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Biomedical subjects

D Mason

Publications and source records attributed to D Mason.

At least 19 recordsLinked to original sources

Glucocorticoids induce the expression of CD8 alpha chains on concanavalin A-activated rat CD4+ T cells: induction is inhibited by rat recombinant interleukin 4.

Rat T lymphocytes, activated in vitro with concanavalin A (Con A), were shown by flow cytofluorographic analysis to contain a population of cells that simultaneously expressed CD4 and the alpha chain of CD8. The inclusion of the glucocorticoid hormone dexamethasone in the culture medium greatly increased both the frequency of these double-positive cells and the level of CD8 alpha chain expression. The level of expression of CD4 was not affected, and the cells that expressed CD8 antigen only also remained unchanged in surface phenotype. Detailed studies demonstrated unequivocally that the CD4+ CD8 alpha + cells were not artifacts produced by the random association of single-positive cells in the flow cytofluorograph, but arose from precursors that were single-positive CD4+ cells before activation. Furthermore, Con A activation of purified CD4+ T cells, in the presence of T cell-depleted accessory cells, showed that CD8+ T cells played no role in the induction process. However, the induction of CD8 alpha chain expression on CD4+ T cells and the enhancement of this expression by dexamethasone were almost completely inhibited by rat recombinant interleukin 4 (IL-4). Detection of mRNA for rat CD8 alpha chain by Northern blot closely paralleled the cell surface expression of CD8 alpha antigen, indicating that dexamethasone and IL-4 had opposing effects on mRNA levels. In contrast, IL-4 and dexamethasone both induced CD8 alpha chain expression on a rat CD4+ T cell clone when this was activated by specific antigen, and, although the effect with IL-4 was relatively weak, it did not antagonize the effect of the glucocorticoid. The possible significance of these results is briefly discussed.

Animals

Monitoring progress toward US preschool immunization goals.

The United States has achieved over 97% immunization of children by school age and has reduced the incidence of vaccine-preventable diseases by more than 90% since the prevaccination era. However, children often do not receive immunizations at the recommended age, and in densely populated urban areas this delay in immunization has led to epidemics of measles. Correctable deficiencies of the immunization delivery system have been identified in these areas. To respond to needs, the public health infrastructure must be strengthened, and active participation from the private sector must be obtained, both in delivery of immunizations and in assessment of performance. Appropriate action must be stimulated by the provision of timely information on immunization coverage and on indicators of program performance at the local level.

Child, Preschool

T-cell subsets in autoimmunity.

The demonstration that functionally different T-cell subsets can be defined by the isoforms of the leukocyte-common antigen, CD45, that they express, has prompted studies on the roles of these subsets in autoimmunity. The results have led to the identification of a particular subset of CD4+ T cells that have the ability to inhibit autoimmune disease. Further, it has been shown that diabetes in the B-B rat can be transferred by in vitro activation of T cells by Staphylococcal enterotoxin suggesting that superantigens may play a role in the pathogenesis of this disease. However, in this system too, it appears that a subset of T cells can inhibit the induction of autoaggressive cells. In other experimental autoimmune diseases there is evidence that CD8+ T cells can be protective and that these cells may mediate this protection by the synthesis of transforming growth factor-beta.

Animals

Autoimmunity.

The immune system has evolved to protect an organism from the pathogens that invade it but the effector mechanisms involved in mediating this protection are potentially lethal to the host itself. Consequently it is essential that they are not elicited by the host's own tissues and, because biochemically self and non-self are very similar, the immune system has had to develop an exquisite capability to distinguish relatively minor differences. There has been considerable progress recently in understanding how this discrimination is achieved although many questions remain. The problem is important in that the mechanisms that ensure self tolerance occasionally fail. The consequences of this failure are the autoimmune diseases, many of which afflict Man. This article reviews what is known about the way that the immune system normally avoids self reactivity and how breakdown in self tolerance can occur.

Antigen-Presenting Cells

Delayed exposure to pulsatile shear stress improves retention of human saphenous vein endothelial cells on seeded ePTFE grafts.

Since significant loss of endothelial cells (ECs) from the surface of a seeded prosthetic graft occurs after implantation, improved cell retention following exposure to flow should increase the likelihood of long-term success with this technology. An in vitro pulsatile flow circuit was developed to study the effects of two variables on cell retention: cell density at the time of seeding and postseeding incubation time. Fibronectin-coated ePTFE grafts (4 mm x 5 cm) were seeded with human saphenous vein ECs at two densities, confluent (1 x 10(5) cells/cm2) or subconfluent (2 x 10(4)), and incubated in vitro for varying time intervals (90 min, 1, 3, or 7 days). Test grafts were exposed to 90 min of pulsatile flow in an in vitro flow circuit, then fixed, and stained, and in situ cell counts (cells/cm2) were determined for nine representative fields per graft. Paired control grafts were treated identically but were not exposed to flow. Cell retention was calculated using the formula: % retention = cells/cm2 perfused graft divided by cells/cm2 control graft. Grafts exposed to flow 90 min after seeding demonstrated significantly lower cell retention when compared to later time points. When cells were seeded at confluent density, maximal retention (92 +/- 3%) occurred 24 hr after seeding. Prolonged culture of cells seeded on ePTFE grafts at confluent density resulted in increased cell loss. In contrast, on grafts seeded at subconfluent density, retention improved as cells grew to confluence (16 +/- 4.5% initially to 82 +/- 7% at 7 days).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Vessel Prosthesis

Genetic variation in the stress response: susceptibility to experimental allergic encephalomyelitis and implications for human inflammatory disease.

Glucocorticoids that are released from the adrenal glands in response to stress can have profound effects on the immune system. Here, Don Mason illustrates how genetic variation in the magnitude of such a response can determine susceptibility to an experimental autoimmune disease in rats and discusses the implications for susceptibility to inflammatory diseases in humans. He also addresses the possible long-term effects of glucocorticoids on the balance between the cell-mediated and the humoral aspects of immunity and how this balance may influence the temporal development of an immune reaction.

Animals

Myelolipoma in a heterotopic adrenal gland: light and electron microscopic findings.

A symptomatic myelolipoma of the heterotopic adrenal gland was diagnosed as the cause of nephrotic syndrome and was surgically removed. Remission of the nephrotic syndrome promptly ensued. Ultrastructurally, the tumor consisted of well-differentiated cells resembling adrenal cortical cells, bone marrow cells in various stages of differentiation, and lipid cells. Some cells that contained fat were of adrenal cortical origin, but the derivation of most lipid cells and of bone marrow elements could not be deduced from the present ultrastructural findings.

Adrenal Gland Neoplasms

Efficient interaction for automated chromosome analysis using asynchronous parallel processes.

It is likely that any practical automated chromosome analysis system will be interactive. To prevent long pauses in the stream of operator interactions, it is necessary, if using standard computer hardware, to configure for asynchronous and parallel operation. A system is presented which uses several computer processors, which can support one or more operators, and which divides processing into interactive and noninteractive sections, smoothes the rate of presentation of interactions, and keeps both the operator and the computer fully employed.

Chromosomes, Human