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)

Lesions caused by a single subtoxic dosis of diquat were studied in rats. After the administration of diquat on the first day it was revealed in highest concentration in the lung, but in two weeks no traces of the drug could be demonstrated. On the first and third day activity of peroxidase in the liver and the number of peroxisomes as well significantly increases. On the first day after the administration of diquat in the lung damage to the surfactanct and increase of the capillary permeability was observed. Later degenerative changes of the pneumocytes I and II type, focal haemorrhagic edema and presence of alveolar macrophages can be revealed. In two and in four weeks a slight pulmonary fibrosis remains to show the damage to the lung. In kidney tubular lesions of toxic origin, in the phase of the regeneration increase of the number of lyosomes could be revealed. On the basis of this study and the data of other authors the possible mechanism of the intoxication with diquat is discussed.
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PMID:[Morphological and toxicological studies of experimental diquat poisoning]. 120 3

Pulmonary changes induced in a murine model by intraperitoneal injections of bleomycin were morphologically studied by light and electron microscopy. The number of pulmonary macrophages and the distribution of fibronectin in these cells were evaluated by acid phosphatase and affinity staining using anti-fibronectin horseradish peroxidase conjugates. The onset of acute inflammation occurred 4 days after intraperitoneal injection of bleomycin and reached its peak on the 14th day post-injection. The inflammatory reaction then gradually decreased. Areas of subpleural fibrosis was observed on day 42. On day 14, the ratio of the macrophage in bleomycin-treated mice to that in control mice was 5:1. Many activated and foamy macrophages were observed at that time. These findings indicate that macrophage turnover activity is remarkably increased during the acute inflammatory phase. Fibronectin was detected in the cytoplasm of macrophages on day 14, 21, and 28. It was also detected in both alveolar capillary and epithelial basal lamina as well as in interstitial collagen fibers. On day 42, fibronectin staining was strongly positive in areas of subpleural fibrosis. These results suggest that fibronectin released from pulmonary macrophages plays a role in the process of pulmonary fibrosis.
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PMID:[A morphological study of pulmonary macrophages in bleomycin-injected murine models]. 137 83

Multiple reactive oxygen species-induced epithelial injury by glucose, glucose oxidase, and lactoperoxidase instillation in the lung results in a progressive interstitial fibrosis. To test the hypothesis that multiple pulmonary inflammatory responses alone would not result in fibrosis, three sequential inflammatory reactions were produced at weekly intervals in hamster lungs via intratracheal instillation of human recombinant C5a. Numbers of neutrophils and total inflammatory cells in bronchoalveolar lavage (BALF) increased significantly at 24 h after each C5a treatment compared with saline controls. Neutrophils increased by 3-, 33-, and 34-fold compared with the corresponding controls at 24 h after the first, second, and third doses, respectively, but returned to control levels by six days postinstillation. LTB4 levels increased by 24% and 20% compared with the corresponding controls at 24 h after the first and second doses but were not different from controls at other times. Hydroxyproline levels in treated animals did not differ significantly from control levels throughout the study. Protein levels were significantly increased at 24 h after the second and third doses and six days after the third dose compared with the corresponding controls. Occasional foci of neutrophils in alveolar spaces were observed at 24 h after each dose, but they decreased in frequency after six days. No foci of neutrophils were observed six days after the final dose, although some epithelial degeneration was observed by transmission electron microscopy. Our results indicate that pulmonary inflammation resulting from repeated influx of neutrophils in response to multiple instillations of C5a in the lung does not cause sufficient injury to result in pulmonary fibrosis.
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PMID:Repeated episodes of C5a-induced neutrophil influx do not result in pulmonary fibrosis. 165 81

Oxidant-mediated epithelial injury and repair processes may promote the development of pulmonary fibrosis. The authors examined this hypothesis by inducing oxidant injury in hamsters with intratracheally instilled mixtures of glucose, glucose oxidase (GO) and lactoperoxidase at weekly intervals. Solutions containing denatured GO (DE) served as a control treatment. One and six days after each treatment, anesthetized animals were sacrificed and lavaged, and their lungs and plasma were preserved for further study. Although DE-treatment consistently evoked a transient, neutrophil-rich inflammatory response, no significant biochemical or morphologic changes were detected at the ensuing 6-day time points. In contrast, repeated GO treatments prolonged inflammation and injured the alveolar epithelium, evidenced by significantly greater levels of neutrophils and macrophages in bronchoalveolar lavage fluid (BALF) and increased BALF levels of protein, beta-glucuronidase and lactic dehydrogenase activities. Active GO also altered BALF lymphocytes and monocytes, but no discernable pattern emerged. Fibrotic, consolidated parenchyma appeared after the second and third GO exposures, coinciding with increased levels of total collagen, prolyl hydroxylase activity, and anti-oxidant enzyme activities. Although alveolitis and type II cell hyperplasia were observed after the initial treatment, polyplike nodules covered by hyperplastic, undifferentiated epithelium were evident after the third treatment. After each exposure, GO-treated animals had larger volumes of parenchymal lesion than DE-treated hamsters. These data indicate that normal alveolar epithelial repair processes were greatly disrupted by repeated oxidant injury and suggest that repeated and/or continued epithelial injury may contribute to the development of pulmonary fibrosis.
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PMID:Repeated exposures to enzyme-generated oxidants cause alveolitis, epithelial hyperplasia, and fibrosis in hamsters. 175 May 14

Pneumocystis carinii pneumonia occurred in 6 of 17 rhesus monkeys infected with simian immunodeficiency virus and was studied by immunohistochemistry and by scanning and transmission electron microscopy. A monoclonal antibody/streptavidin-biotin-peroxidase staining method was highly sensitive for detecting the organisms in small, early lesions and was much more sensitive and specific than traditional silver impregnation methods. Reprocessing of paraffin wax-embedded lung tissue for scanning electron microscopy and use of a video printer to produce a photographic montage of light microscopic lesions allowed the same areas of tissue to be examined and compared by both methods. The ultrastructural morphology of P. carinii in the rhesus monkey was identical to that in man, as were the histological and electron microscopic lesions, including pulmonary fibrosis. Trophozoites were seen attached to alveolar type I epithelium mainly by intimate apposition to the plasma membrane, but scanning electron microscopy also showed attachment by elongated filopodia. Few macrophages were present in infected alveoli, and though phagocytosis followed by digestion of P. carinii trophozoites was observed, it appeared to occur at a very low level.
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PMID:Pneumocystis carinii pneumonia in simian immunodeficiency virus infection: immunohistological and scanning and transmission electron microscopical studies. 207 17

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

A monoclonal antibody has been made to a peptide that is released by human alveolar macrophages. This enzyme-releasing peptide (ERP) causes neutrophils to secrete azurophilic granule enzymes. Normal subjects, patients with pulmonary fibrosis, and patients with sarcoidosis had similar concentrations of this peptide in their bronchoalveolar lavage fluids. However, patients with the adult respiratory distress syndrome (ARDS) had about 2.7 times higher concentrations in their lavage fluids. The enzyme-releasing activity in the lavage fluids was significantly correlated with 2 indices of the severity of the clinical illness in patients with ARDS, the APACHE score, and the chest radiograph score. The correlation was diminished or ablated by removing the peptide with the monoclonal antibody bound to staphylococcal Sepharose 4B. This peptide accounted for 62.08% (SD = 15.88%) of the enzyme-releasing activity in fluids from lungs of patients with ARDS and 86.39% (SD = 24.46%) of the activity in fluids from lungs of normal control subjects. Therefore, ERP is the major neutrophil enzyme-releasing agent in the bronchoalveolar lavage fluid from patients with ARDS and from normal persons. There was a significant correlation between the neutrophil enzyme-releasing activity and the ERP concentrations in BAL of patients with ARDS. These observations suggest that modulation of neutrophil function by ERP significantly controls the protease and peroxidase loads in the lungs of patients with ARDS.
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PMID:A peptide from alveolar macrophages that releases neutrophil enzymes into the lungs in patients with the adult respiratory distress syndrome. 284 27

Current evidence suggests that bleomycin toxicity may be attributable to its DNA degradative activity possibly via generation of free radicals and O2 metabolites as mediators. Since lipopolysaccharide (LPS) has been known to provide protection against O2 toxicity, which is correlated with increased activity of O2 metabolite-detoxifying enzymes, the effect of this agent on bleomycin-induced pulmonary fibrosis was examined. Endotracheal bleomycin administration caused increased lung collagen synthesis. A single intraperitoneal injection of LPS (500 micrograms/kg) at day zero significantly decreased these increases. Total bleomycin-induced lung collagen increase was also significantly reduced. LPS alone had no significant effect on total lung catalase activity. Glutathiione peroxidase activity, however, was significantly decreased by 15.8% compared to untreated animals at 2 days after LPS treatment and remained unchanged at other time points. In addition, superoxide dismutase activity was significantly elevated by 30% above untreated animals only at 14 days after LPS administration and remained unchanged at other time points. Endotracheal bleomycin administration alone caused significant reductions in catalase activity at 2 days and 2 weeks after treatment, whereas glutathione peroxidase activity increased above control untreated animals at 2 and 4 weeks, respectively. Superoxide dismutase activity was unaffected by bleomycin treatment. Pretreatment with LPS before bleomycin prevented these reductions or caused increases in the activities of these enzymes at 2 days. Glutathione peroxidase was increased and was significantly greater than those animals treated with bleomycin alone. Catalase also was higher in the LPS plus bleomycin group (by 22.2%, p less than 0.05) than the bleomycin group alone. Compared to the effects on lung collagen synthesis and content, LPS treatment resulted in much less dramatic changes in total lung antioxidant enzyme activities. This discrepancy between the intensity of LPS effects on lung O2 metabolite-detoxifying enzymes and that on pulmonary fibrosis implies that the LPS-ameliorating effect on pulmonary fibrosis could not be totally explained by increased ability to detoxify O2 metabolites. Rather, the data would favor the possibility that LPS inhibits bleomycin-induced pulmonary fibrosis either by its known immunosuppressive effects or some other unknown mechanism. The former would be in agreement with previous data which suggest that an intact immune response is necessary for complete expression of the fibrogenic response to bleomycin.
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PMID:Inhibition of bleomycin-induced pulmonary fibrosis by lipopolysaccharide. 620 76

There is substantial tissue reorganization in the interstitium in pulmonary fibrosis. In order to determine the origin of cells in the interstitium of normal or fibrotic rat lung, we stained lung tissue immunohistochemically with antiserums directed against intermediate filament proteins specific for cells of mesenchymal or muscle origin. Vimentin, specific for mesenchymal cells, was isolated from cultured 3T3 fibroblasts, and desmin, specific for muscle cells, was isolated from chicken gizzard and antiserums prepared in guinea pigs. Paraffin-embedded sections of normal or fibrotic rat lung from rats 28 days after treatment with bleomycin sulfate were reacted with each antiserum and stained by the peroxidase-antiperoxidase technique. Antivimentin antiserum stained discrete interstitial cells of both control and fibrotic lung. Smooth muscle surrounding large airways and vascular smooth muscle was not significantly stained with this antiserum but was heavily stained with antidesmin. However, antidesmin did not stain cells in the interstitium of normal or fibrotic rat lung. These results suggest that most cells in the normal as well as in the fibrotic interstitium, including contractile interstitial cells, are probably of mesenchymal (fibroblastic) rather than of smooth muscle origin.
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PMID:Immunohistochemical identification of cell types in normal and in bleomycin-induced fibrotic rat lung. Cellular origins of interstitial cells. 620 36

IPH is an uncommon disease affecting mainly children and adults and has usually a poor prognosis. The basic pathogenesis of the disorder is unknown; many theories have been advanced, but none is proved. A case of IPH in a 35 years old male presenting the atypical feature of a myeloperoxidase deficiency is reported. This unusual feature may be compatible with a generalized redox systems deficiency, which leads, via an impaired flow of iron into alveolar macrophages, to the pulmonary fibrosis.
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PMID:[Idiopathic adult pulmonary hemosiderosis: a new etiopathogenetic hypothesis]. 665 24


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