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Biomedical subjects

Masatoshi Tomita

Publications and source records attributed to Masatoshi Tomita.

8 recordsLinked to original sources

Effect of vitamin D receptor and estrogen receptor gene polymorphism on the relationship between dietary calcium and bone mineral density in Japanese women.

In a longitudinal analysis of the results of bone mineral density (BMD) screenings conducted in local communities, we examined the effect of lifestyle improvements on BMD and investigated the influence of allelic variations of the vitamin D receptor ( VDR) and estrogen receptor ( ER) genes. The subjects were 484 women (age, 24-80 years) who underwent BMD screenings at least twice between 1994 and 2002. We conducted BMD measurements of the lumbar spine by dual-energy X-ray absorptiometry and performed a simple questionnaire survey of lifestyle factors. Women receiving pharmacotherapy, or those with bone fractures, were excluded, leaving 338 women eligible for the study. They were retrospectively divided into three groups: (i) premenopause, women who were at least 5 years preceding menopause; (ii) perimenopause, women who were within 5 years before or after menopause; and (iii) postmenopause, women who were at least 5 years past menopause. There was no correlation at all between improvements of lifestyle factors (i.e., calcium intake from dairy products and time spent walking) and fluctuations in lumbar-spine BMD after 1, 3, or 5 years in the pre-, peri-, and postmenopausal groups. For women in the postmenopausal group, the PP genotype for the ER gene correlated with a significantly higher initial BMD than those with the Pp and pp genotypes ( P = 0.04). After 3 years, presence of the TT genotype of Taq I of VDR gene polymorphism exhibited positive correlations ( r = 0.29, P = 0.03) with the improvements in calcium intake and in lumbar spine BMD for the perimenopausal group, whereas the Tt genotype showed negative correlations ( r = -0.48, P = 0.04). After 1, 3, and 5 years, presence of the Tt genotype showed a tendency toward a negative correlation with the increases in calcium intake and in lumbar spine BMD for the pre- and perimenopausal groups, although almost of these were not significantly different. In this study, we could not prove a positive correlation between the improvement of lifestyle and the fluctuation of BMD within a 5-year timeframe, although the polymorphisms within the VDR gene may have some influence.

Adult↗

Association of vitamin D and estrogen receptor gene polymorphism with the effects of longterm hormone replacement therapy on bone mineral density.

We longitudinally studied whether vitamin D receptor (VDR) and estrogen receptor (ER) gene polymorphisms in Japanese women influenced the effect of longterm hormone replacement therapy (HRT) on bone mineral density (BMD) in the lumbar spine. The 81 subjects were aged 40 to 64 years (mean +/- SEM, 49.5 +/- 0.6 years), and had received sequential or continuous HRT regimens, including 0.625 mg of conjugated equine estrogen and 2.5 to 5 mg of medroxy-progesterone acetate, for at least 3 years. Genomic DNA was extracted from blood cells, and analyzed for restriction fragment length polymorphism, using the restriction endonucleases Taq I, Apa I, and Fok I for VDR, and Pvu II and Xba I for ER. At 1 year, subjects with a Taq I genotype of TT (i.e., site absent) showed a significantly greater increase in BMD with treatment (DeltaBMD) than subjects with the Tt genotype (2.6 +/- 0.5% vs -0.8 +/- 1.4%; P = 0.016). A small difference between genotypes remained at 2 years (3.8 +/- 0.6% vs 0.8 +/- 1.6%; P = 0.069), but no significant difference between genotypes was seen at 3 years. In multiple regression analyses, DeltaBMD at 1 year was significantly affected by VDR- Taq I, Apa I, and ER- Pvu II genotypes and by age at treatment initiation, although at 3 years or more, DeltaBMD was significantly affected only by age. These results indicate that Taq I VDR gene polymorphism predicted the effect on lumbar BMD for the first year of HRT in Japanese women, and that the differences in BMD versus the polymorphism disappeared if the treatment was continued for over 2 years.

Bone Density↗

Effect of haemodialysis on the pharmacokinetics of antineoplastic drugs.

Since renal failure itself creates an immunocompromised situation, malignant tumours in haemodialysis patients are increasing due to the prolonged lifespan of these patients. In treating these patients with anticancer agents, dosage reduction is often recommended to avoid adverse drug reactions, particularly for drugs with extensive renal excretion. On the other hand, if an anticancer drug is removed significantly by haemodialysis, dosage increase would be required to ensure adequate therapeutic efficacy. We address in this review the clinical pharmacokinetic aspects of antineoplastic therapy, and the application of pharmacokinetic principles to the adjustment of dosage of anticancer agents in haemodialysis patients.

Antineoplastic Agents↗

Effects of uncoupling protein 1 and beta3-adrenergic receptor gene polymorphisms on body size and serum lipid concentrations in Japanese women.

OBJECTIVES: To investigate whether the -3826 A-G point mutation of the uncoupling protein 1 (UCP1) gene and the Trp64Arg mutation of the beta3-adrenergic receptor (beta3-AR) gene are associated with increased susceptibility to weight gain and hyperlipidemia in postmenopausal women. METHODS: We genotyped 312 Japanese women for UCP1 and beta3-AR gene polymorphisms, and investigated their effects on anthropometrical parameters, serum lipid concentrations, and their changes after 4 years. RESULTS: Although body mass index (BMI), serum triglyceride, total cholesterol, and low-density lipoprotein levels were significantly higher and high-density lipoprotein levels significantly lower in postmenopausal (n=182) than in premenopausal (n=99) women, there was no significant difference in these parameters between carriers and non-carriers of the G allele in the postmenopausal women. In the premenopausal women, BMI and the 4-year change in body weight (BW) of carriers of the G allele were significantly higher than those of non-carriers of the G allele (P=0.022 and 0.048, respectively). In the postmenopausal women, the 4-year change in the level of serum triglyceride of carriers of the G allele was significantly higher (P=0.049), and the change of high-density lipoprotein was significantly lower (P=0.020) than those of non-carriers of the G allele. The beta3-AR polymorphism showed no apparent affect on these parameters. CONCLUSIONS: The -3826 A-G polymorphism of the UCP1 gene is associated with an increase in BW of premenopausal women and with the 4-year changes in serum triglyceride and high-density lipoprotein levels in postmenopausal women.

Adult↗

Resuspension: decadal monitoring time series of the anthropogenic radioactivity deposition in Japan.

Monthly atmospheric depositions of (90)Sr and (137)Cs have been observed at the Meteorological Research Institute (MRI), Tsukuba, Japan. This study reports temporal trends and levels of (90)Sr and (137)Cs depositions in the 1990s. Although the current (90)Sr and (137)Cs concentrations declined dramatically, they have been found continuously in the deposition samples throughout the 1990s. During this period, the annual (90)Sr ((137)Cs) deposits at MRI ranged from 70-180 (140-350) mBq/m(2)/year. With a sufficiently long time series, the decreasing trend of the deposition evidently differs from the past stratospheric fallout; it is far slower. Thus, reservoirs other than the stratosphere provide small amounts of (90)Sr and (137)Cs to the atmosphere. A simple calculation clearly refutes the significance of the ocean as a potential source of airborne anthropogenic radioactivity. We will demonstrate that these radionuclides in the deposited materials originate from resuspension processes (soil dust suspension processes). The temporal trends of the time series monitoring reveal differences from those in the UNSCEAR Report 2000, which were predicted by a model that disregarded resuspension. The specific activity of (90)Sr ((137)Cs) in the annual depositions exhibited a 10-year (20-year) half-life. Those data were comparable with values reported in the literature for the half-residence time (HRT) of (90)Sr and (137)Cs in Japanese surface soils. They were also comparable to those calculated from nationwide data of (90)Sr and (137)Cs concentrations in the surface soil (0-10 cm) obtained from the Ministry of Education, Culture, Sports, Science and Technology Environmental Radiation Database (the MEXT Database). Regarding the activity ratio of (137)Cs/(90)Sr, the Japanese nationwide surface soil data collected during the 1990s in the MEXT Database (median: 5.3, n = 584) did not accord with that in the deposition samples (average: 2.1, n = 82) at MRI. This supports our previous hypothesis that Asian dust may transport a large fraction of anthropogenic radioactivity into the Japanese atmosphere. We need to study the fate of long-lived anthropogenic radioactivity dispersed in the environment over greater spatial and temporal scales.

Air Pollutants, Radioactive↗

Paclitaxel and carboplatin combination chemotherapy in a hemodialysis patient with advanced ovarian cancer.

BACKGROUND: There are few reports on the pharmacokinetics of paclitaxel combined with carboplatin or on the dose schedule of carboplatin in combination use during hemodialysis in patients with ovarian cancer. CASE: A 40-year-old woman with chronic renal failure on hemodialysis who had FIGO stage III ovarian cancer was treated with debulking surgery and carboplatin/paclitaxel combination chemotherapy. Paclitaxal was administered at 150 mg/m(2) as a 3-h intravenous infusion followed by a 30-min infusion of carboplatin on a nondialysis day. The carboplatin dose was chosen to produce a target area under the concentration/time curve (AUC) of 5.0 microg-min/ml according to the Calvert formula. The pharmacokinetic study showed that the AUCs of free platinum and paclitaxel were 4.43 microg-min/ml and 15.9 microg-h/ml, respectively. Dosing of carboplatin based on the AUC produced an acceptable degree of thrombocytopenia and neutropenia. After the completion of five cycles of the combination chemotherapy, the tumor showed complete response, and the patient remained disease free for 8 months. CONCLUSION: Paclitaxel and carboplatin combination chemotherapy can be given to patients undergoing hemodialysis, with dialysis performed 16 h after the administration and with a dose adjustment of carboplatin to reach a target AUC. In these conditions, tumor response can be obtained.

Adult↗