1.

その他

その他
髙田, 睦子 ; Takata, Mutsuko ; タカタ, ムツコ
出版情報: 博士学位論文要旨 論文内容の要旨および論文審査結果の要旨/金沢大学大学院医学研究科.  平成19年7月  pp.29-,  2007-07-01.  金沢大学
URL: http://hdl.handle.net/2297/19174
概要: 取得学位 : 博士(医学), 学位授与番号 : 医博甲第1819号, 学位授与年月日 : 平成18年12月31日, 学位授与大学 : 金沢大学, 主査教授 : 中尾 眞二, 副査教授 : 金子 周一, 山本 博
2.

論文

論文
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
3.

論文

論文
Noguchi, Tohru ; Kobayashi, Junji ; Yagi, Kunimasa ; Nohara, Atsushi ; Yamaaki, Naoto ; Sugihara, Masako ; Ito, Naoko ; Oka, Rie ; Kawashiri, Masaaki ; Tada, Hayato ; Takata, Mutsuko ; Inazu, Akihiro ; Yamagishi, Masakazu ; Mabuchi, Hiroshi
出版情報: Atherosclerosis 217 (1), pp. 165-170.  217  pp.165-170,  2011-07-01.  Elsevier Ireland Ltd
URL: http://hdl.handle.net/2297/27306
概要: 金沢大学医学系研究科<br />Background: Bezafibrate and fenofibrate show different binding properties against peroxisome proliferato r-activated receptor subtypes, which could cause different clinical effects on circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and on various metabolic markers. Methods: An open, randomized, four-phased crossover study using 400 mg of bezafibrate or 200 mg of fenofibrate was performed. Study subjects were 14 dyslipidemia with impaired glucose tolerance or type 2 diabetes mellitus (61 ± 16 years, body mass index (BMI) 26 ± 3 kg/m2, total cholesterol (TC) 219 ± 53 mg/dL, triglyceride (TG) 183 ± 83 mg/dL, high-density lipoprotein-cholesterol (HDL-C) 46 ± 8 mg/dL, fasting plasma glucose 133 ± 31 mg/dL and HbA1c 6.2 ± 0.8%). Subjects were given either bezafibrate or fenofibrate for 8 weeks, discontinued for 4 weeks and then switched to the other fibrate for 8 weeks. Circulating PCSK9 levels and other metabolic parameters, including adiponectin, leptin and urine 8-hydroxy-2′-deoxyguanosine (8-OHdG) were measured at 0, 8, 12 and 20 weeks. Results: Plasma PCSK9 concentrations were significantly increased (+39.7% for bezafibrate and +66.8% for fenofibrate, p < 0.001) in all patients except for one subject when treated with bezafibrate. Both bezafibrate and fenofibrate caused reductions in TG (-38.3%, p < 0.001 vs. -32.9%, p < 0.01) and increases in HDL-C (+18.0%, p < 0.001 vs. +11.7%, p < 0.001). Fenofibrate significantly reduced serum cholesterol levels (TC, -11.2%, p < 0.01; non-HDL-C, -17.3%, p < 0.01; apolipoprotein B, -15.1%, p < 0.01), whereas bezafibrate significantly improved glucose tolerance (insulin, -17.0%, p < 0.05) and metabolic markers (γ-GTP, -38.9%, p < 0.01; adiponectin, +15.4%, p < 0.05; urine 8-OHdG/Cre, -9.5%, p < 0.05). Conclusion: Both bezafibrate and fenofibrate increased plasma PCSK9 concentrations. The addition of a PCSK9 inhibitor to each fibrate therapy may achieve beneficial cholesterol lowering along with desirable effects of respective fibrates. © 2011 Elsevier Ireland Ltd. All rights reserved. 続きを見る
4.

論文

論文
Tsuchida, Masayuki ; Kawashiri, Masa-aki ; Tada, Hayato ; Takata, Mutsuko ; Nohara, Atsushi ; Ino, Hidekazu ; Inazu, Akihiro ; Kobayashi, Junji ; Koizumi, Junji ; Mabuchi, Hiroshi ; Yamagishi, Masakazu ; 川尻, 剛照 ; 多田, 隼人 ; 野原, 淳 ; 井野, 秀一 ; 稲津, 明広 ; 小林, 淳二 ; 小泉 , 順二 ; 馬渕, 宏 ; 山岸, 正和
出版情報: Circulation journal.  73  pp.963-966,  2009-04-24.  Japanese Circulation Society = 日本循環器学会
URL: http://hdl.handle.net/2297/48511
概要: In 1982, a 49-year-old Japanese woman had been referred to our hospital for further investigation of her hypercholestero lemia. She was diagnosed as heterozygous familial hypercholesterolemia, because of Achilles tendon xanthoma and a family history of primary hypercholesterolemia. Three years later, she had chest pain on effort and angina pectoris was diagnosed by coronary angiography. At that time, she underwent coronary artery bypass grafting surgery with 2 saphenous vein grafts (SVG). Because more aggressive cholesterol-lowering therapy was needed for secondary prevention of coronary artery disease (CAD), weekly low-density lipoprotein (LDL) apheresis was started postoperatively, combined with drug therapy. Since 1986, her serum total cholesterol levels before and after LDL apheresis remained approximately 200 mg/dl and 90 mg/dl, respectively. Although her coronary sclerosis, including the SVG, did not progress appreciably for a period of 20 years, stenotic changes of the aortic valve developed rapidly at age 70, leading to aortic valve replacement surgery in 2005 at age 72. These findings suggest that careful attention to the progression of aortic valve stenosis is needed for extreme hypercholesterolemic patients even under optimal cholesterol-lowering therapy for the secondary prevention of CAD. (Circ J 2009; 73: 963 - 966)<br />出版者照会後に全文公開 続きを見る
5.

論文

論文
Tsuchida, Masayuki ; Kawashiri, Masa-aki ; Teramoto, Ryota ; Takata, Mutsuko ; Sakata, Kenji ; Omi, Wataru ; Okajima, Masaki ; Takamura, Masayuki ; Ino, Hidekazu ; Kita, Yoshihito ; Takegoshi, Tadayoshi ; Inaba, Hideo ; Yamagishi, Masakazu ; 川尻, 剛照 ; 寺本, 了太 ; 坂田, 憲治 ; 岡島, 正樹 ; 高村, 雅之 ; 井野, 秀一 ; 稲葉, 英夫 ; 山岸, 正和
出版情報: Circulation journal.  73  pp.1243-1247,  2009-06-25.  Japanese Circulation Society = 日本循環器学会
URL: http://hdl.handle.net/2297/48501
概要: Background: Although acute coronary syndrome (ACS) and stroke are known to increase after earthquake, few data exist reg arding the effect of earthquake on these cardiovascular events in rural areas. Methods and Results: The Noto Peninsula earthquake with a magnitude of 6.9 occurred at 9:45 a.m. on 25 March 2007. The first case of ACS occurred approximately 15 min later, whereas cerebral hemorrhage (CH) occurred 72 h after the onset of earthquake. During the 35 days after earthquake, among 49 patients who were attended by local ambulance, 5 patients with ACS (10.2%) and 8 with CH (16.3%) were documented and 4 died. The total number of both ACS and CH cases was greater than the averages for the same period of the past 3 years in this area (2.0 vs 5 and 2.3 vs 8, P<0.01). Interestingly, the most cases of ACS had occurred within 7 days after earthquake and for CH not until 35 days later. Conclusions: Even in rural areas a severe earthquake results in increased incidence of ACS and CH, which can occur at different times after the event, although the effects of other environmental factors should be further investigated. (Circ J 2009; 73: 1243-1247)<br />出版者照会後に全文公開 続きを見る
6.

論文

論文
Tada, Hayato ; Kawashiri, Masaaki ; Noguchi, Tohru ; Mori, Mika ; Tsuchida, Masayuki ; Takata, Mutsuko ; Nohara, Atsushi ; Inazu, Akihiro ; Kobayashi, Junji ; Yachie, Akihiro ; Mabuchi, Hiroshi ; Yamagishi, Masakazu
出版情報: Clinica Chimica Acta.  400  pp.42-47,  2009-02-01.  Elsevier
URL: http://hdl.handle.net/2297/14392
概要: 金沢大学附属病院循環器内科<br />Background: The objective of this study was to develop a new and simple method for measuring low-dens ity lipoprotein receptor (LDLR) activity using peripheral lymphocytes enabling us to clinically diagnose familial hypercholesterolemia (FH) and ascertain the involved mutations (such as K790X mutation), that might not be clearly detected in the conventional method. Methods: Our method comprised the following 2 features: first, we used anti-CD3/CD28 beads to stimulate T-lymphocytes to obtain a uniform fraction of lymphocytes and maximum up-regulation of LDLR. Second, we excluded the possibility of overestimation of lymphocyte signals bound only to its surface, by adding heparin to the cultured lymphocytes used for the LDLR assay. Results: Based on the genetic mutation, the FH subjects were divided into 2 groups, K790X, (n = 20) and P664L, (n = 5), and their LDLR activities was measured by this method, which was found to be 55.3 ± 8.9% and 63.9 ± 13.8%, respectively, of that of the control group (n = 15). In comparison, the LDLR activity was 86.1 ± 11.6% (K790X) and 73.3 ± 6.3% (P664L) of that of the control group when measured by the conventional method, indicating that impairment of LDLR function in FH K790X subjects was much more clearly differentiated with our method than with the conventional method (paired t-test, p < 0.0001). The levels of LDLR expression also showed similar tendencies, that is, 89.4 ± 13.2% (K790X) and 76.9 ± 17.4% (P664L) of that of the control group when measured by the conventional method, and 78.1 ± 9.7% (K790X) and 70.3 ± 26.5% (P664L) when measured by our new method. In addition, we confirmed that there was little influence of statin treatment on LDLR activity among the study subjects when our method was used. Conclusion: These results demonstrate that our new method is applicable for measuring LDLR activity, even in subjects with an internally defective allele, and that T-lymphocytes of the FH K790X mutation possess characteristics of that allele. © 2008 Elsevier B.V. All rights reserved. 続きを見る