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)

Increased amounts of plasminogen activator enzymes were found in the large Dupuytren's nodules in the so-called active phase of the disease. A prospective study in 15 patients who had operations investigated possible relationships between fibrinolytic capacity of the palmar nodules (assessed by the fibrin plate method) and the recurrence of contracture. There were substantial analogies and suggestive connections with the results of previous electron microscopic studies. Combined with the presence of myofibroblasts, the high increase of plasminogen activator enzymes in the fascial nodules may be regarded as a predictive marker for possible recurrence after surgical treatment of Dupuytren's contracture.
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PMID:Possible role of plasminogen activator content of the palmar nodules in recurrence of Dupuytren's contracture. 369 26

Considering the proved interaction of fibrin with fibroblasts and the seemingly decisive role of structural and functional changes ("modulation") of these cells in the evolution of Dupuytren's contracture, research has been carried out in order to investigate the fibrinolytic capacity and the possible presence of fibrin/fibrinogen in the palmar fascia of subjects operated upon for Dupuytren's Disease. Fibrin/fibrinogen were detected by a direct immunofluorescence technique and fibrinolytic activity was assessed by a fibrin plate method. A remarkable decrease of fibrinolytic activity and the presence of fibrin/fibrinogen were observed in small nodules in the early stage of disease, whereas large nodules showed a high amount of plasminogen activator enzymes. Small nodules seem to form and increase by progressive adhesion of fibroblasts to the polymerizing fibrin, while high fibrinolytic activity of large nodules probably results from "modulation" of many fibroblasts into contractile myofibroblasts and could therefore be considered as a biochemical sign of the evolutionary phase of Dupuytren's contracture.
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PMID:Fibrin/fibrinogen and fibrinolytic activity of the palmar fascia in Dupuytren's contracture. 395 50

Vimentin-positive, desmin-negative cells were established in culture from the nodule and from apparently normal palmar aponeurosis of a patient with Dupuytren's disease and compared with normal human embryonic and adult fibroblasts or sarcomatous cells. Cells from the nodule display in vitro biological properties that are intermediate between those expressed by normal fibroblasts and sarcoma cells or cells from the nodule transformed with SV40 virus. Thus, they represent an interesting in vitro model of partially transformed human cells. This behavior is not evolutive and justifies the classification of Dupuytren's disease among the benign mesenchymal tumors. The production of high level of plasminogen activator probably explains the local reactive pathology, and could act as a mitogenic stimulus for the proliferation of the nodule itself. Cultures derived from the apparently normal palmar aponeurosis show some but not all the abnormal growth properties of cells from nodules; this may help to explain the onset of local recurrences. Our results suggest that Dupuytren's disease is not strictly local and limited to the nodules, but affects, at least partially, the whole aponeurosis. Dupuytren's nodules could be considered as a model of tumor progression in a benign situation.
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PMID:Abnormal behavior of cultured fibroblasts from nodule and nonaffected aponeurosis of Dupuytren's disease. 619 20

Research and drug developments fostered under orphan drug product development programs have greatly assisted the introduction of efficient and safe enzyme-based therapies for a range of rare disorders. The introduction and regulatory approval of 20 different recombinant enzymes has enabled, often for the first time, effective enzyme-replacement therapy for some lysosomal storage disorders, including Gaucher (imiglucerase, taliglucerase, and velaglucerase), Fabry (agalsidase alfa and beta), and Pompe (alglucosidase alfa) diseases and mucopolysaccharidoses I (laronidase), II (idursulfase), IVA (elosulfase), and VI (galsulfase). Approved recombinant enzymes are also now used as therapy for myocardial infarction (alteplase, reteplase, and tenecteplase), cystic fibrosis (dornase alfa), chronic gout (pegloticase), tumor lysis syndrome (rasburicase), leukemia (L-asparaginase), some collagen-based disorders such as Dupuytren's contracture (collagenase), severe combined immunodeficiency disease (pegademase bovine), detoxification of methotrexate (glucarpidase), and vitreomacular adhesion (ocriplasmin). The development of these efficacious and safe enzyme-based therapies has occurred hand in hand with some remarkable advances in the preparation of the often specifically designed recombinant enzymes; the manufacturing expertise necessary for commercial production; our understanding of underlying mechanisms operative in the different diseases; and the mechanisms of action of the relevant recombinant enzymes. Together with information on these mechanisms, safety findings recorded so far on the various adverse events and problems of immunogenicity of the recombinant enzymes used for therapy are presented.
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PMID:Enzymes approved for human therapy: indications, mechanisms and adverse effects. 2564 40