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Biomedical subjects

J F Kerr

Publications and source records attributed to J F Kerr.

At least 37 records · Page 2Linked to original sources
PubMed1985

Apoptosis as the mode of cell death in antibody-dependent lymphocytotoxicity.

A light and electron microscopic study of antibody-dependent lymphocytotoxicity was carried out with the object of elucidating the mechanisms responsible for the cell killing, the basis for the research being the relationship that has recently been shown to exist between the morphology of cell death and its pathogenesis. Chang liver cells coated with a rabbit anti-human antibody were used as targets and normal human peripheral-blood lymphocytes as effector cells. Cytotoxicity assays using release of 51Cr demonstrated extensive K-cell killing, thus validating the suitability of the model for morphological studies. Cell death displaying the features of apoptosis correlated with K-cell activity. A small amount of cell death by classical necrosis was observed, but its extent appeared to be unrelated to the presence of lymphocytes, to pre-treatment of the target cells with antibody, or to the magnitude of 51Cr release. The results support evidence indicating that lymphocytotoxicity depends on activation of a self-destruct program within the target cell. They do not favour a mechanism involving the production of plasma membrane lesions analogous to those responsible for complement-mediated immune cytolysis.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1984

The role of apoptosis in atrophy of the small gut mucosa produced by repeated administration of cytosine arabinoside.

Progressive atrophy of ileal crypts and villi following daily administration of cytosine arabinoside to mice was found to be the result of suppression of mitosis and marked enhancement of apoptosis in the crypt epithelium. The amount of apoptosis produced by each dose decreased as the atrophy advanced. Mucosal regeneration after cessation of administration of the drug was due to increased mitosis in the crypts, and was associated with complete restoration of susceptibility of the crypt cells to further doses. During early regeneration, the wave of increased mitosis was accompanied by a wave of mildly increased apoptosis.

Animals↗
PubMed1984

Successive waves of apoptosis in the rat prostate after repeated withdrawal of testosterone stimulation.

In rats with castration-induced ventral prostatic atrophy, testosterone treatment resulted in reconstitution of the normal weight and histological structure of the gland within 10 d. Subsequent withdrawal of the hormone was followed by rapid involution, which was effected by a combination of extensive loss of epithelial cells by apoptosis and decrease in the size of the cells that remained. The wave of apoptotic deletion was similar to that accompanying the initial involution after castration, and in both cases the rate of apoptosis fell to very low levels by 20 d. Two further consecutive episodes of involution produced by sequential administration and withdrawal of testosterone were also accompanied by similar waves of apoptosis. The results provide quantitative evidence supporting suggestions that apoptosis may be of major kinetic significance in the involution of endocrine-dependent glandular tissues. The majority of the epithelial cells remaining after the completion of involution were able to survive continuing androgen deprivation, but with renewed testosterone stimulation they repeatedly generated populations that once again responded to withdrawal with massive cellular death. The factors determining the selective susceptibility of individual cells in these populations clearly merit investigation.

Animals↗
PubMed1979

The nature of piecemeal necrosis in chronic active hepatitis.

On the basis of histological studies, it is proposed that the type of liver-cell death in piecemeal necrosis is apoptosis. The characteristic inconspicuousness of apoptosis explains why the mode of hepatocyte elimination in piecemeal necrosis has hitherto remained obscure. Cell-mediated immune attack induces apoptosis, not classical necrosis, and the occurrence of apoptosis in piecemeal necrosis links the observed morphological changes in chronic active hepatitis with the other evidence for an autoimmune pathogenesis. It is significant that apoptosis does not evoke inflammation or fibroplasia. In attempting to elucidate the cause of the fibrosis that accompanies progression to cirrhosis in chronic hepatitis, it may thus be more relevant to study the effect on fibroblasts of substances liberated during lymphocyte-hepatocyte interactions than the death of the hepatocytes.

Autoimmune Diseases↗
PubMed1979

Apoptosis. Its nature and implications for dermatopathology.

Apoptosis is a distinctive mode of cell death with characteristic morphologic features which serves as a balance to mitosis in regulating the size of animal tissues. In contrast to coagulative necrosis, the cytologic features of apoptosis suggest active self-destructive rather than progressive disintegration. It typically affects scattered individual cells which condense and bud to produce many membrane-bounded fragments in which organelles appear intact when viewed by the electron microscope. These apoptotic bodies are then phagocytosed and digested by cells resident in the tissue. Apoptosis, unlike coagulative necrosis, does not itself evoke an inflammatory response. Apoptosis is a feature of such diverse processes as deletion of phylogenetic vestiges during normal embryonic development, involution of endocrine-dependent organs after withdrawal of trophic hormones, cell-mediated immune attack on tissues, and therapeutically induced regression of neoplasms. Apoptosis has received scant attention in dermatopathology. However, it is now known to be an important feature of lichen planus, certain drug eruptions, the skin lesions of graft-versus-host reactions, the regression of plane warts, and the effects of ultraviolet damage. It is also involved in the kinetics of cutaneous neoplasms. In some of these situations, apoptotic bodies have, in the past, been given names such as Civatte bodies, colloid bodies, single-cell necrobiosis, sunburn cells, and dyskeratotic cells without their basic nature having been recognized.

Animals↗
PubMed1977

An electron microscopic study of the mode of donor cell death in unmodified rejection of pig liver allografts.

The only type of cell death found in pig liver allografts 1 week after technically successful operation was apoptosis. Its extent paralleled the degree of mononuclear cell infiltration of the liver parenchyma, and mononuclear cells were found applied to the surfaces of hepatocytes showing early stages of the process. The results suggest that cellular immune attack induces apoptosis of donor cells, and that the action is a direct one. However, implication of other factors such as vascular damage in the induction of apoptosis in the grafts could not be excluded.

Animals↗
PubMed1975

An electron-microscope study of the mode of cell death induced by cancer-chemotherapeutic agents in populations of proliferating normal and neoplastic cells.

Deletion of scattered single cells by ultrastructurally typical apoptosis was observed to take place continuously in the lining of the small intestinal crypts of normal mice, and in untreated Crocker mouse ascites tumours. Injection of the cancer-chemotherapeutic agents actinomycin D, mitomycin C, cytosine arabinoside and cycloheximide massively enhanced the rate of apoptosis in each situation, the morphology of cell death induced by these drugs being fundamentally different from that of coagulative necrosis, which developed without treatment in the centres of solid nodules that grew after subcutaneous inoculation of the tumour. In the crypt lining, where the predominant cell type affected appeared to be epithelial, the apoptotic bodies were either extruded into the lumen or rapidly phagocytosed and degraded by adjacent viable cells. But bodies in the ascites tumour were rarely ingested by uninvolved cells, presumably because of their wide dispersal in a fluid medium, and the stages in their development were seen more clearly than has been possible in solid tissues, where phagocytosis is ususlly rapid: they eventually underwent a change resembling coagulative necrosis or in-vitro autolysis. Reports suggesting that cancer-chemotherapeutic agents enhance autophagy in solid malignant neoplasms require confirmation, for secondary lysosomes of any sort were found to be uncommon in the treated ascites tumours, and there is little doubt that phagocytosed apoptotic bodies have been mistaken for autophagic vacuoles in the past. The significance of the fact that cancer-chemotherapeutic agents induce a type of cell death that is found in normal tissues is at present unknown.

Animals↗
PubMed1975

Early jaundice after pig liver transplantation.

Of a series of pigs surviving orthotopic liver allotransplantation with end-to-end anastomosis of the bile duct, 70% were noted to be jaundiced at the end of the first week after transplantation. Seven animals in a subsequent series were investigated biochemically, but operative cholangiography, and by liver biopsy seven days after transplantation, when the jaundice was maximal. There was definite cholangiographic obstruction in only one animal, and this finding was subsequently confirmed at autopsy. This was also the only animal in which bile culture was positive. Jaundiced animals appeared to have more marked histological evidence of rejection than non-jaundiced ones. The jaundice was probably a result of transient rejection and usually resolved spontaneously without immunosuppression.

Animals↗
PubMed1975

Atypical fibroxanthoma of skin: an electron microscope study.

The ultrastructure of two atypical fibroxanthomas of skin is described. Most of the tumour cells were elongate, and contained abundant rough endoplasmic reticulum, well developed Golgi zones, and numerous small vesicles and filaments, the latter sometimes being related to masses of electron-dense material near the plasma-lemma. Their nuclei often showed deep surface indentations. The appearances were similar to those found in the socalled myfibroblasts that occur in granulation tissue. Multinucleated giant cells and lipid-laden cells in the tumours appeared to be merely modified forms of the basic cells type.

Aged↗