Search PubMed⌕ Search

Biomedical subjects

A H Wyllie

Publications and source records attributed to A H Wyllie.

At least 145 records · Page 8Linked to original sources
PubMed1982

Hormone-induced cell death. Purification ad properties of thymocytes undergoing apoptosis after glucocorticoid treatment.

A high proportion of cortical thymocytes obtained from suckling rats undergo apoptosis on exposure in vitro to the glucocorticoid methylprednisolone. The apoptotic cells can be separated from apparently normal thymocytes by isopyknic centrifugation on Percoll gradients. This experimental system provides homogeneous populations of apoptotic cells and thus permits a more incisive study of this physiologic mode of cell death than has been hitherto possible. It is shown that apoptosis involves a sharp but transient increase in buoyant density, concomitant with the appearance of characteristic morphologic changes in nucleus and cytoplasm. More than 80% fo the chromatin of apoptotic cells has a molecular weight sufficiently low to resist sedimentation at 27,000g and consists of short oligonucleosome chains, apparently as a result of endogenous endonuclease activity. By contrast, the chromatin of thymocytes that retain normal density (whether treated or control) is of high molecular weight. Apoptotic cells, unlike those of normal density, show little or no incorporation of nucleosides and amino acids into macromolecules. These investigators were unable to detect populations of cells intermediate between apoptotic and normal in buoyant density, morphologic characteristics, chromatin cleavage, or leucine incorporation, but evidence is presented suggesting that thymidine and uridine incorporation may fall prior to development of apoptosis.

Animals↗
PubMed1982

Action of deoxycoformycin on human T cell colonies in vitro.

The potent adenosine deaminase inhibitor, deoxycoformycin (dCF), is currently under evaluation in the treatment of lymphoid malignancy. We show that dCF inhibits the growth in soft agar of T cell colonies from PHA stimulated human peripheral blood lymphocytes. In contrast to previous attempts to develop an in vitro model for analysis of the drug's action, concentrations lower than 10(-9)M are effective, and no 'priming' by pharmacological concentrations of adenosine is required. Maximum inhibition is obtained when dCF is present over the first 4 hr of cellular exposure to PHA. T cells already proliferating in response to PHA are less sensitive to dCF, implying that S-phase events are not primary targets of the drug's action. Colony inhibition does not appear to be due to alteration in the production of, or sensitivity to, soluble T cell growth factors. In suspension cultures, dCF at concentrations up to 10(-5)M fails to inhibit early PHA-induced volume changes, or later mitosis, in peripheral blood lymphocytes. The results show that there is a critical dCF sensitive step early in PHA stimulation. It involves those T cells capable of forming colonies and may be conditioned by the cellular microenvironment.

Adult↗
PubMed1981

Chromatin changes in apoptosis.

Murine lymphoid cell lines and rat thymocytes treated in vitro with glucocorticoid hormones provide a convenient system for studying the nuclear changes in apoptosis. Morphologically the nucleolus disintegrates and chromatin undergoes an unusual generalized condensation. This is associated with excision of most of the nuclear DNA to short but well-organized chains of nucleosomes, apparently by an endogenous non-lysosomal nuclease. The process is dependent upon macromolecular synthesis and probably is mediated, at least remotely, by the classical steroid-receptor-gene activation pathway. A similar process of chromatin condensation and excision can be produced by the calcium-magnesium ionophore A23187. In other circumstances of 'programmed cell death', analogous chromatin condensation, excision and requirements for macromolecular synthesis have been documented.

Animals↗
PubMed1980

Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation.

In near-physiological concentrations, glucocorticoid hormones cause the death of several types of normal and neoplastic lymphoid cell, but the mechanisms involved are unknown. One of the earliest structural changes in the dying cell is widespread chromatin condensation, of the type characteristic of apoptosis, the mode of death frequently observed where cell deletion seems to be 'programmed'. It is shown here that this morphological change is closely associated with excision of nucleosome chains from nuclear chromatin, apparently through activation of an intracellular, but non-lysosomal, endonuclease.

Animals↗
PubMed1976

High tyrosinase activity in albino Xenopus laevis oocytes.

Tyrosinase was measured in oocytes of the recently described albino mutant (apap) of Xenopus laevis. Although these oocytes show no pigmentation and the eggs are known to contain no melanosomes, tyrosinase - which is probably the only enzyme necessary for melanin synthesis from tyrosine - was increased more than twofold relative to the wild type. Tyrosinase recovered from albino and wild type oocytes showed the same Km with respect to tyrosine, and this was not altered by previous gonadotrophin stimulation in vivo. The tyrosinase assay, based on [14]tyrosine incorporation into acid-insoluble products, was of greater sensitivity than previously described methods of the same type, through removal of low molecular weight material from the oocyte homogenate prior to incubation, and the use of tyrosine of high specific activity.

Albinism↗
PubMed1972

Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics.

The term apoptosis is proposed for a hitherto little recognized mechanism of controlled cell deletion, which appears to play a complementary but opposite role to mitosis in the regulation of animal cell populations. Its morphological features suggest that it is an active, inherently programmed phenomenon, and it has been shown that it can be initiated or inhibited by a variety of environmental stimuli, both physiological and pathological.The structural changes take place in two discrete stages. The first comprises nuclear and cytoplasmic condensation and breaking up of the cell into a number of membrane-bound, ultrastructurally well-preserved fragments. In the second stage these apoptotic bodies are shed from epithelial-lined surfaces or are taken up by other cells, where they undergo a series of changes resembling in vitro autolysis within phagosomes, and are rapidly degraded by lysosomal enzymes derived from the ingesting cells.Apoptosis seems to be involved in cell turnover in many healthy adult tissues and is responsible for focal elimination of cells during normal embryonic development. It occurs spontaneously in untreated malignant neoplasms, and participates in at least some types of therapeutically induced tumour regression. It is implicated in both physiological involution and atrophy of various tissues and organs. It can also be triggered by noxious agents, both in the embryo and adult animal.

Adrenal Glands↗