ヒト角膜における細胞種特異的な遺伝子発現およびクロマチン構造解析

学位の種別: 課程博士審査委員会委員 : (主査)東京大学教授 佐藤 伸一, 東京大学准教授 鯉沼 代造, 東京大学講師 柳 靖雄, 東京大学講師 脇 裕典, 東京大学講師 柿木 章伸University of Tokyo(東京大学

Psychological factors that promote behavior modification by obese patients

<p>Abstract</p> <p>Background</p> <p>The weight-loss effect of team medical care in which counseling is provided by clinical psychologists was investigated in an university hospital obesity (OB) clinic. Nutritional and exercise therapy were also studied. In our previous study, we conducted a randomized, controlled trial with obese patients and confirmed that subjects who received counseling lost significantly more weight than those in a non-counseling group. The purpose of this study was to identify the psychological characteristics assessed by ego states that promote behavior modification by obese patients.</p> <p>Methods</p> <p>147 obese patients (116 females, 31 males; mean age: 45.9 ± 15.4 years) participated in a 6-month weight-loss program in our OB clinic. Their psychosocial characteristics were assessed using the Tokyo University Egogram (TEG) before and after intervention. The Wilcoxon signed rank test was used to compare weight and psychological factors before and after intervention. Multiple regression analysis was used to identify factors affecting weight loss.</p> <p>Results</p> <p>Overall, 101 subjects (68.7%) completed the program, and their data was analyzed. The subjects mean weight loss was 6.2 ± 7.3 kg (<it>Z </it>= 7.72, <it>p </it>< 0.01), and their mean BMI decreased by 2.4 ± 2.7 kg/m²(<it>Z </it>= 7.65, <it>p </it>< 0.01). Significant differences were observed for the Adult (A) ego state (0.68 ± 3.56, <it>Z </it>= 1.95, <it>p </it>< 0.05) and the Free Child (FC) ego state (0.59 ± 2.74, <it>Z </it>= 2.46, <it>p </it>< 0.01). The pre-FC ego state had a significant effect on weight loss (β = 0.33, <it>p </it>< 0.01), and a tendency for changes in the A ego state scores to affect weight loss (β = - 0.20, <it>p </it>= 0.06) was observed.</p> <p>Conclusion</p> <p>This study of a 6-month weight-loss program that included counseling by clinical psychologists confirmed that the A ego state of obese patients, which is related to their self-monitoring skill, and the FC ego state of them, which is related to their autonomy, were increased. Furthermore, the negative aspects of the FC ego state related to optimistic and instinctive characteristics inhibited the behavior modification, while the A ego state represented objective self-monitoring skills that may have contributed to weight loss.</p

Peptidyl prolyl isomerase Pin1-inhibitory activity of d-glutamic and d-aspartic acid derivatives bearing a cyclic aliphatic amine moiety

AbstractPin1 is a peptidyl prolyl isomerase that specifically catalyzes cis–trans isomerization of phosphorylated Thr/Ser-Pro peptide bonds in substrate proteins and peptides. Pin1 is involved in many important cellular processes, including cancer progression, so it is a potential target of cancer therapy. We designed and synthesized a novel series of Pin1 inhibitors based on a glutamic acid or aspartic acid scaffold bearing an aromatic moiety to provide a hydrophobic surface and a cyclic aliphatic amine moiety with affinity for the proline-binding site of Pin1. Glutamic acid derivatives bearing cycloalkylamino and phenylthiazole groups showed potent Pin1-inhibitory activity comparable with that of known inhibitor VER-1. The results indicate that steric interaction of the cyclic alkyl amine moiety with binding site residues plays a key role in enhancing Pin1-inhibitory activity

Surgical management of infants with mitral valve stenosis or atresia without diminutive ascending aorta

The surgical strategy in infants with mitral valve stenosis or atresia without diminutive ascending aorta remains to be established, including the potential for biventricular repair as a definitive operation. Our surgical experience of six infants with mitral valve stenosis (4patients) or atresia (2patients) without diminutive ascending aorta was evaluated based on three important factors:left ventricular volume;the nature of the systemic outflow obstruction; and the type of mitral valve anomaly. Two patients with systemic outflow tract diameter less than 65% of normal underwent systemic outflow tract reconstruction, and the other patients with outflow tract diameter more than 68%of normal were able to maintain systemic circulation without repair. Only one patient with mitral valve stenosis without left ventricular outflow tract obstruction underwent a successful open mitral valvotomy as a biventricular repair after first-stage palliation. The left ventricle of the other patients did not grow after first-stage palliation. Due to progressive subaortic narrowing, pulmonary artery banding should be avoided in patients with mitral atresia due to absent atrioventricular connection who are future Fontan candidates. Most patients with this lesion can be expected to become candidates for safe Fontan-type repair

Molecular liver cancer prevention in cirrhosis by organ transcriptome analysis and lysophosphatidic acid pathway inhibition

Cirrhosis is a milieu that develops hepatocellular carcinoma (HCC), the second most lethal cancer worldwide. HCC prediction and prevention in cirrhosis are key unmet medical needs. Here we have established an HCC risk gene signature applicable to all major HCC etiologies: hepatitis B/C, alcohol, and non-alcoholic steatohepatitis. A transcriptome meta-analysis of >500 human cirrhotics revealed global regulatory gene modules driving HCC risk and the lysophosphatidic acid pathway as a central chemoprevention target. Pharmacological inhibition of the pathway in vivo reduced tumors and reversed the gene signature, which was verified in organotypic ex vivo culture of patient-derived fibrotic liver tissues. These results demonstrate the utility of clinical organ transcriptome to enable a strategy, namely, reverse-engineering precision cancer prevention

Reactions of (polypyrazolylborato)(benzonitrile)rutheniums with terminal alkynes: Reactivity changeover by triethylamine toward arylalkyne polymerization or formation of (arylmethyl)(carbonyl) complexes

Reactions of (κ 3-polypyrazolylborato)(benzonitrile) rutheniums [RuCl{B(4-Ypz) 4}(PhCN) 2] {4-Ypz; 4-bromo-1-pyrazolyl (Y = Br) and 1-pyrazolyl (Y = H) groups} with terminal alkynes were studied. For the reactions with arylalkynes HC≡C(aryl) in the presence of NEt 3, (arylmethyl)(carbonyl)rutheniums [Ru{CH 2(aryl)}{B(4-Ypz) 4}(CO)(PhCN)] were yielded, indicating alkyne C≡C bond cleavage, whereas in the absence of NEt 3, arylalkyne polymerization proceeded instead of the (arylmethyl)ruthenium formation. Reasonably attributed reaction mechanism shows significant role of the vinylidene intermediates "Ru=C=CH(aryl)"