PubMed Health⌕ Search

Biomedical subjects

R Burrell

Publications and source records attributed to R Burrell.

At least 19 recordsLinked to original sources
PubMed1991

Immunocytochemical determination of the role of alveolar macrophages in endotoxin processing in vitro and in vivo.

Endotoxin (lipopolysaccharide or LPS) inhalation has been implicated in increased pulmonary edema, most likely due to activation of an inflammatory response. The purpose of this study was to determine the cell types in the lung responsible for binding inhaled lipid A from Enterobacter agglomerans LPS. Five-hour exposures of aerosolized lipid A resulted in measurable pulmonary edema in hamsters, as determined by the accumulation of lung water. Immunocytochemistry was used to localize the inhaled lipid A in the cell types in the lung. Alveolar macrophages had decreased levels of lipid A as compared to unexposed controls, suggesting a possible metabolism by the macrophages. In vitro exposure of macrophages to lipid A resulted in a time-dependent clearance of lipid A which was inversely related to its concentration. Alveolar macrophages thus appear to be responsible for the removal of inhaled lipid A in this model and may initiate the physiological events which bring about pulmonary edema.

Administration, Inhalation↗
PubMed1991

The role of platelet-activating factor in the pulmonary response to inhaled bacterial endotoxin.

Quantitative morphometric analyses were carried out on animals subjected to aerosols of bacterial endotoxin (LPS) to further define the role of platelet-activating factor (PAF) in the development of pulmonary injury. Hamsters were exposed to either saline aerosol or dilute aerosols of LPS (4 micrograms/m3) for standard lengths of time. Within each aerosol exposure group, animals were further subdivided into groups receiving either the PAF receptor binding antagonist, RP 48740, or saline injections. LPS inhalation resulted in decreased fixed lung volume, increased sequestration of polymorphonuclear leukocytes and platelets in pulmonary capillaries, increased type I epithelial and endothelial cellular volumes, increased cellular interstitium, and increased endothelial pinocytotic vesicles. Treatment with RP 48740 either attenuated or abolished the ability of inhaled LPS to induce these structural alterations. The PAF antagonist also inhibited LPS-induced increases in pulmonary capillary permeability. It is concluded that PAF is one of the major injury-promoting mediators released upon inhalation exposure to environmentally realistic concentrations of bacterial endotoxin. A major but not exclusive target of this mediator is the pulmonary vascular endothelium.

Animals↗
PubMed1991

Microbiological agents as health risks in indoor air.

Ambient air may be contaminated with or carry significant levels of a variety of potentially harmful microorganisms. There are three major sources of such microbes: a) those arising from microbial decomposition of various substrates associated with particular occupations (e.g., "moldy" hay leading to hypersensitivity pneumonitis), b) those associated with certain types of environments (e.g., Legionnaires' bacteria in water supplies), and c) those stemming from infective individuals harboring a particular pathogen (e.g., tuberculosis). This presentation deals primarily with important microorganisms from occupational and environmental sources and clearly differentiates from case to case transmission via droplet nuclei infection. Microorganisms that are uniformly injurious are differentiated from those that are more opportunistic (i.e., those that cause problems only in people with preexisting debilities). Such microorganisms are categorized according to whether they are allergenic, infectious, or capable of inducing toxic or inflammatory reactions when inhaled. Representative examples from each of these categories, which include bacteria, fungi, rickettsia, and amoebae, are discussed. The conditions responsible for the entrance of significant numbers of these microbes into the air, the mechanisms by which they produce injury, and the methods of prevention are also considered. With attention given to some of the basic sources and requirements for such microorganisms to reproduce and enter the ambient air environment, it is a relatively simple matter to prevent the occurrence of health problems.

Air Microbiology↗
PubMed1990

Toxic risks from inhalation of bacterial endotoxin.

A potential risk for workers exposed to inhalation of endotoxin, as well as the primary tissue changes, is the possibility of subsequent development of adult respiratory distress syndrome. Accordingly, hamsters were administered one hour aerosols of Enterobacter agglomerans and allowed to rest for six hours to produce maximum microlesions in the lung. One hour before this peak, the animals were injected intravascularly with the same suspension used in the aerosol. After one hour the animals were killed and bronchopulmonary lavages were made for analysis of free lung cells. As anaesthesia alone has been reported to be one of the operative procedures that enhance the effect of previous exposure to endotoxin, controls had to include sham anaesthesia with no intravascular injection. Endotoxin inhalation induced significant increases in total number of pulmonary leucocytes, mostly neutrophils, but with a concomitant relative decrease in number of alveolar macrophages. These polymorphonuclear neutrophils are not seen in morphometric analysis of the alveoli. Of greater interest was the large increase in erythrocytes suggesting pulmonary haemorrhages. Such changes were not due to intravenous bacterial alone, and were only significant when the bacteria were inhaled. Taken together with the other known inflammatory effects of inhaled bacteria or bacteria containing endotoxin, such inhalation in an occupational setting constitutes an increasingly recognised risk for workers.

Aerosols↗
PubMed1988

Modulation of pulmonary inflammation after endotoxin inhalation with a platelet-activating factor antagonist (48740 RP).

An acute pulmonary response was induced in guinea pigs and hamsters by inhalation of bacterial endotoxin in the form of a purified lipopolysaccharide (LPS). Pretreatment with the platelet-activating factor (PAF) antagonist, 48740 RP, inhibited damage to endothelial cells, decreased vascular permeability and the number of neutrophils in the airways 24 h after exposure to LPS. The increase in the number of platelets in the airways caused by endotoxin was not affected. The results suggest that PAF modulates early inflammation after endotoxin inhalation.

Administration, Inhalation↗
PubMed1988

Mediators of pulmonary injury induced by inhalation of bacterial endotoxin.

The purpose of this study has been to further define the pathophysiologic aspects of lung injury caused by the inhalation of endotoxin (LPS) using the morphometric approach to identify mediators that influence distal lung structure and function. Hamsters were divided into 3 groups 24 h prior to low dose LPS inhalation exposure (4 micrograms/m3 for 5 h): (1) pretreated with cobra venom factor to deplete complement in vivo, (2) pretreated with indomethacin to block prostaglandin production, and (3) untreated control group. Both pretreatments abolished LPS-induced decreases in lung volume as well as increases in capillary PMN and platelets seen in untreated control animals. Neither pretreatment had any effect on the LPS-induced decreases of other capillary leukocytes. Similarly, both methods of pretreatment failed to block increases in cellular interstitium of distal capillary septa induced with LPS alone. LPS provoked changes in capillary endothelium, especially seen as an increase in numerical density of endothelial pinocytotic vesicles. Decomplementation failed to alter this increase, but indomethacin pretreatment blocked the effect. Neither treatment had any effect on their size. Low dose LPS inhalation also altered pulmonary capillary permeability to a 125I-BSA probe, which was found in significantly greater amounts in LPS-exposed lungs than in those of saline aerosol control lungs, but was not present in the air space as evidenced by negligible counts in bronchoalveolar lavages. It is evident that endotoxin on the epithelial side of the air-blood barrier leads to changes on the other side of that barrier.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Morphometric changes of the lung induced by inhaled bacterial endotoxin.

Due to the ubiquitous nature of airborne endotoxin, an understanding of pulmonary alterations which follow inhalation of environmentally realistic concentrations of purified bacteria derived lipopolysaccharide (LPS) is important. Using LPS derived from Enterobacter agglomerans, a bacterium found in cotton and cotton mill dust, aqueous aerosols (effective LPS concentration 4 micrograms/m3) were generated and used to expose either normal hamsters (N = 6) or those rendered endotoxin tolerant by pre-ip injection of 0.1 LD50 LPS. Control groups (normal--N = 6; tolerant--N = 6) received saline aerosol only. At 6 hr after 5-hr aerosol exposure, lungs of all animals were fixed, processed for light and transmission electron microscopy, and subject to qualitative and to multitiered morphometric analysis using standard point counting techniques. Qualitative evaluation of TEM micrographs from LPS aerosolized-nontolerant hamsters showed endothelial alteration (focal disruption, subendothelial space formation, and cytoplasmic blebbing) but volume and number of endothelial cells were not changed indicating only slight, focal endothelial damage. Quantitatively, septal capillary blood space in nontolerant, LPS aerosolized hamsters showed increased Vv of PMNs and platelets. These changes were not seen in tolerant induced-LPS aerosolized hamsters. Independent of tolerization treatment, LPS inhalation led to a decrease in fixed lung volume and an increase in numerical density of endothelial pinocytotic vesicles. It is concluded that the inhalation of realistic, environmental levels of bacterial endotoxin may induce significant changes in distal lung and may be important in the pathogenesis of byssinosis and adult respiratory distress syndrome.

Aerosols↗
PubMed1985

Comparative toxicity studies between bacterial lipopolysaccharide (endotoxin) and N-formyl methionyl peptide as factors in the pathogenesis of byssinosis.

Comparative in vivo and in vitro studies were made on bacterial lipopolysaccharide (LPS) and the chemotactic peptide NF-Met-Leu-Phe with a view toward studying their possible role in the pathophysiology of byssinosis. In contrast to LPS, chemotactic peptides did not cause Limulus amebocyte lysate gelation, nor did they induce the release of endogenous pyrogen. Inhalation of LPS caused a peripheral leukocytosis in rabbits 30 min after aerosol administration, whereas peptide inhalation caused a significant leukopenia in the same period. Cellular analysis of guinea pig bronchial lavages after LPS aerosol challenge revealed immediate decreases in all cell types, with subsequent, large increases of macrophages and granulocytes 4-24 h after aerosolization. Inhalation challenge with NF-Met-Leu-Phe induced no significant cellular changes. It was concluded that it is unlikely that these microbial products could be confused with each other when administered in pure form by the inhalation route.

Animals↗
PubMed1978

Complement activation by cell wall fractions of Micropolyspora faeni.

The ability of several cell wall fractions of Micropolyspora faeni, a thermophilic actinomycete associated with farmer's lung disease, to activate complement is reported. Cell walls, obtained by mechanical disruption, were purified by enzyme treatment and chemical extractions. Fractions containing the most purified cell walls were most active in consuming complement, as measured by reduction of hemolytic complement levels of normal human serum. Cell wall fractions activated the alternative complement pathway, as shown by monitoring the conversion of C3 proactivator (factor B) to C3 activator (activated factor B) in the presence of specific cation chelators. Selective degradation of cell walls by lysozyme resulted in a decreased ability to consume complement and implicated peptidoglycan as the major complement-reactive component. The role of this nonspecific complement activation in relation to farmer's lung disease is discussed.

Cell Wall↗
PubMed1978

Mitogenicity of cell wall fractions of Micropolyspora faeni.

Cell wall fractions of Micropolyspora faeni, a causative agent of hypersensitivity pneumonitis, have been shown to possess non-specific mitogenic activity for guinea pig, rabbit and human lymphocytes. This activity was unrelated to endotoxin and may not be associated with peptidoglycan. This lymphocyte proliferation stimulus may play a role in the adjuvant properties of this organism and in the etiology of hypersensitivity lung disease.

Animals↗
PubMed1977

Production of thermophilic actinomycete-hay aerosols for use in experimental hypersensitivity pneumonitis.

An investigation of the factors that influence the production of dense aerosols of Micropolyspora faeni and Thermoactinomyces vulgaris from hay cultures revealed that the density, freshness, and moisture content of the hay were important influences. Dry aerosols were produced under optimum conditions from hay cultures of either actinomycete and from sterile hay for inhalation challenges to unimmunized rabbits. Depressions in arterial oxygen tensions and hemolytic complement were monitored after such challenge. This investigation showed that hay cultures are capable of inciting a hypersensitivity-like reaction in the lungs, even in the absence of immunization to the organisms contained within the hay, but the entire hypersensitivity reaction cannot be attributed to M. faeni and T. vulgaris alone. Hay itself or other microbial or chemical components appear to have some heat-stable component that possibly contributes to the pathogenesis of the disease.

Aerosols↗
PubMed1977

Improved methods of producing precipitating aspergillus antigens.

Improved methods for producing Aspergillus fumigatus antigens capable of giving sensitive and reproducible results by counterimmunoelectrophoresis (CIEP) are described. Among the factors investigated were the source of casein hydrolysate used for N source, method of incubating the CIEP slide following a run, effect of freeze pressing and lyophilization, age of culture and ratio of C to N source in the medium.

Antigens, Fungal↗
PubMed1977

III. Mediators of allergic reactions. Endogenous and exogenous stimulating or suppressor substances. Mediators of experimental hypersensitivity pneumonitis.

Using a physiologic model of hypersensitivity pneumonitis where depressions of arterial oxygen tension in unimmunized rabbits are monitored following aerosol challenge with Aspergillus terreus spores, attempts were made to assess the nature of the cellular and pharmacologic mediators of the impairment. Unlike normal animals no PaO2 depressions were obtained following aerosol challenge in either rabbits deficient in C6 or in rabbits made thrombocytopenic with antiplatelet serum. Such aerosols were also shown to produce platelet count depressions of up to 45% in normal rabbits. Finally, in vitro evidence of histamine release was obtained following incubation of Aspergillus extract, platelets and autologous serum from unimmunized rabbits. It was concluded that Aspergillus-induced pulmonary disease may be initiated by platelet release of mediators such as histamine stimulated by nonspecific complement activation.

Aerosols↗