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Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Elastase-induced emphysema is associated with changes in all components of connective tissue, including elastin. The abnormal restructuring of lung parenchyma that occurs after elastase administration in hamsters might reflect an abnormal balance of elastin, collagen, and glycosaminoglycan in lung parenchyma. To test this hypothesis, we measured total amounts and levels of accumulation over 24 hr of connective tissue elements in lung explants at several points over a 1-year period after a single elastase treatment in hamsters. We found acute, early changes in the metabolism of elastin, collagen, and glycosaminoglycan consistent with degradation of elastin and increased turnover of collagen and glycosaminoglycan. By day 21 after elastase treatment, lung elastin had returned to control values, then rose and stayed elevated throughout the remainder of the study period. Total collagen levels rose in both control and elastase-treated lungs by the same amount over the year period. However, incorporation of 14C-proline into collagen hydroxyproline was elevated only in elastase-treated lungs over the period of 21 to 360 days. Incorporation of 14C-glucosamine into glycosaminoglycan was greatest over the period of 1 to 5 days after treatment and total levels also peaked at this time. By day 21 both incorporation of glucosamine and total levels of glycosaminoglycan had returned to normal, where they remained. The ratios of glycosaminoglycan to elastin and glycosaminoglycan to collagen were calculated over the period of 21 to 360 days to determine whether the long-term relative balance of these components had changed in elastase-treated lungs. We found that a steady-state imbalance existed between heparan sulfate and collagen and heparan sulfate and elastin, suggesting that an inappropriate amount of heparan sulfate was present relative to the amounts of collagen and elastin. We conclude that administration of elastase results in changes in the long-term balance of lung connective tissue components.
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PMID:The balance of lung connective tissue elements in elastase-induced emphysema. 655 73

Starvation and elastase-induced changes in rat lung structure, biochemistry, and function were compared as models of human pulmonary emphysema. Ten-week-old male rats were instilled intratracheally with either porcine pancreatic elastase in saline (E) or with saline alone. A group of the saline-instilled rats were fed one third of their normal food intake until a 45% loss of body weight occurred (S). The remaining saline-instilled rats served as control animals (C). Post-treatment evaluations included in vivo respiratory function, lung histopathologic and morphometric analyses, lung tissue proteinolytic activity, and lung collagen. The E rats had in vivo respiratory function changes more similar to human emphysema than those of S rats. All lung volume subdivisions were decreased in S rats and increased in E rats. The volume-pressure curve of S rats was shifted to the right of the C curve, whereas that of E rats was shifted to the left. Forced expiratory flow rates of E rats were decreased at all lung volumes, but those of S rats were not. Both E and S rats had larger terminal air spaces and less alveolar surface area than did C rats. The S rats had more collagen per gram lung and higher proteinolytic activity than did C or E rats. These results show that, although starvation induces some changes characteristic of human emphysema, elastase-treatment provides a model more similar to the human disease.
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PMID:A comparison of starvation and elastase models of emphysema in the rat. 656 48

Rats and guinea pigs, pretreated with intratracheally administered elastase or saline, were exposed to 1.03 mg/m3 (NH4)2SO4; MMAD, 0.42 micron. Identically treated controls were sham exposed. Measurements and evaluation of structural changes were conducted using morphometric techniques on SEM photographs and by applying subjective ratings. Pathology studies were conducted by light and electron microscopy. All examination methods confirmed elastase-induced emphysema, which was aggravated by (NH4)2SO4 exposure in the rat. Ammonium sulfate exposure of saline-treated animals produced measurable degrees of enlargement of alveoli, and alveolar ducts and sacs. Electron microscopy revealed increased interstitial collagen in affected lung areas of elastase-treated, (NH4)2SO4-exposed animals. Alveolar-pore size was significantly increased in elastase-treated animals (control and exposed) but not in saline-treated, exposed animals. The data suggest a possible difference between elastase and (NH4)2SO4 in the mechanisms responsible for the increased diameter of alveolar structures. Hypertrophy and hyperplasia of nonciliated epithelial cells of the small airways and of the Type II alveolar cells were observed in otherwise untreated guinea pigs exposed to (NH4)2SO4 but not in elastase-treated guinea pigs, nor in any of the rats.
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PMID:Effects of ammonium sulfate aerosol exposure on lung structure of normal and elastase-impaired rats and guinea pigs. 656 15

An extracellular connective tissue matrix, made up of components found in the pulmonary alveolar interstitium, was generated in vitro and used as a culture surface and substrate for proteolysis by human alveolar macrophages (AM) and neutrophil elastase (NE). The ability of human AM to modulate NE-mediated degradation of elastin and collagen in the surrounding matrix was studied to gain insights into the inflammatory process that accompanies the pathogenesis of emphysema in humans. Neutrophil elastase that had been internalized by AM showed a diminished but more prolonged time course of matrix proteolysis than did a similar amount of NE added to the matrix in the absence of AM. Collagen and elastin degradation were quantitated by release of hydroxylysine and desmosine, respectively, into the culture medium. Significantly more hydroxylysine and desmosine were released by AM that had internalized NE than by AM or by culture medium alone. When 14 X 10(6) AM were added to the extracellular matrix, followed 2 h later by addition of 2 micrograms of NE, collagen and elastin degradation measured at 24 h were not significantly different from that which occurred when matrix was incubated with NE in the absence of AM. Collagen degradation, determined in the same cultures during the period from 24 to 96 h, was significantly greater when matrix was incubated with both AM and NE. These findings suggest that AM can release previously internalized NE in an enzymatically active form and that AM may enhance collagen degradation in matrix that was also exposed to NE.
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PMID:Alveolar macrophage modulation of proteolysis by neutrophil elastase in extracellular matrix. 656 97

This presentation reports on newer animal models and techniques that we and others have developed. These models attempt to predict in a reasonable experimental time frame the occurrence of structural changes in the lungs that are the basis of various chronic diseases. Since the major chronic diseases of the lung parenchyma involving what we think of as well-understood structural changes are pulmonary fibrosis and emphysema, I will discuss in detail ways of looking at effects of air pollutants on lung collagen and lung elastin metabolism.
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PMID:Biochemical alterations of lung structure as predictors of chronic lung disease. 665 17

The effect of age on the induction of emphysema in hamsters was investigated by administering porcine pancreatic elastase endotracheally to old (18 months of age) and young (4 months of age) hamsters; age-matched untreated animals served as controls. Lung volumes, quasi-static deflation volume pressure relations, and mean linear intercept, an index of alveolar size, were measured. Elastase-treated young hamsters demonstrated an increased volume of air in the lungs at a transpulmonary pressure of 25 cm H2O and an increased mean linear intercept. The lungs of old elastase-treated animals showed less pronounced changes than those of young hamsters in lung volume at transpulmonary pressure of 25 cm H2O and in mean linear intercept. Untreated old hamsters had a larger lung volume at a transpulmonary pressure of 25 cm H2O and an 85% increase in total lung collagen. Age-related alterations in connective tissues may account for the increased resistance of old lungs to injury by pancreatic elastase.
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PMID:Response of the aging hamster lung to elastase injury. 691 19

Hydroxyproline transfer to an incubation medium was studied in ten emphysematous, nine relapsing pneumothorax, and eight control samples surgically removed from 2 females and 25 males, ranging in age from 17 to 69 years. Total hydroxyproline in the lung pieces, expressed as a fraction of DNA, was not modified. A large increase of dialyzable and nondialyzable hydroxyproline fraction was observed in the incubation medium of biopsies from emphysema dn pneumothorax groups. Although the pneumothorax group had average values between controls and emphysema, some pneumothorax patients exhibited very high content of soluble hydroxyproline, suggesting a common pattern between some relapsing pneumothorax and emphysema. These findings could not be due to extracellular degradation during the processing of the samples since the results were not affected by the presence of protease inhibitors. These observations suggest that individuals with emphysema and pneumothrax have abnormalities in lung collagen structure and/or biosynthesis resulting in increased degradation of this macromolecule.
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PMID:Increased content of neutrosoluble collagen and dialyzable hydroxyproline in panacinar emphysema and spontaneous pneumothorax. 710 63

A 30 year old woman with marked joint hypermobility had severe, progressive lung disease, seizures, aneurysms of the sinuses of Valsalva and myocardial infarction documented during life. She died of intractable ventricular fibrillation, and postmortem examination showed myocardial injury in the distribution of the left coronary artery but no occlusive coronary artery disease. Severe panacinar emphysema was found in the lungs. Cerebral heterotopias with peculiar vascularization were present and were a likely cause of the seizure disorder. Electron microscopy showed dermal collagen fibrils to be heterogeneous in size, reduced in number, and irregular and frayed in appearance. This patient had a form of the Ehlers-Danlos syndrome, different from the 10 distinct variants described thus far, associated with lethal internal manifestations.
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PMID:Ehlers-Danlos syndrome with abnormal collagen fibrils, sinus of Valsalva aneurysms, myocardial infarction, panacinar emphysema and cerebral heterotopias. 731 50

In collagen content of four emphysematous lungs as defined by radiological, physiological and anatomical tests were studied. They were compared to three control lungs and five lungs removed from patients with relapsing pneumothorax (PNO). Morphologically, emphysematous lungs were characterized by patchy disorganization of collagen fibers, involving microfibrillar areas or elastoid laminae. Elastic fibers were at times found in plugs. Such abnormalities were also present, but less frequently in the PNO group. Biochemically, emphysematous lungs showed an increase of soluble proteins removed by CaCl2 extraction, which were associated with a decrease in insoluble proteins in extracted by TCA. Total hydroxyproline, expressed as a fraction of deoxyribonucleic acid (DNA) content, was not modified, but an increase of dialyzable and undialyzable fraction was observed in MEM medium. The PNO group showed the same modifications in terms of mean values, but individual results were more scattered. Results of in vitro 14C-proline incorporation did not show any modification of collagen biosynthesis, except in 2 emphysematous lungs. The results indicate that the PNO group is nearer to the emphysematous group than the controls. This suggests that patients with relapsing PNO may develop emphysema but it has to be further substantiated. The results here presented indicate that soluble hydroxyproline is an index either of abnormal synthesis or of excessive collagenolysis.
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PMID:Biochemical and anatomical study of collagen and associated macromolecules in pulmonary panacinar emphysema and spontaneous pneumothorax. 738 18

The pattern of change in arterial oxyhemoglobin saturation (SpO2) measured by pulse oximetry (PO) during exercise, including daily activities, was studied in 23 patients with interstitial lung disease (ILD), 19 of whom had idiopathic pulmonary fibrosis, 3 collagen vascular disease, and 1 BOOP. Hypoxemia, as detected by PO appeared without dyspnea at the beginning of exertion or at a mild workload. Exercise usually induced significant changes in the same fashion first in heart rate, then in SpO2, and then in dyspnea, but stair climbing had a different pattern. Workload at the lactate threshold (LT) and symptom-limited maximal exercise (SL) in a bicyclergometer incremental exercise test correlated well with distance walked in a 10-minute walking test (10-eMD) (p < 0.01). Similarly, the degree in desaturation in each exercise test was closely correlated (p < 0.01). Exertional hypoxemia was more prominent in patients with ILD than in those with chronic pulmonary emphysema. Nevertheless, dyspne changed less per change in SpO2 in ILD patients. We conclude that prolonged monitoring of SpO2 by PO will disclose the presence of exertional desaturation in ILD patients.
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PMID:[Exertional hypoxemia evaluated by pulse oximetry in patients with interstitial lung diseases]. 760 20


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