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Biomedical subjects

L J DeGroot

Publications and source records attributed to L J DeGroot.

At least 181 records · Page 10Linked to original sources
PubMed1982

Effect of indomethacin on phytohemagglutinin-stimulated peripheral blood lymphocytes in thyroid autoimmune diseases.

Suppressor lymphocyte function was evaluated in control subjects and in patients with autoimmune thyroid disease, utilizing an assay in which indomethacin was added to lymphocyte cultures to inhibit prostaglandin-producing suppressor cells. This assay is based on the observation that the addition of indomethacin, a potent prostaglandin synthesis inhibitor, to phytohemagglutinin-stimulated peripheral blood lymphocytes should cause an increase in the incorporation of iododeoxyuridine in control subjects and a smaller increase in diseases with reduced prostaglandin-producing suppressor cells. The addition of indomethacin, 1 microgram/ml, stimulated iododeoxyuridine incorporation in phytohemagglutinin-stimulated cultures in control subjects to an index value of 1.43 (i.e., the increment in iododeoxyuridine incorporation with both indomethacin and phytohemagglutinin was 43% greater than the incorporation with phytohemagglutinin alone). The stimulation index was significantly lower in patients with Graves' disease who were toxic and untreated (1.18 +/- 0.25, mean +/- SD; P less than 0.003). Patients who were toxic while receiving antithyroid drugs or after radioiodine therapy or patients euthyroid after treatment had a mean stimulation index in the normal range, although the spread of data was very large in these groups. Responses in patients with Hashimoto's thyroiditis were also quite variable. The average response was 1.74 +/- 0.72, with 40% of the patients showing a high stimulation index. This study supports our previous investigations in which we used different assay systems for measuring suppressor-cell function in patients with thyroid autoimmune diseases and indicates that a defect in suppressor lymphocyte function is measureable by another technique. The abnormality persists in some cases after metabolic control has been achieved, but usually returns toward normal over months or years.

Adolescent↗
PubMed1982

Decreased suppressor T-lymphocytes in autoimmune thyroid diseases detected by monoclonal antibodies.

Monoclonal antibodies reacting with cell surface antigens of helper (T4), suppressor (T8) T cells and common T-cell antigen (T3) were used by an immunofluorescence technique to enumerate peripheral T-lymphocytes in 42 patients with Graves' disease and 16 patients with Hashimoto's thyroiditis. The percentages of total T cells (cells which react with anti-T3) and helper/inducer cells (cells which react with anti-T4) among peripheral mononuclear cells in Graves' and Hashimoto's patients were not significantly different from those found in normal controls, except for a decrease in cells which react with anti-T3 in toxic Graves' disease without medication. The most important finding was a decrease in the percentage of cytotoxic/suppressor T cells (cells which react with anti-T8) in toxic Graves' disease and Hashimoto's thyroiditis. In patients with Graves' disease who were hyperthyroid or euthyroid on propylthiouracil treatment and euthyroid after radioactive iodide treatment, the percentage of cells which react with anti-T8 was also decreased, but this did not reach statistical significance. These findings support the hypothesis of defects in suppressor T-lymphocytes in autoimmune thyroid diseases.

Adolescent↗
PubMed1982

Serum thyroglobulin in the management of patients with thyroid cancer.

We have reviewed our experience with the management of patients with thyroid cancer to assess the potential benefits of employing the serum thyroglobulin assay in patient management programs and to determine the optimal conditions for this application. Serum thyroglobulin levels were found to be more reliable when obtained from hypothyroid patients. Levels of thyroglobulin greater than 10 ng/mL appeared to be abnormally elevated in both thyroidectomized patients prior to radioactive iodine therapy (group 1) and in thyroidectomized patients after radioactive iodine therapy (group 2). Elevated thyroglobulin levels were found to be useful indicators of the presence of metastatic disease, whereas normal thyroglobulin levels were reliable indicators of the absence of metastases. In group 1 patients, elevated thyroglobulin levels reliably predicted the presence of important total body scan uptake. In group 2 patients, normal thyroglobulin levels reliably predicted the absence of total body scan uptake. The serum thyroglobulin assay can substantially reduce the need for repetitive total body scanning in the follow-up of group 2 patients with thyroid cancer.

Adenocarcinoma↗
PubMed1981

Suppression of PHA-induced lymphocyte blastogenesis by concomitant presence of PPD in the culture.

PHA-induced lymphocyte blastogenic response was remarkably suppressed by the simultaneous presence of PPD in cultures of lymphocytes derived from individuals sensitized to PPD, but not affected by the presence of PPD when the cultures contained lymphocytes from an individual not sensitized to the protein. This double stimulation blastogenesis study with PHA and a specific antigen is feasible as a simple and rapid test to measure cell-mediated immunity to the antigen.

Antigens, Bacterial↗
PubMed1981

Congenital goiter and the development of metastatic follicular carcinoma with evidence for a leak of nonhormonal iodide: clinical, pathological, kinetic, and biochemical studies and a review of the literature.

We report a large kindred of patients with congenital goiter, followed for 15 yr, in which two siblings (one male and one female) developed metastatic follicular thyroid carcinoma. These two patients were evaluated by iodine kinetic analysis. None of the classical defects of T4 biosynthesis was present in either patient. Rather, both patients had extremely rapid rates of iodine turnover, with elevated 131I uptake and excessive spillage of iodide in the urine. Serum iodoalbumin was present, probably as a nonspecific result of glandular hyperplasia. Iodine kinetic analysis after the ingestion of potassium perchlorate and methimazole was compatible with a leak of nonhormonal iodide from the thyroid. It is not possible to determine whether this iodide leak is the primary pathogenetic defect or is secondary to another unidentified abnormality. The unprecedented development of metastatic thyroid cancer in patients with congenital goiter occurred, in both instances years after subtotal thyroidectomy without thyroid hormone replacement therapy, suggesting a role for TSH in the genesis of human thyroid cancer. On the basis of our study of these patients and a review of the literature, we conclude that TSH is likely to be a factor in the induction of human follicular thyroid carcinoma.

Adenocarcinoma↗
PubMed1980

Binding of iproniazid to the polymeric forms of iodide peroxidase.

14C labelled iproniazid binds to iodide peroxidase more effectively in low ionic strength buffer than in high ionic strength buffer, suggesting preferential binding to the monomeric form of iodide peroxidase. During column chromatography, under conditions that separate iodide peroxidase into multiple forms, iproniazid is bound selectively to the monomeric form. Thus, this antithyroid agent appears to bind preferentially to the monomeric enzyme form, or possibly to cause dissociation of the polymeric to the monomeric form.

Animals↗
PubMed1980

A new solid-phase radioimmunoassay to measure IgG secreted by cultured human lymphocytes.

We describe a simple solid-phase radioimmunoassay (RIA) to detect IgG based on competitive binding between radiolabeled and unlabeled IgG for anti-IgG antibody physically adsorbed to the wells of polyvinyl microtiter plates. The assay is sensitive (1 ng), rapid, and is particularly suited for studies of in vitro IgG secretion by human peripheral blood lymphocytes, since such studies require large numbers of cultures. Conditions which permit measurement, by means of this assay, of helper and suppressor T cell effects on IgG production by human B cells in culture are described.

Animals↗
PubMed1980

Release of thyrotropin receptor from thyroid plasma membranes: effect of hydrocortisone, propranolol, and adenosine 3',5'-monophosphate.

Soluble TSH receptors were released into the medium when bovine thyroid plasma membranes were incubated in 0.01 M Tris-HCl, pH 7.5, at 0 or 20 C. This is a conventional hypotonic medium used in binding assays. The characteristics of binding of bovine [125I]TSH to the released TSH receptor were almost the same as those of binding to TSH receptors solubilized by lithium 3,5-diiodosalicylate or to the original plasma membrane. Released TSH receptor had two binding sites with Ka values of 0.7 x 10(10) and 0.1 x 10(8) M-1. T3, T4, KI, methimazole, and propylthiouracil had no effect on spontaneous TSH receptor release or on bovine [125I]TSH binding to solubilized TSH receptor. Hydrocortisone (10(-5)--10(-3) M) and d,l-propranolol (10(-3) M) inhibited receptor release. cAMP increased the release of TSH receptor. Hydrocortisone, d,l-propranolol, and cAMP had no effect on bovine [125I]TSH binding to solubilized or released TSH receptor. d,l-Propranolol and hydrocortisone may act as membrane-stabilizing agents. cAMP stimulation of release suggests that the release mechanism could depend upon a protein kinase-phosphoprotein system. Although these studies were conducted with membranes in an unphysiological medium, receptor release may occur normally and could be a source of circulating antigen related to production of antireceptor antibody in autoimmune thyroid diseases. Release of receptors during incubation in vitro may affect the results of studies of hormone-receptor interaction.

Animals↗
PubMed1980

Description and partial characterization of thyroid hormone-specific and thyroid hormone-dependent rat liver nuclear proteins.

A fraction of readily elutable rat liver nuclear proteins (nuclear globulins), analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, contains two proteins which reflect the thyroid status of the animal. The larger (n-band) protein is abundant in normal rat nuclei but diminished in hypothyroidism by thyroidectomy or hypophysectomy and restored with T3 treatment. It is also diminished in starvation, during which time T3 treatment of concurrent hypothyroxinemia is ineffective in tis restoration. Refeeding restores the n-band protein in starved normal rats but not in starved thyroidectomized (Tx) rats. GH does not restore this protein in either Tx or hypophysectomized (Hx) rats. The dual requirements of euthyroidism and adequate nutrition imply that the n-band protein is thyroid hormone dependent but not thyroid hormone specific. The smaller of the two nuclear globulins, the t-band protein, is prominent in Tx or Hx rats and is not altered by additional hypometabolic factors (starvation) or by nonthyroid hormone related hypermetabolic stimuli (refeeding or GH treatment of Hx rats). It is reduced in normal or T3-treated Tx or Hx rats regardless of simultaneous hypometabolic states (starvation or nonthyroid hormone-related deficiencies of hypopituitarism) or hypermetabolic states (refeeding, liver regeneration, or hyperthyroidism). The t-band protein thus appears to be inversely thyroid hormone specific in its concentration. Electrophoretic and chromatographic analysis suggest that the n-band protein is a 125,000 mol wt subunit of a 290,000 mol wt holoprotein. The t-band protein is a 70,000 mol wt peptide which exists, in part, as a monomer but largely as a subunit of a protein complex with a mol wt greater than 100,000.

Animals↗