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Use of Human Embryonic Stem Cell-Derived Cardiomyocyte Clusters to Assess Potential for Chronic Treatment with Compounds to Cause QT Prolongation

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Pharmacology & Pharmacy 2014年第4期5卷 364-371页

作者： Taro Hihara Kazuto Yamazaki Tomohiko Taniguchi Takashi Yoshinaga Masashi Ito Kohei sawada Biomarkers and Personalized Medicine CFU Eisai Product Creation Systems Eisai Co. Ltd. Tsukuba Japan Biopharmaceutical Assessment CFU Eisai Product Creation Systems Eisai Co. Ltd. Tsukuba Japan Next Generation Systems CFU Eisai Product Creation Systems Eisai Co. Ltd. Tsukuba Japan

Drug-induced QT prolongation is a serious clinical issue in developing novel drug candidates and marketing drugs. A major cause of QT prolongation is direct inhibition of human ether-à-go-go-related gene (hERG) channels. Reduction in repolarization-related channel expression levels on plasma membranes is another mechanism that induces QT prolongation. Recently, we established a system for assessing the risk of QT prolongation by using human embryonic stem cell-derived cardiomyocyte clusters (hES-CMCs) in which the field potential duration (FPD) or corrected FPD (FPDc) was measured as an indicator of drug-induced QT interval prolongation. Here, we examined whether this system was able to detect FPDc prolongation caused by pentamidine or probucol, both of which can induce QT prolongation after long-term treatment. hES-CMCs were treated with pentamidine or probucol, and the FPDc of the same clusters was measured 10 min, 4 h, and 24 h after the start of treatment. Concentration-dependent FPDc prolongation was observed at 24 h, but not at 10 min, with pentamidine or probucol treatment. These results suggest that the hES-CMC-based assessment system can be used to detect both acute (at 10 min) and delayed (at 24 h) QT prolongation risk on the same platform by simple alteration of the extended culture period.

关键词： Human Embryonic Stem Cell-Derived Cardiomyocytes Field Potential Duration QT Prolongation Chronic Treatment Risk Assessment

New Indoor Accelerated Weathering Condition for Approximating Molecular Weight Distribution of Outdoor-Exposed LDPE

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Journal of Chemistry and Chemical Engineering 2015年第8期9卷 481-493页

作者： Takashl Miwa Yukitoshi Takeshita Yuichi Akage Masamitsu Watanabe Masaaki Takaya Takashi sawada NTT Device Technology Labs NTT Corporation 3-1 Morinosato-Wakamiya Atsugi-shi Kanagawa 2430198 Japan Technical Assistance and Support Center NIT East Corporation 1-2-5 kamata-honcho Ota-ku Tokyo 1440053 Japan

LDPE （low-density polyethylene） photo degraded through various accelerated weathering tests has the molecular weight distribution curves unlike that through outdoor exposure. The authors therefore developed new weathering test condition based on the existing accelerated weathering test using a xenon arc lamp. Samples of LDPE were photo degraded using various accelerated weathering test conditions and outdoor exposure. The physical properties and chemical structures of the photo degraded samples were studied through a tensile test, infrared spectroscopy, and gel chromatography. The authors found that the molecular weight distribution curve of a sample photo degraded using a xenon lamp at a higher BPT （black panel temperature）（73 ~C） was more similar to that of an outdoor-exposed sample than that of a sample photo degraded at the standard BPT （63 ~C）. It is considered that higher temperature accelerates radical recombination, consequently recreating molecular enlargement similar to the outdoor-exposed sample. Multiple regression analysis using newly introduced Mp （peak-top molecular weight） and Mw （weight-average molecular weight） as explanatory variables was conducted, which successfully enabled the authors to provide a simple explanation for the decrease in polymer tensile strength.

关键词： LDPE photo degradation molecular weight distribution accelerated weathering test outdoor exposure molecular enlargement.

Adaptability of Epoxy Asphalt to Pavement for Steel Plate Deck

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Adaptability of Epoxy Asphalt to Pavement for Steel Plate De...

Acylcarnitine: Useful biomarker for early diagnosis of hepatocellular carcinoma in non-steatohepatitis patients

ISAP2012重载沥青路面和桥面铺装专题会议

作者： Masao Yoshimi Hidekazu Maeda Etsuhiro sawada Shinichi Takei Engineering Research Lab./Taiyu Kensetsu Co. Ltd Overseas Business Headquarters/Taiyu Kensetsu Co. Ltd

＜正＞Pavement for steel plate deck has some peculiar forms of damage,therefore we have to choose an appropriate mixture and construction method for long term *** have been researching with the focus on the superior durability of epoxy asphalt mixture for a long time[1-2].And we developed suitable epoxy resin which is plant mixing type for pavement for steel plate *** we confirmed epoxy asphalt mixture is the best pavement that can keep durability against crack,rutting,and blistering,*** to these results from laboratory tests,trial constructions,and actual constructions we reached the conclusion that epoxy asphalt pavement is the most suitable as the pavement for steel plate *** have already built many epoxy asphalt pavements at several construction sites that have good condition for long term service on steel plate *** will introduce capability,workability,and serviceability of epoxy asphalt pavement on steel plate deck from our experience.

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来源： cnki会议评论

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World Journal of Gastrointestinal Oncology 2019年第10期11卷 887-897页

作者： Hiroaki Takaya Tadashi Namisaki Mitsuteru Kitade Naotaka Shimozato Kosuke Kaji Yuki Tsuji Keisuke Nakanishi Ryuichi Noguchi Yukihisa Fujinaga Yasuhiko sawada Soichiro Saikawa Shinya Sato Hideto Kawaratani Kei Moriya Takemi Akahane Hitoshi Yoshiji Third Department of Internal Medicine Nara Medical University

BACKGROUND Early diagnosis of hepatocellular carcinoma(HCC)is necessary to improve the prognosis of ***,the currently available tumor biomarkers are insufficient for the early detection of *** is essential in fatty acid metabolic pathways.A recent study reported that a high level of acylcarnitine may serve as a useful biomarker for the early diagnosis of HCC in steatohepatitis(SH)*** contrast,another study reported that the level of acetylcarnitine(AC2)-one of the acylcarnitine species-in non-SH patients with HCC was decreased vs that reported in those without *** To investigate the usefulness of acylcarnitine as a biomarker for the early diagnosis of HCC in non-SH *** Thirty-three non-SH patients(14 with HCC and 19 without HCC)were enrolled in this *** samples were obtained from patients at the time of *** levels of acylcarnitine and AC2 in the serum were determined through tandem mass *** levels of vascular endothelial growth factor(VEGF)and VEGF receptor 2(VEGFR-2)were determined by enzymelinked immunosorbent *** and multivariate analyses were used to determine early diagnostic factors of *** The level of acylcarnitine was significantly lower in non-SH patients with HCC vs those without HCC(P<0.05).In contrast,the level of lens culinaris agglutininreactive fraction ofα-fetoprotein(AFP)-AFP-L3%-was significantly higher in non-SH patients with HCC vs those without HCC(P<0.05).However,the levels of total carnitine,free carnitine,AFP,des-γ-carboxy prothrombin,VEGF,and VEGFR-2 were not different between patients with and without *** multivariate analysis showed that a low level of acylcarnitine was the only independent factor for the early diagnosis of *** patients with a low level of AC2 had a significantly higher level of VEGF vs those with a high level of AC2(P<0.05).CONCLUSION The metabolic pathways of fatty acids may differ between SH HCC and non-SH HCC

关键词： Acylcarnitine Acetylcarnitine Biomarker Hepatocellular carcinoma Angiogenesis Carnitine palmitoyltransferase 1 Oxidative stress

Biomarkers for the early diagnosis of hepatocellular carcinoma

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World Journal of Gastroenterology 2015年第37期21卷 10573-10583页

作者： Nobuhiro Tsuchiya Yu sawada Itaru Endo Keigo Saito Yasushi Uemura Tetsuya Nakatsura Department of Gastroenterological Surgery Graduate School of MedicineYokohama City University Division of Cancer Immunotherapy Exploratory Oncology Research and Clinical Trial Center National Cancer Center

Hepatocellular carcinoma(HCC) is the fifth most common cancer and the second leading cause of cancer-related deaths worldwide. Although the prognosis of patients with HCC is generally poor, the5-year survival rate is > 70% if patients are diagnosed at an early stage. However, early diagnosis of HCC is complicated by the coexistence of inflammation and cirrhosis. Thus, novel biomarkers for the early diagnosis of HCC are required. Currently, the diagnosis of HCC without pathological correlation is achieved by analyzing serum α.fetoprotein levels combined with imaging techniques. Advances in genomics and proteomics platforms and biomarker assay techniques over the last decade have resulted in the identification of numerous novel biomarkers and have improved the diagnosis of HCC. The most promising biomarkers,such as glypican-3, osteopontin, Golgi protein-73 and nucleic acids including microRNAs, are most likely to become clinically validated in the near future. These biomarkers are not only useful for early diagnosis of HCC, but also provide insight into the mechanisms driving oncogenesis. In addition, such molecular insight creates the basis for the development of potentially more effective treatment strategies. In this article,we provide an overview of the biomarkers that are currently used for the early diagnosis of HCC.

关键词： α-fetoprotein α-fetoprotein-L3 Biomarker Des-γ-car

Detection of Spherical Gold Fiducials in kV X-Ray Images Using Intensity-Estimation-Based Method

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International Journal of Medical Physics, Clinical Engineering and Radiation Oncology 2018年第1期7卷 115-130页

作者： Masaki Kokubo Masahiro Yamada Akira sawada Nobutaka Mukumoto Yuki Miyabe Takashi Mizowaki Masahiro Hiraoka Division of Radiation Oncology Institute of Biomedical Research and Innovation Kobe Japan Department of Radiation Oncology Kobe City Medical Center General Hospital Kobe Japan Department of Radiation Oncology and Image-Applied Therapy Graduate School of Medicine Kyoto University Kyoto Japan Department of Radiological Technology Faculty of Medical Science Kyoto College of Medical Science Nantan Japan

Fiducial marker detection algorithms in kilovoltage x-ray images using physical characteristics of transmission x-ray have been proposed. It, however, has been suggested recently that factors besides transmission x-ray affect x-ray images. The purpose of this study was to develop a new fiducial detection algorithm using fiducial intensity estimation based on physical characteristics of x-ray images with gold fiducials. First, x-ray images of a fiducial on a water-equivalent phantom were acquired. It was observed that the ratio of background to fiducial intensity in the images decreased as phantom thickness increased. Based on the negative correlation, we identified a function for estimating fiducial intensity that consists of background intensity and the amount of scattered radiation by the other x-ray source of an orthogonal imaging system and a treatment beam. Then, we developed an algorithm that extracts fiducial candidates using the estimation function. Its performance was measured using x-ray images which had 3824 fiducials altogether. The average number of false-positive detection of the proposed algorithm in single image was one-tenth of an algorithm considering only transmission x-ray. The proposed algorithm detected 99.5% of all fiducials under an error of 1.0 mm, while the other algorithm detected 94.7% or less (Clinical trial number: UMIN000005324).

关键词： Fiducial Marker Detection Intensity Estimation

Association between ADAMTS13 activity-VWF antigen imbalance and the therapeutic effect of HAIC in patients with hepatocellular carcinoma

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World Journal of Gastroenterology 2020年第45期26卷 7232-7241页

作者： Hiroaki Takaya Tadashi Namisaki Kei Moriya Naotaka Shimozato Kosuke Kaji Hiroyuki Ogawa Koji Ishida Yuki Tsuji Daisuke Kaya Hirotestu Takagi Yukihisa Fujinaga Norihisa Nishimura Yasuhiko sawada Hideto Kawaratani Takemi Akahane Masanori Matsumoto Hitoshi Yoshiji Department of Gastroenterology Nara Medical UniversityKashiharaNara 634-8522Japan Department of Blood Transfusion Medicine Nara Medical UniversityKashiharaNara 634-8522Japan

BACKGROUND Prediction of HAIC treatment response is important for improving the prognosis in patients with hepatocellular carcinoma(HCC).The progression of HCC is related to hypercoagulability and *** is known that ADAMTS13 and von Willebrand factor(VWF)are related to *** addition,previous study reported that the association between ADAMTS13 and VWF,and angiogenesis via vascular endothelial growth factor(VEGF).Recently,ADAMTS13 and VWF have been associated with the prognosis in patients with various kinds of cancer undergoing *** To investigate whether ADAMTS13 and VWF become useful biomarkers of treatment response in HCC patients before the initiation of HAIC *** Seventy-two patients were enrolled in this ***13 activity(ADAMTS13:AC),VWF antigen(VWF:Ag)and VEGF levels were determined via enzyme-linked immunosorbent *** and multivariable analyses were performed to determine the predictive factors of treatment response in patients with HCC undergoing HAIC *** ADAMTS13:AC levels in HCC patients with stable disease(SD)+partial response(PR)of HAIC treatment were significantly higher than those with progressive disease(PD)(P2.7)had higher VEGF levels than those with low ratio(≤2.7).Multivariable analysis revealed that VWF:Ag/ADAMTS13:AC ratio was a predictive factor of HAIC treatment *** VWF:Ag/ADAMTS13:AC ratio may become a useful biomarker of treatment response in HCC patients before the initiation of HAIC treatment.

关键词： ADAMTS13 Von Willebrand factor Vascular endothelial growth factor Biomarkers Hepatocellular carcinoma HAIC

Experimental and Numerical Analysis of Rock Block Stability Using a Remotely Positioned Laser Doppler Vibrometer

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Journal of Civil Engineering and Architecture 2014年第5期8卷 624-632页

作者： Guichen Ma Kazuhide sawada Atsushi Yashima Fumiaki Uehan Osamu Murata Hideki Saito Yasunori Ootsuka Engineering Headquarters O YO Corporation Saitama 331-8688 Japan Department of Civil Engineering Gifu University Gifu 501-1193 Japan Structural Mechanics Laboratory Railway Technical Research Institute Tokyo 185-8540 Japan

This paper examines a new method of evaluating the stability of a rock slope using a remotely positioned LDV （laser Doppler vibrometer）. We conducted an experiment using physical models and performed a numerical analysis to evaluate the new method. The physical model included：（l） concrete blocks on an artificial soil slope with two block sizes and three slopes; （2） concrete blocks bonded to the concrete base with different contact area. The LDV measurements agreed with conventional seismometer measurements. The dominant frequency of the blocks varied with the stability and dominant frequency and the amplitude varied with the block size. The numerical model was used to examine a concrete block adhered to a concrete base with different contact areas. The dominant frequency of the blocks determined using the numerical model agreed with those obtained from the physical experiments. We analyzed different sized blocks to examine the scaling effects. The dominant frequency of the blocks was inversely related to the block size. These results demonstrated the effectiveness of LDV for evaluating the stability of rock slopes and cleared the block size scaling effects.

关键词： Field measurements risks and hazards rock failure rock mass stability analysis.

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清爽发型

国际服装技术 2007年第8期 194-201页

作者： Yoko sawada Xiyanfeng（翻译）

在太阳散发灿烂光芒的季节，发型也转换成夏日的款式。LUCi的建议是在炎热的每天里也能时尚惬意的度过，需要轻盈以及清凉感的发型。通过剪发以及烫发实现炎夏最新的发型，为大家呈现上多种发型款式。

关键词：发型款式时尚烫发