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Biomedical subjects

Minoru Irahara

Publications and source records attributed to Minoru Irahara.

At least 19 recordsLinked to original sources
PubMed2007

Effect of bed rest during pregnancy on bone turnover markers in pregnant and postpartum women.

OBJECTIVE: The aims of our study were to evaluate the changes in bone turnover markers during pregnancy and puerperium as a longitudinal study and to elucidate the effect of bed rest during pregnancy on bone turnover markers in pregnant and postpartum women. METHODS: The study population comprised 27 Japanese pregnant women aged 23-40 years. All women were recruited for the longitudinal study from the outpatients clinic of the Department of Obstetrics and Gynecology, Tokushima University Hospital. Concentrations of serum bone-specific alkaline phosphatase (BAP), urinary cross-linked type I collagen N-telopeptides (NTx), serum NTx and urinary C-terminal telopeptide of type I collagen (CTx) were measured at 10, 26, 30 and 36 weeks of pregnancy and at 4 days and 1 month postpartum. In addition, we recruited 15 pregnant women (aged 25-35 years) who were treated by bed rest before 30 weeks of pregnancy for threatened premature delivery and compared bone turnover markers in these women with those in 22 normal pregnant women (aged 22-39 years). Concentrations of serum BAP, serum NTx, urinary NTx and urinary CTx were measured at 30 and 34 weeks of pregnancy and at 4 days and 1 month postpartum. RESULTS: In the longitudinal study, serum BAP concentration at 1 month postpartum was significantly higher than that at any stage of pregnancy and that at 4 days postpartum. Urinary concentration of NTx increased gradually during pregnancy and showed a peak at 36 weeks of pregnancy, followed by a decrease in the postpartum period. Serum NTx concentration and urinary CTx concentration showed the same patterns of change as that of urinary NTx concentration. In the comparison study, urinary concentrations of NTx and CTx at 30 and 34 weeks of pregnancy in women with bed rest were significantly (p<0.0001 and p<0.001, respectively) higher than those in normal pregnant women. Serum NTx concentration at 34 weeks of pregnancy in women with bed rest was also significantly (p=0.0029) higher than that in normal pregnant women. Serum BAP concentration at 34 weeks of pregnancy in women with bed rest was significantly (p=0.0038) higher than that in normal pregnant women, and these high levels were maintained during puerperium. Serum BAP concentration at 34 weeks of pregnancy was significantly correlated with duration of bed rest (r=0.767, p=0.0041). CONCLUSION: Immobilization due to bed rest during pregnancy is associated with increases in bone turnover markers in pregnant and postpartum women. Concentrations of bone resorption markers increased rapidly at the start of bed rest, while the concentration of a bone formation marker gradually increased toward puerperium.

Adult↗
PubMed2006

Changes in serum cytokine concentrations during the menopausal transition.

OBJECTIVE: The purpose of the present study was to clarify the changes in serum concentrations of 17 cytokines in healthy women during the menopausal transition by using a multiplexed cytokine assay and to clarify the associations of these cytokines with serum estradiol concentration. METHODS: Sixteen premenopausal, 54 perimenopausal and 52 postmenopausal women were enrolled in this study. Seventeen cytokines in serum samples were measured simultaneously using a Bio-Plex human cytokine 17-Plex assay. RESULTS: Serum IL-6 concentration showed a weak positive correlation with age (r=0.196, p<0.05). Postmenopausal women for whom less than 5 years had passed since menopause showed significant (p<0.05) increase in serum concentrations of IL-2, GM-CSF and G-CSF, while serum IL-4 concentration was significantly (p<0.05) increased in postmenopausal women for whom more than 5 years had passed since menopause. Serum estradiol concentration showed a significant negative correlation with serum IL-6 concentration and weak negative correlations with serum concentrations of IL-2, IL-8 and GM-CSF. CONCLUSION: We were able to simultaneously measure the levels of 17 cytokines using a highly sensitive cytokine assay, and we found that the changes in serum cytokine concentrations during the menopausal transition differed. We also found that serum IL-6 concentration during the menopausal transition was negatively correlated with serum estradiol concentration.

Adult↗
PubMed2006

Reduction of perifollicular arterial blood flow resistance after hCG administration is a good indicator of the recovery of mature oocytes in ART treatment.

PURPOSE: To demonstrate our hypothesis that a correlation exists between oocyte maturity and a decrease in intraovarian blood flow resistance in assisted reproductive technology (ART) treatment cycles, oocyte maturity and total antioxidant status (TAOS) in follicular fluid was examined. METHODS: A total of 59 cycles involving 51 infertile patients undergoing ART treatment in our hospital were recruited in this study. The ART cycles were divided into two groups: deeply decreased (DD) group and not-deeply decreased (NDD) group, according to the pulsatility index (PI) values for perifollicular arterial blood flow before and after hCG administration. The PI values that showed a decrease in their PI after hCG administration of 10% or more were defined "deeply decreased" and showed a decrease of less than 10% were considered "not-deeply decreased." The recovery rates of mature and immature oocytes and TAOS in follicular fluid were compared between the two groups. RESULTS: Mature and immature oocyte recovery rates in the DD group (62.5% and 17.2%) were significantly higher and lower, respectively, than those in the NDD group (41.7% and 38.3%, p < 0.05). The TAOS (1.55 +/- 0.44 mmol/L) of the DD group was significantly lower than that in the NDD group (1.68 +/- 0.47 mmol/L, p < 0.05). CONCLUSIONS: The decrease in intraovarian arterial blood flow resistance measured after hCG administration may be a good indicator of retrieving mature oocyte.

Blood Flow Velocity↗
PubMed2006

Change in serum undercarboxylated osteocalcin concentration in bilaterally oophorectomized women.

OBJECTIVE: We investigated changes in serum undercarboxylated osteocalcin (ucOC) concentrations, bone turnover markers and spine bone mineral density (BMD) in women who had undergone bilateral oophorectomy during the premenopausal period. METHODS: The study population comprised 141 bilaterally oophorectomized and 32 premenopausal women for a cross-sectional study. The longitudinal study consisted of 21 bilaterally oophorectomized women. Serum ucOC concentration, serum concentrations of intact osteocalcin (OC) and bone-specific alkaline phosphatase (BAP) as bone formation markers, urine N-telopeptide (NTx) concentration as a bone resorption marker and serum parathyroid hormone (PTH) concentration were measured. RESULTS: Serum concentration of ucOC in women at 1 month after bilateral oophorectomy was significantly (p<0.05) higher than that in premenopausal women and the high level was sustained after surgical menopause. On the other hand, serum OC concentration at 1 month after surgical menopause was not different from that in premenopausal women. In the longitudinal study, serum ucOC concentration at 1 month after surgical menopause was significantly (p<0.05) increased compared to that before bilateral oophorectomy, while serum OC concentrations before and at 1 month after surgical menopause were not significantly different. CONCLUSION: The results of this study showed that serum ucOC concentration rapidly increases in women after bilateral oophorectomy and that change in serum ucOC concentration after surgical menopause is different from change in serum OC concentration.

Adult↗
PubMed2006

Association of interleukin-8 with hot flashes in premenopausal, perimenopausal, and postmenopausal women and bilateral oophorectomized women.

OBJECTIVE: The purpose of this study was to identify serum cytokine concentrations in premenopausal, perimenopausal, and postmenopausal women and bilateral oophorectomized women with hot flashes. METHODS: Serum concentrations of 17 cytokines were simultaneously measured using a multiplexed human cytokine assay in 129 premenopausal, perimenopausal, and postmenopausal women and 50 bilateral oophorectomized women. RESULTS: Serum IL-8 concentrations in midlife women and bilateral oophorectomized women with severe hot flashes were significantly higher than the concentrations in women without hot flashes and women with mild and moderate hot flashes. Serum macrophage inflammatory protein-1beta concentration in women with severe hot flashes was significantly higher than those in women without hot flashes and women with mild and moderate hot flashes. CONCLUSION: Serum IL-8 concentrations in premenopausal, perimenopausal, and postmenopausal women and bilateral oophorectomized women with hot flashes were significantly higher than those in women without hot flashes. IL-8 may be associated with peripheral vasodilation in women with hot flashes.

Adult↗
PubMed2006

Myeloid-related protein-8/14 is associated with proinflammatory cytokines in cervical mucus.

Myeloid-related protein-8 (MRP-8), MRP-14, and MRP-8/14 are found in a variety of inflammatory conditions and are involved in the host defense system. The objective of this study was to determine the concentrations of MRP-8, MRP-14, and MRP-8/14 in human cervical mucus and the associations between MRP-8/14 and proinflammatory cytokines. Samples of cervical mucus were obtained using a syringe from sexually active women (n=97) during the preovulatory phase. Samples from seven women were obtained using a swab placed in the cervical canal during the proliferative, preovulatory, and luteal phases. Concentrations of MRP-8, MRP-14, MRP-8/14, IL-1alpha, IL-6, IL-8, and granulocyte elastase were measured using an ELISA. The mean levels of MRP-8, MRP-14, and MRP-8/14 in cervical mucus were 1.87, 0.46, and 23.90microg/ml, respectively. The concentration of MRP-8/14 showed positive correlations with concentrations of IL-1alpha (p<0.0001), IL-8 (p<0.0001), and granulocyte elastase (p<0.0001). However, there were no significant differences in MRP-8/14 levels in the cervical mucus of each patient during the menstrual cycle. MRP-8/14 was mainly detected in human cervical mucus and showed a positive correlation with proinflammatory cytokines. The MRP-8/14 level in cervical mucus may be useful as a marker of inflammation of the uterine cervix.

Adult↗
PubMed2006

Intraovarian arterial blood flow resistance in oligomenorrheal infertile women.

PURPOSE: Intraovarian arterial blood flows before and after follicular rupture in ovulation induced cycles were examined by transvaginal color flow Doppler imaging. The changes observed in the intraovarian arterial resistance before and after ovulation in relation to the regularity of menstruation and several other parameters were analyzed. METHODS: In a prospective study, 22 patients undergoing infertility treatment in our center were recruited. Patients were divided into two subgroups, according to their menstrual regularity (regular menstrual group and oligomenorrheal group) and 42 cycles were studied. All patients received the same FSH low-dose stimulation treatment. The relationship between the post and preovulatory arterial pulsatility indexes (PI) was analyzed. Cycles that showed a decrease in their PI after ovulation of 10% or more were considered "profoundly decreased cycles." Cycles from the same patients without ovulatory stimulation (natural cycles) were used as control. RESULTS: In the regular menstrual group the rate of profoundly decreased cycles during FSH stimulation was 63.2%, which was similar to the rate observed in natural cycles. In the oligomenorrheal group the rate of profoundly decreased cycles during natural cycles was 14.3%, but in FSH ovulation induction cycles this rate was significantly increased (47.6%, p < 0.05). In addition, the pregnancy rate per cycle in the oligomenorrheal group was significantly higher than that in the regular menstrual group (p = 0.03). CONCLUSIONS: Oligomenorrheal patients presented a higher rate in the decrease of their PI values after FSH stimulation, which is essential to achieve pregnancy. This elevated rate of reduction implies that oligomenorrheal patients have increased incidence of disturbance in their ovulatory process when compared to normal cycling patients. Thus, ovulation induction with FSH, in oligomenorrheal patients resulted in a higher pregnancy rate in this group.

Adult↗
PubMed2006

Essential role of IkappaB kinase alpha in thymic organogenesis required for the establishment of self-tolerance.

IkappaB kinase (IKK) alpha exhibits diverse biological activities through protein kinase-dependent and -independent functions, the former mediated predominantly through a noncanonical NF-kappaB activation pathway. The in vivo function of IKKalpha, however, still remains elusive. Because a natural strain of mice with mutant NF-kappaB-inducing kinase (NIK) manifests autoimmunity as a result of disorganized thymic structure with abnormal expression of Rel proteins in the thymic stroma, we speculated that the NIK-IKKalpha axis might constitute an essential step in the thymic organogenesis that is required for the establishment of self-tolerance. An autoimmune disease phenotype was induced in athymic nude mice by grafting embryonic thymus from IKKalpha-deficient mice. The thymic microenvironment that caused autoimmunity in an IKKalpha-dependent manner was associated with defective processing of NF-kappaB2, resulting in the impaired development of thymic epithelial cells. Thus, our results demonstrate a novel function for IKKalpha in thymic organogenesis for the establishment of central tolerance that depends on its protein kinase activity in cooperation with NIK.

Animals↗
PubMed2006

The signaling pathways linking to lysophosphatidic acid-promoted meiotic maturation in mice.

The signaling pathways linking to lysophosphatidic acid-promoted meiotic maturation in mice were studied. When mouse oocyte-cumulus cells complexes were cultured with 10(-5) M lysophosphatidic acid (the LPA group), the rate of oocyte nuclear maturation was significantly increased. Additions of pertussis toxin, genistein, U73122, Ro320432, PD98059 or SB203580 significantly suppressed the increase in lysophosphatidic acid-stimulated nuclear maturation rate. These results suggested that Gi/o-coupled lysophosphatidic acid receptors activate phosphatidylinositol-specific phospholipase C, and result in ERK and MAP kinase activation, which is triggered by diacylglycerol-dependent protein kinase C. When intracellular cAMP concentrations of oocytes in the LPA and control groups were measured using the acetylation assay, the intracellular cAMP concentration of an oocyte in the LPA group was significantly lower than the control oocyte (0.117+/-0.04 fmol/oocyte vs. 0.176+/-0.036 fmol/oocyte, p<0.05). In conclusion, our results suggested that lysophosphatidic acid stimulates phospholipase C through a Gi-protein linked receptor on the surface of mouse cumulus cells and stimulates both extracellular signal-regulated kinase and p38 mitogen-activated kinase, resulting in the closure or loose of gap junctions between cumulus cells and the oocyte. The resultant early decrease of oocyte cAMP levels may promote nuclear maturation of mouse oocytes in vitro.

Animals↗
PubMed2006

Differences in insulin sensitivity in pregnant women with overweight and gestational diabetes mellitus.

AIM: The purpose of the present study was to investigate changes in insulin sensitivity using homeostasis model assessment (HOMA) and the quantitative insulin sensitivity check index (QUICKI) in normal-weight and overweight women with normal glucose tolerance (NGT) and gestational diabetes mellitus (GDM) during pregnancy. METHODS: Ninety-two pregnant women in the first trimester, 202 in the second trimester and 154 in the third trimester were enrolled in this study. Fasting plasma glucose and insulin concentrations were measured in all women in the first, second and third trimesters. HOMA indices (insulin resistance, HOMA-IR and beta-cell function, HOMA-beta) and QUICKI were calculated from fasting glucose and insulin concentrations. RESULTS: HOMA-IR values in overweight women with NGT and in women with GDM were significantly (p < 0.01) higher than those in normal-weight women with NGT. HOMA-IR in women with GDM increased significantly (p < 0.05) during pregnancy, but HOMA-IR values in normal-weight and overweight women with NGT did not change significantly with advance of gestation. QUICKI values in overweight women with NGT and in women with GDM were also significantly (p < 0.01) lower than those in normal-weight women with NGT, and QUICKI in women with GDM decreased significantly (p < 0.05) during pregnancy. HOMA-beta in normal-weight women with NGT increased significantly (p < 0.01) during pregnancy. CONCLUSION: We showed that insulin sensitivities determined by using HOMA-IR and QUICKI in overweight women with NGT and women with GDM were lower than those in normal-weight women with NGT, and that insulin sensitivity in women with GDM declined with advance of gestation.

Adult↗
PubMed2006

Effect of vitamin K2 treatment on carboxylation of osteocalcin in early postmenopausal women.

OBJECTIVE: We examined the serum level of undercarboxylated osteocalcin (uc OC), which is a sensitive marker of vitamin K status, and levels of bone turnover markers in early postmenopausal women receiving vitamin K2 treatment with or without vitamin D3. METHODS: Thirty-four postmenopausal women with a mean age of 53 years whose bone mineral density (BMD) was less than 0.809 g/cm2 (osteopenia and osteoporosis) were treated with vitamin K2 or with a combination of vitamin K2 and vitamin D3. Seventeen women received daily oral administration of 45 mg vitamin K2 and 17 women received daily oral administration of 45 mg vitamin K2 plus 0.75 microg 1alpha-hydroxyvitamin D3. Serum levels of uc OC, intact osteocalcin (OC) and bone alkaline phosphatase (BAP), urinary deoxypyridinoline (DPD) levels and BMD at the lumbar spine were measured before and at 1 and 2 years after the start of treatment. RESULTS: Serum uc OC levels in women treated with vitamin K2 alone and with both vitamin K2 and vitamin D3 decreased significantly (p < 0.05). Serum levels of intact OC and BAP in women treated with vitamin K2 did not show significant changes, while those in women who received the combined treatment decreased significantly (p < 0.05). On the other hand, urinary DPD level in women treated with vitamin K2 did not change, while that in women who received the combined treatment tended to decrease (p < 0.1). CONCLUSION: Serum uc OC levels in early postmenopausal women who received vitamin K2 decreased due to carboxylation of uc OC. Combined treatment with vitamin K2 and vitamin D3 may be effective for sustaining BMD in early postmenopausal women whose bone turnovers are highly activated.

Alkaline Phosphatase↗
PubMed2006

Comparison and problems of measured values of LH, FSH, and PRL among measurement systems.

Several measurement systems are used for LH, FSH, and PRL in Japan, but the comparison of the measured values is difficult in some cases. In this study, we compared the measured values of 3 types of measurement systems widely used in Japan, SPAC-S, ARCHITECT, and Centaur, in females with a normal menstrual cycle and with various ovulatory disorders. Variant LH was discriminated by the criterion, SPAC-S LH/ARCHITECT LH ratio <0.5. Excluding the variant LH, the correlation of the measured LH values among the measurement systems was high, 0.94-0.99, and the value measured by ARCHITECT LH and Centaur LH was slightly higher than that measured by SPAC-S LH. As for FSH, the correlation was also high, 0.94-1.00, and the value measured by ARCHITECT FSH and Centaur FSH was slightly lower than that measured by SPAC-S FSH. The important judgment criterion of polycystic ovary syndrome (PCOS), a high level of LH relative to FSH, has been set to 1.0 or higher LH/FSH using SPAC-S. When the regression line of the LH/FSH ratio among the measurement systems was investigated, it can be said that 1.25 or higher by ARCHITECT and 1.40 or higher by Centaur are appropriate for the judgment criteria of a high level of LH relative to FSH. As for PRL, the correlation was high, 0.96-0.99, but the value showed large differences among the systems. For the diagnosis of hyperprolactinemia, the higher limit of the normal range may be 15 ng/mL for SPAC-S, 30 ng/mL for ARCHITECT, and 24 ng/mL for Centaur.

Adolescent↗
PubMed2006

Clinical trials for drug approval: a pilot study of the view of doctors at Tokushima University Hospital.

The development of new and useful pharmaceutical drugs is essential in order to improve the quality of drug therapeutics. Clinical trials play a central role in drug development. Over time, the clinical trial infrastructure has improved and is now integrating the contribution of clinical research coordinators (CRC). Nevertheless, the attitude of doctors towards clinical trials still favors conventional/historical methodologies. In the present study, we explored the view of doctors towards clinical trials for drug development, in order to improve communication among participants, sponsors, and investigators.A questionnaire was designed for this pilot study. The questionnaire included general attitudes, difficult points, the benefit of doctors in participating as investigators, special attention requirements, and the expected role of CRC in clinical trials for drug approval. In addition, the appropriate use of the outpatient clinic was examined. The questionnaire was provided to doctors in each department of Tokushima University Hospital in 2000 and 2004. Because of the small number of subjects included in this pilot study, no statistical analysis is presented. A total of 89 (81%) and 62 (56%) doctors among 110 responded to the survey in 2000 and 2004, respectively. Inquiries about the familiarity of the physicians with clinical trials for drug approval revealed that 84% in 2000 and 66% in 2004 were aware of such trials. The attitude towards participating as investigators in the clinical trials was favorable, with a response of 66% in 2000 and 58% in 2004. Patients' refusal and the informed consent process were considered difficult areas by many doctors. Expected roles of CRC included activities based on the nurse's specialty. Although many doctors agreed to take care of the study participants separately from the clinical practice, they lacked the time to do so. In spite of the doctors' workload reduction by introduction of the CRC concept, their views regarding clinical trials for drug approval remain conventional. Further refinement in the support process by CRC should be considered in our hospital, and the views of the doctors should be investigated in a larger study, in order to promote clinical trials for drug approval in Japan.

Attitude of Health Personnel↗
PubMed2005

Serum estrogen level after hormone replacement therapy and body mass index in postmenopausal and bilaterally ovariectomized women.

OBJECTIVE: The objective of this study was to determine the relationships of serum estrogen levels after hormone replacement therapy (HRT) every other day and every day with body mass index (BMI) in postmenopausal and bilaterally ovariectomized women. METHODS: Eighty-six postmenopausal and 51 bilaterally ovariectomized women who had been suffering from vasomotor symptoms such as hot flush or atrophy of the vagina were randomly treated with HRT every other day or every day. Seventy-four patients received oral administration of 0.625 mg conjugated equine estrogen (CEE) and 2.5 mg medroxyprogesterone acetate (MPA) every other day, and 63 patients received oral administration of 0.625 mg CEE and 2.5 mg MPA every day as conventional HRT. RESULTS: Eighty-four postmenopausal and 50 bilaterally ovariectomized women completed this study. Serum estradiol levels after HRT every day in postmenopausal and bilaterally ovariectomized women were significantly (P <0.05 and <0.01, respectively) correlated with BMI, while those after HRT every other day were not correlated with BMI. The differences between estradiol levels after 12 months of treatment and initial estradiol levels were also significantly (P <0.01) correlated with BMI in both postmenopausal and bilaterally ovariectomized women who received HRT every day but not in women who received HRT every other day. Serum estrone level after HRT every day and the difference between estrone level after 12 months of treatment and initial estrone level were significantly (P <0.05 and <0.01, respectively) correlated with BMI only in bilaterally ovariectomized women. CONCLUSION: Serum estradiol levels after HRT every day increase more in overweight women than in non-overweight postmenopausal and bilaterally ovariectomized women. The results of the present study regarding the relationship between serum estradiol levels after HRT and BMI should be useful for selecting dosages of drugs to be used in HRT.

Administration, Oral↗
PubMed2005

Intrauterine hemodynamic change in TTTS: the alterations in the inferior vena cava waveform in the donor fetus.

BACKGROUND: Significant hemodynamic changes are commonly observed in both fetuses in twin-twin transfusion syndrome. METHODS AND RESULTS: We describe two donor fetus cases in twin-twin transfusion syndrome associated with abnormal waveform patterns in the inferior vena cava after therapeutic amnioreduction. Subsequent echocardiographic examinations demonstrated progressive deterioration of the cardiac function in the recipient fetuses. CONCLUSIONS: We suggest that alterations in the inferior vena cava waveform in the donor fetuses may contribute to the accurate prediction of deterioration in fetal circulation after amnioreduction.

Adult↗