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Biomedical subjects

V V Row

Publications and source records attributed to V V Row.

At least 55 records · Page 3Linked to original sources

Effect of human chorionic gonadotropin on human thyroid tissue in vitro.

Thyroid stimulating substances other than TSH have been found in certain disease states associated with hyperthyroidism. The thyroid stimulator associated with the thyrotoxicosis of trophoblastic disease is uncertain; however, recent evidence suggests a role for hCG. To explore the thyroid stimulating properties of hCG further, we examined the ability of hCG to displace [1252]TSH from receptors on human thyroid membrane and to generate cyclic-AMP (c-AMP) from human thyroid slices. Human chorionic gonadotropin at a concentration of 40 IU/ml displaced labeled TSH from human thyroid membranes and, at a concentration of 69 IU/ml, hCG caused the generation of c-AMP in thyroid slices. These results suggest that hCG can bind to the TSH receptor on thyroid cells and can stimulate them to produce c-AMP at concentrations of hCG within the range that is found in trophoblastic disease.

Chorionic Gonadotropin↗

Comparison of thyroid antigens by the experimental production of precipitating antibodies to human thyroid fractions and the identification of an antibody which competes with long-acting thyroid stimulator (LATS) for thyroid binding.

Antibodies were raised to various sub-cellular fractions of human thyroids, (of Graves' disease, Hashimoto's thyroiditis, and non-toxic goitre). With one exception it was found that antibodies to the Graves' thyroid fractions crooss-reacted with both the non-toxic goitre and Hashimoto's thyroiditis fractions. This exception was in the antiserum to the Graves' 105 000 x g pellet (Gr4) which contained an anr the Hashimoto's (/) thyroid preparations. The antibody-antigen between A-1 and Gr4 could be blocked by the addition of LATS (or TSH) to the antigen, thus suggesting that A- 1 might be a LATS-like immunoglobulin. These results suggest that the TSH receptor can be produced in vivo. Production of such an antibody to the TSH receptor would permit the development for the first time fo a good animal model of Graves' disease.

Antibody Specificity↗

Demonstration of the production of human thyroid-stimulating immunoglobulins (HTSI) by Graves' lymphocytes cultured in vitro with phytohaemagglutinin (PHA).

The lymphocytes from patients with Graves' disease or from healthy subjects have been cultured in vitro either alone or with phytohemagglutinin (PHA). After six days the culture supernatants have been assayed for their human thyroid-stimulating activity by measuring increases in adenosine 3',5' monophosphate (cyclic AMP) in human thyroid slices with which the supernatants have been incubated. Significant levels of human thyroid stimulator activity were found in the culture in which Graves' lymphocytes were cultured with PHA. This activity has been abolished by precipitation of the IgG from the culture supernatant with goat antihuman IgG serum. In contrast, when Graves' lymphocytes were cultured alone, or when control lymphocytes were cultured either alone or with PHA, there was no overall significant production of human thyroid-stimulating immunoglobulin (HTSI). It is concluded that Graves' lymphocytes can be stimulated by PHA to produce HTSI in vitro. Since PHA is known to stimulate only the T lymphocytes, which do not themselves elaborate immunoglobulins as the B lymphocytes do, the above observations indicate a cooperation between T and B lymphocytes in the production of HTSI, at least in this system.

Cells, Cultured↗

Thyroid antigen stimulates lymphocytes from patients with Graves' disease to produce thyroid-stimulating immunoglobulin (TSI).

Circulating lymphocytes from patients with Graves' disease and from control subjects were cultured in vitro alone, with normal human thyroid tissue homogenates, and with other nonthyroid human tissue homogenates. The supernatants of these cultures were assayed for human thyroid-stimulating activity by incubation with human thyroid slices in which increases in cAMP levels were then measured. Human thyroid stimulator activity was demonstrated in 16 out of 20 experiments in which lymphocytes from patients with active untreated Graves' disease (with hyperthyroidism) were cultured with normal thyroid homogenate, in 4 out of 17 experiments when control lymphocytes were similarly cultured, and in one out of 12 experiments in which the lymphocytes from the patients with Graves' disease were cultured with liver or gastric mucosa homogenate. Thyroid-stimulating activity was abolished by precipitation of the globulin from the supernatant by goat anti-human globulin serum. These results demonstrate that normal human thyroid tissue homogenates can specifically stimulate most lymphocytes from patients with Graves' disease and lymphocytes from a few normal subjects to produce human thyroid-stimulating immunoglobulins in vitro. This suggests that the human thyroid-stimulating immunoglobulins are auto-antibodies to normal thyroid constituents, but the possiblity that an antigenic change in the thyroid initiates the disease cannot be entirely excluded. The findings suggest that the prime change in Graves' disease is immunologic, perhaps a failure of immunological suppression.

Antigens↗