Search PubMed⌕ Search

Biomedical subjects

D Mason

Publications and source records attributed to D Mason.

At least 91 records · Page 5Linked to original sources
PubMed1996

CD4+CD8- thymocytes that express L-selectin protect rats from diabetes upon adoptive transfer.

Previous studies have shown that insulin-dependent diabetes can be induced in normal PVG.RT1u rats by a protocol of adult thymectomy and irradiation. The injection of CD4+ T cells from non-irradiated syngeneic donors prevents the onset of disease in approximately 50% of pre-diabetic recipients but all rats are protected if a particular subset of CD4+ cells is transferred. These protective cells express TCR alpha beta and have a memory phenotype, being CD45RClow RT6+. Further studies have demonstrated that the transfer of CD4+CD8- thymocytes, like that of unfractionated CD4+ peripheral T cells, also protects approximately half of recipients from diabetes suggesting that, as with the peripheral T cells, a functional heterogeneity may exist amongst CD4+CD8- thymocytes. In this study, we show that L-selectin is expressed by 50-60% of all CD4+CD8- thymocytes from 6-week-old rats. Adoptive transfer of these populations into thymectomized and irradiated rats revealed that the protection from diabetes observed by CD4+CD8- thymocytes was mediated almost entirely by the L-selectin+ subset. Cells with this phenotype were also able to mediate both humoral and cell mediated responses, providing primed B cells with help for secondary antibody responses and mediating local graft-versus-host reactions. L-selectin- CD4+CD8- thymocytes failed to mediate these responses. These data indicate that CD4+CD8- thymocytes must mature to the stage of L-selectin expression, before they can mediate normal T cell function. The implications of these results are discussed with respect to the possible role of murine NK1.1+ thymocytes in the control of autoimmunity.

Adoptive Transfer↗
PubMed1996

Effects of cytokines and glucocorticoids on endogenous class II MHC antigen expression by activated rat CD4+ T cells. Mature CD4+ CD8- thymocytes are phenotypically heterogeneous on activation.

By the use of mixed leukocyte cultures it was shown that a population of allogeneically activated rat T cells synthesize and express class II MHC antigens, in confirmation of other studies. Compatible with the finding that the MHC molecules detected on these cells were of T cell origin rather than passively acquired, it was found that mRNA for class II transactivator could readily be detected in the T cells stimulated in these cultures. In contrast there was no evidence that mouse T cells synthesized class II MHC antigens. The size of the population of activated rat T cells expressing class II MHC antigens was affected by the presence of IL-4 and glucocorticoids in the activating cultures. However, whereas IL-4 increased the frequency of thymocytes and peripheral T cells expressing class II antigens in culture, glucocorticoids diminished this frequency. The expression of class II MHC antigens by allogeneically activated thymocytes demonstrated a novel heterogeneity amongst mature CD4+ CD8- thymocytes that could not readily be accounted for in terms of differences in maturity of the cells, in the affinity of the TCR for the stimulating ligands or in the stage in the cell cycle. The data suggest that CD4+ single-positive thymocytes do not constitute a homogeneous population differing only in TCR clonotypes.

Animals↗
PubMed1996

Whole language and deaf bilingual-bicultural education--naturally!

This position paper discusses how the tenets of Whole Language and Deaf Bilingual-Bicultural Education complement each other. It stresses that Whole Language is based on natural processes through which children can translate their constructs of personal experiences, observations, and perspectives into modes of communication that include written language and, in the present case, American Sign Language. The paper is based on two emphases: (a) Whole Language emphasizes a two-way teaching/learning process, teachers learning from children, and vice versa; and (b) Deaf Bilingual-Bicultural Education emphasizes American Sign Language as a language of instruction and builds on mutual respect for the similarities and differences in the sociocultural and socioeducational experiences and values of Deaf and hearing people. Both Whole Language and Deaf Bilingual-Bicultural Education attempt to authenticate curriculum by integrating Deaf persons' worldviews as part of educational experience.

Canada↗
PubMed1995

General dental practice--challenges and opportunities: a personal view.

This second paper in the Future of Dentistry series considers the implications for general dental practice of trends in health care nationally and internationally. Its main objective is to increase awareness of the major changes occurring in primary care which provide the dental profession with new challenges and opportunities. It is important that the dental profession is given its proper place in the changing scene and that general dental practice is not isolated from new developments in primary health care.

Delivery of Health Care, Integrated↗
PubMed1995

Prevention of experimental allergic encephalomyelitis in rats by targeting autoantigen to B cells: evidence that the protective mechanism depends on changes in the cytokine response and migratory properties of the autoantigen-specific T cells.

Previous experiments from this laboratory have shown that Lewis rats were protected from experimental allergic encephalomyelitis (EAE) induced by the injection of myelin basic protein (MBP) in Freund's complete adjuvant if they were treated with the encephalitogenic peptide of MBP covalently linked to mouse anti-rat immunoglobulin (Ig) D. It was suggested that this protection developed because the antibody-peptide conjugate targeted the peptide to B cells and that this mode of presentation induced a Th2-like T cell response that controlled the concomitant encephalitogenic Th1 reaction to the autoantigen. The current experiments were carried out to test this hypothesis and to examine the alternative explanation for the protective effect of the conjugate pretreatment, namely that it induced a state of nonresponsiveness in the autoantigenspecific T cells. It was shown that EAE induction was suppressed in Lewis rats when the antibody-peptide conjugate was injected intravenously 14 and 7 d before immunization with MBP in adjuvant, but that anti-MBP antibody titers were at least as high in these animals as in controls that were not pretreated with the conjugate before immunization. Lymph node cells from these pretreated animals, while proliferating in vitro to MBP as vigorously as those from controls, produced less interferon gamma and were very inferior in their ability to transfer disease after this in vitro activation. In contrast, these same lymph node cells from protected rats generated markedly increased levels of messenger RNA for interleukin (IL)-4 and IL-13. When these in vitro experiments were repeated using the encephalitogenic peptide rather than MBP as the stimulus, the proliferative response of lymph node cells from pretreated donors was less than that from controls but was still readily detectable in the majority of experiments. Furthermore, the cytokine expression induced by the peptide was similar to that elicited by whole MBP. While these results support the original hypothesis that the anti-IgD-peptide conjugate pretreatment protected rats from EAE by inducing a Th2-type cytokine response, a totally unexpected finding was that this pretreatment greatly reduced the level of leukocyte infiltration into the central nervous system. This result provides a direct explanation for the protective effect of the pretreatment, but it raises questions regarding migratory and homing patterns of leukocytes activated by different immunological stimuli.

Amino Acid Sequence↗
PubMed1995

Activation of CD4+ T cells in the presence of a nondepleting monoclonal antibody to CD4 induces a Th2-type response in vitro.

In vitro experiments using purified rat CD4+ T cells in primary and secondary mixed leukocyte cultures (MLC) have been carried out to explore the mechanism of inhibition of cell-mediated autoimmune disease in the rat by a nondepleting monoclonal antibody (mAb) to CD4. Previous work has shown that W3/25, a mouse anti-rat CD4 mAb of immunoglobulin G1 isotype, completely prevents the development of the paralysis associated with experimental allergic encephalomyelitis (EAE) in Lewis rats, but does so without eliminating the encephalitogenic T cells. The in vitro experiments described in this study have shown that when CD4+ T cells were activated in the presence of the anti-CD4 mAb in a primary MLC, the synthesis of interferon (IFN) gamma, but not interleukin (IL) 2, was completely inhibited. After secondary stimulation, now in the absence of the mAb, the synthesis of IL-4 and IL-13 mRNA was greatly enhanced compared with that observed from CD4+ T cells derived from primary cultures in which the mAb was omitted. As IL-4 and IL-13 are known to antagonize cell-mediated immune reactions, and as EAE is cell-mediated disease, the data suggest that the W3/25 mAb controls EAE by modifying the cytokine repertoire of T cells that respond to the encephalitogen. The capacity for the mAb to suppress IFN-gamma synthesis provides, in part, an explanation for this change in cytokine production. These findings are discussed in terms of what is known of the factors that determine which cytokine genes are expressed on T cell activation. Possible implications for the evolution of T cell responses in human immunodeficiency virus infection are also discussed.

Animals↗
PubMed1995

The role of subsets of CD4+ T cells in autoimmunity.

It is generally considered that T cells which are reactive with self-antigens are effectively eliminated by two processes: clonal deletion and the induction of T cell anergy. More recently, it has been shown that some potentially autoreactive T cells remain unactivated because the self-antigens for which they are specific are not presented on competent antigen-presenting cells. All these mechanisms of self-tolerance may be regarded as passive in the sense that the autoreactive cells are either deleted or are intrinsically non-responsive. If this view of self-tolerance is adopted, then one would predict that rendering animals relatively lymphopoenic should not give rise to autoimmune disease. This prediction is not verified by experiment. Rats rendered relatively lymphopoenic by adult thymectomy followed by repeated low dose gamma-irradiation develop a high incidence of autoimmune diabetes. Furthermore, it has been shown that the reconstitution of these rats with a specific subset of CD4+ T cells from syngeneic donors prevents the development of this disease. The protective cells have the CD45RClow phenotype, they are resistant to adult thymectomy and the majority of them appear to be non-activated in the donor rats. In contrast, the CD45RChigh CD4+ subset does not provide protection from diabetes. Instead, on injection into athymic rats, it gives rise to pathological changes in a variety of organs: stomach, pancreas, liver, thyroid and lung. In addition, the CD45RClow CD4+ subset prevents these manifestations of autoimmunity in these circumstances. Recently, we have shown that CD4+ CD8- thymocytes are a highly potent source of cells that have the ability to control autoimmune diabetes in rats. It appears that the thymus has three distinct functions: positive selection; negative selection; and the generation of a population of cells that seem specialized for the control of autoimmunity.

Animals↗
PubMed1995

Quality assurance in health sciences literature searching: applying the ISO 9000 quality standard.

Medicine is a literature-based discipline. Ensuring that the literature review which precedes a significant piece of medical research has met predetermined standards is essential. A list of items reviewed carries no guarantees that all appropriate items have been included in the survey of the literature, or that appropriate sources have been efficiently searched. This would be a matter for concern in any discipline. In medicine it is a matter of life and death. Quality assurance procedures that offer guarantees of the standards built into the process, rather than quality control which measures only outputs, can provide the necessary reassurance. The ISO 9000 quality standard offers a much needed quality assurance process. A methodology for applying the ISO 9000 standard to the task of searching the medical literature is outlined in this paper. A new role for medical librarians in promoting a rigorous methodology in the literature review equal to that of the research it supports is defined.

Community Participation↗
PubMed1994

The changing role of the dentist.

This paper considers some of the specific factors which have changed the role of the dentist in a historical context. The impact of post-war developments on postgraduate education, the Nuffield Inquiry of 1980 and the Dental Strategy Review Group are examined. The broader scope of the dentist and dental auxiliaries in general dental practice in the light of changes in disease patterns is described. The benefits to patient care of involving the general dental practitioner and the dental team in primary care services are emphasised. There is a need to educate and train all health care professionals together to promote multidisciplinary teamwork in clinical practice. Change is inevitable but is to be welcomed more than feared.

Dentists↗
PubMed1994

Allelic exclusion of alpha chains in TCRs.

Although the beta chains of alpha beta+ T cells exhibit allelic exclusion it has recently been shown that approximately 20-30% of such cells express both alpha chain alleles on their surface. Potentially these cells have dual specificity, and it has been suggested that they may play a role in autoimmunity and alloreactivity. The analysis presented in this paper examines critically the possibility that the observed violation of allelic exclusion of alpha chain expression arises as a natural consequence of alpha chain rearrangement and intrathymic positive selection. It is concluded that, subject to certain identified conditions being satisfied, the observed frequency of T cells expressing two alpha chains is compatible with such a mechanism. However, it is an essential assumption of the theory that, of the two alpha beta chain complexes on these cells, only one mediates positive selection. It follows that to what extent both receptors are actually functional depends on whether an alpha beta chain complex that has failed to satisfy the criterion of positive selection can mediate antigen recognition in the periphery. In principle the answer to this question may be different if one is considering autoreactivity or alloreactivity. Finally, attention is drawn to the apparent discrepancy between the frequency of peripheral T cells expressing two alpha chains and the failure to find T cell clones of this phenotype. Possible explanations are discussed.

Alleles↗
PubMed1994

Investors in people: journey to continuous development.

Examines the experience of one NHS Unit in Wales as it carried through a strategic decision to meet the National Standard for Effective Investment in People (IiP). Argues that the IiP blueprint for improving personal and organizational performance has never been more important to an NHS undergoing radical change. Seeks to encourage more NHS organizations to be measured against the standard in the areas of commitment, regular review of training and development, continuous development of employee skills, knowledge and attitudes, and evaluating the effectiveness of the training investment in achieving business goals.

Humans↗
PubMed1994

Putting the case for the nurse. Handling and avoiding clinical negligence claims.

Claims for clinical negligence against nursing and medical staff can be a daunting prospect for those involved. This article provides practical advice on situations where nurses may become involved and actions that should be taken when a serious, potentially litigative incident occurs. It also recommends how nurses can avoid claims by handling patients' complaints satisfactorily.

Defensive Medicine↗