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)

Both DL-alpha-difluoromethylornithine (DFMO) and ethanol have been reported to inhibit the growth of fibroblasts in cell culture. The objectives of the present study were to determine whether these compounds could be used to inhibit the growth of fibroblasts in vivo, with a bleomycin-induced mouse model of pulmonary fibrosis. DBA/2J mice were given a single endotracheal injection of bleomycin, 10 nmol. In addition to bleomycin (BLM), groups of animals received 2% DFMO in drinking water for 4 days prior to BLM and 18 days after (BLM DFMO), 6% ethanol in drinking water for 7 days prior to BLM and 21 days after (BLM E7), 6% ethanol in drinking water for 21 days initiated on the day of BLM intubation (BLM E), or DFMO, E7, and BLM in combination (BLM DFMO E7). Animals died or were killed 21 days after bleomycin treatment and lungs were evaluated by histopathologic criteria. DFMO failed to alter the incidence or severity of fibrotic lesions, increased the severity of epithelial metaplasia (p less than 0.05), and reduced the lung disease index (from 56.3 to 42.1%, p less than 0.05) and mortality from 83.3 to 41.7% (p less than 0.025). In contrast to the unsatisfactory response to DFMO, pretreatment with ethanol (BLM E7) reduced the incidence of interstitial fibrosis from 91.3 to 71.4% (p less than 0.05) and confluent fibrosis from 73.9 to 20.0% (p less than 0.005). The severity of lesions was also reduced by ethanol, resulting in an 18.5% decrease in interstitial fibrosis, a 25.9% decrease in epithelial metaplasia, and a 55.4% reduction in the lung disease index (all p less than 0.01). However, when ethanol and DFMO were administered in combination, the beneficial effects of ethanol alone were not observed, and only the lung disease index was decreased.
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PMID:Studies of the effects of alpha-difluoromethylornithine and ethanol on the pathogenesis of bleomycin-induced pulmonary fibrosis in mice. 619 67

Collagenolytic enzyme release in alveolar structures is probably one of the initial events leading to impaired balance between collagen synthesis and degradation in the connective matrix of the lung, resulting in pulmonary fibrosis. The collagenolytic activity was determined in the bronchoalveolar fluid of 40 normal subjects or patients with miscellaneous pulmonary diseases and was found to be present in seventeen, viz.: 7/7 patients with interstitial fibrosis, irrespective of its origin: 4/4 patients with radiation pneumonitis; 4/15 patients with sarcoidosis and 2/2 patients with transient eosinophilic pneumopathy. There was no evidence of fibrosis in the 23 patients who showed no collagenolytic activity. Thus, collagenolytic enzymes are present in the alveolar structures of patients with interstitial pulmonary diseases of diverse origin capable of leading to fibrosis. Monitoring the release of this enzyme by bronchoalveolar lavage could be useful to evaluate the risk of fibrosis in such patients.
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PMID:[Fibrotic interstitial pneumopathies. Collagenolytic activity of the alveolar fluid]. 622 16

72 cases of diffuse interstitial lung diseases were observed from 1969 to 1976. Specimens removed from 47 patients were subjected to the whole spectrum of reactions. According to variation of both elastin and collagen, the following groups were outlined: group A: mycobacteriosis, farmer's lung, sarcoidosis and silicosis; group B: chronic eosinophilic pneumonia, lymphocytic interstitial pneumonia, post-tuberculous pulmonary fibrosis, and group C: X-ray pneumopathy, desquamative interstitial pneumonia, sclerodermic pneumopathy and chronic pulmonary fibrosis (primary chronic fibroadenomyosis). Each of these groups presents a close relationship between histochemical, radiological, clinical and functional findings.
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PMID:Diffuse interstitial lung diseases: a histochemical approach. 623 29

Silicosis and asbestosis are two forms of fibrotic lung disease resulting from the inhalation of inert materials indigestible by pulmonary alveolar macrophages. Results of studies of the host response to these particulates have not always been consistent. It is clear, however, that after phagocytosis, both cause alveolar macrophage damage, with resultant release of macrophage products, including fibrogenic factors and chemotactic factors for neutrophils. The latter cells also release lysosomal enzymes and free radicals when exposed to silica and asbestos. The net effect of these observations suggests that the combination of tissue damage and fibroblast stimulation results in the pulmonary fibrosis characterizing these diseases. Patients with silicosis and asbestosis have normal or decreased cell-mediated and increased humoral immunity with a high incidence of circulating immune complexes and autoantibodies. Whether these abnormalities are related to the pathogenesis of pulmonary fibrosis or are epiphenomena remains to be determined.
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PMID:Current concepts about the pathogenesis of silicosis and asbestosis. 628 50

This paper presents new findings obtained using animal models on the basic mechanisms of asbestos-induced lung disease. Recent, highly visible reviews on the subject have clearly pointed out that little is known about the cellular mechanisms through which inhaled asbestos fibers cause the well known, debilitating lung disease - asbestosis (i.e. interstitial pulmonary fibrosis). During the past five years, my colleagues and I have published a series of papers in which we have attempted to elucidate, in a rat model of asbestosis, the initial events of 1) asbestos fiber deposition, 2) translocation of fibers to the lung interstitium, 3) the response of pulmonary macrophages and the mechanisms through which these cells are attracted to sites of initial asbestos deposition, and 4) the developmental pathogenesis of the earliest anatomic lesion consequent to asbestos exposure.
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PMID:The early pathogenesis of asbestos-induced lung disease. 633 Aug 76

Interactions between two or more toxic agents can produce lung damage by chemical-chemical interactions, chemical-receptor interactions or by modification, by a first agent, of the cell and tissue response to a second agent. Interactions may occur by simultaneous exposure and if exposure to the two agents is separated in time. Chemical-chemical interactions have been mostly studied in the toxicology of air pollutants, where it was shown that the untoward effect of certain oxidants may be enhanced in the presence of other aerosols. Interactions at the receptor site have been found in isolated perfused lung experiments. Oxygen tolerance may be an example, when pre-exposure to one concentration of oxygen mitigates later exposure to 100% oxygen by modifying cellular and enzymatic composition of the lung. Damage of the alveolar zone by the antioxidant butylated hydroxytoluene (BHT) can be greatly enhanced by subsequent exposure to oxygen concentration which, otherwise, would have little if any demonstrable effect. The synergistic interaction between BHT and oxygen results in a resulting interstitial pulmonary fibrosis. Acute or chronic lung disease may then be caused not only by one agent, but very likely in many instances by the interaction of several agents.
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PMID:The role of toxicological interactions in lung injury. 637 96

The clinical significance of antibodies to the Jo-1 antigen in connective tissue diseases was studied. Clinical diagnoses of 11 patients who had anti-Jo-1 antibody were: polymyositis 8, dermatomyositis 1, and overlap syndrome 2 (polymyositis--systemic lupus erythematosus 1, polymyositis--scleroderma 1). All the patients who had anti-Jo-1 antibody showed interstitial pulmonary fibrosis, and in 2 patients anti-Jo-1 antibodies were detected before the appearance of lung disease.
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PMID:The precipitating antibody to an acidic nuclear protein antigen, the Jo-1, in connective tissue diseases. A marker for a subset of polymyositis with interstitial pulmonary fibrosis. 640 55

The case of a 33-year-old female patient with rheumatoid arthritis who developed a severe pulmonary fibrosis during chrysotherapy of 3.5 months' duration is reported. The course of the fibrosis was progressive and led to respiratory insufficiency and death. The microscopic picture revealed a honeycomb lung with perialveolar proliferation of connective tissue and mononuclear cell infiltration. The clinical and temporal circumstances gave evidence that this pulmonary fibrosis is possibly to be interpreted as a gold-induced lung disease, though a causal connection could not be established with absolute security. However, gold-induced pulmonary fibrosis is usually completely reversible and has no fatal outcome: this would be the first report of a lethal outcome of a gold-induced pulmonary fibrosis. The clinical data of 39 further cases of gold-induced pulmonary fibrosis published elsewhere are presented.
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PMID:[Fatal pulmonary fibrosis caused by gold therapy?]. 642 74

Increased synthesis of type I collagen, leading to increased ratios of type I to type III collagen in the lungs, has been observed in the lungs of animals with experimental pulmonary fibrosis. Similar changes in collagen type ratios have been observed in lungs of humans dying of idiopathic pulmonary fibrosis and of adult respiratory distress syndrome. In this study, lung collagen type ratios were examined in infants with acute and chronic lung disease. Tissue from the right lower lobes of neonates was obtained post mortem. Specific collagen types were quantitated by solubilization of lung collagen with CNBr and fractionation of the resulting mixture of peptides by column chromatography and polyacrylamide gel electrophoresis. Ratios of type I/III collagen were calculated for each lung sample using two independent pairs of marker peptides for these determinations. In some cases the ratio of type V to type III collagen in these same lung samples was also quantitated. We observed a significant increase in the ratio of type I/III collagen in infants with a premortem diagnosis of chronic lung disease, usually preceded by respiratory distress syndrome. We also observed two infants with large changes in collagen type ratios who might have had pulmonary fibroplasia secondary to intrauterine lung disease. These data suggest that there may be several subsets of infants with respiratory distress syndrome, each having a different prognosis.
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PMID:Elevated ratios of type I/III collagen in the lungs of chronically ventilated neonates with respiratory distress. 651 44

In order to assess the clinical effectiveness of an oral prostaglandin E1 derivative, OP-1206, five patients with chronic obstructive pulmonary disease and two with pulmonary fibrosis were studied from the standpoint of hemodynamics and nine others with chronic lung disease from the standpoint of respiratory function. Oral intake of OP-1206 resulted in a significant decrease in the pulmonary arterial pressure (p less than 0.01), total pulmonary vascular resistance (p less than 0.01), pulmonary arteriole resistance (p less than 0.01), and total systemic vascular resistance (p less than 0.05), and an increase in the cardiac index (p less than 0.05) and oxygen delivery (p less than 0.01) with insignificant changes of PaCO2, PaO2 and pH. There was no clinical improvement of lung function after OP-1206 intake. OP-1206 is a potent vasodilator, improving cardiac performance in patients with chronic lung disease and possibly preventing the progress of cor pulmonale in this kind of patient.
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PMID:OP-1206, a prostaglandin E1 derivative. Effects of oral administration to patients with chronic lung disease. 669 97


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