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Biomedical subjects

A R Poole

Publications and source records attributed to A R Poole.

At least 199 records · Page 11Linked to original sources
PubMed1978

Early rheumatoid-like lesions in rabbits injected with foreign serum: relationship to localization of immune complexes in the lining tissues of joints and cellular content of synovial fluid.

Immune complex localization in joint tissues and white cell effusion into the joint space as well as synovial lesions are shown to occur in rabbits injected intravenously with bovine serum. Synovial lesions of one knee were found to be associated with immune complexes in joint tissues of the contralateral knee (because of the experimental design very few rabbits had both immunofluorescence and histology performed on the same joint). There was also a week correlation between moderate and gross synovial lesions and cellular effusions of the same joint. Cartilage proteoglycan depletion was seen in some injected animals and this was related to lining cell hyperplasia. Rabbits from different breeding colonies displayed different incidences of lesions suggesting an environmental or genetic influence on the development of rheumatoid-like lesions.

Animals↗
PubMed1978

Influence of methylprednisolone of the sequential redistribution of cathepsin D and other lysosomal enzymes during myocardial ischemia in rabbits.

Occlusion of the circumflex coronary artery induced a profound redistribution in ischemic rabbit myocardium of several lysosomal acid hydrolases, including cathepsin D, B-acetylglycosaminidase, and acid phosphatase. 30-45 min after ligation non-sedimentable cathepsin D activity rose from 36% of the total activity to 42-48%, and in immunohistochemical preparations cathepsin D appeared to have diffused from lysosomes into the cytosol of injured cells. A pharmacologic dose of methylprednisolone (50mg/kg) significantly delayed the subcellular redistribution of cathepsin D and the other hydrolases in ischemic heart. Thus, in treated hearts the nonsedimentable activity of cathepsin D rose to only 38% after 30 min of ischemia and 42% after 45 min (P is less than 0.05 compared to untreated ischemia at each time). Similarly, unlike untreated hearts, noevidence of enzyme diffusion from lysosomes could be demonstrated immunohistochemically in corticosteroid-treated ischemic hearts for over 45 min. After 1-2 h of ischemia, however, steroid-protected myocytes deteriorated and the biochemical activity and anatomical distribution of cathepsin D were indistinguishable from untreated ischemic hearts. This study demonstrates that corticosteroid pretreatment does not prevent alterations in cardiac lysosomes during severe ischemia indefinitely, but does delay their development significantly.

Acetylglucosaminidase↗
PubMed1977

Rheumatoid-like joint lesions in rabbits injected intravenously with bovine serum.

Rheumatoid-like synovial lesions have been produced experimentally in 21% of rabbits receiving intravenous injections of bovine serum by various regimens. They were characterized by lining cell hyperplasia, accumulations, often follicular, of lymphocytes and plasma cells just under the lining layer, sometimes with extensive fibroplasia and pannus formation with cartilage erosion.

Animals↗
PubMed1977

Altered distribution of lysosomal cathepsin D in ischemic myocardium.

To determine the influence of cardiac ischemia on the activity and subcellular localization of lysosomal cathepsin D, anesthetized rabbits were subjected to ligation of the circumflex coronary artery. Total enzyme activity remained unchanged throughout the 2-h ischemic period, but the subcellular distribution of cathepsin D, as analyzed by biochemical and immunohistochemical techniques, was altered dramatically. A marked increase in nonsedimentable (i.e., 40,000-g supernate) activity developed by 30-45 min and increased further by 2 h. Simultaneously, the immunofluorescent localization of cathepsin D was also changed significantly. Within 30-60 min after occlusion, the fine, particulate staining observed in control myocytes was replaced by bright fluorescent patches composed of large granules. Many of these structures displayed prominent halos of diffuse fluorescent staining in the neighboring myocytic cytoplasm, apparently outside lysosomes per se. After 2 h, when nonsedimentable activity was maximally elevated, most of the fluorescent particles had disappeared completely. During this same interim there was no detectable change in the distribution of lysosomal cathepsin D within interstitial cells. These results are consistent with the hypothesis that an early feature of cardiac ischemia is the release of cathepsin D from myocytic lysosomes into the cytosol of damaged cells.

Animals↗
PubMed1975

The localization of retinol-binding protein in rat liver by immunofluorescence microscopy.

The localization of immunoreactive retinol-binding protein (RBP) in rat liver was studied by immunofluorescence microscopy. The study employed specific antisera to rat RBP prepared in a rabbit and in a sheep. The indirect, two-stage method of localizing tissue antigens was employed, and livers of both normal and vitamin A-deficient rats were examined. Fab' fragments of immunoglobulins were used, to minimize non-specific labelling of the frozen sections of liver. With these techniques, the specific immune staining of RBP was observed within liver parenchymal cells. This staining appeared as both particulate and diffuse within the cytoplasm of the parenchymal cells, and was not concentrated within one region of the liver cell or lobule. Staining for RBP was not observed in nuclei or in cells other than parenchymal cells. Similar particulate and diffuse immune staining for RBP was observed in liver sections from both vitamin A-deficient and normal rats. More intense immune staining appeared to be present in the sections of vitamin A-deficient animals, in good correlation with the expected higher levels of RBP in deficient as compared to normal liver. When liver sections were exposed to an antiserum to rat albumin, instead of one to rat RBP, immune cytoplasmic staining was observed which was entirely of a diffuse nature, and did not appear particulate or granular. The findings suggest that RBP, unlike albumin, is localized in part within cytoplasmic vesicles or granules which are large enough to be detected with immunofluorescence, and which are present in livers of both normal and vitamin A-deficient animals. The nature of these putative RBP-containing particles remains to be explored.

Animals↗
PubMed1975

Immunocytochemical localization of cathepsin D in rabbit skin.

The lysosomal proteinase cathepsin D has been localized in rabbit skin by immunocytochemical techniques. The enzyme was found in the basal layer of the epidermis, hair follicles, sebaceous glands, fibroblasts, and endothelial cells. An autoradiographic technique, using the Fab' fragment of IgG, was also used for more effective identification of cell types that contain cathepsin D.

Animals↗
PubMed1975

Dietary control of cardiac lysosomal enzyme activities.

Prolonged starvation in rats is accompanied by consistent increases in the total cardiac activity and the nonsedimentable activity of cathepsin D, the major detectable lysosomal acid proteinase in the heart. Fluorescent staining of rabbit hearts with specific anticathepsin D antiserum reveals that the increase occured predominantly in myocytes, but increased formation of autophagic vacuoles cannot be demonstrated in the myocardial cells by electron microscopy. No changes in cathepsin D occur in animals fed pure carbohydrate or pure fat diets for similar periods, indicating that it is caloric deficiency and not dietary protein deficiency that alters catheptic activity. At the same time that cardiac cathepsin D activity increases markedly, acid phosphatase increases slightly, and the activity of beta-acetyl-glucosaminidase is significantly lower than in hearts of fed rats. The data are compatible with the hypothesis that increased activity of lysosomal acid proteinase may contribute to the net protein catabolism and cardiac atrophy that accompany starvation, especially late in the period of food deprivation. A generalized activation of all lysosomal enzymes does not occur with starvation, however, and the activities of some lysosomal enzymes in the heart decrease.

Animals↗
PubMed1973

Immunoinhibition of intracellular protein digestion in macrophages.

Specific anti-(rabbit cathepsin D) serum, previously shown to inhibit cathepsin D, arrested the intracellular digestion of sheep IgG and radiochemically labeled hemoglobin and proteoglycan in rabbit alveolar macrophages. In the presence of antiserum, cells remained viable, but became very vacuolated. Both sheep IgG and hemoglobin were demonstrated immunocytochemically in vacuoles most of which could also be shown to contain cathepsin D. When the antiserum was removed, cells regained their normal morphology, and digestion of endocytosed proteins returned to normal. These results indicate that cathepsin D can be inhibited within lysosomes of viable cells, in which it plays a major role in the intracellular digestion of certain proteins.

Animals↗