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)

Upon treatment with agents such as thrombin, collagen or concanavalin A, blood platelets change shape, secrete serotonin and phosphorylate two proteins having molecular weights of approximately 20,000 and 40,000. We have analyzed the relationship of this protein phosphorylation to shape change and release aided by the fact that while shape change occurs independently of extracellular calcium, release of serotonin displays a rather strict calcium requirement. Under limited calcium conditions, where virtually no serotonin release occurs, (Con A)-stimulated phosphorylation is uninhibited. Divalent cations (Mg++, Co++ and Zn++) also inhibit release but not phosphorylation. The microtubule effectors colchicine and D2O show concomitant effects on release and phosphorylation, indicating a microtubule involvement prior to phosphorylation. Papaverine inhibits release and phosphorylation while not strongly influencing shape change, suggesting that shape change does not require phosphorylation. We therefore conclude that phosphorylation of these proteins takes place after shape change but prior to release, and although it may be required for secretion to occur, the two processes are easily separated. Thus phosphorylation of these proteins is not likely to be an integral component of the release mechanism.
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PMID:A study of protein phosphorylation in shape change and Ca++-dependent serotonin release by blood platelets. 51 63

This report details the results of studies performed in nine patients with homozygous beta-thalassemia evaluating platelet function and prostaglandin formation. Platelet malonyldialdehyde (MDA) formation in the presence of N-ethyl maleimide (NEM 1 mM) or thrombin (0.5 u/ml) was used as an indicator of platelet prostaglandin synthesis. The data on the nine patients revealed two distinct subgroups of patients. Six of nine thalassemics, demonstrated platelet abnormalities. Their mean bleeding time was 7.5 +/- 2.5 min (1 SD), significantly prolonged (P less than 0.005) when compared to a value of 3.5 +/- 1.0 min in normal controls. MDA formation in the presence of NEM was significantly decreased (P less than 0.005) to 2.41 +/- 0.49 (1 SD) when compared to a control value of 3.24 +/- 0.33 nmoles MDA/10(9) platelets. Similarly, the mean value for thrombin induced MDA was 0.98 +/- 0.18 nmoles which was decreased (P less than 0.02) when compared to a value of 1.26 +/- 0.2 in the controls. Platelet aggregations with adenosine diphosphate (ADP), epinephrine, and collagen were abnormal in all six patients. However, when platelets from these patients were mixed with platelets from donors who had ingested aspirin 2-8 hr before donation mutual correction and secondary irreversible aggregation of the mixture resulted. No mutual correction was observed when the thalassemic platelets were preincubated with aspirin in vitro before mixing with platelets from donors who had recently ingested aspirin. Although the total amount of platelet malonyldialdehyde formed by the thalassemic platelets in response to NEM and thrombin was decreased when compared to normal controls, this reduction was not the cause of the platelet aggregation abnormalities. This appears to be so because the amount of MDA, and, thus, prostaglandin endoperoxides synthesized by these platelets in response to external stimuli was sufficient to cause irreversible aggregation of platelets from donors who had recently ingested aspirin, and were, therefore, unable to synthesize their own endogenous platelet endoperoxides. In the remaining three patients, bleeding times, platelet aggregation, and MDA formation was normal. No correlation was observed between the platelet abnormalities noted and the magnitude of iron overload, presence of fibrin degradation products, liver function abnormalities, or the use of iron chelators in the individual patient. Family studies were normal. Although the platelet dysfunction does not appear to be of major significance in the usual patient with thalassemia major under normal circumstances, antiplatelet aggregating agents should be used with caution. Aspirin inhibits platelet endoperoxide and prostaglandin formation and this effect may potentiate the platelet dysfunction present in some patients with thalassemia major.
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PMID:Platelet dysfunction in homozygous beta-thalassemia. 52 94

Platelet functions studied in 163 unselected diabetics compared with 163 controls had the following characteristics: hyperagregation induced by ADP (1.2 muM and 0.6 muM), delayed platelet disagregation (ADP: 0.6 muM), normal agregation in the presence of collagen and thrombin. Platelet hyperagregation induced by ADP was marked in both sexes in cases of retinopathy and in women after the age of 50. By contrast, no correlation was demonstrated between the degree of hyperagregation and age, weight, the duration of diabetes, blood glucose control, lipid profile, vascular complications other than retinopathy and the nature of treatment.
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PMID:[Platelet functions in diabetes with angiopathy (author's transl)]. 53 70

Bleeding times of mink with the Chediak-Higashi (CH) syndrome was markedly prolonged. Platelet counts were normal but there was an impaired platelet aggregation response to collagen. The metabolic adenine nucleotide pool of platelets from normal and CH mink was labeled with 14C-adenine and the platelets were gel-filtered. Gel-filtered platelets (GFP) from CH mink contained only 37.9% of the adenosine triphosphate (ATP) and 9.6% of the adenosine diphosphate (ADP) found in normal platelets and the ATP/ADP ratio was similar to the 14C-ATP/14C-ADP ratio. Platelet content of Ca2+, Mg2+, and in particular 5-hydroxytryptamine was decreased. When GFP were incubated with thrombin to induce maximal secretion, only negligible amounts of ATP and ADP were released. The specific activity of the extracellular nucleotides approximated that within the platelet. These findings suggest that the stored nucleotide pool in CH platelets is virtually absent and that the abnormalities in platelet function may be due, in part, to the essential absence of secretable ADP and serotonin. The release of Ca2+ and Mg2+ by CH platelets was 56% and 27.8% of normal, respectively.
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PMID:Characterization of platelets from normal mink and mink with the Chediak-Higashi syndrome. 53 91

Addition of N-acetyl neuraminic acid (sialic acid, NANA) to citrated rat platelet-rich plasma significantly inhibited aggregation induced by near-threshold concentration of ADP, collagen or thrombin. In heparinized rat platelet-rich plasma aggregation of platelets induced by endotoxin or tumour cells of various origins was also inhibited by sialic acid. It is suggested that exogenous or endogenous sialic acid may act against various aggregating stimuli on the platelet membrane by masking a common factor through which various aggregating agents exert their effect.
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PMID:Inhibition by N-acetyl neuraminic (sialic) acid of platelet aggregation induced by different stimuli. 54 28

Impairment of platelet function is well recognized in the neonate. The abnormalities include a reduction in platelet factor 3 activity and availability, a reduction in the release of nonmetabolic storage pool ADP and ATP, and platelet factor 4 following stimulation, decreased adhesiveness, and impaired aggregation with ADP, epinephrine, collagen, and thrombin. Whether the cause of the platelet abnormality and the impairment in platelet secretion is due to a "storage pool deficiency" or an "aspirin-like defect" has been unclear. However, recent data suggests that the neonatal platelet possesses neither a significant deficiency in prostaglandin synthesis nor a significant decrease in storage pool adenine nucleotides. The abnormalities noted appear most likely to be due to a membrane-related phenomenon.
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PMID:Platelet function in the neonate. 54 16

The alpha-1 acid glycoprotein (orosomucoid; AAG) is a normal constituent of human plasma (650+/-215 microgram ml(-1)) which increases in concentration as much as fivefold in associations with acute inflammation and cancer, and thus is recognized as an acute phase protein. AAG consists of a single polypeptide chain, has a molecular weight of 44,100, and contains approximately 45% carbohydrate including 12% sialic acid; it is the most negatively charged of the plasma proteins. Certain of the biological properties of AAG are related to its sialic acid content; thus, clearance and immunogenicity of AAG are markedly increased on desialisation. The biological functions of AAG are largely unknown. AAG has the ability to inhibit certain lymphocyte re-activities including blastogenesis in response to concanavalin A, phytohaemagglutinin and allogeneic cells, and these inhibitory effects are enhanced in association with desialisation. In view of these observations, a report that unphysiologically large (5--15 mg ml(-1)) amounts of AAG inhibit the platelet aggregation induced by ADP and adrenaline, and evidence that a sialic acid-deficient species of AAG appears elevated in several chronic disease states, we compared the effects of AAG and its desialised counterpart (AAG-D) on platelet aggregation. We report that desialisation of AAG is associated with increased expression of activity inhibitory to the platelet aggregation otherwise observed on stimulation with ADP, collagen or thrombin.
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PMID:Inhibition of platelet aggregation by native and desialised alpha-1 acid glycoprotein. 55 Dec 86

The three topical hemostatic agents--gelatin paste, microfibrillar collagen, and gelatin sponge soaked in thrombin--individually were effective in reducing bleeding from cancellous bone, as tested on the femoral surface of trochanteric osteotomies during total hip replacement. During a three-minute interval, the spontaneous reduction in bleeding in eight control hips to which no agent was applied was 11 per cent. Gelatin paste gave a reduction of 85 per cent; gelatin sponge soaked in thrombin, a reduction of 75 per cent; and microfibrillar collagen, a reduction of 47 per cent. None of these agents interfered with healing of the trochanteric osteotomy.
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PMID:Topical hemostatic agents for bone bleeding in humans. A quantitative comparison of gelatin paste, gelatin sponge plus bovine thrombin, and microfibrillar collagen. 56 56

The fibrin-agar plate method was used to estimate fibrinolytic activity from the luminal surfaces of aorta and vena cava with or without denudation of endothelium in rabbits. Diffuse endothelial denudation was accomplished by air-dry injury to the luminal surfaces for 24 hours prior to sacrifice. The segments individually obtained from the aorta and vena cava were immediately turned inside out in a cylindrical fashion and soaked in a vial containing plasminogen-rich solution. The vials were kept in a refrigerator at 4 degrees C for 4 hours. Five microliter of the solution was dropped on a fibrin-agar plate containing 0.08% fibrinogen (plasminogen free) and 1.4% agar in 0.01 M phosphate buffer with a pH of 7.4. A thrombin solution was then added to the plates, which were incubated for 18 hours at 37 degrees C in a moist chamber. The fibrinolytically digested areas revealed no comparative difference in fibrinolytic activity between the aorta and the vena cava either in the experimental or control group. However, a plasminogen activator was detected on the luminal surfaces of both the aorta and the vena cava with endothelial denudation as well as in normal controls. These results suggest that luminal fibrinolytic activity may be located not only in endothelial cells but possibly in other sources as well. Further examination of the interaction between the tissue activator and the inhibitor and determination of their localization are needed. Thrombogenesis may be an important factor in atherogenesis; in certain circumstances, detachment of the endothelial cells exposes underlying collagen fibrils and subsequently initiates the aggregation of platelets and cellular proliferation in the intima. There are, however, many unresolved questions concerning the precise mechanisms of development, resolution and organization of thrombi.
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PMID:Measurement of endothelial fibrinolytic activity in aorta and vena cava in rabbits: a fibrin-agar plate method. 57 77

Influence of melphalan on some platelet functions, plasmatic coagulation and fibrinolysis "in vitro" was investigated, using different concentrations of the drug (25, 50 and 250 mug/ml). The lowest concentration slightly inhibited adrenaline and/or collagen-induced platelet aggregation. Following the highest concentration of the drug, strong inhibition of aggregation was recorded, regardless of the inducer used. Melphalan was also shown to inhibit release of aggregating activity and release of platelet factor 4, as well as availability of platelet factor 3 and platelet acid phosphatase. The intensity of inhibition depended on both, melphalan concentration and the time of preincubation. In contrast to this, adhesion of platelets to glass slide was not found to be influenced by melphalan. Similarly, melphalan did not induce (in any concentration) loss of LDH from platelet cytoplasma, while triton X-100 or freezing and thawing of platelets caused significant increase of LDH activity. From coagulation tests studied, only thrombin time and reptilase time was found to be moderately prolonged in the presence of melphalan. Authors assumed that melphalan acts as a specific inhibitor of release reaction and can induce an acquired thrombocytopathy. The platelet membrane is not damaged by the drug, as was confirmed by the investigation of LDH activity. Influence on coagulation indicates some antithrombin effect of the drug. Although presented results were obtained in vitro, analogous changes in vivo could be suspected. Thus, impairement of platelet functions might play a part in haemorrhagic complications accompanying, in some cases, melphalan therapy.
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PMID:Influence of cytotoxic drugs on platelet functions and coagulation in vitro. IV. Melphalan. 57 17


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