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Biomedical subjects

Noriko Yoshimura

Publications and source records attributed to Noriko Yoshimura.

28 records · Page 2Linked to original sources

[Effectiveness of measuring bone mineral density in preventing osteoporosis].

A self-administrated questionnaire was performed to clarify the actual circumstances of community-based screening for osteoporosis. The results revealed that only 25 percent of communities performed follow-up of high-risk participants, representing a disappointing result for assessing evidence of the benefits of measuring bone mineral density in preventing osteoporosis. Secondly, a review of the literature was performed to clarify the benefits of measuring bone mineral density in preventing osteoporosis. The review revealed that increased measurements could predict fractures among elderly and peri- and postmenopausal women, and elderly men.

Absorptiometry, Photon↗

Intratumoural mRNA expression of genes from the oestradiol metabolic pathway and clinical and histopathological parameters of breast cancer.

INTRODUCTION: The expression of the oestrogen receptor (ER) is one of the more important clinical parameters of breast cancer. However, the relationship between the ER and its ligand, oestradiol, and the enzymes that synthesise it are not well understood. The expression of mRNA transcripts of members of the oestradiol metabolic and signalling pathways including the ER was studied in detail. METHOD: mRNA transcripts for aromatase (CYP19), 17-beta-hydroxysteroid dehydrogenase I, 17-beta-hydroxysteroid dehydrogenase II, ERalpha, ERbeta, steroid sulfatase (STS), oestradiol sulfotransferase (EST), cyclin D1 (CYCLD1) and ERBB2 were fluorometrically quantified by competitive RT-PCR using an internal standard in 155 breast carcinomas. In addition, the transcripts of CYP19 were analysed for alternative splicing/usage of exon 1 and an alternative poly A tail. RESULTS: A great variability of expression was observed, ranging from 0 to 2376 amol/mg RNA. The highest levels were observed for STS and EST, and the lowest levels (close to zero) were observed for the 17-beta-hydroxysteroid dehydrogenase isoenzymes. The levels of mRNA expression were analysed with respect to clinical and histopathological parameters as well as for disease-free survival. High correlation of the mRNA expression of STS, EST and 17-beta-hydroxysteroid dehydrogenase in the tumours suggested a common regulation, possibly by their common metabolite (oestradiol). Hierarchical clustering analysis in the 155 patients resulted in two main clusters, representing the ERalpha-negative and ERalpha-positive breast cancer cases. The mRNA expression of the oestradiol metabolising enzymes did not follow the expression of the ERalpha in all cases, leading to the formation of several subclasses of tumours. Patients with no expression of CYP19 and patients with high levels of expression of STS had significantly shorter disease-free survival time (P > 0.0005 and P < 0.03, respectively). Expression of ERbeta mRNA was a better prognostic factor than that of ERalpha in this material. CONCLUSION: Our results indicate the importance of CYP19 and the enzymes regulating the oestrone sulfate metabolism as factors of disease-free survival in breast cancer, in addition to the well-known factors ER and ERBB2.

Adult↗

Characteristics and course of bone mineral densities among fast bone losers in a rural Japanese community: the Miyama Study.

The aim of this study was to clarify and compare the temporal course of bone mineral density (BMD) between fast bone losers and normal residents in Miyama Village, a rural Japanese community. BMD was measured over a 10-year period in a cohort study in Miyama Village, Wakayama Prefecture, Japan, to provide information on rate of bone loss in the mature and elderly population. Subjects ( n=400) were selected by sex and age stratum from the full list of residents born in 1910-1949, with 50 men and 50 women in each age decade. Baseline BMD of the lumbar spine and proximal femur was measured using dual energy X-ray absorptiometry in 1990, 1993, 1997 and 2000. In the cohort, 171 men and 189 women completed the follow-up survey performed in 1993. After calculating the rate of bone loss between 1990 and 1993, the greatest tertile from the distribution of bone loss was categorized as fast bone losers, with the remainder considered as normal subjects. Changes in BMD were compared between normal subjects and fast bone losers over the 10-year period. Mean rate of change for BMD at both lumbar spine and femoral neck in fast bone losers recovered to levels similar to those in normal subjects over 7 years of observation. By contrast, BMD at the lumbar spine and femoral neck decreased steeply over the 10-year period in both groups, and mean BMD for fast bone losers was significantly lower than that of normal subjects ( P<0.05). These differences were apparent only at the lumbar spine in both men and women, even after adjusting for age. These results indicate that fast bone loss is a transient phenomenon rather than a fixed status, although individuals who have been categorized as fast bone losers at some stage continue to display low BMD in the lumbar spine.

Aged↗

Unique regulation of expression of human aromatase in the placenta.

The expression of human placental aromatase is transcriptionally regulated through the promoter region of exon 1a (I.1) of the gene. We examined the transcriptional regulation by using human choriocarcinoma-derived JEG-3 cells which also express aromatase mRNA transcribed under the control of the placenta-specific promoter of the exon 1a. Aromatase in the cells was induced by forskolin (cAMP) and phorbol ester (TPA) in both levels of the activity and the mRNA. However, any elements responsible for the cAMP-responsiveness have not yet identified. To identify and characterize the specific elements, CAT assay of the placenta-specific promoter was performed. We reconstructed an 11.5 kb gene structure consisting of exons 1a (I.1), 1b (I.4), 1c (I.3), and 1d (PII) and their proximal promoter regions to mimic the native structure of human aromatase gene and performed a promoter assay by the transient expression of a CAT reporter carrying the mini-gene structure. The construct was transcribed from exon 1a in JEG-3 cells and exon 1b in HepG2 cells to produce tissue-specific mRNAs from the exons 1-CAT hybrid gene, indicating that the mini-gene structure contained promoter regions essential for the tissue-specific expression. However, unexpectedly exons 1-CAT hybrid mRNA in JEG-3 cells was not induced by forskolin. Then, we prepared JEG-3 cells transformed by incorporation of the exons 1-CAT hybrid gene into the chromosomal DNA. The cells stably expressed the hybrid reporter gene which was transcribed from exon 1a and induced by forskolin and TPA. These results suggest that enhancers on the promoter regions of exons 1b, 1c, and 1d might interact with a transcriptional machinery of exon 1a in the induction by forskolin and TPA. Finally, a beta-galactosidase gene connected with the 11.5 kb gene structure was introduced into mouse eggs to produce transgenic mice. The hybrid gene was transcribed from exon 1c in the gonadal tissues of all lines of the transgenic mice in accordance with the tissue-specificity of human aromatase gene, whereas it was not transcribed from exon 1a, but from exons 1b and 1c in the all placentae. The results suggest that the mouse placenta might lack in the transcriptional elements or factors essential for the placenta-specific expression of human aromatase gene.

Animals↗

[Exercise and physical activities for the prevention of osteoporotic fractures: a review of the evidence].

According that osteoporosis is the common condition in an aging society such as in Japan, much progress has been made in understanding the treatment and prevention of osteoporosis. Among potential risk factors, exercise and physical activities have been recognized as lifestyle factors that might influence the risk of osteoporosis and osteoporotic fractures. To assess the relationship between exercises including physical activities and the risk for low bone mass and osteoporosis-related fractures, a literature search over past 13 years was conducted. Accumulating evidence indicates that exercises decrease the risk for hip fractures among middle aged and older men and women. Exercises also help to maintain muscle strength, muscle volume, balance, and joint flexibility, which might prevent falls and fall-related fractures. One randomized controlled trial showed back-stretching exercise reduced the risk for vertebral fractures. The literature search also indicates that high-impact and/or weight-bearing exercise might increase the bone density in the elderly and the peak bone mass among young women, while there is no association between moderate or lower-impact exercise and bone mineral density. Future research should be required to evaluate the types and quantity of physical activity needed for the prevention of osteoporosis.

Aged↗

[Predictive factors for bone loss].

A clear understanding of the pattern and determinants of bone loss in later life is required to the design of preventive strategies against osteoporosis. However, there have been few longitudinal studies of changes in bone mineral density (BMD) in the general population. The objective of this review was to characterise the determinants of bone loss and assess whether they could predict the bone loss in the future. Aging, female sex, perimenopausal period were significantly associated with the rate of bone loss. Anthropometric measurements at baseline were also related significantly to change in bone density. Baseline values and the change of weight, height and BMI were statistically significant predictors for bone loss. By contrast, longitudinal cohort study showed the difference of residence was no longer associated with the bone loss. Furthermore, what the rate of bone change was different from birth cohort was introduced. Thus, the comparison of the data obtained in same strata at the present and 10 years ago, there were significant generation gaps in men in their 60s and in women in their 50s. Concerning bone metabolic markers, some markers were significantly related to the change of lumbar BMD, however, the coefficient for determination for these markers in the prediction of bone loss was only less than 10%. It therefore was concluded that bone metabolic markers might not be sufficiently helpful to predict the change of BMD in individuals. Other factors including new biochemical markers and lifestyle factors should be considered in a clinical diagnosis.

English Abstract↗

The relationship between endogenous estrogen, sex hormone-binding globulin, and bone loss in female residents of a rural Japanese community: the Taiji Study.

The aim of this study was to clarify the relationship between endogenous estrogen, sex hormone-binding globulin (SHBG), and bone loss in pre-, peri-, and postmenopausal female residents of Taiji, a rural Japanese community. From a list of inhabitants aged 40 to 79 years, 200 participants-50 women in each of four age decades-were randomly selected, and baseline bone mineral density (BMD) at the lumbar spine and proximal femur were measured by dual-energy X-ray absorptiometry in 1993. Total estradiol (total E2) and SHBG were measured, and SHBG-unbound E2 (UBE2) was calculated using SHBG and the percent SHBG-unbound fraction ratio. BMD was measured again 3 years later, in 1996. Participants with ovariectomy or hysterectomy were excluded, and the remaining participants were categorized into four groups: premenopausal ( n = 38), perimenopausal ( n = 14), postmenopausal group 1 (5 years or less since menopause; n = 18), and postmenopausal group 2 (6 years or more since menopause; n = 74). The mean value of total E2 was highest in the premenopausal group (49.1 pg/ml), followed by the perimenopausal group (26.4 pg/ml), and the postmenopausal groups (0.83 pg/ml in postmenopausal group 1 and 0.96 pg/ml in postmenopausal group 2). The means for UBE2 showed the same pattern across the groups. After the multiple regression analysis of BMD at follow-up and endogenous estrogens, in premenopausal women, there were no significant associations between BMD at follow-up and serum total E2 and UBE2. In perimenopausal women, however, serum total E2 and UBE2 were significantly correlated with trochanteric BMD at follow-up ( P < 0.05); and in postmenopausal group 2, they were significantly correlated with lumbar spine and Ward's triangle BMD at follow-up ( P < 0.001 at lumbar spine, P < 0.05 at Ward's triangle). Concerning the association between BMD at follow-up and SHBG, in the premenopausal group, serum levels of SHBG were negatively correlated with BMD at the femoral neck ( P < 0.05). In regard to partial regression coefficients for the change rates of BMD over 3 years and serum estrogens and SHBG concentrations, in perimenopausal women, UBE2 was correlated with the change rate of BMD at Ward's triangle ( P < 0.05), and in postmenopausal group 1, serum levels of SHBG were significantly negatively related to change in BMD at the trochanter ( P < 0.01). No other relationships with change in BMD were observed at any sites. These findings suggest that serum E2, UBE2, and SHBG levels differentially predict BMD levels in groups of differing menstrual status. It would, however, be difficult to predict bone loss in middle-aged and elderly Japanese women over a 3-year period using these indices alone.

Adult↗

Incidence of Parkinson disease in Wakayama, Japan.

To estimate an accurate annual incidence of Parkinson disease in Wakayama, a mail survey was conducted in 1998. A questionnaire was delivered to each clinic where Parkinson disease would be potentially diagnosed. The survey was conducted in February 1998 by the Research Committee on Parkinson disease of Wakayama. A total of 792 clinics and 87 hospitals were listed as candidates. Physicians in these 879 medical facilities were asked and instructed to register all newly diagnosed patients with Parkinson disease in 1997 according to the diagnostic criteria proposed by the Japanese Research Committee on Neuro-degenerative Diseases. Of 879 facilities, 873 ones including 81 hospitals replied (response rate: 99%). A total of 229 patients were reported as newly diagnosed cases in 1997. Of these cases, 183 cases were classified as Yahr I to III. The annual incidence rate was 16.9 per 100,000 population (95% confidence interval: 14.5-19.3). Male-to-female ratio was 1:1.4 as a whole, and the dominant age stratum was 70 to 79 years old. When Parkinson disease incidence was observed from northern part of Wakayama to south by district, crude rates (95% CIs) were 15.9(12.9-18.9), 18.1(12.0-24.2), and 19.3(13.4-25.2). After age-adjustment using the Japanese Model Population in 1985, differences of Parkinson disease incidence became attenuated and adjusted rates (95% CIs) turned to 10.8(9.1-12.7), 10.4(8.6-12.2), and 9.9(6.9-12.9), respectively.

Adult↗