Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0037116 (silicosis)
 1,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study the long-term effect of inhaled asbestos, guinea-pigs were exposed to airborne amosite at a concentration of 49 mg/m3, 2 h/day for 3 or 6 weeks and examined up to 2 years after exposure. Macrophages in lung lavage fluid (LLF) were increased at 16, 24 and 93 weeks and lymphocytes at 24 weeks. Examination of lung wall cells (LWC) 2 years after exposure compared to cells obtained by LLF showed higher proportions of LWC lymphocytes and neutrophils. Percoll gradient centrifugation of these cells showed a higher proportion of high density macrophages in LLF from the amosite-exposed animal and an increased number of low density lymphocytes in the LW. Cathepsin D was increased in LLF at 8 and 24 weeks and in alveolar macrophages 24 weeks and 2 years after exposure. Fibroblast cultures exposed to LLF did not show any statistical significant changes in their collagen synthesis. Histology 93 weeks after exposure showed macrophage and mediastinal lymph node accumulation of asbestos, as well as collagen in alveolar walls. Granulomas were found in the vicinity of blood vessels and in connection with the bronchioles. The data suggest that amosite at low doses ultimately causes fibrosis with a reaction pattern different from that seen in silicosis. The inflammation and fibrosis seems to develop only within the interstitium.
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PMID:Lung cell reactions in guinea pigs after inhalation of asbestos (amosite). 254 92

Bronchoalveolar lavage (BAL) was performed in 89 patients with diffuse interstitial lung disorders of varied aetiology and 19 normal control subjects over a period of 7 years. Alveolar macrophage was the predominant cell in BALF in normal control subjects. Increased neutrophils were found in BALF in patients with cryptogenic fibrosing alveolitis (CFA) and fibrosing alveolitis associated with collagen vascular diseases. BALF lymphocytosis was seen in patients with chronic hypersensitivity pneumonitis, sarcoidosis, miliary tuberculosis, silicosis and carcinomatosis. Diagnosis of alveolar microlithiasis was made in one patient with the help of BALF examination. One patient developed anaphylactic reaction to the topical xylocaine solution and there was no mortality with the procedure.
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PMID:Bronchoalveolar lavage fluid (BALF) analysis in interstitial lung diseases--a 7-year experience. 263 54

The activities of prolyl 4-hydroxylase, galactosylhydroxylysyl glucosyltransferase (GGT) and lysyl oxidase (three enzymes catalysing post-translational modifications of collagen) were measured in the lungs of rats exposed to silica (DQ12). Circulatory levels of GGT were also estimated. Rats were killed after 24 h and at 6, 12 and 24 weeks after a single intratracheal instillation of either 12.5 or 25 mg of silica (DQ12). Control animals received saline. The total activity of the three enzymes in the lungs of the exposed animals was significantly increased at all times (P less than 0.05). The circulatory levels of GGT were also increased though some differences failed to reach significance. Thus increased activities of enzymes of collagen biosynthesis correlated with the development of silicosis and occurred within 24 h of treatment. This suggests that the changes responsible for the eventual development of fibrosis are operative within hours of dust exposure.
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PMID:Collagen biosynthesis enzymes in lung tissue and serum of rats with experimental silicosis. 286 66

A murine model of experimental silicosis has been developed after the intratracheal injection of alpha-quartz crystals. Pulmonary inflammation was monitored by increases in wet lung weight and cell number and protein content of the lung lavage fluid; fibrosis was assessed by measuring increases in hydroxyproline content of the lungs. Acute pulmonary cellular inflammation occurred between weeks 1 and 2, followed by a chronic inflammatory response at week 12. Lung hydroxyproline content, an indication of collagen deposition, was initiated as early as 1 week after silica injection and continued to increase steadily over time. The inflammatory and fibrotic changes induced by silica appeared to be a specific effect of the injection of this toxic particulate and not the result of the introduction of a foreign body, because mice injected with silica crystals were found to have significantly greater increases in acute cellular inflammation and chronic collagen deposition than did mice injected with latex beads. A possible role for the immune system in modulating silica-induced damage was suggested by the variability in response of six different strains of mice (C3H/He, CBA/J, Balb/c, DBA/2, C57BL/6, C57BL/10), which differed at specific genetic loci. Both strains with high (DBA/2) and low (C3H/He) response demonstrated similar patterns of inflammation and fibrosis over a period of 12 weeks. This model demonstrates great potential in future studies for elucidating the role of the immune system in the development of pulmonary inflammation and fibrosis induced by toxic inorganic particulates.
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PMID:Kinetics of inflammatory and fibrotic pulmonary changes in a murine model of silicosis. 298 21

The role of the complement system in the pathogenesis of crystal-induced pulmonary inflammation and fibrosis was evaluated using a mouse model of silicosis and congenitally complement-deficient mice. Mice lacking the fifth component of complement (B10.D2/o) were compared to C5-sufficient animals (B10.D2/n) for pulmonary changes following intratracheal instillation of silica crystals. Complement-deficient mice demonstrated a significant reduction compared to complement-sufficient mice in both cell number and protein content of lung lavage fluid throughout the 12 weeks following silica exposure. Lung hydroxyproline content (indicative of collagen deposition) was equivalent for both strains and significantly higher than controls at all time points following silica instillation. Moreover, studies in vitro have shown that silica crystals are capable of activating complement via the alternative pathway. These studies indicate that the complement system may be responsible for some of the pulmonary inflammation, but not fibrosis elicited by silica exposure.
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PMID:The role of complement in experimental silicosis. 301 83

In spite of several studies, both in vivo and in vitro, the pathogenesis of silicosis remains unclear, mainly in those mechanisms related to fibrogenesis. In this study, we analyzed the concentration, biosynthesis, and degradation of collagen in silica-treated rats 7, 15, 30, 45, and 60 days after instillation. Our results showed a significant increase in collagen content and biosynthesis from the 15th day onward. However, our most remarkable finding was related to collagenolytic activity. In this sense, the silicotic rats presented a trimodal behavior: some animals showed an increased degradation, others had similar values to those of the controls, and others exhibited a decrease of collagenolytic activity. Altogether, these results suggest that collagen deposition in silicotic lungs is due to a rise in biosynthesis and, at least in some animals, to a decrease in degradation. Nevertheless, the steps of collagenolysis must be studied in more detail.
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PMID:Collagen metabolism in experimental lung silicosis. A trimodal behavior of collagenolysis. 314 93

Possibilities of increasing the content of collagen in heart, spleen and liver have been tested in rats affected by silicosis induced by intratracheal administration of 50 mg of siliceous earth dust suspension. An increased level of collagen has been found in rats' hearts after 9 months, whereas in spleens after 6 and 9 months of experiment. In the liver of rats suffering from experimental silicosis, no changes which would clearly indicate the fibrosis of this organ were found. In addition, the animals administered with dust exhibited inhibited physiological growth of the body weight and liver weight.
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PMID:[Experimental silicosis. Analysis of collagen levels in the heart, spleen and liver of rats in experimental silicosis]. 358 94

This study was conducted through regular pneumonoconiosis examination according to the law on 1,096 employees of medium and small-sized ceramic enterprises in Tokai district in 1981-82. Interview examination with BMRC questionnaire, X-ray examination and measurement of urinary hydroxyproline to creatinine ratio (HOP ratio) were carried out in order to elucidate the relationship between silicosis and urinary HOP ratio and to demonstrate the effect of smoking on pneumofibrosis. Grade of silicosis was classified into five types (0 to 4) based on the Japanese Classification of Radiographs of Pneumoconioses. In evaluating the behavior of urinary HOP ratio, when smoking factor is added in the early grade of pneumofibrosis (type 1 and type 2), collagen decomposition rate is rapidly repressed and fibroplastic conditions develop to the final grade as type 3 and 4, although smoking itself does not seem to induce pneumofibrosis. To exclude the effects of smoking, nonsmoking group was used for measurement of HOP ratio by grade. The HOP ratio in type 0 was lowest and HOP ratio increased in the order of type 1 and type 2. The turning point was found in type 2 and their HOP ratio decreased one after another. The turning point shifted from type 2 to type 3 in the case of non-smokers without any index symptoms by BMRC questionnaire and also shifted to type 1, in the case of non-smokers with them. Shifting of turning point suggests that index symptoms also promote fibroplastic activities.
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PMID:[Behavior of urinary hydroxyproline and the effect of cigarette smoking in silicosis]. 377 97

Rats were intratracheally instilled with 50 mg of size-fractionated crystalline quartz to induce silicosis. Lungs were analyzed 1, 4, 6, and 9 months after instillation for their content of the reduced difunctional collagen crosslinks dihydroxylysinonorleucine (DHLNL) and hydroxylysinonorleucine (HLNL), of the nonreducible trifunctional (mature) crosslink, hydroxypyridinium (OHP), and of hydroxylysine. Ratios of DHLNL: HLNL were elevated in silicotic lung collagen at all times sampled, due both to increased levels of DHLNL and decreased amounts of HLNL. Hydroxylysine content of collagen in the silicotic lungs was also increased as compared with age-matched control rats. Hydroxypyridinium content of silicotic lung collagen was less than control values at 1 month, but was significantly increased to about 120%, 150%, and 175% of the age-matched control values at 4, 6, and 9 months after silica instillation, respectively. The increased levels of OHP in lung collagen were temporally correlated with the appearance of mature silicotic nodules in these lungs. We conclude that the large amounts of excess collagen deposited in silicotic lungs differs biochemically from normal lung collagen despite maintenance of the normal ratio of major collagen types in silicotic lungs.
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PMID:Collagen crosslinking in lungs of rats with experimental silicosis. 381 40

A variety of silicotic lesions derived from thoracic silicosis via lymphohematogenous spread to the liver, spleen, bone marrow, and extrathoracic lymph nodes are described. The morphologic features of these lesions depend on the extent of macrophage aggregation, the occurrence of fibrogenesis, and the development of necrosis and degradative changes in macrophages and adjacent extracellular matrix, presumably caused by lysosomal enzymes released from macrophages. Ultrastructurally, the degenerative alterations of matrix material include longitudinal splitting and breakage of collagen fibrils into segments one and three quarters the length of the original fibrils and deposition of flocculent electron-dense material either focally or diffusely around collagen fibrils. The corresponding changes viewed light microscopically are those of fibrinoid necrosis. The sclerohyaline nodule, the characteristic lesion of silicosis, includes all of these features as it evolves through nodular histiocytic and subsequent fibrohistiocytic phases. Its ultimate morphology appears to be determined by the reassembly of the degraded matrix into non-native, fibrous long-spacing collagen via a spiny collagen intermediary. The sclerohyaline nodule occurs infrequently in the spleen and liver, although less typical lesions caused by silica alone or admixed with other dusts seem to occur more commonly in these organs. These lesions appeared as loose or nodular histiocytic or fibrohistiocytic aggregates. Nonspecific fibrous nodules or more extensive fibrosis, as seen in portal triads, may represent advanced stages of such lesions. Acute or healed focal segmental glomerulonephritis occurred in 40 per cent of the cases, suggesting that it may be an important remote effect of silicosis. Continuous destruction of lymphocytes adjacent to silicotic nodules may be an antigenic source of the high concentration of autoimmune reactants described in silicosis.
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PMID:Extrapulmonary silicosis: a clinical, morphologic, and ultrastructural study. 398 8


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