Search PubMed⌕ Search

Biomedical subjects

R Burrell

Publications and source records attributed to R Burrell.

At least 19 recordsLinked to original sources
PubMed1994

Human responses to bacterial endotoxin.

The literature concerning human responses to bacterial endotoxin, in particular to the purified lipopolysaccharide derivative, has been critically reviewed and summarized. Papers selected for review are those that reported studies of human subjects in a normal state of health administered defined doses of either intravenous or aerosol inhaled material. Emphasis was placed on cardiovascular, pulmonary, metabolic, and inflammatory parameters. The information detailed here can be applied to understanding the pathophysiology of human consequences to spontaneous, clinical diseases induced by this highly inflammatory and ubiquitous substance.

Adrenocorticotropic Hormone↗
PubMed1993

Keyhole limpet hemocyanin immunotherapy of murine bladder cancer.

The current treatment of choice for superficial bladder cancer, bacillus Calmette-Guérin, has significant adverse side effects. We have compared two alternative immunotherapies--crude keyhole limpet hemocyanin (KLH) and Immucothel, a KLH modified for clinical use (Biosyn)--in an intralesional mouse model of bladder cancer (MBT2). Crude KLH required either immunization before tumor transplant or frequent intralesional therapy after transplantation to be effective. In addition, Immucothel required pre-immunization to be effective, and increasing the frequency and dosage of post-transplant immunization was not effective without pre-immunization. Preliminary investigations into the KLH-induced anti-tumor mechanism(s) suggest that natural killer cell activity may be involved. Both crude KLH and Immucothel appear to be effective immunotherapies of use in the treatment of transitional cell carcinoma.

Animals↗
PubMed1993

Human immune toxicity.

This review examines xenobiotic toxicity to the immune system, stressing in particular those aspects of most relevance to humans. Immunotoxicity is examined especially from three points of view: by what immunological component is affected, by classes of foreign agents that adversely affect the human immune system and by critical evaluation of human case reports and epidemics. Mechanisms by which xenobiotics interrupt cytokine networks are emphasized. The concept that microbial agents, both environmental as well as infectious, may act as immunotoxicants, either alone or in synergism with conventional agents is introduced. Instances of human immunotoxicology are critically evaluated in terms of clinical relevance, i.e. whether increased susceptibility to opportunistic infections or tumor emergence takes place in the affected individuals.

Animals↗
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↗
PubMed1983

Purification of haptoglobin and its effects on lymphocyte and alveolar macrophage responses.

Clinical observations made on a patient with acute hypersensitivity pneumonitis revealed that the patient's serum contained a mitogenic inhibitor and an extremely high haptoglobin (Hp) level; this led to an investigation of the role of Hp in lymphocyte function. Hp was isolated and purified from acute phase rabbit serum by a new method using DE-52 anion exchange chromatography and preparative isoelectric focusing in a range of pH 3.0-5.0. This technique produced a homogenous, biologically active product in fewer steps and in higher yields than existing techniques. Purified rabbit Hp significantly inhibited polyclonal lymphocyte mitogenic responses to PHA or Con A in a dose-response fashion. Hp also significantly inhibited B-cell mitogenesis at a high concentration (200 mg/100 ml) in response to LPS while it enhanced B-cell mitogenesis at lower concentrations (50 and 100 mg/100 ml). Purified Hp had no effect on monoclonal, antigen-specific (BSA) mitogenesis. Rabbit alveolar macrophages produced significant amounts of prostaglandin E in vitro in response to LPS but Hp had no effect on this production. However, Hp alone caused approximately the same amount of stimulation of PGE production by alveolar macrophages as did LPS alone. The ability of Hp to modulate lymphocyte as well as macrophage function seems to indicate that Hp plays a role in the moderation of inflammation. This ability to moderate inflammation, especially in the lungs, may play an important role in regulating tissue damage and disease following inhalation of inflammatory aerosols.

Alveolitis, Extrinsic Allergic↗
PubMed1983

Importance of anti-lung antibody in farmer's lung disease.

The presence of anti-lung antibody was evaluated in 20 patients with farmer's lung disease. Antibody was found in 14. In patients with disease of less than five years' duration, there was no evidence of any significant differences in vital capacity, total lung capacity, diffusion capacity, and PaO2 between those with and without anti-lung antibody. However, in patients with disease of longer than five years' duration, the diffusion capacity was lower in the anti-lung antibody-positive group (p less than 0.05). The prevalence of abnormalities of vital capacity and diffusion capacity and fibrosis on chest roentgenograms was higher in those who had anti-lung antibody and disease of more than five years' duration. The study suggests that anti-lung antibody is present before permanent measurable physiologic abnormality occurs and may potentiate the pulmonary damage during subsequent episodes.

Adult↗
PubMed1983

Differential toxicity of inhaled gram-negative bacteria.

The toxicity by inhalation of various gram-negative bacteria, isolated from settings associated with inhalation disease, was studied by a variety of means. These microorganisms were not equally toxic. Citrobacter freundii aerosol challenges of rabbits provoked significant (up to fivefold) increases in plasma haptoglobin 24 to 48 h after inhalation. Other strains tested failed to provoke such statistically consistent increases. Measurements of C-reactive protein in these same animals did not lead to as reliable results, due to the variability of the responses. Mice responded differently to inhalation in that haptoglobin responses were either unaffected or depressed. When a strain of mice was used that exhibits more severe inflammatory responses to endotoxin (C3H/HeJ), C. freundii and Escherichia coli aerosols provoked significant haptoglobin increases. Free lung cell analyses demonstrated that the macrophage and neutrophil responses differed depending on the strain of bacteria used. Again, C. freundii induced the greatest responses. When murine B lymphocytes were stimulated with lipopolysaccharide preparations from different gram-negative bacteria, distinctly different dose-response curves were obtained. The types of responses obtained indicate that (i) brief inhalation of bacterial aerosols previously thought to be innocuous may lead to pulmonary inflammation, and (ii) that these bacteria differ in their toxicity, with C. freundii being the most toxic organism of the five studied.

Aerosols↗