Search PubMed⌕ Search

Biomedical subjects

G N Beall

Publications and source records attributed to G N Beall.

At least 37 records · Page 2Linked to original sources
PubMed1984

Studies of complement activation and IgG subclass restriction of anti-thyroglobulin.

Using a sensitive radioimmunoassay, it was demonstrated that autoantibodies to human thyroglobulin (hTg) did not activate complement upon interaction with solid phase adsorbed hTg. Since IgG4 immunoglobulins do not activate complement, we studied sera containing large amounts of anti-thyroglobulin (anti-Tg) with a sensitive radioimmunoassay for IgG4 anti-Tg. Antibodies of the IgG4 subclass were detected in the sera of each of the eight patients studied and not in control subjects. Quantitative assays of IgG4 anti-Tg were performed by comparing the removal of anti-Tg and total IgG4 during immunoadsorption of anti-Tg. The contribution of IgG4 anti-Tg antibodies to the total quantity of anti-Tg ranged from 6 to 30%, an amount inadequate to explain the lack of complement activation by anti-Tg.

Autoantibodies↗
PubMed1982

Production of human antithyroglobulin in vitro, IV. Specific stimulation by antigen.

Peripheral blood lymphocytes from patients whose serum contains antithyroglobulin are capable of producing antithyroglobulin (anti-Tg) in vitro when stimulated with insolubilized Tg and suboptimal amounts of pokeweed mitogen. Antigen stimulation of anti-Tg production was demonstrated in 6 of 10 experiments in which a 1:10,000 dilution of pokeweed mitogen was also included. Larger concentrations of antigen appeared to inhibit anti-Tg synthesis. Regulation of antigen-stimulated anti-Tg production by the patients' T cells was not different from regulation by the T cells of normal subjects. Both T help and T suppression of antigen-induced antibody synthesis was demonstrated with patients' T cells. These experiments continue to provide evidence that production of the autoantibody anti-Tg is related to an abnormality of B cells.

Adult↗
PubMed1982

Improved radioassay for human antithyroglobulin.

Human antithyroglobulin (anti-HTg) in serum and tissue cultures can be assayed by coprecipitation with 125I-labelled human thyroglobulin (HTg). Co-precipitation of the antibody from different sera gives roughly parallel curves, so that a standard serum can be used for quantitiation of other sera. By assessing the binding of 125I-labelled HTg in antigen excess we estimate the antibody content of the standard serum to be 0.14 ng anti-HTg per ml. Shortened incubation minimizes non-specific binding of HTg to serum globulins and obviates pre-assay absorption of HTg. Radioassay for thyroglobulin antibodies in serum correlated with values obtained by solid-phase competitive-binding assay (SPCB). One unit in our assay corresponds to 0.014 unit by the latter assay and to 0.12 units of MRC. Research Standard A. We confirm that serum thyroglobulin seriously interferes with SPCB assay, giving what appears to be positive results for anti-HTg where none is detected with our assay. Values for anti-HTg are depressed by serum HTg but only in the presence of very high concentrations in serum.

Antibodies↗
PubMed1981

Production of human anti-thyroglobulin in vitro. III. The role of immunoglobulin-bearing cells.

We assayed the production of an IgG autoantibody, anti-thyroglobulin (anti-Tg), in vitro by peripheral blood lymphocytes from patients with autoimmune thyroid diseases. We subfractionated B cell populations and tested them for anti-Tg production with excess numbers of T cells in the presence of pokeweed mitogen. When lymphocytes with surface membrane IgM were depleted by treatment with anti-mu and complement, the remaining mu cells, ineffective in forming IgM, were capable of producing anti-Tg, although less well than untreated cells. Separation of B cells into IgM- and IgM+ fractions after rosetting with anti-mu coated ox red blood cells produced an IgM- fraction capable of making decreased amounts of anti-Tg, while the IgM+ fraction was inactive. We found no evidence for IgG+ precursor cells for anti-Tg formation. We conclude that the long-lived memory cells responsible for anti-Tg production in vitro are not typical IgM-bearing cells. They may lack IgM or carry a form of IgM that is poorly bound by anti-mu.

Autoantibodies↗
PubMed1979

Antithyroglobulin (ATG) production by peripheral blood leukocytes in vitro.

Antithyroglobulin is produced in vitro by pokeweed mitogen stimulation of peripheral blood lymphocytes from patients whose serum contains the autoantibody. Antithyroglobulin synthesis requires T lymphocyte help but is suppressed by larger numbers of T lymphocytes. T cells from both patients and normals perform both of these functions.

Antibody Formation↗
PubMed1979

Studies of the TSH radioreceptor assay.

We have examined several variables in the reagents and procedures used in the TSH radioreceptor assay, the binding of iodinated TSH to its thyroidal receptor. We found that iodinated bovine TSH (S.A. 30 U/mg) was more effectively bound to receptor than iodinated human TSH (S.A. 7.3 U/mg). Iodination of TSH was the Bolton-Hunter acylation method apparently prevented binding to TSH receptor. Surgically removed human thyroid tissue specifically bound 10.3 +/- 1.0 (mean +/- SEM) of added [125I]TSH, but post-mortem human thyroid bound only 3.9 +/- 0.4% of [125I]TSH (p less than 0.001). Maximal binding of [125I]TSH was found at pH 5.8. Many tissue preparations contained activity, possibly due to proteases, which inactivated TSH, and inclusion of a protease inhibitor, aprotinin, significantly increased specific binding.

Animals↗
PubMed1978

Serum protein inhibition of thyrotropin binding to human thyroid tissue.

We used a modification of the TSH radioreceptor assay to detect TSH-binding inhibition (TBI) activity in serum and serum fractions from normal subjects and patients with Graves' disease. TBI activity is present in normal IgG prepared by DEAE-Sephadex chromatography and in normal globulins prepared by precipitation at 1.6 M ammonium sulfate. Other normal serum proteins also had TBI activity when large concentrations were tested. Gel filtration chromatography and powder block electrophoresis were used to prepare fractions of normal and Graves' disease sera. In these fractions from normal serum. TBI activity was found in both gamma-globulin and alpha-globulin-albumin fractions electrophoretically and in both 7S and 4S peaks from gel filtration. TBI activity from Graves' disease patients' sera was similarly distributed, but relatively more TBI accompanied the electrophoretic gamma-globulins. Sepharose Protein-A and anti-IgG were used as immunoabsorbents to isolate and purify IgG from normal and Graves' disease sera. TBI activity in IgG was proportional to the IgG concentration, indicating that the TBI which migrates as a gamma-globulin electrophoretically is an IgG and thus may possibly be an antibody. Inhibitory activity found in normal serum globulins and the non-IgG fractions of both normal and abnormal sera seriously interferes with attempts to use the TSH radioreceptor assay to study the hypothesized anti-TSH, receptor antibody in the serum of patients with Graves' disease.

Chromatography, Affinity↗
PubMed1978

Specificity studies of leukocytic catecholamine receptors.

Using tritium-labeled dl(+/-)epinephrine, we have extended previous studies demonstrating binding of epinephrine to human leukocytes. We have now further assessed the biological significance of this catecholamine binding by comparing the specificity of binding by human leukocytes with the ability of these compounds to inhibit epinephrine-stimulated adenyl cyclase. Binding is specific for catechols, but does not distinguish between physiologically active and inactive stereo isomers, nor between alpha- and beta-adrenergic agonists. Although 2.5 X 10(-4) M 1(-)DOPA, dopamine, d(+)epinephrine and serotonin failed to stimulate leukocytic adenyl cyclase and prevented adenyl cyclase stimulation by 2.5 X 10(-4) M 1(-)epinephrine, the inhibition of adenyl cyclase by d(+)epinephrine is noncompetitive. This catechol-binding site is clearly not the beta-adrenergic receptor. Its physiological significance, if any, remains to be elucidated.

Adenylyl Cyclase Inhibitors↗