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Biomedical subjects

P C Major

Publications and source records attributed to P C Major.

At least 19 recordsLinked to original sources

Serologic changes in pneumoconiosis and progressive massive fibrosis of coal workers.

Serum from 109 coal workers with simple pneumoconiosis, 114 with progressive massive fibrosis, and 130 with normal chest radiographics as control subjects was examined for rheumatoid and antinuclear factors, and antibodies against both native human IgG and Mycobacterium tuberculosis. A significantly greater prevalence of autoantibodies was observed in subjects with pneumoconiosis than in control subjects; however, a rheumatoid factor prevalence of 16% with observed inthe control subjects. No serologic differences were observed between subjects with simple pneumoconiosis and those with progressive massive fibrosis.

Adult↗

Cotton dust and complement in vivo.

Cotton grown in Stoneville, Mississippi and harvested by three different methods was examined for anticomplementary activity in human serum in vivo. Subjects exposed to cotton dust in a model cardroom for six hours showed changes in C3c and CH50 after exposure to closed boll harvested, bract removed cotton dust when compared with a group of normal, unexposed controls. Decreases in C3c, :C4, and C3A were associated with decreases in FEV1 after exposure to closed boll harvested bract intact cotton dust. The data from this preliminary study suggest in vivo associations between inhalation of cotton dusts and complement which appear to be independent of endotoxin contamination. These findings suggest a relationship between cotton dust inhalation and complement-mediated respiratory impairment.

Adolescent↗

Immune mechanisms in byssinosis.

The pathogenesis of byssinosis has been attributed to several different immunopathologic mechanisms, including a type III (immune complex) pulmonary injury. To further examine this type III theory, sera (Monday preshift) from 59 cotton textile workers were examined by gel diffusion and counterimmunoelectrophoresis for precipitating antibodies to aqueous extracts of cotton bract, carpels, stems, leaves, immature cotton bract, carpels, stems, leaves, immature cotton lint, and cardroom cotton dust. Sera were also collected from 35 nonexposed normal volunteers and examined similarly. No true precipitating antibodies to these extracts could be detected in any of the control or worker serum samples. The aqueous extracts of cardroom cotton dust and cotton stems were found to contain naturally occurring components that precipitated (in agarose gel) beta-lipoprotein and gamma-globulins (mostly IgG) in a nonimmunologic manner. Sera from normal human controls and cotton textile workers all produced identical patterns of reaction with these two extracts. Treatment of these extracts with polyvinylpolypyrrolidone, a specific insoluble adsorbent for polyphenolic tannins, eliminated this pseudoimmune reaction. Although the role this pseudoimmune reaction may play in the pathogenesis of byssinosis is still unknown, it demonstrates the problems associated with laboratory-based investigations of the immunologic aspects of byssinosis.

Antibodies↗

HLA-B8 in sarcoidosis.

One hundred and seventy-four unrelated white patients with biopsied and clinically diagnosed sarcoidosis and a reference population of 97 were tested for HLA antigens. Selected comparisons showed a statistically significant association of HLA-B8 with the sarcoidosis group (28.9%) when compared to the reference group (15.5%).

Chromosome Mapping↗

Immunology of clinically inactive sarcoidosis: serum factors.

Sera from 84 white patients with inactive sarcoidosis were analyzed for immunoglobulins, complement, autoantibodies, alpha 1-antitrypsin and lysozyme. The levels of serum factors were compared with levels in serum from a reference population which was matched for age, sex, ethnic background and geographic location. IgG, IgA, IgD, and C3 levels were similar for both groups, as were frequencies of rheumatoid factor, antinuclear antibody and anti-DNA antibody. Lysozyme levels were significantly lower in the inactive sarcoidosis group but the acute phase reactants alpha 1-antitrypsin, IgM as well as complement consumption were increased. The data suggest that the underlying etiological events of sarcoidosis continue, albeit at a subclinical level.

Adult↗

Complement activation by commercial allergen extracts of cereal grains.

Commercial allergen extract preparations of whole cereal grains were examined in vitro for their reactivity with the human haemolytic complement cascade. Total haemolytic complement was consumed in a dose-dependent manner which did not correlate with the protein nitrogen content or bacterial endotoxin contamination of the extracts. Alternative pathway activation was shown by C3 conversion in the presence of EGTA while classical complement components C1, C4 and C2 were also much decreased in serum which was free of detectable specific antibody. Very small amounts of allergen extract initiated the formation of complement-dependent factors which were chemotactic for human polymorphonuclear leucocytes. These data suggest a potential for complement activation in vivo by ingestion, inhalation, or injection of cereal grain products.

Allergens↗

Extracts of airborne grain dusts activate alternative and classical complement pathways.

This study investigated the action of aqueous extracts of airborne grain dusts on the human alternative and classical complement pathways. Extracts were shown to consume hemolytic complement in vitro in a dose-dependent manner. No relationship was determined between complement activity ranking and either protein or endotoxin levels. Differential serum chelation with EDTA or EGTA showed that the alternative pathways were activated, while hemolytic titers of the early complement components (C1, C4, C2 and C3) showed that the classical pathway was also involved. Extract-treated sera were chemotactic for human polymorphonuclear leukocytes and complement was required. The in vitro data suggest the potential for the in vivo contribution of the activation of the complement cascade (by either pathway) in eliciting pulmonary pathophysiology after the inhalation of airborne grain dusts.

Chelating Agents↗

SEM studies on the in vivo uptake of Aspergillus terreus spores by alveolar macrophages.

Pulmonary reactions to fungal spores constitute an important aspect of occupational pneumoconioses. Experimental models using aerosols of Aspergillus terreus spores produce an acute, complement dependent, hypoxic reaction in rabbits. The purpose of this study was to explore the possible role of the alveolar macrophage in initiating this reaction. Rabbits and rats were intratracheally injected with Aspergillus spores and the fate of the spores was studied at various times thereafter by light and scanning electron microscopy complemented by heavy metal staining and backscattered electron imaging. The uptake of spores by macrophages on the surface of the alveoli and airways was extremely rapid and was virtually complete by 3 hrs. Very few polymorphonuclear leukocytes were seen in the lungs of exposed animals. Penetration of the lung epithelium by spores was minimal and was not directly observed. Alveolar clearance followed by mucociliary clearance of the spores was observed in the rats. Failure of the clearance mechanisms at the level of the respiratory bronchiole produced necrotising lesions that contained numerous free spores. This study illustrates the value of heavy metal stains combined with backscattered electron imaging for observing surface and subsurface features in biological tissues.

Animals↗

In vitro activation of the alternative pathway of complement by settled grain dust.

Settled grain dust was collected from several active grain elevators in the Superior-Duluth areas of the United States. Particle size distribution (47% less than 5 micrometer) and endotoxin contamination (429 ng/gm) of the dust were similar to those reported for the airborne parent dust. Human complement uas activated in vitro in a dose-response manner which could be quantified. This hemolytic consumption was via the alternative pathway as defined by ethylenediaminetertraacetic acid/ethylene-glycol-bis-(beta-amino-ethyl ether) N,N'-tetraacetic acid (EDTA/EGTA) differential serum chelation, factor B conversion, and complement reductions in serum from guinea pigs deficient in C4. It is proposed that continuous low-dose exposure to aerosolized, biologically active rafter dust could contribute to the respiratory insult of grain workers.

Complement Activation↗

Activation of the alternative pathway of complement by grain. I. C3PA conversion and quantification of complement consumption by rye.

Ground whole rye and airborne rye dust of comparable size distribution were tested for their ability to activate the complement cascade via the alternative pathway. Precipitin-negative pooled normal human serum was incubated with increasing amounts of the two rye dusts. Electrophoresis of the resultant supernatant fluids demonstrated the conversion of the proactivator of the third component of complement to the gamma-migrating activator of the third component. This activation was completely prevented by pre-treating the serum with the chelator EDTA, while pre-treatment with EGTA allowed suboptimal arc conversion, strongly implying that complement was activated via the alternative pathway. Quantification of the supernanant fluids showed dose-dependent complement consumption as defined by both CH100 immunodiffusion and CH50 tube haemolytic techniques. Airborne rye dust showed a greater quantitative potential than ground whole rye for activating the alternative pathway. These results indicate the possibility of the direct action of airborne organic dusts on the induction of inflammatory sequelae in the lungs of both sensitized and unsensitized individuals.

Air Pollutants↗