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Biomedical subjects

L Bowman

Publications and source records attributed to L Bowman.

At least 91 records · Page 5Linked to original sources

Toxicity of metallic ions in the lung: effects on alveolar macrophages and alveolar type II cells.

Airborne metallic particulates are associated with fossil-fueled power plants, automobile exhausts, metal mining, and metallurgical smelters. Therefore, the possible toxic effects of metals on the lung are of environmental and occupational concern. In this investigation we determined the effects of in vitro exposure to metallic ions on the following parameters: oxygen consumption and membrane integrity of alveolar macrophages and type II cells, and chemiluminescence of zymosan-stimulated alveolar macrophages. Cu2+ and Zn2+ exhibited marked toxicity to isolated alveolar macrophages and type II cells, while V3+ exhibited intermediate toxicity. In contrast, short-term in vitro exposure to As5+ and Se4+ had little effect on alveolar macrophages and type II cells. Although the data suggest that exposure to certain metals may be harmful to the lung, the various pulmonary parameters tested in this investigation display differing susceptibility to metal exposure. That is, metals are less toxic to alveolar type II cells than to alveolar macrophages. Our data also indicate that chemiluminescence is the most sensitive assay for monitoring the viability of alveolar macrophages, while oxygen consumption is a sensitive assay for type II cells.

Animals↗

Incorporation of [3H]palmitate into disaturated phosphatidylcholines in alveolar type II cells isolated by centrifugal elutriation.

In order to study synthesis of pulmonary surfactant materials, we measured incorporation of [3H]palmitate into disaturated phosphatidylcholines (PC) in alveolar type II cells isolated by centrifugal elutriation. The time course for this process is not linear and, at high external palmitate levels (1 mM), incorporation is maximal in 4-5 h. Incorporation is dependent on extracellular palmitate with a Vmax (at 1 mM) of 1.66 nmol palmitate incorporated into disaturated PC/4.2 X 10(5) cells per 2 h and a K1/2 of 0.1 mM palmitate. Addition of an optimal amount of extracellular choline (0.05 mM) increases Vmax and decreases K1/2 for palmitate. Incorporation of palmitate is dependent upon cell number, inhibited by extracellular Ca2+ and stimulated by external Mg2+. Cholinergic and beta-adrenergic agonists do not increase incorporation. Pulmonary lavage fluid inhibits incorporation of palmitate into disaturated PC, suggesting there is negative feedback involved. Disaturated PC which has been recently synthesized (i.e., over a 2 h period) is broken down intracellularly by type II cells when they are suspended in palmitate-free medium. These results indicate that (1) several factors, such as substrate levels, cell number, Ca2+, Mg2+ and amount of surfactant present, are involved in the regulation of palmitate incorporation into disaturated PC; (2) disaturated PC which has been recently synthesized may be broken down by type II cells; and (3) surfactant synthesis in freshly isolated cells differs slightly from that reported by other investigators in type II cells maintained in primary cell culture.

Animals↗

The prevalence of dental fear and avoidance: a recent survey study.

This study evaluates the current incidence of dental fear and avoidance in the general population. A telephone survey, using a random dialing procedure, was used as a means of data collection. Results indicated that 11.7% of the respondents reported high dental fear, and another 17.5% reported moderate dental fear. Results also disclosed that 36.5% of those surveyed had not been to the dentist in over a year. Approximately 15.5% of the respondents surveyed had some degree of dental fear and were dental avoiders (using the criterion of no dental visitation for at least one year). These findings highlight the fact that additional attention and research efforts still need to be dedicated to dealing with the highly fearful and avoidant dental patient.

Adult↗

Transport properties of isolated type II alveolar epithelial cells.

Type II cells are granular cells located in the alveolar epithelium. In addition to the synthesis and secretion of surfactant, these pneumocytes exhibit several other interesting properties. Although type II cells possess a high permeability to sodium, they maintain a low free intracellular sodium concentration by the presence of a Na-K pump. The activity of the Na-K pump is high and can result in substantial net movement of solute and water. Therefore, type II cells may employ this pumping capacity to play a significant role in the transepithelial transport of water. Type II cells are also relatively resistant to oxidant damage and play a role in the regeneration of the alveolar epithelium after oxidant injury. Ascorbate is a known antioxidant that is accumulated by type II cells via a specialized transport system for the uptake of ascorbate and sodium. The presence of this specialized transport system in type II cells and alveolar macrophages may explain in part why these cells are more resistant to oxidant injury than other pneumocytes.

Animals↗

Volcanic ash: toxicity to isolated lung cells.

Samples of volcanic ash from Mount St. Helens were collected from Spokane, Washington, after the major eruption of May 18, 1980. The toxicity of ash to the lung was estimated by monitoring the effects of in vitro and in vivo exposure on various physiological parameters of isolated lung cells. Volcanic ash had little effect on O2 consumption of rabbit type II pneumocytes, O2 consumption or superoxide release of resting rat alveolar macrophages, or membrane integrity of rat alveolar macrophages. Ash also caused no significant lipid peroxidation in rat lung microsomes. However, volcanic ash did inhibit superoxide anion release from zymosan-stimulated rat alveolar macrophages. Since superoxide is an antibacterial substance, this result suggests that exposure to volcanic ash may adversely affect the ability of alveolar macrophages to protect the lung from infection.

Animals↗

Transmembrane potential changes during phagocytosis in rat alveolar macrophages.

Studies were carried out to measure changes in the transmembrane potential of rat alveolar macrophages during exposure of the cells to zymosan particles or to the membrane perturbant, phorbol-12-myristate-13-acetate (PMA), and to determine if changes in membrane potential are related to superoxide anion release. Exposure of the cells to either zymosan or PMA leads to membrane depolarization, which precedes superoxide anion release. Furthermore, the magnitude of the depolarization is dependent upon the concentration of either zymosan or PMA. During exposure of the alveolar macrophages to increasing levels of zymosan, there is an increase in the amount of superoxide released as well as an increase in the magnitude of the depolarization. Incubation of the cells in medium containing 150 mM K+, a medium which causes membrane depolarization, leads to superoxide release from resting cells and a decrease in the amount of superoxide released from cells exposed to zymosan. These results indicate that release of superoxide anion from rat alveolar macrophages is related to membrane depolarization and suggest that the transmembrane potential change may act as a signal to initiate the phagocytotic responses of the cells.

Animals↗

Factors which affect superoxide anion release from rat alveolar macrophages.

In order to investigate some of the characteristics of superoxide anion release from alveolar macrophages, the effects of substances known to influence superoxide release from polymorphonuclear leukocytes (PMN) were studied in rat alveolar macrophages. There is a relatively small, but constant, amount of superoxide released from alveolar macrophages at rest. The amount released increases 5- to 6-fold and becomes maximal in about 20-30 min following exposure to unopsonized zymosan particles. The rate of superoxide release is maximal only 2 min after exposure of the cells to particles, i.e., long before particle uptake is complete. In addition to particles, release of superoxide anion can be stimulated by phorbol-12-myristate-13-acetate (PMA). Lectins and chemotactic factors, which stimulate release in PMN, have little or no effect in alveolar macrophages. Superoxide release during exposure to zymosan appears to be dependent upon extracellular Ca++. Also, the release mechanism can be affected by the addition of cyclic AMP or various protein modifiers to the medium. Since many of these findings differ from those reported by others for PMN, the control of superoxide anion release from alveolar macrophages and PMN is probably different.

Animals↗

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↗

Transmembrane potential and ionic content of rat alveolar macrophages.

The cell volume, cell water, intracellular ionic concentrations, and transmembrane potential of rat alveolar macrophages were determined. The measurements were made on cells which had been separated from the medium by centrifugation through dibutyl phthalate in order to greatly reduce the trapped extracellular space. The mean cell volume of the alveolar macrophages is 1,525 cubic microns and 72% of this volume is water. The intracellular fluid is high in Na+ (97 mM) and lower in K+ (50 mM) and the intracellular Cl- concentration in 64 mM. The transmembrane potential, as measured from the equilibrium distribution of tritiated triphenylmethyl phosphonium and by using the fluorescent probe, Di-S-C3(5), is approximately -37 millivolts. Neither Na+, K+, nor Cl- is distributed at equilibrium. However, the K+ permeability of alveolar macrophage membranes appears to be greater than Na+ permeability.

Animals↗

Cognitive flexibility in hypnosis: response to change communication from the hypnotist.

It was predicted that modification of response as it indexes cognitive flexibility in the hypnotic subject is related to susceptibility to hypnosis and the difficulty of the hypnotic task attempted. Experiment 1 isolated two distinct hypnotic tasks (easy and difficult); alternative forms of each item conveyed either clear or unclear structure concerning the response that was perceived as most appropriate. In Experiment 2, 101 subjects were administered hypnotic induction procedures and tested for modification of response on both items; for each subject, the hypnotist posed a conflict in communication by plausibly requesting an alteration in response from the behavior that the subject had chosen to indicate previously. Change data demonstrated that hypnotic subjects modified their behavior in hypnosis, but their cognitive flexibility was much more relevant to easy than to difficult tasks. Results highlight a further dimension of role enactment as well as the special role cognitive skills in play in our understanding of performance on hypnotic test items.

Adult↗

Hemoglobin potentiates the production of reactive oxygen species by alveolar macrophages.

The objectives of this investigation were (1) to determine the effects of hemoglobin on the production of reactive oxygen species by activated rat alveolar macrophages, (2) to determine a possible mechanism for these effects, and (3) to determine which part of the hemoglobin molecule is responsible for these effects. Production of reactive oxygen species by phorbol myristate acetate (PMA)-stimulated cells was assessed by measuring luminol-enhanced chemiluminescence (CL). Hemoglobin enhances PMA-stimulated CL in a dose-dependent manner. The effect is maximal at 0.5-1.0 microM hemoglobin where PMA-induced CL is increased by approximately 20-fold. Superoxide anion release from PMA-stimulated cells is not affected by hemoglobin. However, the hemoglobin-induced enhancement of PMA-stimulated CL is inhibited by superoxide dismutase, catalase, dimethylthiourea, or deferoxamine. These results suggest that hydroxyl radical may be formed from hydrogen peroxide which is derived from superoxide anion. Measurements of electron spin resonance spectra following spin trapping of radicals verify that hydroxyl radicals are produced by the cells in the presence of PMA and hemoglobin. The hemoglobin effects appear to require iron in a protoporphyrin complex, because hemin stimulates PMA-induced CL, whereas neither ferrous nor ferric iron has any effect. These findings taken together suggest that hemoglobin can act as a biological Fenton reagent to enhance the production of reactive oxygen species from alveolar macrophages and potentially contribute to lung damage during leakage of blood into the alveolar spaces.

Animals↗

Sry-negative XX sex reversal in the German shorthaired pointer dog.

Present hypotheses indicate that a testis differentiation cascade in mammals is induced by Sry, a gene encoding a DNA binding protein of the high mobility group (HMG) class. In XX sex reversal, individuals lacking a Y chromosome develop testicular tissue. Sry translocation from the Y to the X chromosome has been found in some, but not all, of these individuals. XX sex reversal in the German shorthaired pointer dog may be a model of Sry-negative XX sex reversal in humans. The purposes of this study were to report the familial occurrence of sex reversal and determine whether the conserved Sry HMG box, the region of the Sry protein essential for testis induction, is present in genomic DNA of affected dogs. Canine Sry HMG box sequences were used as primers in polymerase chain reactions. A 104 bp Sry HMG box product was generated from normal males, but not from females or XX sex reversed dogs. Parallel control reactions using hypoxanthine phosphoribosyl transferase primers generated a 177 bp product from all dogs. The pedigree of affected dogs and the absence of Sry HMG box sequences in their genomic DNA suggest that this disorder is due to a mutant autosomal gene in the testis differentiation cascade.

Animals↗

Hepatocellular carcinoma in children associated with Gardner syndrome or familial adenomatous polyposis.

PURPOSE: Gardner syndrome, a variant of familial adenomatous polyposis, is characterized by colonic polyps that undergo malignant change and benign and malignant extracolonic lesions. Tumors frequently associated with Gardner syndrome include carcinoma of the ampulla of Vater, papillary carcinoma of the thyroid, and, in children, hepatoblastoma. The childhood malignancies often precede the appearance of other manifestations by several years. PATIENTS AND METHODS: Two patients are described. Gardner syndrome was diagnosed in a 15-year-old girl with fibrolamellar hepatocellular carcinoma after desmoid tumors and colonic polyposis developed. Classic hepatocellular carcinoma was also diagnosed in a 9 1/2-year-old boy with familial adenomatous polyposis. RESULTS: In patient 1, the diagnosis of fibrolamellar hepatocellular carcinoma preceded the diagnosis of Gardner syndrome by almost 2 years. The diagnosis was confirmed by identifying a germline mutation of the adenomatous polyposis coli (APC) gene. This is the first patient reported with fibrolamellar hepatocellular carcinoma associated with Gardner syndrome. Patient 2 had a strong family history of familial adenomatous polyposis but no manifestations of Gardner syndrome. He was not tested for the APC mutation. The current literature and previously reported cases of hepatocellular carcinoma in patients with Gardner syndrome or familial adenomatous polyposis are reviewed. CONCLUSIONS: Because hepatocellular carcinoma is uncommon in the pediatric and adolescent population, it is important to consider the possibility of Gardner syndrome or familial adenomatous polyposis in these patients.

Adenomatous Polyposis Coli↗