Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alpha 2-macroglobulin, a major glycoprotein component of plasma, is unique in its capacity to bind and inhibit the proteolytic activities of all classes of proteinases. Since proteinases implicated in cancer dissemination (type-IV collagenase, plasminogen activator, cathepsins B) are normal constitutents of blood, we have explored the hypothesis that elevated tissue levels of activated proteinases bound to alpha 2M might be detected in plasma of patients with cancer. To test this premise, blood was collected from 149 subjects (33 healthy controls, 31 patients with infections and non-malignant diseases, 16 with myeloproliferative disease, 10 with gastrointestinal cancer, 7 with genito-urinary cancer, 16 with lung cancer, 14 with lymphoma, 11 with miscellaneous cancers and 11 with chronic lymphocytic leukemia and myeloma). Plasma was assayed for alpha 2M-proteinase complexes using a sandwich ELISA which employs a mouse monoclonal antibody (MAb) that binds to a neo-antigenic determinant on complexed alpha 2M and a rabbit polyclonal anti-native human alpha 2M antibody. The concentration of complexed alpha 2M in healthy controls was 14.2 +/- 9.8 micrograms/ml (mean +/- standard deviation). No significant differences in complexed alpha 2M were noted between normal and cancer groups (range 7.4-14.6 micrograms/ml). On the basis of these data, we propose that, in patients with cancer, activated proteinases are bound locally to inhibitors in the tissues and are not available to form complexes with plasma alpha 2M. An alternative explanation is that proteinases are not secreted in excess by cancer cells in vivo.
 ...
PMID:Proteinase-alpha 2 macroglobulin complexes are not increased in plasma of patients with cancer. 171 Feb 7

The physiologic mechanisms that influence plasma levels of von Willebrand factor (vWF) are poorly understood but include race, blood group, age, pregnancy, exercise, and adrenergic and neurohumoral stimuli. Inherited abnormalities in von Willebrand's disease (vWD) are associated with a defect of the vWF gene on chromosome 12, but in some cases, coexistence of impaired response of plasminogen activator and telangiectasia suggests the presence of a regulatory defect or more extensive endothelial perturbation. Three broad types of vWD are recognized; in addition, a platelet-type vWD (pseudo-vWD) is due to an abnormal platelet receptor for vWF. The prevalence of vWD, which is difficult to determine because of variations in severity even within a kindred, is reportedly as high as 1%. In a survey of European patients, the prevalence of treated vWD varied from 4.5 to 24 per million. Preliminary results of an international survey of vWD indicate that about 3% of treated patients have seroconversion to human immunodeficiency virus, 50% of whom have symptoms. Inhibitor of vWF occurs in type III vWD after treatment and is associated with the presence of gene deletions. Acquired vWD may complicate lymphoproliferative and autoimmune disorders, and proteolytic degradation of vWF complicates myeloproliferative disorders. The level of vWF is increased during pregnancy and in vascular and other disorders; it may be involved in the pathogenesis of atherosclerosis. High-molecular-weight multimers of vWF and a cofactor are thought to promote the formation of microthrombi in thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome. Thus, study of vWD has shed light on pathogenetic mechanisms in a wide range of disorders.
 ...
PMID:von Willebrand factor: clinical features of inherited and acquired disorders. 207 62

Plasminogen activators (PA) convert the inactive proenzyme plasminogen into plasmin, which is involved in the process of fibrinolysis, tissue remodeling, and cell migration. There are two distinct forms of PA: urokinase (u-PA) and tissue-type plasminogen activator (t-PA). t-PA has higher affinity for fibrin and is the main form involved in thrombolysis. By in situ chromosomal hybridization and Southern blot analysis of somatic cell hybrid DNA, we have assigned the human t-PA gene to chromosome 8, bands 8p12----q11.2. We have detected a common EcoRI restriction fragment length polymorphism within the t-PA gene that thus provides a precisely localized highly informative marker for genetic linkage studies. The t-PA gene localization coincides with a translocation breakpoint observed in myeloproliferative disorders. Whereas leukemic cells usually secrete both types of PA, a correlation exists between acute myeloid leukemic cells that release only t-PA and failure to respond to chemotherapy.
 ...
PMID:Human tissue-type plasminogen activator gene located near chromosomal breakpoint in myeloproliferative disorder. 309 43

The aim of this study was to investigate whether abnormalities in the fibrinolytic system and in the naturally occurring anticoagulant proteins could contribute to the thrombotic risk in essential thrombocythemia. Euglobulin lysis time, fibrin plate lysis area, tissue plasminogen activator antigen, and activity and plasminogen activator inhibitor antigen were measured before and after venous occlusion in a group of 16 patients with essential thrombocythemia and in 16 healthy age and sex matched controls. In addition, resting levels of antithrombin III, D-dimer, prothrombin fragment 1 + 2, and protein C and S were assessed. The results were related to the presence or absence of a thrombotic history. The results demonstrated that the patients had a significantly elevated fibrin plate lysis area and significantly decreased plasminogen activator antigen, both at baseline and after venous occlusion. They also had significantly decreased levels of plasma protein C and total protein S. There was a modest, non-significant elevation in the plasma concentration of D-Dimer and F 1 + 2. Those patients with a history of thrombosis had significantly lower protein C levels compared with individuals without a thrombotic history. We conclude that patients with essential thrombocythemia have evidence of activated fibrinolysis in the resting state and after stimulation. This, and the decreased levels of protein C and total protein S, may be secondary to chronic clinically occult thrombosis occurring in myeloproliferative disorders.
 ...
PMID:Low proteins C and S and activation of fibrinolysis in treated essential thrombocythemia. 763 71

Plasminogen activator inhibitor (PAI-1), a member of the serine protein family, is the most active in vivo inhibitor of fibrinolysis induced by plasminogen, tissue plasminogen activator (tPA), and urokinase type plasminogen activator (uPA). While the association between elevated PAI-1 and thrombogenesis has been well studied for several disease processes, including coronary disease, postoperative deep vein thrombosis (DVT), myocardial infarction, malignancy, and diabetes, few studies have concentrated on the correlation between elevated PAI-1 levels and thrombogenesis in patients with myeloproliferative disorders. Essential thrombocythemia (ET), a chronic myeloproliferative disorder, characterized by the overproduction of poorly functioning platelets, is associated with both thrombotic and hemorrhagic life-threatening complications. Although the events resulting in thrombogenesis in such patients may be multifactorial in nature, an association between elevated PAI-1 levels and thrombus formation has been proposed. Herein we present a patient diagnosed with ET complicated by multiple episodes of arterial thrombosis. Elevations in PAI-1 levels were documented repeatedly. The role of elevated PAI-1 when associated with other disease processes is also discussed.
 ...
PMID:Clinical implications of elevated PAI-1 revisited: multiple arterial thrombosis in a patient with essential thrombocythemia and elevated plasminogen activator inhibitor-1 (PAI-1) levels: a case report and review of the literature. 1043 40

The three-dimensional structure of an acidic phospholipase A(2) purified from the venom of Deinagkistrodon acutus (Agkistrodon acutus) was determined in a new crystal form by molecular replacement at 0.28 nm resolution with a crystallographic R factor of 21.9% (R-free=25.7%) and reasonable stereochemistry. Being similar to the previous reported crystal form, a significant conformational adaptation of segment 14-23 at the dimer interface was observed. This segment was related to the "interface recognition site" (IRS). It was found that a positively charged residue at position 34 seems to be a common feature for most of hemolytic PLA(2)s belonging to group II. Structural comparison between the two crystal forms showed that NaCl had significant effects on the crystal packing, thus leading to dramatic changes of the unit cell parameters. In the new crystal form, MPD (2-methyl-2, 4-pentanediol) molecules exist in the hydrophobic channel of the enzyme.
 ...
PMID:Structure of an acidic phospholipase A(2) from the venom of Deinagkistrodon acutus in a new crystal form. 1201 36

Hemostatic disorders are a major clinical problem in patients with myeloproliferative neoplasms (MPNs) and they are the second most common cause of death in MPN patients, after infections. The aim of this study was to assess the fibrinolytic potential of the blood of patients with MPNs. The study involved 112 patients with MPNs diagnosed at the Hematology Clinic Dr J. Biziel University Hospital No. 2 in Bydgoszcz, Poland. The study group included 63 patients with essential thrombocythemia, 29 with polycythemia vera, 11 with chronic myelogenous leukemia (CML) and nine with primary myelofibrosis. The control group consisted of 25 healthy volunteers who were age and sex-matched. The following parameters were determined: concentration of tissue plasminogen activator antigen (t-PA:Ag), plasminogen activator inhibitor type 1 antigen concentration (PAI-1:Ag), D-dimer, thrombin-antithrombin complexes, fibrinogen, activated partial thromboplastin time and international normalized ratio. The study showed significantly increased t-PA:Ag, PAI-1:Ag and D-dimer levels in patients with MPNs. Moreover, we found increased concentrations of thrombin-antithrombin complexes and fibrinogen, as well as elevated platelet counts. Detailed analysis revealed that t-PA:Ag concentration was elevated in patients with essential thrombocythemia, CML and polycythemia vera. Concentration of PAI-1:Ag was increased in patients with essential thrombocythemia and polycythemia vera; D-dimer was significantly higher in essential thrombocythemia, polycythemia vera, CML and primary myelofibrosis patients. Increased concentrations of t-PA:Ag and D-dimer indicate secondary activation of the fibrinolytic system in patients with MPNs. Elevated levels of PAI-1 in MPN patients may result from its increased production by elevated number of activated platelets and vascular endothelial damage. PAI-1 by having an inhibitory effect on fibrinolysis manifests its procoagulant activity.
 ...
PMID:Selected parameters of hemostasis in patients with myeloproliferative neoplasms. 2450 38