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)

Twelve healthy volunteers received either a single oral dose of molsidomine (4 mg), isosorbide-5-mononitrate (ISMN, 20 mg), or placebo in a randomized, double-blind fashion. Blood was drawn prior to, as well as 30 and 60 min after intake of the respective drug. Platelet aggregation and the plasma levels/activity of plasminogen activator (tPA) and its inhibitor (PAI-1) were determined. In contrast to ISMN and placebo, molsidomine provoked a significant reduction in platelet aggregability. No alteration in plasma tPA concentrations was observed independent of whether molsidomine, ISMN, or placebo was applied. However, plasma PAI-1 activity was considerably reduced following molsidomine, but not altered following ISMN or placebo. We conclude that a single oral dose of molsidomine, but not of ISMN inhibits platelet aggregation and increases the fibrinolytic potential in healthy volunteers.
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PMID:[Thrombocyte aggregation and fibrinolysis in healthy probands treated with molsidomine, isosorbide-5-mononitrate and placebo]. 177 34

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

Changes of plasminogen activator (PA) and its inhibitor (PAI-1) activity and antigen have been investigated during PMSG/hCG induced ovulation in rhesus monkeys. It has been demonstrated that the ovarian tissue type PA (tPA) activity, which reaches maximum prior to ovulation and declines thereafter, is closely related to follicular rupture; significant increases in urokinase type PA (uPA) only occurs in granulosa cells after ovulation. Since the secretory activity of ovarian PAI-1 reaches its peak level 12-24 h earlier than tPA the rapid decrease in PAI-1 activity in the approach of ovulation is correlated with the elevation of tPA activity. It is, therefore, suggested that a counterbalance of tPA and PAI-1 activity within the ovary may play an important role in the ovulation mechanism, whereas uPA may be involved in the regulation of corpus luteum formation.
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PMID:[Changes of ovarian plasminogen activator and inhibitor during gonadotropin-induced ovulation in rhesus monkeys]. 179 10

The antigen levels of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) were assayed in the plasma and in the euglobulin fraction, and their contributions to the euglobulin clot lysis time (ECLT) and t-PA activity were analyzed. Total and free PAI-1 levels in both fractions showed significant positive correlation with ECLT (p less than 0.001), whereas t-PA antigen level did not have a high correlation coefficient with ECLT. t-PA activity showed significant negative correlation with ECLT (p less than 0.001) and positive correlation with free t-PA level (p less than 0.001), which was calculated by the ratio of the concentrations of t-PA-PAI-1 complex and the free PAI-1. Thus free t-PA seems to dissolve the euglobulin clot and its concentration seems to be controlled by the concentration of free PAI-1. These findings were confirmed by the analyses of the effects of C1-inactivator and antibody against t-PA to regular ECLT and kaolin activated ECLT, the latter of which was only inhibited by the addition of C1-inactivator whereas the former was inhibited by anti-t-PA antibody.
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PMID:PAI-1 plays an important role in the expression of t-PA activity in the euglobulin clot lysis by controlling the concentration of free t-PA. 179 99

This article reviews the evidence supporting a relationship between an enhanced tissue injury, increased fibrin formation, defective fibrinolysis, and the evolution of the complications of late diabetic disease. Particular attention is drawn to the role of a defective endothelial cell mediated fibrinolysis with respect to increased fibrin formation and a delayed tissue repair in diabetic patients. Reviewed are studies that indicate that it is possible in patients with diabetes by means of sulfonylurea compounds to increase endothelial cell-produced t-PA without affecting PAI-1. It is advocated that potent compounds should be searched for, with the capability to modify the hemostatic process of the diabetic endothelial cell in order to express more fibrinolytic activity independent of the patient's metabolic state in an attempt to delay the complications of late diabetes.
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PMID:Induction and possible role of fibrinolysis in diabetes mellitus. 180 11

Prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin complexes (TAT), as well as other coagulation and fibrinolysis parameters, were studied in a series of 13 patients affected by thrombotic thrombocytopenic purpura (TTP) or hemolytic-uremic syndrome (HUS). Fragment F1 + 2 was found to be increased in all patients at diagnosis (patients' range, 1.21-19.03 nmol/l; normal limits, 0.28-1.08 nmol/l), and remained also higher than normal after treatment with plasma exchange (patients' range, 1.5-4.01 nmol/l). Even though the analysis of fibrinolysis markers did not show a definite state of hypo or hyperfibrinolysis in the systemic circulation, enhanced circulating D-dimer levels (0.53-12.6 micrograms/ml, normal levels of 0.03-0.29 micrograms/ml) indicated that a certain grade of fibrin lysis was present at previously formed thrombi. Plasma PAI-1 activities either on admission (9.2-38.2 U/ml) and after plasma exchange therapy (2.6-38.6 U/ml) showed a behavior irrespective of t-PA:Ag changes, and post-plasmapheresis values remained high only in patients with fatal neurological outcome. Nevertheless, no correlations between clinical and laboratory data could be established useful for the TTP/HUS prognosis. We conclude that increased thrombin generation occurring in damaged areas is appropriately inhibited by antithrombin III in the systemic circulation, avoiding consumption coagulopathy to develop in uncomplicated patients. In addition, fibrinolysis data suggest that elevated PAI-1 may decisively favor the development of microvascular thrombi.
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PMID:Thrombin generation and fibrinolysis in the thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. 151 82

Plasminogen activator activity (PAA), plasminogen activator inhibition (PAI) and plasmin inhibition (PI) have been studied with spectrophotometric methods in extracts of human, bovine, ovine and rat kidneys of both sexes. In all species studied, renal PAA (cortex or medulla) was higher in females than in males. The PAA was also higher in the medulla than in the cortex in all species and both sexes. The PAA was due to both types of plasminogen activator; tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). In the human kidney (cortex or medulla) the measurement of t-PA antigen showed that t-PA is higher in females than in males; t-PA is also higher in the medulla than in the cortex in both sexes. The PAI showed the opposite pattern in all species studied; it was lower in females than in males. It was also lower in the medulla than in the cortex. PAI-1 was identified in the human kidney. Sex-related differences in renal PAA or PAI almost disappeared after bilateral orchidectomy in rats. PI showed no sex or regional differences in the species studied. Sex-related differences in renal PAA and PAI in man and various animal species might be of physiological or pathophysiological importance.
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PMID:Sex-related differences in plasminogen activator activity and plasminogen activator inhibition of human and animal kidneys: effect of orchidectomy or ovariectomy. 180 59

Approximately 35 years ago, it was discovered that spontaneous fibrinolytic activity in blood showed a sinusoidal variation with a period of 24 h; it increased severalfold during the day, reaching a peak at 6:00 p.m. and then dropped to trough levels at 3:00-4:00 a.m. The range of the fluctuation and the 24-h mean levels were highly reproducible within an individual; moreover, the timing of the oscillation was remarkably consistent among individuals, with a fixed phase relationship to external clock time. The biorhythm could not be accounted for simply by variations in physical activity, body posture, or sleep/wake schedule. Gender, ethnic origin, meals, or resting levels of blood fibrinolytic activity also did not influence the basic features of the rhythm. Older subjects, compared to younger ones, showed a blunted diurnal increase in fibrinolytic activity in blood. Recent studies have established that, of the known components of the fibrinolytic system, only tissue-type plasminogen activator (tPA) and its fast-acting inhibitor, plasminogen activator inhibitor-1 (PAI-1), show a marked circadian variation in plasma. In contrast, levels of plasminogen, alpha 2-antiplasmin, urinary-type plasminogen activator, and a reversible tPA inhibitor vary little or none during the 24 h. Quenching antibodies to tPA have shown that the circadian rhythm of fibrinolytic activity in blood is due exclusively to changes in tPA activity. However, the 24-h fluctuation of plasma tPA activity is phase shifted in relation to the rhythm of immunoreactive tPA, but shows a precise phase inversion with respect to the 24-h variation of PAI-1 activity and antigen. Therefore, plasma tPA activity, as currently measured in vitro, is tightly and inversely related to the levels of PAI-1 throughout the 24-h cycle. The factors controlling the rhythmicity of plasma PAI-1 are not fully elucidated but probably involve a humoral mechanism; changes in endothelial function, circulating platelet release products, corticosteroids, catecholamines, insulin, activated protein C, or hepatic clearance do not appear to be responsible. Shift workers on weekly shift rotations show a disrupted 24-h rhythm of plasma tPA and PAI-1. In acute and chronic diseases, the circadian rhythmicity of fibrinolytic activity may show a variety of alterations, affecting the 24-h mean, the amplitude, or the timing of the fluctuation. It is advisable, therefore to define the 24-h pattern of plasma tPA and PAI-1 in patient groups, before levels based on a single blood sampling time are compared to those of a control population.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Circadian variation of fibrinolytic activity in blood. 181 84

We report a comparison of fibrinolytic variables between 10 Caucasians on a predominantly European diet and 10 Greenland Eskimos on a traditional Inuit diet containing a substantial amount of fish and sea animals. We studied the diurnal variation in tissue type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) antigens and activities during a 24-h period. Blood samples were taken every 4 h. The variations of the sinusoidal curves were evaluated by the Friedman chi 2 test. t-PA and PAI-1 antigen in plasma fluctuated significantly during the 24 h (Eskimos p less than 0.00007 and p less than 0.0007; Caucasians p less than 0.00003 and p less than 0.02), with a peak in the early morning and a nadir in the afternoon. This also held true for PAI activity (Eskimos p less than 0.0008; Caucasians p less than 0.01), whereas t-PA activity showed an inverse but still significant pattern (Eskimos p less than 0.006; Caucasians p less than 0.0008). Amplitudes, areas underneath, and overall medians of the sinusoidal curves did not deviate between the two groups with respect to t-PA and PAI. In contrast to the significant variation of t-PA and PAI, the plasma concentrations of fibrin degradation products (D-Dimer), a measure of effective fibrinolysis, remained constant during the 24 h, and the absolute differences between groups did not reach statistical significance. These findings suggest that circadian variation of fibrinolytic activators and inhibitors is a basic biologic phenomenon, which is not affected by life-style, dietary habits, or ethnic differences.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chronobiology of coronary risk markers in Greenland Eskimos: a comparative study with Caucasians residing in the same Arctic area. 181 85

The activity of tissue plasminogen activator-plasminogen activator inhibitor-1 (t-PA-PAI-1) complex to convert plasminogen to plasmin was examined by using fibrin autography and casein zymography where plasminogen was added or removed for casein layer. Fibrin autography was more sensitive to the activity of t-PA even in the complex with PAI-1, but casein zymography was more sensitive to plasmin. The inhibitory activity of PAI-1 toward t-PA diminished when plasma was clotted, thus in the presence of fibrin. These results indicate that t-PA-PAI-1 complex has a catalytic activity even in the absence of fibrin, but the activity is enhanced in its presence.
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PMID:The activation of plasminogen by T-PA-PAI-1 complex in the absence of fibrin. 183 80


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