Rationale: Eosinophils are “end cell” leucocytes, associated with allergy, asthma and helminthiasis. At sites of inflammation, eosinophils may modulate immune response through expression of the extra-hepatic tryptophan-catabolising enzyme, Indoleamine 2, 3-dioxygenase (IDO). Kynurenines, products of tryptophan cleavage, induce apoptosis of T-cells, including thymocytes. Eosinophils naturally home to the thymi in mammals. Thymus is a primary lymphoid organ, where T-cells develop and undergo selection. My hypothesis is that eosinophils homing to the thymi participate in T-cell development through their expression of IDO. Methods: Immunohistochemistry revealed eosinophils in thymic tissue. Immunocytochemistry and flow cytometry were used to locate IDO protein expression in the thymus particularly in thymic eosinophils. RT-PCR and real-time PCR determined the presence of IDO mRNA in the thymus. Results: thymic eosinophils express IDO and infiltrate compartments associated with negative selection. The highest IDO transcription correlated with the influx of eosinophils and prevalence of immature thymocytes. / Experimental Medicine

No description available.

This thesis describes the chemical investigation of three marine sponges from Antarctica and the total syntheses of natural products erebusinone (12) and its derivative, erebusinonamine (52). Investigation of the yellow Antarctic marine sponge Isodictya setifera resulted in the isolation of two secondary metabolites, purine analog (32) and 3-hydroxykynurenine (24). Chemical investigation of Isodictya setifera led to the isolation of six secondary metabolites which included 5-methyl-2-deoxycytidine (25), uridine (28), 2-deoxycytidine (31), homarine (37), hydroxyquinoline (33), 3-hydroxykynurenine (24). The latter two compounds were found to be intermediates of tryptophan catabolism in crustaceans. From the Antarctic marine sponge Isodictya antractica ceramide analog (39) was isolated and its chemical structure was assigned by a combination of spectroscopic and chemical analyses. Stereochemistry was determined by modified Mosher's method. Erebusinone (12), a yellow pigment isolated from the Antarctic marine sponge Isodictya erinacea has been implicated in molt inhibition and mortality against the Antarctic crustacean amphipod, Orchomene plebs, possibly serving as a precursor of a xanthurenic acid analog. Thought to act as a 3-hydroxykynurenine 24 mimic, erebusinone (12) may be involved chemical defense. This appears to be the first example in the marine realm of an organism utilizing tryptophan catabolism to modulate molting as a defensive mechanism. To further investigate the bioactivity and ecological role of erebusinone (12), the synthesis of this pigment was carried out in an overall yield of 44% involving seven steps which were economical and convenient. Erebusinonamine (52) was also similarly synthesized in eight steps with an overall yield of 45%.

京都大学 / 0048 / 新制・課程博士 / 博士(人間健康科学) / 甲第20296号 / 人健博第44号 / 新制||人健||4(附属図書館) / 京都大学大学院医学研究科人間健康科学系専攻 / (主査)教授 高桑 徹也, 教授 三谷 章, 教授 浅野 雅秀 / 学位規則第4条第1項該当 / Doctor of Human Health Sciences / Kyoto University / DFAM

Amino acids derived from the degradation of casein in cheese serve as precursors for the generation of key flavor compounds. Microbial degradation of tryptophan (Trp) is thought to promote formation of aromatic compounds that impart putrid fecal or unclean flavors in cheese, but pathways for their production have not been established. This study investigated tryptophan catabolism by Lactobacillus casei LC301 and LC202 and Lactobacillus helveticus CNRZ32 and LH212 cheese flavor adjuncts in carbohydrate starvation (pH 6.5, 30 or 37°C, no sugar) and cheese-like conditions (pH 5.2, 4% NaCl, 15°C, no sugar). Enzyme assays of cell-free extracts revealed both species of Lactobacillus catabolized tryptophan to indole lactic acid via indole pyruvic acid through transamination followed by dehydrogenation. Micellar electrokinetic capillary chromatography of culture supernatants showed these enzymes also catalyzed the reverse reactions, i.e., conversion of indole lactic acid to tryptophan. Tryptophan decarboxylase activity was detected in Lactobacillus cell-free extracts, but tryptamine was not detected in culture supernatants. Analysis of culture supernatants showed that tryptophan metabolism in Lactobacillus casei did not differ between the two conditions of incubation as it did in Lactobacillus helveticus LH212 and CNRZ32. Lactobacillus helveticus LH212, for example, did not catabolize Trp in carbohydrate starvation but did in cheese-like conditions. While cells of L. helveticus CNRZ32 did not catabolize Trp in either condition, they catabolized indole pyruvic acid to only Trp in carbohydrate starvation and to both Trp and indole lactic acid in cheese-like conditions. Micellar electrokinetic capillary chromatography of culture supernatants incubated under either starvation or cheese-like conditions showed Lactobacillus casei strains produced more indole lactic acid, and Lactobacillus helveticus strains favored tryptophan anabolic reactions. Based on the results obtained in this study, a putative pathway for the catabolism of tryptophan by lactobacilli in cheese is proposed.