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Biomedical subjects

Takumi Kurabayashi

Publications and source records attributed to Takumi Kurabayashi.

17 recordsLinked to original sources

Randomized trial comparing low-dose hormone replacement therapy and HRT plus 1alpha-OH-vitamin D3 (alfacalcidol) for treatment of postmenopausal bone loss.

We conducted a prospective, randomized, multicenter, open-label 2-year trial with 76 postmenopausal women aged > or =60 years with low (T-score less than -1) lumbar bone mineral density (BMD). The hormone replacement therapy (HRT) group received a low dose of conjugated estrogen (CEE) at a dose of 0.31 mg/day +/- medroxyprogesterone acetate (MPA) 2.5 mg/day. Group HRT/D received the same dose of HRT together with alfacalcidol in a daily dose of 1.0 microg/day. Changes in lumbar BMD measured by dual energy X-ray absorptiometry (DXA) were followed every 6 months for 2 years. The lumbar BMD of group HRT increased 3.37% [95% confidence interval (CI) 1.6%-5.2%], 4.00% (95%CI 1.6%-6.4%), and 2.32% (95%CI -0.7% to 5.3%) at 12, 18, and 24 months, respectively, when the baseline value was taken as 0%. Lumbar BMD of group HRT/D showed a significant increase beyond 6 months. The percent increases for this group at 6, 12, 18, and 24 months were 6.18 (95%CI 1.3%-6.6%), 6.18% (95%CI 3.9%-8.5%), 7.17% (95%CI 4.3%-10.0%), and 8.75% (95%CI 6.0%-11.5%), respectively. In addition, there was a significant difference in the changes of the lumbar BMD between the two groups at 24 months, suggesting that the combination of HRT and alfacalcidol is more effective than HRT alone in terms of the BMD effect. This study is the first prospective trial demonstrating an additive effect of alfacalcidol on lumbar BMD in postmenopausal women receiving low-dose HRT. It suggests that the combination therapy can be considered to be a promising mode of treatment for bone loss after menopause.

Absorptiometry, Photon↗

Association of polymorphisms in the beta2 and beta3 adrenoceptor gene with polycystic ovary syndrome.

OBJECTIVE: To investigate polymorphisms of the beta2 and beta3 adrenoceptor (BAR-2 and BAR-3, respectively) genes associated with insulin-resistant polycystic ovary syndrome (PCOS) pathogenesis. STUDY DESIGN: Fifty-nine infertile Japanese women with PCOS and 97 healthy Japanese controls were studied. Blood metabolites and genomic DNA polymorphisms of BAR-2 (Arg16Gly and Gln27Glu) and BAR-3 (Trp64Arg) were analyzed. RESULTS: The PCOS group had significantly higher weight, body mass index, lipidemia and insulin resistance as compared to the control group. Glu 27 allele frequency in BAR-2 was significantly higher in PCOS patients as compared to the controls (0.07 vs 0.02, chi2 = 5.91, p = 0.02, OR 4.63, 95% CI 1.35-5.93), while Gly 16 allele frequency was only slightly higher in the PCOS group as compared to the controls (0.58 vs. 0.47, chi2 = 3.06, p = 0.08, OR 1.51, 95% CI 0.95-2.40). The Arg 64 allele frequency of BAR-3 was not significantly different between the 2 groups. Women with the Gly/Gly genotype for codon 16 or with either the Gln/Glu or Glu/Glu genotype for the codon 27 polymorphism of BAR-2 had significantly higher insulin resistance than those with the Arg/Arg and Gln/Gln genotypes. CONCLUSION: The polymorphism in codon 27 (Gln27Glu) of BAR-2 is linked to the expression of PCOS in Japanese women.

Adult↗

Prognostic factors for ovulatory response with clomiphene citrate in polycystic ovary syndrome.

OBJECTIVE: To evaluate prospectively the prognostic factors for ovulatory responses following clomiphene citrate (CC) administration in polycystic ovary syndrome (PCOS). STUDY DESIGN: Fifty-nine infertile patients with a diagnosis of PCOS were recruited. Ovulation was induced using 100 mg/day CC administered daily from days 5 to 9 of the cycle. Endocrine and metabolic parameters between responder and non-responder groups were analyzed. RESULTS: For a 75-g fasting glucose load (75-g OGTT), blood glucose levels at 60 and 120 min, the area under the curve (AUC) and blood insulin levels at 120 min in the non-responder group (n=25) were significantly higher than those in the responder group (n=34), although the measurements of fasting blood glucose and insulin were not significantly different between the two groups. In the receiver operating characteristic curves, the most appropriate cutoff point was 120 mg/dl for the blood glucose level at 120 min and 9000 for the blood glucose x insulin level at 120 min. There were no significant differences in the clinical characteristics or in the endocrine and metabolic parameters between conceived (n=9) and non-conceived groups (n=21). CONCLUSION: The levels of blood glucose and blood glucose x insulin at 120 min after 75-g OGTT could be good biochemical markers of CC resistance in PCOS. No predictors of conception following CC therapy were identified by this study.

Administration, Oral↗

Effects of testosterone on cancellous bone, marrow adipocytes, and ovarian phenotype in a young female rat model of polycystic ovary syndrome.

OBJECTIVE: To investigate the effects of testosterone on cancellous bone and marrow adipocytes in a young female rat model of polycystic ovary syndrome (PCOS). DESIGN: Comparative and controlled study. SETTING: University animal research laboratory. PATIENT(S): Fifty-one Sprague-Dawley rats. INTERVENTION(S): The rats were divided into four groups based on the day of testosterone propionate (0.1 mg/weight (g)) injection: no testosterone treatment (control group, C); injected on the ninth day after birth (9D); injected 4 weeks after birth (4W); and injected 8 weeks after birth (8W). About 16 weeks after birth, all animals were killed. MAIN OUTCOME MEASURE(S): Bone mineral density (BMD) and bone and fat histomorphometry for the proximal tibia and serum hormonal parameters were measured. RESULT(S): The ovaries of group 9D showed many cystic follicles without corpora lutea. The BMD of group 9D (0.309 +/- 0.023 g/cm2) was significantly higher than the other groups groups (CONT, 0.262 +/- 0.017; 4W, 0.256 +/- 0.017; 8W, 0.256 +/- 0.022 g/cm2; P < .0001). Based on bone histomorphometry, group 9D had a higher bone volume (BV/TV), lower bone formation (OV/BV, OS/BS, sLS/BS, MAR, BFR/BS), lower bone resorption (ES/BS, Oc.S/BS), and lower rate of longitudinal growth compared to the other groups. Based on fat histomorphometry, group 9D had a lower bone fat volume and number of fat cells in the bone marrow compared to the other groups. On the other hand, groups 4W and 8W showed similar values of bone and fat histomorphometric parameters to group C. CONCLUSION(S): Female rats receiving testosterone within nine days of birth develop polycystic ovaries, high bone volume, low bone turnover, and lower fat content in the bone marrow.

Adipocytes↗

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↗

Advanced gastric cancer and a concomitant pregnancy associated with disseminated intravascular coagulation.

Gastric cancer associated with pregnancy is extremely rare and the prognosis is generally grave. A 31-year-old Japanese women, 41 weeks pregnant, displayed disseminated intravascular coagulation (DIC), although clinical symptoms and diagnostic examinations did not indicate an obstetrical cause. She went into labor spontaneously and vaginally delivered a 3248-g normal female infant, after receiving a blood transfusion. On the day 5 postpartum, a gastroduodenal fiberscope examination indicated advanced gastric cancer. She was also diagnosed with bilateral chronic subdural hematoma and underwent an operation to allow drainage. It was not possible to treat her curatively, so she was treated conservatively for DIC. She died on day 13 postpartum. Necropsy of the iliac bone indicated bone marrow metastasis of adenocarcinoma. This is the first known case of a pregnant woman with DIC occurring as the first manifestation of advanced gastric cancer.

Adenocarcinoma↗

Incarceration of the retroverted uterus at term gestation.

Incarceration of the retroverted uterus is a rare complication of pregnancy and rarely persists until term. The diagnosis is extremely difficult to make and a cesarean section should be performed in such cases. A 33-year-old Japanese woman was admitted at 40 weeks gestation for evaluation of preeclampsia. Vaginal examination revealed that the uterine cervix could hardly be visualized, although the fetal head was impacted in the pelvis. These findings suggested incarceration of the retroverted uterus. Magnetic resonance imaging (MRI) was performed and clarified the exact anatomical relationship and confirmed the diagnosis. She therefore underwent a cesarean section and a male infant weighing 3552 g was delivered with Apgar scores of 9 and 10 at 1 and 5 minutes, respectively. At surgery she was found to have an adhesion between the uterus and the pouch of Douglas. MRI is a useful tool in correctly making the diagnosis of uterine incarceration and facilitates preparation for a cesarean section.

Adult↗

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↗

Endometrial abnormalities in infertile women.

OBJECTIVE: To analyze retrospectively the frequency, long-term prognosis and pregnancy rate in infertile women diagnosed with endometrial hyperplasia or carcinoma by endometrial biopsy. STUDY DESIGN: From 1989 to 2000, endometrial biopsies were performed on 2,573 patients to investigate the cause of infertility. The main outcome measures were frequency, long-term prognosis and pregnancy rate for patients with each type of endometrial abnormality. RESULTS: Twenty-four patients (0.93%) were diagnosed with an endometrial abnormality. Of them, 10 were diagnosed with simple hyperplasia, 7 with complex hyperplasia, 3 with complex hyperplasia with atypia and 4 with endometrial carcinoma. All 4 patients (0.16%) with endometrial carcinoma were infertile as a result of complications arising from polycystic ovary syndrome. Two of them underwent hysterectomies. High-dose medroxyprogesterone acetate therapy combined with assisted reproductive technology resulted in pregnancy in 1 of the 2 patients with endometrial carcinoma. CONCLUSION: Of infertile women, 0.93% have endometrial abnormalities, and those with polycystic ovary syndrome have a high risk of endometrial carcinoma. Assisted reproductive technology combined with high-dose medroxyprogesterone acetate may be effective means of overcoming infertility, allowing women with endometrial carcinoma to readily achieve pregnancy.

Adult↗

Effects of antioxidant treatment in oligozoospermic and asthenozoospermic men.

OBJECTIVE: To evaluate the effect of sairei-to, an herbal medicine, as an antioxidant in oligozoospermia and asthenozoospermia (nonnormozoospermia). STUDY DESIGN: Forty-seven nonnormozoospermic and 16 normozoospermic men were the subjects of this prospective clinical study. After sairei-to (9.0 g/d) was administered daily to the 2 groups for 3 months, sperm parameters, serum hormones and superoxide dismutase (SOD) activity in the serum and the seminal plasma was analyzed. The testicular artery was also assessed. RESULTS: After therapy, serum hormones and SOD activity did not change significantly in either group. Although men with normozoospermia did not undergo a significant change in sperm conditions or testicular artery flow, total sperm concentration (17.1 +/- 20.0 versus 28.7 +/- 35.5 x 10(6)/mL, P = .02) and sperm motility (30.1% +/- 21.6 versus 45.8% +/- 24.4, P < .0001) were significantly increased, and the pulsatility index of the testicular artery (2.03 +/- 0.84 versus 1.64 +/- 0.48, P = .04) was significantly decreased in nonnormozoospermia. CONCLUSION: Treatment with the herbal antioxidant sairei-to improves sperm condition and testicular artery flow in nonnormozoospermia.

Antioxidants↗

[Menopause and bone metabolism].

Hypoestrogenemia in climacterium causes high turnover bone metabolism, relative dominance of bone resorption, and osteopenia. Women have severe bone loss in climacterium. The objective for the prevention of osteoporosis in this period is to detect the high risk women of osteoporosis with bone mineral densitometry or bone metabolic markers and to start the preventive therapy, i. e. food, exercise and drug, as soon as possible. Therefore, menopause is very important period to prevent osteoporosis in future.

English Abstract↗