but not superoxide dismutase or catalase, protected the gastric mucosa 24 h after endothelin-1 injection. Oxypurinol antagonized both the vasoconstrictor effect of endothelin-1 and the decrease in gastric ATP. All treatments on the second day after endothelin-1 injection significantly reduced gastric mucosal damage. Xanthine oxidase-derived oxygen radicals contributed largely to the exacerbation but they did not mediate the onset of endothelin-1-induced gastric ulcer. Pretreatment with probucol (500 mg/kg, p.o.) also protected the gastric mucosa from endothelin-1-induced mucosal injury by its antioxidant activity. Oxypurinol was gastroprotective through its vasoactive and energy saving actions. The haemodynamic background of endothelin-1-induced gastric ulcer consists of long lasting ischaemia and subsequent “reperfusion” which may be responsible for the late burst of oxygen radicals.

We previously reported that the gastric mucosa emits fluorescence of porphyrins at the onset of gastric lesions induced by hemorrhagic shock. In this study, we investigated whether the fluorescent substance concerns with the gastric mucosal injuries induced by diflofenac, a nonsteroidal antiinflammatory drug (NSAID). In the gastric mucosa treated with diclofenac, lesions were generated and myeloperoxidase activity increased. Diclofenac administration also increased thiobarbituric acid-reactive substances, a index of tissue peroxidation. After diclofenac treatment, the gastric mucosal fluorescence intensities rose. HPLC analysis demonstrated that the fluorescent substances were mesoporphyrin and protoporphyrin, which were the same as found in hemorrhagic shock. Pretreatment of the tissue with radical scavenging substances, catalase and troxipide, restrained the increase of mucosal fluorescence intensity, tissue peroxidation, and lesion formation. These findings indicate that diclofenac treatment induced the generation of porphyrins as well as tissue peroxidation in gastric mucosal tissue. This study suggests that autofluorescence observation is a useful tool to identify diclofenac-induced gastric injury.

Autofluorescence observations enable scientists to sensitively identify various lesions. Non-steroidal anti-inflammatory drugs such as aspirin and indomethacin are well known to induce gastric mucosal injuries. Our purpose was to clarify whether the observation of mucosal autofluorescence could help us to recognize indomethacin-induced gastric lesion formation. Gastric mucosal fluorescence intensity and gastric lesion scores were time-sequentially measured after indomethacin treatment in rats. To identify the localization of autofluorescent substances, stomach cryosections were observed with an epifluorescence microscope. Fluorescent substances from damaged tissue were also analyzed by high-performance liquid chromatography. In addition, to elucidate whether oxidative stress directly generates fluorescent substances from heme, we investigated the reaction between hydrogen peroxide and hemoglobin in a cell-free system. Treatment with indomethacin induced gastric lesions by tissue peroxidation, with mucosal fluorescence intensity increasing time-dependently. The fluorescence products were mesoporphyrin and protoporphyrin, and they were localized in disrupted mucosal tissue. In the cell-free system, porphyrins were directly generated by hydrogen peroxide from hemoglobin. These findings indicate that indomethacin treatment increased the intensity of porphyrin fluorescence. Gastric mucosal lesion formation can be sensitively detected with fluorescence observations.

Background and Aims: Telomerase activity is thought to be necessary for cellular immortality and carcinogenesis. The mRNA that encodes the telomerase catalytic subunit (hTERT) has recently been identified, and expression of hTERT mRNA is thought to regulate activation of telomerase. To determine at what stage of carcinogenesis cells begin to express hTERT, we analysed hTERT mRNA expression in gastric carcinoma and precancerous conditions, focusing on chronic gastritis with or without intestinal metaplasia. Methods: Using reverse transcription-polymerase chain reaction, hTERT gene expression was investigated in 18 gastric cancers and 60 specimens of chronic gastritis. Telomerase activity was evaluated using telomeric repeat amplification protocol. Results: Sixteen of 18 (89%) gastric carcinomas expressed hTERT mRNA, and this expression was unrelated to histological type or depth of invasion. Telomerase activity was found in seven of eight (88%) gastric cancer tissues, all of which expressed hTERT mRNA. Expression of hTERT mRNA was positive in 14 of 60 (23%) specimens of chronic gastritis, and was most prominent in seven of 15 (47%) specimens of gastric mucosa with intestinal metaplasia. Expression of the hTERT gene was significantly more frequent in chronic gastritis with intestinal metaplasia than in gastritis without intestinal metaplasia (P = 0.030). In addition, hTERT gene expression was not correlated with age, sex, biopsy site, histological grade of inflammatory cells, glandular atrophy and lymph follicles, or infection with Helicobacter pylori. None of eight normal gastric mucosa expressed hTERT mRNA. Conclusions: Our results indicate that hTERT mRNA is expressed in precancerous conditions as well as in gastric cancer, and that hTERT gene expression is induced at an early stage of gastric carcinogenesis.

Carbothermic reduction was adapted to convert mixtures of cerium oxide and praseodymium oxide into cerium–praseodymium mixed dicarbides (Ce x Pr 1− x C 2 ). XRD results indicate that the lattice parameters of Ce x Pr 1− x C 2 vary continuously with x and that the complete miscibility exists between CeC 2 and PrC 2 .

Celiac axis stenosis is frequently associated with pancreaticoduodenal artery aneurysms. Although the cause of stenosis was not clear in most of the reported cases, compression of the median arcuate ligament of the diaphragm was found to be responsible for the stenosis in 7 of 42 reported cases of this type of aneurysm. We report a case of aneurysm caused by compression of the median arcuate ligament of the diaphragm and celiac plexus. An asymptomatic 43-year-old Japanese man was admitted with a low echoic lesion in the uncus of pancreas. Computed tomographic scan and angiogram revealed stenosis of the celiac axis and two aneurysms in the inferior posterior pancreaticoduodenal artery. The celiac plexus and median arcuate ligament were divided surgically and normal flow was reestablished in the celiac axis. One of the aneurysms was resected and the afferent artery of the other aneurysm was ligated. In the setting of pancreaticoduodenal artery aneurysm associated with celiac axis stenosis, management of stenosis should be considered in addition to local treatment of the aneurysm. In this context, division of median arcuate ligament and celiac plexus or aorto-celiac bypass may normalize the flows in the pancreaticoduodenal arcade and could be effective in preventing aneurysm reformation.

Endothelin-1 (ET-1) is produced from inactive precursor big ET-1 by endothelin-converting enzyme-1 (ECE-1), a membrane-bound metalloprotease, structurally similar to another metalloprotease, neutral endopeptidase 24.11 (NEP). Although both phosphoramidon and thiorphan are metalloprotease inhibitors, the ECE activity is inhibited by phosphoramidon but not by thiorphan, a specific inhibitor of NEP. Therefore, to investigate whether an ECE inhibitor can prevent indomethacin-induced gastric mucosal damage in rats, we compared the effects between the two metalloprotease inhibitors on both gastric mucosal integrity and the levels of ET-1 and big ET-1 in gastric tissue. Phosphoramidon significantly decreased ET-1 levels, causing a concomitant big ET-1 increase and dose-dependently attenuated indomethacin-induced gastric mucosal damage. By contrast, thiorphan neither changed the ratio of ET-1/big ET-1 nor attenuated the damage. In conclusion, the prevention of gastric mucosal damage by an ECE inhibitor indicates that endogenous ET-1 may play an important role in the pathogenesis of indomethacin-induced gastric mucosal damage.

Omeprazole, a substituted benzimidazole, is known to inhibit acid secretion from parietal cells in gastric glands, and is widely utilized as a drug for peptic ulcer. To clarify the ultrastructural changes in parietal cells from long-term treatment with a therapeutic dose of omeprazole, biopsy specimens of the gastric mucosa obtained from peptic ulcer patients were morphometrically analyzed before and after omeprazole treatment. Before treatment with omeprazole, parietal cells in both the stimulated and resting stages were observed; the stimulated cells possessed smaller amounts of tubulovesicles in the cytoplasm and numerous profiles of microvilli in the intracellular canaliculi, whereas the cells in the resting phase showed numerous profiles of tubulovesicles and poorly developed microvilli in the canaliculi. Eight weeks after the onset of omeprazole treatment, the amounts of both tubulovesicles in the cytoplasm and microvilli in the intracellular canaliculi drastically decreased. These decreases in the profiles of the membrane structures with a proton pump occurred concomitantly with a significant increase in autophagic vacuole/autolysosome-like structures. These results suggest that the membrane structures with proton pump are not recycled between tubulovesicles and microvilli of intracellular canaliculi in parietal cells after omeprazole treatment, but may be sequestrated into autophagosomes and degraded by lysosomal enzymes.

The results of conventional x-ray radiotherapy for loco-regionally advanced esophageal carcinoma have been disappointing because it is usually difficult to administer a sufficiently high radiation ...

Recently increased production of endothelin-1 has been implicated in the pathogenesis of gastric ischemia-reperfusion injury. We have investigated the effects of endothelin converting enzyme inhibition on local gastric ischemia-reperfusion injury in rats by using two metalloprotease inhibitors, phosphoramidon and thiorphan. In presence of exogenous 0.15M HCI intragastrically, local ischemia was induced by the clamping of left gastric artery for 15 min and reperfusion was done for 30 min. In separate group of rats, phosphoramidon (10-60 mg/kg) or thiorphan (60 mg/kg) were given as i.v. bolus injection immediately before the induction of ischemia. Phosphoramidon dose dependently attenuated the macroscopic and microscopic mucosal injuries while thiorphan did not. These results indicate that phosphoramidon-sensitive endothelin converting enzyme activity is highly present in stomach and phosphoramidon, by inhibiting the conversion of big endothelin-1 to endothelin-1 attenuated the gastric mucosal damage in this model.

Endothelin-1 has been reported to be responsible for gastric mucosal damage in various experimental models. We evaluated the role of endogenous endothelin-1 in the pathogenesis of gastric mucosal damage induced by indomethacin and HCl in the rat. Rats were given indomethacin (25 mg/kg) subcutaneously, and 15 min later, 0.2N HCl intragastrically. Gastric mucosal damage, gastric endogenous endothelin-1, and gastric mucosal hemodynamics were measured. The effects of bosentan, a mixed endothelin receptor antagonist, on gastric mucosal integrity and hemodynamics were assessed. Gastric endogenous endothelin-1 was significantly elevated at 20 min, gastric mucosal blood flow began to decrease significantly at 25 min, and gastric damage occupied 52.2% of the total glandular mucosa at 135 min after injection of indomethacin. Intragastric pretreatment with bosentan (5, 10, 30, and 60 mg/kg) significantly attenuated gastric damage, to 26.1%, 7.7%, 3.6%, and 1.6%, respectively, of the total glandular mucosa. Bosentan (60 mg/kg) prevented the initial decrease of blood flow and, even at 135 min, improved blood flow and hemoglobin oxygen saturation significantly. We suggest that indomethacin-induced endogenous endothelin-1 diminishes gastric mucosal blood flow and tissue oxygenation and ultimately causes gastric damage. Endogenous endothelin-1 may play an important role in the pathogenesis of the acute gastric mucosal lesions induced by indomethacin and HCl.

We investigated the role of an endogenousvasoconstrictor peptide endothelin-1 (ET-1) and freeradicals in local gastric ischemia-reperfusion injury inrats. Local gastric ischemia was induced by clamping the left gastric artery for 15 min andreperfusion was done for 10-30 min in the presence of150 mM exogenous HCl intragastrically. Local gastricischemia and reperfusion resulted in significantmacroscopic and microscopic gastric mucosal damage togetherwith elevation of gastric tissue ET-1 concentration.Gastric tissue ET-1 was found to increase after 15 minof ischemia alone and also with 30 min of reperfusion. A novel nonpeptide endothelin receptorantagonist, bosentan, or a combination of radicalscavengers (superoxide dismutase, catalase, anddeferoxamine) both attenuated gastric mucosal injury.However, the greater protection observed with bosentan thanwith radical scavengers might reflect a preferentialrole of endothelin-1 in this type of injury.

We recently reported a 16.0 mm in length new type of instrument with an inner cylinder of 10.3 mm for endoscopic variceal ligation (EVL). This device is capable of shooting three elastic O bands consecutively in rapid succession without removing the endoscope. The aspirated volume of variceal tissue with the new instrument is larger than that obtained with the Stiegmann ligator. We performed EVL in 16 cases with esophageal varices and seven with solitary gastric varices. EVL was performed for prophylaxis in all cases. The esophageal varices disappeared in all 16 cases after ulcer formation. The procedure was performed once in 14 cases and twice in the remaining two. Three patients died of hepatic failure during the follow-up period which ranged from four to 16 months. Six and 12 month cumulative recurrence rates were 30% and 48%, respectively. All gastric varices disappeared after a single EVL session. There was one variceal recurrence during the follow-up period. Computed tomography and/ or arterioportography performed previously had shown patent gastro-renal shunt in five cases. No changes in the shunts were observed after treatment. No serious complications attributable to EVL were encountered in this series. Therefore, this method is potentially useful for the treatment of not only esophageal varices but also gastric varices.

The introduction of the electronic endoscope has opened the way to tremendous possibilities in handling endoscopic images in terms of filing, storage and retrieval. Although there have been many approaches to retaining endoscopic data, no system has been found to be applicable to all endoscopy units. An integrated filing system that allows storage and recall of endoscopic data in a rapid and convenient manner is essential for a busy endoscopy unit. A hybrid filing system developed by combining analog and digital devices is currently in use in many endoscopy units and fulfills this purpose to some extent. We have developed an on-line system of endoscopic image filing together with a local area network by connecting the hospital host computer, different endoscopy units and terminals located in distant places within the hospital. This system assured filing of digitalized endoscopic and endoscopic ultrasound images together with simultaneous rapid and reliable access to the filed data. Future improvements will include simultaneous recording of endoscopic reports and application of image analyzing software.

Bosentan, a new type of orally effective, mixed (ETA+ETB) endothelin receptor antagonist has been recently introduced and tested in a variety of experimental models. We studied the effect of bosentan on the changes in gastric mucosal hemodynamics and mucosal integrity, induced by the exogenous application of endothelin-1, in rats. Bosentan (10 mg/kg iv) pretreated rats were injected with endothelin-1 (500-1000-2000 pmol/kg, iv) and gastric mucosal hemodynamics were monitored. After combined oral (30 mg/kg) and systemic pretreatment with bosentan we studied the effects of submucosal injection of endothelin-1 (50 pmol) on blood flow and gastric mucosa. Bosentan antagonized the vasodilator, vasoconstrictor and ulcerogenic effects of endothelin-1 in the rat gastric mucosa. These results show that bosentan can be a useful probe in the study of endogenous endothelin in the gastrointestinal tract.