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T Michimata

Publications and source records attributed to T Michimata.

At least 19 recordsLinked to original sources
PubMed2003

Decrease of T-helper 2 and T-cytotoxic 2 cells at implantation sites occurs in unexplained recurrent spontaneous abortion with normal chromosomal content.

BACKGROUND: In normal pregnancy, predominant type 2 cytokines help maintain pregnancy, and a T-helper (Th)1 type response is associated with unexplained recurrent spontaneous abortion (RSA). However, Th2 and T-cytotoxic (Tc)2 cells have not been localized at the implantation site in RSA. METHODS: Twenty-one cases with RSA were classified into RSA with normal chromosomal content (RSA-N, n = 10) and RSA with abnormal chromosomal content (RSA-A, n = 11). As a control, we selected 15 gestational age-matched cases of induced abortion with no history of spontaneous abortion. We immunostained paraffin-embedded decidual sections for a specific Th2 and Tc2 cell marker termed 'chemo-attractant receptor-homologous molecule expressed on Th2 cells (CRTH2)' and T-cell markers CD3 and CD8. The numbers and percentages of Th2 (CRTH2(+)CD8(-)CD3(+)) and Tc2 (CRTH2(+)CD8(+)) cells were compared between the decidua basalis and decidua parietalis. RESULTS: Th2 and Tc2 cells accumulated in the decidua basalis in normal pregnancy. Accumulation of Tc2 cells and both Th2 and Tc2 cells decreased in the decidua basalis in RSA-A and RSA-N respectively. The number and percentage of Th2, and Tc2 cells in the decidua parietalis were similar in normal pregnancy, RSA-A and RSA-N. CONCLUSION: Decreased Th2 and Tc2 cells at the implantation site may contribute to RSA-N.

Abortion, Habitual↗
PubMed2001

A novel surface molecule of Th2- and Tc2-type cells, CRTH2 expression on human peripheral and decidual CD4+ and CD8+ T cells during the early stage of pregnancy.

It has been demonstrated that pregnancy induces the immunomodulation of cytokine responses away from the Th1 paradigm and towards the Th2 paradigm. In this study, we examined the expression of CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2) on decidual CD4+ and CD8+ T cells during the early stages of pregnancy. Examination of the cytokine profile revealed that CRTH2 was expressed on CD4+-type-2 T helper (Th2-type) and CD8+-type 2 T cytotoxic (Tc2-type) cells. The percentages of CRTH2+ cells in CD3+/CD4+ T cells and CD3+/CD8+ T cells were significantly higher in the decidua than in the peripheral blood. These results indicate the significance of Th2- and Tc2-type cells of the decidua in the maternal immune system, presumably through their production of cytokines which may contribute to the maintenance of pregnancy.

Adult↗
PubMed2001

Characterization of NKT cells in human peripheral blood and decidual lymphocytes.

PROBLEM: To examine whether natural killer (NKT) cells are present in human pregnancy decidua. METHOD OF STUDY: We calculated the percentage of CD3+CD161+Valpha 24+-NKT cells in peripheral blood and early pregnancy decidua, and analyzed intracellular cytokines, interleukin (IL)-4 and interferon (IFN)gamma in NKT cells using flow cytometry. RESULTS: A distinct subset of CD3+ CD161+ lymphocytes expressing an invariant antigen receptor encoded by the Valpha24 and Vbeta11 segment was accumulated in the decidua. In pregnant subjects the percentages of NKT cells were significantly increased in the decidua compared with peripheral blood. Both NKT cells in the decidua and the peripheral blood had an ability to rapidly produce cytokine associated with Th1 (IFNgamma) and Th2 (IL-4). Interestingly, the percentages of IL-4 and IFNgamma producing NKT cells were significantly higher in the decidua compared with the peripheral blood. CONCLUSIONS: These findings suggest that NKT cells might control the Th1/Th2 balance by producing IL-4 and IFNgamma at the feto-maternal interface.

Adult↗
PubMed1999

Quantitative analysis of peripheral blood Th0, Th1, Th2 and the Th1:Th2 cell ratio during normal human pregnancy and preeclampsia.

We calculated the percentage of Th1, Th2, Th0 cells and the Th1:Th2 cell ratio of peripheral blood from normal pregnant subjects and preeclampsia patients using flow cytometry which can analyse both the surface marker, CD4, and intracellular cytokines, interleukin (IL)-4 and interferon (IFN)-gamma. In normal pregnancy, the percentage of Th1 cells was significantly lower in the third trimester, and the ratios of Th1:Th2 were significantly lower in the second and third trimester than in nonpregnant subjects. In contrast, the percentage of Th1 cells and the ratios of Th1:Th2 in preeclampsia were significantly higher than in normal third trimester pregnant subjects. The percentage of Th2 cells in preeclampsia was significantly lower than in third trimester of normal pregnancy. Additionally, peripheral blood mononuclear cells from these subjects and patients were cultured with phytohemagglutinin stimulation, and IL-4 and IFN-gamma concentrations were determined in the supernatant by enzymed linked immunosorbent assays. The percentage of Th1 and Th2, and the ratios of Th1:Th2 were correlated with cytokine (IFN-gamma and IL-4) secretion level. These results demonstrated that Th2 cells were predominant in the second and third trimesters of normal pregnancy, but Th1 cells predominated in preeclamptic patients.

Female↗
PubMed1999

Distribution of Th1, Th2, and Th0 and the Th1/Th2 cell ratios in human peripheral and endometrial T cells.

PROBLEM: To examine whether normal pregnancy involves type 2 T-helper (Th2) immune condition or not. METHOD OF STUDY: We measured the percentage of Th0, Th1, and Th2 and the Th1/Th2 cell ratios of human peripheral blood and endometrial T cells using flow cytometry, which can analyze both the surface marker CD3, and intracellular cytokines, interleukin 4 (IL-4) and interferon gamma (IFNgamma). RESULTS: No significant differences were found in the percentages of Th1, Th2, and Th0 and the Th1/Th2 cell ratios in the peripheral blood T cells of nonpregnant women and women in early pregnancy. On the other hand, the percentage of Th1 cells was highest during the proliferative phase of the endometrium, followed by the secretory phase and early pregnancy decidua. The percentage of Th2 cells was highest in early pregnancy decidua and lowest during the proliferative phase of the endometrium. The Th1/Th2 ratio was 147.48+/-96.68 during the proliferative phase of the endometrium, 37.74+/-21.33 during the secretory phase, and 1.31+/-0.48 in the early pregnancy decidua. CONCLUSIONS: These data indicate that Th1 cells predominate in the nonpregnant endometrium, especially during the proliferative phase, while Th2 cells predominate in early pregnancy decidua.

Adult↗
PubMed1996

Sex and age differences in soluble guanylate cyclase activity in human platelets.

Soluble guanylate cyclase is a key enzyme of nitric oxide (NO)-related intracellular signal transduction in platelets. In the present study, we investigated the effects of sex and age on the enzyme activity in human platelets. Soluble guanylate cyclase activity was determined by generation of cyclic GMP in platelet cytosol. No significant differences in the basal activity of soluble guanylate cyclase were observed between in men and women, and between in young and old subjects. However, soluble guanylate cyclase activity in response to sodium nitroprusside, an exogenous NO donor, was higher in young men than in young and old women. Furthermore, the enzyme activity was lower in old than in young men, but there were no differences in female platelets between from young and old subjects. The present data suggest that NO-related signal transduction system in the platelet is affected by sex and age, which, to certain extent, contributes to different sensitivity of human platelets.

Adult↗
PubMed1996

Nitric oxide-dependent soluble guanylate cyclase activity is decreased in platelets from male NIDDM patients.

To elucidate the underlying mechanisms of platelet dysfunction in diabetes mellitus, we examined the activity of soluble guanylate cyclase (sGC), a key enzyme in the nitric oxide (NO)-related signalling pathway, in platelets from NIDDM (non-insulin dependent diabetes mellitus) patients. The sGC activity was determined by measuring the amount of cyclic GMP produced in platelet cytosol. In the first study, we investigated the platelet sGC activity in untreated NIDDM patients without diabetic complications. In the male NIDDM patients, sodium nitroprusside (SNP) caused a significantly lower sGC response than that in age-matched control male subjects, while the enzyme activity of female diabetics did not differ from that in the controls. Secondly, we investigated effects of diabetic-associated factors on the enzyme activity in the male NIDDM patients. There was no difference in the SNP-stimulated sGC activity in platelets from male diabetics between with and without retinopathy. In the male diabetic patients with retinopathy, however, the platelet sGC activity was slightly increased by treatment with insulin. Interestingly, the changes in enzyme activity did not correlate with plasma glycosylated hemoglobin A1c levels in diabetic patients. The impairment of the NO-related signalling pathway may contribute to the platelet dysfunction observed in patients with diabetes mellitus.

Adult↗
PubMed1994

[TRH receptor-related signal transduction mechanism].

TRH receptor-related signal transduction mechanism in the pituitary cells and the central nervous system was reviewed. In pituitary cells, TRH binds to its specific receptor on the cell membrane, followed by hydrolysis of inositol phospholipids by activation of phospholipase C leading to an increase in inositol 1,4,5-trisphosphates (IP3) and diacylglycerol (DG). IP3 mobilizes intracellular Ca2+, which activates Ca2+ and Calmodulin dependent protein kinase (Ca-CaM kinase) and DG activates protein kinase C (PKC). Both Ca-CaM kinase and PKC phosphorylates several proteins in the nucleus, plasma membranes, and cytosol resulting in cell responses including hormone secretion and gene expression. Protein dephosphorylation is also involved in TRH action in the pituitary. In the central nervous system, TRH possesses different intracellular signaling systems, which vary with brain regions.

Animals↗
PubMed1992

Okadaic acid inhibits the release of TSH in response to TRH and K+ from rat anterior pituitaries.

The effects of okadaic acid, a non-phorbol-12-tetradecanoate-13-acetate (non-TPA)-type tumor promoter and a potent inhibitor of protein phosphatases, on thyroid-stimulating hormone (TSH) secretion from the rat anterior pituitary were examined. Preincubation of anterior pituitaries with okadaic acid caused a time- and concentration-related decrease in a subsequent thyrotropin-releasing hormone (TRH)-stimulated TSH secretion, whereas it did not cause any changes in basal secretion of TSH. In addition, okadaic acid inhibited a subsequent high K(+)-induced TSH secretion. In contrast, ionomycin-induced TSH secretion was not inhibited by pretreatment with okadaic acid. The present results suggest that okadaic acid may block the release of TSH by inhibition of Ca2+ influx through voltage-sensitive and/or receptor-operated Ca2+ channels.

Animals↗
PubMed1992

Thyroid hormone affects the hydrolysis of inositol phospholipids in the rat hypothalamus.

We have attempted to elucidate the effect of thyroid hormone on phospholipase C-linked inositol phospholipid hydrolysis in the rat hypothalamus. Hypothalamic slices of each animal, euthyroid control, hypothyroid, and thyroxine (T4)-supplemented hypothyroid rats were labeled with [3H]myoinositol in the presence of 5 mM LiCl, and then incubated for 60 min in KHG buffer containing either vehicle or 1 mM ouabain, a Na-K ATPase inhibitor. Hypothyroidism caused a significant increase in both basal and ouabain-stimulated accumulation of [3H]inositol phosphate ([3H]IP) in hypothalamic slices, whereas supplement with T4 to hypothyroid rats resulted in a complete restoration of hypothalamic [3H]IP formation to the value of euthyroid control. The present results indicate that thyroid hormone affects phospholipase C-linked inositol phospholipid hydrolysis in the hypothalamus, suggesting that negative feedback action of thyroid hormone may occur at a post-receptor site in the hypothalamus.

Animals↗
PubMed1992

Inhibitory effects of okadaic acid on thyrotropin and prolactin secretion from rat anterior pituitaries.

The present study was undertaken to elucidate the effects of okadaic acid, a potent inhibitor of protein phosphatases, on thyrotropin (TSH) and prolactin (PRL) secretion, and on the hydrolysis of inositol phospholipids in rat anterior pituitaries. Preincubation of anterior pituitaries with okadaic acid caused a dose dependent decrease in TRH- and K(+)-induced TSH secretion, whereas basal secretion of TSH was not affected by pretreatment with okadaic acid. In contrast, okadaic acid resulted in a marked inhibition in both basal, and TRH- and K(+)-stimulated PRL release from anterior pituitaries. In addition, pretreatment with okadaic acid caused a slight, but significant decrease in the formation of [3H]inositol phosphate ([3H]IP) in rat anterior pituitaries. The present study suggests that okadaic acid blocks the release of TSH and PRL by inhibiting Ca2+ influx and that inhibitory effects of okadaic acid on PRL release are, at least in part, due to the inhibition of inositol phospholipid hydrolysis.

Animals↗
PubMed1992

Thyroid hormones regulate the formation of inositol phosphate in response to thyrotropin-releasing hormone in rat anterior pituitaries.

The effects of thyroid hormones on TSH secretion and inositol phospholipid hydrolysis in response to thyrotropin-releasing hormone (TRH) in rat anterior pituitaries were examined. Experimental hypothyroidism caused a significant increase in [3H]inositol phosphate ([3H]IP) formation in response to TRH in rat anterior pituitaries with a concomitant elevation of blood TSH. In contrast, administration of thyroxine (T4) to hypothyroid rats resulted in a complete restoration of blood TSH and TRH-stimulated [3H]IP formation to the euthyroid control value. Furthermore, in vitro pre-treatment of anterior pituitaries with triiodothyronine (T3) produced a dose-dependent decrease in both TSH secretion and the formation of [3H]IP in response to TRH. These results indicate that thyroid hormones regulate TRH receptor-linked inositol phospholipid hydrolysis in the rat anterior pituitary, suggesting that negative feedback action of thyroid hormone occurs at post receptor event in the rat anterior pituitary, which may, to a certain extent, be responsible for the underlying mechanism of T3 inhibition of TSH secretion.

Animals↗
PubMed1991

Glucose affects the release of thyrotropin-releasing hormone from the rat hypothalamus.

We have attempted to elucidate the effect of glucose concentrations on the release of thyrotropin-releasing hormone (TRH), a brain neuropeptide possessing glucoregulatory function, from rat hypothalamic slices in vitro. Rat hypothalamic slices were preincubated for 60 min at 37 degrees C in Krebs-Ringer bicarbonate (KRB) buffer (pH 7.4) containing varying concentrations of glucose (10, 5, 2.5 and 1 mM), and then tissues were incubated in KRB buffer, followed by stimulation with 60 mM K+ or 1 mM ouabain. In addition, after inducing hypoglycemia by insulin administration in the rat, hypothalamic tissues were dissected out and preincubated in KRB buffer (10 mM glucose) and then incubated in fresh KRB buffer containing 1 mM ouabain. A decrease in the glucose concentration of incubation medium caused a dose-dependent decrease in both K(+)- and ouabain-stimulated TRH release from rat hypothalamic slices. Furthermore, the ouabain-stimulated TRH release from the hypothalamus of rats with insulin-induced hypoglycemia was significantly reduced (45% of control values; p less than 0.01). The present results indicate that in vitro and in vivo hypoglycemia resulted in a significant decrease in the release of TRH from the hypothalamus, suggesting that circulating glucose levels affect TRH release which, in turn, might be responsible for peripheral glucoregulation.

Animals↗
PubMed1991

Hypothyroidism inhibits the formation of inositol phosphate in response to carbachol in the striatum of adult rat.

The effects of hypothyroidism on the muscarinic cholinergic receptor-coupled inositol phospholipid hydrolysis in the adult rat brain were examined. Tissue slices of striatum, hippocampus, and cortex from either euthyroid or hypothyroid rats were labeled with [3H]myoinositol and incubated with carbachol, a muscarinic cholinergic agonist. In other experiments, crude plasma membranes of each brain region obtained from either euthyroid or hypothyroid rats were incubated with [3H]N-methylquinuclidinyl benzilate ([3H]NMeQNB), a muscarinic cholinergic antagonist, in the presence or absence of atropine. Carbachol produced a significant increase in [3H]inositol phosphate ([3H]IP) formation in each brain region in a dose dependent manner. Hypothyroidism caused a marked decrease in carbachol-stimulated [3H]IP formation in the striatum, whereas it did not affect the formation of [3H]IP in the cortex or hippocampus. In contrast, the affinity constant and the maximal binding of [3H]NMeQNB to plasma membranes in these regions were not changed by hypothyroidism. The present results suggest that thyroid hormones might participate in regulating the muscarinic cholinergic neurotransmission in the striatum of adult rat.

Animals↗
PubMed1990

Stimulation by a TRH precursor, TRH-Gly, of TSH and PRL secretion in rats: effect of starvation.

The hypophysial activities of a possible direct precursor of thyrotropin (TSH)-releasing hormone (TRH), TRH-Gly, were evaluated in estrogen, progesterone-primed rats under urethane anesthesia. Intravenous administration of TRH-Gly in doses of 2-200 micrograms caused a significant and dose-dependent increase in blood TSH and prolactin (PRL). The stimulatory activity of TRH-Gly was 170 to 400-times less potent than that of TRH. The lower potency was confirmed by the action of TRH-Gly on the anterior pituitary cells in vitro. In starved rats, TRH-Gly apparently stimulated TSH and PRL secretion in a dose-dependent manner, and the stimulatory activity increased in starved rats as compared to normal controls. TRH-Gly did not affect [3H-MeHis]TRH binding in pituitary plasma membranes. These data imply that large amounts of TRH-Gly may have significant biological activities and these are potentiated in the starved condition.

Animals↗
PubMed1989

Actinomycin D affects thyrotropin-releasing hormone-induced heterogeneous forms of glycosylated thyroid-stimulating hormone in rat anterior pituitary.

Actinomycin D and cycloheximide were used to clarify the tight relationship between protein synthesis and heterogeneous carbohydrate synthesis of rat pituitary thyroid-stimulating hormone (TSH) under thyrotropin-releasing hormone (TRH) stimulation in vitro. Rat anterior pituitaries were incubated with [3H]glucosamine in the presence of TRH, cycloheximide and actinomycin D at 37 degrees C for 3 and 6 h. The TSH fraction of pituitary homogenates was obtained using affinity chromatography coupled with anti-TSH globulin, and was analyzed by isoelectric focusing. Anterior pituitary in the presence of TRH showed heterogeneous components of [3H]glucosamine-labeled TSH with 6 different isoelectric points (components I-VI). Radioactivities of the components increased with the incubation period. Cycloheximide changed these heterogeneous components. Actinomycin D also caused a striking change in the heterogeneity of pituitary [3H]glucosamine-labeled TSH: components I and II decreased and components III and IV increased as compared to the control group after a 6-hour incubation. The present study implies that actinomycin D affects the TRH-induced heterogeneous components of pituitary TSH glycosylation. The data indicate that messenger RNA is essential for the normal processing of carbohydrate synthesis of pituitary TSH.

Animals↗
PubMed1989

An analogue of thyrotropin-releasing hormone, DN1417, decreases naloxone binding in the rat brain.

We explored whether thyrotropin-releasing hormone may affect opioid receptors in the rat brain. Adult male rats were intraperitoneally injected twice a day with varying doses of DN1417, a potent analogue of thyrotropin-releasing hormone, for 2 days, and opioid receptors of the brain (hypothalamus, striatum, hippocampus, midbrain, ponsmedulla, and cortex) homogenates were determined using [3H]naloxone. Intraperitoneal injection of DN1417 in a dose of 0.3 mg/100 g body wt resulted in a significant reduction in naloxone binding of the striatum as compared with the saline-injected group, whereas naloxone binding of other brain regions was not affected by DN1417. DN1417 produced a dose-dependent decrease in naloxone binding of the striatum. The affinity constant of naloxone binding was similar between the saline- and DN1417-injected groups. In vitro addition of DN1417 did not interfere with the brain naloxone binding. The distribution of 3H-labeled DN1417 injected peritoneally did not differ among the brain regions. The present data imply that the opioid antagonistic action of thyrotropin-releasing hormone may be due, at least in part, to the significant decrease in the striatal opioid binding in the rat brain.

Animals↗