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Biomedical subjects

A Churg

Publications and source records attributed to A Churg.

At least 73 records · Page 4Linked to original sources
PubMed1994

Deposition and clearance of chrysotile asbestos.

Studies of human lungs indicate that, for virtually all types of exposure, the relative proportion of amphibole asbestos retained in the lung far exceeds the proportion in the original dust and, conversely, the relative proportion of chrysotile is far less than that in the original dust. Although amphiboles appear to accumulate in lung in proportion to exposure and chrysotile does not, failure of chrysotile deposition is probably not the reason for the disproportionate retention of amphibole fibres. The available data suggest that chrysotile is deposited in the parenchyma but is cleared extremely rapidly, with the vast bulk of fibres removed from human lungs within weeks to months after inhalation; by comparison, amphibole clearance half-lives are of the order of years to decades. The mechanisms of preferential chrysotile clearance remain uncertain, but fragmentation of chrysotile into short fibres, possibly accompanied by extremely rapid dissolution of such fibres, appears to be important in this process. Chrysotile fibres do penetrate to the periphery of the lung, so that differences in mesothelial pathogenicity of chrysotile and amphiboles in regard to mesothelioma are not caused by failure of chrysotile to reach the pleura. The theory that the tremolite contaminant rather than the chrysotile itself is the cause of 'chrysotile-induced' disease (especially mesothelioma) is consistent with the available human data, but the contrary ideas that disease is caused either by the total transient burden of inhaled chrysotile fibres or by a small, sequestered, long-retained fraction of chrysotile fibres still need to be excluded.

Animals↗
PubMed1994

Cigarette smoke causes rapid cell proliferation in small airways and associated pulmonary arteries.

To determine whether smoke could directly affect the cells of the small airways and the small vessels, we exposed Sprague-Dawley rats to the whole smoke of 7 cigarettes/day for 1, 2, or 7 days. Three hours before the rats were killed, 5-bromo-2'-deoxyuridine (BrdU) was administered. Labeled nuclei were counted in histological sections stained with antibodies to BrdU. In smokers, pulmonary artery walls at the level of the membranous bronchioles (MB), respiratory bronchioles (RB), and alveolar ducts (AD) showed significant increases in labeled nuclei at all three times; increases in endothelial labeling were only present in vessels associated with AD. Significantly increased labeling was also seen in the epithelium and walls of MB and RB themselves at all time periods. However, there was no correlation between labeling indexes in matched pairs of airways and vessels. Smoke had no effect on the labeling of mesothelial and submesothelial cells. We conclude that cigarette smoke rapidly causes proliferation of intrinsic cells in the airways and small vessels; this effect may lead eventually to airway wall muscular hyperplasia and fibrosis (small airways disease) and to vascular changes associated with pulmonary hypertension. However, the lack of correlation between labeling indexes in the vessels and airways suggests that different mediators are involved at these two sites. At least over the time course of this experiment, smoke does not cause proliferation of mesothelial or submesothelial cells.

Animals↗
PubMed1994

Fiber burden and patterns of asbestos-related disease in workers with heavy mixed amosite and chrysotile exposure.

To attempt to determine the mineralogic factors that relate to the appearance of specific types of asbestos-related disease in workers with heavy mixed exposure to amphiboles and chrysotile, we analyzed the pulmonary asbestos fiber burden in a series of 144 shipyard workers and insulators from the Pacific Northwest. Amosite was found in all lungs, and tremolite and chrysotile in most lungs, but the vast majority of fibers were amosite. Tremolite and chrysotile concentrations were significantly correlated, indicating that the tremolite originated from chrysotile products, but no correlation was found between tremolite or chrysotile concentration and amosite concentration. Time since last exposure was correlated with decreasing amosite concentration and the calculated clearance half time was about 20 yr. In a multiple regression analysis that accounted for the presence of more than one disease in many subjects, a high concentration of amosite fibers was correlated with the presence of airway fibrosis and asbestosis, whereas subjects with mesothelioma, lung cancer, pleural plaques, or no asbestos-related disease had about the same, much lower, amosite concentration. No relationship was found between the concentration of chrysotile or tremolite and any disease. Analysis of fiber size measures (length, width, aspect ratio, surface, mass) showed that pleural plaques were strongly associated with high aspect ratio amosite fibers and suggested that mesotheliomas were associated with low aspect ratio amosite fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Iron enhances uptake of mineral particles and increases lipid peroxidation in tracheal epithelial cells.

The factors that determine whether an exogenous mineral particle will be taken up by tracheobronchial epithelial cells are unclear. We have previously proposed that active oxygen species play a role in this process, most likely through iron-catalyzed formation of hydroxyl radical and subsequent lipid peroxidation of cell membranes. To further examine this hypothesis, we prepared rat tracheal explant cultures and exposed them for 1 h to suspensions of amosite asbestos or titanium dioxide (rutile) that had been preincubated with varying concentrations of a mixture of ferrous and ferric chloride. Explants were then maintained in organ culture in air/CO2 for 1 wk to allow particle or fiber uptake to occur. Particles or fibers in the tracheal epithelium were determined by light microscopic morphometry. Similarly treated explants were assayed for malondialdehyde as a measure of lipid peroxidation in the epithelial cells. Asbestos fibers without added iron caused lipid peroxidation, but this was not true of titanium dioxide particles. For both types of dust, increasing adsorbed iron concentrations were associated with increasing particle uptake and increasing lipid peroxidation. These observations suggest that cationic iron may play a major role in particle uptake by tracheobronchial epithelia, and that particle uptake is also related to iron-mediated lipid peroxidation.

Adsorption↗
PubMed1994

Persistence of natural mineral fibers in human lungs: an overview.

Virtually all available data on persistence of naturally occurring mineral fibers in human lungs have been derived from studies of asbestos fiber loads. These studies indicate that, although both amphibole and chrysotile asbestos fibers are found in the lungs of the general population and exposed workers, amphibole fibers are universally present in disproportionately large and chrysotile fibers in disproportionately small amounts compared to their known abundance in the original inhaled dusts. Why this should be remains unclear. Most reports have shown that fiber accumulation is proportional to measured exposure for amphiboles, but this is not generally true for chrysotile. Very little information is available on actual fiber clearance rates from human lungs. For amosite and crocidolite, estimated clearance half-times are measured in years to decades, whereas for chrysotile the available, rather indirect, data suggest that the vast majority of fibers are cleared within months, although some fibers may be sequestered and very slowly cleared. Overall these studies suggest that the differences between amphibole and chrysotile fiber burdens in man reflect much faster clearance of chrysotile fibers, rather than a failure of chrysotile deposition. A variety of other naturally occurring fibers are commonly found in human lungs, but there are no data on their rates of accumulation or disappearance.

Animals↗
PubMed1994

Localized malignant mesothelioma. A clinicopathologic and flow cytometric study.

Six examples of malignant mesothelioma appearing as a localized pleural mass are described. There were four women and two men, ranging in age from 42 to 76 years. A history of asbestos exposure was obtained from three patients. The tumors ranged in size from 2.8 to 10 cm. Two were pedunculated and four were sessile with broad-based pleural attachments. Histologically, three tumors were purely epithelioid and three were biphasic. Immunohistochemical stains in all six cases were positive for cytokeratin and negative for carcinoembryonic antigen. Five were also positive for epithelial membrane antigen. Five were negative for Leu-M1, while one showed focal staining in a peripheral membrane pattern. Electron microscopy in two purely epithelioid tumors showed long, thin microvilli, well-developed desmosomes, and numerous tonofilaments. Flow cytometry showed an aneuploid DNA content in four tumors and a diploid content in one. Flow cytometry in five cases identified a DNA aneuploid cell population in four tumors and a diploid population in one. Three patients showed signs of local recurrences 4, 7, and 18 months after excision and died of their disease 12, 10, and 24 months after diagnosis, respectively. Three patients are well with no evidence of disease 8, 24, and 96 months after diagnosis. These findings indicate that malignant mesotheliomas of the pleura may rarely appear as a localized mass. The biologic behavior of such tumors is difficult to predict, but some patients survive disease-free for a long time after surgical excision.

Adult↗
PubMed1993

Absence of amosite asbestos in airway mucosa of non-smoking long term workers with occupational exposure to asbestos.

There is considerable experimental evidence that asbestos fibres are taken up by epithelial cells, and that uptake of fibres is associated with various deleterious, particularly mutagenic, effects. It is not known, however, if asbestos fibres are taken up by human bronchial epithelial cells in vivo. To investigate this question, the amosite asbestos content of the mucosa of seven different airways and four parenchymal sites supplied by these airways in six necropsy lungs from heavily exposed never-smoking long term shipyard and insulation workers without asbestosis was examined. Amosite asbestos was readily found in moderately high concentration in all parenchymal samples, but 33 of 40 airway samples that could be evaluated showed no amosite fibres. The seven positive airways had fibre concentrations that were always much lower than the parenchymal concentrations, and these very few fibres may have been contaminants from the parenchyma. These data suggest that, at least in non-smokers, amosite asbestos either does not penetrate into or does not accumulate in human airway mucosa. These findings also call into question the idea that asbestos acts as a direct airway carcinogen in humans.

Aged↗
PubMed1993

Fiber burden and patterns of asbestos-related disease in chrysotile miners and millers.

To examine how fiber type, fiber concentration, and fiber size correlate with the presence of asbestos-related disease in workers with heavy chrysotile exposure, we used analytic electron microscopy to determine the fiber content of the lungs of 94 long-term chrysotile miners and millers from the region of Thetford Mines, Quebec. Mesothelioma, airway fibrosis, and asbestosis were strongly associated with a high tremolite fiber concentration, whereas pleural plaques and carcinoma of the lung showed no relationship to tremolite burden. Similar patterns were seen for chrysotile concentration, but further analysis suggested that the apparent effect of chrysotile probably was due to the high correlation (r = 0.70) between chrysotile and tremolite concentration rather than to an independent effect of chrysotile. Increased tremolite-chrysotile ratio was marginally associated with the presence of pleural plaques but not with any other disease. Very high correlations (r > 0.90) between the concentrations of fibers longer or shorter than 8 microns prevented assessment of the effects of long compared with short fibers. Pleural plaques were very strongly associated with higher mean tremolite fiber aspect ratios, but no differences in mean fiber size (length, width, aspect ratio, surface area, and mass) were seen for any other disease. Total fiber size measures (total fiber length/g and others) showed differences similar to fiber concentration for mesothelioma, airways fibrosis, and asbestosis, but no one measure was clearly better than another or better than fiber concentration. We conclude that, in this population of heavily exposed chrysotile miners and millers, the presence of airways fibrosis and asbestosis and, probably, mesothelioma reflects high tremolite burden.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Effects of cigarette smoke on epithelial uptake of non-asbestos mineral particles in tracheal organ culture.

Cigarette smoke is believed to increase the pulmonary retention of many different types of mineral dusts, but the mechanisms of this process are unclear. We have previously shown, using a tracheal organ culture system, that exposure to cigarette smoke directly increases the uptake of asbestos fibers by tracheal epithelial cells, and that this process is mediated by active oxygen species. To determine whether the same effects are seen with other types of mineral dust, we exposed rat tracheal explants to cigarette smoke or air (control) and then to a variety of dusts generally considered "inert" or of low pathogenicity. Explants were maintained in organ culture to allow dust uptake, and segments fixed and prepared for light microscopy at various times up to 1 wk; particle uptake was determined morphometrically. We observed that cigarette smoke significantly increased the epithelial uptake of nonfibrous titanium dioxide and talc, and of fibrous silicon carbide, but not of fibrous or nonfibrous iron oxide, nonfibrous silicon carbide, or fibrous wollastonite. Scavengers of active oxygen species (catalase) or agents that prevent the formation of active oxygen species (deferoxamine) blocked the effects of smoke in enhancing titanium dioxide uptake but did not block the effects of smoke on talc uptake. These observations indicate that cigarette smoke may potentiate the effects of many types of dust, including relatively inert dusts, by directly increasing the numbers of particles entering the tracheobronchial epithelium and eventually reaching the interstitium. However, smoke does not directly enhance the uptake of every dust.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Rat pleural mesothelial cells show damage after exposure to external but not internal cigarette smoke.

The combination of cigarette smoke and high-level occupational asbestos exposure produces a synergistic increase in the incidence of lung cancer; however, smoking does not affect the incidence of mesothelioma. Here we present the results of tests of two theories that have been proposed to explain this phenomenon; namely, that pleural mesothelial cells are resistant to cigarette smoke-induced damage and that the pleural connective tissue acts as a barrier that prevents smoke from reaching the mesothelial cells. To test these hypotheses, excised whole rat lung preparations were exposed to either internal (intratracheal) or external (pleural surface) smoke. For comparison, additional excised lung preparations were exposed to solutions of hydrogen peroxide either externally or intratracheally. Mesothelial cells exposed to external smoke showed widespread, dose-dependent uptake of Trypan blue. Mesothelial cells did not take up Trypan blue after exposure to internal smoke. Bronchial epithelial cells exposed to internal smoke did show uptake, but to a lesser degree than externally exposed mesothelial cells. Examination by scanning and transmission electron microscopy showed that internal smoke did not affect mesothelial cell ultrastructure, whereas external smoke produced obvious mesothelial cell damage and mesothelial cell detachment. Catalase and deferoxamine, scavengers of active oxygen species, provided protection against smoke-induced mesothelial cell injury, but inactivated catalase did not. External hydrogen peroxide produced a very similar, dose-dependent pattern of Trypan blue uptake and ultrastructural changes. Intratracheal hydrogen peroxide also damaged mesothelial cells, but the extent of damage was always less than with comparable concentrations of external hydrogen peroxide.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Asbestos-related disease in the workplace and the environment: controversial issues.

Asbestos-related diseases continue to be sources of controversy for epidemiologist, clinician, and pathologist. Most investigators agree that the different fiber types behave differently in the lung, with chrysotile being rapidly removed, and amphibole persisting. These differences in biologic behavior probably account for the much greater disease potential of amphibole (amosite and crocidolite) compared with chrysotile asbestos, particularly in regard to mesothelioma induction in man. Asbestosis is defined as diffuse interstitial fibrosis of the lung caused by asbestos exposure, and this is the only condition to which the term asbestosis should be applied. The classical pathologic diagnostic criteria for asbestosis, namely the presence of diffuse interstitial fibrosis resembling usual interstitial pneumonia, and asbestos bodies visible in ordinary tissue sections, have proved to withstand the test of time. Cases without asbestos bodies visible in routine or iron-stained tissue sections almost never turn out to be asbestosis. It should be remembered that workers with asbestos exposure develop all of the interstitial lung diseases to which the remainder of the populace is subject; some of these conditions are treatable and should not be misdiagnosed as asbestosis, which is not treatable. There is strong epidemiologic and pathologic evidence that the only association of asbestos exposure and lung cancer is the association of asbestosis and lung cancer. Thus, a lung cancer should only be attributed to asbestos exposure when asbestosis is present on clinical or pathologic grounds. The histologic type and location of the tumor are irrelevant in this regard. Analytical electron microscopy indicates that chrysotile asbestos does induce mesothelioma in man, but that extremely high levels of retained fibers, levels as high as those seen in cases of asbestosis, are required for this event to occur. The weight of the evidence suggests that exposure of the general population to the very low levels of chrysotile that are found in some public building (levels not greatly different from ambient air) will never produce mesothelioma, asbestosis, or lung cancer because these diseases all appear to require quite high-level occupational chrysotile exposure. Even if one accepts the ideas (probably wrong) that any level of asbestos exposure carries a risk of cancer, and that mathematical extrapolation of risk from high-level occupational exposure to low-level building exposure is scientifically valid, the calculated risks are much smaller than real everyday risks such as driving to work. Thus, exposure to asbestos at environmental levels appears to produce no real dangers to health.

Asbestos↗
PubMed1993

Cigarette smoke causes rapid lipid peroxidation of rat tracheal epithelium.

Cigarette smoke-induced lipid peroxidation may be an important mechanism of smoke toxicity, but attempts to demonstrate peroxidation of pulmonary tissues after smoke exposure have yielded conflicting results. To examine this question, we exposed rat tracheal explants to whole smoke for 10 minutes followed by air recovery for periods up to 50 minutes (test), or to air alone (controls) and measured conjugated diene levels in the tissue. A dose-related increase in conjugated diene levels was seen in explants exposed to 1, 3 or 6 puffs of smoke. After exposure to 6 puffs of smoke, there was a progressive increase in conjugated diene levels during the first 10 minutes of air recovery; thereafter, test levels remained at about 1.5 times control. Pretreatment of the explants with superoxide dismutase, catalase, or deferoxamine prevented the increase in conjugated diene levels, and inactivation of the enzymes destroyed their protective effect. We conclude that cigarette smoke rapidly produces lipid peroxidation in tracheal segments in vitro, that the severity of the process is directly related to the amount of smoke exposure, and that inflammatory cells are not required for this effect. Lipid peroxidation in this system appears to be mediated by active oxygen species.

Animals↗
PubMed1992

Effects of cigarette smoke on the clearance of short asbestos fibres from the lung and a comparison with the clearance of long asbestos fibres.

Long asbestos fibres are generally considered to have greater disease-producing potential than short asbestos fibres. However, recent reports have suggested that short fibre asbestos appears to be as effective an inducer of macrophage growth factors and toxic oxygen species as long fibre asbestos, but that short fibres are readily removed from lung and do not gain access to tissues. Because smoke is believed to impair the clearance of asbestos fibres from lung, we examined the clearance of a short (geometric mean length 1.3 microns) amosite preparation administered by intratracheal instillation to guinea-pigs. Half the animals in each group were exposed to the smoke of 10 cigarettes daily. Animals were sacrificed 1 day, 1 week, or 1 month later, the macrophages recovered by lavage, and fibre concentrations and sizes determined by analytical electron microscopy in macrophages and lung tissue. A 30-fold increase was seen in total numbers of fibres retained in macrophages in smokers compared to non-smokers by 1 month, and there was an eightfold increase in retention of short fibres in the lung tissue by 1 month. By contrast, a long fibre amosite preparation (geometric mean length 8.9 microns) showed approximately the same increase in fibre retention in macrophages, but only a twofold increase in tissue retention. We conclude that (1) cigarette smoke markedly impairs the clearance of short amosite fibres from the lung with enhanced retention of fibres in both macrophages and tissue; (2) the effects of smoke on short fibre tissue retention appear to be greater than those on long fibre retention; (3) with the long fibre preparation, smoke causes increased tissue retention of relatively shorter fibres; (4) for both fibre size experiments, the increase in total fibres in macrophages in smoke-exposed animals reflects an increase in the total number of fibre-containing macrophages, rather than an increase in the number of fibres phagocytized per macrophage; (5) enhanced short fibre retention markedly increases total fibre surface area, a parameter which has been suggested as a measure of fibre toxicity, to the point where short fibres might under some circumstances have roughly the same potential toxicity as long fibres. These observations suggest that short asbestos fibres could play an important role in the pathogenesis of some types of asbestos-related disease in cigarette smokers.

Animals↗
PubMed1991

Pulmonary hypertension induced by amosite asbestos: a physiological and morphologic study in the guinea pig.

Although there is increasing evidence that mineral dust exposure will produce obstructive lung disease, there is little information on the effects of mineral dust on the pulmonary vascular system. To examine whether exposure to amosite asbestos would affect the pulmonary vasculature and produce pulmonary hypertension, we instilled 5 mg amosite asbestor intratracheally into guinea pigs. After periods of 3 and 6 months, we examined their pulmonary and pulmonary vascular function, and compared these data to those obtained from groups of control animals. We found that, at both time periods, there was pulmonary arterial hypertension, with alteration of the vascular pressure-flow relationships. This was accompanied by abnormalities in the structure of the small pulmonary arterioles. The animals also showed airflow obstruction, with air trapping and an upward shift of the pressure-volume curve. There was evidence of emphysema, and the animals were moderately hypoxic. We found no consistent increase in inflammatory cells either in lavage or peripheral blood, and the histamine dose-response curves were similar in control and asbestos-exposed animals at 6 months. We conclude that intratracheal instillation of asbestos in the guinea pig produces pulmonary hypertension associated with modest hypoxia, emphysema, and airflow obstruction. Whether pulmonary hypertension reflects emphysema-induced hypoxia and loss of vascular bed, or is related to the brief but intense inflammatory infiltrate induced by asbestos, is unclear.

Animals↗
PubMed1991

Influence of weight on pulmonary function in the adult guinea pig.

We examined a group of 63 adult female Hartley strain guinea pigs with weight ranging from 625 to 1,200 g in order to ascertain whether pulmonary function tests including lung volumes, pressure-volume curves, and flow-volume curves were affected by the weight of the animal. We found that there was a weight effect on total lung capacity, vital capacity, residual volume, and the forced expiratory flow between 25 and 75% of total lung capacity, although there was no effect on other parameters of airflow. Flow-volume curves for each animal could be accurately fitted to a mathematical equation, and this equation did not vary with the animals' weight. Pressure-volume curves were affected by animal weight, but could be accurately fitted to a weight-corrected equation. We conclude that when pulmonary function tests are performed on adult guinea pigs, lung volumes may be altered in proportion to the weight of the animal. When pressure-volume or flow-volume curves are being considered, although weight can either be corrected for or has no bearing on the shape of the curve, there is a large between-animal variation, and it may be necessary to use large experimental groups when it is impossible to use the same animal as its own control.

Animals↗