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Biomedical subjects

H Kido

Publications and source records attributed to H Kido.

At least 127 records · Page 7Linked to original sources
PubMed1993

Antithrombotic effect of an anti-glycoprotein IIB/IIIA antibody in primate lethal thrombosis.

We investigated the antithrombotic effect of anti-glycoprotein (GP) IIb/IIIa antibody in a primate model of lethal thrombosis. Eight monkeys were injected intravenously with an anti-CD9 antibody (MALL13). They died within 5 min and displayed severe thrombocytopenia. Histological examination showed multiple platelet thrombi in the pulmonary microvasculature, but no thrombi in the liver, kidneys, or spleen. In contrast, monkeys pretreated with an anti-GPIIb/IIIa antibody (NNKY1-32) at 30 min before MALL13 administration did not die, and the thrombocytopenia in these animals did not develop as rapidly or become as severe. These results suggest that the antiCD9 antibody caused lethal pulmonary thrombosis in vivo, and that pretreatment with the anti-GPIIb/IIIa antibody was able to prevent this thrombosis.

Animals↗
PubMed1993

The alpha-type 85-kDa subunit of phosphatidylinositol 3-kinase is phosphorylated at tyrosines 368, 580, and 607 by the insulin receptor.

We have shown previously that insulin stimulated the tyrosine phosphorylation of the alpha-type 85-kDa subunit (p85) of phosphatidylinositol (PI) 3-kinase in vitro and in vivo. In the present work, we identified the major tyrosine phosphorylation sites of the alpha-type p85 by the insulin receptor. [32P]Phosphopeptides obtained from lysylendopeptidase digestion of phosphorylated alpha-type p85 in intact cells after insulin treatment were analyzed using reverse-phase high performance liquid chromatography and thin layer electrophoresis. The tyrosine phosphorylation sites of alpha-type p85 in vivo were assigned to three major phosphopeptides, designated p1, p2, and p3. Highly purified insulin receptor also phosphorylated the purified p85 of PI 3-kinase from the bovine thymus at p1. The purified glutathione S-transferase (GST)-p85 (alpha-type) fusion protein and its truncated proteins from Escherichia coli were also phosphorylated by the purified insulin receptor at p1, p2, and p3 in vitro. Analysis of [32P]phosphopeptide of the truncated GST-p85 (alpha-type) fusion proteins and radiosequence analysis revealed that the p1, p2, and p3 phosphopeptides were phosphorylated at tyrosines 607, 580, and 368, respectively. In addition, phenylalanine substitutions at tyrosine 607 and 580 reduced the p1 and p2 phosphopeptides in vivo, respectively. We conclude that the alpha-type p85 of PI 3-kinase was phosphorylated at tyrosines 368, 580, and 607 by the insulin receptor in vivo.

Amino Acid Sequence↗
PubMed1993

Flow cytometric analysis of changes in cytoskeletal proteins during platelet destruction and activation using a monoclonal antibody against platelet myosin.

We developed a new monoclonal antibody directed against platelet myosin (NNKY6-19). Using this antibody, we analyzed platelet cytoskeletal changes related to stimulation with thrombin and to long-term storage. Immunoelectron microscopy showed increased binding of NNKY6-19 to pseudopods and the open canalicular system during treatment with thrombin (0.1 U/ml) and during storage for 7 days. Flow cytometry also showed increased binding to platelets by NNKY6-19 and an antiactin monoclonal antibody during storage. The binding of NNKY6-19 showed an increase greater than that with the antiactin antibody after storage of platelets for 7 days and after thrombin treatment. These findings indicated that the increased binding of NNKY6-19 had some relationship to changes in intracellular myosin and platelet morphology. Thus use of NNKY6-19 allowed analysis of subtle changes related to platelet activation, which differed from those detected by antibodies against platelet glycoproteins or by the antiactin antibody. This antibody appears to provide a simple method for studying changes in platelet cytoskeletal and surface proteins.

Actins↗
PubMed1993

Antibody against the carboxyl terminus of the F2 subunit of Sendai virus fusion glycoprotein inhibits proteolytic activation.

Rabbit antibody, F2C12, was prepared against a synthetic peptide of 13 amino acids corresponding to the C-terminus of the F2 subunit of Sendai virus F protein. F2C12 was shown to bind specifically to the F2 subunit, irrespective of proteolytic cleavage of the F protein. F2C12 did not affect the infectivity, hemolytic, and cell fusion activities of activated virus, but F2C12 did inhibit proteolytic cleavage of the precursor F0 to subunits, F1 and F2, by trypsin, factor Xa from chick embryos and Tryptase Clara from rat lungs. When F2C12 was added to the chorioallantoic cavity of chick embryos, cleavage activation of Sendai virus was inhibited. Intranasal administration of F2C12 to Sendai virus-infected rats suppressed activation and multiplication of progeny virus in the lungs. These results indicate that proteolytic cleavage of the F protein, with a single arginine residue at the cleavage site, occurs extracellularly in the allantoic cavity of chick embryos and in the bronchial lumen of rats.

Allantois↗
PubMed1993

A membrane-bound metallo-endopeptidase from rat kidney: its immunological characterization.

The structure and location of a membrane-bound metallo-endopeptidase, previously purified from rat kidney [Yamaguchi et al. (1991) Eur. J. Biochem. 200, 563-571], were examined by immunochemical and immunohistochemical methods with a rabbit polyclonal antibody against the purified enzyme. On treatment with endoglycosidase F, the subunit of the purified enzyme (molecular mass = 88 kDa) was converted to a smaller form (78.5 kDa), indicating that the enzyme contained at least 11% N-linked carbohydrate. Treatment of kidney membranes with papain resulted in release of the enzyme, as shown by Western blotting analysis of the solubilized fraction. Immunoassays of rat tissues showed that only the kidney, and small and large intestine expressed significant amounts of the antigen. Moreover, immunohistochemical studies showed that the antigen was confined to the luminal surfaces of the proximal renal tubules and the intestinal villi. Thus, like another kidney membrane metallo-endopeptidase, meprin [Kounnas et al. (1991) J. Biol. Chem. 266, 17350-17357], the purified enzyme is shown to be a glycoprotein that is probably anchored in the plasma membrane, and located in the luminal surface of microvillar membranes of the kidney and intestine. These results indicate that our enzyme and meprin have clear structural and topological similarities.

Animals↗
PubMed1993

Platelet activation induced by an antiplatelet autoantibody against CD9 antigen and its inhibition by another autoantibody in immune thrombocytopenic purpura.

In a patient with immune thrombocytopenic purpura (ITP), we found a novel platelet-activating IgG (act-IgG) and an inhibitory IgG (inhi-IgG) that prevented activation induced by both CD9 monoclonal antibody (mAb) and the act-IgG. Purified IgG from the patient plasma caused a rise in [Ca2+]i and the aggregation of normal platelets, and bound to a 24 kD membrane protein. This aggregation was inhibited by aspirin, staurosporine, an inhibitor of protein kinase C, and F(ab')2 fragments of MALL13, a CD9 mAb. When the platelet count of this patient rose to normal range, the act-IgG disappeared. About 2 weeks later, the relapse of thrombocytopenia was observed. The purified IgG obtained in this period did not activate platelets but inhibited both the rise in [Ca2+]i and platelet aggregation stimulated by NNKY 1-19, a CD9 mAb, as well as the act-IgG, and bound to a 40 kD membrane protein. The inhi-IgG prevented the binding of IV-3, a mAb against Fc gamma receptor II (Fc gamma RII), but did not prevent the binding of NNKY 1-19 to its antigen. We suggest that the activating autoantibody recognized CD9 antigen and activated both the thromboxane- and phospholipase C-dependent pathways, while the inhibitory autoantibody recognized the Fc gamma RII and inhibited CD9 antibody-induced platelet activation mediated via this receptor.

Adult↗
PubMed1993

IgG inhibits the increase of platelet-associated C3 stimulated by anti-platelet antibodies.

We investigated the increase of platelet-associated IgG and complement component 3 (C3) caused by the in vitro action of anti-platelet MoAbs, and the effect of mouse and human IgG on these events. Anti-glycoprotein IIb/IIIa and anti-glycoprotein Ib MoAbs caused a slight increase of C3, but not of platelet-associated IgG. In contrast, anti-CD9 and anti-Fc gamma II receptor MoAbs caused an increase of both platelet-associated C3 and IgG. In particular, three MoAbs which activated the complement system caused a marked increase of C3. When platelet-rich plasma was treated with aspirin and prostaglandin E1 before incubation with antibodies, the increase of platelet-associated IgG was inhibited in all cases. In contrast, the increase of platelet-associated C3 was scarcely influenced. These results suggest that the binding to platelets of platelet-activating antibodies caused the increased expression of IgG molecules on the platelet surface and a possible increase of platelet-associated IgG. However, the increase of platelet-associated C3 appeared to depend on specific characteristics of the antibodies tested, such as a complement-activating effect. In addition, intact mouse or human IgG inhibited the increase of platelet-associated C3 caused by complement-activating antibodies, while F(ab')2 mouse or human IgG had no such effect. This suggested that the Fc portion of IgG may block the increase of C3 mediated by anti-platelet antibodies.

Animals↗
PubMed1993

Effects of AE0047 on renal haemodynamics and function in anaesthetized dogs.

1. The effects of AE0047, a newly developed calcium channel blocker, on renal haemodynamics and function were investigated and compared with those of nicardipine in anaesthetized dogs. 2. Intravenous injection of AE0047 (10 and 30 micrograms/kg) caused a dose-related fall in blood pressure (BP). The AE0047-induced fall in BP was of slow onset and long lasting. AE0047 at 10 micrograms/kg elicited a slight increase in renal blood flow (RBF) and urine formation. 3. When AE0047 was infused intrarenally at non-hypotensive doses (25 and 50 ng/kg per min), there was no significant increase in RBF. However, the glomerular filtration rate increased significantly after drug infusion. Intrarenal arterial (i.r.a.) infusion of AE0047 led to dose-related increases in urine flow (UF), urinary excretion of electrolytes (Na+, K+ and Cl-) and fractional excretion of electrolytes. The AE0047-induced increase in urine formation was of very slow onset and progressed even after the cessation of the AE0047 infusion. 4. The intrarenal arterial infusion of nicardipine at same doses as AE0047 produced significant increases in urine formation, but these effects were immediately restored to the control values after cessation of the nicardipine infusion. 5. It was shown that AE0047 has a long-lasting diuretic effect and that AE0047-induced diuresis may be due to inhibitory effects on sodium and water reabsorption in the renal tubules.

Anesthesia↗
PubMed1993

Time course of dopamine-D2 and serotonin-5-HT2 receptor occupancy rates by haloperidol and clozapine in vivo.

In vivo occupancy of dopamine-D1, D2 and serotonin-5-HT2 receptors by haloperidol 10 mg/kg and clozapine 20 mg/kg were studied. Rats were injected intravenously with [3H]-YM-09151-2, [3H]-SCH23390, or [3H]-ketanserin 10 min after the administration of the tested drugs. Fifteen to 240 min after the ligand injection, the receptor occupancy rates of the drugs in the striatum and frontal cortex were calculated. Clozapine demonstrated the higher 5-HT2 and lower D2 occupancies in the respective regions. A dose-response analysis of D2 and 5-HT2 receptor occupancy by the drugs consolidated the higher 5-HT2 binding affinity of clozapine in comparison with haloperidol. The present methodology may serve as an accurate tool to evaluate the peculiarity of various antipsychotics.

Animals↗
PubMed1993

Effects of kami-kihi-to (jia-wei-gui-pi-tang) on autoantibodies in patients with chronic immune thrombocytopenic purpura.

We studied the effect of Kami-kihi-to (Jia-Wei-Gui-Pi-Tang) on the production of autoantibodies in ten patients with chronic immune thrombocytopenic purpura. After administration of Kami-kihi-to, platelet count was increased in seven of the ten patients (p < 0.05). Using Western blotting, we demonstrated the disappearance of autoantibody reaction with antigen in one patient. However, platelet-associated IgG was decreased in eight of ten patients (p < 0.05). Kami-kihi-to appears to promote the suppression of autoantibodies in patients with chronic immune thrombocytopenic purpura. No side effects were observed in any patient. Thus, Kami-kihi-to may be a useful and safe drug in the management of chronic immune thrombocytopenia purpura.

Administration, Oral↗
PubMed1993

Diffuse cerebral hypoperfusion in epileptic patients observed from quantitative assessment with single photon emission computed tomography using N-isopropyl-(iodine-123)-p-iodoamphetamine.

Quantitative assessment of regional cerebral blood flow (rCBF) in the bilateral cerebral and cerebellar cortices was performed in 15 epileptic adult patients receiving chronic high-dose antiepileptic drug therapy and 22 normal volunteers matched for sex and age, using single photon emission computed tomography with N-isopropyl-(iodine-123)-p-iodoamphetamine. The entire averaged rCBF value in the epileptic patients, i.e. 52.8 +/- 13.7 ml/10 g/min (range: 25-78 ml/100 g/min), was significantly lower as compared with that in the normal subjects, i.e. 69.1 +/- 14.2 ml/100 g/min (range: 46-102 ml/100 g/min). Six of the 15 patients showed absolute rCBF values less than the minimum of the normal range, i.e. 46 ml/100 g/min, in all or most of the measured brain tissues. There was a significant correlation between the diffuse cerebral hypoperfusion and simultaneous ingestion of phenytoin and phenobarbital. The possible effects of antiepileptic drugs on rCBF are discussed.

Adult↗
PubMed1993

Probable cerebellar abnormality on N-isopropyl-(iodine-123)-p-iodoamphetamine single photon emission computed tomography scans in an epileptic patient receiving long-term high-dose phenytoin therapy.

Quantitative assessment of regional cerebral blood flow (rCBF) was performed in a 22-year-old man with intractable temporal lobe epilepsy on long-term high-dose phenytoin (PHT) therapy, using single photon emission computed tomography (SPECT) with N-isopropyl-(iodine-123)-p-iodoamphetamine. In all the SPECT scans repeated three times with changes in the PHT dose, absolute rCBF values were lower in most of the cerebral and cerebellar regions measured, as compared with 5 normal subjects matched for sex and age, and 22 normal subjects including the 5 men. Both the cerebellar to frontal rCBF ratio and cerebellar to cerebral rCBF ratio in the patient persistently showed low values, probably reflecting abnormal relative cerebellar hypoperfusion, whereas X-ray computed tomography and magnetic resonance brain imaging showed no abnormal findings. However, this probable cerebellar abnormality on SPECT was to some degree reversible with decreases in the PHT dose. These results suggest the utility of SPECT scans for early detection of cerebellar abnormalities known to be often present in epileptic patients, and imply a risk of long-term high-dose PHT therapy.

Adult↗
PubMed1993

Periodic production of antiplatelet autoantibody directed against GPIIIa in cyclic thrombocytopenia.

We report here a female patient with cyclic thrombocytopenia associated with antiplatelet autoantibodies. There was an inverse relationship between the level of platelet-associated IgG and platelet count. Bone marrow megakaryocytes were normal in number even during the thrombocytopenia. The binding of monoclonal antibodies (mAbs) against glycoprotein (GP) IIb/IIIa to patient platelets was significantly inhibited in the thrombocytopenic phase, while these mAbs normally bound to patient platelets obtained during the normal platelet count. Western blotting and mAb-specific immobilization of platelet antigens showed that both plasma autoantibody and the eluted IgG from the patient platelets bound to GPIIIa. These results suggest that the periodic production of antiplatelet autoantibody against GPIIIa caused cyclic destruction of platelets in this patient.

Adult↗
PubMed1993

Purification of a trypsin-type protease from human umbilical vein endothelial cells which is highly sensitive to the Kunitz inhibitor domain peptide of Alzheimer's disease amyloid protein precursor.

A trypsin-type protease was purified to enzymatic homogeneity from human umbilical vein endothelial cells by sequential affinity chromatographies. The enzyme specifically hydrolyzed dibasic substrates with leucine at the P3 positions, but scarcely hydrolyzed the other substrates tested. The enzyme was strongly inhibited by the Kunitz inhibitor domain peptide of Alzheimer's disease amyloid protein precursor (Ki value, 0.35 nM) and by the microbial inhibitors leupeptin and anti-pain. These results, together with a previous finding of a significant increase in the expression of Alzheimer's amyloid protein precursors (beta APPs) with the Kunitz inhibitor domain in Alzheimer's disease, suggest that the activity of the trypsin-type protease is suppressed by an increase of beta APPs with inhibitor activity in Alzheimer's disease, resulting in aberrant intracellular protein catabolism including degradation of beta APPs and beta-protein deposition.

Amino Acid Sequence↗
PubMed1993

Electron immunohistochemical localization in rat bronchiolar epithelial cells of tryptase Clara, which determines the pneumotropism and pathogenicity of Sendai virus and influenza virus.

The intracellular localization in rat bronchiolar epithelial cells of a novel trypsin-like protease named tryptase Clara, a possible activator of inactive viral fusion glycoprotein of influenza A and wild-type Sendai virus in the respiratory tract, was examined by electron microscopy. In thin sections embedded in LR White, gold particles indicating immunoreactivity of tryptase Clara were detected specifically in secretory granules of Clara cells. No immunoreactivity was detected in bronchiolar ciliated cells, alveolar cells including epithelial Type I and II cells, or alveolar macrophages. Some granules enveloped in a thin membrane and labeled intensely with immunogold particles were seen protruding from peripheral and submembrane regions and a few were observed free in the airway lumen. Scanning electron microscopy also revealed smooth droplets along the main body of Clara cells. These data suggest that tryptase Clara is secreted into the bronchiolar lumen. These findings are the first to show the subcellular localization of tryptase Clara in rat bronchioles and suggest the site of proteolytic activation of the progeny of enveloped pneumotropic viruses, such as Sendai virus and influenza virus.

Animals↗
PubMed1993

[Effects of intravenous administration of nasaruplase, a plasminogen pro-activator, on left ventricular function and systemic hemodynamics in a canine model of acute myocardial infarction].

The thrombolytic effects and changes in left ventricular function after intravenous administration of nasaruplase were examined in a canine thrombus model of acute myocardial infarction. When 8 U/kg/min of nasaruplase was intravenously administered after 30 min of coronary arterial occlusion, coronary recanalization was achieved in 78.6% (11/14) of the animals with little change in plasma fibrinogen concentration. There was no further decrease in cardiac output, left ventricular ejection fraction or regional wall motion immediately after reperfusion, compared with 30 min after coronary arterial occlusion. However, all these parameters returned to pre-occlusion levels one week after reperfusion. Nasaruplase markedly reduced infarct size as well as cardiac hypertrophy following coronary arterial occlusion, demonstrating suppression of the development of ischemic myocardial damage. These results indicate that coronary thrombolytic therapy with intravenous administration of nasaruplase is useful for the treatment of acute myocardial infarction.

Animals↗