Differences in the behavioral effects of single-stage and serial lesions of the hippocampus.
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Biomedical subjects
Publications and source records attributed to G Freeman.
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Rats were exposed to either NO2 or O3 to determine whether nonciliated cells (Clara cells) could divide and differentiate into ciliated cells in the terminal bronchioles. Dividing cells were labeled with tritiated thymidine, visualized in the light and electron microscopes using autoradiographic techniques, and studied for up to 15 days after labeling. Electron microscopic autoradiography 1 hour after injection of tritiated thymidine showed that all labeled cells in the terminal bronchioles were nonciliated. However, 4 days after injection of tritiated thymidine, 67.8 per cent of the labeled cells were nonciliated and 32.2 per cent were ciliated. Light microscopic autoradiography showed that the new labeled ciliated cell population was stable for up to 15 days. These results indicate that nonciliated cells divide and the sister cells may form new ciliated and nonciliated cells. Thus, nonciliated cells can act as progenitor cells for the terminal bronchiolar epithelium.
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The epithelial response in the terminal bronchioles and alveoli was examined after exposure to approximately 0.5 and 0.9 ppm ozone (O(3)). Loss of ciliated cells from the terminal bronchiole was pronounced after 6 to 10 hours of exposure; however, nonciliated cells were resistant to injury from O(3). In contrast, type 1 alveolar lining cells were very sensitive to O(2) and were severely damaged or removed from significant areas of the proximal alveoli after as little as 2 hours of exposure to 0.5 ppm. The basement lamina was left devoid of an epithelium with the exception of type 2 cells, which were very resistant and retained a relatively normal appearance. Under continuous exposure, repair of the lesion area was accomplished in approximately 48 hours through proliferation of the type 2 cells. The new cells were cuboidal at first but subsequently became more squamous in appearance. Exposure for 8 to 10 hours followed by residence in clean air resulted in a proliferative response at 48 hours, about equal to that observed after continuous exposure.
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This research was undertaken to study the kinetics of Type 2 cell division and the fate of the Type 2 sister cell following exposure to NO(2). To accomplish this, male rats were exposed to NO(2). Dividing cells were labeled with (3)H-TdR and studied with autoradiographic technics in the light and electron microscopes for up to 72 hours after labeling. The kinetics of cell division were determined from a curve constructed from the percent of labeled mitotic figures. The fate of the Type 2 sister cells was determined by studying tissues at 24, 48 and 72 hours after labeling with (3)H-TdR. The results show that Type 2 cells may divide and the sister cells transform into Type 1 cells. These data support an interpretation of the mechanism for cell renewal of the alveolar epithelium in which Type 2 cells are the progenitor cells for Type 1 cells.
The purpose of this research was to study cell division of alveolar macrophages following exposure of rats to NO(2). Dividing cells were labeled with (3)H-TdR and studied for 12 hours after labeling. The kinetics of cell division were determined from a curve constructed from the percent of labeled mitotic figures. Dividing alveolar macrophages were localized in alveoli near the openings of terminal bronchioles. There were no morphologic differences observed between labeled and unlabeled macrophages. Estimates of the durations of the various phases of the cell cycle gave approximate values of: G(2), 1 hour; t(2), 1.8 hour; M, 2.8 hours; and S, 5.8 hours. This evidence, combined with that of others, is compatible with an interpretation for alveolar cell renewal in which marrow-derived cells enter the alveoli and become macrophages. While in the alveoli, the cells may divide and thus increase their numbers. Eventually the macrophages are extruded from the alveoli. Alveolar macrophages were classified as a dividing, transient renewing cell population.
Beagle dogs exposed for 8 hours a day to 3 ppm O(3) for 18 months showed cytologic changes that indicate metabolic alterations. The endoplasmic reticulum of the type 2 alveolar epithelial cells in the proximal alveoli were frequently dilated and contained a moderately electron-dense substance having a periodicity of approximately 754 A. This condition was accompanied by a substantial reduction in the lamellar membranes in the characteristic lamellar bodies of the type 2 cells, suggesting a sequestering of protein in the endoplasmic reticulum. In addition, endothelial cells contained paracrystalline arrays of cytoplasmic membranes not observed in control animals.
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