Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving viable micro-organism
Patent
1996-02-21
1998-05-19
Kight, John
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving viable micro-organism
435 4, 435 71, 435 791, 435 692, 435 24, 435212, 435975, 435 13, 435 39, 424 9464, C12Q 106, G01N 3353
Patent
active
057534578
DESCRIPTION:
BRIEF SUMMARY
This case was filed under 35 USC 371 as the national stage of International Application PCT/EP9402127 filed Jun. 28, 1994 published as WO95/01452 Jan. 12, 1995.
DESCRIPTION
A method for the quantification of active plasminogen-activator-inhibitor-type-1 (PAI-type-1) present in a sample, a method for preparing a reference curve for use in the quantification, a kit for carrying out the method of quantification and a carrier such as a microtitre plate comprising immobilised antibody directed against plasminogen activator.
The subject invention lies in the field of haemostasis. The subject invention is directed at a method for the quantification of active plasminogen-activator-inhibitor-type-1 (PAI-type-1) present in a sample. The subject invention is also directed to a method for preparing a reference curve for use in the quantification and as a kit for carrying out the method of quantification and is also directed to a carrier such as a microtitre plate comprising immobilised antibody directed against plasminogen activator.
BACKGROUND OF THE INVENTION
Thrombosis, the development of blood clots (thrombi) in veins and arteries forms a serious complication of vascular diseases and is often the cause of an acute myocardial infarction. Thrombosis can be prevented in two ways, by preventing or decreasing the activation of the clotting system and the blood platelets or by activating the so-called fibrinolysis system in such a manner that the forming clot is degraded as fast as it is formed. The inner cellular layer of arteries and veins, the so-called endothelium plays an important role in these processes. The endothelium provides proteins that inhibit the coagulation process and produces the various factors that prevent the aggregation of blood platelets. Furthermore the endothelium controls the degradation of a forming thrombus by constitutive secretion of the protein "tissue-type plasminogen activator", also indicated as "t-PA", a protein that activates the fibrinolysis process. t-PA can also quickly be released from storage pools in the endothelium and a relatively large fibrinolytic activity can be targeted to threatened sites within the vein or artery with subsequent prevention of formation of a thrombus.
The fibrinolysis system is also capable of dissolving a clot that has already formed. A known example of this last situation is treatment of an acute myocardial infarction with the fibrinolysis enzyme t-PA. This new clinical application has enjoyed great interest over the past few years. In contrast to using t-PA for thrombolytic therapy, relatively little research has been carried out directed at manipulations of the availability of endogenous (i.e. made by the body itself) circulating t-PA, despite observations that a lowered fibrinolytic capacity (mainly t-PA activity) in blood is related to an increased risk of thrombosis. Above all the fibrinolytic effect of t-PA is maximal if it is already present during coagulation, i.e. t-PA that is added later is a lot less effective. This also explains the high doses of t-PA required for thrombolytic therapy and reinforces the importance of a sufficiently high endogenous t-PA activity level. For prevention of thrombosis therefore not only inhibiting the coagulation process could be considered, but also increasing the availability of t-PA via stimulation of endogenous t-PA production.
t-PA circulating in the blood is produced by endothelial cells in the wall of the arteries or veins. These endothelial cells synthesize t-PA, show a basal secretion of t-PA (constitutive secretion) and also contain a cellular stock of t-PA that can be secreted upon stimulation of the endothelial cell (acute secretion, also known as "release"). Such a cellular t-PA stock is a very powerful local defence mechanism: local physiological triggers of thrombus development (for example thrombus degradation products) will result in a strongly increased acute secretion of t-PA. The activity of t-PA in blood is, however, not only determined by the amount of t-PA but also by the amount of a
REFERENCES:
patent: 5520911 (1996-05-01), Anderson et al.
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Schleef et al., "Immunoradiometric Assay to Measure the Binding of a Specific Inhibitor to Tissue-Type Plasminogen Activator", J. Lab. Clin. Med. 1985, 106, 408-415, Nov. 1985.
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Akzo Nobel N.V.
Blackstone William M.
Burnett Friedrich N.
Kight John
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