PubMed Health⌕ Search

Biomedical subjects

F Hirahara

Publications and source records attributed to F Hirahara.

At least 19 recordsLinked to original sources
PubMed2006

Paradoxical discrepancy between the serum level and the placental intensity of PP5/TFPI-2 in preeclampsia and/or intrauterine growth restriction: possible interaction and correlation with glypican-3 hold the key.

There have been controversies whether maternal serum placental protein 5 (PP5)/tissue factor pathway inhibitor (TFPI)-2 is increased in the patients with preeclampsia and/or intrauterine growth restriction (IUGR). Here, we have estimated the serum PP5/TFPI-2 in these patients by a sandwich enzyme-linked immunosorbent assay with a newly developed monoclonal antibody, coupled with placental immunohistochemical studies of their placentae with semiquantitative scoring. Serum PP5/TFPI-2 level was significantly elevated only in the patients with preeclampsia alone (p=0.033), while PP5/TFPI-2 was detected significantly less intensely in the placentae of the same patients (p=0.035) in immunohistochemistry, as compared to Controls. A proteoglycan present on the placental villous surface, glypican-3, showed the same pattern of staining as PP5/TFPI-2, and there was a positive correlation (C.I.=0.506, p=0.004) between the immunohistochemical scores for these. Further experiments using HepG2 cells transfected with PP5/TFPI-2 suggested that glypican-3 could anchor PP5/TFPI-2 on the placental villi. A possibility that a decrease in glypican-3 in the placenta increases the outflow of PP5/TFPI-2, which in turn increases its serum level, was proposed. Preeclampsia and IUGR, often regarded to have the same pathological basis in common, showed distinct distributions of PP5/TFPI-2, which could be a clue to elucidate the pathogenesis of preeclampsia and IUGR.

Adult↗
PubMed2005

The effect of gamma-tocopherol administration on alpha-tocopherol levels and metabolism in humans.

BACKGROUND: The bioavailability of gamma-tocopherol and metabolites of vitamin E after gamma-tocopherol administration is not well understood. We investigated the effect of gamma-tocopherol administration on the levels and metabolism of alpha- and gamma-tocopherol in healthy volunteers. METHODS: We measured two metabolites of vitamin E (2,5,7,8-tetramethyl-2-(2'-carboxyethyl)-6-hydroxychroman (alpha-CEHC) and 2,7,8-trimethyl-2-(2'-carboxyethyl)-6-hydroxychroman (gamma-CEHC)) in plasma and urine by high-performance liquid chromatography with electrochemical detection (HPLC-ECD) during administration of gamma-tocopherol. Two groups of volunteers were enrolled. The gamma-tocopherol group received two gamma-tocopherol capsules (each containing 186.4 mg of gamma-tocopherol and 5 mg of alpha-tocopherol) for 28 days, while the control group received d-alpha-tocopherol at 5 mg/day, which was the same dose as that given to the gamma-tocopherol group. Blood and urine samples were obtained on days 0, 14, 28, 35, 42, and 56 after the initiation of gamma-tocopherol administration. RESULTS: The plasma gamma-tocopherol concentration increased markedly during administration of gamma-tocopherol and the plasma gamma-CEHC concentration increased along with that of gamma-tocopherol. The plasma alpha-tocopherol concentration decreased significantly during gamma-tocopherol administration. The plasma concentration of alpha-CEHC decreased significantly and urinary excretion of alpha-CEHC tended to increase in the gamma-tocopherol group. Urinary sodium secretion was significantly increased at 1 week after the cessation of gamma-tocopherol administration, but there was no significant difference of urine volume between the two groups. CONCLUSION: Metabolism of alpha-tocopherol is accelerated and the plasma alpha-tocopherol concentration is decreased during gamma-tocopherol administration.

Adult↗
PubMed2001

Transplacental genetic immunization after intravenous delivery of plasmid DNA to pregnant mice.

A number of factors influence the development of tolerance, including the nature, concentration, and mode of Ag presentation to the immune system, as well as the age of the host. The studies were conducted to determine whether immunizing pregnant mice with liposome-encapsulated DNA vaccines had an effect on the immune status of their offspring. Two different plasmids (encoding Ags from HIV-1 and influenza virus) were administered i.v. to pregnant mice. We examined the uptake of plasmid DNA by the fetuses until the 21st postcoital day, but little such transfer occurred in early pregnancy. At 9.5 days postconception with cationic liposomes, injected plasmid was present in the tissues of the fetus, consistent with transplacental transfer. When the offspring of vaccinated dams were immunized with DNA vaccine, they mounted stronger Ag-specific immune responses than controls, and were protected against challenge by homologous influenza virus after vaccination. Moreover, such immune responses were strong in the offspring of mothers injected with DNA plasmid 9.5 days after coitus. These results suggest that DNA-vaccinated mothers confer the Ag-specific immunity to their progeny.

AIDS Vaccines↗
PubMed2001

Cyclophosphamide and 5-fluorouracil act synergistically in ovarian clear cell adenocarcinoma cells.

Chemosensitivity to the drugs plays a crucial role in the treatment of ovarian cancer. In this study, we evaluate the cytotoxicity of chemotherapeutic agents in six ovarian cancer cell lines; four clear cell adenocarcinoma and two serous papillary adenocarcinoma, using seven single drugs and seven sets of drug combinations with tetrazolium-based semiautomated colorimetric (MTT) assay. The drug concentration which produced 50% growth inhibition (IC50) of cisplatin was within clinically achievable range in five cell lines. The area under the curve (AUC) at IC50 of cyclophosphamide was below the clinically achievable AUC in two serous papillary cell lines. Paclitaxel was more effective in clear cells than serous papillary cells. The intensification of cytotoxicity was observed in the combinations of paclitaxel and cisplatin, and cyclophosphamide and cisplatin or 5-fluorouracil irrespective of histopathological characteristics of the original tumor. Our results indicate that ovarian cancer cell lines respond to chemotherapeutic agents heterogeneously depending upon histopathological features, indicating individualized regimens may improve survival in ovarian cancer patients.

Adenocarcinoma, Clear Cell↗
PubMed2001

Expression of serine proteinase inhibitor PP5/TFPI-2/MSPI decreases the invasive potential of human choriocarcinoma cells in vitro and in vivo.

OBJECTIVE: PP5/TFPI-2/MSPI is a Kunitz-type serine proteinase inhibitor with broad inhibitory spectra, abundantly produced by placenta and detected in the blood of pregnant women. Expression of PP5/TFPI-2/MSPI is exclusively detected in syncytiotrophoblasts of placenta, but is barely detectable in choriocarcinoma cells, a trophoblast-derived malignant tumor. Chromosome 7, in which the PP5/TFPI-2/MSPI gene is localized, is frequently lost in various types of tumors. We attempted to elucidate the relation between PP5/TFPI-2/MSPI expression and the malignant properties of choriocarcinoma cells. METHODS: Human choriocarcinoma cells, JAR, were transfected with either a human PP5/TFPI-2/MSPI expression vector or an empty vector, and stable clones were obtained. Messenger RNA expression, protein secretion/localization, growth rate, and plating efficiency were evaluated. In vitro migration and invasive activity were determined by transwell chamber experiments. In vivo tumor growth was evaluated by the subcutaneous injection of cells to nude mice and followed by histological examination. RESULTS: Expression of mRNA and protein of PP5/TFPI-2/MSPI were confirmed, and a high producing clone and a low producing clone were chosen for further analysis. The majority of secreted PP5/TFPI-2/MSPI protein was revealed to associate with the extracellular matrix. Expression of PP5/TFPI-2/MSPI did not affect the growth and migration of the tumor cells, but enhanced their plating efficiency. Its expression significantly inhibited invasion through the Matrigel. Invasive growth into the subcutaneous muscle layer was not evident in the nude mouse tumors of the PP5/TFPI-2/MSPI-expressing cells. CONCLUSION: PP5/TFPI-2/MSPI-expressing choriocarcinoma cells showed suppressed potential of invasion in vitro and in vivo. It is suggested that loss or suppression of PP5/TFPI-2/MSPI expression may result in the acquisition of invasiveness in choriocarcinoma cells.

Animals↗
PubMed2001

A longitudinal study of disturbances of the hypothalamic-pituitary-adrenal axis in women with progestin-negative functional hypothalamic amenorrhea.

OBJECTIVE: To longitudinally evaluate disturbances of the hypothalamic-pituitary-adrenal (HPA) axis in women with secondary progestin-negative hypothalamic amenorrhea. DESIGN: Retrospective cohort study. SETTING: Yokohama City University, Yokohama, Japan. PATIENT(S): Twenty-four women with progestin-negative hypothalamic amenorrhea. INTERVENTION(S): Administration of human corticotropin-releasing hormone (hCRH) and treatment with a combination of estrogen and progesterone. MAIN OUTCOME MEASURE(S): Plasma cortisol and ACTH concentrations and period required for recovery from amenorrhea. RESULT(S): Plasma ACTH concentrations 30 and 60 minutes after injection of hCRH and the percent maximum increment (%Cmax) of ACTH were significantly lower in the amenorrheic patients compared with the control group patients. The basal cortisol was significantly higher, and the %Cmax of cortisol was significantly lower. In the 16 patients who recovered from amenorrhea, there was a significant positive correlation (Y = 1.93X-10.8, r = 0.629) between the basal cortisol concentrations (X) and the period for recovery (Y). The serum E2 gradually increased before recovery, and this E2 increase was preceded by changes in the plasma cortisol concentration and the %Cmax values of cortisol and ACTH. CONCLUSION(S): The CRH test might be useful for evaluating the roles of stress and for estimating the period required for recovery in hypothalamic amenorrhea.

Adrenocorticotropic Hormone↗
PubMed2001

Release property of progesterone from a mixed-base suppository consisting of Witepsol W35 and Witepsol E85.

The mechanism of drug release from progesterone suppositories that consist of two types of hard fat (Witepsol W35 and Witepsol E85) was investigated. The strength, the thermodynamic characteristics, the surface structures, the drug release property, methylene blue penetration into suppositories, and change of surface structure after the dissolution test were employed for detecting characteristics of progesterone suppositories. The formulation with a mixing ratio of Witepsol W35 and Witepsol E85 at a 1:1 ratio showed the maximum strength value. The peak temperature of the suppositories showed a tendency to increase with increases in the ratio of Witepsol E85. The maximum height of the profiles measured with laser microscopy, from 20.8 microm to 29.2 microm, reached a maximum after 3 h of the dissolution test. When the suppositories were immersed in pH 7.4 phosphate buffer containing 0.5% methylene blue at 37 degrees C, the penetrating area increased with time. The weight of the suppositories also increased with time. According to these findings, it was suggested that the release of drug from a mixed type of suppository containing progesterone was via the matrix and pores.

Adjuvants, Pharmaceutic↗
PubMed2001

Treatment of fetal congenital complete heart block with maternal administration of beta-sympathomimetics (terbutaline): a case report.

We report a case of fetal congenital heart block treated with maternal administration of beta-sympathomimetics. The case was diagnosed as fetal complete heart block associated with maternal anti-Ro/SS-A antibody at 22 weeks of gestation. By fetal sonography, the ventricular rate was revealed to be 60 beats/min and mild cardiomegaly was shown. We initiated maternal administration of a sympathomimetic, specifically terbutaline, to prevent fetal heart failure. An increase in the fetal ventricular rate and an improvement in cardiac function were both achieved during the treatment. A viable infant was delivered by an elective cesarean section without complications at term. Maternal administration of the beta-adrenergic agent terbutaline is suggested to be effective for improving fetal congenital heart block in order to prevent heart failure in utero.

Adult↗
PubMed2001

Immortalized gonadotropin-releasing hormone neurons (GT1-7 cells) exhibit synchronous bursts of action potentials.

Although it has been assumed that synchronized firing of gonadotropin-releasing hormone (GnRH) neurons is necessary for pulsatile GnRH secretion, there is no clear evidence for this. In the present study we simultaneously recorded spontaneous action potentials from multiple cells. Immortalized GnRH neurons (GT1-7 cells) were cultured on a multi-electrode dish (MED) and action potentials recorded by an extracellular recording method. One to two weeks after the beginning of culture, spontaneous action potentials appeared, exhibiting bursts composed of 5-10 action potentials. Burst activity was intermittent and periodic with mean burst intervals of 13.3 s. Furthermore, burst activity was recorded almost simultaneously from several micro-electrodes, suggesting that electrical activities of GT1-7 cells were synchronized with each other. Periodic bursts were completely and reversibly blocked by 1-5 microM tetrodotoxin, indicating that voltage-dependent Na(+) channels are involved in their generation. gamma-Aminobutyric acid (GABA) given at a 10-microM concentration shortened inter-burst intervals, whereas 10 microM bicuculline lengthened them. Finally, the gap junctional blockers n-octyl alcohol (1 mM) and carbenoxolone (100 microM) reversibly blocked periodic burst activity. The present study provides direct evidence that the electrical activity of GT1-7 cells exhibits synchronous and periodic bursts composed of action potentials. In addition, endogenous GABA is involved in GT1-7 cells in determining burst frequency. Although the precise mechanism of synchronized burst activities needs to be clarified, gap junctional communications among GT1-7 cells are at least partially involved.

1-Octanol↗
PubMed2000

Effects of naloxone on the serum luteinizing hormone level and the number of Fos-positive gonadotropin-releasing hormone neurons in immature female rats.

To examine developmental changes in the number of gonadotropin-releasing hormone (GnRH) neurons activated by an opioid receptor antagonist in female rats, blood sampling and double-labeled immunocytochemistry for Fos and GnRH were performed after the injection of naloxone (NAL) in immature (postnatal d16 and d30) and mature female rats. Three age groups of rats were perfused with 4% paraformaldehyde-PB 90 min after the subcutaneous injection of NAL (2.5 mg/kg) or saline. All tissue incubation and staining for double-labeled immunocytochemistry were simultaneously performed. Although no significant developmental change was observed in the total number of GnRH neurons (p0.05), NAL-induced increases in serum luteinizing hormone (LH) concentrations were much greater in the d16 group than those in the d30 and mature groups (p<0.01). Conversely, Fos-positive GnRH neurons were rarely observed in d16, and some Fos-positive GnRH neurons were observed in the d30 group (p<0.05 vs. saline) and the mature group (p<0.01 vs. saline). These results suggest that opiatergic inhibitory system on GnRH neuron in immature female rats is different from that in mature female rats.

Age Factors↗
PubMed2000

Detection of pulmonary metastasis of low-grade endometrial stromal sarcoma 25 years after hysterectomy.

Endometrial stromal sarcoma (ESS) is a rare uterine sarcoma. Low-grade ESS occasionally recurs or metastasizes after long disease-free periods, a fact that may complicate the diagnosis. Here we report a case of multiple lung metastases in a 68-year-old woman who had been disease-free for 25 years after hysterectomy for a uterine tumor. Biopsy revealed that the tumor was composed of oval cells with slight nuclear atypism but without mitotic figures, suggesting a low-grade neoplasm. Immunostaining for intermediate filaments revealed strong positivity for vimentin and weak positivity for alpha-smooth muscle actin. In addition, immunostaining for estrogen and progesterone receptors, performed under suspicion of low-grade ESS, was positive. The uterine tumor resected many years before had shown a similar morphology. Thus, it was demonstrated that the lung neoplasm was a metastatic low-grade ESS that had appeared after many disease-free years. A review of the literature revealed that this case had the longest recorded interval between the occurrence of the initial ESS and the development of distant metastases. When low-grade sarcoma appears in the lungs of female patients, it is important to consider the possibility of low-grade ESS. Detailed information on the past clinical history, together with immunostaining for estrogen and progesterone receptors, are important diagnostic keys.

Disease-Free Survival↗
PubMed2000

Polyunsaturated fatty acids in the food chain in Japan.

The amount of polyunsaturated fatty acids (PUFAs) in the food chain in Japan is reviewed on the basis of the newest nutrition survey data. The Japanese are currently consuming, on average, approximately 26% of energy as fats with ratios of polyunsaturated to saturated fats and n-6 to n-3 fatty acids of approximately 1.2:1 and 4:1, respectively. The significant contributors to this relatively high n-3 PUFA intake are not only fish and shellfish but also edible vegetable oils, almost exclusively rapeseed and soybean oils. Thus, the dietary habits of the Japanese have made possible a high n-3 PUFA intake within a low-fat regimen. In this context, the gradual decline, particularly in younger persons, in fish consumption habits weighs on our minds. Analyses of health indexes, including the increased average life span, support the superiority of the current Japanese eating pattern that harmonizes with the Western regimens. However, at present it cannot be disregarded that food intake varies considerably in all age groups, and only a limited number of people are consuming the recommended allowance for dietary fats.

Adult↗
PubMed2000

The predictive value of biochemical markers of bone turnover for bone mineral density in postmenopausal Japanese women.

To examine the predictive value of biochemical markers of bone turnover for bone loss pre- and postmenopausally, we measured two markers of bone formation, bone-specific alkaline phosphatase (BALP) and intact osteocalcin (OC); four markers of bone resorption, urinary cross-linked N-telopeptides of type I collagen (NTx), type I collagen C-telopeptide breakdown products (CTx), hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP); serum OC N-terminal (OC-N); and two serum cytokines, soluble interleukin-6 receptor (sIL-6R) and IL-1r antagonist at baseline and 1 year, as well as lumbar spine bone mineral density (BMD) at baseline and 1, 2, 3, 4, and 5 years after trial in 82 premenopausal (44.8 +/- 5.4 years old) and 325 postmenopausal (60.2 +/- 6.1 years old) healthy Japanese women. In premenopausal women, stratification of the baseline value of each biochemical marker into quartiles did not cause any significant difference in the change in BMD. Stratification of the NTx baseline value in postmenopausal women showed significant differences in rate of bone loss to the first year among those subjects with each quartile (Q1 [0.28 +/- 0.28%], Q2 [-0.32 +/- 0.34%], Q3 [-1.50 +/- 0.31%], and Q4 [-2.43 +/- 0.35%]) except for the difference between Q1 and Q2. The predictive value of NTx for BMD was greater in early postmenopausal women within 5 years after menopause than in late postmenopausal women with more than 5 years since menopause (YSM). Quartile analysis of the other biochemical markers and serum cytokines did not show any significant capacity for differentiating between bone loss rates. Moreover, when the changes in the lumbar spine BMD to the second and third years were stratified into quartiles by the baseline NTx, the ratios of bone loss to the second and the third years were significantly higher in those women with higher NTx (Q4; -3.15 +/- 0.56% and -4.06 +/- 0.57%, respectively) than in those with lower NTx (Q1; -0.74 +/- 0.44% and -1.03 +/- 0.51%, respectively). In conclusion, baseline urinary NTx was the most sensitive predictor of bone loss in the lumbar spine after 1, 2, and 3 years. Markers of bone resorption can be used clinically to predict future BMD in postmenopausal women.

Adult↗
PubMed1999

Classification of polycystic ovary syndrome into three types according to response to human corticotropin-releasing hormone.

OBJECTIVE: To evaluate disturbances of the hypothalamic-pituitary-adrenal axis in women with polycystic ovary syndrome (PCOS). DESIGN: Retrospective cohort study. SETTING: Yokohama City University, Yokohama, Japan. PATIENT(S): Sixty women with PCOS and 19 women with normal menstruation. INTERVENTION(S): Administration of human corticotropin-releasing hormone (hCRH), dexamethasone suppression testing, and stimulation of ovulation with clomiphene citrate. MAIN OUTCOME MEASURE(S): Plasma cortisol and ACTH levels, plasma androstenedione and DHEAS levels, and ovulation rates. RESULT(S): In women with PCOS, plasma ACTH and cortisol levels were significantly higher and the plasma ACTH level after the administration of hCRH was higher than in controls. Based on the response to hCRH, patients with PCOS could be classified into three categories: those with a normal response to hCRH (group 1), those with an exaggerated response of ACTH to hCRH (group 2), and those with a high basal level of cortisol and a poor response to hCRH (group 3). In groups 2 and 3, DHEAS levels were significantly higher, suppression of androstenedione by dexamethasone was significantly greater, and ovulation rates with clomiphene citrate were significantly lower than in group 1. CONCLUSION(S): This classification provides insight into the underlying cause of PCOS and thus is useful in selecting appropriate treatment.

17-alpha-Hydroxyprogesterone↗
PubMed1999

Risk of recurrence of fetal chromosomal aberrations: analysis of trisomy 21, trisomy 18, trisomy 13, and 45,X in 1,076 Japanese mothers.

OBJECTIVE: To evaluate the risk of recurrence of fetal chromosomal aberrations in women who had offspring with numeric chromosomal abnormalities. SUBJECTS AND METHODS: This collaborative study consisted of 1,076 Japanese women with a history of offspring with trisomy-21, -18, -13, or 45,X. Second-trimester amniocenteses were performed, resulting in 1,248 fetal karyotypes that were analyzed with reference to prior offspring karyotypes and maternal age. RESULTS: Of the 842 women with trisomy-21 offspring, 10 conceived another such fetus. In 2 women with 3 or more such offspring, parental mosaicism of trisomy-21 was suspected. The incidence of recurrence of trisomy-21 increased with age, and significantly exceeded the incidence of trisomy-21 fetuses in the general population. None of the 170 women with trisomy-18 offspring, and none of the 46 women with trisomy-13 offspring, had another such fetus. Of the 18 women with 45,X offspring, 1 with mos 45,X/46,XX had another such fetus. CONCLUSIONS: The risk of recurrence of trisomy-21 is affected by maternal age and parental germline mosaicism. The risk of recurrence of trisomy-18 or -13 appears to be much lower than that of trisomy-21. Women who give birth to more than 1 offspring with 45,X should be examined for mos 45,X/46,XX.

Adult↗
PubMed1999

[Trend of vitamin E].

The term vitamin E covers several related tocopherols and tocotrienols (alpha-, beta-, gamma-, delta-tocopherols and tocotrienols), which have been isolated from natural sources, but the most active of these is the alpha-form, Fig. 1). Vitamin E is an essential nutrient for higher animals including man. A daily recommended level of this vitamin has been established in 1989, and been revised in 1999. In man, a limited number of deficiency symptoms (Cerebella ataxia, Muscular weakness et. al.) have been noted in adults but only after prolonged impairment of fat absorption and genetic defects. The beneficial effects of this vitamin intake are reported by many studies.

Adult↗