Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344329 (collapse)
 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 23-year-old male with complete collapse of the right lung due to spontaneous pneumothorax was admitted 11 days after its onset. Paying close attention to the re-expansion pulmonary edema (REPE), water seal drainage was performed. Following couple episodes of persistent severe cough, four hours later, he developed dyspnea and began to expectorate frothy massive sputum. Chest X-ray revealed pulmonary edema of the entire right lung field. Measurement of total proteins and neutrophil elastase in airway exudates showed 5.5 g/dl (ratio to plasma, 0.89) and 7000 micrograms/l, respectively. Because of marked difference of compliance between bilateral lungs, management with right and left-separated mechanical ventilation and PEEP applied only to the right lung was performed. Although transient mediastinal deviation to the left was observed, successful management was achieved by the maneuver. High concentrations of total proteins and neutrophil elastase in edema fluid suggest that increased vascular permeability due to endothelial cell injury via activated neutrophils is mainly responsible for REPE. In the present case, rapid expansion of the collapsed lung accelerated by severe cough seems to be a predisposing factor of REPE. In patient with prolonged pneumothorax, suppression of cough is thought to be important for the prevention of REPE even with water seal drainage.
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PMID:[A case of re-expansion pulmonary edema following water seal drainage for spontaneous pneumothorax--management with right and left-separated mechanical ventilation]. 163 63

Airflow limitation in COPD is a result partially of bronchospasm, but it is also caused by a reduction in airway caliber, the number of small airways, airway collapse because of loss of connective tissue support, excess mucus in the airways, and edema of the airway wall. Structural changes also occur because of long-term destruction of interstitial connective tissue, including elastin. Therefore, in addition to the traditional aim of reversing bronchospasm with bronchodilators, disease-modifying approaches are being investigated. The enzyme neutrophil elastase is implicated in the induction of bronchial disease causing structural changes in lungs, impairment of mucociliary clearance, and impairment of host defenses. The precise mechanism pathway of neutrophil elastase is uncertain, but the effects of influencing the pathway in order to slow disease progression are being investigated. Oxidants may also have a role in the development of COPD, with increased levels activating airway cells and cytokine production.
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PMID:New approaches to the management of COPD. 1067 77

We describe herein the design and in vitro biochemical evaluation of a novel class of mechanism-based inhibitors of human leukocyte elastase (HLE) that inactivate the enzyme via an unprecedented enzyme-induced sulfonamide fragmentation cascade. The inhibitors incorporate in their structure an appropriately functionalized saccharin scaffold. Furthermore, the inactivation of the enzyme by these inhibitors was found to be time-dependent and to involve the active site. Biochemical, HPLC, and mass spectrometric studies show that the interaction of these inhibitors with HLE results in the formation of a stable acyl complex and is accompanied by the release of (L) phenylalanine methyl ester. The data are consistent with initial formation of a Michaelis-Menten complex and subsequent formation of a tetrahedral intermediate with the active site serine (Ser(195)). Collapse of the tetrahedral intermediate with tandem fragmentation results in the formation of a highly reactive conjugated sulfonyl imine which can either react with water to form a stable acyl enzyme and/or undergo a Michael addition reaction with an active site nucleophilic residue (His(57)). It is also demonstrated herein that this class of compounds can be used in the design of inhibitors of serine proteases having either a neutral or basic primary substrate specificity. Thus, the results suggest that these inhibitors constitute a potential general class of mechanism-based inhibitors of (chymo)trypsin-like serine proteases.
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PMID:Mechanism-based inactivation of human leukocyte elastase via an enzyme-induced sulfonamide fragmentation process. 1528 10

Previous work has shown that endothelial cell (EC)-derived matrix metalloproteinases (MMPs) regulate regression of capillary tubes in vitro in a plasmin- and MMP-1 dependent manner. Here we report that a number of serine proteases can activate MMP-1 and cause capillary tube regression; namely plasma kallikrein, trypsin, neutrophil elastase, cathepsin G, tryptase and chymase. Plasma prekallikrein failed to induce regression without coactivators such as high molecular weight kininogen (HMWK) or coagulation Factor XII. The addition of trypsin, the neutrophil serine proteases (neutrophil elastase and cathepsin G) and the mast cell serine proteases (tryptase and chymase) each caused MMP-1 activation and collagen type I proteolysis, capillary tubular network collapse, regression and EC apoptosis. Capillary tube collapse is accompanied by collagen gel contraction, which is strongly related to the wound contraction that occurs during regression of granulation tissue in vivo. We also report that proMMP-10 protein expression is markedly induced in ECs undergoing capillary tube morphogenesis. Addition of each of the serine proteases described above led to activation of proMMP-10, which also correlated with MMP-1 activation and capillary tube regression. Treatment of ECs with MMP-1 or MMP-10 siRNA markedly delayed capillary tube regression, whereas gelatinase A (MMP-2), gelatinase B (MMP-9) and stromelysin-1 (MMP-3) siRNA-treated cells behaved in a similar manner to controls and regressed normally. Increased expression of MMP-1 or MMP-10 in ECs using recombinant adenoviral delivery markedly accelerated serine protease-induced capillary tube regression. ECs expressing increased levels of MMP-10 activated MMP-1 to a greater degree than control ECs. Thus, MMP-10-induced activation of MMP-1 correlated with tube regression and gel contraction. In summary, our work demonstrates that MMP-1 zymogen activation is mediated by multiple serine proteases and MMP-10, and that these events are central to EC-mediated collagen degradation and capillary tube regression in 3D collagen matrices.
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PMID:MMP-1 activation by serine proteases and MMP-10 induces human capillary tubular network collapse and regression in 3D collagen matrices. 1587 Jan 7

Eppin has two potential protease inhibitory domains: a whey acid protein or four disulfide core domain and a Kunitz domain. The protein is also reported to have antibacterial activity against Gram-negative bacteria. Eppin and its whey acid protein and Kunitz domains were expressed in Escherichia coli and their ability to inhibit proteases and kill bacteria compared. The Kunitz domain inhibits elastase (EC 3.4.21.37) to a similar extent as intact eppin, whereas the whey acid protein domain has no such activity. None of these fragments inhibits trypsin (EC 3.4.21.4) or chymotrypsin (EC 3.4.21.1) at the concentrations tested. In a colony forming unit assay, both domains have some antibacterial activity against E. coli, but this was not to the same degree as intact eppin or the two domains together. When bacterial respiratory electron transport was measured using a 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay, eppin and its domains caused an increase in the rate of respiration. This suggests that the mechanism of cell killing may be partly through the permeablization of the bacterial inner membrane, resulting in uncoupling of respiratory electron transport and consequent collapse of the proton motive force. Thus, we conclude that although both of eppin's domains are involved in the protein's antibacterial activity, only the Kunitz domain is required for selective protease inhibition.
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PMID:Functional domains of the human epididymal protease inhibitor, eppin. 1833 57