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Biomedical subjects

B Rees Smith

Publications and source records attributed to B Rees Smith.

87 records · Page 5Linked to original sources
PubMed1984

A structural comparison of guinea pig thyroid and fat TSH receptors by photoaffinity labelling.

TSH receptors from guinea pig thyroid and epididymal fat have been covalently crosslinked to 125I-labelled TSH conjugated to N-hydroxysuccinimidyl-4-azidobenzoate. Analysis by SDS-PAGE and autoradiography showed bands corresponding to TSH subunits (Mr 14 000) and intact TSH (Mr 28 000; subunits crosslinked) and two at higher Mr separated by 14 000. The latter bands represented one or two subunits of TSH crosslinked to a subunit of the TSH receptor with Mr 57 000 (fat) or 60 000 (thyroid). These Mr values were reduced by trypsin treatment to 43 000 and 50 000, respectively. Analysis under nonreducing conditions showed that both fat and thyroid receptors have a second disulphide linked subunit of Mr 30 000.

Adipose Tissue↗
PubMed1984

A receptor assay for the measurement of TSH receptor antibodies in unextracted serum.

A receptor assay for TSH receptor antibodies is described in which unextracted serum, detergent solubilised TSH receptors and 125I-labelled TSH are used. The assay was rapid and reproducible with coefficients of inter-assay variation of 12.3%, 2.1 and 2.6% at mean inhibition of TSH binding values of 11, 53, and 79 respectively. Assay sensitivity could be increased by reducing the volume of receptors used but some increase in the scatter of values obtained with individual normal sera was also observed. Comparison of human and porcine TSH receptor preparations indicated that porcine tissue gave greater sensitivity. Analysis of different groups of patients and normal subjects (n = 21) showed the absence of detectable TSH receptor antibody activity in 16 patients with rheumatoid arthritis, 10 with multinodular goitre and 12 with Hashimoto's disease. However the antibody was readily detectable in 28 out of 28 Graves' patients (treated and untreated) who were hyperthyroid at the time of assay.

Autoantibodies↗
PubMed1984

A water-soluble fragment of the thyroid-stimulating hormone receptor which binds both thyroid-stimulating hormone and thyroid-stimulating hormone receptor antibodies.

Previous studies have shown that freezing and thawing of human thyroid homogenates releases a water-soluble substance which reversibly binds to TSH-receptor antibodies. This substance has been designated long-acting thyroid stimulator absorbing activity (LAA). We now describe a new method for measuring LAA based on the TSH-receptor assay and application of the technique to the study of LAA. Our results indicate that LAA is a heat-labile glycoprotein which co-elutes with haemoglobin on gel filtration. Furthermore, LAA is retarded by columns of Sepharose-TSH but not by Sepharose coupled to human chorionic gonadotrophin, normal immunoglobulin G or bovine serum albumin, suggesting that LAA contains a binding site for TSH as well as for TSH-receptor antibodies. It would seem therefore that LAA is a water-soluble fragment of the TSH receptor possibly resulting from proteolytic cleavage of the receptor at a site close to the cell surface.

Antibodies↗
PubMed1984

Characterization of lymphoid cells in the thyroid of patients with Graves' disease.

The distribution and function of lymphoid cells has been investigated in thyroid glands obtained at operation from 16 patients with Graves' disease (GD) using a peroxidase technique to enumerate total T and B lymphocytes as well as helper and suppressor T cell subsets in tissue sections. A spectrum of lymphocytic infiltration was observed and the increase from minimal numbers of immune cells in some GD thyroids to focal thyroiditis in others appeared to be due to a rise in all the lymphoid cell types analysed and was not the result of major change in any one lymphoid compartment. T cells were diffusely distributed whereas B cells tended to occur in aggregates. Small numbers of OKT6+ cells (possibly antigen presenting cells) were observed although these were less numerous than in lymphoid organs such as tonsil. Lymphoid cell suspensions prepared from the thyroid tissue of five of seven GD individuals treated pre-operatively with propranolol synthesized thyroid autoantibodies spontaneously in culture and this synthesis was decreased in the presence of pokeweed mitogen. Since the OKT8+ T cell subset has been shown to suppress immunoglobulin production by lymphocyte cultures containing mitogen, it appears that the suppressor T cells, which are readily demonstrable in GD thyroid sections, are functional. It seems unlikely, therefore, that a defect in this type of suppression is responsible for the initiation or perpetuation of the autoimmune response to thyroid antigens in GD.

Adult↗
PubMed1984

Defective regulation of the immune response to tetanus toxoid in Hashimoto's disease.

The humoral immune response to tetanus toxoid has been studied in patients with Hashimoto's disease. Although the magnitude of the response was similar to that observed in normal subjects, the Hashimoto patients demonstrated an inability to regulate their levels of tetanus toxoid antibody. This apparent defect in the control of antibody synthesis may be an important factor in both the initiation and perpetuation of autoimmune thyroid disease.

Adolescent↗
PubMed1984

The distribution of microsomal and thyroglobulin antibody activity among the IgG subclasses.

The IgG subclass distribution of autoantibodies to thyroglobulin (TgAb) and thyroid microsomes (MicAb) in 13 Hashimoto's sera has been investigated using an ELISA technique based on monoclonal anti-subclass antibodies. Considerable subclass restriction was observed with TgAb predominantly but not exclusively associated with IgG4 (mean %TgAb activity associated with IgG4 = 60%) and MicAb predominantly associated with IgG 1 (mean = 49%) and IgG4 (mean = 38%). The tendency for TgAb to be associated with IgG4 accorded with the weak complement fixing properties of this antibody whereas the association of MicAb with IgG1 was consistent with its complement fixing and cytotoxic properties.

Autoantibodies↗
PubMed1983

The IgG subclass distribution of thyroglobulin antibody synthesized in culture.

Thyroglobulin autoantibodies synthesized by Hashimoto lymphocytes in culture and present in serum have been analysed in terms of their IgG subclass distribution. The autoantibodies produced in vitro were frequently IgG4 or IgG1, whether pokeweed mitogen or Epstein-Barr virus was used to stimulate the cultures, and the subclass distribution of these thyroglobulin antibodies was similar to that observed in the patients' serum. It appears therefore that the antibodies synthesized in vitro in response to polyclonal B-cell activators resemble those produced in vivo, and it seems likely that both pokeweed mitogen and Epstein-Barr virus influence the same B-cell precursors of autoantibody-synthesizing cells, albeit by different mechanisms.

Adolescent↗
PubMed1983

Enrichment and depletion of thyroglobulin autoantibody synthesizing lymphocytes.

Lymphocyte populations enriched for (or depleted of) a receptor for thyroglobulin (Tg) have been prepared from Hashimoto peripheral blood mononuclear cells (PBM) by rosetting with Tg coated erythrocytes. Removal of Tg binding cells from PBM or B cell preparations resulted in greater than 85% reduction in their ability to synthesize Tg antibody when stimulated with pokeweed mitogen (PWM) or EB virus (EBV); the depletion was specific since the ability of Tg receptor negative cells to secrete microsomal antibody and total IgG was unimpaired. Hashimoto lymphocytes (PBM or B cells) enriched for Tg binding cells produced only small amounts of Tg antibody when cultured with PWM even in the presence of irradiated T cells and monocytes; exposure to autoantigen followed by mitogen appeared to be inhibitory. However, the Tg receptor positive fraction was readily activated by EBV to synthesize Tg antibody with a specific activity 4-10 times higher than that secreted by unfractionated lymphocytes. The ability to isolate Tg specific B cells from peripheral blood will facilitate the development of EBV transformed cell lines secreting monoclonal Tg antibody and such antibodies will provide invaluable probes in the investigation of autoimmune thyroid disease.

Aged↗
PubMedDate not supplied

Assessment of adrenocortical function and autoantibodies in a baby born to a mother with autoimmune polyglandular syndrome Type 2.

We describe the case of a baby born to a mother with Addison's disease in the context of Autoimmune Polyendocrine Syndrome Type 2. Adrenal cortex autoantibodies and steroid 21-hydroxylase autoantibodies were detectable in the sera of both mother and baby, suggesting the transplacental passage of these autoantibodies. Adrenal autoantibodies were present in the baby's serum at delivery, at 3, 6 and till 34 months of age but no signs of clinical or subclinical adrenal insufficiency were found in the baby during the observation period. These data suggest that the presence of adrenal autoantibodies in serum alone is not a sufficient cause for the development of autoimmune adrenalitis.

Addison Disease↗