Hirosaki, Japan
Hirosaki, Japan

Time filter

Source Type

Yoshida T.,Inabe General Hospital | Kato K.,Gifu Prefectural Tajimi Hospital | Yokoi K.,Gifu Prefectural Tajimi Hospital | Oguri M.,Red Cross | And 7 more authors.
International Journal of Molecular Medicine | Year: 2010

Dyslipidemia is an important risk factor for myocardial infarction (MI). We previously showed that gene polymorphisms associated with MI differed among individuals with different lipid profiles. We further examined whether genetic variants that confer susceptibility to MI might differ among individuals with low or high serum concentrations of triglycerides, high density lipoprotein (HDL)-cholesterol, or low density lipoprotein (LDL)-cholesterol. The study population comprised 5270 Japanese individuals, including 1188 subjects with MI and 4082 controls. The 150 polymorphisms examined in the present study were selected by genome-wide association studies of MI and ischemic stroke with the use of the Affymetrix GeneChip Human Mapping 500K Array Set. The initial Chi-square test revealed that the A→G polymorphism (rs12632110) of SEMA3F was significantly (false discovery rate <0.05) associated with MI among individuals with high serum HDL-cholesterol or among those with low serum LDL-cholesterol. Subsequent multivariable logistic regression analysis with adjustment for covariates revealed that rs12632110 was significantly (P<0.01) associated with MI in individuals with high serum HDL-cholesterol or with low serum LDL-cholesterol. The genetic variants that confer susceptibility to MI differ among individuals with different lipid profiles, and the genetic component for the development of MI is more apparent in individuals at low-risk (high HDL- and low LDL-cholesterol levels) compared to those at high-risk. Stratification of subjects according to lipid profiles may thus be important for personalized prevention of MI based on genetic information.


Yoshida T.,Inabe General Hospital | Kato K.,Gifu Prefectural Tajimi Hospital | Yokoi K.,Gifu Prefectural Tajimi Hospital | Oguri M.,Red Cross | And 7 more authors.
Experimental and Therapeutic Medicine | Year: 2010

Hypertension and diabetes mellitus are important risk factors for chronic kidney disease (CKD). The purpose of the present study was to identify genetic variants that confer susceptibility to CKD in individuals with or without hypertension or diabetes mellitus, thereby contributing to the personalized prevention of CKD in such individuals separately. The study population comprised 5835 unrelated Japanese individuals, including 1763 subjects with CKD and 4072 controls. The 150 polymorphisms were selected by genome-wide association studies of ischemic stroke and myocardial infarction with the use of the Gene chip human mapping 500K array Set (affymetrix). The genotypes for these polymorphisms were determined by a method that combines polymerase chain reaction and sequence-specific oligo nucleotide probes with suspension array technology. the χ2 test, multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that two different polymorphisms were significantly (P<0.005) associated with the prevalence of CKD in individuals with or without hypertension or diabetes mellitus: the a→G (lys625arg) polymorphism of CDH4 (rs6142884) in individuals without diabetes mellitus, and the c→t polymorphism of PTPRN2 (rs1638021) in individuals with hypertension and diabetes mellitus. No polymorphism.


Oguri M.,Red Cross | Kato K.,Gifu Prefectural Tajimi Hospital | Yokoi K.,Gifu Prefectural Tajimi Hospital | Yoshida T.,Inabe General Hospital | And 7 more authors.
American Journal of Hypertension | Year: 2010

Background Hypertension is a major risk factor for cardiovascular disease. Although genetic studies have suggested that several genetic variants increase the risk for hypertension, the genes that underlie genetic susceptibility to this condition remain to be identified definitively. The purpose of the present study was to identify genetic variants that confer susceptibility to hypertension in Japanese individuals. Methods A total of 5,734 Japanese individuals from two independent populations were examined: Subject panel A comprised 2,066 hypertensive individuals and 824 controls; and subject panel B comprised 834 hypertensive individuals and 2,010 controls. The 150 polymorphisms examined in the present study were selected by genome-wide association studies of myocardial infarction and ischemic stroke with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix). Results The χ2-test revealed that 10 polymorphisms were significantly (P <0.05) related to the prevalence of hypertension in subject panel A. To validate the relations, these polymorphisms were examined in subject panel B. The A→G polymorphism (rs645106) of SDK1 and the C→G polymorphism (rs12078839) of RABGAP1L were significantly associated with hypertension in subject panel B. Multivariable logistic regression analysis with djustment for covariates, as well as a stepwise forward selection procedure revealed that the A→G polymorphism of SDK1 was significantly associated with hypertension in both subject panels A and B, with the G allele protecting against this condition. Conclusions SDK1 may be a susceptibility gene for hypertension in Japanese individuals, although the functional relevance of the identified polymorphism was not determined. © 2010 American Journal of Hypertension, Ltd.


Yoshida T.,Inabe General Hospital | Kato K.,Gifu Prefectural Tajimi Hospital | Yokoi K.,Gifu Prefectural Tajimi Hospital | Oguri M.,Red Cross | And 7 more authors.
International Journal of Molecular Medicine | Year: 2010

Although genetic epidemiological studies have implicated several genetic variants as risk factors for hemorrhagic stroke, the genetic determinants of this condition remain largely unknown. We examined an association of genetic variants with intracerebral or subarachnoid hemorrhage among Japanese individuals. The study population comprised 4,304 unrelated Japanese individuals, including 377 subjects with intracerebral hemorrhage, 205 subjects with subarachnoid hemorrhage, and 3,722 controls. The 150 polymorphisms examined in the present study were selected by genome-wide association studies of ischemic stroke and myocardial infarction with the use of the GeneChip Human Mapping 500K Array Set. The chi-square test, multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that the C→T polymorphism (rs1324694) of ERLIN1, the C→T polymorphism (rs12679196) of TRAPPC9, and the G→T polymorphism (rs16936752) of WNK2 were significantly (P<0.05) associated with the prevalence of intracerebral hemorrhage, and that the A→G polymorphism (rs3111754) of ITM2C and the A→G polymorphism (rs10986769) of MAPKAP1 were significantly associated with the prevalence of subarachnoid hemorrhage. Genotypes for ERLIN1, TRAPPC9, and WNK2 may prove informative for assessment of the genetic risk for intracerebral hemorrhage, and those for ITM2C and MAPKAP1 may be beneficial in assessment of the genetic risk for subarachnoid hemorrhage in Japanese individuals.


Fujimaki T.,Gifu Prefectural Tajimi Hospital | Kato K.,Gifu Prefectural Tajimi Hospital | Yokoi K.,Gifu Prefectural Tajimi Hospital | Yoshida T.,Inabe General Hospital | And 8 more authors.
International Journal of Molecular Medicine | Year: 2010

Although chronic kidney disease (CKD) is recognized as an important risk factor for myocardial infarction (MI), genetic factors underlying predisposition to MI in individuals with or without CKD remain largely unknown. The aim of the present study was to identify genetic variants that confer susceptibility to MI in individuals with or without CKD in order to allow prediction of genetic risk for such individuals separately. The study population comprised a total of 4344 individuals, including 1247 individuals with CKD (506 subjects with MI and 741 controls) and 3097 individuals without CKD (833 subjects with MI and 2264 controls). The 150 polymorphisms examined in this study were selected by genome-wide association studies of ischemic stroke and MI with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix) and determined by a method that combines the polymerase chain reaction and sequencespecific oligonucleotide probes with suspension array technology. In individuals with CKD, no polymorphism was significantly related to MI. In individuals without CKD, an initial screen by the Chi-square test revealed that the C→T polymorphism of CLEC16A (rs9925481) and the A→G polymorphism of LAMA3 (rs12373237) were significantly (false discovery rate for allele frequencies of <0.05) associated with MI. Subsequent multivariable logistic regression analysis with adjustment for covariates revealed that the C→T polymorphism of CLEC16A (dominant model; P=0.0003; odds ratio, 0.66) and the A→G polymorphism of LAMA3 (recessive model; P=0.0087; odds ratio, 0.75) were significantly (P<0.05) associated with MI. A stepwise forward selection procedure also revealed that these polymorphisms were significant and independent determinants of MI. CLEC16A and LAMA3 may be susceptibility loci for MI in Japanese individuals without CKD. Determination of genotypes for CLEC16A and LAMA3 may prove informative for assessment of the genetic risk for MI in such individuals.


Yoshida T.,Inabe General Hospital | Kato K.,Gifu Prefectural Tajimi Hospital | Yokoi K.,Gifu Prefectural Tajimi Hospital | Oguri M.,Red Cross | And 7 more authors.
International Journal of Molecular Medicine | Year: 2010

Although metabolic syndrome has been recognized as a risk factor for ischemic stroke, genetic factors associated with ischemic stroke in individuals with metabolic syndrome remain unknown. We examined an association of genetic variants with ischemic stroke among individuals with or without metabolic syndrome. The study population comprised 4,387 unrelated Japanese individuals, including 1,884 individuals with metabolic syndrome (240 subjects with ischemic stroke and 1,644 controls) and 2,503 individuals without metabolic syndrome (280 subjects with ischemic stroke and 2,223 controls). The 150 polymorphisms examined in the present study were selected by genome-wide association studies of ischemic stroke and myocardial infarction with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix). The initial chi-square test revealed that the C→T polymorphism (rs9925481) of CLEC16A and the A→G polymorphism (rs4923918) of SPTBN5 were significantly (P<0.005) associated with ischemic stroke among individuals with metabolic syndrome. No polymorphism was significantly associated with ischemic stroke among individuals without metabolic syndrome. Multivariable logistic regression analysis with adjustment for covariates and a stepwise forward selection procedure revealed that the A→G polymorphism (rs4923918) of SPTBN5 was significantly (P<0.005), and the C→T polymorphism (rs9925481) of CLEC16A was almost significantly, associated with ischemic stroke in individuals with metabolic syndrome. Genetic variants that confer susceptibility to ischemic stroke may differ among individuals with or without metabolic syndrome. Stratification of subjects according to the presence or absence of metabolic syndrome may thus be important for personalized prevention of ischemic stroke based on genetic information.


Fujimaki T.,Gifu Prefectural Tajimi Hospital | Kato K.,Gifu Prefectural Tajimi Hospital | Yokoi K.,Gifu Prefectural Tajimi Hospital | Oguri M.,Red Cross | And 9 more authors.
Atherosclerosis | Year: 2010

Objective: The purpose of the present study was to identify genetic variants that confer susceptibility to myocardial infarction (MI) in Japanese individuals. Methods: The study population comprised 5014 Japanese individuals, including 1444 subjects with MI and 3570 controls. The 150 polymorphisms examined in the present study were selected by a genome-wide association study for ischemic stroke with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix), and were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Results: An initial screen by the chi-square test revealed that the A→G polymorphism of SEMA3F (rs12632110), the C→T polymorphism of CLEC16A (rs9925481), the A→G polymorphism of LAMA3 (rs12373237), and the C→G polymorphism of PCSK2 (rs6080699) were significantly (false discovery rate for allele frequencies of <0.05) associated with MI. Subsequent multivariable logistic regression analysis with adjustment for covariates and a stepwise forward selection procedure revealed that the A→G polymorphism of SEMA3F (dominant model; P= 0.0014; odds ratio, 0.76), the C→T polymorphism of CLEC16A (dominant model; P= 0.0009; odds ratio, 0.75), the A→G polymorphism of LAMA3 (recessive model; P= 0.0099; odds ratio, 0.80), and the C→G polymorphism of PCSK2 (recessive model; P= 0.0155; odds ratio, 1.19) were significantly (P<. 0.05) associated with the prevalence of MI. Conclusion: Determination of these genotypes may prove informative for assessment of the genetic risk for MI in Japanese individuals. © 2009 Elsevier Ireland Ltd.


Fukumoto Y.,Kyoto University | Fukumoto Y.,Japan Society for the Promotion of Science | Ikezoe T.,Kyoto University | Yamada Y.,Kyoto Prefectural University of Medicine | And 7 more authors.
European Journal of Applied Physiology | Year: 2012

Enhanced echo intensity (EI) on an ultrasound image of skeletal muscle indicates changes in muscle quality, including increases in intramuscular fibrous and adipose tissues. However, it is not known whether muscle quality assessed from the EI of computer-aided gray-scale analysis of an ultrasound image is associated with the muscle strength or body composition of a subject. The objectives of this study were to investigate whether muscle quality assessed from EI measured using gray-scale analysis is associated with muscle strength independently of age or muscle thickness (MT), and to examine the relationship between muscle EI and body composition. Ninetytwo healthy women with a mean age of 70.4 ± 5.5 years (range, 51-87 years) dwelling in Kyoto, Japan, participated in the study. The MT, subcutaneous fat thickness (FT), and EI of the quadriceps femoris on the right extremity were assessed from transverse ultrasound images. Knee extensor isometric strength was used as a measure of the quadriceps femoris muscle strength. EI was significantly correlated with quadriceps strength independently of age or MT, and stepwise regression analysis revealed that MT and EI were independently associated with quadriceps strength. Importantly, EI showed no significant correlations with FT, percentage of body fat (%BF), or body mass index (BMI), while FT, BMI, and %BF did not significantly influence muscle strength. These data suggest that muscle quantity (i.e., MT) and muscle quality assessed from EI measured using computer-aided gray-scale analysis independently contribute to muscle strength in middle-aged and elderly persons. © Springer-Verlag 2011.


Yoshida H.,Hirosaki University | Mimura J.,Hirosaki University | Imaizumi T.,Hirosaki University | Matsumiya T.,Hirosaki University | And 7 more authors.
Hirosaki Medical Journal | Year: 2010

Optimization of neuronal function and survival is an important goal in the treatment of cerebrovascular diseases in order to avoid or improve devastating long-term sequelae. Nerve growth factor (NGF) is essential for neuronal growth and survival in the central nervous system (CNS). Vascular endothelial growth factor (VEGF) is a potent mitogen specific for endothelial cells and a stimulator of neovascularization. VEGF also enhances vascular permeability, which may promote the development of brain edema during cerebral ischemia These molecules affect the outcome of ischemia/reperfusion injury in the CNS. Edaravone, a brain-penetrant, free radical scavenger, is known to ameliorate postischemic neuronal dysfunction. Transcription factor Nrf2 (nuclear factor-erythroid 2-related factor 2), a master regulator of antioxidant responses, plays an important role in the coordinated expressions of stress-inducible genes. Astrocytes express various genes involved in the regulation of neuronal functions, and the regulation of astrocyte gene expressions may be a potential therapeutic target in brain injury. This review aims to appraise the effects of radical scavenger edaravone and a natural Nrf2-inducer as neuroprotective agents in human astrocytes, particularly under an experimental model for hypoxia/reoxygenation.


Osanai T.,Hirosaki University | Fujiwara N.,Reimeikyo Rehabilitation Hospital | Sasaki S.,Hirosaki Stroke Center | Metoki N.,Hirosaki Stroke Center | And 8 more authors.
Annals of Medicine | Year: 2010

Background and purpose. Homocysteine (Hcy) is an independent predictor of stroke. Coupling factor 6 (CF6) is regulated by nuclear factor kappa B (NF-κB) signaling which is activated by Hcy. We tested the hypothesis that CF6 is elevated with Hcy in stroke. We also examined the effect of vitamin treatment on CF6 and Hcy levels. Methods and results. The 59 Japanese patients with a recent history of stroke were randomly assigned to a group without vitamin treatment (Group 1, n 29) and to a group with treatment with both folic acid and vitamin B12 for 2 months (Group 2, n 30). The CF6 level was elevated in the patients with stroke compared with that in controls (n 64) at admission. In a multiple regression model, the plasma CF6 level was weakly correlated to the total Hcy (tHcy) level. In Group 1, the plasma tHcy and CF6 levels were unchanged. In Group 2, however, they were both decreased, and there was a weak positive correlation between the decreases in plasma levels of CF6 and tHcy. Conclusion. CF6 is elevated in patients with stroke independently of risk factors. Since Hcy and vitamin treatment affect CF6 levels in stroke, CF6 appears to be a novel molecule for the pathogenesis and treatment of stroke. © Informa UK Ltd.

Loading Hirosaki Stroke Center collaborators
Loading Hirosaki Stroke Center collaborators