Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Radiographic iodized contrast media impair the antithrombin effect of the fibrin clot. The extent of the impairment correlates with dosage and lipophilicity. Normally, 90% of the thrombin activity of 2.3 IU/ml are inactivated by a fibrin clot generated by 2 mg/ml fibrinogen. The effect is due to contrast media-induced protein denaturation with subsequent impairment of thrombin binding to the fibrin clot. Two hepatogenic, two ionic, nephrotopic, and four nonionic contrast media were assayed by this test system at different concentrations. Clear-cut differences were found between the three main groups. Smaller, yet statistically significant, differences could be established between ioglicate and diatrizoate and between iosimide, iopromide or iohexol and iotrolan. No differences were found between iotroxate and iodoxamate. The results are in concordance with the partition coefficients (water/n-butanol) of these contrast media. The assay sensitivity is suitable as a screening system of the chemotoxicity of contrast media. It is easily performed, inexpensive, and assays the clinically important contrast media interaction with fibrinogen.
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PMID:Comparative assays of the chemotoxicity of iodinated radiographic contrast media based on impairment of fibrin antithrombin activity. 256 97

We describe our new endoscopic procedure for correction of ureterovesical reflux by endoscopic injection of the patient's own heparinized blood behind the ureteral orifice. Before drawing out the needle, small amounts of thrombin and protamine were injected to prevent the injected blood from leaking. Of the 16 ureters treated (13 patients) with international grade I-III reflux, 9 showed complete absence of reflux. The technique is advantageous because it is technically simple and injection can be repeated until the reflux had disappeared. Furthermore, no complications such as distant migration of injected material or escape from the bladder mucosa have been observed. However, the treatment is not consistently successful in cases of high-grade reflux. After the operation, mucosal swelling of ureteral orifice and narrowing of the intramuscular ureter were observed by ultrasonography. The mean pressure of the intramuscular ureter increased 10 cm H2O after the operation. These consequences of the operation may prevent vesicoureteral reflux.
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PMID:Long-term results and curative mechanisms of vesicoureteral reflux by endoscopic injection of blood. 281 47

Thrombin stimulation of human platelets initiates a membrane depolarization attributable to a Na+ influx into, and an alkalinization of, the cytoplasm, both of which follow a similar rapid time scale and thrombin-dose dependence. These responses precede secretion of the contents of the dense granules (serotonin) and, after 1 minute, of lysosomes (beta-glucuronidase). We have evaluated these parameters in the presence of 2H2O in order to determine if the Na+ influx and H+ efflux are sequential or simultaneous. NMR evidence indicates that 2H2O equilibration in rapid, and virtually complete within the 3 min prestimulation platelet equilibration period. In response to an 0.05 U/ml addition of thrombin, the rate of depolarization is 70-80% slower in 2H2O than in H2O. The time to reach maximal depolarization is 5 to 10 seconds longer in 2H2O, the extent of depolarization 60% inhibited, and the pH change 85% inhibited. The serotonin secretion is unaltered, while the beta-glucuronidase secretion is 130-180% enhanced. Dimethylamiloride inhibits the Na+ influx and the pH change completely. These results suggest that the Na+ and H+ fluxes across the plasma membrane are interdependent but neither simultaneous nor electroneutral. Furthermore, granule secretion, previously shown by us to be independent of the existent Na+ gradient, depends on the cytoplasmic K+ and H+ concentrations.
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PMID:Sequential sodium-proton exchange in thrombin-induced human platelets. 282 Apr 94

The authors examined the in vitro effects of serum generated by the action of alpha-thrombin on citrated whole blood or plasma. Serum samples were assessed for their ability to induce neutrophil aggregation, neutrophil adherence to cultured endothelial cell monolayer, and superoxide anion generation. The results indicated that both blood- and plasma-derived sera induced similar increases in neutrophil aggregation. Both sera also induced neutrophil adherence to cultured bovine pulmonary artery endothelial monolayer. The adherence increased in a time-dependent manner, producing little change after 5 minutes, and reached maximal response at 60 minutes. Full potency of the neutrophil adherence was evident with serum samples obtained after clotting time of 20 minutes but not at 5 minutes clotting time. The adherence-inducing activity of serum was gradually lost after storage at -20 C and was abolished by 100 C treatment for 2 minutes. In contrast, heating serum to 56 C for 30 minutes did not alter the adherence-inducing activity. Both ether and aqueous fractions obtained after ether extraction of serum possessed adherence-promoting activities, indicating that multiple factors (both lipid and water soluble) were involved. Pretreatment of the endothelium with serum resulted in increased endothelial adhesiveness, but the serum pretreatment failed to induce adhesiveness to subendothelial matrix, indicating that endothelial cells play an active role in acquiring the adhesive property. Serum obtained from thrombin-generated whole blood also resulted in a modest degree of neutrophil superoxide anion generation, but this did not occur with plasma-derived serum. The results indicate that serum factors obtained by clotting blood with thrombin induce neutrophil aggregation and neutrophil adherence to the endothelium as well as superoxide production. These factors appear to be generated in the plasma phase, because the responses were similar in blood- and plasma-derived serum.
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PMID:Thrombin-induced generation of neutrophil activating factors in blood. 282 93

To elucidate the role of the phosphoinositide signal transduction system in endothelial endothelial prostacyclin production, endothelial cells from human umbilical veins previously labelled with 3H-inositol were incubated with thrombin or histamine. Water-soluble inositol phosphates were separated on anion exchange columns. Both agonists evoked transient bursts of inositol phosphate production with inositol trisphosphate peaking at 15 seconds in histamine-stimulated cells and at 60 seconds in thrombin-stimulated cells. The inositol phosphate production was closely linked to prostacyclin production. After stimulation, there was concurrent desensitization to prostacyclin production and formation of inositol phosphates. Arachidonic acid and the Ca2+-ionophore A23187 did not affect inositol phosphate production in concentrations sufficient to increase prostacyclin production 20-fold, and they did not affect desensitization to a subsequent thrombin stimulation. The phorbol ester 12-o-tetradecanoyl phorbol 13-acetate, a stimulator of protein kinase C, inhibited thrombin-induced generation of inositol phosphates, enhanced A23187-mediated prostacyclin production, and had complex effects on thrombin-mediated prostacyclin production, but had no effect on its production from extrinsic arachidonic acid. The current data suggest that production of inositol phosphates is a link in receptor stimulation of endothelial cells to produce prostacyclin and that associated activation of protein kinase C affects both the generation of second messengers and the release of arachidonic acid.
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PMID:Role of phosphoinositides in the regulation of endothelial prostacyclin production. 283 64

The present study examines the effects of water soluble extracts of gas-phase cigarette smoke on intracellular transglutaminase activities of intact, murine, bone marrow-derived macrophages maintained in culture. Western blotting of cell lysates utilizing noncross-reactive antisera indicate that mouse bone marrow-derived macrophages contain both tissue-type transglutaminase and factor XIII-associated transglutaminase. This finding is also supported by data indicating that the intracellular transglutaminase activity of these cells contains thrombin-dependent and -independent components. Macrophages incubated with cigarette smoke solutions for 15 minutes at 37 degrees C display a dose-dependent decrease (maximum inhibition = 55%, p less than .001) in tissue-type (thrombin-independent) transglutaminase activity, as compared to control cells incubated with phosphate-buffered saline. Factor XIII (zymogen) is not inactivated following incubation of macrophages with smoke extracts. Smoke exposure under the conditions employed has no effect on either cell viability or adherence. Incubation with 2 microM retinoic acid for 24 hours leads to a modest (2-fold) induction of tissue transglutaminase, but does not induce factor XIII; in contrast, incubation with 10% homologous serum for 24 hours results in a decrease in factor XIII, but does not affect tissue transglutaminase. These data indicate that: bone marrow-derived macrophages contain factor XIII as well as tissue-type transglutaminase; and gas-phase cigarette smoke can inactivate tissue transglutaminase within viable murine bone marrow-derived macrophages, but cannot inactivate zymogenic factor XIII.
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PMID:Characterization of two distinct transglutaminases of murine bone marrow-derived macrophages: effects of exposure of viable cells to cigarette smoke on enzyme activity. 288 87

In an earlier study we reported the effect of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] in releasing Ca2+ from highly purified human platelet intracellular membrane vesicles. [Authi & Crawford (1985) Biochem. J. 230, 247-253]. We have now investigated the metabolic and functional consequences of introducing Ins(1,4,5)P3 into saponin-permeabilized platelets. Washed human platelets when resuspended in a suitable medium were permeabilized with saponin (10-14 micrograms/ml) to allow entry of low-Mr water-soluble molecules without significant release of the cytoplasmic marker enzyme protein lactate dehydrogenase. Saponin-permeabilized platelets show identical platelet responses (shape change, aggregation and release of 5-hydroxy[14C]tryptamine) to both collagen (5 micrograms/ml) and thrombin (0.1 unit/ml) as obtained with intact cells, indicating that there is minimal disturbance to the surface membrane receptor topography for these two agonists. Ins(1,4,5)P3 (1-10 microM) added to saponin-treated platelets (but not to intact platelets) induced dose-related shape change, aggregation and release of 5-hydroxy[14C]tryptamine which at maximal doses was comparable with responses obtained with thrombin or collagen. The cyclo-oxygenase inhibitors indomethacin and aspirin, if added prior to saponization and Ins(1,4,5)P3 addition, completely inhibited both aggregation and release of 5-hydroxy[14C]tryptamine (EC50 for indomethacin, 50 nM; for aspirin, 30 microM). We believe that Ins(1,4,5)P3 induces the release of Ca2+ from intracellular storages sites which stimulates the Ca2+-dependent phospholipase A2 releasing arachidonic acid from membrane phospholipids. Arachidonic acid is then converted to the aggregatory prostanoids (prostaglandin H2 and thromboxane A2) resulting in the observed responses. This concept is supported by the use of the thromboxane receptor antagonists EPO 45 and EPO 92, both of which also completely inhibit Ins(1,4,5)P3-induced responses in saponin-permeabilized platelets. Electron microscopy of the platelet preparations revealed that thrombin- and collagen-induced platelet aggregates of intact and saponized cells were identical, showing extensive pseudopod formation and dense granule release. The Ins(1,4,5)P3-induced aggregates also showed similar dense granule release but an almost total absence of pseudopod formation. These results are discussed in the light of the second messenger role of Ins(1,4,5)P3 in stimulus-response coupling in platelets.
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PMID:Metabolic and functional consequences of introducing inositol 1,4,5-trisphosphate into saponin-permeabilized human platelets. 293 27

Gold sodium thiomalate is a pale yellow powder which forms a colorless solution when added to sterile water. The marketed form of gold sodium thiomalate is a pale yellow solution. The yellow color develops as a result of the sterilization process. This study demonstrates that the physical change induced in the drug by the sterilization process has no effect on the action of gold sodium thiomalate on the serine esterase thrombin, nor on the inhibition of the mixed lymphocyte response. Thus it is unlikely that the yellow component is responsible for benefit in rheumatoid arthritis. If the components creating the yellow color cause toxicity, the preparation and/or formulation of the drug should be changed.
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PMID:Biological action of colorless and yellow solutions of gold sodium thiomalate on thrombin activity and the mixed lymphocyte reaction. 297 3

The present study examined the influence of activation on platelet deformability. Aspiration of cells after exposure to thrombin, adenosine 5' -diphosphate, or the calcium ionophore A23187 at concentrations producing shape change and stickiness revealed significant changes from control cells. At the lowest negative pressure, 4 X 10(-2) dynes/cm (-1 cm H2O), there were no differences in lengths of membrane segments aspirated from control and activated platelets. Each subsequent increase in negative pressure up to 35 X 10(-2) dynes/cm (-7.5 cm H2O) resulted in significantly longer aspirated segments on activated cells compared to control cells. Greater negative pressures did not cause further increases in lengths of membrane segments drawn into the pipette. Thus, activation, which results in constriction of the circumferential microtubule, makes more membrane available for aspiration as negative pressure is increased. In both control and activated platelets, the microtubule coils served as a barrier to further lengthening of aspirated membrane segments as negative pressure was increased beyond 35 X 10(-2) dynes (-7.5 cm H2O).
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PMID:Micropipette aspiration of human platelets after exposure to aggregating agents. 301 Sep 20

The proton resonances of the following synthetic linear human fibrinogen-like peptides were completely assigned with two-dimensional NMR techniques in solution: Ala(1)-Asp-Ser-Gly-Glu-Gly-Asp(7)-Phe-Leu-Ala-Glu-Gly(12)-Gly(13)-Gly(14)- Val(15)-Arg(16)-Gly-Pro-Arg-Val-Val-Glu-Arg (F10), Ala-Asp-Ser-Gly-Glu-Gly-Asp-Phe-Leu-Ala-Glu-Gly-Gly(13)-Gly(14)-Val-Arg (F11), and Gly-Pro-Arg-Val-Val-Glu-Arg (F12). No predominant structure was found in the chain segment from Ala(1) to Gly(6) for F10 in both H2O and dimethyl sulfoxide. The previous suggestion that there is a hairpin loop involving residues Gly(12) to Val(15) in the A alpha chain of human fibrinogen is supported by the slow backbone NH exchange rates of Gly(14) and Val(15), by an unusually small NH chemical shift of Val(15), and by strong sequential NOE's involving this region in F10. This local chain fold within residues Asp(7) to Val(20) may place the distant Phe residue near the Arg(16)-Gly(17) peptide bond which is cleaved by thrombin.
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PMID:High-resolution NMR studies of fibrinogen-like peptides in solution: resonance assignments and conformational analysis of residues 1-23 of the A alpha chain of human fibrinogen. 316 91


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