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Y Motoyama

Publications and source records attributed to Y Motoyama.

At least 37 records · Page 2Linked to original sources
PubMed1999

[Brain surface clear cell ependymoma: case report].

We report a case of brain surface clear cell ependymoma. A 13-year-old boy presented with complaints of right hypesthesia. Computed tomography and magnetic resonance image showed a left fronto-parietal cystic, calcified mass lesion. He underwent total resection of the tumor including cyst wall. The tumor located on the surface of the parietal lobe was sharply demarcated from the surrounding brain tissue and there was no continuity with the ventricular wall. Histological examination of the surgical specimens showed oligodendroglioma-like cells that had round unclei, clear cytoplasm which formed perivascular pseudorosettes, and immunoreactivity for glial fibrillary acidic protein (GFAP). Electromicroscopically, microvilli were seen. The findings were compatible with clear cell ependymoma. The cyst wall was lined with a layer of single cuboidal cells and, immunohistochemically, had no basal membrane. The inner surface of the cyst was positive for EMA, and the cuboidal cells were positive for GFAP. We discuss possible mechanisms for tumor growth in our case and the histogenesis of its cyst.

Adolescent↗
PubMed1998

Comparison of the antithrombotic effects of FK633, GPIIb/IIIa antagonist, and aspirin in a guinea pig thrombosis model.

Antiplatelet and antithrombotic effects of FK633 (a GPIIb/IIIa antagonist) and aspirin were compared. FK633 at 0.32 mg/kg i.v. or aspirin at 10 mg/ kg i.v. inhibited ex vivo collagen-induced aggregation by >50% for 1 hour in guinea pigs. However, aspirin was very weak in inhibiting ADP-induced aggregation. In vivo antithrombotic effects of FK633 and aspirin were compared using a FeCl3-induced carotid artery thrombosis model in guinea pigs. Pretreatment with 0.32 mg/kg i.v. of FK633 significantly prevented occlusive thrombus formation, but aspirin at 10 mg/kg i.v. did not. In thrombolysis experiments, adjunctive use of FK633 (0.32 mg/kg i.v.) with rt-PA (0.3 mg/kg bolus+1.0 mg/kg/hr) achieved reperfusion in five of five animals without reocclusion. Aspirin (10O mg/kg i.v.) with rt-PA also achieved reperfusion in three of five animals with high incidence of reocclusion. These results suggest that FK633 may be a more effective antithrombotic agent than aspirin due to its agonist-independent antiplatelet effects.

Animals↗
PubMed1998

Augmentation of the inhibitory effect of FK480, a CCK-A receptor antagonist, on pancreatic exocrine secretion by achlorhydria.

The effect of intraluminal acid and cholecystokinin (CCK) receptor blockade on the pancreatic secretory response was examined in rats. Blockade of gastric acid secretion by YM022 (CCK-B receptor antagonist) or famotidine (histamine-2 receptor antagonist) resulted in a significant suppression of casein-stimulated pancreatic exocrine secretion as determined by juice volume and amylase secretion. Ligation of the gastric pylorus, which leads to complete prevention of gastric acid from entering the duodenum, also suppressed pancreatic exocrine secretion. FK480 (CCK-A receptor antagonist) inhibited pancreatic exocrine secretion dose dependently at doses of 0.01-1.0 mg/kg. When submaximal doses of FK480 and YM022 were treated concomitantly, pancreatic exocrine secretion was inhibited more profoundly than when treated solely. Hydrochloric acid (HCl; 0.05 N), injected into the duodenum, stimulated pancreatic exocrine secretion to a level comparable to that exhibited by intraduodenal casein. This effect of HCl was inhibited by FK480 (1.0 mg/kg) but not by YM022 (1.0 mg/kg). These findings suggest that inhibition of gastric acid secretion leads to the suppression of pancreatic exocrine secretion through mechanisms mediated by CCK-A receptors.

Achlorhydria↗
PubMed1998

[Bilateral aplasia of the internal carotid artery: a case report].

We report a case of bilateral aplasia of the internal carotid arteries. A 59-year-old man was admitted with generalized convulsions. Computed tomography and magnetic resonance imaging of the head showed normal findings. Three-dimensional computed tomography, angiography, and intra-arterial digital subtraction angiograms showed bilateral aplasia of the internal carotid arteries. The bilateral ophthalmic arteries were filled from the hypoplastic carotid arteries, and the anterior and middle cerebral arteries were filled from the basilar artery via the posterior communicating arteries. Associated with this bilateral aplasia of the internal carotid arteries, intracranial aneurysms and megadolicho-basilar anomaly were reported. Angiography is to be recommended if IC aplasia is suspected.

Carotid Artery, Internal↗
PubMed1997

[Ruptured traumatic aneurysms of the peripheral anterior cerebral artery: study of delayed hemorrhage after closed head injury].

We report three cases of ruptured traumatic aneurysms of the peripheral anterior cerebral artery after closed head injury. These cases were all young men with closed head injury due to traffic accidents. Consciousness level on admission was coma in all three cases. Case 1 was a 19-year-old man with interhemispheric hematoma on initial CT, then 7 days later his consciousness cleared. However, 14 days later he suddenly lapsed into a deep coma with a severe frontal hemorrhage. Case 2 was a 13-year-old boy. Plain skull films demonstrated a frontal depressed fracture, but CT scan showed no bleeding. Four days later his consciousness cleared but 11 days after trauma, he lapsed into a deep coma with a frontal hemorrhage. Case 3 was a 22-year-old man. Initial CT showed a slight ventricular hemorrhage. Fourteen days later, his consciousness had almost cleared, but then he lapsed into a deep coma with a large frontal hemorrhage 11 weeks after the trauma. These patients all died within a few days after intracranial bleeding. All patients underwent cerebral angiography but none of them showed filling defect. Autopsy was performed and ruptured aneurysms were found on the distal anterior cerebral artery that had no relation to the branch of bifurcation. Histological examination demonstrated a lack of elastic lamina and media in all of these three cases, so each of them was a victim of so-called false aneurysm. Twenty reported cases of ruptured traumatic aneurysms of the peripheral cerebral artery with delayed hemorrhage after closed head injury were reviewed. Factors in the traumatic aneurysm showed no relation to the duration of disturbed consciousness. Within one month, delayed hemorrhage due to ruptured traumatic aneurysm occurred. None of the delayed hemorrhages involved subarachnoid hemorrhage. Subdural hematoma was seen in the distal middle cerebral artery and frontal hemorrhage was found in the distal anterior cerebral artery. We consider that frontal hemorrhage is a predictive finding for the type of delayed hemorrhage due to traumatic aneurysm in the distal anterior cerebral artery.

Accidents, Traffic↗
PubMed1996

The anti-platelet and anti-thrombotic effects of FK633, a peptide-mimetic GPIIB/IIIA antagonist.

The anti-platelet and anti-thrombotic properties of FK633, a peptide mimetic GPIIb/IIIa antagonist were studied. In human platelet rich plasma, FK633 inhibited ADP-, collagen-, thrombin-, and PAF-induced platelet aggregation with IC50 values of 103, 87, 98, and 239 nM, respectively. RGDS acted similarly, but it's potency was about 1,000 times weaker than FK633, FK633 inhibited 125I-fibrinogen binding to human washed platelet with an IC50 of 88 nM. FK633 did not inhibit alphavbeta3, alpha5beta1, and alphavbeta1 integrin-mediated cellular adhesion up to 1.0mM, while RGDS inhibited all these interactions. In dogs, bolus injection of FK633 at 0.1 mg/kg significantly suppressed ex vivo ADP-induced platelet aggregation (>40% inhibition) and thrombus formation at stenosed and injured coronary artery, but did not prolong template bleeding time. However, FK633 inhibited >90% ADP-induced aggregation at 0.32 mg/kg, causing significant prolongation of the bleeding time. Thus, FK633 is a specific GPIIb/IIIa antagonist with potent anti-thrombotic effect in vivo, but careful dosing study might be necessary to avoid the bleeding complications in the clinic.

Animals↗
PubMed1996

Effects of growth temperature on the fatty acid composition of the free-living nematode Caenorhabditis elegans.

The effects of growth temperature on the fatty acid compositions of the phosphatidylcholine (PC), phosphatidylethanolamine (PE), and total lipid (TL) fractions of the free-living nematode Caenorhabditis elegans were investigated. A reduction in growth temperature from 25 to 15 degrees C caused the proportions of eicosapentaenoic acid (20:5n-3) to increase from 23.6 to 32.5% in the PC, from 7.4 to 10.8% in the PE, and from 12.9 to 19.9% in the TL fractions. Conversely, the levels of dihomo-gamma-linolenic acid (20:3n-6) and arachidonic acid (20:4n-6) in these phospholipid fractions and the TL fraction both decreased with decreasing growth temperature. Analysis of the positional distribution of fatty acids in the PC fraction revealed that the change in the composition of C20 polyunsaturated fatty acid was obvious in position sn-2. Lowering the growth temperature induced an increase in the level of the diacyl subclass of PE from 58% at 25 degrees C to 71% at 15 degrees C, with a concomitant decrease in the levels of the alkylacyl and alkenylacyl subclass of PE of C. elegans. These changes observed in the phospholipids of C. elegans might be one mechanism for adaptation to low temperature.

Adaptation, Physiological↗
PubMed1996

Pentamidine is a specific, non-peptide, GPIIb/IIIa antagonist.

Pentamidine was previously shown to act on glycoprotein (GP) IIb/IIIa (Cox et al., Thromb Haemost 1992; 68: 731). In this paper we study the effect of pentamidine on other RGD-dependent receptors. In a cell adhesion assay, pentamidine was 500 times more potent than RGDS at inhibiting platelet adhesion to fibrinogen. While RGDS inhibited platelet adhesion to fibronectin, endothelial cell adhesion to vitronectin or fibronectin, 293 cell adhesion to vitronectin, IMR 32 cell adhesion to fibronectin and C32 cell adhesion to vitronectin; pentamidine failed to inhibit these interactions at doses as high as 1 mM. Resting platelets fixed in the presence of 1 mM RGDS had increased binding of fibrinogen, i.e., RGDS activated GPIIb/IIIa, while pentamidine at 100 microM had no effect. Similarly, RGDS induced the binding of an anti-LIBS monoclonal antibody, while pentamidine had no effect. Pentamidine partially, but significantly, inhibited lysosome and alpha-granule release induced by the thrombin agonist peptide, while RGDS had no effect. Neither pentamidine nor RGDS affected ADP-induced Ca2+ influx. Pentamidine had no effect on ADP-induced intracellular pH changes while RGDS prevented the pH from returning to normal. Thus, pentamidine is a non-peptide GPIIb/IIIa antagonist that is non-activating and is specific for GPIIb/IIIa.

Amino Acid Sequence↗
PubMed1995

FK409, a new nitric-oxide donor, suppresses smooth muscle proliferation in the rat model of balloon angioplasty.

The effect of FK409, a new nitric-oxide (NO) donor, on neointimal formation of rat carotid arteries following balloon injury was studied. The intimal thickening at 14 days was strongly suppressed by twice daily administration of FK409 at 10 mg/kg from 2 days before to 13 days after injury. The neointima area and neointima/media ratio were decreased by 48.0% (P < 0.01) and 38.5% (P < 0.01), respectively, compared with control. On the other hand, isosorbide dinitrate (ISDN), a classical nitro-vasodilator, did not suppress intimal thickening even at 100 mg/kg twice a day. An in vivo 5-bromo-2'-dedoxyuridine (BrdU) uptake study revealed that FK409 inhibited the proliferative response of smooth muscle cells (SMC) in media at early stage of injury. In fact, the neointimal formation at 14 days was inhibited by the short term administration of FK409 only from the day of injury to 4 days after at 10 mg/kg twice a day. In cultured rat SMC, FK409 (1-10 mumol/l) markedly enhanced intracellular c-GMP and inhibited the proliferation in 10% FBS-containing medium. These results suggest that FK409 suppresses intimal thickening following balloon injury of the rat carotid artery by inhibition of SMC proliferation.

Angioplasty, Balloon↗
PubMed1995

Effect of TFC-612, a 7-thia prostaglandin E1 derivative, on a peripheral arterial occlusive disease model in rats.

TFC-612, methyl 6-[((1R,2S,3R)-3-hydroxy-2-[(1E,3S,5R)-3-hydroxy-5- methyl-1-nonenyl)-5-oxocyclopentyl]-thio]-hexanoate, inhibited the progression of the lesion in a lauric acid-induced peripheral arterial occlusive model at 1.0 mg/kg p.o. or 1.0 microgram/rat/h s.c. in rats. Aspirin (32 mg/kg, p.o.), an anti-platelet drug, did not suppress the lesion growth. On the other hand, ketanserin (10 mg/kg, p.o.), a 5-HT2 antagonist, also inhibited the progression of the lesion. In vitro, TFC-612 inhibited rat platelet aggregation induced by collagen and ADP with IC50 values of 5.4 ng/mL and 9.5 ng/mL, respectively. Aspirin also inhibited collagen-induced aggregation with an IC50 value of 6.3 micrograms/mL, but not ADP-induced aggregation at 180 micrograms/mL. Ketanserin had no effect on either aggregation at 40 micrograms/mL. In ex vivo experiments, aspirin inhibited platelet aggregation induced by collagen at 10 and 32 mg/kg in rats. However, TFC-612 showed significant inhibition only at 10 mg/kg. TFC-612 and ketanserin increased dermal blood flow in the rat paw at 1.0 microgram/kg i.v. and 100 micrograms/kg i.v., respectively. Aspirin had no effect on blood flow at 3.2 mg/kg i.v. These results suggest that the improvement of microcirculation, in addition to anti-platelet action by TFC-612, contributes to its inhibitory effect in a peripheral arterial occlusive model in rats.

Alprostadil↗
PubMed1995

Automated measurement of alpha-amylase isoenzymes with 6(3)-deoxymaltotriose as selective amylase inhibitor.

We developed an automated method for measurement of alpha-amylase isoenzymes in serum by a single kinetic assay (SKA) and a double kinetic assay (DKA) with 2-chloro-4-nitrophenyl-6(5)-azido-6(5)-deoxy-beta-maltopentaoside as a substrate and 6(3)-deoxymaltotriose (DOG3) as a novel selective amylase inhibitor. DOG3 showed a large difference in inhibitory activity between human pancreatic alpha-amylase (HPA; 86.9% inhibition) and salivary alpha-amylase (32.1% inhibition) at 0.33 mmol/L. Constant inhibition was obtained immediately after addition of DOG3. The inhibitory effect did not change with variation in concentrations of amylase up to approximately 3000 U/L. The results obtained by SKA correlated well with those obtained by three methods: monoclonal antibody (r = 0.988), wheat germ inhibitor (r = 0.989), and DKA (r = 0.995). The within-run and between-run CVs for HPA were 0.63-2.32% on SKA, 0.69-1.81% on DKA. No significant interferences by endogenous serum compounds were observed with the proposed methods.

Autoanalysis↗
PubMed1994

Antiplatelet agents based on cyclooxygenase inhibition without ulcerogenesis. Evaluation and synthesis of 4,5-bis(4-methoxyphenyl)-2-substituted-thiazoles.

The syntheses, biological evaluations, and structure-activity relationships of a series of 4,5-bis-(4-methoxyphenyl)-2-substituted-thiazoles as potent antiplatelet agents with vasodilatory activity are described. 2-Guanidino-4,5-bis(4-methoxyphenyl)thiazole (3), designed from two parent compounds (itazigrel and timegadine), showed inhibitory activity of malondialdehyde (MDA, IC50 = 31 microM) production which is formed from the cyclooxygenase (CO)-catalyzed oxygenation of arachidonic acid in the synthesis of prostanoids in platelets, with vasodilatory activity (ED50 = 2.0 microM). Further structure-activity relationship studies on 3 culminated in the preparation of 4,5-bis(4-methoxyphenyl)-2-[(1-methylpiperazin-4-yl)carbonyl]thiaz ole (10a, FR122047) which exhibited potent inhibitory activity on MDA synthesis in vitro (IC50 = 0.088 microM) and platelet aggregation in guinea pigs ex vivo (100% inhibition even 6 h after 1.0 mg/kg administration) with vasodilatory activity in vitro (ED50 = 6.2 microM). Moreover, 10a demonstrated no ulcerogenesis effect in rats even at 100 mg/kg dosage (safety margin in rats is more than 70 while that of aspirin is only 1.2) in spite of its potent CO inhibition (IC50 = 0.43 microM14), while the use of aspirin, a CO inhibitor and the most popular thromboembolic drug, is restricted by the side effect. Pharmacokinetic studies on 10a have revealed that 10a is detectable in platelet-rich plasma but not in platelet-poor plasma 1 day after oral administration, which indicates that 10a tends to be localized in platelets. This property could be responsible for its low toxicity and reduction of side effects in clinical studies.

Animals↗
PubMed1994

Effect of TFC-612, a 7-thia prostaglandin E1 derivative, on intimal thickening after endothelial injury with balloon catheter in rats.

The effect of TFC-612, methyl-6-[(1R,2S,3R)-hydroxy-2-](1E,3S,5R)-3- hydroxy-5-methyl-1-nonenyl]-5-oxocyclopentyl)thio] hexanoate, on intimal thickening of carotid artery 14 days after endothelium denudation with a balloon catheter was examined in rats. This compound significantly suppressed the neointimal area and the ratio of intimal and medial layer by 41.1% and 31.4%, respectively, at 3.2 micrograms/rat/h s.c. infusion. At this dose, this compound did not inhibit platelet aggregation induced by either collagen or ADP. It did not inhibit bromodeoxyuridine incorporation into medial smooth muscle cells at 3 days after injury. In in vitro experiments, TFC-612 did not inhibit the [3H]thymidine uptake into cultured smooth muscle cells, but it showed significant inhibition of smooth muscle cell migration induced by platelet-derived growth factor (PDGF) at more than 10(-9) M. This compound increased cyclic AMP levels dose dependently in cultured smooth muscle cells at more than 10(-8) M. These results suggest that TFC-612 inhibits intimal thickening by inhibition of smooth muscle cell migration from media to intima through cyclic AMP elevation.

Alprostadil↗
PubMed1994

Studies on anti-platelet agents. IV. A series of 2-substituted 4,5-bis(4-methoxyphenyl)pyrimidines as novel anti-platelet agents.

The syntheses and structure-activity relationships of a series of 2-substituted 4,5-bis(4-methoxyphenyl)pyrimidines, designed on the basis of structural analyses of several cyclooxygenase (CO) inhibitors, and their derivatives as anti-platelet agents based on CO inhibition are described. Among them, 4,5-bis(4-methoxyphenyl)-2-morpholinopyrimidine (8) and 4,5-bis(4-methoxyphenyl)-2-(3,5-dimethylmorpholin-4-yl)pyrimidine (9) showed potent inhibitory activity on malondialdehyde, formed by the CO-catalyzed oxygenation of arachidonic acid (A.A.) in prostanoids, production in vitro (73.4% inhibition at 10(-8) M and IC50 = 1.4 x 10(-8) M, respectively). Certain compounds were also examined in ex vivo studies. Of these compounds, 4,5-bis(4-methoxyphenyl)-2-(1-methyl-1,2,3,6-tetrahydropyrid-4-yl) pyrimidine (11a) exhibited potent and long-lasting anti-platelet activity ex vivo, that is, 11a showed 97% inhibition of platelet aggregation induced by A.A. even 24h after oral administration of 3.2 mg/kg in guinea pigs, and 60-70% inhibition at 6 h after lower doses (1.0 mg/kg). The ex vivo activity of 11a is more than three times that of aspirin (aspirin showed 81% inhibitory activity on platelet aggregation induced by A. A. at 6 h after oral administration at 10 mg/kg in this study). Compound 11a also showed vasodilatory activity (ED50 = 5.3 x 10(-6) M, while aspirin has no vasodilatory activity at 6.0 x 10(-4) M).

Animals↗
PubMed1994

Studies on anti-platelet agents. V. Synthesis and structure-activity relationship of 3-substituted 5,6-bis(4-methoxyphenyl)-1,2,4-triazines.

The syntheses and structure-activity relationships of a series of 3-substituted 5,6-bis(4-methoxyphenyl)-1,2,4-triazines as anti-platelet agents based on cyclooxygenase (CO) inhibition are described. Of these compounds, 1-[5,6-bis(4-methoxyphenyl)-1,2,4-triazin-3-yl]carbonyl-4-methylpi perazine (10) exhibited potent CO inhibition in vitro (IC50 = 2.8 x 10(-7) M) with vasodilatory activity (ED50 = 4.5 x 10(-5) M). Compound 10 also showed potent ex vivo activities, completely preventing platelet aggregation induced by arachidonic acid and collagen at 6 h after oral administration of 3.2 and 1.0 mg/kg. The ex vivo potency of 10 is more than three times that of aspirin. Moreover, 10 demonstrated no gastrointestinal side effect in rats even at 100 mg/kg in spite of its potent CO inhibition activity, while aspirin, the most widely-used anti-platelet drug, showed gastrointestinal side effects in a dose-dependent manner (32, 100, and 320 mg/kg) in our study. These results suggested that 10 is a very attractive candidate for development as an anti-platelet drug since an aspirin-like anti-platelet agent, based on CO inhibition and being free from gastrointestinal side effects, is a major goal of thromboembolic research.

Animals↗
PubMed1994

Studies on anti-platelet agents. II. Synthesis and platelet-inhibitory activity of 5-methyl-4-(3-pyridyl)-2-(substituted benzimidazol-5-yl)imidazoles.

A series of 5-methyl-4-(3-pyridyl)-2-(substituted benzimidazol-5-yl)imidazole derivatives was synthesized and tested for anti-platelet and vasodilatory activities. Some compounds were found to have potent activities and low acute toxicity. In particular, 5-methyl-4-(3-pyridyl)-2-(7-chloro-6-methoxy-2- methylbenzimidazol-5-yl)imidazole (26) and 5-methyl-4-(3-pyridyl)-2-(7-chloro-3-methoxy-2-methylbenzimidazol- 5-yl)imidazole (33) exhibited 63% or 51% inhibition at a dose of 10 mg/kg for anti-patelet activity ex vivo in rats, respectively, while they showed no toxicity even at 180 or 100 mg/kg, respectively. Compound 33 also exhibited potent vasodilatory activity (ED50 = 11 micrograms/ml). Enzyme studies on these imidazoles showed that the novel imidazoles inhibit some enzymes which are involved in the platelet aggregation cascade such as cyclooxygenase, phosphodiesterase (PDE), and thromboxane A2 synthetase. The enzyme assay also suggested that the inhibitory activity on PDE may account for the vasodilatory activity of these imidazoles.

Animals↗