2022/04/21 更新

写真a

シノハタ リョウコ
篠畑 綾子
SHINOHATA Ryoko
所属
保健学域 助教
職名
助教

学位

  • 博士(保健学) ( 岡山大学 )

  • 修士(保健学) ( 大阪大学 )

研究分野

  • その他 / その他  / 病態検査学

  • ライフサイエンス / 栄養学、健康科学

所属学協会

 

論文

  • A high-fat/high-cholesterol diet, but not high-cholesterol alone, increases free cholesterol and apoE-rich HDL serum levels in rats and upregulates hepatic ABCA1 expression

    Ryoko Shinohata, Misako Shibakura, Yujiro Arao, Shogo Watanabe, Satoshi Hirohata, Shinichi Usui

    Biochimie   197   49 - 58   2022年6月

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    担当区分:筆頭著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.biochi.2022.01.011

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  • Low plasma apolipoprotein E-rich high-density lipoprotein levels in patients with metabolic syndrome. 査読 国際誌

    Ryoko Shinohata, Yuhei Shiga, Shin-Ichiro Miura, Satoshi Hirohata, Misako Shibakura, Tomoe Ueno-Iio, Shogo Watanabe, Yujiro Arao, Shinichi Usui

    Clinica chimica acta; international journal of clinical chemistry   510   531 - 536   2020年11月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: High-density lipoprotein (HDL) containing apolipoprotein E (apoE-rich HDL) represents a small portion of plasma HDL. We recently established a method for measuring plasma apoE-rich HDL. This study aimed to investigate the relationship between metabolic syndrome (MetS) and apoE-rich HDL levels. METHODS: The apoE-rich HDL-cholesterol (HDL-C) levels and metabolic characteristics of 113 patients were analyzed. RESULTS: The MetS group (n = 58) had significantly lower apoE-rich HDL-C and a lower apoE-rich HDL-C/HDL-C ratio (apoE-HDL (%)) compared to the non-MetS group. The prevalence of MetS was increased when apoE-HDL (%) decreased. In simple regression analyses, apoE-HDL (%) was significantly inversely correlated with visceral fat area (rs = -0.370, P < 0.001) and plasma triglycerides (rs = -0.447, P < 0.001) and positively correlated with low-density lipoprotein (LDL) mean particle size (rs = 0.599, P < 0.001) and HDL mean particle size (rs = 0.512, P < 0.001). Stepwise multiple regression analysis revealed that LDL mean particle size, a component of the atherogenic lipoprotein profile, was an independent predictor of apoE-HDL (%) (adjusted R2 = 0.409). CONCLUSIONS: Plasma apoE-rich HDL levels might be a valuable indicator of MetS. These findings may help further understand HDL subfraction analysis in cardiometabolic diseases.

    DOI: 10.1016/j.cca.2020.08.020

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  • Bile Acid Metabolism is an Intermediary Factor between Non-Alcoholic Steatohepatitis and Ischemic Heart Disease in SHRSP5/Dmcr Rats 査読

    Shota Kumazaki, Mayu Nakamura, Shun Sasaki, Rina Tagashira, Nozomi Maruyama, Ikumi Sato, Shusei Yamamoto, Shang Ran, Shinichi Usui, Ryoko Shinohata, Takashi Ohtsuki, Satoshi Hirohata, Kazuya Kitamori, Mari Mori, Yukio Yamori, Shogo Watanabe

    Journal of Nutrition & Food Sciences   09 ( 04 )   2019年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Longdom Group  

    DOI: 10.35248/2155-9600.19.9.763

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  • A High-Fat and High-Cholesterol Diet Induces Cardiac Fibrosis, Vascular Endothelial, and Left Ventricular Diastolic Dysfunction in SHRSP5/Dmcr Rats.

    Shogo Watanabe, Shota Kumazaki, Katsuhiro Kusunoki, Terumi Inoue, Yui Maeda, Shinichi Usui, Ryoko Shinohata, Takashi Ohtsuki, Satoshi Hirohata, Shozo Kusachi, Kazuya Kitamori, Mari Mori, Yukio Yamori, Hisao Oka

    Journal of atherosclerosis and thrombosis   25 ( 5 )   439 - 453   2018年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIM: Non-alcoholic steatohepatitis (NASH) increases cardiovascular risk regardless of risk factors in metabolic syndrome. However, the intermediary factors between NASH and vascular disease are still unknown because a suitable animal model has never been established. The stroke-prone (SP) spontaneously hypertensive rat, SHRSP5/Dmcr, simultaneously develops hypertension, acute arterial lipid deposits in mesenteric arteries, and NASH when feed with a high-fat and high-cholesterol (HFC) diet. We investigated whether SHRSP5/Dmcr affected with NASH aggravates the cardiac or vascular dysfunction. METHOD: Wister Kyoto and SHRSP5/Dmcr rats were divided into 4 groups of 5 rats each, and fed with a SP or HFC diet. After 8 weeks of HFC or SP diet feeding, glucose and insulin resistance, echocardiography, blood biochemistry, histopathological staining, and endothelial function in aorta were evaluated. RESULTS: We demonstrate that SHRSP5/Dmcr rats fed with a HFC diet presented with cardiac and vascular dysfunction caused by cardiac fibrosis, endothelial dysfunction, and left ventricular diastolic dysfunction, in association with NASH and hypertension. These cardiac and vascular dysfunctions were aggravated and not associated with the presence of hypertension, glucose metabolism disorder, and/or obesity. CONCLUSIONS: SHRSP5/Dmcr rats may be a suitable animal model for elucidating the organ interaction between NASH and cardiac or vascular dysfunction.

    DOI: 10.5551/jat.40956

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  • Lavender Essential Oil and Its Main Constituents Inhibit the Expression of TNF-α-induced Cell Adhesion Molecules in Endothelial Cells.

    Michinori Aoe, Tomoe Ueno-Iio, Misako Shibakura, Ryoko Shinohata, Shinichi Usui, Yujiro Arao, Satoru Ikeda, Nobuaki Miyahara, Mitsune Tanimoto, Mikio Kataoka

    Acta medica Okayama   71 ( 6 )   493 - 503   2017年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Lavender essential oil (Lvn) has anti-inflammatory effects in an ovalbumin-sensitized murine model of asthma, and inhibits inflammatory cell infiltration into the lungs. The anti-inflammatory effects of Lvn on cell adhesion molecules are not clear. Here we evaluated the effects of Lvn and its main constituents, linalyl acetate (LA) and linalool (LO), on the expression of tumor necrosis factor-alpha (TNF-α)-induced cell adhesion molecules in murine brain endothelial bEnd.3 cells and human umbilical vein endothelial cells (HUVECs). The bEnd.3 cells were treated with Lvn, LA, or LO and subsequently stimulated with TNF-α. The mRNA expression levels of cell adhesion molecules were detected using RT-PCR. E-selectin and P-selectin protein and phosphorylated-NF-κB p65 were detected by western blotting. The effects of Lvn on HUVECs were measured by RT-PCR. In bEnd.3 cells, Lvn and LA suppressed TNF-α-induced E-selectin, P-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and phosphorylated-NF-κB p65 in the nucleus; LO did not suppress P-selectin or phosphorylated-NF-κB p65. Lvn inhibited TNF-α-induced E-selectin mRNA in HUVECs. These results indicate that Lvn and LA inhibit TNF-α-induced cell adhesion molecules in endothelial cells through the suppression of NF-κB activation. Consequently, Lvn or other essential oils including LA may be useful as alternative anti-inflammatory medicines.

    DOI: 10.18926/AMO/55586

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  • A rapid and precise method for measuring plasma apoE-rich HDL using polyethylene glycol and cation-exchange chromatography: a pilot study on the clinical significance of apoE-rich HDL measurements. 国際誌

    Toru Ikeda, Ryoko Shinohata, Masaaki Murakami, Kazuyoshi Hina, Shigeshi Kamikawa, Satoshi Hirohata, Shozo Kusachi, Arisa Tamura, Shinichi Usui

    Clinica chimica acta; international journal of clinical chemistry   465   112 - 118   2017年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: High-density lipoprotein (HDL) containing apolipoprotein E (apoE-rich HDL) represents only a small portion of plasma HDL. Reliable methods for determining and isolating apoE-rich HDL have not been well studied. METHODS: We established a novel analytical method for apoE-rich HDL using polyethylene glycol and a cation-exchange column (PEG-column method). Furthermore, we examined biochemical correlates of apoE-rich HDL-cholesterol (HDL-C) in 36 patients who underwent coronary computed tomographic angiography. RESULTS: Our PEG-column method demonstrated high reproducibility (coefficient of variation <3.52%) and linearity up to 15mg/dl for apoE-rich HDL-C concentrations. Isolated apoE-rich HDL exhibited a larger diameter (14.8nm) than apoE-poor HDL (10.8nm) and contained both apoE and apoA-I. ApoE-rich HDL-C concentrations correlated significantly with triglycerides (rs=-0.646), LDL size (rs=0.472), adiponectin (rs=0.476), and other lipoprotein components. No significant correlation was obtained with the coronary calcium score. Multiple regression analysis revealed that plasma triglycerides and adiponectin concentrations remained significant independent predictors of apoE-rich (adjusted R2=0.486) but not apoE-poor HDL-C. CONCLUSIONS: The PEG-column method demonstrated, to various degrees, significant correlations between HDL subfractions and several lipid-related biomarkers involved in an atherogenic lipoprotein profile. Our separation technique for apoE-rich HDL is useful to clarify the role of apoE-rich HDL in atherosclerosis.

    DOI: 10.1016/j.cca.2016.12.016

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  • 模擬試験成績の推移を利用した学生学力の定量的判断と指導方法の検討

    北脇 知己, 篠畑 綾子, 片岡 幹男, 池田 敏

    臨床検査学教育   6 ( 2 )   119 - 127   2014年9月

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    記述言語:日本語   出版者・発行元:(一社)日本臨床検査学教育協議会  

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  • Lavender essential oil inhalation suppresses allergic airway inflammation and mucous cell hyperplasia in a murine model of asthma. 国際誌

    Tomoe Ueno-Iio, Misako Shibakura, Kanayo Yokota, Michinori Aoe, Tomoko Hyoda, Ryoko Shinohata, Arihiko Kanehiro, Mitsune Tanimoto, Mikio Kataoka

    Life sciences   108 ( 2 )   109 - 15   2014年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIMS: Lavender essential oil (Lvn) has been reported to have anti-inflammatory effects. Bronchial asthma is characterized by bronchial allergic inflammation with airway remodeling. Therefore, we evaluated the anti-inflammatory effect of Lvn on experimentally induced bronchial asthma in a murine model. MAIN METHODS: BALB/c mice were sensitized by an intraperitoneal injection of ovalbumin (OVA) at days 0 and 14, and subsequently challenged with nebulized OVA on days 28-30 (Control-Asthma group). Mice in the treatment group inhaled Lvn on days 14-31 (Lvn-Asthma group). The allergic inflammatory response was determined on days 32 and 33. KEY FINDINGS: An increase in airway resistance was inhibited in the Lvn-Asthma group than in the Control-Asthma group. The Lvn-Asthma group showed lower total cell numbers and eosinophils in bronchoalveolar lavage (BAL) fluids and peribronchial and perivascular tissues when compared with the Control-Asthma group. The Lvn-Asthma group also had less mucin hyperplasia than the Control-Asthma group. Furthermore, the Lvn-Asthma group showed lower interleukin (IL)-5 and IL-13 cytokine levels in BAL fluids, as well as reduced IL-4 and IL-5 mRNA expression in lung tissue, compared with the Control-Asthma group and determined by FlowCytomix and reverse transcriptase-polymerase chain reaction (RT-PCR), respectively. In addition, Lvn inhalation reduced Muc5b mRNA expression in the lungs without significantly changing the expression of Muc5ac mRNA. SIGNIFICANCE: Lvn inhibits allergic inflammation and mucous cell hyperplasia with suppression of T-helper-2 cell cytokines and Muc5b expression in a murine model of asthma. Consequently, Lvn may be useful as an alternative medicine for bronchial asthma.

    DOI: 10.1016/j.lfs.2014.05.018

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  • Association of serum levels of arachidonic acid and eicosapentaenoic acid with prevalence of major adverse cardiac events after acute myocardial infarction.

    Masayuki Ueeda, Takenori Doumei, Yoichi Takaya, Nobuhiko Ohnishi, Atsushi Takaishi, Satoshi Hirohata, Toru Miyoshi, Ryoko Shinohata, Shinichi Usui, Shozo Kusachi

    Heart and vessels   26 ( 2 )   145 - 52   2011年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We studied the association of serum levels of arachidonic acid (AA) and eicosapentaenoic acid (EPA) with the prevalence of major adverse cardiac events (MACE) after acute myocardial infarction (AMI). We measured serum AA and EPA on admission in 146 consecutive AMI patients. The primary clinical endpoint was occurrence of MACE, defined as cardiac death, occurrence of heart failure, reinfarction, recurrent angina pectoris, and requirement of coronary intervention. Common logarithmic transformed serum levels of AA (logAA) and EPA (logEPA) were used in the analyses. The optimum cutoff point of each fatty acid used to distribute patients into two groups for Kaplan-Meier analysis was determined by receiver operating characteristic curves analysis. MACE occurred in 40 patients (27.4%). Kaplan-Meier analysis disclosed that the group with a logAA above the cutoff point [145.3 μg/mL (logAA 2.162)] showed a higher prevalence of MACE than those with a logAA below the cutoff point (P < 0.01). Conversely, the prevalence of MACE was significantly higher in the group with a logEPA below the cutoff point [52.3 μg/mL (logEPA 1.719)] compared to the group with a logEPA above it (P < 0.01). Similar to logAA, logAA/logEPA showed significant differences in the MACE-free curve between the two groups (cutoff 1.301, P < 0.001). Cox proportional hazards regression analysis suggested that logAA, logEPA, and logAA/logEPA were independently associated with the prevalence of MACE. Although the present study included a limited number of patients with single-time point measurement, the results suggested an association of logAA, logEPA, and logAA/logEPA with the prevalence of MACE after AMI. The present study warrants further studies involving a large number of patients to confirm that the serum levels of these fatty acids and their ratios are predictors of MACE after AMI.

    DOI: 10.1007/s00380-010-0038-8

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  • Connective tissue growth factor induction in a pressure-overloaded heart ameliorated by the angiotensin II type 1 receptor blocker olmesartan. 国際誌

    Mutsumi Iwamoto, Satoshi Hirohata, Hiroko Ogawa, Takashi Ohtsuki, Ryoko Shinohata, Toru Miyoshi, Faruk O Hatipoglu, Shozo Kusachi, Kazuhide Yamamoto, Yoshifumi Ninomiya

    Hypertension research : official journal of the Japanese Society of Hypertension   33 ( 12 )   1305 - 11   2010年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Connective tissue growth factor (CTGF) is a secreted protein that regulates fibrosis. We hypothesized that CTGF is induced in a pressure-overloaded (PO) heart and that blocking the angiotensin II type 1 receptor would reduce CTGF expression. Accordingly, we administered olmesartan and compared its effects with other antihypertensive drugs in a PO heart. CTGF induction was determined in a rat PO model, and olmesartan, hydralazine or saline was continuously administered. The effects of olmesartan on CTGF induction, myocyte hypertrophy and fibrosis were evaluated. The effect of olmesartan on cardiac function was also examined in CTGF- and transforming growth factor-beta 1 (TGF-β1)-infused rats. CTGF was increased in the PO heart 3 days after aortic banding and was markedly distributed around the perivascular fibrotic area. After 28 days, blood pressure was not significantly different in the olmesartan and hydralazine groups, but olmesartan treatment reduced CTGF distribution in PO hearts. Olmesartan was associated with a significantly reduced myocyte hypertrophy index (4.77±0.48 for olmesartan and 6.05±1.45 for saline, P<0.01), fibrosis area (32.0±15.5% compared with the saline group, P<0.05) and serum TGF-β1 level (62.6±10.6 ng ml⁻¹ for olmesartan and 84.4±7.2 ng ml⁻¹ for hydralazine, P<0.05). In addition, cardiac function was significantly preserved in the olmesartan group compared with the saline group. Finally, olmesartan ameliorated the cardiac dysfunction in CTGF- and TGF-β1-infused rats. Olmesartan attenuated CTGF induction, reduced perivascular fibrosis and ameliorated cardiac dysfunction in a PO heart. Our results provide insight into the beneficial effects of olmesartan on PO hearts, independent of blood-pressure lowering.

    DOI: 10.1038/hr.2010.189

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  • Significant relationship between changes in brachial-ankle pulse wave velocity relative to blood pressure elevation and coronary artery disease. 国際誌

    Issei Komatsubara, Shinichi Inoue, Rie Koumoto, Shigeru Matano, Tomoki Kitawaki, Satoshi Hirohata, Toru Miyoshi, Hiroko Ogawa, Ryoko Shinohata, Shozo Kusachi

    Coronary artery disease   21 ( 7 )   407 - 13   2010年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: Based on well-established physiological theories, we studied correlations between changes in brachial-ankle pulse wave velocity (baPWV) relative to blood pressure (BP) elevation (elasticity of large-to-medium-sized arteries), and coronary artery disease (CAD). METHODS: The baPWV (in centimeters/second) and BP (in millimeters of mercury) were determined in 101 patients before, during, and/or after a cold pressor test using a volume-plethysmographic system. RESULTS: Significantly higher rates of increase in PWV relative to changes in BP were observed in the CAD(+) group than in the CAD(-) group when mean BP [median (25th-75th percentiles): 14.8 (8.3-24.9) vs. 8.6 (5.7-11.4) cm/s/mmHg, P<0.0001], and systolic [10.1 (6.0-17.5) vs. 6.4 (4.4-10.6) cm/s/mmHg, P=0.0023] and diastolic BP [21.0 (14.0-34.4) vs. 10.8 (6.8-16.1) cm/s/mmHg, P<0.0001] were used as BP indices. Similarly, the rates of increase in baPWV showed a significant correlation with the extent of CAD. The rate of increase in baPWV obtained using the mean, systolic and diastolic BP as indices showed an area under the receiver operating characteristic curve of 0.68-0.76, sensitivity of 65-75%, and specificity of 65-75% for the detection of CAD. The area under the receiver operating characteristic curve, sensitivity, and specificity for the rate of increase were slightly higher than those for baseline baPWV and baseline baPWV/baseline BP ratio, but not to a significant degree. CONCLUSION: The rate of increase in baPWV relative to BP elevation determined by cold pressor test is significantly and moderately correlated with CAD. To identify patients with CAD, the rate of increase in baPWV relative to changes in BP can provide considerable, but limited, information.

    DOI: 10.1097/MCA.0b013e32833e1c19

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  • Filtered QRS duration on signal-averaged electrocardiography correlates with ventricular dyssynchrony assessed by tissue Doppler imaging in patients with reduced ventricular ejection fraction

    Tatsuya Tahara, Taiji Sogou, Chisato Suezawa, Hitoshi Matsubara, Norihiro Tada, Sho Tsushima, Tomoki Kitawaki, Ryoko Shinohata, Shozo Kusachi

    Journal of Electrocardiology   43 ( 1 )   48 - 53   2010年1月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.jelectrocard.2009.06.005

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  • ADAMTS1 is a unique hypoxic early response gene expressed by endothelial cells. 国際誌

    Omer F Hatipoglu, Satoshi Hirohata, M Zeynel Cilek, Hiroko Ogawa, Toru Miyoshi, Masanari Obika, Kadir Demircan, Ryoko Shinohata, Shozo Kusachi, Yoshifumi Ninomiya

    The Journal of biological chemistry   284 ( 24 )   16325 - 16333   2009年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin motifs 1) is a member of the matrix metalloproteinase family. We have previously reported that ADAMTS1 was strongly expressed in myocardial infarction. In this study, we investigated whether hypoxia induced ADAMTS1 and investigated its regulatory mechanism. In hypoxia, the expression level of ADAMTS1 mRNA and protein rapidly increased in endothelial cells, but not in other cell types. Interestingly, the induction of ADAMTS1 by hypoxia was transient, whereas vascular endothelial growth factor induction by hypoxia in human umbilical vein endothelial cells (HUVEC) increased in a time-dependent manner. CoCl2, a transition metal that mimics hypoxia, induced ADAMTS1 in HUVEC. The phosphatidylinositol 3-kinase inhibitor LY294002 dose-dependently inhibited the increase of ADAMTS1 mRNA expression in hypoxia. We characterized the promoter region of ADAMTS1, and the secreted luciferase assay system demonstrated that hypoxia induced luciferase secretion in the culture medium 4.6-fold in HUVEC. In the promoter region of ADAMTS1, we found at least three putative hypoxia-inducible factor (HIF) binding sites, and the chromatin immunoprecipitation assay revealed HIF-1 binding to HIF binding sites in the promoter region of ADAMTS1 under hypoxia. Recombinant ADAMTS1 protein promoted the migration of HUVEC under hypoxic conditions. In summary, we found that ADAMTS1 is transiently induced by hypoxia in endothelial cells, and its transcription is mediated by HIF-1 binding. Our data indicate that ADAMTS1 is a novel acute hypoxia-inducible gene.

    DOI: 10.1074/jbc.M109.001313

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  • The 3'-untranslated region of ADAMTS1 regulates its mRNA stability.

    Omer Faruk Hatipoglu, Satoshi Hirohata, Kursat Oguz Yaykasli, Mehmet Zeynel Cilek, Kadir Demircan, Ryoko Shinohata, Tomoko Yonezawa, Toshitaka Oohashi, Shozo Kusachi, Yoshifumi Ninomiya

    Acta medica Okayama   63 ( 2 )   79 - 85   2009年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin motifs 1) is an inflammatory-induced gene. We have previously reported that ADAMTS1 was strongly but transiently expressed in the infarcted heart. In this study, we investigated whether a 3'-untranslated region (UTR) affects the mRNA stability of this gene. When stimulated with tissue necrosis factor (TNF)-alpha, the expression level of ADAMTS1 mRNA rapidly increased, but the induction of ADAMTS1 mRNA peaked at 6h after stimulation, after which the expression levels of ADAMTS1 mRNA decreased. The 3'-UTR ADAMTS1 mRNA contains multiple adenine and uridine-rich elements, suggesting that the 3'-UTR may regulate gene stability. The addition of actinomycin D, an RNA synthesis inhibitor, demonstrated the decay of induced ADAMTS1 mRNA by TNF-alpha. Furthermore, a region containing multiple AUUUA motifs within the ADAMTS1 3'-UTR destabilized transfected Enhanced Green Fluorescence Protein (EGFP) mRNA expression. These results demonstrated that the ADAMTS1 3'-UTR may regulate the expression of ADAMTS1 mRNA.

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  • Hyaluronan receptors involved in cytokine induction in monocytes. 国際誌

    Hitoshi Yamawaki, Satoshi Hirohata, Toru Miyoshi, Katsuyuki Takahashi, Hiroko Ogawa, Ryoko Shinohata, Kadir Demircan, Shozo Kusachi, Kazuhide Yamamoto, Yoshifumi Ninomiya

    Glycobiology   19 ( 1 )   83 - 92   2009年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    During inflammation, lower molecular weight fragments of hyaluronan accumulate, and this is known to be inflammatory and immune-stimulatory. In diseases such as inflammatory bowel disease, inflammatory cells bind to hyaluronan; however, the cellular response and molecular mechanism of hyaluronan-hyaluronan receptor interactions in mononuclear cells are not well understood. The expression of hyaluronan receptors in peripheral blood mononuclear cells (PBMC) was examined. PBMC were stimulated with lower and higher molecular weight hyaluronan (molecular weight 100-150 kDa and 2700 kDa) and the induction of proinflammatory cytokines (interleukin-6 (IL-6) and monocyte chemoattractant protein (MCP-1)) was compared by enzyme-linked immunoabsorbant assay (ELISA). Cells were coincubated with various signaling pathway inhibitors. In addition, neutralizing antibodies against CD44 and TLR4 were added and the effects on PBMC were investigated. Finally, mononuclear cells from CD44-null and toll-like receptor 4 (TLR4) mutant mice were both stimulated with lower molecular weight hyaluronan. Among the hyaluronan receptors, TLR4 and CD44 were markedly expressed on PBMC. Hyaluronan-stimulated PBMC enhanced the attachment to the extracellular matrix. Lower molecular weight hyaluronan induced IL-6 and MCP-1 production in PBMC, but high-molecular-weight hyaluronan did not induce IL-6 and MCP-1 production. An anti-CD44 antibody attenuated the induction of both IL-6 and MCP-1 in lower molecular weight hyaluronan-stimulated PBMC. In both TLR4 mutant and CD44-null mice, the induction of IL-6 by lower molecular weight hyaluronan stimulation was decreased. SB203580 completely abolished IL-6 production in both TLR4 mutant and CD44-null mononuclear cells, while PD98059 abolished IL-6 production in CD44-null mononuclear cells. Hyaluronan receptors, CD44 and TLR4, play distinct roles in cytokine induction in hyaluronan-stimulated mononuclear cells.

    DOI: 10.1093/glycob/cwn109

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  • Serum N-3 polyunsaturated fatty acid levels correlate with the extent of coronary plaques and calcifications in patients with acute myocardial infarction.

    Masayuki Ueeda, Takenori Doumei, Yoichi Takaya, Ryoko Shinohata, Yusuke Katayama, Nobuhiko Ohnishi, Atsushi Takaishi, Toru Miyoshi, Satoshi Hirohata, Shozo Kusachi

    Circulation journal : official journal of the Japanese Circulation Society   72 ( 11 )   1836 - 43   2008年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The relationship between serum fatty acid levels and the extent of coronary plaques and calcification was examined in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: The serum levels of the n-3 polyunsaturated fatty acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) and the n-6 polyunsaturated fatty acids (arachidonic acid (AA) and dihomo-gamma-linolenic acid (DGLA)) were determined using gas chromatography on admission of 95 consecutive patients with their first AMI and 17 controls. Using multidetector-row computed tomography, soft plaques and calcification lesions were scored according to the extent of coronary involvement. Serum logarithmic transformed (log) EPA and logDHA levels were inversely correlated with soft plaque scores (r=-0.546, p<0.0001 and r=-0.377, p<0.0001, respectively). Serum logAA and logDGLA levels were not significantly correlated with soft plaque scores. Serum logEPA and logDHA levels were significantly, but weakly, correlated with calcification scores. Multivariate analysis with clinical characteristics and risk factors selected serum n-3 polyunsaturated fatty acid levels as independent factors associated with the extent of coronary soft plaques. CONCLUSION: The present study demonstrates a significant correlation between serum n-3 polyunsaturated fatty acid levels and the extent of coronary soft plaques and calcification in AMI patients.

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  • Increased blood pressure levels relative to subjective feelings of intensity of exercise determined with the Borg scale in male patients with hypertension. 国際誌

    Eriko Mayumi, Aya Nishitani, Yoko Yuki, Takaaki Nakatsu, Shinji Toyonaga, Keiichi Mashima, Hiroko Ogawa, Satoshi Hirohata, Shinichi Usui, Ryoko Shinohata, Kousaku Sakaguchi, Shozo Kusachi

    Clinical and experimental hypertension (New York, N.Y. : 1993)   30 ( 3 )   191 - 201   2008年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We examined the hemodynamic responses to exercise and symptoms in 37 male patients with untreated essential hypertension, and compared the findings with those in 32 age-matched healthy male volunteers by performing a graded symptom-limited exercise test using a bicycle ergometer. The subjective feeling of intensity of exercise was determined using the Borg scale. In the relationship between Borg scores and blood pressure (BP), patients with hypertension showed higher systolic BP and diastolic BP relative to the Borg scores than the controls. Consequently, patients with hypertension showed significantly higher systolic BP with Borg scores < or = 3 (subjective symptoms < or = moderately hard) than the controls (177.8 +/- 27.0 vs. 143.7 +/- 17.9 mmHg, p < 0.0001). Similarly, significantly higher diastolic BP with Borg scores < or = 3 was observed in patients with hypertension than in the controls (101.6 +/- 12.0 vs. 82.6 +/- 11.6 mmHg, p < 0.0001). The pulse pressure with Borg scores < or = 3 was also significantly higher in patients with hypertension than in the controls (76.2 +/- 20.6 vs. 61.0 +/- 13.6 mmHg, p < 0.0001). Hypertensive patients showed a decrease in the high-frequency power of heart rate variability at initial low-load exercise. In conclusion, the present study revealed that there was a greater BP response relative to the Borg score in patients with hypertension than in the controls. Autonomic nerve activity may contribute to some extent to these different relations. A determination of the relationship between the subjective feeling of intensity of the exercise and BP levels caused by a given intensity of load is essential before exercise training in patients, at least in males, with hypertension to avoid increasing the risk of cardiovascular events in association with excessive exercise training.

    DOI: 10.1080/10641960802068436

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  • Association of augmentation index of radial pressure wave form with diurnal variation pattern of blood pressure in untreated patients with essential hypertension. 国際誌

    Ryoko Shinohata, Takaaki Nakatsu, Yoko Yuki, Aya Nishitani, Keiichi Mashima, Shinji Toyonaga, Hiroko Ogawa, Satoshi Hirohata, Shinichi Usui, Tomoki Kitawaki, Shozo Kusachi

    Journal of hypertension   26 ( 3 )   535 - 43   2008年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: The augmentation index of the radial pulse wave has been reported to be a sensitive aortic stiffness marker in relatively young but not in older individuals. We studied the relationship between augmentation index and the diurnal blood pressure profiles. PATIENTS AND METHODS: Twenty-four-hour ambulatory blood pressure monitoring was performed in 90 untreated patients with uncomplicated essential hypertension. The patients were classified into four groups: dippers, extreme dippers, nondippers, and risers. Augmentation index was calculated as the percentage of the second systolic peak relative to the first systolic peak. RESULTS: No significant differences in the averaged whole 24-h systolic or diastolic blood pressure were observed in the whole set of patients or in subgroup patients with age 60 years or under. In the whole set of patients (58.7 +/- 12.9 years), there were significant differences in augmentation index between patients with abnormal (other than dippers) and normal diurnal blood pressure profiles (dippers). In subgroup patients with age 60 years or below (49.1 +/- 9.1 years, n = 48), the abnormal diurnal blood pressure profile group showed significantly higher augmentation index (89.6 +/- 10.3%) than dippers (80.5 +/- 11.8%). The area under the curve in the receiver operating characteristics curve for distinguishing between dippers than other dippers was 0.73 (P < 0.01). Multivariate analysis demonstrated that abnormal diurnal blood pressure profile was independently associated with increase in augmentation index. In contrast, these relationships were not significant in the over 60 years subgroup patients (69.8 +/- 5.6 years old, n = 42). CONCLUSIONS: The present study revealed that augmentation index was associated with dipping blood pressure patterns in untreated hypertensive patients aged 60 years or younger. Augmentation index determination would be useful for initial assessment in connection with possible abnormal diurnal blood pressure variability in patients with age 60 years or younger.

    DOI: 10.1097/HJH.0b013e3282f2fdb6

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  • Higher incidence and serum levels of minor cardiac biomarker elevation in sirolimus-eluting stent (Cypher) than bare metal stent implantations. 国際誌

    Tetsushi Seitou, Masaaki Murakami, Issei Komatsubara, Hiroshi Kawamura, Keizo Yamamoto, Kazuyoshi Hina, Satoshi Hirohata, Ryoko Shinohata, Yoshifumi Ninomiya, Shozo Kusachi

    Coronary artery disease   19 ( 2 )   63 - 9   2008年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: Minor cardiac biomarker elevation after percutaneous coronary intervention has long-term prognostic significance. The sirolimus-eluting stent (Cypher) has been reported to require high postinflation pressure for optimal implantation. We examined the incidence of minor cardiac biomarker elevation induced by Cypher implantation. METHODS: We measured the serum concentration of cardiac troponin-I (cTnI) 24 h after stenting and those of creatine kinase isoenzyme MB and creatine kinase before, immediately after, and 6, 12 and 24 h after implantation in patients who underwent Cypher stent (CS group; n=53) or bare metal stent (BMS group; n=57) implantation. RESULTS: No significant difference in clinical background was observed between the two groups. When a cutoff cTnI value of 0.50 ng/ml was used, the CS group showed a significantly higher incidence of cTnI elevation (35.8%, 19/53) than the BMS group (14.0%, 8/57) (P<0.05). Similarly, the incidence of cTnI > or = 0.03 ng/ml tended to be higher in the CS group (88.7%, 47/53) than in the BMS group (73.7%, 42/57: 0.05<P<0.10). Furthermore, the CS group showed significantly higher cTnI levels than the BMS group (1.32+/-2.38 vs. 0.34+/-0.91 ng/ml. P<0.001). Essentially, similar results were obtained for serum creatine kinase isoenzyme MB and creatine kinase. Among clinical, lesion and procedural characteristics, postinflation pressure for stenting was significantly higher only in the CS group (18.2+/-2.8 atm) than in the BMS group (14.0+/-2.7 atm) (P<0.001). CONCLUSIONS: The results demonstrated that CS implantation increases the incidence of minor cardiac biomarker elevation compared with BMS. The difference in postinflation pressure could account for the results.

    DOI: 10.1097/MCA.0b013e3282f2f189

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  • Association of elevated plasma B-type natriuretic peptide levels with paroxysmal atrial fibrillation in patients with nonobstructive hypertrophic cardiomyopathy. 国際誌

    Hiroko Matsuura, Takashi Murakami, Kazuyoshi Hina, Keizo Yamamoto, Hiroshi Kawamura, Taiji Sogo, Ryoko Shinohata, Shinichi Usui, Yoshifumi Ninomiya, Shozo Kusachi

    Clinical biochemistry   41 ( 3 )   134 - 9   2008年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: To investigate the relationship between the plasma B-type natriuretic peptide (BNP) level and the occurrence of atrial fibrillation (AF) in nonobstructive hypertrophic cardiomyopathy (HCM) patients. METHODS: Patients (n=97) were classified into chronic AF (CAF; n=14), paroxysmal AF (PAF; n=18) and normal sinus rhythm (NSR; n=65) groups. The plasma BNP values were analyzed with logarithmic transformation. RESULTS: The PAF group showed significantly higher plasma BNP levels than the NSR group [mean (range; -l SD and +1 SD); 248.3 (143.5, 429.5) vs. 78.2 (27.9, 218.8 ng/L), p<0.0001]. The CAF group also showed significantly higher plasma BNP levels than the NSR group [291.1 (161.4, 524.8 ng/L), p<0.0001]. Multivariate analysis with other clinical factors selected association of PAF as one of the factors that increased the plasma BNP level. CONCLUSIONS: The present study indicated that plasma BNP level is clinically useful for identification of nonobstructive HCM patients who have a risk of PAF.

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  • Serum interferon-gamma-inducible protein 10 level was increased in myocardial infarction patients, and negatively correlated with infarct size. 国際誌

    Kazuya Koten, Satoshi Hirohata, Toru Miyoshi, Hiroko Ogawa, Shinichi Usui, Ryoko Shinohata, Mutsumi Iwamoto, Tomoki Kitawaki, Shozo Kusachi, Kosaku Sakaguchi, Tohru Ohe

    Clinical biochemistry   41 ( 1-2 )   30 - 7   2008年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: We examined the serum levels of interferon-gamma-inducible protein 10 (IP-10), an inflammation-induced chemokine, in acute myocardial infarction (AMI). DESIGN AND METHODS: The subjects were 33 AMI patients, 20 stable angina pectoris patients (AP) and 20 normal subjects. In AMI patients, blood samples were collected before percutaneous coronary intervention (PCI) and on days 3, 7 and 28. RESULTS: Patients with AMI showed significantly higher serum IP-10 levels (137.5+/-79.8 pg/mL) than control subjects (91.2+/-40.1 pg/mL) and patients with AP (93.3+/-41.1 pg/mL). The serum IP-10 level before PCI was negatively correlated with infarct size, as indicated by cumulative release of creatine kinase (CK) and peak CK and its isoenzyme CK-MB. Stepwise multiple regression analysis revealed that the serum IP-10 level before PCI was an independent predictor of cumulative CK release. CONCLUSIONS: The serum IP-10 level was increased in AMI, and a higher level of serum IP-10 before PCI may be informative regarding infarct size.

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  • Use of plasma B-type natriuretic peptide level to identify asymptomatic hypertensive patients with abnormal diurnal blood pressure variation profiles: nondippers, extreme dippers, and risers. 国際誌

    Takaaki Nakatsu, Ryoko Shinohata, Keiichi Mashima, Yoko Yuki, Aya Nishitani, Shinji Toyonaga, Hiroko Ogawa, Satoshi Hirohata, Shinichi Usui, Shozo Kusachi

    Hypertension research : official journal of the Japanese Society of Hypertension   30 ( 7 )   651 - 8   2007年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We examined the relationship between plasma B-type natriuretic peptide (BNP) level and diurnal variability pattern of blood pressure (BP). Twenty-four-hour ambulatory BP monitoring was performed in 98 patients with asymptomatic essential hypertension, and the patients were classified into four groups according to their circadian BP variation profiles: dippers (n=29), nondippers (n=36), extreme dippers (n=19), and risers (n=14). Plasma BNP was measured by enzyme immunoassay. Based on the distribution pattern of BNP values, the values were analyzed after logarithmic transformation. Significant differences in plasma BNP levels among the types of circadian BP variations were demonstrated by analysis of variance (p<0.0005). Nondippers and risers showed significantly higher plasma BNP levels (mean [range: -1 SD and +1 SD]: 16.1 [6.3, 41.6] pg/mL and 29.2 [15.9, 53.4] pg/mL, respectively) than dippers (8.4 [3.7, 19.1] pg/mL). The area under the receiver operating characteristics curve for distinguishing patients with abnormal circadian BP variation from those with normal variation was 0.72, indicating that plasma BNP levels were useful for distinguishing between these patients. Specificity of 69% and sensitivity of 72% were obtained with a cut-off value of 10.5 pg/mL (log plasma BNP, 1.02) for distinguishing the abnormal diurnal BP profile group from the normal group. In conclusion, hypertensive patients with abnormal diurnal BP variation patterns (nondippers, extreme dippers, and risers) showed higher plasma BNP levels than those with normal circadian BP variation (dippers). Plasma BNP level is clinically useful for the identification of hypertensive patients who have abnormal circadian BP variability, which increases the risk of cardiovascular events.

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  • Cloning and reporter analysis of human mitochondrial phosphoenolpyruvate carboxykinase gene promoter. 国際誌

    Miwako Suzuki, Tomoyuki Yamasaki, Ryoko Shinohata, Miho Hata, Hiromu Nakajima, Norio Kono

    Gene   338 ( 2 )   157 - 62   2004年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Phosphoenolpyruvate carboxykinase (PEPCK) is one of the key regulatory enzymes in gluconeogenesis. In human liver, PEPCK is about equally distributed in both cytosol (PEPCK-1) and mitochondria (PEPCK-2). The human pepck2 gene and cDNA have been reported, but the cloning of the promoter region of the pepck2 gene has not been elucidated yet. We isolated and characterized human genomic P1-artificial chromosome (PAC) clones carrying the human pepck2 gene promoter. The oligocapping method revealed that the transcriptional start point (tsp) of the human pepck2 gene is located at 97 bp upstream of the first adenine residue of the translation start site. We also determined the nucleotide sequence to 1819 bp upstream of tsp. Sequence analysis of this region revealed that it contained several potential regulatory elements, including five GC boxes and three CCAAT boxes. Reporter analysis using transient transfection with firefly luciferase synthetic gene indicated 5' flanking region up to 822 bp, and 317 bp upstream of tsp had transcriptional activity. These results suggest that these regions of the human pepck2 gene play an important role for its expression.

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  • Nafamostat mesilate is an extremely potent inhibitor of human tryptase.

    Shuji Mori, Yoshinori Itoh, Ryoko Shinohata, Toshiaki Sendo, Ryozo Oishi, Masahiro Nishibori

    Journal of pharmacological sciences   92 ( 4 )   420 - 3   2003年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Previously, nafamostat mesilate was found to be a potent inhibitor of human tryptase. In present study, we performed a kinetic study to determine its K(i) value for tryptase and compared it with that of gabexate mesilate. Nafamostat mesilate inhibited human tryptase in a competitive manner. The apparent K(i) value was estimated to be 95.3 pM, which was 1000 times lower than that of gabexate mesilate (95.1 nM). These results strongly indicated that nafamostat mesilate is an extremely potent inhibitor of tryptase and suggested that some of its beneficial effects in the treatment of clinical status may be due to tryptase inhibition.

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  • Histidine-rich glycoprotein plus zinc reverses growth inhibition of vascular smooth muscle cells by heparin. 国際誌

    Shuji Mori, Ryoko Shinohata, Makoto Renbutsu, Hideo Kohka Takahashi, Yang-Il Fang, Kiyonori Yamaoka, Motoi Okamoto, Itaru Yamamoto, Masahiro Nishibori

    Cell and tissue research   312 ( 3 )   353 - 9   2003年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Vascular smooth muscle cell (SMC) hyperplasia is known to be an important component in the pathogenesis of arteriosclerosis and restenosis. Although heparin has been well recognized as the representative molecule suppressing SMC growth in vitro, attempts to use heparin as a therapeutic anti-restenosis drug have not favorably influenced the angiographic or clinical outcome after angioplasty in some clinical trials. In this study, we have examined the effect of histidine-rich glycoprotein (HRG), a relatively abundant serum glycoprotein (~100 micrograms/ml in human serum), on the growth inhibition of cultured vascular SMC by heparin. Vascular SMC growth was significantly inhibited by heparin, giving nearly 85% inhibition with 100 micrograms/ml heparin. HRG reversed heparin-induced SMC growth inhibition in a dose dependent manner; 75% restoration of cell growth was observed when 100 micrograms/ml of HRG was co-added with 100 micrograms/ml heparin. Interestingly, micromolar concentrations of the zinc ion (0-10 microM), compatible with concentrations released from activated platelets, were found to enhance the restorative action of HRG. Western blot experiment demonstrated no significant amounts of the HRG moiety in fetal bovine serum, eliminating the possible contribution of contaminant HRG from culture media. These findings indicate that HRG, in combination with the zinc ion, plays a role in modulating the SMC growth response in pathophysiological states and explain the lack of success of heparin as a therapeutic anti-restenosis drug in clinical trials.

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  • 甲状腺機能低下性ミオパチーにおける運動筋のプリン体分解亢進

    篠畑 綾子, 山崎 知行, 鈴木 美和子, 河野 典夫

    痛風と核酸代謝   25 ( 2 )   129 - 135   2001年12月

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    記述言語:日本語   出版者・発行元:(一社)日本痛風・尿酸核酸学会  

    標記ミオパチーの48歳女例.部分的阻血下前腕運動試験を行い,運動に伴う筋プリン体代謝の変動を検討した.その結果,運動負荷により血清アンモニア,イノシン,ヒポキサンチン値の著しい高反応が認められ,筋プリン体異化の亢進していることが明らかになった.又,本例では,甲状腺ホルモン製剤投与後ミオパチーは軽快し,運動負荷時にみられた血清アンモニア等の過大上昇反応も著明に改善したことから,筋プリン体の異化亢進は甲状腺ホルモンの不足に基づく可逆的な変化であると考えられた

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書籍等出版物

  • わかる!検査値とケアのポイント 第2版

    大久保 昭行, 井上, 智子( 担当: 分担執筆)

    医学書院  2015年12月  ( ISBN:4260016199

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    総ページ数:598   記述言語:日本語

    CiNii Books

    ASIN

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講演・口頭発表等

  • 試薬間におけるコレステロール値の差異を直接測定法にて比較検討したホモCETP欠損症の1例

    肥田 和之, 臼井 真一, 篠畑 綾子, 石井 貴大, 大井 祐貴子, 須藤 梨沙, 渡邉 聡子, 天田 雅文, 松下 裕一, 武田 昌也

    第63回日本糖尿病学会年次学術集会  2020年 

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  • Analysis of Serum HDL Subclass in Mouse Obesity Models by Cation-Exchange Chromatography

    R. Shinohata, M. Shibakura, T. Ueno-Iio, Y. Arao, S. Watanabe, S. Hirohata, M. Okazaki, S. Usui

    71st AACC Annual Scientific Meeting & Clinical Lab Expo.  2019年 

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  • Analysis of serum HDL subclass from rats with non-alcoholic fatty liver disease induced by high-fat and high-cholesterol diet.

    R. Shinohata, S. Watanabe, S. Hirohata, K. Nakajima, M. Okazaki, S. Usui

    70th AACC Annual Scientific Meeting & Clinical Lab Expo  2018年 

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  • ApoE-rich HDL in pre-heparin plasma may be HDL remnants which remain in the circulation

    S. Usui, R. Shinohata, K. Miyashita, S. Hirohata, M. Shibakura, I. Fukamachi, K. Nakajima

    69th AACC Annual Scientific Meeting & Clinical Lab Expo  2017年 

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  • Most of the hepatic triglyceride lipase (HTGL) is bound to apoE-rich HDL in post-heparin plasma

    K. Nakajima, S. Usui, R. Shinohata, K. Miyashita, S. Imamura, J. Kobayashi, T. Machida, H. Sumino, M. Murakami

    European Atherosclerosis Society (EAS)  2016年 

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  • LDL particle size associates with apoE-containing HDL in patients who undergo coronary computed tomographic angiography

    R. Shinohata, T. Ikeda, M. Murakami, K. Hina, S. Kamikawa, S. Hirohata, S. Kusachi, K. Nakajima, S. Ikeda, S. Usui

    68th AACC Annual Scientific Meeting & Clinical Lab Expo  2016年 

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  • Hepatic triglyceride lipase is mainly distributed on apoE-rich HDL in post-heparin plasma

    S. Usui, R. Shinohata, K. Nakajima, K. Miyashita, S. Imamura, K. Sato, F. Okajima, J. Kobayashi, T. Shirakawa, Y. Shimomura, T. Machida, H. Sumino, M. Murakami

    AACC Annual Meeting & Clinical Lab Expo  2015年 

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  • 模擬試験成績を利用した学生学力向上度の定量的判断と指導方法の検討

    北脇知己, 篠畑綾子, 片岡幹男, 池田敏

    日本臨床検査学教育学会学術大会  2014年 

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  • A Novel Method Using Cation-exchange and Heparin Affinity Columns Arranged Tandemly to Determine ApoE-containing HDL-cholesterol in Unpretreated Whole Serum

    S. Usui, T. Ikeda, R. Shinohata, M. Okazaki, S. Ikeda, S. Kusachi

    AACC Annual Meeting & Clinical Lab Expo  2014年 

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  • 模擬試験を利用した臨床検査技師国家試験の合格率推定

    北脇知己, 篠畑綾子, 片岡幹男, 池田敏

    第8回日本臨床検査学教育学会学術大会  2013年 

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  • 12誘導心電図による左室肥大診断におけるQT dispersionの診断的意義

    泉 礼司, 篠畑 綾子, 草地 省蔵

    日本臨床検査医学会学術集会  2011年 

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  • アンジオテンシンII受容体拮抗薬(オルメサルタン)によるサイトカイン発現抑制効果と心機能保持効果

    大月 孝志, 篠畑 綾子, 廣畑 聡, 草地 省蔵, 二宮 善文

    日本結合組織学会学術大会・マトリックス研究会大会合同学術集会  2011年 

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  • アンジオテンシンII 受容体拮抗薬(オルメサルタン)による心負荷モデルラットのCTGF発現抑制効果

    大月孝志, 廣畑聡, 岩本睦, 篠畑綾子, 草地省蔵, 二宮善文

    日本結合組織学会学術大会,マトリックス研究会大会 合同学術集会  2010年 

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  • Purification of human histidine rich glycoprotein with neutrophil chemotactic activity

    Mori S, Shinohata R, Wake H, Takahashi HK, Nishibori M

    第76回日本生化学会大会  2003年 

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  • 抗核抗体陽性SLE患者血漿中の抗ヒスチジンリッチ糖タンパク質抗体

    森 秀治, 唐下 博子, 篠畑 綾子, 高橋 英夫, 西堀 正洋

    日本臨床検査医学会  2003年 

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  • ヘパリン誘導性血管平滑筋増殖阻害に及ぼすHistidine rich glycoproteinの作用

    森 秀治, 篠畑 綾子, 連佛 誠, 高橋 英夫, 岡本 基, 山岡 聖典, 山本 格, 西堀 正洋

    第75回日本生化学会大会  2002年 

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  • Histidine rich glycoprotein exhibits chemotactic activity for human neutrophils

    Shinohata R, Mori S, Wake H, Takahashi HK, Nishibori M

    第76回日本生化学会大会  2002年 

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  • 甲状腺機能低下性ミオパチーにおける運動筋のプリン体分解亢進

    篠畑綾子, 山﨑知行, 鈴木美和子, 河野典夫

    第34回日本痛風・核酸代謝学会総会  2001年 

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  • ヒトホスホエノールピルビン酸カルボキシキナーゼ 2遺伝子プロモーターのクローニング

    山崎 知行, 鈴木 美和子, 篠畑 綾子, 中島 弘, 濱口 朋也, 冨田 晃司, 宮川 潤一郎, 難波 光義, 花房 俊昭, 松澤 佑次

    日本糖尿病学会学術集会  2000年 

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▼全件表示

受賞

  • 優秀賞

    2008年   財団法人 福田記念医療技術振興財団  

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共同研究・競争的資金等の研究

  • メタボリックシンドロームの発症・進展におけるアポE含有HDLの関与の可能性

    研究課題/領域番号:21K11622  2021年04月 - 2024年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    臼井 真一, 篠畑 綾子, 下廣 寿

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

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  • コレステロールと脂肪摂取の相乗作用による非アルコール性脂肪肝疾患の発症メカニズム

    研究課題/領域番号:21K05470  2021年04月 - 2024年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    篠畑 綾子, 臼井 真一, 柴倉 美砂子

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    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

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  • COPD治療に最適なアロマセラピーを用いた呼吸リハビリテーションの構築

    研究課題/領域番号:19K10901  2019年04月 - 2023年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    柴倉 美砂子, 森本 美智子, 篠畑 綾子, 宮原 信明, 飯尾 友愛

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    ヒト単球系細胞THP-1をマクロファージに分化させて、精油と慢性閉塞性肺疾患(COPD)治療薬で処理した後に、タバコ抽出液(CSE)で刺激して、炎症性サイトカイン発現、シグナル伝達経路および貪食能を指標として、精油とCOPD治療薬との相乗作用を検討する計画であった。予備実験において、指標として用いるCSE誘導性炎症性サイトカインの発現は、ラベンダー精油とユーカリ精油で抑制されることを明らかにしていたが、再現性を確認した。また、CSE活性化シグナル伝達経路に対する精油の作用を明らかにするために、活性酸素などのストレス刺激によって活性化されるNF-κB、p38 MAPK、JNK経路について検討した。CSE刺激によってNF-κB、p38 MAPK、JNK経路はすべて活性化されるが、精油はJNK経路を抑制することが明らかになった。精油が抑制するCSE誘導性炎症性サイトカインとシグナル伝達経路が判明し、精油の作用を評価する指標が確立できた。また、CSE刺激によってマクロファージの貪食能が低下する傾向は確認できているが、貪食能に対する精油の作用は検討できていない。
    次に精油とCOPD治療薬との相乗作用を明らかにするために、まずCOPD治療薬である長時間作用性抗コリン薬(チオトロピウム)単独でのCSE誘導性炎症性サイトカインへの作用を調べたところ、明らかな発現抑制を認めなかった。そこで、COPD治療薬をテオフィリンに変更して同様の実験を行ったところ、高濃度でCSE誘導性炎症性サイトカインの発現抑制傾向が確認できた。しかし、精油とテオフィリンとの相乗作用については、まだ検討できていない。また、ラベンダー精油やユーカリ精油と同じ作用を持つ精油のスクリーニングも検討できていない。

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  • 適度なアルコール摂取による動脈硬化予防効果の分子メカニズム基盤の確立

    研究課題/領域番号:18K05488  2018年04月 - 2021年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    臼井 真一, 廣畑 聡, 柴倉 美砂子, 篠畑 綾子

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    配分額:4420000円 ( 直接経費:3400000円 、 間接経費:1020000円 )

    1.前年度に引き続き,HepG2細胞のHDL生合成におけるエタノールの影響を検討した。ゲルろ過クロマトグラフィによる解析ではエタノールにより培養上清中のHDL-コレステロールの増加傾向,HDL粒子径の大型化,LDLコレステロールの増加が見られた。これらの変化がどのようなメカニズムによるものなのか,HDL代謝に直接的に関与する蛋白質(ABCA1, HTGL, LCAT,CETPなど)についてウエスタンブロット解析を実施したが,これまでの検討ではエタノールによる明らかな変動は認められなかった。また,コレステロール代謝やLDL代謝の変化が間接的にHDL代謝へ影響を及ぼしている可能性を考え,SREBP2, CYP7A1, MTP, LDLレセプターなどの蛋白発現も分析したが,いずれも一定の傾向をもった結果が得られなかった。
    2.今年度は新たに動物実験を開始した。1%エタノールをSDラットに自由摂取させ,10週後に血清および各臓器を採取した。飼料と飲料の摂取量はコントロール群(水飲料)に比べエタノール摂取群で少ない傾向があったが,体重変化には有意差が見られなかった。肝臓組織はエタノールによる脂肪肝の発症は見られず,肝障害のマーカーである血清ALT,AST値もコントロール群と有意差がなく良好な結果であった。血清脂質分析では,エタノール摂取により総コレステロールの減少傾向が見られ,HDL-コレステロールは予想に反して減少傾向であった。血清アポE濃度およびHDL-アポE濃度は低下していた。HDLサブクラス解析では,アポE-rich HDLが減少傾向であった。脂質組成では,HDLの遊離コレステロール比率が減少している傾向が見られた。これらの結果は,アルコール摂取がHDL-コレステロール量だけでなく,クオリティーの変化に関与している可能性を示唆している。

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  • HDLを介した肝内コレステロール搬出に基づく非アルコール性脂肪肝炎の予防戦略

    研究課題/領域番号:18K11073  2018年04月 - 2021年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    篠畑 綾子, 臼井 真一

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    今年度は新たに動物実験を開始した。脂質組成の異なる4種の飼料[通常飼料(MF),高コレステロール飼料(HC)、高脂肪飼料(HF)、高脂肪・高コレステロール飼料(HFC)]で10週間SDラットを飼育し、肝臓における脂肪蓄積と血清HDLの関連を検討した。
    1. HF群およびHFC群はMF群に比べ、飼料摂取量が少なく体重が低値であった。HC群は飼料摂取量に差は見られなかったが、体重が低値傾向だった。肝臓組織はHC群とHFC群で有意な脂肪蓄積が見られた。肝臓に蓄積したコレステロール量は両群に差は見られなかったが、HFC群の方がトリグリセライドの蓄積量が多かった。また、HFC群では肝線維化も観察され、血清ALT値もHC群よりも増加していたことから、HFC群の方が肝障害の程度がより強く、非アルコール性脂肪肝炎に近い病態であることが確認できた。
    2. 血清総コレステロールはMF群に比べ、HC群とHFC群で有意な増加が見られたが、HDL-コレステロールは予想に反してHC群で減少、HFC群で増加していた。HFC群では大型HDLが増加しており、増加したコレステロールは遊離コレステロールがメインであった。大型HDLに含まれるアポEはHFC群で増加、HC群で減少していた。これらの結果から、肝臓における脂質蓄積がHDLの量や質に深く関連している可能性が示唆された。
    3. HC群とHFC群に見られたHDLの変動要因を明らかにするために、肝臓におけるHDL関連蛋白質の発現を調べた。これまでのところ、アポA1、アポE、SR-BI(HDLレセプター)、LCATなどの遺伝子発現については両群で差は見られなかった。現在、他の遺伝子発現や蛋白質レベルでの発現解析を進めている。

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  • 生活習慣病におけるアポE含有HDLの役割

    研究課題/領域番号:15K01715  2015年04月 - 2018年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    臼井 真一, 廣畑 聡, 篠畑 綾子

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    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

    本研究では,血清アポE含有HDLの定量測定法を開発し,肥満モデルマウスでアポ含有HDLが増加することを示した。臨床検体の検討では,重回帰分析により,肥満に深く関わる中性脂肪やアディポネクチンがアポE含有HDL-コレステロールの有意な予測因子であることを明らかにした。しかし,脂肪細胞の培養実験では,アポE含有HDLが脂肪蓄積に関与するデータは得られなかった。一方,肝細胞の培養実験では高グルコース培地によりアポE含有HDLの生成が増加し,細胞内へのグルコース取り込みがアポE含有HDLの生成に深く関与していることが示唆され,糖代謝とアポE含有HDLの生成との関連において今後新たな展開が期待される。

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  • ヒアルロン酸の変形性関節炎アップストリーム治療薬としての新展開と関節保護作用

    研究課題/領域番号:25462372  2013年04月 - 2016年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    大月 孝志, 廣畑 聡, 西田 圭一郎, 藤渕 航, 篠畑 綾子, 草地 省蔵, 二宮 善文

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    配分額:4940000円 ( 直接経費:3800000円 、 間接経費:1140000円 )

    1)ヒアルロン酸(HA)によるサイトカイン誘導性アグリカナーゼ発現抑制micro RNAの検出
    分解系酵素を制御すると考えられる複数のmiRNAを検出した。2) OAモデルラットへのHA投与の長期効果 長期(9w)投与試験では有意な軟骨損傷抑制効果は見られたが、効果は中期間より減少した。3) メカニカルストレスのヒアルロン酸受容体遺伝子発現への影響 軟骨細胞のHA受容体CD44、ICAM1mRNA発現変動は見られなかった。4)メカニカルストレスによるマトリックスタンパク発現への影響 弱いメカニカルストレス刺激で軟骨細胞のマトリックスタンパク、アグリカン、2型コラーゲン遺伝子発現が増大した。

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  • 血漿CTGFの高血圧性心肥大バイオマーカーとしての有用性-基礎的検討

    研究課題/領域番号:21790537  2009年 - 2010年

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    篠畑 綾子

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    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

    本研究では圧負荷モデルラットにおける心肥大の発生と血中結合組織成長因子(CTGF)濃度の推移との関連について検討を行った。血中CTGF濃度は左室壁肥厚をきたさない術後3日目から2週目にかけて、一部の圧負荷ラットで高値例が認められたが、圧負荷群と対照群(sham群)で統計学的には有意な差は認められなかった。術後3週目以降に圧負荷ラットにて左室壁厚に有意な増加が認められたが、その血中CTGF濃度は2群間で有意な差は認められなかった。

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