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Background: Dysmotility of the gastroduodenal region and delayed gastric emptying have been considered to play roles in non-ulcer dyspepsia. In addition, it has been reported that Helicobacter pylori induced inflammation of the gastric mucosa may affect gastric motility. Aim: To evaluate the effects of H. pylori eradication therapy on gastrointestinal motility and symptoms in non-ulcer dyspepsia patients. Methods: A total of 46 non-ulcer dyspepsia patients were examined for gastric emptying, antral myoelectrical activity, H. pylori infection, and symptom scores. In H. pylori-positive non-ulcer dyspepsia patients, gastric emptying, antral myoelectrical activity, and symptom scores were also analysed 2 months after being cured of H. pylori infection. Results: A total of 67.4% of the non-ulcer dyspepsia patients were H. pylori-positive. Both abnormal gastric emptying and antral myoelectrical activity were observed in non-ulcer dyspepsia patients. H. pylori-positive non-ulcer dyspepsia patients were divided into three groups according to their gastric emptying: the delayed gastric emptying group, the normal gastric emptying group, and the rapid gastric emptying group. In the delayed and rapid gastric emptying groups, the gastric emptying and symptom scores were improved significantly by the eradication therapy. However, there was no improvement in symptom scores in the normal gastric emptying non-ulcer dyspepsia group by the eradication therapy. Conclusions: Disturbed gastric emptying and antral myoelectrical activity play roles in non-ulcer dyspepsia. Helicobacter pylori infection inducing disturbed gastric emptying, may cause some non-ulcer dyspepsia symptoms. Gastric emptying and symptom scores are improved by H. pylori eradication therapy in non-ulcer dyspepsia patients with disturbed gastric emptying. H. pylori eradication therapy is effective in H. pylori-positive non-ulcer dyspepsia patients with disturbed gastric emptying.

c-Kit is a receptor tyrosine kinase, and it isencoded by the mouse W locus. Mutant W/Wvmice develop spontaneous gastric antral ulcers. The aimof the present study was to investigate the pathogenesis of these gastric ulcers and to examine theeffects of two antiulcer drugs; a proton pump inhibitor(2{[4-(3-methoxypropoxy)-3-methylpyridine-2-yl]methyl-sulfinyl}-1H-benzimidazole sodium salt, rabeprazole) and a mucosal protective drug(geranylgeranylacetone, GGA), on the gastric ulcers. Theinhibition of the gastric acid secretion by rabeprazole(30 mg/kg body weight, subcutaneous injection once a dayfor six weeks) significantly increased the gastriculcer formation compared to the controls. In contrast,the GGA treatment (100 mg/kg body weight, oraladministration for six weeks) significantly inhibited the ulcer formation. Bile reflux was seen inthese mutant mice, and they showed no cyclic intensecontractions in the gastric antrum. These resultssuggest that bile reflux due to the disturbance ofgastric antral movement is a cause of the spontaneousgastric ulcers in W/Wv mice.

A collection of 20 strains of Helicobacter pylori from several regions of the world was studied to better understand the population genetic structure and diversity of this species. Sequences of fragments from seven housekeeping genes (atpA, efp, mutY, ppa, trpC, ureI, yphC ) and two virulence-associated genes (cagA, vacA) showed high levels of synonymous sequence variation (mean percentage Ks of 10-27%) and lower levels of non-synonymous variation (mean percentage Ka of 0.2-5.6%). Cluster analysis of pairwise differences between alleles revealed the existence of two weakly clonal groupings, which included half of the strains investigated. All six strains isolated from Japanese and coastal Chinese were assigned to the 'Asian' clonal grouping, probably reflecting descent from a distinct common ancestor. The clonal groupings were not totally uniform; recombination, as measured by the homoplasy test and compatibility matrices, was extremely common within all genes tested, except cagA. The fact that clonal descent could still be discerned despite such frequent recombination possibly reflects founder effects and geographical separation and/or selection for particular alleles of these genes.

This study aimed to investigate the natural course of early rheumatoid arthritis (RA) after treatment for 15 years based on the present data of patients who had been enrolled in a 1 year study of early RA conducted by the Japan Rheumatism Foundation in 1981 and 1982. An examination form was mailed to each doctor who had participated in the previous study requesting them to record the present data of the patients. The patients were requested to fill out the AIMS2 questionnaire. Patients had been randomly assigned into three treatment groups: those treated with gold, with d-penicillamine and without slow acting antirheumatic drugs (SAARDs). Information was obtained concerning 74 of 161 patients who had completed the previous 1 year study. Clinical remission was observed in 20 of 74 patients. The current status of RA by physician’s assessment was reported to be well controlled in 32 of 48 cases (66.7%); however, no remarkable improvement was seen in erythrocyte sedimentation rate (ESR, and the number of painful joints compared with the values at entry 15 years previously. Radiographical stages showed progression and the average score of AIMS2 had deteriorated in most cases. High ESR, progression of joint damage and positive rheumatoid factors at the early stage of RA were suggested to be factors relating to QOL deterioration. These results suggest that it would be difficult to modify the natural course of RA by currently used treatment strategies with SAARDs.

Background: Primary and acquired resistance to antibiotics is an important factor in determining the reason for treatment failure in Helicobacter pylori infection. We examined the relationship between the susceptibility of H. pylori isolates and the efficacy of chemotherapy. Methods: The minimal inhibitory concentrations (MICs) of metronidazole (MNZ), clarithromycin (CLAR) and amoxycillin (AMOX) of 320 H. pylori pre-treatment isolates were determined by the agar dilution method. In 290 patients with peptic ulcers, H. pylori infection was treated by dual or triple combination therapies for 2 weeks: one proton pump inhibitor (30 mg/day lansoprazole or 20 mg/day omeprazole) and one or two antibiotics (500 mg AMOX, 200 mg CLAR or 250 mg MNZ twice a day). MICs were also determined after the treatment failure. Results: Among the drugs tested, for MNZ and CLAR, 8.1% and 9.1% of the isolates, respectively, were resistant, while no isolate was resistant to AMOX. After unsuccessful treatment using MNZ and CLAR, 66.7% and 70.6% of the isolates changed from sensitive to resistant, respectively. All isolates were sensitive to AMOX after treatment failure. Conclusions: The failure of the H. pylori treatment results in the induction of resistance to CLAR and/or MNZ. Regimens with a high cure rate should be used in order to prevent the generation of acquired resistance to antibiotics.

Several tests for the diagnosis of Helicobacter pylori [H. pylori) infection have been employed in clinical studies. To minimize inaccuracies of these tests, we developed a new method which combines the 13C-urea breath test (UBT) with phenol red dye spraying endoscopy. We have designated this innovation the endoscopic 13C-urea breath test (EUBT). EUBT was conducted on 103 patients with gastroduodenal diseases. After the collection of a baseline breath sample, gastroduodenal endoscopy was performed. Twenty milliliters of 0.05% phenol red solution containing 100 milligrams of 13C-urea was sprayed onto the entire gastric mucosa. A breath sample was collected 15 minutes after spraying. We measured 13CO2 in the breath samples by ratio mass spectrometry. Two biopsy specimens each from the antrum and the middle corpus were obtained for culture and histological examination. The mean EUBT values (±standard deviation) in H. pylori -positive and negative patients were 38.56±30.34%< and 0.19± 0.18%), respectively. The cut-off value for EUBT was 0.73%. The sensitivity and specificity of EUBT were 100% and 95.5%, as compared with culture, and 100% and 95.5%, as compared with histological evaluation. The EUBT value of the patients with the diffuse staining type (50.28±31.26%) was significantly higher than that of patients with the regional staining type (26.76±23.17%). EUBT is an accurate method of detecting H. pylori infection and a good indicator of the distribution of the infection within the stomach.

Approximately 50% of Helicobacter pylori strains produce a cytotoxin that is encoded by vacA and that induces vacuolation of eukaryotic cells. Mosaicism in vacA alleles was reported, and there are three different families of vacA signal sequences (s1a, s1b, and s2) and two different families of middle-region alleles (m1 and m2). In addition, the vacA genotype of a strain is associated with its cytotoxin phenotype and its capacity to induce peptic ulceration. To clarify the strain diversity of H. pylori in Japan, 87 Japanese clinical isolates of H. pylori (40 from patients with chronic atrophic gastritis, 25 from patients with duodenal ulcer, 16 from patients with gastric ulcer, 3 from patients with both duodenal and gastric ulcers, and 3 from patients with intestinal type gastric cancer) were characterized by vacA typing by PCR and DNA sequencing. Eighty-four of the 87 isolates were s1a/m1, one was s1b/m1, and two could not be typed. Moreover, all isolates in this study were cagA positive. There were no distinct differences between the cytotoxin-producing strains and cytotoxin-nonproducing strains within the 0.73-kb middle region. Japanese strains were highly homologous, with more than 96% identity in this region, in which maximum divergence has been reported. In addition, there were no associations between the specific vacA types and the level of in vitro cytotoxin activity or the clinical consequences. These results indicate that the cagA-positive, s1a/m1-type strains are common in Japan, regardless of the vacA phenotype or clinical outcome.

The clinical efficacy of an extracorporeal granulocyte removal column (G-1) was investigated in two groups of patients with rheumatoid arthritis (RA) . Group I (n=85) received a total of 4 apheresis, one apheresis per week ; Group II (n=79) received a total of 8 apheresis, two apheresis per week. In both groups, the duration of each apheresis was 60 minutes, at a flow rate of 30 ml/minute. With respect to safety, 164 cases (patients), with respect to efficacy and usefulness, 143 cases and with respect to maintained effectiveness, 65 eases were assessed and the following results were obtained.1) Two weeks after the last apheresis, overall improvement was 49.7% ; in Group I, 50.6% ; in Group II, 48.4%. Overall safety was 94.5% ; in Group, 96.5% ; in Group II, 92.4%. Overall usefulness was 49.7% ; in Group I, 50.6% ; in Group II, 48.4%. The results of the two groups were not significantly different.2) At 12 weeks after the end of the treatment with G-1, the overall maintained effectiveness was 72.3% ; in Group I, 81.6% and in Group II, 59.3% ; indicating continuation of effects for 12 weeks after 4 weeks treatment. In both groups, the effectiveness of G-1 assessed at the conclusion of observations period was statisti-cally significant (p

Telaprevir, a non-structural (NS)3/4A protease inhibitor, is a direct-acting antiviral drug that inhibits viral replication. Triple therapy with telaprevir, pegylated interferon, and ribavirin is a standard therapeutic regimen for patients with genotype 1b chronic hepatitis C virus (HCV) infection and a high viral load. Several factors, including mutations in the NS5A gene, are important predictors of the efficacy of interferon therapy. In this study, we examined the mutational diversity of NS5A and its impact on the efficacy of triple therapy. We enrolled patients with genotype 1b chronic HCV infection and a high viral load (31 males/17 females; mean age, 57.6 years), who were treated with triple therapy. This study was conducted at Kobe University Hospital and at three affiliated hospitals in Hyogo prefecture, Japan, between November 2011 and June 2013. A sustained viral response after 12 weeks (SVR12) was achieved in 37/48 patients (77%). Based on intent-to-treat analysis, SVR12 was significantly greater in patients with the major allele than in those with the minor allele for the IL28B single nucleotide polymorphism (SNP; 88 vs. 56%; P

Previous studies using cultured cells showed that primary cilia are present in quiescent cells, but are absent in proliferating cells. We studied here the relationship between the presence or absence of primary cilia and the cell cycle arrest of normal epithelial cells and cancer cells in the human normal breast and breast cancer tissues. In normal breast tissues, although most epithelial cells were nonproliferating as estimated by the immunofluorescence staining of the proliferation marker Ki-67, primary cilia were present only in 20-40% of the epithelial cells. In breast cancer tissues, primary cilia were not observed in any of the breast cancer cells. Furthermore, primary cilia were hardly observed in the nonproliferating cancer cells in the orthotopic and metastatic human breast cancer xenograft tumors in mice. These results indicate that the absence of primary cilia does not necessarily represent the proliferating phases of normal epithelial cells and cancer cells.

The MR-endoscope system can perform magnetic resonance (MR) imaging during endoscopy and show the images obtained by using endoscope and MR. The MR-endoscope system can acquire a high-spatial resolution MR image with an intraluminal radiofrequency (RF) coil, and the navigation system shows the scope's location and orientation inside the human body and indicates MR images with a scope view. In order to conveniently perform an endoscopy and MR procedure, the design of the user interface is very important because it provides useful information. In this study, we propose a navigation system using a wireless accelerometer-based controller with Bluetooth technology and a navigation technique to set the intraluminal RF coil using the navigation system. The feasibility of using this wireless controller in the MR shield room was validated via phantom examinations of the influence on MR procedures and navigation accuracy. In vitro examinations using an isolated porcine stomach demonstrated the effectiveness of the navigation technique using a wireless remote-control device.

The goal of this study is to establish novel medical technologies by combining magnetic resonance imaging (MRI) with endoscopy to improve diagnostic precision and the safety of endoscopic surgeries. One of the key components of the integrated magnetic resonance (MR) endoscope system is a radio-frequency (RF) coil; this detects the MR signal from tissue and should be placed inside the body. Resonance characteristics such as the resonant frequency and the impedance of the RF coil, which affect the quality of MR images, change depending on the electric properties of the surrounding tissue and the coil deformation. Therefore, the technique of remote tuning and matching of the RF coil was developed, and its feasibility was investigated using a developed intracavitary RF coil, 1.5 tesla MR scanner, and models of phantom and resected porcine stomach. As a result, the frequency tuning and impedance matching was remotely adjusted in both models. In addition, the signal-to-noise ratio (SNR) of MR images was improved up to 134%. The developed remote tuning and matching technique was able to adjust the resonant characteristics of RF coil and can contribute the improvement of MR image quality, which would facilitate safe and precise endoscopy and endoscopic surgeries.

Early detection and accurate discrimination of pancreatic cancer from chronic inflammation are major clinical problems. In our article ([1][1]), we evaluated diagnostic performance of serum metabolomics based on gas chromatography mass spectrometry, and we concluded that our model possessed higher

To investigate the utility of ozone nanobubble water (NBW3) for the treatment of Helicobacter pylori in the stomach, we tested the influence of pepsin concentrations and pH levels on the disinfective activity of NBW3, and the cytotoxicity of NBW3 against mammalian cells and mucosa.Different concentrations of pepsin were dissolved in NBW3, and the bactericidal activity was tested on H. pylori. NBW3 was adjusted to different pH levels (2.0-7.4) and the bactericidal activity on H. pylori was also tested. To examine the cytotoxicity of NBW3, AGS cells, human gastric epithelial cells, were treated with NBW3 and the viability of the cells was evaluated in vitro. Furthermore, NBW3 was administered to mice and gastric mucosal damage was evaluated by histology.Pepsin reduced the disinfective activity of NBW3 on H. pylori in a pepsin concentration-dependent manner. NBW3 showed stable disinfective activity at all pH levels examined. Cytotoxicity of NBW3 against human gastric epithelial cells and gastric mucosa was not observed in our experimental setting.NBW3 can sustain its disinfective activity in wide range of pH levels and show no cytotoxicity on mammalian cells and tissue. Pepsin can inhibit NBW3 activity in a dose-dependent manner.

Background Conducting randomized controlled trial (RCT) for each of the risk factors associated with prophylactic pancreatic duct stent (PPDS) for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is difficult owing to the volume of cases and ethical considerations. In this study, we tried to reveal the degree of preventive effects of PPDS for each individual risk factor within the high-risk group of PEP using the propensity score analysis. Methods The clinical data of 1131 ERCP practices performed at Kobe University Hospital from April 2006 to February 2009 were collected prospectively. We investigated their clinical characteristics including the risk factors of PEP, the use of PPDS and complications of ERCP. We conducted the stratification analysis using the propensity score matching analysis. Results In 210 propensity score-matched ERCPs, PPDS proved to be effective in preventing PEP in patients with a history of pancreatitis (odds ratio 0.11, 95% CI 0.01–0.76, P = 0.01) and cases of difficult cannulation (requiring more than 30 min) (odds ratio 0.13, 95% CI 0.01–1.14, P = 0.08). Conclusions Patients with a history of pancreatitis and cases of difficult cannulation are strongly recommended for PPDS placement. The propensity score analysis can be adapted to the ERCP-related analysis with many procedure-related factors with using retrospective data, and may be adapted to investigate the matters that are unsuitable for RCT by volume and ethical issue.

Objective: Definitive chemoradiotherapy (CRT) with 5-fluorouracil (5-FU) and cisplatin (CDDP) is one of the standard therapies for esophageal squamous cell carcinoma (ESCC); however, inter-individual variations in clinical outcomes have yet to be investigated. In the present study, single nucleotide polymorphisms (SNPs) in SLC23A2 gene were retrospectively evaluated in 49 Japanese patients with ESCC who were treated with a definitive 5-FU/CDDP-based CRT, and the predictive values for the clinical response, severe acute toxicities, and long-term survival were assessed. Methods: A course consisted of the continuous infusion of 5-FU at 400 mg/m2/day for days 1-5 and 8-12, the infusion of CDDP at 40 mg/m2/day on days 1 and 8, and radiation at 2 Gy/day on days 1 to 5, 8 to 12, and 15 to 19, with a second course being repeated after a 2-week interval. The SLC23A2 SNPs rs2681116, rs13037458, rs1715364, rs4987219, and rs1110277 were evaluated. Results: The rs2681116 and rs13037458 had a tendency to predict the clinical response (p=0.144 and 0.085, respectively) and long-term survival (p=0.142 and 0.056, respectively). The rs4987219 and rs1110277 correlated with severe acute leukopenia (p=0.025) and stomatitis (p=0.019), respectively. Conclusions: Further investigations with a larger number of patients or an in vitro study are needed to confirm the predictive values of genetic polymorphisms in SLC23A2.

Background & aims To improve the clinical course of ulcerative colitis (UC), more accurate serum diagnostic and assessment methods are required. We used serum metabolomics to develop diagnostic and assessment methods for UC. Methods Sera from UC patients, Crohn's disease (CD) patients, and healthy volunteers (HV) were collected at multiple institutions. The UC and HV were randomly allocated to the training or validation set, and their serum metabolites were analyzed by gas chromatography mass spectrometry (GC/MS). Using the training set, diagnostic and assessment models for UC were established by multiple logistic regression analysis. Then, the models were assessed using the validation set. Additionally, to establish a diagnostic model for discriminating UC from CD, the CD patients' data were used. Results The diagnostic model for discriminating UC from HV demonstrated an AUC of 0.988, 93.33% sensitivity, and 95.00% specificity in the training set and 95.00% sensitivity and 98.33% specificity in the validation set. Another model for discriminating UC from CD exhibited an AUC of 0.965, 85.00% sensitivity, and 97.44% specificity in the training set and 83.33% sensitivity in the validation set. The model for assessing UC showed an AUC of 0.967, 84.62% sensitivity, and 88.23% specificity in the training set and 84.62% sensitivity, 91.18% specificity, and a significant correlation with the clinical activity index (r s = 0.7371, P Conclusions Our models demonstrated high performance and might lead to the development of a novel treatment selection method based on UC condition.

Improvements in analytical technologies have made it possible to rapidly determine the concentrations of thousands of metabolites in any biological sample, which has resulted in metabolome analysis being applied to various types of research, such as clinical, cell biology, and plant/food science studies. The metabolome represents all of the end products and by-products of the numerous complex metabolic pathways operating in a biological system. Thus, metabolome analysis allows one to survey the global changes in an organism's metabolic profile and gain a holistic understanding of the changes that occur in organisms during various biological processes, e.g., during disease development. In clinical metabolomic studies, there is a strong possibility that differences in the metabolic profiles of human specimens reflect disease-specific states. Recently, metabolome analysis of biofluids, e.g., blood, urine, or saliva, has been increasingly used for biomarker discovery and disease diagnosis. Mass spectrometry-based techniques have been extensively used for metabolome analysis because they exhibit high selectivity and sensitivity during the identification and quantification of metabolites. Here, we describe metabolome analysis using liquid chromatography-mass spectrometry, gas chromatography-mass spectrometry, and capillary electrophoresis-mass spectrometry. Furthermore, the findings of studies that attempted to discover biomarkers of gastroenterological cancer are also outlined. Finally, we discuss metabolome analysis-based disease diagnosis.

Objectives Nucleotide analogs such as entecavir (ETV) ameliorate liver function in chronic hepatitis B or cirrhotic patients, but we cannot predict in which patients this will occur before ETV treatment. We aimed to develop a new pretherapeutic predictive model for the amelioration of liver function after treatment. Patients and methods We carried out a case-control study involving 88 chronic hepatitis B or cirrhotic patients who underwent ETV treatment at Kobe University Hospital. Blood biochemical and virological examinations were performed before and 1 year after ETV treatment. Child's score as an indicator of liver function was also evaluated at the same time. Factors associated with amelioration of Child's score 1 year after ETV treatment were assessed by multivariate analyses. A predictive model of Child's score amelioration was established. Results Multivariate analyses showed that albumin (Alb) and prothrombin time (PT) before ETV treatment were independent factors for Child's score amelioration after the treatment (P=0.001 and 0.030, respectively). The decreases in Alb and PT before the treatment were significantly related to the decrease in Child's score 1 year after the treatment (P=0.001 and 0.006, respectively). The following predictive model of Child's score amelioration was developed: P=1-(1/(1+Exp(-2.215×Alb-0.058×PT+12.543))). The model could well discriminate area under ROC at 0.819 (95% confidence interval: 0.707-0.932). The optimal cutoff point was 0.185, and sensitivity and specificity were 83.3 and 73.9%, respectively. Conclusion Alb and PT before ETV treatment were related to amelioration of liver function after treatment. With our model, the probability of amelioration of liver function after treatment could be better estimated.

Nectin-like molecule 2 (Necl-2)/cell adhesion molecule 1 (CADM1) is shown to be down-regulated by the promoter hypermethylation and/or loss of heterozygosity at chromosome 11q23.2 in many types of cancers, including lung and breast cancers, and is proposed to serve as a tumor suppressor. However, the incidence of these epigenetic and genetic abnormalities of Necl-2 is 30–60% in these cancers, and other mechanisms for the suppression of Necl-2 are presumed to be present. We previously showed that Necl-2 interacts in cis with ErbB3 and suppresses the heregulin (HRG)-induced ErbB2/ErbB3 signaling for cell movement and death. We studied here the relationship between Necl-2 and microRNA-199a (miR-199a) that is up-regulated or down-regulated in a variety of cancers. miR-199a did not directly target the Necl-2 mRNA or affect its mRNA level in human lung cancer A549 cells and human embryonic kidney HEK293 cells. Necl-2 was at least sialylated by the sialyltransferase ST6 β-galactosamide α-2,6-sialyltransferase 1 (ST6GAL1). miR-199a targeted ST6GAL1 and reduced both the sialylation and the protein level of Necl-2. In addition, miR-199a enhanced the HRG-induced ErbB2/ErbB3 signaling. These results indicate that the suppressive role of Necl-2 in the HRG-induced ErbB2/ErbB3 signaling is regulated by miR-199a at least through the reduction of the ST6GAL1-catalyzed sialylation of Necl-2 and/or through the reduction of the protein level of Necl-2 presumably by the protein degradation.

The patient was a 60-year-old man with encephalopathy without liver cirrhosis. CT angiography revealed a patent ductus venosus between the anterior segmental branch of the portal vein and the middle hepatic vein. Coils were framed in the patent ductus venosus and then used to fill in the frame. After treatment, transarterial portography showed that the shunt flow of the ductus venosus had decreased significantly. After one day, the patient's disturbance of consciousness disappeared. Our case involved the adult-onset of a patent ductus venosus, which is extremely rare. This case is the first in which coil embolization was successfully achieved in a noncirrhotic elderly patient with a patent ductus venosus.

Detection of early gastric cancer (EGC) in the remnant stomach is increasing because of follow-up endoscopic surveillance programs. Endoscopic treatment appears to be desirable for EGC in the remnant stomach because it is less invasive than surgical resection. In this retrospective study, to evaluate the feasibility of endoscopic submucosal dissection (ESD) for EGC in an anastomotic site, treatment results of ESD for EGC in an anastomotic site and in remnant stomach not involving an anastomotic site were compared. In total, 11 EGC lesions of anastomotic sites in 11 patients and 22 EGC lesions of remnant stomach not involving an anastomotic site in 21 patients were treated by ESD. All lesions were successfully treated by en bloc resection. There were three patients with perforations in the anastomotic site group. Although resected specimen size and tumor size were larger in the anastomotic site group than in the non-anastomotic site group (P

We describe a 69-year-old man with a history of multiple gastroduodenal ulcers, presenting with the onset of obstructive jaundice. Abdominal CT, MRI and EUS demonstrated a sheet-like mass in the pancreaticoduodenal groove. EUS-FNA did not reveal malignancy. Conservative treatment did not improve his clinical condition and repeated acute pancreatitis occurred during his treatment. Thus, pancreaticoduodenectomy was performed. Histopathological findings showed a duodenal ulcer penetrating the pancreas and infiltration of inflammatory cells and fibrosis in the pancreaticoduodenal groove. The spread of inflammation associated with the duodenal ulcer may have been one of the causes of groove pancreatitis.

The vacuolating cytotoxin and urease secreted by Helicobacter pylori are thought to be virulent factors. Because vacuolation is potentiated by the presence of ammonium ion, which is produced by urease in vitro, it is of interest to examine whether cytotoxin and urease work reciprocally in the development of atrophic gastritis or duodenal ulcer. In the present study, patients (all H. pylori-positive) were divided into four groups: mild atrophic gastritis (group 1; nine patients), severe atrophic gastritis (group 2; 36 patients), duodenal ulcer with mild atrophic gastritis (group 3; 19 patients) and duodenal ulcer with severe atrophic gastritis (group 4; 12 patients). Cytotoxin production and urease activity of H. pylori isolated from these patients were analysed. Cytotoxin production was observed in four of nine (44.4%), 28 of 36 (77.8%), 11 of 19 (57.9%) and eight of 12 (66.7%) isolates from groups 1, 2, 3 and 4, respectively. Cytotoxin-producing H. pylori isolates were found significantly more in patients with severe atrophy than in patients with mild atrophy (P = 0.048). The mean of relative activity of cytotoxin in H. pylori isolate was 1.6 +/- 2.3, 7.9 +/- 7.4, 5.8 +/- 6.0 and 9.0 +/- 9.1 in groups 1, 2, 3 and 4, respectively. Helicobacter pylori isolates from severe atrophy or duodenal ulcer patients in groups 2 or 4 possessed significantly higher activity than those from non-ulcer patients in group 1 (P = 0.017 and 0.030, respectively). The mean of urease activity was 8.6 +/- 4.6, 10.0 +/- 5.9, 10.0 +/- 8.5 and 11.2 +/- 7.7 IU/mg in groups 1, 2, 3 and 4, respectively. These differences indicated no statistical significance. In each H. pylori isolate, the production of cytotoxin and urease were independent, which indicated that there was no reciprocal effect between them in vivo. Thus, cytotoxin-producing H. pylori isolates were more prevalent in patients with severe atrophic gastritis and the cytotoxin activities of H. pylori isolates from the patients with severe atrophic gastritis or duodenal ulcer were much higher than those from the patients with mild atrophic gastritis, which suggested that vacuolating cytotoxin may be a disease-inducing factor.

Ductal cancers of the pancreas frequently express markers of gastrointestinal epithelial cells. Cathepsin E (CTSE) is a non-secretory, intracellular, but non-lysosomal proteinase found in the highest concentration in the superficial epithelial cells of the stomach. The aims of our study were to examine the expression of CTSE in the pancreas, to establish an assay system of CTSE and to evaluate the diagnostic usefulness of CTSE in the pancreatic juice. Eleven patients with pancreatic ductal adenocarcinoma, 10 with mucin-producing adenoma, 3 with intraductal papillary hyperplasia and 43 with chronic pancreatitis were examined. Surgically resected pancreatic tissues were subjected to immunohistochemistry for CTSE. Pancreatic juice was collected from the patients and subjected to sandwich ELISA and Western analysis for detecting CTSE. Positive staining for CTSE was observed in pancreatic ductal adenocarcinoma by immunohistochemistry. CTSE was also expressed in mucin-producing adenoma, intraductal papillary hyperplasia and mucinous hyperplasia. CTSE in the pancreatic juice was present in 8 of 11 patients with pancreatic ductal adenocarcinoma, 5 of 10 patients with mucin-producing tumor, 1 of 3 patients with intraductal papillary hyperplasia and 4 of 43 patients with chronic pancreatitis. The detection frequency of CTSE in the pancreatic juice was significantly higher in the patients with pancreatic ductal adenocarcinoma than in the patients with chronic pancreatitis. Our findings suggest that the expression of CTSE is associated with the pathogenesis of pancreatic ductal adenocarcinoma, that CTSE in the pancreatic juice seems to be a useful marker for a definitive diagnosis and that CTSE may be expressed at a relatively early stage of multistep carcinogenesis in pancreatic lesions.

Cathepsin E (CE) is the only known aspartic proteinase that exists as a homodimer consisting of two fully catalytically active monomers, which are covalently bound by a disulfide bond between two cysteine residues at the NH2-terminal region (Cys43 in human pro-CE). To understand the physiological significance of the dimer formation, the monomeric mutant of human CE was constructed by site-directed mutagenesis (Cys43 ->Ser43) and expressed in Chinese hamster ovary (CHO) cells. Immunolocalization of the mutant protein at both the light and electron microscopic levels revealed the monomeric CE to be associated predominantly with the endoplasmic reticulum and the non-lysosomal endocytic organelles. The cellular localization of the monomeric protein was compatible with that of the wild-type (dimeric form) of recombinant human CE expressed in the same cells. The monomeric protein was generated primarily as the 46-kDa pro-CE with a high-mannose-type oligosaccharide chain in the cells. In addition to the maximal activation at around pH 3.5, a substantial proportion of the monomeric pro-CE was converted to the mature form by incubation at pH 7 and 37 degrees C for 5 min. In contrast, the dimeric pro-CE was scarcely activated by treatment at pH7. Although catalytic properties of the in vitro-activated monomeric CE appeared to be indistinguishable from those of the dimeric forms of natural and recombinant CE, the monomeric form was more unstable to pH and temperature changes than these dimeric forms. These results indicate that the dimerization of CE is not necessarily required for proper folding to express activity, correct intracellular localization and carbohydrate modification, but that it may be essential to structurally stabilize the molecule in vivo.

To study gastric mucosal interleukine-8 (IL-8) mRNA expression, the cytotoxin-associated gene A (cagA) mutation, and serum pepsinogen (PG) I/II ratio related risk in Thai gastric cancer.There were consent 134 Thai non-cancer volunteers who underwent endoscopic narrow band imaging examination, and 86 Thais advance gastric cancer patients who underwent endoscopic mucosal biopsies and gastric surgery. Tissue samples were taken by endoscopy with 3 points biopsies. The serum PG I, II, and Helicobacter pylori (H. pylori) immunoglobulin G (IgG) antibody for H. pylori were tested by enzyme-linked immunosorbent assay technique. The histopathology description of gastric cancer and non-cancer with H. pylori detection was defined with modified Sydney Score System. Gastric mucosal tissue H. pylori DNA was extracted and genotyped for cagA mutation. Tissue IL-8 and cyclooxygenase-2 (COX-2) mRNA expression were conducted by real time relative quantitation polymerase chain reaction. From 17 Japanese advance gastric cancer and 12 benign gastric tissue samples, all were tested for genetic expression with same methods as well as Thai gastric mucosal tissue samples. The multivariate analysis was used for the risk study. Correlation and standardized t-test were done for quantitative data, P value0.05 was considered as a statistically significant.There is a high non cagA gene of 86.8 per cent in Thai gastric cancer although there are high yields of the East Asian type in the positive cagA. The H. pylori infection prevalence in this study is reported by combined histopathology and H. pylori IgG antibody test with 77.1% and 97.4% of sensitivity and specificity, respectively. The serum PG I/II ratio in gastric cancer is significantly lower than in the non-cancer group, P = 0.045. The serum PG I/II ratio of less than 3.0 and IL-8 mRNA expression ≥ 100 or log10 ≥ 2 are significant cut off risk differences between Thai cancer and non-cancer, P = 0.03 and P0.001, respectively. There is a significantly lower PGI/II ratio in Japanese than that in Thai gastric cancer, P = 0.026. Serum PG I/II ratio at cut off less than 3.0 and IL-8 mRNA expression Raw RQ100 or log102 are significantly difference between Thai cancer group when compared to non-cancer group, P = 0.013 and P0.001, respectively. In the correlation study, low PG I/II ratio does not associate with chronic atrophic gastritis severity score in Thais non-cancer cases. However, there is a trend, but not significant convert correlation between IL-8 mRNA expression level and low PG I/II ratio in Thai positive H. pylori infection. The high expression of IL-8 gene demonstrates a poorer prognosis by stage and histology.Predominant gastric mucosal IL-8 mRNA expression level, H. pylori infection, and low PG I/II ratio are relative risks for Thai gastric cancer without correlation with cagA mutation.

Conventionally, long-segment Barrett's esophagus (LSBE) has been considered a high-risk background for the occurrence of Barrett's adenocarcinoma in Western countries, and random biopsy has been proposed for surveillance, aiming to detect early cancer. However, accurate detection of a lesion and diagnosis of the expansion are difficult by this blind method. Herein, we report a case of early Barrett's adenocarcinoma derived from LSBE that was successfully detected by narrow-band imaging with magnifying endoscopy.

An endoscopic tube-tip type urease sensor was developed for the purpose of on-site detection of Helicobacter pylori (H. pylori) using a pH-sensitive field effect transistor (pH-FET). The sensor is composed of an endoscopic-tube connected to a feed pump with a urea solution and a pH-FET attached to a sensor holder at the open end of the tube. The urease activity on the gastric wall can be measured by bringing the sensor into contact with the gastric wall just after replacing gastric juice with the urea solution. The presence of H. pylori causes a pH change in the urea solution inside the sensor holder in 20 seconds due to the strong urease activity of this bacterial species. After measurement, the sensor is detached from the wall, and washed with urea solution by turning on the urea pump. A measurement at one site is completed within 30 seconds. Repetition of the procedure makes multi-site measurements possible. In preliminary evaluations, it was found that clinical sensitivity and specificity were 89% and 86%, respectively, using standard bacteriological testing results as a reference.

4106Background: We have previously revealed that circulating levels of apolipoprotein A2 (apoA2) isoforms apoA2-ATQ/AT (C-terminal truncations of apoA2 homo-dimer) are significantly decreased in ea...