デキストランとポリリジンから作成した生体適合性接着剤の分解スピードを変化させることによる、胸骨正中切開後の胸骨裏面の癒着防止性能に関する研究

京都大学新制・論文博士博士(医学)乙第13587号論医博第2307号新制||医||1070(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 安達 泰治, 教授 森本 尚樹, 教授 伊達 洋至学位規則第4条第2項該当Doctor of Medical ScienceKyoto UniversityDFA

Expression of Renin-Angiotensin System Components in the Taste Organ of Mice

The systemic renin-angiotensin system (RAS) is an important regulator of body fluid and sodium homeostasis. Angiotensin II (AngII) is a key active product of the RAS. We previously revealed that circulating AngII suppresses amiloride-sensitive salt taste responses and enhances the responses to sweet compounds via the AngII type 1 receptor (AT1) expressed in taste cells. However, the molecular mechanisms underlying the modulation of taste function by AngII remain uncharacterized. Here we examined the expression of three RAS components, namely renin, angiotensinogen, and angiotensin-converting enzyme-1 (ACE1), in mouse taste tissues. We found that all three RAS components were present in the taste buds of fungiform and circumvallate papillae and co-expressed with αENaC (epithelial sodium channel α-subunit, a salt taste receptor) or T1R3 (taste receptor type 1 member 3, a sweet taste receptor component). Water-deprived mice exhibited significantly increased levels of renin expression in taste cells (p < 0.05). These results indicate the existence of a local RAS in the taste organ and suggest that taste function may be regulated by both locally-produced and circulating AngII. Such integrated modulation of peripheral taste sensitivity by AngII may play an important role in sodium/calorie homeostasis

A case with giant right coronary artery aneurysm in a patient with Behçet's disease

Behçet's disease is a chronic, relapsing, multi-systemic inflammatory disorder characterized by recurrent orogenital aphthous ulcers, uveitis, and skin lesions. Vascular involvement affects the veins more commonly than the arteries of these patients. Arterial involvement may include aneurysm formation, occlusive disease, and stenosis, with the most common sites being the abdominal aorta and femoral and pulmonary arteries. Thus, coronary arterial involvement is very rare but can cause serious complications when it occurs. In this report, we present a 28-year-old male patient with Behçet's disease who developed a giant right coronary artery aneurysm with minimal cardiac manifestation of a recently developed slight palpitation. The patient underwent surgical repair. We present the results of cardiovascular imaging and histopathological examinations. Our case demonstrates the necessity of regular cardiovascular examination for patients with Behçet's disease, even for those without cardiac symptoms

Drinking Ice-Cold Water Reduces the Severity of Anticancer Drug-Induced Taste Dysfunction in Mice

Taste disorders are common adverse effects of cancer chemotherapy that can reduce quality of life and impair nutritional status. However, the molecular mechanisms underlying chemotherapy-induced taste disorders remain largely unknown. Furthermore, there are no effective preventive measures for chemotherapy-induced taste disorders. We investigated the effects of a combination of three anticancer drugs (TPF: docetaxel, cisplatin and 5-fluorouracil) on the structure and function of mouse taste tissues and examined whether the drinking of ice-cold water after TPF administration would attenuate these effects. TPF administration significantly increased the number of cells expressing apoptotic and proliferative markers. Furthermore, TPF administration significantly reduced the number of cells expressing taste cell markers and the magnitudes of the responses of taste nerves to tastants. The above results suggest that anticancer drug-induced taste dysfunction may be due to a reduction in the number of taste cells expressing taste-related molecules. The suppressive effects of TPF on taste cell marker expression and taste perception were reduced by the drinking of ice-cold water. We speculate that oral cryotherapy with an ice cube might be useful for prophylaxis against anticancer drug-induced taste disorders in humans

Genomic Sequencing Identifies ELF3 as a Driver of Ampullary Carcinoma

Ampullary carcinomas are highly malignant neoplasms that can have either intestinal or pancreatobiliary differentiation. To characterize somatic alterations in ampullary carcinomas, we performed whole-exome sequencing and DNA copy-number analysis on 60 ampullary carcinomas resected from clinically well-characterized Japanese and American patients. We next selected 92 genes and performed targeted sequencing to validate significantly mutated genes in an additional 112 cancers. The prevalence of driver gene mutations in carcinomas with the intestinal phenotype is different from those with the pancreatobiliary phenotype. We identified a characteristic significantly mutated driver gene (ELF3) as well as previously known driver genes (TP53, KRAS, APC, and others). Functional studies demonstrated that ELF3 silencing in normal human epithelial cells enhances their motility and invasion