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Biomedical subjects

Takayuki Hosoi

Publications and source records attributed to Takayuki Hosoi.

At least 19 recordsLinked to original sources
PubMed2007

(--)-epigallocatechin gallate enhances prostaglandin F2alpha-induced VEGF synthesis via upregulating SAPK/JNK activation in osteoblasts.

Catechin, one of the major flavonoids presented in plants such as tea, reportedly suppresses bone resorption. We previously reported that prostaglandin F(2alpha) (PGF(2alpha)) stimulates the synthesis of vascular endothelial growth factor (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase in osteoblast-like MC3T3-E1 cells. To clarify the mechanism of catechin effect on osteoblasts, we investigated the effect of (--)-epigallocatechin gallate (EGCG), one of the major green tea flavonoids, on the VEGF synthesis by PGF(2alpha) in MC3T3-E1 cells. The PGF(2alpha)-induced VEGF synthesis was significantly enhanced by EGCG. The amplifying effect of EGCG was dose dependent between 10 and 100 microM. EGCG did not affect the PGF(2alpha)-induced phosphorylation of p44/p42 MAP kinase. SB203580, a specific inhibitor of p38 MAP kinase, and SP600125, a specific inhibitor of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), reduced the PGF(2alpha)-induced VEGF synthesis. EGCG markedly enhanced the phosphorylation of SAPK/JNK induced by PGF(2alpha) without affecting the PGF(2alpha)-induced phosphorylation of p38 MAP kinase. SP600125 markedly reduced the amplification by EGCG of the SAPK/JNK phosphorylation. In addition, the PGF(2alpha)-induced phosphorylation of c-Jun was amplified by EGCG. These results strongly suggest that EGCG upregulate PGF(2alpha)-stimulated VEGF synthesis resulting from amplifying activation of SAPK/JNK in osteoblasts.

Animals↗
PubMed2007

Polymorphisms in pro- and anti-inflammatory cytokine genes and susceptibility to atherosclerosis: a pathological study of 1503 consecutive autopsy cases.

Atherosclerosis is a chronic inflammatory disease in the intima of the arterial wall, where cytokines play a crucial role in the pathogenesis of this disease. However, the question of whether or not genetic variations in the cytokine genes could influence the development of atherosclerosis has been poorly investigated. We investigated the relationship of nine common single-nucleotide polymorphisms (SNPs) in tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-10, IL-4 and transforming growth factor (TGF)-beta1 with the atherosclerotic severity in 10 different arteries based on 1503 consecutive autopsies of elderly Japanese subjects registered in the Japanese SNPs for geriatric research (JG-SNP) study. The -1031C allele of TNF-alpha was a significant protective factor for atherogenesis in the carotid, femoral and intracranial arteries [odds ratio (OR): 0.72, 0.73 and 0.70, respectively]. The -511T of IL-1beta and the +29T of TGF-beta1 were significant risk factors for atherogenesis in the subclavian and intracranial arteries (OR: 1.35 and 1.48, respectively). In contrast, conventional risk factors for atherogenesis, such as hypertension and diabetes mellitus, conferred independent risks for almost all arteries. Functional SNPs in TNF-alpha, IL-1beta and TGF-beta1 genes play a role in atherogenesis, although their influences are less pronounced than those of conventional risk factors and appear to be limited to specific arteries in the Japanese elderly.

Aged↗
PubMed2007

Q89R polymorphism in the LDL receptor-related protein 5 gene is associated with spinal osteoarthritis in postmenopausal Japanese women.

STUDY DESIGN: An association study investigating the genetic etiology for spinal osteoarthritis. OBJECTIVE: To determine the association of single-nucleotide polymorphism (SNP) causing an amino-acid change (Q89R) in the low-density lipoprotein receptor-related protein 5 (LRP5) coding region with spinal osteoarthritis. SUMMARY OF BACKGROUND DATA: Wnt/beta-catenin signaling pathway regulates bone density through a Wnt coreceptor LRP5. This pathway is also involved in cartilage development and homeostasis, suggesting that genetic variation in LRP5 gene may affect the pathogenesis of cartilage-related diseases, such as osteoarthritis. METHODS: We evaluated the presence of osteophytes, endplate sclerosis, and narrowing of disc spaces in 357 Japanese postmenopausal women. Missense coding SNP for Q89R of LRP5 gene was determined using TaqMan polymerase chain reaction (PCR) method. RESULTS: We found that subjects without the R allele (QQ; n = 321) had a significantly lower osteophyte formation score than did subjects bearing at least one R allele (QR + RR; n = 36) (7.80 vs. 10.89, P = 0.0019 by analysis of covariance). CONCLUSIONS: We suggest that a genetic variation at the LRP5 gene locus is associated with spinal osteoarthritis, in line with the involvement of the LRP5 gene in the bone and cartilage metabolism.

Aged↗
PubMed2006

A functional single nucleotide polymorphism in the vitamin-K-dependent gamma-glutamyl carboxylase gene (Arg325Gln) is associated with bone mineral density in elderly Japanese women.

The vitamin-K-dependent gamma-glutamyl carboxylase (GGCX) carboxylates vitamin-K-dependent proteins including bone Gla protein (osteocalcin) and matrix Gla protein, which play important roles in bone metabolism. Therefore, GGCX polymorphism might explain in part individual susceptibility to osteoporosis. In the present study, polymorphisms in the exons of this gene were screened in Japanese elderly women and a non-synonymous single nucleotide polymorphisms (SNP) were found; c.8762 G>A; (Arg325Gln). When the kinetic parameters of GGCX325-Gln and GGCX325-Arg were compared in vitro, Vmax/Km was significantly higher for GGCX325-Gln (944.4+/-9.21 pmol/30 min/mg/mM FLEEL) than for GGCX325-Arg (671.9+10.79 pmol/30 min/mg/mM FLEEL) (p=0.018). Then, association study of this polymorphism with forearm bone mineral density (BMD) of Japanese postmenopausal women (n=500, age 73.6+/-5.74) was conducted. As a result, the body mass index (BMI)-adjusted Z score in the subpopulation older than 75 years (n=207) was higher in those with 325-Gln (0.650+/-0.883, mean+/-SD) than those with 325-Arg/Gln or 325-Arg (0.133+/-0.650) (p=0.0383). This is the first report to demonstrate the different activities of GGCX between the common genotypes and their association with BMD.

Aged↗
PubMed2006

Postprandial reactive hypoglycemia in an oldest-old patient effectively treated with low-dose acarbose.

We recently encountered a 96-year-old Japanese woman who suffered from frequent hypoglycemia. Endocrinological and imaging data eliminated the possibility of insulinoma, whereas oral glucose tolerance testing revealed impaired glucose tolerance and subsequent reactive hypoglycemia. The patterns between insulin or C-peptide secretions and glucose excursions demonstrated that the discrepancy occurred in the late postprandial stage. Administration of small doses of alpha-glucosidase inhibitor (alpha-GI) dramatically inhibited the rapid rise and subsequent precipitous fall of plasma glucose. Reactive hypoglycemia may be one of the important cause of hypoglycemia in the elderly, and alpha-GI could effectively and safely prevent such hypoglycemic attacks in those patients.

Acarbose↗
PubMed2006

A case of type 2 diabetes mellitus in an elderly patient with rapid attenuation of insulin secretion that resembled fulminant type 1 DM but with incomplete beta cell damage.

We recently encountered a 66-year-old Japanese man who had suffered from acute hyperglycemia following flu-like symptoms during treatment of type 2 diabetes. Despite significantly increased plasma glucose levels, HbA1c was only slightly elevated. The possibility of autoimmune type 1 diabetes was excluded because of negative islet-related autoantibodies. Serum levels of pancreatic exocrine enzymes, amylase, lipase, and elastase-l were elevated. However, the insulin-secreting function of his islets was not severely damaged. This case is particularly notable for two reasons. First, it showed a fulminant type 1 diabetes-like clinical onset, but his beta cell function was fairly preserved. Second, it developed during the treatment of type 2 diabetes in an elderly patient.

Aged↗
PubMed2006

The sample size required for intervention studies on fracture prevention can be decreased by using a bone resorption marker in the inclusion criteria: prospective study of a subset of the Nagano Cohort, on behalf of the Adequate Treatment of Osteoporosis (A-TOP) Research Group.

In drug developments for osteoporosis, large-scale and longterm fracture prevention studies have been required. We investigated whether or not it was possible to reduce the sample size and observation period under new selection criteria for an osteoporotic fracture-prevention study. A Poisson regression model was used to identify independent risks for incident vertebral fracture in 515 postmenopausal women who had had no intervention for osteoporosis; this group was a subset of Nagano Cohort participants. The total observation period for this group was 2,577 person-years, and a total of 146 new vertebral fractures were observed. Risk assessment for incident vertebral fracture among numerical covariates revealed that the following items showed significant independent risks for incident fractures; namely, baseline age (hazard ratio [HR]; 1.84; 95% confidence interval (CI), 1.44-2.35; P < 0.001), number of preexisting vertebral fractures (HR, 1.28; 95% CI, 1.17-1.40; P < 0.001), baseline lumbar bone mineral density (LBMD) (HR, 0.79; 95% CI, 0.71-0.88; P < 0.001), and urinary excretion of deoxypyridinoline (DPD) (HR, 1.18; 95% CI, 1.03-1.35; P = 0.016). Because the initial urinary excretion of DPD was found to be a risk for incident vertebral fracture, in addition to the conventional risks, we assessed whether or not the sample size or observation period could be reduced by the incorporation of the urinary excretion of DPD into the selection criteria of a fracture-prevention study. The assessment of sample size was calculated, using the log rank test, at a two-tailed significance level of 5% and with a power of 80%. When osteoporotic patients with preexisting fracture were selected (conventional criteria), the 3-year probability of vertebral fracture was estimated as 14.3% in the present population. On the other hand, the new vertebral fracture rate during 3 years in the osteoporotic patients with preexisting fracture plus high urinary DPD (HR, above 1.0); (new selection criteria) was estimated as 23.2%. When the HR between test drug and placebo was changed from 0.4 to 0.8, the required sample size for any level of HR showed a 40% reduction for the new selection criteria compared to the conventional criteria. Therefore, the addition of urinary DPD level to the selection criteria is useful to reduce sample size in an osteoporosis fracture-prevention study.

Aged↗
PubMed2006

[Bone and bone related biochemical examinations. Bone and collagen related metabolites. Structure and metabolisms of collagen].

Collagens are the most abundant proteins in mammals. They are the major structural proteins in bone as well as other organs. The synthesis of collagens is regulated by numerous growth factors, cytokines and hormones. The higher structure of collagen is derived from the series of biosynthesis including its characteristic primary amino acid structure and post-translational modifications. The degradation products of collagen have been utilized as markers for bone turnover.

Collagen↗
PubMed2006

[Vitamin-D analogues for osteoporosis].

Vitamin Ds are among the drugs for osteoporosis with the longest history. Recently, novel properties are being found in vitamin Ds and new analogues are under development. Especially, ED-71 developed in Japan has advantageous actions in the osteoporosis treatment and will be used clinically soon.

Bone Density↗
PubMed2006

[Prevention of osteoporosis by foods and dietary supplements. Vitamin K and bone metabolism].

Many reports have indicated the significant correlation between low vitamin K intakes and the increased prevalence of osteoporotic fractures. The role of vitamin K in bone metabolism is assumed to be mediated by carboxylation of vitamin-K-dependent proteins. In addition, recent researches suggest the novel action of vitamin K(2) via nuclear receptors. The role of vitamin K in the prevention as well as the treatment of osteoporosis should be more emphasized.

Bone and Bones↗
PubMed2005

Distinct association of gene polymorphisms of estrogen receptor and vitamin D receptor with lumbar spondylosis in post-menopausal women.

Contribution of genetic backgrounds to the etiology of lumbar spondylosis has been suggested by epidemiological studies. This study was designed to determine the association of restriction fragment length polymorphisms (RFLPs) of estrogen receptor (ER), vitamin D receptor (VDR), parathyroid hormone (PTH) and interleukin-1beta (IL-1beta) genes with the radiological severity of lumbar spondylosis at the disk level from L1/2 to L5/S1 in Japanese post-menopausal women. ER and VDR RFLP haplotypes were associated with the severity of spondylosis in the upper levels (L1/2 and L2/3) more than in the lower levels. Association of ER genotype was more pronounced in the group younger than average than in the older group, while that of VDR genotype was more significant in the older group. Neither PTH nor IL1-beta RFLP was associated with the severity at any levels in either stratified group. We thus conclude that ER and VDR genes may contribute to lumbar spondylosis in a distinct manner: estrogen sensitivity influences the severity in the early phase after menopause while vitamin D plays an important role at older ages when the contribution of estrogen loss is weaker.

Female↗
PubMed2005

The Val158Met polymorphism of the catechol-O-methyltransferase gene is associated with the PSA-progression-free survival in prostate cancer patients treated with estramustine phosphate.

OBJECTIVE: The aim of our study is to find out the good responders for estramustine phosphate (EMP) therapy in patients with prostate cancer. We have focused on the metabolism of EMP and studied the association between a functional single-nucleotide polymorphism in the catechol-O-methyltransferase gene (Val158Met of COMT) and PSA-progression-free survival in Japanese patients with prostate cancer treated by EMP. METHODS: Seventy-two Japanese patients with previously untreated prostate cancer who were found to be eligible for low-dose EMP therapy were enrolled in the study. Genotyping of the Val158Met polymorphism of COMT was conducted by both the polymerase chain reaction-based restriction fragment length polymorphism method and TaqMan assay. RESULTS: Patients with the Val/Val genotype of COMT had a significantly higher PSA-progression-free rate as compared to those with the Val/Met or Met/Met genotype (p=0.027). The adjusted hazard ratio of biochemical PSA failure for the Val158Met genotype of COMT was 2.164 (95% CI, 1.111 to 5.525). CONCLUSIONS: The Val158Met polymorphism of COMT is associated with the PSA-progression-free rate of EMP-treated patients in prostate cancer.

Aged↗
PubMed2005

Multi-detector row CT imaging of vertebral microstructure for evaluation of fracture risk.

UNLABELLED: We applied MDCT for in vivo evaluation of the microarchitecture of human vertebrae. Microstructure parameters, such as structure model index, Euler's number, and bone volume fraction, revealed higher relative risk for prevalent vertebral fracture than did BMD obtained by DXA. Thus, microstructure analysis by MDCT, together with simultaneously obtained volumetric BMD values, is useful for clinical assessment of fracture risk. INTRODUCTION: BMD measurement by DXA alone has limitations in predicting fracture, and methods for clinical assessment of bone quality, such as microstructure, are awaited. This study was undertaken to examine the applicability of multidetector row CT (MDCT) for in vivo evaluation of trabecular microstructure. MATERIALS AND METHODS: Optimal conditions for MDCT scanning were determined at a spatial resolution of 250 x 250 x 500 mum, using muCT data of excised human vertebra specimens as a reference. We analyzed the trabecular microstructure of the vertebrae of 82 postmenopausal women (55-76 years old), including 39 women with and 43 without a recent vertebral fracture. RESULTS: Microstructure indices obtained by MDCT scanning revealed higher relative risk for prevalent vertebral fracture (OR: 16.0 for structure model index, 13.6 for bone volume fraction, and 13.1 for Euler's number) than did spinal BMD obtained by DXA (OR: 4.8). MDCT could also provide volumetric BMD data, which had higher diagnostic value (OR: 12.7) than did DXA. CONCLUSION: Vertebral microarchitecture can be visualized by MDCT, and microstructure parameters obtained by MDCT, together with volumetric BMD, provided better diagnostic performance for assessing fracture risk than DXA measurement.

Absorptiometry, Photon↗
PubMed2005

Association of single nucleotide polymorphisms in the promoter region of the pro-opiomelanocortin gene (POMC) with low bone mineral density in adult women.

Among multiple factors influencing osteoporosis, genetic variations involved in bone-mineral metabolism can affect risks predisposing to the disease onset. Here, we studied single-nucleotide polymorphisms (SNPs) in the pro-opiomelanocortin (POMC) gene for possible association with bone mineral density (BMD) among 384 adult Japanese women and observed significant correlation between adjusted BMD and three SNPs in the promoter region (r>0.14, p<0.01). The most significant correlation was observed for -2353G/A (r=-0.16, p=0.002); homozygous carriers of the major (G) allele had the highest BMD (0.405+/-0.054 g/cm2) while heterozygous carriers were intermediate (0.390+/-0.053 g/cm2) and homozygous A-allele carriers had the lowest BMDs (0.369+/-0.048 g/cm2). Although no association was detected between these SNPs and body weight or body mass index (BMI), significant association was detected between the -2313A/C genotype and plasma total cholesterol level (r=-0.12, p=0.019). We propose that POMC is among the likely susceptibility genes for osteoporosis and may also be involved in dyslipidemia.

Adult↗
PubMed2005

Epidemiology of hip fracture in Japan: incidence and risk factors.

Hip fracture is the most serious complication of osteoporosis and has been recognized as a major public health problem. The prevention of hip fractures is an high-priority issue because of the rapid increase of the number of elderly people in Japan. The General Research Committee for the Prevention and Treatment of Osteoporosis in Silver Health Science Researches sponsored by the Ministry of Health and Welfare (Director, Hajime Orimo) first undertook a nationwide survey of femoral neck fracture in 1987. This nationwide survey has been continued every 5 years, in 1992, 1997, and 2002. The total number of new cases was nearly 120,000 in the latest survey, and has been rising in every survey. Total number of new cases was about 1.4 times the baseline 1987 figures in 1992, 1.7 times in 1997, and 2.2 times in 2002. The total number of new female patients was about three times higher than that of new male patients, a finding identical to those of the previous surveys. The incidences of hip fracture (per 10,000) according to sex and age was increased in both men and women, particularly among individuals 80 years old or over. The Epidemiological Research Group on Osteoporosis, Ministry of Health and Welfare (Chairman; Hajime Orimo) undertook a nation-wide case-control study to clarify the risk factors for hip fractures among Japanese in 1994. Cases of hip fracture in people aged 65-89 were selected from 21 hospitals in seven areas of Japan. Two sex- and age-matched controls were selected from the same residential area for each case using resident registration lists. During this 1-year survey, 249 cases of hip fractures (43 men and 206 women) were reported. The following risk factors for hip fractures were identified using multivariate analysis: past history of stroke with hemiplegia, sleep disturbance, sleeping in a Western-style bed, and drinking more than 3 cups of coffee daily.

Age Distribution↗