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Mototsugu Kato

Publications and source records attributed to Mototsugu Kato.

At least 19 recordsLinked to original sources
PubMed2006

Resistance to experimental colitis depends on cytoprotective heat shock proteins in macrophage migration inhibitory factor null mice.

Macrophage migration inhibitory factor plays an important role in inflammatory diseases. We investigated the role of macrophage migration inhibitory factor (MIF) in the development of dextran sulfate sodium (DSS)-induced colitis using MIF null ((-/-)) mice. MIF(-/-) mice given 3% DSS showed no clinical and histological feature of colitis in contrast to wild-type (WT) mice. Lack of MIF suppressed the up-regulation of TNF-alpha and IFN-gamma as Th1-derived cytokines, and increased the level of IL-4 as Th2-derived cytokine in the colon tissues. Moreover, we found that the expressions of heat shock protein (HSP)40 and HSP70 were markedly up-regulated in the colon of MIF(-/-) mice in response to DSS compared with WT mice. Additionally, quercetin, an inhibitor of HSP synthesis, inhibited the up-regulation of HSP40 and 70 expressions and developed DSS-induced colitis in MIF(-/-) mice. Our findings in this study provide more information in the role of MIF in colitis.

Animals↗
PubMed2006

Overexpression of the oncoprotein prothymosin alpha triggers a p53 response that involves p53 acetylation.

Activation of the tumor suppressor protein p53 is a critical cellular response to various stress stimuli and to inappropriate activity of growth-promoting proteins, such as Myc, Ras, E2F, and beta-catenin. Protein stability and transcriptional activity of p53 are modulated by protein-protein interactions and post-translational modifications, including acetylation. Here, we show that inappropriate activity of prothymosin alpha (PTMA), an oncoprotein overexpressed in human cancers, triggers a p53 response. Overexpression of PTMA enhanced p53 transcriptional activity in reporter gene assays for p53 target gene promoters hdm2, p21, and cyclin G. Overexpressed PTMA resulted in increased mRNA and protein levels for endogenous p53 target genes, hdm2 and p21, and in growth suppression. In contrast, reduction of endogenous PTMA through RNA interference decreased p53 transcriptional activity. Histone acetyltransferases (HATs) act as p53 coactivators and acetylate p53. PTMA, known to interact with HATs, led to increased levels of acetylated p53. PTMA did not increase the transcriptional activity of an acetylation-deficient p53 mutant, suggesting that p53 acetylation is an indispensable part of the p53 response to PTMA. Chromatin immunoprecipitation assays showed that excess PTMA associates with the p21 promoter and results in increased levels of acetylated p53 at the p21 promoter. Our findings indicate that overexpressed PTMA elicits a p53 response that involves p53 acetylation.

Acetylation↗
PubMed2006

The pharmacodynamic effect of omeprazole 10 mg and 20 mg once daily in patients with nonerosive reflux disease in Japan.

BACKGROUND: To evaluate the pharmacodynamic effect, efficacy, and safety of omeprazole 10 mg and 20 mg once daily in patients with nonerosive reflux disease (NERD) in Japan. METHODS: A total of 37 patients were randomized to omeprazole 10 mg or omeprazole 20 mg once daily for 4 weeks. Eligible patients had a history of moderate-to-severe heartburn for 2 days or more per week during the last 1 month or longer prior to the study screening, grade M or grade N on Hoshihara's modification of the Los Angeles classification (i.e., no sign of mucosal break on esophagogastroduodenoscopy), and heartburn episodes for 2 days or more per week during the last week of the observation period while taking antacids. Ambulatory 24-h intraesophageal pH was monitored on the day before treatment and on the last day of treatment. The occurrence of a heartburn episode was recorded during pH monitoring. The primary endpoint was the change in the percentage of time with intraesophageal pH < 4 during the 24-h period before and after omeprazole treatment. RESULTS: Both omeprazole 10 mg and omeprazole 20 mg once daily reduced the percentage of time with intraesophageal pH < 4. The percentage reduction in time with intraesophageal pH < 4 after treatment with omeprazole was associated with a reduced number of heartburn episodes. Patients with grade M or grade N esophagus had similar pH profiles and NERD characteristics (e.g., pH holding time, symptom index) and comparable responses to omeprazole. No serious, drug-related adverse events were reported. CONCLUSIONS: Omeprazole 10 mg or 20 mg reduces the percentage of time with intraesophageal pH < 4, is efficacious, and is well tolerated in patients with NERD in Japan, regardless of the patient's endoscopic classification.

Adult↗
PubMed2006

Histologic results of EMR for esophageal lesions diagnosed as high-grade intraepithelial squamous neoplasia by endoscopic biopsy.

BACKGROUND: Biopsy specimens obtained from esophageal lesions detected in endoscopic screening with iodine staining have often been diagnosed as high-grade intraepithelial squamous neoplasia (WHO 2000). However, a management strategy for such lesions has not been established. The purpose of this study was to perform EMR for such lesions and to determine the actual tumor stage in patients with complete resection and the outcomes after EMR. PATIENTS: During the study period, 51 patients were found to have esophageal lesions diagnosed as high-grade intraepithelial squamous neoplasia by using endoscopic iodine staining in biopsy specimens. All of the patients underwent EMR, and resected specimens were reviewed microscopically. RESULTS: Histologic examination of totally resected specimens revealed that 12 (23.5%) of the 51 patients had tumor invasion of the lamina propria mucosae and that 4 (7.8%) had tumor invasion of the muscularis mucosae. The remaining 35 patients (68.6%) were confirmed to have high-grade intraepithelial squamous neoplasia. The invasive focus in all of the 16 lesions of invasive squamous-cell carcinoma was surrounded by high-grade intraepithelial squamous neoplasia. After a median of 23 months of follow-up, there were two recurrences, and those patients required second EMR. CONCLUSIONS: Histologic results suggested that high-grade intraepithelial squamous neoplasia of the esophagus has characteristics of carcinoma in the preinvasive stage. EMR should be performed for esophageal lesions diagnosed by endoscopic biopsy as high-grade intraepithelial squamous neoplasia, not only because of its probable malignant potential but also because more than 30% of such lesions are actually invasive carcinoma.

Aged↗
PubMed2006

Endoscopic submucosal dissection for treatment of early stage hypopharyngeal carcinoma.

BACKGROUND: Early detection of hypopharyngeal carcinoma is increasingly possible and patients with such early lesions can be treated with endoscopic resection. OBJECTIVE: To identify the optimal relationship between the mucosal defect of the hypopharynx and malfunction of the hypopharynx after endoscopic resection of early hypopharyngeal carcinoma. DESIGN: Case series. SETTING: Referral center in Japan. PATIENTS: Four patients with early-stage squamous cell carcinoma of the hypopharynx underwent endoscopic submucosal dissection (ESD). By using ESD, an accurate incision line close to the tumor margin could be confirmed while performing treatment. ESD was performed with a small-caliber-tip transparent hood (ST-hood) to open the incision line for better visualization of the submucosa. MAIN OUTCOME MEASUREMENTS: Feasibility of en bloc resection, complications, and recurrence after ESD. RESULTS: No early or late complications due to treatment occurred in the patients. Histological examination of resected specimens revealed that 2 patients had carcinoma in situ and 2 patients had tumor invasion of the subepithelium. There was no local recurrence or distant metastasis in any of the patients during the follow-up period (3-14 months). CONCLUSIONS: We consider that ESD is the optimal method for endoscopic resection not only because it enables an en bloc resected specimen to be obtained but also because it can prevent removal of excess mucosa of the hypopharynx, which is a very narrow and important organ related to swallowing and speech.

Aged↗
PubMed2006

Design and planned analyses of an ongoing randomized trial assessing the preventive effect of Helicobacter pylori eradication on occurrence of new gastric carcinomas after endoscopic resection.

BACKGROUND: A causal relationship between Helicobacter pylori infection and gastric cancer has been established. A nonrandomized study has shown eradication of H. pylori after endoscopic resection (ER) of early gastric cancer inhibits development of new carcinomas. SUBJECTS AND METHODS: Eligible subjects are patients with H. pylori infection who are newly diagnosed with early gastric cancer and plan to have ER or who are in the post-resection follow-up phase after ER time of enrollment. Patients are randomly allocated to the eradication or the control arms (no eradication and standard of care). Patients will be evaluated by endoscopy at 0.5, 1, 2, and 3 years after randomization. Diagnosis of a new carcinoma at another site of the stomach is defined as primary endpoint, and recurrence of tumors at the resection site as a secondary endpoint. In addition to intention-to-treat and per-protocol analyses using proportional hazards models, time to recurrence will be compared between treatment and control using multiple logistic regression analyses. In the latter two situations, the models will be adjusted for the factors exerting significant influences on the results. RESULTS: Five hundred and forty-two subjects have been enrolled into the study and are being followed-up. CONCLUSIONS: This study will have the statistical power to demonstrate whether H. pylori eradication therapy exerts any clinically relevant inhibitory effects on occurrence or recurrence of gastric cancer. In addition, it will be able to test the hypothesis that H. pylori infection is a promoter in gastric carcinogenesis.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2005

Real-time monitoring of a digestive tract marker to reduce adverse effects of moving organs at risk (OAR) in radiotherapy for thoracic and abdominal tumors.

PURPOSE: To evaluate the feasibility of real-time monitoring of a fiducial marker in/near the digestive tract and to analyze the motion of organs at risk to determine a reasonable internal margin. METHODS AND MATERIALS: We developed two methods to insert a fiducial marker into/near the digestive tract adjacent to the target volume. One method involves an intraoperative insertion technique, and the other involves endoscopic insertion into the submucosal layer of the normal digestive tract. A fluoroscopic real-time tumor-tracking radiotherapy system was used to monitor the marker. RESULTS: Fourteen markers (2 in the mediastinum and 12 in the abdomen) were implanted intraoperatively in 14 patients with no apparent migration. Seventeen of 20 markers (13/14 in the esophagus, 1/2 in the stomach, and 3/4 in the duodenum) in 18 patients were implanted using endoscopy without dropping. No symptomatic adverse effects related to insertion were observed. The mean/standard deviation of the range of motion of the esophagus was 3.5/1.8, 8.3/3.8, and 4.0/2.6 mm for lateral, craniocaudal and anteroposterior directions, respectively, in patients with intrafractional tumor motion less than 1.0 cm. CONCLUSION: Both intraoperative and endoscopic insertions of a fiducial marker into/near the digestive tract for monitoring of organs at risk were feasible. The margin for internal motion can be individualized using this system.

Abdominal Neoplasms↗
PubMed2005

In vitro induction of resistance to metronidazole, and analysis of mutations in rdxA and frxA genes from Helicobacter pylori isolates.

In clinical Helicobacter pylori isolates, metronidazole resistance has been associated with mutations in the rdxA and frxA genes. The aim of this study was to examine the role of the rdxA and frxA genes after the in vitro induction of metronidazole resistance. A total of five suscep-tible H. pylori isolates were initially exposed to different subinhibitory metronidazole concentrations to induce in vitro resistance to metronidazole. Susceptible and resistant strains after the in vitro induction of resistance were examined to evaluate mutations of the rdxA and frxA genes by sequence analysis. After the in vitro induction of resistance, analysis revealed that two and four susceptible strains developed resistance when cultured with 0.3 microg/ml and 0.6 microg/ml of metronidazole, respectively. Before and after the induction of resistance, none of the susceptible strains that developed low and moderate levels of resistance presented any mutation in either of the evaluated genes, whereas strains with high-level metronidazole resistance contained a simple mutation of the frxA gene, but no specific changes in the rdxA gene. Strains with moderate-level resistance contained both single and multiple mutations of rdxA and frxA, respectively, and the low-level-metronidazole-resistant strain contained a single mutation in the frxA gene, without any significant change in the rdxA gene. In this study, the strains that developed resistance were mainly associated with mutations of the frxA gene, suggesting the possibility that inactivation of this gene could originate metronidazole resistance. The results after the in vitro induction of resistance to metronidazole suggested the presence of additional metronidazole resistance mechanisms, other than mutations of the rdxA and/or frxA genes.

Anti-Infective Agents↗
PubMed2005

Geranylgeranylacetone protects mice from dextran sulfate sodium-induced colitis.

OBJECTIVE: Geranylgeranylacetone (GGA) has recently been reported to induce heat shock protein (HSP) 70, which has a protective function against inflammation. We investigated the therapeutic effects of oral administration of GGA on dextran sulfate sodium (DSS)-induced colitis in mice. MATERIALS AND METHODS: BALB/c mice were given 3% DSS solution orally for 7 days to induce colitis. The disease activity of colitis was assessed clinically every day, and histology in the colon was evaluated at 7 days post-DSS. The levels of myeloperoxidase (MPO) activity, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma in the colon tissues were also examined. In addition, expression of HSPs 25, 40, 70 and 90 in the colon tissue was determined by Western blot analysis. Mice were orally administered GGA (50-500 mg/kg) when treatment of DSS started. RESULTS: It was found that GGA significantly reduced the clinical severity of colitis and suppressed the levels of MPO activity, TNF-alpha and IFN-gamma induced by DSS in the colon. On the other hand, GGA enhanced the expression of HSP70 in the colon of mice given DSS. CONCLUSIONS: Taken together, these results suggest that GGA is a new anti-inflammatory drug that could be useful in the treatment of colitis such as inflammatory bowel disease.

Administration, Oral↗
PubMed2005

Polaprezinc (N-(3-aminopropionyl)-L-histidinato zinc) ameliorates dextran sulfate sodium-induced colitis in mice.

OBJECTIVE: Polaprezinc (N-(3-Aminopropionyl)-L-histidinato zinc), an anti-ulcer drug, has been reported to have an anti-inflammatory action in several inflammatory diseases. The aim of this study was to investigate the effect of polaprezinc on dextran sulfate (DSS)-induced colitis in mice. MATERIAL AND METHODS: Mice with colitis induced by DSS were intrarectally treated with polaprezinc (15 mg/kg) or zinc sulfate (7.5 mg/kg) every day after the administration of DSS for 7 days. Disease activity index (DAI) and histological tissue damage were assessed. Levels of myeloperoxidase (MPO) activity, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma in the colon were measured. Expression of heat shock protein (HSP) 25 and HSP70 in the colon was analyzed by Western blot analysis. RESULTS: DAI and histological scores were remarkably reduced in polaprezinc-treated mice with DSS-induced colitis. Polaprezinc suppressed the increase of MPO activity and the production of TNF-alpha and IFN-gamma in the colon tissues of mice with DSS-induced colitis. Expression of HSP25 and HSP70 was remarkably up-regulated in the colon tissues of polaprezinc-treated mice during DSS treatment. CONCLUSIONS: Polaprezinc suppresses DSS-induced colitis in mice, partly through inhibition of production of pro-inflammatory cytokine, suppression of neutrophils accumulation and cytoprotection by overexpression of HSPs. Polaprezinc could be useful in the treatment of inflammatory bowel diseases.

Analysis of Variance↗