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Biomedical subjects

T Asano

Publications and source records attributed to T Asano.

At least 793 records · Page 44Linked to original sources
PubMed1985

Intracellular Ca++ antagonist, HA1004: pharmacological properties different from those of nicardipine.

Pharmacological properties of N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA1004), a newly synthesized intracellular Ca++ antagonist, were studied by comparing its cardiovascular actions with those of nicardipine, a Ca++ entry blocker. Both i.a. and i.v. injections of HA1004 produced a dose dependent increase in vertebral, coronary and renal blood flow, respectively, in pentobarbital-anesthetized dogs. Continuous infusion of atropine, propranolol or aminophylline exerted no significant effect on the HA1004-induced vasodilation. A Ca++ entry blocker, nicardipine, increased vertebral and coronary blood flow after injections but did not produce an increase in renal blood flow, thereby suggesting notable differences between the cardiovascular effects of HA1004 and the Ca++ entry antagonist, nicardipine. HA1004 inhibited KCl, phenylephrine and prostaglandin F2 alpha-induced contraction of isolated canine renal arterial preparations, in a dose-dependent fashion, whereas nicardipine was much less effective in blocking the contraction of the preparations induced by phenylephrine and prostaglandin F2 alpha. HA1004 inhibited the phenylephrine-induced contraction of the renal artery in the absence of Ca++. HA1004 neither depressed the amplitude nor the duration of the slow action potentials of isolated guinea-pig hearts. These results suggest that HA1004 is a Ca++ antagonist of different class from Ca++ entry blockers such as nicardipine.

Action Potentials↗
PubMed1985

Platelet binding properties of monoclonal lupus autoantibodies produced by human hybridomas.

The platelet binding properties of human monoclonal lupus autoantibodies have been studied. These IgM autoantibodies, produced by human X human hybridomas derived from lymphocytes of patients with systemic lupus erythematosus, are known to bind to single-stranded DNA. Four anti-DNA antibodies that express the dominant 16/6 idiotype--HF2-1/17, HF2-18/2, HF2-1/13b, and HF3-16/6--bound to glutaraldehyde-fixed platelets. In contrast, HF6-21/28, HF9-11/3, and polyclonal IgM bound poorly to platelets. [35S]Methionine was incorporated into HF2-1/17, and the interaction of the intrinsically radiolabeled HF2-1/17 with fixed platelets was evaluated in a solution phase radioimmunoassay. [35S]Methionine HF2-1/17 bound to fixed platelets and could be displaced by equivalent amounts of HF2-1/17, HF2-18/2, HF2-1/13b, and HF3-16/6. HF2-1/17 bound with greater affinity to fresh platelets and to thrombin-activated platelets than to glutaraldehyde-fixed platelets. Single-stranded DNA competed with platelets for the HF2-1/17 combining site. Treatment of fresh platelets with nuclease I, trypsin, chymotrypsin, and neuraminidase did not alter the binding of antibody to the platelet surface. No binding of antibody to phospholipid micelles was observed. Purified IgM autoantibodies did not inhibit platelet aggregation induced with ADP, thrombin, or ristocetin in platelet-rich plasma. These results indicate that the human IgM monoclonal anti-DNA autoantibodies that express the dominant 16/6 idiotype are polyspecific, bind to platelets, and interact with a platelet epitope that does not appear to involve DNA, protein, or sialic acid. These antibodies interact with platelets through the same sites responsible for antibody-DNA binding.

Antibodies, Monoclonal↗
PubMed1985

[Artificial renal supports in surgery--present status and problems].

Clinical and surgical situation and problems of the blood purification as an artificial renal supports, including hemodialysis, hemofiltration and hemoadsorption, were studied especially fields related with treatment of acute renal failure (ARF), surgeries in the patients treated with chronic hemodialysis and supportive care for the cadaveric renal transplantation. ARF: Our experimental data using septic rats showed that hemoadsorption activated host's reticuloendothelial function and consequently increased survival rate of septic rats. Clinically, similar results were observed by the combination of hemodialysis and hemoadsorption, and the survival rate of ARF with multiple organ failure increased to 68% (21 out of 31 cases) from 30% (8 out of 27) in the patients treated with only hemodialysis. Surgery in the chronic hemodialysis patients: One hundred twenty two operations have been done among the patients treated with chronic hemodialysis in our clinic. However, 15 in emergency cases were died within post operative period. There is no operative death in scheduled operations including total esophagectomy and simultanous radical operation of gall bladder cancer and colon cancer. Pre- and post operative supportive management with immunopotentiator, opsonic protein, coagulative factors and intravenous hyperalimentation with branched chain rich amino acid solution should be added routinely to artificial renal supports in pre- and post operative period. Cadaveric renal transplantation: Eighty-seven percent of cadaveric renal transplantation in our clinic were needed artificial renal support in early phase of post transplantation period because of insufficient renal function by acute tubular necrosis. Necessity of the acceptance of brain death category in Japan is strongly pleaded.

Acute Kidney Injury↗
PubMed1984

Reconstitution of catecholamine-stimulated binding of guanosine 5'-O-(3-thiotriphosphate) to the stimulatory GTP-binding protein of adenylate cyclase.

The stimulatory GTP-binding protein (Gs) of adenylate cyclase, purified from rabbit liver, and beta-adrenergic receptors, partially purified 1000-4000-fold from turkey erythrocyte plasma membranes, were coreconstituted into unilamellar phospholipid vesicles. The molar ratio of Gs to receptors in the vesicles varied from 3 to 10 in different preparations, as measured by guanosine 5'-O-(3-[35S]thiotriphosphate) [( 35S]GTP gamma S) binding to Gs and [125I]iodocyanopindolol binding to receptors. Activation of reconstituted Gs by GTP gamma S was stimulated up to 10-fold by the addition of the beta-adrenergic agonist (-)-isoproterenol. Activation was assayed functionally by reconstitution with the catalytic unit of adenylate cyclase. Because of the relative purity of this preparation, the quasi-irreversible binding of [35S]GTP gamma S could also be measured in the vesicles and was shown to parallel the functional activation of Gs under all conditions. Most of the assayable Gs in the vesicles could interact with the receptors and undergo agonist-stimulated activation. Agonist-stimulated activation and [35S]GTP gamma S binding were complete in less than 3 min, even under suboptimal conditions, and could go to completion in less than 20 s under maximal stimulation. Agonist-stimulated binding did not require appreciable free Mg2+ (less than 0.1 mM). Activation in the absence of agonist was stimulated by free Mg2+, but maximal activation took up to 10 min in the presence of 50 mM MgCl2. Reconstitution increased the stability of Gs to thermal denaturation. The addition of beta-adrenergic agonist further stabilized Gs, presumably by the formation of a stable agonist-receptor-Gs complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Catecholamine-stimulated guanosine 5'-O-(3-thiotriphosphate) binding to the stimulatory GTP-binding protein of adenylate cyclase: kinetic analysis in reconstituted phospholipid vesicles.

The stimulatory GTP-binding protein of adenylate cyclase, Gs, and beta-adrenergic receptors were reconstituted into unilamellar phospholipid vesicles. The kinetics of the quasiirreversible binding of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) to Gs, equivalent to Gs activation by nucleotide, was studied with respect to the stimulation of this process by beta-adrenergic agonists and Mg2+. The rate of GTP gamma S binding displayed apparent first-order kinetics over a wide range of nucleotide, agonist, and Mg2+ concentrations. In the absence of agonist, the apparent first-order rate constant, kapp, was 0.17-0.34 min-1 and did not vary significantly with the concentration of nucleotide. At 50 mM MgCl2, kapp increased somewhat, to 0.26-0.41 min-1, and remained invariant with the nucleotide concentration. In the presence of agonist, kapp was dependent on nucleotide concentration. At 10(-9) M GTP gamma S, the addition of (-)-isoproterenol caused at most a 2-fold stimulation of kapp. However, kapp measured in the presence of isoproterenol increased as an apparently saturable function of the GTP gamma S concentration, such that isoproterenol caused a 17-fold increase in kapp at 1 microM GTP gamma S. The effect of isoproterenol on kapp also appeared to saturate at high isoproterenol concentration, yielding a kapp approximately 6 min-1 at high concentrations of both nucleotide and agonist. These data suggest that the receptor-agonist complex acts by increasing the rate of conversion of a lower affinity Gs-GTP gamma S complex to the stable activated state.

Animals↗
PubMed1984

Activation of the inhibitory GTP-binding protein of adenylate cyclase, Gi, by beta-adrenergic receptors in reconstituted phospholipid vesicles.

beta-Adrenergic receptors and the inhibitory GTP-binding protein, Gi of the adenylate cyclase system were reconstituted into phospholipid vesicles by the method described previously for reconstituting receptors and the stimulatory GTP-binding protein, Gs (Brandt, D. R., Asano, T., Pedersen, S. E., and Ross, E. M. (1983) Biochemistry 22, 4357-4362). In the receptor-Gi vesicles, beta-adrenergic agonists stimulated both the high-affinity binding of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) to Gi and GTPase activity to an extent similar to that observed in vesicles containing beta-adrenergic receptors and Gs. Stimulation required receptors and displayed appropriate beta-adrenergic specificity. The prior treatment of receptor-Gi vesicles with islet-activating protein (pertussis toxin) plus NAD markedly inhibited both the isoproterenol-stimulated binding of GTP gamma S and the isoproterenol-stimulated GTPase activity. No contamination of Gi by Gs was apparent. These data suggest that receptors that typically stimulate adenylate cyclase activity may also activate the inhibitory system, perhaps as one mechanism of desensitization.

Adenylate Cyclase Toxin↗
PubMed1984

Microbial kinetics of beta-lactam antibiotics against Escherichia coli.

Microbial kinetics of Escherichia coli NIHJ JC-2 and E. coli B/r were investigated in the presence of beta-lactam antibiotics. To maintain a constant drug concentration during the experiment, a novel technique, using a dialysis membrane tube containing the drug solution, was successfully employed. The drug-affected generation curves of E. coli exhibited common features. After the addition of drug, an apparent lag period was noted, followed by a first-order decrease of the sensitive organisms and, 6 h later, by a regrowth of resistant organisms, depending on the antibiotic concentration used. The relationship between the apparent generation rate constant, kapp, and the antibiotic concentration was found to be nonlinear. This phenomenon is consistent with a saturable receptor site model for the drug action. A good linear free energy relationship was observed between the microbial kinetic parameter, kmax, and the alkaline degradation rate constants, kOH, of the cephalosporins studied.

Anti-Bacterial Agents↗
PubMed1984

Kinetic analysis and characterization of the bacterial regrowth after treatment of Escherichia coli with beta-lactam antibiotics.

The generation curves of Escherichia coli B/r and E. coli NIHJ JC-2 in the presence of several beta-lactam antibiotics were studied from the kinetic point of view. Apparent first-order regrowth of resistant organisms was observed approximately 6 h after addition of these antibiotics. The time courses of apparent viable counts could be interpreted in terms of the sum of the viable counts of sensitive and resistant organisms. To clarify the nature of the regrowth, experiments involving a second addition of antibiotic, single colonization by subculture, and synchronous cell culture were carried out. Several possible explanations for the results are discussed, including beta-lactamase production, selection in terms of membrane permeability, and mutation to acquire drug resistance. A selection process or a modification of membrane permeability caused by contact with the drug seems to be the most probable reason for the regrowth of the organisms.

Ampicillin↗
PubMed1984

Amelioration of ischaemic cerebral oedema by a free radical scavenger, AVS: 1,2-bis(nicotinamido)-propane. An experimental study using a regional ischaemia model in cats.

The effect of a free radical scavenger, AVS: 1,2-bis(nicotinamido)-propane, on the blood flow, oedema, and energy metabolites in the cortical area rendered ischaemic by the occlusion of the middle and the internal cerebral arteries was studied using cats. The development of cortical oedema was assessed by the changes in the specific gravity as well as the water and electrolyte contents of the cortical samples obtained 4 h after the arterial occlusion. Compared to the control group receiving saline, the AVS group exhibited a significant amelioration of cortical oedema, whereas no effect of AVS on the cortical blood flow was observed. The decrease of the energy charge and the increase of lactate in the ischaemic cortical area were less pronounced in the AVS groups. These data indicate that AVS possesses an action to mitigate the development of cortical oedema following regional ischaemia. The possible mechanism of action of AVS is discussed in reference to the free radical hypothesis.

Animals↗
PubMed1984

Role of IA-positive cells in the beneficial effect of donor blood transfusion and induction of suppressor cells in cardiac allotransplantation of rats.

An attempt was made to reveal the role of Ia-positive cells in the beneficial effect of pretransplant donor-specific blood transfusion (DST) and induction of suppressor cells in the cardiac allotransplantation of rats. Mean graft survival time (MST) of F344 (RT1 1v1) hearts transplanted in WKA (RT1k) rats was 6.5 +/- 0.8 days. Pretreatment of recipients with 1 ml DST 10 days before grafting prolonged it to 56.5 +/- 38.1 days. Plasma or erythrocytes did not prolong MST at all, whereas pretreatment with 1 X 10(7) lymphocytes prolonged MST significantly. B enriched cells separated on a nylon-wool column prolonged MST, but T-enriched cells did not. Treatment of lymphocytes with interspecies crossreactive monoclonal anti-Ia antibody and complement eliminated the ability of lymphocytes to prolong MST, suggesting an important role of Ia-positive cells in the beneficial effect of DST. The role of Ia-positive cells in prolonging graft survival, was analyzed by a cell and serum transfer experiment. MST of F344 heart allografts transplanted in sublethally irradiated (500 rads) WKA rats was 17.4 +/- 4.0 days. MSTs of allografts in rats irradiated and treated with serum or spleen cells of blood-conditioned rats were 23.2 +/- 1.6 (P less than 0.05) and 5.2 +/- 0.7 (NS) days, respectively. On the other hand, MSTs of the grafts in rats irradiated and treated with serum or spleen cells harvested from rats that had accepted grafts for 30 days were 18.7 +/- 1.9 (NS) and 63.8 +/- 29.9 (P less than 0.01) days, respectively. The results indicate that the initial role of a serum factor in prolonging graft survival induced by DST containing Ia-positive cells was followed by activating suppressor cells by the presence of the allograft.

Animals↗
PubMed1984

Effects of hypoxia and reoxygenation on tissue ATP level and electrical and mechanical function of isolated guinea pig ventricular muscles.

The myocardial ATP level in guinea pig ventricular muscles was determined during hypoxia and reoxygenation and compared with the cardiac electrical and mechanical function. The action potential duration (APD), contractile force (CF) and tissue ATP level were depressed gradually depending on the N2 concentration in the medium. Time course studies revealed that the membrane electrical activity and the ATP content did not show parallel evolution, although changes in CF coincided with changes in ATP level.

Action Potentials↗
PubMed1984

Nature of the vasoactive substance in CSF from patients with subarachnoid hemorrhage.

The purpose of this experiment was to study the nature of vasoactive substance in cerebrospinal fluid (CSF) from patients with aneurysmal subarachnoid hemorrhage. The authors have examined the effects of disulfide bond-reducing agents, a sulfhydryl group oxidizing agent, and specific antagonists of so-called "classical" neurotransmitters on the in vitro isometric contraction of canine basilar arterial strips induced by bloody human CSF. The disulfide bond-reducing agents dithiothreitol (10(-4) M) and dithioerythritol (10(-4) M) suppressed the contraction induced by bloody CSF by an average of 40.3% and 61.2%, respectively. This suppression was achieved under conditions that did not alter KCl-induced contraction. The sulfhydryl group oxidizing agent, 5,5'-dithiobis-(2-nitrobenzoic acid), 10(-4) M, reversed the inhibitory effect of dithioerythritol on the contractile response to bloody CSF. No significant suppression of any response in any preparation was observed with methysergide (10(-7) M), mepyramine (10(-7) M), phenoxybenzamine (10(-5) M), propranolol (10(-6) M), or atropine (10(-6) M). These results indicate that disulfide bonds in the arterial smooth-muscle cells are involved in the contractile responses of canine basilar artery to bloody CSF. Prostaglandins, hemoglobin, and lipid hydroperoxides may all be spasmogens in bloody CSF, while serotonin, histamine, norepinephrine, and acetylcholine are probably not involved.

Animals↗
PubMed1984

Special toxicology--physical dependence potential, antigenicity and mutagenicity--of mabuterol.

The physical dependence potency of dl-1- (4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert.-butyl-amino-ethanol hydrochloride (mabuterol) was tested in male rats dosed with 20, 100 and weekly increasing doses of 20, 40, 60, 80 and 100 mg/kg over 7 weeks. The results were compared with those after the same increasing dosages of morphine. 10 males were used per group. The effects of the antagonist levallorphan on drug dependency were also studied. No withdrawal signs were observed in any mabuterol-treated groups. No antigenic potency of mabuterol was found in a series of studies on guinea pigs and rats. In a series of mutagenicity studies (Ames-test, DNA repair test and micronucleus test) it could be demonstrated that mabuterol is not a mutagen.

Adrenergic beta-Agonists↗