Project/Area Number |
14570514
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Gastroenterology
|
Research Institution | Tokyo Women's Medical University |
Principal Investigator |
SAITOH Toshihito Tokyo Women's Medical University, Dept.Intenal Medicine, Assistant of Professor, 医学部, 講師 (50246609)
|
Co-Investigator(Kenkyū-buntansha) |
FUKUSHIMA Yasushi University of Tokyo, Dept.Internal Medicine, Resident, 医学部, 医員
TAKAHASHI Haruki Tokyo Women's Medical University, Dept.Intenal Medicine, Assistant of Professor, 医学部, 助手 (00246612)
OHSTUKA Hiroko Tokyo Women's Medical University, Dept.Intenal Medicine, Assistant of Professor, 医学部, 助手 (20307606)
|
Project Period (FY) |
2002 – 2003
|
Project Status |
Completed (Fiscal Year 2003)
|
Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
|
Keywords | gastroesophagal reflux / model mouse / pH monitoring / differential display |
Research Abstract |
The study was conducted to determine the changes in the squamous epithelial mucosa of oesophagus induced by a reflux of gastric acid to Barrett's oesophagus and oesophageal adenocarcinoma mainly from the viewpoint of the molecular mechanism. A mouse model for gastroesophageal acid reflux was prepared by dilating the gastroesophageal junction with a balloon or by anastomosing the oesophagus and the body of stomach. A pH monitor suitable for small animals was produced to establish a monitoring method using the pH monitor for the esophagus of the mice. Model mice for gastroesophageal reflux were bred with control mice up to 50 weeks after surgery. The pH changes in the mice were measured for 6-12 hours per day at intervals of several days to investigate the degree of gastric acid reflux. The pH of all the model mice was confirmed to be lower than 4 for 20-60% of the period of measurement. These mice were used as mouse models for gastroesophageal reflux. Oesophageal mucosa samples were removed at 7 time points, Week 2, 4, 6, 12, 30, 40 and 50 to examine them histopathologically. Even in Week 2, inflammatory cell infiltrates, abnormal glandular epithelial cell arrangement and a partial change in the duct were noted. RNA was extracted from samples of epithelial dysplasia removed in Week 12 or later and the difference in gene expression was examined in comparison with that of the oesophageal mucosa of the control mice using the differential display method, subtraction technique and cDNA array system. As the result, a difference in gene expression was detected in 7 specimens out of the 24 specimens.
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