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Biomedical subjects

H Minaguchi

Publications and source records attributed to H Minaguchi.

At least 73 records · Page 4Linked to original sources

A case of tracheal agenesis delivered of a patient with mosaic Turner's syndrome.

We describe a female infant with tracheal agenesis associated with severe complicated malformations including the cardiovascular system. The patient was born of a mother with mosaic Turner's syndrome at 35 weeks of gestation after premature rupture of the membranes during treatment for polyhydramnios. The patient died 2 days after birth and the autopsy disclosed tracheal agenesis and associated multiple anomalies.

Abnormalities, Multiple↗

Characterization of matrix-degrading proteinases and their inhibitors secreted by human gynecological carcinoma cells.

Matrix-degrading proteinases secreted by tumor cells play crucial roles in tumor cell invasion and metastasis. Serum-free conditioned media of 7 human gynecological carcinoma cell lines were examined for proteinases and their inhibitors by using gelatin zymography, reverse zymography and immunoblotting. All of three ovarian adenocarcinoma cell lines secreted urokinase-type plasminogen activator. Among them, a mucinous cystadenocarcinoma cell line also secreted tissue-type plasminogen activator, plasmin-like enzyme and trypsinogen. On the other hand, two ovarian undifferentiated carcinoma cell lines mainly secreted glatinase A or B. A choriocarcinoma cell line secreted multiple metalloproteinases in the highest amount, whereas an endometrial adenocarcinoma cell line (HEC-1) derived from an early clinical stage hardly secreted any gelatinolytic enzyme. The five high proteinases producers hardly secreted the corresponding inhibitors, such as tissue inhibitor of metalloproteinases (TIMP)-1, -2 or plasminogen activator inhibitor-1. In contrast to these highly malignant cell lines, a poor proteinase producer, HEC-1, secreted a large amount of TIMPs. Therefore, an enhanced proteolytic tendency appears to be associated with gynecological cancer cells established from highly malignant tumors.

Adenocarcinoma, Clear Cell↗

Posthemorrhagic hydrocephalus in a fetus with severe tachycardia.

Although posthemorrhagic hydrocephalus has been observed in premature infants, few cases of its intrauterine occurrence in fetuses have been reported. We report a case of posthemorrhagic hydrocephalus in a fetus with severe tachycardia. This case indicates that its possible occurrence should be considered in a case of a preterm fetus with distress.

Adult↗

Regulation of human decidual function by epidermal growth factor.

In order to clarify a regulatory mechanism of epidermal growth factor (EGF) in the decidualization process, EGF gene expression, the change in EGF receptor, and the cell proliferative effect of EGF in the human endometrium/decidua were assessed in both in vivo and in vitro decidualization systems. Northern blot hybridization showed that, although no hybridized band was found in the proliferative and secretory phase endometria, a specific band of 5 kb was detected in decidua of early pregnancy as well as in in vitro medroxyprogesterone acetate-induced decidual cells. In situ hybridization revealed that prepro-EGF mRNA was observed in the stromal cells of decidua. Scatchard plot analysis of 125I-EGF-binding studies for the homogenates from these endometria/decidua revealed that its binding sites increased in accordance with the decidualization process, and its dissociation constant remained unchanged. EGF had a stimulatory action on cell proliferation in the early pregnant decidual cells. These results demonstrate that EGF production, EGF receptor, and decidual cell growth increase in accordance with the process of decidualization, suggesting that EGF may play an important role in the regulation of decidualization in human endometrium through an autocrine/paracrine system.

Blotting, Northern↗

Epidermal growth factor stimulates the cell growth of the PA-1 teratocarcinoma cell line in an autocrine/paracrine fashion.

In order to investigate the biological significance of epidermal growth factor (EGF) in the cell function of teratocarcinoma cells, we examined the production, binding and cell proliferative effect of EGF in PA-1 human ovarian teratocarcinoma cell line. The immunoreactivity of EGF in PA-1 cell-conditioned medium was detected by human EGF radioimmunoassay, and prepro-EGF mRNA was demonstrated in PA-1 cells by Northern blot analysis. An [125I]EGF binding study showed the presence of EGF receptor with very high binding affinity and relatively low numbers of binding sites in PA-1 cells. Furthermore, the growth of PA-1 cells was stimulated by EGF and inhibited by anti-EGF monoclonal antibody. These results suggest strongly that EGF plays an important role in controlling the growth of teratocarcinoma cells as an autocrine/paracrine growth factor.

Blotting, Northern↗

Effects of epidermal growth factor and transforming growth factor alpha on the mouse trophoblast outgrowth in vitro.

In order to analyze the involvement of growth factors in the implantation mechanism, we examined the direct effects of epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha) on trophoblast outgrowth of the mouse blastocyst in vitro. ICR mouse blastocysts were cultured for 4 days on a culture plate in medium containing EGF or TGF-alpha or conditioned medium obtained from cultured endometrial epithelial cells. Blastocysts were also co-cultured with endometrial epithelial cells. The trophoblast outgrowth of these cultured blastocysts was observed daily and the percentage of outgrowing embryos was calculated and analyzed statistically by the chi-squared test. Analysis for the specific binding of 125I-EGF in outgrown trophoblasts was carried out by autoradiography. The co-culture (days 3 and 4) and the presence of EGF (10 ng/ml, day 4), TGF-alpha (1 ng/ml, day 3; 10 ng/ml, days 2 and 3; 50 ng/ml, days 2-4) or conditioned medium (days 3 and 4) significantly stimulated the rate of trophoblast outgrowth. Preincubation of the conditioned medium with monoclonal anti-EGF or anti-TGF-alpha antibody suppressed the stimulatory effect of the conditioned medium on trophoblast outgrowth. The specific 125I-EGF binding in outgrown trophoblasts was demonstrated by autoradiography. These results suggest that EGF and TGF-alpha play an important role in the implantation process by directly stimulating trophoblast development.

Animals↗

Effect of gonadotropin-releasing hormone agonist on the bone mineral density of patients with endometriosis.

OBJECTIVE: To examine changes in bone mineral density (BMD) of patients treated with GnRH agonist (GnRH-a) by dual-energy X-ray absorptiometry and to understand factors related to bone loss. DESIGN: Prospective controlled trial examining BMD during and after GnRH-a therapy every 24 weeks for 18 months in patients with endometriosis compared with nontreated controls. SETTING: Outpatients clinic at a university hospital and its affiliated outpatient clinic. PATIENTS: Twenty-two patients with endometriosis as GnRH-a-treated group, 12 healthy women with normal menstrual cycle, and 7 patients with mild endometriosis as control group. INTERVENTIONS: Patients were treated with a GnRH-a (buserelin acetate) at 900 micrograms/d by nasal spray for 24 weeks. RESULTS: The significance of differences in change-rates at all measured points in both groups was assessed by analysis of variance. The interaction between treatment and period was significant, and only week 24 of the GnRH-a-treated group was significantly lower compared with baseline. The reduction rate of BMD was high in patients 33 years of age or younger compared with those who were 34 years of age or older. According to a multiple-regression model, the most important factor related to bone loss was the post-treatment serum levels of E2. CONCLUSION: At the end of treatment, BMD was significantly lower than that of the control group, and the reduction rate was 3.4%. A factor related to bone loss was degree of ovarian suppression.

Adult↗

Direct effects of gonadotropin-releasing hormone on the ovary in rats and humans.

In order to know whether gonadotropin-releasing hormone (GnRH)-like substances play a role as local regulators in the ovary, localization of the GnRH receptor, and the effects of GnRH agonist (GnRHa) on the cyclic AMP system in the rat ovary was studied. In addition, effects of GnRH antagonist on the rat ovary and effects of GnRHa on steroidogenesis in the human ovary were also examined. In the rat, localization of the GnRH receptor was observed to change with follicular development, and GnRHa decreased follicle-stimulating-hormone-stimulated cAMP production. On the other hand, GnRH antagonist showed the tendency to promote ovarian function. In the human ovary, GnRHa seemed to inhibit steroidogenesis directly, in vivo and in vitro. These data suggested that GnRH/GnRH-like substances play a role as local regulators in the ovary.

Animals↗

Gene expression of epidermal growth factor in human endometrium during decidualization.

Although there are some reports, including our previous study, indicating the existence and biological action of epidermal growth factor (EGF) in human decidua, the site of its synthesis remains unknown. To clarify the EGF production during decidualization at a molecular level, gene expression of EGF in human endometrium/decidua was examined by Northern blot analysis and in situ hybridization. Northern blot hybridization using 32P-labeled human prepro-EGF complementary DNA was carried out for nonpregnant human endometria from hysterectomized uteri of leiomyoma, decidua from early pregnancy, and in vitro decidualized endometrial cells by medroxyprogesterone acetate (MPA). Although no hybridized band was found in the proliferative and secretory phase endometria, a specific band of 5 kilobases, in agreement with the size of human prepro-EGF messenger ribonucleic acid, was detected in decidua of early pregnancy as well as in in vitro MPA-induced decidual cells. In situ hybridization revealed that prepro-EGF messenger ribonucleic acid was observed in the stromal cells of decidua. These results demonstrate that the EGF gene is expressed in the process of decidualization, suggesting that EGF may play an important role in the decidualization process of human endometrium.

Blotting, Northern↗

Establishment and characterization of carcinosarcoma cell line of the human uterus.

BACKGROUND: The histogenesis of carcinosarcoma is still unknown. METHODS: A new human uterine cell line, EMTOKA, derived from a carcinosarcoma of the uterus, has been passed successfully in cell culture for more than 2 years. The cell line was established on April 11, 1989, in a uterine tumor of a 64-year-old Japanese woman who had a simple hysterectomy. The pathologic examination of the cultured material showed papillary and tubular adenocarcinoma (carcinomatous elements) and spindle-shaped fiber cells and chondrosarcoma (sarcomatous element). RESULTS: The cultured cells showed a cell-to-cell variability and at least five cell types, which included columnar cell, small epithelial cell, moderately sized or large epithelial-like cell, malignant tumor giant cell, and spindle cell types. The EMTOKA cells were transplantable to nude mice and produced tumors that consisted of the same carcinomatous and sarcomatous elements as those observed in the original tumor. The double labeling analysis of vimentin and cytokeratin showed that a large number of cultured cells had positive results for vimentin and a small number of cells had positive results for cytokeratin. Only a very small number of EMTOKA cells stained for vimentin and cytokeratin. The number of cells that expressed neither vimentin nor cytokeratin was very low. CONCLUSIONS: These findings may support the hypothesis that a uterine carcinosarcoma may be derived from a single stem cell that does not express both of the intermediate filaments.

Animals↗

Occult hyperprolactinemia in infertile women.

OBJECTIVE: To define the hypersensitive status of PRL secretion in normoprolactinemic infertile women and determine the incidence of occult hyperprolactinemia among them. DESIGN: The potential for PRL secretion was examined in 463 women. SETTING: Outpatient clinic in a university hospital. PATIENTS: Three hundred sixty-seven infertile women and 96 healthy volunteers. INTERVENTIONS: Patients were treated with bromocriptine, 2.5 or 5 mg/d for 3 months. MAIN OUTCOME MEASURES: Prolactin response to thyrotropin-releasing hormone (TRH), circadian rhythm, and serum PRL changes during the menstrual cycle. RESULTS: Approximately 15% of infertile women showed an exaggerated response to TRH, and 95% among them had clinical disorders such as galactorrhea, luteal insufficiency, and menstrual disturbances. Bromocriptine proved effective in 90% of these women. Transient hyperprolactinemia was observed at night in 80% of normal PRL responders who had galactorrhea. Bromocriptine was effective in 75% of these women. Transient hyperprolactinemia during the menstrual cycle was observed in 43% of normal PRL responders with luteal insufficiency, 85% of whom responded to treatment with bromocriptine. CONCLUSION: In infertile women, the TRH test helps in the selection of patients who may respond to bromocriptine. Among normal PRL responders, 60% of patients with galactorrhea and 47% of those with luteal insufficiency recovered after bromocriptine treatment. From these results, patients who exhibit clinical abnormalities such as galactorrhea and luteal insufficiency should undergo extensive PRL testing.

Adult↗

Antiendometrial autoantibodies are generated in patients with endometriosis.

PROBLEM: Our aim was to investigate endometrial antigens involved in the autoimmunity of endometriosis. METHOD: We detected endometrial antigens against which autoantibodies directed with Western blotting. RESULTS: Thirteen (72.2%), 14 (77.8%), and 15 (83.3%) of 18 serum samples from endometriosis patients had antibodies reactive against endometrial antigen wtih MW of 26 kd, 34 kd, and 42 kd, respectively, while 6 (33.3%), 8 (44.4%), and 8 (44.4%) of 18 samples from normal control women reacted against these antigens, respectively. The frequencies of antibodies to the endometrial antigens were significantly (P < 0.05) higher in the endometriosis patients than in the normal control women. Antibodies in peritoneal fluid (PF) reacted against antigens with MW of 26, 34, 38, 42, and 64 kd, while those from the normal control reacted against antigens with MW of 38, 42, and 64 kd. Serum samples from normal fertile males did not show any reactivity against these endometrial antigens. CONCLUSIONS: Our results show that autoantibodies reactive against endometrial antigens are present in patients with endometriosis.

Adult↗

Ontogenesis and distribution of epidermal growth factor immunoreactivity and binding activity in the mouse fetal and neonatal tissues.

Epidermal growth factor (EGF) immunoreactivity, EGF binding activity, and their ontogenic changes were investigated in placenta, amnion, and various organs of mouse fetus and neonate. EGF immunoreactivity was detected in all organs examined such as fetal and neonatal liver, brain, lung, intestine, placenta, and amnion. The fetal tissues having relatively higher EGF content were amnion, liver, and intestine. The tissue distribution of EGF immunoreactivity in the fetus did not differ from that in neonate. As for its ontogenesis, EGF immunoreactivity was almost constant during fetal development in liver, brain, and placenta, whereas it gradually increased in intestine. Scatchard plot analysis of EGF receptor, which was also demonstrated in all organs studied, revealed that EGF receptor in these tissues showed curvi-linear profile and its affinity was very high. Unlike EGF immunoreactivity, EGF binding activity showed tissue distributional difference between fetus and neonate except skin; EGF binding activity was relatively high in heart, kidney, lung, and intestine in the fetus, whereas it was high in liver, kidney, heart, and lung in the neonate. As for its ontogenesis, EGF receptor increased in liver as gestation proceeded, while it decreased in intestine. These results suggest that the biological importance of EGF in fetal development may be variable among fetal organs despite the ubiquitous existence of EGF and its receptor in many fetal tissues.

Animals↗

Immunological modulation of lymphocyte subpopulation in cervical cancer tissue by sizofiran and OK-432.

The intimate correlation between marked lymphocyte infiltration in the cancer tissue and the superior clinical prognosis has been reported in human cancers. Sizofiran (SPG), a polysaccharide consisting of beta-1,3-D-glucopyranosyl linkage with beta-1,6-D-glucopyranosyl branches, or OK-432, a heat- and penicillin-treated, lyophilized preparation of the Su strain of Streptococcus pyogenes of human origin, was administered intratumorally to nine patients with advanced uterine cervical carcinoma before radical hysterectomy to assess their immunological modulating properties to tumor-infiltrating lymphocyte subpopulations immunohistochemically. The degree of infiltration of CD3- and CD5-positive cells increased moderately or markedly in the stroma surrounding the lesion in both SPG group and OK-432 group, as well as that of CD4- and CD8-positive cells, from that before administration. The density of infiltration of CD3-positive, CD4-positive, and CD8-positive cells in the lesion increased slightly or moderately in both groups after administration. As for CD16-positive cell infiltration, both SPG and OK-432 increased its degree in the stroma lining the lesion while SPG alone augmented its degree in the lesion. This augmentation of lymphocyte infiltration in situ induced by intratumoral administration of SPG and OK-432 is expected to lead to a favorable prognosis of patients with cervical cancer.

Adult↗

Mechanisms involved in the pituitary desensitization induced by gonadotropin-releasing hormone agonists.

OBJECTIVE: We investigated the mechanisms of desensitization induced by gonadotropin-releasing hormone agonist in the pituitary. STUDY DESIGN: Effects of gonadotropin-releasing hormone agonist on the pituitary were studied in vitro and in vivo in the rat. In the clinical study serum luteinizing hormone was measured by radioimmunoassay with a polyclonal luteinizing hormone antibody (luteinizing hormone-radioimmunoassay) and by immunoradiometric assay with monoclonal luteinizing hormone antibodies (luteinizing hormone-immunoradiometric assay) during gonadotropin-releasing hormone agonist treatment. RESULTS: In the in vitro study bead-attached pituitary cells that were desensitized with a continuous infusion of 10(-7)mol/L gonadotropin-releasing hormone responded to 50 mmol/L K+. In the in vivo study gonadotropin-releasing hormone binding sites and rat luteinizing hormone beta-messenger ribonucleic acid in the pituitary decreased during gonadotropin-releasing hormone agonist treatment, but serum levels of rat luteinizing hormone did not decrease. In addition, a disparity between luteinizing hormone-radioimmunoassay and luteinizing hormone-immunoradiometric assay was demonstrated during gonadotropin-releasing hormone agonist treatment. CONCLUSION: Pituitary desensitization in response to gonadotropin-releasing hormone agonist may not be wholly receptor mediated and a nonreceptor process may be involved.

Animals↗

Biological monitoring of workers exposed to acetone in acetate fibre plants.

Concentrations of acetone in urine, alveolar air, and blood were measured by gas chromatography with flame ionisation detection for 110 subjects occupationally exposed to acetone (mean 372 ppm) in three factories. Significant relations were found between the time weighted average environmental concentration and the concentration in the biological samples. The strongest correlation was between the concentration of acetone in urine and the degree of exposure (r = 0.71, 95% CI 0.64-0.77). This suggests that urinary acetone concentration is the best biological index of occupational exposure to acetone.

Acetone↗

Health profiles of workers exposed to acrylonitrile.

The objective of this study was to reveal the health effects of acrylonitrile (AN) in seven Japanese acrylic fiber manufacturing factories. The study subjects were 157 AN-exposed male shift workers who had been exposed to AN for 17 years on the average and 537 control workers whose working conditions were similar to those of the AN-exposed workers. The seven factories were classified into two groups according to their AN exposure levels in 1987, and also into three groups on the basis of 1976 exposure levels. The most highly exposed group of subjects showed a mean AN concentration of 1.13 ppm by personal sampling. Medical examination failed to detect any health effects attributable to long-term exposure to AN, although the existence of some symptoms of acute irritation could not be completely ruled out. The results of this study may provide a "no observed effects level" for human on-the-job exposure with regard to the health effects examined here.

Acrylonitrile↗