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| 1.
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Sakamoto, Aiji ; Kawashiri, Masaaki ; Ishibashi-Ueda, Hatsue ; Sugamoto, Yuka ; Yoshimuta, Tsuyoshi ; Higashikata, Takeo ; Ogino, Hitoshi ; Tada, Hayato ; Konno, Tetsuo ; Hayashi, Kenshi ; Yamagishi, Masakazu
概要:
We examined the expression of ephrin-B1 and its cognate receptor EphB2, key regulators of angiogenesis and embryogenesis
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, in human abdominal aortic aneurysm (AAA) and analyzed their functional roles in cell migration. From 10 patients (9 males and 1 female; age, 68.5 ± 2.4) who underwent vascular surgery for AAA, we obtained AAA and adjacent control tissues. Using real-time RT-PCR, we analyzed expression of ephrin-B1 and EphB2. We also histologically localized these molecules in AAA tissues. Finally, effects of ephrin-B1 and EphB2 on inflammatory cell chemotaxis were examined by cell migration assay. Expression levels of ephrin-B1 (0.410 ± 0.046 versus 1.198 ± 0.252, P = 0.027) and EphB2 (0.764 ± 0.212 versus 1.272 ± 0.137, P = 0.594) were higher in AAA than normal control. Both ephrin-B1 and EphB2 were expressed in macrophages, T lymphocytes, and endothelial cells within AAA. In chemotaxis assay, ephrin-B1 and EphB2 inhibited mononuclear-cell chemotaxis induced by stromal derived factor-1 down to 54.7 ± 12.7 (P = 0.01) and 50.7 ± 13.1 (P = 0.01), respectively. These data suggest that ephrin-B1 and EphB2 might be functional in human adult inflammatory cells and involved in the pathogenesis of AAA, although specific roles of these molecules should further be sought. © 2012 Aiji Sakamoto et al.
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| 2.
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Sakamoto, Aiji ; Kawashiri, Masaaki ; Ishibashi-Ueda, Hatsue ; Sugamoto, Yuka ; Yoshimuta, Tsuyoshi ; Higashikata, Takeo ; Ogino, Hitoshi ; Tada, Hayato ; Konno, Tetsuo ; Hayashi, Kenshi ; Yamagishi, Masakazu
概要:
We examined the expression of ephrin-B1 and its cognate receptor EphB2, key regulators of angiogenesis and embryogenesis
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, in human abdominal aortic aneurysm (AAA) and analyzed their functional roles in cell migration. From 10 patients (9 males and 1 female; age, 68.5 ± 2.4) who underwent vascular surgery for AAA, we obtained AAA and adjacent control tissues. Using real-time RT-PCR, we analyzed expression of ephrin-B1 and EphB2. We also histologically localized these molecules in AAA tissues. Finally, effects of ephrin-B1 and EphB2 on inflammatory cell chemotaxis were examined by cell migration assay. Expression levels of ephrin-B1 (0.410 ± 0.046 versus 1.198 ± 0.252, P = 0.027) and EphB2 (0.764 ± 0.212 versus 1.272 ± 0.137, P = 0.594) were higher in AAA than normal control. Both ephrin-B1 and EphB2 were expressed in macrophages, T lymphocytes, and endothelial cells within AAA. In chemotaxis assay, ephrin-B1 and EphB2 inhibited mononuclear-cell chemotaxis induced by stromal derived factor-1 down to 54.7 ± 12.7 (P = 0.01) and 50.7 ± 13.1 (P = 0.01), respectively. These data suggest that ephrin-B1 and EphB2 might be functional in human adult inflammatory cells and involved in the pathogenesis of AAA, although specific roles of these molecules should further be sought. © 2012 Aiji Sakamoto et al.
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| 3.
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Oka, Rie ; Shibata, Kyoko ; Sakurai, Masaru ; Kometani, Mitsuhiro ; Yamagishi, Masakazu ; Yoshimura, Kenichi ; Yoneda, Takashi ; 大家, 理恵 ; 柴田, 恭子 ; 櫻井, 勝 ; 米谷, 充弘 ; 山岸, 正和 ; 吉村, 健一 ; 米田, 隆
概要:
金沢大学附属病院研修医・専門医総合教育センター<br />We aimed to clarify how the trajectories of 1-hour postload plasma glucose (PG) and 2-hour
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PG were different in the development of type 2 diabetes. Using data of repeated health checkups in Japanese workers from April 2006 to March 2016, longitudinal changes of fasting, 1-hour, and 2-hour PG on the oral glucose tolerance test were analyzed with a linear mixed effects model. Of the 1464 nondiabetic subjects at baseline, 112 subjects progressed to type 2 diabetes during the observation period (progressors). In progressors, 1-hour PG and 2-hour PG showed gradual increases with slopes of 1.33 ± 0.2 and 0.58 ± 0.2 mg/dL/year, respectively, followed by a steep increase by which they attained diabetes. Until immediately before the diabetes transition, age- and sex-adjusted mean level of 2-hour PG was 149 ± 2.7 mg/dL, 34 ± 2.7 (30%) higher compared to nonprogressors, while that of 1-hour PG was 206 ± 4.1 mg/dL, 60 ± 4.3 mg/dL (41%) higher compared to nonprogressors. In conclusion, diabetes transition was preceded by a mild elevation of 2-hour PG for several years or more. The elevation in 1-hour PG was larger than that of 2-hour PG until immediately before the transition to diabetes. © 2017 Rie Oka et al.<br />Embargo Period 12 months
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| 4.
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Shimojima, Masaya ; Yuasa, Shinsuke ; Motoda, Chikaaki ; Yozu, Gakuto ; Nagai, Toshihiro ; Ito, Shogo ; Lachmann, Mark ; Kashimura, Shin ; Takei, Makoto ; Kusumoto, Dai ; Kunitomi, Akira ; Hayashiji, Nozomi ; Seki, Tomohisa ; Tohyama, Shugo ; Hashimoto, Hisayuki ; Kodaira, Masaki ; Egashira, Toru ; Hayashi, Kenshi ; Nakanishi, Chiaki ; Sakata, Kenji ; Yamagishi, Masakazu ; Fukuda, Keiichi
概要:
Alteration of the nuclear Ca2+ transient is an early event in cardiac remodeling. Regulation of the nuclear Ca2+ transie
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nt is partly independent of the cytosolic Ca2+ transient in cardiomyocytes. One nuclear membrane protein, emerin, is encoded by EMD, and an EMD mutation causes Emery-Dreifuss muscular dystrophy (EDMD). It remains unclear whether emerin is involved in nuclear Ca2+ homeostasis. The aim of this study is to elucidate the role of emerin in rat cardiomyocytes by means of hypertrophic stimuli and in EDMD induced pluripotent stem (iPS) cell-derived cardiomyocytes in terms of nuclear structure and the Ca2+ transient. The cardiac hypertrophic stimuli increased the nuclear area, decreased nuclear invagination, and increased the half-decay time of the nuclear Ca2+ transient in cardiomyocytes. Emd knockdown cardiomyocytes showed similar properties after hypertrophic stimuli. The EDMD-iPS cell-derived cardiomyocytes showed increased nuclear area, decreased nuclear invagination, and increased half-decay time of the nuclear Ca2+ transient. An autopsied heart from a patient with EDMD also showed increased nuclear area and decreased nuclear invagination. These data suggest that Emerin plays a crucial role in nuclear structure and in the nuclear Ca2+ transient. Thus, emerin and the nuclear Ca2+ transient are possible therapeutic targets in heart failure and EDMD. © The Author(s) 2017.
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| 5.
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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
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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.
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| 6.
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Sugihara, Masako ; Oka, Rie ; Sakurai, Masaru ; Nakamura, Koshi ; Moriuchi, Tadashi ; Miyamoto, Susumu ; Takeda, Yoshiyu ; Yagi, Kunimasa ; Yamagishi, Masakazu
概要:
Objective Early studies have indicated that body fat shifts from peripheral stores to central stores with aging. The obj
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ective of this study was to investigate age-related changes in abdominal fat distribution of Japanese men and women of the general population over a wide range of body mass indices (BMI). Methods A total of 2,220 non-diabetic, apparently healthy Japanese adults (1,240 men and 980 women; age range 40-69 years) were included in the study sample. All subjects underwent a CT scan at the level of the umbilicus, and the areas of visceral adipose tissue (AT) and subcutaneous AT were quantified. Results When the subjects were stratified by BMI into 18.5-23.0 kg/m2, 23.0-27.5 kg/m2, and 27.5 kg/m2 or higher, visceral AT was positively correlated with age in all of the BMI strata in both genders (p<0.01). In contrast, subcutaneous AT was negatively correlated with age in men with BMIs in excess of 23.0 kg/m2 (p< 0.01) and not at all in women. The mean levels of subcutaneous AT were over 2-fold greater than visceral AT in women aged 60-69 years in any BMI stratum. Conclusion In Japanese men and women, visceral AT was increased with age in all BMI strata in both genders, whereas subcutaneous AT was decreased with age in men with BMIs in excess of 23.0 kg/m2 and not at all in women. Even with these age-related changes in abdominal fat distribution, women retained the subcutaneous-dominant type of fat distribution up to 70 years. © 2011 The Japanese Society of Internal Medicine.
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| 7.
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Moriuchi, Tadashi ; Oka, Rie ; Yagi, Kunimasa ; Miyamoto, Susumu ; Nomura, Hideki ; Yamagishi, Masakazu ; Mabuchi, Hiroshi ; Kobayashi, Junji ; Koizumi, Junji
概要:
Objective High-normal, the intermediate category between normal fasting glucose (NFG) and impaired fasting glucose (IFG)
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, was introduced in the criteria of the disordered glucose metabolism in 2008. The aim of this study was to investigate the risk for future incidence of type 2 diabetes of the subjects with high-normal and to examine how other metabolic variables could be useful for their risk stratification. Methods A historical cohort study was conducted from 2001 to 2008, inclusive, in 4,165 non-diabetic employees at public schools (2,229 men and 1,936 women; age 45.8±5.9 years, range 25-55 years). They were classified at baseline as NFG with fasting plasma glucose (FPG)<100 mg/dL, high-normal with FPG 100-109 mg/dL, and IFG with FPG 110-125 mg/dL. The incidence of type 2 diabetes (defined either by FPG 126 mg/dL or by receiving treatments) was measured. Results The cumulative incidence during a mean follow-up of 5.1 years were 16/3,364 (0.5%), 40/613 (6.5%), and 53/188 (28.2%) in subjects with NFG, high-normal, and IFG, respectively. Multivariate-adjusted odds ratios for the incidence were still significant both in high-normal and IFG compared to NFG. Body mass index (BMI) and alanine aminotransaminase (ALT) were associated with the incidence of type 2 diabetes independently of FPG categories (p<0.05). Conclusion The future incidence of type 2 diabetes in subjects with high-normal was significantly higher than in those with NFG in this population. BMI and ALT can improve risk stratification in high-normal subjects. © 2010 The Japanese Society of Internal Medicine.
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| 8.
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Funada, Akira ; Goto, Yoshikazu ; Maeda, Tetsuo ; Teramoto, Ryota ; Hayashi, Kenshi ; Yamagishi, Masakazu
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Background:There is sparse data regarding the survival and neurological outcome of elderly patients with out-of-hospital
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cardiac arrest (OHCA).Methods and Results:OHCA patients (334,730) aged ≥75 years were analyzed using a nationwide, prospective, population-based Japanese OHCA database from 2008 to 2012. The overall 1-month survival with favorable neurological outcome (Cerebral Performance Category Scale, category 1 or 2; CPC 1-2) rate was 0.88%. During the study period, the annual 1-month CPC 1-2 rate in whole OHCA significantly improved (0.73% to 0.96%, P for trend <0.001). In particular, outcomes of OHCA patients aged 75 to 84 years and those aged 85 to 94 years significantly improved (0.98% to 1.28%, P for trend=0.01; 0.46% to 0.70%, P for trend <0.001, respectively). However, in OHCA patients aged ≥95 years, the outcomes did not improve. Multivariate logistic regression analysis indicated that younger age, shockable first documented rhythm, witnessed arrest, earlier emergency medical service (EMS) response time, and cardiac etiology were significantly associated with the 1-month CPC 1-2. Under these conditions, elderly OHCA patients who had cardiac etiology, shockable rhythm and had a witnessed arrest had acceptable 1-month CPC1-2 rate; 7.98% in cases where OHCA was witnessed by family, 15.2% by non-family, and 25.6% by EMS.Conclusions:The annual 1-month CPC 1-2 rate after OHCA among elderly patients significantly improved, and the resuscitation of elderly patients in a selected population is not futile.
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| 9.
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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
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金沢大学医学系研究科<br />Background: Bezafibrate and fenofibrate show different binding properties against peroxisome proliferato
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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.
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| 10.
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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
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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
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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.
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