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Biomedical subjects

A Miyake

Publications and source records attributed to A Miyake.

At least 19 recordsLinked to original sources

Activin A increases cytosolic free calcium concentration in rat pituitary somatotropes.

The effect of activin A on the cytosolic free calcium concentration ([Ca2+]i) in normal rat pituitary cells was examined using a calcium sensitive fluorescent dye, indo 1 AM, and a digital imaging fluorescent microscope system. The cells showing an increase in [Ca2+]i in response to activin A were then characterized by comparison with cells responding to growth hormone releasing hormone (GRH), thyrotropin releasing hormone (TRH), corticotropin releasing hormone (CRH), and gonadotropin releasing hormone (GnRH) in monolayer cultures of normal rat pituitary cells. Activin A increased [Ca2+]i in some cells in a mixed population of normal rat pituitary cells. The cells that responded to activin A also responded to GRH. Most of these cells were not affected by other tropic hormones (CRH, TRH, and GnRH), but a few cells responded to both GRH and TRH. None of the activin A-responding cells responded to CRH or GnRH, and none of the CRH- or GnRH-responding cells responded to activin A. In a preparation of somatotropes purified 80-90% by fluorescence-activated cell sorting, activin A increased [Ca2+]i in 30% of the cells that shows a [Ca2+]i-response to GRH. These findings suggest direct involvement of somatotropes in activin A-induced biological events in the rat pituitary gland.

Activins

Relationship of age at menarche and subsequent fertility.

We investigated retrospectively the relationship between the age at menarche and reproductive ability in 2278 married women. Those who had a pregnancy experienced menarche at a mean age (+/- SEM) of 13.7 +/- 0.1 years, and those who were infertile had menarche at a mean age of 14.0 +/- 0.2 years, difference in the times of onset of menarche being significant (P less than 0.05). Moreover, a group in whom menstruation started after the age of 18 years had a significantly higher rate of infertility (15.7%) than the others (5.0%). Irregular menstruations during the first few years after menarche was also related to decreased reproductive ability. These findings indicate the importance of menarche before the age of 18 for normal reproductive functioning.

Adolescent

Regulation of intracellular Mg2+ by superoxide in amnion cells.

Changes of intracellular free Mg2+ concentration ([Mg2+]i) in human amnion cells induced by superoxide anion were determined using a highly Mg(2+)-sensitive fluorescent dye Mg(2+)-fura2 or Mg(2+)-indol. Superoxide anion, produced by addition of xanthine oxidase to hypoxanthine, induced decrease of [Mg2+]i. The decrease was significantly inhibited by an anion channel blocker, 4,4'diisothiocyano-2,2' disulfonic acid stilbene (DIDS). Superoxide dismutase (SOD), injected into cells by cell fusion, also inhibited the change of [Mg2+]i, but catalase did not. Superoxide anion induced prompt increase of intracellular pH (pHi) as well as decrease of [Mg2+]i and subsequently activated the increase of intracellular free Ca2+ ([Ca2+]i) and the release of arachidonate. In contrast to superoxide anion, NH4Cl which induces increase of pHi in amnion cells increased [Mg2+]i. The elevation of basal level of [Mg2+]i by Mg(2+)-ionophore inhibited the change of [Ca2+]i and the release of arachidonate induced by superoxide anion. These results suggest that superoxide anion, transported through anion channels into cells, decreases [Mg2+]i directly, not due to a pH-effect and that the decrease of [Mg2+]i may regulate biological functions of the cells via increase of [Ca2+]i.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid

Triplet pregnancy involving complete hydatidiform mole and two fetuses: genetic analysis by deoxyribonucleic acid fingerprint.

A case of a triplet pregnancy involving a dizygous twin pregnancy and a complete hydatidiform mole after therapy with human menopausal gonadotropin and human chorionic gonadotropin is reported. Two female fetuses, two placentas in one mass with two amnions and two chorions, and a tumor mass with a grapelike appearance were spontaneously delivered at 19 weeks of gestation. The deoxyribonucleic acid fingerprints of the two placentas and tumor tissue were compared with those of the parents. The fingerprints of the placentas showed patterns different from each other; however, all their polymorphic fragments could be traced back to either the father or mother. All polymorphic fragments of the tumor tissue were inherited only from the father (androgenesis). These results indicated that this triplet pregnancy involved a dizygous twin pregnancy and a complete hydatidiform mole.

Adult

In vitro and in vivo activities of SCE-2787, a new parenteral cephalosporin with a broad antibacterial spectrum.

SCE-2787, a new cephalosporin having a condensed azolium moiety in the 3 position and an aminothiadiazolyl group in the 7 beta side chain, was evaluated for its in vitro and in vivo activities in comparison with those of ceftazidime, flomoxef, cefpirome, and E1040. Against methicillin-susceptible strains of Staphylococcus aureus and Staphylococcus epidermidis, SCE-2787 was more active than ceftazidime and E1040 and was as active as flomoxef and cefpirome, with MICs for 90% of strains tested (MIC90s) being 1.56 micrograms/ml or less. SCE-2787 was also active against Pseudomonas aeruginosa, for which the MIC90 was 6.25 micrograms/ml, which was lower than that of cefpirome and comparable to that of ceftazidime. SCE-2787 was marginally active against methicillin-resistant strains of staphylococci and Enterococcus faecalis, although its MIC90s were the lowest among those of the antibiotics tested. The activities of SCE-2787 against Streptococcus species, most members of the family Enterobacteriaceae, and Haemophilus influenzae exceeded those of ceftazidime and flomoxef and were comparable to those of cefpirome. Furthermore, MIC90s of SCE-2787 were significantly lower than those of ceftazidime for ceftazidime-resistant isolates of Citrobacter freundii and Enterobacter cloacae. SCE-2787 was resistant to hydrolysis by various types of beta-lactamases, including the Bush group 1 beta-lactamases, and had low affinities for these enzymes, with Km or Ki values of greater than 100 microM. The in vitro activity of SCE-2787 was reflected in its efficacy in mouse protection tests. Thus, SCE-2787 appears to be a promising cephalosporin that should be further evaluated in clinical trials.

Animals

Binding sites for interleukin-6 in the anterior pituitary gland.

Interleukin-6 (IL-6) binding site in the rat anterior pituitary gland was characterized using radioiodinated human recombinant (hr) IL-6. Results showed that the anterior pituitary gland contained 170 binding sites per cell of a single class with a dissociation constant of 2.7 x 10(-9) M. The binding of 125I-hrIL-6 to the rat anterior pituitary gland was competitively inhibited by unlabeled hrIL-6, but not by hrIL-1 alpha, hrIL-1 beta, hrIL-2 or hr-interferon-gamma, indicating these binding sites are specific for IL-6. We also demonstrated mouse IL-6 receptor gene expression in the rat anterior pituitary gland by Northern blot analysis. Furthermore, the IL-6 receptor was detected on human gonadotrophs by the double immunofluorescence method. Our findings demonstrate the presence and expression of IL-6 binding site in the rat anterior pituitary gland and the presence of IL-6 binding site on human gonadotrophs, suggesting the important role of IL-6 binding site in pituitary hormone release in both species.

Animals

Atrial and brain natriuretic peptides enhance dopamine accumulation in cultured rat hypothalamic cells including dopaminergic neurons.

Dopamine accumulation in hypothalamic cells by atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was analyzed using newborn rat hypothalamic cells in culture. Both ANP and BNP caused a dose-dependent increase in [3H]-dopamine accumulation in the cells. ANP increased [3H]-dopamine accumulation significantly within 20 min. The effects of ANP and BNP on dopamine accumulation paralleled an increase in intracellular cGMP concentration. (Bu)2-cGMP and sodium nitroprusside, a stimulator of the soluble form of guanylate cyclase, also enhanced [3H]-dopamine accumulation. ANP had no effect on efflux of [3H] radioactivity after [3H]-dopamine uptake. These results suggest that a change in cGMP is one of the intermediate steps in dopamine accumulation in hypothalamic cells by ANP and BNP.

Animals

Hysteroscopic assessment of midsecretory-phase endometrium, with special reference to the luteal-phase defect.

To investigate the functional aspects of secretory-phase endometrium, hysteroscopy was performed in 61 patients for in vitro fertilization-embryo transfer (IVF-ET), and 50 women for infertility evaluation. All women had normal ovulatory cycles. The hysteroscopic assessment of secretory-phase endometrium was made by characterizing the glandular openings (GO) and vasculature. The assessments were classified as 'good': characterized by ring-type GO and well-developed vessels; and 'poor': characterized by dot and/or punctate-type GO and fine vasculature. In the 30 patients classified 'good' prior to the IVF cycle, there was a higher pregnancy rate (40%) than in 'poor' ones (13%). Thirty of 50 infertile women were classified 'good', and their average age was lower than that of the remaining 20 in the 'poor' group. Preovulatory estradiol was significantly higher in the 'good' than in the 'poor' group. From an analysis of 20 patients with a 'poor' assessment, it was demonstrated that the maturation of secretory-phase endometrium was affected by a failure of folliculogenesis, progesterone secretion, endometrial growth and menstrual shedding.

Adult

Immunohistochemical evidence that rat FSH cells contain beta II-subspecies of protein kinase C.

Immunocytochemical double-staining analysis revealed that in the rat anterior pituitary 86% of cells containing the beta II-subspecies of protein kinase C also contained follicle stimulating hormone (FSH), and that 22% of these FSH cells expressed the beta II-subspecies. These findings suggest a close relationship between the beta II-subspecies of protein kinase C and FSH regulation.

Animals

No inhibitory effects of gestrinone and medroxyprogesterone acetate on the estrogen production by ovaries of hypophysectomized rats stimulated by gonadotropins.

The in vivo effects of gestrinone (R2323) and medroxyprogesterone acetate (MPA) on the estrogen production by rat ovaries were investigated. Hypophysectomized immature female rats treated with 2.5 or 5 IU of pregnant mare serum gonadotropin (PMS) were daily given vehicle only, gestrinone (0.5 mg/kg body weight) or MPA (10 mg/kg body weight), and the activities of 3 beta-hydroxysteroid dehydrogenase, 17 alpha-hydroxylase, 17, 20-lyase, 17 beta-hydroxysteroid dehydrogenase and aromatase in ovaries of these rats were measured. Gestrinone suppressed the 3 beta-hydroxysteroid dehydrogenase activity and increased activities of 17 alpha-hydroxylase, 17, 20-lyase and aromatase in ovaries stimulated by 5 IU of PMS, while MPA suppressed activities of 17 alpha-hydroxylase and aromatase in these ovaries. On the other hand, the aromatase activity in ovaries stimulated by 2.5 IU of PMS was suppressed by gestrinone and increased by MPA, and neither gestrinone nor MPA affected the production of aromatizable androgens from progesterone by these ovaries. Thus, gestrinone and MPA administrated in vivo showed divergent influences on steroidogenic enzyme activities in ovaries, but they did not affect the serum concentration of estradiol-17 beta. The present results suggest that neither gestrinone nor MPA reduced estrogen production by the rat ovary under the gonadotropin stimulation although they influenced some process of its steroidogenesis.

17-Hydroxysteroid Dehydrogenases

Intraventricular administration of thyrotrophin-releasing hormone (TRH) suppresses prolactin secretion and synthesis: a possible involvement of dopamine release by TRH from rat hypothalamus.

The administration of thyrotrophin-releasing hormone (TRH) causes a variety of dopamine-related biological events. To understand the specific role of TRH on rat hypothalamic dopamine neurones, we examined the in-vivo effects of intraventricular (i.c.v.) infusion of TRH on the release and synthesis of prolactin in the rat pituitary gland and on the changes in binding of [3H]MeTRH and dopamine turnover rates in rat hypothalamus. We have also examined the in-vitro effects of TRH on the release of [3H]dopamine from dispersed tuberoinfundibular dopamine neurones. Female rats were treated with i.c.v. infusions of 1 mumol TRH/1 daily for 1, 3 and 7 days using Alzet osmotic pumps. Following 7 days of treatment the serum prolactin concentrations were significantly decreased. A reduction in hypothalamic TRH-binding sites (Bmax) was also apparent but the dissociation constant (Kd) was unaffected. Northern blot analysis of total RNA isolated from the pituitary glands of control animals using 32P-labelled prolactin cDNA as a probe indicated the presence of three species of prolactin gene transcripts of approximately 3.7, 2.0 and 1.0 kb in size, and these were decreased by TRH treatment. We examined the turnover rate of dopamine in the rat hypothalamus when TRH was administered i.c.v. for 7 days. There was a significant increase in 3,4-dihydroxyphenylacetic acid/dopamine ratio with TRH treatment. Moreover, exposure to TRH stimulated [3H]dopamine release from rat tuberoinfundibular neurones in a time- and dose-dependent manner. Dopamine receptor antagonists such as SCH23390 and (-)sulpiride, and other neuropeptides such as vasoactive intestinal peptide and oxytocin did not affect TRH-stimulated [3H]dopamine release.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid

Studies on condensed-heterocyclic azolium cephalosporins. III. Synthesis and antibacterial activity of 7 beta-[2-(2-amino-5-substituted-thiazol-4-yl)-2 (Z)-alkoxyiminoacetamido]-3-(condensed-heterocyclic azolium)methyl-3-cephem-4- carboxylates.

As a part of our research on the synthesis of cephalosporins bearing condensed-heterocyclic azolium groups at the 3 position in the cephalosporin nucleus, we describe herein the synthesis of 7 beta-[2-(2-amino-5-halogeno-, methylthio-, methylsulfinyl-, methylsulfonyl- and sulfothiazol-4-yl)-2(Z)-alkoxyiminoacetamido] cephalosporins and their antibacterial activity. Among the compounds prepared, 7 beta-[2-(2-amino-5-chlorothiazol-4-yl)-2(Z)- methoxyiminoacetamido]-3-(imidazo[1,5-a]-pyridinium-1-yl)methyl-3-cephem -4-carboxylate (14) showed good antibacterial activity against both Staphylococcus aureus including methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, whereas the antibacterial activity against other Gram-negative bacteria was a slightly lower than that of 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-methoxyiminoacetamido]-3-(im ida zo [1,2-a]pyridinium (I-1) and imidazo[1,5-a]pyridinium (I-4)-1-yl)methyl-3-cephem-4-carboxylates.

Anti-Bacterial Agents

Studies on condensed-heterocyclic azolium cephalosporins. IV. Synthesis and antibacterial activity of 7 beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)- alkoxyiminoacetamido]-3-(condensed-heterocyclic azolium)methyl cephalosporins including SCE-2787.

The synthesis and in vitro antibacterial activity of 7 beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-alkoxyiminoacetami do] cephalosporins bearing various condensed-heterocyclic azolium groups at the 3 position in the cephalosporin nucleus are described. The thiadiazolyl cephalosporins showed good antibacterial activity against both Gram-positive and Gram-negative bacteria and the MICs of the thiadiazolyl cephalosporins against Pseudomonas aeruginosa was more potent than that of the corresponding 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-alkoxyiminoacetamido]-3- (condensed-heterocyclic azolium)methyl cephalosporins. Also, the thiadiazolyl cephalosporins bearing (imidazo[1,2-b]-pyridazinium-1-yl)methyl groups at the 3 position showed antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Among the cephalosporins tested, 7 beta-[2-(5- amino-1,2,4-thiadiazol-3-yl)-2(Z)-methoxyiminoacetamido]-3-(imidaz o[1,2- b]pyridazinium-1-yl)methyl-3- cephem-4-carboxylate (4, SCE-2787) which exhibited the most potent antibacterial activity and the broadest antibacterial spectrum was selected as a parenteral cephalosporin candidate for further biological evaluation.

Cephalosporins

Studies on condensed-heterocyclic azolium cephalosporins. V. Synthesis and antibacterial activity of 3-(condensed-triazolo-pyridinium, -pyrimidinium, and -pyridazinium)-methyl cephalosporins.

As a part of our studies on cephalosporins bearing condensed-heterocyclic azolium methyl groups at the 3 position in the cephalosporin nucleus, we describe here the synthesis and antibacterial activity of 7 beta-[2-(2-aminothiazol-4-yl)2(Z)-methoxyiminoacetamido] cephalosporins (1-16, 7 beta-[2-(2-amino-5-chlorothiazol-4-yl)-2(Z)- methoxyiminoacetamido] cephalosporins (17,18) and 7 beta-[2-(5-amino- 1,2,4-thiadiazol-3-yl)-2(Z)-methoxyiminoacetamido) cephalosporins (19-23) containing a variety of condensed-heterocyclic triazolium methyl groups at the 3 position in the cephalosporin nucleus. These cephalosporins exhibited potent antibacterial activity, and it appears that condensed-heterocyclic triazolium as well as condensed-heterocyclic imidazolium rings are effective moieties for improving antibacterial activity and the spectrum of activity. Among the cephalosporins tested, 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-methoxyiminoacetamido]-3-(5- methyl[1,2,3]triazolo-[1,5-alpha]pyridinium-1-yl)methyl-3-cephem-4- carboxylate (9) and 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-methoxyiminoacetamido]-3-(6- methoxy[1,2,4]triazolo[1,5-alpha]pyridinium-1-yl)methyl-3-cephem-4- carboxylate (11) showed good antibacterial activity.

Cephalosporins

[Roles of calcium ion in reproductive physiology].

Physiological role and importance of calcium ion has been investigated based on the study of the mechanism of muscle contraction. Furthermore, calcium ion has been proved to have a wide variety of biological roles in hormonal secretion, cell proliferation and reproduction as well as in muscle contraction. In this lecture, I would like to show a method to measure intracellular calcium ion concentrations ([Ca2+]i) and to give a general information about the roles of calcium ion to induce various cell activities. Then I would like to talk about the changes in intracellular calcium concentration ([Ca2+]i) and their meaning in the field of reproductive physiology including uterine muscle contraction, pituitary LH secretion, and fertilization. 1) Uterine muscle contraction and calcium ion The function of calcium ion is most intensively investigated in muscle contraction. We show [Ca2+]i increase in cultured myometrial cells. This increase is inhibited by omission of extracellular calcium or addition of calcium channel blockers. These results support usefulness of Ca2+ channel blockers in treating threatened premature delivery. We also report the action of MgSO4 as an inhibitory agent of [Ca2+]i increase stimulated by oxytocin. 2) Pituitary gonadotropin secretion and calcium ion Pituitary LH secretion is regulated by gonadotropin releasing hormone (GnRH). GnRH induces rapid increases and then sustained releases of LH secretion. By the omission of extracellular calcium, or by addition of Ca2+ channel blockers, the sustained phase of LH secretion is abolished. GnRH also increase [Ca2+]i in a very similar manner to that of LH secretion. The [Ca2+]i increase is essential in LH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium

The novel natural product YM-26567-1 [(+)-trans-4-(3-dodecanoyl-2,4,6- trihydroxyphenyl)-7-hydroxy-2-(4-hydroxyphenyl)chroman]: a competitive inhibitor of group II phospholipase A2.

(+)-trans-4-(3-dodecanoyl-2,4,6-trihydroxyphenyl)-7-hydroxy-2-(4- hydroxyphenyl)chroman (YM-26567-1), a novel natural product isolated from the fruit of Horsfieldia amygdaline, dose-dependently inhibited group II phospholipase A2 (PLA2) prepared from rabbit platelet with an IC50 value of 6.7 microM (4.6-9.6 microM, n = 4). In contrast to irreversible PLA2 inhibitors such as manoalide and p-bromophenacyl bromide, the PLA2 inhibition of YM-26567-1 was independent of preincubation time. Lineweaver-Burk analysis revealed that YM-26567-1 behaved as a competitive inhibitor of rabbit platelet PLA2 with a Ki value of 1.6 +/- 0.3 microM (n = 5). Although YM-26567-1 also competitively inhibited group I PLA2 derived from porcine pancreas, the Ki value was approximately 10-fold greater for porcine pancreas than for rabbit platelet PLA2. In vivo, topical application of YM-26567-1 to the mouse ear inhibited 12-O-tetradecanoylphorbol-13-acetate (1 micrograms/ear)-induced mouse ear edema in a dose-dependent manner with a 50% effective dose of 28 micrograms/ear (13-63 micrograms/ear, n = 10/dose), but did not improve arachidonic acid (4 mg/ear)-induced mouse ear edema at 1 mg/ear. These results suggest that YM-26567-1 is a competitive PLA2 inhibitor showing a higher affinity for group II than group I PLA2, and that it may act as a potent anti-inflammatory compound through its direct inhibition of PLA2.

Animals

[Ultrastructural observation of eosinophils in bronchoalveolar lavage fluid in eosinophilic pneumonia].

To investigate the morphological changes of local eosinophils in the lungs, we observed the ultrastructure of eosinophils in bronchoalveolar lavage fluid (BALF) from patients with eosinophilic pneumonia. We also measured the BALF concentration of eosinophil cationic protein (ECP) as an index of the activation of eosinophils. The eosinophils in BALF from patients with eosinophilic pneumonia showed various ultrastructural changes compared to eosinophils in BALF of the control patient. Changes included degranulation or disintegration of specific granules, cytoplasmic vacuolation, increased lipid droplets and the appearance of Charcot-Leiden crystals. These changes of BALF eosinophils were more prominent than those of peripheral blood eosinophils. ECP concentration (mean +/- SD) in BALF from patients with eosinophilic pneumonia was 12.2 +/- 7.78 micrograms/l which was significantly higher than the concentrations in patients with bronchial asthma not during an attack (1.36 +/- 2.08 micrograms/l) and in healthy control subjects (2.14 +/- 4.62 micrograms/l). These results suggest that local eosinophils in the lungs are activated and degranulated by various stimuli and undergo structural degeneration in eosinophilic pneumonia.

Adult

[A case of gold lung with positive lymphocyte stimulation test to gold, using bronchoalveolar lymphocytes].

Gold lung, a gold-induced pneumonitis, is considered to be caused by hypersensitivity reaction to gold. We performed lymphocyte stimulation test (LST) to determine the response to gold, using lymphocytes obtained by bronchoalveolar lavage (BAL) from a patient with gold lung. A 57-year-old man was admitted with progressive shortness of breath following a skin eruption. He had been receiving weekly sodium gold thiomalate (Shiosol) for rheumatoid arthritis, with a cumulative dose of 485 mg. Chest roentgenogram showed diffuse interstitial infiltrates. LST for the response to gold, using peripheral lymphocytes, was positive. T cell lymphocytosis was observed in BAL, and transbronchial lung biopsy showed lymphocytic alveolitis and granulation tissue in alveolar ducts. From these findings, we diagnosed gold lung. Prednisolone (PSL) was started with an initial dose of 30 mg/day and resulted in a rapid improvement. As the dose of PSL was tapered, the patient's condition deteriorated and he was treated with a maintenance dose of 10 mg PSL. The second BAL revealed persistent lymphocytosis, and LST using bronchoalveolar lymphocytes for response to gold was positive. LST using peripheral lymphocytes was also positive, but was weaker than that using bronchoalveolar lymphocytes. This is the first report in Japan of a positive LST for response to gold, using bronchoalveolar lymphocytes from a patient with gold lung. This case suggests that the presence of activated lymphocytes against gold in the lung is cumulative, and that cell-mediated hypersensitivity is related to gold lung.

Arthritis, Rheumatoid