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)

To explore mechanisms of coagulation activation in adenocarcinoma of the prostate, the occurrence and distribution of components of coagulation and fibrinolysis pathways in situ were studied by means of immunohistochemical techniques applied to frozen sections of fresh malignant and benign hyperplastic prostatic tissue obtained at transurethral resection. Fibrinogen was distributed throughout the perivascular and tumor connective tissue in both malignant and benign disease but was not present in adjacent areas of normal prostate. Antibodies specific for fibrin and D-dimer crosslink sites stained vascular endothelium focally in both malignant and benign tissues. Both neoplastic cells and benign hyperplastic glandular epithelial cells stained weakly and in a patchy distribution for tissue factor and focally for low-molecular-weight urokinase-type plasminogen activator. Focal staining of vascular endothelium was also observed for tissue plasminogen activator and plasmin-antiplasmin complex neoantigen. By contrast, no tissue staining was observed for factor VII, factor X, factor XIII "a" subunit, high-molecular-weight urokinase-type plasminogen activator, plasminogen activator inhibitors 1 to 3, protein C, and protein S. Thus, the similarity in findings between benign hyperplastic and neoplastic prostate tissue, the lack of either an intact tumor cell-associated coagulation pathway or fibrin formation, and the presence of fibrin on vascular endothelium are consistent with the concept that coagulation activation in prostatic cancer may not be due to a direct effect of the tumor cells on the clotting mechanism. Rather, such activation may be induced by a soluble tumor product that activates procoagulant activity on certain host (for example, vascular endothelial) cells. These findings, together with the lack of effect of warfarin anticoagulation on the clinical course of patients with prostatic cancer, contrast with findings in certain other tumor types and suggest that coagulation activation may not contribute to progression of adenocarcinoma of the prostate.
 ...
PMID:Fibrin formation on vessel walls in hyperplastic and malignant prostate tissue. 170 19

Tumor necrosis factor (TNF) may be involved in the disturbance of the procoagulant-fibrinolytic balance in septicemia, leading to microvascular thrombosis. To assess the dynamics of the fibrinolytic response to TNF in humans, we performed a crossover saline-controlled study in six healthy men, investigating the effects of a bolus intravenous injection of recombinant human TNF (50 micrograms/m2) on the stimulation and inhibition of plasminogen activation as well as on plasmin activity and inhibition. TNF induced a brief fourfold increase in the overall plasma plasminogen activator (PA) activity peaking after 1 h (p less than 0.0001), which was associated with rises in the antigenic levels of urokinase-type plasminogen activator (p less than 0.0001) and tissue-type plasminogen activator (p less than 0.0001). Plasminogen activator inhibitor type I antigen remained unchanged in the first hour, but showed a rapid eightfold increase thereafter (p less than 0.0001), which coincided with the decrease in PA activity. Generation of plasmin activity in the first hour was signified by an 11-fold rise in D-dimer levels (p less than 0.0001); inhibition of plasmin was reflected by a 36-fold rise in plasmin-alpha 2 antiplasmin complexes (p less than 0.0001), as well as by a transient 16% decrease in alpha 2-antiplasmin activity (p less than 0.01). In conclusion, TNF induced an early activation of the fibrinolytic system becoming maximal in 1 h, with a rapid inhibition thereafter. Earlier observations in the same subjects showed sustained coagulation activation for 6-12 h. The observed disbalance between the procoagulant and fibrinolytic mechanisms after TNF injection confirms the in vivo relevance of the effects of TNF on vascular endothelium in vitro and may explain the tendency towards microvascular thrombosis in septicemia.
 ...
PMID:Fibrinolytic response to tumor necrosis factor in healthy subjects. 171 36

Fibrinolytic activity was measured in a 14-day placebo-controlled study of propranolol and the calcium antagonist isradipine in 20 mildly hypertensive patients (diastolic blood pressure 95-115 mm Hg) compared with 24 healthy volunteers. The parameters under study included euglobulin clot-lysis time, and tissue-plasminogen activator activity and its inhibitor (PAI). The two drugs exerted equal antihypertensive effects in the patients who had raised blood pressure, but had markedly different actions on the fibrinolytic system. Propranolol substantially reduced the fibrinolytic activity in both the hypertensive and healthy control groups. Isradipine, on the other hand, had no effect on fibrinolytic activity in the controls, but augmented the activity in the hypertensive subjects. The possible mechanisms for the different actions of the two agents may be related to the vascular endothelium.
 ...
PMID:Does antihypertensive therapy affect the natural protection against thrombosis? 172 Apr 83

The development of hemodialysis treatment has remarkably improved the prognosis of chronic hemodialysis (HD) patients. However, as the patient's survival time is prolonged, vascular damages due to the abnormalities of calcium and lipid metabolism and hypertension has become the important complications in HD patients. In addition to coagulation and fibrinolysis, vascular endothelial function has been pursued to clarify the pathogenesis for occurrence of thrombosis in HD patients with more than ten years' duration. Twenty-two HD patients including twelve of less than ten years' duration and ten of more than ten years' were subjected to this study. Twelve healthy controls were also involved in this study. Fibrinopeptide A (FPA) and thrombin-antithrombin III complex (TAT) as indexes of coagulation, antithrombin III (AT III) as an index of coagulation inhibitor and D-dimer as an index of fibrinolysis were measured. A special attention has been focused in changes in the levels of tissue plasminogen activator (t-PA) activity and antigen and plasminogen activator inhibitor-1 (PAI-1) as indexes of fibrinolysis capacity, representing parameters of vascular endothelial functions. Levels of FPA, TAT and D-dimer were significantly higher in HD patients when compared with those in healthy controls. In particular, levels of FPA were significantly higher in HD patients with more than ten years' duration as compared to those in HD patients with less than ten years'. AT III values were significantly lower in HD patients with more than ten years' duration than those in healthy controls. T-PA activity and antigen levels were significantly lower in HD patients than those in healthy controls. T-PA activity levels were lower in HD patients with more than ten years' duration than those in HD patients with less than ten years'. Among HD patients, a significant negative correlation was found between t-PA activity and hemodialysis duration. PAI-1 values in HD patients were not significantly differ from those in healthy controls. These results suggest that in spite of increased coagulability, fibrinolytic capacity of vascular endothelium decreased in HD patients, and that the incidence is accelerated as hemodialysis duration is prolonged. Therefore, it is concluded that long-term HD patients are in the state of a higher risk of thrombosis.
 ...
PMID:[Long-term hemodialysis and changes in variables of coagulation and fibrinolysis]. 177 13

The vascular endothelium, which envelopes the circulating blood in a continuous monolayer, is not only a physical barrier between blood and vessel wall, but a highly complex "organ" which is involved in the regulation of blood vessel tone and permeability, blood coagulation, angiogenesis, leukocyte and platelet reactivity, phagocytosis of bacteria and the metabolism of many vascular mediators. This article focuses on the biosynthesis, biological actions and interactions of endothelium-derived vasoactive mediators, namely, prostacyclin, endothelium-derived relaxing factor--now characterized as nitric oxide--and endothelin, in the regulation of blood vessel tone under physiological and pathophysiological conditions. The formation of these highly vasoactive substances in modulated by changes in intracellular messengers (cyclic adenosine monophosphate, cyclic guanosine monophosphate, calcium), by interactions of endothelium with blood-borne cells and plasma constituents and finally by the interaction of these mediators themselves. The current evidence supports the view that nitric oxide plays a pivotal role for the regulation of blood vessel tone under physiological conditions, while the generation of prostacyclin is primarily an important defense mechanism to maintain a sufficient blood vessel patency and tissue viability under conditions of a compromised blood supply. Although the physiological role of the endothelium-derived vasoconstrictor peptide endothelin-1 is less well defined, it is apparent that any potential harmful vasoconstrictor effects resulting from an enhanced formation of endothelin under pathophysiological conditions are modulated by the simultaneous generation of prostacyclin, nitric oxide and tissue-plasminogen activator, thus preventing excessive vasoconstriction and thrombotic occlusion of the vascular bed concerned.
 ...
PMID:Biosynthesis and interaction of endothelium-derived vasoactive mediators. 178 95

Scatter factors (SFs) are heat- and trypsin-sensitive cytokines secreted by fibroblastic and vascular smooth muscle cell lines which stimulate motility of normal epithelium, carcinoma cells, and vascular endothelium. Human and mouse SFs have been purified and identified as 90 kD heterodimeric proteins consisting of heavy (58 kD) and light (31 kD) disulfide-bonded subunits. Partial amino acid sequence data from SF-derived tryptic peptides indicate marked sequence homology with hepatocyte growth factors, suggesting a common multigene family. In this chapter we describe the regulation by SF of vascular endothelial cell chemotaxis and chemokinesis; migration from microcarrier beads to flat surfaces; invasion through porous filters coated with reconstituted basement membrane; secretion of plasminogen activator; and in vitro capillary-like tube formation on a basement membrane surface.
 ...
PMID:Scatter factor stimulates migration of vascular endothelium and capillary-like tube formation. 183 33

New trends in tests for coagulation and fibrinolysis and advances in diagnosis for the hypercoagulable state and utilization of immunological techniques such as various polyclonal and monoclonal antibodies are reported. We discussed (1) the new markers for hypercoagulable states, (2) differential diagnosis of disseminated intravascular coagulation (DIC) and abnormalities of coagulation in liver cirrhosis (LC), and (3) new markers for fibrinolysis and vascular function. Thrombin-antithrombin III complex (TAT) levels were higher in thrombotic diseases than in healthy controls. Therefore, TAT should be a good marker for hypercoagulation as fibrinopeptide A (FPA) and soluble fibrin monomer complex (SFMC). Measurement of TAT, plasma-alpha 2 plasmin inhibitor complex (PIC), and D dimer were useful for differential diagnosis of DIC and liver cirrhosis. t-PA-PAI complex correlated well with t-PA, but not with fibrinolytic parameters such as PIC. The t-PA-PAI complex may be a good marker for the function of the vascular endothelium.
 ...
PMID:[A new advance in theory of blood coagulation and fibrinolysis and its practical application]. 190 12

Previous studies have suggested that the plasminogen activator (PA)/plasmin system has important roles in the pathogenesis of epithelial defects and stromal ulceration. The current studies were performed to localize PA species and identify them as tissue-type PA (tPA) or urokinase-like PA (uPA) as the two have distinct regulatory properties potentially related to the mechanisms of defect formation and ulceration. To determine the locations and types of PA species, antibodies to tPA or to uPA or the drug amiloride (a drug that inhibits uPA but not tPA) were incorporated into fibrin/fibronectin (Fn) clots overlying frozen sections to block regional fibrinolysis. Normal rabbit eyes showed tPA activity in association with corneal epithelium, corneal endothelium, and ciliary body/iris. After epithelial scrape or alkali burn, corneal tPA activity was detected initially in the defect zone colinear with fibrin/Fn and was symmetrical to resurfacing epithelium. The observation that initial fibrinolysis occurs in the defect zone, known to contain fibrin/Fn, suggests that tPA from blood (limbal vascular endothelium) and/or from corneal epithelium has become bound to (and activated on) the fibrin/Fn. PA activity was also associated with the leading edges of migrating epithelium post-scrape and post-burn and was not inhibited by antibodies to either tPA or uPA but was inhibited by amiloride. After complete closure of the primary defect post-scrape, only tPA appeared to be associated with the epithelium in that all PA activity was inhibited by antibodies to tPA. The observation that leading edge activity post-burn, in correlation with the formation of secondary defects, continues to be inhibitable by amiloride but not by antibodies to tPA suggests that uPA remains abnormally on the leading edge, and that sustained uPA activity in that location results in inappropriate degradation of subepithelial fibrin/Fn to result in a defect. Successful regulation of uPA activity at the leading edge of corneal epithelium post-burn would be expected to be useful therapeutically in the healing of epithelial defects and the prevention of stromal ulceration.
 ...
PMID:Pathogenesis of corneal epithelial defects: role of plasminogen activator. 190 16

Fibrin is a major component of atherosclerotic plaques, and there may also be situations in which intravascular fibrin is formed in contact with the endothelium. The studies to be presented describe the distribution of fibrinogen/fibrin I, fibrin II, and fragments D and D-dimer in normal vessels and atherosclerotic plaques of increasing severity and also describe some functional effects of fibrin on normal endothelium. Immunohistochemical studies using three specific monoclonal antibodies with the avidin-biotin complex immunoperoxidase technique demonstrated that little fibrinogen/fibrin I or fibrin II and no D/D-dimer were detected in normal aortas. In early lesions and in fibrous plaques, fibrinogen/fibrin I and fibrin II were distributed in long threads and around vessel wall cells. D/D-dimer was not seen in early lesions. In advanced plaques all three molecular forms were detected in areas of loose connective tissue, in thrombi, and around cholesterol crystals. Thus increased fibrin formation and degradation may be associated with progression of atherosclerotic disease. Additionally, the presence of fibrin II around vessel wall cells suggests that these cells may be involved in the fbgn to fibrin transition within the vessel wall. The second aspect of the work to be presented concerns effects of fibrin on vascular endothelium. Fibrin formed on the surface of cultured human umbilical vein endothelial cells stimulated production of prostacyclin and tissue plasminogen activator by the cells in a time- and dose-dependent manner. Stimulation of prostacyclin was completely inhibited by indomethacin and partially inhibited by actinomycin D, cycloheximide, and trifluoperazine, while stimulation of t-PA synthesis was completely inhibited by actinomycin D and cycloheximide and partially inhibited by cytochalasin D, vinblastine, and trifluoperazine.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Fibrin and the vessel wall. 210 20

Coronary artery rethrombosis can complicate initially effective thrombolytic therapy. Platelets interacting with injured vascular endothelium in a region along the coronary artery with reduced luminal cross-sectional area contribute to rethrombosis. The purpose of this study was to investigate the potential of the F(ab')2 fragment of the murine monoclonal antibody 7E3 [7E3 F(ab')2] to prevent rethrombosis after intracoronary clot lysis with recombinant tissue-type plasminogen activator (rt-PA) in an experimental model. The 7E3 F(ab')2 binds to the platelet glycoprotein IIb/IIIa complex (GPIIb/IIIa), thereby preventing platelet-fibrinogen interaction and intravascular thrombus formation. Experimental coronary artery thrombosis was produced in the anesthetized dog by application of direct anodal current to the intimal surface of the left circumflex coronary artery in the region of an external stenosis. Lysis of the established intracoronary thrombus was achieved with the intravenous administration of rt-PA (25 mg) after which the animals were randomized into two groups. Group 1 (n = 10) served as the control, receiving the saline diluent, and group 2 (n = 9) received 7E3 F(ab')2, given as a single intravenous injection (0.8 mg/kg). The times required for occlusive thrombus formation, rt-PA-induced thrombolysis, and rethrombosis (if it occurred) were similar in the animals treated with saline and those treated with 7E3 F(ab')2. The initial left circumflex coronary artery blood flow was similar in both groups but decreased to a negligible level in group 1. In group 2, left circumflex coronary artery blood flow declined modestly (24 +/- 2 to 10 +/- 2 ml/min). Rethrombosis occurred in all animals in group 1 but in only two of nine animals in group 2 (p less than 0.05). Oscillations in coronary blood flow preceded rethrombosis in group 1, whereas 7E3 F(ab')2 stabilized left circumflex coronary artery blood flow patterns during the course of teh experimental protocol (5.2 +/- 0.9 vs. 0.7 +/- 0.4 oscillations, respectively; p less than 0.05). Thrombus mass recovered from the left circumflex coronary artery at the conclusion of each experiment was greater in group 1 as compared with group 2 (7.0 +/- 2.3 vs. 1.5 +/- 0.7 mg, respectively; p less than 0.05). The area of left ventricle at risk for infarction was similar in both groups but infarct size, infarction/at risk assessed histochemically, was larger in group 1 than group 2 (35 +/- 9% vs. 6 +/- 4%, respectively; p less than 0.05). Platelet aggregation induced by ADP and arachidonic acid was similar at baseline for all of the animals.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Antiplatelet antibody [7E3 F(ab')2] prevents rethrombosis after recombinant tissue-type plasminogen activator-induced coronary artery thrombolysis in a canine model. 210 75


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>