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)

A group of 200 g male Sprague-Dawley rats was injected with 75 mg of quartz (less than 5 mu particle size) and changes in lung DNA, noncollagenous protein, total lipids, and collagen were studied after 6, 24, 72, 96, and 144 hr. Another group of rats received 10, 30, 59, and 75 mg quartz and the above lung analysis was performed 6 days later. Control rats received saline only. Both sets of experiments indicate that striking changes in the above parameters occur very early. The sequence of statistically significant changes was: lung weight (24 hr), DNA (24 hr), noncollagenous proteins (72 hr), total lipids (72 hr), collagen (144 hr). At the dose of 30 mg quartz/lung all the above parameters were significantly increased within 6 days after the lung injury. It is proposed that in early stages of experimental silicosis an excessive amount of collagen accumulates in the lung. Later, some of the deposited collagen is resorbed. This indicates that in the course of the silicotic fibroproliferative inflammation, the balance between collagen deposition and degradation varies.
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PMID:Early changes in the chemical composition of the rat lung after silica administration. 22 75

The type II pneumocyte changes in silicosis are characterized by hyperplasic and hypertrophic epithelial cells, and increased surfactant phospholipids in the bronchoalveolar lavage fluids (BALF). To assess the proliferative activity of alveolar lining fluids, BALF were applied on type II cell cultures. The growth-promoting activity was studied by tritiated thymidine incorporation for 24 h, and the cell number was measured by an electronic counting after a 48-h exposure time. Human BALF from 3 subsets of workers exposed to silica, staged according to ILO classification (silica exposed-workers without disease: hSWD n = 6; workers with simple silicosis: hSS n = 7; workers with confluent silicosis: hCS n = 5), were compared to healthy volunteers (hC n = 6). Sheep BALF from our model of silicosis and control animals (sS and sC) were studied at months 0, 6, and 24 of exposure. A clear enhancement was found in type II cell DNA synthesis under the effect of either normal and silicotic human or sheep BALF, in comparison to the negative control (p less than .05). In addition hSWD and hSS BALF as sS BALF at 20% dilution (peak activity) were significantly more stimulating than the normal alveolar fluids from the same species (p less than .05). The highest sheep BALF stimulatory activity was found at month 6 (170% of increase vs control, p less than .05) and clearly correlated with the high cellularity of BALF. The thymidine incorporation was supported by changes in cell counts. Sheep silicotic BALF run through G50 columns identified at least 3 molecular weight (MW) areas of mitogenic activity between 30 and 5 kDa. Biochemical characteristics of growth factors in the above MW range (PDGF, FGF, TGF alpha, EGF) were tested. Increased mitogenic activity of type II cells eluted from heparin sepharose columns loaded with silicotic sheep BALF, at 0.5 and 1 M NaCl, corresponded to the removal areas of PDGF- and acidic FGF-like heparin-binding molecules. The high proliferative activity on type II cells of the latter two molecules, alone or in combination with other growth factors, was demonstrated in vitro (greater than 9 x control). In conclusion, a stimulatory activity for type II cell growth was found in the normal human and sheep alveolar lining fluid. This activity was clearly enhanced in the early stages of human and sheep silicosis. The BALF type II cell growth factors had biochemical characteristics consistent with the PDGF- and FGF-like molecules.
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PMID:Silica-exposed lung fluids have a proliferative activity for type II epithelial cells: a study on human and sheep alveolar fluids. 132 31

In a survey done in East Germany between 1981 and 1988, we found that 93 of 120 male scleroderma patients had long-term exposure to silica dust. We describe our findings in 12 patients with scleroderma and silicosis. The exposure time to silica dust was between 3 and 34 years; the interval between the beginning of exposure and the onset of scleroderma averaged 27.3 years (range 9 to 40 years). Antinuclear antibodies in titers between 80 and 10,240 with nucleolar and/or speckled patterns were found in 10 patients, antibodies against double-stranded DNA in three, Scl-70 (topoisomerase I) in three, and anticentromere antibodies in five. The following markers of collagen metabolism were increased in serum: beta-galactosidase in 12 patients, laminin peptide-P1 in 10 patients, N-terminal procollagen type III peptide in 10, and urinary sialic acid excretion in 7. We propose that crystalline particles of silica less than 5 microns may be phagocytosed by macrophages and release lymphokines and monokines, which activate fibroblasts and enhance their collagen and glycosaminoglycan synthesis. In addition, silica may act as an adjuvant to increase immune reactivity.
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PMID:Silica-induced scleroderma. 215 53

The activation of collagen synthesis during development of silicotic fibrosis was studied in rats exposed, in dusting chambers, to respirable SiO2 for periods of 2, 4, 6 or 12 months. Control animals were exposed similarly to clean air or TiO2. Development of fibrosis was followed by histological examination, measurement of lung weight and determination of lung collagen content (as hydroxyproline). A steady increase in lung weight and collagen content together with changes in cellularity and metabolic activity of the lungs, as ascertained by chemical determination of DNA and RNA, were measured in the lungs of the SiO2-exposed animals. Hybridization of total lung RNA, extracted at each time point, with cDNA probes specific for type I and type III procollagen mRNA levels showed that the development of fibrosis was associated with increased levels, as compared to age matched controls, of pulmonary procollagen mRNAs. Interestingly, the highest levels of procollagen mRNAs were observed in young (pretreatment control) animals, suggesting that during pulmonary development collagen metabolism in lungs is even greater than during development of fibrosis. In rats exposed to SiO2 the increase in type III procollagen mRNA occurred earlier than the increase in type I procollagen mRNAs. These observations demonstrate both age-dependent and silicosis-related changes in pulmonary procollagen mRNA levels. The results suggest that development of silicosis is associated with an altered capacity of the lungs to regulate collagen accumulation.
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PMID:Characterization of excessive collagen production during development of pulmonary fibrosis induced by chronic silica inhalation in rats. 247 54

Tetrandrine has been used for the treatment of silicosis in China. The potential genotoxic and carcinogenic hazards of this drug were studied using the Salmonella/histidine reversion assay and the SOS/Umu test. The results show that tetrandrine was weakly mutagenic to Salmonella typhimurium TA98 with metabolic activation and did not induce SOS response. However, tetrandrine increased the mutagenic activity of benzo[alpha]pyrene, trinitrofluorenone (TNF), 2-aminoanthracene (2AA), diesel emission particles, airborne particles, and cigarette smoke condensate by more than 100%; the activity of aflatoxin B1 and fried beef was increased by over 75%. It also increased the 2AA and TNF-induced SOS response by more than 300%. These results indicated that tetrandrine was a weak promutagen inducing frameshift mutations and was a potent genotoxic enhancer. The mechanism for the genotoxic enhancement is not known. However, the fact that the increase in mutagenicity was noted only in TA98 and not in TA1538 suggested that the enhancement of genotoxicity by tetrandrine may result from an increase in error-prone DNA repair.
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PMID:Genotoxicity and genotoxic enhancing effect of tetrandrine in Salmonella typhimurium. 264 34

Silicosis is a chronic progressive granulomatous and fibrotic lung disease caused by inhaled silica. Although the causative agent is known, the pathogenesis, especially the immunologic response, is not well understood. We examined two important components of cell-mediated immune responses in the lungs of rats with silica-induced lung disease, i.e., class II (Ia) antigen expression and IL-1 production. The relative density of Ia was examined on isolated alveolar macrophages and type II cells with a solid-phase cellular radioimmunoassay and the percent of Ia positive cells was determined by an indirect immunofluorescent technique. There was a three-fold increase of Ia expression on the alveolar macrophages and nearly a two-fold increase on type II cells from rats with silicosis compared to normal rats. The percent of alveolar type II cells positive for Ia increased by 20%, and the alveolar macrophages increased by 40%. IL-1 in supernatants from cultured alveolar macrophage was measured by the amount of DNA synthesis in an IL-1 dependent cell line (D10). A six-fold increase in IL-1 secretion was noted in macrophage supernatants derived from silica-treated animals. We conclude that in this animal model of silicosis, a local amplification of cell-mediated immune responses may be instrumental in the pathogenesis.
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PMID:Increased expression of class II antigens of the major histocompatibility complex on alveolar macrophages and alveolar type II cells and interleukin-1 (IL-1) secretion from alveolar macrophages in an animal model of silicosis. 278 20

Hepatic silicosis was induced in rats by an intravenous injection of saline-suspended silica, 40 mg/kg of body weight. Changes in the liver were examined by biochemical, histological and histochemical methods. Infiltration of the liver parenchyma by polymorphonuclear leucocytes was observed only on the first day after silica treatment. Formation of silicotic nodules began on the first day by clustering of liver macrophages. A 22% increase in liver weight and a 67% increase in total liver DNA reflected accumulation of cells in the liver by day 28 after silica injection. Local cell division contributed to this increase. Almost all cells in the nodules contained carbon when the rats had been given ink before silica. Macrophages showed high activity of lysosomal esterases on the first few days after silica treatment; the activity disappeared later. Large granulomas containing hundreds of cells including lymphocytes were seen 226 days after treatment. Hydroxyproline content per gram of liver tissue increased by 35% and 58% by day 80 and 162, respectively. Connective tissue formed capsules around the nodules and grew to their inside. Activities of lysosomal enzymes, beta-D-galactosidase and acid proteases, in serum were increased by 20% and 300%, respectively, 35 days after treatment. Neither malondialdehyde concentration nor superoxide dismutase activity was elevated in silicotic liver.
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PMID:Formation of granulomas in liver of silica-treated rats. 309 24

Silicosis is usually attributed to fibroblast stimulation by secretion of damaged alveolar macrophages (AMs), but the role of polymorphonuclear leukocytes (PMNs) and of continuing cell injury in the pathogenesis has not been fully studied. Mice given intratracheal injections of 2 mg of silica received 3H-thymidine 1 hour before death at intervals to 20 weeks. Cellular populations and lysosomal content of lavage fluids were correlated with morphology, DNA synthesis, and collagen content of the lung. The initial response involved rapid PMN and AM recruitment to the alveoli. Some free particles crossed Type 1 epithelial cells, and silica was found in interstitial macrophages. Focal Type 1 cell damage was rapidly repaired by Type 2 cell proliferation. Although PMN numbers dropped after a few days, they never reached control levels and rose again after 8 weeks; the number of AMs fell to control values from 2 to 8 weeks, then increased again. Glucosaminidase and glucuronidase levels in the lavage fluid were much higher than control levels throughout the study. Increased DNA synthesis by interstitial cells occurred from 2 days to 20 weeks; increased collagen synthesis was found from 4 weeks onward. The continuing inflammatory response of the lung to silica suggests may contribute to fibroblastic stimulation.
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PMID:Role of polymorphonuclear leukocytes in silica-induced pulmonary fibrosis. 648 44

In a 59-year old sand-blaster, histologically proven silicosis was complicated by systemic lupus erythematosus (SLE) and focal glomerulonephritis with IgG, IgA and ClQ deposits. Nothing likely to facilitate SLE was detected by investigating the familial background, the HLA phenotype and the complement system. This type of SLE differs from drug-induced lupus-like syndromes by a high level of anti-double helix DNA antibodies and by the renal lesions observed. The connection between silicosis and SLE lies in changes in humoral immunity, i.e. polyclonal activation and production of antinuclear antibodies. A decrease in the number of suppressor T-cells may also be held responsible.
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PMID:[Pulmonary silicosis and disseminated lupus erythematosus]. 663 73

Antiserum against the fibrogenesis controlling macrophage RNase was produced in rabbits. It caused an inhibition of 57% in the RNase activity in vitro. A distinct dose-response relationship was observed in the inhibiting effect of the antiserum on RNase-induced 3H-thymidine incorporation into cultured granulation-tissue fibroblasts. The antifibrogenic properties of the antiserum were also tested in vivo. Rat lungs were made silicotic by intratracheal administration of SiO2. This treatment clearly increased the following parameters: wet weight, DNA, RNA, nitrogen and hydroxyproline content of the lung tissue, and protein concentration, RNase activity, and cell count of the lung lavage fluid. Also, the RNase activity of the lavage fluid cells was increased. Periodical intratracheal administration of the anti-RNase antiserum, optimally at 1:1,000 dilution, decreased the DNA, RNA, and hydroxyproline content of the lung tissue, each by about 30%. The RNase activity of lavage fluid cells was decreased by about 60%. In conclusion the antiserum had no effect on the normal lungs, but it significantly suppressed the development of silicosis.
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PMID:Antifibrogenic effects of antiserum against the macrophage RNase. 683 34


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