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)

The levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor (PAI) and other substances of coagulation-fibrinolysis, such as fibronectin (Fn) and von willebrand factor (vWF) as well as the activity content of antithrombin-III(AT-III) in plasma were determined in 20 patients with acute myocardial infarction (AMI). In 11 of them these measurements were carried out before and after the treatment with urokinase (UK1000 000 IU). The results suggested that the function of coagulation-fibrinolytic system was disturbed in AMI. Thrombolytic treatment with UK could interfere and improve the stabilization of fibrinolytic activity in the body, but these actions last only short time. Some substances of coagulation showed change with UK treatment.
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PMID:[The kinetics of plasma coagulation fibrinolysis levels in acute myocardial infarction before and after treatment with intravenous urokinase]. 190 71

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.
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PMID:Pathogenesis of corneal epithelial defects: role of plasminogen activator. 190 16

The authors report on the influence of plasminogen activators (PA) on implantation of TA3Ha mammary tumor cells in the healing hepatic wounds of syngeneic strain A mice. Intravenously injected TA3Ha cells, although they rarely metastasize to the liver, formed tumors in the hepatic wounds of a significant percent (42%, P less than 0.0001) of mice. The frequency of tumor formation declined as the interval between surgery and tumor cell inoculation was increased. Furthermore, preexposure of cells to fibrinogen, fibronectin, laminin, or peptides containing the arginine-glycine-aspartic acid-serine residues dramatically reduced the frequency of tumor formation in the hepatic wounds. These results indicate that TA3Ha cells interact with fibrinogen-related proteins in the wound to aid their attachment and growth. Because these proteins are susceptible to digestion by plasmin, PA were used in this study to examine whether administration of these drugs to the mice would modulate tumor formation in the liver wounds. Among the PA tested, human plasmin B-chain-streptokinase complex (B-SK) and recombinant tissue plasminogen activator (t-PA) inhibited tumor implantation in a dose-related manner. Administration of 900 units (U) of B-SK or 3300 U of t-PA per mouse reduced the frequency of tumor formation from 42% to 0% (P = 0.02) and 11% (P = 0.02), respectively. The B-SK was complexed with p-nitrophenyl-p-guanidinobenzoate; it did not activate the plasminogen or inhibit tumor formation in the hepatic wounds. Although urokinase activated the plasminogen, it did not inhibit tumor implantation in the hepatic wound. Heparin, an anticoagulant that prevents conversion of fibrinogen to fibrin without being fibrinolytic, had no influence on tumor formation in the hepatic wounds. The PA can generate plasmin that digests the cell attachment proteins in wounds and consequently inhibits tumor cell attachment.
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PMID:Inhibition of tumor implantation at sites of trauma by plasminogen activators. 191 15

We immunohistochemically examined 186 lung adenocarcinomas for the presence of prognostic indicators of local growth of tumor, invasiveness and metastasis. Of the examined tumors, 67% showed a high expression of transforming growth factor alpha (TGF alpha); 50% for epidermal growth factor (EGF), 45% for EGF receptor (EGFR), and 30% for urokinase type plasminogen activator (uPA). In the EGFR-high cases, the 5-year survival rates of patients with high TGF alpha and low TGF alpha were 36% and 85%, respectively. In the EGFR-low cases, there was no statistical difference between the two groups. These findings suggested the presence of autocrine growth mechanisms. On the other hand, the high expression of uPA was modulated by TGF alpha and/or EGF. The 5-year survival rates of patients with high uPA and low uPA were 20% and 51%, respectively. The tumors with high expression of uPA showed degradation of the matrix components, including laminin and fibronectin. These findings suggested that uPA played a role to break through the surrounding basement membrane of blood and lymphatic vessels, and connective tissue for their growth and metastasis. We wish to emphasize the usefulness of the immunohistochemical evidences, such as autocrine growth mechanism and breakdown of extracellular matrix, as a possible parameters of tumor development, invasiveness and metastasis.
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PMID:[Immunohistochemical evidences of prognostic parameters associated with tumor development of pulmonary adenocarcinoma]. 194 64

Essential mixed cryoglobulinemia (EMC) is a rheumatic disorder characterized by widespread vasculitis. To better define the nature of the vasculitic process and to possibly outline assessment methods reliable for using in a clinical context, we studied plasma levels of three endothelial related peptides: fibronectin (FN), von Willebrand factor (vWF) and tissue plasminogen activator (t-PA), and those of thrombin-antithrombin III complexes (TAT) as markers of activation of the coagulation in 21 patients and in 16 controls. In EMC we found a picture consisting of reduced FN and increased vWF, t-PA, and TAT levels, suggesting a condition of endothelial cell damage with thrombin formation in vivo. Since we previously demonstrated the presence of chronic disseminated intravascular coagulation in these patients, we may assume that endothelial cells stressed by cryoprecipitation or stimulated by soluble mediators may be actively involved in the vasculitic process and possibly express procoagulant properties. This is a good example of the complex interplay existing between autoimmunity and coagulation mechanisms. We also suggest that FN, vWF, t-PA and TAT should be considered as additional clinical parameters when evaluating patients with EMC.
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PMID:Clinical significance of endothelial damage markers in essential mixed cryoglobulinemia. 195 Mar 76

Thy-1 antigen is expressed at high levels in the thymus and in adult brain of rodents however its function remains undetermined. We report that immobilised Thy-1 binds laminin, fibronectin and the less active precursor form of the tissue type plasminogen activator (t-PA) yet it does not bind urokinase. The incorporation of serine protease inhibitors within the experimental procedures suggested that Thy-1 bound to the lysine-containing, protein-binding domain of t-PA thus leaving the active site available to interact with other proteins. By using an immunocytochemical approach designed to maximally preserve Thy-1 antigenicity, we were able to demonstrate that in the adult rat peripheral nervous system (PNS) Thy-1 was seen to co-localise with laminin on the Schwann cell membranes and accumulated at the nodes of Ranvier within sciatic nerve. The only neuronal structures to express Thy-1 within the PNS were the unmyelinated nerve fibres. In the adult rat central nervous system (CNS), the most distinct and novel association of Thy-1 was its presence along the myelin forming glial cells and their fibres.
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PMID:Thy-1 is a neuronal and glial surface antigen which interacts with matrix proteins and plasminogen activator. 198 Oct 41

This study assessed the potential harmfulness of particles in the lung by measuring their ability to elicit and maintain an inflammatory response and to damage lung tissue. It compared the inflammogenicity of two nondurable, biological particulates (Corynebacterium parvum and zymosan) with a pathogenic mineral dust (quartz) and a nonpathogenic dust (titanium dioxide) by dosing rats via the intratracheal route and measuring the consequent alveolitis. The magnitude and duration of the inflammatory response were assessed by measuring the total number of leucocytes and the percentage of neutrophils obtained by bronchoalveolar lavage. Two key functional parameters of the lavaged leucocytes--ability to degrade fibronectin and production of plasminogen activator--were also measured. A marked inflammatory response had occurred by one day after instillation, characterised by increases in total leucocyte numbers and percentage of neutrophils in the bronchoalveolar lavages, with all four test materials. In all but the quartz exposed animals, the inflammation subsided rapidly thereafter, approaching control levels by 15 days after injection; in the quartz exposed animals the alveolitis persisted for up to 30 days. All of the inflammogens generated chemotaxins in rat serum in vitro and so, by analogy, might also be expected to generate chemotactic activity in alveolar lining fluid which could contribute to the generation of an inflammatory response. The cellular inflammatory response was accompanied by a concomitant increase in the proteolytic activity of the bronchoalveolar lavage leucocytes but production of plasminogen activator remained unchanged. In vitro exposure to the inflammogens had no effect on the proteolytic activity against fibronectin or on the plasminogen activator activity of bronchoalveolar leucocytes.
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PMID:Persistent biological reactivity of quartz in the lung: raised protease burden compared with a non-pathogenic mineral dust and microbial particles. 199 61

The capacity of solid tumours to invade the surrounding tissue and to metastasize, is correlated with the formation and degradation of structural elements in the vicinity of the tumour cells. Substances with both procoagulant activity and fibrinolytic activity are important factors in the formation or degradation of a "fibrin-fibronectin-gel matrix". This gel is subsequently transformed into the extracellular matrix, which, together with cells, will form the tumour stroma. When analyzing tumour stroma degradation products, it is obvious that the protease plasmin catalyses the disintegration of fibrin and fibronectin. Additional compounds of the tumour stroma and of the basal membrane are also, at least in part, broken down by plasmin or other proteases, such as collagenase IV and cathepsin D. The plasminogen activator urokinase (uPA) seems to play a central role as it was shown that elevated content of uPA is correlated with a high risk of early relapse and shorter overall survival, at least in breast cancer. It has been shown, that by means of quantifying uPA, patients with a relative high or low risk can even be selected within the classical risk groups, which so far are defined by the locoregional extension of the tumour and the hormone receptor status only. Evidently, as uPA content in human breast cancer tissue is an independent prognostic factor, one may speculate, that those experimental or in vitro data, which correlated increase in uPA-synthesis with malignancy, may be of direct relevance for human tumour biology. Moreover, due to these recent observations on the prognostic significance of tumour-associated proteases, new aspects for the selection of risk collectives within the node-negative breast cancer patients for adjuvant therapy have to be considered. It may well be possible, that one may affect tumour invasion and metastasis by inhibiting protease action of solid tumours by disturbing the binding of proteases to tumour cell surface receptors. As it is only a quantitative aspect, which separates benign physiological processes from tumour cell pathophysiology, experimental evidence suggests, that less drastic forms of palliative therapy can be proposed.
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PMID:[Clinical and prognostic significance of tumor-associated proteases in gynecologic oncology]. 204 Apr 18

The duration of preincubation of aspirated oocytes is essential for successful in vitro fertilization. The duration has to be varied according to the maturity of the oocyte and the follicle. The maturity of the oocyte corona-cumulus complex is assessed primarily by light microscopy. Additional information is provided by measurements of steroids, pituitary hormones, and proteins (such as inhibin, alpha 1-Antitrypsin, fibrinogen, plasminogen activator, collagenolytic enzymes, alpha 2-macroglobulin, fibronectin, glycosaminoglycans, insulin, insulin-like-growth-factors) in the follicular fluid. Complex measurements of so-called regulators of oocyte maturation (cAMP, oocyte maturation inhibitor, prostaglandins) is of high academic interest. Cytologic parameters, the chemotactic activity of the granulosa cells and serial ultrasound studies are of practical importance for evaluating the maturity of the growing follicle.
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PMID:[Criteria of the maturity of follicle and oocyte within the scope of in vitro fertilization. An overview]. 204 77

Recombinant variants of tissue plasminogen activator (t-PA) containing either substitutions or deletions of amino acids within the fibronectin finger-like domain (residues 6-50) were found to exhibit widely varying in vivo clearance profiles in rats and fibrinolytic activity in 125I-fibrin clot lysis assays. Clearance was not significantly affected by changes in the densely charged region of amino acid residues 7-10. Deletions or substitutions of amino acids in the region 14-32 decreased both fibrinolytic activity and the clearance of the enzyme. Modifications within the predicted omega loop of residues 37-41 affected clearance only to a small degree, whereas amino acid alterations in the region of residues 42-49 resulted in as much as a 6-fold decrease in the rate of clearance with only relatively minor decreases in the fibrinolytic activity of the variants. The cumulative results distinguish discrete sections of the NH2-terminal region of the enzyme as determinants of in vivo clearance and fibrinolytic activity of t-PA. In addition, the fibrinolytic activity of a variant containing the substitutions Gln42----Asn, His44----Glu, and Asn117----Gln, when compared with wild-type t-PA in an in vivo rabbit venous clot lysis model, was found to have similar lytic efficacy at approximately one-fourth the dose. We conclude that decreases in the in vivo clearance of t-PA can result in more potent thrombolytic agents in vivo, even though the in vitro fibrinolytic activity of the enzyme may be somewhat impaired.
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PMID:Site-directed mutagenesis in human tissue-plasminogen activator. Distinguishing sites in the amino-terminal region required for full fibrinolytic activity and rapid clearance from the circulation. 210 43


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