Development of a Novel Output Value for Quantitative Assessment in Methylated DNA Immunoprecipitation-CpG Island Microarray Analysis

In DNA methylation microarray analysis, quantitative assessment of intermediate methylation levels in samples with various global methylation levels is still difficult. Here, specifically for methylated DNA immunoprecipitation-CpG island (CGI) microarray analysis, we developed a new output value. The signal log ratio reflected the global methylation levels, but had only moderate linear correlation (r = 0.72) with the fraction of DNA molecules immunoprecipitated. By multiplying the signal log ratio using a coefficient obtained from the probability value that took account of signals in neighbouring probes, its linearity was markedly improved (r = 0.94). The new output value, Me value, reflected the global methylation level, had a strong correlation also with the fraction of methylated CpG sites obtained by bisulphite sequencing (r = 0.88), and had an accuracy of 71.8 and 83.8% in detecting completely methylated and unmethylated CGIs. Analysis of gastric cancer cell lines using the Me value showed that methylation of CGIs in promoters and gene bodies was associated with low and high, respectively, gene expression. The degree of demethylation of promoter CGIs after 5-aza-2'-deoxycytidine treatment had no association with that of induction of gene expression. The Me value was considered to be useful for analysis of intermediate methylation levels of CGIs

トランスクリプトーム解析によるヒト肺線維芽細胞におけるIL-13シグナリングの解明

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 中島 淳, 東京大学教授 岡崎 仁, 東京大学准教授 森川 鉄平, 東京大学特任准教授 池田 祐一, 東京大学講師 永井 純正University of Tokyo(東京大学

Fabrication of Planar Power Inductor for Embedded Passives in LSI Package for Hundreds Megahertz Switching DC–DC Buck Converter

Recently, research and development of integrated low-voltage dc-dc converter to LSIs has been active. In order to realize such integrated dc power supply, power magnetic devices must be integrated in it. The authors have fabricated planar power inductor embedded in LSI package for hundreds megahertz switching dc-dc buck converter. In this study, two types of planar power inductors have been fabricated: one was spin-sprayed Zn-ferrite thick film magnetic core inductor, and the other was composite magnetic core (Fe-based amorphous/polyimide) inductor. Footprint of the fabricated inductors was 850 x 850 mu m(2), their inductance was about 10 nH, and the quality factor Q was about 20 at 100 MHz. The rating current which depends on the superimposed dc characteristic was at least up to 2 A.ArticleIEEE TRANSACTIONS ON MAGNETICS. 47(10):3204-3207 (2011)journal articl

Fabrication of Planar Power Inductor for Embedded Passives in LSI Package for Hundreds Megahertz Switching DC-DC Buck Converter

Recently, research and development of integrated low-voltage dc-dc converter to LSIs has been active. In order to realize such integrated dc power supply, power magnetic devices must be integrated in it. The authors have fabricated planar power inductor embedded in LSI package for hundreds megahertz switching dc-dc buck converter. In this study, two types of planar power inductors have been fabricated: one was spin-sprayed Zn-ferrite thick film magnetic core inductor, and the other was composite magnetic core (Fe-based amorphous/polyimide) inductor. Footprint of the fabricated inductors was 850 x 850 mu m(2), their inductance was about 10 nH, and the quality factor Q was about 20 at 100 MHz. The rating current which depends on the superimposed dc characteristic was at least up to 2 A.ArticleIEEE TRANSACTIONS ON MAGNETICS. 47(10):3204-3207 (2011)journal articl

中大脳動脈瘤手術における術中MEPの一過性増大に関する検討

Objective: To study clinical significance of augmentation of intraoperative motor evoked potentials (MEPs) during direct open surgery for middle cerebral artery (MCA) aneurysms. Methods: Between 2009 and 2017, 134 MCA aneurysm surgeries were performed with intraoperative MEP monitoring. The frequency and cause of augmentation with >50% increase of MEP amplitude from baseline were studied. Factors associated with MEP augmentation were investigated. Results: MEP augmentation was demonstrated in 9 patients. All 9 events were observed just after application of the temporary clip to the parent artery. The ratio of the maximum amplitude to baseline was 2.6 ± 1.1 at an mean of 2.4 ± 1.1 minutes after parent artery occlusion. Ten patients who did not show MEP augmentation after parent artery occlusion were compared with the patients showing MEP augmentation. The distance of the temporary clip point from the midline was smaller in patients with MEP augmentation compared with patients without MEP augmentation (P = 0.033). Conclusions: MEP augmentation was thought to be an early ischemic sign preceding a significant decrease in MEPs during MCA aneurysm surgery. Transient augmentation of MEPs was more frequently observed in cases with a temporary clip applied to the more proximal part of the MCA.博士（医学）・乙第1445号・令和元年12月5日© 2019 Elsevier Inc. All rights reserved

Heart Disease, Other Circulatory Diseases, and Onset of Major Depression among Community Residents in Japan: Results of the World Mental Health Survey Japan 2002-2004

We examined whether selected circulatory diseases (heart disease, stroke, diabetes and hypertension) were associated with an increased risk of major depression in the Japanese community population. Face-to-face household surveys were carried out in 7 areas, and a total of 2,436 persons participated (overall response rate: 58.4%) from 2002 to 2004. The WHO Composite International Diagnostic Interview 3.0 was used to diagnose major depression according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and additional interviews assessed the presence of circulatory diseases. Using data from a random subsample of the respondents (n=832), we conducted Cox proportional hazards models to calculate hazard ratios for the onset of major depression with comorbid circulatory diseases as a time-dependent covariate. Heart attack was significantly associated with the onset of major depression (hazard ratio [HR], 7.51 [95%Confidential Interval (CI), 1.36-41.45]) after adjusting for sex, birth cohort, smoking, alcohol intake, and education. Heart disease (HR, 2.12 [95% CI, 0.79-5.70]), diabetes (HR, 2.36 [95% CI, 0.42-13.34]) and hypertension (HR, 0.97 [95% CI, 0.37, 2.50]) were not significantly associated. There were no subjects who developed major depression after stroke. These results suggest that heart attack, and maybe also heart disease and diabetes, affect the onset of major depression.</p

Depletion of R270C Mutant p53 in Osteosarcoma Attenuates Cell Growth but Does Not Prevent Invasion and Metastasis In Vivo

Novel therapeutic targets are needed to better treat osteosarcoma, which is the most common bone malignancy. We previously developed mouse osteosarcoma cells, designated AX (accelerated bone formation) cells from bone marrow stromal cells. AX cells harbor both wild-type and mutant forms of p53 (R270C in the DNA-binding domain, which is equivalent to human R273C). In this study, we showed that mutant p53 did not suppress the transcriptional activation function of wild-type p53 in AX cells. Notably, AXT cells, which are cells derived from tumors originating from AX cells, lost wild-type p53 expression, were devoid of the intact transcription activation function, and were resistant to doxorubicin. ChIP-seq analyses revealed that this mutant form of p53 bound to chromatin in the vicinity of the transcription start sites of various genes but exhibited a different binding profile from wild-type p53. The knockout of mutant p53 in AX and AXT cells by CRISPR&ndash;Cas9 attenuated tumor growth but did not affect the invasion of these cells. In addition, depletion of mutant p53 did not prevent metastasis in vivo. Therefore, the therapeutic potency targeting R270C (equivalent to human R273C) mutant p53 is limited in osteosarcoma. However, considering the heterogeneous nature of osteosarcoma, it is important to further evaluate the biological and clinical significance of mutant p53 in various cases