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M Takebayashi

Publications and source records attributed to M Takebayashi.

At least 19 recordsLinked to original sources
PubMed1997

Plasma levels of cyclic GMP, immune parameters and depressive status during interferon therapy. A prospective study in Japan.

In this report, we investigated the relationship between depressive symptoms and plasma interferon (IFN)-alpha-like immunoreactivity, cyclic GMP (cGMP) and soluble interleukin-2 receptor (sIL-2R) levels during IFN therapy. An altered mood state was observed in 5 of 26 patients. IFN-alpha-like immunoreactivity in the depressed group tended to be elevated. cGMP levels of depressed patients were significantly greater than those of control subjects before and 6 weeks after IFN therapy. However, sIL-2R levels were not different between the two groups. These results suggest that a number of patients suffered from depression during IFN therapy and that patients had greater concentrations of cGMP levels.

Aged↗
PubMed1996

gamma-Aminobutyric acid increases intracellular Ca2+ concentration in cultured cortical neurons: role of Cl- transport.

The effect of gamma-aminobutyric acid (GABA) on intracellular Ca2+ concentration ([Ca2+]i) in cultured prenatal rat cortical neurons was investigated using fluorescence imaging. GABA or muscimol, but not baclofen, increased [Ca2+]i in a dose-dependent manner. The GABAA receptor antagonists, bicuculline and picrotoxin, inhibited the GABA response. Furosemide, an inhibitor of the Na+/K+/2Cl- cotransporter, inhibited the GABA response in a noncompetitive manner. Ethacrynic acid, an inhibitor of an ATP-dependent Cl- pump, also inhibited the GABA-induced increased in [Ca2+]i. These results suggest a role for Cl- transport processes in the GABA response. The coapplication of GABA and high K+ led to a non-additive increase in the GABA response. The GABA response was also inhibited by nifedipine, a voltage-gated Ca2+ channel blocker, and abolished by the absence of extracellular Ca2+. Results indicate that the GABA response shares a common pathway of Ca2+ movement with the high K(+)-induced response. These observations suggest that the stimulation with GABA results in Ca2+ influx through voltage-gated Ca2+ channels, and that these effects are dependent on Cl- transport systems.

Animals↗
PubMed1996

Effect of citalopram on the desensitization of serotonin-2A receptor-mediated calcium mobilization in rat glioma cells.

1. The authors have investigated the effect of citalopram, an effective antidepressant drug with selective serotonin (5-HT) uptake inhibition, on 5-HT-2A receptor-mediated intracellular calcium (Ca2+) rise in C6 cultured cells. 2. Citalopram, at concentrations of 10 and 30 mu M, did not significantly reduce the Ca2+ mobilization induced by 10 mu M 5-HT, indicating that citalopram has little affinity for 5-HT-2A receptors. 3. Citalopram did not alter a subsequent response to 5-HT after citalopram was pre-applied to the cells. 4. However, citalopram inhibited the desensitization of 5-HT-2A receptors. When the cells were pretreated with citalopram and 5-HT, the subsequent response to 5-HT was significantly greater than that obtained following pretreatment with 5-HT alone. 5. To investigate the mechanism of action of citalopram on the desensitization of 5-HT-2A receptors, NaF-induced cGMP generation was measured. Citalopram inhibited the generation of cGMP induced by NaF in C6 cells as well as W-7. 6. These results indicate that citalopram antagonized the desensitization of 5-HT-2A receptor-mediated Ca2+ mobilization and this antagonism may be mediated by a calmodulin-dependent pathway in C6 glioma cells.

Animals↗
PubMed1996

Design and synthesis of C-linked fucosides as inhibitors of E-selectin.

Two series of C-linked fucosides as mimetics for the tetrasaccharide sialyl Lewis X have been synthesized and tested as inhibitors of E-Selectin. The fucopeptides have been prepared from three key intermediates, including alpha-C-allyl fucose, natural and unnatural amino acids bearing hydroxyl groups and an alpha, omega-diacid moiety for the imitation of the essential three parts of SLex, i.e., the Fuc, Gal, and NeuAc. The nature and distance of the linkage of the fucose moiety to the amino acids as well as the distance between the amino acids and the terminal carboxylic acid group turned out to be crucial for the biological activity. In addition the necessity of both OH groups (4- and 6-OH) in the Gal part could be confirmed. Conformational NMR study of the most active mimetic supports the structure-activity relationship. A second series of mimetics was prepared, where Fuc and Gal moieties were purely C-linked. In the synthesis of beta-C-allyl galactose an intramolecular 1,2-hydride shift led to an interesting side product. However, the substituted glycosidic oxygens led to a substantial loss of conformational constrain, which could not be compensated and resulted in low activity.

E-Selectin↗
PubMed1996

Differential regulation of intracellular signaling systems by sodium fluoride in rat glioma cells.

We investigated the rapid and slow effects of NaF on intracellular signaling systems such as Ca2+ homeostasis and cyclic GMP (cGMP) generation in rat glioma C6 cells, using the Ca2+-sensitive dye fura-2 and cGMP enzyme immunoassay. We found that the following: (a) NaF enhanced cGMP generation in a concentration-dependent manner. This enhancement was abolished by pretreatment with 100 microM BAPTA tetraacetoxymethal ester or in the presence of W-7 in a concentration-dependent manner. N G-Monomethyl-L-arginine (NMMA), a competitive inhibitor or nitric oxide synthase (NOS), also inhibited the NaF-induced generation of cGMP. These results suggest that NaF-induced cGMP generation occurs via a calcium/calmodulin- and NOS-dependent pathway. (b) The basal intracellular Ca2+ concentration ([Ca2+]i) was transiently greater at 1 and 3 h after pretreatment with NaF. W-7 and W-13 antagonized the increase in [Ca2+]i, whereas NMMA had little effect. This suggests that the NaF-induced change in basal [Ca2+] was mediated by a calmodulin-dependent pathway but was independent of a NOS-sensitive pathway. (c) The serotonin (5-HT)-induced intracellular mobilization of Ca2+ was reduced by pretreating the cells with NaF. The reduction in Ca2+ mobilization was antagonized by genistein, a tyrosine kinase inhibitor. W-7, W-5, and H-8 had no effect. Results suggest that NaF differentially regulated the cGMP generation. basal [Ca2+]i, and 5-HT2A receptor function in C6 glioma cells.

Animals↗
PubMed1995

Cyclic GMP generation mediated by 5-HT-2 receptors via nitric oxide-dependent pathway and its effect on the desensitization of 5-HT-2 receptors in C6 glioma cells.

Serotonin (5-HT)-2 receptor-mediated cGMP generation was investigated in comparison with calcium (Ca2+) mobilization in C6 glioma cells. 5-HT enhanced cGMP generation, and risperidone and ketanserin potently blocked the response. These results indicate that 5-HT-2 receptors are responsible for the cGMP generation. 5-HT-induced cGMP production was completely abolished by BAPTA, an intracellular Ca2+ chelating agent, or NG-mono-methyl-L-arginine(NMMA), a nitric oxide synthase (NOS) inhibitor, suggesting that 5-HT-induced cGMP generation was through nitric oxide (NO)-dependent pathway. 5-HT (10 microM)-elicited Ca2+ mobilization and cGMP generation were reduced to 40 and 15% after pretreatment with 10 microM 5-HT for 4 hours. NMMA did not modify 5-HT-induced desensitization of either Ca2+ mobilization or cGMP generation, suggesting that NO pathway is independent of the desensitization. The present study has demonstrated the nature of 5-HT-2 receptor-mediated cGMP generation in C6 glioma cells.

Animals↗
PubMed1995

Effect of acute treatment with sodium valproate on catecholamine and serotonin synthesis in mouse cerebral cortex.

We examined the effect of sodium valproate (VPA) on monoamine synthesis in the mouse cerebral cortex by measuring the accumulation of L-3,4-dihydroxyphenylalanine and 5-hydroxytryptophan following inhibition of aromatic L-amino acid decarboxylase. Treatment with VPA decreased catecholamine synthesis, in a dose-dependent manner, with maximum inhibition 60 min following treatment. Muscimol, a GABAA receptor agonist, also decreased catecholamine synthesis, although baclofen, a GABAB receptor agonist, did not. Picrotoxin, a GABAA receptor antagonist, inhibited the VPA-induced decrease in catecholamine synthesis. However, serotonin synthesis was not significantly changed by VPA. These results suggest that acute treatment with VPA reduces the synthesis of catecholamines via GABAA receptors.

Animals↗
PubMed1995

Modulation by sigma ligands of intracellular free Ca++ mobilization by N-methyl-D-aspartate in primary culture of rat frontal cortical neurons.

Despite substantial data on radioligand binding to the sigma receptor, neither the physiologic function nor the intracellular mechanism of this receptor is known. In this study, we examined the effect of sigma ligands on Ca++ influx induced by N-methyl-D-aspartate (NMDA) in single primary cultured rat frontal cortical neurons with fluorescence video microscopy. All sigma ligands tested reduced the NMDA-induced increase in intracellular Ca++ concentration ([Ca++]i) in a dose-dependent manner with IC50 values in the low micromolar range. Inhibition by haloperidol and (+)-N-cyclopropylmethyl-N-methyl-1,4-diphenyl-1-ethyl-but-3-en-1-ylam ine hydrochloride (JO1784) was noncompetitive; but, exogenous glycine (100 microM) did not alter their IC50 values. In addition, haloperidol (1 microM) enhanced Mg+(+)-mediated inhibition of the NMDA-induced [Ca++]i increase (IC50 = 0.45 +/- 0.01 mM vs. an IC50 = 0.98 +/- 0.06 mM for Mg++ alone). Selective sigma receptor ligands (JO1784, (+)-pentazocine) caused a greater reduction of the sustained phase of the Ca++ response to NMDA, whereas haloperidol and DTG reduced both the initial and sustained phase of the response to a similar degree. The rank order of potencies for inhibition of both the sustained Ca++ response phase and (+)-[3H]SKF-10047 binding (Roman et al., J. Pharm. Pharmacol. 42: 439-440, 1989) were similar. These findings suggest that sigma 1 ligands indirectly modulate NMDA receptor complex function through sigma 1 receptors and that sigma ligands facilitate the desensitization of the Ca++ response to NMDA.

Animals↗
PubMed1994

Local distribution of odor responsivities of mouse olfactory receptor neurons.

The local distribution of odor responsivity was studied in isolated mouse olfactory neurons retaining their original spatial relationships in intact tissue. The selectivity for three odorants and population of responsive cells were estimated from the odor-induced increase in cytoplasmic calcium. It was found that cells with different odor selectivities coexisted with a shorter distance than cells of the same type. Cells with a similar odor responsivity were arranged somewhat more densely than a complete random distribution. The results indicated the coexistence of different subtypes of odor responsive cells in the septal epithelium with sparse clustering of similarly responsive cells.

Animals↗
PubMed1994

Tuning specificities to aliphatic odorants in mouse olfactory receptor neurons and their local distribution.

1. Odor responses to two homologous series of n-fatty acids (nFA) and n-aliphatic alcohols (nAA) with a straight chain of three to nine carbons were examined by measuring odor-induced [Ca2+]i increase in mouse olfactory receptor neurons (ORNs) isolated by the tissue-printing method. 2. One-third of the ORNs responsive to nFA and/or nAA were alternately sensitive to either type of odorant. Their sensitivities were usually near maximal for one or two odorants and decreased with differences in the carbon chain length from the tuned odorants. 3. Two-thirds of the ORNs responsive to nFA and/or nAA were sensitive to both types of odorants. Most of them were also tuned to one or two odorants in each series with similar carbon chain lengths and showed a decrease of sensitivity with increasing stereochemical discrepancy, similar to nFA/nAA discriminating ORNs. 4. In 10 of 20 non-nFA/nAA discriminating ORNs, the sensitivity to nFA was > 10 times greater than to nAA, and 80% of them were localized in a central region of olfactory epithelium on the septum wall where ORNs preferentially project to the dorsomedial or centromedial regions of the olfactory bulb. In addition, the sensitivity to three series of n-aliphatic odorants with an added amino group was examined. Sensitivity became higher as the electronegativity of the functional groups increased, suggesting that a hydrogen bond might partly mediate affinity in one type of non-nFA/nAA discriminating ORNs. 5. The diversity in odorant tuning specificity and sensitivity of the individual ORNs indicated that their receptor sites were finely tuned to the stereochemical structures of numerous odorants by changes in the three-dimensional size and intermolecular positions of the hydrophobic domains for hydrophobic bond, as well as the proton-acceptor or donor for the hydrogen bond and the electrical charge for the ionic bond. 6. The subpopulation of ORNs tuned to an individual odorant increased as the length of carbon chain of the odorant increased from three to nine. This tendency was more marked for nFA than for nAA in the case of non-nFA/nAA discriminating ORNs. 7. Data obtained by the in vitro approach using the tissue-printing method suggested that three or more subtypes of ORNs, which were similar in some cases and significantly different in other cases, were located within close proximity to one another.

Animals↗
PubMed1992

Simultaneous recording of [Ca2+]i increases in isolated olfactory receptor neurons retaining their original spatial relationship in intact tissue.

A new method is described for isolating olfactory receptor neurons suitable for simultaneous recording of odorant responses in several cells. This method, called "tissue printing" by Cassab and Varner, was used to isolate cells for measurement of odorant-induced increases in cytosolic-free calcium concentration ([Ca2+]i) using the Ca2+ indicator dye fura-2. A large number of receptors could be isolated from a piece of olfactory epithelium (about 300 microns square), preserving their normal morphology and relative local topology to that in the intact olfactory tissue. The probability that there are one or more receptor cells with odorant-induced responses in [Ca2+]i per preparation was 4 times higher with cells isolated by the tissue printing than with those obtained by the pipetting method. The responses of 2 receptor cells separated by 28 microns in the recording chamber differed for 2 odorants: isoamyl acetate and citralva. The method was useful for isolating receptor neurons without losing their morphological features and for investigating the spatial distribution of odorant responsiveness of each receptor over the olfactory epithelium.

Animals↗
PubMed1992

Stimulants from gardeniae fructus for cultured endothelial cell proliferation.

Bioassay-guided fractionation of Gardeniae Fructus extract (GFE), which stimulates the proliferation of cultured endothelial cells, led to the isolation of glycerol and D-mannitol. Both compounds significantly increased the incorporation of [3H]thymidine and [14C]leucine into the acid-insoluble fraction of bovine aortic endothelial cell layers in culture. This clearly indicated that glycerol and D-mannitol are active components of GFE on endothelial cell proliferation. On the other hand, they did not change the number of cultured vascular smooth muscle cells from bovine aorta. Glycerol and D-mannitol may be beneficial drugs for vascular disorders.

Animals↗
PubMed1991

Two types of increases in free Ca2+ evoked by odor in isolated frog olfactory receptor neurons.

Olfactory transduction involves second messenger-related enzymes and cAMP-gated, K+ and Ca2+ channels, which are known to be regulated by Ca2+. We report here that cytosolic free Ca2+ concentration ([Ca2+]i) in olfactory receptor neuron was increased by odorants or forskolin and Ca2+ influx contributed to the adaptation. The increases in [Ca2+]i were below two to three-fold of resting level and transient for 26 s (mean value, n = 18). The increases were due to two pathways: Ca2+ influx and release. The slow increases in [Ca2+]i by forskolin resembled those by citralva. It was suggested that the responses to citralva were accompanied by increases in intracellular cAMP and Ca2+ influx or release leading to transient increases in [Ca2+]i.

Animals↗
PubMed1989

[Promoting effect of bile acids on gastric carcinogenesis induced by MNNG in rats].

The promoting effect of bile acids on the development of gastric carcinoma was examined in rats treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). At the first experiment, two hundred and fifteen male Wistar rats were divided into 5 groups; after oral administration MNNG (120 micrograms/ml) for 24 weeks, group 1 received tap water, group 2 administered of chenodeoxycholic acid (CDCA) solution, group 3 had deoxycholic acid (DCA) solution for the next 12 weeks. Group 4 received CDCA solution and group 5 received DCA solution for 36 weeks without MNNG. At the second experiment, fifty one rats were divided into 3 groups; for the first 12 weeks, group 1 received tap water, group 2 CDCA and group 3 DCA. These 3 groups received MNNG for the next 24 weeks followed by tap water for 12 weeks. The incidence of gastric adenocarcinoma in MNNG-treated rats was significantly higher in group 3 (63.6%) as compared with that in group 1 (36.7%) in the first experiment. No carcinoma lesions was found in groups 4 and 5. In the second experiment, no significant changes was observed among 3 groups. Undifferentiated adenocarcinomas were identified in groups 2 and 3, especially treated with MNNG plus bile acids. The result suggested a promoting effect of bile acids, especially DCA, in stomach carcinogenesis.

Adenocarcinoma↗
PubMed1987

Prognostic significance of lymph vessel involvement in gastric cancer.

We studied the prognostic significance of lymph vessel involvement in the gastric wall in 226 patients with advanced gastric cancer. There was no close correlation between the gross morphology of the cancer and the incidence of lymph vessel invasion. However, the more severe the degree of lymph vessel involvement, the higher was the incidence of lymph node metastasis. Severe lymph vessel invasion was found most frequently in poorly differentiated adenocarcinoma of the medullary type. Among patients with scirrhous carcinoma there were some in whom lymph vessel involvement was overlooked on routine histologic examination. Because the depth of lymph vessel invasion of the gastric wall was significantly related to the clinical course, we consider this to be of supplementary predictive value.

Carcinoma↗
PubMed1987

Pathological characteristics of gastric cancer that develop hematogenous recurrence, with special reference to the site of recurrence.

The pathologic characteristics of gastric cancer in 57 patients with hematogenous recurrence were pathologically analyzed by the site of recurrence. In recurrence of gastric cancer that developed in the liver, macroscopic observation revealed that cancers of Borrmann type 2 and 3 were most frequent. Microscopic examination revealed that the rate of occurrence of the medullary type of differentiated or poorly differentiated adenocarcinoma were high and that there were relatively frequent invasion by cancerous cells of the blood vessel that were closely related to the hematogenous metastasis. On the other hand, with respect to recurrence of gastric cancer that had developed in the lung or bone, Borrmann type 3 and 4, respectively, were more frequently observed. In these cases, microscopic analysis revealed that these cancers were poorly differentiated adenocarcinomas. In gastric cancer with bone recurrence, the rate of recurrence of the scirrhous type of tumor were higher than that of other types. It is important, for the management of patients after gastric cancer surgery, to predict possible hematogenous recurrence and its site by evaluation of the pathologic characteristics of the gastric cancer.

Adenocarcinoma↗