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Biomedical subjects

S Kondo

Publications and source records attributed to S Kondo.

At least 991 records · Page 55Linked to original sources
PubMed1987

Inhibition of human factor VIIa-tissue factor activity by placental anticoagulant protein.

Previous studies indicated that human placental anticoagulant protein, a member of the lipocortin family, prolonged the clotting time of normal plasma when clotting was induced by brain thromboplastin or by kaolin in the presence of cephalin and calcium. Using a two-stage amidolytic assay to assess factor X activation and a tritiated peptide release assay to assess factor IX activation, we have examined the ability of purified preparations of placental anticoagulant protein (Mr = 36.5 kDa) to inhibit the activation of either factor X or factor IX by a complex of human factor VIIa-tissue factor. Placental anticoagulant protein markedly inhibits factor X and factor IX activation by factor VIIa-tissue factor in a non-competitive manner with Ki values of 40 nM and 70 nM, respectively. Placental anticoagulant protein had no effect on factor Xa amidolytic activity, and its inhibitory activity was not diminished by prior incubation with antibody raised against partially purified plasma extrinsic pathway inhibitor. Binding of placental anticoagulant protein to phospholipid vesicles, crude tissue factor and purified, relipidated human brain tissue factor apoprotein was observed only in the presence of calcium ions. These results indicate that placental anticoagulant protein is a potent factor VIIa-tissue factor inhibitor and suggests that its mechanism of action involves binding to the phospholipid portion of the tissue factor lipoprotein.

Annexins↗
PubMed1987

Characterization of a protein C activator from Agkistrodon contortrix contortrix venom.

The protease from Southern Copperhead venom that activates protein C was purified to homogeneity by sulfopropyl (SP)-Sephadex C-50 ion-exchange chromatography, Sephadex G-150 gel filtration, and Mono-S fast protein liquid chromatography. The purified enzyme is a glycoprotein containing 16% carbohydrate, and migrated as a single band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent molecular mass of 40,000 kDa. The enzyme is composed of a single polypeptide chain possessing an NH2-terminal sequence of Val-Ile-Gly-Gly-Asp-Glu-Cys-Asn-Ile-Asn-Glu-His. The purified venom protein C activator hydrolyzed several tripeptide p-nitroanilides. The amidolytic and proteolytic activities of the enzyme were readily inhibited by phenylmethanesulfonyl fluoride, p-amidinophenylmethanesulfonyl fluoride, chloromethyl ketones, and human antithrombin III. Covalent binding of diisopropyl fluorophosphate to the enzyme was confirmed using a tritium-labeled preparation of the inhibitor. The venom protease readily activated human and bovine protein C at 1:1000 enzyme:substrate weight ratio. The protease also cleaved human prothrombin, factor X, factor IX, factor VII, and fibrinogen. Prothrombin coagulant activity decreased upon incubation with the venom protease, and the rate of this reaction was reduced in the presence of calcium. Factor X and factor IX coagulant activity increased upon incubation with the venom protease in the presence of calcium, and decreased in the absence of calcium. Human factor VII clotting activity decreased slightly upon incubation with the venom protease. Although the venom protease did not clot human fibrinogen, it nonetheless cleaved the A alpha chain of fibrinogen, and this cleavage appeared to be associated with a measurable increase in the clottability of the protease-treated fibrinogen by thrombin. These data demonstrate that the protein C activator from Southern Copperhead venom is a typical serine protease with a relatively broad specificity.

Amino Acid Sequence↗
PubMed1987

Antithrombin III microheterogeneity in antithrombin III deficiency and in the antithrombin III abnormality, "antithrombin III Toyama".

Antithrombin III (AT III) microheterogeneity was investigated in 12 cases of congenital AT III deficiency and 2 cases of congenital AT III abnormality by isoelectric focusing (IEF) and immunofixation. In congenital AT III deficiency, IEF and immunofixation revealed AT III as 8 bands which was indistinguishable from normal control in terms of the number of bands and the isoelectric point (pI) of each band. In the proband of the congenital AT III abnormality, however, IEF and immunofixation showed AT III as 8 bands which shifted slightly but definitely to the acidic side compared to those of normal subjects. This change in pI of the abnormal AT III was considered to reflect the amino acid replacement in the polypeptide chain of the abnormal AT III molecule.

Adult↗
PubMed1987

Regulation of factor VIIa activity in plasma: evidence that antithrombin III is the sole plasma protease inhibitor of human factor VIIa.

The inhibition of human factor VIIa by antithrombin III and normal human plasma was studied in the presence and absence of heparin. In the absence of heparin, no apparent inhibition of factor VIIa was observed in either system. In the presence of heparin, factor VIIa activity was inhibited 50% by purified antithrombin III and plasma in 90 min and 75 min, respectively. No inhibition of factor VIIa was observed in heparinized plasma previously depleted of antithrombin III by immunoaffinity adsorption. Incubation of factor VIIa with antithrombin III-heparin or heparinized plasma resulted in the formation of a covalent complex with an apparent molecular weight of 100 kilodaltons. These data indicate that antithrombin III appears to be the sole plasma protease inhibitor of human factor VIIa, and the expression of its inhibitory activity against factor VIIa is absolutely dependent upon the presence of exogenous heparin.

Antithrombin III↗
PubMed1987

Isolation of a protein C activator from southern copperhead venom.

A protease from the venom of the Southern Copperhead snake (Agkistrodon contortrix contortrix) that activates protein C was purified to homogeneity by a combination of sulfopropyl (SP)-Sephadex C-50, Sephadex G-150 and Mono-S column chromatography. The purified enzyme is a glycoprotein, and migrated as a single band in sodium dodecylsulfate-polyacrylamide gel electrophoresis with an apparent molecular weight of 37,000 under non-reducing conditions. Upon reduction with 2-mercaptoethanol, the enzyme exhibited a Mr of 40,000. The purified enzyme prolonged the clotting time of human plasma in a dose- and temperature-dependent manner. Purified bovine protein C was completely activated within 10 minutes upon incubation with the purified protease at a 1:500 enzyme: substrate ratio. This reaction was markedly inhibited by calcium ions. The purified venom protein C activator had no effect on human fibrinogen.

Animals↗
PubMed1987

Growth factors and receptors of lymphocytes.

To understand molecular mechanisms of clonal expansion of lymphocytes we have isolated cDNA clones for two lymphokines, interleukins (IL) 4 and 5 that induce proliferation and maturation of B-lymphocytes. Structures of IL-4 and IL-5 revealed a remote homology with other lymphokines such as IL-3 and gamma-interferon. IL-4 and IL-5 were shown to affect not only B-lymphocytes but also T-lymphocytes and several other cells derived from bone marrow stem cells. We have also studied the structure and function of the IL-2 receptor: our focus was the molecular basis for the high and low affinity states of the receptor encoded by the identical cDNA. We propose the affinity conversion model that the high-affinity state of the IL-2 receptor is a ternary complex of IL-2, the IL-2 receptor, and a postulated "converter protein", which is fewer in number than the receptors.

Animals↗
PubMed1987

Production of virus-like particles by the transposable genetic element, copia, of Drosophila melanogaster.

Using the calcium-phosphate procedure the plasmid cDm2055, which carries the copia transposable element of Drosophila melanogaster, was co-transfected with the Neor-carrying plasmid pSVCneo-1 into the D. hydei cell line KUN-DH-33 which was free of copia. The Neor transfectants stably carried both plasmids as tandem oligomers integrated in the chromosome and virus-like particles (VLP) were produced specifically in the transfectants that received the copia plasmid. The particles were quite similar in various aspects such as size, morphology, density, RNA content and molecular weight of the major protein component, to retrovirus-like particles (RVLP) that spontaneously appear in cultured cells of D. melanogaster: the reverse transcriptase activity however seemed to be low compared to that of the D. melanogaster RVLP. This finding demonstrates that the retrovirus-like particles (RVLP) in Drosophila cultured cells are produced by the transposable genetic element copia resident in the host chromosomes.

Animals↗
PubMed1987

Bladder carcinoma with Werner syndrome.

Werner syndrome is a rapid premature aging disease and is considered chromosomal instability syndrome, occasionally associated with malignancy. Urologic malignancy associated with this syndrome is unusual. Herein we report a case of Werner syndrome with urinary bladder carcinoma.

Adult↗
PubMed1987

Defect in UV-induced unscheduled DNA synthesis in cultured epidermal keratinocytes from xeroderma pigmentosum.

DNA repair synthesis in 8 explant-outgrowth cultures of epidermal cells isolated from variant and complementation groups A and E of xeroderma pigmentosum (XP) was examined by measuring unscheduled DNA synthesis (UDS) on autoradiographs. The extents of UDS in XP epidermal cells were compared with those in normal epidermal cells obtained from 26 subjects. In both normal and XP epidermal cells, UDS was induced dose-dependently by radiation at doses of 5-20 J/m2. XP epidermal cells showed various extents of defect in DNA repair depending on the type of XP. In XP-A, the extent of UDS in epidermal cells was very low, being seen in only 3-10% of the normal epidermal cells. But epidermal cells isolated from XP-E and XP-variants exhibited relatively high levels of residual DNA repair; i.e., 69-84% of the control in XP-E and 67-85% in XP-variant. The extents of UDS in XP epidermal cells were almost the same as those in fibroblastic cells isolated from the same specimens.

Autoradiography↗
PubMed1987

Preliminary experimental results of gas recycling subsystems except carbon dioxide concentration.

Oxygen concentration and separation is an essential factor for air recycling in a CELSS. Furthermore, if the value of the plant assimilatory quotient is not coincident with that of the animal respiratory quotient, the recovery of O2 from the concentrated CO2 through chemical methods will become necessary to balance the gas contents in a CELSS. Therefore, oxygen concentration and separation equipment using Salcomine and O2 recovery equipment, such as Sabatier and Bosch reactors, were experimentally developed and tested.

Air Conditioning↗
PubMed1987

Thermoluminescence dosimetry of gamma rays from the Hiroshima atomic bomb at distances of 1.27 to 1.46 kilometers from the hypocenter.

Sixteen ornamental tile samples were collected from 1982 to 1983 from the rooftops of two buildings at Hiroshima University, Hiroshima, Japan. Quartz grains 50-150 microns in size extracted from the samples were analyzed for their thermoluminescence (TL) intensities. Conversion of TL intensity to 60Co gamma exposure resulted in the following estimates: 40.5 to 27.6 mC kg-1 (157 to 107 R) for five samples (one each) collected from five sites at distances of 1.27 to 1.34 km from the hypocenter of the atomic bomb detonated in 1945; 23.7 +/- 1.4 mC kg-1 (92 +/- 5 R) for three samples from one site at a distance of 1.39 km; 21.4 to 17.0 mC kg-1 (83 to 66 R) for three samples (one sample per site) from three sites at distances of 1.40 to 1.43 km; 19.8 +/- 1.3 mC kg-1 (77 +/- 5 R) for four samples from one site at a distance of 1.45 km; and 13.2 mC kg-1 (51 R) for one sample at a distance of 1.46 km. At face value, these estimates are greater by a factor of about 2.5 than previous estimates based on the tentative 1965 radiation dose estimates for atomic bomb survivors (a tentative dosimetry model proposed in 1965), but agree within +32% to -13% (+15% on the average) with recent estimates using modern computational techniques using an improved model of the atomic bomb explosion.

Cobalt Radioisotopes↗
PubMed1987

Significance of renal hyaline arteriolosclerosis and tubulo-interstitial change in IgA glomerulonephropathy and focal glomerular sclerosis.

The relationship between glomerular sclerosis and hyaline arteriolosclerosis (HA) or tubulo-interstitial (T-I) change was investigated in 66 patients with IgA glomerulonephropathy (IgA-GN) and in 12 patients with idiopathic focal segmental glomerulosclerosis (FGS). More than a 10% incidence of global sclerosis was noted in 15 patients with IgA-GN and in 9 patients with FGS. There was no significant discrepancy of age between patients with IgA-GN and those with FGS (IgA-GN: 37.5 +/- 12.5; FGS: 35.7 +/- 10.3). In patients with IgA-GN, 7 out of 15 were HA-positive (46.7%), whereas in patients with FGS, 7 out of 9 were HA-positive (77.8%). However, a close correlation was observed between glomerular sclerosis and T-I change only in patients with IgA-GN (r = 0.82; p less than 0.001). The results suggested that in the case of IgA-GN, T-I change was related to the prognosis of glomerular sclerosis. In addition, it is assumed that a possible correlation exists between FGS and HA.

Adolescent↗
PubMed1987

Moment analysis of intravenous, intraduodenal, buccal, rectal and percutaneous nifedipine in rats.

The pharmacokinetics and bioavailability of intravenous, intraduodenal, buccal, rectal and percutaneous nifedipine were studied in rats to evaluate the influence of route of administration. Plasma concentrations of nifedipine were determined by electron capture gas-liquid chromatography with preliminary oxidation of the drug to its pyridine analog. Pharmacokinetic evaluations were carried out by noncompartmental analysis of plasma concentration-time curves based on the statistical moment theory. The moments were computed by fitting a polyexponential function to the discrete time-course data of plasma concentration using the iterative least-squares method. A good computer fit to biexponential kinetics and a short mean residence time were observed after intravenous administration (i.v.). The linear distribution and disposition of nifedipine was found within the dosing range tested (0.025-0.100 mg/kg, i.v.). The systemic availability of nifedipine after intraduodenal administration was on the average between 52% and 57%, indicating that nifedipine is extensively metabolized during first passage through the liver. Avoidance of first-pass metabolism was investigated following buccal, rectal and percutaneous administration to rats. These nonportal routes of administration gave approximately 10-30% increases in systemic availability compared to that from intraduodenal nifedipine delivery. Moment analysis revealed variations of mixing condition of nifedipine at the dosing site. It was shown that the absorption occurs in a mammillary manner after intraduodenal and rectal administration. On the other hand, there is steady-state absorption of the drug from the buccal route of administration. Following percutaneous administration, the drug seems to be absorbed catenary to some degree.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Buccal↗
PubMed1987

Enhancement of transdermal delivery by superfluous thermodynamic potential. I. Thermodynamic analysis of nifedipine transport across the lipoidal barrier.

In vitro techniques were used to test certain concepts regarding the enhancement of the transdermal delivery of nifedipine from topical vehicles. Tested vehicles include the volatile solvent acetone, nonvolatile solvents such as propylene glycol and isopropyl myristate, volatile/nonvolatile mixtures, and those mixtures with a polymer additive. An ethylene-vinyl acetate (EVA) copolymer membrane was used as the lipoidal barrier for the diffusing drug. Not merely the rate of transport per unit area, but the activity coefficient and the diffusion coefficient of the penetrating agent in the barrier were obtained. Despite the 10,000-fold difference in the vehicle concentration, water and several hydrophilic vehicles containing finely ground suspensions of the drug produced nearly the same rate of penetration. Some lipophilic solvents affected the barrier function of the EVA membrane to promote penetration of the drug. It has been found that the activity coefficient in the EVA membrane is very susceptible to wide variations by imbibition of such solvents. From volatile/nonvolatile mixtures, a transient enhancement in the transport of nifedipine across the membrane was observed. The increase in the flux was accounted for by the increase in the thermodynamic activity of the drug in the nonvolatile vehicle caused by the evaporation of the volatile component. The eventual decrease in penetration was the result of the drug precipitation from the supersaturated solution. The precipitation was inhibited and/or retarded during the entire time course of the experiments when a polymer additive was present. The steady-state fluxes from mixtures with a polymer additive were higher by about 3 to 5 times than that of the control experiment.

Biological Transport↗
PubMed1987

Enhancement of transdermal delivery by superfluous thermodynamic potential. II. In vitro-in vivo correlation of percutaneous nifedipine transport.

Nifedipine was selected as a representative compound to investigate a method for improving transdermal bioavailability. The general strategy explored to improve the percutaneous transport of nifedipine was the manipulation of thermodynamics of the drug substance by the use of volatile/nonvolatile systems as vehicles. To investigate the potential of the strategy, diffusion studies were conducted using an ethylene-vinyl acetate copolymer (EVA) membrane and full-thickness excised abdominal skin of rats. Little penetration through EVA membrane or rat skin was found either from the volatile solvent ethanol (EtOH) or from the nonvolatile solvent diethyl sebacate (DES). When the vehicle was changed to a mixed solvent containing both EtOH and DES in a volume ratio of 75:25, penetration through EVA membrane or rat skin was increased up to 3 to 4 times, compared with those values for DES. The increase in the penetration was accounted for by the increase in the thermodynamic activity of the drug in the nonvolatile vehicle caused by the evaporation of the volatile component. The bioavailability of percutaneous nifedipine in rats was determined from the drug solutions containing different proportions of EtOH and DES. Once again, the highest bioavailability was achieved from the mixed solvent containing EtOH and DES in a volume ratio of 75:25. The area under the plasma nifedipine concentration-time curve for the mixed solvent was higher by about 4 times than that for DES.

Administration, Cutaneous↗
PubMed1987

Enhancement of transdermal delivery by superfluous thermodynamic potential. III. Percutaneous absorption of nifedipine in rats.

The bioavailability of percutaneous nifedipine was studied in rats. To improve the transdermal delivery of nifedipine, concentration changes due to loss of a volatile component in the vehicle were utilized. The percutaneous absorption of nifedipine was enhanced from binary solvent systems of acetone and propylene glycol (PG) or isopropyl myristate (IPM), compared with the results from simple PG or IPM saturated with the drug. In contrast, no appreciable increases in the percutaneous absorption of nifedipine from PG or IPM above controls were observed for pretreatment of the dosing site with acetone. From a ternary vehicle of volatile/nonvolatile-hydrophile/nonvolatile-lipophile solvent system, i.e., acetone-PG-IPM, a very dramatic enhancement in the bioavailability of nifedipine was noted. In addition, a marked increase in the penetration of PG from the ternary solvent system was found, compared with the result from the binary solvent system of acetone and PG. Nifedipine solutions with the volatile component eventually caused precipitation at the dosing site and so reduced the plasma nifedipine concentration. The precipitation was inhibited or retarded when polymer additives were incorporated in the ternary solvent system, and the high plasma nifedipine concentrations were maintained. This effect was not diminished when the formulation was administered immediately after the evaporation of acetone. The area under the plasma nifedipine concentration-time curve from the ternary solvent system with a polymer additive was higher by about 75 times than that from PG saturated with the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrylic Resins↗
PubMed1987

The time course of changes in force and cyclic AMP levels produced by isoproterenol and forskolin in isolated rabbit detrusor muscle.

The effects of forskolin and isoproterenol on contractile force and cyclic AMP (cAMP) levels were compared in rabbit detrusor. Both forskolin and isoproterenol produced relaxation of rabbit detrusor and an increase in cAMP levels in the tissue. Although the relaxant response to forskolin was similar to that of isoproterenol, the increase in cAMP levels induced by forskolin was significantly larger than that induced by isoproterenol. These results suggest that there is a discrepancy in the relaxation responses and cAMP levels in response to forskolin and isoproterenol.

Animals↗