※一部利用できない機能があります
| 1.
論文 |
論文
|
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
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
|
||||
| 2.
論文 |
論文
|
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
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
|
||||
| 3.
論文 |
論文
|
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
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
|
||||
| 4.
論文 |
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
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
|
||||
| 5.
論文 |
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
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
|
||||
| 6.
論文 |
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
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
|
||||
| 7.
論文 |
論文
|
Oka, Rie ; Yamada, Takayoshi ; Nakanishi, Chiaki ; Konno, Tetsuo ; Kawashiri, Masa-aki ; Hayashi, Kenshi ; Nohara, Atsushi ; Inazu, Akihiro ; Yamagishi, Masakazu ; 大家, 理恵 ; 八木, 邦公 ; 今野, 哲雄 ; 川尻, 剛照 ; 林, 研至 ; 野原, 淳 ; 稲津, 明広 ; 山岸, 正和
概要:
金沢大学医薬保健研究域医学系<br />Aim: The commonly observed relationship between increased visceral adiposity and metabolic abnormali
…
ties may be partly mediated by a concomitant increase in liver fat content. We evaluated the independent association between the level of alanine aminotransferase (ALT) as a surrogate marker of the liver fat content and the incidence of metabolic abnormalities after adjusting for the amount of visceral adipose tissue (AT). Methods: The subjects included 1,118 Japanese individuals (44% women) who underwent computed tomography to assess the amount of visceral AT on medical checkups. Cross-sectional associations between the serum ALT, visceral AT and metabolic risk factors were examined. Results: The ALT level and visceral AT were found to show a significant correlation (r =0.41 in men and r =0.36 in women, p<0.001). In a multivariable linear regression analysis, the ALT level and visceral AT were found to be independently associated with blood pressure in men and triglycerides and 2-hour post-challenge glucose in both genders (p<0.01), whereas only visceral AT was found to be associated with HDL-cholesterol (p<0.01). When the participants were classified into four subgroups based on the 75th percentiles of ALT and visceral AT, the low-ALT/high-visceral AT group, but not the high-ALT/low-visceral AT group, had a significantly higher odds ratio for low HDL-cholesterol among both genders (p<0.05) and for hypertriglyceridemia in men only (p<0.05). Meanwhile, the high-ALT/low-visceral AT group, but not the low-ALT/high-visceral AT group, had a significantly higher odds ratio for IGT among women (p<0.05). Conclusions: Although the ALT level and visceral AT were found to be independently associated with most metabolic risk factors, visceral AT had a dominant association with dyslipidemia in both genders, while the ALT level appeared to have a closer association with IGT in women.<br />出版者照会後に全文公開
続きを見る
|
||||
| 8.
論文 |
論文
|
Mabuchi, Hiroshi ; Nohara, Atsushi ; Noguchi, Tohru ; Kobayashi, Junji ; Kawashiri, Masaaki ; Tada, Hayato ; Nakanishi, Chiaki ; Mori, Mika ; Yamagishi, Masakazu ; Inazu, Akihiro ; Koizumi, Junji ; Hokuriku FH Study Group
概要:
金沢大学医学系研究科<br />Aim: Familial hypercholesterolemia (FH) is caused by mutations of FH genes, i.e. LDL-receptor (LDLR), PC
…
SK9 and apolipoprotein B (ApoB) gene. We evaluated the usefulness of DNA analysis for the diagnosis of homozygous FH (homo-FH), and studied the frequency of FH in the Hokuriku district of Japan. Methods: Twenty-five homo-FH patients were recruited. LDLR mutations were identified using the Invader assay method. Mutations in PCSK9 were detected by PCR-SSCP followed by direct sequence analysis. Results: We confirmed 15 true homozygotes and 10 compound heterozygotes for LDLR mutations. Three types of double heterozygotes for LDLR and PCSK9 were found. No FH patients due to ApoB mutations were found. The incidences of homo-FH and hetero-FH in the Hokuriku district were 1/171,167 and 1/208, respectively. Conclusions: Our observations underlined the value of FH gene analysis in diagnosing homo-FH and confirmed extraordinarily high frequency of FH in the Hokuriku district of Japan. © 2010 Elsevier Ireland Ltd.
続きを見る
|
||||
| 9.
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
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
|
||||
| 10.
論文 |
論文
|
Nozue, Tsuyoshi ; Higashikata, Toshinori ; Inazu, Akihiro ; Kawashiri, Masa-aki ; Nohara, Atsushi ; Kobayashi, Junji ; Koizumi, Junji ; Yamagishi, Masakazu ; Mabuchi, Hiroshi
概要:
Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive sterol storage disease caused by a mutated sterol 27-
…
hydroxylase (CYP27A1) gene. We analyzed the CYP27A1 gene in two Japanese CTX patients. The CYP27A1 gene was amplified by PCR and screened by PCR-SSCP. The nucleotide sequence was analyzed to confirm mutations. Case 1 was a compound heterozygote for Arg104Gln in exon 2 and Arg441Gln in exon 8. To our knowledge, this is the first report in which the Arg104Gln mutation is identified in CTX patients. Probably case 2 would be a compound heterozygote for Arg441Trp in exon 8 and a mutation that was not identified. © 2010 The Japanese Society of Internal Medicine.
続きを見る
|
||||
| 11.
論文 |
論文
|
11. Difference between Fasting and Nonfasting Triglyceridemia: the Influence of Waist Circumference.
Oka, Rie ; Kobayashi, Junji ; Miura, Katsuyuki ; Nagasawa, Shinya ; Moriuchi, Tadashi ; Hifumi, Senshu ; Miyamoto, Susumu ; Kawashiri, Masa-aki ; Nohara, Atsushi ; Inazu, Akihiro ; Takeda, Yoshiyu ; Mabuchi, Hiroshi ; Yagi, Kunimasa ; Yamagishi, Masakazu ; 小林, 淳二 ; 川尻, 剛照 ; 野原, 淳 ; 稲津, 明広 ; 武田, 仁勇 ; 馬渕, 宏 ; 八木, 邦公 ; 山岸, 正和
概要:
Aim: Postprandial hypertriglyceridemia is recognized as an independent risk factor for cardiovascular disease. The aim o
…
f this study was to identify differences between fasting and postprandial TG levels, focusing on the influence of waist circumference. Methods: Subjects included 1,505 men and 798 women aged 3865 years who were not taking medications for diabetes or dyslipidemia. Fasting TG levels were measured after an overnight fast, and postprandial TG levels were measured 2 hours after a standardized rice-based lunch (total 740 kcal, 20 g fat, 30 g protein, and 110 g carbohydrates) in the afternoon on the same day. Results: Fasting and postprandial TG levels were highly correlated in both men (r=0.86, p<0.001) and women (r=0.84, p<0.001). Waist circumference was positively correlated with fasting TG (r=0.38 in men and r=0.36 in women) and postprandial TG (r=0.42 in men and r=0.45 in women), respectively. On multiple regression analyses, the association of waist circumference with postprandial TG was still significant (standardized β=0.10 in men and standardized β=0.15 in women, p<0.001) after the inclusion of HbA1c, age, high-density-lipoprotein (HDL)-cholesterol, alcohol consumption, and fasting TG in the regression model. Conclusion: Postprandial TG has a better relation with waist circumference than fasting TG.<br />出版者照会後に全文公開
続きを見る
|
||||
| 12.
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
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
|
||||
| 13.
論文 |
論文
|
Tada, Hayato ; Kobayashi, Junji ; Kawashiri, Masa-aki ; Miyashita, Kazuya ; Nohara, Atsushi ; Inazu, Akihiro ; Nakajima, Katsuyuki ; Mabuchi, Hiroshi ; Yamagishi, Masakazu
概要:
Background: This study was performed to compare the effects of three different lipid-lowering therapies (statins, ezetim
…
ibe, and colestimide) on lipoprotein lipase and endothelial lipase masses in pre-heparin plasma (pre-heparin LPL and EL mass, respectively) from patients with familial hypercholesterolemia (FH). FH is usually treated by coadministration of these three drugs. Methods: The pre-heparin LPL and EL masses were measured in fresh frozen plasma drawn and stored at various time points during coadministration of the three drugs from patients with heterozygous FH harboring a single mutation in the LDL receptor (n = 16, mean age 63 years). The patients were randomly divided into two groups based on the timing when ezetimibe was added. Results: Plasma LPL mass concentration was significantly reduced by rosuvastatin at 20 mg/day (median = 87.4 [IQR: 71.4-124.7] to 67.5 [IQR: 62.1-114.3] ng/ml, P < 0.05). In contrast, ezetimibe at 10 mg/day as well as colestimide at 3.62 g/day did not alter its level substantially (median = 67.5 [IQR: 62.1-114.3] to 70.2 [IQR: 58.3-106.2], and to 74.9 [IQR: 55.6-101.3] ng/ml, respectively) in the group starting with rosuvastatin followed by the addition of ezetimibe and colestimide. On the other hand, the magnitude in LPL mass reduction was lower in the group starting with ezetimibe at 10 mg/day before reaching the maximum dose of 20 mg/day of rosuvastatin. Plasma EL mass concentration was significantly increased by rosuvastatin at 20 mg/day (median = 278.8 [IQR: 186.7-288.7] to 297.0 [IQR: 266.2-300.2] ng/ml, P < 0.05), whereas other drugs did not significantly alter its level. Conclusion: The effects on changes of LPL and EL mass differed depending on the lipid-lowering therapy, which may impact the prevention of atherosclerosis differently. © 2016 Tada et al.
続きを見る
|
||||
| 14.
論文 |
論文
|
Yamaaki, Naoto ; Yagi, Kunimasa ; Kobayashi, Junji ; Nohara, Atsushi ; Ito, Naoko ; Asano, Akimichi ; Nakano, Kaoru ; Liu, Jianhui ; Okamoto, Takuya ; Mori, Yukiko ; Ohbatake, Azusa ; Okazaki, Satoko ; Takeda, Yoshiyu ; Yamagishi, Masakazu
概要:
Background. Although retinol-binding protein 4 (RBP4) associates with insulin resistance and remnant-like particles trig
…
lyceride (RLP-TG) elevated in the insulin resistant state, few data exist regarding the relationship between RBP4 and RLP-TG. Subjects and Methods. The study included 92 Japanese type 2 diabetic mellitus (T2DM) male patients (age 60.5 ± 13.6 years, body mass index (BMI) 24.7 ± 4.1 kg/m2, waist circumference (WC) 88.4 ± 10.7 cm, and HbA1c (NGSP) 7.2 ± 1.9 %). Patients on medications affecting insulin sensitivity, including fibrates, biguanides, and thiazolidinedione, were excluded. Visceral fat area (VFA) and subcutaneous fat area (SFA) were measured by computed tomography. Results. RBP4 levels showed a significant positive correlation with RLP-TG (r = 0.2544 and P = 0.0056), TG (r = 0.1852 and P = 0.041), RLP-TG/TG (r = 0.23765 and P = 0.0241), and age (r = - 0.2082 and P = 0.0219), although there was no significant correlation with VFA, SFA, adiponectin levels, or homeostasis model of assessment insulin resistance (HOMA-R). Multiple regression analysis revealed that RBP4 was an independent determinant of RLP-TG (P = 0.0193) but was not a determinant of TG. Conclusions. RBP4 correlates positively with serum RLP-TG independent of fat accumulation in T2DM. RBP4 may regulate remnant metabolism independent of glycemic control in T2DM. © 2013 Naoto Yamaaki et al.
続きを見る
|
||||
| 15.
論文 |
論文
|
Tada, Hayato ; Kawashiri, Masa-aki ; Yoshida, Taiji ; Teramoto, Ryota ; Nohara, Atsushi ; Konno, Tetsuo ; Inazu, Akihiro ; Mabuchi, Hiroshi ; Yamagishi, Masakazu ; Hayashi, Kenshi ; 多田, 隼人 ; 川尻, 剛照 ; 寺本, 了太 ; 野原, 淳 ; 稲津, 明広 ; 馬渕, 宏 ; 山岸, 正和 ; 林, 研至
概要:
Background:It has been shown that serum lipoprotein(a) [Lp(a)] is elevated in familial hypercholesterolemia (FH) with mu
…
tation(s) of the LDL receptor (LDLR) gene. However, few data exist regarding Lp(a) levels in FH with gain-of-function mutations of the PCSK9 gene.Methods and Results:We evaluated 42 mutation-determined heterozygous FH patients with aPCSK9gain-of-function mutation (FH-PCSK9, mean age 52, mean LDL-C 235 mg/dl), 198 mutation-determined heterozygous FH patients with aLDLRmutation (FH-LDLR, mean age 44, mean LDL-C 217 mg/dl), and 4,015 controls (CONTROL, mean age 56, mean LDL-C 109 mg/dl). We assessed their Lp(a), total cholesterol, triglycerides, HDL-C, LDL-C, use of statins, presence of hypertension, diabetes, chronic kidney disease, smoking, body mass index (BMI) and coronary artery disease (CAD). Multiple regression analysis showed that HDL-C, use of statins, presence of hypertension, smoking, BMI, and Lp(a) were independently associated with the presence of CAD. Under these conditions, the serum levels of Lp(a) in patients with FH were significantly higher than those of the CONTROL group regardless of their causative genes, among the groups propensity score-matched (median Lp(a) 12.6 mg/dl [IQR:9.4–33.9], 21.1 mg/dl [IQR:11.7–34.9], and 5.0 mg/dl [IQR:2.7–8.1] in the FH-LDLR, FH-PCSK9, and CONTROL groups, respectively, P=0.002 for FH-LDLR vs. CONTROL, P=0.002 for FH-PCSK9 vs. CONTROL).Conclusions:These data demonstrate that serum Lp(a) is elevated in patients with FH caused by PCSK9 gain-of-function mutations to the same level as that in FH caused by LDLR mutations. (Circ J 2016; 80: 512–518)<br />出版者照会後に全文公開
続きを見る
|
||||
| 16.
論文 |
論文
|
Kobayashi, Junji ; Murase, Yuko ; Asano, Akimichi ; Nohara, Atsushi ; Kawashiri, Masa-aki ; Inazu, Akihiro ; Yamagishi, Masakazu ; Mabuchi, Hiroshi ; 小林, 淳二 ; 野原, 淳 ; 川尻, 剛照 ; 稲津, 明広 ; 山岸, 正和 ; 馬渕, 宏
概要:
Objective: To clarify the effects of walking with a pedometer on metabolic parameters, including adiponectin (APN). Meth
…
ods: We recruited 44 male Japanese volunteers (age, 37 ± 9 yrs; body mass index (BMI), 24.2 ± 2.9 kg/m2; fasting plasma glucose (FPG), 96 ± 11 mg/dL; total cholesterol (TC) 190 ± 26 mg/dL; triglycerides (TG) 119 ± 80 mg/dL; HDL-C56 ± 14 mg/dL). Subjects were instructed to walk with a pedometer and record the number of steps they walked every day for 50 days. Serum adiponectin (APN) levels were measured by enzyme immunoassay. Treatment effects were examined by Wilcoxon's rank test. Results: The average number of steps was 8211 ± 2084 per day. There were significant reductions in BMI, sBP, TG and TNF-α levels after 50 days, but no changes in adiponectin levels. We then divided the subjects into 2 groups according to the steps walked per day, namely, more than 8000 steps (MT group, n=22) and less than 8000 steps (LT group, n=22) and found that the reduction in TG and BP was observed only in the MT group. Conclusions: Walking with a pedometer is effective for improving metabolic parameters, such as TG and blood pressure, but is not sufficient to increase adiponectin levels in Japanese men.<br />出版者照会後に全文公開
続きを見る
|
||||
| 17.
論文 |
論文
|
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 ; 馬渕, 宏 ; 山岸, 正和 ; 林, 研至
概要:
Aim: The Japan Atherosclerosis Society (JAS) guidelines for the prevention of atherosclerotic diseases 2012 (JAS2012) pr
…
oposed 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. Methods: 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. Results: 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). Conclusions: Lipid management is inadequate in community-based settings, particularly, in subjects with CKD and secondary prevention.<br />出版者照会後に全文公開
続きを見る
|
||||
| 18.
論文 |
論文
|
Oka, Rie ; Yagi, Kunimasa ; Sakurai, Masaru ; Nakamura, Koshi ; Nagasawa, Shin-ya ; Miyamoto, Susumu ; Nohara, Atsushi ; Kawashiri, Masa-aki ; Hayashi, Kenshi ; Takeda, Yoshiyu ; Yamagishi, Masakazu ; 八木, 邦公 ; 櫻井, 勝 ; 中村, 幸志 ; 野原, 淳 ; 川尻, 剛照 ; 林, 研至 ; 武田, 仁勇 ; 山岸, 正和
概要:
Aim: The enlargement of visceral adipose tissue (VAT) is considered to mediate the close relationship between obesity an
…
d insulin resistance. We aimed to determine whether a stronger association of VAT compared to subcutaneous adipose tissue (SAT) with insulin resistance could be confirmed and generalized in non-diabetic Japanese men and women. Methods: Participants were 912 non-diabetic Japanese (636 men and 276 women, mean age 52.4±7.0 years, and mean BMI 24.9±3.1 kg/m2). VAT and SAT were measured through the use of computed tomography scanning. Homeostatic model for the assessment of insulin resistance (HOMA-IR) and Matsuda insulin sensitivity index (ISI) were calculated based on results from the oral glucose tolerance test. Results: For both genders, subjects in higher tertiles of SAT as well as VAT showed significantly higher levels of HOMA-IR and lower levels of Matsuda ISI (p<0.001). In multiple regression analyses with VAT and SAT included in the model, only VAT, but not SAT, was independently associated with Matsuda ISI in women (p<0.001), whereas both SAT and VAT were independently associated with HOMA-IR and with Matsuda ISI in men (p<0.001). When VAT and waist circumference were jointly included in the model, only VAT, but not waist circumference, was independently associated with Matsuda ISI in women (p<0.001) but not in men. Conclusion: VAT had a stronger association with insulin resistance than SAT or waist circumference in women but not in men. BMI showed a comparable association with insulin resistance to VAT in this population.<br />出版者照会後に全文公開
続きを見る
|
||||
| 19.
論文 |
論文
|
Tada, Hayato ; Kawashiri, Masa-aki ; Okada, Hirofumi ; Endo, Saori ; Toyoshima, Yuka ; Konno, Tetsuo ; Nohara, Atsushi ; Inazu, Akihiro ; Takao, Akira ; Mabuchi, Hiroshi ; Yamagishi, Masakazu ; Hayashi, Kenshi ; 多田, 隼人 ; 川尻, 剛照 ; 今野, 哲雄 ; 野原, 淳 ; 稲津, 明広 ; 馬渕, 宏 ; 山岸, 正和 ; 林, 研至
概要:
Whole exome sequencing (WES) technologies have accelerated genetic studies of Mendelian disorders, yielding approximatel
…
y 30% diagnostic success. We encountered a 13-year-old Japanese female initially diagnosed with familial hypercholesterolemia on the basis of clinical manifestations of severe hypercholesterolemia (initial LDL cholesterol=609 mg/dl at the age of one) and systemic intertriginous xanthomas with histories of recurrent self-limiting episodes of fever and arthritis. Both her phenotypes seemed to co-segregate in a recessive manner. We performed WES on this patient, who was considered a proband. Among 206,430 variants found in this individual, we found 18,220 nonsense, missense, or splice site variants, of which 3,087 were rare (minor allele frequency ≤ 0.01 or not reported) in 1000 Genome (Asian population). Filtering by assuming a recessive pattern of inheritance with the use of an in silico annotation prediction tool, we successfully narrowed down the candidates to the compound heterozygous mutations in the ABCG5 gene (c.1256G＞A or p.Arg419His/c.1763-1G＞A [splice acceptor site]) and to the double-compound heterozygous mutations in the MEFV gene (c.329T＞C/C or p.Leu110Pro/c.442G＞C/C or p.Glu148Val). The patient was genetically diagnosed with sitosterolemia and familial Mediterranean fever using WES for the first time. Such a comprehensive approach is useful for identifying causative mutations for multiple unrelated inheritable diseases.<br />出版者照会後に全文公開
続きを見る
|
||||
| 20.
論文 |
論文
|
Nozue, Tsuyoshi ; Kawashiri, Masa-aki ; Higashikata, Toshinori ; Nohara, Atsushi ; Inazu, Akihiro ; Kobayashi, Junji ; Koizumi, Junji ; Yamagishi, Masakazu ; Mabuchi, Hiroshi ; 川尻, 剛照 ; 野原, 淳 ; 稲津, 明広 ; 小林, 淳二 ; 小泉, 順二 ; 山岸, 正和 ; 馬渕, 宏
概要:
We retrospectively evaluated the frequency and identified the factors associated with the development of aortic stenosis
…
(AS) in 96 patients with heterozygous familial hypercholesterolemia (FH). The frequency of AS was 31% (4/13) and that of critical stenosis was 15% (2/13) in older patients over the age of 70 years. All 4 patients with AS were female aged more than 70 years who were diagnosed with FH when aged more than 60 years. There were no significant differences in conventional coronary risk factors; however, the age at cardiac catheterization, age at diagnosis of FH and the cholesterol-years score (CYS) with AS were significantly higher than those without AS (p=0.006, p=0.017, p=0.021, respectively). In multiple regression analysis, CYS was a significant independent predictor for the development of AS (p=0.037) in 13 older patients over the age of 70 years. These results suggest that physicians should be aware that AS needs attention in older patients with heterozygous FH, especially women who have been diagnosed late in life and those who have been inadequately treated.<br />出版者照会後に全文公開
続きを見る
|
||||
| 21.
論文 |
論文
|
Ohtani, Rumiko ; Inazu, Akihiro ; Noji, Yoshihiro ; Wakasugi, Takanobu ; Miwa, Kenji ; Tada, Hayato ; Kawashiri, Masa-aki ; Noguchi, Tohru ; Nohara, Atsushi ; Kobayashi, Junji ; Koizumi, Junji ; Yamagishi, Masakazu ; Mabuchi, Hiroshi
概要:
Thesis of Ohtani, Rumiko / 大谷 留珠子 博士学位論文(金沢大学 / 大学院医薬保健学総合研究科)<br />Background: The half of hyperalphalipoproteinemia (H
…
ALP) in Japan is caused by CETP gene mutations. Other than two prevalent mutations (D442G and Intron 14 splicing donor site +. 1G>A), some rare CETP mutations are found in Japanese HALP subjects. Methods: CETP gene analysis of genomic DNA from subjects was performed by restriction fragment length polymorphism (RFLP) and sequencing analysis. Mutations which were suspected to cause a splicing defect or a protein secretion defect were investigated in COS-1 cells transfected with a CETP minigene construct or a cDNA expression vector. Results: Each of three subjects was identified as a carrier of CETP gene mutation of a compound heterozygote of c.653_654delGGinsAAAC and Intron 14 splicing donor site +. 1G>A, a heterozygote of c.658G>A or a homozygote of L261R. The c.658G>A mutation was located at the last nucleotide of exon 7, and it was confirmed to cause splicing abnormality revealed by the CETP minigene analysis. The L261R CETP was not secreted to conditioned media of the cells. Conclusions: Three novel CETP gene mutations are responsible for HALP by CETP deficiency. It is predicted that there are more rare CETP gene mutations in Japanese, and these multiple rare mutations alone or a combination with each of prevalent mutations is responsible for mild-to-moderate or marked HALP, respectively. © 2011 Elsevier B.V.
続きを見る
|
||||
| 22.
論文 |
論文
|
Tada, Hayato ; Kawashiri, Masa-aki ; Ohtani, Rumiko ; Noguchi, Tohru ; Nakanishi, Chiaki ; Konno, Tetsuo ; Hayashia, Kenshi ; Nohara, Atsushi ; Inazu, Akihiro ; Kobayashi, Junji ; Mabuchi, Hiroshi ; Yamagishi, Masakazu
概要:
Background: Autosomal recessive hypercholesterolemia (ARH) is an extremely rare inherited hypercholesterolemia, the caus
…
e of which is mutations in low-density lipoprotein (LDL) receptor adaptor protein 1 (LDLRAP1) gene. Methods: A total of 146 heterozygous familial hypercholesterolemic (FH) patients with a mutation in LDLR gene were screened for genes encoding proprotein convertase subtilisin/kexin type 9 (PCSK9) and LDLRAP1. Results: Among the 146 subjects, we identified a 79-year-old Japanese female with double mutations in LDLR gene (c.2431A > T) and LDLRAP1 gene (c.606dup). Two other relatives with double mutations in those genes in her family were also identified. Although the proband exhibited massive Achilles tendon xanthoma and coronary and aortic valvular disease, serum LDL-C level of subjects with double mutations was similar with that of subjects with single LDLR mutation (284.0 ± 43.5 versus 265.1 ± 57.4 mg/dl). Conclusion: Additional mutation in LDLRAP1 may account for severer phenotype in terms of xanthoma and atherosclerotic cardiovascular disease in FH patients. © 2011 Elsevier Ireland Ltd. All rights reserved.
続きを見る
|
||||
| 23.
論文 |
論文
|
Tada, Hayato ; Kawashiri, Masa-aki ; Ohtani, Rumiko ; Noguchi, Tohru ; Nakanishi, Chiaki ; Konno, Tetsuo ; Hayashi, Kenshi ; Nohara, Atsushi ; Inazu, Akihiro ; Kobayashi, Junji ; Mabuchi, Hiroshi ; Yamagishi, Masakazu
概要:
Background: Autosomal recessive hypercholesterolemia (ARH) is an extremely rare inherited hypercholesterolemia, the caus
…
e of which is mutations in low-density lipoprotein (LDL) receptor adaptor protein 1 (LDLRAP1) gene. Methods: A total of 146 heterozygous familial hypercholesterolemic (FH) patients with a mutation in LDLR gene were screened for genes encoding proprotein convertase subtilisin/kexin type 9 (PCSK9) and LDLRAP1. Results: Among the 146 subjects, we identified a 79-year-old Japanese female with double mutations in LDLR gene (c.2431A > T) and LDLRAP1 gene (c.606dup). Two other relatives with double mutations in those genes in her family were also identified. Although the proband exhibited massive Achilles tendon xanthoma and coronary and aortic valvular disease, serum LDL-C level of subjects with double mutations was similar with that of subjects with single LDLR mutation (284.0 ± 43.5 versus 265.1 ± 57.4. mg/dl). Conclusion: Additional mutation in LDLRAP1 may account for severer phenotype in terms of xanthoma and atherosclerotic cardiovascular disease in FH patients. © 2011 Elsevier Ireland Ltd.
続きを見る
|
||||
| 24.
論文 |
論文
|
Tada, Hayato ; Kawashiri, Masa-aki ; Ohtani, Rumiko ; Noguchi, Tohru ; Nakanishi, Chiaki ; Konno, Tetsuo ; Hayashi, Kenshi ; Nohara, Atsushi ; Inazu, Akihiro ; Kobayashi, Junji ; Mabuchi, Hiroshi ; Yamagishi, Masakazu
概要:
Background: Autosomal recessive hypercholesterolemia (ARH) is an extremely rare inherited hypercholesterolemia, the caus
…
e of which is mutations in low-density lipoprotein (LDL) receptor adaptor protein 1 (LDLRAP1) gene. Methods: A total of 146 heterozygous familial hypercholesterolemic (FH) patients with a mutation in LDLR gene were screened for genes encoding proprotein convertase subtilisin/kexin type 9 (PCSK9) and LDLRAP1. Results: Among the 146 subjects, we identified a 79-year-old Japanese female with double mutations in LDLR gene (c.2431A > T) and LDLRAP1 gene (c.606dup). Two other relatives with double mutations in those genes in her family were also identified. Although the proband exhibited massive Achilles tendon xanthoma and coronary and aortic valvular disease, serum LDL-C level of subjects with double mutations was similar with that of subjects with single LDLR mutation (284.0 ± 43.5 versus 265.1 ± 57.4. mg/dl). Conclusion: Additional mutation in LDLRAP1 may account for severer phenotype in terms of xanthoma and atherosclerotic cardiovascular disease in FH patients. © 2011 Elsevier Ireland Ltd.
続きを見る
|
||||
| 25.
論文 |
論文
|
Tada, Hayato ; Kawashiri, Masa-aki ; Okada, Hirofumi ; Teramoto, Ryota ; Konno, Tetsuo ; Yoshimuta, Tsuyoshi ; Sakata, Kenji ; Nohara, Atsushi ; Inazu, Akihiro ; Kobayashi, Junji ; Mabuchi, Hiroshi ; Yamagishi, Masakazu ; Hayashi, Kenshi
概要:
The aims of this study were (1) to determine whether the accumulation of coronary plaque burden assessed with coronary c
…
omputed tomography angiography (CCTA) can predict future events and (2) to estimate the onset and progression of coronary atherosclerosis in patients with familial hypercholesterolemia (FH). Consecutive 101 Japanese patients with heterozygous FH (men= 52, mean age 56 ± 16years, mean low-density lipoprotein cholesterol 264 ± 58mg/dl) who underwent 64-detector row CCTA without known coronary artery disease were retrospectively evaluated by assigning a score (0 to 5) to each of 17 coronary artery segments according to the Society of Cardiovascular Computed Tomography guidelines. Those scores were summed and subsequently natural log transformed. The periods to major adverse cardiac events (MACE) were estimated using multivariable Cox proportional hazards models. During the follow-up period (median 941days), 21 MACE had occurred. Receiver operating characteristic curve analyses identified a plaque burden score of 3.35 (raw score 28.5) as the optimal cutoff for predicting a worse prognosis. Multivariate Coxregression analysis identified the presence of a plaque score ≥3.35 as a significant independent predictor of MACE (hazard ratio= 3.65; 95% confidence interval 1.32 to 25.84, p<0.05). The regression equations were Y= 0.68. X- 15.6 (r= 0.54, p <0.05) in male and Y= 0.74. X- 24.8 (r= 0.69, p <0.05) in female patients with heterozygous FH. In conclusion, coronary plaque burden identified in a noninvasive, quantitative manner was significantly associated with future coronary events in Japanese patients with heterozygous FH and that coronary atherosclerosis may start to develop, on average, at age 23 and 34years in male and female patients with heterozygous FH, respectively.
続きを見る
|
||||
| 26.
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
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
|
||||
| 27.
論文 |
論文
|
Ohtsuji, Michio ; Yagi, Kunimasa ; Shintaku-Kubota, Miyuki ; Kojima-Koba, Yukiko ; Ito, Naoko ; Sugihara, Masako ; Yamaaki, Naoto ; Chujo, Daisuke ; Nohara, Atsushi ; Takeda, Yoshiyu ; Kobayashi, Junji ; Yamagishi, Masakazu ; Higashida, Haruhiro
概要:
金沢大学附属病院<br />AIMS/HYPOTHESIS: ADP-ribosyl-cyclase activity (ADPRCA) of CD38 and other ectoenzymes mainly generate cycli
…
c adenosine 5'diphosphate-(ADP-) ribose (cADPR) as a second messenger in various mammalian cells, including pancreatic beta cells and peripheral blood mononuclear cells (PBMCs). Since PBMCs contribute to the pathogenesis of diabetic nephropathy, ADPRCA of PBMCs could serve as a clinical prognostic marker for diabetic nephropathy. This study aimed to investigate the connection between ADPRCA in PBMCs and diabetic complications. METHODS: PBMCs from 60 diabetic patients (10 for type 1 and 50 for type 2) and 15 nondiabetic controls were fluorometrically measured for ADPRCA based on the conversion of nicotinamide guanine dinucleotide (NGD(+)) into cyclic GDP-ribose. RESULTS: ADPRCA negatively correlated with the level of HbA1c (P = .040, R(2) = .073), although ADPRCA showed no significant correlation with gender, age, BMI, blood pressure, level of fasting plasma glucose and lipid levels, as well as type, duration, or medication of diabetes. Interestingly, patients with nephropathy, but not other complications, presented significantly lower ADPRCA than those without nephropathy (P = .0198) and diabetes (P = .0332). ANCOVA analysis adjusted for HbA1c showed no significant correlation between ADPRCA and nephropathy. However, logistic regression analyses revealed that determinants for nephropathy were systolic blood pressure and ADPRCA, not HbA1c. CONCLUSION/INTERPRETATION: Decreased ADPRCA significantly correlated with diabetic nephropathy. ADPRCA in PBMCs would be an important marker associated with diabetic nephropathy.
続きを見る
|
