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Biomedical subjects

A Santora

Publications and source records attributed to A Santora.

10 recordsLinked to original sources

Functional epithelial cell line cloned from rat parathyroid glands.

Primary cultures of rat parathyroid cells were developed in medium containing 5% calf serum, 1% Nutridoma-SP (a serum-free medium supplement from Boehringer Mannheim), and 0.7 mM calcium. The PT-r strain was purified by successive colony isolations and maintained differentiated characteristics (secretion of bioactive and radioimmunoactive parathyroid hormone into the culture medium, sensitivity to calcium regulation, and modulation by secretin) for 7 months in continuous culture. These cultured cells are epithelioid, display diploid chromosome numbers, and do not show a transformed phenotype. There has been no decrease in the rate of cell division or decline in parathyroid hormone secretion since the cell line was established. This clonal cell line provides an important system for further studies on the biology of the parathyroid cell.

Animals

Selective resistance to parathyroid hormone in cultured skin fibroblasts from patients with pseudohypoparathyroidism type Ib.

We measured cAMP production in response to agonists in cultured skin fibroblasts from subjects with pseudohypoparathyroidism type Ib (PHP Ib; normal phenotype, resistance to PTH only, normal guanine nucleotide stimulatory coupling protein activity) and skin fibroblasts from normal subjects. There were no significant differences in basal or prostaglandin E1- and forskolin-stimulated cAMP production in PHP Ib vs. normal fibroblasts. Fibroblasts from 7 of 10 subjects with PHP Ib had significantly reduced peak cAMP responses to PTH [3.95 +/- 0.88 vs. 15.9 +/- 4.2 pmol/100 micrograms protein (mean +/- SD); n = 7 for both groups; P less than 0.001]. PTH-stimulated cAMP production was significantly reduced in the 7 subjects with PHP Ib at all concentrations of PTH tested [3-1000 ng/ml human PTH-(1-34)]. In the other 3 subjects with PHP Ib, the cAMP response to PTH was either normal (2 subjects) or above the normal range (1 subject). Thus, skin fibroblasts from many, but not all, subjects with PHP Ib have selective resistance to PTH in terms of cAMP response. Since the defect is hormone specific and persists in culture, we suggest that an intrinsic defect in the PTH receptor may cause PTH resistance in certain subjects with PHP Ib. The cause of PTH resistance in the subjects with a normal cAMP response to PTH is not known, but the data suggest heterogeneity even within the PHP Ib subgroup.

Adolescent

The inhibitory guanine nucleotide regulatory protein modulates agonist-stimulated cAMP production in rat osteosarcoma cells.

We identified the subunits of the stimulatory and inhibitory guanine nucleotide binding proteins (Gs and Gi, respectively) associated with adenylate cyclase in rat osteosarcoma (ROS) cells. Pertussis toxin catalyzed ADP-ribosylation of Gi alpha in ROS cells increased agonist (PTH and isoproterenol)-stimulated, but not basal, cAMP production. The effect of pertussis toxin was dose and time dependent, and slowly reversible (T 1/2 approximately 30 h) during continued culture without toxin. Pertussis toxin treatment of ROS cell lines (17/2.8 and 24/l) with markedly different agonist responsiveness increased agonist-stimulated cAMP production in proportion to the response without toxin treatment. Pertussis toxin treatment further increased cAMP response to PTH in dexamethasone treated cells. We conclude that ROS cells contain functional Gi which modulates agonist-stimulated cAMP formation. Alterations in ROS cAMP responsiveness caused by steroids, and the reduced responsiveness of the 24/1 cell line, however, are unlikely to be due to changes in Gi.

Adenylate Cyclase Toxin

A factor produced by cultured rat Leydig tumor (Rice 500) cells associated with humoral hypercalcemia stimulates adenosine 3',5'-monophosphate production via the parathyroid hormone receptor in human skin fibroblasts.

The Rice-500 Leydig cell tumor of Fischer rats is associated with humoral hypercalcemia in vivo and produces a factor that stimulates cAMP formation in cultured rat osteosarcoma cells. We found that cultured human skin fibroblasts respond to both human PTH-(1-34) and the factor produced by cultured rat Leydig tumor cells with a dose-dependent rise in cAMP formation. The time courses for stimulation of the two agents were similar, and stimulation by both was blocked by the competitive PTH antagonist [8,18-norleucine,34-tyrosine]bovine PTH-(3-34) amide. These data suggest that PTH-like factors secreted by a murine tumor are capable of interacting with the human PTH receptor.

Adult

Morphologic and functional studies of a rat hypercalcemia-associated testicular tumor maintained in cell culture.

The Rice H500 tumor is a transplantable nonmetastasizing testicular tumor of Fischer rats associated with hypercalcemia and increased urine cyclic adenosine monophosphate (AMP) excretion, features similar to those of the clinical syndrome of humoral hypercalcemia of malignancy. Tumor cells can be maintained in tissue culture; one million cells grown in culture reinoculated in Fischer rats reproduce the syndrome of tumor growth and lethal hypercalcemia. Infusion of concentrated, serum-free cell culture supernatant into parathyroidectomized rats produced an increase in urine cyclic AMP similar to that produced by an infusion of bovine parathyroid hormone. Light and electron microscopic appearance of the H500 tumor in vivo and in vitro is similar to previous descriptions of a hypercalcemia-associated rat testicular tumor believed to be of Leydig cell origin. Ultrastructural characteristics of microvilli, intracellular glandlike lumina, and cell-cell attachments, however, suggest an epithelial origin. Absence of smooth endoplasmic reticulum typical of steroid-secreting Leydig cells suggest these cells are not actively involved in steroid synthesis and secretion. The ultrastructure of this tumor is sufficiently different from that of normal Leydig cells that the cell of origin is unclear. Nonetheless, this tumor provides a useful model of hormonally mediated tumor-associated hypercalcemia.

Animals

Skeletal response in rats following the implantation of hypercalcemia-producing Leydig cell tumors.

The effect of Rice H-500 Leydig cell tumor tissue on bone in rats was assessed by morphometric analysis and tetracycline labeling of the lower femoral metaphyses. The rats in which tumor was implanted showed hypercalcemia, increased osteoclastic bone resorption, inhibition of bone formation with reduction in the bone apposition rate, and a loss in trabecular volume compared with the control rats. There was no evidence of tumor metastasis to bone. The results are consistent with the hypothesis that the Leydig cell tumor secretes a humoral factor capable of causing systemic bone resorption.

Animals

Projecting physician requirements in a two-county region in Ohio.

A methodology for projecting physician requirements in a geographical region is presented. The procedure incorporates variables defining physician workloads, rates of retirement and estimated population changes to determine the future needs for health care practitioners. A case study using data from a two-county region of northeastern Ohio is included to illustrate the applicability of the projection methodology.

Health Planning

Persistent hyperparathyroidism caused by incomplete parathyroid resection and a hyperfunctioning parathyroid autograft.

A case of familial primary hyperparathyroidism occurred in which persistent hypercalcemia was caused by hyperplastic parathyroid tissue left in the neck and mediastinum after initial surgery and by a hyperfunctioning parathyroid autograft in the forearm. Successful therapy required parathyroid localization and resection of tissue from the neck, mediastinum, and forearm. Parathyroid tissue should be autotransplanted at the time of initial surgery only when total parathyroidectomy is judged likely to have been achieved.

Adult