Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the course of a pilot study, the effects of fibrinolysis treatment with rt-PA (Actilyse, Thomae, Biberach; 100 mg) on the recovery of hearing and hemorheologic parameters were investigated in 12 patients suffering from sudden hearing loss. The authors' approach was based on two considerations, (1) the possibility that, in cases of sudden hearing loss, the oxygen supply to the cochlea is totally or partially blocked by a microthrombus which could be dissolved by rt-PA and (2) the fact that lysis markedly improves the flow characteristics of the blood (as has been demonstrated in studies with streptokinase and urokinase). This human-plasminogen activator, produced by genetic engineering, is superior (also in terms of possible side-effects) to other lysin enzyme preparations (streptokinase, urokinase) because of its highly selective effects on thrombi (low activation of plasma plasminogen) and its short half-life (approx. 4 min). In nine of 12 patients, the treatment brought about a marked improvement in hearing or its complete restitution (three of the patients has initially been deaf in the affected ear). In the three nonresponders there was serologic evidence of an inner-ear infection (neuroborreliosis, cytomegaly, influenza B). The most interesting rheologic effect was the reduction of plasma viscosity (average decrease about 18%), since such a reduction cannot be attained with other, comparable rheologic measures (isovolemic or hypervolemic hemodilution). In spite of the convincing hemorheologic effects, fibrinolysis cannot yet be recommended as treatment for sudden hearing loss. Further studies have still to be done on spontaneous healing, the effects of hemorheologic measures on the blood circulation of the inner ear, and on the oxygen requirements of the ear affected by hearing loss.
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PMID:[Fibrinolytic therapy in sudden deafness with recombinant tissue-type plasminogen activator. Hemorheologic and therapeutic effects]. 191 Mar 64

Gel permeation methods have been commonly used to screen combinatorial libraries synthesized on a solid support. We report here three screens of combinatorial libraries using gel permeation assays. These include a simple enzymatic assay to identify inhibitors of the influenza enzyme neuraminidase, and two more complex assays designed to screen for inhibitors of the interleukin-8 (IL-8)-IL-8 receptor and the urokinase-urokinase receptor interactions, respectively. The IL-8 ligand-receptor assay makes use of IL-8 receptor-expressing cells attached to a membrane, thus enabling washing steps as part of the assay. The urokinase ligand-receptor assay employs an enzyme-linked immunosorbent assay-type format, previously thought to be amenable only to well-based assays. The results of these three screens are reported here, including the discovery of a novel series of acyclic inhibitors of neuraminidase. The development of complex assays in a gel permeation format allows for the routine screening of combinatorially as well as noncombinatorially made compound collections against virtually any kind of target, and is being widely used in our high throughput screening operations.
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PMID:Complex gel permeation assays for screening combinatorial libraries. 1168 31

A critical step in the influenza virus replication cycle is the cleavage activation of the HA precursor. Cleavage activation of influenza HA enables fusion with the host endosome, allowing for release of the viral genome into the host cell. To date, studies have determined that HA activation is driven by trypsin-like host cell proteases, as well as yet to be identified bacterial proteases. Although the number of host proteases that can activate HA is growing, there is still uncertainty regarding which secreted proteases are able to support multicycle replication of influenza. In this study, we have determined that the kallikrein-related peptidases 5 and 12 are secreted from the human respiratory tract and have the ability to cleave and activate HA from the H1, H2, and H3 subtypes. Each peptidase appears to have a preference for particular influenza subtypes, with kallikrein 5 cleaving the H1 and H3 subtypes most efficiently and kallikrein 12 cleaving the H1 and H2 subtypes most efficiently. Cleavage analysis using HA cleavage site peptide mimics revealed that the amino acids neighboring the arginine cleavage site affect cleavage efficiency. Additionally, the thrombolytic zymogens plasminogen, urokinase, and plasma kallikrein have all been shown to cleave and activate influenza but are found circulating mainly as inactive precursors. Kallikrein 5 and kallikrein 12 were examined for their ability to activate the thrombolytic zymogens, and both resulted in activation of each zymogen, with kallikrein 12 being a more potent activator. Activation of the thrombolytic zymogens may therefore allow for both direct and indirect activation of the HA of human-adapted influenza viruses by kallikrein 5 and kallikrein 12.
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PMID:Cleavage activation of human-adapted influenza virus subtypes by kallikrein-related peptidases 5 and 12. 2361 74

Influenza A viruses (IAV) mutate rapidly and cause seasonal epidemics and occasional pandemics, which result in substantial number of patient visits to the doctors and even hospitalizations. We aimed here to identify inflammatory proteins, which levels correlated to clinical severity of the disease. For this we analysed 102 cytokines and growth factors in human nasopharyngeal aspirate (NPA) samples of 27 hospitalized and 27 outpatients diagnosed with influenza A(H1N1)pdm09 virus infection. We found that the relative levels of monocyte differentiation antigen CD14, lipocalin-2 (LCN2), C-C-motif chemokine 20 (CCL20), CD147, urokinase plasminogen activator surface receptor (uPAR), pro-epidermal growth factor (EGF), trefoil factor 3 (TFF3), and macrophage migration inhibitory factor (MIF) were significantly lower (p<0.008), whereas levels of retinol-binding protein 4 (RBP4), C-X-C motif chemokine 5 (CXCL5), interleukin-8 (IL-8), complement factor D (CFD), adiponectin, and chitinase-3-like 1 (CHI3L1) were significantly higher (p<0.008) in NPA samples of hospitalized than non-hospitalized patients. While changes in CD14, LCN2, CCL20, uPAR, EGF, MIF, CXCL5, IL-8, adiponectin and CHI3L1 levels have already been correlated with severity of IAV infection in mice and humans, our study is the first to describe association of CD147, RBP4, TFF3, and CFD with hospitalization of IAV-infected patients. Thus, we identified local innate immune profiles, which were associated with the clinical severity of influenza infections.
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PMID:Protein profiling of nasopharyngeal aspirates of hospitalized and outpatients revealed cytokines associated with severe influenza A(H1N1)pdm09 virus infections: A pilot study. 2744 5