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Biomedical subjects

H Kido

Publications and source records attributed to H Kido.

At least 145 records · Page 8Linked to original sources
PubMed1993

[Inhibition of eosinophil peroxidase release by chymotrypsin type protease inhibitors from activated human eosinophils].

Eosinophils contain many cytotoxic mediators including eosinophil peroxidase (EPO) in their granules and these mediators are released by various pathophysiological stimuli, resulting in severe damage to various epithelia. However, little is known about the intracellular mechanism of the degranulation. Here we report that eosinophils isolated from patients with bronchial asthma who were not taking corticosteroid hormone had significant amidolytic activities on Suc-Ala-Ala-Pro-Phe-MCA, and also that the activity was completely inhibited by chymostatin (1 x 10(-4) M), eglin C (1 x 10(-4) M), and peptide boronic acid (1 x 10(-4) M), indicating that eosinophils contain a chymotrypsin-like serine protease in the fraction eluted in 50 mM potassium phosphate buffer, pH 8.0 containing 2 M NaCl. Among the various types of protease inhibitors examined, one of the chymotrypsin-type proteases chymostatin (1 x 10(-4) M), but none of the other types of proteases such as leupeptin and E-64, markedly inhibited the EPO release (c.a. 60%) from eosinophils stimulated by immunoglobulin-G (2.5 mg protein/ml beads) in the presence of rhIL-5 (10 ng/ml) or platelet-activating factor (1 x 10(-7) M), although it had no effect on the release by calcium ionophore A23187 (1 x 10(-7) M).

Adult↗
PubMed1993

Probable cerebellar abnormality on 123I-IMP SPECT scans in epileptic patients with long-term high-dose phenytoin therapy. Based on observation of multiple cases.

Quantitative assessment of regional cerebral blood flow (rCBF) in the bilateral cerebral and cerebellar cortices was performed in 13 epileptic patients receiving long-term high-dose phenytoin (PHT) therapy, using single photon emission computed tomography (SPECT) with N-isopropyl-(iodine 123) p-iodoamphetamine. In 4 of the 13 patients, both the cerebellar to frontal rCBF ratio and cerebellar to cerebral rCBF ratio showed low values as compared with those in 22 normal subjects matched for sex and age, probably reflecting abnormal relative cerebellar hypoperfusion. None of the 4 patients showed any abnormal findings on X-ray computed tomography or magnetic resonance brain imaging. The patients with a history of acute PHT intoxication tended to show the abnormal relative cerebellar hypoperfusion. 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

Quantitative assessment of regional cerebral blood flow with 123I-IMP in normal adult subjects.

Quantitative assessment of regional cerebral blood flow (rCBF) in the bilateral cerebral and cerebellar cortices was performed in 22 normal adult subjects consisting of an early twenties group (5 men and 9 women, 20-22 years) and middle age group (3 men and 5 women, 41-52 years), using single photon emission computed tomography (SPECT) with N-isopropyl-(iodine 123) p-iodoamphetamine. Absolute rCBF values in each region in the 22 subjects ranged from 46 to 102 ml/100 g/min (mean 69.1, standard deviation 13.7 ml/100 g/min). The absolute rCBF values were significantly higher in women than in men, and in the early twenties group than in the middle age group. In addition, based on each absolute rCBF value, the interhemispheric asymmetry, anterior to posterior ratio and cerebellar to frontal ratio in rCBF were calculated. These results may be useful as indexes for detecting organic and functional brain abnormalities in various neuropsychiatric diseases.

Adult↗
PubMed1992

Salvage of infarcted myocardium by angiogenic action of basic fibroblast growth factor.

Coronary collateral vessels reduce damage to ischemic myocardium after coronary obstruction. Factors that stimulate collateral formation are expected to have ameliorating effects on myocardial infarction. In a canine experimental myocardial infarct model, intracoronary injection of basic fibroblast growth factor (bFGF) improved cardiac systolic function and reduced infarct size. Treatment with bFGF increased the number of arterioles and capillaries in the infarct. Thus, the angiogenic action of bFGF might lead to a reduction in infarct size. The application of bFGF might bring about a therapeutic modality for the salvage of infarcted myocardium.

Animals↗
PubMed1992

Isolation and characterization of a novel trypsin-like protease found in rat bronchiolar epithelial Clara cells. A possible activator of the viral fusion glycoprotein.

A novel trypsin-like protease associated with rat bronchiolar epithelial Clara cells, named Tryptase Clara, was purified to homogeneity from rat lung by a series of standard chromatographic procedures. The enzyme has apparent molecular masses of 180 +/- 16 kDa on gel filtration and 30 +/- 1.5 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. Its isoelectric point is pH 4.75. Studies with model peptide substrates showed that the enzyme preferentially recognizes a single arginine cleavage site, cleaving Boc-Gln-Ala-Arg-4-methylcoumaryl-7-amide most efficiently and having a pH optimum of 7.5 with this substrate. The enzyme is strongly inhibited by aprotinin, diisopropylfluorophosphate, antipain, leupeptin, and Kunitz-type soybean trypsin inhibitor, but inhibited only slightly by Bowman-Birk soybean trypsin inhibitor, benzamidine, and alpha 1-antitrypsin. Immunohistochemical studies indicated that the enzyme is located exclusively in the bronchiolar epithelial Clara cells and colocalized with surfactant. An immunoreactive protein with a molecular mass of 28.5 kDa was also detected in airway secretions by Western blotting analyses, suggesting that the 30-kDa protease in Clara cells is processed before or after its secretion. Proteolytic cleavage of the hemagglutinin of influenza virus is a prerequisite for the virus to become infectious. Tryptase Clara was shown to cleave the hemagglutinin and activate infectivity of influenza A virus in a dose-dependent way. These results suggest that the enzyme is a possible activator of inactive viral fusion glycoprotein in the respiratory tract and thus responsible for pneumopathogenicity of the virus.

Amino Acid Sequence↗
PubMed1992

A membrane-bound metallo-endopeptidase from rat kidney. Characteristics of its hydrolysis of peptide hormones and neuropeptides.

A membrane-bound metallo-endopeptidase that hydrolyzes human parathyroid hormone (1-84) and reduced hen egg lysozyme between hydrophilic amino acid residues was isolated from rat kidney [Yamaguchi et al. (1991) Eur. J. Biochem. 200, 563-571]. In this study, the hydrolyses of various peptide hormones and neuropeptides by the metallo-endopeptidase were examined using an automated gas-phase protein sequencer. The purified enzyme hydrolyzed the oxidized insulin B chain and substance P most rapidly, followed by big endothelin 1, neurotensin, angiotensin 1, endothelin 1, rat alpha-atrial natriuretic peptide and bradykinin, in this order. The enzyme mainly cleaved these peptides at bonds involving a hydrophilic amino acid residue. However, it cleaved bonds between less hydrophilic amino acid pairs in several short peptides, e.g. at the His5-Leu6 bond in oxidized insulin B chain, the Ile28-Val29 bond in big endothelin-1 and the Ile5-His6 and Phe8-His9 bonds in angiotensin 1. The enzyme cleavage sites of oxidized insulin B chain and angiotensin 1 were different from the reported sites cleaved by meprin and by endopeptidase 2, respectively. Kinetic determination of bradykinin hydrolysis by the purified enzyme yielded values of Km = 18.1 microM and kcat = 0.473 s-1, giving a ratio of kcat/Km = 2.62 x 10(4) s-1.M-1. The Km value was about 20-fold lower than that reported for meprin and endopeptidase 2. These results indicate that the membrane-bound metallo-endopeptidase from rat kidney is distinguished from meprin and endopeptidase 2 in its substrate specificity and is not parathyroid hormone specific, but has potential capacities to inactivate various biologically active peptide hormones and neuropeptides in vivo.

Amino Acid Sequence↗
PubMed1992

Effects of ticlopidine on monoclonal anti-CD9 antibody-induced platelet aggregation and microparticle generation.

We analyzed the effects of ticlopidine on platelet aggregation and on microparticle (MP) formation when platelets were exposed to a monoclonal anti-CD9 antibody (NNKY1-19) in vitro. Even when NNKY1-19-induced platelet aggregation was completely inhibited by preincubation with anti-GPIIb/IIIa antibody or Arg-Gly-Asp-Ser, or by using washed platelets from a Glanzmann's thrombasthenia patient, the formation of MP was still observed. Prostaglandin E1 and protein kinase C antagonists (H-7 and staurosporine) inhibited both NNKY1-19-induced aggregation and MP formation. Ticlopidine or aspirin plus apyrase scarcely affected NNKY1-19-induced platelet aggregation, except to prolong the lag time. However, ticlopidine significantly inhibited MP formation (p less than 0.01). These results suggest that ticlopidine inhibits NNKY1-19-induced MP formation by a different mechanism to that of the other antagonists, and that this mechanism is unrelated to the inhibition of platelet aggregation.

Adenosine Triphosphate↗
PubMed1992

Brain regional pharmacokinetics of biperiden in rats.

The pharmacokinetic profiles of biperiden (BP) in blood and in specific brain regions were investigated in rats after acute i.v. administration. The regional brain-to-blood unbound concentration ratios (Kpf) were also determined after 16 h intravenous infusion of BP. The Kpf values ranged from 30 to 75 in the different brain regions and showed decreasing concentrations in the following order: pons + medulla oblongata, basal ganglia, amygdala, hypothalamus, thalamus, mesencephalon, bulbus olfactorius + septum, hippocampus, frontal cortex, occipital cortex, cerebellum. The relationship between BP and acetylcholine (ACh) concentrations in the brain regions was examined. ACh levels in the various brain regions ranged from 8 to 44 ng g-1 tissue. There was a significant correlation between the Kpf values of BP and the levels of ACh in the brain regions except for the pons + oblongata. BP concentrations in the brain regions after BP administration were predicted based on the physiological pharmacokinetics. There was reasonable agreement between the model predictions and the observed data.

Acetylcholine↗
PubMed1992

Differences between platelet and microparticle glycoprotein IIb/IIIa.

Glycoprotein (GP) IIb and IIIa are major constituents of the platelet membrane which are involved in forming the fibrinogen receptor on activated platelets. We used flow cytometry to study the effects of ethylene-diamine tetraacetic acid (EDTA) on the membrane GPIIb/IIIa complexes of platelets and microparticles, and to study the effects of cations on dissociated GP complexes. Microparticles were detected by both the volume signal and by fluorescence using an FITC-conjugated anti-GPIb antibody (NNKY5-5). When platelets were stimulated with ADP, calcium ionophore A23187, or thrombin, fibrinogen binding to the platelet surface increased markedly. However, fibrinogen binding to microparticles showed little increase in response to such agonists. Microparticle GPIIb/IIIa complexes were dissociated by incubation with EDTA at 37 degrees C but did not reassociate after treatment with divalent cations (Ca2+, Mg2+, and Mn2+) in contrast to platelet GPIIb/IIIa complexes. These results suggest that some interaction of GPIIb/IIIa and linked structures like the platelet cytoskeleton may be involved in the reassociation of dissociated GPIIb and GPIIIa, perhaps explaining the failure of reassociation of microparticle GPIIb/IIIa (i.e., the fibrinogen binding to microparticles).

Adenosine Diphosphate↗
PubMed1992

Anti-phospholipid antibodies bind to platelet microparticles in idiopathic (autoimmune) thrombocytopenic purpura.

We recently reported that IgM antibody-related microparticles exist in some patients with idiopathic thrombocytopenic purpura (ITP) [14]. In this study, we investigated the relationship between antiphospholipid (cardiolipin and phosphatidylinositol) antibodies and microparticles in 56 ITP patients. We used an ELISA to detect anti-phospholipid antibodies. IgG antibodies against cardiolipin and phosphatidylinositol were detected in 13 and 12 patients, respectively. The titers of IgG antibodies against these phospholipids did not correlate with the platelet-associated IgG level or the platelet count. Next, we investigated the binding of anti-phospholipid antibodies to platelets and microparticles. Microparticles were obtained by incubating washed platelets with collagen plus thrombin. ITP plasma containing IgG-class anti-phospholipid antibodies showed significantly increase binding to microparticles compared with plasma without such antibodies (p less than 0.001). Our results suggest that anti-phospholipid antibodies could affect the function of platelet microparticles in ITP.

Antibodies↗
PubMed1992

A novel loop diuretic, torasemide, inhibits thromboxane A2-induced contraction in the isolated canine coronary artery.

We examined the effect of a novel antihypertensive diuretic, torasemide, on the vasoconstriction induced by TXA2 in the isolated canine coronary artery. Carbocyclic thromboxane A2 (CTA2), a stable analogue of the potent coronary vasoconstrictor thromboxane A2, exhibited a slow onset and progressive contraction of isolated canine coronary arteries at 2 x 10(-8) M. Torasemide (10(-7) approximately 10(-4) M) elicited a dose-dependent vasodilating action in the isolated canine coronary arteries contracted by CTA2, whereas indapamide or furosemide had little effect on this preparation. The maximum vasodilating response to torasemide was 45 +/- 12% of vasodilating effect induced by 10(-4) M papaverine. These results suggest that torasemide is a promising antihypertensive agent with a coronary protective effect.

Animals↗
PubMed1992

Diuretic action of the novel loop diuretic torasemide in the presence of angiotensin II or endothelin-1 in anaesthetized dogs.

The effects of torasemide (0.1 and 1 mg kg-1, i.v.) and furosemide (3 mg kg-1) on renal haemodynamics and excretory responses in the presence of angiotensin II and endothelin-1 was examined in anaesthetized dogs. Angiotensin II or endothelin-1 was continuously infused into the renal artery throughout the experiment and a bolus of torasemide or furosemide was injected into the bracheal vein. Continuous intrarenal arterial (i.r.a.) infusion of angiotensin II, at a dose of 5 ng kg-1 min-1, increased renal vascular resistance (RVR) and decreased renal blood flow (RBF) and glomerular filtration rate (GFR), but had no effect on systemic mean arterial pressure (MAP). Urinary excretion of sodium (UNaV) and urine flow (UF) were significantly decreased during angiotensin II infusion. Intravenous injections of torasemide in the presence of angiotensin II caused a dose-dependent increase in UF, UNaV and urinary excretion of potassium (UKV), while a decrease in RVR was accompanied by an increase in RBF. UKV was greater in the furosemide group than in the torasemide group, despite both groups having the same degree of aquaresis and natriuresis. Continuous i.r.a. infusion of endothelin-1, 1.5 ng kg-1 min-1, produced effects similar to those of angiotensin II on renal haemodynamics; however, the onset of action was extremely slow compared with the effects produced by angiotensin II. Endothelin-1 caused a significant decrease in UF, UNaV and UKV only at a later period, despite a relatively early depression of renal haemodynamics. Torasemide and furosemide also produced a sufficient diuretic action in this model.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1992

Torasemide, but not frusemide, increases intracellular cAMP and cGMP content in the aorta of the renal hypertensive rat.

Repeated oral administration of the novel loop diuretic torasemide (3 mg kg-1) and frusemide (30 mg kg-1) for 7 days, elicited a significant fall in the systolic blood pressure in the one-kidney, one-clip Goldblatt renal hypertensive rat (RHR). The hypotensive action was greater in the torasemide group than in the frusemide group. Furthermore torasemide increased intracellular cAMP and cGMP content in aorta of RHR. Frusemide caused no effect. It is hypothesized that the increase in adenosine- or guanosine-nucleotides is involved in the antihypertensive action of torasemide, but not in that of frusemide.

Animals↗
PubMed1992

Tryptase Clara, an activating protease for Sendai virus in rat lungs, is involved in pneumopathogenicity.

Tryptase Clara is an arginine-specific serine protease localized exclusively in and secreted from Clara cells of the bronchial epithelium of rats (H. Kido, Y. Yokogoshi, K. Sakai, M. Tashiro, Y. Kishino, A. Fukutomi, and N. Katunuma, J. Biol. Chem. 267:13573-13579, 1992). The purified protease was shown in vitro to behave similarly to trypsin, cleaving the precursor glycoprotein F of Sendai virus at residue Arg-116 and activating viral infectivity in a dose-dependent manner. Anti-tryptase Clara antibody inhibited viral activation by the protease in vitro in lung block cultures and in vivo in infected rats. When the enzyme-specific antibody was administered intranasally to rats that were also infected intranasally with Sendai virus, activation of progeny virus in the lungs was significantly inhibited. Thus, multiple cycles of viral replication were suppressed, resulting in a reduction in lung lesions and in the mortality rate. These findings indicate that tryptase Clara is an activating protease for Sendai virus in rat lungs and is therefore involved in pulmonary pathogenicity of the virus in rats.

Animals↗
PubMed1992

[The vasospasmolytic effects of nicorandil, cromakalim and pinacidil on 3,4-diaminopyridine-induced phasic contractions in canine coronary arteries as an experimental vasospasm model].

The spasmolytic mechanisms of nicorandil, a novel antianginal drug, were investigated using 3,4-diaminopyridine (3,4-DAP)-induced phasic contractions of isolated canine coronary arteries in comparison with those of cromakalim and pinacidil. Nicorandil (10(-4) M), cromakalim (10(-6) M) and pinacidil (10(-5) M) suppressed the phasic contractions. Pretreatment with glibenclamide (10(-6) M), a specific blocking agent of ATP-sensitive K+ channel, eliminated the suppression of phasic contractions by these drugs; glibenclamide completely eliminated the suppression by cromakalim, while the eliminations against nicorandil and pinacidil were incomplete. The recoveries of peak tensions were only 56.8% and 76.1% for nicorandil and pinacidil, respectively. Nicorandil and pinacidil may suppress the phasic contractions via K+ channel opening and additional mechanisms. Methylene blue (10(-7)-10(-5) M) alone, a guanylate cyclase inhibitor, had no effect on the suppression of phasic contractions by nicorandil. In the presence of glibenclamide (10(-6) M), however, the pretreatment with methylene blue significantly augmented the recovery of peak tension for nicorandil. These results indicate that K+ channel openers may suppress the phasic contractions induced by 3,4-DAP via ATP-sensitive K+ channels, and that additionally, nicorandil may suppress the phasic contractility through guanylate cyclase stimulation, as a nitrate.

4-Aminopyridine↗