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Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although pulmonary fibrosis results from exposure to a high level of asbestos, the relative contributions of increased synthesis and/or reduced degradation of total collagen and of any specific type of collagen are not clear. To examine collagen turnover, rats were instilled with crocidolite fibers via the trachea and killed at 1, 2, 4, 6, and 8 weeks. The left lobe was used to determine collagen synthesis by incubating lung pieces with [3H]proline and subsequently measuring 3-hydroxyproline (HYP). Collagenolytic activity was estimated from the release of soluble HYP after incubation of lung homogenates for 48 h. Ratios of collagen types I and III were assayed by gel electrophoresis, both on whole lung and on the labeled homogenate. As fibrosis develops, both total HYP and HYP per dry weight increase at 2 weeks and continue to rise over the experimental period with no differences in the ratio of total types I:III collagens. However, newly synthesized collagen showed an increase in type III at 2 weeks and later a higher proportion of type I collagen when compared with the control. Total collagenolytic activity of asbestos-treated lungs was the same as controls when expressed per dry weight, but was reduced when calculated per unit of collagen. However, active collagenolytic activity was lower than control values when expressed by HYP content and per dry weight at all times after asbestos. The results suggest that reduced degradation of collagen contributes to the fibrotic process in addition to the progressive increase in collagen synthesis, particularly the type I form.
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PMID:Collagen synthesis and degradation during the development of asbestos-induced pulmonary fibrosis. 157 28

Chronic interstitial lung disease complicates collagen vascular disorders in more than 5% of cases and is an important cause of morbidity and mortality in this patient population. An alveolitis characterizes the early phases of the lung lesion; perpetuation of this inflammatory process may result in irreversible pulmonary fibrosis and respiratory failure. In this chapter, we review the role of conventional studies (such as chest radiographs and pulmonary function tests) and newer diagnostic modalities (such as bronchoalveolar lavage, gallium scanning, and thin-section computed tomographic scanning) to identify patients with active alveolitis who are at risk for functional deterioration. While optimal treatment is controversial, the role of corticosteroids, immunosuppressive/cytotoxic, and antifibrotic agents is discussed.
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PMID:Pulmonary complications of collagen vascular disease. 158 May 81

Increased lung collagen and increased collagen synthesis by lung fibroblasts is well recognized in pulmonary fibrosis. gamma-Interferon has been shown to inhibit collagen synthesis by fibroblasts. To understand its effect on lung fibroblasts we compared how this lymphokine affects the growth and collagen synthesis of normal and fibrotic human lung fibroblasts. The results showed that gamma-IFN inhibited DNA synthesis in all fibroblast strains examined. Both collagen production and type 1 mRNA levels were reduced in three normal and two fibrotic cell strains exposed to gamma-IFN, while they were not affected in one strain from fibrotic lung. Even though an occasional cell was unaffected by the gamma-IFN, collagen mRNA level was reduced in most cells and it remained reduced for 48 h after removing the gamma-IFN. These results show that gamma-IFN inhibits the growth of fibroblast cultures derived from normal and fibrotic human lungs and suppresses collagen synthesis in most of these cells.
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PMID:Effect of gamma-interferon on collagen synthesis by normal and fibrotic human lung fibroblasts. 158 92

Systemic Sclerosis is a multisystemic disease characterized by sclerosis of the skin and visceral organs, vasculopathy (Raynaud's phenomenon) and autoantibodies. The criteria for the classification of the disease requires either proximal scleroderma (major criteria) or the presence of 2 of the 3 minor features namely sclerodactyly, digital pitting scars and bibasilar pulmonary fibrosis. There are 3 subsets of this condition--diffuse variant, limited variant (CREST syndrome) and Overlap Syndrome (where patients have features of other rheumatic diseases). There are localized forms of scleroderma and pseudoscleroderma states. The presenting features of Systemic Sclerosis are usually Raynaud's, skin changes and arthralgia. Systemic complaints like breathlessness, dyspepsia, etc depending on the organ involved may be present. Management starts with patient education regarding the disease, skin care, exercises and regular medical check-up. There is no miracle cure but much can be done to improve the quality of life of the patient. Nifedepine and other drugs may improve Raynaud's phenomenon. Drugs can be used to treat other complications. Various medication have been tested as disease modifying drugs for scleroderma. These include drugs which inhibit collagen like D-penicillamine, colchicine, and immunosupressive drugs like cyclosporin. Ketotifen, a mast cell stabilizer has been reported to be effective in scleroderma. As it is a relatively safe drug, clinical trials are underway.
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PMID:Systemic sclerosis. 162 Nov 27

Fifty-six males workers exposed to rock wool during production, and 20 referents were examined. Exposure, evaluated by personal sampling, ranged from 0.05 to 0.74 fibres/ml (median 0.15). The subjects underwent a medical examination, chest X-ray according to ILO recommendations and pulmonary function tests. In all subjects the serum levels of type III procollagen N-terminal propeptide (PIIINPs) were determined. No evidence of pulmonary fibrosis, nor work-related lung diseases were observed. PIIINPs mean values in the exposed (9.8 ng/ml; 2.8 S.D.) were slightly higher, but not significantly different when compared to referents (8.5 ng/ml; 2.5 S.D.). No significant correlation between PIIINPs and rock wool exposure (both airborne levels and exposure duration) was observed. Furthermore, peptide levels were not related to pulmonary function test results. Our results suggest that occupational exposure to rock wool fibres lower than 0.75 fibres/ml for less than 20 years does not induce definite cases of pulmonary fibrosis nor an increase of type III collagen synthesis in the lung.
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PMID:[The determination of serum amino-terminal procollagen type-III propeptide (PIIINP) in occupational exposure to rock wool fiber]. 163 Apr 1

Intratracheal injection of bleomycin in rats results in the development of patchy pulmonary fibrosis. We investigated events associated with remodeling of lung structure by light and electron microscopic immunolocalization of fibronectin, laminin, and type IV collagen. Animals were studied from 2 to 60 days after injection of bleomycin. In the acute phase of injury, staining of fibronectin was prominent in fibrinous exudates, whereas during healing it was mainly associated with the surface of fibroblasts. The early accumulation of fibronectin in alveolar exudates is probably the result of leakage of plasma. During the reparative phase, fibronectin may be synthesized locally since it is selectively associated with the fibroblast surface. Staining with antibodies to type IV collagen and laminin identified the basal lamina and also helped to define the tissue boundaries despite the presence of intense exudation. It highlighted two processes in the acutely injured lung that lead to abnormal lung architecture: collapse of alveoli and invasion of air spaces by fibroblasts. In some healed lesions at 20 and 60 days, the immunostaining still outlined atelectatic lung. Electron microscopy of these lesions showed collagenous synechiae between approximated alveolar walls. We suggest that alveolar collapse and intraalveolar fibrosis in areas of collapse play an important role in bleomycin-induced pulmonary fibrosis and probably other types of fibrosis. They readily explain the loss of lung volume and compliance characteristic of fibrotic lung.
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PMID:Remodeling of the lung in bleomycin-induced pulmonary fibrosis in the rat. An immunohistochemical study of laminin, type IV collagen, and fibronectin. 169 71

Constant 7-day subcutaneous infusion of bleomycin (100 mg/kg) induces pulmonary fibrosis in C57Bl/6N mice, whereas BALB/cN mice are relatively resistant. In contrast, cyclophosphamide (200 mg/kg, ip) induces fibrosis in BALB/cN mice, whereas C57Bl/6N mice are resistant. The effect of these drugs on the pulmonary levels of mRNA encoding the major basement membrane components, laminin and type IV collagen, relative to poly (A+)RNA was determined in both C57Bl/6N and BALB/cN mice. In the sensitive C57Bl/6N mice, bleomycin increased alpha 1IV and alpha 2IV procollagen mRNA/poly (A+)RNA twofold in the absence of increases in laminin A, B1, and B2 mRNA/poly (A+)RNA. In the relatively resistant BALB/cN mice, bleomycin did not alter alpha 1IV procollagen mRNA/poly (A+)RNA and only transiently increased laminin A, B1, B2, and alpha 2IV procollagen mRNA/poly (A+)RNA. Similarly, cyclophosphamide increased alpha 1IV and alpha 2IV procollagen mRNA/poly (A+)RNA twofold in the sensitive BALB/cN mice and not in C57Bl/6N mice. Laminin mRNAs/poly (A+)RNA were not increased by cyclophosphamide in either strain. Thus, in these models, pulmonary fibrosis is preceded by a coordinate increase in steady-state levels of mRNA encoding basement membrane procollagen but is not associated with an increase in laminin gene expression.
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PMID:Bleomycin and cyclophosphamide increase pulmonary type IV procollagen mRNA in mice. 169 33

This study examines the hypothesis that mediators from lung endothelial cells could promote lung collagen synthesis in pulmonary fibrosis. Since bleomycin induces pulmonary fibrosis in humans and animals, the effects of this drug on endothelial cells were examined. Endothelial cell conditioned media were prepared in the presence of various doses of bleomycin, and tested for their ability to stimulate lung fibroblast collagen synthesis. The results show a dose-dependent stimulation of endothelial cell secretion of collagen synthesis stimulatory activity by bleomycin, which peaked at a dose greater than or equal to 100 ng/ml. Stimulation was selective for collagenous protein synthesis. Gel filtration analysis showed most of the activity to reside in fractions with an estimated molecular mass range of 10-27 kD. The activity was inhibited by anti-transforming growth factor-beta (TGF-beta)antibody, but not by nonimmune control IgG. The presence of TGF-beta was confirmed using the mink lung epithelial cell assay. Northern blotting revealed significant increases in TGF-beta mRNA in bleomycin-stimulated endothelial cells. Thus in vitro stimulation of endothelial cells by bleomycin upregulates TGF-beta production, presumably by increased transcription. In view of the chemotactic and matrix synthesis stimulatory properties of this cytokine, such an increase in TGF-beta production may play an important role in bleomycin-induced pulmonary fibrosis.
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PMID:Stimulation of rat endothelial cell transforming growth factor-beta production by bleomycin. 170 97

Intratracheal instillation of bleomycin in hamsters initiates a series of events that mimic human interstitial pulmonary fibrosis. Because glycosaminoglycans and particularly hyaluronan (hyaluronic acid, HA), may play an important role in the extracellular matrix response to early injury and subsequent fibrosis, this study was undertaken to define the early time course of changes in HA and hyaluronidase. Hamsters were given either 1 unit bleomycin sulfate in 0.2 ml saline or 0.2 ml saline (control), and randomly selected animals from both groups were killed at Days 3, 5, 6, 7, 9, and 17. Glycosaminoglycan fractions prepared from lung tissue of individual animals were analyzed for HA. The maximal HA content was reached 6 days after instillation of bleomycin and was 14.6-fold the normal value. The weight of injured lungs was 2.3-fold the control value. Thus, the increase in HA content was 30-fold. By Day 7 the HA content had dropped sharply. It then declined gradually to approximately double control values at Day 17. The specific activity of lysosomal hyaluronidase was the same in bleomycin-treated lungs and control lungs. Total units of the enzyme were increased in injured lungs, even at the time of maximal HA content, indicating active turnover of HA. The maximal HA content occurs prior to the rise in collagen and elastin biosynthesis. This observation in addition to the magnitude of the increase and its abrupt decline suggest that HA may be an important initiating factor for pathologic changes in lung extracellular matrix components.
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PMID:Early changes in lung tissue hyaluronan (hyaluronic acid) and hyaluronidase in bleomycin-induced alveolitis in hamsters. 170 35

Bleomycins are a family of compounds produced by Streptomyces verticillis. They have potent tumour killing properties which have given them an important place in cancer chemotherapy. They cause little marrow suppression, but pulmonary toxicity is a major adverse effect. The mechanisms of cell toxicity are well described based on in vitro experiments on DNA. The bleomycin molecule has two main structural components: a bithiazole component which partially intercalates into the DNA helix, parting the strands, as well as pyrimidine and imidazole structures, which bind iron and oxygen forming an activated complex capable of releasing damaging oxidants in close proximity to the polynucleotide chains of DNA. This may lead to chain scission or structural modifications leading to release of free bases or their propenal derivatives. The mechanisms are well described based on in vitro experiments on DNA, but how they relate to intact cells in whole animals is more tenuous. Bleomycin is able to cause cell damage independent from its effect on DNA by induction lipid peroxidation. This may be particularly important in the lung and in part account for its ability to cause alveolar cell damage and subsequent pulmonary inflammation. The lung injury seen following bleomycin comprises an interstitial oedema with an influx of inflammatory and immune cells. This may lead to the development of pulmonary fibrosis, characterized by enhanced production and deposition of collagen and other matrix components. Several polypeptide mediators capable of stimulating fibroblasts replication or excessive collagen deposition have been implicated in this, but the precise role of these in bleomycin-induced fibrosis is yet to be demonstrated. Current therapy for bleomycin-induced lung damage is inadequate, with corticosteroids most often used. Given the mechanism of action described above, antioxidants and iron chelators might be beneficial. Although, studies to date are equivocal and there is insufficient evidence to promote their use clinically. Novel drugs are currently being developed and it is hoped these may be more useful.
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PMID:Mechanisms of bleomycin-induced lung damage. 171 38


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