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Association of ITPA polymorphism with outcomes of peginterferon-α plus ribavirin combination therapy

World Journal of Gastrointestinal Pharmacology and Therapeutics 2013年第3期4卷 54-60页

作者： Tatsuya Fujino Yoko Aoyagi Mariko Takahashi ryoko yada Naoko Yamamoto Yuki Ohishi Akihiko Nishiura Motoyuki Kohjima Tsuyoshi Yoshimoto Kunitaka Fukuizumi Manabu Nakashima Masaki Kato Kazuhiro Kotoh Makoto Nakamuta Munechika Enjoji Laboratory for Clinical Investigation National Hospital Organization Nagasaki Medical CenterOhmuraNagasaki 856-8562Japan Clinical Research Institute National Hospital Organization Kyushu Medical CenterFukuoka 814-0180Japan Faculty of Pharmaceutical Sciences Fukuoka UniversityFukuoka 814-0180Japan Department of Medicine and Bioregulatory Science Graduate School of Medical SciencesKyushu UniversityFukuoka 814-0180Japan

AIM:To analyzed the association between inosine triphosphatase(ITPA)(rs1127354) genotypes and sustained virological response(SVR) rates in peginterferon(Peg-IFN)α + ribavirin(RBV) ***:Patients who underwent Peg-IFNα + RBV combination therapy were enrolled(n = 120) and they had no history of other IFN-based *** in hemoglobin levels during therapy,cumulative reduction of RBV dose,frequency of treatment withdrawal,and SVR rates were investigated in each ITPA ***:In patients with ITPA CC genotype,hemoglobin decline was significantly greater and the percentage of patients in whom total RBV dose was < 60% of standard and/or treatment was withdrawn was significantly higher compared with CA/AA ***,SVR rates were equivalent between CC and CA/AA genotypes,and within a subset of patients with Interleukin 28B(IL28B)(rs8099917) TT genotype,SVR rates tended to be higher in patients with ITPA CC genotype,although the difference was not ***:ITPA CC genotype was a disadvantageous factor for Peg-IFNα + RBV treatment in relation to completion rates and RBV ***,CC genotype was not inferior to CA/AA genotype for SVR *** full-length treatment is accomplished,it is plausible that more SVR is achieved in patients with ITPA CC variant,especially in a background of IL28B TT genotype.

关键词： Chronic hepatitis C Interleukin 28B Inosine triphosphatase Peginterferon Ribavirin

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Leptin transiently antagonizes ghrelin and long-lastingly orexin in regulation of Ca^(2+) signaling in neuropeptide Y neurons of the arcuate nucleus

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World Journal of Gastroenterology 2008年第41期14卷 6347-6354页

作者： Daisuke Kohno Shigetomo Suyama Toshihiko yada Division of Integrative Physiology Department of Physiology Jichi Medical University School of Medicine Yakushiji 3311-1 Shimotsuke

AIM： To explore the mechanism for interactions of leptin with ghrelin and orexin in the arcuate nucleus （ARC） activating neuropeptide Y （NPY） neurons during physiological regulation of feeding, METHODS： Single neurons from ARC of adult rats with matured feeding function were isolated. [Ca2＋]i was measured to monitore their activities. The time course of leptin effects on ghrelin-induced versus orexin-induced [Ca2＋]i increases in NPY neurons was studied. RESULTS： Administration of ghrelin or orexin-A at 101~ mol/L increased cytosolic Ca2~ concentration （[Ca2＋]~） in NPY neurons isolated from the ARC of adult rats. Upon administration of leptin at 10^-14-10^-12 mol/L, ghrelin-induced [Ca2＋]i increases were initially （〈 10 min） inhibited but later restored, exhibiting a transient pattern of inhibition. In contrast, orexin-induced [Ca2＋]i increases were inhibited by leptin in a long- lasting manner. Furthermore, a prior administration of leptin inhibited orexin action but not ghrelin action to increase ICa 2＋li, CONCLUSION： Leptin counteracted ghrelin effects transiently and orexin effects long-lastingly in NPY neurons. The transient property with which leptin counteracts ghrelin action in NPY neurons may allow the fasting-associated increase in ghrelin levels to activate NPY neurons in the presence of physiological leptin and to stimulate feeding.

关键词： Leptin Ghrelin Orexin Arcuate nucleus Neuropeptide Y Ca2+ Feeding Phosphatidylinositol 3-kinase Phosphodiesterase 3 Signal transducer and activator of transcription 3

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An effective scatter correction method based on single scatter simulation for a 3D whole-body PET scanner

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Chinese Physics B 2009年第7期18卷 3066-3072页

作者：高飞 Yamada ryoko Watanabe Mitsuo 刘华锋 State Key Laboratory of Modern Optical Instrumentation Zhejiang University Central Research Laboratory Hamamatsu Photonics K.K.

Hamamatsu SHR74000 is a newly designed full three-dimensional （3D） whole body positron emission tomography （PET） scanner with small crystal size and large field of view （FOV）.With the improvement of sensitivity,the scatter events increase significantly at the same time,especially for large *** Carlo simulations help us to understand the scatter phenomena and provide good references for scatter correction. In this paper,we introduce an effective scatter correction method based on single scatter simulation for the new PET scanner,which accounts for the full 3D scatter *** the results from Monte Carlo simulations,we implement a new scale method with special concentration on scatter events from outside the axial FOV and multiple scatter *** effects of scatter correction are investigated and evaluated by phantom experiments;the results show good improvements in quantitative accuracy and contrast of the images,even for large objects.

关键词： positron emission tomography scatter correction single scatter simulation Monte Carlo

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Preventive approach against drug-induced pulmonary fibrosis through the suppression of epithelial-mesenchymal transition

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BIOCELL 2022年第8期46卷 1861-1865页

作者： MASASHI KAWAMI ryoko YUMOTO MIKIHISA TAKANO Graduate School of Biomedical and Health Sciences Hiroshima UniversityHiroshima7348553Japan

A number of drugs induce pulmonary injury and subsequently lead to serious lung diseases such as pulmonary fibrosis as the adverse drug ***,an effective preventive approach against drug-induced pulmonary fibrosis has not been established due to poor understanding of common preventive targets in a variety of drugs showing pulmonary ***-mesenchymal transition(EMT),a cellular phenotypic change of the epithelial to mesenchymal state,contributes to the development of pulmonary fibrosis through the conversion of damaged alveolar epithelium into *** several drugs with pulmonary toxicity have been reported to induce EMT,EMT serves as a bridge between the drugs and pulmonary *** evidence supports the potential of EMT as a preventive target against drug-induced pulmonary ***,since there are mechanistic differences between the main pharmacological effect and EMT induced by the drug,prevention based on EMT suppression would be possible and would contribute to continuous clinical treatment with the drug to avoid EMT-mediated serious pulmonary ***,targeting EMT seems to be adequate for exerting a preventive effect since EMT in damaged alveolar epithelial cells occurs prior to the development of the pathophysiological state of the whole lung in a bleomycin-induced lung injury rat *** viewpoint deals with the benefits and perspectives of preventive approaches against druginduced pulmonary fibrosis through the suppression of EMT,which has rarely been addressed.

关键词： Drug-induced lung injury Epithelial-mesenchymal transition Pulmonary fibrosis α-smooth muscle actin

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Effects of Deformation and Phase Transformation Microstructures on Springback Behavior and Biocompatibility in β-Type Ti-15Mo Alloy

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Acta Metallurgica Sinica(English Letters) 2022年第4期35卷 621-635页

作者： Sujie Zhang Xiaohua Min yada Li Weiqiang Wang Ping Li Mingjia Li School of Materials Science and Engineering Dalian University of TechnologyNo.2 Linggong RoadGanjingzi DistrictDalian 116024China

This study examined the mechanical properties, springback behavior from three-point bending loading–unloading tests and biocompatibility from human osteoblast cell adhesion and proliferation experiments in Ti-15Mo alloy with different microstructures. The springback ratio increased after the appearance of deformation microstructures including {332} twins and dislocations, due to the increased bending strength and unchanged Young’s modulus. By contrast, the change in springback ratio was dependent on the competing effect of the simultaneous increase in bending strength and Young’s modulus after phase transformation, namely, the isothermal ω-phase formation. Good cell adhesion and proliferation were observed on the alloy surface, and they were not significantly affected by the deformation twins, dislocations and isothermal ω-*** diversity of deformation and phase transformation microstructures made it possible to control the springback behavior effectively while keeping the biocompatibility of the alloy as an implant rod used for spinal fixation devices.

关键词： Titanium alloys Spinal fixation Springback behavior Deformation microstructures Phase transformation Biocompatibility

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Phase Behavior and Crystal Structure of Perovskite-Type Rare Earth Complex Oxides

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Journal of Rare Earths 2006年第6期24卷 668-672页

作者： Migaku Kobayashi ryoko Katsuraya Tsubasa Nara Yusuke Tomita Hiromi Nakano Naoki Kamegashira Department of Chemistry and Biochemistry Numazu College of Technology 3600 Ooka Numazu 410-8501 Japan Ryukoku University Seta Otsu 520-2194 Japan Department of Materials Science Toyohashi University of Technology Tempaku-cho Toyohashi 441-8580 Japan

Several compounds of rare earth complex oxides containing manganese and titanium were synthesized in Ar, and their crystal structures were analyzed by powder X-ray diffraction data and Rietveld method. Structures of A0.67Ln0.33 Mn0.33Ti0.6703（A = Ca or Sr and Ln = rare earth） were found to have orthorhombic symmetry with the space group Pnrna, and their interatomic distances and bond angles were obtained. This space group was also derived from electron microscopic study. Electrical conductivity of Cao.67Ln0.33Mn0.33Ti0.6703 for several rare earth elements showed a semiconducting property with the activation energy of 0.4 eV. Some of these compounds of the strontium system show the antiferromagnetic properties below 10 K.

关键词： perovskite crystal structure X-ray diffraction alkaline earth rare earth manganese titanium oxide

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Characterization of MT-2 cells as a human regulatory 7 cell-like cell line

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Cellular & Molecular Immunology 2016年第6期13卷 132-134页

作者： ryoko Hamano Xueqiang Wu Yitao Wang Joost J Oppenheim Xin Chen Laboratory of Molecular Immunoregulation Cancer Inflammation Program Center for Cancer Research NCI Frederick MD USA Division of Rheumatology Kanazawa University Kanazawa Ishikawa Japan State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences University of Macao Macao SAR China

The paucity of naturally occurring CD4^＋FoxP3^＋ regulatory T cells （Tregs） and difficulties in the identification and isolation of such cells are major obstacles in the study of human Tregs. The availability of human Treg-like cell lines is likely to facilitate a better understanding of the molecular basis of Treg function and aid the discovery of pharmacological reagents to regulate Treg activity in a disease state.

关键词： eg细胞人类调控表征调节性T细胞分离鉴定分子基础细胞功能

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Immediate virological response predicts the success of shortterm peg-interferon monotherapy for chronic hepatitis C

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World Journal of Gastroenterology 2010年第12期16卷 1506-1511页

作者： Masayoshi yada Akihide Masumoto Naoki Yamashita Kenta Motomura Toshimasa Koyanagi Shigeru Sakamoto Department of Hepatology Iizuka Hospital

AIM:To investigate the efficacy of short-term peginterferon(PEG-IFN)monotherapy for chronic hepatitis C patients who achieved an immediate virological ***:Defining an"immediate virological response(IVR)"as the loss of serum hepatitis C virus(HCV) RNA 7 d after the first administration of PEG-IFNα,we conducted a 12-wk course of PEG-IFNα2a monotherapy without the addition of ribavirin for 38 patients who had low pretreatment HCV RNA load and exhibited *** patients included 21 men and 17 women,whose ages ranged from 22 to 77 years(mean±SD:52.0±17.8 years).There were 4 patients with HCV genotype 1b,23 patients with genotype 2a and 4 patients with genotype *** genotype was not determined for the remaining 7 *** were categorized into a sustained virological response(SVR)group,if serum HCV RNA remained negative for 24 wk after the end of treatment,or into a relapse ***:Based on the intention-to-treat analysis,35 patients(92.1%)achieved *** patient(2.6%)relapsed with serum HCV RNA 12 wk after the end of *** patients(5.3%)withdrew from the study during the 24-wk follow-up *** regard to the HCV RNA genotype,the SVR rates were 100%(4/4) for genotype 1b,95.7%(22/23)for genotype 2a and 100%(4/4)for genotype *** SVR rate in 7 patients,whose HCV RNA genotypes were not determined,was 71.4%(5/7).CONCLUSION:Short-term PEG-IFNα2a monotherapy is highly effective for chronic hepatitis C patients who have low pretreatment HCV RNA load and exhibit IVR.

关键词： Chronic hepatitis C Immediate virological response Interferon therapy

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Hepatocellular carcinoma or interferon-based therapy history attenuates sofosbuvir/ribavirin for Japanese genotype 2 hepatitis C virus

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World Journal of Gastroenterology 2018年第13期24卷 1478-1485页

作者： Masayoshi yada Masayuki Miyazaki Kosuke Tanaka Akihide Masumoto Kenta Motomura Department of Hepatology Iizuka Hospital

AIM To investigate the real-world efficacy and safety of sofosbuvir/ribavirin(SOF/RBV) therapy for Japanese patients with genotype 2 hepatitis C virus(GT2-HCV).METHODS A total of 182 patients with GT2-HCV infection who received SOF/RBV therapy for 12 wk at our hospital were enrolled. The patients comprised 122 men and 60 women(age range: 17-84 years; mean age ± SD: 60.1 ± 12.1 years). Relationships between virological response and clinical data were examined by logistic regression analyses. RESULTS The proportions of patients with liver cirrhosis and history of hepatocellular carcinoma(HCC) were 29.0% and 17.3%, respectively. The proportion of patients with prior interferon(IFN)-based therapy was 25.6%. SOF/RBV therapy rapidly decreased HCV RNA levels. Several patients required RBV dose reduction because of anemia or fatigue. Four patients discontinued the therapy. The rates of sustained virological response at 12 wk after the end of treatment were 87.9%(intention to treat: 160/182) and 94.1%(per protocol: 159/169). Multivariate analyses showed that history of HCC or IFN-based therapy independently reduced the efficacy of SOF/RBV therapy. CONCLUSION SOF/RBV therapy for GT2-HCV is safe, highly tolerated, and effective. History of HCC or IFN-based therapy independently reduces the efficacy of this treatment.

关键词： Sofosbuvir Ribavirin Genotype 2 Hepatitis C virus Interferon-based therapy Hepatocellular carcinoma

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Design and evaluation of an extended-release matrix tablet formulation; the combination of hypromellose acetate succinate and hydroxypropylcellulose

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Asian Journal of Pharmaceutical Sciences 2017年第2期12卷 149-156页

作者： Sachiko Fukui Hideki Yano Shuichi yada Tsuyoshi Mikkaichi Hidemi Minami Formulation Technology Research Laboratories Daiichi Sankyo Co.Ltd.1-2-58HiromachiShinagawa-kuTokyo 140-8710Japan Drug Metabolism&Pharmacokinetics Research Laboratories Daiichi Sankyo Co.Ltd.1-2-58HiromachiShinagawa-kuTokyo 140-8710Japan

The purpose of this study was to develop an extended-release(ER) matrix tablet that shows robust dissolution properties able to account for the variability of pH and mechanical stress in the GI tract using a combination of enteric polymer and hydrophilic polymer. Hypromellose acetate succinate(HPMCAS) and hydroxypropylcellulose(HPC) were selected as ER polymers for the ER matrix tablet(HPMCAS/HPC ER matrix tablet). Oxycodone hydrochloride was employed as a model drug. Dissolution properties of the HPMCAS/HPC ER matrix tablets were evaluated and were not affected by the pH of the test medium or paddle rotating *** a USP apparatus 3(bio-relevant dissolution method), dissolution profiles of the HPMCAS/HPC ER matrix tablets containing oxycodone hydrochloride were similar to that of the reference product(OxyC ontin). Moreover, in vivo performance after oral administration of the HPMCAS/HPC ER matrix tablets to humans was simulated by GastroP lus based on dissolution profiles from the USP apparatus 3. The plasma concentration-time profile simulated was similar to that of the reference product. These results suggest that the combination of HPMCAS and HPC shows a robust dissolution profile against pH and paddle rotating speed and indicates the appropriate extended-release profile in humans.

关键词： Extended-release matrix tablet Hypromellose acetate succinate Hydroxypropylcellulose Robust dissolution USP apparatus 3

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