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)

In order to determine biological aggressiveness of settled dusts (mechanical, crumbled) and dusts collected using the gravimetric method, experimental studies were carried out, including: 1) evaluation of the physicochemical parameters (size of dust particles, content of silica, metals and other chemical compounds), 2) evaluation of the haemolytic activity, 3) experimental evaluation of fibrogenic potentials by means of: a) intraperitoneal test--to identity morphological type of reactive changes in the peritoneum and b) intratracheal test--to determine the level of hydroxyproline (collagen) in lungs and the morphological type of reactive changes. Albino rats were used for the experiment. The animals were divided into ten groups which received a single intratracheal injection of 50 mg of mining dust in 0.9% NaCl suspension. Comparative evaluation of biological aggressiveness of mining dusts was conducted basing on the findings of collagen levels in lungs. After the end of the experimental period (3 and 6 months, respectively) histopathological a examination of the lungs and mediastinal lymph nodes was made and the collagen levels in the pulmonary tissue (following Stegemann) were determined. As evidenced by the results of the pathomorphological examination and a statistical analysis: 1) after intratracheal injection the mining dusts induced changes within the respiratory system e.g. inflammatory process and emphysema. The exposure also brought about double increase of collagen level as compared to the control group, 2) histopathological study of the lungs and lymph nodes did not reveal progressive development of fibrogenic changes, 3) cytotoxic test showed differences in the haemolytic activity of settled dust and dusts collected by the gravimetric method.
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PMID:[Biological testing of the fibrogenic effect of dust from the "Sosnowiec" mine on the lung tissue]. 140 42

The tight-skin (Tsk) mouse is a genetic model of pulmonary emphysema linked to a deficiency of serum antielastase. In this mouse occurrence of connective tissue abnormalities in various organs (systemic scleroderma) has been reported. The aim of the present work was to study lung collagen synthesis and deposition in Tsk mice. No differences in the collagen synthesis rate and morphology at the ultrastructural level were found in Tsk mice at birth. At 2 months of age, a marked increase in collagen was observed within the alveolar septa. At this time, an increased lung collagen synthesis, assessed by determining prolyl hydroxylase activity and incorporation of radiolabeled proline, was found in Tsk mice with respect to control mice. However, due to the ongoing parenchymal destruction, the values of total lung collagen at 6 and 12 months of age were only moderately but significantly increased with respect to those observed at 2 months. As a consequence, a progressive accumulation of lung collagen fibers was observed in the residual septa. The increase in collagen deposition was accompanied by a relative increase in type I collagen. Although the data in the literature would suggest a genetic cause for the lung collagen change in Tsk mice, the data presented here indicate that the change in lung collagen metabolism may be a part of a remodeling process taking place after lung destruction.
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PMID:Lung collagen synthesis and deposition in tight-skin mice with genetic emphysema. 158 42

The mammalian pulmonary blood-gas barrier is well known to be extremely thin. For example, in the human lung, half of the area of the barrier (the 'bulging' part) has a thickness of only 0.2-0.4 micron. We show here that the barrier is also immensely strong. This is an essential requirement because the capillary wall stresses during heavy exercise become very large (about 7 x 10(4) N/m2 = 70 kPa) when capillary pressure increases to 30 mmHg. Stress failure of the pulmonary capillary wall consistently occurs in experimental rabbit preparations at abnormally high pressures exceeding 40 mmHg and may be the cause of bleeding into the lung in galloping racehorses. The great strength of the thin side of the blood-gas barrier can be attributed to the extracellular matrix, especially the type IV collagen which is predominantly located in the very thin lamina densa. The alveolar wall is therefore particularly vulnerable to injurious agents which attack type IV collagen such as autoantibodies in Goodpasture's Syndrome and perhaps neutrophil elastase in emphysema. The combination of extreme thinness and great strength of the blood-gas barrier poses a unique design requirement.
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PMID:Strength of the pulmonary blood-gas barrier. 162 33

The susceptibilities of normal rats and rats with preexisting pulmonary emphysema to chronically inhaled diesel exhaust were compared. Rats were exposed 7 h/day, 5 days/wk for 24 months to diesel exhaust at 3.5 mg soot/m3, or to clean air as controls. Emphysema was induced in one-half of the rats by intratracheal instillation of elastase 6 wk before exhaust exposure. Measurements included lung burdens of diesel soot, respiratory function, bronchoalveolar lavage, clearance of radiolabeled particles, pulmonary immune responses, lung collagen, excised lung weight and volume, histopathology, and mean linear intercept of terminal air spaces. Parameters indicated by analysis of variance to exhibit significant interactions between the influences of emphysema and exhaust were examined to determine if the effects were more than additive (indicating increased susceptibility). Although 14 of 63 parameters demonstrated emphysema-exhaust interactions, none indicated increased susceptibility. Less soot accumulated in lungs of emphysematous rats than in those of nonemphysematous rats, and the reduced accumulation had a sparing effect in the emphysematous rats. The results did not support the hypothesis that emphysematous lungs are more susceptible than are normal lungs to chronic exposure to high levels of diesel exhaust. The superimposition of effects of emphysema and exhaust, however, might still warrant special concern for heavy exposures of emphysematous subjects.
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PMID:Influence of preexisting pulmonary emphysema on susceptibility of rats to inhaled diesel exhaust. 169 74

From August 1990 to August 1991, sixteen patients with bullae or blebs (pneumothorax 9, giant bullae 5, bullous emphysema 2) were treated by CO2 laser ablation under limited thoracotomy. We found the irradiation of bullae or blebs by CO2 laser quite effective in eliminating these bullous lesions which were often multiple and inoperable by conventional methods. Histological examination revealed the wall of bullae where CO2 laser was applied became thick with dense fibrous tissues and degenerated collagen fibers which, however, were not disrupted. The procedure was safe and we were able to operate patients with disabling emphysema. Because CO2 laser can penetrate only 0.2-0.3 mm of tissue thickness, it is suitable for the ablation of bullous lesions which have thin walls and rapidly shrink and collapse by irradiation leaving thick walled scar tissues. Removing multiple bullae and blebs in patients with bullous emphysema can improve gas exchange by reducing dead spaces and elevating the diaphragm which is often flat and downward displaced because of hyperinflation in these patients. We are planning to incorporate thoracoscopy for this operation to make the procedure less invasive.
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PMID:[Application of laser in the treatment of spontaneous pneumothorax and emphysema]. 173 44

Proteinase 3 (PR-3) is a human polymorphonuclear leukocyte (PMNL) serine proteinase that degrades elastin in vitro and causes emphysema when administered by tracheal insufflation to hamsters (Kao, R. C., Wehner, N. G., Skubitz, K. M., Gray, B. H., and Hoidal, J. R. (1988) J. Clin. Invest. 82, 1963-1973). We have determined the primary structure of several PR-3 peptides and have analyzed catalytic properties of the enzyme. The enzyme has considerable amino acid sequence homology with two other well characterized PMNL neutral serine proteinases, elastase and cathepsin G. Furthermore, the NH2-terminal amino acid sequence of PR-3 is identical to that of the target antigen of the anti-neutrophil cytoplasmic autoantibodies associated with Wegener's granulomatosis. PR-3 degrades a variety of matrix proteins including fibronectin, laminin, vitronectin, and collagen type IV. It shows no or minimal activity against interstitial collagens types I and III, respectively. The analysis of peptides generated by PR-3 digestion of insulin chains and the activity profile against a panel of chromogenic synthetic peptide substrates show that PR-3 prefers small aliphatic amino acids (alanine, serine, and valine) at the P1 site. The elastase-like specificity of PR-3 is consistent with its striking sequence homology to elastase at substrate binding sites. PR-3 is inhibited by alpha 1-proteinase inhibitor (ka = 8.1 x 10(6) M-1 S-1; delay time = 25 ms) and alpha 2-macroglobulin (ka = 1.1 x 10(7) M-1 S-1; delay time = 114 ms) but not by alpha 1-anti-chymotrypsin. In contrast to elastase and cathepsin G, PR-3 is not inhibited by secretory leukoprotease inhibitor and is weakly inhibited by eglin c. Thus, PR-3 is distinct from the other PMNL proteinases.
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PMID:Characterization of proteinase-3 (PR-3), a neutrophil serine proteinase. Structural and functional properties. 203 50

The important processes in fetal pulmonary development are devoted to gain large surfaces for gas exchange and surfactant production. Basement membrane components, collagen fibers and elastic fibers are formed immediately around the epithelium in the early stage of lung development. Primordia of alveolar septa composed of elastic fibers and smooth muscle cells, develop in the glandular stage and form alveolar septa by protruding into the glandular lumina in later stages. The differentiation of alveolar walls, including the appearance of surfactant-producing cells, begins earlier in the proximal portion than in the distal portion of primitive alveoli. The process of fibrosis and regeneration in lung fibrosis defectively mimics the embryogenesis of the lung. Pulmonary structural remodeling occurs when the epithelial basement membrane, a scaffold for regenerating epithelial cells, is lost because of intra-alveolar fibrosis. In panacinar emphysema, simple and dilated air spaces are formed by the degradation of elastic fibers in alveolar septa, and this process may be reverse to the formation of alveolar septa in developing lung.
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PMID:[Development of connective tissue and surfactant production in fetal lung]. 204 Dec 53

We studied lung structure and function in Fischer-344 and Sprague Dawley rats to compare the pathophysiologic features of the aged lung in animal strains. Both strains were maintained under identical conditions of minimal exposure to injurious environmental agents. We measured the number, size, and surface area of alveoli, pressure-volume characteristics and connective tissue content of lungs at midlife (12 or 14 months of age) and old age (24 months of age). Results showed differences in the older versus younger group of the Sprague Dawley strain as indicated by enlarged air spaces [154 +/- 21 (SEM) versus 118 +/- 13 micromicroliter] (p less than 0.05), increased collagen (hydroxyproline content 4.1 +/- 0.1 versus 3.0 +/- 0.1 mg/lung) (p less than 0.05), and a leftward shifted pressure-volume curve. There was no change in surface area or alveolar number. The structural lesions are consistent with air space enlargement with fibrosis and not emphysema. In contrast, no major changes were found in the lungs with age in Fischer-344 rats. We hypothesize that in the Sprague Dawley strain the aging process impairs the ability of the lung to maintain normal structure and function. Two strains of rats which differ pathologically in old age may be useful in the study of the effects of aging on the lung.
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PMID:Strain specific respiratory air space enlargement in aged rats. 209 71

While elastin degradation is a hallmark of pulmonary emphysema, it is likely that elastin synthesis also occurs. However, the supramolecular structure and function of the newly synthesized elastin are abnormal. Very little is known about the regulation of elastin synthesis during the development of emphysema when prominent collections of mononuclear phagocytes are found in and near the alveolar interstitium. Transforming growth factor-beta (TGF-beta) is an important regulator of collagen and fibronectin production in wound healing, which is also accompanied by an influx of mononuclear phagocytes. We hypothesized that TGF-beta may influence elastin production by fibroblasts in the pulmonary interstitium. Therefore, we examined the influence of TGF-beta on the production of elastin by postconfluent cultures of neonatal rat lung fibroblasts. Elastin production was quantitated by analyzing the incorporation of [3H]valine into the soluble elastin precursor tropoelastin (TE). The incorporation of [3H]valine into TE was approximately 2-fold greater in the presence of 40 or 100 pM TGF-beta than in its absence. The intracellular, free [3H]valine pool was increased by 18% in the presence of TGF-beta. Therefore, TGF-beta-related differences in the precursor pool size were not solely responsible for the observed increase in [3H]valine incorporation. Northern analysis demonstrated that the increase in TE was accompanied by a smaller but significant increase in the steady-state level of elastin mRNA. Thus, the observed increase in TE production can be at least partially attributed to a pretranslational effect of TGF-beta.
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PMID:Transforming growth factor-beta increases elastin production by neonatal rat lung fibroblasts. 220 40

Xifukang is a compound preparation of Chinese herbs consisting of Hanbane grugs mainly. Since 1987, the significant efficiency have been obtained in treatment of 53 patients suffering from silicosis by self-control study. The results indicated that the clinical manifestations including dyspnea, cough, sputum production, chest pain, weakness, etc. were markedly improved (P less than 0.01) and measurements of pulmonary function (FVC, FEV and MVV) significant enhanced (P less than 0.01). After treatment 20 cases roentgenogram exam showed that the lung's clarity and the limited emphysema were improved, the silicolic nodule and mass-mergence opacity of 3 cases lessened in some degree. By discussing the effect of Xifukang which might lower the collagen protein content of experimental silicosis of Wistar rats and improve pathomorphous. The authors concluded that the therapeutic mechanism of Xifukang could be the actions of this remedy on promoting blood circulation to eliminate blood stasis dredging microcirculation, increasing ventilation/perfusion (VA/Q), protecting dust-cells, resisting fibrosis, regulating immune function, enhancing lung clearance, postponing and preventing development of silicosis.
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PMID:[Clinical therapeutic effect of xifukang in 53 patients with silicosis]. 220 23


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