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Tada, Hayato ; Kawashiri, Masa-aki ; Nohara, Atsushi ; Inazu, Akihiro ; Kobayashi, Junji ; Yasuda, Kenji ; Mabuchi, Hiroshi ; Yamagishi, Masakazu ; Hayashi, Kenshi ; 多田, 隼人 ; 川尻, 剛照 ; 野原, 淳 ; 稲津, 明広 ; 小林, 淳二 ; 馬淵, 宏 ; 山岸, 正和 ; 林, 研至
出版情報: Journal of Atherosclerosis and Thrombosis.  24  pp.338-345,  2017.  日本動脈硬化学会 = Japan Atherosclerosis Society
URL: http://hdl.handle.net/2297/00053012
概要: 金沢大学附属病院循環器内科<br />Aim: The Japan Atherosclerosis Society (JAS) guidelines for the prevention of atherosclerotic disease s 2012 (JAS2012) proposed lipid management targets; however, less data is available regarding the attainment rates of each target in community-based settings. Therefore, we assessed the attainment rates of lipid management targets among subjects who underwent Japanese specific health checkups.\nMethods: A total of 85,716 subjects (male=29,282, 34.2%) aged 40–74 years who underwent specific health checkups from 2012 to 2014 in Kanazawa city, Japan, were included in this study. We evaluated the attainment rates of the lipid management targets according to the JAS2012 guideline and investigated the clinical characteristics of the subjects without achieving the targets.\nResults: The target for LDL cholesterol (LDL-C) was the least attained in all risk categories, 89, 72, 50, and 34% for category I, II, III, and secondary prevention, respectively, in 2014. In addition, these rates inversely correlated with the grade of risk categories (p-value for trends <0.001). Attainment rate of the LDL-C target in the suspected chronic kidney disease (CKD) group was significantly lower than in the groups with diabetes, stroke, or absolute risk in category III (49.2, 60.3, 63.5, 54.4%, respectively, p-value <0.001 for each). Moreover, the attainment rate of the LDL-C target was significantly lower in subjects that did not receive lipid-lowering therapy than in those who received it in the secondary prevention (27.7 and 40.6%, respectively, p-value <0.001).\nConclusions: Lipid management is inadequate in community-based settings, particularly, in subjects with CKD and secondary prevention.<br />This article distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License. 続きを見る
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Imamura, S. ; Kobayashi, Junji ; Sakasegawa, S. ; Nohara, Atsushi ; Nakajima, Kenichi ; Kawashiri, Masa-aki ; Inazu, Akihiro ; Yamagishi, Masakazu ; Koizumi, Junji ; Mabuchi, Hiroshi ; 小林, 淳二 ; 野原, 淳 ; 中嶋, 憲一 ; 川尻, 剛照 ; 稲津, 明広 ; 山岸, 正和 ; 小泉, 順二 ; 馬渕, 宏
出版情報: Journal of Lipid Research.  48  pp.453-457,  2007-02.  American Society for Biochemistry and Molecular Biology
URL: http://hdl.handle.net/2297/00050262
概要: 金沢大学医薬保健研究域医学系<br />The objective of this study was to establish a hepatic lipase (HL) assay method that can be applied to automatic clinical analyzers. Seventy-four hyperlipidemic subjects (men/women 45/29) were recruited. Lipase activity was assayed measuring the increase in absorbance at 546 nm due to quinonediimine dye production. Reaction mixture R-1 contained 50 mM Tris-HCl (pH 9.5), 0.5 mM glycerol-1,2-dioleate, 0.4% (unless otherwise noted) polyoxyethylenenonylphenylether, 3 mM ATP, 3 mM MgCl2, 1.5 mM CaCl2, monoacylglycerol-specific lipase, glycerol kinase, glycerol-3-phosphate oxidase, 0.075% N,N-bis-(4-sulfobutyl)-3-methylaniline-2 Na, peroxidase, ascorbic acid oxidase. Reaction mixture R-2 contained 50 mM Tris-HCl (pH9.5), 0.15% 4-aminoantypirine. Automated assay for activity was performed with a Model 7080 Hitachi analyzer. In the lipase assay, 160 μl of R-1 was incubated at 37°C with 3 μl of samples for 5 min, and 80 μl of R-2 was added. Within-run coefficient of variations was 0.9-1.0%. Calibration curve of lipase activity was linear (r = 0.999) between 0 and 320 U/l. Analytical recoveries of purified HL added to plasma were 96.6-99.8%. HL activity in postheparin plasma measured in this method had a closer correlation with HL mass by a sandwich ELISA (r = 0.888, P , 0.0001) than those in the conventional method using [ 14C-]triolein (r = 0.730, P < 0.0001). This assay method for HL activity can be applied to an automatic clinical analyzer. Copyright © 2007 by the American Society for Biochemistry and Molecular Biology, Inc. 続きを見る
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論文
Tada, Hayato ; Kawashiri, Masa-aki ; Nohara, Atsushi ; Inazu, Akihiro ; Kobayashi, Junji ; Mabuchi, Hiroshi ; Yamagishi, Masakazu ; 多田, 隼人 ; 川尻, 剛照 ; 野原, 淳 ; 稲津, 明広 ; 小林, 淳二 ; 馬渕, 宏 ; 山岸, 正和
出版情報: Journal of Atherosclerosis and Thrombosis.  22  pp.1-9,  2015.  Japan Atherosclerosis Society = 日本動脈硬化学会
URL: http://hdl.handle.net/2297/00050270
概要: 金沢大学医薬保健研究域医学系<br />Autosomal recessive hypercholesterolemia (ARH) is an extremely rare inherited disorder, the cause of which is mutations in the low-density lipoprotein (LDL) receptor adaptor protein 1 (LDLRAP1) gene. Only 36 families with 14 different mutations have been reported in the literature to date. The clinical phenotype of ARH is milder than that of homozygous familial hypercholesterolemia (FH) caused by LDL receptor gene mutations. Recently, the lipoprotein metabolism of ARH was investigated in both humans and mice by several investigators, including ourselves. Based on these findings the preserved clearance of LDL receptor-dependent very-LDL (VLDL) may be a possible mechanism underlying the responsiveness to statins and the milder phenotype of ARH. Although ARH has been described as being “recessive,” several studies, including ours, have indicated that a heterozygous carrier status of the LDLRAP1 gene is associated with mild hypercholesterolemia and exacerbates the phenotype of FH resulting from LDL receptor gene mutations. This review summarizes current understanding regarding ARH and its causative gene, LDLRAP1, and attempts to provide new insight into novel pharmacological targets for treating dyslipidemic patients. © Journal of Atherosclerosis and Thrombosis. All right received.<br />出版者照会後に全文公開 続きを見る
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Mabuchi, Hiroshi ; Higashikata, Toshinori ; Nohara, Atsushi ; Lu, Hong ; Yu, Wen Xin ; Nozue, Tsuyoshi ; Noji, Yoshihiro ; Katsuda, Shoji ; Kawashiri, Masa-aki ; Inazu, Akihiro ; Kobayashi, Junji ; Koizumi, Junji ; 馬渕, 宏 ; 野原, 淳 ; 川尻, 剛照 ; 稲津, 明広
出版情報: Journal of Atherosclerosis and Thrombosis.  12  pp.35-40,  2005-02-23.  Japan Atherosclerosis Society = 日本動脈硬化学会
URL: http://hdl.handle.net/2297/48755
概要: 出版者照会後に全文公開
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Mabuchi, Hiroshi ; Higashikata, Toshinori ; Kawashiri, Masa-aki ; Katsuda, Shoji ; Mizuno, Mihoko ; Nohara, Atsushi ; Inazu, Akihiro ; Koizumi, Junji ; Kobayashi, Junji ; 馬渕, 宏 ; 川尻, 剛照 ; 野原, 淳 ; 稲津, 明広 ; 小泉, 順二 ; 小林, 淳二
出版情報: Journal of Atherosclerosis and Thrombosis.  12  pp.111-119,  2005-06-07.  Japan Atherosclerosis Society = 日本動脈硬化学会
URL: http://hdl.handle.net/2297/48756
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Kobayashi, Junji ; Murano, Shunichi ; Kawamura, Isao ; Nakamura, Fumie ; Murase, Yuko ; Kawashiri, Masa-aki ; Nohara, Atsushi ; Asano, Akimichi ; Inazu, Akihiro ; Mabuchi, Hiroshi ; 小林, 淳二 ; 川尻, 剛照 ; 野原, 淳 ; 稲津, 明広 ; 馬渕, 宏
出版情報: Journal of Atherosclerosis and Thrombosis.  13  pp.221-226,  2006-11-02.  Japan Atherosclerosis Society = 日本動脈硬化学会
URL: http://hdl.handle.net/2297/48760
概要: 出版者照会後に全文公開
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Kobayashi, Junji ; Nohara, Atsushi ; Kawashiri, Masaaki ; Inazu, Akihiro ; Koizumi, Junji ; Nakajima, Katsuyuki ; Mabuchi, Hiroshi
出版情報: Clinica Chimica Acta.  378  pp.7-12,  2007-03-01.  Elsevier BV
URL: http://hdl.handle.net/2297/3653
概要: 金沢大学大学院医学系研究科<br />Lipoprotein lipase (LPL) is a lipolytic enzyme involved in catalyzing hydrolysis of triglycerides (TG ) in chylomicrons and very low-density lipoprotein (VLDL) particles. Over the last decade, increasing attention has been paid to the clinical significance of measuring serum LPL protein mass without heparin injection to the study subjects. In earlier studies, this marker was utilized to classify LPL deficient subjects, which is an extremely rare metabolic disorder with a frequency of one in one million. Later, researchers paid more attention to the clinical significance of measuring this parameter in more common metabolic disorders. Studies have shown that pre-heparin plasma or serum LPL mass has significant relationships with serum lipids and lipoproteins, visceral fat area, insulin resistance, and even the development of coronary atherosclerosis in cross-sectional studies, although this might be a metabolic surrogate marker with almost no catalytic activities, which does not appear to be involved in catalyzing hydrolysis of TG in TG-rich lipoproteins. Recently, a prospective study has demonstrated that low serum LPL concentration predicts future coronary events. Taken together, we suggest that pre-heparin LPL mass in plasma or sera provide us with useful and important information on the development of metabolic disorders leading to atherosclerotic disease. © 2006 Elsevier B.V. All rights reserved. 続きを見る
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Kawashiri, Masaaki ; Higashikata, Toshinori ; Nohara, Atsushi ; Kobayashi, Junji ; Inazu, Akihiro ; Koizumi, Junji ; Mabuchi, Hiroshi
出版情報: Circulation Journal.  69  pp.515-520,  2005-05-01.  日本循環器学会
URL: http://hdl.handle.net/2297/7212
概要: 金沢大学大学院医学系研究科 <br />Background: Colestimide, a 2-methylimidazole-epichlorohydrin polymer, is a new bile-acid-sequesterin g resin, that is 4-fold as powerful at lowering low-density lipoprotein cholesterol (LDL-C) as the conventional resin (cholestyramine). Moreover, colestimide has excellent patient compliance because it is available in tablet form. Methods and Results: The clinical efficacy of colestimide coadministered with atorvastatin on lipid and apolipoprotein concentrations was examined in 15 patients (M/F = 10/5, mean±SE age=54±9 years) with heterozygous familial hypercholesterolemia (FH). After a period of wash-out of any lipid-lowering drugs, atorvastatin (20-40mg) was administered to patients for at least 8 weeks, and then 3 g of colestimide was administered for a further 8 weeks. Total and LDL-C significantly (<0.0001) decreased by 35% from 361 to 233mg/dl and 41% from 274 to 161 mg/dl, respectively. Addition of colestimide caused a further significant 12% and 20% reduction, respectively, from the initial values to 205 and 129 mg/dl, respectively. Colestimide was also effective in reducing serum LDL-C concentrations in heterozygous FH patients with hypertriglyceridemia (triglycerides ≥150mg/dl). Conclusions: When monotherapy with atorvastatin is insufficient to treat severely hypercholesterolemic patients, such as those with heterozygous FH, colestimide acts to reinforce the action of statins. 続きを見る
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Kawashiri, Masaaki ; Higashikata, Toshinori ; Takata, Mutsuko ; Katsuda, Shoji ; Miwa, Kenji ; Nohara, Atsushi ; Inazu, Akihiro ; Kobayashi, Junji ; Shimizu, Masami ; Koizumi, Junji ; Mabuchi, Hiroshi
出版情報: Circulation Journal.  69  pp.746-751,  2005-06-01.  日本循環器学会
URL: http://hdl.handle.net/2297/7216
概要: 金沢大学大学院医学系研究科 <br />A 38-year-old Japanese woman was admitted to hospital for further examination of systemic xanthomas. She had a past history of genital bleeding during her third delivery at the age of 21 years. She was diagnosed with Sheehan's syndrome. Her serum total cholesterol and triglyceride concentrations were 500 and 898 mg/dl, respectively. She was also diagnosed as having type III hyperlipoproteinemia on the basis of the presence of a broad-β-band on agarose gel electrophoresis and extremely high concentrations of very-low-density lipoprotein cholesterol (310 mg/dl). The diagnosis was later confirmed by her apolipoprotein E isoforms (E2/E2) and genotypes (epsilon2/epsilon2). Thyroid and corticosteroid hormone replacement therapy cured the xanthomas, but also elevated her blood pressure. The serum concentration of intermediate-density lipoprotein cholesterol was consistently high, whereas that of low-density lipoprotein cholesterol was relatively low during the follow-up. Coronary atherosclerosis had already developed by the age of 38 years, and progressed significantly over the following 28 years. Severe stenotic lesions were observed in the bilateral renal arteries and carotid arteries, and in the abdominal aorta when she was 66 years old. These findings suggest that the continuous elevation of intermediate-density lipoprotein cholesterol for a long period contributed to the development of the atherosclerotic lesions. 続きを見る
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Yagi, Kunimasa ; Hifumi, Senshu ; Nohara, Atsushi ; Higashikata, Toshinori ; Inazu, Akihiro ; Mizuno, Kiyoo ; Namura, Masanobu ; Ueda, Kosei ; Kobayashi, Junji ; Shimizu, Masami ; Mabuchi, Hiroshi
出版情報: Circulation Journal.  68  pp.623-627,  2004-07-01.  日本循環器学会
URL: http://hdl.handle.net/2297/7204
概要: 金沢大学大学院医学系研究科 <br />Background: The aim of the present study was to clarify the risk factors of several types of arterio sclerosis lesions in Japanese individuals with heterozygous familial hypercholesterolemia (FH): renal arteriosclerosis (RAS), abdominal aortic sclerosis (AOS), iliac arteriosclerosis (IAS) and coronary artery disease (CAD). Methods and Results: Coronary angiography (CAG) and abdominal aortic angiography (AAA) were performed in 117 consecutive heterozygous FH subjects (79 men, 38 women; age 22-76). RAS (stenotic lesion or aneurysm) was observed in 39 cases (33%), predominantly in the proximal portion (74%) and both sides equally (right/left=27/23). Most cases of RAS (64%) presented with <25% stenosis. The differences in the contributing risk factors for the progression and development of RAS, AOS, IAS and CAD in FH were then analyzed. Multiple logistic regression analyses showed independent risk factors for formation of atherosclerosis in each artery were: age alone for RAS; age and plasma low-density lipoprotein cholesterol (LDL-C) for AOS; age, LDL-C and high-density lipoprotein cholesterol (HDL-C) for IAS; and HDL-C and diabetes mellitus for CAD. Conclusion: In Japanese subjects with heterozygous FH, there are distinct risk factors for the development and progression of atherosclerosis in the renal, iliac, abdominal aorta, and coronary arteries. 続きを見る