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Biomedical subjects

R L Boyd

Publications and source records attributed to R L Boyd.

At least 19 recordsLinked to original sources
PubMed1999

A central role for thymic emigrants in peripheral T cell homeostasis.

After initial seeding by thymic emigrants, homeostatic regulation of the T cell pool has been thought to occur entirely within the periphery. Here we report that the degree of thymic emigration directly affects the number and the CD4/CD8 ratio of peripheral T cells. We demonstrate that the increase in T cell pool size caused by the engraftment of 2, 6, or 9 thymic lobes correlates almost exactly with the number of emigrants exported from those grafts in the previous 3 weeks, regardless of how long the graft has been in place. The extent of the increase supports the concept of a 3-week period after thymic export in which emigrant T cells are exempt from peripheral T cell homeostasis. This apparent exclusion of recent thymic emigrants from the niche-based regulation of peripheral T cell numbers ensures repertoire turnover throughout adult life and provides the basis of a direct and previously unrecognized role for the thymus in the regulation of peripheral T cell homeostasis.

Animals↗
PubMed1999

Thymic shared antigen-2: a novel cell surface marker associated with T cell differentiation and activation.

Thymic shared Ag-2 (TSA-2) is a 28-kDa, glycophosphatidylinitosol-linked cell surface molecule expressed on various T cell and thymic stromal cell subsets. It is expressed on most CD3-CD4-CD8-, CD4+CD8+, and CD3highCD4-CD8+ thymocytes but is down-regulated on approximately 40% of CD3highCD4+CD8- thymocytes. Expression on peripheral TCR-alphabeta+ T cells is similar to that of CD3+ thymocytes, although a transient down-regulation occurs with cell activation. Consistent with the recent hypothesis that emigration from the thymus is an active process, recent thymic emigrants are primarily TSA-2-/low. TSA-2 expression reveals heterogeneity among subpopulations of CD3highCD4+CD8- thymocytes and TCR-gamma delta+ T cell previously regarded as homogenous. The functional importance of TSA-2 was illustrated by the severe block in T cell differentiation caused by adding purified anti-TSA-2 mAb to reconstituted fetal thymic organ culture. While each CD25/CD44-defined triple-negative subset was present, differentiation beyond the TN stage was essentially absent, and cell numbers of all subsets were significantly below those of control cultures. Cross-linking TSA-2 on thymocytes caused a significant Ca2+ influx but no increase in apoptosis, unless anti-TSA-2 was used in conjunction with suboptimal anti-CD3 mAb. Similar treatment of mature TSA-2+ T cells had no effect on cell survival or proliferation. This study reveals TSA-2 to be a functionally important molecule in T cell development and a novel indicator of heterogeneity among a variety of developing and mature T cell populations.

Aging↗
PubMed1999

Thymic microenvironment and NZB mice: the abnormal thymic microenvironment of New Zealand mice correlates with immunopathology.

There are distinct microenvironmental abnormalities of thymic architecture in several murine models of SLE defined using immunohistochemistry and a panel of mAb dissected at thymic epithelial markers. To address the issue of the relationship between the thymic microenvironment and autoimmunity, we studied backcross (NZB x NZW) F1 x NZW mice in which 50% of offspring develop nephritis associated with proteinuria and anti-DNA antibodies. We reasoned that if thymic abnormalities are associated with development of disease, the correlation of abnormalities with lupus-like disease in individual backcross mice will form the foundation for identification of the mechanisms involved. In parallel, we directed a genetic linkage analysis, using markers previously shown to be linked to nephritis and IgG autoantibody production, to determine if such loci were similarly associated with microenvironmental changes. Our data demonstrate that all (NZB x NZW) F1 x NZW backcross mice with disease have microenvironmental defects. Although the microenvironmental defects are not sufficient for development of autoimmune disease, the severity of thymic abnormalities correlates with titers of IgG autoantibodies to DNA and with proteinuria. Consistent with past studies of (NZB x NZW) F1 x NZW mice, genetic markers on proximal chromosome 17 (near MHC) and distal chromosome 4 showed trends for linkage with nephritis. Although the markers chosen only covered about 10-15% of the genome, the results demonstrated trends for linkage with thymic medullary abnormalities for loci on distal chromosome 4 and distal chromosome 1. We believe it will be important to define the biochemical nature of the molecules recognized by these mAbs to understand the relationships between thymic architecture and immunopathology.

Animals↗
PubMed1999

Fluoroscopy-guided retrieval of a sheared endotracheal stylet sheath from the tracheobronchial tree in a premature infant.

Endotracheal intubation of premature infants with respiratory distress is a commonly performed procedure in the neonatal intensive care unit. We report a rare complication of this procedure, shearing of the plastic sheath that is bonded to and surrounds the stylet used to assist intubation and lodging of the sheared stylet in the tracheobronchial tree of a small premature infant. We suggest a method for removing the plastic foreign body using fluoroscopy and an Amplatz gooseneck snare directed through the existing endotracheal tube, a technique not previously reported.

Alloys↗
PubMed1999

Long-term monitoring of adult periodontitis patients in supportive periodontal therapy: correlation of gingival crevicular fluid proteases with probing attachment loss.

The aim of this retrospective study was to determine if a chairside assay for neutral protease activity in gingival crevicular fluid (GCF) could provide an early indication of site-specific disease activity, as defined by probing attachment loss. Clinical measures and assay data were collected at 6-month intervals over an average period of 26 months (range from 24 to 36 months). 38 subjects were selected from a pool of previously-treated chronic adult periodontitis patients who were in periodontal maintenance at intervals of 3 to 6 months. GCF samples were collected from a total of 71 tooth sites exhibiting prior attachment loss, and analyzed for neutral protease activity (NPA). Positive BOP and positive NPA scores were classified as true positives if sites subsequently lost at least 1 mm of attachment over the next 12 months, as confirmed by linear regression analysis. As a predictor of breakdown, the NPA assay had an accuracy of 94% and a risk ratio of 37.6 as compared to values of 58% and 1.5 for BOP. When only the subset of sites > or = 7 mm were considered, the NPA assay had a calculated accuracy of 92% versus a value of 50% for BOP. These results indicate that the assay appears to differentiate between bleeding at sites exhibiting only chronic inflammation with no attachment loss and bleeding at sites undergoing active attachment loss.

Adult↗
PubMed1998

The role of the thymus and recent thymic migrants in the maintenance of the adult peripheral lymphocyte pool.

The thymus is essential for the initial seeding of T cells to the periphery, but its role in maintaining the adult T cell pool remains poorly defined. We investigated whether changes to the rate of T cell export could form part of the mechanism(s) controlling the homeostatic regulation of the size and composition of the peripheral T cell pool. Using neonatal thymi grafted under the kidney capsule, we found that irrespective of whether the pool was oversupplied (by thymic grafts) or undersupplied (due to neonatal thymectomy), the thymic export rate was constant from both the host and graft thymus, and the periphery remained constant in size. Recent thymic emigrants (RTE) were also tracked to determine the extent of their acceptance into the T cell pool of a normal mouse. As a population, RTE are phenotypically mature, but were distinct from resident T cells in the periphery, being released in a CD4/CD8 ratio approximately twice that of established peripheral T cells. This export ratio is similar to that of T cells in the mature thymic compartment, but soon after entry into the periphery, the ratio falls, indicating separate thymic and peripheral regulation of the CD4/CD8 ratio. RTE may also be preferentially incorporated into the periphery, causing displacement of resident T cells, thus maintaining the size of the peripheral pool. Although not vital for the maintenance of a functional T cell pool, the acceptance of RTE in a "full" peripheral pool would ensure that the T cell receptor repertoire is kept diverse and that the T cell population encompasses a broad range of naive as well as memory T cells.

Animals↗
PubMed1998

Etiology and sequelae of root resorption.

This article reviews the current status of investigation into apical root resorption within the context of orthodontic treatment. Treatment and patient factors that have traditionally been investigated are discussed, along with the results of current research in this area. The need for rethinking traditional research strategies in the quest for identifying both control and causative mechanisms is explored. Finally, proposals for key areas of future interest are highlighted.

Animals↗
PubMed1998

Positive selection of low responsive, potentially autoreactive T cells induced by high avidity, non-deleting interactions.

Using a novel cell suspension model we investigated the relative abilities of nominal peptide and variants thereof to modulate de novo positive selection of lymphocytic choriomeningitis virus (LCMV)-specific TCR transgenic T cells. Confirming our earlier findings intermediate concentrations (10(-7) to 10(-5) M) of the nominal agonist peptide, p33, induced CD8 co-receptor down-modulation at the level of the entire receptor and the CD8beta chain as a consequence of high but non-deleting signal interactions. Agonist peptide variants caused down-modulation of the CD8beta chain but to a lesser degree. An antagonist peptide capable of inducing positive selection did not cause such modifications of the co-receptor. The positively selected TCRhiCD8alpha alpha and TCRhiCD8- cells were functional but not as efficient as TCRhiCD8alphabeta cells, presumably due to lower avidity interactions in the absence of the CD8beta chain or entire co-receptor. CD8beta mRNA was absent in these cells and was not up-regulated when further stimulated with fresh antigen-presenting cells pulsed with 10(-5) M p33. Effectively our data suggest that it is not the agonist or antagonist nature of a peptide per se but the overall strength of signalling that determines whether a cell will be positively or negatively selected, or die by neglect. Furthermore the agonist/antagonist properties of peptides defined at the level of mature T cell function do not unequivocally predict their effect on positive/negative selection. The ability of the T cell to down-modulate its CD8 co-receptor in response to high but non-deleting peptide interactions during positive selection allows the survival of T cells with a broader range of affinities and represents a possible mechanism by which low responsive but potentially autoreactive cells may escape into the periphery.

Acetyltransferases↗
PubMed1998

An adult thymic stromal-cell suspension model for in vitro positive selection.

Presented here is a cell-suspension model for positive selection using thymocytes from alphabeta-TCR (H-2Db-restricted) transgenic mice specific to the lymphocytic choriomeningitis virus (LCMV) on a nonselecting MHC background (H-2d or TAP-1 -/-), cocultured with freshly isolated adult thymus stromal cells of the selecting MHC type. The thymic stromal cells alone induced positive selection of functional CD4- CD8+ cells whose kinetics and efficiency were enhanced by nominal peptide. Fibroblasts expressing the selecting MHC alone did not induce positive selection; however, together with nonselecting stroma and nominal peptide, there was inefficient positive. These results suggest multiple signaling in positive selection with selection events able to occur on multiple-cell types. The ease with which this model can be manipulated should greatly facilitate the resolution of the mechanisms of positive selection in normal and pathological states.

Animals↗
PubMed1998

Thymic-shared antigen-1 (TSA-1). A lymphostromal cell membrane Ly-6 superfamily molecule with a putative role in cellular adhesion.

The seeding and colonization of the thymus by bone marrow stem cells and the maturation of these cells into mature T lymphocytes are dependent on cell-surface recognition events between different cell lineages within the thymic microenvironment. Positive and negative selection processes within the thymus produce a peripheral T-cell repertoire capable of recognizing peptides derived from foreign antigen bound to self MHCmolecules. In addition to the TCR/MHC-peptide interaction, many other cell-surface molecules act in concert to regulate the kinetics of cellular interactions and intracellular signaling events during thymopoiesis. We have investigated the complexity of the thymic stroma by using monoclonal antibodies to clone cell-membrane molecules of thymic stromal cells. Thymic-shared antigen-1 (TSA-1) is a molecule of interest because it is expressed by both immature thymocytes and stromal cells. We report herein the structural and evolutionary relationships between TSA-1 and molecules of the Ly-6 superfamily (Ly-6SF), and present evidence that TSA-1 functions as a cell-surface receptor by binding a cognate cell target molecule on the surface of a subset of thymocytes.

Amino Acid Sequence↗
PubMed1997

A comparative analysis of the murine thymic microenvironment in normal, autoimmune, and immunodeficiency states.

It is widely accepted that the thymic microenvironment regulates normal thymopoiesis through a highly coordinated and complex series of cellular and cytokine interactions. A direct corollary of this is that abnormalities within the microenvironment could be of etiologic significance in T-cell-based diseases. Our laboratory has developed a large panel of monoclonal antibodies (mAbs) that react specifically with epithelial or nonepithelial markers in the thymus. We have taken advantage of these reagents to characterize the thymic microenvironment of several genetic strains of mice, including BALB/cJ, C57BL/6J, NZB/BlnJ, SM/J, NOD/Ltz, NOD/Ltz-scid/sz, C57BL/6J-Hcphme/Hcphme, and ALY/NscJcl-aly/aly mice, and littermate control animals. We report herein that control mice, including strains of several backgrounds, have a very consistent phenotypic profile with this panel of monoclonal antibodies, including reactivity with thymic epithelial cells in the cortex, the medulla and the corticomedullary junction, and the extracellular matrix. In contrast, the disease-prone strains studied have unique, abnormal staining of thymic cortex and medulla at both the structural and cellular levels. These phenotypic data suggest that abnormalities in interactions between developing thymocytes and stromal cells characterize disease-prone mice.

Animals↗
PubMed1997

Clinical and laboratory evaluation of powered electric toothbrushes: in vivo determination of average force for use of manual and powered toothbrushes.

Mechanical oral hygiene instruments are intended to aid in the removal of stain and dental plaque from tooth surfaces. Certain home hygiene procedures, however, can lead to soft and hard tissue trauma. Power assisted brushing instruments are gaining in popularity, yet there is limited information on the interaction of these home care instruments with commercial dentifrices, and the resultant impact on oral tissues. In this study, the average forces applied during in vivo toothbrushing were determined for three powered brushing instruments (Rota-dent, Interplak and Braun Oral-B Plaque Remover) and a manual toothbrush (Oral-B P40). The Rota-dent instrument was found to be used with the lowest brushing pressure followed, in order, by the Braun Oral-B Plaque Remover. Interplak and the manual toothbrush. The average amount of dentifrice applied to the three powered brush heads was directly related to the size of the head, with Rota-dent typically receiving the least and Interplak the most applied dentifrice.

Adolescent↗
PubMed1997

Clinical and laboratory evaluation of powered electric toothbrushes: laboratory determination of relative abrasion of three powered toothbrushes.

Previously established data on average forces applied to various brushing instruments during in vivo toothbrushing were incorporated into a laboratory abrasion model. The apparatus included a specially constructed and standardized brushing machine and utilized an acrylic resin substrate. Three powered brushing instruments (Rota-dent, Interplak and Braun Oral-B Plaque Remover) and a manual toothbrush (Oral-B P40), were compared in this model. The system demonstrated excellent precision and could distinguish between brushing instruments with as little as 10% difference in abrasivity. It was found that brushing abrasivity increased in the order of Rota-dent < Braun < Interplak.

Acrylic Resins↗
PubMed1997

Clinical and laboratory evaluation of powered electric toothbrushes: laboratory determination of relative interproximal cleaning efficiency of four powered toothbrushes.

The clinical brushing data from the paper entitled, Clinical and Laboratory Evaluation of Powered Electric Toothbrushes: In Vivo Determination of Average Force for Use of Manual and Powered Toothbrushes, by Boyd et al. in this Special Issue, were incorporated into a laboratory cleaning model. Utilizing a standardized brushing machine and a methyl methacrylate substrate, four powered brushing instruments were tested for cleaning efficiency: Rota-dent. Braun Oral-B. Interplak and Sonicare, and a manual toothbrush (Oral-B P40). The Sonicare powered brushing instrument was tested at the manufacturer's recommended brushing force of 0.5 N as well as a calculated force of 1.0 N. The results showed that the Rota-dent was more efficient (p < 0.01-0.001) in removing stain from both flat and interproximal surfaces than any of the other tested brushes. These results, together with those reported by McLey, et al. in Clinical and laboratory Evaluation of Powered Electric Toothbrushes: Laboratory Determination of Relative Abrasion of Three Powered Toothbrushes in this Special Issue, demonstrate that the rotary action Rota-dent instrument has the most efficient combination of low abrasion and high cleaning efficiency of the four powered brushes and the manual brush when all instruments were tested using clinically documented pressures.

Analysis of Variance↗