Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of interstitial vs. alveolar macrophages in the generation of pulmonary fibrosis after silica was examined. Using whole body irradiation to delay the inflammatory response and so retard particulate clearance, many more instilled silica particles reached the interstitial macrophages in the first 2 weeks than after silica alone. This was followed by greatly increased fibroblast proliferation and deposition of collagen in the irradiation plus silica group, which developed large interstitial granulomas at the sites of silica retention. Although alveolar macrophages containing silica were seen in both silica groups, more interstitial particles were observed after combined irradiation and silica, significantly more silica was recovered in a residue from the lungs at 16 weeks, and pulmonary fibrosis at 8-16 weeks was greater than in all other groups. The results indicate that increased fibroblast growth and collagen synthesis in vivo are associated with phagocytosis of silica by interstitial macrophages rather than by free alveolar macrophages. It is suggested that transfer of a macrophages-derived growth factor to fibroblasts is more efficient when it occurs within the pulmonary interstitium.
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PMID:Enhanced macrophage-fibroblast interactions in the pulmonary interstitium increases fibrosis after silica injection to monocyte-depleted mice. 253 18

We used cultured human diploid lung fibroblasts as a model system to examine the effects of recombinant IFN-gamma on synthesis of collagen, matrix deposition of newly synthesized collagen, and the expression of cell surface receptors for collagen. Using [3H]proline-labeled cells we found that IFN-gamma resulted in dose-dependent inhibition of fibroblast collagen synthesis. Pulse-chase experiments to analyze compartmentalization of newly synthesized collagen showed that the decrease in collagen synthesis was confined to the soluble pool of procollagen in the medium, while extracellular matrix associated collagen was not changed, indicating that a larger proportion of newly synthesized collagen was deposited into the matrix in IFN-gamma exposed fibroblasts (34.2 vs. 25.3%). This increase in the efficiency of collagen matrix deposition was associated with enhanced expression of a cell surface receptor for collagen as detected by indirect immunofluorescence labeling and analysis by flow cytometry. Fibroblasts (IMR-90) cultured in the presence of IFN-gamma (1,000 U/ml) exhibited a twofold increase in mean linear fluorescence intensity compared with cells cultured under control conditions. The distribution of log fluorescence intensity in both control and IFN-gamma exposed cells was normally distributed about the mean, indicating that discrete subpopulations with respect to receptor expression were not present. Increased fluorescence intensity and log normal distribution of fluorescence intensity also were identified in IFN-gamma-treated lung fibroblasts from a normal adult individual and two strains obtained from patients with pulmonary fibrosis. These results indicate that IFN-gamma modulates fibroblast collagen matrix deposition as well as collagen synthesis. The associated increase in collagen receptors suggests that cytokine-mediated modulation of the cell surface maybe a contributing factor in regulation of fibroblast collagen accumulation in the extracellular matrix or in cellular interaction with collagen-containing matrix. Such an effect could modulate the interaction of fibroblasts with extracellular matrix at sites of inflammation and play an important role in the remodeling of matrix during repair from tissue injury.
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PMID:Effects of interferon-gamma on expression of cell surface receptors for collagen and deposition of newly synthesized collagen by cultured human lung fibroblasts. 254 Feb 18

Macrophage-derived products have been implicated in fibroblast stimulation following particle deposition in the lung. To assess the role of macrophages in the alveolus versus those in the interstitium in the induction of pulmonary fibrosis, we compared the pulmonary response to silica when phagocytosis occurred predominantly in each of these compartments. One group of mice received intratracheal silica which was phagocytosed largely by alveolar macrophages (AM). A second group was exposed to whole body irradiation prior to receiving the same dose of silica. This prevented the usual efflux of PMN and monocytes into the air sacs, allowing passage of silica particles across the alveolar epithelium to reach the interstitial macrophages (IM). In the irradiation plus silica group, many large interstitial granulomas were formed at 2-4 weeks, and collagen levels were significantly greater than in all other groups at 16 weeks. More silica was found in a lung tissue residue and in lymph nodes of these animals. Pulmonary fibrosis was limited to interstitial areas where there was a high level of retained silica, whereas peripheral regions of the lung, where free AM containing silica were found, did not show fibrosis of the alveolar walls. The results suggest that factors secreted by IM in response to silica are more effective in stimulating fibrogenesis than secretions made by the AM into the alveolar space.
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PMID:Silica-induced pulmonary fibrosis involves the reaction of particles with interstitial rather than alveolar macrophages. 254 46

We report a 52-years-old female patient with collagen disease and pulmonary hypertension. Denopamine, beta-adrenergic agonist, decreased her high pulmonary arterial pressure and improved dyspnea on exercise after long term use. She had suffered from Raynaud's phenomenon, pulmonary fibrosis, shortening of lingual frenulum and positive ANA and RA test. Although her pulmonary fibrosis had been well controlled by azathioprine, dyspnea on exercise became worse, so she admitted to our hospital for further examination in Feb 1988. Right heart catheterization revealed her high pulmonary arterial pressure (mean 29 mmHg). Under right heart catheterization, denopamine markedly decreased her pulmonary arterial pressure and increased her cardiac output. After about 6 weeks' use of denopamine, her mean pulmonary arterial pressure decreased to 15 mmHg, PO2 increased from 43 to 62 mmHg and dyspnea improved. Denopamine has been regarded as a selective beta 1-adrenergic agonist. In this case, denopamine might have beta 2-agonist effect to dilate pulmonary vasculature, or have secondary effect to increase PO2 by the improvement of cardiac function. Denopamine might be useful for pulmonary hypertension with collagen diseases.
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PMID:[Denopamine responsive pulmonary hypertension in a patient with collagen disease]. 257 12

Bleomycin is a commonly used antineoplastic compound that can produce a dose- and time-dependent pneumonitis and fibrosis in humans. The mechanism of bleomycin-induced fibrosis is not known. However, current data suggest that the production of oxygen radicals by way of a ferrous ion-molecular oxygen mechanism might be related to the pulmonary fibrosis. Therefore, we evaluated the possibility that parenterally administered deferoxamine, an iron chelating compound, could modulate the morphologic and biochemical estimates of bleomycin-induced lung fibrosis in hamsters. Deferoxamine pretreatment and daily injection for 21 days after intratracheally administered bleomycin resulted in a 33% reduction in lung collagen accumulation compared with that after bleomycin treatment alone. However, fibrosis was still present in the bleomycin-deferoxamine group; the animals showed a 142 and 150% increase in lung collagen compared with that in saline- and deferoxamine-treated control animals, respectively. Morphologic estimates of the severity of fibrosis in the bleomycin-deferoxamine treatment group were reduced when compared with the bleomycin treatment group alone, but was increased compared with saline- and saline-deferoxamine-treated control animals. These data indicate that deferoxamine treatment reduces the severity of bleomycin-induced pulmonary fibrosis in hamsters. The mechanism might be by the prevention of iron-catalyzed, free-radical formation.
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PMID:The effect of deferoxamine on bleomycin-induced lung fibrosis in the hamster. 258 89

In pulmonary fibrosis the connective tissue framework and the mechanical properties of the lung are profoundly altered. Changes in amounts or distributions of each component of lung tissue (collagen, elastin, and ground substance such as glycosaminoglycans) might be expected to produce changes in viscoelastic properties of lung parenchyma and lead to mechanical inefficiency of the lungs. In order to evaluate the viscoelastic properties of the alveolar wall of fibrotic lungs, we analysed stress relaxation curves (SRL) of lung tissue in hamsters. Golden hamsters were divided into two groups: control (group C) and a group treated intratracheally with bleomycin (group B). Small piece of the alveolar wall tissue (80 x 80 x 1000 microns) was extended, and SRC was recorded for 3 minutes at the fixed extended length. Relaxation times (Tm) were used as indices of tissue viscoelastic properties. Three different Tm (Tm1: short, Tm2: moderate, and Tm3: long relaxation times) were obtained using the method of residuals. In group B, Tm3 (long relaxation time) was significantly larger than Tm3 in the other. Our results in relaxation time suggested that alveolar walls become more viscous with fibrosis. This rise in tissue viscosity with fibrosis may have been due to altered properties of the increased elastic fibers.
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PMID:[Viscoelastic properties of the alveolar wall in experimental pulmonary fibrosis]. 258 99

Fibroblasts in healthy adult lung are quiescent, synthesizing little collagen. We studied lung biopsies from 30 patients with pulmonary fibrosis, using immunohistochemistry with monoclonal antibodies against the propeptides of type I collagen to localize fibroblasts actively synthesizing collagen. Adjacent sections were stained with antibodies to type III and IV collagen, fibrin, cytokeratin, plasma fibronectin, or EDIIIa-containing "cellular" fibronectin (cFN). In rapid pulmonary fibrosis, including the proliferative phase of diffuse alveolar damage, organizing pneumonia, and subacute idiopathic fibrosis, collagen-synthesizing cells were numerous in organizing exudate filling airspaces but were also seen in the interstitium of the alveolar walls, interlobular septa, and walls of blood vessels. The new matrix deposited in the airspaces also contained type III collagen and EDIIIa-containing fibronectin. In chronic pulmonary fibrosis, more than half of the biopsies showed foci of collagen synthesis and cFN deposition near the air-tissue interface. The foci were consistently localized outside remnants of basal lamina and therefore within airspaces. The results indicate that (1) fibrosis in chronic idiopathic pulmonary fibrosis results mainly from organization of exudate within airspaces, just as it does after acute lung injury, and (2) during this process, fibroblasts increase their synthesis of collagen and fibronectin coordinately. Foci of active matrix deposition provide evidence for the progressive nature of chronic pulmonary fibrosis.
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PMID:An immunohistochemical study of architectural remodeling and connective tissue synthesis in pulmonary fibrosis. 260 97

Establishing the diagnosis of drug-induced pneumonitis is always difficult and requires that the following criteria be met: administration of the drug on a long-term basis; knowledge that the drug is able to induce pulmonary disorders; occurrence during therapy of interstitial pneumonitis with clinical, radiological and functional characteristics of this type of lung disease; exclusion of all other causes of interstitial pneumonitis (cardiac failure, infections, collagen vascular diseases, malignancies); bronchoalveolar lavage specimen, revealing lymphocytosis with an inverted CD4/CD8 lymphocyte ratio, isolated or associated with neutrophil and/or eosinophil alveolitis; finally, full recovery within several weeks or months after drug withdrawal unless irreversible pulmonary fibrosis has occurred. Certain specific characteristics correspond to the therapeutic class of the drug, i.e. antimicrobial, cardiovascular, antiinflammatory, neurological, metabolic, antiallergy or some other drugs.
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PMID:[Drug-induced pneumopathies (excluding cytostatic drugs)]. 261 Apr 52

Reactive oxygen species (ROS) have been closely associated with a number of pathological disorders, including interstitial pulmonary fibrosis. While models of ROS-induced fibrosis offer advantages over chemically-induced fibrosis, the biochemical and morphological features of ROS-induced fibrosis have yet to be extensively documented. In this study, we evaluated the effect of initial ROS dose on lung injury and repair. Male hamsters received a single dose of glucose, glucose oxidase and lactoperoxidase via the intratracheal route. From 3 to 14 days post-treatment, a significant dose-related body weight loss was observed. There was a trend towards greater mortality with increasing dose. After 2 weeks, we noted significant, dose-related increases in lung levels of collagen, lipid peroxidation products, nucleic acids, and protein. Similarly, total lung catalase, lactic dehydrogenase and glutathione reductase activities were also elevated significantly above control values in a dose-related fashion. A concurrent, dose-dependent thickening of alveolar septa in ROS-treated lungs was composed of epithelial hyperplasia, hyperemia, edema and accumulations of interstitial fibers and macrophages. Interstitial and alveolar macrophages in ROS-induced lesions were enlarged and contained numerous primary and secondary lysosomes. These results demonstrate that, in the hamster lung, injury induced by enzyme-generated ROS can initiate dose-dependent fibroproliferative changes which eventuate into interstitial fibrosis.
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PMID:Dose-related effects of enzyme-generated oxidants on the biochemistry and morphology of the hamster lung. 267 4

The major cause of death in paraquat poisoning is a rapidly progressive respiratory failure due to an oxidative insult to the alveolar epithelium with subsequent fulminant obliterating fibrosis. The present study evaluates the effectiveness of vitamin E in combination with colchicine in ameliorating paraquat lung injuries in rats. Vitamin E is a biologic antioxidant interfering with lipid peroxidation, and colchicine reduces collagen synthesis which is significantly augmented in pulmonary fibrosis. Eight normal rats were given a single i.p. dose of paraquat at 15 mg/kg. The treated group included eight animals that received, in addition to i.p. paraquat (15 mg/kg), daily doses of vitamin E (100 mg/kg i.p.) and colchicine (0.1 mg/kg i.p.). All the rats in the paraquat group died within 42 to 96 h, six of them within 60 h, following severe respiratory failure. The treated rats developed a somewhat milder form of respiratory insufficiency, six of them dying within 48 to 72 h. Less severe intra-alveolar hemorrhages were observed in this group. Two rats survived, and these had only mild emphysema on autopsy at 21 days. Our preliminary results suggest that the combination of vitamin E with colchicine may be effective in ameliorating lung injuries caused by paraquat, and warrant further studies.
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PMID:Effectiveness of vitamin E and colchicine in amelioration of paraquat lung injuries using an experimental model. 270 31


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