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Y Masuda

Publications and source records attributed to Y Masuda.

At least 397 records · Page 22Linked to original sources
PubMed1995

[Lewis-x, a sugar chain structure, suppresses the epileptic seizure in El mouse].

El mouse is a mutant strain with genetic epileptogenicity. Epileptic convulsion of El mouse has been shown to be related to metabolical and structural abnormalities in the hippocampal neuron. Gamma-globulin purified from the human serum has a marked anti-convulsive effect in El mouse. Human IgG, 80% of the gamma-globulin, has the reactivity indicating the presence of Lewis-x structure in the sugar chain. In the present study, the author found that 3'-fucosyllactose, the terminal structure of Lewis-x, suppressed the tonic-clonic convulsion of El mouse. Lewis-x is a ligand of granular membrane protein-140 on the surfaces of the vascular endothelial cell and platelet. The vascular endothelial cell and platelet produce platelet-derived growth factor-BB, which prolongs the life-span of the hippocampal neuron and accelerates the formation of its axon and dendrite. The vascular endothelial cell and platelet in El mouse may be activated by 3'-fucosyllactose, and may secrete platelet-derived growth factor-BB, which, in turn, may reduce the sensitivity to have epileptic convulsions in El mouse. Moreover, the author found that the fraction having Lewis-x reactivity obtained from the serum of El mouse had much reactivity of NeuAc alpha 2-6Gal. The sialic acid in Lewis-x structures of El mouse may reduce the ability of the Lewis-x structure to activate the endothelial cell and platelet. The findings in this study indicate that sugar chain structures and their metabolisms are closely related to the mechanism of genetic seizure susceptibility of El mouse.

Animals↗
PubMed1995

Modulation of extraluminally induced vasoconstrictions by endothelium-derived nitric oxide in the canine basilar artery.

The present study was undertaken to investigate the role of endothelium in extraluminally induced vasospasm of the cerebral artery using isolated perfused canine basilar arteries. The extraluminal applications of high K+ and prostaglandin F2 alpha (PGF2 alpha) induced concentration-dependent vasoconstriction. Both constrictive responses were significantly enhanced by denuding endothelium. Additionally, the responses in the endothelium-intact arteries were markedly augmented by intraluminal perfusion with NG-monomethyl-L-arginine (L-NMMA). These results suggest that the inhibition of nitric oxide (NO) synthase in endothelium enhances increase in transmembrane Ca(2+)-influx which is a common constrictive mechanism to the vasoconstrictors. The augmentative action induced by L-NMMA was inhibited by intraluminal perfusion of L-arginine, but not by D-arginine. Furthermore, the augmentation was not observed in the arteries without endothelium. These results suggest that the endothelium may have a great significance on responsiveness to extraluminal vasoactive substances and that endothelium-derived NO may modulate the extraluminally induced vasoconstriction which is responsible for cerebral vasospasm after subarachnoid hemorrhage.

Amino Acid Oxidoreductases↗
PubMed1995

[Effects of chronic ethanol intake on sugar chain structures of IgG in mice].

IgG is an N-glycosylated glycoprotein, and is secreted from B lymphocyte. Transferrin is also an N-glycosylated glycoprotein secreted from hepatic cell. We have investigated, by lectin-ELISA method, reactivities of sugar chain structures, which are Gal (beta 1, 4) GlcNAc, Fuc (alpha 1, 3 or 6) Gal, NeuAc (alpha 2, 6) Gal, galactose, poly mannoses and NeuAc (alpha 2, 3) Gal, in IgG or transferrin of ddY mice that were given ethanol solution for 3 weeks. In the investigation, we have found that the all reactivities of sugar chain structures in IgG and transferrin remarkably reduced. We have also found that Lewis-X (Gal (beta 1, 4) GlcNAc (3, 1 alpha Fuc)-), which is functional sugar chain structure in the IgG, was markedly reduced with dose-dependent manner. These findings indicate that ethanol decreases activities of glycotransferases in some cells which produce and secrete N-glycosylated glycoproteins. It has been reported that human erythrocyte has also N-glycosylated glycoproteins in the membrane, and its sialic acid and galactose are reduced after chronic ethanol intake. The past and present findings indicate that sugar chain structures of N-glycosylated glycoproteins in both serum and cell membranes are reduced after chronic ethanol intake. Though functions of sugar chain structures of N-glycosylated glycoproteins remain unclear, if functional structures like Lewis-X exist in N-glycosylated glycoproteins, the change of the sugar chain structures may have some relations to diseases occurring after chronic ethanol intake.

Alcoholism↗
PubMed1995

[Tissue retention of hydroxy and methylsulfonyl metabolites of 2, 2', 4, 4'-tetrachlorobiphenyl in rats].

Previously, we have identified a large number of methylsulfonyl metabolites in tissues of mink treated with Clophen A50. Most of them were found to be derived from CBs with a 2, 5-dichlorophenyl or a 2, 3, 6-trichlorophenyl ring. It is further necessary to investigate if CBs with a 2, 4-dichlorophenyl ring could be biotransformed to the sulfur-containing metabolites in animals. In the present study, 2, 2', 4, 4'-tetrachlorobiphenyl (TCB) was administered i.p. to rats, and liver, lung, kidney, adipose tissue and blood were analyzed for the unchanged CB and its metabolites. Both hydroxy and methylsulfonyl metabolites were detected in all tissues analyzed. Major metabolites were identified as 3-OH-2, 2', 4, 4'-TCB, 5-5-OH-2, 2', 4, 4'-TCB, 5-MeSO(2)-2, 2', 4, 4'-TCB and 6-MeSO(2)-2, 2', 4, 4'-TCB. Total level of the four metabolites was estimated to be 1.5 micrograms/g wet weight in the liver, corresponding to similar level of the unchanged CB. The concentration ratios of 3-OH- to 5-OH-TCB and 5-MeSO2- to 6-MeSO(2)-TCB were about 2:3 and 2:1, respectively, in liver and kidney. These results indicate that CBs with a 2, 4-dichlorophenyl ring can provide both hydroxy and methylsulfonyl metabolites that are retainable in tissues of rats.

Adipose Tissue↗
PubMed1995

[Preliminary studies on the retention of hydroxylated PCDF metabolites in rat blood].

We recently reported that certain hydroxylated PCB (OH-CB) metabolites were selectively retained in blood of rats experimentally dosed with PCB (Aroclor 1254), and also in blood of seals and humans environmentally exposed to PCBs. We also showed that metabolism in vivo of polychlorinated dibenzofurans (PCDFs) gave rise to a large number of hydroxylated PCDF (OH-CDF) metabolites, excreted in faeces, after oral administration to rats of PCDFs mixture (1, 2, 7, 8-tetraCDF 14%, 2, 3, 7, 8-tetraCDF 35%, 1, 2, 3, 7, 8-pentaCDF 48%). These results suggest that OH-CDFs could be present in blood. In the present study, potential retention of OH-CDF metabolites in blood (serum) was investigated in a female Wistar rat exposed to the PCDFs mixture. Serum was analyzed for the methylated OH-CDFs by gas chromatography (GC) and GC-mass spectrometry. Two major metabolites were determined in serum 1 day after oral administration. These were identified to be 3-OH-2, 4, 7, 8-tetraCDF (A) and 3-OH-2, 4, 7, 8, 9-pentaCDF (B) by comparison with synthesized reference compounds. 3-OH-2, 4, 7, 8-tetraCDF and 1, 2, 3, 7, 8-pentaCDF, respectively, via 3, 4(6, 7)-epoxide intermediate and subsequent NIH-shift of the 3(7)-chlorine to the 4(6)-position. The amounts of 3-OH-2, 4, 7, 8-tetraCDF and 3-OH-2, 4, 7, 8, 9-pentaCDF in the serum (5.72 g) analyzed accounted for 0.018% of 2, 3, 7, 8-tetraCDF and 0.003% of 1, 2, 3, 7, 8-pentaCDF dosed, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

[Change of PCDF and PCB concentrations in the blood of Yucheng and Yusho patients for 25 years].

The blood samples of 3 Yucheng patients collected 6-7 times from 1980 to 1993 and 5 Yusho patients collected 6-8 times from 1982 to 1993 were analyzed for congeners of polychlorinated dibenzofurans (PCDF) and polychlorinated biphenyls (PCB) by high resolution gas chromatography-mass spectrometry and gas chromatography-electron capture detection. In the blood of Yucheng patients, the high concentrations of 3 PCDF congeners, 2,3',4, 4',5-penta-CB and 5 PCB congeners were eliminated at half-lives of 2.4-2.9, 1.7 and 4.1-6.1 years, respectively, while in Yusho patients, 14 years after the incident, their half-lives were converted to longer times as observed 3.2-13.4, 24.0 and 13.7-34.2 years, respectively. In the same Yucheng and Yusho patients, the half-lives of the 5 PCB congeners were about twice longer than those of the 3 PCDF congeners. PCBs are more retainable than PCDFs in human blood.

Adult↗
PubMed1995

Effect of 2, 3, 4, 7, 8-pentachlorodibenzofuran and its analogues on induction of sister chromatid exchanges in cultured human lymphocytes.

We have been already contaminated with various chemicals including highly toxic organochlorine compounds such as 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), 2, 3, 4, 7, 8-pentachlorodibenzofuran (PenCDF) and 3, 4, 5, 3', 4'-pentachlorobiphenyl (Co-PenCB). In this study, in order to evaluate the genotoxicity of the three chemicals, we have examined their effects on the induction of sister chromatid exchanges (SCEs), which has been frequently utilized as an indicator of biological and genetic damage due to exposure to carcinogens or mutagens, in cultured human lymphocytes in the absence or presence of 7, 8-benzoflavone (ANF) and the following results were obtained. 1) TCDD, PenCDF and Co-PenCB significantly increased the frequency of SCEs with almost the same dose-dependent manner in terms of the concentration of TCDD toxic equivalent. 2) 8 x 10(-5) MANF significantly enhanced the frequency of SCEs and the simultaneous treatment of ANF and either of TCDD, PenCDF or Co-PenCB seemed to exert an additive effect as SCEs inducer. 3) TCDD, PenCDF and Co-PenCB were considered to be very potent inducers of SCEs, because their 50% effective concentration in SCEs enhancement were only 5 to 10 times higher than the level of the adipose tissue in healthy Japanese, namely, 70ppt as TCDD. Consequently, the respective TCDD toxic equivalency factors of 0.5 and 0.2 for PenCDF and Co-PenCB seemed to be reasonable so far as the induction of SCEs was employed as an indicator of the genotoxic potency.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Influence of five methylsulphonyl PCB congeners on frequency of micronucleated cells in cultured human lymphocytes by cytokinesis block method.

The lungs and blood of Yusho patients and healthy Japanese people have already been contaminated with methylsulphonyl polychlorinated biphenyls (MSF-PCBs) at relatively high concentration. Therefore, we should give due attention to their biological and toxicological effects to man. In this study, in order to mainly evaluate non-S-dependent genotoxicity of five MSF-PCB congeners, namely, 3-MSF-4, 5, 3', 4'-tetrachlorobiphenyl (TCB), 3-MSF-4, 5, 2', 3'-TCB, 3-MSF-2, 5, 2', 4', 5'-pentachlorobiphenyl (PenCB), 4-MSF-2, 5, 2', 3', 4'-PenCB and 4-MSF-2, 5, 2', 3', 5', 6'-hexachlorobiphenyl (HCB). We have examined their effects on the induction of micronucleated cells, which has been frequently used to estimate the dose of ionizing radiation and truly radiomimetic, non-S-dependent, clastogens, in cultured human lymphocytes in the absence or presence of 2, 3, 4, 7, 8-pentachlorodibenzofuran (PenCDF), 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) or 3, 4, 5, 3', 4'-pentachlorobiphenyl (Co-PenCB). The following results were obtained. 1) 4 x 10(-5) M7, 8-benzoflavone (ANF) significantly enhanced the frequency of micronucleated cells and all of the five MSF-PCB congeners failed to induce the formation of micronucleated cells at doses of 5.2 to 9.6 ppm, which were about 35,000 times higher than the concentrations in the lungs and adipose tissue of healthy Japanese people.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗
PubMed1995

Vasopressor effect of lysophosphatidic acid on spontaneously hypertensive rats and Wistar Kyoto rats.

Intravenous injection of lysophosphatidic acid (LPA, 1-acyl-sn-glycerol-3-phosphate) into conscious, spontaneously hypertensive rats (SHR) promptly elicited hypertension in a dose-dependent manner, its effect being significantly higher than in conscious, age-matched Wistar Kyoto strain rats (WKY). There was, however, no difference between the potencies of LPA in raising the mean blood pressure of SHR and WKY anesthetized with pentobarbital. The releases of norepinephrine, angiotensin II, prostaglandin and leukotriene were found not to be involved in the vasopressor effect of LPA in SHR, although thromboxane seemed to be slightly related to the action of LPA.

Animals↗
PubMed1995

[Relationship between static images of 13N ammonia positron emission tomography and left ventricular wall motion in patients with coronary artery disease].

Observed myocardial activities in static image of 13N ammonia positron emission tomography (PET) contains factors about not only myocardial blood flow but also wall motion, wall thickness and glutamine synthetase activity. Those factors may help to delineate myocardial viability in 13N ammonia static image. To assess the role of 13N ammonia static image in prediction of reversibility of regional wall motion abnormalities after revascularization, we studied 20 patients with coronary artery disease. Of these patients, 15 patients underwent successful coronary revascularization (8 PTCA, 7 CABG). Regional 13N concentration before revascularization was expressed as a percent of maximal myocardial concentration and compared with regional wall motion. Wall motion was assessed by visual analysis using left ventriculography. Regional myocardial 13N concentration in normal, hypokinetic, akinetic and dyskinetic segments was 85 +/- 9.3%, 75 +/- 11%*, 71 +/- 17%* and 58 +/- 7.7%*#+, respectively (*p < 0.05 vs. normal, #p < 0.05 vs. hypokinesis, +p < 0.05 vs. akinesis). The segments with functional improvement showed significantly higher concentration of 13N than those without functional recovery (80 +/- 9.7% vs. 67 +/- 8.3%, p < 0.05). By using an optimized threshold value for normalized 13N activities, the sensitivity and specificity reached to 67% and 100%, respectively, to predict functional recovery. Our data suggested that myocardial 13N concentration in static PET image is closely related to the left ventricular wall motion in the patients with coronary artery disease and that it has a possible value of prediction of myocardial viability.

Ammonia↗
PubMed1995

Studies on calcium antagonistic and alpha 1-adrenergic receptor blocking activities of monatepil maleate, its metabolites and their enantiomers.

The calcium antagonistic and alpha 1-adrenergic receptor blocking activities of monatepil maleate (CAS 103377-41-9, (+/-)-N-(6,11-dihydrodibenzo [b, e] thiepin-11-yl) -4-(4-fluorophenyl)-1-piperazinebutanamide monomaleate, AJ-2615), a novel calcium antagonist, its metabolites and their enantiomers were studied in vitro. Monatepil maleate inhibited calcium-induced contractions of rat thoracic aorta (pA2 = 8.71) and l-phenylephrine-induced contractions of rabbit superior mesenteric artery (IC50 = 56.6 nmol/l). The calcium antagonistic activities of the metabolites of monatepil maleate (AJ-2615-sulfoxide A, AJ-2615-sulfoxide B and AJ-2615-sulfone) were 1/10 of that of monatepil maleate. However, their alpha 1-adrenergic receptor blocking activities were similar to or slightly more potent than that of monatepil maleate. The potencies of the calcium antagonistic activities of monatepil maleate and its enantiomers [(S)-AJ-2615 and (R)-AJ-2615] were in the order of (S)-AJ-2615 > monatepil maleate > (R)-AJ-2615 whereas no difference was observed among them in alpha 1-adrenergic receptor blocking activity. In calcium antagonistic and alpha 1-adrenergic receptor blocking activities, there was no difference between the enantiomers of monatepil maleate metabolites. In conclusion, there was a difference with several times in calcium antagonistic activity between the two enantiomers of monatepil maleate but not in their alpha 1-adrenergic receptor blocking activity.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1995

A modified method for quantitative measurements of cholinergic and adrenergic sialogogue-induced salivation in mice.

A modified procedure based on that reported by Richter is described for the quantitative measurement of salivation induced by sialogogues in mice. As a new immobilizing technique for mice, the present method uses a combination of light anesthesia produced by a low dose (1.0 g/kg, i.p.) of urethane and a fixing plate, instead of deep anesthesia induced by a high dose (1.8 g/kg, i.p.) of urethane. Unlike Richter's method, the immobilizing technique described here did not potentiate the toxicity of sialogogues and hence no mice died within 48 h after the end of the experiment. This method could easily measure salivation induced by cholinergic agonists (pilocarpine and bethanechol) and adrenergic agonists (phenylephrine and isoproterenol), dose-dependently. Thus, the present method may be useful for studying salivation responses induced by various types of sialogogues under less toxic experimental conditions in mice.

Animals↗
PubMed1995

Effect of argatroban on the formation of artificial thrombus on dogs.

In the present study, we have investigated the effects of a synthetic antithrombin, Argatroban, and an antiplatelet agent. Ticlopidine hydrochloride, on the weight of artificial thrombus. These drugs at various concentrations were added to canine bloods, which were adjusted to 20%, 40% and 60% of haematocrit, and an artificial thrombus was formed using a modification of Chandler's method. Argatroban inhibited the formation of artificial thrombus, and this marked inhibition was observed especially in the experiment using blood with a high value of Ht. On the other hand, Ticlopidine hydrochloride did not inhibit the formation of artificial thrombus. From these results, it becomes clear that the mechanism of inhibitory action of Argatroban on artificial thrombus formation is based on the inhibition of thrombin activity and not on the inhibition of platelet aggregation. In addition, it is suggested that Argatroban inhibits the aggregation of red blood cells in the manner of direct or indirect action.

Animals↗
PubMed1994

Muscarinic receptor-mediated calcium efflux from cultured bovine adrenal chromaffin cells.

The effect of stimulation of the muscarinic receptor on Ca2+ mobilization in cultured bovine adrenal chromaffin cells was examined. Acetylcholine (ACh) increased the uptake of 45Ca2+ and [Ca2+]i whose levels decreased with time after reaching peaks. It also enhanced the efflux of 45Ca2+ from the cells. Its effect was inhibited by the specific muscarinic receptor antagonist atropine (Atr), but not by the nicotinic receptor antagonist hexamethonium (C6). The increase in muscarine (Mus)-stimulated 45Ca2+ efflux was reduced concentration-dependently by deprivation of extracellular Na+. These results suggest that muscarinic stimulation of the ACh receptor stimulates Na+/Ca2+ exchange in cultured bovine adrenal chromaffin cells.

Acetylcholine↗
PubMed1994

Dose escalation of biweekly cyclophosphamide, doxorubicin, vincristine, and prednisolone using recombinant human granulocyte colony stimulating factor in non-Hodgkin's lymphoma.

BACKGROUND: Several uncontrolled trials have suggested that dose intensity of chemotherapy is a crucial determinant of treatment outcome for patients with non-Hodgkin's lymphoma (NHL). To explore the possibility of increasing dose intensity, a dose-escalation study of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) using recombinant human granulocyte colony stimulating factor (rhG-CSF) was initiated. METHODS: First, the feasibility of standard dose CHOP (750 mg/m2 cyclophosphamide intravenously [i.v.] on Day 1;50 mg/m2 doxorubicin i.v. on Day 1; 1.4 mg/m2 vincristine i.v. on Day 1; and 100 mg/body prednisolone orally on Days 1-5) repeated biweekly at the original dose was assessed. rhG-CSF was given subcutaneously at doses of 2-5 micrograms/kg every day or every other day on Days 3-13. The safety of increasing the dose of cyclophosphamide during biweekly CHOP then was tested. Besides the standard dose (750 mg/m2), two dose levels of cyclophosphamide were set (1200 mg/m2 and 1500 mg/m2 in patients younger than 61 years of age, and 1200 mg/m2 in patients 61-75 years old). RESULTS: Twenty-seven patients with NHL who had received minimal or no previous treatment were enrolled in this study. In the 750 mg/m2 group, 9 patients received 3-6 cycles of treatment (mean, 3.9 cycles), in the 1200 mg/m2 group, 10 patients received 3-6 cycles (mean, 4.8), and in the 1500 mg/m2 group, all 8 patients received 6 cycles. No significant differences among the groups were observed in the extent and the duration of neutropenia in each cycle, and a leukocyte count of more than 3000/microliters on Day 15 was achieved in all 131 cycles. Hemoglobin values and platelet counts, however, decreased in the later cycles in the 1500 mg/m2 group. Two patients were hepatitis-B virus carriers, one of whom died of fulminant hepatitis after completion of six cycles. Another patient developed a transient increase of transaminases after the second cycle. One other patient developed Grade 4 mucositis (World Health Organization scale). The numbers of patients who achieved complete and partial responses, respectively, were 4 (50%) and 2 (25%) in the 750 mg/m2 group, 8 (80%) and 2 (20%) in the 1200 mg/m2 group, and 8 (100%) and 0 (0%) in the 1500 mg/m2 group. CONCLUSIONS: The dose of cyclophosphamide in biweekly CHOP can be increased up to 1500 mg/m2 with no increase in the incidence of treatment-related early mortalities without any organ damage in younger patients. The efficacy of this dose intensification of CHOP currently is being investigated in a multicenter prospective randomized trial using three different dose levels of cyclophosphamide.

Adult↗
PubMed1994

Inhibition by ouabain of palytoxin-induced catecholamine secretion and calcium influx into cultured bovine adrenal chromaffin cells.

The effect of ouabain on palytoxin (PTX)-induced catecholamine secretion from cultured bovine adrenal chromaffin cells was examined in relation to its effect on calcium (Ca2+) influx into the cells. Ouabain showed concentration-dependent inhibition of catecholamine secretion induced by PTX. Ouabain also inhibited [45Ca]2+ influx induced by PTX, this inhibition being parallel with that of catecholamine secretion. The inhibitory effects of ouabain on PTX-induced catecholamine secretion and [45Ca]2+ influx were both overcome by increasing the concentrations of PTX, indicating that ouabain inhibited the actions of PTX in a competitive manner. These results suggest that the ouabain-sensitive (or-binding) site on the cell membrane might be the target site of action of PTX, which causes an increase in Ca2+ permeability and initiation of catecholamine secretion.

Acrylamides↗
PubMed1994

Cloning and expression of a complementary DNA encoding the bovine receptor for pituitary adenylate cyclase-activating polypeptide (PACAP).

A cDNA encoding a pituitary adenylate cyclase-activating polypeptide (PACAP) receptor was cloned from a bovine brain cDNA library using a synthetic oligonucleotide probe corresponding to the partial N-terminal amino acid sequence of the PACAP receptor purified from the bovine brain. The cloned cDNA encoded a polypeptide of 513 amino acid residues with seven putative transmembrane domains. The deduced amino acid sequence exactly matched the N-terminal amino acid sequence of the purified PACAP receptor. It also shared an apparent similarity with the vasoactive intestinal peptide (VIP), secretin, growth hormone releasing hormone, calcitonin, and glucagon receptors, suggesting that the PACAP receptor is a member of the secretin receptor subfamily of the guanine nucleotide-binding regulatory protein-coupled receptor family. Northern blot analysis showed that the size of the major mRNA band which hybridized with the cDNA was about 7 kb in the bovine cerebral-cortex and hippocampus. An expression vector containing the cloned cDNA for the PACAP receptor was introduced into Chinese hamster ovary (CHO) cells. The affinity of PACAP receptors expressed on the transfected CHO cells was quite similar to that of natural PACAP receptors on the bovine brain membranes. Competitive binding experiments showed that PACAP38 displaced the binding of 125I-labeled PACAP27 to the receptors on the CHO cells more efficiently than PACAP27, while VIP was less effective. In addition, both of PACAP27 and PACAP38 elevated the levels of cAMP and inositol phosphates in the transformed CHO cells. These results indicate that the PACAP receptors encoded by the cloned cDNA are identical to the purified PACAP receptors, and that they can stimulate dual signaling cascades.

Amino Acid Sequence↗