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T Hosoi

Publications and source records attributed to T Hosoi.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Perspectives of post-genomic medical care in osteoporosis].

Osteoporosis is a multifactorial disease for which genetic and environmental factors are determinants. Recently, polymorphisms of many bone metabolism-related genes have been examined in the association study with bone mineral density and fracture incidence. Some showed significant correlation and others not. In addition, genome-wide QTL analysis was done using genome-wide random markers and showed some hot loci. However, the statistical power of each gene and locus are low and the genes to determine human bone mineral density have not been obtained. The accumulating information of genome science will help understand the pathogenesis of osteoporosis and find the useful ways for the prevention and the treatment of this disease.

Bone Density↗
PubMed2001

[Calcium requirement for the maintenance of bone mass].

The bone mineral density of middle-aged and elderly people is determined by the peak bone mass obtained in the adolescent period and the bone loss in the later stage of life. The rapid bone loss observed in the postmenopausal women is largely explained by estrogen deficiency. On the other hand, aging-dependent decrease of bone mass commonly seen in women and men may be attributed to the change in calcium metabolism. In Japan, the calcium intake would be less than the amount sufficient to keep positive calcium balance and to maintain bone mass.

English Abstract↗
PubMed2001

[Drug therapy for osteoporosis associated with reumatoid arthritis (bisphosphonates)].

Rheumatoid arthritis (RA) causes local and systemic bone loss due the increased bone resorption. Because the bisphosphonates are potent inhibitors for bone resorption, these drugs will be the major regimen to treat RA-associated osteoporosis. In addition, some reports suggest that bisphosphonates may modulate the pathogenesis of RA itself. Further study of bisphosphonates may help improve the treatment of RA.

English Abstract↗
PubMed2001

[Not Available].

Explore the source record for details and available documents.

Journal Article↗
PubMed2000

An estrogen receptor beta isoform that lacks exon 5 has dominant negative activity on both ERalpha and ERbeta.

An alternatively spliced isoform of human estrogen receptor beta (ERbeta) has been isolated from normal human testis mRNA that is coexpressed with wild-type ERbeta by reverse transcription polymerase chain reaction (RT-PCR). Sequence analysis of the ERbeta isoform PCR product reveals the absence of 139 bp that corresponds to the entire exon 5 of wild-type ERbeta, which predicts to lack part of the hormone-binding domain. The transient expression of the exon 5-deleted isoform of ERbeta (ERbetaDelta5) had no effect on basal transactivation activity of an estrogen-responsive luciferase reporter gene. This finding was in contrast to the previous reports that the exon 5-deleted isoform of ERalpha (ERalphaDelta5) acts as a dominant positive receptor, increasing basal gene transactivation itself. Moreover, when ERbetaDelta5 was cotransfected with the wild-type ERalpha or ERbeta, it behaved as a dominant negative receptor that inhibited not only estradiol-stimulated transactivation by ERbeta but also that by ERalpha. The ligand-independent nuclear localization of ERbetaDelta5 was confirmed by immunohistochemistry, and the coexpression of the isoform and the wild-type receptors could be observed in a single cell that transfected with both receptor cDNAs. These findings indicate that ERbetaDelta5 has a potential as a dominant negative receptor that blocks both ERalpha and ERbeta signaling pathways, suggesting some physiological roles of this isoform as an "ER inhibitor".

Alternative Splicing↗
PubMed2000

Impaired estrogen sensitivity in bone by inhibiting both estrogen receptor alpha and beta pathways.

Although it is well established that estrogen deficiency causes osteoporosis among the postmenopausal women, the involvement of estrogen receptor (ER) in its pathogenesis still remains uncertain. In the present study, we have generated rats harboring a dominant negative ERalpha, which inhibits the actions of not only ERalpha but also recently identified ERbeta. Contrary to our expectation, the bone mineral density (BMD) of the resulting transgenic female rats was maintained at the same level with that of the wild-type littermates when sham-operated. In addition, ovariectomy-induced bone loss was observed almost equally in both groups. Strikingly, however, the BMD of the transgenic female rats, after ovariectomized, remained decreased even if 17beta-estradiol (E(2)) was administrated, whereas, in contrast, the decrease of littermate BMD was completely prevented by E(2). Moreover, bone histomorphometrical analysis of ovariectomized transgenic rats revealed that the higher rates of bone turnover still remained after treatment with E(2). These results demonstrate that the prevention from the ovariectomy-induced bone loss by estrogen is mediated by ER pathways and that the maintenance of BMD before ovariectomy might be compensated by other mechanisms distinct from ERalpha and ERbeta pathways.

Animals↗
PubMed2000

Expression of leptin receptors and induction of IL-1beta transcript in glial cells.

To examine the role of leptin in the immune function of the brain, we examined the effect of leptin on interleukin-1beta (IL-1beta) expression in mouse primary cultured glial cells. The expression of leptin receptor isoforms Ob-Ra and Ob-Rb mRNA was detected by RT-PCR analysis of total RNA from primary cultured glial cells. Protein of leptin receptor was also expressed in mouse primary cultured glial cells as evaluated by Western blotting analysis. Leptin increased the expression of IL-1beta mRNA evaluated by RT-PCR. The expression of IL-1beta transcript peaked 2 to 6 h after leptin application. These results indicate that leptin could induce IL-1beta transcript in the brain and that one of the target cells of the leptin-induced IL-1beta transcript may be a glial cell.

Animals↗
PubMed2000

Association of estrogen receptor beta gene polymorphism with bone mineral density.

Chromosomal mapping of the human estrogen receptor beta (ERbeta) gene by fluorescence in situ hybridization (FISH) reveals that ERbeta is located at human chromosome 14, region q23-24.1, where the aberration of DNA copy number in the bone disorders is frequently involved. Then, we investigated the association between dinucleotide (cytosine-adenine; CA) repeat polymorphism located in the flanking region of ERbeta gene and bone mineral density (BMD) in 204 healthy postmenopausal Japanese women. The genotype was classified into "A" through "O" according to the number of the repeats, from 18 to 32. BMD was expressed in Z score (a deviation from the weight-adjusted average BMD of each age using the standard deviation as a unit). When we separate the subjects into two groups bearing at least one I allele (26 CA repeats) and those who did not, the former subjects had significantly higher Z score of L2-4 BMD (mean +/- standard deviation; 0.674 +/- 1.53 vs 0.128 +/- 1.38; P = 0.027). These data suggest that genetic variation at the ERbeta locus may be associated with some determinants for BMD and the possible involvements of this polymorphism in the cause of postmenopausal osteoporosis in Japanese women.

Base Sequence↗
PubMed2000

Possible involvement of the p57(Kip2) gene in bone metabolism.

We previously uncovered that growth stimulation of rat primary osteoblasts by transforming growth factor-beta1 (TGF-beta1) resulted in a dramatic decrease in p57(Kip2), a member of cyclin-dependent kinase (CDK) inhibitors, through the proteasomal degradation pathway (Urano et al., J. Biol. Chem. 274, 12197-12200, 1999). Here we demonstrated that the amount of p57 protein increases markedly, when rat calvarial primary osteoblasts treated with 1,25-dihydroxyvitamin D3 transit from proliferation toward differentiation. Next, we have analyzed the association of four amino acids deletion polymorphism of p57 and bone mineral density (BMD). The p57 genotype was determined in 154 postmenopausal Japanese women. When we separated the subjects into two groups, one having one or two copies of deletion polymorphism and the other without the deletion, the former subjects had higher BMD (Z score of total body, 0.67 +/- 0.93 vs 0. 23 +/- 0.90, mean +/- standard deviation; P = 0.021). Taken together, these findings suggest that the p57 regulated in the osteoblast proliferation and differentiation may play a role in determination of bone mineral density and pathogenesis of osteoporosis.

Aged↗
PubMed2000

Association of bone mineral density with polymorphism of the human calcium-sensing receptor locus.

A strong correlation between bone mass and genetic factors has been shown in twins and family studies. Some of the genes involved would regulate bone metabolism, bone formation, and resorption, all processes that determine bone mass. One candidate genes, calcium-sensing receptor (CASR) in the parathyroid gland, regulates calcium homeostasis by sensing decreases in extracellular calcium level and effecting an increase in secretion of parathyroid hormone (PTH) and calcium (Ca) reabsorption in the kidney. We have investigated a possible association between the CA-repeat polymorphism at the human CASR gene locus and the bone mineral density (BMD) of radial bone in 472 postmenopausal Japanese women. Genotypes were classified into nine groups according to the number of CA repeats present, from 20 to 12. BMD was expressed as the adjusted BMD, which was the body mass index (BMI), and age-adjusted average BMD. The 247 women who had an A3 allele (228 bp, containing 18 repeats of CA) had significantly lower adjusted BMD (mean +/- SD: 0.303 +/- 0.059 versus 0.316 +/- 0.063 g/cm(2); P = 0.0308) than the participants (n = 201) who did not carry an allele of that size. This result suggests that genetic variation at the CASR gene locus is associated with some determinants for BMD in postmenopausal women.

Aged↗
PubMed2000

Trends in the incidence of hip fracture in Japan, 1987-1997: the third nationwide survey.

The third nationwide survey for hip fracture incidence was conducted in 1997 following the first such survey in 1987 and the second in 1992. The purpose of this study was to investigate the trends in the incidence and regional distribution of this disease during 10 years. Of 10271 orthopedic institutions in Japan, 4503 were selected as subjects for the study using the optimum allocation method. Questionnaires concerning new patients with hip fracture were mailed. The replies were obtained from 2930 institutions by the end of December 1998; the response rate was 65.1%. The number of new patients was estimated to be 89900-94900 [mean, 92400; 20100-21400 (20800) men and 69600-73600 (71600) women]. The number of cases in 1997 was about 1.7 times higher than that in the first survey and 1.2 times higher than that in the second survey. The age-specific incidence (per 10000 per year) in men and women in 1997 was 0.30 and 0.13, respectively, for age under 40 years; 0.91 and 0.60, 40-49 years; 2.00 and 2.39, 50-59 years; 5.12 and 9.07, 60-69 years; 17.3 and 40.8, 70-79 years; 57.4 and 147.8, 80-89 years; and 128.9 and 281.0, for age over 90 years. The incidence was increased compared with that of the first survey, and similar to the second survey, excepting that of women aged 80 years or older. Concerning regional differences, hip fracture incidence was relatively low in the eastern area compared to the western area in Japan, which was a trend identical to that in the previous nationwide surveys.

Adult↗
PubMed2000

Association of methylenetetrahydrofolate reductase (MTHFR) polymorphism with bone mineral density in postmenopausal Japanese women.

The pathogenesis of osteoporosis is controlled by genetic and environmental factors. Considering the high prevalence of osteoporosis in homocystinuria, abnormal homocysteine metabolism would contribute to the pathogenesis of osteoporosis. It is known that the polymorphism of methylenetetrahydrofolate reductase (MTHFR), the enzyme catalyzing the reduction of 5, 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, correlates with hyperhomocysteinemia. In this study, we examined the association of this polymorphism with bone mineral density (BMD). BMD was measured by dual-energy X-ray absorptiometry (DXA) in 307 postmenopausal women. MTHFR A/V polymorphism was analyzed using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). We compared BMD, clinical characteristics, and bone metabolic markers among MTHFR groups (AA, AV, VV). The groups did not differ in terms of baseline data. The values of lumbar spine BMD and total body BMD were as follows: lumbar spine: AA, 0.91 +/- 0.18, AV, 0.88 +/- 0.16, VV, 0.84 +/- 0.14 g/cm(2); total body: AA, 0.97 +/- 0.11, AV, 0.96 +/- 0.11, VV, 0.93 +/- 0.09 g/cm(2). In the VV genotype, lumbar spine BMD values were significantly lower than those of the women with the AA genotype (P = 0.016) and total body BMD was significantly lower than those of the women with AA genotype (P = 0.03) and AV genotype (P = 0.04). This is the first report that suggests that the VV genotype of MTHFR is one of the genetic risk factors for low BMD.

Aged↗
PubMed2000

Association of bone mineral density with polymorphism of the human matrix Gla protein locus in elderly women.

The contribution of genetic factors has been implicated in the determination of bone mass in twin and family studies. Some of the genes involved would regulate bone metabolism, bone formation, and resorption, all processes that determine bone mass. One candidate gene matrix Gla protein gene (MGP), has been implicated in the pathogenesis of bone loss through a repression of bone formation. To analyze the genetic background for osteoporosis in elderly women, we have investigated a possible association between the CA repeat polymorphism at the human MGP gene locus and bone mineral density (BMD) of radial bone in 460 elderly Japanese women. Genotypes were classified into six groups according to the number of CA repeats present, from 13 to 18 (alleles A1 through A6). BMD was expressed as the adjusted BMD (ADJBMD), which was the body mass index (BMI)- and age-adjusted average BMD. The 214 women who lacked an A2 allele (212 bp, containing 17 repeats of CA) had significantly lower adjusted BMD than the participants (n = 246) who possessed an allele of that size (mean +/- SD; 0.303 +/- 0.062 vs 0.315 +/- 0.062 g/cm2; P = 0.0382). This result suggests that genetic variation at the MGP locus is associated with some determinants for BMD in elderly women. Therefore, this locus should serve as one of the genetic markers for osteoporosis.

Aged↗
PubMed2000

Identification of a novel polymorphism of estrogen receptor-alpha gene that is associated with calcium excretion in urine.

A novel variation of the estrogen receptor-alpha (ERalpha) gene was identified by polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP). It is one base substitution in codon 325 (CCC [allele M] to CCG [allele m]) in exon 4 of the human ERalpha gene. This substitution did not cause an amino acid change. We categorized 306 unrelated Japanese postmenopausal women into three genotypes: MM, Mm, and mm; the frequency of each genotype was 26.5%, 43.1%, and 30.4%, respectively. Then, the association of this polymorphism with bone mineral density (BMD) of lumbar spine and bone-calcium metabolic markers was studied. There was no significant difference in BMD of the lumbar spine or most of the bone metabolic markers. However, the urinary calcium (Ca) excretion ratio (u-Ca/Cre) corrected by creatinine was significantly lower in the genotype mm group compared with the genotype MM group (MM vs mm, 0.247 +/-0.158 vs 0.200 +/- 0.105; P < 0.05). We examined the relationship of restriction fragment length polymorphisms (RFLPs) (PvuII, XbaI) in intron 1 and the polymorphism in exon 4. The frequency of genotype MM was higher in the genotype PPxx, which was reported to be associated with lower BMD in the same population of Japanese postmenopausal women. The ER polymorphism identified in this study might be related to some biological mechanisms that regulate calcium metabolism.

Bone Density↗
PubMed2000

Association of estrogen receptor beta (ESR2) gene polymorphism with blood pressure.

We investigated the association between a dinucleotide (cytosine-adenine; CA) repeat polymorphism located in the flanking region of the human estrogen receptor beta (ESR2) gene and systemic blood pressure in 187 healthy postmenopausal Japanese women. The genotype was classified as "A" through "O" according to the number of these repeats from 18 to 32. When we separated the subjects into two groups-- bearing at least one "I" allele (26 CA repeats) and those who did not--we found that the former subjects had significantly higher systolic blood pressure than the latter (mean +/- SD, 146.0 +/- 25.0 vs 136.6 +/- 23.4; P = 0.032). These data suggest that genetic variation at the ESR2 locus may be associated with some determinants of blood pressure, and that there is a possible involvement of this polymorphism in causing hypertension in Japanese women.

Aged↗
PubMed2000

Association of bone mineral density with a dinucleotide repeat polymorphism at the calcitonin (CT) locus.

Calcitonin (CT), a calcium-regulating hormone, lowers the calcium level in serum by inhibiting bone resorption. Because CT may play a role in the pathogenesis of osteoporosis, genetic variations in or adjacent to the CT gene may be associated with variations in bone mineral density (BMD). The present study examined the correlation between a dinucleotide (cytosine-adenine; CA) repeat polymorphism at the CT locus and BMD in 311 Japanese postmenopausal women (mean age, 64.1 years). Seven alleles were present in this population; each allele contained 10, 11, 16, 17, 18, 19, or 20 CA repeats. Thus, we designated the respective genotypes A10, A11, A16, A17, A18, A19, and A20. The A10 and A17 alleles were the predominant alleles in the population studied. Z scores (a parameter representing deviation from the age-specific weight-adjusted average BMD) were compared between individuals that possessed one or two alleles of each genotype and those that did not possess the allele. Subjects who possessed one or two A10 alleles had lower BMD Z scores than those who did not (lumbar 2-4 BMD Z score; -0.148 +/- 1.23 vs 0.182 +/- 1.54; P = 0.04). No significant relationships were observed between allelic status and background data or biochemical parameters. The significant association observed between BMD and genetic variations at the CT locus implies that polymorphism at this locus may be a useful marker for the genetic study of osteoporosis.

Aged↗
PubMed2000

Shear bond strengths of polymethyl methacrylate to cast titanium and cobalt-chromium frameworks using five metal primers.

STATEMENT OF PROBLEM: Poor chemical bonding of a denture base resin to cast titanium frameworks often introduces adhesive failure and increases microleakage. PURPOSE: This study examined the shear bond strengths of a denture base resin to cast pure titanium, Ti-6Al-4V, and a cobalt-chromium alloy using various adhesive primers. MATERIAL AND METHODS: Disks (6.0 mm diameter, 2.5 mm thick) were cast of the 3 alloys. The disk surfaces were grit-blasted with 50 microm alumina and treated with 5 different metal primers (Metal Primer II ¿MP]; Cesead Opaque primer ¿OP]; Meta Base ¿MB]; experimental primer ¿EP]; Siloc bonding system ¿SI]). A denture base resin (Palapress Vario) was then applied on the disks with hole-punched sticky tape (bonding area of 5.0 mm) and a Teflon (PTFE, New Age Industries Inc, Willow Grove, Pa.) ring (6.0 mm diameter x 2.0 mm thick). Specimens without primer were also prepared as controls. All specimens were immersed in 37 degrees C water and thermocycled up to 2,000 cycles. Shear bond strength values were determined at a crosshead speed of 0.5 mm/min. Data were statistically analyzed using 3-way ANOVA, followed by 1-way ANOVA and the Scheffé multiple range test. RESULTS: Primers significantly (P <.05) improved shear bond strengths of denture base resin to all metals, among which no significant differences were found. Specimens primed with OP, MP, and EP showed higher bond strengths than did those primed with MB. After thermocycling, the bond strengths of MB and SI decreased substantially; MB showed the least durability (22.8% to 35.5% decrease) among the primers. CONCLUSION: The application of 5 primers significantly improved the shear bond strengths of a denture base resin to cast CP titanium, Ti-6Al-4V, and Co-Cr alloy. OP and MP primers exhibited greater bond strength and durability than did MB and SI.

Analysis of Variance↗