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Biomedical subjects

R Burrell

Publications and source records attributed to R Burrell.

At least 37 records · Page 2Linked to original sources

The role of precipitins and complement activation in the etiology of allergic lung disease.

An experimental model of allergic lung disease has been described that is monitored by analysis of arterial oxygen tension following aerosol challenge with antigen. Rabbits immunized to a classical soluble antigen, human serum albumin (HSA), to the point where severe Arthus skin reactivity was demonstrable, were aerosol-challenged with antigen. Arterial oxygen tension measurements made on pre- and post-challenge samples yielded early, late, and continuous response patterns, reminiscent of those obtained in humans following provocation testing. Aerosol challenge of unimmunized animals with HSA resulted in no change from baseline conditions. Unimmunized rabbits exposed to small and massive (10X) aerosols of Aspergillus spores also demonstrated various postchallenge depressions in arterial oxygen tension as well as decreased levels in hemolytic complement activity, depending on the species of fungus and dose of spores used. Unimmunized animals pretreated with cobra venom factor in a manner known to achieve complement depletion failed to respond with altered arterial oxygen tensions following similar aerosol challenge. It is postulated that although precipitins may play a role in artificial disease initiated by soluble antigens, nonspecific complement activation may be more important in understanding the etiology of spontaneous disease in humans brought about by inhalation of moldy particulate matter.

Administration, Intranasal

Induction of fibrogenesis by lung antibody-treated macrophages.

Using a modification of an in vitro model of fibrogenesis, lung connective tissue antibodies have been shown to stimulate macrophages to release a collagen stimulating factor acting on fibroblast target cells. This stimulation was measured by increased hydroxyproline production from fibroblasts that had reached stationary growth phase. In subcytotoxic amounts, this antibody had no such effect directly on fibroblasts. These findings further illustrate the value of studying fibrogenesis by the in vitro method.

Animals

The effect of respiratory immunization on cell-mediated immune effector cells of the lung.

In order to understand the mechanisms of cellular immune injury in hypersensitivity pneumonitis, the effect of type of antigen on cell-mediated immunity in guinea-pigs receiving respiratory immunization was studied. Lymphocytes obtained by pulmonary lavage were compared with those from peritoneal exudate following immunization with either a soluble protein, human serum albumin, or a particulate suspension of Thermoactinomyces vulgaris. Assays were obtained without mixing cells from these two sources. Statistically significant increases (13-22%) in the number of alveolar rosette-forming cells (RFC) were found in the animals immunized with either antigen, but only the particulate T. vulgaris was also capable of inducing a systemic increase of such cells. That this increase in RFC could be due to specifically reactive lymphocytes was demonstrated by the production of antigen-stimulated macrophage migration inhibition. Some evidence was obtained that indicated that T. vulgaris could act both as a non-specific B-cell stimulant and a specific T-cell activator. The concept of a hypothetical pulmonary 'barrier' is discussed which must be overcome to induce systemic immune responses following respiratory immunization. T. vulgaris must be added to the list of known agents or means for overcoming this 'barrier'.

Aerosols

Effects of clonidine on baroreceptor function in anesthetized dogs.

The effects of clonidine (15-30 mug/kg i.v.) on carotid sinus and other baroreceptors were investigated in anesthetized dogs. In 14 control dogs, right carotid sinus pressure was controlled by retrograde perfusion through the common carotid artery at constant flow with femoral arterial blood. Graded reductions in heart rate and blood pressure induced by graded increases in carotid sinus pressure were prevented, whereas reflex bradycardias associated with norepinephrine pressor activity were potentiated by clonidine. Norepinephrine-induced bradycardia, although reduced, still persisted after chronic bilateral sinusectomy and these responses were also potentiated by clonidine. In contrast, clonidine did not potentiate reflex bradycardia in dogs 20 days after aortic stripping. In intact dogs, clonidine inhibited the response to bilateral carotid artery occlusion and to carotid sinus nerve stimulation. These studies suggest that clonidine can inhibit carotid sinus baroreceptor function and simultaneously potentiate other, presumably aortic, baroreceptor activity.

Anesthesia

Immunological studies of experimental coalworkers' pneumoconiosis.

A comparative immunological and microbiological study of experimental coalworkers' pneumoconiosis (CWP) was made in rats and mice subjected to long-term exposures of coal-mine dust aerosols. Such aerosols were realistically prepared at a concentration equal to the maximal level of respirable dust permitted by Federal standards and animals were exposed for lengths of time equal to human work contact. Among the factors studied were the production of IgA and lung reactive antibody, lung microflora and changes in pulmonary clearance. Additional experiments were concerned with the effects of passively administered lung antibody on the pulmonary clearance. It was found that both species responded immunologically in a similar manner to humans with CWP in that IgA levels were significantly elevated and lung reactive antibodies were stimulated. Coal-mine dust inhalation had little effect on the pulmonary inactivation of inhaled bacteria, but the concomitant occurrence of passively administered lung reactive antibody seemed to enhance the inactivation.

Animals

Further studies on the effect of lung antibodies on the pathogenesis of tuberculosis.

A study was made to further clarify the role of lung reactive antibodies in tuberculous infection. Following intravenous infection with viable tubercle bacilli, mice received mouse anti-mouse lung antibodies for three weeks. Control groups consisted of tuberculous mice receiving non-lung antibody containing fluid and uninfected mice. A method was developed for quantitating tuberculous infection in these different groups by expressing the number of lesions produced per unit of cross-sectional surface area of the lung. Passive administration of lung antibodies was found to significantly potentiate the number of tuberculous lesions. It was concluded that the antibody in some way lowered the resistance of the tissue to invasion.

Animals