Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autoprothrombin II-A anticoagulant was isolated from bovine prothrombin. Purified prothrombin was applied to DEAE-cellulose chromatography after incubation with thrombin. Four protein peaks were obtained where the third peak corresponded to the anti-coagulant effect. The fractions under the third peak were pooled together and the anticoagulant effect was evaluated with different methods. From 25,470 +/- 2,800 U of prothrombin, 5,800 +/- 1,400 U of inhibitor were obtained. The inhibitor was found to be most effective at pH 7.2--7.8. In vitro, the inhibitor inhibited the thrombin time and the plasma clotting time highly significantly but had no effect on euglobulin lysis time and fibrin plates. In vivo, when injected into rabbits, the inhibitor effect was also significant on the same tests. The autoprothombin II-A anticoagulant had a protective effect on DIC formation with rabbit brain thromboplastin administration. This protective effect was found to be statistically significant.
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PMID:Some properties of autoprothrombin II-A anticoagulant. 61 78

To test the possibility that a functionally abnormal fibrinogen may exist in some patients with liver disease, we studied the plasma and purified fibrinogens of five patients whose plasma thrombin times were prolonged at least 40% over normal controls. In no patient was there evidence of disseminated intravascular coagulation and/or fibrinolysis. No abnormalities were detected by immunoelectrophoresis of plasmas or purified fibrinogens. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of reduced patient fibrinogens showed normal mobility and amount of Aalpha, Bbeta, and gamma chains. Alkaline polyacrylamide gel electrophoresis and gradient elution, DEAE-cellulose chromatography of admixtures of radio-iodinated patient (125)I-fibrinogen and normal (131)I-fibrinogen showed identical mobility in the gel and simultaneous elution from the column, respectively. Thrombin and Reptilase (Abbott Scientific Products Div., Abbott Laboratories, South Pasadena, Calif.) times of purified patient fibrinogens were prolonged, and calcium ions improved but did not completely correct these defects. Increasing amounts of thrombin progressively shortened the clotting times of patient fibrinogens but not to the level of normal. Addition of equal amounts of patient fibrinogen to normal fibrinogen resulted in a prolongation of the thrombin time of the normal protein. Thrombin-induced fibrinopeptide release was normal. Fibrin monomers prepared from patient plasmas and purified fibrinogens demonstrated impaired aggregation at low (0.12) and high (0.24) ionic strength. These studies demonstrate that some patients with liver disease and prolonged plasma thrombin times have a dysfibrinogenemia functionally characterized by an abnormality of fibrin monomer polymerization.
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PMID:Dysfibrinogenemia associated with liver disease. 87 92

A new platelet aggregating protein (PAP) was purified from the plasma of a patient with acute thrombotic thrombocytopenic purpura (TTP) using A1 (OH)3 adsorption, PEG fractionation, DEAE cellulose chromatography, lentil lectin Sepharose 4B chromatography and gel filtration HPLC. The M. W. of this PAP was estimated to be 59,000. It induced the aggregation of washed platelets from normal subjects and the same patient after recovery. The antigenic material was present in 2 out of 6 other TTP patients but was absent in 7 normal subjects, two patients with DIC and two patients with ITP. The aggregation of washed platelets by PAP was concentration dependent and required energy metabolism, Ca2+ and fibrinogen. PAP was present in the plasma of a subset of TTP patients and was likely the cause of platelet thrombi in the microvessels in these patients.
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PMID:[Purification and some properties of platelet aggregating protein (PAP) from the plasma of a patient with thrombotic thrombocytopenic purpura]. 259 93

A novel platelet-agglutinating protein (PAP) was purified approximately 2,000-fold from the plasma of a patient with thrombotic thrombocytopenic purpura (TTP) by ammonium sulfate fractionation, DEAE-Sephacel and concanavalin A-Sepharose chromatographies. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, with and without reduction, this preparation revealed a major protein band with a molecular weight of 37,000, and a minor band with a molecular weight of 32,000-34,000. After elution from the gel, only the 37,000-mol wt protein corresponding to the major band induced the platelet agglutination. When four normal plasmas and the recovery plasma from the same TTP patient were subjected to the similar purification steps, the 37,000-mol wt major band was absent. The 125I-PAP bound to the platelets in a concentration-dependent manner. The platelet agglutination induced by PAP was not inhibited by hirudin, heparin in the presence of antithrombin III, phenylmethylsulfonyl fluoride, apyrase, aspirin, or prostaglandin I2. However, it was inhibited by IgG from normal adults and from the same TTP patient after recovery. The anti-37,000-mol wt PAP antiserum prepared in the rabbit formed a single precipitin line against the highly purified PAP. Using this antiserum in the Western immunoblotting, the 37,000-mol wt protein band was found in the three TTP plasmas, of which the platelet-agglutinating activity was inhibited by the anti-37,000-mol wt PAP IgG. The 37,000-mol wt immunoprecipitin band was absent in the plasmas obtained from another two TTP patients, two normal subjects, two patients with idiopathic thrombocytopenic purpura, and two patients with disseminated intravascular coagulation. These results suggest that the 37,000-mol wt PAP is present only in certain cases of TTP, and is likely to be responsible for the formation of platelet thrombi in the microcirculation.
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PMID:Novel platelet-agglutinating protein from a thrombotic thrombocytopenic purpura plasma. 393 64

After being envenomated by the timber rattlesnake, a patient was found to have a platelet count of 5000 per microliter, prothrombin time and activated partial thromboplastin time both greater than 150 sec, plasma fibrinogen 0 mg/dl, and fibrinogen split products 2560 microgram/ml. However, this patient did not appear to have acute disseminated intravascular coagulation since coagulation factors II-XII were normal. We postulated that this venom contained, in addition to a fibrinogen clotting enzyme, a platelet activating protein, Crotalocytin. Crotalocytin was purified from crude timber rattlesnake venom by Sephadex G-100 gel-filtration, low ionic strength precipitation, and DEAE-A50 Sephadex chromatography. By sodium dodecyl sulfate gel electrophoresis and gel-filtration Crotalocytin was a single chain polypeptide, molecular weight 55,000. Thrombocytopenia after timber rattlesnake bite appeared to be due to a protein that directly activated platelets. Timber rattlesnake bite mimicked the clinical presentation of disseminated intravascular coagulation.
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PMID:Crotalocytin: recognition and purification of a timber rattlesnake platelet aggregating protein. 743 9

A simplified technique using DEAE-cellulose chromatography for the preparation of factor VII deficient substrate was developed in order to reduce the high cost of individual factor VII assay in the routine coagulation laboratory. The substrate prepared from cryo-removed human and bovine plasma had a high correlation (r = 0.9929) with two of the most popular imported commercial substrates available (DADE, Ortho). When compared several other imported commercial substrates of equal quality, the prepared substrate was 3,000 to 6,000 times cheaper. Using the prepared factor VII deficient substrate along with other commercial substrates available, two hundred and fifty patients with malaria (fifty cases of P. vivax and two hundred cases of P. falciparum) were studied for coagulation and fibrinolysis abnormalities. Only P. falciparum infections showed prolonged PT and aPTT which correlated with the degree of parasitemia (r = 0.0972). Factors V, VII, and IX were the most sensitive parameters in the expression of coagulation defects and most coagulation abnormalities were due to liver involvement. Plasmin activity was normal in P. vivax patients but it was significantly increased in P. falciparum patients with > 5% parasitemia. Only two of the complicated cases of P. falciparum patients showed the evidence of DIC.
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PMID:A new method for factor VII deficient substrate preparation and coagulation studies in malaria. 788 82

Thromboembolic complications associated with prothrombin complex concentrate treatment may be related to the high levels of factors II and X in these products. We report here results from preclinical safety studies with a human coagulation factor IX product (AlphaNine; Alpha Therapeutic Corp., Los Angeles, Calif.) that contains no detectable factor II or VII and less than 10 units of factor X/100 units of factor IX. This product was manufactured from virally inactivated factor IX complex with a barium citrate adsorption step followed by affinity chromatography yielding factor IX concentrate with a specific activity of about 86 factor IX units/mg protein. Electrophoresis and immunoblot analysis indicated that the factor IX represents about 65% of the protein in this product. The virus inactivation step incorporated into the manufacturing process (incubation with n-heptane at 60 degrees C for 20 hours) was shown to inactivate at least 8.6 logs of type 1 human immunodeficiency virus. The barium citrate adsorption and affinity chromatography steps were found to remove 2.0 logs of the marker virus, vaccinia, and the DEAE ion-exchange chromatography used to produce factor IX complex was found to remove 1.4 logs of the marker virus, Sindbis. Analysis of three separate manufacturing lots with the polymerase chain reaction revealed no evidence of hepatitis C virus. The purified factor IX was nonthrombogenic when tested at doses of 450 units/kilogram in a rabbit stasis (Wessler) model, whereas the prothrombin complex concentrates were found to be thrombogenic at doses of less than 50 units/kg. There was no evidence of DIC in a porcine model after infusion of 200 units/kg of coagulation factor IX, as manifested by negative fibrin monomer tests, the absence of fibrin in blood vessels at autopsy, little or no change in prothrombin times and partial thromboplastin times, and only moderate decreases in platelet levels after infusion.
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PMID:Human coagulation factor IX: assessment of thrombogenicity in animal models and viral safety. 844 88

The growth and shortening of microtubules in dynamic instability is known to be modulated by microtubule-associated proteins (MAPs). A full understanding of the mechanism of dynamic instability requires that one distinguish which of its aspects are mediated by microtubule-associated proteins (even in small residual concentrations) and which are intrinsic properties of the tubulin lattice itself. This paper addresses two of those aspects: whether MAPs cause the rescue events of dynamic instability (i.e., the transitions from shortening to growth) and whether MAPs are responsible for the marked variability of the rates at which microtubules grow and shorten. Very pure tubulin was prepared by sequential chromatographies on phosphocellulose and DEAE-Sephadex. Analysis by electrophoresis and immunoblotting showed it to be essentially MAP-free; it contained fewer than one MAP molecule per 10000 tubulin dimers. When its dynamic instability was studied by video-DIC microscopy, rescues were found to occur at a mean frequency of one per 4 microns of shortening. Variability of rates of growth and shortening, which is observed on the length scale of a few micrometers, was not changed by removal of MAPs. Because the mean distance between bound MAP molecules was calculated to be greater than 14 microns in these experiments, it is concluded that they cannot cause either rescue or variability of rates.
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PMID:Dynamic instability of microtubules assembled from microtubule-associated protein-free tubulin: neither variability of growth and shortening rates nor "rescue" requires microtubule-associated proteins. 888 45