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C D Arnaud

Publications and source records attributed to C D Arnaud.

At least 55 records · Page 3Linked to original sources
PubMed1985

Localization studies in patients with persistent or recurrent hyperparathyroidism.

Preoperative localization studies are essential for patients who have undergone previous parathyroid operations. This is because the remaining parathyroid glands are more difficult to identify at operation because of increased scarring with loss of normal tissue planes and because the remaining abnormal parathyroid tissue is more likely to be situated in an ectopic position. This investigation concerns the accuracy of preoperative localization studies in 36 consecutive patients. All patients had symptoms and clinical and laboratory data diagnostic of primary (31 patients) or secondary (five patients) hyperparathyroidism. Ultrasonography was performed in all 36 patients; 18 (50%) were positive, 14 (39%) were negative, and four (11%) were false positive examinations. Eight of the negative study results occurred in patients with abnormal parathyroid glands situated in the mediastinum. Computerized tomography (CT) was performed in 25 patients. There was an equal number of positive (11; 44%) and negative (11; 44%) studies with three (12%) false positive test results. CT was helpful in identifying substernal lesions and other abnormal parathyroid glands situated in ectopic positions. Thallium chloride 201-technetium 99m pertechnetate scans were used in 22 patients. There was an equal number of positive (eight; 36%) and negative (eight; 36%) studies. Six patients (27%) had false positive scans. One or more of these noninvasive tests was positive in 27 of the 36 patients (75%). Highly selective venous catheterization for the measurement of immunoreactive parathyroid hormone concentrations localized the elusive parathyroid tumor in 12 of the 16 patients (75%) overall and in six of the nine patients (66%) whose tumors were not identified by other studies. One patient had both a false positive ultrasound and thallium chloride 201-technetium 99m pertechnetate scan. Preoperative localization studies were therefore very helpful for locating hyperfunctioning parathyroid glands in patients with recurrent or persistent hyperparathyroidism, and 75% of the tumors were identified by noninvasive studies. Seventy-five percent of the tumors not identified by noninvasive studies were localized by selective venous catheterization. Most tumors not identified by noninvasive studies were mediastinal or ectopic in position.

Adult↗
PubMed1982

Photoaffinity labeling of the canine renal receptor for parathyroid hormone.

Studies were undertaken to identify and characterize components of the parathyroid hormone receptor. An analog of the bovine parathyroid hormone(1-34) sequence was derivatized at the 23-tryptophan position with the photoreactive reagent 2-nitro-5-azidophenylsulfenyl chloride. 2-Nitro-5-azidophenylsulfenyl-bovine parathyroid hormone (NAPS-bPTH) analog retained full biological activity with respect to receptor binding and activation of adenylate cyclase in canine renal cortical plasma membranes. 125I-bPTH(1-34) analog was also derivatized without loss of receptor-binding activity. When 125I-NAPS-bPTH(1-34) analog was incubated with canine renal plasma membranes and then photolyzed, at least two 125I-labeled membrane components were identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The incorporation of 125I radioactivity into one of these components (Mr congruent to 60,000) was inhibited when incubation and photolysis were performed in the presence of excess, unlabeled bPTH(1-34). Furthermore, photolysis of membranes in the presence of NAPS-bPTH(1-34) analog led to activation of adenylate cyclase which persisted following washing to remove noncovalently bound peptide, suggesting a functional, covalent hormone-receptor complex had been formed. We conclude that the M r congruent to 60,000 membrane component may be a part of the renal receptor for parathyroid hormone.

Adenylyl Cyclases↗
PubMed1982

Parathyroid hormone receptors in avian bone cells.

We have demonstrated binding of synthetic bovine parathyroid hormone (1-34) [bPTH-(1-34)] to embryonic avian bone cells in monolayer culture. The binding sites have qualitative and quantitative characteristics of a physiologically important parathyroid hormone (PTH) receptor. At apparent steady state (60 min at 24 degrees C), 5-10% of electrolytically labeled, receptor-purified 125I-labeled bPTH-(1-34) bound specifically to the cells whereas nonspecific binding was less than 1% of the added labeled hormone. Scatchard analysis showed a single order of PTH binding sites (Kd = 0.6 nM) with approximately 10,000 sites per cell. In this bone cell system, PTH bound to its binding site and stimulated cAMP accumulation over the same concentration range. Bovine PTH-(1-84) bound to the cells with the same apparent affinity as bPTH-(1-34).

Adenylyl Cyclases↗
PubMed1982

Parathyroid hormone receptor in intact embryonic chicken bone: characterization and cellular localization.

The specific localization and the characterization of the parathyroid hormone (PTH) receptor in bone have been studied using 18-d embryonic chick calvariae and biologically active, electrolytically labeled [125I] bovine PTH(1-34). Binding was initiated by adding [125I]-bPTH(1-34) to bisected calvariae at 30 degrees C. Steady state binding was achieved at 90 min at which time 10 mg drg wt of calvaria specifically bound 17% of the added [125I]bPTH(1-34). Nonspecific binding in the presence of 244 nM unlabeled bPTH(1-34) was less than 2%. Insulin, glucagon, and calcitonin (1 microgram/ml) did not compete for PTH binding sites. Half-maximal inhibition of binding was achieved at concentrations of unlabeled bPTH(1-34) or bPTH(1-84) of about 10 nM. The range of concentration (2-100 nM) over which bPTH(1-34) and bPTH(1-84) stimulated cyclic 3'5'adenosine monophosphate (cAMP) production was similar to that which inhibited the binding of [125I]bPTH(1-34). Light microscope autoradiograms showed that grains were concentrated over cells (osteoblasts and progenitor cells) at the external surface of the calvariae and in trabeculae. In the presence of excess unlabeled PTH, labeling of control autoradiograms was reduced to near background levels. No labeling of osteocytes or osteoclasts was observed. At the electron microscopic level, grains were localized primarily over cell membranes. A quantitative analysis of grain distribution suggested that cellular internalization of PTH occurred.

Animals↗
PubMed1981

Guanyl nucleotide potentiation of parathyroid hormone-stimulated adenylate cyclase in chicken renal plasma membranes: a receptor-independent effect.

We investigated the interaction of guanyl nucleotides with the parathyroid hormone (PTH) receptor-adenylate cyclase system in chicken renal plasma membranes. Micromolar concentrations of guanosine triphosphate and its hydrolysis-resistant analog 5'-guanylimidodiphosphate [Gpp(NH)p] increased both basal and PTH-stimulated adenylate cyclase activity. The enzyme activation produced by the amino-terminal 1--34 peptide of bovine PTH [bPTH-(1--34)] was potentiated by both guanyl nucleotides, although quantitatively greater effects were seen with Gpp(NH)p. The apparent activation constant for bPTH-(1--34) stimulation of adenylate cyclase, 16 nM, was reduced to 3.7 nM in the presence of 1.0 microM Gpp(NH)p. The interaction of guanyl nucleotides with the PTH receptor was evaluated by measurement of specific 125I-labeled bPTH-(1--34) binding to chicken renal plasma membranes in the presence and absence of Gpp(NH)p. There was no effect of the guanyl nucleotide on the rate of binding or dissociation of 125I-labeled bPTH-(1--34) from its renal receptor. Scatchard analysis of steady state PTH binding revealed that 1.0 microM Gpp(NH)p had minimal effect on either the affinity of PTH receptors (Kd increased from 25 nM to 30 nM) or their number (total number of binding sites increased from 8.6 to 9.4 pmol/mg protein). Separate experiments demonstrated a concentration-dependent effect on Gpp(NH)p to decrease the apparent activation constant for bPTH-(1--34) stimulation of adenylate cyclase, with no detectable guanyl nucleotide effect on the affinity of PTH receptors. The results suggest that guanyl nucleotides may enhance the coupling of occupied PTH receptors to adenylate cyclase independent of direct nucleotide effects on renal PTH receptors.

Adenylyl Cyclases↗
PubMed1980

Controlled trial of the effects of 1,25-dihydroxycholecalciferol in patients treated with regular dialysis.

In a double-blind controlled study, 15 patients received 1,25-dihydroxycholecalciferol (1,25[OH]2D3) (0.5-1.5 microgram/day) and 16 patients received vitamin D3 (D3) (400-1,200 IU/day). The patients receiving 1,25(OH)2D3 had a rise in mean serum calcium concentration from 9.05 +/- 0.15 to 10.25 +/- 0.20 mg/dl (p less than .001) with a return to 9.37 +/- 0.16 (p less than .001) in the post-control period; however, hypercalcemia (greater than 11.5 mg/dl) occurred in 5 of 15 patients. Likewise, patients who received 1,25(OH)2D3 but not those given D3 had a reversible decrease in immunoreactive parathyroid levels. 9 of 12 patients given D3 had serial iliac crest bipsies showing histologic deterioration, while 6 of 7 patients who received 1,25(OH)2D3 were improved or unchanged (p less than 0.025). Bone mineral and calcium content decreased in patients on D3 (p less than .05) but not in those on 1,25(OH)2D3. We conclude that the administration of 1,25(OH)2D3 to dialysis patients: (1) has a calcemic effect. (2) decreases levels of immunoreactive parathyroid hormone, and (3) is associated with histologic improvement in bone disease.

Adult↗
PubMed1980

The renal parathyroid hormone receptor-adenylate cyclase system in vitro and in vivo.

High affinity parathyroid hormone (PTH) receptors in chicken renal plasma membranes were identified and quantitated using bPTH((1-34) labeled by electrolytic iodination and purified by a membrane absorption procedure. Parallel studies of PTH-receptor binding and activation of adenylate cyclase indicated that these activities were coupled. The PTH sensitivity of the renal receptor-adenylate cyclase system was similar in vivo and in vitro (Km congruent to 20 nM), whereas a 'physiologic' concentration of circulating bPTH (1-34) infused into thyroparathyroidectomized/ultimobranchial-ectomized chickens was estimated to be at least 40 times lower. Small increments in cellular cyclic AMP levels are apparently sufficient to mediate actions of PTH on the kidney.

Adenylyl Cyclases↗
PubMed1980

The effect of age on serum immunoreactive parathyroid hormone in normal and osteoporotic women.

Serum iPTH was measured in a large series of normal and osteoporotic women as a function of age, with radioimmunoassays using three antisera: GP-1M, which recognizes primarily a region within the 44--68 amino acid sequence of PTH; CH-12M, which appears to recognize primarily intact hormone; and CH-14M, which recognizes primarily a region within the 1--34 amino acid sequence of PTH. In normal women 20 to 90 years of age, serum iPTH increased significantly with age (p less than 0.001); the proportional increase was greater when measured with antiserum GP-1M (80%) than when measured with antiserum CH-12M (30%), which suggests that the increase in circulating carboxyl fragments of PTH was greater than the increase in circulating intact PTH. In 40 patients with postmenopausal osteoporosis, the mean value for serum iPTH assayed by antiserum GP-1M did not differ significantly from that for age-matched normal women; however, three osteoporotic patients had elevated values and thus appear to represent a separate population. When these subjects were excluded, mean serum iPTH assayed by antiserum GP-1M also was lower than normal (p less than 0.001). The mean value for serum iPTH was lower in osteoporotic patients than in normal subjects when assayed by either antiserum CH-12M (p less than 0.001) or antiserum CH-14M (p less than 0.001). Values for serum phosphate and renal tubular phosphate resorption, both indices of PTH function, were increased (p less than 0.005) in the osteoporotic subjects. Although creatinine clearance decreased with age in both normal and osteoporotic subjects, partial correlations with age held constant showed no relationship between creatinine clearance and serum iPTH. This suggests that a decrease in renal function was not the major factor accounting for the rise in serum iPTH with age. We conclude that serum iPTH increases with aging but that for any given age, it is either normal or low in patients with postmenopausal osteoporosis.

Adult↗