Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors present the results obtained using a therapeutic combinaison of plasminogen-urokinase in vivo in 14 premature infants suffering from respiratory distress. 86 % survived, a considerable improvement over classical survival rates. In addition it appeared that the duration of oxygen therapy was shorter, secondary to limitation of extension of the disease.
 ...
PMID:[Treatment of hyaline membrane disease with the plasminogen urokinase combination]. 77 95

Hyaline membrane disease (HMD) is leading single cause of death of newborn, premature infants. The "hyaline membranes" consist chiefly of fibrin. The clinical manifestation of HMD is the respiratory distress syndrome (RDS). Infants with RDS were treated with urokinase-activated human plasmin in a previous clinical trial. Survival rate was increased in the plasmin treated group as compared to the placebo recipients. However, cost and difficulty in the preparation of the enzyme made this treatment impractical. We, as well as others, have shown the premature infants lack serum plasminogen; thus they are unable to develop effective fibrinolysis and are defenseless against pulmonary fibrin deposition. Therefore, plamsinogen was tested as a possible preventive agent in RDS due to HMD. In a double blind, randomized study, infants between 1 and 2.5 kg birth weight received plasminogen or placebo shortly after birth, and were then followed for development of RDS. After 100 infants were entered into the study, the code was broken and results were evaluated to assure safety of the procedure. Among the 100 infants, 51 received placebo, 49 received plasminogen. Among the infants who received placebo, seven developed mild, and ten developed severe respiratory distress; of these ten, five died with histopathologically documented HMD. Two infants died from causes other than HMD. Among the 49 infants treated with plasminogen, 13 developed mild and three developed severe respiratory distress. There was no death due to HMD. Two deaths were due to other causes. Factors placing the infant at risk from HMD (degree of prematurity, sex, cesarean section, bleeding episodes during pregnancy, maternal diabetes) were found to be evenly distributed between control and treated groups. Since completing the first phase of the study, data of an additional 277 infants has become available. Although the code was not broken in this series, a preliminary look at mortality data in comparison with mortality data of the first series of 100 (in which the code was broken) suggests that preventive activity of plasminogen has been maintained in the second phase of the study.
 ...
PMID:Studies on the prevention of respiratory distress syndrome of infants due to hyaline membrane disease with plasminogen. 79 69

Premature infants who have self-limited respiratory distress syndrome (RDS) rapidly improve, whereas infants with a complicated respiratory course are more likely to develop bronchopulmonary dysplasia (BPD), a chronic lung disorder that is the result of prolonged lung injury and impaired healing. The balance of competing activities of coagulation and fibrinolysis may contribute to the premature lung's response to acute injury and determine, in part, whether there is early resolution or protracted alveolar inflammation. To determine the relative activities of the coagulation and fibrinolytic pathways in neonatal lung injury, procoagulant (PC) and plasminogen activator (PA) activities were measured in undiluted cell-free lung lavage samples obtained serially over the first 28 days of life from 11 infants with self-limited RDS, 11 infants with evolving BPD, and 5 mechanically ventilated control infants without lung disease. Lung lavage from all three groups contained readily detectable procoagulant activity due mainly to the tissue factor-Factor VII complex. Plasminogen activator activity was relatively high in control lavage samples but depressed on the first day of life in the two groups of infants with lung disease: median, 0.3814 IU/ml (control); 0.0541 IU/ml (RDS); and 0.0454 IU/ml (BPD), p < 0.05 in each case compared with control. Two infants with severe lung disease had no detectable plasminogen activator activity in lung lavage on the first day of life. Depressed fibrinolytic activity correlated with severity of lung disease assessed radiographically and by pulmonary function measurements. Plasminogen activator activity was due to both tissue plasminogen activator and urokinase.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Disordered pathways of fibrin turnover in lung lavage of premature infants with respiratory distress syndrome. 148 46

Nude mice given inoculations s.c. of a human squamous carcinoma--HEp3 (1.5 x 10(6) cells/mouse)--developed invasive tumors that produced high levels of urokinase-type plasminogen activator (uPA) and metastasized predictably to the lungs and lymph nodes of the host. To investigate the role of uPA in invasion and metastasis, mice given inoculations of tumor cells were treated daily with s.c. injections of specific, anti-human uPA antibodies (rabbit polyclonal, 150 inhibitory units; mouse monoclonal, 3000 inhibitory units/mouse/day). Control mice received either saline or preimmune rabbit immunoglobulins. A total of approximately 50 mice was studied. The tumors were surgically excised 10 to 17 days postinoculation when weighing 1 to 2 g. Antibody administration was discontinued after tumor excision. Two strategies were used: (a) following the removal of tumors the mice were maintained and observed until respiratory distress, indicative of lung metastasis, was evident; or (b) their lungs were examined for evidence of metastasis on the day of tumor removal. While histological sections of s.c. tumors excised from control mice indicated extensive local invasion, evidence of invasion was absent in most tumors excised from mice in which tumor uPA was inhibited by the antibody (P less than 0.025). The inhibition of local invasion did not, however, lead to a reduced incidence of distant metastasis. Since we found that the presence of HEp3 tumors in mice elicits a pronounced granulocytosis, we propose that this response may facilitate the spread of tumor cells by a mechanism independent of endogenous tumor proteases.
 ...
PMID:Inhibition of urokinase-type plasminogen activator by antibodies: the effect on dissemination of a human tumor in the nude mouse. 198 89

Pulmonary embolism following postoperative deep venous thrombosis is a very serious complication with a high mortality rate. Though this disorder has been thought to be rare in Japanese, its occurrence seems to be increasing recently because of changes in eating habits, increase of average age and the frequent practice of venous catheterization. Two cases of the pulmonary embolism following deep venous thrombosis after surgery are reported, and possible causes of the deep venous thrombosis are discussed. Case 1: A 48 year-old obese female was operated on for a posterior fossa dural arteriovenous malformation. On the 4th postoperative day, she developed a pain and swelling in the left leg and low back pain. On the 18th postoperative day, she fell into a state of shock following the sudden onset of a severe back pain and respiratory distress. After diagnosis of the pulmonary embolism, she was immediately treated with urokinase, warfarin and aspirin. Her obesity was considered to be one of the risk factors of the postoperative deep venous thrombosis. Case 2: A 62 year-old female with a ruptured cerebral aneurysm could not get out of bed because of postoperative mental disturbance. A central venous pressure catheter was inserted into the right femoral vein for two weeks postoperatively. One month after surgery, she complained of swelling and a dull pain in the right leg without cardiorespiratory symptoms. Lung perfusion scintigraphy showed asymptomatic pulmonary embolism. She was treated immediately. Both long bed rest and femoral venous catheterization were considered as risk factors possibly leading to deep venous thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Postoperative pulmonary embolism in neurosurgical practice: report of two cases]. 321 Dec 80

To evaluate the availability of the fibrinolytic system in patients suffering from acute respiratory distress syndrome, ARDS, induced by septicemia or trauma, the following parameters were analysed: fibrinogen, FG, antithrombin III, AT III, plasma prekallikrein, PPK, plasminogen, PG, alpha 2-antiplasmin, alpha 2-AP, alpha 2-macroglobulin, alpha 2-MG, urokinase-inhibitor, UK-I, streptokinase-inhibitor, SK-I, C1-inhibitor, C1-I, alpha 1-antitrypsin, alpha 1-AT, and fibrinogen-fibrin degradation products, FDP. Survivors and non-survivors of septicemia induced ARDS showed a characteristic feature: marked increase of FG and pronounced decrease of AT III and PPK in the coagulation system; concerning the fibrinolytic system a decrease of PG, alpha 2-AP and alpha 2-MG as well as an increase of inhibitors of PG-activators (PG-antiactivators) UK-I, SK-I, C1-I and alpha 1-AT; the FDP-titer was elevated. This constellation of parameters is interpreted as indicative of a marked procoagulant stimulation rendering the organism a state of hypercoagulability coinciding with a diminished availability of the fibrinolytic system, due to exhaustion of the fibrinolytic potential and increase of PG-antiactivators. In the trauma group initially the rise of FG, SK-I, C1-I and alpha 1-AT is absent independent of the outcome, but develops with progression of the disease. As ARDS is more frequently associated with septicemia, diminished availability of the fibrinolytic system simultaneously with increased procoagulant stimulation may be a particular pathophysiologic mechanism in the pathogenesis of ARDS.
 ...
PMID:Fibrinolysis inhibition in acute respiratory distress syndrome. 386 24

The acute respiratory distress syndrome being a critical complication of septic shock limits the patient's survival. A significant advance in treatment is the use of positive end-expiratory pressure ventilation (PEEP). As microthrombosis of the lung microcirculation seems to be one of the pathogenetic factors of RDS, fibrinolytic treatment may be tried as an additional therapeutic possibility, even in life-threatening situations. In this case we report on the treatment of shock lung resulting from septic shock occurring after diagnostic amniocentesis in the 16th week of pregnancy, this being a rare complication. By applying the principles of treatment described above --"Super PEEP" with 20 cm H2O and fibrinolysis with urokinase despite the presence of absolute contraindications--the respiratory insufficiency could be controlled.
 ...
PMID:[Intensive care of acute respiratory distress syndrome in septic shock--a case report (author's transl)]. 699 68

Streptokinase, urokinase, tissue plasminogen activator and similar drugs can all cause lysis of venous thrombi and pulmonary emboli, but there is small evidence that accelerated lysis achieves a significantly better clinical outcome, on average, in the shorter or longer term, than heparin alone. Thrombolytic therapy for deep leg vein thrombosis aims to restore flow and to preserve venous valves, and so to prevent chronic post-phlebitic disability, but no trial has convincingly demonstrated that the last can be achieved in more than a few patients. Only a small minority of people with extensive proximal thrombosis develop disabling post-phlebitic venous insufficiency, and there are no good clinical predictors of this outcome. As a result, any widespread use of thrombolytics would bring an immediate risk of major bleeding to many people who will never be destined to develop a clinically important problem. Thrombolytic therapy after venous thrombosis should be avoided except, perhaps, in a few carefully selected patients with severe obstruction. The case for using thrombolytics after recent pulmonary embolism is strongest in the limited number of patients with ongoing hypoxia, respiratory distress, pulmonary hypertension and right heart failure, because thrombolytic therapy often achieves an impressive and almost immediate clinical benefit in this clinical setting. Whether early relief from pulmonary artery obstruction translates into longer-term advantage over heparin remains uncertain, however, because no comparative trial has ever shown these drugs to reduce mortality after pulmonary embolism. In all cases, both the physician and the patient must balance the certainty of an immediate bleeding risk against the uncertainty of a better than marginal real benefit.
 ...
PMID:Thrombolytic therapy for venous thrombosis and pulmonary embolism. 1033 Oct 98

Exposure to chromium(VI) increases the incidence of cancer, respiratory distress, and pulmonary fibrosis. The latter is a pathological disorder characterized by decreased urokinase-type plasminogen activator (uPA) activity and fibrinolysis. In this study, treatment of alveolar type II cells (A549) with 1 to 5 microM chromium(VI) for 4 and 12 h decreased both the specific activity and the amount of uPA protein. Chromium reduced uPA protein levels by inhibiting protein synthesis and had no effect on uPA mRNA levels or the rate of uPA protein degradation. In contrast, both mRNA and protein levels for the uPA receptor (uPAR) were increased by treatment with concentrations of chromium(VI) that did not completely inhibit protein synthesis. The chromium-induced increase in uPAR resulted from increased message stability. These data indicate that chromium has differential effects on expression of the proteins in the pulmonary fibrinolytic cascade. The net loss of uPA activity may promote fibrosis following inhalation of chromium(VI).
 ...
PMID:Inhibition of protein synthesis by chromium(VI) differentially affects expression of urokinase and its receptor in human type II pneumocytes. 1043 62

Changes in the alveolar hemostatic balance in severe pneumonia were compared with those in the acute respiratory distress syndrome (ARDS). Analysis was performed in bronchoalveolar lavage fluids (BALF) of patients with ARDS triggered by nonpulmonary underlying events in the absence of lung infection (ARDS; n = 25), pneumonia demanding mechanical ventilation (PNEU-vent; n = 114), spontaneously breathing patients with pneumonia (PNEU-spon; n = 40), and ARDS in combination with lung infection (ARDS+PNEU; n = 43); comparison with healthy control subjects (n = 35) was performed. In all groups of patients, BALF total procoagulant activity was increased by nearly two orders of magnitude, being largely attributable to the tissue factor pathway of coagulation. Concomitantly, markedly reduced overall fibrinolytic capacity (fibrin plate assay) was noted in the lavage fluids of all patients. BALF levels of urokinase-type plasminogen activator were significantly reduced throughout, whereas the lavage concentrations of tissue-type plasminogen activator did not differ from those in control subjects. In addition, markedly enhanced levels of plasminogen activator- inhibitor I and alpha(2)-antiplasmin were noted in ARDS, ARDS+PNEU, and PNEU-vent, but not in PNEU-spon. In all groups of patients, the changes in the lavage enzymatic activities were paralleled by manifold increased BALF concentrations of fibrinopeptide A and D-dimer, reflecting in vivo coagulation processes. Within the overall number of patients with pneumonia, changes in the alveolar hemostatic balance were more prominent in alveolar and interstitial pneumonia than in bronchopneumonia. Acute inflammatory lung injury, whether triggered by nonpulmonary systemic events or primary lung infection, is thus consistently characterized by both enhanced procoagulant and depressed fibrinolytic activities in the alveolar lining layer, with the appearance of fibrin formation in this compartment. Profile and extent of changes in severe pneumonia demanding respirator therapy are virtually identical to those in ARDS, whereas somewhat less prominent alterations of the alveolar hemostatic balance are noted in spontaneously breathing patients with pneumonia.
 ...
PMID:Alveolar fibrin formation caused by enhanced procoagulant and depressed fibrinolytic capacities in severe pneumonia. Comparison with the acute respiratory distress syndrome. 1067 85


1 2 Next >>