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J D Crapo

Publications and source records attributed to J D Crapo.

At least 145 records · Page 8Linked to original sources
PubMed1984

Liposome-mediated augmentation of brain SOD and catalase inhibits CNS O2 toxicity.

Enzymes specific for O-2 and H2O2 metabolism [superoxide dismutase (SOD) and catalase] can be delivered to the rat brain following entrapment in liposomes and intravenous injection and will protect against hyperbaric O2-induced convulsions in rats. Liposome-mediated superoxide dismutase and catalase augmentation of brain enzyme activity was 2.7-fold and 1.9-fold, respectively, 15 min after intravenous injection of superoxide dismutase plus catalase-entrapped liposomes. Rats treated with liposomes containing superoxide dismutase plus catalase 2 h before 6 ATA 100% O2 exposure had the time to convulsion extended three times that of controls. This protective effect was dose-dependent and was primarily due to augmentation of catalase activity. These findings show O-2 and H2O2 are important mediators of hyperbaric O2-induced central nervous system toxicity and that liposome-mediated augmentation of brain antioxidant enzymes has a biological effect.

Animals↗
PubMed1984

Protection against oxygen toxicity by intravenous injection of liposome-entrapped catalase and superoxide dismutase.

Survival of rats exposed to 100% oxygen was increased from 69.5 +/- 1.5 to 118.1 +/- 9.9 h (mean +/- SEM, P less than 0.05) when liposomes containing catalase and superoxide dismutase were injected intravenously before and during exposure. The increased survival time in 100% oxygen was also associated with significantly less fluid in the pleural cavity. Rats injected with catalase- and superoxide dismutase-containing liposomes, which had increased survival in 100% oxygen, had increased lung wet weight upon autopsy compared with saline-injected controls (2.9 +/- 0.2 g/lung vs. 4.8 +/- 0.4 g/lung, mean +/- SE, P less than 0.05). Intravenous injection of control liposomes along with catalase and superoxide dismutase in the suspending buffer decreased the mean pleural effusion volume 89% and had no significant effect on survival time. Lung catalase and superoxide dismutase activities were increased 3.1- and 1.7-fold, respectively, 2 h after a single intravenous injection of liposomes containing catalase or superoxide dismutase. Superoxide dismutase activity was also significantly greater than controls in both air- and 100% oxygen-exposed rat lungs, when enzyme activity was assayed 24 h after cessation of injection of control and oxygen-exposed rats with enzyme-containing liposomes every 12 h for 36 h. Free superoxide dismutase and catalase injected intravenously in the absence of liposomes did not increase corresponding lung enzyme activities, affect pleural effusion volume, lung wet weight, or extend the mean survival time of rats exposed to 100% oxygen. The clearance of liposome-augmented 125I-labeled catalase from lung and plasma obeyed first order kinetics according to a one-compartment model. When clearance of liposome-augmented catalase activity or radioactivity were the parameters used for pharmacokinetic studies, the half-life of augmented lung catalase was 1.9 and 2.6 h, respectively. The half-life of liposome-entrapped catalase and superoxide dismutase activity in the circulation was 2.5 and 4 h, respectively, while intravenously injected catalase and superoxide dismutase had a circulation half-life of 23 and 6 min, respectively.

Animals↗
PubMed1984

Scanning electron microscopy of vascular casts in experimental ocular vasoproliferation.

Scanning electron microscopy of vascular casts was used to investigate three experimental models of neovascularization. In each experimental situation, the casts provided a valuable three dimensional representation of the newly formed blood vessels and permitted subclassification of the vessels within normal and proliferating vascular networks. They defined also the predominant origin of new vessels from venules and capillaries, and enabled the evolution of proliferating vessels into arterioles and venules to be documented. Although vascular casts must be interpreted with caution in light of the possibility of incomplete filling and other artifacts, they are a valuable tool in the study of ocular vasoproliferation.

Animals↗
PubMed1984

Fiber localization and its relationship to lung reaction in rats after chronic inhalation of chrysotile asbestos.

Inhalation of chrysotile asbestos fibers causes interstitial lung disease in animals and man. For examination of the anatomic localization of inhaled asbestos and its relationship to alveolar tissue responses of the lung during and after chronic exposure, male and female Fischer 344 rats were exposed to aerosolized chrysotile for 7 hours/day, 5 days/week for 3 or 12 months. A number of exposed animals were kept in filtered air for an additional 12 months. Lung tissue from randomly selected animals in each group was studied by morphometric analysis of electron micrographs. Our findings show that during exposure to asbestos fibers, macrophages and alveolar epithelial cells contain statistically significant amounts of asbestos and are associated with histologic changes indicating marked epithelial injury. Increased amounts of fibers are also localized in the lung interstitium with continued exposure to asbestos and are associated with a progressive interstitial fibrotic reaction. Following cessation of exposure, macrophages and epithelial cells are cleared of fibers and resolve toward normal proportions. However, significant clearance of fibers from the lung interstitium does not occur after cessation of exposure, and there is a continuing process of fibrogenesis. These data provide new insights related to the pathogenesis of diffuse lung disease and the role each alveolar tissue compartment plays in the early and late phases of the disease.

Animals↗
PubMed1984

Reimplantation response in isografted rat lungs. Analysis of causal factors.

The function of transplanted lungs may be critically impaired in the early postoperative period by the reimplantation response. Several factors of the transplantation procedure, such as disruption of hilar structures (hilar stripping), stenotic anastomoses, and graft ischemia, are considered to cause this reimplantation response. In this study the individual contributions of these factors have been analyzed in rats, after isogeneic transplantation or hilar stripping of left lungs. Marck's technique for orthotopic transplantation of the left lung in rats was refined so that an 85% postoperative survival rate was achieved. Transplanted and hilar-stripped lungs were investigated by lung perfusion scintigraphy and chest roentgenography at regular intervals up to 168 days after operation. Macroscopic and histologic morphology was examined at corresponding intervals. Our results show that perfusion and ventilation of lung grafts are independently affected by distinct factors of the transplantation procedure. Hilar stripping did decrease graft perfusion transiently. Permanent decrease of perfusion was found to be caused by stenosis of the anastomosed pulmonary artery. Hilar stripping also impaired ventilation, by causing interstitial and alveolar edema. After transplantation, edema and consequent impairment of ventilation were aggravated by graft ischemia, proportionally to its duration. Our improved technique for transplantation of left lungs in rats provides a new opportunity for investigating the immunologic problems of lung transplantation.

Animals↗
PubMed1984

Pulmonary macrophage accumulation and asbestos-induced lesions at sites of fiber deposition.

Inhaled chrysotile asbestos fibers are deposited at alveolar duct bifurcations and subsequently are phagocytized there by pulmonary macrophages. The characteristics of the rapid macrophage response at alveolar duct bifurcations following asbestos inhalation has been further evaluated. Significant numbers of pulmonary macrophages accumulated at sites of asbestos deposition within 48 h after a 1-h exposure, whereas duct surfaces of sham-exposed animals were essentially devoid of macrophages. The influx of macrophages was associated with a significantly increased bifurcation tissue area (p less than 0.025), and this alteration persisted for at least 1 month. Two thirds of the accumulated macrophages from alveolar duct bifurcations could be removed by bronchoalveolar lavage. Macrophages recovered by lavage had significant changes (p less than 0.01) in their morphology and in their phagocytic and chemotactic capacities. These cellular alterations could play a role in the pathogenesis of asbestos-related lung disease.

Animals↗
PubMed1983

Liposome-mediated augmentation of superoxide dismutase in endothelial cells prevents oxygen injury.

Increased intracellular production of oxygen radicals is a major etiology of cell damage from many quinoid antibiotics, environmental toxicants, and hyperoxia. Enhancing the intracellular content of protective enzymes can provide a means of limiting biological damage caused by free radicals. Liposomal entrapment and intracellular delivery of superoxide dismutase to cultured porcine aortic endothelial cells increased the specific activity of cellular superoxide dismutase 6 to 12-fold. This augmented superoxide dismutase activity persisted in cultured endothelial cell monolayers and rendered these cells resistant to oxygen-induced injury. Culture of confluent endothelial cells in hyperoxia increased 51Cr and lactate dehydrogenase release in an oxygen concentration-dependent manner. Superoxide dismutase-augmented endothelial cells were resistant to oxygen damage compared to untreated controls, in a superoxide dismutase concentration-dependent manner. Free superoxide dismutase in the absence or presence of liposomes containing no enzyme had no effect on cellular enzyme activity and did not protect from oxygen damage. Liposomes made from saturated fatty acid-containing phospholipids had a small but significant protective effect on oxygen-induced cell damage. These liposomes probably increased endothelial cell membrane saturated lipid content and thereby decreased peroxidative damage when the cells were exposed to hyperoxia. Conversely, preincubation of cells with arachidonic acid increased cell arachidonic acid content, sensitivity to hyperoxia, and hyperoxia-induced production of thiobarbituric acid material. These data suggest that intracellular delivery of superoxide dismutase prevents oxygen-induced cell damage and that superoxide is an important mediator of cellular oxygen toxicity.

Animals↗
PubMed1983

Positive correlation between superoxide dismutase and resistance to paraquat toxicity in the green alga Chlorella sorokiniana.

Paraquat (10-30 microM) exerted a dose-dependent and light-dependent toxicity on Chlorella sorokiniana. Paraquat was also seen to increase the superoxide dismutase content of these cells and to cause the appearance of a new electrophoretically distinct isozyme. Cells grown in the absence of paraquat contained one manganese-superoxide dismutase and two iron-superoxide dismutases, while the paraquat-grown cells contained an additional manganese-superoxide dismutase. Cells which were grown in the presence of 25 microM Paraquat, and which therefore possessed elevated levels of superoxide dismutase, were resistant to 30 microM Paraquat, whereas control cells were bleached and killed by this level of Paraquat. Electron micrography and chemical analysis revealed that Paraquat decreased the starch content of the cells and caused a failure of dividing cells to separate. It appears that Paraquat increases the photoproduction of O2- in C. sorokiniana and that an increase in the cell content of superoxide dismutase is an adaptive response which provides protection against this herbicide.

Cell Division↗
PubMed1983

Characterization of three types of chrysotile asbestos after aerosolization.

Jeffrey Mine and Coalinga Mine chrysotile, two asbestos samples prepared for experimental research by the National Institute of Environmental Health Sciences, and the UICC B chrysotile reference sample have been characterized in the aerosolized state using gravimetric measurements, light microscopy, scanning electron microscopy, and x-ray energy spectrometry. These methods revealed (1) a greater "respirable" mass fraction in the Jeffrey and UICC B preparations compared to the Coalinga sample, (2) for fibers greater than 5 microns in length and less than 3 microns in diameter, Jeffrey Mine chrysotile contained a significantly greater fraction of fibers longer than 40 microns in length compared to the UICC B or Coalinga Mine chrysotiles, and (3) Jeffrey and UICC B chrysotile contained no fibers or fiber clusters which exceeded 2 microns in diameter while Coalinga chrysotile contained numerous fibers and fiber clusters which were greater than 2 microns in diameter. The characterization of these chrysotile preparations in the aerosolized state, in particular the Coalinga Mine chrysotile, demonstrated different fiber length and fiber width distributions when compared with previous characterizations of samples that had been dispersed in a liquid medium by ultrasonification. These observations emphasize the importance of determining size distribution of fibers in the aerosolized state for inhalation studies and the size distribution of fibers in a liquid suspension for oral ingestion, instillation, or injection studies. Because of differences in length-width distributions, each of the studied chrysotile preparations would be expected to have different patterns of deposition in the alveolar regions of the lung after an inhalation exposure.

Aerosols↗
PubMed1983

Comparison of total lung diffusion capacity and the membrane component of diffusion capacity as determined by physiologic and morphometric techniques.

Morphometric estimates of diffusion capacity have traditionally been calculated for oxygen (DLO2) while physiologic techniques have been used to determine diffusion capacity for carbon monoxide (DLCO). Morphometric estimates of DLCO and Dm were determined for carbon monoxide so that the results can be directly compared to those obtained using physiologic techniques. Multiple gas rebreathing techniques were used to measure total lung diffusion capacity (DLCO), membrane component of diffusion capacity (Dm) and pulmonary capillary blood volume (Vc) in five anesthetized dogs. After the rebreathing measurements were made, the lungs were inflation fixed with glutaraldehyde and subjected to morphometric analysis. The morphometric estimate of diffusion capacity was three times higher than the physiologic estimate. The major components of diffusion capacity, Dm and theta Vc were found to be of approximately equal size when measured physiologically (Dm = 34 and theta Vc = 27 ml X min-1 X mm Hg-1). In contrast, the morphometric estimate of Dm was about six times higher than the morphometric estimate of theta Vc. The widely different ratios of the two major subcomponents of the total lung diffusion capacity as measured by these two different techniques suggest that the same lung function is not being accurately measured by at least one of these two techniques. Differences in results for DLCO cannot be explained by differences in the physiologic state of the animal at the time the measurement was made. Morphometric analysis predicts that Vc is the major term affecting the value of DLCO whereas the physiologic techniques predict that both Dm and Vc contribute substantially to the value of DLCO.

Animals↗
PubMed1983

Morphometric characteristics of cells in the alveolar region of mammalian lungs.

Morphometric procedures have been used to study the characteristics of cells in the alveolar region of the lungs of rats, dogs, baboons, and humans. Compared with the other species, human lungs were found to contain greater numbers of macrophages and to have larger alveolar type II, endothelial, and interstitial cells. The thickness of the interstitium and the pulmonary capillary endothelium were also significantly greater in the human lungs. These differences in human lung anatomy may be due to increased exposure to airborne pollutants and to tobacco smoke. Despite the above differences and the fact that there are large variations in size and functional characteristics of the lungs of these mammals, an overall striking similarity in characteristics of individual lung cells was found. The distribution of cells in alveolar tissue was remarkably constant between species as was the average volume and surface area of most cell types. Computer-aided three-dimensional reconstruction techniques were used to determine the spatial relationship of organelles in individual alveolar type II cells from rats. A three-dimensional reconstruction of cells permits quantification of number, size, surface area, and volume of subcellular organelles and correlations of their three-dimensional spatial relationships.

Animals↗
PubMed1983

Reaction of rat lungs to inhaled chrysotile asbestos following acute and subchronic exposures.

Inhalation of asbestos fibers can cause fibrotic and neoplastic diseases in the lung. The early in vivo interactions between fibers and lung tissue that initiate these diseases have received little study. Male and female Fischer 344 rats were placed in inhalation chambers and exposed to 9.06 +/- 1.83 mg/m3 (average respirable mass) of chrysotile asbestos for 1 hr, 1 day, 7 hr/day for 5 days, or 5 days/week for 3 months. Qualitative examination of the tissue showed that, after 1 day, fibers were found not only in the alveolar macrophages, but also in the epithelium and interstitium of the alveolar region. After 3 months, numerous fibers were present in the epithelium and interstitium. Morphometric analysis of this tissue showed that these compartments were also the most significantly changed as a result of asbestos exposure. The majority of epithelial changes were attributable to a 57% increase in the number of type II cells and a 90% increase in their average cell volume. The interstitial cell population increased 58% with a 40% increase in the average cell volume. There was no significant increase in the volume of noncellular interstitium. A morphologic characterization of the interstitial cells showed that interstitial macrophages accounted for almost the entire increase in this population and that 88% of the fiber-containing cells were macrophages. Several interstitial macrophages contained membrane-bound inclusions which were shown by x-ray energy spectrometry to be microcalcifications. They were composed of rings of calcium phosphate granules around asbestos fibers. These microcalcifications may indicate sublethal cell injury caused by the presence of asbestos fibers in the cell cytoplasm. Fibers which enter but do not kil alveolar cells may be an essential component for the pathogenesis of lung disease caused by asbestos inhalation.

Animals↗
PubMed1983

Morphologic aspects of the protection by endotoxin against acute and chronic oxygen-induced lung injury in adult rats.

Small doses of endotoxin are reported to protect against O2-induced lung injury in rats. To better understand the cellular basis of this effect, we morphometrically analyzed the extent to which endotoxin modified the changes in lung ultrastructure occurring in adult rats exposed acutely to 100% O2 for 60 hours or chronically to 85% O2 for 7 days. In rats exposed to 100% O2, endotoxin resulted in 34% less volume of noncellular interstitium (i.e., less interstitial edema) and 42% less volume of cellular interstitium; however, interstitial edema and cellularity were still more than in air-exposed controls. Endotoxin did not significantly prevent decreases in endothelial cell number and capillary surface area or increases in intracapillary neutrophil volume caused by 100% O2. There was also no change in the number of type I and type II epithelial cells and alveolar macrophages. In rats exposed chronically to a sublethal tolerance-inducing level (85%) of O2, endotoxin resulted in 36% more endothelial cells (i.e., less of a decrease from control values) and 30% less interstitial cells (i.e., less of an increase from control values). The increase in number of type II epithelial cells and the degree of endothelial cell hypertrophy caused by 85% O2 were not altered. We conclude that endotoxin resulted in significant protection against O2-induced changes in ultrastructure; this occurred mainly in the capillary endothelium and interstitium. The primary effect may be a reduction in damage to, and death of, endothelial cells leading secondarily to less of an increase in capillary permeability, less interstitial (and alveolar) edema, and less proliferation and recruitment of interstitial cells. There was no evidence of a mitogenic effect on type II epithelial cells or change in number of either alveolar macrophages or intravascular neutrophils.

Animals↗
PubMed1983

Structural and biochemical adaptive changes in rat lungs after exposure to hypoxia.

Rats exposed to 10 to 11 per cent oxygen for 7 days develop tolerance to hyperoxia and can survive for prolonged periods in 100 per cent oxygen. This preexposure to hypoxia is associated with a 180 per cent increase in the activity of the mangani superoxide dismutase but no increase in activity of copper-zinc superoxide dismutase, glucose-6-phosphate dehydrogenase, or the mitochondrial enzymes, cytochrome oxidase and succinate cytochrome c reductase. Cyanide-insensitive oxygen uptake is also increased after this exposure to hypoxia suggesting that an enhanced rate of production of partially reduced species of oxygen may occur. Morphometric and morphologic studies of lung structure demonstrate that no substantial change in cell population characteristics occur in the lungs of animals exposed to hypoxia, but there are ultrastructure changes in the cytoplasm of pulmonary capillary endothelial cells consistent with focal hypertrophy and enhanced metabolic activity of these cells.

Adaptation, Physiological↗
PubMed1982

Morphologic changes in the lung during the lifespan of Fischer 344 rats.

Pulmonary structure and function were quantitatively investigated over the lifespan of the Fischer 344 rat by morphometric and physiologic techniques. Male animals 1 week, 6 weeks, 5 months, 14 months, and 26 months of age and female animals 5 months, 14 months, and 26 months of age were studied. All alveolar tissue compartments demonstrated significant increases in volume, surface area, and cell number during the first 5 months of life. From 5 to 26 months of age, remodelling in the epithelial and interstitial compartments continued to take place while the endothelial compartment remained relatively unchanged. In the epithelial compartment the ratio of type II cells to type I cells lining the alveolar surface decreased as age increased. In the interstitial compartment the volume of the noncellular components of the interstitium increased by 39% in males and by 89% in females from 5 to 26 months of age. Physiologic measurements of lung volumes in males at 6 weeks, 14 months, and 26 months demonstrated progressive increases in vital capacity (VC) and total lung capacity (TLC). Morphometric pulmonary-diffusion capacity (DLO2) increased in males from 1 week to 5 months of age and remained relatively unchanged from 5 to 26 months of age in both sexes.

Aging↗