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)

Phorbol myristate acetate (PMA) added to human synovial fibroblast cultures caused a dose-dependent increase in the production of plasminogen activator inhibitor-type 1 (PAI-1). In addition, PMA inhibited endogenous and interleukin-1 (IL-1) induced plasminogen activator (PA) activity, while increasing mRNA PAI-1 levels. Other protein kinase C (PKC) activators, mezerein and teleocidin B4, caused similar effects. The simultaneous addition of the PKC antagonists, H-7 or staurosporine, prevented the inhibition of PA activity by PMA. This study shows that activation of PKC inhibits PA and stimulates PAI production in human synovial fibroblasts. These results suggest that activation of PKC may play an important role in regulating increased PA production associated with joint destruction in rheumatoid arthritis (RA).
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PMID:Modulation of synovial fibroblast plasminogen activator and plasminogen activator inhibitor production by protein kinase C. 174 33

To assess the role of fibrinolytic system, 19 patients with rest angina and insignificant coronary artery stenosis and 23 controls performed symptom-limited multistage exercise. Vasospasm was angiographically demonstrated in 12 patients. Pre- and peak exercise blood samples from each patient were assayed to determine the fibrinolytic components. The patients displayed significantly increased PAI activity both under the basal conditions (p less than 0.01) and at peak exercise (p less than 0.01) as compared with the controls. However, the values of other fibrinolytic components, such as t-PA antigen, t-PA/PAI-1 complex and free PAI-1 antigen, in the controls and patients were similar. Nineteen patients were divided into two groups according to PAI activity levels under basal conditions. Nine patients displayed high PAI activity (more than the mean + 1 SD of the control value) under the basal conditions. When compared to the remaining 10 patients, the high PAI activity group had both a significantly short time interval from the last attack to the time of getting the blood sample (p less than 0.05), and a worse short-term prognosis (p less than 0.05). Thus, the level of PAI activity under basal conditions reflected the extent of disease activity, suggesting that PAI activity may be a useful clinical indicator of the severity of rest angina in patients without significant coronary stenosis.
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PMID:Plasminogen activator inhibitor activity as a possible indicator of disease activity in rest angina with angiographically insignificant coronary artery stenosis. 175 2

The influence of molsidomine on endogenous fibrinolytic activity was studied in a double-blind, randomized, placebo-controlled trial involving 12 male healthy volunteers. When measured 3 h after oral intake of molsidomine (16 mg, slow-release formulation) the activity of tissue plasminogen activator (t-PA) in plasma was significantly increased from 1.1 +/- 0.1 to 1.6 +/- 0.1 IU/ml. In contrast, the activity of plasminogen activator inhibitor (PAI-I) decreased from 17 +/- 2 to 12 +/- 1 AU/ml. The ratio of t-PA/PAI-I (x 100), calculated as index for the endogenous fibrinolytic activity increased significantly from 8.1 +/- 1.1 to 14.5 +/- 1.6. The ratio was unaltered after intake of placebo. Additionally, collagen-induced platelet aggregation was significantly inhibited following intake of molsidomine. The results demonstrate a significant increase in endogenous fibrinolytic activity after oral intake of molsidomine. These effects may be of therapeutic value in patients with coronary heart disease and unstable angina.
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PMID:[Effect of molsidomine on fibrinolytic activity: a double-blind, randomized study]. 177 35

The fibrinolytic response to venous occlusion was studied in 17 patients with inflammatory bowel disease: 7 with Crohn's disease, 10 with ulcerative colitis and compared with those obtained in 20 controls. Patients with inflammatory bowel disease showed decreased tissue-type plasminogen activator antigen release (t-PA Ag), no significant Von Willebrand antigen release (vWF Ag), and a residual plasminogen activator inhibitor activity (PAI activity) after venous occlusion. These modifications were more important in the evolutive colitis group compared with the remission group. Hypofibrinolysis, as defined by a defective t-PA release, and a residual PAI activity after venous occlusion might contribute to digestive and/or extra digestive thrombotic manifestations observed during the course of inflammatory bowel diseases.
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PMID:[Impaired fibrinolytic response to the venous occlusion test in patients with cryptogenic colitis]. 178 49

Five criteria for poor response to a 20 min venous occlusion test were applied to 58 patients 3 months or more after acute deep vein thrombosis (DVT). The criteria were arbitrarily defined as the last 5 percentiles of response distributions in an age- and sex-matched healthy control group of 51 subjects. The criteria were: 1. euglobulin clot lysis time after venous occlusion greater than or equal to 140 min; 2. t-PA activity after venous occlusion less than or equal to 0.04 IU/ml; 3. increase in t-PA antigen above resting value less than or equal to 2-fold; 4. ratio between t-PA antigen increase and resting PAI activity less than or equal to 0.5 ng/IU; 5. PAI activity after venous occlusion greater than or equal to 6 IU/ml. The last criterion of poor response was the only one that was significantly more frequently reached by patients than by controls: 28% (p less than 0.005) of all DVT patients and 35% (p less than 0.005) of the subgroup with idiopathic DVT (N = 34) were found to be poor responders. The percentage of poor responders according to the other four criteria was 7-11% in all patients and 9-15% in the subgroup with idiopathic DVT and thus was not significantly higher than in controls (5% by definition). It was concluded that residual PAI activity after venous occlusion might be a useful criterion for prospective studies on recurrence of DVT.
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PMID:Poor fibrinolytic response to venous occlusion by different criteria in patients with deep vein thrombosis. 178 30

The content of PAI was measured in carcinoma tissues from the stomach and colorectum divided macroscopically into three portions: the central part of the carcinoma, the marginal part of the carcinoma containing some normal mucosa, and the normal mucosa. The PAI-1 antigen was highest in the central part of the carcinoma. On the other hand, no PAI-1 antigen or activity was observed in the normal mucosa. The PAI-1 in the carcinoma tissues showed a nonlytic zone with a molecular weight of 54 kd by reverse fibrin autography, and this 54 kd band reacted with anti-PAI-1 immunoglobulin G (IgG) on an immunoblotted nitrocellulose membrane. The contents of PAI-2 in the carcinoma tissues were not significantly different from those in the normal mucosa of the stomach and colorectum, respectively. In both the stomach and colorectal carcinomas, the highest value of u-PA/total PA (sum of u-PA and t-PA) was observed in the central part of the carcinoma, followed by the marginal part of the carcinoma, and was lowest in the normal mucosa. We conclude that increased levels of PAI-1 in malignant tissue of the stomach and colorectal tract may serve to modulate extracellular proteolysis by u-PA.
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PMID:Plasminogen activator inhibitor in stomach and colorectal carcinomas. 179 98

Diabetic patients are prone to develop vascular complications. Increased procoagulatory factors and a reduced fibrinolytic potential are considered as thrombogenic risk factors, although controversy remains. In epidemiological and dietary intervention studies fish or fish oil, rich in the two n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have demonstrated a potential to reduce cardiovascular disease. We compared the plasmatic coagulatory and fibrinolytic profile of 13 near normoglycaemic type I diabetics almost free of cardiovascular disease with healthy volunteers, matched for age and sex. Except for fibrinogen levels and tPA activity being elevated and soluble fibrin and fibrinopeptide A being reduced, no differences could be discerned between type I diabetics and controls in all investigated plasmatic parameters. In a dietary intervention study we investigated the effects of 5.4 g EPA and 2.7 g DHA per day during and after a 4-week dietary supplementation in the diabetic patients. The factors, inhibitors and activation products of coagulation and fibrinolysis measured were at best transiently affected by the diet. Only plasminogen activator inhibitory activity in plasma significantly increased during the dietary supplementation and returned to prediet values after cessation of n-3 fatty acids. Changes in PAI activity were negatively correlated to changes in serum triglycerides. We conclude that well adjusted type I diabetics show an almost unchanged haemostatic profile compared to matched healthy controls. A dietary intervention with n-3 fatty acids in these patients does not affect the plasmatic haemostatic pattern except for an increase in PAI activity.
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PMID:Plasmatic factors of haemostasis remain essentially unchanged except for PAI activity during n-3 fatty acid intake in type I diabetes mellitus. 183 69

Six patients (three males and three females), mean age 35.2 years (range 31-43 years), with extensive venous thrombosis were studied. Initial laboratory data indicated that all patients had normal antithrombin III (ATIII), four patients had low protein C (PC), three patients had low protein S (PS) and two patients had low plasminogen. Four patients had high fibrinogen and all patients had reduced tissue-type plasminogen activator activity, elevated tissue plasminogen activator inhibitor and low fibrinolytic activity. All patients were treated with danazol, 5-7 mg/kg orally once daily. In all patients there was significant elevation of ATIII, PC, PS, and plasminogen, reduction in plasma fibrinogen and PAI and enhancement of fibrinolysis. During the 12-36 months period of follow-up, there were no symptoms or signs that suggested recurrence of thrombosis. Apart from weight gain of 5-10 kg and disturbed menstrual cycle in two women, no major side effects were seen. These data suggest that danazol is potentially useful therapy that may increase levels of natural anticoagulants in patients with thrombotic illnesses in which ATIII, PC and PS are low or normal. Further studies are needed to confirm these observations.
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PMID:Significant elevation of protein C and protein S levels in thrombotic disorders by low dose danazol. 183 83

Two major plasminogen activator inhibitors (PAI-1 and PAI-2) increase in the peripheral circulation during pregnancy in humans. PAI-1 is of vascular endothelial origin whereas PAI-2 is produced primarily by human placental tissues. This study was undertaken to determine a) if PAI-1 and PAI-2 are also present in the baboon and b) their association with pregnancy. Citrated plasma was obtained from pregnant baboons sequentially at 15 +/- 3-day intervals between Days 30 and 140 of pregnancy. PAI activity increased significantly (p less than 0.05) at Day 120 (15.3 IU/ml) and 140 (21.8 IU/ml) of gestation and returned to baseline (2.6 IU/ml) 48 h post cesarean section. Placental tissues obtained at cesarean section during the third trimester were either placed in explant culture, fixed for immunocytochemistry, or frozen for RNA extraction. Western blot analysis of tissue culture media (TCM) indicated that the polyclonal antibody to PAI-1 reacted with a major band (Mr 47 000) in TCM from placental tissues while the PAI-2 antibody reacted primarily with a doublet (Mr 67 000 and 69 000) in these same media. PAI-1 was immunocytochemically localized primarily in the chorioamniotic tissue (CAM-D) and PAI-2 was found predominantly in placental villi. Slot blot hybridization with cDNAs to PAI-1 and PAI-2 indicated that the mRNA for PAI-2 was found primarily in placental villi, whereas the mRNA for PAI-1 was present in all three tissue compartments.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunological and molecular characterization of plasminogen activator inhibitors 1 and 2 in baboon (Papio anubis) placental tissues. 187 36

Plasma levels of tissue-plasminogen activator.plasminogen activator inhibitor (t-PA.PAI) complex and active PAI were assayed in 58 cases of disseminated intravascular coagulation (DIC). A significant elevation of both parameters was observed in most cases of DIC, especially in patients with non-Hodgkin lymphoma, sepsis, or some patients with acute leukemia, but no such elevation was observed in patients with acute promyelocytic leukemia (APL). The levels of both parameters were higher in cases of DIC with multiple organ failure (MOF) than in those without MOF. Since no elevation of t-PA.PAI complex was observed in most cases of APL, t-PA did not seem to play an important role in the activation of fibrinolytic system in APL. Active PAI, which reflects the inhibitory regulation in fibrinolytic system, was considered to play a role in the progression of MOF. Plasma levels of active PAI were low in the cases of APL, which had no complication of MOF.
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PMID:Changes in plasma levels of tissue-plasminogen activator/inhibitor complex and active plasminogen activator inhibitor in patients with disseminated intravascular coagulation. 130 60


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