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

An antibody to plasminogen activator (PA) produced by the cultured cells of the pig kidney cell strain LLC-PK1 (LP100) was used to localize PA on the cell's free (unattached) surface. Localization was accomplished by the unlabeled antibody enzyme method (PAP) at the light microscopic level and at the electron microsopic level. Localization was commonly more intense at cell to cell junctions and was associated with blebs and vesiculation in this area. We are proposing that membrane shedding by blebs and vesiculation may be the mechanism of PA release in the LLC-PK1 (LP100) cell strain.
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PMID:Immunocytochemical localization of plasminogen activator on porcine kidney cell strain: LLC-PK1 (LP100). 8 72

Infusion of desamino-d-arginine vasopressin (DDAVP) results in an increase in plasma plasminogen activator activity. Whether this increase results in the generation of plasmin in vivo has never been established. A novel sensitive radioimmunoassay (RIA) for the measurement of the complex between plasmin and its main inhibitor alpha 2-antiplasmin (PAP complex) was developed using monoclonal antibodies preferentially reacting with complexed and inactivated alpha 2-antiplasmin and monoclonal antibodies against plasmin. The assay was validated in healthy volunteers and in patients with an activated fibrinolytic system. Infusion of DDAVP in a randomized placebo controlled crossover study resulted in all volunteers in a 6.6-fold increase in PAP complex, which was maximal between 15 and 30 min after the start of the infusion. Hereafter, plasma levels of PAP complex decreased with an apparent half-life of disappearance of about 120 min. Infusion of DDAVP did not induce generation of thrombin, as measured by plasma levels of prothrombin fragment F1+2 and thrombin-antithrombin III (TAT) complex. We conclude that the increase in plasminogen activator activity upon the infusion of DDAVP results in the in vivo generation of plasmin, in the absence of coagulation activation. Studying the DDAVP induced increase in PAP complex of patients with thromboembolic disease and a defective plasminogen activator response upon DDAVP may provide more insight into the role of the fibrinolytic system in the pathogenesis of thrombosis.
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PMID:Plasminogen activation in vivo upon intravenous infusion of DDAVP. Quantitative assessment of plasmin-alpha 2-antiplasmin complex with a novel monoclonal antibody based radioimmunoassay. 137 12

The presence and localization of the plasmin system components urokinase (UPA), tissue type plasminogen activator (TPA), plasminogen (PG), a neoantigen expressed by the plasmin-alpha 2-antiplasmin complex, and plasmin inhibitors alpha 2-antiplasmin (AP) and alpha 2-macroglobulin (MG) have been tested by immunofluorescence on sections of 11 benign and 40 malignant lesions of the breast in an attempt to apply a morphological approach to the problem of tumor invasion in vivo. In benign lesions, TPA was seen in secretions of mammary glands and MG was seen in edematous zones. In one involuting lactating adenoma, UPA, TPA, PG, PAP, and AP were associated with glandular cells. UPA was detected in 11 carcinomas, TPA in 22, PG in 31, PAP in 12, AP in 23, and MG in all 40. All these components were essentially present in invasive territories, with a cellular labeling for UPA and TPA and a fluorescent staining frequently at the periphery of tumoral foci for PG and PAP. AP was more closely associated with cancer cells than MG, which was present in the stroma. Intraductal proliferations were rarely positive and there was no correlation between the localization of PG and the distribution of a basement membrane glycoprotein laminin. These data argue strongly for the involvement of the plasmin system in the infiltrating process of the stroma. This system seems to play a limited role in the breakdown of basement membrane in breast carcinomas in vivo.
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PMID:Detection of the plasmin system in human mammary pathology using immunofluorescence. 242 83

The aim of the present study was to find out whether plasminogen activator inhibitor type-1 (PAI-1) controls the formation of plasmin in patients with ischaemic heart disease. We examined PAI activity, PAI-1 antigen, tissue type plasminogen activator (t-PA) activity, t-PA antigen, plasmin-alpha2-antiplasmin complex (PAP-complex) and fibrin degradation products D-dimer in 62 patients before (unstimulated) and after infusion of 1-desamino-8-D-arginine vasopressin (DDAVP; stimulated). DDAVP was used in a standardized dose to trigger the release of t-PA from the vascular endothelium. We observed that under basal conditions (unstimulated) median plasma t-PA activity for the whole group of patients was 86.5 mIU/ml (0-900), and after stimulation 2550 mIU/ml (0-6800), P < 0.0001; median plasma concentration of t-PA antigen was 14.7 ng/ml (7.0-115.5) under basal conditions, and after stimulation 34.1 ng/ml (15.8-58.6), P < 0.0001; median plasma PAI activity was 16.9 IU/ml (1.5-144.8) under basal conditions, and after stimulation 3.1 IU/ml (0-118.5), P < 0.0001; median plasma concentration of PAI-1 antigen was 21.5 ng/ml (8.1-132.2) under basal conditions, and after stimulation 14.9 ng/ml (4.8-149.0), P < 0.0001; the median plasma concentration of PAP-complex was 469.5 ng/ml (185.0-1802.0) under basal conditions, and after stimulation 695.5 (243.0-2292.0), P < 0.0001; median plasma concentration of D-dimer was 298.0 ng/ml (103.0-948.0) under basal conditions, and after stimulation 296.5 ng/ml (97.0-917.0), P < 0.0008.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasminogen activator inhibitor type-1 determines plasmin formation in patients with ischaemic heart disease. 748 12

Although thrombolytic therapy is used widely for treatment of acute myocardial infarction (AMI), thrombolysis itself increases thrombin activity and may cause reocclusion of infarct-related vessels. Direct percutaneous transluminal coronary angioplasty (PTCA) is an effective treatment for AMI; however, it is not clear what effects PTCA has on coagulation and fibrinolysis. We investigated coagulation and fibrinolytic factor concentrations before and after direct PTCA. Plasma levels of thrombin-antithrombin III complex (TAT), D-dimer, plasmin-(alpha 2-antiplasmin complex (PAP), tissue-type plasminogen activator (t-PA) antigen and plasminogen activator inhibitor (PAI)-1 antigen were followed in twelve patients treated with direct PTCA for AMI. Before PTCA, only TAT concentrations were significantly elevated compared to normal controls. D-dimer, TAT, PAP and PAI-1 concentrations were similar before and after PTCA. Eleven patients had no recurrent ischaemia and no restenosis on follow-up coronary angiography. These data confirm that direct PTCA is less likely than thrombolysis to affect coagulation and fibrinolysis.
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PMID:Effects of direct percutaneous transluminal coronary angioplasty treatment of acute myocardial infarction on plasma levels of haemostatic and fibrinolytic factors. 750 63

Although studies with interleukin-1 receptor antagonist (IL-1ra) in animal models have shown that IL-1 contributes to mortality in sepsis, the mechanisms whereby IL-1 mediates lethal effects are not well established. A possible mechanism is that IL-1 enhances the activation and release of other inflammatory mediator systems such as coagulation, fibrinolysis, neutrophils, and secretory-type phospholipase A2 (sPLA2). We investigated this possibility by assessing the effect of intravenously injected recombinant human IL-1 alpha (rhIL-1 alpha) on these plasma parameters in baboons. In addition, we examined the course of these inflammatory parameters in baboons after a challenge with a lethal dose of Escherichia coli and while receiving a 24-hour constant infusion of IL-1ra or placebo. Intravenous administration of IL-1 alpha (10 micrograms/kg) induced the formation of thrombin, as evidenced by the appearance of thrombin-antithrombin III (TAT) complexes into the circulation (peak levels, 188 +/- 92 ng/mL at 2 hours), as well as the activation of fibrinolysis, assessed by circulating plasmin-alpha 2-antiplasmin complexes (PAP complexes; peak levels, 0.4% +/- 0.03% of fully activated plasma at 1 hour), the release of tissue-type plasminogen activator (t-PA; peak levels, 6 +/- 2 ng/mL at 2 hours), and its inhibitor, plasminogen activator inhibitor (PAI; peak levels, 724 +/- 246 ng/mL at 4 hours). Il-1 alpha administration also induced the release of sPLA2 (maximal levels, 336 +/- 185 ng/mL at 8 hours), but not degranulation of neutrophils. In the septic baboons, a significant reduction of the formation of thrombin (peak TAT levels decreased from 582 +/- 78 ng/mL to 219 +/- 106 ng/mL; P < .005), the release of t-PA (peak levels decreased from 37 +/- 11 ng/mL to 17 +/- 2 ng/mL; P < .001), and its inhibitor, PAI (peak levels decreased from 2,639 +/- 974 ng/mL to 1,110 +/- 153 ng/mL; P <.001), was observed in the group receiving IL-1ra compared to that receiving placebo. The release of neutrophilic elastase was also significantly attenuated in IL-1a-treated animals (peak levels, 1,024 +/- 393 and 655 +/- 104 ng/mL in control and treatment groups, respectively; P < .05). The difference between sPLA2 levels in both groups, although higher in the controls (maximal levels, 3,140 +/- 1,435 ng/mL in control v 2,217 +/- 1,375 ng/mL in IL-1ra-treated group), was not significant. Thus, IL-1 contributes to activation of various other mediator systems in severe sepsis in nonhuman primates. We propose that these effects may explain the lethal actions of IL-1 in this sepsis model and suggest a similar role for IL-1 in severe human sepsis.
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PMID:Contribution of interleukin-1 to activation of coagulation and fibrinolysis, neutrophil degranulation, and the release of secretory-type phospholipase A2 in sepsis: studies in nonhuman primates after interleukin-1 alpha administration and during lethal bacteremia. 762 Jan 56

Apoptosis in the androgen-sensitive Dunning R3327 PAP prostatic adenocarcinoma was studied during the post castration period of 14 days and compared with the ventral prostate. The mRNA expression of testosterone repressed prostatic message-2 and tissue-type plasminogen activator in the Dunning tumor and in the ventral prostate was analyzed by Northern blot experiments and immunohistochemical procedures. The degree of endonuclease-degraded genomic DNA was examined by gel electrophoresis. Apoptotic tumor epithelial cells were identified with in situ end labeling. Epithelial cells incorporating bromodeoxyuridine (BrdUrd) after castration in the ventral prostate and the Dunning tumors were localized with immunostaining. Androgen ablation resulted in an induction of testosterone repressed prostatic message-2 and tissue-type plasminogen activator transcripts in the normal prostate with a peak at approximately 2 to 5 days post castration. These transcript levels in the Dunning prostatic tumors did not show any induction during the same period. Immunohistochemical staining for sulfated glycoprotein-2 and tissue-type plasminogen activator confirmed this difference between the tumor tissue and the ventral prostate at the transcriptional level. The determination of DNA integrity showed similar results in that the degree of DNA fragmentation in the tumor was much lower than the initial and marked degradation of DNA in the ventral prostate. The number of in situ end-labeled epithelial tumor cells were not increased by castration. BrdUrd immunodetection showed that castration induced an initial increase in the number of BrdUrd-positive epithelial cells in the ventral prostate. In the tumors, castration resulted in a decrease in BrdUrd-positive epithelial cells. It was concluded that in the androgen-sensitive prostatic Dunning R3327 PAP adenocarcinoma, the biochemical cascade leading to apoptosis is not activated by androgen withdrawal, as in the ventral prostate.
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PMID:Castration induces apoptosis in the ventral prostate but not in an androgen-sensitive prostatic adenocarcinoma in the rat. 801 87

A possible cause of accelerated atherothrombosis in the syndrome of insulin resistance appears to be an elevated blood concentration of plasminogen activator inhibitor type-1 (PAI-1). Insulin resistance occurs with aging, attributable partly to increased adiposity. Scarce information exists regarding the effects of weight loss in elderly, obese individuals on PAI-1 concentrations. Consequently, weight loss (9 +/- 1 kg) was induced by energy intake restriction in 19 elderly, obese individuals, and its effect on fibrinolytic system peptides was measured. Initially elevated PAI-1 concentrations decreased by 50%, with a simultaneous decrease in the concentration of tissue-type plasminogen activator (t-PA)/PAI-1 complexes but no significant change in t-PA suggested a decrease in inhibition of the fibrinolytic system. The concentration of plasmin/antiplasmin complexes (PAP complex) increased by approximately 20%, indicating augmented fibrinolytic system activity. The decline in PAI-1 correlated with that of the decrease in body weight (r = 0.5, P < 0.05) and fat mass losses (r = 0.46, P < 0.05). The increase in PAP complexes correlated with weight and fat mass losses (r = 0.4 and r = 0.46, respectively; P < 0.05 for both). No correlation was seen between fibrinolytic system variables and baseline concentrations of substrates or insulin, but the change in PAI-1 correlated with the change in plasma triacylglycerols (r = 0.58, P < 0.05). Results indicate that energy restriction sufficient to induce moderate weight loss leads to diminution of elevated plasma PAI-1 and relief of inhibition of the fibrinolytic system in elderly, obese subjects. To the extent that these changes are associated with a decrease in the progression of vasculopathy, weight loss in elderly, obese individuals may be a useful means to reduce cardiovascular morbidity and mortality.
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PMID:Amelioration of the inhibition of fibrinolysis in elderly, obese subjects by moderate energy intake restriction. 866 17

Elevated fibrinogen levels as well as an impaired activity of the fibrinolytic system are regarded as important cardiovascular risk factors. To elucidate a potential interrelation between fibrinogen as an indicator of a hypercoagulable state and the endogenous fibrinolytic function hemostatic and rheological as well as lipid parameters were determined in 224 consecutive patients, who underwent elective coronary angiography. In the selected study population of 81 men and 19 women with fibrinogen concentration either > or = 3.5 g/l (n = 70) or < or = 2.5 g/l (n = 30) hyperfibrinogenemia was found to be significantly associated with increased concentrations of plasmin-alpha 2-antiplasmin complex [PAP [median (25.-75. percentile)], 534 (361-680) micrograms/l vs. 289 (243-440) micrograms/l; p < 0.001] and tissue plasminogen activator (t-PA) antigen [9 (6-11) micrograms/l vs 8 (5-9) micrograms/l; p < 0.05] while this association was lost in the subgroup of patients with angiographically normal coronary arteries (n = 26). In addition to these findings fibrinogen was significantly correlated with PAP (r = 0.40, p < 0.001; n = 224) and t-PA antigen (r = 0.2, p < 0.01; n = 224) after adjustment for age, diabetes mellitus, lipid parameters and leucocyte counts. It can be argued that elevated fibrinogen levels in patients with coronary artery disease are concomitant with an activation of the fibrinolytic system.
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PMID:Activation of the fibrinolytic system in patients with coronary artery disease and hyperfibrinogenemia. 918 12

Pulmonary arterial thrombosis (PAT) may complicate the clinical course of pulmonary hypertension associated with congenital heart disease (so-called Eisenmenger syndrome, ES). In this study, variables were sought that could represent risk factors for the occurrence of this complication. Twenty patients aged 11 to 53 (median, 33) years were studied. The presence of PAT (spiral computed tomography angiography) was correlated with age, gender group, PAP, hematocrit, peripheral oxygen saturation (SpO(2)), and plasma levels of endothelial and coagulation dysfunction markers: von Willebrand factor antigen (vWF:Ag), tissue plasminogen activator (t-PA), and D-dimer (enzyme immunoassay). Patients were classified according to the presence (group 1, N=7), or absence (group 2, N=13) of PAT. Group 1 patients were older (42+/-8 vs. 27+/-10 years in group 2, p=0.0051), had lower SpO(2) (82+/-7% vs. 89+/-6% in group 2, p=0.0462) and increased D-dimer levels (637 vs. 149 ng/mL in group 2, median values, p=0.0235). A trend was observed toward an increase in vWF:Ag (125+/-29 vs. 103+/-18 U/dL in group 2, p=0.0789) and t-PA (15.7 vs. 9.4 ng/mL in group 2, median values, p=0.0689). Age was the main variable influencing the occurrence of PAT in multivariate analysis (p=0.0026), with odds ratio of 1.204 per year. The age of 35 years was 86% sensitive and 85% specific for occurrence of PAT. Age correlated positively with t-PA (r=0.57, p=0.0111). Thus, PAT is highly prevalent in ES as an age-dependent event, probably associated with endothelial dysfunction. Prophylactic anticoagulation should be considered before the age of 30 years, in particular in subjects with low SpO(2) and increased D-dimer levels.
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PMID:Age-dependent likelihood of in situ thrombosis in secondary pulmonary hypertension. 1524 78


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