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

We studied damage and repair of lung connective tissue in rats exposed to toxic amounts of oxygen by measuring lung content of collagen and elastin and the number of collagen fragments in lung lavage fluid after exposure to 98% O2 for 60 h. Lung collagen was decreased 17%, and collagen fragments in lavage fluid were increased 4- to 5-fold in O2-exposed rats compared with those in control rats. No biochemical evidence of elastin degradation was found. Mild emphysematous changes and a leftward shift of fluid-filled, pressure-volume curves were induced within 2 wk after recovery from exposure to O2. Administration of the lathyrogen beta-aminopropionitrile worsened the emphysematous lesion produced by hyperoxia, suggesting that replacement of connective tissue during repair limits the extent of emphysema. We conclude that lung collagen is degraded and an emphysematous lesion is produced by relatively short exposure to toxic amounts of oxygen.
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PMID:Damage and repair of lung connective tissue in rats exposed to toxic levels of oxygen. 381 7

Emphysema is produced by severe food restriction in rats and is postulated to result from depletion of lung connective tissue. We studied (1) whether total dietary protein depletion worsens nutritional emphysema, and (2) whether the reduced content of lung connective tissue in nutritional emphysema results from lack of accumulation caused by impaired lung growth or by a net loss from the lung. Lewis rats weighing 200 g were restricted to one third food intake with or without protein for 6 wk. Lungs were assessed by morphometry, pressure-volume (P-V) measurements, and content of collagen and elastin. Emphysema was found by morphometry (but not by P-V measurements) in food-restricted rats, and contrary to expectation, emphysema was less severe in those depleted of protein. Collagen and elastin content were reduced in emphysematous lungs; however, the levels were not below those found prior to nutritional intervention, suggesting that lack of growth, not depletion, accounts for the reduced content.
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PMID:Nutritional emphysema in the rat. Influence of protein depletion and impaired lung growth. 387 94

Serum enzyme activity in 81 patients with various medical and dermatologic problems was determined with succinyl-(L-alanyl)3-p-nitroanilide as substrate. Values exceeding the limit of mean +/- 3 SD in healthy controls were detected in 16 patients. The highest activity, greater than 80 times the mean in the controls, was found in a 20-year-old patient with severe pulmonary emphysema and cutis laxa. The enzyme activity in the patient's serum was enhanced by Ca2+ and was inhibited by metal chelators but not by serine protease inhibitors. The pH optimum of the enzyme was 7.6. The enzyme was partially purified by gel filtration chromatography. Enzyme activity eluted in two major peaks with apparent molecular weights of greater than 10(7) daltons (peak I) and approximately 2.5 X 10(5) daltons (peak II). When compared with the elution patterns in the patient's mother and a healthy control, the elevated enzyme activity in the patient's serum was associated with peak I. The partially purified enzyme in peak I was not complexed with alpha 2-macroglobulin. The peak I enzyme was capable of degrading tropoelastin and a synthetic dinitrophenyl peptide at a glycyl-isoleucyl sequence, but not native or denatured collagen.
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PMID:Characterization and partial purification of a neutral protease from the serum of a patient with autosomal recessive pulmonary emphysema and cutis laxa. 388 13

Six cases of recurrent pneumothorax requiring surgical intervention in the dog were reviewed. Radiography was not useful in identifying the source of air leakage. A median sternotomy approach was useful for identifying and removing involved lung tissue. All 6 dogs had microscopic evidence of bullous emphysema. Bronchiolitis, thickened pleura, and bronchiolar smooth muscle hypertrophy also were noticed. Underlying mild obstructive lung disease alone or in combination with a defect in pulmonary collagen probably predisposed these dogs to bullous emphysema and recurrent pneumothorax. Of the 6 dogs, 3 survived for at least 2 years after surgery.
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PMID:Bullous emphysema and recurrent pneumothorax in the dog. 399 51

Four families of macromolecules make up the pulmonary fibrous connective tissue which one finds in all connective tissue: collagen elastin, the proteoglycans and the structural glycoproteins. The regulation of the synthesis of these macromolecules and their arrangement and interaction within the intracellular space are conditions necessary for the development and maintenance of a normal pulmonary fibrous connective tissue. The quantitative relationship of these macromolecules changes with age; it is also profoundly modified in chronic obstructive lung disease. An understanding of the pathogenesis of the modifications, requires the study of the regulatory mechanisms involved in the synthesis and degradation of the macromolecules of the pulmonary connective tissue. In recent years we have made some progress in the domain of the regulation of the synthesis and degradation of collagen, but we still know very little about elastin. Over the past few years our laboratory has isolated several cellular elastases which probably intervene in these processes. Elastoplastic proteases have been isolated from platelets, leucocytes, macrophages, fibroblasts and smooth muscle cells. Human serum and purified lipoproteins also possess an elastolytic activity which is easily measured in clinic. Which of these enzymes is responsible for the lysis of the elastic laminae seen in emphysema has not yet been established. It seems possible that one important factors in certain pathological states is the faulty protection given by modified serum inhibitors. Our recent studies with Mrs Ch. LAMFUMA and Mrs MOCZAR suggest an important role for the structural glycoproteins in the pulmonary connective tissue. It is possible that qualitative an or quantitative modifications in these glycoproteins could also play an important role in pathology.
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PMID:[Pulmonary fibrous ground substance. Macromolecules of the intercellular matrix]. 611 Dec 65

A mild form of emphysema was produced in pigs raised on a copper-deficient, zinc-supplemented diet. The copper-requiring enzyme, lysyl oxidase, catalyzes the cross-linking of tropoelastin into mature elastin. Zinc further inhibits the activity of lysyl oxidase. Lungs from animals raised on copper-deficient, zinc-supplemented diets of demonstrate perforations in alveolar walls and diminished amounts of elastin bronchi and pulmonary arteries. Mean linear intercepts are greater and alveolar internal surface areas are less than those in control animals, fulfilling the generally accepted definition of emphysema. Physiologic confirmation is provided by a leftward shift of the saline volume-pressure curves when compared with those in control animals. Ultrastructurally, the alveolar walls are effaced and pores of Kohn are enlarged. There are areas in which elastin is absent leaving remnant microfibrils, and there are other changes consistent with active elastin synthesis. Biochemical data demonstrate no difference in elastin content as micrograms/ml of fat-free dry weight but do demonstrate increased collagen content in experimental animal lungs compared with that in control lungs. Ultrastructural similarities to enzyme-induced models of emphysema suggest the presence of elastin degradation in our model. We speculate that although the copper-deficient, zinc-supplemented state may stimulate protein synthesis in general, elastin is being degraded by endogenous means, but collagen is not.
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PMID:A copper-deficient, zinc-supplemented diet produces emphysema in pigs. 612 18

The effectiveness of a genetically engineered mutant of human alpha 1-antitrypsin (358 Met----Val) as an inhibitor of connective tissue breakdown was tested in a model of inflammation. The degradation of basement membrane collagen by stimulated neutrophils was efficiently inhibited by a tenfold lower concentration (0.2 mg/ml) of the mutant inhibitor than of the normal alpha 1-antitrypsin (2.4 mg/ml). Effective inhibition by normal alpha 1-antitrypsin occurred at much lower concentrations when azide or catalase was added, or when normal neutrophils were replaced by those from a donor with chronic granulomatous disease. These results confirm that neutrophils augment tissue proteolysis by the oxidative inactivation of the methionine at the reactive centre of alpha 1-antitrypsin. The replacement of this methionine by valine gives an effective inhibitor that is not inactivated by neutrophil oxidants. The availability of this genetically engineered mutant suggests the possibility of prophylaxis of lung dysplasias, notably emphysema, and of the shock syndromes associated with massive neutrophil activation.
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PMID:A genetically engineered mutant of alpha 1-antitrypsin protects connective tissue from neutrophil damage and may be useful in lung disease. 615 Oct 45

Mineral particles are customarily inhaled as mixtures, though one component may predominate and determine the response. Although the lesions often possess a characteristic structure, according to the main type of particle deposited, morphology affords little indication of pathogenesis. Being a major element in the evolution of dust lesions, macrophage behavior has been examined extensively in vitro after treatment with mineral particles, attention being directed to membrane and biochemical changes; however, no clear lead to the origin of the lesions has emerged. Pulmonary fibrosis, as one of the ultimate consequences of dust accumulation, required a direct in vitro approach in which the products of the macrophage-particle interaction were utilized to provoke collagen formation by fibroblasts in a two-phase system. By this means, silica and asbestos stimulated connective tissue formation and application of the technique to coal dusts appears promising. Coal workers may develop a peculiar type of emphysema in relation to lesions whose fibrous content is comparatively small. Type II alveolar epithelium is also stimulated by inhaled particles and lipid accumulation follows. Alveolar lipidosis interferes with the fibrotic response by preventing contact between macrophage and particles. This phenomenon may account in part for anomalies, apparent in coal workers, between epidemiological findings and dust composition. Carcinogenesis is a well-recognized feature of asbestos exposure, but, as with fibrosis, risk prediction on the basis of in vitro tests of cytotoxicity is premature and may not be valid.
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PMID:Pulmonary toxicology of silica, coal and asbestos. 632 72

Collagen is the major structural protein of the lung. At least five genetically distinct collagen types have been identified in lung tissue. However, the precise role of collagen in nonrespiratory lung function is not well understood, in part because of the difficulties inherent in studying lung collagen, regardless of the type of assay used. A major problem is the insolubility of lung collagen; generally less than 20% of total lung collagen can be solubilized as intact chains, even with harsh extraction procedures. Since such collagen may not be representative of total lung collagen, errors in quantitating collagen types, for example, may arise from using such material. Measurement of total lung collagen content may also pose problems, unless appropriate parameters of normalization are chosen. Biopsy dry weight, protein content, and DNA content, for example, may all change in certain disease states. Despite these difficulties, a number of changes in lung collagen have been documented in experimental pulmonary fibrosis, including increased collagen content, increased collagen synthesis rates, and changes in collagen type ratios. Many questions remain. For example, why do diverse toxic substances appear to cause essentially the same fibrotic response, even though initial sites of damage may vary? Conversely, why do similar toxic substances, such as ozone and NO2, cause diverse responses (fibrosis and emphysema, respectively)? Much work remains to be done to elucidate the mechanisms underlying the lung's choice of response.
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PMID:Collagen biosynthesis. 642 77

Thioglycollate-elicited mouse peritoneal macrophages were cultured in contact with the mixture of extracellular matrix proteins produced by rat smooth muscle cells in culture. Both live macrophages and their conditioned media hydrolyzed glycoproteins, elastin, and collagen. Live macrophages also degraded extracellular connective tissue proteins secreted by endothelial cells and fibroblasts. The glycoproteins in the matrix markedly inhibited the rate of digestion of the other macromolecules, particularly elastin. When plasminogen was added to the matrix, activation of plasminogen to plasmin resulted in the hydrolysis of the glycoprotein components, which then allowed the macrophage elastase easier access to its substrate, elastin. Thus, although plasmin has no direct elastinolytic activity, its presence accelerated the rate of hydrolysis of elastin and therefore the rate of matrix degradation. These findings may be important in an understanding of disease states, such as emphysema and atherosclerosis, that are characterized by the destruction of connective tissue.
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PMID:Degradation of connective tissue matrices by macrophages. II. Influence of matrix composition on proteolysis of glycoproteins, elastin, and collagen by macrophages in culture. 645 Feb 58


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