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Biomedical subjects

R S Sundick

Publications and source records attributed to R S Sundick.

At least 37 records · Page 2Linked to original sources
PubMed1985

Induction of autoimmune thyroiditis in chickens by dietary iodine.

Clinical studies have suggested that excess dietary iodine promotes autoimmune thyroiditis; however, the lack of a suitable animal model has hampered investigation of the phenomenon. In this study, different amounts of potassium iodide were added to the diets of chicken strains known to be genetically susceptible to autoimmune thyroiditis. Administration of iodine during the first 10 weeks of life increased the incidence of the disease, as determined by histology and the measurement of autoantibodies to triiodothyronine, thyroxine, and thyroglobulin. Further support for the relation between iodine and autoimmune thyroiditis was provided by an experiment in which iodine-deficient regimens decreased the incidence of thyroid autoantibodies in a highly susceptible strain. These results suggest that excessive consumption of iodine in the United States may be responsible for the increased incidence of autoimmune thyroiditis.

Animals↗
PubMed1985

Analysis of lymphocytes infiltrating the thyroid gland of Obese strain chickens.

Lymphocytes were isolated from the infiltrated thyroid glands of 2- to 5-wk-old Obese strain (OS) chickens with spontaneous autoimmune thyroiditis (SAT). Immunofluorescence analysis performed by using a panel of monoclonal and polyclonal antibodies revealed that 60% of thyroid infiltrating leukocytes (TIL) were mature T cells, a large portion of which seemed to be in an activated state bearing Ia-like antigens (10%) as well as a surface determinant associated with T cell activation (16%), i.e., possibly the receptor for interleukin 2 (IL 2). Furthermore, a relatively high plasma cell content (5%) was observed. TIL exhibited high proliferative responses to T cell mitogens (concanavalin A, phytohemagglutinin) and IL 2, but only weak responses to the B cell mitogen LPS from Salmonella typhimurium. When injected into newly hatched, MHC-identical, irradiated normal chickens, TIL induced both the production of autoantibodies and thyroid infiltration. Peripheral lymphocytes from spleen and blood and thymocytes from the same OS donors had no effect. Analysis of chemically (cyclophosphamide) bursectomized OS chickens suggested that an intact B cell system was not obligatory for the induction of SAT. TIL from these chickens consisted of 77% T cells and less than 1% B lymphocytes, yet were capable of inducing severe thyroid infiltration upon transfer into normal recipients. These findings emphasize the importance of the T cell system in the initiation of SAT.

Animals↗
PubMed1985

Enhanced response to Con A and production of TCGF by lymphocytes of obese strain (OS) chickens with spontaneous autoimmune thyroiditis.

The mitogenic response to Con A and the production of T cell growth factor or interleukin 2 (IL 2) by splenic and peripheral blood lymphocytes of obese strain (OS) chickens with spontaneous autoimmune thyroiditis have been investigated. By using an optimized method with Con A-coated chicken erythrocytes (MRC), lymphocytes of OS chickens were found to exhibit significantly elevated mitogenic responses as compared with cells from either Normal White Leghorn chickens (NWL) or animals of the Cornell C-Strain (CS), from which the OS has originally been developed. This difference was observed throughout ontogeny up to 15 mo of age, and was associated with increased levels of IL 2 activity in the culture supernatants. The elevated responsiveness of OS T lymphocytes was also found to be manifested in the expression of receptors for IL 2, because Con A-stimulated lymphocytes of OS birds were significantly more effective than those from normal controls in absorbing IL 2 activity from conditioned media (CM) of stimulated spleen cells. High concentrations of CM were suppressive in IL 2 assays, signaling the presence of an inhibitory factor(s) in addition to IL 2. An additional indication for defective immunoregulation was that CM from OS lymphocyte cultures showed significantly less of this suppressive activity in comparison with CM of normal (NWL and CS) lymphocyte cultures. Finally, the spontaneous uptake of 125IUdR of embryonic and early post hatching OS spleen lymphocytes was consistently and significantly enhanced. This difference, however, in contrast to the one observed in Con A responses, was found to decrease with age. The data are discussed in view of the contradictory results concerning T cell functions reported for several autoimmune states in mammals.

Aging↗
PubMed1985

Analysis of triiodothyronine and thyroxine-binding autoantibodies in chickens susceptible to autoimmune thyroiditis.

This report reveals a surprisingly high incidence of thyroid hormone (T3 and T4) autoantibodies (THA) and thyroglobulin autoantibodies in a closed flock of untreated Cornell strain (CS) White Leghorn chickens. This flock is closely related to the Obese strain chicken, which develops a severe spontaneous autoimmune thyroiditis. A sensitive electrophoretic autoradiographic assay for THA was developed. This assay was applied to the study of autoantibodies to T3 and T4 in the sera of adult female CS chickens. Of 109 females, 29.4% had antibodies to T3 and 18.4% had antibodies to T4. The incidence of thyroglobulin antibodies, determined by passive hemagglutination, was 15.6%. The presence of THA affected RIA measurements because serum T3 and T4 hormone concentrations appeared elevated in those birds with moderate to high antibody levels. There was major variance in the electrophoretic heterogeneity of the THA from individual chickens; i.e., some of the sera contained antibodies to T3 or T4 that appeared to be monoclonal, whereas other sera exhibited polyclonal multi-banded patterns. To determine if antibodies reactive with T3 and T4 (which are haptens) were generated by antibody responses to the T3/T4 sites on the thyroglobulin molecule, competitive binding assays were performed to determine the relative binding affinities of the antibodies for the haptens (T3/T4) and the "hapten-conjugate" (thyroglobulin). In these assays, thyroglobulin competed with the haptens, thus supporting the above hypothesis.

Animals↗
PubMed1985

The induction of tolerance to thyroglobulin significantly reduces the severity of thyroiditis in obese strain chickens.

Obese strain chickens develop severe spontaneous autoimmune thyroiditis several weeks after hatching, characterized by mononuclear cell infiltration and antibodies to thyroglobulin (Tg). The presence of antibodies to Tg suggests that Tg is an important antigen in this disease, but it does not provide definitive evidence. To clarify this point, Obese strain chicks were tolerized at hatching with Tg and then examined up to 6 wk later for antibodies to Tg, thyroid pathology, and function. Various tolerance regimens were tested. The optimal conditions were i.v. injection of Tg within 24 hr of hatching, and injection of at least 1 mg. Tg isolated from normal thyroid glands was satisfactory, and it did not have to be deaggregated. Tolerance induced by the above procedure significantly retarded all parameters of autoimmunity, although by 6 wk of age some of the tolerized chicks had severe thyroiditis. Multiple weekly injections of Tg were no more effective than a single injection at hatching. Interestingly, a single injection at hatching was very effective, yet it was cleared from the circulation within 24 hr. In summary, tolerance induced with Tg had a profound effect on the disease and thus provides good evidence for the role of Tg in this disease.

Animals↗
PubMed1983

The decreased growth rate of obese strain chicken thyroid cells provides in vitro evidence for a primary target organ abnormality in chickens susceptible to autoimmune thyroiditis.

The obese (OS) strain of chickens develops severe autoimmune thyroiditis, whereas its progenitor, the Cornell (CS) strain, rarely does. To detect possible developmental abnormalities in the OS thyroid, CS and OS embryonic thyroid epithelia were cultured in vitro and compared in several assays for growth and DNA metabolism. It was found that OS thyroid cells incorporated less tritiated thymidine, reached lower saturation densities, and possessed a significantly longer doubling time (26.1 hr) than CS cells (17.6 hr). The decreased growth rate of OS thyroid cells correlated with their inability to condition their own media. These abnormalities in the embryonic development of OS thyroid cells were discussed in the context of factors predisposing to autoimmune thyroiditis.

Animals↗
PubMed1983

Analyses of the serum concentrations and antigenic determinants of thyroglobulin in chickens susceptible to autoimmune thyroiditis.

These studies revealed an abnormal elevation in serum thyroglobulin (Tg) concentrations of the thyroiditis-prone OS chicks. Their serum levels, measured by a sensitive and specific RIA, remained high for the first 2 wk of age, a time preceding significant lymphoid infiltration of their thyroid glands. The elevated serum Tg levels probably resulted from, or were related to, hyperactivity of the OS thyroid gland. Reducing the activity of the OS thyroid gland by exogenous administration of T4 caused a temporary but significant reduction in thyroidal infiltration and the synthesis of Tg antibodies. In addition to the analysis of serum concentrations of Tg, a competitive binding RIA was developed to determine whether unique antigenic determinants exist on Tg isolated from OS thyroid glands. This was proved to be unlikely because OS chicks produced autoantibodies that fully cross-reacted with Tg isolated from normal chicken thyroid glands. The relationships between intrinsic thyroid hyperactivity, high serum Tg levels, the sensitization of OS thymocytes, and thyroiditis are discussed.

Aging↗
PubMed1981

Spontaneous autoimmune thyroiditis in chickens. II. Evidence for autoresponsive thymocytes.

A major factor involved in the spontaneously occurring autoimmune thyroiditis of OS chickens is the presence of thyroid reactive cells in the thymus of young OS chicks. This was determined by transferring OS and normal strain thymocytes to T cell-depleted histocompatible normal chickens and examining the recipients for thyroiditis. Although both thymocyte populations reconstituted T cell function, only the OS thymocytes induced thyroiditis. Additional evidence for hyperactivity of the young OS thymus was provided by studying the in situ uptake of a radiolabeled thymidine analogue.

Animals↗
PubMed1977

Genetic and cellular control of spontaneous autoimmune thyroiditis in OS chickens.

B-locus genotypes have been defined in Obese strain (OS) chickens that spontaneously develop autoimmune thyroiditis (SAT), and in White Leghorn Cornell C strain (CS) chickens from which the OS was selected. The B-locus influences SAT, and some possible mechanisms are discussed. Thymic abnormalities in OS, as contrasted with CB birds, are also discussed and may play a role in SAT, as may an intrinsic defect in the thyroid gland itself.

Animals↗
PubMed1976

Abnormal response to minor histocompatibility antigens in Obese strain chickens.

Obese strain chickens, which spontaneously develop autoimmune thyroiditis, were tested for their ability to tolerate skin allografts. Several procedures known to prolong graft survival in normal strains were employed. These included the use of skin matched at the major histocompatibility locus, grafting on the day of hatching, thymectomy, and x-irradiation. A dramatic difference between the Obese and the normal Cornell strain (the strain from which Obese was derived) was detected when both were thymectomized and grafted at hatching. Under these conditions eight of 13 normal but only one of 16 Obese strain birds retained their grafts for 50 days. This suggests the presence of an abnormal thymus or thymus-derived suppressor T cells in Obese strain chickens.

Age Factors↗
PubMed1976

Increased iodine uptake by obese strain thyroid glands transplanted to normal chick embryos.

The Obese strain (OS) of chickens spontaneously develops autoimmune thyroiditis. Since a defect or abnormality of the thyroid gland may be involved in this disease experiments were performed to compare the iodine uptake of OS with normal thyroid glands. To minimize the interaction of the OS immune system with the thyroid gland during these studies, thyroids were removed from 16-day-old embryos and transferred to the chorioallantoic membrane (CAM) of 9-day-old normal White Leghorn (NWL) embryos. NWL thyroid glands were transferred to the same CAM. Six days later the 20-hr 131I uptake of the transplants was determined. Twenty OS thyroid lobes had a mean 131I uptake of 2960 +/- 740 cpm, whereas the NWL thyroids incorporated significantly less iodine (890 +/- 160 cpm; p less than 0.025). These results, along with a previous report suggest that an abnormality of the thyroid gland might be an important factor in the development of autoimmune thyroiditis.

Animals↗