カラコルム出土1348年漢蒙碑文─嶺北省右丞郎中總管收糧記─

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副腎白質ジストロフィーの分子遺伝学研究並びに造血幹細胞移植による治療

学位の種別:課程博士University of Tokyo(東京大学

新発現の蒙漢合璧少林寺聖旨碑

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ソ連科学アカデミ-東洋学研究所レニングラード支部所蔵ウイグル文書二件

「内陸アジア言語の研究」第5号 (Studies on the Inner Asian Languages)NOTE: 松川節(訳

Prevalence of Hypertension, Diabetes Mellitus, and Dyslipidemia in Patients with Chronic Obstructive Pulmonary Disease

Recent studies have shown that chronic obstructive pulmonary disease (COPD) causes various extrapulmonary comorbidities. In addition, cardiovascular disease, the pathogenesis of which involves atherosclerosis, has been emphasized as a cause of mortality in patients with COPD. In the present study, we investigated the presence of classical risk factors for atherosclerosis in 183 patients with COPD. The prevalence of comorbidities (hypertension, diabetes mellitus [DM], and dyslipidemia) was investigated and compared with that in a general population. In patients with COPD, the prevalence of hypertension, DM, and dyslipidemia was 43.2%, 15.8%, and 25.7%, respectively, with the prevalence of DM and dyslipidemia significantly higher in patients than in the general population. Furthermore, there were significant differences in the prevalence of the three disorders in patients with COPD. For example, the prevalence of hypertension was significantly higher than that of diabetes mellitus in patients aged 60-69 years and higher than the prevalence of DM and dyslipidemia in patients aged ≥ 70 years. Regardless of age, hypertension was noted in the greatest number of patients. In conclusion, a high proportion of patients with COPD were found to have the classical risk factors for atherosclerosis. In particular, the prevalence of DM and dyslipidemia was significantly higher in COPD patients than in the general population

Enhanced in vivo osteogenesis by nanocarrier-fused bone morphogenetic protein-4

Purpose: Bone defects and nonunions are major clinical skeletal problems. Growth factors are commonly used to promote bone regeneration; however, the clinical impact is limited because the factors do not last long at a given site. The introduction of tissue engineering aimed to deter the diffusion of these factors is a promising therapeutic strategy. The purpose of the present study was to evaluate the in vivo osteogenic capability of an engineered bone morphogenetic protein-4 (BMP4) fusion protein. Methods: BMP4 was fused with a nanosized carrier, collagen-binding domain (CBD), derived from fibronectin. The stability of the CBD-BMP4 fusion protein was examined in vitro and in vivo. Osteogenic effects of CBD-BMP4 were evaluated by computer tomography after intramedullary injection without a collagen-sponge scaffold. Recombinant BMP-4, CBD, or vehicle were used as controls. Expressions of bone-related genes and growth factors were compared among the groups. Osteogenesis induced by CBD-BMP4, BMP4, and CBD was also assessed in a bone-defect model. Results: In vitro, CBD-BMP4 was retained in a collagen gel for at least 7 days while BMP4 alone was released within 3 hours. In vivo, CBD-BMP4 remained at the given site for at least 2 weeks, both with or without a collagen-sponge scaffold, while BMP4 disappeared from the site within 3 days after injection. CBD-BMP4 induced better bone formation than BMP4 did alone, CBD alone, and vehicle after the intramedullary injection into the mouse femur. -Bone-related genes and growth factors were expressed at higher levels in CBD-BMP4-treated mice than in all other groups, including BMP4-treated mice. Finally, CBD-BMP4 potentiated more bone formation than did controls, including BMP4 alone, when applied to cranial bone defects without a collagen scaffold. Conclusion: Altogether, nanocarrier-CBD enhanced the retention of BMP4 in the bone, thereby promoting augmented osteogenic responses in the absence of a scaffold. These results suggest that CBD-BMP4 may be clinically useful in facilitating bone formation

Genetic Analysis, Expression in Eschericia coli of Aconitase from Chemolithotrophic Acidithiobacillus thiooxidans

An aconitase from Acidithiobacillus thiooxidans was purified and characterized, and its gene was cloned. The cloned aconitase gene (acn) was expressed in Escherichia coli JM 109; aconitase activity was found in the cell extarct. The acn gene encodes a 646-amino acid polypeptide and is located upstream of the isocitrate dehydrogenase gene (icd). A. thiooxidans aconitase showes high sequence similar to pig heart aconitase and E.coli aconitase B. Twenty-five of twenty-seven active site residues assigned in pig heart aconitase are conserved in A. thiooxidans aconitase. The enzyme was purified by DEAE-Toyopearl 650M column chromatogrophy. The purified enzyme had an optimum pH of 7.5 and an optimum temperature of 60 C. Thermal inactivation studies of the purified enzyme revealed the enzyme activity to be uninfluenced after one hour incubation at 40 c. Enzyme activity was retained 100% after incubation of the enzyme at pH 6.0-9.0 for 60min. The A. thiooxidans aconitase was composed of a single polypeptide chain with a molecular mass of 66 kDa

A novel, visible light-induced, rapidly cross-linkable gelatin scaffold for osteochondral tissue engineering

Osteochondral injuries remain difficult to repair. We developed a novel photo-cross-linkable furfurylamine-conjugated gelatin (gelatin-FA). Gelatin-FA was rapidly cross-linked by visible light with Rose Bengal, a light sensitizer, and was kept gelled for 3 weeks submerged in saline at 37 degrees C. When bone marrow-derived stromal cells (BMSCs) were suspended in gelatin-FA with 0.05% Rose Bengal, approximately 87% of the cells were viable in the hydrogel at 24 h after photo-cross-linking, and the chondrogenic differentiation of BMSCs was maintained for up to 3 weeks. BMP4 fusion protein with a collagen binding domain (CBD) was retained in the hydrogels at higher levels than unmodified BMP4. Gelatin-FA was subsequently employed as a scaffold for BMSCs and CBD-BMP4 in a rabbit osteochondral defect model. In both cases, the defect was repaired with articular cartilage-like tissue and regenerated subchondral bone. This novel, photo-cross-linkable gelatin appears to be a promising scaffold for the treatment of osteochondral injury

MicroRNA-125b regulates the expression of aggrecanase-1 (ADAMTS-4) in human osteoarthritic chondrocytes

INTRODUCTION: Increased expression of aggrecanase-1 (ADAMTS-4) has emerged as an important factor in osteoarthritis (OA) and other joint diseases. This study aimed to determine whether the expression of ADAMTS-4 in human chondrocytes is regulated by miRNA. METHODS: MiRNA targets were identified using bioinformatics. Chondrocytes were isolated from knee cartilage and treated with interleukin-1 beta (IL-1β). Gene expression was quantified using TaqMan assays and protein production was determined by immunoblotting. Luciferase reporter assay was used to verify interaction between miRNA and target messenger RNA (mRNA). RESULTS: In silico analysis predicted putative target sequence of miR-125b on ADAMTS-4. MiR-125b was expressed in both normal and OA chondrocytes, with significantly lower expression in OA chondrocytes than in normal chondrocytes. Furthermore, IL-1β-induced upregulation of ADAMTS-4 was suppressed by overexpression of miR-125b in human OA chondrocytes. In the luciferase reporter assay, mutation of the putative miR-125b binding site in the ADAMTS-4 3'UTR abrogated the suppressive effect of miR125. CONCLUSIONS: Our results indicate that miR-125b plays an important role in regulating the expression of ADAMTS-4 in human chondrocytes and this identifies miR-125b as a novel therapeutic target in OA