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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
出版情報: International Journal of Vascular Medicine.  pp.127149-,  2012-01-01.  Hindawi Publishing Corporation
URL: http://hdl.handle.net/2297/32857
概要: We examined the expression of ephrin-B1 and its cognate receptor EphB2, key regulators of angiogenesis and embryogenesis, 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. 続きを見る
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Funada, Akira ; Goto, Yoshikazu ; Maeda, Tetsuo ; Teramoto, Ryota ; Hayashi, Kenshi ; Yamagishi, Masakazu
出版情報: Circulation Journal.  80  pp.1153-1162,  2016-01-01.  日本循環器学会 = The Japanese Circulation Society
URL: http://hdl.handle.net/2297/44912
概要: Background:There is sparse data regarding the survival and neurological outcome of elderly patients with out-of-hospital 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. 続きを見る
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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
出版情報: American Journal of Cardiology.  115  pp.724-729,  2015-03-15.  Elsevier
URL: http://hdl.handle.net/2297/41369
概要: The aims of this study were (1) to determine whether the accumulation of coronary plaque burden assessed with coronary computed 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
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Yoshida, Shohei ; Tada, Hayato ; Yamagishi, Masakazu
出版情報: Therapeutic Apheresis and Dialysis.  19  pp.624-626,  2015-12-01.  Blackwell Publishing Ltd
URL: http://hdl.handle.net/2297/43949
概要: 発行後1年より全文公開
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Furuta, Takuya ; Tsubokawa, Toshinari ; Takabatake, Shu ; Ohtake, Hiroshi ; Watanabe, Go ; Yamagishi, Masakazu
出版情報: Internal Medicine.  50  pp.1025-1028,  2011-01-01.  The Japanese Society of Internal Medicine = 日本内科学会
URL: http://hdl.handle.net/2297/28341
概要: 金沢大学附属病院循環器内科<br />Early and accurate diagnosis of infective aortic aneurysms (IAA) is critical for adequate treat ment to optimize patient outcome. We report the case of an 84-year-old man who complained of severe back pain with high fever and was finally diagnosed as Escherichia coli-related IAA. Computed tomography showed a periaortic soft tissue density and irregular fringe adjacent to the non-dilated abdominal aorta suggesting the presence of pseudoaneurysm. In addition to intravenous antibiotic injection, an aneurysmectomy with extensive debridement and an in situ graft, were successfully performed. The case emphasizes the potential for rapid IAA change and the need for frequent radiologic follow-up. © 2011 The Japanese Society of Internal Medicine. 続きを見る
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Kim, Fae ; Yamada, Kazunori ; Inoue, Dai ; Nakajima, Kenichi ; Mizushima, Ichiro ; Kakuchi, Yasushi ; Fujii, Hiroshi ; Narumi, Kenta ; Matsumura, Masami ; Umehara, Hisanori ; Yamagishi, Masakazu ; Kawano, Mitsuhiro
出版情報: Internal Medicine.  50  pp.1239-1244,  2011-01-01.  The Japanese Society of Internal Medicine = 日本内科学会
URL: http://hdl.handle.net/2297/28339
概要: 金沢大学附属病院リウマチ・膠原病内科<br />Immunoglobulin G4 (IgG4)-related tubulointerstitial nephritis (TIN) is often accompanied b y autoimmune pancreatitis (AIP) or chronic sclerosing dacryoadenitis and sialoadenitis. However, IgG4-related TIN without AIP or lacrimal and/or salivary gland lesions has not been well recognized. Here, we report a case of IgG4-related TIN associated with hepatic inflammatory pseudotumor without AIP or lacrimal and/or salivary gland lesions. A 58-year-old Japanese man with epigastralgia underwent contrast-enhanced computed tomography (CT), which revealed multiple low-density lesions in both kidneys and a low density hepatic mass. Laboratory tests showed an extremely high level of serum IgG4. Percutaneous renal and hepatic biopsies showed diffuse infiltration of lymphocytes and IgG4-positive plasma cells with fibrosis in both tissues. Two months after administration of oral prednisolone, both lesions decreased in size on follow-up CT, and the serum cre-atinine level also improved. No recurrence has been detected for two years with a maintenance dose of pred-nisolone. © 2011 The Japanese Society of Internal Medicine. 続きを見る
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Tada, Hayato ; Kawashiri, Masa-aki ; Masuta, Eiichi ; Yamagishi, Masakazu
出版情報: Internal Medicine.  49  pp.1457-1458,  2010-01-01.  Japanese Society of Internal Medicine = 日本内科学会
URL: http://hdl.handle.net/2297/25029
概要: 金沢大学附属病院循環器内科
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Matsumura, Masami ; Kakuchi, Yasushi ; Hamano, Ryoko ; Kitajima, Susumu ; Ueda, Akihito ; Kawano, Mitsuhiro ; Yamagishi, Masakazu
出版情報: Internal Medicine.  46  pp.1585-1587,  2007-09-25.  日本内科学会 = Japanese Society of Internal Medicine
URL: http://hdl.handle.net/2297/16750
概要: 金沢大学附属病院 リウマチ・膠原病・腎臓内科<br />Systemic capillary leak syndrome is characterized by recurrent hypovolemic shock attri butable to increased systemic capillary leakage. A 26-year-old woman was admitted because of recurrent episodes of hypovolemic shock. Hemoconcentration, hypoalbuminemia, and monoclonal gammopathy were observed. We diagnosed systemic capillary leak syndrome. Three years later, she again had an attack of systemic capillary leak syndrome complicated with pretibial compartment syndrome. This case emphasizes the importance of muscle compartment pressure monitoring during volume resuscitation in patients with systemic capillary leak syndrome. © 2007 The Japanese Society of Internal Medicine. 続きを見る
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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 lo w-density 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
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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
出版情報: Experimental diabetes research.  2008  pp.89758-,  2008-12-01.  Hindawi Publishing Corporation
URL: http://hdl.handle.net/2297/18975
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 cyclic 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
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Tada, Hayato ; Kawashiri, Masaaki ; Watanabe, Go ; Yamagishi, Masakazu
出版情報: Internal Medicine.  48  pp.859-,  2009-01-01.  Japanese Society of Internal Medicine = 日本内科学会
URL: http://hdl.handle.net/2297/18718
概要: 金沢大学附属病院検査部
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Al Mahmuda, Naila ; Yokoyama, Shigeru ; Huang, Jian-Jun ; Liu, Li ; Munesue, Toshio ; Nakatani, Hideo ; Hayashi, Kenshi ; Yagi, Kunimasa ; Yamagishi, Masakazu ; Higashida, Haruhiro
出版情報: International Journal of Molecular Sciences.  17  pp.00772-,  2016-05-01.  Multidisciplinary Digital Publishing Institute (MDPI)
URL: http://hdl.handle.net/2297/45573
概要: Autism Spectrum Disorder (ASD) is a group of neurodevelopmental disorders with complex genetic etiology. Recent studies have indicated that children with ASD may have altered folate or methionine metabolism, suggesting that the folate-methionine cycle may play a key role in the etiology of ASD. SLC19A1, also referred to as reduced folate carrier 1 (RFC1), is a member of the solute carrier group of transporters and is one of the key enzymes in the folate metabolism pathway. Findings from multiple genomic screens suggest the presence of an autism susceptibility locus on chromosome 21q22.3, which includes SLC19A1. Therefore, we performed a case-control study in a Japanese population. In this study, DNA samples obtained from 147 ASD patients at the Kanazawa University Hospital in Japan and 150 unrelated healthy Japanese volunteers were examined by the sequence-specific primer-polymerase chain reaction method pooled with fluorescence correlation spectroscopy. p < 0.05 was considered to represent a statistically significant outcome. Of 13 single nucleotide polymorphisms (SNPs) examined, a significant p-value was obtained for AA genotype of one SNP (rs1023159, OR = 0.39, 95% CI = 0.16-0.91, p = 0.0394; Fisher’s exact test). Despite some conflicting results, our findings supported a role for the polymorphism rs1023159 of the SLC19A1 gene, alone or in combination, as a risk factor for ASD. However, the findings were not consistent after multiple testing corrections. In conclusion, although our results supported a role of the SLC19A1 gene in the etiology of ASD, it was not a significant risk factor for the ASD samples analyzed in this study. © 2016 by the authors; licensee MDPI, Basel, Switzerland. 続きを見る
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Munesue, Toshio ; Yokoyama, Shigeru ; Nakamura, Kazuhiko ; Anitha, Ayyappan ; Yamada, Kazuo ; Hayashi, Kenshi ; Asaka, Tomoya ; Liu, Hong-Xiang ; Jin, Duo ; Koizumi, Keita ; Islam, Mohammad Saharul ; Huang, Jian-Jun ; Ma, Wen-Jie ; Kim, Uh-Hyun ; Kim, Sun-Jun ; Park, Keunwan ; Kim, Dongsup ; Kikuchi, Mitsuru ; Ono, Yasuki ; Nakatani, Hideo ; Suda, Shiro ; Miyachi, Taishi ; Hirai, Hirokazu ; Salmina, Alla ; Pichugina, Yu A. ; Soumarokov, Andrei A. ; Takei, Nori ; Mori, Norio ; Tsujii, Masatsugu ; Sugiyama, Toshiro ; Yagi, Kunimasa ; Yamagishi, Masakazu ; Sasaki, Tsukasa ; Yamasue, Hidenori ; Kato, Nobumasa ; Hashimoto, Ryota ; Taniike, Masako ; Hayashi, Yutaka ; Hamada, Jun-ichiro ; Suzuki, Shioto ; Ooi, Akishi ; Noda, Mami ; Kamiyama, Yuko ; Kido, Mizuho A. ; Lopatina, Olga ; Hashii, Minako ; Amina, Sarwat ; Malavasi, Fabio ; Huang, Eric J. ; Zhang, Jiasheng ; Shimizu, Nobuaki ; Yoshikawa, Takeo ; Matsushima, Akihiro ; Minabe, Yoshio ; Higashida, Haruhiro
出版情報: Neuroscience Research.  67  pp.181-191,  2010-06-01.  Elsevier / the Japan Neuroscience Society = 日本神経科学学会
URL: http://hdl.handle.net/2297/24571
概要: 金沢大学医薬保健研究域医学系<br />The neurobiological basis of autism spectrum disorder (ASD) remains poorly understood. Given t he role of CD38 in social recognition through oxytocin (OT) release, we hypothesized that CD38 may play a role in the etiology of ASD. Here, we first examined the immunohistochemical expression of CD38 in the hypothalamus of post-mortem brains of non-ASD subjects and found that CD38 was colocalized with OT in secretory neurons. In studies of the association between CD38 and autism, we analyzed 10 single nucleotide polymorphisms (SNPs) and mutations of CD38 by re-sequencing DNAs mainly from a case-control study in Japan, and Caucasian cases mainly recruited to the Autism Genetic Resource Exchange (AGRE). The SNPs of CD38, rs6449197 (p< 0.040) and rs3796863 (p< 0.005) showed significant associations with a subset of ASD (IQ > 70; designated as high-functioning autism (HFA)) in the U.S. 104 AGRE family trios, but not with Japanese 188 HFA subjects. A mutation that caused tryptophan to replace arginine at amino acid residue 140 (R140W; (rs1800561, 4693C>T)) was found in 0.6-4.6% of the Japanese population and was associated with ASD in the smaller case-control study. The SNP was clustered in pedigrees in which the fathers and brothers of T-allele-carrier probands had ASD or ASD traits. In this cohort OT plasma levels were lower in subjects with the T allele than in those without. One proband with the T allele who was taking nasal OT spray showed relief of symptoms. The two variant CD38 poloymorphysms tested may be of interest with regard of the pathophysiology of ASD. © 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. 続きを見る
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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
出版情報: Atherosclerosis.  214  pp.404-407,  2011-02-01.  Elsevier
URL: http://hdl.handle.net/2297/26608
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 (LDL R), PCSK9 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
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Oka, Rie ; Kobayashi, Junji ; Inazu, Akihiro ; Yagi, Kunimasa ; Miyamoto, Susumu ; Sakurai, Masaru ; Nakamura, Koshi ; Miura, Katsuyuki ; Nakagawa, Hideaki ; Yamagishi, Masakazu
出版情報: Metabolism: Clinical and Experimental.  59  pp.748-754,  2010-05-01.  Elsevier
URL: http://hdl.handle.net/2297/23920
概要: 金沢大学大学院医学系研究科<br />北陸中央病院内科<br />We investigated the relative impacts of visceral adiposity and insulin resi stance on the metabolic risk profile in middle-aged Japanese men. A cross-sectional study was conducted in 636 nondiabetic Japanese men with a mean age of 51.6 years. Visceral adipose tissue (AT) was assessed using computed tomography, and insulin resistance was determined by the homeostasis model assessment of insulin resistance (HOMA-IR). Metabolic risk factors were diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III metabolic syndrome criteria: (1) hypertriglyceridemia, (2) low high-density lipoprotein cholesterol, (3) hypertension, (4) impaired fasting glucose, and (5) impaired glucose tolerance. Visceral AT and HOMA-IR were significantly and positively correlated with each other (r = 0.41, P < .001). Using the 75th percentile value as a cut point, those with isolated large visceral AT showed significantly greater odds ratios for each of the 5 risk factors measured except impaired fasting glucose, whereas those with isolated high HOMA-IR showed significantly greater odds ratios for each of the 5 risk factors except hypertriglyceridemia and impaired glucose tolerance, compared with the control group. The combined group (increased visceral AT and HOMA-IR) had the highest odds ratios for all studied risk factors. On logistic regression analysis using visceral AT and HOMA-IR as continuous independent variables, they were each independently associated with most of the metabolic risk factors and their clustering. In conclusion, neither visceral AT nor HOMA-IR stands out as the sole driving force of the risk profile; each makes a significant contribution to metabolic abnormalities in Japanese men. © 2010 Elsevier Inc. All rights reserved. 続きを見る
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Zoshima, Takeshi ; Matsumura, Masami ; Suzuki, Yasunori ; Kakuchi, Yasushi ; Mizushima, Ichiro ; Fujii, Hiroshi ; Yamada, Kazunori ; Yamagishi, Masakazu ; Kawano, Mitsuhiro
出版情報: Modern Rheumatology.  23  pp.1029-1033,  2013-09-01.  Japan College of Rheumatology 日本リウマチ学会 / Springer Verlag (Germany)
URL: http://hdl.handle.net/2297/32840
概要: We describe a patient with refractory cutaneous polyarteritis nodosa (CPAN) with hepatitis B virus (HBV) carrier status who was successfully treated with tumor necrosis factor alpha (TNF-α) blockade, using etanercept, and we review 5 similar cases. We administered etanercept because of the occurrence of repeated flares despite aggressive therapy. C-reactive protein normalization; prednisolone dose-sparing; and absence of any adverse events, including HBV reactivation with nucleotide analogue administration, or renal dysfunction, have been achieved for 8 months. TNF-α blockade should be considered for intractable CPAN. © 2012 Japan College of Rheumatology.<br />In Press → 出版者照会後に全文を公開. 続きを見る
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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
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 proli ferator-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
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Zoshima, Takeshi ; Matsumura, Masami ; Suzuki, Yasunori ; Kakuchi, Yasushi ; Mizushima, Ichiro ; Fujii, Hiroshi ; Yamada, Kazunori ; Yamagishi, Masakazu ; Kawano, Mitsuhiro
出版情報: Modern Rheumatology.  23  pp.1029-1033,  2013-09-01.  Japan College of Rheumatology 日本リウマチ学会/ Springer Verlag (Germany)
URL: http://hdl.handle.net/2297/36280
概要: We describe a patient with refractory cutaneous polyarteritis nodosa (CPAN) with hepatitis B virus (HBV) carrier status who was successfully treated with tumor necrosis factor alpha (TNF-α) blockade, using etanercept, and we review 5 similar cases. We administered etanercept because of the occurrence of repeated flares despite aggressive therapy. C-reactive protein normalization; prednisolone dose-sparing; and absence of any adverse events, including HBV reactivation with nucleotide analogue administration, or renal dysfunction, have been achieved for 8 months. TNF-α blockade should be considered for intractable CPAN. © 2012 Japan College of Rheumatology.<br />This is the pre-peer reviewed version of the following article: http://informahealthcare.com/doi/abs/10.3109/s10165-012-0732-8, which has been published in final form at http://dspace.lib.kanazawa-u.ac.jp/dspace/handle/2297/36280 . 続きを見る
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Demura, Masashi ; Wang, Fen ; Yoneda, Takashi ; Karashima, Shigehiro ; Mori, Shunsuke ; Oe, Masashi ; Kometani, Mitsuhiro ; Sawamura, Toshitaka ; Cheng, Yuan ; Maeda, Yuji ; Namiki, Mikio ; Ino, Hidekazu ; Fujino, Noboru ; Uchiyama, Katsuharu ; Tsubokawa, Toshinari ; Yamagishi, Masakazu ; Nakamura, Yasuhiro ; Ono, Katsuhiko ; Sasano, Hironobu ; Demura, Yoshiki ; Takeda, Yoshiyu
出版情報: Journal of Hypertension.  29  pp.1185-1195,  2011-06-01.  Wolters Kluwer Health / Lippincott Williams & Wilkins
URL: http://hdl.handle.net/2297/27783
概要: 金沢大学医薬保健研究域医学系<br />Objective: Nuclear receptors are involved in a wide variety of functions, including aldosteron ogenesis. Nuclear receptor families NR4A [nerve growth factor-induced clone B (NGFIB), Nur-related factor 1 (NURR1) and neuron-derived orphan receptor 1 (NOR1)] and NR2F [chicken ovalbumin upstream promoter-transcription factor 1 (COUP-TFI), COUP-TFII and NR2F6) activate, whereas NR5A1 [steroidogenic factor 1 (SF1)] represses CYP11B2 (aldosterone synthase) gene transcription. The present study was undertaken to elucidate the mechanism of differential regulation of nuclear receptors between cardiovascular and adrenal tissues. Methods: We collected tissues of artery (n = 9), cardiomyopathy muscle (n = 9), heart muscle (noncardiomyopathy) (n = 6), adrenal gland (n = 9) and aldosterone-producing adenoma (APA) (n = 9). 5′-rapid amplification of cDNA ends (RACE) identified transcription start sites. Multiplex reverse-transcription PCR (RT-PCR) determined use of alternative noncoding exons 1 (ANEs). Results: In adrenocortical H295R cells, angiotensin II, KCl or cAMP, all stimulated CYP11B2 transcription and NR4A was upregulated, whereas NR2F and NR5A1 were downregulated. 5′-RACE and RT-PCR revealed four ANEs of NGFIB (NR4A1), three of NURR1 (NR4A2), two of NOR1 (NR4A3) and two of SF1 (NR5A1) in cardiovascular and adrenal tissues. Quantitative multiplex RT-PCR showed NR4A and NR5A1 differentially employed multiple ANEs in a tissue-specific manner. The use of ANEs of NGFIB and NURR1 was significantly different between APA and artery. Changes in use of ANEs of NGFIB and NOR1 were observed between cardiomyopathy and noncardiomyopathy. The NR4A mRNA levels in artery were high compared with cardiac and adrenal tissues, whereas the NR5A1 mRNA level in adrenal tissues was extremely high compared with cardiovascular tissues. Conclusion: NR4A and NR5A1 genes are complex in terms of alternative promoter use. The use of ANEs may be associated with the pathophysiology of the heart and adrenal gland. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. 続きを見る
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Moriuchi, Tadashi ; Oka, Rie ; Yagi, Kunimasa ; Miyamoto, Susumu ; Nomura, Hideki ; Yamagishi, Masakazu ; Mabuchi, Hiroshi ; Kobayashi, Junji ; Koizumi, Junji
出版情報: Internal Medicine.  49  pp.1271-1276,  2010-07-01.  Japanese Society of Internal Medicine = 日本内科学会
URL: http://hdl.handle.net/2297/28981
概要: Objective High-normal, the intermediate category between normal fasting glucose (NFG) and impaired fasting glucose (IFG), 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. 続きを見る
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Matsumura, Masami ; Ito, Kiyoaki ; Kawamura, Rika ; Fujii, Hiroshi ; Inoue, Ryo ; Yamada, Kazunori ; Yamagishi, Masakazu ; Kawano, Mitsuhiro
出版情報: Internal Medicine.  50  pp.2357-2360,  2011-01-01.  The Japanese Society of Internal Medicine = 日本内科学会
URL: http://hdl.handle.net/2297/29568
概要: A 53-year-old woman with systemic lupus erythematosus presented with a 3-day history of fever and coughing. Diagnosis of pneumococcal bronchitis was made based on symptoms and positivity of pneumococcal urinary antigen test. On day 3, severe low back pain acutely occurred. Pneumococcal vertebral osteomyelitis and psoas abscess was diagnosed 17 days later by yield of penicillin-susceptible S. pneumoniae strain in blood cultures and drainage fluid. Although pneumococcal urinary antigen test is a useful tool for the diagnosis of pneumococcal pneumonia, we should consider the possibility of pneumococcal infections other than pneumonia or overwhelming bacteremia in immunosuppressive patients when urinary antigen test is positive © 2011 The Japanese Society of Internal Medicine. 続きを見る
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Matsumura, Masami ; Kawamura, Rika ; Inoue, Ryo ; Kawano, Mitsuhiro ; Yamagishi, Masakazu
出版情報: Modern Rheumatology.  21  pp.305-308,  2011-06-01.  Japan College of Rheumatology = 日本リウマチ学会 / Springer Verlag (Germany)
URL: http://hdl.handle.net/2297/29569
概要: 金沢大学医薬保健研究域医学系医学教育研究センター<br />Cryptococcal meningitis is a recognized complication of systemic lupus erythematosus (SLE), with high mortality rates, particularly in those treated with immunosuppressive agents. We describe a patient diagnosed simultaneously with cryptococcal meningoencephalitis and SLE and reviewed four similar cases reported in the literature. In our case, profound low CD4 lymphocyte count and low complement levels were observed. The patient was treated with prednisolone, fluconazole, and 5-flucytosine and evinced good clinical improvement. This case suggests that intrinsic immunological abnormality related to SLE predisposed to opportunistic infections. © 2010 Japan College of Rheumatology. 続きを見る
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Gamou, Tadatsugu ; Sakata, Kenji ; Tada, Hayato ; Konno, Tetsuo ; Hayashi, Kenshi ; Ino, Hidekazu ; Yamagishi, Masakazu ; Kawashiri, Masa-aki ; on behalf of the MILLION Study Group
出版情報: Circulation journal.  81  pp.1490-1495,  2017-09-25.  Japanese Circulation Society = 日本循環器学会
URL: http://hdl.handle.net/2297/48523
概要: Background:The MILLION study, a prospective randomized multicenter study, revealed that lipid and blood pressure (BP)-lo wering therapy resulted in regression of coronary plaque as determined by intravascular ultrasound (IVUS). In the present study we performed additional analysis to investigate the associated factors with regression of coronary plaque. Methods and Results:We investigated serial 3D IVUS images from 68 patients in the MILLION study. Standard IVUS parameters were assessed at both baseline and follow-up (18–24 months). Volumetric data were standardized by length as normalized volume. In patients with plaque regression (n=52), plaque volumenormalizedsignificantly decreased from 64.8 to 55.8 mm3(P<0.0001) and vessel volumenormalizedsignificantly decreased from 135.0 to 127.5 mm3(P=0.0008). There was no difference in lumen volumenormalizedfrom 70.1 to 71.8 mm3(P=0.27). There were no correlations between % changes in vessel volume and cholesterol or BP. On the other hand, negative correlations between % change in vessel volume and vessel volumenormalizedat baseline (r=−0.352, P=0.009) or plaque volumenormalizedat baseline (r=−0.336, P=0.01) were observed. Conclusions:The current data demonstrated that in patients with plaque regression treated by aggressive lipid and BP-lowering therapy, the plaque regression was derived from reverse vessel remodeling determined by vessel volume and plaque burden at baseline irrespective of decreases in lipids and BP.<br />出版者照会後に全文公開 続きを見る
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Araki, Daisuke ; Fujii, Hiroshi ; Matsumura, Masami ; Yamagishi, Masakazu ; Yachie, Akihiro ; Kawano, Mitsuhiro
出版情報: Internal Medicine.  50  pp.1843-1848,  2011-01-01.  The Japanese Society of Internal Medicine = 日本内科学会
URL: http://hdl.handle.net/2297/36515
概要: Hemophagocytic syndrome (HPS) is a severe, potentially life-threatening disorder characterized by an excessive activation of macrophages, such as may occur in the setting of lupus. A 62-year-old Japanese woman treated with etanercept for rheumatoid arthritis developed persistent fever, cytopenia, coagulopathy, and hyperferritinemia. Simultaneously, lupus-like features including pleuritis, hypocomplementemia, and positive autoantibodies were observed. She was diagnosed with HPS related to etanercept-induced lupus, and underwent immunosuppressive therapy with successful recovery. To our knowledge, this is the first case of etanercept-induced lupus accompanied by HPS. This case suggests that HPS should be considered as a complication during TNF-α inhibitor therapy. 続きを見る
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Funada, Akira ; Masuta, Eiichi ; Fujino, Noboru ; Hayashi, Kenshi ; Ino, Hidekazu ; Kita, Yoshihito ; Ikeda, Hiroko ; Fujii, Takahiko ; Nakanuma, Yasuni ; Yamagishi, Masakazu
出版情報: International Heart Journal.  51  pp.214-217,  2010-01-01.  International Heart Journal Association
URL: http://hdl.handle.net/2297/31473
概要: Hypertrophic cardiomyopathy (HCM) is associated with gene mutations that encode sarcomeric proteins. However, the relationship between genotype and histopathologic fndings is unclear. We report on two autopsy cases with advanced HCM associated with deletion of lysine 183 mutation in the cardiac troponin I gene. One case, a 74-year-old female exhibited dilated cardiomyopathy-like features. Transmural scarring was diffuse and circumferential, involving the whole left ventricle, especially the ventricular septum which was replaced with extensive fbrosis and showed marked wall thinning. The other case, a 92-year-old male revealed typical HCM fndings. Patchy scars which corresponded to replacement fbrosis were found extending from the septum to the anterior wall. These two autopsy cases indicate the clinical heterogeneity of HCM even within the same disease-causing mutation and suggest that the degree and extent of fbrosis determine differences in the clinical manifestations of HCM. This is the frst autopsy report that demonstrates identical sarcomeric gene mutations causing different clinical manifestations and histologic fndings. The fndings suggest that additional genetic or environmental factors infuence the phenotypic expressions and clinical courses of HCM caused by genetic mutation of sarcomeric proteins. 続きを見る
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Matsumura, Masami ; Suzuki, Yasunori ; Yamagishi, Masakazu ; Kawano, Mitsuhiro
出版情報: Internal Medicine.  51  pp.1283-1284,  2012-05-15.  Japanese Society of Internal Medicine = 日本内科学会
URL: http://hdl.handle.net/2297/31966
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Matsumura, Masami ; Suzuki, Yasunori ; Yamagishi, Masakazu ; Kawano, Mitsuhiro
出版情報: Internal Medicine.  51  pp.121-121,  2012-01-01.  日本内科学会 = The Japanese Society of Internal Medicine
URL: http://hdl.handle.net/2297/30111
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Yaegashi, Takanori ; Furusho, Hiroshi ; Chikata, Akio ; Usui, Soichiro ; Kaneko, Shuichi ; Yamagishi, Masakazu ; Takamura, Masayuki
出版情報: Journal of Medical Case Reports.  8  pp.158-,  2014-05-01.  BioMed Central
URL: http://hdl.handle.net/2297/39039
概要: Introduction. Right ventricular septal pacing is thought to be better than right ventricular apical pacing for shortening the QRS duration and for preserving left ventricular function. However, right ventricular septal pacing may not be effective in all cases. In this case report, we present a rare case in which right ventricular septal pacing induced thoroughly separated right and left ventricular excitation despite the presence of a relatively narrow QRS wave during atrium-only pacing. Case presentation. We report a case of 63-year-old Japanese man with cardiomyopathy with an implantable cardioverter defibrillator placement for ventricular tachycardia. Three years after implantation, he developed second-degree atrio-ventricular block. Therefore, atrio-ventricular sequential pacing was started; then his heart failure was much worsened. His electrocardiogram showed a dissociated biphasic QRS wave during right ventricular high-septal pacing, despite the presence of a non-fragmented QRS morphology during atrium-only pacing. An activation map during right ventricular high-septal pacing showed that right ventricular conduction started at the pacing site and ended at the right ventricular basal inferior site. Subsequently after a 10ms interval, left ventricular conduction started at the left ventricular posteroseptum and ended at the left ventricular lateral wall. These data indicate that during right ventricular high-septal pacing, the first component of the QRS wave supposedly reflects only right ventricular excitation and the second component only left ventricular excitation. Also due to the intracardiac electrograms, it was assumed that this phenomenon was caused by transversely limited severe transseptal conduction disturbance. Conclusion: It should be noted that even ventricular septal pacing could evoke harmful interventricular dyssynchrony due to transversely limited severe septal conduction disturbance, despite the presence of a relatively narrow QRS wave. © 2014 Yaegashi et al.; licensee BioMed Central Ltd. 続きを見る
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Karashima, Shigehiro ; Yoneda, Takashi ; Kometani, Mitsuhiro ; Ohe, Masashi ; Mori, Shunsuke ; Sawamura, Toshitaka ; Furukawa, Kenji ; Seta, Takashi ; Yamagishi, Masakazu ; Takeda, Yoshiyu
出版情報: Hypertension Research.  39  pp.133-137,  2016-03-01.  日本高血圧学会 = Japanese Society of Hypertension
URL: http://hdl.handle.net/2297/44875
概要: The mineralocorticoid receptor (MR) is expressed in the kidneys and in adipose tissue, and primary aldosteronism (PA) is associated with metabolic syndrome. This study assessed the effects of MR blockade by eplerenone (EPL) and spironolactone (SPL) on blood pressure (BP) and metabolic factors in patients with PA. Fifty-four patients with PA were treated with one of two MRAs, EPL (25-100 mg daily, n=27) or SPL (12.5-100 mg daily, n=27) for 12 months. Visceral (VAT) and subcutaneous adipose tissue were quantified using CT and FatScan imaging analysis software. Body mass index, homeostasis model assessment-insulin resistance (HOMA-IR), serum creatinine, potassium and lipids, urinary albumin excretion (UAE) and plasma aldosterone concentration (PAC) and plasma renin activity (PRA) were measured before and after treatment. EPL and SPL decreased BP and increased serum potassium levels to similar degrees. PAC and PRA did not differ between the two groups. Although treatment with the MRAs did not change HOMA-IR or serum lipids, they significantly decreased UAE and VAT (P<0.05). These results suggest that EPL and SPL are effective and safe for the treatment of PA. The long-term metabolic and renal effects of these MRAs should be further investigated. © 2016 The Japanese Society of Hypertension. All rights reserved.<br />Embargo Period 6 months 続きを見る
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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
出版情報: Journal of Atherosclerosis and Thrombosis.  16  pp.633-640,  2009-11-11.  Japan Atherosclerosis Society = 日本動脈硬化学会
URL: http://hdl.handle.net/2297/48533
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
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Tsuchida, Masayuki ; Kawashiri, Masa-aki ; Tada, Hayato ; Takata, Mutsuko ; Nohara, Atsushi ; Ino, Hidekazu ; Inazu, Akihiro ; Kobayashi, Junji ; Koizumi, Junji ; Mabuchi, Hiroshi ; Yamagishi, Masakazu
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
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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
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
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Okada, Toshihide ; Mibayashi, Hiroshi ; Hasatani, Kenkei ; Hayashi, Yoshiaki ; Tsuji, Shigetsugu ; Kaneko, Yoshibumi ; Yoshimitsu, Masashi ; Tani, Takashi ; Zen, Yoh ; Yamagishi, Masakazu
出版情報: World Journal of Gastroenterology.  15  pp.4587-4592,  2009-09-01.  Baishideng Publishing Group
URL: http://hdl.handle.net/2297/48241
概要: We report a case of two pseudolymphomas of the liver in a 63-year-old Japanese woman with primary biliary cirrhosis. One of the lesions was found incidentally during a medical examination, presenting as a 10 mm hypodense nodule that revealed hyperdensity in the early phase and hypodensity in the late phase in computed tomography (CT) after injection of contrast medium. Retrospectively, the 10 mm nodule had first been discovered as a 4 mm nodule during CT 4 years previously. Superparamagnetic iron oxide-enhanced MRI revealed another 4 mm hyperintense nodule in segment 6 in addition to the 10 mm hyperintense nodule in segment 7. CT during arterial portography revealed two hypointense nodules. Findings with other imaging modalities such as ultrasonography, magnetic resonance imaging, and hepatic angiography were consistent with hepatocellular carcinoma. A right posterior segmentectomy was performed, and the lesions were microscopically diagnosed as pseudolymphoma. To the best of our knowledge, only 31 other cases of this disease have ever been reported, with a highly asymmetrical male:female ratio of 1:9.7. Although we could find only one case of transformation of hepatic pseudolymphoma into lymphoma in the liver, the exact nature of development from benign pseudolymphoma to malignant lymphoma is still not fully understood and cases of hepatic lymphoma need to be followed carefully. © 2009 The WJG Press and Baishideng. All rights reserved. 続きを見る
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Demura, Masashi ; Yoneda, Takashi ; Karashima, Shigehiro ; Higashikata, Toshinori ; Mabuchi, Hiroshi ; Kawano, Mitsuhiro ; Yamagishi, Masakazu ; Takeda, Yoshiyu
出版情報: Journal of Medical Case Reports.  4  pp.347-,  2010-10-29.  BioMed Central
URL: http://hdl.handle.net/2297/48399
概要: Introduction: The combination of a pituitary prolactinoma and an aldosterone-producing adrenal adenoma is extremely rare. To the best of our knowledge, double endocrine tumors in association with heart-hand syndrome have not previously been reported. Case Presentation: A 21-year-old Japanese woman presented with galactorrhea and decreased visual acuity.A large pituitary adenoma with an increased level of serum prolactin was apparent by computed tomography. She additionally showed mild hypertension (136/90mmHg)accompanied by hypokalemia. The plasma aldosterone concentration was increased. Computed tomography showed a mass in the right adrenal gland. No other tumors were found despite extensive imaging studies. Physical and radiographic examinations showed skeletal malformations of the hands and feet, including hypoplasia of the first digit in all four limbs. An atrial septal defect was demonstrated by echocardiography. Similar digital and cardiac abnormalities were detected in our patient's father, and a clinical diagnosis ofhereditary heart-hand syndrome was made. Conclusion: No established heart-hand syndrome was wholly compatible with the family's phenotype. Her father had no obvious endocrine tumors, implying that the parent of transmission determined variable phenotypic expression of the disease: heart-hand syndrome with multiple endocrine tumors from the paternal transmission or no endocrine tumor from the maternal transmission. This suggests that the gene or genes responsible for the disease may be under tissue-specific imprinting control. 続きを見る
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Oe, Kotaro ; Araki, Tsutomu ; Konno, Tetsuo ; Ino, Hidekazu ; Yamagishi, Masakazu
出版情報: Internal Medicine.  49  pp.799-800,  2010-04-15.  Japanese Society of Internal Medicine = 日本内科学会
URL: http://hdl.handle.net/2297/48444
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Sugihara, Masako ; Oka, Rie ; Sakurai, Masaru ; Nakamura, Koshi ; Moriuchi, Tadashi ; Miyamoto, Susumu ; Takeda, Yoshiyu ; Yagi, Kunimasa ; Yamagishi, Masakazu
出版情報: Internal Medicine.  50  pp.679-685,  2011-04-01.  Japanese Society of Internal Medicine = 日本内科学会
URL: http://hdl.handle.net/2297/48446
概要: Objective Early studies have indicated that body fat shifts from peripheral stores to central stores with aging. The objective 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. 続きを見る
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Narumi, Kenta ; Kondoh, Atsushi ; Udagawa, Takeshi ; Hara, Hidehiko ; Goto, Naoko ; Ikarashi, Yoshinori ; Ohnami, Shumpei ; Okada, Toshihide ; Yamagishi, Masakazu ; Yoshida, Teruhiko ; Aoki, Kazunori
出版情報: Cancer Science.  101  pp.1686-1694,  2010-07-01.  Japanese Cancer Association = 日本癌学会
URL: http://hdl.handle.net/2297/48253
概要: Type I interferon (IFN) protein is a cytokine with pleiotropic biological functions that include induction of apoptosis, inhibition of angiogenesis, and immunomodulation. We have demonstrated that intratumoral injection of an IFN-α-expressing adenovirus effectively induces cell death of cancer cells and elicits a systemic tumor-specific immunity in several animal models. On the other hand, reports demonstrated that an elevation of IFN in the serum following an intramuscular delivery of a vector is able to activate antitumor immunity. In this study, we compared the intratumoral and systemic routes of IFN gene transfer with regard to the effect and safety of the treatment. Intratumoral injection of an IFN-α adenovirus effectively activated tumor-responsive lymphocytes and caused tumor suppression not only in the gene-transduced tumors but also in distant tumors, which was more effective than the intravenous administration of the same vector. The expression of co-stimulatory molecules on CD11c+ cells isolated from regional lymph nodes was enhanced by IFN gene transfer into the tumors. Systemic toxicity such as an elevation of hepatic enzymes was much lower in mice treated by intratumoral gene transfer than in those treated by systemic gene transfer. Our data suggest that the intratumoral route of the IFN vector is superior to intravenous administration, due to the effective induction of antitumor immunity and the lower toxicity. © 2010 Japanese Cancer Association. 続きを見る
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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
出版情報: International Journal of Vascular Medicine.  2012  pp.127149-,  2012-09-15.  Hindawi Publishing Corporation
URL: http://hdl.handle.net/2297/48407
概要: We examined the expression of ephrin-B1 and its cognate receptor EphB2, key regulators of angiogenesis and embryogenesis, 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. 続きを見る
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Shimojima, Masaya ; Kawashiri, Masa-aki ; Nitta, Yutaka ; Yoshida, Taiji ; Katsuda, Shouji ; Kaku, Bunji ; Taguchi, Tomio ; Hasegawa, Akira ; Konno, Tetsuo ; Hayashi, Kenshi ; Yamagishi, Masakazu
出版情報: American Journal of Cardiovascular Research.  2  pp.84-88,  2012-05-15.  e-Century Publishing
URL: http://hdl.handle.net/2297/48420
概要: Although intensive lipid lowering by statins can enhance plaque stability, few data exist regarding how early statins change plaque composition and morphology in clinical setting. Therefore, to examine early changes in plaque composition and morphology by intensive lipid lowering with statins, we evaluate coronary plaques from acute coronary syndrome (ACS) before and 3 weeks after lipid lowering by coronary CT angiography. We enrolled 110 patients with suspected ACS and underwent coronary CT. We defined plaque as unstable when CT number of plaque< 50HU and remodeling index (lesion diameter/reference diameter) >1.10. Rosuvastatin (5 mg/day) or atorvastatin (20 mg/day) were introduced to reduce low density lipoprotein cholesterol (LDL-C). Then, CT was again performed by the same condition 3 weeks after lipid lowering therapy. Total 10 patients (8 men, mean age 72.0 years), in whom informed consent regarding serial CT examination was obtained, were analyzed. Among them, 4 patients who denied to have intensive lipid lowering were served as controls. In remaining 6 patients, LDL-C reduced from 129.5±26.9 mg/dl to 68.5±11.1 mg/dl after statin treatment. Under these conditions, CT number of the targeted plaque significantly increased from 16.0±15.9 to 50.8±35.0 HU (p<0.05) and remodeling index decreased from 1.22±0.11 to 1.11±0.06 (p<0.05), although these values substantially unchanged in controls. These results demonstrate that MDCT-determined plaque composition as well as volume could be changed within 3 weeks after intensive lipid lowering. This may explain acute effects of statins in treatment of acute coronary syndrome. 続きを見る
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Daida, Hiroyuki ; Takayama, Tadateru ; Hiro, Takafumi ; Yamagishi, Masakazu ; Hirayama, Atsushi ; Saito, Satoshi ; Yamaguchi, Tetsu
出版情報: Cardiovascular Diabetology.  11  pp.87-,  2012-07-25.  BioMed Central
URL: http://hdl.handle.net/2297/48353
概要: Background: The incidence of cardiac events is higher in patients with diabetes than in people without diabetes. The Coronary Atherosclerosis Study Measuring Effects of Rosuvastatin Using Intravascular Ultrasound in Japanese Subjects (COSMOS) demonstrated significant plaque regression in Japanese patients with chronic coronary disease after 76 weeks of rosuvastatin (2.5 mg once daily, up-titrated to a maximum of 20 mg/day to achieve LDL cholesterol <80 mg/dl).Methods: In this subanalysis of COSMOS, we examined the association between HbA1c and plaque regression in 40 patients with HbA1c ≥6.5% (high group) and 86 patients with HbA1c <6.5% (low group).Results: In multivariate analyses, HbA1c and plaque volume at baseline were major determinants of plaque regression. LDL cholesterol decreased by 37% and 39% in the high and low groups, respectively, while HDL cholesterol increased by 16% and 22%, respectively. The reduction in plaque volume was significantly (p = 0.04) greater in the low group (from 71.0 ± 39.9 to 64.7 ± 34.7 mm3) than in the high group (from 74.3 ± 34.2 to 71.4 ± 32.3 mm3). Vessel volume increased in the high group but not in the low group (change from baseline: +4.2% vs -0.8%, p = 0.02). Change in plaque volume was significantly correlated with baseline HbA1c.Conclusions: Despite similar improvements in lipid levels, plaque regression was less pronounced in patients with high HbA1c levels compared with those with low levels. Tight glucose control during statin therapy may enhance plaque regression in patients with stable coronary disease.Trial registration: ClinicalTrials.gov, Identifier NCT00329160. © 2012 Daida et al.; licensee BioMed Central Ltd. 続きを見る
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Tada, Hayato ; Kobayashi, Junji ; Kawashiri, Masa-aki ; Miyashita, Kazuya ; Nohara, Atsushi ; Inazu, Akihiro ; Nakajima, Katsuyuki ; Mabuchi, Hiroshi ; Yamagishi, Masakazu
出版情報: Lipids in Health and Disease.  15  pp.66-,  2016-04-02.  BioMed Central
URL: http://hdl.handle.net/2297/48355
概要: Background: This study was performed to compare the effects of three different lipid-lowering therapies (statins, ezetimibe, 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
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Mori, Kiyoo ; Yamada, Kazunori ; Konno, Tetsuo ; Inoue, Dai ; Uno, Yoshihide ; Watanabe, Michio ; Okuda, Miho ; Oe, Kotaro ; Kawano, Mitsuhiro ; Yamagishi, Masakazu
出版情報: Internal Medicine.  54  pp.1231-1235,  2015-01-01.  Japanese Society of Internal Medicine = 日本内科学会
URL: http://hdl.handle.net/2297/48449
概要: We herein report the case of a 65-year-old man with pericardial involvement associated with autoimmune pancreatitis. Chest CT imaging showed pericardial thickening. The patient responded to corticosteroid therapy, and the pericardial thickening resolved. Multiple organs are involved in immunoglobulin G4 (IgG4)- related disease (IgG4-RD); however, only a few cases of IgG4-related chronic constrictive pericarditis have been reported. To our knowledge, this is the first reported case of IgG4-RD with pericardial involvement at an early stage. This case indicates that recognizing pericardial complications in autoimmune pancreatitis is important and that CT imaging may be useful for obtaining the diagnosis and providing follow-up of pericardial lesions in cases of IgG4-RD. © 2015 The Japanese Society of Internal Medicine. 続きを見る
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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
出版情報: Journal of Diabetes Research.  2013  pp.143515-,  2013-07-01.  Hindawi Publishing Corporation
URL: http://hdl.handle.net/2297/48398
概要: Background. Although retinol-binding protein 4 (RBP4) associates with insulin resistance and remnant-like particles triglyceride (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
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Fukushima, Yoshifumi ; Daida, Hiroyuki ; Morimoto, Takeshi ; Kasai, Takatoshi ; Miyauchi, Katsumi ; Yamagishi, Sho-ichi ; Takeuchi, Masayoshi ; Hiro, Takafumi ; Kimura, Takeshi ; Nakagawa, Yoshihisa ; Yamagishi, Masakazu ; Ozaki, Yukio ; Matsuzaki, Masunori
出版情報: Cardiovascular Diabetology.  12  pp.5-,  2013-07-01.  BioMed Central
URL: http://hdl.handle.net/2297/48242
概要: Background: The Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome (JAPAN-ACS) trial demonstrated that early aggressive statin therapy in patients with ACS significantly reduces plaque volume (PV). Advanced glycation end products (AGEs) and the receptors of AGEs (RAGE) may lead to angiopathy in diabetes mellitus (DM) and may affect on the development of coronary PV. The present sub-study of JAPAN-ACS investigates the association between AGEs and RAGE, and PV.Methods: Intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) was undertaken, followed by the initiation of statin treatment (either 4 mg/day of pitavastatin or 20 mg/day of atorvastatin), in patients with ACS. In the 208 JAPAN-ACS subjects, PV using IVUS in non-culprit segment > 5 mm proximal or distal to the culprit lesion and, serum levels of AGEs and soluble RAGE (sRAGE) were measured at baseline and 8-12 months after PCI.Results: At baseline, no differences in the levels of either AGEs or sRAGE were found between patients with DM and those without DM. The levels of AGEs decreased significantly with statin therapy from 8.6 ± 2.2 to 8.0 ± 2.1 U/ml (p < 0.001), whereas the levels of sRAGE did not change. There were no significant correlations between changes in PV and the changes in levels of AGEs as well as sRAGE. However, high baseline AGEs levels were significantly associated with plaque progression (odds ratio, 1.21; 95% confidence interval, 1.01 - 1.48; p = 0.044) even after adjusting for DM in multivariate logistic regression models.Conclusions: High baseline AGEs levels were associated with plaque progression in the JAPAN-ACS trial. This relationship was independent of DM. These findings suggest AGEs may be related to long-term glucose control and other oxidative stresses in ACS.Trial registration: NCT00242944. © 2013 Fukushima et al.; licensee BioMed Central Ltd. 続きを見る
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Onoe, Tamehito ; Konoshita, Tadashi ; Tsuneyama, Koichi ; Hamano, Ryoko ; Mizushima, Ichiro ; Kakuchi, Yasushi ; Yamada, Kazunori ; Hayashi, Kenshi ; Kuroda, Masahiro ; Kagitani, Satoshi ; Nomura, Hideki ; Yamagishi, Masakazu ; Kawano, Mitsuhiro
出版情報: American Journal of Case Reports.  14  pp.20-25,  2013-01-28.  International Scientific Information
URL: http://hdl.handle.net/2297/48240
概要: Background: Situs inversus is a rare complication of cystic kidney diseases. Only three genes, INVS (NPHP2), NPHP3 and PKD2 have been proved to be responsible for some cases, while the responsible genes in many others are still unknown. Case Reports: Here we report two male patients with situs inversus combined with cystic kidney disease without any family history of polycystic kidney disease. Their renal function was normal in childhood but culminated in end stage renal disease in middle age. No pathogenic mutations were found in mutation analysis of INVS, IFT88, PKD2, UMOD or NPHP3 in them. Conclusions: Past reported cases of situs inversus and cystic kidney diseases were divided into three groups, i.e., gestational lethal renal dysplasia group, infantile or juvenile nephronophthisis group and polycystic kidney disease group. The present patients are different from each of these groups. Moreover, the renal lesions of the present two cases are quite different from each other, with one showing mildly atrophic kidneys with small numbers of cysts and the other an enlarged polycystic kidney disease, suggesting very heterogeneous entities. 続きを見る
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Chujo, Daisuke ; Foucat, Emile ; Takita, Morihito ; Itoh, Takeshi ; Sugimoto, Koji ; Shimoda, Masayuki ; Yagi, Kunimasa ; Yamagishi, Masakazu ; Tamura, Yoshiko ; Yu, Liping ; Naziruddin, Bashoo ; Levy, Marlon F. ; Ueno, Hideki ; Matsumoto, Shinichi
出版情報: Cell Transplantation.  21  pp.2783-2795,  2012-09-01.  Cognizant Communication Corporation
URL: http://hdl.handle.net/2297/48419
概要: Islet transplantation is one of the most promising therapies for type 1 diabetes (T1D). A major issue in islet transplantation is the loss of graft function at late phase. Several studies suggested the involvement of islet-specific T-cells in such islet graft dysfunction. In this study, we investigated the breadth and type of glutamic acid decarboxylase 65 (GAD65)-specific T-cells in T1D patients after allogeneic islet transplantation. Peripheral blood mononuclear cells (PBMCs) were obtained from islet-transplanted T1D patients during insulin-independent period and cultured for 7 days with pools of GAD65 overlapping peptides in the presence of IL-2. Cytokine secretion profiles of peptide-reactive T-cells were analyzed after a short-term restimulation with the same peptides by a multiplex bead-based cytokine assay and by an intracytoplasmic cytokine detection assay. Robust GAD65-specific CD4(+) and CD8(+) T-cell responses were detected in patients who eventually developed chronic graft dysfunction. Multiple GAD65 peptides were found to induce specific T-cell responses in these patients, indicating that the repertoire of GAD65-specific T-cells was broad. Furthermore, GAD65-specific CD4(+) T-cells were composed of heterogeneous populations, which differentially expressed cytokines including IFN-γ and type 2 cytokines, but not IL-10. In contrast, patients who showed only marginal GAD65-specific T-cell responses maintained substantially longer graft survival and insulin independence. In conclusion, our study suggests that the emergence of islet-specific T-cells precedes the development of chronic graft dysfunction in islet-transplanted patients. Thus, our observations support the hypothesis that these islet-specific T-cells contribute to the development of chronic islet graft dysfunction. 続きを見る
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Ma, Wen-Jie ; Hashii, Minako ; Munesue, Toshio ; Hayashi, Kenshi ; Yagi, Kunimasa ; Yamagishi, Masakazu
出版情報: Molecular Autism.  4  pp.22-,  2013-07-01.  BioMed Central
URL: http://hdl.handle.net/2297/48354
概要: Background: The human oxytocin receptor (hOXTR) is implicated in the etiology of autism spectrum disorders (ASDs) and is a potential target for therapeutic intervention. Several studies have reported single-nucleotide polymorphisms (SNPs) of the OXTR gene associated with ASDs. These SNPs, however, reside outside the protein-coding region. Not much is known about genetic variations that cause amino acid substitutions that alter receptor functions. Methods. Variations in the OXTR gene were analyzed in 132 ASD patients at Kanazawa University Hospital in Japan and 248 unrelated healthy Japanese volunteers by re-sequencing and real-time polymerase chain reaction-based genotyping. Functional changes in variant OXTRs were assessed by radioligand binding assay and measurements of intracellular free calcium concentrations ([Ca§ssup§2+§esup§]§ssub§i§esub§) and inositol 1,4,5-trisphosphate (IP§ssub§3§esub§) levels. Results: Six subjects (4.5%) in the ASD group and two in the control group (0.8%) were identified as heterozygotes carrying the R376G variation (rs35062132; c.1126C>G); one individual from the ASD group (0.8%) and three members of the control group (1.2%) were found to be carrying R376C (c.1126C>T). The C/G genotype significantly correlated with an increased risk of ASDs (odds ratio (OR) = 5.83; 95% confidence interval (CI) = 1.16 to 29.33; P = 0.024, Fisher's exact test). Consistently, the G allele showed a correlation with an increased likelihood of ASDs (OR = 5.73; 95% CI = 1.15 to 28.61; P = 0.024, Fisher's exact test). The frequencies of the C/T genotype and the T allele in the ASD and control groups did not differ significantly. We also examined changes in agonist-induced cellular responses mediated by the variant receptors hOXTR-376G and hOXTR-376C. OXT-induced receptor internalization and recycling were faster in hOXTR-376G-expressing HEK-293 cells than in cells expressing hOXTR-376R or hOXTR-376C. In addition, the elevation in [Ca§ssup§2+§esup§]§ssub§i§esub§ and IP§ssub§3§esub§ formation decreased in the cells expressing hOXTR-376G and hOXTR-376C tagged with enhanced green fluorescent protein (EGFP), in comparison with the cells expressing the common-type hOXTR-376R tagged with EGFP. Conclusions: These results suggest that the rare genetic variation rs35062132 might contribute to the pathogenesis of ASDs, and could provide a molecular basis of individual differences in OXTR-mediated modulation of social behavior. © 2013 Ma et al.; licensee BioMed Central Ltd. 続きを見る
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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
出版情報: Scientific Reports.  7  pp.44312-,  2017-03-14.  Nature Publishing Group
URL: http://hdl.handle.net/2297/48359
概要: Alteration of the nuclear Ca2+ transient is an early event in cardiac remodeling. Regulation of the nuclear Ca2+ transient 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. 続きを見る
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Oe, Kotaro ; Araki, Tsutomu ; Hayashi, Kenshi ; Yamagishi, Masakazu
出版情報: Internal Medicine.  56  pp.381-382,  2017-02-01.  Japanese Society of Internal Medicine = 日本内科学会
URL: http://hdl.handle.net/2297/48443
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Kojima, Sunao ; Matsui, Kunihiko ; Sakamoto, Tomohiro ; Ishihara, Masaharu ; Kimura, Kazuo ; Miyazaki, Shunichi ; Yamagishi, Masakazu ; Tei, Chuwa ; Hiraoka, Hisatoyo ; Sonoda, Masahiro ; Tsuchihashi, Kazufumi ; Shimoyama, Nobuo ; Honda, Takashi ; Ogata, Yasuhiro ; Ogawa, Hisao ; The Japanese Acute Coronary Syndrome Study (JACSS) Investigators
出版情報: Circulation journal.  71  pp.301-307,  2007-02-25.  Japanese Circulation Society = 日本循環器学会
URL: http://hdl.handle.net/2297/48517
概要: Background There is conflicting information about whether nitrate treatment aggravates long-term prognosis, so the prese nt retrospective study was designed to determine the effects of long-term nitrate therapy on major adverse events after acute myocardial infarction (AMI) in the coronary interventional era. Methods and Results Using the Japanese Acute Coronary Syndrome Study database, 1,236 consecutive patients who were hospitalized within 48 h of onset of symptoms of AMI from January to December 2003 were evaluated. All-cause mortality, cardiac events and cardiovascular events were lower in patients treated with nitrates than in the untreated controls. However, these crude comparisons included several confounding factors on nitrate prescription. To minimize the effect of selection bias on outcomes, the technique of propensity score matching for clinical characteristics was used and distortion of effective nitrate treatment was excluded as much as possible. The results of propensity score matching showed that nitrate therapy had no impact on all-cause mortality, cardiac events and cardiovascular events at 30, 60 or 90 days, 6 months, 1 year, and 2 years follow-up. Conclusions Long-term nitrate therapy after AMI neither improves nor aggravates prognosis. Prospective randomized clinical trials are warranted to determine the effects of long-term nitrate therapy for secondary prevention of AMI. (Circ J 2007; 71: 301 - 307)<br />出版者照会後に全文公開 続きを見る