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Biomedical subjects

S Hamano

Publications and source records attributed to S Hamano.

At least 145 records · Page 8Linked to original sources
PubMed1990

[Inhibitory effects of OKY-046.HCl, a selective thromboxane (TX) A2 synthetase inhibitor, on platelet activating factor (PAF)-induced airway hyperresponsiveness in guinea pigs].

We studied the inhibitory effects of OKY-046.HCl on PAF-induced airway hyperresponsiveness (AHR) in guinea pigs. 1) Inhalation of PAF (1 or 10 micrograms/ml) caused AHR to acetylcholine (ACh) aerosol and increased TXB2 generation in broncho-alveolar lavage fluid (BALF) at 30 min and 60 min, but the AHR and the TXB2 generation disappeared at 2 hr. OKY-046.HCl (100 mg/kg, intraduodenally) inhibited the AHR, which was accompanied by its inhibition of the TXB2 generation. However, no changes of 6-keto-PGF1 alpha in BALF were found. 2) There were no changes in the number of leukocytes; the activities of alkaline phosphatase, N-acetyl-beta-D-glucosaminidase, and lactate dehydrogenase; and the LTC4/D4/E4 in BALF. 3) In bronchus-lung preparations, PAF (1 microgram/min) also caused the AHR and increased TXB2 generation. OKY-046.HCl (100 micrograms/min) inhibited the AHR and TXB2 generation. 4) PAF (1 microgram/ml) evoked TXB2 generation in BALF from normal guinea pigs. OKY-046.HCl (10(-4)M) inhibited its increase. 5) Stable TXA2 (STA2, 1 ng/ml) inhalation also caused AHR to ACh at 30 min. STA2 (0.45 ng/min) also caused the AHR in bronchus-lung preparations. These results suggest that OKY-046.HCl can inhibit PAF-induced AHR by suppressing the generation of TXA2. We also supposed that TXA2 is released from lung parenchyma, airway epithelium and cell components in BALF.

Acrylates↗
PubMed1990

Inhibitory action of OKY-O46.HCl, a specific TXA2 synthetase inhibitor, on platelet activating factor (PAF)-induced airway hyperresponsiveness of guinea pigs: role of TXA2 in development of PAF-induced nonspecific airway hyperresponsiveness.

We studied a role of TXA2 in the development of PAF-induced nonspecific airway hyperresponsiveness in guinea pigs using a TXA2 synthetase inhibitor (OKY-O46.HCl) and a stable TXA2 mimetic agent (STA2). Inhalation of PAF (1 microgram/ml) and STA2 (1 or 10 ng/ml) increased the airway response to acetylcholine (ACh), histamine, leukotriene D4 and electrical vagal stimulation. Intraduodenal administration (i.d.) of OKY-O46.HCl (100 mg/kg) inhibited PAF-induced airway hyperresponsiveness. However, OKY-046.HCl (30 mg/kg, i.v.) did not suppress STA2-induced airway hyperresponsiveness. Neither hexamethonium (1 mg/kg, i.v.) nor hemicholinium-3 (10 mg/kg, i.v.) prevented the increase in the airway response to ACh after inhalation of PAF and STA2. In the presence of atropine (0.5 mg/kg, i.p.), PAF-induced airway hyperresponsiveness to histamine did not change. OKY-046.HCl (100 mg/kg, i.d.) inhibited the increase in ACh (10(-8) M)-induced 45Ca uptake into the lung tissue from PAF-inhalated guinea pigs. Inhalation of STA2 increased the number (Bmax) of muscarinic and H1-histaminergic receptors in the lung tissue from guinea pigs, but no changes were found on beta-adrenoceptors. These results suggest that TXA2 should act on the smooth muscle cells or alter functions of muscarinic and H1-histaminergic receptors, except beta-adrenoceptors, and then increase the membrane permeability to extracellular Ca2+. We also assume that OKY-046.HCl can inhibit PAF-induced nonspecific airway hyperresponsiveness by suppressing the generation of TXA2.

Acrylates↗
PubMed1990

Stimulatory action of Ba2+ on catecholamine biosynthesis in cultured bovine adrenal chromaffin cells: possible relation to protein kinase C.

The effect of Ba2+ on the catecholamine biosynthetic activity was studied by measuring the formation of [14C]catecholamines from L-[14C]tyrosine in cultured adrenal chromaffin cells. In the absence of Ca2+, [14C]catecholamine formation was markedly stimulated by Ba2+, and this stimulation was observed in a manner dependent on its concentration. The stimulation of [14C]catecholamine formation by relatively low concentrations of Ba2+ was suppressed by polymyxin B, a typical inhibitor of Ca2+/phospholipid-dependent protein kinase (protein kinase C); and this inhibitory action of polymyxin B was attenuated by increasing the Ba2+ concentration. On the other hand, a tendency toward the enhancement of Ba2+-stimulated [14C]catecholamine formation was observed by a protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate (TPA). In contrast to the acute effect of TPA, [14C]catecholamine formation stimulated by Ba2+ was reduced by long-term exposure of chromaffin cells to a high concentration of TPA, which has already been reported to cause the reduction of protein kinase C activity as a result of the down-regulation of this enzyme. These findings suggest that Ba2+ stimulates catecholamine biosynthesis, probably through its direct action on protein kinase C in adrenal chromaffin cells.

Adrenal Glands↗
PubMed1990

[Single photon emission computed tomography of the brain in Sturge-Weber syndrome using N-isopropyl-p-[123I] iodoamphetamine--a comparative study with X-ray computed tomography].

Single photon emission computed tomography (SPECT) of the brain using N-isopropyl-p-[123I] iodoamphetamine (123I-IMP) was performed in 11 children with port wine stain on the face or head, aged 1.0-14.2 years at investigation. Four cases without neurologic symptoms had no specific abnormality on SPECT and X-ray computed tomography (CT). In 4 cases of so-called Sturge-Weber syndrome with developmental quotients (DQ) or intelligence quotients (IQ) more than 80 and the neurologic symptoms consisting of seizures and hemiplegia, SPECT showed localized reduction of IMP accumulation, and CT exhibited calcification, atrophy and enhancement in 2 cases of 3 with contrast medium infusion in the same areas. In 3 cases with DQ of 50-60 and severer neurologic symptoms, SPECT showed diffuse reduction or defect of IMP accumulation in the ipsilateral hemisphere, and CT exhibited remarkable atrophy, calcifications and enhancement in 2 cases with contrast medium infusion in the same hemisphere. In one case with severe neurologic symptoms, SPECT performed at an early stage showed high IMP accumulation in the ipsilateral hemisphere.

Adolescent↗
PubMed1989

Inhibitory action of carvedilol, a novel alpha, beta-adrenoceptor antagonist, on catecholamine secretion and calcium influx in cultured bovine adrenal chromaffin cells.

The effect of carvediolol on the secretory function was studied using cultured bovine adrenal chromaffin cells. Carvedilol caused the concentration-dependent inhibition of catecholamine secretion evoked by carbamylcholine, high K+ or veratridine. The drug also caused the inhibition of radioactive calcium uptake stimulated by these secretagogues into the cells, and the inhibition of calcium uptake was observed in parallel with that of catecholamine secretion. The inhibitory action of carvedilol on catecholamine secretion was shown to be similar to that caused by a classical beta-adrenoceptor antagonist, propranolol. Furthermore, although the level of carbamylcholine-stimulated catecholamine secretion inhibited by diltiazem, a potent calcium channel antagonist, was significantly raised by elevating the calcium concentration in the reaction mixture, increasing the concentration of calcium ions in the mixture failed to induce any substantial influence on the secretion inhibited by carvedilol, as well as propranolol, under the same experimental conditions. These results seem to indicate that carvedilol may cause the inhibition of catecholamine secretion through its blocking action on calcium influx into the cells, and suggest the possibility that the inhibitory action of carvedilol on calcium influx is presumably based on its stabilizing action on the plasma membranes rather than its blocking action on the calcium channels in the chromaffin cell.

Adrenal Glands↗
PubMed1989

Production and characterization of monoclonal antibodies against particulate guanylate cyclase in porcine kidney.

Three monoclonal antibodies (Ig G1 type) to particulate guanylate cyclase from porcine kidney cortex have been produced by fusing spleen cells from immunized BALB/c mouse with P3X63 myeloma cells. The antibodies were detected by their ability to bind immobilized antigen and by immunoprecipitation of enzyme activity. After subcloning by limiting dilution, hybridomas were injected intraperitoneally into mice to produce ascitic fluid. The antibodies recognized a 180,000 dalton protein in Lubrol-PX extract of porcine kidney cortex membrane, and when immobilized on Sepharose 4B, they co-precipitated both [125I]human atrial natriuretic peptide (ANP)-receptor complex and guanylate cyclase activity. The antibodies caused a greater increase in generation of cGMP than that of ANP.

Animals↗
PubMed1989

Myosin light-chain kinase inhibitor, 1-(5-chlornaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine (ML-9), inhibits catecholamine secretion from adrenal chromaffin cells by inhibiting Ca2+ uptake into the cells.

For determination of whether myosin light-chain kinase (MLCK) is involved in the secretory mechanism of adrenal chromaffin cells, the effect of a preferential inhibitor of the enzyme, 1-(5-chlornaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine (ML-9), on catecholamine secretion from cultured bovine adrenal chromaffin cells was studied. ML-9 did not affect basal catecholamine secretion, but inhibited catecholamine secretion stimulated by acetylcholine, high K+, veratridine or palytoxin. At similar concentrations to those inhibiting the secretion of catecholamine, ML-9 also inhibited increased [45Ca]2+ uptake by the cells induced by these stimulants. However, it did not inhibit catecholamine secretion induced by the Ca2+ ionophore A23187. Moreover, it did not affect catecholamine secretion from digitonin-permeabilized cells induced by a micromolar Ca2+ concentration in the presence of Mg ATP. These results indicate that ML-9 inhibits catecholamine secretion from adrenal chromaffin cells by inhibiting the transmembrane Ca2+ uptake mechanism, but not by inhibiting the intracellular Ca2+-dependent mechanism. The possible role of MLCK in stimulus-secretion coupling in adrenal chromaffin cells is discussed.

Acetylcholine↗
PubMed1989

Beneficial effect of low molecular weight heparin on the hemodialysis model in dogs.

The effect of FR-860, one of low molecular weight heparins, was investigated on the hemodialysis model in dogs for comparison with that of conventional unfractionated heparin (UF-heparin). In a bolus injection model, FR-860 at 12.5-100 U/kg prolonged the dialysis time (the time until the arterial circuit pressure reaching 500 mmHg) in a dose-dependent manner and UF-heparin at 50 U/kg also prolonged it. Additionally, FR-860 (12.5-50 U/kg/hr) and UF-heparin (25 and 50 U/kg/hr) continuously inhibited the rise of the arterial circuit pressure in an infusion model. In both models, the efficacy of FR-860 was more potent than that of UF-heparin. FR-860 and UF-heparin decreased the amount of blood loss remaining in the dialyzer in the infusion model. During hemodialysis, both FR-860 and UF-heparin showed activated plasma anti-F.Xa activity, prolongation of aPTT and such of thrombin time in a dose-dependent manner in those models. However, FR-860 was higher in anti-F.Xa activity and weaker in prolongation of aPTT and thrombin time than UF-heparin. These results suggest that FR-860 is more beneficial in in efficacy and higher in safety against the bleeding risk than UF-heparin hemodialysis.

Animals↗
PubMed1989

In vitro capacitation of boar ejaculated spermatozoa: effect of conditioned media prepared from preincubated sperm suspension.

The fertilizing ability of boar ejaculated spermatozoa was examined in vitro after preincubation at a concentration of 2.5 x 10(8)/ml for 4 hr in several conditioned media (CM). For preparation of CM, boar spermatozoa were incubated in a modified Krebs-Ringer bicarbonate solution (TYH) at concentrations of 20 to 40 x 10(8)/ml for several hours up to 4 hr; then their supernatant fluids were collected by centrifugation. When boar ejaculated spermatozoa were preincubated in TYH alone, 14.1% of oocytes were penetrated by them as we reported previously. On the other hand, preincubating them with CM, their fertilizing ability was elevated according as the incubation time of CM preparation was lengthened. The fertilization rate reached 75.0%, using 4 hr-incubated CM for the preincubation medium. The effect of CM was not deteriorated by heat treatments (56 degrees C, 30 min, or 100 degrees C, 5 min). The components of CM were separated at a molecular weight of 25,000 by ultrafiltration, and high fertilization rate (69.8%) was obtained when low molecular weight fraction was used for the preincubation medium. Sperm extracts prepared from directly frozen-thawed sperm suspension and 0.1-10 mM of taurine or hypotaurine had no effect on the fertilizing ability of boar spermatozoa. These results suggest that substances stimulating boar sperm capacitation were accumulated from viable spermatozoa into the medium during incubation and that the effective substances were heat-stable and of low molecular weight and were not taurine and hypotaurine.

Animals↗
PubMed1989

[Antithrombotic effects of low molecular weight heparin (FR-860) in rabbits].

Effects of low molecular weight heparin (FR-860) were investigated on the arterio-venous (A-V) shunt model and on the in vitro blood coagulation system compared to conventional unfractionated heparin (UF-heparin) in rabbits. In the A-V shunt model, FR-860 (12.5-50 U/kg, i.v.) and UF-heparin (25 and 50 U/kg, i.v.) dose-related inhibited thrombotic formation in the tube of the A-V shunt at 30 min after starting blood circulation. Both FR-860 and UF-heparin dose-relatedly increased the anti-F.Xa activity at 5 min after starting blood circulation. However, FR-860 showed weaker effects in a prolongation of the aPTT, PT and thrombin time than UF-heparin in the A-V shunt model. Neither FR-860 nor UF-heparin had any influence on platelet aggregation. FR-860 also had a weaker effect in the prolongation of the plasma recalcification time, aPTT and PT than UF-heparin in vitro. FR-860 showed equipotent efficacy on the anti-F.Xa activity and had weak anti-thrombin activity compared to that of UF-heparin in vitro. These results suggest that the antithrombotic effect of FR-860 mainly depends on its anti-F.Xa activity but not on the antithrombin activity. Therefore, FR-860 is more efficient and lower in bleeding risk than UF-heparin in hemodialysis and thrombotic disorders.

Animals↗
PubMed1989

[Effects of low molecular weight heparin (FR-860) on coagulative and fibrinolytic activities].

We studied the effects of FR-860 on coagulative and fibrinolytic activities in human plasma compared to conventional unfractionated heparin (UF-heparin). Both FR-860 and UF-heparin dose-dependently prolonged the recalcification time, activated partial thromboplastin time, prothrombin time, factor Xa (F.Xa) clotting time and thrombin time. These effects of FR-860 were weaker than that of UF-heparin. FR-860 showed equipotent efficacy on the anti-F.Xa activity, and weak antithrombin activity compared to UF-heparin. FR-860 had no effects on the activity of ATIII and fibrinolytic activity. UF-heparin shortened the urokinase-activated euglobulin lysis time and showed antiplasmin activity, but did not influence the activities of ATIII, plasminogen and alpha 2-plasmin inhibitor. UF-heparin decreased the fibrinogen level at higher doses. These efficacies of FR-860 were weaker than that of UF-heparin. These results suggest that FR-860 is more efficient and lower in bleeding risk than UF-heparin in clinical use.

Adult↗
PubMed1989

Effects of cytoskeleton-disrupting agents on tyrosine transport into cultured bovine adrenal chromaffin cells.

The effects of various cytoskeleton-disrupting agents on tyrosine transport into chromaffin cells were examined to assess the possibility of cytoskeleton involvement in the regulation of precursor supply for catecholamine synthesis. Tyrosine transport was markedly increased by cytochalasin B. Vinblastine also stimulated tyrosine transport, although its effect was less pronounced than that of cytochalasin B. While colchicine failed to cause any significant increase in the transport under the same conditions. These results therefore suggest a possible role of microfilaments as a factor regulating tyrosine transport into chromaffin cells.

Adrenal Medulla↗
PubMed1988

Development of the human motor trigeminal nucleus.

The morphometric features of the motor trigeminal nucleus of the developing human brain were examined using complete serial celloidin sections of 13 brains, including 10 fetal brains. Our results suggest that the developmental processes of the motor trigeminal nucleus should be divided into four stages as follows: (1) primary stage, characterized by the early neuronal differentiation; (2) secondary or preparatory stage; (3) tertiary stage, characterized by massive neuronal death, and (4) postnatal stage, characterized by the maturation of neuropils. There were differences between the neuronal death observed in human and animal brains. Possible implications of these observations for the development of the nervous system are discussed.

Adolescent↗