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Biomedical subjects

R S Decker

Publications and source records attributed to R S Decker.

At least 73 records · Page 4Linked to original sources
PubMed1980

The distribution of lysosomal cathepsin D in cardiac myocytes.

Lysosomal cathepsin D has been localized with the electron microscope employing an indirect immunohistochemical method using peroxidase labeled, monospecific antibody Fab' subunits. The acid proteinase has been demonstrated within secondary lysosomes of cardiac myocytes and interstitial cells, but not in components of the Golgi apparatus or endoplasmic reticulum. Incubations with a variety of peroxidatic inhibitors suggests that the staining that is observed in secondary lysosomes is attributable to the peroxidase-labeled antibody and not to endogenous oxidation of DAB. The protocol outlined here provides a reproducible method to localize the major lysosomal acid proteinase of the heart at the subcellular level.

Animals↗
PubMed1980

Lysosomal alterations in hypoxic and reoxygenated hearts. II. Immunohistochemical and biochemical changes in cathepsin D.

Sublethal hypoxic injury in rat and rabbit hearts was accompanied by a biochemical redistribution of cathepsin D activity from the particulate to the supernatant fraction of the tissue homogenate, which was partially reversible on reoxygenation. Immunofluorescent staining for cathepsin D failed to reveal major anatomic release of the acid hydrolase until necrosis was present, suggesting that the earlier biochemical redistribution was primarily a result of increased lysosomal fragility during homogenization, with significant intracellular diffusion of the enzyme occurring only as irreversible damage took place. Hypoxia produced enlargement of both cathepsin-D-staining lysosomes and nonstaining vacuoles, as well as their aggregation. These changes were intensified during reoxygenation and recovery of reversibly damaged hearts, suggesting a possible role for the lysosomal-vacuolar apparatus in myocytic repair following hypoxic injury.

Animals↗
PubMed1980

Lysosomal alterations in hypoxic and reoxygenated hearts. I. Ultrastructural and cytochemical changes.

Rabbit hearts perfused under hypoxic conditions underwent progressive subcellular damage, which becomes irreversible by one hour. During the first 20 minutes of perfusion, minor dilation of mitochondria and condensation of nuclear chromatin were the only salient features of cell injury. By 40 minutes moderate mitochondrial swelling was evident in hypoxic myocytes. Moreover, an increase in degenerating mitochondria and autophagic vacuoles was apparent. Reperfusion after either 20 or 40 minutes of hypoxia restored contractility, and injured myocytes underwent a cellular repair process that involved a dramatic increase in lysosomal autoplagy. One hour of hypoxia yielded irreversibly injured myocytes. Upon reoxygenation, some of these cells displayed typical changes of necrosis, but others apparently underwent an abortive repair process involving the formation of large, probably nonfunctional lysosomes. These observations suggest that lysosomal autophagy is important in the efforts at repair that cardiac cells initiate during and after hypoxia.

Acid Phosphatase↗
PubMed1980

Resistance to ischemic damage in hearts of starved rabbits: Correlation with lysosomal alterations and delayed release of cathepsin D.

Prolonged starvation produces dramatic changes both in the lysosomal properties of the heart and in its energy stores and, therefore, might be expected to alter some of the characteristic cardiac responses to ischemia. To test this possibility we ligated the circumflex coronary artery of rabbits that had been fed normally or starved for 6 days. Ultrastructural evidence of myocytic damage following 30 to 120 minutes of ischemia was much less severe in the starved animals than in the normally fed group. The development of signs of irreversible injury (e.g., osmiophilic densities in mitochondria) was delayed for 1 hour or more by starvation. A similar delay occurred in the biochemical redistribution of cathepsin D activity and in the cytoplasmic release of acid hydrolases from lysosomes and sarcoplasmic reticulum. These results indicate a marked protective effect of starvation against myocardial ischemia. In addition, both in starved and in fed animals, ischemically induced release of lysosomal enzymes was closely linked temporally to the development of subcellular damage.

Acid Phosphatase↗
PubMed1980

The role of lysosomes in the heart.

In many tissues there is strong evidence that lysosomes and lysosomal hydrolytic enzymes play important roles in the normal turnover of tissue proteins and other macromolecules. Alterations in the activities and/or availability of lysosomal enzymes are believed to be responsible for alterations in the rate of degradation of many tissue components. It has also been suggested that abnormal release and activation of lysosomal enzymes during ischemia and other potentially lethal events may contribute to the tissue damage that ultimately ensues. Proof that lysosomes are important in cardiac physiology and pathology has not yet been obtained. Circumstantial evidence tends to link lysosomal alterations with changes in protein degradation following many interventions, but this is not always the case. Ischemia is accompanied by leakage of lysosomal enzymes into the cytosol before signs of irreversible damage have appeared, but this association may be coincidental rather than causal. Investigation in the area of cardiac lysosomes has increased markedly in the past 5-10 years. With the development of improved techniques for measuring lysosomal function in heart tissue, there is every reason to expect major breakthroughs in this area of research in the near future.

Animals↗
PubMed1979

Predetermined time standards: their application in workshop settings.

There is a need for a simple, quickly applied tool which can correlate performance of the handicapped individual with that of the able-bodied worker and be easily utilized by nontechnical personnel. Efforts at both the Cerebral Palsy Center and the Rehabilitation Center in Atlanta demonstrated that the third generation of Methods-Time-Measurement (MTM-3) satisfies these criteria. As every motion involved in an operation is detailed and a corresponding time value applied, the over-all result reflects a normal rate of accomplishment more accurately than the usual methods and is especially useful in bidding jobs for the workshop. MTM-3 also has a place in the evaluation section to verify or correct existing standards on bench-type work samples and to develop more meaningful time distribution charts relating to a specific population at a center. In studies of disabled individuals, MTM-3 yields a more accurate determination of the actual degree of disability than the American Medical Association's existing estimated percentages in regard to motor skills.

Persons with Disabilities↗
PubMed1978

Retrograde responses of developing lateral motor column neurons.

Removing the right hind limb of Rana pipiens larvae at different stages during development initiates diverse responses within lateral motor column (LMC) neurons whose axons have entered the limb and are forming neuromuscular junctions; Severing the hind limb at stage V inhibits the future differentiation of LMC neurons and, ultimately, 95% of the presumably injured cells degenerate; Ultrastructural observations indicate that the affected neurons become pyknotic, but display little evidence of lysosomal involvement. However, a quite different reaction is encountered when limb ablation is delayed to stage X. At this stage, LMC neurons rapidly disclose an intense retrograde response, which includes the genesis of numerous secondary lysosomes in degenerating cells; If, however, limb removal is postponed until stage XV or XX then a clasic chromatolysis can be recognized in axotomized neurons. The intensity of the chromatolysis appears to be inversely related to the age of the neurons. This investigation tends to support the premise that differentiating LMC neurons pass through three crucial stages in their development which can be identified following axotomy.

Acid Phosphatase↗
PubMed1978

Gap junctions and ACTH sensitivity in Y-1 adrenal tumor cells.

Initial studies of adrenocorticotropin-sensitivity (ACTH-sensitive) and ACTH-insensitive Y-1 adrenal cortical tumor cell lines suggest a relationship between responsiveness to ACTH and the presence of gap junctions. An ACTH-sensitive clone of Y-1 cells possesses gap junctions and these junctions appear to enlarge with ACTH treatment. GAP junctions have not been observed, however, in an ACTH-insensitive clone of Y-1 tumor cells even when stimulated to produce cyclic adenosine monophosphate and steroids with cholera toxin.

Adrenal Gland Neoplasms↗
PubMed1978

Influence of methylprednisolone on ultrastructural and cytochemical changes during myocardial ischemia. Selective effects on various cell inclusions and organelles including lysosomes.

Occlusion of the circumflex branch of the coronary artery of rabbit hearts for 45 minutes elicits structural and cytochemical changes in myocytes similar to those observed in ischemic dog myocardium, which are indicative of irreversible cell injury. When methylprednisolone is administered prior to occluding the artery, myocytes are transiently protected and many of the electron microscopic signs of irreversible damage are delayed for 15 minutes or more. During this period, the steroid preferentially protects mitochondria, lysosomes, and sarcolemma from the ischemic changes that normally develop. However, some other events, including depletion of glycogen and margination of nuclear chromatin, are only minimally influenced by the therapy, if at all. In all hearts, treated and untreated, the development of severe cell damage, whenever it occurs, is closely associated with cell swelling, mitochondrial dilation with concomitant appearance of amorphous osmiophilic densities, and abnormalities in and, ultimately disappearance of lysosomes, suggesting that damage to cell membranes is a central event in the progression of reversible injury to irreversible infarction and that protection of membrane integrity should be a reasonable aim in efforts to ameliorate or delay ischemic injury.

Animals↗
PubMed1977

Lysosomal properties during thyroxine-induced lateral motor column neurogenesis.

This investigation illustrates that thyroid hormones and not prolactin regulate lysosomal activity during hormone-stimulated lateral motor column (LMC) development in Rana pipiens larvae. Administering a single dose of DL-thyroxine to normal or hypophysectomized larvae induces a 4-8 fold increase in lysosomal acid hydrolase activity within 5 or 6 days. During this interval, the physical properties of lysosomes are dramatically altered with the granules becoming extremely labile to treatments known to disrupt membranes. Nevertheless, thyroxine does not directly influence lysosomal stability; it apparently induces the synthesis and packaging of enzymes through a mechanism requiring de movo production of RNA and protein. The subcellular distribution and physical characteristics of the enzymes are then modified during neuronal death. Such information suggests that changes in lysosomal activity which accompany LMC neurogenesis are indicative of neuronal death, and that these events are controlled by thyroid hormones.

Acid Phosphatase↗
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↗