Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several laboratories, including our own have reported the synthesis and activity of certain low relative molecular mass inhibitors of mammalian serine proteases, especially human leukocyte elastase (HLE, EC 3.4.21.37), an enzyme whose degradative activity on lung elastin has been implicated as a major causative factor in the induction of pulmonary emphysema, and which is present in the azurophil granules of human polymorphonuclear leukocytes (PMN). Normally, these granules fuse with phagosomes containing engulfed foreign material (such as bacteria), and HLE, in combination with other lysosomal enzymes, catabolizes the particles. Under certain pathological conditions, however, PMN become attached to host protein (elastin fibres, basement membrane, connective tissue, immune complexes), and in response to this adherence, the granules may fuse with the PMN outer membrane and release their contents, including HLE, directly onto the tissue. Besides emphysema, HLE may also contribute to the pathogenesis of disease states such as adult respiratory distress syndrome, and its potential involvement in rheumatoid arthritis makes HLE inhibitors of considerable interest. It is known that cephalosporin antibiotics (for example, cephalothin (compound I, Table 2)) are acylating inhibitors of bacterial serine proteases which help synthesize the cell wall by performing a transpeptidation reaction on a peptidyl substrate bearing a D-Ala-D-Ala terminus. We now report that neutral cephalosporins (that is, compounds not bearing a free carboxyl at position C-4) can be modified to become potent time-dependent inhibitors of HLE.
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PMID:Cephalosporin antibiotics can be modified to inhibit human leukocyte elastase. 363 99

Chronic obstructive pulmonary disease (COPD), characterized by intermittent exacerbations and clinical subphenotypes like emphysema and chronic bronchitis, poses a significant risk of lung cancer (LC) development. Metabolomic studies of COPD are scarce, and those of LC patients with COPD subphenotypes have not been investigated. To study metabolite profile alteration in LC patients with different COPD subphenotypes, lung paracancer tissue from 10 LC (CON) patients, 10 LC patients with emphysema (E), and 9 LC patients with chronic bronchitis (CB) were analyzed using gas chromatography-mass spectrometry. Multivariate analysis indicated a distinct separation between LC patients with COPD subphenotypes and LC patients. Overall, 60, 55, 33 and 63 differential metabolites (DM) were identified in comparisons between CB vs CON, E vs CON, CB vs E, and CB + E vs CON, respectively, and of these, 8 DM were shared in all comparisons. Among the high altered metabolites, E samples showed higher 'acetol' than CON samples, and lower 'azelaic acid', '3-methylglutaric acid' and 'allose'. CB samples showed higher 'turanose' and 'o-phosphoserine' and lower 'anandamide' than CON and E samples. In CB and E samples, 'galactonic acid', '2-mercaptoethanesulfonic acid', 'D-alanyl-D-alanine' '3-methylglutaric acid', 'glycine', 'L-4-Hydroxyphenylglycine' and 'O-phosphonothreonine' had common alteration trends compared with those of CON samples. 'Glycine', 'L-4-Hydroxyphenylglycine' and 'O-phosphonothreonine' were significantly enriched in glycine, serine and threonine metabolism pathways. The total differential metabolites detected were remarkably altered in pyrimidine, beta-alanine and purine metabolism. Our study provided altered DM patterns of lung paracancer tissue, the key metabolites and their enriched metabolic pathways in LC patients with different COPD subphenotypes.
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PMID:Metabolomic analysis of lung cancer patients with chronic obstructive pulmonary disease using gas chromatography-mass spectrometry. 3279 77