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Biomedical subjects

M Mikuni

Publications and source records attributed to M Mikuni.

At least 73 records · Page 4Linked to original sources
PubMed1990

[Evaluation of tumor marker in ovarian dermoid cyst].

Since ovarian dermoid cyst originates in parthenogenesis of the oocyte, it contains various kinds of tissues. Therefore, some tumor markers are expected to be positive. Clinical features of 174 pathologically confirmed dermoid cysts between Jan., 1985 and Aug., 1989 were reviewed, especially concerning tumor markers. The age of the patients was 11 years to 71 years (Mean 35.0 +/- 0.9 years). The weight of the dermoid cyst was 5g to 2.540g (mean 225.9 +/- 26.3g), while most of them were below 200g. The site of the tumors was similar on both the right and left. CA19-9 showed the highest positive rate of 45.5% (40/80). CA125 was second 12.7% (16/126) in markers with more than 20 examined cases, while the rate for AFP, Ferritin, CEA, LDH and TPA was 2.7% (3/110), 2.6% (1/38), 1.6% (2/128), 0.6% (1/161), 0% (0/24), respectively. SCC, IAP and beta 2-MG were examined in less than 20 cases and the positive rate was 18.8% (3/16), 9.1% (1/11) and 8.3% (1/12), respectively. There was no significant relationship between tumor weight and the CA19-9 concentration. In some cases, the serum CA19-9 concentration was followed up after the operation. The half life of CA19-9 was clinically estimated at 4.9 +/- 1.1 days.

Adolescent↗
PubMed1989

A neurochemical study of a new mutant mouse presenting myoclonus-like involuntary movement: a possible model of spontaneous serotonergic hyperactivity.

The involuntary movements resembling the serotonin (5-HT) syndrome induced by 5-HT agonist, which is composed with symptoms such as head twitch, hind leg abduction and so on, are neurochemically evaluated in the new mutant mouse, Wriggle Mouse Sagami (WMS). Ritanserin (5-HT2 antagonist) and prazosin (alpha 1-adrenergic antagonist) both inhibited the symptoms, had a decrease in the number of times they fell down and prolonged the duration of sitting up, while SCH 23390 (dopamine1 antagonist) and YM-0911-2 (dopamine2 antagonist) did not affect them. Metergoline (5-HT1 and 5-HT2 antagonist) suppressed the locomotor activity, making it difficult to determine if it ameliorated the symptoms. The concentration of a metabolite of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) was higher than control values diffusely in the CNS except in the cerebral cortex. The accumulation of 5-HTP after the administration of amino acid decarboxylase inhibitor NSD 1015 was significantly enhanced in the hypothalamus, median raphe, cerebellum and pons. An increase in 5-HT and NA was also noted in the cerebellum. GABA was increased in the striatum. In the binding assay, the number of [3H]ketanserin binding sites was increased and that of [3H]prazosin binding sites was decreased in the striata. Meanwhile, no significant difference was observed either in the number of binding sites (Bmax) or the affinity (KD) in the [3H]5-HT binding study. The number of [3H]muscimol binding sites in the cerebellum was reduced with the dissociation constant (KD) unchanged. These results suggest the involvement of 'hyperserotonergic' neural systems, possibly due to the enhanced 5-HT synthesis, in the manifestation of the involuntary movements of WMS, with noradrenergic and GABAergic modification. WMS can be a useful model to study the function of the serotonergic system in the CNS.

Animals↗
PubMed1989

Epinephrine stimulates inositol phospholipid metabolism by activating alpha-2 adrenergic receptors in human platelets.

The metabolism of inositol phospholipids in response to epinephrine was investigated in intact human platelets. In platelets prelabelled with [3H]-myo-inositol in Ca2+-free HEPES buffer containing 10 mM LiCl, epinephrine caused an accumulation of inositol-1-phosphate in a concentration-dependent manner. The EC50 value for epinephrine was 5 microM. Yohimbine (1 microM), a selective alpha-2 adrenergic receptor antagonist, inhibited 88% of the epinephrine (10 microM) response, whereas prazosin (1 microM), a selective alpha-1 adrenergic receptor antagonist, failed to inhibit the response. Yohimbine inhibited the epinephrine (10 microM) response in a concentration-dependent manner. The inhibition constant (Ki) value for yohimbine was 60.3 nM. These data indicate that epinephrine stimulates phosphoinositide (PI) turnover by activating adrenergic receptors of the alpha-2 type in human platelets. In addition, this PI response elicited by epinephrine was found to be inhibited in a concentration-dependent manner by treatment of platelets with dibutyryl cyclic AMP and 8-bromo-cyclic GMP which are known as potent inhibitors for platelet activation, and may therefore be a useful biochemical index for the study of the function of human alpha-2 adrenergic receptors.

Blood Platelets↗
PubMed1989

Stress adaptation and hypersensitivity in 5-HT neuronal systems after repeated foot shock.

The relationship between adaptation to stress and change in sensitivity of the 5-hydroxytryptamine (5-HT) neuronal system was studied in rats exposed to repeated foot shock stress for up to 10 days. Although hypolocomotion, freezing behavior and loss of weight were observed after in the initial stress, relief from these behavioral changes developed by the 3rd and persisted for another 7 days, indicating the development of stress adaptation. Following an IP injection of 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), rats exposed to the stress for 10 days, but not for 5 days, displayed enhanced forepaw treading, tremor and Straub tail compared to control rats. These results suggest that the hypersensitivity of the 5-HT system after repeated stress may be in part related to the neuronal mechanism of stress adaptation. However, since hypersensitivity was not observed after exposure for 5 days, when adaptation was maximal, it is proposed that the 5-HT system may participate in the maintenance of adaptation rather than its development. On the other hand, no change in 5-HT1, 5-HT1a and 5-HT2 receptor binding assays was found after chronic stress, suggesting that the hypersensitivity of 5-HT system may not be accompanied with changes in the numbers of 5-HT receptor binding sites. The results of beta-adrenergic receptor binding determined simultaneously were also discussed with reference to previous reports of stress-induced reduction in beta-adrenergic receptor density.

Adaptation, Physiological↗
PubMed1989

[The importance of uterine vascular systems in the maintenance of pregnancy].

The mesometrial artery (MA), which is the final part of the uterine artery in guinea pig, supplies nutrients and oxygen to the fetus and placenta during pregnancy. Accompanying fetal growth, MA increases 8-fold in diameter, and 30- to 50-fold in weight, protein content and deoxyribonucleic acid (DNA) content. The importance of MA in the maintenance of pregnancy was examined by comparing the proliferative rate of MA during pregnancy and abortion induced by antiprogesterone RU38486 30 mg/kg. MA was incubated in Medium 199 with 185kBq/ml 3H-thymidine for 4h and the rate of 3H-incorporation into MA was used as the proliferative rate. The proliferative rate of MA during the first trimester (day less than 20) was 2,825 +/- 1,036 Bq/mg.h, which is almost 100 times higher than the rate in diestrus animals. During the later course of pregnancy, the proliferative rate decreased logarithmically, being 352 +/- 58 (40 less than or equal to d less than 50), 158 +/- 23 (50 less than or equal to d less than 60) and 75 +/- 10 (60 less than or equal to d). The proliferative rate of MA was measured also in animals which received RU38486 30 mg/kg at 24-48 h prior to the measurement and whose fetuses were still alive. The proliferative rates of MA in such animals decreased markedly to 141 +/- 21 (40 less than or equal to d less than 50) and 37 +/- 8 (50 less than or equal to d less than 60) (p less than 0.01), which means that the proliferation of MA is reduced even before the death of the fetus.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Spontaneous↗
PubMed1987

[Mechanism of action of various psychotropic agents on serotonin receptors and the transmembrane signal control].

The effects of subchronic administration of various psychotropic agents on the density of 5HT 2 receptor binding sites in rat cerebral cortex were investigated. In addition to antidepressant agents, some neuroleptic drugs including chlorpromazine (CPZ), spiperon, and cisflupentixol reduced the numbers of 5HT-2 receptor binding sites after 21 days treatment. The more selective D-2 antagonist haloperidol and sulpiride were totally ineffective in this regard. Anxiolytic agents, benzodiazepine derivatives were also ineffective. Central 5, 7-DHT-induced lesion of 5HT neurons demonstrated that intact 5HT neurons were not required for the reduction of 5HT-2 receptors by desipramine (DMI). Co-administration of DMI and alpha-2 antagonist yohimbine (YOH) produced down-regulation of 5HT-2 receptors within 3 days, whereas each agent alone did not produce such effect. The effect of 3-day treatment with mianserin (MIA, alpha-2 and 5HT-2 antagonist) alone and DMI plus YOH producing 5HT-2 down-regulation, were not prevented by the pretreatment with DSP-4 which selectively destroyed NE neurons. These results suggest that the synaptic availability of 5HT may not be required for DMI-induced down regulation of 5HT-2 receptor binding sites, and the mechanisms mediated through postsynaptic alpha-2 and 5HT-2 receptors are important factors in the regulation of 5HT-2 receptor density. Evidence suggests that the 5HT-1 receptor site is functionally linked to adenylate cyclase in the brain, but a biochemical effector system which is linked to the 5HT-2 receptor site has not been found. The metabolism of inositol phospholipids in response to 5HT was, therefore, investigated in human platelets using sensitive radioisotopic method of Berridge (1983). In platelets prelabeled with 3H-myo-inositol, in Ca++ free HEPES buffer containing 10 mM LiCl, 5HT caused a dose-dependent accumulation of inositol-1-phosphate (IP1) during 15 min incubation. A maximal increase in IP1 formation was observed at 30 microM of 5HT and the EC50 value was 4 microM. Ketanserin, a selective 5HT-2 receptor antagonist was a potent inhibitor of 5HT-stimulated IP1 accumulation, with a Ki value of 12 nM, but a selective 5HT-1 antagonist, (-)-propranolol (1 microM) failed to block the 5HT response. These results indicate that 5HT is activating 5HT-2 receptors, but not 5HT-1 in human platelets. CPZ and imipramine inhibited 5HT-stimulated IP1 accumulation, with Ki values of 124 nM and 2.56 microM, respectively.

Animals↗
PubMed1986

Differential effect of subchronic treatment with various neuroleptic agents on serotonin2 receptors in rat cerebral cortex.

In addition to antidepressant drugs, some neuroleptic (NL) drugs reduce serotonin2 (5-HT2) receptor binding sites after chronic administration. The present study was undertaken to characterize further this property of NL drugs. Scatchard analysis of [3H]spiperone binding in rat cerebral cortex revealed that 21-day treatment with chlorpromazine (CPZ), cis-flupenthixol, and thioridazine reduced 5-HT2 radioligand binding density by 60, 27, and 18%, respectively. The more selective dopamine-D2 antagonists haloperidol and sulpiride were totally ineffective in this regard. No reduction in 5-HT2 ligand binding sites occurred after 1 day of treatment with CPZ but 3-days of treatment was effective and this reduction persisted, although diminished, for at least 72 h after the last injection. cis-Flupenthixol and d-butaclamol were also effective after 3 days of treatment but trans-flupenthixol and l-butaclamol were not, indicating stereo-specificity of the response mechanism. Female rats showed the same response to CPZ as did male rats. Central 5,7-dihydroxytryptamine-induced lesions of 5-HT neurons demonstrated that intact 5-HT neurons were not required for the reduction of 5-HT2 receptor ligand binding by CPZ. Since CPZ has high affinity for many receptors, including alpha 1, histamine1, and muscarinic receptors, the role of these effects in producing 5-HT2 receptor down-regulation was considered by studying the effects of prazosin, atropine, and pyrilamine administration on 5-HT2 radioligand binding. Results indicate that no one of these actions appears to account for the down-regulation of 5-HT2 receptors by CPZ. Several of these effects, in combination, or some unique mechanism, may be involved.

5,7-Dihydroxytryptamine↗
PubMed1984

Interaction of (+)- and (-)-3-PPP with the dopamine receptor in the anterior pituitary gland.

The interaction of the enantiomers of the novel dopamine agonist, 3-PPP (3-hydroxyphenyl)-N-n-piperidine) with the dopamine receptor in the anterior pituitary gland was examined. Both (+)- and (-)-3-PPP were effective in suppressing the elevation in serum prolactin (PRL) concentrations in rats treated with alpha-methyl-paratyrosine, an inhibitor of dopamine synthesis. The (+)-enantiomer was slightly more potent than the (-)-enantiomer in this regard. In addition, the secretion of PRL from anterior pituitary tissue under in vitro conditions was significantly inhibited by both isomers of 3-PPP, with (+)-3-PPP being approximately 10 times more potent than (-)-3-PPP. Both (+)- and (-)-3-PPP displaced 3H-(-)-N-n-propylnorapomorphine (3H-NPA) and 3H-spiperone from bovine anterior pituitary membranes. The Hill coefficients of (+)- and (-)-3-PPP for the displacement of 3H-spiperone were 0.6 and 0.7, respectively. These results are consistent with the view that the (+)- and (-)-enantiomer exhibit dopamine agonist effects at dopamine receptor sites in the anterior pituitary gland. However, (+)-3-PPP demonstrated marked differences in affinity for 3H-NPA- and 3H-spiperone labeled-sites, whereas (-)-)3-PPP showed the same order of affinity for these two sites. In view of these results and the fact that (-)-3-PPP has also been characterized as a dopamine antagonist at postsynaptic receptor sites in the striatum, (-)-3-PPP might be best described as a partial agonist at pituitary dopamine receptors. Moreover, these data are suggestive of a similarity, at least on a pharmacological basis, between dopamine autoreceptors and dopamine receptors in the anterior pituitary gland.

Animals↗
PubMed1984

Reduction of serotonin-2 receptors in rat cerebral cortex after subchronic administration of imipramine, chlorpromazine, and the combination thereof.

Combined administration of antidepressant and neuroleptic drugs has been reported to have a synergistic effect in the treatment of psychotic depression. The effects of subchronic administration of imipramine, chlorpromazine, or the combination, on serotonin 2 (5-HT2) receptors labeled by 3H-spiroperidol in rat cerebral cortex were studied to determine whether this synergism might be related to an effect on these receptors, which have been linked to the therapeutic action of antidepressants. Treatment with imipramine or chlorpromazine alone for 14 days decreased the density of 5-HT2 receptor binding sites in rat cortex; the combination of the two drugs produced a greater reduction in 5-HT2 binding sites than imipramine or chlorpromazine alone. Thus, the clinical synergism of this combination may be related, in part to the more extensive decrease in 5-HT2 binding sites it produces. The ability of chlorpromazine alone to decrease 5-HT2 binding sites might be relevant to reports that it has an independent antidepressant action.

Animals↗
PubMed1984

Influence of pimozide on hypothalamo-pituitary function in children with behavioral disorders.

Hypothalamo-pituitary functions were examined in thirteen children with behavioral disorders (six with hyperkinesia, four with autism, two with tic and one with schizophrenia) before and during treatment with pimozide, an antidopaminergic drug. The mean (+/- S.E.M.) basal serum PRL level (24.5 +/- 4.2 ng/ml) during pimozide treatment was significantly higher than that (12.4 +/- 3.2 ng/ml) before treatment. Hyperresponse of PRL to TSH releasing hormone (TRH) was observed in five (three with hyperkinesia, one with tic and one with autism) of the thirteen patients before treatment and in seven (four with hyperkinesia, two with autism and one with tic) during treatment. Mean TSH response during treatment was not significantly different from that before treatment. However, three of the four autistic children showed hyperresponse of TSH to TRH before treatment, whereas only one also showed a hyperresponse during treatment. The pimozide treatment had no demonstrable influence on GH or cortisol secretion in response to insulin-induced hypoglycemia, or on serum T4 and T3 levels.

Adolescent↗
PubMed1983

Effects of combined administration of imipramine and chlorpromazine on beta- and alpha 2-adrenergic receptors in rat cerebral cortex.

Administration of the combination of antidepressant and neuroleptic drugs has been reported to have a synergistic effect in the treatment of delusional depression. The effects of chronic coadministration of imipramine (IMIP) and chlorpromazine (CPZ) on beta-adrenergic and alpha 2-adrenergic binding sites in rat cerebral cortex were studied. The combination caused the same reduction in the number of beta-adrenergic receptors as IMIP alone. No changes in alpha 2-adrenergic receptors were observed with IMIP and/or CPZ.

Animals↗
PubMed1983

Effect of a novel benzamide, YM-09151-2, on rat serum prolactin levels.

YM-09151-2(cis-N-(1-benzyl-2-methylpyrrolidin-3-yl) -5-chloro-2-methoxy-4-methylaminobenzamide) is a new benzamide which has been reported to be an antagonist of dopamine (DA) at D1-type DA receptors. In the present study, we have examined the extent of the interaction of YM-09151-2 with D2-type DA receptors in the anterior pituitary gland of the rat. YM-09151-2 was found to be a potent antagonist of these receptors as extremely low doses of this compound produced a marked, dose-dependent elevation of serum prolactin concentrations. This benzamide was also a potent blocker of DA-induced inhibition of prolactin release in vitro and was very effective in displacing 3H-spiperone from bovine pituitary membranes: IC50, 1.04nM. These results are consistent with recent evidence that YM-09151-2 is also a potent antagonist of the D2-type receptors in the intermediate lobe of the rat pituitary gland.

Animals↗
PubMed1981

Circadian variation of cyclic AMP in the rat pineal gland.

This study was carried out to investigate circadian variation of cyclic AMP contents in the rat pineal glands, using the high-energy microwave radiation technique. The pattern of cyclic AMP concentration in the pineal gland showed a distinct circadian variation, with the maximum level at 0200 and the lowest at 1400. The administration of propranolol completely blocked the dark-induced increase in the pineal cyclic AMP level at 0200, and the administration of isoproterenol induced a threefold, rapid increase in the cyclic AMP level at 1400, although it did not change the level at 0200.

Animals↗