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Biomedical subjects

L J DeGroot

Publications and source records attributed to L J DeGroot.

At least 199 records · Page 11Linked to original sources
PubMed1979

Adenosine 3',5'-monophosphate-dependent protein kinase activity in soluble thyrotropin receptor complex.

cAMP-dependent protein kinase activity was present in a soluble TSH receptor fraction. The Km of this enzyme was 2.2 X 10(-6) M for casein substrate in the absence or presence of 10(-5) M cAMP. A [3H]cAMP-binding protein was also found in this fraction. The Ka for [3H]cAMP-binding was 0.11 X 10(6) M-1, with a total binding capacity of 3 nmol/mg protein. After fractionation using a continuous sucrose density gradient, one of the several [125I]iodobovine TSH-binding peaks corresponded to a [3H]cAMP-binding peak. After fractionation on a sucrose density gradient containing 0.4 M NaCl at pH 6.5, a major peak of protein kinase activity was shown. This protein kinase activity was stimulated by adding 10(-5) M cAMP. A peak of [3H]cAMP-binding activity corresponded to the same peak. Protein kinase activity in the receptor fraction was stimulated by adding 6 mg/ml bovine TSH. The soluble TSH receptor fraction also has an adenylate cyclase activity stimulated by TSH. These results suggest that some TSH receptors released from thyroid plasma membranes have associated adenylate cyclase activity and cAMP-dependent protein kinase activity. The receptor, cyclase, and kinase activities may exist in a functional primary receptor unit which is spontaneously released from plasma membranes.

Animals↗
PubMed1979

Cyclic nucleotide-dependent protein kinase modulators in thyroid tissue.

A heat-stable protein which inhibits cAMP dependent protein kinase was prepared from the bovine thyroid 100,000 X g supernatant. This protein inhibited the cAMP-dependent protein kinase both from bovine thyroid cytosol and bovine thyroid plasma membranes. The inhibitory effect was noncompetitive with histone as substrate of the cytosolic enzyme. The stimulatory modulator for cGMP-dependent protein kinase was separated from the 100,000 X g supernatant by Sephadex G-100 gel filtration. The stimulatory modulator had no stimulating effect on cAMP-dependent phosphorylation, and the inhibitory modulator of cAMP-dependent enzyme had no effect on cGMP-requiring phosphorylations. The inhibitory modulator may regulate cAMP-dependent protein kinase activity in cytosol and plasma membrane, and the stimulatory modulator for cGMP-dependent protein kinase may have a role in thyroid function independent of the cAMP-requiring system.

Animals↗
PubMed1979

Changes in thyroid-stimulating immunoglobulins during antithyroid therapy.

Thyroid-stimulating immunoglobulin (TSI) activity was measured by radioreceptor assay in sera from patients with Graves' disease, Hashimoto's thyroiditis, and thyroid cancer. In untreated Graves' disease (47 cases), TSI index was significantly lower [76.7 +/- 1.4 (SE)] than the average of a normal control group (30 cases; 94.4 +/- 1.9). In untreated Hashimoto's thyroiditis (25 cases), it was also significantly lower (83.0 +/- 2.4). In patients with thyroid cancer (19 cases), there was no significant difference from normal controls. After 131I treatment, the TSI index in Graves' disease decreased during 2--4 months, then increased and reached normal levels in 1 yr. During propylthiouracil treatment, the TSI index increased and reached a normal level in 5--6 months without the decreasing phase seen after 131I treatment. Free T4 index values were gradually decreased by both treatments. There was no significant relationship between TSI index and thyroid antibodies (microsomal antibodies and thyroglobulin antibodies) in untreated Graves' disease or Hashimoto's thyroiditis. It is concluded that 1) in the sera of patients with Graves' disease and Hashimoto's thyroiditis, there are immunoglobulin Gs that can displace TSH binding to thyroid membranes; 2) these immunoglobulins Gs are different from the classic antithyroid antibodies; and 3) 131T treatment of Graves' disease may enhance TSI production during the first 1--2 months after therapy.

Adult↗
PubMed1979

Studies on suppressor cell function in thyroid diseases.

Suppressor cell function of peripheral mononuclear cells has been examined in patients with Graves' disease, Hashimoto's thyroiditis, and thyroid cancer, as well as in healthy subjects. Suppressor cell function was assessed through two methods: 1) measurement of enhanced blastogenesis after 24-h preculture and 2) concanavalin A-inducible suppressor activity. The results from the two tests were coincident and indicate that suppressor cell function was significantly decreased in the Graves' disease population but not changed in either the Hashimoto's thyroiditis or the thyroid cancer groups compared to healthy controls. The impairment of suppressor cell function in the Graves' disease population was still observed when patients became euthyroid by treatment with antithyroid drugs, although the treated patients had improved suppressor cell function compared to untreated patients (P = NS). Low activity of suppressor cell function in the Graves' disease population might be a constitutional character based on an inherited abnormality specific for the disease population.

Adolescent↗
PubMed1979

Roentgenographic contrast agents inhibit triiodothyronine binding to nuclear receptors in vitro.

The ability of roentgenographic contrast agents to inhibit binding of [125I]T3 to nuclear receptors was studied during incubation of rat liver nuclei or nuclear extracts in vitro and after ip administration of the agents in vivo. Ipodate, iodipamide, iopanoic acid, and diatrizoate inhibited binding of [125I]T3 in vitro. The most potent inhibitor was ipodate, which produced 50% inhibition of binding at 1.2 X 10(-4) M. When given orally in acute in vivo experiments, ipodate did not diminish binding to liver nuclear receptors. Ipodate appeared to inhibit in vivo metabolism of [125I]T3.

Animals↗
PubMed1978

Cushing's syndrome due to adrenal adenoma with persistent diurnal cortisol secretory rhythm.

A 41-yr-old female with presumed Cushing's syndrome was found to have a diurnal cortisol rhythm characterized by low values of 8:00 a.m. and consistently high values at 4:00 p.m. and midnight. Hourly sampling of plasma cortisol over 24 hr confirmed this rhythm, as did measurement of urinary free cortisols in samples collected every 6 hr over 24 hr. Hypercortisolemia was not suppressed by 2 mg of dexamethasone given every 6 hr for 24 hr. The adrenal tissue was responsive to ACTH. Iodocholesterol scanning revealed unilateral activity, and the patient's syndrome was cured by resection of an adrenal adenoma. In this patient a diurnal cortisol secretory pattern was present due to the secretory activity of the adenoma. The cause of the abnormal but persistent diurnal pattern is unknown.

17-Hydroxycorticosteroids↗
PubMed1978

Thyroid hormone receptors from liver nuclei: characteristics of receptor from normal, thyroidectomized, and triiodothyronine-treated rats; measurement of occupied and unoccupied receptors, and chromatin binding of receptors.

The capacity and characteristics of liver nuclear receptors for T3 have been compared in normal rats, thyroidectomized rats, and thyroidectomized rats treated with different doses of T3. Receptor capacity was unchanged, with the exception of a decrease of total nuclear receptors in rats treated with 15 microgram T3/day, which is believed due to lack of complete dissociation of the endogenously bound hormone during incubation in vitro. During incubation of the isolated nuclei in 0.32 M sucrose plus 1 mM MgCl2 plus 20 mM Tris-Cl buffer, pH 7.85, about 50% of the nuclear receptors were released to the medium and no effect of T3 treatment on the amount released was found. The affinity of the receptors free in solution was 50% higher than that of receptors retained in the nuclei. Receptors from normal and thyroidectomized rats were studied by ultracentrifugation through sucrose gradients. No difference in sedimentation coefficient was found between the groups of rats, whether the receptors were filled with the labeled hormone before or after centrifugation and separation of the gradient fractions. Occupied and unoccupied receptor capacity was estimated by incubation of receptor preparations at 20 and 0 C for 2 h. Observed capacity at 20 C represents unoccupied plus approximately 80% of occupied sites, while observed capacity at 0 C represents unoccupied plus 10% of occupied site. Binding of receptors to the chromatin was studied by incubating nuclear extract from normal rats with chromatin and measuring the amount of receptor that was not bound and remained free in the supernatant. Receptor not bound to chromatin was incubated at 0 and 20 C, with a saturating concentration of [125I]T3, to measure occupied and unoccupied sites. Both occupied and unoccupied receptor decrease in the supernatant after incubation with the chromatin when the concentration of chromatin in the incubation medium is increased. No saturation of the chromatin-binding sites was achieved by increasing the concentration of receptor several-fold, and no difference in the binding of occupied and unoccupied receptors to chromatin was observed. These data rule out the possibility that the concentration of receptors in the nucleus is under control of the hormone. Major molecular changes of the receptor that could be induced by T3, such as dissociation into subunits, are also ruled out. Binding studies to the chromatin are not necessarily conclusive, as nonspecific binding may be masking the physiological binding of the receptors to a limited number of acceptor sites.

Animals↗
PubMed1978

Thyroglobulin inhibition of thyrotropin binding to thyroid plasma membrane.

The effect of thyroglobulin (TG) on binding of TSH to thyroid plasma membranes was studied in vitro. Human and bovine thyroid plasma membranes have specific binding sites for bovine [125I]TSH. The binding of [125I]TSH is inhibited by the addition of purified TG (100 ng/microgram/ml). The inhibitory mechanism appears to be noncompetitive when subjected to Lineweaver-Burk analysis. Incubation of TG with TSH did not show an interaction, as assessed by sucrose gradient centrifugation. Plasma membranes prepared from human thyroid tissue have specific binding sites for human TG, as shown by [125I]TG binding assay. The TG binding was not affected by adding low concentrations of unlabeled bovine TSH. In the presence of very high concentrations of TSH, TG binding was increased. Hemoglobin, beta-lactoglobin, and ovalbumin did not have an inhibitory effect on [125I]TSH and [125I] TG binding to membrane preparations. Both [125I]TSH and [125I]TG binding were inhibited by 10 mM neuraminic acid. These results suggested that 1) TG released from thyroid gland may have a regulatory effect on TSH binding to its specific receptor, and 2) there are specific binding sites for TG on the thyroid plasma membrane.

Animals↗
PubMed1978

Abnormalities of triiodothyronine binding to lymphocyte and fibroblast nuclei from a patient with peripheral tissue resistance to thyroid hormone action.

T3 binding to lymphocyte nuclei has been studied in normal individuals and in a patient (MaG) with peripheral resistance to thyroid hormone action. This syndrome is defined by the presence of hypothyroidism or euthyroidism with high plasma levels of thyroid hormone. T3 bound to a single set of binding sites in normal adult lymphocyte nuclei with a mean Ka of 8.9 +/- 7.1 x 109 M-1, and a capacity of 4.4 +/- 2.9 fmol/100 micrograms DNA. A single binding site was also disclosed in MaG's lymphocytes with a Ka of 0.43 x 109 M-1 and a capacity of 10.5 fmol/100 micrograms DNA. This low affinity was not due to the presence of high plasma T3 level in the patient, since administration of 100 micrograms T3 to normal adult volunteers induced the presence of two different binding sites. The mechanism responsible for this phenomenon is unknown. To binding was also studied using cultured fibroblasts which were incubated in serum-less medium before the binding experiments. One single binding site (Ka, 1.9 x 10(10) M-1, capacity, 12.9 fmol/100 micrograms DNA) was detected in normal fibroblast nuclei. In contrast, a curvilinear Scatchard plot was obtained when MaG's fibroblasts were used. This result could be compatible with the presence of either two different binding sites or negative cooperativity. In support of the latter possibility, Hill plots gave a number lower than unity. The results suggest that the syndrome of peripheral tissue resistance to thyroid hormone action due to a defect at the level of the nuclear receptor. The possible existence of similar syndromes due to an alteration at the level of a post-T3-binding mechanism is not eliminated.

Adolescent↗
PubMed1978

Natural history of radiation-associated thyroid cancer.

The clinical courses of 91 patients with radiation-associated thyroid cancer were compared with courses in a control population. Radiation-associated carcinoma appears to be a disease of younger persons, and 90% of the tumors are papillary. No anaplastic or medullary tumors were observed. Ninety percent of the tumors were larger than those found in an autopsy series that surveyed for "biologically benign" thyroid tumors. There was a higher incidence of multicentric disease, locally invasive disease, and distant metastases in the population that had had x-ray exposure. Although the population with x-ray exposure had had more aggressive treatment, more recurrences were present in patients who had had radiation therapy. The death rate was similar in both groups. Parathyroid adenoma occurred more frequently in the population that had radiation exposure than in controls and appears to be a radiation-associated illness.

Adenoma↗