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Biomedical subjects

R Volpé

Publications and source records attributed to R Volpé.

At least 145 records · Page 8Linked to original sources
PubMed1977

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↗
PubMed1977

The role of autoimmunity in hypoendocrine and hyperendocrine function: with special emphasis on autoimmune thyroid disease.

There is considerable evidence to suggest that the organspecific autoimmune endocrinopathies are primary disorders of the lympoid system. Although proof is not complete, the basic genetic defect in each condition may be one of immune surveillance, that is, a defect in suppressor "T" lymphocytes. Combinations of two or more of these conditions may be due to the concurrence of two or more specific defects in immune control, as well as the random appearance of the appropriate self-directed "forbidden" clones of lymphocytes. In this concept, there is no need for antigenic alteration (only antigenic availability) to initiate these disorders. Both cell-mediated and humoral immunity seem essential, with roles for immune complexes and "killer" cells as well. Antireceptor antibodies are of particular interest in Graves' disease, where they are stimulatory: other antireceptor antibodies have been found that are blocking antibodies, and others may merely bind without either stimulating or blocking.

Addison Disease↗
PubMed1976

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↗
PubMed1976

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↗
PubMed1976

The pathogenesis of Graves' disease.

Graves' disease may prove to be due to a genetic defect in immune surveillance or control, which then permits a randomly mutating thyroid-directed clone of T-lymphocytes to survive, interact with previously normal thyroid cell membrane antigen, and set up a localized cell-mediated immune response. The T-lymphocytes so interacting then cooperate with and direct groups of B-lymphocytes, which consequently produce TSI's: the stimulation of the thyroid parenchymal cells is a direct result of TSI stimulation. PHA stimulates Graves' lymphocytes to produce TSI's by first stimulating T-lymphocytes, which in turn interact with B-lymphocytes, which produce the TSI's. Normal thyroid antigen can stimulate sensitized lymphocytes to produce TSI's, which in turn can interact with normal thyroid cell membranes. This and other evidence suggests that there need not be any thyroidal antigenic change necessary to initiate hyperthyroidism. Stress may be related to the immunologic induction of the disease; it appears that remissions, other than those due to thyroid cell destruction, are immunologic. Exophthalmos may also prove to be an autoimmune disorder resulting from a closely related, but possibly not identical, defect in immunologic surveillance. Other related autoimmune diseases may result from similar related defects in immunologic surveillance, as well as from the random mutation of the appropriate forbidden clone.

Adolescent↗
PubMed1975

Thyroiditis: current views of pathogenesis.

From indirect and circumstantial evidence it would appear that subacute thyroiditis is probably a viral infection of the thyroid gland. The thyroid may respond in the stereotyped manner to any one of a number of viruses. Despite the available evidence, however, the viral theory has yet to be finally proven. Autoimmunity does not appear to be a primary factor in the initiation of subacute thyroiditis, although transient immunologic responses occur as a secondary phenomenon. Autoimmune thyroiditis, on the other hand, is almost certainly a primary immunologic disease, and likely is due to a specific inherited defect in immunologic control. It would appear that both cell-mediated immunity and humoral immunity (i.e., T and B lymphocytes) are necessary for the full expression of this disorder.

Autoimmune Diseases↗