Hes1遺伝子は細胆管由来の肝内胆管癌の発生に重要な役割を果たす

京都大学新制・課程博士博士(医学)甲第23369号医博第4738号新制||医||1051(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 武藤 学, 教授 松田 道行, 教授 小川 誠司学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

New Approach to Short-Range Ordering in GP(2) Zones in Al-3.82wt. % Cu Alloy

X-ray diffuse scatteing intensity measurement has been carried out for the Al-3,82% Cu single crystal in which GP (2) zones are found. The two dimensional equiintensity contour maps in h(1) h(2) 0 plane are obtained from surveying around several reflections. The diffuse intensity around 2 1 0 reflection, which shows a cross like streak, is carefully examined. Warren-Cowley short-range order parameters, a(i), are estimated from the diffuse intensities around 2 1 0 reflection. The component of the intensities coming from atomic displacements was subtracted from the total diffuse intensity. It is found that the equi-intensity contours after the correction of the atomic displacements shows an anisotropic distribution and the GP(2) zone is an ellipsoid with a modified layer structure

ノウ キョケツ ニタイスル Heat shock protein 70 ノ ホゴ サヨウ シンセイジ マウス ノウ キョケツ テイサンソ フカ モデル オ モチイテ

Apoptosis is implicated in neonatal brain injury among various forms of cell death. Here we show that over-expression of heat shock protein (Hsp) 70, an anti-apoptotic protein, protects the neonatal brain from hypoxic/ischemic (H/I) injury and the pathways involved in the protection. In our study, postnatal day 7 (P7) transgenic mice over-expressing rat Hsp70 (Tg) and their wild type littermates (Wt) underwen unilateral common carotid artery ligation followed by 30 min exposure to 8% O_2. Significant neuroprotection was observed in Tg versus Wt mice on P12, correlating with high level of constitutive but not inducible Hsp70 in the Tg. Western blot analysis showed that translocation of cytochrome c, but not apoptosis-inducing factor (AIF), from mitochondria into cytosol was significantly reduced in Tg 24 hrs after H/I compared to Wt mice. Reduced caspase-9 cleavage was also observed in Hsp70 Tg mice compared to Wt littermates 24 hrs after H/I. Co-immunoprecipitation detected more Hsp70 bound to Apaf-1 and AIF in Tg than Wt mice 24 hrs after H/I, inversely correlating with the amount of nuclear but not cytosolic AIF translocation.　In conclusion, Hsp70 could suppress the activation of caspase-9 by reducing cytochrome c release via mitochondria and directly interacting with Apaf-1 in the apoptotic pathway during neonatal H/I injury. Also interaction between Hsp70 and AIF might have reduced downstream events leading to cell death, including the reduction of nuclear AIF translocation in the neonatal brains of Hsp70 Tg mice after H/I. We hope that those findings may help identify new potential targets for anti-ischemic therapy.　Key word: Heat shock protein 70, hypoxic/ischemia, apoptosi

シンケイ ハッセイ ト キョケツセイ ノウ ショウガイ

Neuronal self-renewal following injuries to the adult brain has been clarified by many recent studies. Ischemic brain injuries have now been demonstrated as a trigger for neurogenesis via endogenous neural stem cells or progenitor cells located in the dentate subgranular zone, the subventricular lining of the lateral ventricle, and the posterior periventricle adjacent to the hippocampus. New neurons migrate to the granule cell layer or to the damaged CA1 region and striatum, where they express morphological markers characteristic of the local neurons. If the new neurons are fully integrated and become functional, a novel therapeutic strategy might be developed for stroke in humans.　Key words : stem cell, neurogenesis, strok

Targeting Inflammation in the Diagnosis, Management, and Prevention of Cardiovascular Diseases

Inflammation plays an important role in the development and progression of cardiovascular diseases (CVDs). Hypertension and hyperlipidemia are the key risk factors of CVDs and induce inflammation in the heart and vessels. Unhealthy diet, infection, and smoking coupled with genetic factors lead to the development of CVDs as well as induce inflammation. Risk factors of CVDs such as hypertension and hyperlipidemia along with diabetes activate nuclear factor kappa B, which regulates the transcription of immunoglobulin free light chain (FLC) κ in B cells and the production of multiple inflammatory molecules, leading to inflammation. FLCs are novel biomarkers of inflammation, and their levels have been associated with overall mortality in a general population and with cardiovascular outcomes. In this review, the role of inflammation in the pathogenesis of CVDs, new biomarkers of inflammation, and dietary options counterbalancing inflammatory processes, such as the polyphenol-rich French maritime pine bark extract Pycnogenol, are discussed