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)

Treatment of hamster lungs with porcine pancreatic elastase (PPE) causes emphysema and a decrease in lung elastin content, which returns to control level by Day 30. To explore the mechanism of alveolar wall remodeling after elastolytic injury, we examined the expression of elastin and alpha1(I) collagen mRNAs by in situ hybridization at 1, 2, 3, 5, 7, and 30 d after intratracheal PPE. The lungs of control animals displayed weak signals for elastin and alpha1(I) collagen mRNA in pleura, large arteries, veins, and airways. There was little or no signal in respiratory air space walls. Increased expression of elastin and alpha1(I) collagen mRNA began by Day 1 after PPE and reached an asymptote by Day 3 that was maintained by elastin until Day 7; expression of alpha1(I) collagen mRNA waned earlier. Elastin and, to a lesser extent, alpha1(I) collagen mRNA were heavily expressed in pleura, blood vessels, and airways. Analysis of serial sections showed elastin message was minimal in the walls of respiratory air spaces and when present, at 3, 5, and 7 d, was primarily found at the free margins of alveolar septa. Collagen message was very sparse in respiratory air space walls. By 30 d, elastin mRNA expression was reduced but still above control levels and emphysema was widespread and severe. Rank score of elastin mRNA expression in individual subpleural air spaces showed a positive correlation with air space size. In conclusion, most expression of elastin and alpha1(I) collagen mRNA occurs in the pleura, airway, and vascular walls. In respiratory air space walls, expression of elastin mRNAs occurs in damaged tissue at free septal margins.
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PMID:Remodeling of alveolar walls after elastase treatment of hamsters. Results of elastin and collagen mRNA in situ hybridization. 970 Jan 35

Diffusely emphysematous lungs are not always effectively contracted by laser therapy; however, which type of diffuse emphysema that responds to laser therapy remains unclear. We macroscopically and histopathologically examined human lung tissue, which was resected from patients with carcinoma, after irradiation with an Nd:YAG laser. Forty-six lung lobes were irradiated with a non-contact mode Nd:YAG laser at a power setting 15 watts. Macroscopically, twenty samples of normal lungs revealed moderate contraction, fourteen samples of predominantly centrilobular diffuse emphysema showed significant contraction, and eight samples of predominantly panlobular diffuse emphysema with a slight elastic network showed slight contraction. Histopathologically, the normal lungs showed amorphous change of the collagen and severely contracted elastic fibers (amorphous degeneration) at the pleura and some parenchymal coagulation; the predominantly centrilobular diffuse emphysema showed contraction of elastic fibers and collagen (coagulative degeneration) in the pleura and adequate contraction of the elastic fibers in the parenchyma and the predominantly panlobular diffuse emphysema showed only slight coagulation of the visceral pleura and very little coagulation of the parenchyma. On ex-vivo lung, panlobular emphysema was inadequately contracted by laser therapy, due to elastic recoil. Centrilobular emphysema responded to laser treatment, due to the severe contraction of the elastic fibers.
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PMID:Which type of diffuse emphysema is adequately contracted by the Nd:YAG laser. An ex-vivo experiment. 975 Apr 38

Chronic inhalation of coal dust can cause several lung disorders, including simple coal workers pneumoconiosis (CWP), progressive massive fibrosis (PMF), chronic bronchitis, lung function loss, and emphysema. This review focuses on the cellular actions and interactions of key inflammatory cells and target cells in coal dust toxicity and related lung disorders, i.e. macrophages and neutrophils, epithelial cells, and fibroblasts. Factors released from or affecting these cells are outlined in separate sections, i.e. (1) reactive oxygen species (ROS) and related antioxidant protection mechanisms, and (2) cytokines, growth factors and related proteins. Furthermore, (3) components of the extracellular matrix (ECM), including the modifying role of ROS, cytokines, proteases and antiproteases are discussed in relation to tissue damage and remodelling in the respiratory tract. It is recognised that inhaled coal dust particles are important non-cellular and cellular sources of ROS in the lung, and may be significantly involved in the damage of lung target cells as well as important macromolecules including alpha-1-antitrypsin and DNA. In vitro and in vivo studies with coal dusts showed the up-regulation of important leukocyte recruiting factors, e.g. Leukotriene-B4 (LTB4), Platelet Derived Growth Factor (PDGF), Monocyte Chemotactic Protein-1 (MCP-1), and Tumor Necrosis Factor-alpha (TNF alpha), as well as the neutrophil adhesion factor Intercellular Adhesion Molecule-1 (ICAM-1). Coal dust particles are also known to stimulate the (macrophage) production of various factors with potential capacity to modulate lung cells and/or extracellular matrix, including O2-., H2O2, and NO, fibroblast chemoattractants (e.g. Transforming Growth Factor-beta (TGF beta), PDGF, and fibronectin) and a number of factors that have been shown to stimulate and/or inhibit fibroblast growth or collagen production such as (TNF alpha, TGF beta, PDGF, Insulin Like Growth Factor, and Prostaglandin-E2). Further studies are needed to clarify the in vivo kinetics and relative impact of these factors.
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PMID:Mechanisms and mediators in coal dust induced toxicity: a review. 1002 91

To characterize the changes in the extracellular matrix in smoking-related pulmonary emphysema, we undertook immunohistochemical studies in lung tissues from controls (n = 7), from patients with mild (n = 11) and severe (n = 8) emphysema, and from patients with lung fibrosis (n = 6). We studied collagens, laminin, fibronectin, proteoglycans (PGs), and beta1-integrins. The majority of the patients with severe emphysema showed diminished staining for the interstitial PGs, decorin and biglycan, in the peribronchiolar area, compared with patients in the control and fibrosis groups. Only a minority of patients with mild emphysema showed this diminished staining. In contrast, decorin and biglycan were well preserved in the perivascular area of all of the specimens from the emphysema group. Heparan sulfate PG staining was diminished in the respiratory airspace walls of patients with emphysema and fibrosis. Staining for Types I, III, and IV collagen, as well as for laminin, fibronectin, and the integrins, showed no differences between the four groups. The specific loss of interstitial PGs may be crucial for elastic recoil loss and subsequent bronchiolar obstruction, as seen in patients with smoking-related emphysema.
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PMID:Proteoglycan changes in the extracellular matrix of lung tissue from patients with pulmonary emphysema. 1043 Feb 74

The tight-skin (Tsk) and beige (bg) mutants of the C57B1/6J strain of mouse spontaneously develop air-space enlargement reminiscent of human emphysema. To determine if this enlargement is accompanied by matrix destruction, as in the human disease, we examined the elastin and collagen matrices of the lungs of both mutants. The ultrastructure of these matrix components was separately visualized by scanning electron microscopy following controlled alkali digestion, which preserves collagen, and formic acid digestion, which enables visualization of elastin. Significant elastin destruction suggestive of an elastolytic process was observed in the lungs of Tsk mice. Thickening of elastin lamellae was observed in the lungs of bg mice, suggesting that congenital matrix remodeling may underlie air-space enlargement in this strain.
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PMID:Ultrastructure of lung elastin and collagen in mouse models of spontaneous emphysema. 1051 82

Emphysema is commonly defined as enlargement of airspaces distal to terminal bronchioles accompanied by destruction of alveolar walls, but without obvious fibrosis. Morphometric techniques were used to correlate changes in components of the alveolar septa surrounding enlarged airspaces in human emphysema with the mean linear intercept (Lm) of those airspaces. Alveolar and capillary surface density decreased with increased Lm, but the ratio of these surface densities to each other remained close to normal for mild to moderate increases in Lm. This suggests that the decreased gas exchange observed in emphysema is initiated by a total loss of septa and not by selective pathological changes of the microvasculature. Increases in septal wall thickness directly correlated with increases in Lm. For the mild to moderate emphysema lesions included in this study, an increase of 100% in Lm correlated with a 130% increase in the relative volume of the alveolar septal interstitium. Significant increases occurred in both elastin (0.14 to 0.56 microm(3)/microm(2) basement membrane [BM]) and collagen (0.49 to 1. 63 microm(3)/microm(2) BM). The increase in elastin and collagen raises the possibility of a remodeling process in the connective matrix in alveolar walls. Whether or not the new connective tissue represents a disordered, nonfunctional regional response needs to be determined.
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PMID:Cellular and connective tissue changes in alveolar septal walls in emphysema. 1058 33

Homozygous mutant klotho (KL(-/-)) mice exhibit multiple phenotypes resembling human aging. In the present study, we focused on examining the pathology of the lungs of klotho mice and found that it closely resembled pulmonary emphysema in humans both histologically and functionally. Histology of the lung of KL(-/-) mice was indistinguishable from those of wild-type littermates up to 2 wk of age. The first histologic changes appeared at 4 wk of age, showing enlargement of the air spaces accompanied by destruction of the alveolar walls, and progressed gradually with age. In addition to these changes, we observed calcium deposits in type I collagen fibers in alveolar septa and degeneration of type II pneumocytes in 8- to 10-wk-old KL(-/-) mice. Pulmonary function tests revealed prolonged expiration time in KL(-/-) mice, which is comparable with the pathophysiology of pulmonary emphysema. The expression level of messenger RNA for type IV collagen, surfactant protein-A and mitochondrial beta-adenosine triphosphatase was significantly increased in KL(-/-) mice, which may represent a compensatory response to alveolar destruction. Additionally, the heterozygous mutant klotho mice also developed pulmonary emphysema late in life, around 120 wk of age. These findings indicate that klotho gene expression is essential to maintaining pulmonary integrity during postnatal life. The klotho mutant mouse is a useful laboratory animal model for examining the relationship between aging and pulmonary emphysema.
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PMID:Disruption of the klotho gene causes pulmonary emphysema in mice. Defect in maintenance of pulmonary integrity during postnatal life. 1061 62

Recent studies have suggested that macrophage-derived metalloproteases are the critical mediators of cigarette smoke-induced emphysema, in contrast to earlier hypotheses that this process was mediated by neutrophil elastase. To determine whether smoke can acutely induce connective tissue breakdown in the lung and to examine the mediators of this process, we exposed C57-BL/6 mice to whole cigarette smoke and used high-performance liquid chromatography to examine lavage fluid levels of desmosine (DES), a marker of elastin breakdown, and hydroxyproline (HP), a marker of collagen breakdown. Smoke produced a dose-response increase in lavage neutrophils, DES, and HP, but not lavage macrophages (MACs). This effect was evident by 6 h after exposure to two cigarettes. Pretreatment with an antibody against polymorphonuclear leukocytes (PMNs) reduced lavage PMNs to undetectable levels after smoke exposure, did not affect MAC numbers, and prevented increases in lavage DES and HP. Intraperitoneal injection of a commercial human alpha1-antitrypsin (alpha1AT) 24 h before smoke exposure increased serum alpha1AT levels approximately 3-fold and completely abolished smoke-induced connective tissue breakdown as well as the increase in lavage PMNs, again without affecting MAC numbers. We conclude that in this model cigarette smoke can acutely induce connective tissue breakdown and that this effect is mediated by neutrophil-derived serine proteases, most likely neutrophil elastase. Exogenous alpha1AT is protective and appears to inhibit both matrix degradation and PMN influx, suggesting that alpha1AT has anti-inflammatory as well as antiproteolytic effects in this system.
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PMID:Acute cigarette smoke-induced connective tissue breakdown is mediated by neutrophils and prevented by alpha1-antitrypsin. 1065 46

There are several unsolved clinical findings in patients with idiopathic pulmonary fibrosis (IPF); (i) predominance of fibrosis in the lower lung fields, (ii) digital clubbing, and (iii) patchy distribution of pulmonary fibrosis. To explain these unsolved problems, we hypothesized that regenerated or premature bronchoepithelial cells may circulate in the blood in patients with IPF. To prove this, we performed the reverse transcriptase-polymerase chain reaction (RT-PCR) for cytokeratin 19 (CK19) and pulmonary surfactant protein A (SPA) in peripheral blood in patients with IPF and pulmonary fibrosis associated with collagen vascular disorders. In addition, 20 patients with chronic pulmonary emphysema as a disease control and 19 normal volunteers were also evaluated for the existence of circulating bronchoepithelial cells. RT-PCR analysis showed that CK19 was expressed in 12 of 38 blood samples (31.6%) of IPF and pulmonary fibrosis associated with collagen vascular disorders, seven of 20 (35.0%) blood samples of chronic pulmonary emphysema, and four of 19 (21.1%) blood samples of normal volunteers. mRNA for SPA was positive in eight of 38 (21.1%) blood samples of IPF. In contrast, SPA expressing cells were not detected in any blood samples obtained from patients with chronic pulmonary emphysema or normal volunteers. This evidence suggests that there were some circulating bronchoepithelial cells expressing mRNA for SPA in peripheral blood of patients with IPF and pulmonary fibrosis associated with collagen vascular disorders.
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PMID:Circulating bronchoepithelial cells expressing mRNA for surfactant protein A in patients with pulmonary fibrosis. 1086 11

During a series of studies investigating the maturational response to antenatal glucocorticoids, we observed that 70% of lambs delivered at 128 d gestation (term = 150 d), 24 h after a single injection of 0.5 mg/kg betamethasone or betamethasone + L-thyroxine (15 microgram/kg), developed pulmonary interstitial emphysema (PIE), compared with less than 5% of control animals or animals delivered 48 h or 7 d after hormone treatment. This study examined whether the lungs of animals that developed PIE were functionally or structurally different from those that did not. Lambs were mechanically ventilated for 40 min after cesarean section delivery. Hormone-treated animals with PIE were ventilated at similar peak inspiratory pressure (PIP) to control animals, whereas those without PIE were able to be ventilated at significantly lower PIP. Volume-dependent elastance (E2V), which provides an index of overdistension during mechanical ventilation, was lowest in PIE animals. Alveolar architecture was distorted in almost all ventilated animals, the most severe distortion occurring in PIE animals. There was no evidence of excessive alveolar wall thinning in PIE animals, although parenchymal collagen was 30% lower, and elastin 120% higher than in control animals. PIE was associated with structural differences, but not with overventilation.
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PMID:Pulmonary interstitial emphysema 24 hours after antenatal betamethasone treatment in preterm sheep. 1098 35


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