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Biomedical subjects

B R Smith

Publications and source records attributed to B R Smith.

At least 199 records · Page 11Linked to original sources
PubMed1989

Human thyroglobulin autoantibodies of subclasses IgG2 and IgG4 bind to different epitopes on thyroglobulin.

IgG autoantibodies to thyroglobulin (Tg) in the serum of patients with autoimmune thyroid disease only recognize a very limited number of epitopes, probably between four and six (Nye, Pontes De Carvalho & Roitt, 1980) on the large Tg molecule (660,000 MW), but attempts to characterize the epitopes have been unsuccessful so far (Male et al., 1985). The distribution of Tg autoantibodies between the IgG subclasses also tends to be restricted and individual patients possess characteristic 'fingerprints' of high affinity IgG1 and/or IgG4 Tg antibodies with smaller amounts of IgG2 Tg antibody (McLachlan et al., 1987, 1988). We have therefore investigated the possibility that Tg autoantibodies of different IgG subclasses interact with different epitopes on Tg.

Autoantibodies↗
PubMed1989

Highly sensitive assays of autoantibodies to thyroglobulin and to thyroid peroxidase.

These highly sensitive assays are based on the interaction between thyroid autoantibodies and 125I-labeled autoantigens. Serum samples are incubated with labeled thyroid peroxidase (TPO) or thyroglobulin (Tg) to allow the formation of antibody-labeled antigen complexes. The complexes are then precipitated by addition of solid-phase Protein A. In the presence of high concentrations of TPO antibody or Tg antibody, more than 50% of the respective labeled antigen was precipitated, whereas only 1-2% was precipitated in the absence of autoantibody. Interassay CVs were 3.2% and 5.7%, respectively, for the anti-TPO and anti-Tg assays. There was no cross-reactivity between Tg antibody and TPO antibody. Results correlated highly significantly with results from other assay systems based on antigen-coated cells or plastic supports, but the assays described here were considerably more sensitive. Scatchard analysis of the assay data provided information on the affinity and serum concentration of TPO autoantibodies (ka approximately 10(9) L/mol and concentrations up to 1 g/L) and Tg autoantibodies (ka approximately 4 x 10(10) L/mol and concentrations up to 1 g/L). Overall, these assays provide a sensitive, precise, and convenient system for measuring and investigating the properties of thyroid autoantibodies.

Antibody Specificity↗
PubMed1989

Monoclonal and oligoclonal gammopathy after bone marrow transplantation.

Serial serum protein electrophoreses were performed on 60 patients undergoing allogeneic and syngeneic bone marrow transplantation (BMT). More than 50% of patients (31 of 60) developed transient oligoclonal and monoclonal gammopathies that appeared an average of 84 days posttransplantation (range 27 to 336 days) and persisted an average of 175 days (range 14 to 652 days). Immunofixation analysis revealed 82% of the M components to be of the immunoglobulin G (IgG) type and 18% to be IgM; 56% were kappa and 44% were lambda. A strong correlation between development of graft versus host disease (GVHD) and appearance of M components was observed (73% incidence in GVHD patients v 27% in non-GVHD patients, P = .0003). Two of the three syngeneic graft recipients also developed monoclonal gammopathies. Evidence of oligoclonal circulating B-cell populations was found in 68% of patients posttransplantation by flow cytometric B-cell clonal excess assay. No correlation of recovery of particular B- or T-lymphocyte subsets and development of M components was seen. The development of transient oligoclonal and monoclonal gammopathies after transplantation may be a ubiquitous finding reflecting recapitulation of early B-cell ontogeny.

B-Lymphocytes↗
PubMed1988

Flow cytometric analysis of circulating lymphocytes following human marrow transplantation.

Study of patients following marrow transplantation has revealed a number of phenotypically unusual cell types that appear to have unique functional correlates in vitro and possible unique clinical correlates in vivo. These include unusual T lymphocytes, such as the Leu4+ Leu2+ but Leu1- T cell; unusual NK cells, such as the Leu2+ Leu11+ NK cell; and unusual B lymphocytes, such as the Leu1+ B cell. Study of these cells both qualitatively to determine further aspects of their structure and function and quantitatively to determine their pattern of normal temporal reconstitution and how that varies under differing clinical conditions should continue to provide improved prognostic and diagnostic testing of postmarrow transplant patients. Furthermore, future study may help to provide information of use in designing improved therapeutic approaches.

Antigens, Surface↗
PubMed1988

Magnetic resonance microscopy of chick embryos in ovo.

Magnetic resonance imaging (MRI) of the live 11-day chick embryo with special radiofrequency coils and 3-D imaging methods has produced contiguous 1.25-mm-thick slices with 200-microns pixel resolution, permitting definition of cardiac chambers, cerebral ventricles, spinal cord, liver, and lungs. It was the objective of this study to image younger chick embryos in ovo with higher spatial resolution through the application of implanted radiofrequency coils. Fertilized Arbor Acre eggs were windowed at 9, 6, and 4 days. Circular coils 18 mm in diameter tuned to 85.5 MHz were suspended around the developing embryo. The eggs were sealed with tape and maintained at 37 degrees C during the imaging procedure. MRI was performed in a 2.0-Tesla GE system utilizing a 3-D Fourier transform acquisition in sagittal and axial planes with a partial saturation sequence (TR = 400 ms, TE = 27 ms). Approximately 1 hour of imaging time was required to obtain 16 contiguous 600-microns-thick slices with 50-microns pixel resolution. Embryos remained viable through the imaging procedure. Embryos were photographed, fixed, and cleared for correlative anatomical study. Vitelline vessels, dorsal aorta, aortic arches, cardinal veins, and cardiac chambers were identified as areas of decreased signal intensity. Cerebral ventricles and the vitreous portion of the eye have signal intensities that are less than adjacent neural, scleral, and lens tissue. Further refinements in MR instrumentation and imaging sequences promise improvements in resolution and offer the potential for sequential observations of the intact embryo.

Animals↗
PubMed1988

Primary hyperparathyroidism presenting as a "peripheral" giant cell granuloma.

A case of primary hyperparathyroidism is reported in which the initial presentation was an intraoral lesion clinically resembling a peripheral giant cell granuloma. A brief review of hyperparathyroidism is included. Of interest is the fact that most cases of hyperparathyroidism today are found in asymptomatic patients in whom the disease is discovered on routine blood chemistry analysis.

Adenoma↗
PubMed1988

Fate of primary orbital dermis-fat grafts in guinea pigs.

A year-long study was undertaken to serially evaluate the tissue changes occurring in dermis-fat graft (DFG) after orbital implantation in nine guinea pigs. Methods used to evaluate the DFGs were histology, magnetic resonance imaging, morphometric analysis, and clinical observations. The histology of a 1-year-old failed human dermis-fat graft has been included for completeness. The study reveals that clinically successful DFGs have a fibrous capsule surrounding the DFG. Minimal revascularization was present. The grafts appear to undergo continual histological changes for approximately 9 months before a steady-state condition ensues. Of interest are changes in the deep-orbital fat posterior to the DFG.

Adipose Tissue↗
PubMed1988

Regulation of cytotoxic T lymphocyte-mediated graft rejection following bone marrow transplantation.

Cytotoxic T lymphocytes have been implicated as the effector cell mediating graft rejection following human allogeneic bone marrow transplantation. We have studied a BMT patient who rejected haploidentical T cell-depleted marrow. In vitro studies demonstrated that the circulating lymphocytes were CD3+ and CD8+, of recipient origin, and exhibited selective cytotoxicity against donor-specific class I major histocompatibility complex antigens. Cytotoxicity was inhibited by monoclonal antibodies directed against CD3, CD8, CD2, and lymphocyte function-associated antigen-1 on the T cell, and against MHC class I proteins on the target cell. Furthermore, these circulating cells inhibited the in vitro growth and differentiation of enriched donor bone marrow progenitor cells, an inhibition that was partially reversed by anti-CD3 MAb. Donor-specific recipient-derived CTL may mediate resistance to engraftment, and CTL activity may be inhibited by a number of MAb. The implications of these findings for host preparation and treatment are discussed.

Adolescent↗
PubMed1988

Recombinant retroviruses encoding cell surface antigens as selectable markers.

Recombinant retroviruses are frequently used in the transfer and analysis of genes. This report describes new retrovirus vectors that incorporate a cDNA copy of a cell surface antigen to function as a selectable marker. By using techniques based on quantitative cell surface immunofluorescence, these vectors allow the rapid detection and isolation of infected cells. These vectors also allow the rapid detection of packaging cell lines producing large amounts of recombinant retroviruses. Potential applications of these vectors are demonstrated.

Antigens, Surface↗
PubMed1988

Phenotypic and functional characterization of human cytolytic T cells lacking expression of CD5.

Although the CD5 (T1) antigen was initially described as a pan-T cell membrane glycoprotein, we report that 14 of 40 normal individuals were found to have 5% or greater of their blood mononuclear cells characterized as CD3 (T3)+ but CD5- by dual immunofluorescence flow cytometry. These cells expressed normal quantities of surface CD3 and CD2 but low levels of CD7, were CD8+ and CD4-, and CD16-. In order to determine whether cells of this phenotype were functional, six CD5- cytolytic T lymphocyte (CTL) clones isolated from normal individuals were studied. The CD5- CTL clones all demonstrated normal cytolytic activity against appropriate target cells. Monoclonal antibodies (MAbs) directed against CD3, CD8, CD2, and lymphocyte function-associated antigen 3, but not against CD5, inhibited cytolytic activity. Changes in intracellular calcium [( Ca2+]i) in response to anti-CD5 and anti-CD3 MAbs were measured. Stimulation by anti-CD5 MAb alone did not give rise to a change in [Ca2+]i. However, under conditions of limiting concentrations of anti-CD3 MAb, preincubation of normal CD5+, but not CD5-, clones with anti-CD5 MAb led to a dramatic enhancement in the ability of anti-CD3 MAb to elicit a rise in [Ca2+]i. We conclude that CD5- T lymphocytes represent a normal lymphoid phenotype. Although CD5 may be involved in T cell activation when present, these CD5- CTL clones appear to express normal cytolytic activity.

Antibodies, Monoclonal↗
PubMed1988

Pulmonary clearance of vasoactive drugs: N-oxidation of SK&F 86466 in the isolated perfused rat lung.

The contribution of the lung to the systemic clearance of the alpha receptor antagonist SK&F 86466 in rats was determined using the isolated perfused rat lung. Lungs were perfused with a blood-free medium containing SK&F 86466 at initial concentrations ranging from 0.26 to 5.1 microM at a flow rate of 104 ml/min. During the perfusion the concentration of SK&F 86466 in the perfusion medium declined monoexponentially. The half-life (8.0 +/- 1.8 min), steady state volume of distribution (205 +/- 16 ml), clearance (18.3 +/- 2.4 mL/min) and extraction ratio (0.18 +/- 0.02) were independent of the initial concentration of SK&F 86466. The free fraction of SK&F 86466 in the perfusion medium, determined by equilibrium dialysis, was 0.598. The average intrinsic clearance of SK&F 86466 in the lung, calculated using the flow rate, free fraction and clearance, was 37.4 ml/min. The concentration of the N-oxide metabolite of SK&F 86466 (SK&F 102102) in the perfusion medium increased with time, and at the end of the perfusion was approximately equal to the initial concentration of SK&F 86466. The pharmacokinetics of SK&F 86488 in lungs from rats pretreated with the suicide substrate inhibitor of cytochrome P-450 1-aminobenzotriazole were identical to the kinetics in lungs from control animals. The pretreatment regimen used reduced the activity of ethoxycoumarin-O-deethylase in lung microsomes by 70% and reduced P-450 content to below the limit of detection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1988

Phase I/II study of recombinant human granulocyte-macrophage colony-stimulating factor in aplastic anemia and myelodysplastic syndrome.

We performed a phase I/II study of the administration of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) to patients with aplastic anemia or myelodysplastic syndrome. Doses ranging from 15 to 480 micrograms/m2 were administered as a one-hour or four-hour intravenous infusion daily for 7 days or as a 12-hour infusion for 14 days. Temporary improvements were seen in granulocyte counts, monocyte counts, and reticulocyte counts in six of eight patients with aplastic anemia and five of seven patients with myelodysplastic syndromes. The patients with myelodysplastic syndromes had larger increases in granulocyte, monocyte, and reticulocyte counts than did those with aplastic anemia, and they also had increases in the numbers of eosinophils (two of seven), immature myeloid cells (two of seven), and myeloblasts (two of seven) that were not observed in patients with aplastic anemia. There was no reduction in erythrocyte transfusion requirements, and no effect was observed on platelet counts. There was only minimal toxicity consisting of transient low-back discomfort, anorexia, myalgias/arthralgias, and low-grade fever. Our data suggest that GM-CSF is well tolerated and is more likely to result in elevations of blood counts in patients with myelodysplasia than in patients with aplastic anemia, but the role of GM-CSF therapy in these disorders remains to be determined.

Adolescent↗
PubMed1988

Phase I/II study of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) in bone marrow failure.

We performed a Phase I/II study of the administration of recombinant human GM-CSF to patients suffering from severe bone marrow failure, either due to aplastic anemia or myelodysplastic syndrome. Doses ranging from 15 micrograms/m2 to 480 micrograms/m2 were administered as an intravenous infusion daily for 7 days. Temporary improvements were seen in granulocyte counts, monocyte counts and reticulocyte counts. There was no reduction in erythrocyte transfusion requirements and no effect was observed on platelet counts. There was only minimal toxicity consisting of transient low back discomfort, anorexia, myalgias/arthralgias, and low grade fever. Our data suggest that prolonged use of GM-CSF might benefit some patients with severe marrow failure.

Adult↗
PubMed1988

Cytoplasmic transfer between endothelium and lymphocytes: quantitation by flow cytometry.

Interactions between human lymphocytes and vascular endothelial cells in coculture have been examined using a newly developed fluorescence flow cytometric technique. Endothelium and blood lymphocytes are capable of bidirectional transfer of a cytoplasmic fluorescent dye, suggesting a novel path of communication between circulating blood cells and the vessel wall. This method also may be applicable to the analysis of other heterocellular interactions.

Animals↗
PubMed1987

Photoaffinity labelling of the TSH receptor on FRTL5 cells.

An investigation of the properties of TSH receptors on FRTL5 cells using affinity labelling with a 125I-labelled photoactive derivative of TSH is described. Our studies suggest that FRTL5 cells contain 2 principal types of cell surface TSH receptors. One form, probably a precursor, consists of a single polypeptide chain (Mr 120,000) with an intrachain loop of amino acids formed by a disulphide bridge. The other type of receptor consists of a water-soluble A chain (Mr 55,000) linked to an amphiphilic B chain (Mr 35,000) by a disulphide bridge. The 2 chain structure is probably derived from the single chain 120,000 protein by enzymatic cleavage of peptide sequences within the loop of amino acids formed by the intrachain disulphide bridge.

Affinity Labels↗