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Biomedical subjects

M J Reasor

Publications and source records attributed to M J Reasor.

At least 91 records · Page 5Linked to original sources

Toxicity of metal ions to alveolar macrophages.

Significant concentrations of metals are found in the respirable particulate effluents associated with metallurgical smelters. In this investigation the effects of the metallic ions lead, cadmium, iron, mercury, aluminum, chromium, and nickel on various aspects of alveolar macrophage function were studied. The production of antibacterial substances (ie, reactive forms of oxygen) by these cells and oxygen consumption are very sensitive to the metals. Particle uptake displays moderate sensitivity, while lysosomal enzyme activity and membrane integrity are fairly resistant to metals. In addition, the effects of the organic solvents carbon tetrachloride, toluene, and xylene on alveolar macrophage function were tested. These solvents were found to inhibit oxygen consumption and the release of antibacterial substances while not greatly affecting membrane integrity. The results of these experiments indicate that some metals and some organic substances are toxic to alveolar macrophage function.

Animals↗

Cumene hydroperoxide-mediated lipid peroxidation in rat alveolar macrophages following induction of phospholipidosis with chlorphentermine.

Rats were treated for 4 weeks with chlorphentermine hydrochloride (30 mg/kg, i.p., 5 days/seek), a regimen which causes a profound phospholipidosis in the alveolar macrophages (AMs). The susceptibility of these lipid-laden cells to lipid peroxidation was examined and compared to AMs from control (untreated) rats. Lipid peroxidation was induced in cells in vitro by incubation with cumene hydroperoxide (10(-5) M--10(-3) M). A dose dependent increase in malonyl dialdehyde (MDA) formation was observed with both populations of AMs. Two to three times more MDA was found in lipidotic AMs than controls at the higher dose of cumene hydroperoxide. Under these conditions, less loss of cellular viability resulted with the lipidotic AMs than controls. The partial depletion of reduced glutathione in the cells led to an even greater MDA formation by both cell-types with the lipidotic AMs being more markedly affected. Both populations of AMs experienced a greater loss of viability associated with loss of reduced glutathione with the control AMs showing more toxicity than the lipidotic cells. Therefore, while the induction of phospholipidosis renders AMs more suspectible to lipid peroxidation, they show less of a loss in cellular viability than control cells. The previously reported augmentation in the antioxidant defense mechanisms in the lipidotic cells may be partially responsible for these results.

Animals↗

Comparison of the interaction of tricyclic antidepressants with human polymorphonuclear leukocytes as monitored by the generation of chemiluminescence.

The interation of imipramine with human polymorphonuclear leukocytes (PMNs) results in a chemiluminescence (CL) response which has been attributed to the electronic excitation of the imipramine molecule resulting from a reaction of the drug with reactive oxygen species. In order to determine what portion of the tricyclic molecule is involved in this reaction, the interaction of other tricyclics with PMNs was monitored by chemiluminescence. It was observed that tricyclic antidepressants having a carbon atom at position 5 of the ring moiety (amitriptyline, for example) did not yield CL with either resting or zymosan-activated PMNs. In fact this group of compounds inhibited the zymosan-induced CL response. However, CL was observed, with both resting and metabolically-activated PMNs, from several tricyclics having a heterocyclic nitrogen at position 5. These included imipramine, desipramine, opipramol and iprindole. Chlorimipramine, which has a chlorine atom at position 3 of the ring system, failed to yield CL with resting or stimulated cells. Similarly, imipramine N-oxide failed to yield CL with resting cells, but enhanced CL was observed with zymosan-activated PMNs. On the basis of these observations it appears that some aspect of the ring moiety, other than just a heterocyclic nitrogen, facilitates a reaction between these molecules and reactive oxygen which culminates in the generation of CL.

Antidepressive Agents, Tricyclic↗

Enrichment of albumin and IgG in the airway secretions of dogs breathing ozone.

A study was undertaken of the acute effect of the inhalation of ozone (1.0-1.5 ppm) on the concentration of proteins in the airway secretions harvested from the trachea of intact anesthetized dogs. Secretions were first collected during a control day during which room air was breathed. The dogs breathed ozone (1.0-1.5 ppm) on a second day. This protocol permitted each dog to serve as its own control. During the inhalation of ozone the concentration of total aqueous-soluble proteins, as well as of albumin and IgG were not significantly effected. However, when expressed as a percentage of total protein, both albumin and IgG were significantly enriched in the secretions. The quantitative changes of certain proteins in airway secretions may be an important reflection of the pulmonary response to ozone.

Administration, Intranasal↗

Tracheobronchial secretions collected from intact dogs. I. Protein and mucous glycoprotein composition.

Tracheobronchial secretions (TBS) were collected in situ from intact, anesthetized dogs, and the protein composition and distribution were studied. TBS were separated into supernatant and pellet phases by centrifugation. The supernatant phase comprised 85%, by weight, of the secretory mixture; yet it contained only 58% of the total protein. Peptides of apparent molecular weights ranging from 16,000 to 154,000 daltons were present in the supernatant phase. Electrophoretic and immunochemical comparisons with canine serum suggested that certain of the peptides were of plasma origin including albumin, IgG, IgA, and IgM. Albumin and IgG comprised approximately 70% of the supernatant phase protein. Three percent of the total TBS protein was contributed by the peptide portion of mucous glycoproteins (mucins), and 97% of the mucin protein separated into the pellet phase. When compared to mucus collected from a canine tracheal pouch, TBS was less concentrated in mucins, and differences were observed in electrophoretic profiles between the two samples.

Animals↗

Tracheobronchial secretions collected from intact dogs. II. Effects of cholinomimetic stimulation.

The effect of cholinomimetic stimulation on the quantity and composition of tracheobronchial secretions (TBS) collected from intact dogs was studied. After the administration of methacholine chloride, the collection rate of TBS increased over threefold within 10 min and returned to the control level by 50 min. Even though there was an increase in the total amount of protein collected, the protein concentration of the secretions decreased initially by 40%, returning to normal by 30 min. This was the result of an apparent dilution of the secretions by nonproteinaceous components. In addition, at 10 min, there was an increase in the protein associated with mucins. These responses were blocked by the preadministration of atropine. When TBS was separated into supernatant and pellet phases by centrifugation, we found that, following methacholine, there was a 35% increase in the ratio of albumin to IgG in the supernatant phase. These results suggest that the increased secretion due to methacholine may result, in part, by a selective filtration of fluid from the interstitial and/or vascular compartment(s) with proteins appearing in the secretory mixture based partially on their size.

Animals↗

Composition of bronchoalveolar lavage effluents from patients with pulmonary alveolar proteinosis.

The lungs of patients with pulmonary alveolar proteinosis were lavaged with saline. The lavage effluents were examined for the presence of unusual components which might be considered characteristic of the disease. Soluble proteins were resolved by electrophoresis on polyacrylamide linear gradient (2.5 to 27 per cent acrylamide) gel slabs and compared with proteins found in the patients' sera and lavage effluents from nondiseased human lungs. Many proteins in lavage effluents from both diseased and nondiseased lungs appeared similar to those found in serum. Several proteins from diseased lungs were not present in serum nor lavage effluents from nondiseased lungs. A number of proteins present in lavage effluents from nondiseased lungs appeared to be absent from lungs with alveolar proteinosis. Particulate components of lavage effluents from diseased and normal lungs were examined and compared using the electron microscope. Many particulate components including degenerate and disintegrating cells, ultrastructurally abnormal alveolar macrophages, and myelin-like structures were present in lavage effluents from diseased lungs but absent from normal lungs. Much of the particulate material resembled cell debris. The insoluble accumulations present in the pulmonary alveoli and airways of patients with alveolar proteinosis do not come from serum leakage nor from hypersecretion of materials normally found in these regions of the lungs. The major insoluble components appear to arise from cellular disintegration and the extracellular formation of myelin-like structures.

Blood Proteins↗

Chemiluminescence resulting from an interaction between imipramine and human polymorphonuclear leukocytes.

The addition of imipramine to a suspension of resting polymorphonuclear leukocytes (PMNs) resulted in the generation of chemiluminescence (CL) (100,000 cpm with 1 X 10(-4)M imipramine). In the presence of a particle (zymosan) capable of activating the PMNs to generate reactive oxygen species, the magnitude of CL observed with 1 X 10(4)M imipramine was greatly enhanced (greater than 1,000,000 cpm). No CL was detected upon the addition of imipramine to PMNs isolated from a chronic granulomatous child or to alveolar macrophages isolated from rats. Another tricyclic antidepressant, amitriptyline, failed to generate CL with PMNs either alone or in the presence of zymosan; however, both imipramine and amitriptyline generated CL upon addition to the xanthine oxidase-purine superoxide generating system. Although the mechanism by which this drug-cell interaction results in the generation of CL is not known, the observations are suggestive that the CL may originate, in part, from the activation of imipramine by some reactive oxygen state(s).

Amitriptyline↗

Collection of normal canine tracheobronchial secretions.

A technique is described for the collection of tracheobronchial secretions from the upper trachea of anesthetized dogs. The method is simple, relatively quantitative, and provides secretory material in quantity suitable for biochemical or rheological studies. In 42 experiments comprising 184 individual samples we have found the collection rate of tracheobronchial secretions to be 1.0 +/- 0.1 mg/min per kg (mean +/- SEM).

Animals↗