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Biomedical subjects

H Minaguchi

Publications and source records attributed to H Minaguchi.

At least 55 records · Page 3Linked to original sources
PubMed1996

The effect of activin-A on the development of mouse preimplantation embryos in vitro.

PURPOSE: Our purpose was to clarify the involvement of transforming growth factor-beta (TGF-beta) family in the regulation of preimplantation embryo development. METHODS: The effects of activin-A and TGF-beta on the rates of morula and blastocyst formations as well as on the cleavage velocity of a mouse two-cell embryo in vitro were analyzed. The gene expressions of these two growth factors in various developmental stages were also studied using RT-PCR. RESULTS: Activin-A at a concentration of 0.2 ng/ml significantly stimulated not only the rate of morula formation but also the velocity of embryo cleavage, whereas no significant effect was found with TGF-beta. RT-PCR revealed that activin-A subunit mRNA, but not TGF-beta mRNA, was detected in preimplantation mouse embryo at any developmental stage. CONCLUSIONS: Activin-A plays an important role in the regulation of preimplantation mouse embryo development in an autocrine fashion.

Activins↗
PubMed1996

Gene expression of gonadotropin-releasing hormone in early pregnant rat and steroid hormone exposed mouse uteri.

While gonadotropin-releasing hormone (GnRH) or GnRH-like substance have been reported to exist in nonhypothalamic tissues such as placenta, gonads, and mammary gland, there have been no reports concerning the detection of GnRH mRNA in uterine tissue. In order to investigate the presence of GnRH in decidual tissues and its possible involvement in the regulation of placental function, we examined the gene for GnRH in the rodent uterus in early pregnancy and in nonpregnant animals treated with female sex steroids. Using RT-PCR and in situ hybridization we found GnRH mRNA transcripts in the rat uterus of 3rd and 6th day gestation and in the mouse uterus treated with estrogen and progesterone. In situ hybridization revealed that GnRH mRNA was localized in the endometrial stromal cells of the 3rd and 6th day of gestation. These results suggest the existence of GnRH gene expression in uterine stromal cells and its possible paracrine effect derived from the decidual cells.

Animals↗
PubMed1996

Transforming growth factor-alpha, like epidermal growth factor, stimulates cell proliferation and inhibits prolactin secretion in the human decidual cells in vitro.

In order to clarify the biological action of transforming growth factor alpha (TGF-alpha) in the human decidua, we investigated the effects of TGF-alpha on cell proliferation and prolactin (PRL) secretion in cultured decidual cells in vitro. TGF-alpha had a stimulatory effect on DNA synthesis in decidual cells and an inhibitory effect on PRL secretion from these cells. These results suggest that TGF-alpha, like epidermal growth factor (EGF), may be one of the substances which regulate decidual function.

Cell Division↗
PubMed1996

Effect of estriol on bone loss in postmenopausal Japanese women: a multicenter prospective open study.

OBJECTIVES: To assess the effects of oral estriol on the bone mineral density (BMD) and bone metabolism in postmenopausal women. METHODS: Seventy-five natural postmenopausal women with a BMD of more than 10% below the peak bone density were treated for 50 weeks with 2 mg/day estriol (E3) cyclically and 0.8 g/day of calcium lactate continuously. BMDs at L2-L4 were measured by dual energy X-ray absorptiometry (DXA). RESULTS: The BMD increased 1.79% (p < 0.01 vs. pretreatment) after 50 weeks, accompanied with decrease of biochemical markers of bone turnover. With regard to climacteric symptoms, Kupperman's menopausal index improved (p < 0.01 vs. pretreatment) after 5 weeks of treatment. As to the incidence of adverse events genital bleeding was observed in only 8.0% of the subjects. Endometrial histology and cytology showed neither abnormalities nor hyperplasia during and after the treatment. CONCLUSIONS: Estriol prevented postmenopausal bone loss and improved climacteric symptoms effectively with low incidence of genital bleeding.

Bone Density↗
PubMed1996

Two pregnancies in a 45,X/46,Xr(X)/46,XX Turner mosaic patient. A case report.

Turner's syndrome associated with an X ring chromosome, r (X), is rare and there has been no report on pregnancy in Turner's syndrome with 45,X/46,Xr (X)/46,XX mosaicism. A patient with this karyotype who lacked the clinical manifestation of characteristic phenotype of Turner's syndrome except for short stature had two pregnancies. This is the first case of successful pregnancy in patient with X,Xr(X),XX mosaic Turner's syndrome.

Adult↗
PubMed1996

Immunohistological localization of tenascin in the human endometrium.

Tenascin (TN) is an extracellular matrix glycoprotein that seems to be involved in embryogenesis, carcinogenesis and wound healing. In order to clarify the biological significance of TN in the human endometrium, we investigated its expression in the normal as well as in the hyperplastic and neoplastic human endometrium, using immunohistochemistry. We also investigated the coexistence of TN with proliferating cell nuclear antigen (PCNA), a marker of cell proliferation, in endometrial carcinoma to further assess the involvement of TN in regulating cell proliferation. TN expression was observed in the stroma surrounding the endometrial gland in the proliferative phase, whereas it could not be found in the secretory phase. The localization of TN and PCNA coincided frequently, as the stromal portion where the expression of TN was observed always showed positive for PCNA. These results suggest that TN is involved in cell proliferation and carcinogenesis in the human endometrium.

Cell Division↗
PubMed1996

Changes in bone mass as determined by ultrasound and biochemical markers of bone turnover during pregnancy and puerperium: a longitudinal study.

In a longitudinal study, we analyzed the speed of sound (SOS) and broadband ultrasound attenuation (BUA) of the os calcis as an index of bone mineral density (BMD) to define the effects of pregnancy and lactation on bone metabolism. We used an ultrasound bone densitometer and measured 6 biochemical markers of bone turnover in 18 healthy women throughout pregnancy and puerperium. The measurement of SOS and BUA by such an ultrasound device was clinically advantageous; not only is it radiation-free technology, but it also correlates highly with BMD measured by conventional X-ray bone densitometry. While a significant decrease in SOS was found in the 3rd trimester of pregnancy as compared with the early stage of pregnancy, there was no difference in both SOS and BUA between the breast-feeding women and the principally formula-feeding women during a 6-month period of puerperium. The analysis of biochemical markers revealed that both bone formation and bone resorption were elevated in the 3rd trimester of pregnancy as well as during puerperium, and that the breast-feeding women had significantly higher bone metabolism than the principally formula-feeding women. These results indicate that bone mass decreases as bone turnover itself is enhanced during pregnancy, while lactation does not substantially affect bone mass during at least 6 months of puerperium, although bone turnover is active.

Adult↗
PubMed1996

Continuous stimulation of gonadotropin-releasing hormone (GnRH) receptors by GnRH agonist decreases pituitary GnRH receptor messenger ribonucleic acid concentration in immature female rats.

Although it is well recognized that continuous administration of gonadotropin-releasing hormone agonist (GnRHa) induces pituitary desensitization, the precise molecular mechanism of this phenomenon is still unclear. To test the hypothesis that pituitary gonadotroph desensitization is mediated by a change in GnRH receptor (GnRH-R) gene expression, the GnRH-R mRNA concentration was analyzed in immature female rats during GnRHa treatment. Northern blot hybridization was used to determine the GnRH-R mRNA concentration several times after an injection of TAP-144-SR, a slow releasing GnRHa. The GnRH-R mRNA readings were 92.7 +/- 9.5%, 49.9 +/- 5.0%, 35.7 +/- 2.3% and 73.8 +/- 5.7% (Mean +/- SD) compared to each control value at 1, 2, 4 and 8 weeks, respectively, after a single injection of 0.94 mg TAP-144 SR. These changes in GnRH-R mRNA coincided with the changes in gonadotropin secretion and LH-beta mRNA in response to GnRH in the results of our previous report. The present results indicate that the reduction of the number of pituitary GnRH-R sites induced by continuous stimulation with GnRHa is regulated at a transcriptional level.

Animals↗
PubMed1996

Reduction of bone mineral density by gonadotropin-releasing hormone agonist, nafarelin, is not completely reversible at 6 months after the cessation of administration.

STUDY OBJECTIVE: To determine the reversibility of bone mineral density after the cessation of GnRH agonist treatment for endometriosis. DESIGN: Longitudinal trial with 6-month treatment period and 6-month follow-up. PATIENTS: 28 Japanese premenopausal women with endometriosis. INTERVENTIONS: Daily dose of 400 micrograms nafarelin was administered for 6 months. MEASUREMENT AND MAIN RESULTS: The spine bone mineral density was measured by dual energy X-ray absorptiometry, and blood and urinary bone metabolic parameters were analyzed. The decrease of lumbar bone mineral density, which took place during treatment, continued during the first 3 months after the cessation of treatment and did not return to the initial baseline level even at 6 months after the withdrawal of treatment. The biochemical parameters, which showed a state of enhanced bone turnover during nafarelin treatment, almost returned to the pretreatment level 6 months after the termination of treatment. CONCLUSION: These results indicate that relatively long period of bone metabolic change might be required to alter the actual bone mineral density after GnRH analog administration.

Administration, Intranasal↗
PubMed1995

Trypsinogen expression in human ovarian carcinomas.

Increased secretion of matrix metalloproteinases and serine proteinases is well known to be associated with cancer invasion and metastasis. We aimed to elucidate the implication of trypsin, a serine proteinase and a representative digestive enzyme in invasion and metastasis of human carcinomas. Northern blot, RT-PCR and Western blot analyses and immunohistochemical studies were performed to detect and analyze trypsinogen expression in 5 ovarian carcinoma cell lines and 10 human ovarian carcinoma tissues using a DNA probe for trypsinogen I, and monoclonal and polyclonal antibodies to human trypsin I. Among the 5 ovarian carcinoma cell lines, only the MCAS (mucinous cystadenocarcinoma) cell line showed a high level of trypsinogen production and mRNA expression by Western and Northern blot analyses, respectively. However, Southern blot analysis of RT-PCR products could detect considerable levels of trypsinogen mRNA in all ovarian cancer cell lines. In Northern analysis of ovarian cancer tissues, all advanced cancer samples showed trypsinogen gene expression. Serous cystadenocarcinomas exhibited particularly high levels of gene expression. Immunohistochemical staining also detected trypsin in ovarian carcinoma tissues. In contrast, normal ovaries and tumors with low malignant potential did not show trypsinogen expression. Our results demonstrate the extra-pancreatic production and distribution of trypsinogen in human ovarian carcinomas.

Adenocarcinoma↗
PubMed1995

Detection of messenger RNA for gonadotropin-releasing hormone (GnRH) but not for GnRH receptors in mouse mammary glands.

While gonadotropin-releasing hormone (GnRH), GnRH-like, or GnRH receptor (GnRH-R) have been reported to exist in several tissues other than brain or anterior pituitary, there is no report concerning GnRH or GnRH-R gene expression in the normal mammary gland. In order to define the production of GnRH as well as GnRH-R in the mammary gland at the molecular level we examined their gene expression in various functional stages of the mouse mammary gland using the reverse transcriptase-polymerase chain reaction (RT-PCR). GnRH mRNA transcripts were found in mouse mammary glands of mid-pregnant, lactating, and 3, 6, 9 days post-lactational mice, whereas GnRH-R mRNA transcripts were not detected in mammary glands of any functional stage. These results suggest a possible biological role of GnRH in mammary gland.

Animals↗
PubMed1995

Establishment and characterization of two human ovarian clear cell adenocarcinoma lines from metastatic lesions with different properties.

Two permanent human ovarian clear cell adenocarcinoma lines (OVISE and OVTOKO) were established from metastatic tumors of two patients who were treated with five to six courses of CAP chemotherapy. The two cell lines grow on monolayers and showed a variety in both size and shape: small or moderately sized cuboidal cells, columnar cells, spindle-shaped cells, and malignant tumor giant cells. The cell lines have been in culture for 4 to 6 years, the passage number varying from 160 to 220. The mean population-doubling time of the two cells was 60 to 70 hr. The OVISE cells shed tumor-associated antigens CA19-9, CA125, and TPA in the culture medium, whereas the OVTOKO cells did not secrete them at detectable levels. Immunohistochemical analysis showed that coexpression of cytokeratins and vimentin was preserved in the two cell lines, which is a feature of cultured epithelial origin. Cytokeratin polypeptides 7, 8, 18, and 19 were expressed in both cell lines. The EGF receptor was more intensely expressed in the OVTOKO cells than in the OVISE cells. The estrogen and progesterone receptors were negative in both cell lines. The two cell lines showed no chemosensitivity to anticancer drugs including cisplatin, doxorubicin, cyclophosphamide, and etoposide. Heterotransplantation of the two cell lines reflected the origin of cells. Intraperitoneal transplantation of the OVTOKO cells yielded peritoneal implantation and distant metastasis, whereas that of the OVISE cells showed no dissemination and metastasis. These new ovarian clear cell adenocarcinoma lines will provide a relevant experimental system for further investigations into the intrinsic alterations responsible for malignant progression and chemoresistance.

Adenocarcinoma, Clear Cell↗
PubMed1995

Marked induction of gelatinases, especially type B, in host fibroblasts by human ovarian cancer cells in athymic mice.

Two human ovarian adenocarcinoma cell lines, MCAS-3 and OVISE-3 were found to secrete little of any type of gelatinase in tissue culture. However, when these cell lines were implanted subcutaneously into nude mice the cyst fluids from the resultant tumors contained gelatinase A and/or B. The enzyme activities, especially of gelatinase B, were much higher in the malignant MCAS-3 tumors than in those of the less malignant OVISE-3 tumor cells. To elucidate the origin of gelatinase B in cyst fluids of the MCAS-3 tumors, murine skin fibroblasts (MSF) were isolated from a subcutaneous tumor in a nude mouse and tested for their proteinase secretion in culture. MSF cells, which secreted some gelatinase A and gelatinase B, were induced to secrete high levels of both enzymes, especially gelatinase B, by co-cultivation with MCAS-3 cells. In addition, gelatinase A activity was induced by incubation of MSF cells with the conditioned medium of either MCAS-3 or OVISE-3 cells, whereas gelatinase B was induced only with that of MCAS-3. Although cytokines or growth factors such as IL-1 beta, TGF-beta 1, TNF-alpha or EGF stimulated the secretion of gelatinases A and B from MSF cells, their effects on gelatinase B activity were far less than that of the MCAS-3 conditioned medium. These results indicate that the major part of gelatinase B activity in the cyst fluids of the ovarian tumors is secreted by host interstitial cells stimulated by tumor-derived humoral factors. Similar tumor cell-host cell interactions may be important in the production of various proteinases in other tumor types.

Animals↗
PubMed1995

Urinary biochemical markers for bone resorption during the menstrual cycle.

In order to analyze the effects of serum ovarian steroid hormones on bone metabolism during the menstrual cycle, we have measured urinary levels of type I collagen cross-linked N-telopeptide (NTx), hydroxylysylpyridinoline (HP), lysylpyridinoline (LP). and hydroxyproline (OH-Pr) in nine healthy Japanese women, aged 22-43 years, with normal ovarian function. The cycles were synchronized by serum LH peaks, and follicular and luteal periods were normalized by lengths. Serum gonadotropins and ovarian sex steroids showed significantly different cyclic variations during the menstrual periods. Urinary NTx remained unchanged during the early follicular period, showed a rise during the mid- and late follicular period, and a fall during the mid- and late luteal periods. There were significant differences in NTx levels between early follicular period and midfollicular period (P < 0.01), or late follicular period (P < 0.05), and between early luteal period and late luteal period (P < 0.05). The levels of HP and LP showed a rise during the early an midfollicular periods and a fall during the midluteal period. The correlation of NTx with urinary OH-Pr was better than with urinary HP or LP (r = 0.731 versus r = 0.449 or r = 0.634). This variation suggests that cyclic changes in serum ovarian sex steroids might modulate bone resorption markers during the menstrual cycle.

Adult↗
PubMed1995

Relation between gestational sac diameter, crown-rump length, and maternal serum estradiol, progesterone, and prolactin levels in early pregnancy.

In 152 patients with an early pregnancy which was subsequently normal, we measured the maternal serum levels of estradiol (E2), progesterone (P4) and prolactin (PRL) as well as the diameter of gestational sac (GS) and the crown-rump length (CRL) of the embryo by transvaginal ultrasonography. The maternal serum level of E2 had the closest statistically significant correlation with both the GS diameter (r = 0.769, P < 0.01) and the CRL (r = 0.736, P < 0.001). P4 and PRL concentrations showed less correlation with embryo development.

Crown-Rump Length↗
PubMed1995

Effects of a gonadotropin releasing hormone agonist on oocyte maturation, fertilization, and embryonal development of mice.

PURPOSE: The effects of a GnRH agonist (GnRHa) on oocyte quality were investigated by assessing the influence of GnRHa on oocytes, and fertilized oocytes were examined in vivo and in vitro. Administration of gonadotropin in conjunction with GnRHa induced a significantly greater degree of germinal vesicle breakdown, significantly higher rates of in vitro fertilization, and significantly faster development of the oocytes than the pregnant mare serum gonadotropin alone RESULTS: The hatching-success rate in the GnRHa treated hypophysectomized mice was higher than in control mice. The rate of in vitro fertilization was also higher in oocytes cultured in the presence of low loses of GnRHa and these effects were reversed by a GnRH antagonist. CONCLUSION: Oocytes obtained following ovarian stimulation with GnRHa were of higher quality than control oocytes, and the efficacy of GnRHa may be due in part to its direct action on the ovary.

Animals↗