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)

We carried out an immunohistochemical study of tissue-type plasminogen activator (PA) and urokinase-type PA, and their inhibitors, PA inhibitor-1 and PA inhibitor-2, using renal biopsy specimens obtained from 86 patients with various forms of glomerulonephritis. The controls were four normal renal tissue specimens. On immunofluorescent observation, granular staining for tissue-type PA was found to be distributed along the glomerular capillary walls. The fluorescence was weak in the normal renal tissue and occasionally intense in the tissues of patients with IgA nephritis, minimal change nephrotic syndrome, and lupus nephritis. PA inhibitor-1 was abundant in the glomerular epithelial cells and scarce in the mesangial area and glomerular capillary lumens of the normal renal tissues. This was confirmed by immunoelectron microscopy using gold staining. The fluorescence of PA inhibitor-1 was weaker in some specimens of nephritic tissues than in the normal renal tissues. Urokinase-type PA and PA inhibitor-2 were negative within the glomeruli in all the specimens. In the glomerulonephritic tissues which were fibrin deposition-positive, tissue-type PA expression in the glomeruli tended to be strong. An association between fibrin deposition and PA inhibitor-1 staining was not clear. These data suggest that expression of tissue-type PA in the glomeruli increases in association with fibrin deposition.
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PMID:Tissue-type plasminogen activator and its inhibitor in human glomerulonephritis. 138 27

Fibrin deposition in kidney is a common event in some forms of human and experimental glomerulonephritis, and is thought to result from local activation of blood coagulation and/or impaired removal by the fibrinolytic system. We studied the urinary procoagulant and fibrinolytic activities in 46 patients with renal disease (26 with IgA nephritis, 13 with other forms of glomerulonephritis and 7 with non-inflammatory kidney disease) and in 15 matched healthy subjects, as possible indicators of the coagulation-fibrinolysis balance in kidney. Procoagulant activity was slightly but not significantly increased in patients with serum creatinine levels higher than 1.5 mg/dl (group II) as compared with patients with normal creatinine (group I) and controls. It was identified as tissue factor by biological criteria (dependence on factor VII). Fibrinolysis studies showed that both plasminogen activator activity and urokinase antigen were significantly lower in group II than in group I patients and controls (P less than 0.0005). Reduced fibrinolytic activity in patients' urine was due to decreased excretion of urokinase since no inhibitor was detected by both fibrin autography and functional assay. No differences were found between patients and controls in plasma fibrinolytic activity, plasminogen activator inhibitor, and procoagulant activity of blood monocytes. The urinary changes in severe renal disease may reflect an unbalance of the coagulation-fibrinolysis equilibrium in kidney and might be of pathogenetic and clinical relevance.
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PMID:Urinary procoagulant and fibrinolytic activity in human glomerulonephritis. Relationship with renal function. 191 Jan 25

The concentrations of two different plasminogen activators(PAs), urokinase (UK), tissue-type plasminogen activator (t-PA) and urinary trypsin inhibitor (UTI) were determined in the urine and blood from 48 normal subjects and 92 patients with glomerulonephritis using highly sensitive enzyme immunoassay (EIA). The values of UK clearance were approximately 1.5-fold larger than those of creatinine clearance and at least 60.8% of UK was reabsorbed in the renal tubules, which suggest that one of major secretion site of UK is located in the outer region of the glomerular basement membrane (GBM), that is glomerular epithelium. Decreased urinary excretion of UK was observed in the glomerular disease depending on their severity and correlated with the increasing degree of FDP D-dimer excretion. On the other hand, the values of t-PA clearance were quite smaller than those of creatinine clearance, which suggest that urinary t-PA originated from the blood circulation or the inner side of the GBM (possibly glomerular endothelium) and filtrated from the GBM. Like UK, urinary t-PA also decreased in glomerular diseases. UTI which is highly anionic and has a comparable size with albumin was excreted increasingly in glomerulo-nephritis due to loss of the anionic charge barrier of the GBM. No significant correlations were noted between UTI excretion and UK or t-PA excretion.
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PMID:Urinary UK, t-PA and urinary trypsin inhibitor in health and glomerular diseases. 251 8

Strains of group A streptococci known to secrete the nephritis strain-associated protein (NSAP), a plasminogen activator, were studied for their ability to produce APSGN in rabbits. A tissue cage model was used to monitor the secretion of NSAP at the focus of infection and histopathological examination of kidney tissue was used to determine glomerular pathology. Animals infected with NSAP positive strains exhibited NSAP deposits in the glomerular tissue by day 7 in the absence of antibody to this molecule with progressive pathology indicative of APSGN three weeks later. Animals infected with the NSAP negative streptococcal strain exhibited no abnormal pathology. The ability of NSAP to bind to kidney tissue suggested that it has unique nephrotropic properties; and its ability to activate plasminogen to plasmin, possibly in situ, suggests that much of the pathological events associated with APSGN may be initiated by plasmin activity.
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PMID:A streptococcal plasminogen activator in the focus of infection and in the kidneys during the initial phase of experimental streptococcal glomerulonephritis. 306 3

The plasminogen activator 960 IU/mg protein activity isolated from cultured fluid of the calf kidney cells was introduced to albino rats (180-200 g) with experimental Heynmann nephritis every day during 4 days. Nephritis caused activation of haemostasis and inhibition of fibrinolysis in the blood. There was increased excretion of the fibrin, fibrinogen degradation products in urine as a results of the local fibrin deposition in diseased kidneys. The fibrinolytic activity of the cortical zone of kidney was markedly decreased. The plasminogen activator, infused to experimental animals, resulted in normalization of the altered indexes.
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PMID:[Effects of tissue-type plasminogen activator from a culture of calf kidney cells on hemostasis and fibrinolysis in experimental nephritis]. 314 31

We report the isolation and purification of the nephritis strain-associated protein (NSAP) first described by Villareal et al. (8). Amino acid analysis, and determination of the first 21 amino-terminal amino acids indicated that this 46 kD protein is a streptokinase. Biochemical analysis confirmed that NSAP could act as a plasminogen activator; immunological investigations indicated that NSAP is antigenically different from streptokinase from group C streptococcus, and possibly represents a unique streptokinase. It is this uniqueness that may contribute to the role of NSAP in the pathogenesis of acute poststreptococcal glomerulonephritis.
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PMID:Purification and partial characterization of the nephritis strain-associated protein from Streptococcus pyogenes, group A. 351 59

Monocyte infiltration and activation of the coagulation system have been implicated in the pathophysiology of glomerulonephritis. In this study, spontaneous procoagulant activity (PCA) was measured in circulating mononuclear cells to determine whether elevated PCA correlated with the presence of proliferative glomerulonephritis in patients with systemic lupus erythematosus (SLE). No increase in PCA was found in 20 patients with end-stage renal failure, 8 patients with glomerulonephritis without SLE, and 10 patients undergoing abdominal surgical or orthopedic procedures as compared with 20 normal controls. In eight patients with SLE but with no apparent active renal disease, PCA was not elevated above normal basal levels. Seven additional patients with SLE who had only mesangial proliferation on biopsy also had no increase in PCA. In contrast, eight patients with focal or diffuse proliferative lupus nephritis, and one patient with membranous nephritis who ultimately developed a proliferative lesion, had a marked increase in PCA with greater than 100 times the base-line levels. The activity was shown to originate in the monocyte fraction of the mononuclear cells and was shown to be capable of cleaving prothrombin directly. The prothrombinase activity was not Factor Xa, because it was not neutralized by anti-Factor X serum and was not inhibited by an established panel of Factor Xa inhibitors. Monocyte plasminogen activator determinations did not correlate with renal disease activity. We conclude that monocyte procoagulant activity, a direct prothrombinase, seems to correlate with endocapillary proliferation in lupus nephritis and could be a mediator of tissue injury.
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PMID:Monocyte procoagulant activity in glomerulonephritis associated with systemic lupus erythematosus. 403 82

Using a modified model of Masugi's nephritis of rats, various enzymatic activities in urine, serum and renal tissue (glomeruli or cortex) were determined at appropriate intervals after the administration of anti-kidney serum and compared with the urinary protein content and the kidney weight. In the urine, alkaline phosphatase (Al-Phosase), acid phosphatase (Ac-Phosase) and N-acetyl-beta-glucosaminidase (NA-beta-Gase) activities remarkably increased after the induction of nephritis, reached their peaks on the 10th day and reverted to almost the normal levels on the 30th day. The patterns of time course of these enzymatic activities were similar to patterns seen in the urinary protein content and the kidney weight. In the serum, the Al-Phosase activity decreased slightly, while NA-beta-Gase activity increased slightly. The Ac-Phosase activity in serum remained at normal levels during the experimental periods. In the glomeruli, the bound activities of these three enzymes decreased with nephritis, showing a negative correlation with results in the urine. On the other hand, fibrinolytic activities in the urine (plasmin-like enzyme) and renal cortex (plasminogen activator) also paralleled the urinary protein content and the kidney weight in the course of the disease. These results suggest that the Al-Phosase, Ac-Phosase and NA-beta-Gase excreted into urine in cases of nephritis may be mostly derived from damaged renal cells and one part of Al-Phosase may also come from the plasma. Moreover, the increase of plasmin-like enzyme in urine is considered to be due to the increase of plasminogen activator in the renal cortex. Thus, the determination of these enzymatic activities in the urine should be useful for evaluating effects of drugs for the treatment of nephritis.
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PMID:Pharmacological studies on experimental nephritic rats (9). Changes in activities of urinary enzymes in the modified type of Masugi's nephritis and their sources. 720 60

Coagulation and fibrinolytic factors in the blood were measured during heparin-urokinase (UK)-pulse combined therapy in order to investigate the background for the availability of the therapy. Five patients with nephritis resistant to conventional treatment were treated with this combined therapy (heparin: 350-450 U/kg day, continuously i.v. during the therapy; UK: 5000 IU/kg/2 hrs, i.v., two times a day, for 3 days = 1 Kur; methylprednisolone 20 mg/kg/2hrs, d.i.v., for 3 days = 1 Kur; 3 Kurs of UK and 3 Kurs of pulse were alternately administered). 1) Blood levels of alpha 2-plasmin inhibitor (alpha 2-PI) antigen were decreased and those of alpha 2-plasmin inhibitor.plasmin complex (alpha 2-PI. PmC) were elevated during 3 Kurs of UK administration. Accordingly, activation of the fibrinolytic system was confirmed during the combined therapy, suggesting that both alpha 2-PI and alpha 2-PI.PmC were relevant in monitoring the fibrinolytic state in blood. 2) Both tissue-plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) levels were sustained continuously in the elevated levels in the blood during both UK administration and pulse therapy. This movement of t-PA and PAI-1 was independent of that of the other fibrinolytic factors, such as alpha 2-PI,alpha 2-PI.PmC and plasminogen. 3) Inflammatory reactants such as fibrinogen, alpha 2-PI,alpha 2-macroglobulin and alpha 1-antitrypsin decreased more significantly during this heparin-urokinase-pulse combined therapy than during our previous combined therapy consisting of only heparin and urokinase. Therefore, we conclude that the anti-inflammatory effect was reinforced by adding the pulse therapy and that the combined therapy had some effect on the release of t-PA from vascular endothelial cells.
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PMID:[Changes in coagulation and fibrinolytic factors observed during heparin-urokinase-pulse combined therapy for nephritis resistant to conventional treatment in children]. 750 45

Markers of endothelial cell activation were measured in 28 patients presenting with various forms of limited or focal type cutaneous vasculitis. Plasma levels of tissue plasminogen activator antigen (t-PA:Ag), plasminogen activator inhibitor type 1 antigen (PAI-1:Ag) and PAI-1 activity, fibrin plate, von Willebrand factor antigen (vWF:Ag), tissue factor (TF) and soluble thrombomodulin (sTM) were measured. In comparison with the control group (n = 20) there was a significant increase in t-PA:Ag, vWF:Ag and TF (P < 0.05, Mann-Whitney U-test) in the cutaneous vasculitis group. This study confirms that measurable degrees of endothelial activation occur in cutaneous vasculitis. Cutaneous vasculitis includes a diverse group of clinical conditions, which are associated with inflammatory changes in cutaneous blood vessels with local fibrin deposition. The aetiology and pathogenesis of the majority of these entities remain unknown. Causative mediators are thought to include immune complexes, anti-endothelial cell antibodies, cytotoxic lymphocytes and viruses. Histologically, immune complexes and complement are frequently detected on the vessel wall, and serologically anti-endothelial antibodies are often detected in patients with vasculitis and in systemic lupus erythematosus (SLE) which correlate with the severity of cutaneous vasculitis, arthritis and nephritis. Lymphocyte-mediated toxicity to endothelial cells has been reported in a small number of patients with giant cell arteritis and Takayasu's arteritis. The vascular endothelium plays a central part in the control of haemostasis. Under physiological conditions endothelial cells present an anticoagulant surface to blood constituents, partially due to surface expression of heparan sulphate and thrombomodulin (TM). Heparan sulphate binds antithrombin III (ATIII), thereby accelerating inactivation of intrinsic coagulation enzymes. Thrombomodulin is an endothelial cell surface glycoprotein which promotes anticoagulation by forming a complex with thrombin which then activates protein C. Activated protein C together with a cofactor, protein S, inactivates FVa and FVIIIa. von Willebrand factor (vWF) is synthesized by endothelial cells, stored in Weibel-Palade bodies and released into the circulation upon endothelial stimulation. vWF mediates the binding of platelets to the subendothelium and is the carrier molecule for FVIIIC. The endothelium controls fibrinolysis by producing t-PA and its inhibitor PAI-1. Inflammatory cytokines such as interleukin-1 (IL-1) and tumour necrosis factor (TNF) activate endothelial cells, causing a shift from an antithrombotic to prothrombotic state, including expression of tissue factor, increased synthesis of PAI-1 and decreased expression of TM. Fibrin deposition and intravascular thrombosis are seen in cutaneous vasculitis syndromes, suggesting local endothelial cell activation. The aim of this pilot study was to assess whether perturbation of the endothelium in cutaneous vasculitis could be detected in the patients' plasma samples. If so, further studies to assess any correlation in levels of these markers with disease activity might prove useful in the future.
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PMID:Endothelial cell activation in cutaneous vasculitis. 868 65


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