Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.4.21.5 (thrombin)
33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Essential thrombocythemia is a myeloproliferative disorder characterized by frequent bleeding and thrombotic complications. On a molecular level, two abnormalities of platelet thrombospondin have been identified: abnormal glycosylation of the intact 185,000-dalton chain has been detected and a shortened form of the thrombospondin chain is present. We have used two monoclonal antibodies and Lens culinaris lectin to probe the structure of thrombospondin in the platelets from three patients with essential thrombocythemia; one patient with polycythemia vera and two patients with secondary thrombocytosis. The presence of abnormal thrombospondin fragments with molecular weights of 160,000 and 30,000 was detected in the intact platelets and in the supernatant from thrombin-treated platelets, in all of the individuals except one of the secondary thrombocytosis patients. Monoclonal antibody binding studies indicate that both fragments are produced by proteolysis at a single site, which results in the removal of a 30,000-dalton fragment from the NH2-terminal. Lens culinaris lectin-binding studies revealed that some of the carbohydrate moieties of thrombospondin are near this cleavage site. The results are consistent with the hypothesis that the abnormal thrombospondin fragments observed under conditions of increased platelet production are due to increased susceptibility to proteolysis which, in turn, may be due to defective glycosylation.
...
PMID:Thrombospondin in essential thrombocythemia. 351 Jun 84

After observing a child with systemic onset juvenile rheumatoid arthritis (S-JRA) who developed purpura fulminans in association with disseminated intravascular coagulation, with subsequent gangrene and autoamputation, we undertook a prospective study of coagulation parameters in children with JRA. Ten consecutive children with S-JRA, 10 children with rheumatoid factor-negative, polyarticular juvenile rheumatoid arthritis (P-JRA), and 10 age- and sex-matched controls were studied. Routine coagulation screening tests were performed, as were tests for plasma fibrinopeptide A (a sensitive measure of intravascular thrombin generation), factor VIII-related antigen (an endothelial cell protein), and platelet factor 4 (a platelet-secreted protein). Our studies suggest that activation of intravascular coagulation is common in systemic onset JRA, but not in rheumatoid factor-negative, polyarticular disease. The coagulopathy may cause severe morbidity. In addition, marked elevations of plasma factor VIII-related antigen suggest perturbation of endothelial cells and vascular involvement in S-JRA, but not in P-JRA. Normal ranges of platelet factor 4 indicate that intravascular platelet consumption does not occur in either type of JRA, despite the thrombocytosis common in both.
...
PMID:Evidence for intravascular coagulation in systemic onset, but not polyarticular, juvenile rheumatoid arthritis. 397 74

The inhibition of human thrombin by antithrombin has been measured in pure systems in the presence of other components of the hemostatic system that might affect the kinetics of the reaction. These included fibrinogen, calcium ions, phospholipid, prothrombin, platelets (both adenosine diphosphate [ADP]-stimulated and -unstimulated), and platelet extracts. Inhibition rates were measured in each case by a discontinuous amidolytic assay over a range of antithrombin concentrations, from 0 to 4.5 mumol/L. Under all conditions, rates of inhibition were proportional to antithrombin concentration. Calcium ions at 5 mmol/L caused a small (20%) reduction in rate, but phospholipid and prothrombin had no additional effect. In contrast, both fibrinogen and platelets significantly changed the rate of inhibition. In the presence of calcium, fibrinogen at concentrations from 0 to 12 mumol/L reduced the rate of inhibition in a competitive manner, giving an apparent Kd for fibrinogen of 6.0 mumol/L. As the plasma fibrinogen level is about 8 mumol/L, one may therefore predict that variations in fibrinogen level will have a significant effect on the rate of thrombin inhibition in plasma. More unexpected was the observation that platelets increase the rate of inhibition: unstimulated platelets increased the rate constant by 40%, and ADP-stimulated platelets increased it by 55%. However, this acceleratory effect could not be mimicked with either a KCI extract or a Triton extract of platelets, and its cause remains unknown. In sum, it has been shown that the rate of inhibition of thrombin can be modulated in at least three ways-antithrombin concentration, fibrinogen concentration, and platelets; each of which can vary independently in vivo. It is well known that defects of the first lead to an increased risk of thrombosis, and it is proposed that this may be substantially caused by changes in the kinetics of inhibition such as those described. Additionally, it is suggested that changes in inhibition rate caused by other components may also be significant, for the same reason, in modulating the clotting system in vivo.
...
PMID:The kinetics of inhibition of thrombin by antithrombin in the presence of components of the hemostatic system. 405 33

To clarify the possible role of persistent thrombocytosis after splenectomy being a predisposing factor causing development of thromboembolism, blood coagulation profiles and platelet functions were studied in 34 cases being 1-18 years post-splenectomy from non-malignant diseases. Persistent thrombocytosis was observed in 16 with significant negative correlation between hemoglobin level and platelet count indicated the role of anemia on persistent post-splenectomy thrombocytosis. Blood coagulation profiles showed accelerated thrombin formation or hypercoagulability as measured by thrombin generation test especially in cases with thrombocytosis, together with decreased fibrinolytic activity and high fibrinogen, but in presence of high antithrombin III activity. Concerning the platelet, the aggregation to ristocetin was defective, the improved aggregation to ADP and adrenaline was achieved only in whom with intact spleen giving defective platelet aggregation. The finding indicated the role of spleen contributing to abnormal platelet aggregation. Another interesting observation was the decreased platelet 5-hydroxytryptamine content in splenectomized cases. The overall changes on blood coagulation and platelets post-splenectomy including those with persistent thrombocytosis did not thoroughly shift to hypercoagulable state, since a high antithrombin III activity and some platelet defect remained. These present findings, therefore, unlikely predisposed to the occurrence of thromboembolism even in those with persistent thrombocytosis.
...
PMID:Blood coagulation and platelet profiles in persistent post-splenectomy thrombocytosis. The relationship to thromboembolism. 408 60

1. Measurements were made of the uptake, metabolism and release of [(3)H]-adrenaline by human platelets in citrated plasma or in an artificial medium.2. Radioactive adrenaline was not taken up at 0-2 degrees C. At 37 degrees C there was a slow uptake which continued for at least 5 hours.3. About half of the radioactivity in the platelets was intact adrenaline. The other half was an acidic metabolite from which adrenaline was released by acid hydrolysis.4. The immediate uptake of adrenaline was proportional to its concentration in the plasma up to at least 1 x 10(-5)M. Uptake measured after 1 h also increased linearly with concentration up to about 1 x 10(-4)M but less with higher concentrations. The highest concentration ratio was about 12.5. The concentration of metabolite in the platelets increased with the concentration of added adrenaline only up to about 2 x 10(-4)M.6. The immediate uptake of adrenaline was partially inhibited by phentolamine and dihydroergotamine. Measurement of uptake both immediately and after 1 h showed that the inhibition produced was not increased beyond about 50% by these drugs or by (+/-)-propranolol, chlorpromazine or amitriptyline up to 1 x 10(-4)M.7. Formation of the metabolite was inhibited by pyrogallol, 8-hydroxyquinoline, or tropolone. This inhibition was associated with a corresponding increase in the adrenaline accumulated intact. Formation of the metabolite was not inhibited by monoamine oxidase inhibitors.8. Reserpine caused a small decrease in the uptake of adrenaline radioactivity in 1 h and a great increase in the proportion recovered as metabolite.9. Thrombin caused the release from platelets of intact adrenaline but not of the metabolite.10. Platelets of albino patients with spontaneous haemorrhages accumulated adrenaline radioactivity at the normal rate but this radioactivity was wholly accounted for by metabolite and not released by thrombin.11. After taking up adrenaline, platelets resuspended in artificial medium at 37 degrees C slowly released both adrenaline and its metabolite. At the same time, the intracellular adrenaline was slowly metabolized.12. The Result suggest that human platelets take up adrenaline by two processes, one of which is inhibited by both alpha- and beta-adrenoceptor blocking agents ad well as by phenothiazines; and that in the platelets adrenaline is partly stored in organelles from which, like 5-hydroxytryptamine, it can be specifically released.
...
PMID:Uptake, metabolism and release of (3H)-adrenaline by human platelets. 548 50

Platelet aggregation was studied at 37 degrees C in citrated whole human blood, using the Ultra Flo 100 Whole Blood Platelet Counter. Aggregation was measured as a fall in the number of single platelets following addition of an aggregating agent. At peak aggregation, the fall in the number of platelets induced by ADP (10 microM), collagen (1 microgram/ml) or thrombin (0.2 U/ml) was about 90%. When blood was incubated with the prostacyclin-analogue ZK36374, the aggregation responses to ADP, collagen and thrombin were reduced with IC50's = 0.5, 1.5 and 3 nM respectively and the corresponding IC100's were: 1, 3 and 12 nM. When ZK36374 was added at peak aggregation, the number of single platelets increased significantly due to disaggregation of preformed platelet aggregates. It is concluded that the present technique represents a rapid, sensitive and more physiological approach for investigating the effects of pharmacological agents on platelet aggregation.
...
PMID:The novel effect of a new prostacyclin analogue ZK36374 on the aggregation of human platelets in whole blood. 619 54

Platelet activation is accompanied by distinct morphological changes from disc-shaped cells to more rounded particles with multiple blebs or psuedopodia. A quenched-flow approach has been used to follow the kinetics and nature of these morphological events. Scanning-electron micrographs revealed very rapid alterations in platelet shape. At 0.5 S after activation with ADP or thrombin, the number of resting disc-shaped particles was nearly halved and short blebbed forms were maximal at 0.5 S. By 1.7 S about 60% of particles were in fully activated or multiple-blebbed form. The calcium ionophore A-23187 caused slightly slower effects. Adrenalin was much less potent, with about 14% of platelets becoming fully activated by 10 S. Control experiments showed only small changes in particle morphology when unactivated platelets were pumped through the reaction tubing and then quenched in glutaraldehyde. The resistive volume of platelets increased by 0.42 fl at 0.5 S after ADP stimulation and was essentially independent of variations in particle shape. These results show that the quenched-flow approach can provide new information about platelet function and that morphological changes begin earlier than previously thought.
...
PMID:Rapid platelet morphological changes visualized by scanning-electron microscopy: kinetics derived from a quenched-flow approach. 642 8

Ulcerative colitis and Crohn's disease are associated with a high risk of thromboembolic complications. The questions whether reported risk factors such as low antithrombin III concentrations, thrombocytosis and spontaneous platelet aggregation are merely related to the activity of the inflammatory process remains to be answered. Therefore we investigated 40 patients with an established colitis or Crohn's disease, without signs of active inflammation (normal history, normal ESR and leucocyte count). Of these patients only one patient revealed thrombocytosis, six patients spontaneous platelet aggregation. All patients had normal beta-thromboglobulin and platelet factor 4 plasma levels. No other prethrombotic abnormalities were encountered. There was normal factor VIII C (increased in three patients), normal VIII C/VIII R Ag ratio (1.2), antithrombin III, normal plasminogen and normal alpha 2-antiplasmin. Normal fibrinopeptide A and B beta (15-42) plasma levels (n = 15) in these patients excluded in vivo thrombin or plasmin generation. We conclude that stable chronic inflammatory bowel disease is in general not associated with prethrombotic coagulation abnormalities.
...
PMID:No evidence for a prethrombotic state in stable chronic inflammatory bowel disease. 665 71

A new type of acquired platelet dysfunction was found in a chronic myeloid leukaemia patient with petechiae and thrombocytosis. Platelet aggregation induced by arachidonic acid (AA), collagen and A23187 was decreased, secondary aggregation by ADP and epinephrine was defective and ristocetin-induced aggregation was completely reversible. No platelet ATP was released by AA and collagen. Only high concentrations of AA (greater than or equal to 2 mM) induced minimal reversible aggregation. 14C-serotonin uptake by the platelet and platelet adenine nucleotide contents were normal. Normal AA metabolism was demonstrated by thin-layer radiochromatographic analysis of the metabolites of 14C-AA and the determination of thiobarbituric acid reactive substances produced by the incubation of AA or thrombin with the platelets. Minimal reversible aggregation was observed when patient's platelet-rich plasma was added to a reaction mixture in which thromboxane A2 (TXA2) had been generated. TXA2 produced by patient's platelets showed normal platelet-aggregating activity. These results suggest that a subnormal platelet response to TXA2 is included as a mechanism for this acquired hypofunction of the platelet.
...
PMID:Subnormal platelet response to thromboxane A2 in a patient with chronic myeloid leukaemia. 680 32

Conventional laboratory methods were used to screen untreated tumor-bearing dogs for hemostatic abnormalities. Excluded from study were dogs with clinical evidence of bleeding. The primary site for neoplastic disease in 100 dogs studied included hemolymphatic system, skin, bone, thyroid gland, oropharynx, mammary gland, and nasal cavity. Eighty-three percent of the dogs had one or more abnormal coagulation tests. Thrombocytopenia occurred in 36 dogs and 3 had thrombocytosis. Twenty-five dogs had hypofibrinogenemia, and 25 had hyperfibrinogenemia. There were 32 dogs with prolongation of the activated partial thromboplastin time, 10 dogs with shortened prothrombin time, and 6 dogs with prolongation of the thrombin time. Sixteen dogs had positive protamine sulfate (paracoagulation) reaction, and 8% had increased plasma fibrin degradation products. The euglobulin lysis time was accelerated in 24% of the dogs, and 15% had schistocytes on blood film. These data indicate that the majority of dogs with advanced neoplasms are likely to have abnormal coagulation tests.
...
PMID:Coagulation abnormalities in dogs with neoplastic disease. 689 2


<< Previous 1 2 3 4 5 6 7 8 9 Next >>

---