Showing papers on "Apoptosis published in 1983"
TL;DR: The results show that each of the various cytotoxic agents tends to act preferentially over a characteristic small range of cell positions, and suggest that normal healthy cells continue to migrate up the crypt and onto the villus in spite of considerable cell death and reduced cell production.
Abstract: The spacial distribution of cell death among the epithelial cells lining the adult mammalian small intestinal mucosa at various times after a range of doses of 10 different drugs as well as after internal or external irradiation (beta particles from tritium, gamma- and X-rays and neutrons) has been recorded. Cell death, expressed as pycnosis or apoptosis, has been recorded for each cell position up the side of the crypts of the small intestine. The results, in the form of distributions of dead cells at each cell position, show that each of the various cytotoxic agents tends to act preferentially over a characteristic small range of cell positions. Since cell position is likely to be related to hierarchical cell position within a family tree or cell lineage, each agent tends to act with greatest efficiency on cells at a particular position within the lineage. Adriamycin and the various forms of radiation tend to kill cells preferentially at cell position 4-5 i.e. on cells very early in the lineage, probably stem cells. Isopropyl-methane-sulphonate, nitrogen mustard and possibly Actinomycin-D act on cell position 6-7, while 5-fluorouracil, Myleran, cyclophosphamide, and cycloheximide tend to kill cells at cell position 7-9. Vincristine and hydroxyurea are the 2 agents that exhibit a specificity for cells highest up the crypt, i.e. latest in transit population of the cell lineage by acting on cell positions 10 or 11. The data also suggest that normal healthy cells continue to migrate up the crypt and onto the villus in spite of considerable cell death and reduced cell production.
238 citations
TL;DR: The constancy of this latent interval suggests glucocorticoids may influence some replication control mechanism unrelated initially to macromolecular biosynthesis, although the intracellular events leading to cytolysis seem likely to differ.
Abstract: The kinetics, specificity and morphology of cytolethal responses have been studied in human glucocorticoid-sensitive and -insensitive lymphoid cell lines (HLCL) and fibroblasts following treatment with high (10(-3)M) and low (10(-6)M) doses of steroid. The high dose cytolethal response appears non-specific occurring in all cell lines with every steroid tested. By contrast, the low dose (pharmacological) cytolethal response requires an active glucocorticoid and a sensitive HLCL. However, both high and low concentrations of steroid induce virtually identical morphological changes in dying cells and similar changes can be induced in cells killed by deliberate feed exhaustion. Although the morphological features in each case resemble apoptosis, the "programmed" physiological form of cell death, the intracellular events leading to cytolysis seem likely to differ. The earliest morphological changes presaging cell death comprise rounding up of cells and condensation of nuclear chromatin. Nuclear changes progress rapidly thereafter and appear to result from detachment of chromatin from the nuclear matrix. The low dose cytolethal response requires the continuous presence of glucocorticoid for periods in excess of 24h, prior to which cell growth appears unaffected. The constancy of this latent interval suggests glucocorticoids may influence some replication control mechanism unrelated initially to macromolecular biosynthesis.
29 citations
TL;DR: The process of cellular budding and formation of apoptotic bodies appears to be specific for cells having well-developed nuclear matrix, such as those from small intestine and liver, however, in these tissues the frequency of apoptosis is relatively low and cannot be considered as the main cause of radiation-induced tissue involution.
14 citations
TL;DR: An orbital embryonal rhabdomyosarcoma, which was excised from the orbit of an 8-year-old girl, was studied by light microscopy and transmission electron microscopy, and showed close apposition between well-preserved tumour rhabDomyoblasts and degenerate or necrotic tumour cells.
Abstract: An orbital embryonal rhabdomyosarcoma, which was excised from the orbit of an 8-year-old girl, was studied by light microscopy and transmission electron microscopy. Cells within the tumour demonstrated by light microscopy diffuse areas of necrosis and isolated single-cell necrosis. There were many viable tumour cells with intracytoplasmic vacuolar structures which contained basophilic granules. Ultrastructural studies showed close apposition between well-preserved tumour rhabdomyoblasts and degenerate or necrotic tumour cells: degenerate cells and condensed cell fragments were observed within the cytoplasm of the well-preserved tumour cells. Some cells which showed degenerative changes had features which suggested that they had ingested more than one degenerate cell on separate occasions. This phenomenon may be regarded as a variant of selective individual cell death, currently referred to asapoptosis, which has not been previously reported in a case of embryonal rhabdomyosarcoma. The patient remains free of tumour recurrence four years following treatment with combined radiotherapy and chemotherapy.
3 citations