Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Measurement of Protein S in human plasma is clinically important because of deficiency of this protein, which functions as a cofactor of the naturally occurring anticoagulant activated Protein C, is a risk factor for venous thromboembolism. We describe a two-site, enzyme-linked immunosorbent assay (ELISA) for measuring Protein S in which a monoclonal IgG directed against the calcium-independent conformation of Protein S is the capture antibody. The range of detection for the assay was 10 to 160 ng of Protein S per milliliter. The coefficients of variation were 4.6%-7.3% within-assay and 7.7%-10.1% between-assay. We compared this assay with an ELISA involving a polyclonal anti-Protein S rabbit IgG as capture antibody (I) and with Laurell's electroimmunoassay (II) to measure Protein S in plasma from 32 normal subjects and 121 patients or individuals expected to have low concentrations of total Protein S (full-term newborns, pregnant women after the 18th week of gestation, patients with disseminated intravascular coagulation or liver cirrhosis, patients receiving therapy with warfarin, and patients with congenital Protein S deficiency). In general, the results obtained with the monoclonal antibody-based ELISA correlated well with those from I (r = 0.94), less well with those from II (r = 0.86).
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PMID:A monoclonal antibody to human protein S used as the capture antibody for measuring total protein S by enzyme immunoassay. 213 55

Thromboembolic complications may occur in inflammatory bowel disease. Recently, we had the opportunity to observe a case of a cerebral arterial thrombosis in a young patient with active ulcerative colitis. Investigation of blood coagulation revealed a temporary Protein C, Protein S and Factor II deficiency. To our knowledge, this is the first reported case of a temporary Protein C and S deficiency in a patient with thrombosis and inflammatory bowel disease.
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PMID:Acquired protein C and S deficiency, inflammatory bowel disease and cerebral arterial thrombosis. 214 95

Several reports have appeared on the increased risk of thromboembolic diseases associated with the use of oral contraceptives (OCs). The increased risk of thromboembolism has been related to increased circulating blood levels of certain factors of both the clotting and fibrinolytic systems seen in OC users. These changes have been associated primarily with the estrogen component of the OC preparations. The two new oral contraceptives under study contain reduced levels of ethinyl estradiol, 30 micrograms and each utilizes a new progestogen--75 micrograms gestodene or 150 micrograms desogestrel. A prospective randomized study was performed with 50 women over one year in which several factors of the hemostatic system were investigated; blood samples were taken in treatment cycles 1, 3, 6 and 12 and 6-8 weeks after cessation of therapy. During treatment with both preparations, factors II, VII, IX, X, XI, XII, VIII clotting activity, and prekallikrein were elevated; factor V was not elevated. Antithrombin III which controls these factors, was decreased by 8-10% after 12 months; Protein C which controls factors V and VIII was not changed. Markedly elevated levels of plasminogen and its unaffected inhibitor alpha antiplasmin were seen in the first and all subsequent treatment cycles; this represents increased potency of the lytic system, which can be looked upon as a compensatory mechanism. There were no differences seen between the gestodene and desogestrel preparations regarding changes in the hemostatic system. As with all other low-dose pills, a history of thromboembolism is a contraindication to their use.
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PMID:Influence of modern low-dose oral contraceptives on hemostasis. 214 6

Protein C (PC) is the central protein in a major antithrombotic regulatory mechanism. Hereditary deficiencies of PC are associated with thrombosis. Therapeutic PC replacement may be an important treatment if pure functional human protein C is available in sufficient quantity. Human PC has been produced on a commercial scale using recombinant techniques. To study the functional properties of recombinant protein C (r-PC), we undertook a comparative investigation of the basic properties of r-PC and plasma protein C (n-PC). Both were isolated by immunopurification methods. Protac C activation proceeded at the same rate and kinetics for both forms. With thrombin-thrombomodulin (T-TM) activation, r-PC is significantly better than the activation of n-PC (for r-PC: Kcat/Km = 378 vs. n-PC: Kcat/Km = 35). No difference in the anticoagulant (aPTT prolongation) or profibrinolytic activities (inactivation of PAI-1 and PAI-3) were observed between activated r-PC and n-PC. Based on these functional studies, recombinant protein C has similar properties to the plasma form of protein C. However, T-TM activation of r-PC occurs faster than the n-PC. The mechanism is unknown, but may be due to the presence of larger amounts of single chain protein C which exists in a conformation more rapidly activated by the T-TM complex.
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PMID:Recombinant human protein C: comparative functional studies with human plasma protein C. 215 50

A 38-year-old patient with cerebral P. falciparum malaria was admitted 12 days after a short trip to Kenya. The serum level of tumor necrosis factor (TNF-alpha) was elevated (251 pg/ml). In contrast, Protein C (plasma activity 36.1%; antigen concentration 31.7%) and protein C inhibitor 1 (activity 0.55 U/ml) levels were decreased. This suggested a state of functional activation of the clotting system which was confirmed by elevated levels (4.8 ng/ml) of circulating thrombin-antithrombin-III-complexes (TAT). Protein S (total and free) and coagulation factor IX levels were within normal range. Under successful antiparasitic therapy, TNF-alpha as well as protein C and protein C inhibitor 1 levels returned to baseline within one week. In the context of other studies that demonstrate procoagulant effects of TNF-alpha, it is remarkable that in the case of complicated P. falciparum malaria, an elevated concentration of TNF-alpha can be paralleled by a decreased plasma level of protein C and an increase in TAT suggesting a procoagulant state.
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PMID:[Malaria tropica with activation of blood coagulation and detection of tumor necrosis factor (NF-alpha) in serum]. 215 19

Thrombomodulin (TM), a major anticoagulant protein at the vessel wall, serves as a potent cofactor for the activation of Protein C by thrombin. Previous work has indicated that (rabbit) TM is a proteoglycan that contains a single polysaccharide chain, tentatively identified as a sulphated galactosaminoglycan, and furthermore suggested that this component may be functionally related to additional anticoagulant activities expressed by the TM molecule [Bourin, Ohlin, Lane, Stenflo & Lindahl (1988) J. Biol. Chem. 263, 8044-8052]. Results of the present study establish that (enzymic) removal of the polysaccharide chain abolishes the inhibitory effect of TM on thrombin-induced fibrinogen clotting as well as the promoting effect of TM on the inactivation of thrombin by antithrombin, but does not affect the ability of TM to serve as a cofactor in the activation of Protein C. Studies of yet another biological activity of rabbit TM, namely the ability to prevent the activation of Factor V by thrombin [Esmon, Esmon & Harris (1982) J. Biol. Chem. 257, 7944-7947], confirmed that TM markedly delays the conversion of the native 330 kDa Factor V precursor into polypeptide intermediates, and further into the 96 kDa heavy chain and 71-74 kDa light-chain components of activated Factor Va. In contrast, the activation kinetics of a similar sample of Factor V incubated with thrombin in the presence of chondroitinase ABC-digested TM did not differ from that observed in the absence of TM. It is concluded that the inhibitory effect of TM on Factor V activation also depends on the presence of the polysaccharide component on the TM molecule.
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PMID:Functional role of the polysaccharide component of rabbit thrombomodulin proteoglycan. Effects on inactivation of thrombin by antithrombin, cleavage of fibrinogen by thrombin and thrombin-catalysed activation of factor V. 216 42

The protein C inhibitor (PCI) concentration and other parameters of the protein C pathway were studied in 19 patients with symptomatic acute deep vein thrombosis before and during the first 5 days of heparin treatment. The mean levels of PCI antigen and activity decreased rapidly and significantly during the first day of heparin therapy from 83 and 84% to 60 and 59% of the pooled normal human plasma (p less than 0.01), respectively, and to 56 and 54% after 5 days of treatment (p less than 0.01). In contrast, antithrombin III decreased progressively 25% during 5 days of heparin treatment. Protein C antigen and activity and total protein S remained unchanged during heparin treatment. Free protein S was decreased before heparin treatment (83%, p less than 0.05) and increased to normal values after 5 days of treatment. C4b-binding protein was significantly increased before and during heparin treatment (p less than 0.01). Activated protein C (APC) complexed to its two major plasma inhibitors, PCI and alpha 1-antitrypsin (alpha 1AT) were measured by specific ELISA's. Before treatment, 18 of the 19 patients studied had increased levels of APC:alpha 1AT complexes with a mean value of 27 +/- 22 ng/ml (range, 6-86 ng/ml) compared to normal values (8 +/- 2 ng/ml) and 12 of the patients also had detectable APC:PCI complex levels with a mean value of 11 +/- 17 ng/ml (range, 5-68 ng/ml). Both APC:inhibitor complexes decreased significantly during heparin treatment.
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PMID:Protein C inhibitor and other components of the protein C pathway in patients with acute deep vein thrombosis during heparin treatment. 216 56

Protein C is a vitamin K-dependent zymogen of a serine protease that is found in blood plasma. The active form, activated protein C, can inhibit blood coagulation and stimulate fibrinolysis. Protein C is synthesized in the liver as a single chain protein. Its synthesis requires several post-translational modifications including carboxylation of glutamic acid residues, hydroxylation of aspartic acid residues, and glycosylation. Plasma protein C levels are sensitive to liver function. Protein C levels fall more rapidly than other vitamin K-dependent proteins when synthesis is altered by the administration of oral anticoagulants. In addition, low protein C levels are highly indicative of abnormal liver function. In one case, homozygous protein C deficiency has been corrected by liver transplantation. In liver transplantation for end-stage liver failure, plasma protein C levels may be a good indicator of the success of the transplantation.
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PMID:Protein C deficiency in liver disease. 218 1

Hemostatic abnormalities are present in a majority of patients with metastatic cancer. These abnormalities can be categorized as 1) increased platelet aggregation and activation, 2) abnormal activation of coagulation cascade, 3) release of plasminogen activator, and 4) decreased hepatic synthesis of anticoagulant proteins like Protein C and antithrombin III. The abnormal activation of coagulation cascade is mediated through release of Tissue Factor, Factor X activators, and other miscellaneous procoagulants from the plasma membrane vesicles of tumor cells. Macrophages of a tumor-bearing host also produce increased amounts of Tissue Factor. Production of Factor X activators and macrophage Tissue Factor is decreased by warfarin. The ability of the tumor cells to produce platelet-aggregating activity and plasminogen activator parallels their metastatic potential in animal and experimental systems. These studies also show that antiplatelet agents and antibodies against plasminogen activator can suppress the metastatic process. One or more laboratory abnormalities of hemostasis can be shown in up to 95% of patients with metastatic cancer. These abnormalities, however, are unable to predict subsequent development of thromboembolic or hemorrhagic complications. Clinical complications occur in 9-15% of the patients in the form of thrombotic or hemorrhagic disorders. The therapy of tumor-related coagulopathy should be guided by its clinical expression. Subclinical DIC should not be treated. Coumadin is generally ineffective for therapy of thrombosis in cancer patients. There is no consensus regarding the use of heparin in acute promyelocytic leukemia (APL). The defibrination in APL may be from disseminated intravascular coagulation as well as systemic fibrinolysis, as shown by decreased alpha 2 antiplasmin levels. In such cases, epsilon aminocaproic acid plus heparin therapy may be of benefit.
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PMID:Hemostasis in malignancy. 174 46

To identify changes in haemostatic balance during continuous oestradiol-progestogen treatment, 60 postmenopausal women with climacteric complaints, mean age 55.4 years (range 44-68) were randomly allocated to receive one of four hormone replacement regimens for one year. All four formulations were administered daily and continuously, each contained 2 mg of 17 beta-oestradiol in combination with either norethisterone acetate, 1 mg (group A) or 0.5 mg (group B) or megestrol acetate, 5 mg (group C) or 2.5 mg (group D). No significant changes occurred during treatment within or between the groups in platelet count, fibrinogen and 2-antiplasmin. Activated partial thromboplastin time was shortened (P less than 0.05) in group D and a decline in factor VII activity and antigen (P less than 0.001) and in ATIII activity (P less than 0.05) was noted in group A. Protein C tended to decline in all treatment groups but statistically significant changes were noted only in groups A and C. Two women developed crural thrombosis during the observation period.
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PMID:Haemostatic changes during continuous oestradiol-progestogen treatment of postmenopausal women. 222 87


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