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)

Three cases of multicentric reticulohistiocytosis showing typical clinical, histologic, and ultrastructural findings are reported. In one, gastric cancer occurred; in the other two cases, severe polyarthritis was the only detectable internal involvement. The serine proteinases, urokinase and tissue-type plasminogen activator, were evaluated both with the autohistographic technique and spectrophotometric assay in lesional skin and synovia. Urokinase levels appeared grossly increased in the lesional synovia and moderately increased in the lesional skin. We suggest that urokinase, presumably released by the activated proliferating histiocytes, may play a major role in the extracellular matrix degradation leading to erosion of cartilage and adjacent bone in multicentric reticulohistiocytosis.
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PMID:Multicentric reticulohistiocytosis. Report of three cases with the evaluation of tissue proteinase activity. 314 26

In the past five years, the authors have performed stereotactic evacuation of hypertensive thalamic hematoma using Komai's CT-stereotactic apparatus in 44 cases. Liquefied hematoma was aspirated through a stereotactic cannula, and solid hematoma difficult to aspirate was dissolved by a plasminogen activator (Urokinase) and drained out through a silastic catheter. The mean ratio of the total volume of evacuated hematoma to the estimated volume by CT image was 83.8%. The recovery from motor paresis and consciousness disturbance was observed during the early postoperative days in most patients. Functional outcome (ADL) at 3 months after operation was as follows: 24 cases (54.5%) recovered to a full or partial (self-cared) social life, 15 (34.1%) required partial care at home and 2 (4.5%) remained bedridden. Although 3 patients died within 1 month after operation, the cause of death in these patients was admitted to have no direct relation to operative procedure or to rebleeding due to the Urokinase injection. Postoperative functional prognosis was not affected by the timing of the operation. The important factors affecting ADL were preoperative neurological grade and CT classification. This stereotactic method apparently exceeded the conventional craniotomy method in the functional outcome.
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PMID:[Stereotactic evacuation of hypertensive thalamic hematomas using plasminogen activator (urokinase)]. 351 66

Correlation between the deposition of alpha 2-plasmin inhibitor (alpha 2-PI), which is one of the inhibitory factors of fibrinolytic activities, in the glomeruli and the effects of urokinase therapy in patients with IgA nephropathy is described. Urokinase (UK) is a plasminogen activator derived from fresh human urine. Urinalysis and measurements of renal function tests, i.e., serum creatinine, blood urea nitrogen, glomerular filtration rate and phenolsulfonphtalein, were performed before and at 8 and 48 weeks after the administration of urokinase. There was marked improvement of proteinuria after UK therapy in patients without deposition of alpha 2-PI in the glomeruli. In contrast, the improvement of proteinuria after UK therapy was not observed in patients with positive deposition of alpha 2-PI in the glomeruli. It was concluded that the administration of UK may be useful for treatment of proteinuria in patients with IgA nephropathy.
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PMID:Significant correlation between the immunofluorescence of alpha 2-plasmin inhibitor in glomeruli and the effects of urokinase therapy in patients with IgA nephropathy. 353 Jan 7

Human carcinoma HEp-3 lost its tumorigenic and metastatic potential upon prolonged culture in vitro. This change was accompanied by a reduced production of plasminogen activator (PA) of the urokinase type (uPA), which is secreted by HEp-3 cells, a change in response to effectors that modulate uPA production, and an alteration of cell morphology. Similar but more rapid changes occurred when malignant HEp-3 cells were exposed to dimethyl sulfoxide (DMSO). uPA activity in the culture medium dropped below 50% of the control level within 6 h after the addition of DMSO and became undetectable after 24 h of treatment. This drop in uPA activity was not caused by an increased production of PA inhibitors. The cell-associated uPA decreased to 25 to 30% of the control level within 6 h of DMSO treatment and remained at this level for at least 96 h; the reduced uPA production was partially accounted for by a rapid decrease in the functional and chemical concentration of uPA mRNA. In contrast, the concentrations of most of the abundant mRNA species did not appear to be significantly affected, and cell growth was only slightly inhibited in the presence of DMSO. Malignant HEp-3 cells treated with DMSO responded to cholera toxin with an enhanced production of uPA, and their morphology became indistinguishable from that of nonmalignant HEp-3 cells grown in vitro for prolonged periods of time. All of the above changes were fully and rapidly reversible. The inhibitory effect of DMSO on PA production appears to be specific for uPA of human cell lines.
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PMID:Effect of dimethyl sulfoxide on human carcinoma cells, inhibition of plasminogen activator synthesis, change in cell morphology, and alteration of response to cholera toxin. 383 48

Tumor promoting phorbol esters and mezerein strongly induced plasminogen activator (urokinase, uPA) synthesis in porcine kidney cell cultures (LLC-PK1). Induction was due to increased uPA-mRNA levels which rose from 10 to 300 molecules/cell within 2 h of exposure to 16 nM phorbol myristate acetate. We have compared the action of tumor promoters with that of 8-bromo-cAMP, another potent inducer of uPA; the similarities between the two kinds of induction were: both involved transcriptional activation of the uPA gene; both were rapid in onset, changes in transcription rate being detectable within 10-20 min; the initial rates of transcription and uPA-mRNA accumulation were substantial and in the same order of magnitude; neither class of inducer required protein synthesis to stimulate uPA transcription. The main contrast between the two types of agents was that the uPA response to tumor promoters was transient whereas that to cAMP compounds was sustained: cultures rapidly lost their response to tumor promoters within 2 h after initial exposure while retaining responsiveness to cAMP-related agents. The cells developed a specific drug-induced desensitization which was slowly reversed after tumor promoters were removed from the culture medium. Since protein kinase C is now well established as the receptor for phorbol-derived and several other tumor promoters it will be of interest to determine whether desensitization occurs at the level of receptor.
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PMID:Induction and desensitization of plasminogen activator gene expression by tumor promoters. 386 68

Considerable interest in plasminogen activators as human thrombolytic drugs has stimulated rapid biotechnologic progresses. These enzymes have been classified in two immunochemically distinct groups: "urokinase-like" activators or u-PA which do not interact with fibrin and "tissue activator-like" activators or t-PA which interact with fibrin. Plasminogen activators are widely distributed in normal and malignant tissues and they are implicated in various physiological and pathological processes. They maintain the functional integrity of the vascular system and their presence may be of importance in tissue remodeling and cell migration. Urokinase and streptokinase are used in human thrombolytic therapy. However, the properties displayed by t-PA suggest that this enzyme may be a superior fibrinolytic agent. The primary structures of urokinase and t-PA are known; both enzymes have been synthesized by DNA technology. In order to produce t-PA in large quantities by gene cloning, intensive studies are conducted by pharmaceutical industries. Clinical trials using t-PA for dissolving thrombi in coronary heart disease, strokes and pulmonary embolism are in progress. This review presents the molecular and structural properties of plasminogen activators, as well as related physiological, pathological and therapeutic aspects.
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PMID:[Plasminogen activators: general aspects and recent developments]. 391 65

Fibrinolytic activity in porcine follicular fluid and plasminogen activator production by porcine granulosa cells in response to gonadotropins is described. Fibrinolytic activity was determined using a solid phase assay in which 125I-fibrinogen was coupled to latex beads. Urokinase plus plasminogen served as the standard. Porcine follicular fluid contained protease inhibitors as evidenced by its ability to inhibit the activity of an urokinase-plasminogen standard. Removal of these inhibitors by acid precipitation revealed plasminogen-dependent and -independent fibrinolytic activity. Cultured granulosa cells produced plasminogen activator in amounts that increased over time. This pattern was most significant in cells stimulated by hCG. Cells incubated with hCG produced significantly more plasminogen activator when compared to those cells cultured in absence of gonadotropin. The enhancement was most marked during the second 48 hrs in culture (p = 0.032). FSH was found to have no stimulatory effect on plasminogen activator production by cultured porcine granulosa cells.
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PMID:Porcine granulosa cell production of plasminogen activator: disparity between the effects of hCG and pFSH. 393 84

Total plasminogen activator (PA) activity, tissue-type PA (t-PA) activity, urokinase-like PA activity, and immunoreactive t-PA were measured in benign breast tumors (fibroadenomas), primary breast carcinomas, axillary node metastases, and chest wall recurrences. Total PA activity did not differ significantly in the different types of tumors. However, benign tumors contained predominantly t-PA activity. Urokinase-like PA activity was significantly higher in the malignant tumors compared with the benign group. Both t-PA activity and immunoreactive t-PA were significantly lower in chest wall recurrences compared with primary carcinomas. The ratio of t-PA to urokinase activity was significantly decreased between stages 1 and 3 in the primary tumors. Also, immunoreactive t-PA levels were significantly lower in stages 2 and 3 compared with stage 1. No correlation was found between PA (either total or its different forms) and tumor grade, histological type, or the presence or absence of axillary node metastases.
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PMID:Multiple forms of plasminogen activator in human breast tumors. 393 24

Damage to the fibrinolytic system preventing the resolution of temporary fibrinous adhesions was repeatedly mentioned as an etiological factor in the process of adhesion formation. We experimentally induced abdominal adhesions in rats by gentle scraping of the entire small bowel. Severe adhesions, sometimes accompanied by intestinal obstruction, developed in all of the control animals. Urokinase, a commonly used and potent fibrinolytic agent and a known plasminogen activator, was administered intragastrically, intraperitoneally, or intravenously at various doses ranging from 5,000 to 100,000 U/kg. Urokinase had no effect on the prevention of abdominal adhesions, nor did it reduce the severity or frequency of adhesion formation.
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PMID:Urokinase does not prevent abdominal adhesion formation in rats. 404 58

The fibrinolytic system was studied in primary biliary cirrhosis (16 patients) and large bile duct obstruction (10 patients, nine of whom had carcinoma). Plasma fibrinolysis (plasminogen activator activity) was decreased and fibrinogen increased in both groups of patients, particularly in those with large duct obstruction. These changes were related to the degree of cholestasis. Plasminogen activator activity was inversely related to serum triglyceride levels in patients with primary biliary cirrhosis. Urokinase inhibitors were decreased in both groups and antiplasmins increased in patients with large duct obstruction; fibrin/fibrinogen degradation products were normal in primary biliary cirrhosis and moderately increased in large duct obstruction. None of these fibrinolytic indices was related to the degree of cholestasis. Fibrinolytic activity and fibrinogen returned almost to normal levels after palliative surgery in the three patients with large duct obstruction who were studied. The decreased plasma fibrinolysis and increased fibrinogen may be due to altered lipid metabolism in cholestatic jaundice. In patients undergoing surgery for large duct obstruction there may be an increased risk of thrombosis.
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PMID:Fibrinolysis in cholestatic jaundice. 412 Aug 48


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