Polymorphonuclear leukocyte lysosomal proteases, cathepsins B and D affect the fibrinolytic system in human umbilical vein endothelial cells

AbstractTo clarify the physiological role played by neutrophil lysosomal protease in cultured human umbilical vein endothelial cells (HUVEC), we studied the effects of cathepsins B and D released from activated polymorphonuclear leukocytes on the fibrinolytic system in HUVEC. Cathepsins B and D reduced the antigens of tissue-type plasminogen activator, and they increased both the antigens and the activity of plasminogen activator inhibitor-1. These results suggest that cathepsins B and D are involved in the thrombotic tendency, since they inhibited the fibrinolytic system in cultured HUVEC

Analysis of Bioconversion and Bacterial Community of Thermophilic Hydrogen Production Using UASB Reactor (Advanced Studies on Sustainable Animal Production: Interrelationships among Human, Animal and Environment, 8th International Symposium of Integrated Field Science)

Poster Sessio

Suzaku observation of Jupiter's X-rays around solar maximum

We report on results of imaging and spectral studies of X-ray emission from Jupiter observed by Suzaku. In 2006 Suzaku had found diffuse X-ray emission in 1\unicode{x2013}5 keV associated with Jovian inner radiation belts. It has been suggested that the emission is caused by the inverse-Compton scattering by ultra-relativistic electrons ($\sim 50$ MeV) in Jupiter's magnetosphere. To confirm the existence of this emission and to understand its relation to the solar activity, we conducted an additional Suzaku observation in 2014 around the maximum of the 24th solar cycle. As a result, we successfully found again the diffuse emission around Jupiter in 1\unicode{x2013}5 keV and also point-like emission in 0.4\unicode{x2013}1 keV. The luminosity of the point-like emission which was probably composed of solar X-ray scattering, charge exchange, or auroral bremsstrahlung emission increased by a factor of $\sim 5$ with respect to 2006, most likely due to an increase of the solar activity. The diffuse emission spectrum in the 1\unicode{x2013}5 keV band was well-fitted with a flat power-law function ($\Gamma = 1.4 \pm 0.1$) as in the past observation, which supported the inverse-Compton scattering hypothesis. However, its spatial distribution changed from $\sim 12 \times 4$ Jovian radius (Rj) to $\sim 20 \times 7$ Rj. The luminosity of the diffuse emission increased by a smaller factor of $\sim 3$. This indicates that the diffuse emission is not simply responding to the solar activity, which is also known to cause little effect on the distribution of high-energy electrons around Jupiter. Further sensitive study of the spatial and spectral distributions of the diffuse hard X-ray emission is important to understand how high-energy particles are accelerated in Jupiter's magnetosphere.Comment: 17 pages, 4 figures, 1 tabl

Effect of Paraquat-Induced Oxidative Stress on Insulin Regulation of Insulin-Like Growth Factor-Binding Protein-1 Gene Expression

Oxidative stress is thought to play a role in the development of insulin resistance. In order to elucidate the molecular effect of oxidative stress on liver insulin signaling, we analyzed the effect of paraquat (1,1-dimethyl-4,4-dipyridynium; PQ)-derived oxidative stress on the expression of insulin-dependent genes and activation of liver insulin signaling pathway. Incubation of primary cultured rat hepatocytes with 2 mM PQ for 6 h impaired the suppressive effect of insulin on insulin-like growth factor-binding protein-1 (IGFBP-1) gene expression, but did not influence glucose-6-phosphatase gene expression. Insulin-dependent phosphorylation or activation of insulin receptor, insulin receptor substrate-1 and -2, phosphatidylinositol 3-kinase, Akt and forkhead in rhabdomyosarcoma were not affected by PQ pre-treatment. In contrast, PQ treatment impaired insulin-dependent phosphorylation of mammalian target of rapamycin (mTOR). These results indicate that PQ-induced oxidative stress impairs insulin-dependent mTOR activation and that this impairment probably causes inhibition of insulin-dependent repression of IGFBP-1 expression

Tendency of long stay patients on a psychiatric ward : Analysis based on medical and nursing records

本研究は,A大学病院精神科に長期入院(90日以上)をしている患者に着目し,年齢や疾患名の傾向などの特徴を明らかにするとともに,これらの実態に照らした看護アプローチのあり方について検討することを目的とした｡対象は,2004年1月1日から12月31日までに入院した延べ229人のうち,90日以上入院した延べ56人である｡診療記録等から在院日数,年齢,性別,疾患名のリストを作成し,傾向を分析した｡90日以上の長期入院患者の平均在院日数は175.1±79.7日であり,年齢層は思春期から40歳台の壮年期までで全体の約7割を占めた｡性別は男性16人,女性40人で,疾患名別では,統合失調症9人(16.1%),うつ病12人(21.4%),摂食障害16人(28.6%),適応障害5人(8.9%),躁うつ病4人(7.1%),強迫性障害1人(1.8%),身体表現性障害1人(1.8%),その他8人(14.3%)であった｡疾患名別の平均在院日数は,摂食障害が214.1日,適応障害が199.6日,統合失調症が180.2日であり,躁うつ病が175.3日であった｡年齢,疾患名,性別による在院日数の差は有意でなかった｡ 摂食障害に代表されるように身体機能の回復に数か月の医学的アプローチが必要な疾患はあるが,これらの中には患者自身の課題解決にむけた支援や家族支援など,保健福祉的アプローチも必要であると思われ,今後,これら事例の経過を質的に分析し,在院日数を長期化させている要因を明らかにする必要がある。This fact-finding survey was carried out to identify attributes of long stay psychiatric patients to improve nursing intervention based on their actual experience in hospital. 56 subjects out of the 229 patients who were admitted to a psychiatric ward at a university teaching hospital during the year 2004 were found to be hospitalized more than 90 days (175.1 ± 79.7 days on average), and all of them agreed to be included in the study (16 males and 40 females). Data were collected from their medical and nursing records. Most of the participants ranged from teens to adults in their forties. They were mostly diagnosed as having depression, schizophrenia, eating disorder, bipolar affective disorder and adjustment disorder. The patients with eating disorder stayed longest (214.1 days on average). followed by patients with adjustment disorders and schizophrenia. It is assumed that, although certain types of disorder need months of medical interventions for restoring physical functions, patients with these disorders also need family and social support as well as nursing interventions to cope with their problems. The results suggest that qualitative studies should be needed to identify factors that necessitate a long stay and make the system more supportive and effective

中枢神経インスリン作用による肝糖代謝制御における迷走神経の役割の解明

金沢大学医薬保健研究域医学系肝糖代謝調節において、中枢神経から迷走神経を介した制御メカニズムの重要性が指摘されている。中枢神経インスリン作用による肝糖代謝制御に、迷走神経とクッパー細胞が関与することが報告されているものの、その分子メカニズムは十分に明らかにされていない。代表者は、１）視床下部がインスリンを感知すると、肝臓へ分布する迷走神経の活動が低下すること、２）視床下部のインスリン作用による肝臓IL-6発現の増加は、α7ニコチン性アセチルコリン受容体（α7nAChR）を介したクッパー細胞活性抑制の減弱により誘導されること、３）肥満では視床下部のインスリン作用での迷走神経の活動変化が消失することを明らかにした。Central insulin action suppresses the gene expression of hepatic gluconeogenic enzymes. The vagus nerve plays an important role in this centrally mediated hepatic response; however, the precise mechanism underlying this brain-liver interaction is unclear. Here, we present our findings that the vagus nerve suppresses hepatic gluconeogenesis via α7-nicotinic acetylcholine receptors (α7-nAchR) on Kupffer cells, and that central insulin action activates hepatic IL-6 release by suppressing vagal activity. In high-fat diet-induced obese and insulin-resistant mice, control of the vagus nerve by central insulin action was disturbed, inducing a persistent increase of inflammatory cytokines. These findings suggest that dysregulation of the α7-nAchR-mediated control of Kupffer cells by central insulin action may affect the pathogenesis of chronic hepatic inflammation in obesity.研究課題/領域番号:26860693, 研究期間(年度):2014-04-01 - 2015-03-3

肥満・インスリン抵抗性における肝糖代謝異常に果たす肝細胞増殖制御機構の役割

肥満・インスリン抵抗性モデルマウスは、肝糖産生の増加と肝肥大を伴う脂肪肝を呈する。本研究では、肝細胞増殖制御が、肥満・インスリン抵抗性状態における肝糖代謝異常に果たす役割を解明するため、肝臓特異的Cyclin D1欠損マウスを作出した。肝臓特異的Cyclin D1欠損マウスは、高脂肪食負荷による肥満・インスリン抵抗性誘導状態、あるいはレプチン受容体欠損肝臓特異的Cyclin D1欠損マウスの随時摂食時において、体重、血糖値で有意な差を生じなかった。今後は、糖脂質代謝パラメーター解析・高インスリン正常血糖クランプなどの表現型解析を行う。Obesity-Insulin resistance is known to increase of hepatic gluconeogenesis and hepatic steatosis associated with enlarged liver. To understand the role of control of hepatic proliferation on disorder of hepatic glucose metabolism, we generated the liver specific Cyclin D1 knockout (KO) mouse. In this KO mouse treated with high fat diet or db/db-background, there was no significant difference in body weight and blood glucose level under ad lib fed conditions. To explain more fully, we will performed hyperinsulinemic-euglycemic clamps in these mice.研究課題/領域番号:24790919, 研究期間(年度):2012-04-01 - 2014-03-3