Thyrotrophin receptors in porcine thyroid membranes, detergent-solubilized thyroid membranes and isolated thyroid cells [proceedings].
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Biomedical subjects
Publications and source records attributed to R Hall.
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Peripheral blood lymphocytes from patients with Hashimoto's thyroiditis have been cultured for 2--3 weeks in Marbrook flasks. During this period, readily detectable amounts of thyroglobulin and microsomal antibodies were synthesized by the cells and secreted into the culture medium. Gel filtration studies indicated that the autoantibodies produced in culture were of a similar molceular weight to the serum antibodies and this provided evidence that autoantibody synthesis in vitro was representative of autoantibody synthesis in vivo. Our data suggest that this culture technique may be used to make a detailed investigation of the human autoimmune disease process.
Total thyroid hormone concentrations have been measured in the course of a large scale community survey to determine the distribution of these variables in the normal population and to assess the effect of age, sex, previously undectected thyroid disease and medication upon these parameters. 2779 subjects were studied. Serum T4 concentrations were normally distributed. A progressive increase in T4 levels with age was noted in the males, and a smaller increase in females which was concealed by the raised T4 values secondary to oral contraceptive therapy in females under the age of 45. Serum T3 levels were also normally distributed. There was a small reduction in T3 with age in the males but this fall was not seen in the females. T3 values were relatively higher in females under the age of 45 but this increase was not noted after exclusion of subjects taking an oral contraceptive. The changes in thyroid hormone concentrations with age are relatively minor (particularly with respect to T3) in a randomly selected sample from an English town. It is suggested that the changes reported by other authors reflect the process of selection used, and the high frequency of undetected thyroid disease, other illness and medication in hospital-based communities.
Mixtures of drug-resistant and sensitive forms of Plasmodium chabaudi were used to infect mice, and the resulting infections were maintained in the absence of drug. Both chloroquine-resistant and pyrimethamine-resistant mutans were able to survive in such mixed infections. The results of experiments on chloroquine resistance indicated an apparent selective advantage of the resistant over the sensitive form.
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A study of immunoglobulin synthesis by human peripheral blood lymphocytes cultured in Marbrook flasks is described. Maximal amounts of immunoglobulin were produced by 3 weeks and most of this was synthesised between 6 and 21 days. In the region of 90% of the immunoglobulin was secreted into the medium. Pokeweed mitogen (PWM) stimulated cultures produced about 10 times as much immunoglobulin as cells cultured in medium only. After 21 days stimulated cultures produced about 150 microgram of IgG, 125 microgram of IgM and 50 microgram of IgA per 10(7) cells.
The association of congenital ophthalmoplegia and facial paresis (Moebius syndrome) with a variety of other developmental somatic defects has been widely recognised. Its co-existence with hypogonadism of hypothalamic/pituitary origin and subclinical peripheral neuropathy has been reported and in this paper we describe the second case of the Moebius syndrome in association with hypogonadotrophic hypogonadism and a progressive peripheral neuropathy of mixed axonal and demyelinating type.
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Thyrotropin (TSH) receptors on retro-orbital muscle and fat have been implicated in the pathogenesis of Graves' exophthalmos and it has been suggested that TSH has a direct effect on human fat metabolism. We have therefore investigated the interaction of biologically active 125I-labelled TSH with membranes prepared from human adipose, retro-orbital and thyroid tissue. Since lymphocytes contain receptors for several polypeptide hormones, TSH binding to lymphocyte membranes was also studied. We were unable to demonstrate TSH receptors in adult human adipose tissue, retro-orbital muscle and fat, or peripheral blood lymphocytes. In contrast, adult and neonatal guinea pig adipose tissue membranes showed similar TSH binding characteristics to guinea pig thyroid membranes.
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We describe here two patients with hypothyroidism due to pituitary-hypothalamic disease in whom basal thyrotrophin (TSH) levels measured by radioimmunoassay (RIA) were elevated yet when measured by a cytochemical bioassay (CBA) were found to be normal. This finding and the absence of the normal rise of thyroid hormones in response to thyrotrophin-releasing hormone (TRH) mediated release of TSH confirms for the first time the secretion of TSH with impaired biological activity. Primary thyroid disease as a cause for the elevated immunoreactive TSH was excluded by the absence of circulating thyroid antibodies and by a normal thyroidal radioiodine uptake response to exogenous TSH.
We have demonstrated TSH binding sites in membranes prepared from guinea pig testis. The binding of TSH to testicular homogenate was localized to the interstitial tissue and showed similar characteristics to the binding of TSH to thyroid membranes with high affinity (Ka = 2.5 X 10(10) M-1) but limited capacity (approximately 0.9-1.7 pg/mg equivalent testis homogenate). In addition, thyroid-stimulating antibodies inhibited the binding of TSH to both testicular and thyroid homogenate but failed to inhibit the binding of hCG to the testis preparation. These data suggested that the TSH-binding site was distinct from the hCG/LH binding site. Testicular and thyroid TSH-binding sites also appeared to demonstrate a similar degree of cross-reactivity with a crude preparation of hCG. In conclusion, our findings suggest that thyroid-stimulators may influence gonadal function. Furthermore, the ability of hCG to inhibit the binding of TSH to thyroid membranes provides a possible mechanism for the known thyroid-stimulating properties of hCG.