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Biomedical subjects

O H Clark

Publications and source records attributed to O H Clark.

At least 217 records · Page 12Linked to original sources

Thyroid-stimulating immunoglobulin bioassay using cultured human thyroid cells.

Modifications are described in the cultured thyroid cell cAMP assay for TSH which make it suitable for the measurement of thyroid-stimulating immunoglobulins. Comparison was made between this assay and two others measuring cAMP responsiveness in human thyroid tissue, namely the thyroid slice and thyroid plasma membrane adenylate cyclase assays, all performed with the same tissue sample. Of immunoglobulin G (IgG) samples from 7 unselected patients with untreated hyperthyroidism associated with Graves' disease, 5 produced significant stimulation of cAMP content in cultured thyroid cells when compared to pooled normal IgG. None of these 7 produced a statistically significant increase in thyroid slice cAMP content when assayed in triplicate, the same replicate number used in the cultured thyroid cell assay. Similarly, none of the same Graves' IgG samples produced significant stimulation (vs. control IgG) in the membrane adenylate cyclase assay, in which sensitivity to TSH stimulation was very poor. With a scaled-down modification of the assay using microtiter wells and acetylation to enhance detection of cAMP in the RIA, significant TSI activity was observed in 15 of 18 (83%) IgG samples from patients with untreated Graves' disease. The data indicate the excellent sensitivity and precision of the thyroid cell cAMP assay, as well as its convenience.

Biological Assay↗

Thyrotropin binding and adenylate cyclase stimulation in thyroid neoplasms.

Experiments were performed to determine whether thyroid-stimulating hormone (TSH) receptors coupled to adenylate cyclase are present in both benign and differentiated malignant thyroid tumors, and to identify abnormalities in the TSH receptor-adenylate cyclase system in neoplastic thyroid tissue. TSH binding and adenylate cyclase assays were performed under the same in vitro cyclase conditions. 125I-bovine TSH was incubated with an 8,000 X g thyroid or thyroid tumor particulate fraction from both normal and most neoplastic tissue two receptor sites were identified. The association constant for the high-affinity receptor from normal thyroid was 10.5 +/- 3.2 nM (mean +/- standard error) with a capacity of 0.8 +/- 0.3 pM/mg particulate protein. The association constant of the high-affinity receptor found in the particulate fraction from the thyroid adenomas was 3.5 +/- 0.5 nM with a capacity of 0.4 +/- 0.1 pM/mg particulate protein; for the thyroid carcinomas the association constant was 1.4 +/- 0.3 nM and the capacity 0.2 +/- 0.1 pM/mg particulate protein. The maximum adenylate cyclase response to TSH for particulate fractions from both benign and malignant tumors was greater (P less than 0.05) than in the particulate fraction from normal adjacent thyroid tissue. There was also a positive correlation between the equilibrium constants for 125I-bTSH binding and adenylate cyclase activation suggesting that binding sites are coupled to cyclase in the neoplastic tissue and that the binding observed in these experiments is of biologic consequence.

Adenocarcinoma↗

Studies on the pathophysiological role of thyroidal prostaglandin E (PGE) in Graves' disease.

A potential role for prostaglandin E (PGE) of thyroid origin in the pathogenesis of the hyperthyroidism of Graves' disease was investigated in vivo. The venous-arterio prostaglandin E (PGE) concentration gradient across the thyroid was measured in 5 patients undergoing subtotal thyroidectomy for Graves' disease. This gradient (161 +/- 14 pg/ml; mean /+- SE) was significantly greater than that found in 11 patients undergoing surgery for hyperparathyroidism and thyroid nodules (64 +/- 20 pg/ml; P < 0.01). This suggests that there is a net increase in PGE output by the thyroid gland in Graves' disease, but the thyroid cell-type responsible for this increased PGE output is unknown. In contrast to previous reports, thyrotropin (TSH) did not stimulate thyroid cell PGE generation in vitro, providing evidence against a role for TSH in this phenomenon. Administration of maximal doses of indomethacin to two thyrotoxic patients did not significantly alter peripheral thyroid hormone concentrations. These data suggest that thyroidal PGE has a function other than to stimulate thyroid hormone secretion in Graves' disease.

Adult↗

Thyroid nodules and thyroid cancer: surgical aspects.

Patients with thyroid nodules must be treated selectively because these nodules develop far more frequently than does thyroid cancer. A thorough clinical history, family history and history of radiation, as well as an accurate physical examination, are very important in determining whether surgical treatment is indicated. Thyroid function tests, a radioactive isotope scan, a thyroid echogram and fine-needle biopsy are also useful. Although there is considerable debate concerning the amount of thyroid tissue that should be removed at operation, the minimal procedure for a "cold," solid thyroid nodule is a total thyroid lobectomy and isthmectomy. This is the treatment of choice for patients with occult papillary thyroid carcinoma. Partial lobectomy is to be discouraged. Near total or total thyroidectomy should be considered for all other patients with differentiated thyroid cancer. Many factors influence the prognosis of patients with thyroid cancer including age, sex, type of thyroid cancer, invasion, symptoms, lymph node metastasis, metastasis to distant sites, extent of the surgical procedure, and use of radioactive iodine and thyroid hormone. With adequate treatment, the prognosis for differentiated thyroid carcinoma is excellent.

Adolescent↗

Hyperparathyroidism due to primary cystic parathyroid hyperplasia.

Cysts of the parathyroid glands are uncommon, and functioning parathyroid cysts that cause primary hyperparathyroidism are rare. A 63-year-old man had primary hyperparathyroidism because of cystic hyperplasia of all four parathyroid glands. He also had squamous cell carcinoma of the soft palate, chronic renal failure, hypertension, type-4 renal tubular acidosis, a hyperplastic thyroid adenoma, and hyporeninemic hypoaldosteronism. To our knowledge, this is the first patient to be described with hyperparathyroidism due to multiple parathyroid cysts. The finding of cystic involvement of all four glands supports the theory that at least some parathyroid cysts are either a result of a common embryologic defect or of retention of parathyoid secretions rather than of cystic infarction of parathyroid adenomas.

Cysts↗

Parathyroid cysts.

Cystic neck masses may be accurately diagnosed by sonography, and some nonfunctioning parathyroid cysts can be cured by percutaneous aspiration. Primary hyperparathyroidism should be considered in all patients with cystic neck masses. Parathyroid cysts can often be recognized from the characteristics of the cyst fluid which is usually clear and colorless, contains elevated parathyroid hormone levels and normal or low thyroid hormone levels, and may contain parathyroid cells. Parathyroid cysts may be multiple; all four parathyroid glands should therefore be identified and appropriately removed or hyperparathyroidism may persist.

Adult↗

Significance of lymph node metastasis in differentiated thyroid cancer.

In age-matched patients with differentiated carcinoma of the thyroid, the tumor recurred in 32 per cent of those with lymph node metastases and in 14 per cent of those without lymph node metastases. Twenty-four per cent of patients with nodal involvement at the initial examination died of thyroid cancer, whereas only 8 per cent of those without nodal involvement died of thyroid cancer. In patients less than forty years old, there were no deaths in those without nodal metastases bu there were three deaths (11 per cent) in patients with nodal metastases. In patients more than forty years old, nine (41 per cent) iwth nodal metastases died of tumor, and four (15 per cent) without nodal metastases died of tumor. In the presence of positive nodes the death rate was substantially greater in the older than in the younger patients. Nodal involvement has an adverse effect on prognosis, but appears to be less important than the age of the patient.

Adult↗