Diacylglycerol kinase ζ inhibits myocardial atrophy and restores cardiac dysfunction in streptozotocin-induced diabetes mellitus

<p>Abstract</p> <p>Background</p> <p>Activation of the diacylglycerol (DAG)-protein kinase C (PKC) pathway has been implicated in the pathogenesis of a number of diabetic complications. Diacylglycerol kinase (DGK) converts DAG to phosphatidic acid and acts as an endogenous regulator of PKC activity. Akt/PKB is associated with a downstream insulin signaling, and PKCβ attenuates insulin-stimulated Akt phosphorylation.</p> <p>Methods and Results</p> <p>We examined transgenic mice with cardiac-specific overexpression of DGKζ (DGKζ-TG) compared to wild type (WT) mice in streptozotocin-induced (STZ, 150 mg/kg) diabetic and nondiabetic conditions. After 8 weeks, decreases in heart weight and heart weight/body weight ratio in diabetic WT mice were inhibited in DGKζ-TG mice. Echocardiography at 8 weeks after STZ-injection demonstrated that decreases in left ventricular end-diastolic diameter and fractional shortening observed in WT mice were attenuated in DGKζ-TG mice. Thinning of the interventricular septum and the posterior wall in diabetic WT hearts were blocked in DGKζ-TG mice. Reduction of transverse diameter of cardiomyocytes isolated from the left ventricle in diabetic WT mice was attenuated in DGKζ-TG mice. Cardiac fibrosis was much less in diabetic DGKζ-TG than in diabetic WT mice. Western blots showed translocation of PKCβ and δ isoforms to membrane fraction and decreased Akt/PKB phosphorylation in diabetic WT mouse hearts. However in diabetic DGKζ-TG mice, neither translocation of PKC nor changes Akt/PKB phosphorylation was observed.</p> <p>Conclusion</p> <p>DGKζ modulates intracellular signaling and improves the course of diabetic cardiomyopathy. These data may suggest that DGKζ is a new therapeutic target to prevent or reverse diabetic cardiomyopathy.</p

高校生における異文化体験と国際的資質の関連 : 海外研修旅行の効果

本研究の目的は， 日本の高校生を対象に，国際的資質が海外研修旅行における異文化体験へ与える影響を検討することであった。3か国のうち1か国を選択して海外研修旅行を経験した高校生158人に対し，国際的資質および異文化体験を測定する賀問紙調査を実施した。その結呆，旅行後の国際的資質が有意に高まったが，その効果量は低かった。また異文化に対する認識の肯定的変化は，旅行の結果高まったほか，旅行前の国際的資質に強く影響受けることが明らかとなった。教育効果の検証における個人要因導入の必要性について考察された。The purpose of this study was lo examine the impact of international disposition on cross-cultural experiences in an oversea school trip among Japanese high school students. 158 high school students who participated in one in three foreign countries\u27 trip answered the questionnaire regarding international disposition and cross-cultural experiences. The results showed that scores of international disposition significantly increased but the effect sizes were moderate. Positively changes of the realization toward other countries also increased and were positively influenced by international disposition before the trip. Application of individual factors to the examination of the teaching effectiveness was discussed

Differential regulation of diacylglycerol kinase isoform in human failing hearts

Evidence from several studies indicates the importance of Gαq protein-coupled receptor (GPCR) signaling pathway, which includes diacylglycerol (DAG), and protein kinase C, in the development of heart failure. DAG kinase (DGK) acts as an endogenous regulator of GPCR signaling pathway by catalyzing and regulating DAG. Expressions of DGK isoforms α, ε, and ζ in rodent hearts have been detected; however, the expression and alteration of DGK isoforms in a failing human heart has not yet been examined. In this study, we detected mRNA expressions of DGK isoforms γ, η, ε, and ζ in failing human heart samples obtained from patients undergoing cardiovascular surgery with cardiopulmonary bypass. Furthermore, we investigated modulation of DGK isoform expression in these hearts. We found that expressions of DGKη and DGKζ were increased and decreased, respectively, whereas those of DGKγ and DGKε remained unchanged. This is the first report that describes the differential regulation of DGK isoforms in normal and failing human hearts

総合科学科におけるキャリア教育を軸としたグローバル人材育成の試み : SGH3年目における1年次生の学年経営実践報告

学年経営は日々の指導の積み重ねによって成される。これさえ行えば何もかもうまく行くというような秘策はない。担任副担任でチームを組み、生徒集団を複数の目で見守りながら、授業や行事を展開していく。本年次は本校総合科学科20年余りの歴史が築きあげたキャリア教育を大切にしながら、スーパーグローバルハイスクール(SGH) の目標であるグローバル人材の育成に向けて取り組んできた。本稿ではその1年間の取り組みについて報告する

平成29年度「産業社会と人間」「キャリアデザイン」「校外学習」実践報告

本校の1年次生は、様々な体験や活動を通して「これからの社会の中で自分はどう生きるのか」を考えていく。3月のカナダ校外学習を見据え、必修科目「産業社会と人間」と「キャリアデザイン」(総合的な学習の時間)で行った活動を中心に、本年度の実践を報告する

A Case of Cystic Adventitial Degeneration of the Left Popliteal Artery Diagnosed by Intravascular Ultrasound

An 87-year-old male was admitted with intermittent claudication of the left calf. We performed lower extremity angiography, which revealed stenosis of the left popliteal artery. Intravascular ultrasound (IVUS) image correctly identified the cystic appearance of visualized extravascular hypodensity, causing extrinsic compression of the lumen. We diagnosed the condition as cystic adventitial degeneration (CAD) of the popliteal artery. We operated a resection of a cyst with the artery and replaced the autovein graft (saphenous vein). After surgery, the patient was free of symptoms. CAD is a rare disease; thus, our IVUS findings may provide unique diagnostic clues in patients with CAD

Soluble Receptor for Advanced Glycation End Products (RAGE) is a Prognostic Factor for Heart Failure

Background: We recently reported that serum levels of pentosidine, one of the well defined advanced glycation end products (AGE), was an independent prognostic factor for heart failure. Receptor for AGEs (RAGE) is expressed in a variety of tissues, and RAGE has a C-truncated secretory isoform of the receptor protein, termed soluble RAGE. In the present study, we measured serum soluble RAGE levels in patients and examined whether serum soluble RAGE predicts prognosis in patients with heart failure. Methods and Results: Serum soluble RAGE concentration was measured in 160 patients with heart failure by a competitive enzyme-linked immunosorbent assay. Patients were prospectively followed during a median follow-up period of 872 days with endpoints of cardiac death or re-hospitalization. Serum soluble RAGE level increased with advancing NYHA functional class. Serum soluble RAGE level was also higher in patients with cardiac events than in event free patients. From the receiver operating characteristic (ROC) curve analysis, the cut-off value of serum soluble RAGE level was determined as 1220 pg/ml. Kaplan-Meier analysis clearly demonstrated that the high soluble RAGE group had a significantly higher incidence of cardiac events than occurred in the low serum soluble RAGE group (P = 0.0004). In the multivariate Cox proportional hazard analysis, soluble RAGE and serum pentosidine were independent risk factors for cardiac events (soluble RAGE: HR 1.90, 95% CI 1.16 . 3.09, P = 0.010; pentosidine: HR 1.59, 95% CI 1.11 . 2.29, P = 0.012). Conclusions: Serum soluble RAGE level is an independent prognostic factor for heart failure, and this novel marker may be useful for risk stratification of patients with heart failure

Pentraxin 3, a new marker for vascular inflammation, predicts adverse clinical outcomes in patients with heart failure

Background: Pentraxin 3 (PTX3) is a novel inflammatory marker produced by endothelial cells, smooth muscle cells and macrophages. The purpose of the present study was to examine the clinical significance of plasma PTX3 levels in patients with heart failure. Methods: We measured plasma PTX3 levels in 196 patients with heart failure and 60 control subjects without heart failure by sandwich ELISA. Patients were prospectively followed during a median follow-up period of 655 days with the end points of cardiac death or progressive heart failure requiring re-hospitalization. Results: Plasma PTX3 concentrations were higher in patients with heart failure than in control subjects (P < 0.0001) and increased as the severity of NYHA functional class advanced (P < 0.0001). A total of 63 cardiac events occurred during a follow-up period, and cardiac event free rate was markedly lower in patients with high PTX3 levels than in those with normal PTX3 levels (44.7% vs. 89.2%, P < 0.0001). The multivariate Cox proportional hazard analysis demonstrated that plasma PTX3 level, but not high sensitive C-reactive protein, was the independent predictor of cardiac events (hazard ratio 1.20, 95% confidence interval 1.03-1.40, P = 0.0162). Patients were divided into 4 groups based on plasma PTX3 values from 1st to 4th quartile. The highest 4th quartile of plasma PTX3 levels was associated with the highest risk of cardiac events (9.23-fold compared to the 1st quartile). Conclusions: Plasma PTX3 level provides important prognostic information for the risk stratification of patients with heart failure