Browsing by Author "Chase, C. C."

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    The adrenal cortex in hypercholesterolaemic rabbits. Histochemical and electron microscopical changes
    (Health & Medical Publishing Group, 1978-2) Rossouw, D. J.; Chase, C. C.; Engelbrecht, F. M.
    The adrenals of rabbits on a cholesterol-rich diet for 35 days showed histopathological changes, a marked increase in weight and a lowering in the ascorbate content. A focal increase in the neutral lipid and cholesterol content was noted mostly in the inner cortical zones; and a characteristic acid phosphatase-positive pattern in areas of infiltrating cells, and an alkaline phosphatase-positive reaction in heterophils in the infiltrated areas. Electron microscopy confirmed that the zona glomerulosa cells were relatively normal in hypercholesterolaemic rabbits, while necrosis and fibrosis were very obvious in the inner two zones. The cellular infiltrate was shown to consist of large, granular mononuclear cells, heterophils, eosinophils, stromal phagocytes, lymphocytes and plasma cells. The possibility that the reaction was of an immunological nature is considered. The morphology of the adrenals of rabbits which were on a cholesterol-rich diet for 35 days and on a normal diet for 6 weeks afterwards, was indistinguishable from that of those rabbits killed after 35 days on a cholesterol-rich diet.
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    The effect of paraquat on the in vitro activity of cytosol, mitochondrial and microsomal enzyme systems
    (Health & Medical Publishing Group, 1984) Rossouw, D. J.; Chase, C. C.; Engelbrecht, F. M.
    Subcellular fractions (mitochondria, microsomes and cytosol) were prepared from the lungs of rabbits and rats to investigate the effects of paraquat (Aldrich Laboratories) on the activity of cytosol and mitochondrial dehydrogenases and on the microsomal respiration and reduced pyridine nucleotide oxidation rate. The normal basal oxygen consumption of rabbit lung microsomes was 1.9 ± 0.3 nmol O2/mg microsomal protein/min, and the oxidation rates of reduced nicotinamide-adenine dinucleotide phosphate (NADPH) and reduced nicotinamide-adenine dinucleotide (NADH) were 4.29 ± 0.53 and 4.0 ± 0.55 nmol/mg microsomal protein/min respectively. One molecule of oxygen can therefore oxidize two molecules of NADPH and NADH, and the generated hydrogen peroxide is probably immediately broken down by the catalase activity of the normal lung microsomal preparation. When Aldrich paraquat (1.0 mM) was added to microsomes metabolizing NADPH (0.5 - 0.75 mM), both the rate of oxygen consumption and the generation of nicotinamide-adenine dinucleotide phosphate (NADP) were significantly (P < 0.001) stimulated over the first 5 minutes, and thereafter returned to within basal limits. When microsomes were preincubated with 1.0 mM paraquat before NADPH was added, the oxygen consumption was substantially lower (10.01 ± 1.01 nmol oxygen/mg microsomal protein/min), while the NADPH oxidation rate was almost similar to the basal rate in the absence of paraquat. This resulted in a striking dissociation in the H/O ratio under these circumstances. The addition of potassium cyanide (KCN) (5.0 mM) prior to paraquat pre-incubation and followed by the addition of NADPH restored the stimulatory effect of paraquat on microsomal respiration and on NADPH oxidation rate. Paraquat (0.01 mM) had no effect on the reaction rates of the following enzyme systems, glucose-6-phosphate dehydrogenase (G-6-PD), glyceraldehyde-3-phosphate dehydrogenase (GAPD), lactate dehydrogenase (LDH), malate dehydrogenase (MDH), and isocitrate dehydrogenase (IDH). However, 0.1 mM paraquat slightly inhibited the mitochondrial IDH system, and 1.0 mM paraquat significantly inhibited all the enzymes tested except for mitochondrial and cytosol MDH. The addition of KCN 5.0 mM led to a total inhibition of the LDH and MDH enzyme systems in vitro, but did not affect the IDH, GAPD and G-6-PD systems. However, when KCN was added before or after the addition of 1.0 mM paraquat to the test systems for IDH, GAPD or G-6-PD the inhibitory effect of paraquat was reversed and the reaction rates returned to normal or almost normal. Paraquat (1.0 mM) had no effect on the nicotinamide-adenine dinucleotide-dependent microsomal respiration, and no basic differences were noted between the responses of rat and rabbit lung microsomes exposed to paraquat in vitro.
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    Die effek van steroied-terapie op die sitologiese en histopatologiese veranderinge tydens eksperimentele ekstrinsieke allergiese alveolitis (hipersensitiwiteitspneumonitis)
    (Health & Medical Publishing Group, 1981) Rossouw, D. J.; Chase, C. C.; Scheepers, J. C. E.
    Acute extrinsic allergic alveolitis was experimentally induced in rabbits using horseradish peroxidase (HRP) as antigen. Bronchoalveolar lavage was performed on the excised lungs and total and differential cellular yields determined, and correlated with the histopathological changes in the lungs as well as the total and differential white blood cell counts. After a single parenteral immunization with HRP without adjuvants, and weekly aerosol challenges with nebulized HRP solution for 3 consecutive weeks, a 3-fold increase in the total cell count as well as very pronounced rise in the percentage of lymphocytes was noticed. Histopathologically, the bronchi-associated lymphoid tissue dw-3 (BALT) became more prominent, an increase in the number of foreign body giant cells was noticed and a focal interstitial and intra-alveolar accumulation of lymphocytes, granulocytes and macrophages could be demonstrated, as well as a mild hyperplasia of type 2 alveolar epithelial cells. Intramuscular injections of methylprednisolone acetate (Depo-Medrol) every 72 hours induced a pronounced peripheral lymphopenia, thymic involution and an almost complete disappearance of the BALT in both the control and HRP-challenged rabbits. Similarly, a marked decrease in the total cell count and percentage of lymphocytes was noticed in the broncho-alveolar fluid of the animals with hypersensitivity pneumonitis. No signs of interstitial or intra-alveolar reactions were seen in the lungs of the experimental animals after 3 weeks of aerosol antigen challenge when treated with steroids. Collectively, these data suggest that the development of hypersensitivity pneumonitis was, at least in part, due to a cell-mediated immunological reaction in the lung. This animal model in which steroid suppression of experimental allergic alveolitis has been demonstrated, may be employed to elucidate the cellular pathogenesis of this disease process.
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    Experimental paraquat poisoning : histological, electron microscopic and autoradiographic changes in the lung
    (Health & Medical Publishing Group, 1984) Rossouw, D. J.; Chase, C. C.; Engelbrecht, F. M.
    Paraquat is a potent and widely used herbicide which acts as a specific pulmonary toxin and causes lung fibrosis in man and animals. Some controversy still exists concerning the details of the morphogenesis of the pulmonary lesions. The lungs of rats exposed to intravenous injections of paraquat and sacrificed 6 - 24 days later were examined by light and electron microscopy. Autoradiography was used to detect possible paraquat accumulation in the lung 5 hours after a single intravenous injection. The findings on microscopy suggested an acute phase of damage to alveolar lining epithelium followed by epithelial regeneration. The most pronounced light and electron microscopic findings were: (1) signs of disruption of the alveolar wall; (ii) type II alveolar epithelial hyperplasia; (iii) mobilization of mononuclear cells, and (iv) migration and accumulation of fibroblast-like cells in the intra-alveolar and interstitial spaces. After three equally spaced intravenous injections of paraquat signs of interstitial connective tissue proliferation could be seen. Autoradiography showed low-grade radioactivity over the alveolar wall, indicating possible active uptake of paraquat by alveolar epithelium; this coincides with in vitro evidence of an active transport mechanism for paraquat by alveolar epithelial cells.