京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13069号 / 論医博第2124号 / 新制||医||1019(附属図書館) / 33220 / 京都大学大学院医学研究科医学専攻 / (主査)教授 小川 修, 教授 篠原 隆司, 教授 斎藤 通紀 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Motility of the small intestine is a result of complex neurochemical and hormonal interactions within the intestine. The net motility (contraction) of the intestine is a balance of the influences from the central nervous system, enteric nervous system and hormonal changes in the body. Recently, the discovery of several peptide neurotransmitters common to the brain and the intestine has stimulated new research into the influence of these novel neurotransmitter candidates on intestinal motility at the level of the enteric (intestinal) nervous system. The present studies examined the contractile actions of three families of peptides, the opioids, tachykinins and motilin. Each of these peptide groups has been localized in the intestine, and suggested to function in the control of intestinal motility. The peptides were administered by intraarterial injection to isolated segments of canine small intestine and the resulting contractile activity measured. The results of these experiments demonstrate that all of these peptides may elicit contractile activity of the intestine in very low doses. These actions were further examined, using pharmacological antagonists, to determine the mechanism of action and the receptor types involved in the contractile actions. The opioid peptide induced responses were found to be mediated by two receptor types, mu and delta, located on the enteric nerve and smooth muscle, respectively. Similarly, the tachykinin induced contractions were also found to be due to actions on two receptor types, SP-P and SP-K, located on the nerve and muscle layers, respectively. These data suggest that the opioids and tachykinins may have multiple functions in the intestine dependent on the site of action and the receptor type involved in the response. Administration of motilin induced long-lasting contractile patterns in the intestine. The results also suggest that the actions of motilin are mediated by intermediate neurons of the enteric plexes which synapse on terminal cholinergic motor neurons.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20671号 / 医博第4281号 / 新制||医||1024(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 万代 昌紀, 教授 小川 修, 教授 溝脇 尚志 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 新制・課程博士 / 博士(理学) / 甲第24452号 / 理博第4951号 / 新制||理||1707(附属図書館) / 京都大学大学院理学研究科生物科学専攻 / (主査)教授 高橋 淑子, 准教授 佐藤 ゆたか, 教授 中務 真人 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

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In this thesis, the relationships among oesophageal motility, bolus clearance and sensory perception of oesophageal stimuli in patients with several dysphagia syndromes were investigated. The work is divided into the following major sections: 1) Current advances in the application of impedance and its utility in distinguishing clearance characteristics between primary and secondary peristalsis; 2) The advances in our understanding of peristaltic motor characteristics, oesophageal bolus clearance and symptom perception in dysphagia syndromes; 3) Peristaltic dysfunction, impaired bolus clearance and symptom perception in gastro-oesophageal reflux disease (GORD) and in patients with globus; 4) TRPV1 expression in oesophageal mucosa in patients with GORD. The main findings from this work are: 1) Secondary peristalsis is less effective as primary peristalsis regarding esophageal transit and clearance of a liquid bolus. 2) In patients with non-obstructive dysphagia (NOD), bolus clearance by both morphologically normal and aberrant secondary peristaltic sequences is impaired. 3) Although, when compared with healthy controls, patients with NOD have a higher prevalence of non-specifically abnormal motor patterns, there is a poor correlation between dysphagia and oesophageal dysmotility. 4) Whereas manometry identified motility abnormalities in one quarter of patients with GORD, impedance demonstrated that the majority of these patients, as well as some patients with normal manometry, had defective bolus clearance. 5) Although patients with erosive GORD have delayed oesophageal bolus clearance, manometric characteristics in these patients are comparable to those seen in non-erosive reflux disease (NERD). These findings are compatible with the hypothesis that abnormal oesophageal bolus clearance may reflect a continuum of dysfunction secondary to increasing oesophageal mucosal damage. 6) Patients with globus are characterized by oesophageal visceral hypersensitivity and aberrant viscerosomatic referral of mechanical and electrical stimuli to the oesophagus. These findings support the hypothesis that oesophageal hypersensitivity with associated viscerosomatic referral patterns are an important pathogenetic mechanism for globus. 7) Patients with erosive GORD exhibit greater gene expression of TRPV1 in oesophageal mucosa when compared with NERD or healthy controls. These findings support the hypothesis that chronic inflammation may lead to the release of mediators which may modulate function of primary sensory neurons.

In this thesis, the relationships among oesophageal motility, bolus clearance and sensory perception of oesophageal stimuli in patients with several dysphagia syndromes were investigated. The work is divided into the following major sections: 1) Current advances in the application of impedance and its utility in distinguishing clearance characteristics between primary and secondary peristalsis; 2) The advances in our understanding of peristaltic motor characteristics, oesophageal bolus clearance and symptom perception in dysphagia syndromes; 3) Peristaltic dysfunction, impaired bolus clearance and symptom perception in gastro-oesophageal reflux disease (GORD) and in patients with globus; 4) TRPV1 expression in oesophageal mucosa in patients with GORD. The main findings from this work are: 1) Secondary peristalsis is less effective as primary peristalsis regarding esophageal transit and clearance of a liquid bolus. 2) In patients with non-obstructive dysphagia (NOD), bolus clearance by both morphologically normal and aberrant secondary peristaltic sequences is impaired. 3) Although, when compared with healthy controls, patients with NOD have a higher prevalence of non-specifically abnormal motor patterns, there is a poor correlation between dysphagia and oesophageal dysmotility. 4) Whereas manometry identified motility abnormalities in one quarter of patients with GORD, impedance demonstrated that the majority of these patients, as well as some patients with normal manometry, had defective bolus clearance. 5) Although patients with erosive GORD have delayed oesophageal bolus clearance, manometric characteristics in these patients are comparable to those seen in non-erosive reflux disease (NERD). These findings are compatible with the hypothesis that abnormal oesophageal bolus clearance may reflect a continuum of dysfunction secondary to increasing oesophageal mucosal damage. 6) Patients with globus are characterized by oesophageal visceral hypersensitivity and aberrant viscerosomatic referral of mechanical and electrical stimuli to the oesophagus. These findings support the hypothesis that oesophageal hypersensitivity with associated viscerosomatic referral patterns are an important pathogenetic mechanism for globus. 7) Patients with erosive GORD exhibit greater gene expression of TRPV1 in oesophageal mucosa when compared with NERD or healthy controls. These findings support the hypothesis that chronic inflammation may lead to the release of mediators which may modulate function of primary sensory neurons.

Thesis (M.S.)--State University of New York at Binghamton, Department of Systems Science and Industrial Engineering, Thomas J. Watson School of Engineering and Applied Science, 2007. / Includes bibliographical references.

Thesis (Ph. D.)--University of Adelaide, 1986. / Includes bibliographical references.