DNAナノテクノロジーとDNAおよびDNAマイナーグルーブバインダーから成る複合体の原子レベルでの理解

京都大学新制・課程博士博士(理学)甲第25128号理博第5035号京都大学大学院理学研究科化学専攻(主査)准教授 板東 俊和, 教授 深井 周也, 教授 秋山 芳展学位規則第4条第1項該当Doctor of ScienceKyoto UniversityDGA

大動脈弁置換術における冷却血液心筋保護液を用いた順行性と逆行性冠灌流法の比較検討 : 術後の血行動態,左右心室機能および心筋逸脱酵素値からみた心筋保護効果の検索

A total of 50 patients undergoing isolated aortic valve replacement received either aortic root (anterograde 〔AGC〕: 25 patients) or coronary sinus (retrograde 〔RGC〕: 25 patients) perfusion with cold blood cardioplegic solution and were compared. The groups were similar with respect to age, sex, preoperative NYHA Class, aortic cross-clamping time and mean dose of cardioplegic solution. There were no significant differences in low cardiac output syndrome, rhythm disturbances and surgical mortality between the two groups. There were also no significant differences in right ventricular stroke work and postoperative cardiac enzymatic levels after surgery in the groups. However, there was a significant improvement in left ventricular stroke work after RGC over that after AGC and significantly more inotropic agents were required with aortic root perfusion than with coronary sinus delivery of cardioplegic solution. These findings indicate that coronary sinus perfusion has benefits not only as a surgical technique but also better preserves the hypertrophied left ventricle more effectively than aortic root perfusion

Nano–bio interaction between human immunoglobulin G and nontoxic, near-infrared emitting water-borne silicon quantum dot micelles

In recent years, the field of nanomaterials has exponentially expanded with versatile biological applications. However, one of the roadblocks to their clinical translation is the critical knowledge gap about how the nanomaterials interact with the biological microenvironment (nano–bio interactions). When nanomaterials are used as drug carriers or contrast agents for biological imaging, the nano–bio interaction-mediated protein conformational changes and misfolding could lead to disease-related molecular alterations and/or cell death. Here, we studied the conformation changes of human immunoglobulin G (IgG) upon interaction with silicon quantum dots functionalized with 1-decene, Pluronic-F127 (SiQD-De/F127 micelles) using UV-visible, fluorescence steady state and excited state kinetics, circular dichroism, and molecular modeling. Decene monolayer terminated SiQDs are accumulated inside the Pluronic F127 shells to form SiQD-De/F127 micelles and were shown to bind strongly with IgG. In addition, biological evaluation studies in cell lines (HeLa, Fibroblast) and medaka fish (eggs and larvae) showed enhanced uptake and minimal cytotoxicity. Our results substantiate that engineered QDs obviating the protein conformational changes could have adept bioefficacy

Bryosphere within an Antarctic moss pillar

第6回極域科学シンポジウム分野横断セッション：[IB2] 地球環境変動の解析と地球生命システム学の構築11月19日（木）　統計数理研究所 セミナー室1（D305

Chiral-odd transversity spin structure function h1(x)h_1(x) of the nucleon in a constituent quark model

We study the chiral-odd transversity spin-dependent quark distribution function $h_1 (x)$ of the nucleon in a constituent quark model. The twist-2 structure functions, $f_1(x)$, $g_1(x)$ and $h_1(x)$ are calculated within the diquark spectator approximation. Whereas an inequality $f_1(x) > h_1(x) > g_1(x)$ holds with the interaction between quark and diquark being scalar, the axial-vector effective quark-diquark interaction, which contributes to the $d$-quark distribution, does not lead to such a simple relation. We find that $h_1(x)$ for the $d$-quark becomes somewhat smaller than $g_1^d (x)$, when we fix the model parameter to reproduce known other structure functions. We also include corrections due to the non-trivial structure of the constituent quark, which is modeled by the Goldstone boson dressing. This improves agreements of $f_1(x)$ and $g_1(x)$ with experiments, and brings further reduction of $h_1^d(x)$ distribution. Consequences for semi-inclusive experiments are also discussed.Comment: 33 pages, latex with 13 figures, to appear in Nuclear Physics A, PostScript file is also available at http://WWW.physik.tu-muenchen.de/~ksuzuki/publication.htm

High-sensitivity c-reactive protein and gamma-glutamyl transferase levels are synergistically associated with metabolic syndrome in community-dwelling persons

<p>Abstract</p> <p>Background</p> <p>Metabolic syndrome (MetS) is associated with an increased risk of major cardiovascular events. Increased high-sensitivity C-reactive protein (hsCRP) levels are associated with MetS and its components. Changes in gamma-glutamyl transferase (GGT) levels in response to oxidative stress are also associated with MetS, and the levels could be modulated by hsCRP.</p> <p>Methods</p> <p>From a single community, we recruited 822 men (mean age, 61 ± 14 years) and 1,097 women (63 ± 12 years) during their annual health examination. We investigated whether increased hsCRP and GGT levels are synergistically associated with MetS and insulin resistance evaluated by Homeostasis of model assessment of insulin resistance (HOMA-IR).</p> <p>Results</p> <p>Of these subjects, 141 men (17.2%) and 170 women (15.5%) had MetS. Participants with MetS had a higher hsCRP and GGT level than those without MetS in both genders, and the HOMA-IR increased significantly in correlation with an increase in hsCRP and GGT. In men, the adjusted odds ratios (95% confidence interval) for MetS across tertiles of hsCRP and GGT were 1.00, 1.69 (1.01-2.80), and 2.13 (1.29-3.52), and 1.00, 3.26 (1.84-5.78) and 6.11 (3.30-11.3), respectively. In women, the respective corresponding values were 1.00, 1.54 (0.92-2.60), and 3.08 (1.88-5.06), and 1.00, 1.70 (1.04-2.79) and 2.67 (1.66-4.30). The interaction between increased hsCRP and GGT was a significant and independent determinant for MetS and insulin resistance in both genders.</p> <p>Conclusions</p> <p>These results suggested that higher CRP and GGT levels were synergistically associated with MetS and insulin resistance, independently of other confounding factor in the general population.</p

Association between fasting plasma glucose and high-sensitivity C-reactive protein: gender differences in a Japanese community-dwelling population

<p>Abstract</p> <p>Background</p> <p>High sensitivity C-reactive protein (hsCRP) is an acute phase reactant and a sensitive marker of inflammation. Hyperglycemia can potentially promote the production of CRP. The aim of this study was to determine whether increased fasting plasma glucose (FPG) levels are associated with elevated hsCRP concentrations by gender.</p> <p>Methods</p> <p>We recruited 822 men (mean age, 61 ± 14 years) and 1,097 women (63 ± 12 years) during their annual health examination from a single community. We cross-sectionally examined whether FPG levels are associated with hsCRP concentrations, and whether this association is independent of gender, body mass index (BMI) and other components of the metabolic syndrome.</p> <p>Results</p> <p>In women only, hsCRP increased significantly and progressively with increasing FPG (r = 0.169, P < 0.001). The stepwise multiple linear regression analysis using hsCRP as an objective variable, adjusted for confounding factors as explanatory variables, showed that FPG as well as age, BMI, systolic blood pressure, high-density lipoprotein cholesterol (HDL-C), uric acid, and high molecular weight adiponectin were significantly associated with hsCRP in women, but not in men. There was significant gender interaction, and an increase in hsCRP levels that was greater in women with BMI ≥ 25 kg/m²and higher FPG than in men.</p> <p>Conclusions</p> <p>These results suggested that hsCRP levels increase continuously across the FPG spectrum starting from the lowest FPG in both men and women. However, increase in hsCRP levels was greater in women than men.</p

Low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio is the best surrogate marker for insulin resistance in non-obese Japanese adults

<p>Abstract</p> <p>Background</p> <p>The aim of the present study was to examine how lipid profiles are associated with insulin resistance in Japanese community-dwelling adults.</p> <p>Methods</p> <p>This cross-sectional study included 614 men aged 58 ± 14 (mean ± standard deviation; range, 20-89) years and 779 women aged 60 ± 12 (range, 21-88) years. The study sample were 1,042 (74.8%) non-obese (BMI < 25.0 kg/m²) and 351 (25.2%) overweight (BMI ≥ 25 kg/m²) subjects. Insulin resistance was defined by homeostasis model assessment of insulin resistance (HOMA-IR) of at least 2.5. The areas under the curve (AUC) of the receiver operating characteristic curves (ROC) were used to compare the power of these serum markers.</p> <p>Results</p> <p>In non-obese subjects, the best marker of insulin resistance was low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio of 0.74 (95% confidence interval (CI), 0.66-0.80). The HDL-C, triglyceride (TG)/HDL-C ratio, and non-HDL-C also discriminated insulin resistance, as the values for AUC were 0.31 (95% CI, 0.24-0.38), 0.69 (95% CI, 0.62-0.75) and 0.69 (95% CI, 0.62-0.75), respectively. In overweight subjects, the AUC for TG and TG/HDL-C ratio were 0.64 (0.58-0.71) and 0.64 (0.57-0.70), respectively. The optimal cut-off point to identifying insulin resistance for these markers yielded the following values: TG/HDL-C ratio of ≥1.50 and LDL-C/HDL-C ratio of ≥2.14 in non-obese subjects, and ≥2.20, ≥2.25 in overweight subjects. In non-obese subjects, the positive likelihood ratio was greatest for LDL-C/HDL-C ratio.</p> <p>Conclusion</p> <p>In non-obese Japanese adults, LDL-C/HDL-C ratio may be the best reliable marker of insulin resistance.</p

A Role of Suppressor of Cytokine Signaling 3 (SOCS3/CIS3/SSI3) in CD28-mediated Interleukin 2 Production

Suppressor of cytokine signaling (SOCS)3 has been characterized as a negative feedback regulator in cytokine-mediated Janus kinase signal transducer and activator of transcription signaling. However, this study shows that T cells from transgenic mice expressing SOCS3 exhibit a significant reduction in interleukin (IL)-2 production induced by T cell receptor cross-linking when T cells are costimulated with CD28. Decreased protein expression in SOCS3+/− mice enhanced CD28-mediated IL-2 production, clearly indicating the correlation between expression level of SOCS3 and IL-2 production ability. The SOCS3 protein interacted with phosphorylated CD28 through its SH2 domain but not the kinase inhibitory region. In addition, a point mutation in the SOCS3 SH2 domain attenuated the inhibition of CD28 function in IL-2 promoter activation. Committed T helper (Th)2 cells exclusively expressed SOCS3 and production of Th2 cytokines, such as IL-4 and IL-5, was much less dependent on CD28 costimulation compared with interferon γ and IL-2 production in Th1 cells. Consistent with this notion, the expression level of SOCS3 in early T cell activation influenced the ability of IL-2 production induced by CD28 costimulation. Therefore, the SOCS3 may play an alternative role in prohibiting excessive progression of CD28-mediated IL-2 production

Rab3a and Rab27b Expression in Nonfunctioning Pituitary Adenomas

Patients with nonfunctioning pituitary adenoma (NFPA) have normal circulating levels of anterior pituitary hormones. Here we examined the expression of exocytic trafficking regulators, Rab27b and Rab3a, in surgically resected pituitary adenoma tissues by immunohistochemical (IHC) analysis using anti-Rab27b and anti-Rab3a antibodies. Among the examined tissues, just over half of the null-cell adenomas and one-third of the gonadotropin-producing adenomas were immunonegative for both Rab27b and Rab3a. However, no Rab-negative samples were observed among the functioning adenomas. These results suggested that downregulated Rab protein expression in anterior pituitary endocrine cells could underlie, at least in part, the hormone-secretion defects of nonfunctioning adenoma cells. Rab27b, Rab3a, and their cellular regulators might therefore be promising pathological markers of patients with NFPA