1.

論文

論文
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
2.

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論文
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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論文
Tada, Hayato ; Kawashiri, Masa-aki ; Okada, Hirofumi ; Teramoto, Ryota ; Konno, Tetsuo ; Yoshimuta, Tsuyoshi ; Sakata, Kenji ; Nohara, Atsushi ; Inazu, Akihiro ; Kobayashi, Junji ; Mabuchi, Hiroshi ; Yamagishi, Masakazu ; Hayashi, Kenshi
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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論文
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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論文
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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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
8.

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論文
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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論文
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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論文
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