Variantes genéticas en el locus 9p21 contribuyen al desarrollo de arteriosclerosis a través de la modulación de ANRIL y CDKN2A/B

Registro creado en correspondencia al grado de doctora de Ada Congrains Castillo.Los estudios de asociación de todo el genoma (GWAS) han identificado variantes genéticas que contribuyen al riesgo de enfermedad cardiovascular (ECV) en el locus del cromosoma 9p21. La región asociada a CVD es adyacente a los dos inhibidores de quinasas dependientes de ciclina (CDKN) 2A y 2B y los últimos exones del ARN no codificante, ANRIL. Todavía no está claro cuál de estas transcripciones o cómo están involucradas en la patogénesis de la aterosclerosis.Genome-wide association studies (GWAS) have identified genetic variants contributing to the risk of cardiovascular disease (CVD) at the chromosome 9p21 locus. The CVD-associated region is adjacent to the two cyclin dependent kinase inhibitors (CDKN)2A and 2B and the last exons of the non-coding RNA, ANRIL. It is still not clear which of or how these transcripts are involved in the pathogenesis of atherosclerosis.Japón. Programa de Promoción de Estudios Fundamentales en el Instituto Nacional de Innovación Biomédica de Japón (HR: 22-2-5), el Ministerio de Educación, Cultura, Deportes, Ciencia y Tecnología de Japón (KK: 22510211) y la Fundación NOVARTIS para la Investigación Gerontológica (KK).Tesi

Survey of the general public's attitudes toward advance directives in Japan: How to respect patients' preferences

BACKGROUND: Japanese people have become increasingly interested in the expression and enhancement of their individual autonomy in medical decisions made regarding medical treatment at and toward the end of life. However, while many Western countries have implemented legislation that deals with patient autonomy in the case of terminal illness, no such legislation exists in Japan. The rationale for this research is based on the need to investigate patient's preferences regarding treatment at the end of life in order to re-evaluate advance directives policy and practice. METHODS: We conducted a cross-sectional survey with 418 members of the general middle-aged and senior adults (aged between 40 and 65) in Tokyo, Japan. Respondents were asked about their attitudes toward advance directives, and preferences toward treatment options. RESULTS: Over 60% of respondents agreed that it is better to express their wishes regarding advance directives (treatment preferences in writing, appointment of proxy for care decision making, appointment of legal administrator of property, stating preferences regarding disposal of one's property and funeral arrangements) but less than 10% of them had already done so. About 60% of respondents in this study preferred to indicate treatment preferences in broad rather than concrete terms. Over 80% would like to decide treatment preferences in consultation with others (22.2% with their proxy, 11.0% with the doctor, and 47.8% with both their proxy and the doctor). CONCLUSION: This study revealed that many Japanese people indicate an interest in undertaking advance directives. This study found that there is a range of preferences regarding how advance directives are undertaken, thus it is important to recognize that any processes put into place should allow flexibility in order to best respect patients' wishes and autonomy

Transport of carbon-bearing dusts from Iraq to Japan during Iraq\u27s War

Rainwater collected during the period of February-April, 2003 in Kanazawa University and Hakui, Ishikawa Prefecture, Japan, was investigated by ion chromatography of the dissolved ions, and Scanning electron microscopy equipped with energy dispersive analyzer (SEM-EDX), electron microprobe analyzer (EPMA), transmission electron microscopy, and X-ray powder diffraction (XRD) analyses of the filtered samples. The pH, Eh, EC, dissolved oxygen (DO) and depleted U (DU) of the rainwater were also measured. The results show a rare case with low pH value of rain and high value of electrical conductivity (EC) in the rainwater during certain period. The NO 3 -, SO 4 2- and NH 4 + concentrations on 26th March, show quite high values after oil field fires on 21st March 2003. The powdery dust and carbon-bearing nm sized particles contained in the rainwater have characteristics different from that of the Asian dust (Kosa). Since 21 March, 2003 the Iraq plunged into the war, the 9 oil field fires were reported on 25 March, 2003 in Rumaylah oil field near the borderline of Kuwait. The first precipitation was caught in Kanazawa on 24 March, 2003. The pH value of the rainwater indicated a strong acid rain (pH 3.6) with black powdery dusts. The acid rain on 27th March to 2nd April (pH 3.4-4.3; 5-17mm) associated with WNW wind (2.7-4.1m/s) has continued to the first 10 days of April in Kanazawa, during the 9 oil fields were burning in Iraq. The EC in rainwater collected from 24 March to 15 April, 2003, shows high concentrations of ions, suggesting high contents of water soluble-carbon particles and soot. In the meantime, it was the highest season of sandstorms at bare dried land in Iraq from the end of March to the beginning of April. Westerly wind blew around 5500m high, and the sandstorm with 2000m wide was transported by strong wind to Zagros 3000m high mountains. The hot wind hit the Zagros Mountains and easily to join and rise to Westerly wind high by a rising air current. The 234U/ 238U activity (around 0.2) in typical depleted uranium (DU) is quite low compared with that (around 1.0) in natural uranium. The contamination of DU from the Iraq conflict may be, if any, negligibly small on undetectable level. On the other hand, the powdery dusts and carbon-bearing particles of rainwater have been produced by combustion of oil field in Iraq and they are directly cycling in our planet by Westerly wind. Black carbon particles are a product of incomplete combustion, and are the principal light-absorbing atmospheric aerosol. The result reminds us of the scientific values of short-term atmospheric environment records during Iraq\u27s War. This has consequences for primary production of powdery dusts coming from Iraq to the atmosphere over half the globe away. © 2004 Elsevier Ltd. All rights reserved

Evaluation by specific inhibitors of metabolic dependence of asexual differentiation processes in Phytophthora capsici (Agriculture)

作用機作がすでに知られている各種特異的阻害剤を用いて, Phytophthora capsiciの無性的生活環における種々の分化の過程の代謝依存性を推察した。RNA合成阻害剤であるアクチノマイシンDは菌糸伸長, 遊走子のう形成, ならびにその発芽を抑制したが, 遊走子の遊泳や被のう胞子の発芽にはほとんど影響しなかった。蛋白合成阻害剤であるシクロヘキシミドはアクチノマイシンDで阻害を受けた過程と, さらに被のう胞子の発芽をも強く阻害した。酸化的リン酸化の阻害剤であるオリゴマイシンはすべての分化過程を阻害したが, 同じ呼吸阻害剤であるアンチマイシンA(電子伝達系阻害剤)は菌糸伸長ならびに被のう胞子の発芽を阻害することができなかった。このことは, それらの過程で電子伝達系が作動していないと考えるよりは, アンチマイシンがそれらの過程において菌の細胞内にとり込まれにくいと考えるほうが妥当である。それと同時に, それらの過程においては物質の透過性をつかさどる菌の原形質膜に何らかの差異があることをも示唆する。このことは菌糸伸長ならびに被のう胞子の発芽過程がナイスタチン(細胞膜のステロール類と結合することにより膜機能を阻害する)に不感受性であることからも示唆される。microtubule阻害剤であるビンブラスチンは遊走子のう形成ならびにその発芽を強く阻害し, また菌糸伸長をも若干阻害した。またmicrofilament阻害剤であるサイトカラシンBは分化のどの過程に対しても顕著な阻害を示さなかった。これらの結果より, それぞれの分化の過程における特定の代謝の依存性が推察された。また, アクチノマイシンDとシクロヘキシミドに対する不感受性によって示された遊走子の遊泳期におけるRNAならびに蛋白合成の不必要は^Cのアミノ酸またヌクレオシドの取り込み実験からも支持された。Metabolic dependence of differentiation processes during asexual life cycle of Phytophthora capsici was evaluated by the use of specific inhibitors whose modes of the action have been known. Actinomycin D, an RNA synthesis inhibitor, interfered with vegetative growth, and formation and germination of zoosporangia of the fungus, but had negligible adverse effects on swimming of zoospores and germination of encysted zoospores. Cycloheximide, a protein synthesis inhibitor, inhibited germination of encysted zoospores besides the processes inhibited by actinomycin D. Oligomycin, an oxidative phosphorylation inhibitor, inhibited all the differentiation processes. Antimycin A, an electron transport inhibitor, however, failed in inhibiting vegetative growth and germination of encysted zoospores. This was probably due to impermeability of the inhibitor through the plasma membrane and qualitative difference in the membrane at those antimycin A-insensitive phases of the fungus was suggested. The difference in the plasma membrane was also indicated by the sensitivity to nystatin, a membrane sterol inhibitor : nystatin did not inhibit vegetative growth and germination of encysted zoospores, but did more and less other processes. Vinblastin, a microtubule inhibitor, inhibited strongly formation and germination of zoosporangia, and swimming of zoospores, and slightly vegetative growth. None of the differentiation processes evaluated was found to be very sensitive to cytochalasin B, a microfilament inhibitor. From these results, possible requirements of the specific metabolisms or functions for the individual differentiation process was postulated. Furthermore, no requirement of RNA and protein synthesis for swimming of zoospores, as indicated by insensitivity to the inhibitors, was confirmed by tracer experiments

Left Ventricular Diastolic Function during the Normal Peripartum Period

Background:Because cardiovascular function and hemodynamics markedly change during pregnancy, our aim was to elucidate left ventricular (LV) diastolic function in pregnant women. Methods and Results:We prospectively collected the data of 397 pregnant women treated between 2012 and 2013. We evaluated their LV systolic and diastolic functions via echocardiography during the 3rd trimester (28–30 weeks’ gestation) and within 4 days of delivery. Additionally, we analyzed the cardiac geometry: relative wall thickness and LV mass index (LVMI). Diastolic dysfunction was defined as early diastolic mitral annulus velocity (e’) 15. The pregnant women were 33.7±5.0 years old and the prevalence of hypertensive disorders in pregnancy (HDP) was 4.0%. LV systolic function was preserved in all pregnant women. However, diastolic function significantly decreased after delivery (mean e’: 12.6 vs. 11.6 cm/s, P<0.0001; median E/e’ ratio: 6.4 vs. 7.3, P<0.0001). Diastolic function after delivery was associated with the prevalence of HDP (P=0.035) and was correlated with age (R=−0.17, P=0.0009) and LVMI (R=−0.30, P<0.0001). However, these changes in diastolic function remained within the normal range and only 1 woman (1/397, 0.3%) had LV diastolic dysfunction after delivery. Conclusions:LV diastolic function decreased after delivery in pregnant women but was within the normal range

A clinical study on urolithiasis I. Recent cases in the department of Urology, Okayama University Hospital.

During the 9-year period from 1972 to 1980, 1069 cases of urolithiasis were seen in the Department of Urology, Okayama University Hospital. The ratio of males to females was 2.1 to 1. The maximum incidence of urolithiasis occurred from the third to fifth decade. The overall recurrence rate was 26.7% , and most recurrence (62.1%) occurred 1-3 years following the removal of initial calculi. Concerning renal calculi, the incidence of residual calculi and postoperative recurrence was dependent on the shape and number of calculi rather than operative methods. Mixed calcium oxalate and phosphate calculi were found most frequently, and calculi containing struvite also were found frequently in females. The components of recurrent calculi were identical to those of initial calculi in most cases (72.8%)

Dose effects of beta-tricalcium phosphate nanoparticles on biocompatibility and bone conductive ability of three-dimensional collagen scaffolds

Three-dimensional collagen scaffolds coated with beta-tricalcium phosphate (β-TCP) nanoparticles reportedly exhibit good bioactivity and biodegradability. Dose effects of β-TCP nanoparticles on biocompatibility and bone forming ability were then examined. Collagen scaffold was applied with 1, 5, 10, and 25 wt% β-TCP nanoparticle dispersion and designated TCP1, TCP5, TCP10, and TCP25, respectively. Compressive strength, calcium ion release and enzyme resistance of scaffolds with β-TCP nanoparticles applied increased with β-TCP dose. TCP5 showed excellent cell-ingrowth behavior in rat subcutaneous tissue. When TCP10 was applied, osteoblastic cell proliferation and rat cranial bone augmentation were greater than for any other scaffold. The bone area of TCP10 was 7.7-fold greater than that of non-treated scaffold. In contrast, TCP25 consistently exhibited adverse biological effects. These results suggest that the application dose of β-TCP nanoparticles affects the scaffold bioproperties; consequently, the bone conductive ability of TCP10 was remarkable