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

A group of 191 patients with systemic scleroderma and 12 patients with silicosis-associated scleroderma were investigated for connective tissue turnover. The serum levels of type III collagen aminopropeptide (P-III-P), the laminin PI (Lam PI) fragment and the acid lysosomal beta-galactosidase (beta-Gal) were determined by specific radioimmunoassays and spectrofluorometry, respectively. Increased levels of type III collagen aminopropeptide strongly correlated with enhanced activity of beta-galactosidase. Both parameters correlated with the clinical course in idiopathic systemic scleroderma and in silicosis-associated scleroderma. Serum levels of Lam PI were also found to be elevated in both groups, although there was no correlation with the severity of the disease. Autoantibodies directed against the DNA topoisomerase Scl-70 and against centromeric proteins were found in a similar range in patients with idiopathic systemic and silicosis-associated scleroderma. These results suggest that P-III-P, Lam PI and beta-Gal are useful serological markers of fibrotic activity and demonstrate similarities between idiopathic systemic scleroderma and scleroderma associated with silica-dust exposure.
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PMID:Type III collagen aminopropeptide and laminin P1 levels in serum of patients with silicosis-associated and idiopathic systemic scleroderma. 211 68

The concentration of type III collagen aminopropeptide and the activity of lysosomal beta-galactosidase were determined in the serum of patients with progressive sclerosis (PS), silicosis and PS associated with silicosis. In PS-patients, the serum levels of both parameters were significantly increased with a high correlation to the stage of the disease and to each other. In patients with silicosis normal serum concentrations of both parameters were found, whereas in all patients suffering from silicosis and PS significantly elevated serum levels were detectable, independent of the stage of PS. Both parameters can also be used as markers of therapy (e.g. with D-penicillamine) and as early indicators for the development of PS in patients with silicosis.
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PMID:[N-procollagen(III)peptide and lysosomal beta-galactosidase in progressive scleroderma and silicosis]. 212 55

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 deposition of silica particles in the lung of man or experimental animals leads to silicosis, a disease of progressive respiratory failure caused by a fibrotic reaction. It has long been suspected that the phagocytosis of silica by pulmonary macrophages induces the secretion of fibrogenic factors. Several potentially fibrogenic cytokines released by macrophages have been identified, including interleukin-1 (IL-1), tumour necrosis factor-alpha (TNF), platelet-derived growth factor, basic fibroblast growth factor and transforming growth factor-beta (TGF-beta). Here we show that TNF plays an important part in silica-induced pulmonary fibrosis in mice in that (1) a single instillation of silica leads to a marked increase in the level of lung TNF messenger RNA which lasts for greater than 70 days, while there are no obvious changes in the amounts of IL-1 alpha or TGF-beta mRNAs; and (2) silica-induced collagen deposition is almost completely prevented by anti-TNF antibody, but is significantly increased by continuous infusion of mouse recombinant TNF.
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PMID:Requirement of tumour necrosis factor for development of silica-induced pulmonary fibrosis. 215 65

Progressive systemic sclerosis (PSS) is a rare disease belonging to the collagen diseases. PSS is frequently observed in workers with an intensive exposure to crystalline silica and with silicosis in the GDR. The recognition as an occupational disease is regulated by law. The elevated beta-galactosidase activity in the serum of patients with silicosis and beginning PSS can be used for detecting of early stages of PSS. References are given to medical care of patients with silicosis and exposure to quartz.
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PMID:[Early detection of scleroderma in quartz dust exposed workers and workers with silicosis by determining serum beta-galactosidase activity]. 215 84

Xifukang is a compound preparation of Chinese herbs consisting of Hanbane grugs mainly. Since 1987, the significant efficiency have been obtained in treatment of 53 patients suffering from silicosis by self-control study. The results indicated that the clinical manifestations including dyspnea, cough, sputum production, chest pain, weakness, etc. were markedly improved (P less than 0.01) and measurements of pulmonary function (FVC, FEV and MVV) significant enhanced (P less than 0.01). After treatment 20 cases roentgenogram exam showed that the lung's clarity and the limited emphysema were improved, the silicolic nodule and mass-mergence opacity of 3 cases lessened in some degree. By discussing the effect of Xifukang which might lower the collagen protein content of experimental silicosis of Wistar rats and improve pathomorphous. The authors concluded that the therapeutic mechanism of Xifukang could be the actions of this remedy on promoting blood circulation to eliminate blood stasis dredging microcirculation, increasing ventilation/perfusion (VA/Q), protecting dust-cells, resisting fibrosis, regulating immune function, enhancing lung clearance, postponing and preventing development of silicosis.
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PMID:[Clinical therapeutic effect of xifukang in 53 patients with silicosis]. 220 23

A single intratracheal injection of 50 mg crystalline silica (quartz) into rats produces silicosis. This animal model may be used to study collagen metabolism during the early, middle, and late phases of lung injury, corresponding respectively to the stages of lung injury, development of discrete granulomas, and development of mature silicotic nodules. The early phase is characterized by a rapid increase in the rate of synthesis of lung collagen (within one week of instillation) and increased deposition of excess lung collagen (significant increases within two weeks of instillation). Later phases are characterized by a continuing increase in deposition of excess lung collagen for at least one year after instillation. Silica-induced fibrosis is unique among all the animal models (and in most human fibrotic diseases) thus far examined, in that the excess collagen deposited in the lung contains normal ratios of the two major collagen types of the lung: types I and III. This collagen is nonetheless biochemically different from normal lung collagen. There are reproducible and characteristic differences in the intermolecular cross-links of the collagen in lungs from rats injected with silica. Within one month of silica instillation (the earliest time point examined thus far), an increased hydroxylysine content of collagen can be appreciated. The reducible dysfunctional cross-links are also more likely to be derived from hydroxylysine (i.e. the ratio of dihydroxylated to monohydroxylated cross-links increases). Within four months of silica instillation (and increasingly thereafter), increased amounts of the mature trifunctional cross-link hydroxypyridinium (derived from three residues of hydroxylysine) can also be appreciated, seemingly paralleling the evolution of mature silicotic nodules in these lungs. These changes in cross-linking of lung collagen seem to be common to all the animal models of pulmonary fibrosis examined, and are also consistent with changes occurring in human fibrotic lungs. Preliminary observations suggest that the locus of cross-linking remains the same: hydroxylysine replaces lysine in the primary structure of a specific collagen alpha chain to form the altered cross-links. Thus, there may be molecular markers for the collagen of fibrosis in diseased lungs.
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PMID:Effects of silica on lung collagen. 242 84

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

Silicosis was produced experimentally in rats by single intratracheal injections of various doses of SiO2 dust. The weight of the lungs as well as the contents of total nitrogen, collagen, nucleic acids (especially RNA), and lipids increased in accordance with the dose and the time interval. Fibrogenic stimulation in vitro was shown by the supernatant of the homogenized lung in the incorporation of proline into incubated granulation tissue or lung fibroblasts. The fibrogenic factor-activity depended more on the time interval after the injection than on the SiO2 dose. Electrophoresis of the soluble proteins in the silicotic rat lungs showed a protein of 16,000 Da, which was dependent on the time interval following SiO2 administration as well as on the dose itself, and which originated from macrophages. This protein was purified by repeated gel-filtration chromatography. It stimulated collagen synthesis in granulation-tissue cells at a concentration of about 10(-10) M in a dose-dependent way. It was acidic by amino acid composition but differed from calmodulin which also increased collagen synthesis in granulation-tissue cells in vitro. The ability of non-fractionated macrophage preparations to stimulate the incorporation of proline into collagen correlated inversely with the gross alkaline RNase activity.
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PMID:Isolation of silica-dependent protein from rat lung with special reference to development of fibrosis. 254 36

The role of the immune system in modulating pulmonary damage evoked by exposure to silica crystals has been examined in a mouse model of experimental silicosis. Congenitally T cell-deficient mice (Balb/c nu/nu) were compared with T cell sufficient mice (Balb/c nu/+) in the degree of silica-induced cellular inflammation on days 3, 5, 7, 30, and 60 after an intratracheal instillation of silica. Cellular inflammation was assessed by increases in the total number and type of inflammatory cell in lung lavage fluid and in lung tissue. Inflammation and/or injury were also measured in the lavage fluid by increases in total protein, angiotensin-converting enzyme and plasminogen activator. No significant difference existed between the two types of mice in total lavage cell number or total protein. In nu/+ mice, the neutrophil predominated early, followed by the macrophage as the major inflammatory cell. However, in nu/nu mice, the neutrophil remained the predominant inflammatory cell throughout the two months postinjection. In addition, angiotensin-converting enzyme levels remained elevated in the nu/nu animals above those in the nu/+ mice whereas plasminogen activator was elevated early (before day 7) in both, and decreased comparably over time. These data suggest that T cells directly or indirectly influence the maintenance of a macrophage infiltrate and the termination of a neutrophil response after exposure to silica. However, it appears that neither T cells nor the cells they influence affect the ultimate amount of collagen deposition.
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PMID:Role for T lymphocytes in silica-induced pulmonary inflammation. 254 72


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