Ehime Proteo Medicine Research Center

Ehime, Japan

Ehime Proteo Medicine Research Center

Ehime, Japan
Time filter
Source Type

Tabara Y.,Program for Medical science | Tabara Y.,Ehime Proteo Medicine Research Center | Miki T.,Ehime Proteo Medicine Research Center | Kohara K.,Ehime Proteo Medicine Research Center
Geriatrics and Gerontology International | Year: 2010

Aim: Aging shifts body composition to comprising more fat and less muscle. Sarcopenia, particularly in the knee extensors, and obesity, particularly visceral obesity, either alone or in combination, may exacerbate age-related physical disability. We investigated the association between age-related quadriceps (Qc) sarcopenia and visceral obesity, as measured by cross-sectional area (CSA), on postural instability. Methods: Mid-thigh muscle CSA and abdominal visceral and subcutaneous fat area at the level of the umbilicus were assessed from computed tomography (CT) images in 410 apparently healthy independent middle-aged to elderly subjects attending the medical check-up program in Ehime University Hospital. Static postural instability using a posturograph and one-leg standing time with eyes open were assessed. Results: Both abdominal visceral fat area and Qc muscle CSA corrected by body weight (BW) were associated with static postural instability, in addition to age and sex, while BW-corrected Qc muscle CSA predicted a short one-leg standing time. The combination of Qc sarcopenia, defined as greater than 1 standard deviation below the mean of a young group (age <60 years), and visceral obesity, defined as a visceral fat area of more than 100 cm2, were associated with static postural instability, while Qc sarcopenia was related to a higher prevalence of one-leg standing time of less than 30 s, irrespective of visceral obesity. Conclusion: Thigh Qc sarcopenia and visceral obesity are associated with postural instability in middle-aged to elderly subjects. These findings suggest that age-related, site-specific fat and muscle mass alterations are associated with functional impairment. Geriatr Gerontol Int 2010; 10: 233-243. © 2010 Japan Geriatrics Society.

Masuki S.,Shinshu University | Mori M.,Shinshu University | Mori M.,Jukunen Taiiku Daigaku Research Center | Tabara Y.,Ehime Proteo Medicine Research Center | And 8 more authors.
Hypertension | Year: 2010

We assessed whether single nucleotide polymorphism rs1042615 of the vasopressin V1a receptor altered the indices of lifestyle-related diseases in middle-aged and older people (mean±SD: 64±7 years), and, if so, whether it also altered the effects of interval walking training (IWT). CC, CT, and TT carriers of rs1042615 (42, 118, and 64 men, respectively; 113, 263, and 154 women, respectively) performed IWT. We included 5 sets of 3-minute fast walking at ≥70% peak aerobic capacity for walking and 3-minute slow walking at 40% peak aerobic capacity per day for ≥4 days per week for 5 months. Before IWT, the body mass index and diastolic blood pressure (DBP) for men were 25.1±0.3 kg/m (mean±SE) and 84±1 mm Hg in TT, higher than the 23.6±0.4 kg/m and 78±1 mm Hg in CC, respectively (P<0.01), differences that disappeared after IWT despite similar training achievement between groups (P>0.6). After IWT, body mass index and DBP decreased in TT (-0.9±0.1 kg/m and-5±1 mm Hg, respectively), more than in CC (-0.5±0.1 kg/m and 1±1 mm Hg, respectively; P<0.05), with a greater decrease in low-density lipoprotein cholesterol in TT than CC carriers (P<0.01). The decreases in DBP and low-density lipoprotein cholesterol were still greater in TT carriers even after adjustment for their pretraining values. On the other hand, for women, these parameters before IWT and their changes after IWT were similar among CC, CT, and TT carriers. Thus, polymorphism rs1042615 of the V1a receptor altered body mass index and DBP in middle-aged and older men and the training-induced responses of DBP and low-density lipoprotein cholesterol, whereas women did not show any of these responses. Copyright © 2010 American Heart Association. All rights reserved.

Masuki S.,Shinshu University | Mori M.,Shinshu University | Tabara Y.,Ehime University | Tabara Y.,Ehime Proteo Medicine Research Center | And 11 more authors.
Journal of Applied Physiology | Year: 2015

No long-term exercise training regimen with high adherence and effectiveness in middle-aged and older people is broadly available in the field. We assessed the adherence to, and effects of, our long-term training program comprising an interval walking training (IWT) and an information technology network system and the factors affecting adherence. Middle-aged and older men and women [n = 696, aged 65 ± 7(SD) yr] underwent IWT. The subjects were instructed to repeat five or more sets of fast and slow walking for 3 min each at ≥70 and 40% peak aerobic capacity for walking (VO2peak), respectively, per day ≥4 days/wk for 22 mo. Adherence was assessed as training days accomplished relative to the target of 4 days/wk over 22 mo. The effects on the VO2peak and lifestyle-related disease score were evaluated every 6 mo. The independent factors affecting adherence were assessed by multiple-regression analysis after adjustment for baseline physical characteristics and other possible covariates, including vasopressin V1a receptor polymorphisms. The adherence over 22 mo averaged 70% and was highly correlated with a 13% reduction in the lifestyle-related disease score (R2 = 0.94, P = 0.006) and with a 12% increase in VO2peak (R2 = 0.94, P = 0.006). The major determinant of higher adherence was lower baseline body mass index (BMI) (P < 0.0001) and male sex (P < 0.0001). For men, in addition to BMI, nonsmokers (P = 0.031) and V1a receptor polymorphisms (P < 0.033) were independent determinants of higher adherence. Thus the long-term IWT program is an effective regimen. Moreover, baseline BMI and sex for all subjects, and smoking and V1a receptor polymorphisms for men, were associated with adherence. Copyright © 2015 by the American Physiological Society.

Hiura Y.,Japan National Cardiovascular Center Research Institute | Tabara Y.,Ehime University | Kokubo Y.,National Cardiovascular Center | Okamura T.,National Cardiovascular Center | And 7 more authors.
Circulation Journal | Year: 2010

Background: The association between single nucleotide polymorphisms (SNPs) at 3-hydroxy-3-methylglutarylcoenzyme A reductase (HMGCR) and low-density lipoprotein-cholesterol (LDL-C) levels has been well replicated in genome-wide association studies (GWAS) of white populations. Recently, the common intronic SNP of HMGCR (rs3846662) has been reported to be a functional variant, influencing the alternative splicing of exon 13. The aim of this study was to examine the association between rs3846662 of HMGCR and the level of LDL-C in Japanese. Methods and Results: Significant differences in LDL-C levels were observed among the genotypes of rs3846662 (P=0.0002 (n=2,686) and P=0.004 (n=2,110)) for the Suita and Ehime samples, respectively. The G allele of rs3846662 was associated with higher LDL-C levels (ß, 3.56; P=4.91×10-5). Consistent with this observation, the risk G allele at rs3846662 was more prevalent in subjects with myocardial infarction (MI) (n=701) than in subjects without MI (n=3,118); 0.559 and 0.511 in MI cases and controls, respectively (nominal P=0.0038). The odds ratio adjusted for age, sex, diabetes, hypertension, and drinking and smoking habits was 1.15 (95% confidence interval 1.04-1.28; P=0.0075). Conclusions: The previously reported association of rs3846662 with LDL-C levels was replicated in the present Suita and Ehime samples. The LDL-associated SNP, rs3846662, appears to confer susceptibility to MI in Japanese.

Tabara Y.,Ehime University | Tabara Y.,Ehime Proteo Medicine Research Center | Kohara K.,Ehime University | Kohara K.,Ehime Proteo Medicine Research Center | And 32 more authors.
Hypertension | Year: 2010

Hypertension is one of the most common complex genetic disorders. We have described previously 38 single nucleotide polymorphisms (SNPs) with suggestive association with hypertension in Japanese individuals. In this study we extend our previous findings by analyzing a large sample of Japanese individuals (n=14 105) for the most associated SNPs. We also conducted replication analyses in Japanese of susceptibility loci for hypertension identified recently from genome-wide association studies of European ancestries. Association analysis revealed significant association of the ATP2B1 rs2070759 polymorphism with hypertension (P=5.3×10; allelic odds ratio: 1.17 [95% CI: 1.09 to 1.26]). Additional SNPs in ATP2B1 were subsequently genotyped, and the most significant association was with rs11105378 (odds ratio: 1.31 [95% CI: 1.21 to 1.42]; P=4.1×10). Association of rs11105378 with hypertension was cross-validated by replication analysis with the Global Blood Pressure Genetics consortium data set (odds ratio: 1.13 [95% CI: 1.05 to 1.21]; P=5.9×10). Mean adjusted systolic blood pressure was highly significantly associated with the same SNP in a meta-analysis with individuals of European descent (P=1.4×10). ATP2B1 mRNA expression levels in umbilical artery smooth muscle cells were found to be significantly different among rs11105378 genotypes. Seven SNPs discovered in published genome-wide association studies were also genotyped in the Japanese population. In the combined analysis with replicated 3 genes, FGF5 rs1458038, CYP17A1, rs1004467, and CSK rs1378942, odds ratio of the highest risk group was 2.27 (95% CI: 1.65 to 3.12; P=4.6×10) compared with the lower risk group. In summary, this study confirmed common genetic variation in ATP2B1, as well as FGF5, CYP17A1, and CSK, to be associated with blood pressure levels and risk of hypertension. © 2010 American Heart Association, Inc.

Tabara Y.,Ehime University | Tabara Y.,Ehime Proteo Medicine Research Center | Osawa H.,Ehime Proteo Medicine Research Center | Osawa H.,Ehime University | And 10 more authors.
Metabolism: Clinical and Experimental | Year: 2011

Recent genomewide association studies have successfully identified several genotypes susceptible to type 2 diabetes mellitus (T2DM). However, only a few studies have investigated whether these variations confer a risk of the future development of T2DM. We conducted a longitudinal genetic epidemiological study to clarify the prognostic significance of the T2DM-associated variants. The sample population consisted of 2037 middle-aged to elderly community residents. Personal health records were obtained from a clinical database administered by the local government. Genotype risk score was calculated by the following variants, namely, KCNQ1, TCF7L2, CDKAL1, HHEX, IGF2BP2, CDKN2AB, SLC30A8, KCNJ11, PPARG, and GCKR. Susceptibility of these variants in Japanese has been confirmed by association analysis. Among the 1824 subjects who did not have T2DM at baseline, 95 cases of T2DM were newly diagnosed during the 9.4-year follow-up period. Mean genotype risk score in these subjects was significantly higher than that in the subjects who remained nondiabetic (9.5 ± 1.8 vs 9.1 ± 2.0, P =.042). Although the initial mean body mass index (24.7 ± 3.2 vs 23.0 ± 2.8, P <.001) and initial glucose (106 ± 18 vs 90 ± 13, P <.001) were also significantly higher in those subjects who developed T2DM, the genotype risk score remained an independent determinant of the development of T2DM even after adjustment for these parameters and possible confounding factors. Per-allele odds ratio for the development of T2DM was 1.12 (95% confidence interval, 1.00-1.25; P =.049). Type 2 diabetes mellitus-susceptible genetic variants identified by a cross-sectional genomewide association study were significantly associated with the future development of T2DM in a general population sample. © 2011 Elsevier Inc.

Kobayashi K.,Ehime University | Takahashi H.,Ehime University | Takahashi H.,Ehime Proteo Medicine Research Center | Inoue A.,Ehime University | And 11 more authors.
Journal of Cellular Biochemistry | Year: 2012

As a result of increased glioblastoma migration and invasion into normal brain parenchyma, treatment of local tumor recurrence following initial treatment in glioblastoma patients remains challenging. Recent studies have demonstrated increased Oct-3/4 expression, a self-renewal regulator in stem cells, in glioblastomas. However, little is known regarding the influence of Oct-3/4 in glioblastoma cell invasiveness. The present study established Oct-3/4-overexpressing glioblastoma cells, which were prepared from human glioblastoma patients, to assess migration, invasion, and mRNA expression profiles of integrins and matrix metalloproteinases (MMPs). Compared with control cells, Oct-3/4 expressing-glioblastoma cells exhibited increased migration and invasion in wound healing and Matrigel invasion assays. Oct-3/4 overexpression resulted in upregulated FAK and c-Src expression, which mediate integrin signals. Vinculin accumulated along the leading edges of Oct-3/4 expressing-glioblastoma cells and associated with membrane ruffles during cell migration. Oct-3/4 expressing-cells exhibited increased MMP-13 mRNA expression and MMP-13 knockdown by shRNA suppressed cell invasion into Matrigel and organotypic brain slices. These results suggested that Oct-3/4 enhanced degradation of surrounding extracellular matrix by increasing MMP-13 expression and altering integrin signaling. Therefore, Oct-3/4 might contribute to tumor promoting activity in glioblastomas. © 2011 Wiley Periodicals, Inc.

Kido T.,Ehime University | Tabara Y.,Ehime University | Tabara Y.,Ehime Proteo Medicine Research Center | Igase M.,Ehime University | And 9 more authors.
Dementia and Geriatric Cognitive Disorders | Year: 2010

Background/Aims: Mobility impairment in older adults has been suggested to be a marker of subclinical structural and functional brain abnormalities. We investigated a possible association between static postural instability and brain abnormalities and cognitive decline. Methods: The study subjects were 390 community residents without definitive dementia (67 ± 7 years old) and 21 patients with Alzheimer's disease (AD). Brain atrophy was measured by MRI. Results: The mobility of the posturography-measured center of gravity (COG) was positively associated with the temporal horn area (THA; r = 0.260; p < 0.001). Subjects who could not stand on one leg for >40 s (n = 102) showed a significantly larger THA (22 ± 18 vs. 14 ± 11 × 10 -2 cm2; p < 0.001). Multiple regression analysis identified COG path length (β = 0.118; p = 0.032) and one-leg standing time (β = 0.176; p = 0.001) as independent determinants of THA. Mild cognitive impairment (MCI) subjects (n = 61) had a significantly enlarged THA compared to that of normal cognitive subjects (22 ± 16 vs. 16 ± 13 × 10-2 cm2; p = 0.002). AD patients showed a more enlarged THA (78 ± 55 × 10-2 cm2). Subjects with cognitive decline showed a significantly shorter one-leg standing time (normal: 50 ± 17 s; MCI: 42 ± 21 s; AD: 18 ± 20s; p < 0.001). Conclusion: Reduced postural stability was an independent marker of brain atrophy and pathological cognitive decline in the elderly. © 2010 S. Karger AG, Basel.

Smirkin A.,Ehime University | Matsumoto H.,Ehime University | Takahashi H.,Ehime University | Takahashi H.,Ehime Proteo Medicine Research Center | And 10 more authors.
Journal of Cerebral Blood Flow and Metabolism | Year: 2010

In a transient 90-min middle cerebral artery occlusion (MCAO) model of rats, a large ischemic lesion is formed where macrophage-like cells massively accumulate, many of which express a macrophage marker, Iba1, and an oligodendrocyte progenitor cell marker, (NG2) chondroitin sulfate proteoglycan (NG2); therefore, the cells were termed BINCs (Brain Iba1+/NG2 + Cells). A bone marrow transplantation experiment using green-fluorescent protein-transgenic rats showed that BINCs were derived from bone marrow. 5-Fluorouracil (5FU) injection at 2 days post reperfusion (2 dpr) markedly reduced the number of BINCs at 7 dpr, causing enlargement of necrotic volumes and frequent death of the rats. When isolated BINCs were transplanted into 5FU-aggravated ischemic lesion, the volume of the lesion was much reduced. Quantitative real-time RT-PCR showed that BINCs expressed mRNAs encoding bFGF, BMP2, BMP4, BMP7, GDNF, HGF, IGF-1, PDGF-A, and VEGF. In particular, BINCs expressed IGF-1 mRNA at a very high level. Immunohistochemical staining showed that IGF-1-expressing BINCs were found not only in rat but also human ischemic brain lesions. These results suggest that bone marrow-derived BINCs play a beneficial role in ischemic brain lesions, at least in part, through secretion of neuroprotective factors. © 2010 ISCBFM All rights reserved.

Inoue A.,Ehime University | Takahashi H.,Ehime University | Takahashi H.,Ehime Proteo Medicine Research Center | Harada H.,Ehime University | And 9 more authors.
International Journal of Oncology | Year: 2010

Glioblastoma is the most malignant type of primary brain tumor that has been shown to contain a small population of cancer stem cells. Recent studies have suggested that cancer stem cells cause tumor recurrence based on their resistance to radiotherapy and chemotherapy. Although the highly invasive nature of glioblastoma cells is also implicated in the failure of current therapies, it is not clear whether cancer stem cells are involved in invasiveness. In this study, we isolated tumor sphere-forming cells bearing cancer stem-like characteristics such as self-renewal, multipotency, drug-resistibility, and in vivo tumorigenicity, from the human glioblastoma cell line U251, under serum-free neural stem cell culture condition, and assessed their migratory and invasive ability. These cells showed enhanced migratory and invasive ability on both Matrigel and organotypic brain slices compared to parental U251 cells. The expression of matrix metalloproteinase (MMP)-13 was specifically expressed in tumor sphere-forming cells derived from U251 and primary human glioma cells. Knockdown of MMP-13 expression by shRNA suppressed the migration and invasion of these cells. The results suggest that the highly invasive potential of cancer stem cells depends on MMP-13 enzymatic activity, thus MMP-13 might be a potential therapeutic target for glioblastomas.

Loading Ehime Proteo Medicine Research Center collaborators
Loading Ehime Proteo Medicine Research Center collaborators