IgA腎症患者の腎生検組織における老化関連因子の発現に関する検討

内容の要旨 , 審査の要旨広島大学(Hiroshima University)博士(医学)Doctor of Philosophy in Medical Sciencedoctora

<Reports on the Nineteenth Annual Meeting of the Tsukuba English Linguistic Society> A Semantic Approach to Verbal Prefixation : With Special Reference to Prefix Over

In this joint reaearch, we are concerned with the words which have the form of "over- + V". The prefix has two senses: one is spatial/temporal sense, and the other is an "excessive" sense. Specifically, we focus on the later case. The excessive over- is notable for some grammatical phenomena. ..

Expression-Based Genome-Wide Association Study Links Vitamin D-Binding Protein With Autoantigenicity in Type 1 Diabetes.

Type 1 diabetes (T1D) is caused by autoreactive T cells that recognize pancreatic islet antigens and destroy insulin-producing β-cells. This attack results from a breakdown in tolerance for self-antigens, which is controlled by ectopic antigen expression in the thymus and pancreatic lymph nodes (PLNs). The autoantigens known to be involved include a set of islet proteins, such as insulin, GAD65, IA-2, and ZnT8. In an attempt to identify additional antigenic proteins, we performed an expression-based genome-wide association study using microarray data from 118 arrays of the thymus and PLNs of T1D mice. We ranked all 16,089 protein-coding genes by the likelihood of finding repeated differential expression and the degree of tissue specificity for pancreatic islets. The top autoantigen candidate was vitamin D-binding protein (VDBP). T-cell proliferation assays showed stronger T-cell reactivity to VDBP compared with control stimulations. Higher levels and frequencies of serum anti-VDBP autoantibodies (VDBP-Abs) were identified in patients with T1D (n = 331) than in healthy control subjects (n = 77). Serum vitamin D levels were negatively correlated with VDBP-Ab levels in patients in whom T1D developed during the winter. Immunohistochemical localization revealed that VDBP was specifically expressed in α-cells of pancreatic islets. We propose that VDBP could be an autoantigen in T1D

Identification of Sorbitol Transporters Expressed in the Phloem of Apple Source Leaves

Sorbitol is a major photosynthetic product and a major phloem-translocated component in Rosaceae (e.g. apple, pear, peach, and cherry). We isolated the three cDNAs, MdSOT3, MdSOT4, and MdSOT5 from apple (Malus domestica) source leaves, which are homologous to plant polyol transporters. Yeasts transformed with the MdSOTs took up sorbitol significantly. MdSOT3- and MdSOT5-dependent sorbitol uptake was strongly inhibited by xylitol and myo-inositol, but not or only weakly by mannitol and dulcitol. Apparent Km values of MdSOT3 and MdSOT5 for sorbitol were estimated to be 0.71mM and 3.2mM, respectively. The protonophore, carbonyl cyanide m-chlorophenylhydrazone (CCCP), strongly inhibited the sorbitol transport. MdSOT3 was expressed specifically in source leaves, whereas MdSOT4 and MdSOT5 were expressed in source leaves and also in some sink organs. MdSOT4 and MdSOT5 expressions were highest in flowers. Fruits showed no or only weak MdSOT expression. Although MdSOT4 and MdSOT5 were also expressed in immature leaves, MdSOT expressions increased with leaf maturation. In addition, in situ hybridization revealed that all MdSOTs were expressed to high levels in phloem of minor veins in source leaves. These results suggest that these MdSOTs are involved in sorbitol loading in Rosacea

Validity and Reliability of the Japanese Version of the 12-item Self-administered World Health Organization Disability Assessment Schedule (WHODAS) 2.0 in Patients with Schizophrenia

It is necessary to assess functional impairment when treating schizophrenia. The World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) has been adopted as a measure of functional disability in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. This study was a secondary analysis from a cross-sectional study of health-related behaviors among patients with schizophrenia. We examined the validity and reliability of the Japanese version of the 12-item WHODAS 2.0 when self-administered by such patients. Participants were 350 outpatients with schizophrenia from a psychiatric hospital. The standard six-factor structure of the WHODAS 2.0 showed a good fit for these participants. The Cronbach’s alpha coefficient was 0.858, showing good internal consistency. The WHODAS 2.0 showed moderate correlations with the modified Global Assessment of Functioning and Kessler 6 scales (r=−0.434 and 0.555, respectively). The results of this study show that the Japanese version of the 12-item self-administered WHODAS 2.0 has good internal consistency and convergent validity among patients with schizophrenia. Further exploration of the usefulness of WHODAS 2.0 in clinical settings is needed

Synthetic study directed toward novel multi-linked heterocycles

金沢大学大学院自然科学研究科生理活性物質科学金沢大学薬学部2-Amino-4-(1-methylindol-3-yl)thiazole (11c) has a characteristic nucleophilic nature at the 5-position and add to the 4-position of acetylpyridinium acetate (13) producing 2-acetylamino-5-(1-acetyl-1,4-dihydropyridin-4-yl)-4-(1-methylindol-3-yl) thiazole (1c). Its structure was established by X-ray single crystallographic analysis. Applying the results, simple syntheses of the related tris- (1a-b and 2-8) and tetrakis-linked heterocycles (9) were achieved

Syntheses of (±)-clavicipitic acid and its derivatives

金沢大学大学院自然科学研究科生理活性物質科学金沢大学薬学

Suzaku Observation of the Metallicity in the Interstellar Medium of NGC 4258

The Suzaku X-ray satellite observed the nearby spiral galaxy NGC 4258 for a total good exposure time of 100 ks. We present an analysis of the Suzaku XIS data, in which we confirm that the 0.5--2 keV spectra of the interstellar medium (ISM) are well-represented by a two-temperature model. The cool and hot ISM temperatures are 0.23+-0.02 and 0.59 +-0.01 keV, respectively. Suzaku's excellent spectral sensitivity enables us to measure the metal abundances of O, Ne, Mg, Si and Fe of the ISM for the first time. The resultant abundance pattern of O, Mg, Si, and Fe is consistent with that of the new solar abundance table of Lodders (2003), rather than Anders & Grevesse (1989). This suggests that the metal enrichment processes of NGC 4258 and of our Galaxy are similar.Comment: 9 pages, 4 figure

Cancer preventive agents 9. Betulinic acid derivatives as potent cancer chemopreventive agents

C-3 Esterifications of betulinic acid (BA, 1) and its A-ring homolog, ceanothic acid (CA, 2), were carried out to provide sixteen terpenoids, 4-19, including nine new compounds (4-12). All synthesized compounds were evaluated in an in vitro antitumor-promoting assay using the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. Among them, compounds 4-6, 11-14, 16, and 17 displayed remarkable inhibitory effects of EBV-EA activation. BA analog 6, which contains a prenyl-like group, showed the most potent inhibitory effect (100, 76, 37, and 11% inhibition of EBA activation at 1000, 500, 100 and 10 mol ratio/TPA, respectively, with IC50 value of 285 mol ratio/32pmol TPA). Compound 6 merits further development as a cancer preventive agent