Showing papers on "Apoptosis published in 1985"

Macrophage recognition of cells undergoing programmed cell death (apoptosis).

Abstract: As a model for the recognition of effete cells by their viable neighbours BALB/c mouse thymocytes were coincubated with isologous peritoneal macrophages The macrophages bound preferentially to thymocytes undergoing apoptosis, a mode of death induced in these cells by treatment with the glucocorticoid hormone methyl-prednisolone Binding occurred in the absence of serum and was inhibited by N,N'-diacetyl chitobiose, N-acetyl glucosamine and, to a lesser extent, by N-acetyl galactosamine and D-galactose L-fucose, D-mannose and N-acetyl neuraminic acid had no effect The results suggest the presence of lectin-like molecules on the surface of the macrophage that recognize changes in the cell-surface carbohydrate of the apoptotic cell The pattern of inhibition of binding by monosaccharides differs from that of previously described endogenous mammalian lectins

The biology of cell death in tumours.

Abstract: The principal objective of this article is to present evidence for the numerical and biological importance of cell death in tumour growth and regression. Much of this death has the morphology of apoptosis, a process observed elsewhere in biology in a variety of circumstances. Recent studies on the mechanism of apoptosis in non-neoplastic cells suggest that a relatively small number of specific intracellular changes are involved. Two of these are described: endonuclease activation within the nucleus, which coincides with the characteristic morphological changes there, and altered expression of surface carbohydrates, which may be responsible for the swift recognition and phagocytosis of apoptotic cells. It seems probable that similar events occur during the apoptosis of tumour cells. Further knowledge of the control of these endogenous mechanisms for effecting cell death could lead to powerful new means of controlling the growth of tumours.

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

Abstract: 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.

Tubular ultrastructure in acute renal failure in man: epithelial necrosis and regeneration.

Abstract: It is not clear whether tubular cell necrosis is present or not in acute renal failure (ARF) of ischaemic type ("acute tubular necrosis"). In order to get quantitative data, using precisely defined criteria for tubular cell necrosis, 25 renal biopsies from 24 patients with ARF (11 obtained in the active phase, 14 in the early recovery period) were compared with 12 control biopsies. In all 1959 proximal cells and 1603 distal cells were analysed by electron microscopy. Cellular disintegration was very rare in all groups. Shrinkage necrosis (apoptosis) was not present in the proximal tubules of the controls and was rare in ARF (1.6-2.1%). In the distal tubules of controls 2.7% of all cells showed shrinkage necrosis. The incidence in ARF was not significantly increased. "Non-replacement sites" in distal tubules (probably loci where cells have recently been desquamated) were significantly increased in number (5.2%) in the active phase in ARF compared to controls and recovery. The relative number of regenerating cells was not increased. These data show that there is no widespread necrosis of tubular cells in ARF. The increased incidence in distal tubules of focal, denuded areas of the basement membrane in the active phase of ARF indicates a slightly increased desquamation of cells and/or a failure to cover such sites by adjacent cells. This process is not restricted to the brief induction phase of ARF but continues during the whole active phase.

Radiation-induced formation of apoptotic bodies in rat thymus.

Abstract: The process of interphase death of thymocytes in whole-body X-irradiated rats were studied. Cell size distribution analysis indicates that cell fragments (= apoptotic bodies) appeared in the thymus and increased in number depending on dose (200-1000 R) and time (2-6 hr) after irradiation with corresponding decrease in normal-size thymocytes. Occurrence of nuclear fragmentation in association with the cellular fragmentation was proved with cytofluorometric determination of DNA content in individual cells. Scanning electron microscopic observations also revealed extensive fragmentation of cells in the irradiated rat thymus. The results show clearly that cells as well as nuclei fragment rapidly into smaller pieces of various sizes in the irradiated rat thymus as commonly observed with apoptosis.

T lymphocytes in infectious mononucleosis. I. T cell death in vitro.

Abstract: A large proportion of T lymphocytes isolated from the peripheral blood of acute infectious mononucleosis (IM) patients rapidly die when cultured in vitro, with greater than 50% dying within 12-15 h of seeding and up to 80% dying within 24 h. The cells die by apoptosis, a morphologically distinct mode of cell death that occurs in circumstances where death is a regulated event such as in embryonic development and hormone-dependent atrophy. In contrast, the level of cell death remained low in cultures of lymphocytes from controls and in the T cell depleted subpopulation from acute IM patients, with less than 2% and 10% of the lymphocytes dying by apoptosis after 36 h in culture, respectively. The rapid death of acute IM T cells in vitro does not involve soluble factors (including the serum fraction) or T cell to T cell contact. It is suggested that this observation may necessitate a re-evaluation of IM T cell function in vitro.

Cell death (apoptosis) in hair follicles and consequent changes in the width of hairs after irradiation of growing follicles.

Abstract: Irradiation of anagen (growing) hair follicles results in a dose-dependent increase in the number of histologically identifiable fragments of dead cells (apoptotic fragments). The incidence of apoptotic fragments is linearly related to dose, increasing at a rate of 2.92 fragments per follicle section per Gy. The effects of doses of 0.2 Gy can be easily detected. Subjective attempts to associate clusters of fragments with dead or dying cells suggests that the number of fragments per cell increases with dose (about 1.7 fragments per cell after 1 Gy to about 2.7 fragments per cell after 5 Gy). There is a natural incidence of cell death in controls (0.13 +/- 0.06 fragments per follicle section with about 1.4 fragments per dead or dying cell). Damage to the follicle cells is expressed in the differentiated product of the follicle, the hair, by a reduction in width. This is probably the cellular basis for the production of dysplastic hairs. The hair width has been measured and is reduced by about 7 per cent for every gray of radiation. The value of the hair and hair follicles as potential biological dosimeters is discussed.

What's new in proliferation and differentiation in malignant tumours?

Abstract: Summary The volume of a tumour is the difference between the integrals of cell production and cell loss. Cell production depends on mitotis. Cells are lost by detachment from external surface, loss into blood vessels and lymphatics and into body cavities. Immunological lysis, macrophagia and apoptosis take place, and there is necrosis due to hypoxia. Cell birth can be measured, cell loss must be calculated. Tumour cells differentiate and mature to varying degrees. An inverse relationship between maturation and proliferation exists. DNA synthesis inhibitors often also induce differentiation. Retrodifferentiation does not take place. Immature tumours are undifferentiated because of a population change, not because of retrodifferentiation. The oncogene theory assumes that proto-oncogenes are part of the normal genome. They can be activated to oncogenes by mutation or by loss of regulatory factors. Onocogenes code for important membrane proteins: growth factors or receptors. It has been proposed that anti-oncogenes also exist, coding for inhibitory growth factors like chalones. Much attention has hitherto been directed to attempts at arresting the birth rate of cells by cytostatic drugs. There is a trend in modern research to find substances that can force the cells into maturation. Lithium, DMSO, vitaminanalogues, human post-endotoxin serum, TPA, 4 NQO, hormones and acetamide have been shown to induce maturation in experimental systems. This area of research is presently gaining considerable impetus.

The effects of fractionated megavoltage X-irradiation on the rat submandibular gland: an assessment by light microscopy and autoradiography.

Abstract: — Twenty‐four rats were divided into groups that received cumulative dosages of 500, 750 and 1000 rads of fractionated megavoltage X‐irradiation. Animals sacrificed three days post‐irradiation showed marked acinar atrophy but no vascular or ductal changes and isolated areas exhibited more severe damage, predominately vacuolation, apoptosis and total cell destruction. The severity of the changes mirrored the total cumulative dosage. Animals sacrificed 14 days post‐irradiation showed a marked return to pre‐irradiation morphological status. Greater recovery was noted in the 1000 rads dose than in the lower dose groups. A marked increase in vascularity reflected the recovery process. Auto‐radiographic estimations using (H) leucine supported the morphological changes only in the 1000 rad groups and these showed the least uptake at three days, but by 14 days exhibited the greatest increase—far above the level of control animals. Apoptosis apparently enables the tissues following repair of reversible damage to return to normal cellular activity. 1985 Australian Dental Association

Progressive Involution and Physiological Death of Smooth Muscle Cells of Rat Incisal Arterioles

Abstract: The sequential morphology of vascular smooth muscle cell involution and physiological cell death was studied by electron microscopy on rat incisors. Concurrently with changes in the pulp of the continuously growing incisor, its arterioles pass through a cycle of growth, remodeling, regression and decay. During the cycle, smooth muscle cells of the arterioles were observed to involute by segregation of cytoplasmic components, formation of autophagic and digestive vacuoles and shedding of cell fragments. Phagocytic vacuoles were found in neighbouring muscle cells and in adventitious macrophages. Concomitant with the involution in some cells, physiological death was observed among other smooth muscle cells. This appears as an apoptosis with sequential transformations of polyribosomes into monoribosomes, nuclear and cytoplasmic condensation, and finally fragmentation followed by phagocytosis mainly by adventitious macrophages. Knowledge of the features of physiological involution and cell death of the vascular smooth muscle cells may be of importance not only in studies of functional remodeling and adaption, but also in the interpretation of vascular lesions.