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論文
Nakahashi, Takuya ; Tada, Hayato ; Sakata, Kenji ; Nomura, Akihiro ; Ohira, Miho ; Mori, Mika ; Takamura, Masayuki ; Hayashi, Kenshi ; Yamagishi, Masakazu ; Kawashiri, Masa-aki ; 多田, 隼人 ; 坂田, 憲治 ; 野村, 章洋 ; 大平, 美穂 ; 森, 三佳 ; 高村, 雅之 ; 林, 研至 ; 山岸, 正和 ; 川尻, 剛照
出版情報: Journal of Atherosclerosis and Thrombosis.  25  pp.709-719,  2018.  日本動脈硬化学会 = Japan Atherosclerosis Society
URL: http://hdl.handle.net/2297/00053009
概要: 金沢大学附属病院循環器内科<br />Aim: To assess whether combining measurements obtained from carotid ultrasonography in addition to th e age, creatinine, and ejection fraction (ACEF) score would improve the predictive ability of outcome in patients with acute coronary syndrome (ACS).\nMethods: We examined 264 patients with ACS (194 men; mean age: 68±11 years) who underwent percutaneous coronary intervention. The carotid plaque score (cPS) and intima–media thickness (cIMT) were determined by carotid ultrasonography. The modified ACEF score was calculated using the following formula: (age/left ventricular ejection fraction) +1 point for every 10 mL/min reduction in creatinine clearance below 60 mL/min per 1.73 m2. The endpoint of this study was major adverse cardiovascular and cerebrovascular events (MACEs), defined as all-cause death, myocardial infarction, stoke, and target vessel revascularization.\nResults: During the median 4-year follow-up, there were 121 incidents of MACEs. Multivariate Cox proportional hazard regression analysis revealed that cPS ≥9.8 (hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.01–2.31) and ACEF score ≥1.20 (HR, 1.62; 95% CI, 1.11–2.39) were significantly associated with MACEs, whereas cIMT was not. When the new combined risk score was calculated by multiplying the cPS by the modified ACEF score, the freedom from MACEs at 5 years was 71% and 31% for the lower and higher scores, respectively (p<0.001). The area under the receiver-operating characteristic curve for MACEs for the ACEF score, cPS, and combined risk score were 0.65, 0.66, and 0.71, respectively (p<0.05).\nConclusion: The cPS offers an incremental predictive value when combined to the simple ACEF score in ACS.<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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Nomura, Akihiro ; Tada, Hayato ; Nohara, Atsushi ; Kawashiri, Masa-aki ; Yamagishi, Masakazu ; 野村, 章洋 ; 多田, 隼人 ; 野原, 淳 ; 川尻, 剛照 ; 山岸, 正和
出版情報: Journal of Atherosclerosis and Thrombosis.  25  pp.741-746,  2018.  日本動脈硬化学会 = Japan Atherosclerosis Society
URL: http://hdl.handle.net/2297/00053010
概要: 金沢大学附属病院先端医療開発センター<br />Aim: Sitosterolemia is an extremely rare, autosomal recessive disease characterized by high plas ma cholesterols and plant sterols because of increased absorption of dietary cholesterols and sterols from the intestine, and decreased excretion from biliary tract. Previous study indicated that sitosterolemic patients might be vulnerable to post-prandial hyperlipidemia, including high remnant-like lipoprotein particles (RLP) level. Here we evaluate whether a loading dietary fat increases a post-prandial RLP cholesterol level in sitosterolemic patients compared to heterozygous familial hypercholesterolemic patients (FH).\nMethods: We recruit total of 20 patients: 5 patients with homozygous sitosterolemia, 5 patients with heterozygous sitosterolemia, and 10 patients with heterozygous FH as controls from May 2015 to March 2018 at Kanazawa University Hospital, Japan. All patients receive Oral Fat Tolerance Test (OFTT) cream (50 g/body surface area square meter, orally only once, and the cream includes 34% of fat, 74 mg of cholesterol, and rich in palmitic and oleic acids. The primary endpoint is the change of a RLP cholesterol level after OFTT cream loading between sitosterolemia and FH. We measure them at baseline, and 2, 4, and 6 hours after the oral fat loading.\nResults: This is the first study to evaluate whether sitosterolemia patients have a higher post-prandial RLP cholesterol level compared to heterozygous FH patients.\nConclusion: The result may become an additional evidence to restrict dietary cholesterols for sitosterolemia. This study is registered at University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN ID: UMIN000020330).<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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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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Tada, Hayato ; Kawashiri, Masa-aki ; Yamagishi, Masakazu ; 多田, 隼人 ; 川尻, 剛照 ; 山岸, 正和
出版情報: Journal of Atherosclerosis and Thrombosis.  24  pp.452-461,  2017.  日本動脈硬化学会 = Japan Atherosclerosis Society
URL: http://hdl.handle.net/2297/00053013
概要: 金沢大学附属病院循環器内科<br />We have learned that low-density lipoprotein (LDL) cholesterol is the cause of atherosclerosis from v arious aspects, including a single case with familial hypercholesterolemia, other cases with different types of Mendelian dyslipidemias, large-scale randomized controlled trials using LDL cholesterol lowering therapies, and Mendelian randomization studies using common as well as rare variants associated with LDL cholesterol levels. There is no doubt that determinations of genotypes in lipid-associated genes have contributed not only to the genetic diagnosis for Mendelian dyslipidemias but also to the discoveries of novel therapeutic targets. Furthermore, recent studies have shown that such genetic information could provide useful clues for the risk prediction as well as risk stratification in general and in particular population. We provide the current understanding of genetic analyses relating to plasma lipids and coronary artery disease.<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
Sakamoto, Aiji ; Sugamoto, Yuka ; Tokunaga, Y. ; Yoshimuta, Tsuyoshi ; Hayashi, Kenshi ; Konno, Tetsuo ; Kawashiri, Masa-aki ; Takeda, Yoshiyu ; Yamagishi, Masakazu ; 林, 研至 ; 今野, 哲雄 ; 川尻, 剛照 ; 武田, 仁勇 ; 山岸, 正和
出版情報: Journal of International Medical Research.  39  pp.522-527,  2011.  SAGE Publications
URL: http://hdl.handle.net/2297/00050263
概要: 金沢大学医薬保健研究域医学系<br />Ephrin B1 and its cognate receptor, Eph receptor B2, key regulators of embryogenesis, are expressed in human atherosclerotic plaque and inhibit adult human monocyte chemotaxis. Few data exist, however, regarding the gene expression profiles of the ephrin (EFN) and Eph receptor (EPH) family of genes in atherosclerosis-related human cells. Gene expression profiles were determined of all 21 members of this gene family in atherosclerosis-related cells by reverse transcription-polymerase chain reaction analysis. The following 17 members were detected in adult human peripheral blood monocytes: EFNA1 and EFNA3 - EFNA5 (coding for ephrins A1 and A3 - A5); EPHA1, EPHA2, EPHA4 - EPHA6 and EPHA8 (coding for Eph receptors A1, A2, A4 - A6 and A8); EFNB1 and EFNB2 (coding for ephrins B1 and B2); and EPHB1 - EPHB4 and EPHB6 (coding for Eph receptors B1 - B4 and B6). THP-1 monocytic cells, Jurkat T cells and adult arterial endothelial cells also expressed multiple EFN and EPH genes. These results indicate that a wide variety of ephrins and Eph receptors might affect monocyte chemotaxis, contributing to the development of atherosclerosis. Their pathological significance requires further study. © 2011 Field House Publishing LLP. 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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論文
Tada, Hayato ; Nohara, Atsushi ; Kawashiri, Masa-aki ; Inazu, Akihiro ; Mabuchi, Hiroshi ; Yamagishi, Masakazu ; 多田, 隼人 ; 野原, 淳 ; 川尻, 剛照 ; 稲津, 明広 ; 馬渕, 宏 ; 山岸, 正和
出版情報: Journal of Atherosclerosis and Thrombosis.  21  pp.1326-1329,  2014.  Japan Atherosclerosis Society = 日本動脈硬化学会
URL: http://hdl.handle.net/2297/00050271
概要: 金沢大学医薬保健研究域医学系<br />We herein report a case of marked transient hypercholesterolemia in a man receiving low-dose mitotan e as adjuvant chemotherapy for adrenocortical carcinoma.A 58-year-old man without any clinical symptoms or history of hypercholesterolemia was admitted to our hospital to treat an adrenocortical carcinoma detected on general screening using computed tomography. He reported no chest symptom and did not exhibit any established risk factors for coronary artery disease, such as diabetes, obesity, hypertension or relevant family history, with the exception of current smoking, on admission. A stress electrocardiogram showed negative findings. The left adrenal tumor as well as left kidney, spleen and distal portion of the pancreas were subsequently resected using radical surgery. The histopathological findings confirmed the preoperative diagnosis of adrenocortical carcinoma. After the operation, treatment with low-dose mitotane (1g/day) was introduced as adjuvant chemotherapy. Interestingly, the patient developed marked hyper-LDL cholesterolemia at a level equivalent to that of familial hypercholesterolemia (LDL cholesterol level ~ 300 mg/ dL) following the introduction of mitotane, without evidence of primary or secondary hypercholesterolemia due to other causes. A coronary angiogram performed to assess the new-onset angina revealed three-vessel disease, which was later revascularized via percutaneous coronary intervention eight months after the start of mitotane therapy. The cholesterol level normalized with the suspension of mitotane. This case suggests that mitotane can cause severe hypercholesterolemia, potentially resulting in coronary atherosclerosis. © 2014, Japan Atherosclerosis Society. All rights reserved.<br />出版者照会後に全文公開 続きを見る
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論文
Tada, Hayato ; Kawashiri, Masa-aki ; Konno, Tetsuo ; Yamagishi, Masakazu ; Hayashi, Kenshi ; 多田, 隼人 ; 川尻, 剛照 ; 今野, 哲雄 ; 山岸, 正和 ; 林, 研至
出版情報: Journal of Atherosclerosis and Thrombosis.  23  pp.241-256,  2016.  Japan Atherosclerosis Society = 日本動脈硬化学会
URL: http://hdl.handle.net/2297/00050285
概要: 金沢大学医薬保健研究域医学系<br />Blood lipid levels are highly heritable and modifiable risk factors for coronary artery disease (CAD ), and are the leading cause of death worldwide. These facts have motivated human genetic association studies that have the substantial potential to define the risk factors that are causal and to identify pathways and therapeutic targets for lipids and CAD. The success of the HapMap project that provided an extensive catalog of human genetic variations and the development of microarray based genotyping chips (typically containing variations with allele frequencies >5%) facilitated common variant association study (CVAS; formerly termed genomewide association study, GWAS) identifying disease-associated variants in a genome-wide manner. To date, 157 loci associated with blood lipids and 46 loci with CAD have been successfully identified, accounting for approximately 12%– 14% of heritability for lipids and 10% of heritability for CAD. However, there is yet a major challenge termed “missing heritability problem,” namely the observation that loci detected by CVAS explain only a small fraction of the inferred genetic variations. To explain such missing portions, focuses in genetic association studies have shifted from common to rare variants. However, it is challenging to apply rare variant association study (RVAS) in an unbiased manner because such variants typically lack the sufficient number to be identified statistically. In this review, we provide a current understanding of the genetic architecture mostly derived from CVAS, and several updates on the progress and limitations of RVAS for lipids and CAD. © 2016, Japan Atherosclerosis Society. All rights reserved.<br />出版者照会後に全文公開 続きを見る
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論文
Tsuji, Shigetsugu ; Nohara, Atsushi ; Hayashi, Yoshiaki ; Yoshida, Isao ; Oka, Rie ; Moriuchi, Tadashi ; Higashita, Tomomi ; Miyamoto, Susumu ; Suzuki, Ayako ; Okada, Toshihide ; Yamagishi, Masakazu ; 野原, 淳 ; 山岸, 正和
出版情報: Journal of Atherosclerosis and Thrombosis.  22  pp.235-246,  2015.  Japan Atherosclerosis Society = 日本動脈硬化学会
URL: http://hdl.handle.net/2297/00050290
概要: 金沢大学医薬保健研究域医学系<br />Aim: The role of gastrectomy in glycemic control has been established in the current era of bariatri c surgery for obesity. Gastrectomy in obese patients is associated with increased levels of high-density lipoprotein cholesterol (HDL-C). However, limited data on the effects of gastrectomy in nonobese patients are available. We herein investigated the long-term plasma lipid changes in nonobese patients who had undergone gastrectomy. Methods: Patients were enrolled as part of routine healthcare examinations from 1984 to 2003. Preoperative and postoperative data from patients who had undergone curative gastrectomy were analyzed for up to 10 years postoperatively. Three age- and sex-matched controls were assigned to each case. Results: Sixty-four nonobese patients without diabetes mellitus or a history of having taken lipidlowering drugs who underwent curative gastrectomy during the study period were enrolled (60 subtotal gastrectomies, four total gastrectomies). The median follow-up period was 7.6 years. The mean body mass index was 9.6% lower one year after gastrectomy (p<0.01), then plateaued with a slight recovery. Intriguingly, the preoperative HDL-C level was 21% higher one year after gastrectomy (p<0.01), increased by another 30% six years after gastrectomy and remained at this level for the rest of the follow-up period. No significant changes in the HDL-C level were observed in the controls. The degree of HDL-C elevation was consistently significant, irrespective of the baseline triglyceride level, HDL-C level or body weight. Conclusions: Gastrectomy in nonobese patients was associated with consistent and distinct longterm HDL-C elevations and body mass index reductions. © 2015 Japan Atherosclerosis Society.<br />出版者照会後に全文公開 続きを見る