Alimentary tract Group

Main Clinical Work
In clinical practice, our group is specialized in diseases of the gastrointestinal tract from the esophagus to the stomach and further to small and large intestine, as well as the pancreas and biliary tract. Our interests are focused on diagnosis and treatment particularly of inflammatory bowel disease (IBD) including ulcerative colitis and Crohn’s disease, tumors of the digestive tract including cancer of the esophagus, stomach, and large intestine, peptic ulcers of the stomach and duodenum. IBD is a general term for inflammatory diseases of the bowel of unknown etiology. Ulcerative colitis and Crohn’s disease are nonspecific inflammatory disease of the gastrointestinal tract of unknown etiology. They resemble each other in several aspects such as the age of susceptible patients, clinical features, and drug therapy. Recent clinical and basic studies have shown, however, that they can be considered diseases of different entities. Typical tumors of the digestive tract include cancer of the esophagus, stomach, and large intestine. Not only instrumental improvement of endoscopes, but also the expansion of dye-spraying endoscopy and magnifying endoscopy has made their early diagnosis considerably possible. In the assessment of extent of tumor penetration, endoscopic ultrasonography is introduced, and indications and limitations of endoscopic surgery have been examined. Ulcers of the stomach and duodenum are common diseases. Their pathogenesis has been attributed formerly to gastric acid and impaired mucosal defense mechanisms. In recent years, however, infection with Helicobacter pylori is shown involved in the pathogenesis. It has been confirmed that eradication of Helicobacter pylori effectively reduced recurrence. In addition, the study on its association with cancer and malignant lymphoma of the stomach has progressed. We have also tackled with second-line regimen for Helicobacter infection after failure of the Japanese standard triple therapy.

Research interests
Our group is broadly interested in gastrointestinal motility, mucosal immunity, and host-microbial interaction in health and disease. We have focused on the digestive motility in various gastrointestinal diseases. Utilizing animal models, we analyze the accommodation reflex in H. pylori associated gastritis and the gastrocolonic responses in irritable bowel syndrome. In addition, we have focused on the significance of ghrelin, which is an endogenous ligand for GHS-R and plays a key role in regulating food intake, in the gastrointestinal motility. As for the mucosal immunity, we have been investigating the pathogenesis of inflammatory disease.Å@Wiskott-Aldrich Syndrome Protein (WASP)-deficiency in mice leads to severe inflammatory bowel disease. This mouse is a novel mouse model for human ulcerative colitis. We are analyzing the therapeutic effects of appendectomy for WASPKO mice under the collaboration with Dr. Scott Snapper, Massachusetts General Hospital. Interestingly, several infectious enteric microbes utilize WASP family members to permit invasion of cells. For example, EPEC forms actin pedestals on the invaded cell surface, utilizing neural(N)-WASP and stimulates host cell signaling. We are now investigating the host signaling pathways activated by EPEC for their pathogenesis. Also, we have been interested in immune and inflammatory responses in esophageal mucosa of patients with GERD.

Staff
Yohei Mizuta, MD.; ymizuta@net.nagasaki-u.ac.jp
Fuminao Takeshima, MD., PhD.; ftake@net.nagasaki-u.ac.jp
Hajime Isomoto, MD.; hhisomot@net.nagasaki-u.ac.jp
Hirotoshi Fukuda
Kenichi Takamori
Naoyuki Yamaguchi
Haruhisa Machida
Maho Ikeda
Chen Shunzen

Publications in 2002
1) Isomoto H, Inoue K, Nishiyama T et al. Five-minute endoscopic urea breath test with 25 mg of 13C-urea for the diagnosis of Helicobacter pylori infection. Eur J Gastroenterol Hepatol 2002, 1093-100.
2) Yoshimura M, Isomoto H, Shikuwa S et al. A case of acute gastric mucosal lesions associated with Helicobacter heilmannii infection. Helicobacter 2002, 322-6.
3) Isomoto H, Inoue K, Mizuta Y et al. Validation of endoscopic 13C-urea breath test with nondispersive infrared spectrometric analysis in the management of Helicobacter pylori Infection. Hepatogastroenterology 2002, 322-6.
4) Isomoto H, Furusu H, Shin M et al. Enhanced expression of transcription factor E2F in Helicobacter pylori-infected gastric mucosa. Helicobacter 2002, 152-62.
5) Isomoto H, Hazama H, Shikuwa S et al. A case of haemorrhagic radiation proctitis: successful treatment with argon plasma coagulation. Eur J Gastroenterol Hepatol 2002, 901-4.
6) Isomoto H, Nishida Y, Fukuda H et al. Two cases of adult T-cell leukaemia/lymphoma with oesophageal involvement. Eur J Gastroenterol Hepatol. 2002; 14(4):449-452.
7) Ohnita K, Isomoto H, Mizuta Y, et al. Helicobacter pylori infection in patients with gastric involvement by adult T-cell leukemia/lymphoma. Cancer. 2002; 94(5):1507-16.