Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the anterior segment of the eye, fibrin clots must be rapidly resorbed to prevent further fibrosis and scarring. The aqueous humor of patients undergoing cataract surgery was analyzed for the presence of components of the fibrinolytic cascade. In 30 patients, aqueous humor and plasma were compared for their content of urokinase-type plasminogen activator (uPA), tissue-type plasminogen activator (tPA), plasminogen activators inhibitors (PAIs), plasminogen, and total proteins. With gel electrophoresis and zymographic assays of serial dilutions of plasma and aqueous humor, all these components were found to be present at lower concentrations in aqueous humor than in plasma. For total proteins, the aqueous/plasma ratio was approximately 0.003, and for plasminogen it was 0.001. Interestingly, the aqueous/plasma ratio for uPA was not as low and varied from 0.01 to 0.03. A significant proportion of the uPA in aqueous humor was present in the two-chain active form. In addition to uPA, aqueous humor contained lower levels of tPA, but no detectable levels of reactive plasminogen activators inhibitors (PAIs). The presence of a relatively high concentration of active uPA shows that the proteolytic balance of the aqueous humor in the anterior chamber of the eye is shifted toward fibrinolysis.
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PMID:Urokinase-type plasminogen activator in human aqueous humor. 163 15

We studied the quantitative fluctuations of tissue plasminogen activator (t-PA) activity and antigen in aqueous humor before and after extracapsular cataract extraction and poly(methyl methacrylate) posterior chamber lens implantation. The t-PA activity level was measured by solid phase bioimmunoassay using monoclonal antibody against an epitope apart from the active site of t-PA, and the antigen by ELISA. In our patients the mean preoperative level of t-PA activity was 0.0664 +/- 0.0472 IU/ml (mean +/- SD) and of the antigen, 0.175 +/- 0.024 ng/ml. The t-PA activity level in aqueous humor was markedly decreased on the first postoperative day (0.0042 +/- 0.0037 IU/ml), recovered on the second day (0.0403 +/- 0.0251 IU/ml), and then progressively decreased from the fourth to the seventh days. The t-PA antigen level in aqueous humor increased on the first (0.366 +/- 0.108 ng/ml) and second (0.403 +/- 0.251 ng/ml) postoperative days and gradually decreased from the fourth to seventh days. Under the intracameral condition of the fibrinolytic system, various factors, e.g., serious inflammation or events affecting the balance of coagulation and fibrinolysis, may induce the decrease or depletion of t-PA activity, followed by the pupillary fibrin membrane formation. We suggest that fluctuations of t-PA activity in aqueous humor may affect fibrinous membrane formation over the IOL surface.
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PMID:Postoperative fluctuations of tissue plasminogen activator (t-PA) in aqueous humor of pseudophakes. 194 85

We analysed the tissue plasminogen activator (TPA) content of the corneal epithelium, endothelium, and stroma and of the lens, as well as the aqueous and vitreous humors, in dog, calf, and monkey eyes. A quantitative estimation of the TPA activity in the corneal tissues by the [125I]fibrin-coated well assay showed similar levels of activity in the corneal epithelium, stroma, and endothelium. However, some differences were observed among the three mammalian species analysed. The values, expressed in urokinase (UK) units of activity per mg protein, ranged from 0.8 +/- 0.22 to 1.03 +/- 0.23 for the epithelium, 0.47 +/- 0.13 to 0.98 +/- 0.2 for the stroma, and 0.48 +/- 0.11 to 0.93 +/- 0.22 for the endothelium. The lens, the vitreous and the aqueous humor yielded low to negligible values. However, by using the enzyme-linked immunosorbent assay (ELISA) method, we detected an appreciable amount of TPA in the lens (9.49 +/- 1.5 ng TPA per ml lens), corneal epithelium (1.43 +/- 0.29 ng TPA per mg protein) and vitreous humor of the dog (5.71 +/- 0.61 ng TPA per ml vitreous humor) and of the calf (5.7 +/- 0.44 ng TPA per ml vitreous humor). Such discrepancies may reflect species-specific variation in the TPA content of the tissues and possibly the limitations of the techniques utilized, because of the problem related to cross-reactivity between the TPA of a given species and the antibody used in the assays.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tissue plasminogen activator in avascular tissues of the eye: a quantitative study of its activity in the cornea, lens, and aqueous and vitreous humors of dog, calf, and monkey. 310 75

By quantitative analysis of tissue plasminogen activator (TPA) in the trabecular endothelium, corneal endothelium, and iris in the eyes of monkeys and dogs, we found significant levels of TPA activity. In a [125I]fibrin-coated well assay, the levels for the dog and monkey were, respectively: trabecular endothelium, 0.2 and 0.5; corneal endothelium, 0.8 and 0.5 IU per mg protein. The iris tissue showed high TPA activity, but its protein content could not be measured with the techniques employed. Activity in the aqueous humor was not detectable. By the ELISA technique, the values (in ng TPA/mg tissue protein) for the dog and monkey were, respectively: trabecular endothelium, 0.16 and 0.44; corneal endothelium, 0.48 and 0.92. Again, iris tissue showed high TPA activity, whereas the aqueous humor showed low activity (0.86 ng/ml). The data obtained with the two methods showed a reasonable consistency, although a direct comparison was not possible because two separate standards were used. The presence of TPA in the trabecular endothelium, corneal endothelium, and iris may be important in modulating the resistance to aqueous outflow under normal conditions as well as those of hyphema.
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PMID:Tissue plasminogen activator in the trabecular endothelium. 311 34

By using an enzyme-linked immunosorbent assay, we detected a significant amount of tissue plasminogen activator (0.8 +/- 0.17 ng/ml) in the aqueous humor of ten normal human eyes. It was also identified on Western blot analysis. The ratio of tissue plasminogen activator to total protein in aqueous humor was about 30 times greater than the ratio of tissue plasminogen activator to total protein in plasma. There was evidence that at least some of the tissue plasminogen activator in the aqueous humor was synthesized locally by the structures bordering the anterior chamber of the eye. Tissue plasminogen activator may be a useful therapeutic modality in clinical conditions of delayed dissolution of fibrin in the eye.
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PMID:Tissue plasminogen activator in human aqueous humor and its possible therapeutic significance. 314 67

Levels of extravascular tissue plasminogen activator activity (PA) and those of inhibitors of PA and of urokinase (UK) present within the anterior chamber of normal and inflamed feline eyes were assessed with the use of a direct PA assay of microsamples of aqueous humor. Purposes of the study were, first, to confirm prior indirect evidence that this extravascular space normally contains higher levels of uninhibited PA, but lower levels of inhibitor activity, than does plasma and, second, to determine patterns of change in these activities under in vivo conditions imposed by a chronic mycobacterial-induced uveitis (CMIU) disease model. The PA assay utilized a 125I-plasminogen substrate whose cleavage by PA contained in samples was both visualized during gel electrophoreis, and quantified by gamma counting. The results provided the first direct evidence that the higher fibrinolytic activity previously observed in normal aqueous in comparison with plasma is in fact associated with higher levels of available (uninhibited) PA (P less than 0.01) The data also indicated that normal aqueous contains a much higher level of PA inhibitor activity than previously suspected--roughly 40 times more than available PA levels. These normal values for PA and inhibitors occupied a relatively narrow, threefold range, in contrast to the wide scattering of individual values that appeared during 18-20 weeks of the chronic inflammation disease model. Despite this, however, the general pattern of observation for all individual eyes during CMIU was a significant increase in levels of both PA and inhibitors. The net effect of CMIU was thus to cause the 1:40 ratio noted above to be tilted more strongly in favor of inhibitor activity, ie, up to 1:80. Increases in local vasopermeability in this disease model were believed contributory to this change. However, local generations of PA and APA in vivo by inflammatory cells, especially monocyte-macrophages, must also be considered. Assays for UK inhibitor showed levels of activity and directions of change that closely followed those of PA inhibitor, which suggests the possibility that they may be identical. It is surmised that the above patterns, along with results of our prior studies, indicate an apparent need for a multistep, strict inhibitory control of plasmin generation and proteolysis in vivo within normal extravascular spaces such as the anterior chamber.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Extravascular plasminogen activator and inhibitor activities detected at the site of a chronic mycobacterial-induced inflammation. 349 1

Prevalence of intraoperative contamination of the eyelids, conjunctival sac, and aqueous humor of 50 canine eyes that underwent elective cataract surgery was determined, and the short-term outcomes for contaminated and noncontaminated eyes were compared by scoring media clarity, pupil size and shape, and behavioral evidence of vision during the initial 30-day postoperative period. Results of bacteriologic culture of anterior chamber samples were positive for 12 of the 50 (24%) eyes, but anterior chamber contamination was unrelated to results of bacteriologic culture of eyelids or conjunctival sac swab samples. Eyes undergoing phacoemulsification were less likely to be contaminated than were eyes undergoing intra- or extracapsular extraction. Eyes undergoing intra- or extracapsular extraction and eyes with anterior chamber contamination had a greater likelihood of developing glaucoma postoperatively. We did not detect an association between intraocular contamination and the surgeon performing the operation, the need for postoperative administration of tissue plasminogen activator, or the presence or absence of diabetes mellitus. Also, we did not detect any differences in outcome between eyes with and without intraocular contamination. Despite intraoperative bacterial contamination of the anterior chamber, bacterial endophthalmitis did not develop in any of the eyes.
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PMID:Intraocular bacterial contamination during cataract surgery in dogs. 778 43

Topically administered tissue plasminogen activator (tPA) was evaluated for its penetration into aqueous humor of clinically normal dogs. Two concentrations of tPA (5 mg/ml and 10 mg/ml) were evaluated in a single-dose study, and a concentration of 5 mg of tPA/ml was used for a multiple-dose study. The contralateral eye served as a nontreated control. Enzyme substrate analysis of aqueous humor was used to determine tPA activity. The activity of tPA in aqueous humor was significantly (P < or = 0.05) greater in treated eyes of all dogs, compared with that in control eyes. Significant differences in activity of tPA were not detected at different doses in treated eyes.
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PMID:Evaluation of intraocular penetration of topically administered tissue plasminogen activator in dogs. 832 49

The uveal layer is thought to hold the largest stores of tissue plasminogen activator (t-PA) within the eye. However, the uveal cell types that contain and could release t-PA to contiguous tissues and fluids have not been clearly identified. In the present study the general distribution pattern of t-PA antigen in fresh rat iris and choroid tissue was determined by immunofluorescence in preliminary light microscopic (LM) cryosections. Transmission electron microscopic (TEM) immunogold localization was then used to detect specific cellular and subcellular sites of t-PA antigen. The primary antibody was rabbit anti-mouse t-PA IgG. The immunofluorescence in preliminary LM cryosections of both tissues was most intense over discrete linear and cross-sectioned structures that resembled the contours of axon bundles. This impression was strengthened when silver impregnation highlighted similar structures in separate sections of the same tissue samples. TEM immunogold labeling of thin sections then confirmed that the t-PA antigen was confined to the axoplasm of both myelinated and unmyelinated perivascular nerve fibers in both the iris and choroid. Gold particles were not observed over axonal membranes, myelin sheaths, Schwann cells, retinal pigment epithelium or vascular endothelial cells. Ultrathin TEM cryosections of the iris showed a localization of some particles over structures that resembled tubules and vesicles within the axoplasm, but not over mitochondria. The axonal location of t-PA was shown by the co-localization of t-PA with an antibody against rat neurofilaments. The typical axon morphology that enclosed the t-PA particle markers in all TEM sections also indicated an axonal location. Separate TEM sections were processed with conventional fixatives and stains to highlight the typical uveal axon morphology, which also confirmed the identity of perivascular axons as the sites of t-PA localization. Affinity of the primary antibody for rat t-PA was shown by an inhibition ELISA against rat uveal tissue extracts and by the inhibition of t-PA activity in aqueous humor. An amidolytic assay was used to quantify t-PA activity. Possible explanations for the preferential immunolocalization of t-PA antigen to the axoplasm of uveal nerve terminals and the need for additional functional studies to confirm a putative neural t-PA synthesis are discussed.
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PMID:Morphologic evidence for a preferential storage of tissue plasminogen activator (t-PA) in perivascular axons of the rat uvea. 923 71

Melanoma cells produce tissue plasminogen activator (t-PA) that plays an important role in tumor invasion and metastasis. The production of t-PA by normal human uveal melanocytes has not been reported previously. In order to explore this possibility, we studied the production of t-PA by cultured human uveal melanocytes and compared that with the production by cultured human uveal melanoma cells and epidermal melanocytes. Human adult uveal melanocytes were isolated and cultured from donor eyes. The cells were cultured in serum-free medium for 48 h and the conditioned medium then collected for the plasminogen activator (PA) activity assay. Free PA activity was tested in an amidolytic assay using a t-PA standard curve. PA type was identified by fibrinography and antihuman t-PA and urokinase plasminogen activator (u-PA) blocking antibodies. Free PA activity was found in the conditioned medium of normal melanocytes and melanoma cells. The predominant PA activity was t-PA. Normal uveal melanocytes produced more t-PA (3.23 +/- 0.73 IU/105 cells/24 h) than that of epidermal melanocytes (1.25 IU/105 cells/24 h) but much less than uveal melanoma cells (11.0 +/- 3.39 IU/105 cells/24 h). Western blot analysis revealed that most t-PA in conditioned media were one-chain t-PA with molecular weight of 69 kDa. Our study indicates that uveal melanocytes may contribute to the free t-PA activity previously found in aqueous humor and choroidal eye cup superfusions. Therefore, this function of uveal melanocytes may play a role in intraocular matrix remodeling, fibrinolysis and aqueous humor outflow.
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PMID:Tissue plasminogen activator is released into cultured medium by cultured human uveal melanocytes. 1221 94


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