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H Minaguchi

Publications and source records attributed to H Minaguchi.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effects of GnRH on protein kinase C activity, Ca2+ mobilization and steroidogenesis of human granulosa cells.

Gonadotropin-releasing hormone (GnRH) and its agonists have been known to directly affect steroid hormone production in human granulosa cells. In this study, we examined effects of GnRH on Ca2+ mobilization, protein kinase C activity and steroidogenesis of human granulosa cells. Human granulosa cells were harvested by aspiration of follicles during oocyte retrieval for IVF. Test substances, that is, GnRH agonist ([D-Ser(TBu)6]-LHRH-EA), 12-O-tetradecanoyl-phorbol-13-acetate (TPA), A23187, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) and nordihydroguaiaretic acid (NDGA) were added to HTF medium with human granulosa cells. At the end of a 5-h incubation period, progesterone and estradiol in the medium were extracted and measured. GnRH agonist (10(-9)M and 10(-8)M) significantly stimulated (P < 0.05) progesterone and estradiol accumulation in the medium. TPA (10(-7)M, 10(-8)M and 10(-9)M) also significantly stimulated (P < 0.05) progesterone accumulation. A23187 (10(-6)M) significantly stimulated progesterone accumulation (P < 0.05) and significantly enhanced (P < 0.05) the stimulatory effect of TPA on progesterone production. H-7 (10(-3)M, 10(-4)M and 10(-5)M) and NDGA (10(-3)M, 10(-4)M and 10(-5)M) significantly inhibited (P < 0.05) the effect of GnRH agonist on progesterone and estradiol production by the granulosa cells. The granulosa cells were loaded with 4 microM Fura 2-AM, and the ratio of the intensities of fluorescent emission at 510 nm with excitation at 340 and 380 nm was calculated at 100-ms intervals. GnRH agonist (10(-7)M and 10(-6)M) increased (P < 0.05) [Ca2+]i significantly as compared with the control. These results suggested that the effects of GnRH on progesterone and estradiol production in human granulosa cells were mediated partially by calcium mobilization and partially by C-kinase activity, and protein kinase C, [Ca2+]i and lipoxygenase were suspected of being important intracellular messages for GnRH in human granulosa cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1998

A placebo-controlled, single-blind study to determine the appropriate alendronate dosage in postmenopausal Japanese patients with osteoporosis. The Alendronate Research Group.

Alendronate (4-amino-1-hydroxybutylidene-1,1-bisphosphonate) is a potent inhibitor of bone resorption. The efficacy and safety of 36 weeks of treatment with alendronate were evaluated in Japanese women with osteoporosis, osteoporotic osteopenia or artificial menopause. The bone mineral density (BMD) of the lumbar vertebrae, markers of bone and calcium metabolism and clinical symptoms were monitored. A total of 113 randomly selected patients with osteoporosis or osteopenia were enrolled in the study, of whom 12 were excluded from the analyses because of lack of data. As a result, 101 patients were evaluated for the safety of the drug. Since eight patients were excluded from the efficacy analysis, 93 were evaluated. The incidence of adverse effects in the placebo (P), alendronate 2.5 mg/day (L) and alendronate 10 mg/day (H) groups increased with increasing dose of alendronate, being 6.1, 14.3 and 18.2%, respectively. The most common adverse effects were gastrointestinal symptoms, none of which was serious. Lumbar BMD increased after 36 weeks of drug administration to 5.21%, 5.64% and -0.90% in the L, H and P groups, respectively (P < 0.001, L vs. P and H vs. P). Serum alkaline phosphatase activity, serum osteocalcin and urinary deoxypyridinoline excretion were significantly decreased in a dose-related manner. Serum calcium and phosphorus were also significantly decreased after alendronate administration. Serum intact PTH was transiently increased. The present results indicate that alendronate effectively decreases bone turnover in a dose-related manner and increases lumbar BMD at a dosage of 2.5 mg/day, the lowest dose used in this study, in Japanese patients with osteoporosis.

Adult↗
PubMed1997

Gene expression of gonadotropin-releasing hormone, but not its receptor, in human endometrium and decidua.

Gonadotropin-releasing hormone (GnRH) has been reported to exist in extrahypothalamic tissues such as the placenta, gonads and mammary glands. While we have reported the presence of GnRH-mRNA in the rodent uterus, there have been no reports concerning gene expression of GnRH and its receptor (GnRH-R) in human endometrial tissue. In order to investigate the role of GnRH as a local regulator in the human endometrium, we examined the gene for GnRH and GnRH-R in non-pregnant endometrium and decidua of early pregnancy. Using reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blot analysis we found GnRH-mRNA but not GnRH-R-mRNA transcripts in the human endometrium and decidua at 7-9 weeks gestation. This is the first report that suggests GnRH gene expression in the human endometrium/decidua.

Blotting, Southern↗
PubMed1997

Gene expression and specific binding of platelet-derived growth factor and its effect on DNA synthesis in human decidual cells.

To clarify the biological significance of platelet-derived growth factor (PDGF) in human decidual cell function, which is important for the maintenance of pregnancy, we investigated gene expression of the PDGF subunits, PDGF-A and PDGF-B, specific binding of the PDGF isoform, and the effect of PDGF dimers on DNA synthesis in human decidual cells. We detected in decidua from early pregnancy the expected DNA bands of PDGF-A and PDGF-B by reverse transcriptase-polymerase chain reaction (RT-PCR) as well as mRNAs of each PDGF subunit by Northern blot hybridization, demonstrating that both PDGF subunits exist in this tissue. Scatchard plot analysis showed that decidual cells had both PDGF-alpha and PDGF-beta receptors. PDGF-AA, -AB and -BB stimulated [3H]-thymidine incorporation in cultured decidual cells in a dose-dependent manner. These results indicate the importance of PDGF in human decidua.

Binding Sites↗
PubMed1997

Uterine carcinosarcoma is derived from a single stem cell: an in vitro study.

Expression of intermediate filaments (IFs) has been suggested to be a reliable marker for differentiating epithelial and non-epithelial tumors. Moreover, the c-erbB-2 and p53 genes are considered to be involved relatively early in the process of human carcinogenesis. In order to elucidate the origin of uterine carcinosarcomas, we analyzed IF, c-erbB-2 and p53 expression in and the ultrastructural characteristics of clones derived from a human uterine-carcinosarcoma cell line, EMTOKA. The expression of IFs and other proteins in the EMTOKA clones was identical to that in the EMTOKA cell line. It and its 7 clones all expressed cytokeratins 8, 17, 18 and 19, vimentin, epithelial membrane antigen, S-100, myoglobin, type-II collagen, alpha-smooth-muscle actin, placental alkaline phosphatase and epidermal-growth-factor receptor. The c-erbB-2 and p53 expression levels of all the cell types of the EMTOKA cell line and its clones were the same. Interestingly, an ultrastructural study showed that the EMTOKA cell line and its clones at early and late passages possessed the characteristics of epithelial cell types without either transitional forms between the epithelial and stromal components or differentiation into sarcomatous components. The results of this study lend particular support to the combination tumor hypothesis that a precursor (stem) cell gives rise both to epithelial and to mesenchymal components during the histogenesis of uterine carcinosarcoma, the epithelial component of which appears to be dominant, suggesting that the established cell lines derived from a common stem cell.

Biomarkers, Tumor↗
PubMed1997

The change in tenascin expression in mouse uterus during early pregnancy.

PURPOSE: Our aim was to examine the changes in spatiotemporal tenascin (TN) expression in mouse uterus during early pregnancy, when the uterine tissue undergoes a tremendous restructuring. METHODS: Using immunohistochemistry and in situ hybridization, the changes in distribution of TN protein in mouse uterine tissues in pregnancy Day 0 through Day 5 were analyzed. RESULTS: Immunoreactive TN and TN mRNA were expressed in the basement membrane of the epithelium as well as in the smooth muscle layer, and their distribution shifted from the subbasement region on Day 0-3 to the smooth muscle layer on Days 4 and 5. CONCLUSIONS: These results indicate that TN expression in the uterus during early pregnancy is spatiotemporally different and may be regulated by a different mechanism.

Animals↗
PubMed1997

Gene expression of transforming growth factor-alpha in human endometrium during decidualization.

PURPOSE: We previously reported the gene expression of epidermal growth factor (EGF) in the process of decidualization in the human endometrium. This study was undertaken to investigate the biological significance of transforming growth factor-alpha (TGF-alpha), which shares a significant sequence homology with EGF, in the regulation of decidualization. METHODS: The gene encoding TGF-alpha was analyzed by Northern blot hybridization in nonpregnant human endometria and decidua from 6 to 8 weeks of gestation as well as in cultured stromal cells with or without medroxyprogesterone acetate. RESULTS: No transcript was detected in proliferative and secretory endometrium, whereas a transcript of 4.8 kb, which was in agreement with the size of human prepro-TGF-alpha mRNA previously reported, was clearly detected in decidua. Transcript of 4.8 kb was also detected in vitro in medroxyprogesterone acetate (MPA)-induced decidual cells, while no TGF-alpha transcript was found in endometrial stromal cells cultured without MPA. CONCLUSIONS: These results suggest that the gene expression of TGF-alpha in uterine stromal cells is enhanced by stimulation from sex steroids and that TGF-alpha, like EGF, functions as one of the regulatory factors for decidualization in the human uterus.

Blotting, Northern↗
PubMed1997

Specific changes of urinary excretion of cross-linked N-telopeptides of type I collagen in pre- and postmenopausal women: correlation with other markers of bone turnover.

Urinary excretion of cross-linked N-telopeptide of type I collagen (NTx) has been reported to be a specific marker of bone resorption [18]. We assessed a new immunoassay for NTx as an indicator of changes in bone resorption caused by spontaneous menopause and compared cross-sectionally the levels of urinary NTx, hydroxylysylpyridinoline (HP), lysylpyridinoline (LP), hydroxyproline (OH-Pr), other serum biochemical indices, and lumbar spine and proximal femur bone mineral density (BMD). Eighty-one Japanese women aged 22-77 participated in this study; 36 were premenopausal and 45 were postmenopausal. Urinary HP, LP, and NTx stayed at low levels in the premenopausal period and rose 21%, 30%, and 67% in the postmenopausal period, respectively. The rise in LP and NTx was statistically significant (P < 0.01), suggesting that NTx is mostly released from bone matrix when bone resorption is accelerated. When premenopausal women were divided into two age groups and postmenopausal women were divided into two groups according to years since menopause (YSM) there were significant differences in LP and NTx between women <4 YSM and women aged <40 and those women aged 41+ (P < 0.01 and P < 0.05, respectively). A significant 110% increase in urinary NTx and a 48% increase in urinary LP were observed in postmenopausal women compared with age-matched premenopausal women aged 45-55. All biochemical markers other than serum PTH correlated significantly with each other (r = 0. 243-0.858, P < 0.05-0.0001). Urinary NTx inversely correlated with lumbar spine BMD. When postmenopausal women were divided into three groups, the correlation between bone resorption and formation markers in women 0-1 YSM was greater than in women 2-10 YSM and in women 11 + YSM, indicating that resorption and formation are coupled at the early postmenopausal period. We conclude that urinary NTx is responsive to changes in bone metabolism caused by estrogen deficiency and may be a more sensitive and specific marker than HP, LP, or OH-Pr in the early postmenopausal years.

Adult↗
PubMed1997

Prolactin secretion in endometriotic patients.

OBJECTIVE: To clarify a significance of prolactin (PRL) for infertility in endometriosis. STUDY DESIGNS: For seventy endometriotic patients with or without infertility, serum PRL concentrations measured by radioimmunoassay before and 30 min after 500 micrograms of thyrotropin-releasing hormone (TRH) injection were analyzed in relation to the Revised American Fertility Society score in endometriosis as well as to the outcome of the treatment for endometriotic infertility. RESULTS: While no significant relationship was found between the basal PRL levels and the stage of endometriosis or the outcome of the treatment for infertility, the PRL value after TRH injection was significantly greater in the patients who did not become pregnant than those who did (P < 0.05). CONCLUSIONS: Occult hyperprolactinemia may be involved in infertility in endometriotic patients.

Adolescent↗
PubMed1997

Pure ovarian ependymoma: report of a case treated with surgery, chemotherapy, irradiation and hyperthermotherapy.

Ependymomas usually develop from neuroectodermal organs. Pure ovarian ependymoma is an extremely rare tumor. We report a patient with ovarian ependymoma who died at the age of 28, 9 years after initial surgery and subsequent intensive combination therapy (chemotherapy, irradiation and hyperthermotherapy) for repeated relapses and metastatic tumors. The diagnosis was confirmed by histopathological and immunohistochemical studies. For recurrent and persistent ependymoma, a combination of the treatment modalities described above is suggested to be beneficial in attenuating the rapid progress and spread of this disease.

Adolescent↗
PubMed1997

Complexity of expression of the intermediate filaments of six new human ovarian carcinoma cell lines: new expression of cytokeratin 20.

Six permanent human ovarian carcinoma cell lines (OVISE, OVTOKO, OVMANA and OVSAYO from clear cell adenocarcinoma, and OVSAHO and OVKATE from serous papillary adenocarcinoma) were established from solid tumours. The cell lines have been in culture for 5-8 years, the passage number varying from 62 to 246. Immunohistochemical analysis has shown that five of the six cell lines express at least six cytokeratin (CK) polypeptides. OVISE and OVSAYO expressed CKs 6, 7, 8, 18, 19 and 15 and/or 16. OVTOKO was positive for CKs 7, 8, 18, 19 and 15 and/or 16. OVSAHO expressed CKs 6, 7, 8, 14, 18, 19 and 15 and/or 16. OVMANA expressed CKs 6, 7, 8, 18, 19, 20 and 15 and/or 16. OVKATE expressed CKs 6, 7, 8, 13, 17, 18, 19, 20 and 15 and/or 16. The expression of CK7, additional expression of vimentin, and clinical and histopathological findings enabled us to confirm that six cell lines had been established from primary ovarian cancers. Two of the six cell lines were positive for CK20, although CK20 was not expressed in the original tumours. The heterotransplanted tumours produced by CK20-positive cells also expressed CK20. This is the first report of ovarian carcinoma cell lines that express CK20 irrespective of their histological type. CK20 has been found in all colon carcinoma cell lines, but only in the mucinous type of ovarian tumours. These new ovarian carcinoma cell lines will therefore provide a relevant experimental system for elucidating the regulatory control mechanisms of intermediate filament expression.

Adenocarcinoma, Clear Cell↗
PubMed1997

Classification of hypothalamic progestin-nonresponsive amenorrhea by secretion pattern of serum LH.

The pathogenesis of hypothalamic progestin-nonresponsive amenorrhea is unclear and this disease often fails to respond to treatment. The pulsatile patterns of diurnal and nocturnal secretion of serum LH as well as serum levels of melatonin were examined to improve the understanding of the pathogenesis and to develop strategies for the management of a severe type of hypothalamic amenorrhea. Four types of LH pulsatile patterns were observed: a) no pulse during the day or night (Group 1); b) more than 1 pulse only at night (Group 2); c) only 1 pulse during the day and more than 2 pulses at night (Group 3); and d) more than 2 pulses during the day and at night (Group 4). Serum estradiol was less than 30 pg/mL, and the serum PRL and PRL response to TRH did not differ among the four groups. The basal level and the pulse amplitude of LH increased successively from Group 1 to Group 4. The serum level of melatonin at night was noticeably increased in Group 1 and correlated negatively with the LH pulse frequency at night. After 6-month hormone replacement therapy with estrogen and progesterone, the rate of improvement in ovarian function were 0%, 33.3%, 57.1% and 67.0% in Groups 1, 2, 3, and 4, respectively. In 5 patients, the LH pulse pattern was re-examined at 6 months, the LH pulsatile pattern was changed from that of Group 1 to that of Group 4, with a decrease in serum concentrations of nocturnal melatonin, indicating improved ovarian function. In conclusion, classification of patients according to the LH secretion pattern is useful in establishing the severity of hypothalamic disturbance in hypothalamic progestin-nonresponsive amenorrhea and in predicting its prognosis; in addition nocturnal melatonin can be used as a marker for severer cases of hypothalamic amenorrhea.

Adolescent↗
PubMed1997

Effects of noradrenaline on GnRH-secreting immortalized hypothalamic (GT1-7) neurons.

Noradrenaline (NA) is one of the most important neurotransmitters involved in the regulation of gonadotropin-releasing hormone (GnRH) secretion. In this study, the effects of NA on GnRH secretion, intracellular Ca2+ concentrations ([Ca2+]i), and membrane potentials were investigated in immortalized hypothalamic neurons (GT1-7) to determine the direct effects of NA on GnRH cells. Cells were perfused in a plastic minicolumn, and GnRH concentrations of the effluents were measured. NA increased the release of GnRH in a dose-dependent manner. Cells were loaded with a 4 microM Fura 2-AM, and the ratio of the intensities of fluorescent emission at 510 nm with excitation at 340 and 380 nm was calculated at 100-ms intervals. NA increased the [Ca2+]i responses of single GnRH cells dose-dependently. The NA-induced [Ca2+]i increase was attenuated in the absence of extracellular calcium and was blocked by the beta-adrenergic antagonist propranolol, but not by the alpha-adrenergic antagonist phentolamine. The cell membrane potential was recorded with a whole-cell patch clamp amplifier with glass-electrodes. NA induced membrane depolarization under current-clamp conditions. The depolarization was also inhibited by propranolol, but not by phentolamine. The results show that NA directly affects the membrane potential of GT1-7 cells via beta-adrenergic receptors and induces Ca2+ mobilization; these effects stimulate GnRH secretion.

Adrenergic alpha-Agonists↗
PubMed1997

Changes in urinary excretions of C-telopeptide and cross-linked N-telopeptide of type I collagen during pregnancy and puerperium.

Previously we reported an increase in bone resorption during pregnancy and lactation by measuring pyridinoline (Pyr) and deoxypyridinoline (D-Pyr). To further assess bone metabolism during peripuerperal periods, we measured the urinary excretions of C-telopeptide (CTX) and cross-linked N-telopeptide (NTX) of type I collagen, new markers of bone resorption. In addition to Pyr and D-Pyr, urinary CTX and NTX were measured by two ELISAs which recognize the corresponding peptide of type I collagen after urine samples were collected cross-sectionally from 230 women who consisted of 187 pregnants, 25 puerperants, and 18 age-matched nonpregnant women. Urinary CTX was also measured longitudinally from 10 pregnants at 5-9, 28-31 and 36-39 weeks of gestation and 1, 3, 6 months after parturition. Similar to the changes in Pyr and D-Pyr, the mean CTX and NTX values significantly increased in the 3rd trimester of pregnancy and remained high during puerperium compared with nonpregnant or early pregnant women (P<0.05). In a longitudinal study, the mean CTX value significantly increased in the 3rd trimester of pregnancy and at 1 month of puerperium compared with that in the early stage of pregnancy (P<0.05). These results further confirm our previous evidence that bone resorption is enhanced during the 3rd trimester of gestation and puerperium and suggest that urinary CTX and NTX measured by ELISA, which is more convenient than HPLC, are useful markers to assess bone resorption during peripuerperal periods.

Adult↗
PubMed1997

Gene expressions of keratinocyte growth factor and its receptor in the human endometrium/decidua and chorionic villi.

Keratinocyte growth factor (KGF) is secreted from mesenchymal fibroblasts and has a mitogenic specificity for epithelial cells in a paracrine fashion. In order to clarify the biological significance of KGF in the human endometrium which undergoes dynamic changes under the influence of sex steroid hormone, we investigated the gene expressions of KGF and its receptor (KGF-R) in the human endometrium in various sex steroid hormone milieus and chorionic villi, by RT-PCR and Northern blot hybridization. The secretory phase endometrium had a KGF mRNA level 10-fold greater than that of the proliferative phase endometrium. Similarly abundant KGF mRNA was found in decidua and pseudopregnant endometrium compared with proliferative phase endometrium. The KGF-R mRNA was detected by RT-PCR in chorionic villi from early pregnancy. These results indicate that the gene for KGF expressed in the human endometrium is mainly regulated by progesterone and that KGF might have a role in the interaction between decidua and chorion in early pregnancy in man.

Blotting, Northern↗
PubMed1997

Change in C-terminal cross-linking domain of type I collagen in urine, a new marker of bone resorption, during and after gonadotropin-releasing hormone agonist administration.

OBJECTIVE: The major side effect of GnRH agonist (GnRHa) therapy is the reduction of bone mass. To analyze bone resorption by GnRHa, we measured the urinary excretion of C-terminal telopeptides of type I collagen (CTX), a new marker of bone resorption. METHODS: We used a new ELISA for CTX (CrossLaps) in a sample of 18 premenopausal women with leiomyoma who were treated with daily administration of 400 micrograms nafarelin or 900 micrograms buserelin for 16 weeks. RESULTS: Urinary CTX excretion increased significantly during GnRHa treatment and then decreased at 12 and 24 weeks after the cessation of GnRHa therapy. Whereas the excretory profile of CTX during GnRHa therapy was almost similar to that of pyridinoline (Pyr) or deoxypyridinoline (D-Pyr), both biochemical markers of bone resorption, the magnitude of the change in CTX was significantly greater than that in Pyr or D-Pyr. CONCLUSIONS: These results indicate that CTX could be a more sensitive marker for bone resorption than the currently used biochemical markers, and that CrossLaps ELISA is useful for therapeutic monitoring during and after GnRHa treatment.

Adult↗