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Biomedical subjects

M Mikuni

Publications and source records attributed to M Mikuni.

At least 37 records · Page 2Linked to original sources

Seminoma in a postmenopausal woman with a Y;15 translocation in peripheral blood lymphocytes and a t(Y;15)/45,X Turner mosaic pattern in skin fibroblasts.

We report an unusual case of a 55 year old Japanese woman with a seminoma but relatively normal menses. The patient was a phenotypic female with late onset menarche (18 years of age), who was amenorrhoeic for the first year, followed by menses of one to three days' slight flow with dysmenorrhoea, but an otherwise normal menstrual history. A typical seminoma was removed from the left adnexal region and an immature testis was identified separately as an associated right adnexal mass. Repeated karyotypic studies on peripheral blood lymphocyte cultures showed only 46,X,-Y,t(Y;15)(q12;p13). Cytogenetic examination of the patient's younger brother, who had fathered three healthy children, showed an identical karyotype. Mosaicism of 46,X,-Y,t(Y;15)(q12;p13)/45,X cell lines was found in skin samples from the patient's elbow and genital regions, although there were no clinical stigmata of Turner syndrome. An androgen receptor binding assay of cultured genital skin fibroblasts was negative. Molecular analysis using Southern blot hybridisation, PCR, and direct DNA sequencing showed that neither the patient nor her brother had a detectable deletion or other abnormalities of Y chromosome sequences, including the SRY (sex determining region of the Y chromosome) gene sequence. These findings suggest that Turner mosaicism of the 45,X cell line may have contributed to this atypical presentation in an XY female, although we cannot exclude abnormalities of other genes related to sex differentiation.

Blotting, Southern↗

The transcription factor C/EBP-beta and its role in ovarian function; evidence for direct involvement in the ovulatory process.

Gonadotropins are responsible for maturation of the ovarian follicle and the oocyte. Ovulation is the ultimate step in this process and involves disintegration of the follicular wall and subsequent release of an oocyte into the oviduct. These events are triggered by a surge of luteinizing hormone (LH). Genes expressed in the ovary, that respond to LH, are likely to be involved in the biochemical pathways that regulate ovulation. The transcription factor C/EBP-beta is induced promptly in the ovary, as a response to an ovulatory dose of gonadotropins. We used an ex vivo perfusion system to demonstrate that a specific reduction in ovarian C/EBP-beta expression inhibits ovulation. In such ovaries the oocytes appeared to be entrapped within the follicle. We have found a correlation between the expression level of the activating isoform of C/EBP-beta and the number of oocytes ovulated in response to gonadotropins. Since a reduction in C/EBP-beta expression does not affect the level of the ovulatory mediator prostaglandin endoperoxide synthase-2 (PGS-2), these findings support the view of C/EBP-beta as an important factor in the ovulatory process and highlight a C/EBP-beta-dependent and PGS-2-independent pathway that takes part in regulation of ovulation.

Animals↗

Prenatal dexamethasone exposure alters brain monoamine metabolism and adrenocortical response in rat offspring.

In this study, it has been clearly demonstrated that prenatal dexamethasone treatment (Dex; 0.05 mg/kg on gestational days 17, 18, and 19) resulted in the significant reductions of 5-hydroxytryptamine (5-HT) turnover in four brain regions, including the neocortex, hippocampus, hypothalamus, and midbrain + pons-medulla (M + P-M) but not in the striatum in the offspring at 3 and 14 wk of life, as well as dopamine turnover in the hypothalamus. [3H]paroxetine binding densities were increased in the hypothalamus and M + P-M at 14 wk of life, which corresponded to increased 5-HT contents in both regions. On the other hand, significantly lower norepinephrine contents in the neocortex and hippocampus were observed in the Dex group compared with the control group at 14 wk of life. In addition, the exposure to new environmental condition elevated blood corticosterone levels and enhanced behavioral activities to a greater extent in the Dex group than in controls at 7 wk of life, suggesting that elevated glucocorticoid levels during the pregnancy mimicked prenatal mild stress, producing developmental alterations in brain monoamine metabolism, endocrine response, and behavior in adult offspring.

3,4-Dihydroxyphenylacetic Acid↗

Erythropoietin, granulocyte-colony stimulating factor, interleukin-1 beta and interleukin-6 during the normal menstrual cycle.

OBJECTIVE: Menstruation and ovulation are the main events during the menstrual cycle. Menstruation may influence the complete blood count because of its blood loss. Since ovulation is an inflammatory-like phenomenon, white blood cell count may change during ovulation. For these reasons, we have investigated the complete blood count and peripheral serum concentrations of associated cytokines during the normal menstrual cycle. MATERIALS AND METHODS: Normal healthy female volunteers (N = 9; age, 21-33 years) with menstrual cycles of 25-33 days recorded basal body temperature every day and venous blood samples were collected three times per week. Complete blood count was performed and erythropoietin, granulocyte-colony, stimulating factor, interleukin-1 beta, interleukin-1 beta, interleukin-6 and hormones (FSH, LH, estradiol and progesterone) were measured. RESULTS: The red blood cell, total white blood cell, granulocyte and platelet counts showed no statistically significant changes during the menstrual cycle when using analysis of variance with the Scheffe F-test. No changes in erythropoietin, interleukin-1 beta and interleukin-6 were seen throughout the menstrual cycle. In contrast, serum granulocyte-colony stimulating factor concentrations increased significantly to 28.0 +/- 3.1 pg/ml (mean +/- S.E.M.) during the ovulatory phase, compared to 10.7 +/- 0.6 pg/ml in other phases. CONCLUSION: These results indicate that menstrual blood loss does not affect the complete blood count and suggest that granulocyte-colony stimulating factor plays and important role in the mechanism of ovulation.

Adult↗

Cell-specific localization of nitric oxide synthases (NOS) in the rat ovary during follicular development, ovulation and luteal formation.

Nitric oxide (NO) has emerged as one of several important intraovarian regulatory factors. In particular, NO has been implicated in the processes of ovulation and atresia-related apoptosis. The aim of the present study was to investigate the presence and distribution of the NO-generating nitric oxide synthase (NOS) enzymes in the ovary during follicular development, ovulation and luteal formation of the equine chorionic gonadotrophin (ECG)/human chorionic gonadotrophin (HCG)-primed rat. NADPH diaphorase activity was used as a histochemical marker for NOS within the ovary. Diaphorase reactivity was most abundant in the stroma (S) of the ovary and in the theca (T) layer of the follicle. In luteinized ovaries, weaker diaphorase reactivity was present within the corpora lutea (CL). Two different isoforms of NOS, the constitutively expressed endothelial NOS (eNOS) and the inducible isoform of NOS (iNOS), were immunolocalized in ovaries of immature rats and in ECG/HCG-primed rats during the periovulatory period from HCG injection until 2 days after ovulation. In addition, ovarian concentrations of eNOS and iNOS were quantified by immunoblotting. Immunoblotting with a monoclonal anti-eNOS antibody demonstrated the presence of eNOS mainly in the residual ovary (ROV) during the periovulatory period. In luteinized ovaries, higher concentrations of eNOS were seen in CL, while those in the ROV at this stage were lower than in the periovulatory ovary. Immature ovaries contained diminutive amounts of eNOS, detectable mostly in the ROV compartment. In contrast, iNOS was barely detectable during follicular development to the preovulatory stage. A slight elevation of iNOS was observed in the granulosa cells at 6 h after the HCG injection. The levels of iNOS during the luteal phase were also low. Immunohistochemical analysis using polyclonal eNOS and iNOS antibodies revealed the localization of these two isoforms primarily in the S and the T of the periovulatory ovary. In luteinized ovaries, positive immunoreactivity was also seen within the CL. With a monoclonal antibody against eNOS, intense immunoreactivity was observed in the S, T and within CL. There was a particularly strong staining in blood vessels. These data demonstrate the presence of an intraovarian NO-generating system. The localization of this system to the S, T and CL suggests a role for NO in the ovulatory process and in the regulation of CL function.

Animals↗

Correlation between cytokine levels of amniotic fluid and histological chorioamnionitis in preterm delivery.

The aim of this study was to investigate the correlation between the cytokine levels in the amniotic fluid (AF) and the histological stage of chorioamnionitis (CAM) in premature labor. AF of 6 cases (7 samples of AF were obtained as one was a twin pregnancy) in whom CAM was diagnosed histologically, and 12 cases without CAM were included in this study. Amniotic fluid was obtained within 24 hours prior to delivery. Cytokine levels (IL-2, -4, -6, TNF-alpha, IFN-gamma) in AF were measured by an ELISA method. Levels of IL-2 and -6 in the CAM-positive group (mean +/-S.E., 52.9 +/- 83.9 pg/ml, and 20,537.9 +/- 8853.7 pg/ml, respectively) were higher than those in the CAM-negative group (i.e. undetectable, and 65.6 +/- 27.5, respectively) with a statistical significance of p < 0.05, p < 0.001, respectively. There was a positive linear relationship between IL-6 levels of AF and the placental histological inflammatory stages of Blanc in the CAM-positive group. From these results it would appear that the IL-6 level in AF is the most sensitive test in the detection of extraamniotic infection or intraamniotic infection in preterm labor with intact membranes and also indicates the severity infection.

Amniocentesis↗

Serotonin-induced 5-HT1A receptor desensitization in C6BU-1 glioma cells transfected with 5-HT1A receptor gene.

In this study, it has been clearly demonstrated that a selective 5-hydroxytryptamine (5-HT)1A agonist, 8-OH-2-(di-n-propylamino)-tetraline (8-OH-DPAT, 1 microM) significantly inhibited forskolin (10 microM)-stimulated cyclic AMP (cAMP) accumulation in the C6BU-1 cells transfected with 5-HT1A receptor gene. Further, this 8-OH-DPAT-induced inhibition of forskolin-stimulated activity was significantly attenuated after pre-exposure to 5-HT (10 microM) for 12 h. Spiperone (10 microM), a 5-HT1A and 5-HT2A antagonist, prevented 5-HT-induced desensitization of 5-HT1A receptor, but a selective 5-HT2A receptor antagonist, ketanserin, did not. In addition, pre-exposure to a selective 5-HT2A agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, 10 microM), for 24 h did not alter the inhibitory effect of 8-OH-DPAT on forskolin-stimulated cAMP accumulation in these transfected cells, suggesting that prolonged exposure to 5-HT induced 5-HT1A receptor desensitization, mediated by 5-HT1A receptor but not 5-HT2A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Regulation of synapse density by 5-HT2A receptor agonist and antagonist in the spinal cord of chicken embryo.

Identification of mechanisms that regulate the number of synapses in the brain has been a key issue for understanding the mechanism of plasticity. Here, we report that the density of synapses can be changed using an antagonist and/or an agonist of serotonin (5-HT) type 2A receptors in the chicken spinal cord. Because of the widespread distribution pattern of 5-HT fibers and 5-HT2A receptors in the central nervous system, 5-HT is thought to play a role in the formation and maintenance of synapses that are involved in normal brain function and mechanism of plasticity.

Amphetamines↗

Serum concentration of endogenous G-CSF in women during the menstrual cycle and pregnancy.

Although granulocyte-colony stimulating factor (G-CSF) is commonly used in the field of supportive therapy for cancer treatment, the serum concentration of endogenous G-CSF in healthy women is still obscure due to the low sensitivity (30 pg mL-1) of the usual enzyme immunoassay. With the development of a highly sensitive (1.0 pg mL-1) chemiluminescent immunoassay by Kiriyama et al., we have clarified the changes of serum G-CSF levels in healthy women during the menstrual cycle and pregnancy. The G-CSF concentration showed a peak value of 27.3 +/- 2.5 pg mL-1 (mean +/- SEM) at the ovulatory phase during the menstrual cycle, which is significantly higher than in all other phases (P < 0.0001, unpaired t-test). A significantly higher value compared to the menstrual cycle, except during the ovulatory phase, was also revealed throughout pregnancy (P < 0.0001, unpaired t-test). These results suggest that G-CSF plays an important role in ovulation and the maintenance of pregnancy.

Adult↗

[Effect of interleukin-2 and interleukin-6 on ovary in the ovulatory period--establishment of the new ovarian perfusion system and influence of interleukins on ovulation rate and steroid secretion].

Cytokines are not only mediators of inflammation and the immune system but are also important factors in cell proliferation, differentiation, and cell-to-cell communication. Cytokines have been identified within follicular fluid and some authors indicated that they are playing some roles in ovulation and ovarian steroidogenesis. Interleukin-2 (IL-2), mainly secreted by activated T-cells, influences other T-cells, B-cells, Macrophages, NKcells, etc. and is a major proliferating and differentiation factor of lymphocytes. Interleukin-6 (IL-6) is known to be secreted from and influence immune cells and/or non-immune cells such as fibroblasts, hepatic cells, endothelial cells, etc. The in vitro ovarian perfusion system has some advantages, compared with in vivo study, that is, it is devoid of systemic or unnecessary factors which are not focused on. In this study, the effects of IL-2 and IL-6 on ovulation and steroidogenesis were examined using the newly developed in vitro ovarian perfusion system and the culture of follicular granulosa cells. In the perfusion experiment, 100 ng/ml of IL-6 suppressed LH (100ng/ml)-induced estradiol (E2) secretion but did not influence progesterone (P4) secretion, while IL-2 had no effect on steroid secretion. Both IL-2 (100ng/ml) and IL-6 (100ng/ml) significantly suppressed LH-induced ovulation (ovulation rate; 8.3 +/- 1.5, mean +/- SE), to 2.2 +/- 1.1 and 3.2 +/- 1.0, respectively. Addition of 1.0, 3.0, 10 ng/ml of IL-6 decreased FSH (50ng/ml)-induced E2 secretion dose-dependently in the culture experiments of granulosa cells. IL-6 also suppressed FSH-induced P4 secretion in concentrations of 3.0 and 10 ng/ml. On the other hand, IL-2 concentrations of 10 and 30 ng/ml increased FSH-induced P4 secretion although 100 ng/ml of IL-2 showed no effect. Any dosage of IL-2 did not influence E2 secretion induced by FSH. All of these results obtained in the present study suggest that IL-2 and IL-6 may directly and/or indirectly suppress some mechanisms of ovulation, but with still unclarified different pathways.

Animals↗

Periodic maternal deprivation-induced potentiation of the negative feedback sensitivity to glucocorticoids to inhibit stress-induced adrenocortical response persists throughout the animal's life-span.

In this study, it was clearly demonstrated that the enhanced negative feedback sensitivity to glucocorticoids to inhibit stress-induced adrenocortical response, which was produced by periodic maternal deprivation (PMD) treatment for the first 3 weeks of life, did persist in rats tested at 66 and 92 weeks of life, suggesting that some stressful experience during early life permanently alters the adrenocortical response to stressful stimuli. This effect of PMD was not accompanied by an increased density of glucocorticoid receptor binding sites in the hippocampus from 93-week-old rats.

Adrenal Cortex↗

Effects of the altered serotonergic signalling by neonatal treatment with 5,7-dihydroxytryptamine, ritanserin or clomipramine on the adrenocortical stress response and the glucocorticoid receptor binding in the hippocampus in adult rats.

The aim of the present study is to investigate the effect of neonatal alterations in 5-HT signalling on the regulation of endocrine stress response in adult rats. The neonatal blockade of 5-HT transmission by 5,7-DHT or ritanserin treatment did not alter the density of glucocorticoid receptor (GR) binding sites in the hippocampus, although a 5,7-DHT-induced lesion was clearly shown to decrease in 5-HT content by greater than 80% in the hippocampus. In addition, the animals pretreated with the blockade of 5-HT transmission during early life did not exhibit a hyperresponsiveness of the adrenocortical response to stress. On the other hand, the neonatal administration of the 5-HT uptake inhibitor, clomipramine, was shown to lower the stress responsiveness of the adrenocortical axis in adulthood.

5,7-Dihydroxytryptamine↗

Periodic maternal deprivation alters stress response in adult offspring: potentiates the negative feedback regulation of restraint stress-induced adrenocortical response and reduces the frequencies of open field-induced behaviors.

The effects of periodic maternal deprivation (PMD) treatment on the adrenocortical stress response and on open-field behavior in adult offspring were investigated. Sprague-Dawley rat pups were deprived of mothers daily for 4.5 h during the first 3 weeks of life. PMD treatment resulted in lower corticosterone levels during restraint stress later in life. The result of dexamethasone suppression test indicated that PMD treatment caused a potentiation of the negative feedback function of adrenocortical response. These effects of PMD were not accompanied by an increased density of the hippocampal glucocorticoid receptor which has been reported to be induced in neonatal handling treatment (brief 15-min maternal deprivation). Serotonin (5-HT)-2 and beta-adrenergic binding sites were also examined in cerebral cortex and no change of binding capacities were induced by PMD treatment. In the open-field test, PMD treatment decreased the number of ambulations and rearings but did not affect a frequency of defecation. From these results, it is suggested that PMD treatment leads rats to be insensitive to environmental stimuli in adulthood.

Adrenal Cortex↗

Metabotropic glutamate receptor in C6BU-1 glioma cell has NMDA receptor-ion channel complex-like properties and interacts with serotonin2 receptor-stimulated signal transduction.

We found in cultured glioma (C6BU-1) cells that excitatory amino acids (EAAs) such as glutamate, N-methyl-D-aspartate (NMDA), aspartate, and metabotropic glutamate receptor agonist trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylate caused an increase in the inositol 1,4,5-trisphosphate formation and the intracellular Ca2+ concentration ([Ca2+]i) in the absence of extracellular Mg2+ and Ca2+. Pertussis toxin treatment abolished this glutamate-induced [Ca2+]i increase. Various antagonists against NMDA receptor-ion channel complex, such as Mg2+, D-2-amino-5-phosphonovalerate (D-APV), HA-966, and MK-801, also inhibited the increase in [Ca2+]i induced by glutamate. These results indicate that these metabotropic EAA receptors coupled to pertussis toxin-susceptible GTP-binding protein and phospholipase C system in C6BU-1 glioma cells have the pharmacological properties of NMDA receptor-ion channel complexes. We also found that in the presence of Mg2+ these metabotropic receptors resemble the NMDA receptor-ion channel complex interacted with 5-hydroxytryptamine2 (5-HT2) receptor signaling. EAAs inhibited 5-HT2 receptor-mediated intracellular Ca2+ mobilization and inositol 1,4,5-trisphosphate formation in a concentration-dependent manner. The inhibitory effect of glutamate was reversed by various NMDA receptor antagonists (D-APV, MK-801, phencyclidine, and HA-966), but L-APV failed to block the inhibitory effect of glutamate. The same result was observed in the absence of extracellular Ca2+. In addition, this inhibitory effect on 5-HT2 receptor-mediated signal transduction was abolished by treatment of C6BU-1 cells with pertussis toxin, whereas 5-HT2 receptor-mediated [Ca2+]i increase was not abolished by pertussis toxin treatment. We can, therefore, conclude that the inhibitory effect of glutamate is not a result of the influx of Ca2+ through the ion channel and that it operates via metabotropic glutamate receptors, having NMDA receptor-ion channel complex-like properties and being coupled with pertussis toxin-sensitive GTP-binding protein and phospholipase C.

2-Amino-5-phosphonovalerate↗

Differential effect of subchronic dexamethasone treatment on serotonin-2 and beta-adrenergic receptors in the rat cerebral cortex and hippocampus.

The effect of the 10-day dexamethasone administration on serotonin-2 (5-HT2) and beta-adrenergic receptor binding sites was evaluated in rat cerebral cortex and hippocampus. The dexamethasone treatment (1, 2 and 5 mg/kg) significantly increased the density of the 5-HT2 receptor binding sites in a dose-dependent manner, whereas a decreased density of beta-adrenergic receptor binding sites was observed in rat cortex. In contrast, there were no significant differences in the densities of the 5-HT2 or beta-adrenergic receptor binding sites in rat hippocampus using dexamethasone. The results suggest that dexamethasone differentially modulates the 5-HT2 and beta-adrenergic receptor binding sites in rat brain.

Animals↗