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C D Arnaud

Publications and source records attributed to C D Arnaud.

At least 73 records · Page 4Linked to original sources
PubMed1978

Carboxyl-terminal fragments of human parathyroid hormone in parathyroid tumors: unique new source of immunogens for the production of antisera potentially useful in the radioimmunoassay of parathyroid hormone in human serum.

We have found large quantities of immunoreactive carboxyl-terminal fragments of human parathyroid hormone )hPTH) in a previously discarded fraction [the 7.5% trichloroacetic acid (TCA)supernate] generated during extraction of intact hPTH from hyperfunctioning parathyroid tissue by the urea-TCA procedure. It is well established that serum RIAs directed toward the carboxyl-terminal region of hPTH are superior to those directed toward the amino-terminal region in the differential diagnosis of patients with suspected chronic parathyroid dysfunction. However, antisera that react with the carboxyl-terminal region of hPTH are not yet available for general use for these assays because of a lack of suitable hPTH immunogens. We immunized seven guinea pigs and two goats with the desalted 7.5% TCA supernate (containing about 2% carboxyl-terminal hPTH fragments); three of the guinea pigs and one goat produced high affinity antisera with predominant specificity for the carboxyl-terminal region of PTH. One of the guinea pig antisera had affinity for hPTH equal to that of our laboratory's best antiserum (GP1M) used in diagnostic RIAs for serum PTH. The use of this byproduct fraction as an immunogen should permit a large scale immunization program in large animals to provide standardized, species-and sequence-specific antisera potentially useful in RIAs for diagnosis of parathyroid disease.

Adenoma↗
PubMed1978

1,25 dihydroxycholecalciferol effects in chronic dialysis. A double-blind controlled study.

1,25 dihydroxycholecalciferol [1,25(OH)2D3] was studied in a double-blind controlled fashion in patients on chronic dialysis. Serum calcium was unchanged in 16 patients on vitamin D3 (D3) (400 to 1200 IU/day). In 15 patients on 1,25(OH)2D3 (0.5 to 1.5 microgram/day), serum calcium increased from 9.05 +/- .15 to 10.25 +/- .20 mg/dl (p less than 0.001), returning to 9.37 +/- .16 mg/dl (p less than 0.001) in the post control period. Patients on D3 showed no reversible decrease in immunoreactive parathyroid hormone levels, but patients on 1,25(OH)2D3 did, from a control of 1077 +/- 258 to 595 +/- 213 microliter equivalents/ml (p less than 0.01), and returned to 1165 +/- 271 microliter equivalents/ml (p less than 0.005). Nine of 12 patients on D3 who underwent serial iliac-crest biopsies showed histologic deterioration, and six of seven who received 1,25(OH)2D3 were improved or unchanged (p less than 0.025). Bone mineral and calcium decreased in patients on D3 (p less than 0.05) but not in those on 1,25(OH)2D3. Hypercalcemia occurred in five of 15 patients. We conclude that 1,25(OH)2D3 has a calcemic effect in chronic dialysis patients, decreases levels of immunoreactive parathyroid hormone, and is associated with histologic improvement in bone disease. Thus, 1,25(OH)2D3 is a valuable adjunct to the management of renal osteodystrophy but requires monitoring of serum calcium to avoid hypercalcemia.

Adult↗
PubMed1978

Importance of the isolation of 25-hydroxyvitamin D before assay.

A protein-binding assay for determination of 25(OH)D was used to analyze the profile of chromatographed ethanol extracts of serum. There were substances in the serum of normal subjects which displaced labeled 25(OH)D3 from the binding protein and which were different from 25(OH)D or 24R,25(OH)2D. Values of 25(OH)D from serum samples without prior chromatography were higher than those obtained with chromatography (40.2 +/- 12.2 ng/ml vs. 22.3 +/- 8.2, mean +/- S.D.). This indicates a need for chromatography before assay to ensure specificity of 25(OH)D measurement.

Binding, Competitive↗
PubMed1978

A syndrome of osteoporosis, increased serum immunoreactive parathyroid hormone, and inappropriately low serum 1,25-dihydroxyvitamin D.

Although most patients with postmenopausal osteoporosis have normal or low values for serum immunoreactive parathyroid hormone (iPTH), we have reported previously that a small subset (about 10% of the total group) have increased values. We studied three patients representative of this latter group. Serum iPTH was two to three times higher than the age-adjusted normal mean, serum ionized calcium and total calcium were in the lower half of the normal range, and serum 1,25-dihydroxyvitamin D [1,25(OH)2D] was in the low-normal range. Six months of treatment of one patient with 0.5 microgram/day of synthetic 1,25(OH)2D improved calcium absorption and balance; however, serum iPTH remained high. After surgical removal of 1,010 mg of hyperplastic parathyroid tissue, serum iPTH decreased to normal. These and other data suggest that increased serum iPTH in these patients was caused by secondary hyperparathyroidism, possibly because of inadequate conversion of 25-OH-D to 1,25(OH)2D.

Aged↗
PubMed1977

The effect of 25-hydroxy vitamin D3 in the osteomalacia of chronic renal failure.

1. Five patients with the osteomalacia of chronic renal failure were given 50--100 nmol of 25-hydroxy vitamin D3 intravenously per day for 24--28 days. 2. In all five patients, during administration of 25-hydroxy vitamin D3 there was a substantial rise in the plasma concentration of 25-hydroxy vitamin D from initially abnormally low values. 3. Significant improvement in bone mineralization, intestinal calcium absorption and muscle strength occurred in the three patients with the greatest rise in plasma 25-hydroxy vitamin D.

Aged↗
PubMed1977

Immunoheterogeneity of parathyroid hormone in venous effluent serum from hyperfunctioning parathyroid glands.

The immunoreactive parathyroid hormone (iPTH) in the plasma of hyperparathyroid man consists largely of carboxyl (COOH)-terminal fragments of the hormone. Although these fragments have been thought to arise principally or solely from peripheral metabolism of intact human PTH {hPTH(1-84)} secreted from the parathyroid gland, there is disagreement about the source of iPTH fragments in vivo. To reexamine this question, we fractionated peripheral and thyroid or parathyroid venous effluent sera from four patients with primary hyperparathyroidism using a high-resolution gel filtration system (Bio-Gel P-150 columns run by reverse flow). The column effluents were analyzed using two PTH radioimmunoassays, one directed toward the amino(NH(2))-terminal region of the molecule, the other toward the COOH-terminal region. In all four thyroid or parathyroid venous effluent sera studied, iPTH was 9-180 times higher than in peripheral serum from the same patient; after fractionation, hPTH(1-84) accounted for only a portion of the total iPTH (35-55% with the assay directed toward the COOH-terminal region of hPTH, >90% with the NH(2)-terminal directed assay.) The remaining iPTH eluted from Bio-Gel P-150 after hPTH(1-84) as NH(2)-or COOH-terminal hPTH fragments. These results suggest that parathyroid tumors secrete large quantities of hPTH fragments. Based on estimates of their molar concentrations in serum, tumor-secreted COOH-terminal hPTH fragments could account for most of these peptides in peripheral serum if their survival times were, as estimated by several other workers, 5-10 times that of hPTH(1-84). We conclude that, in contrast to published information, secretory products of hyperfunctioning parathyroid tissue are probably a major source of serum PTH immunoheterogeneity.

Adult↗
PubMed1976

Bone cells in culture: morphologic transformation by hormones.

Hormones and purine nucleosides and nucleotides induced cultured bone cells to transform transiently from a spherical to a stellate shape. Cytochalasin B also induced the transformation. The change was blocked by colchicine and vinblastine, but not by lumicolchicine or cycloheximide. This morphologic transformation may provide a dynamic model of hormone action and bone cell modulation in vitro.

Animals↗
PubMed1976

Relative biologic activities of human and bovine parathyroid hormones and their synthetic, NH2-terminal (1-34) peptides, as evaluated in vitro with renal cortical adenylate cyclase obtained from three different species.

The relative biologic activities of native human parathyroid hormone, hPTH (1-84), native bovine parathyroid hormone, bPTH (1-84), and their respective synthetic, NH2-terminal, biologically-active (1-34) fragments were compared in vitro using adenylate cyclase preparations from human, chicken, and rat renal cortex. The concentrations of the hormones required for half-maximal stimulation of the enzymes were determined from dose response curves. bPTH (1-84) had greater apparent activity than hPTH (1-84), using rat or chicken renal adenylate cyclase, but, with human renal adenylate cyclase, the apparent activities of the two hormones were equal. Synthetic hPTH (1-34) possessed about 1/10 of the apparent activity of hPTH (1-84) in all three adenylate cyclase systems. However, (GLU22)bPTH (1-34) was about equal inapparent activity to bPTH (1-84) in the three systems. We propose that different rates of hormone degradation at or near renal receptor sites may be responsible for the dependence of the relative biologic activity on the assay system used. In the case of hPTH a peptide chain longer than (1-34) may be required for the full biologic activity of the hormone...

Adenylyl Cyclases↗
PubMed1976

Effects of oral therapy with calcium and vitamin D in primary osteoporosis.

Eighteen patients (17 women and 1 man) with primary osteoporosis were divided into two groups of 9 patients each. Group A received 2.0 to 2.5 g of calcium and 400 units of vitamin D per day orally and was studied before and after short-term (3 to 4 months) treatment; group B received 1.5 to 2.0 g of calcium per day and 50,000 units of vitamin D twice weekly and was studied before, after short-term, and after long-term (1 year) treatment. In group A there was a decrease (P is less than 0.01) in bone-resorbing surfaces (microradiography of bone biopsy samples) after short-term treatment. In group B there was a decrease (P is less than 0.01) in bone-forming and bone-resorbing surfaces after both short-tern and long-term treatment. Fasting-state (morning) serum immunoreactive parathyroid hormone (iPTH) concentrations decreased after short-term treatment (combined data of groups A and B) and after long-term treatment (group B). We conclude that the principal effect of the oral calcium and vitamin D therapy in primary osteoporosis is to decrease bone turnover. The most probable mechanism for this effect on bone is a partial inhibition of PTH secretion.

Administration, Oral↗
PubMed1976

Effects of phosphorus supplementation on serum parathyroid hormone and bone morphology in osteoporosis.

The effect of phosphorus (inorganic phosphate) supplementation was studied in seven postmenopausal women with osteoporosis. Prior to supplementation, all chemical parameters studied in serum and urine were normal. Bone density was below the fifth percentile for age in all but one patient, and the percentage of bone surface involved in resorption was higher than normal. During administration of the phosphorus supplement, fasting serum concentrations of calcium and immunoreactive parathyroid hormone showed no significant changes, while serum phosphorus, urinary calcium, and tubular reabsorption of phosphorus decreased. In four patients studied by balance techniques, calcium balance became positive or less negative. Bone-forming surface decreased and bone-resorbing surface increased in all patients. Bone-resorbing surface was highly correlated with total phosphorus intake. Density of the distal radius changed variably, while density of the midradius increased slightly in all patients.

Aged↗
PubMed1976

Role of hormonal factors in the pathogenesis of postmenopausal osteoporosis.

In 47 women with postmenopausal osteoporosis, pretreatment studies by microradiography, radioimmunoassay and other methods showed increased bone resorption, normal bone formation, and decreased serum immunoreactive parathyroid hormone (PTH). In patients treated with a physiologic replacement dose of estrogen, bone resorption decreased to normal and PTH increased after short-term therapy; bone formation decreased to very low levels after long-term therapy. These data indicate that, in most patients, both an intrinsic abnormality of bone cell function and a disruption of the normal regulation of bone turnover by PTH and sex hormones, as a result of the menopause, are important in the pathogenesis of osteoporosis.

Bone Resorption↗
PubMed1975

Role of parathyroid hormone in the phosphaturia of extracellular fluid volume expansion.

Role of parathyroid hormone in the phosphaturia of extracellular fluid volume expansion. Acute expansion of the extracellular fluid volume increases the urinary excretion of phosphate. The present study examined the importance of increased plasma parathyroid hormone concentration in the phosphaturia accompanying acute extracellular fluid volume expansion (ECVE). Infusion of a calcium-free Ringer's solution into dogs was associated with increased urinary phosphateexcretion and serum immunoreactive parathyroid hormone concentration (iPTH), the latter being significantly correlated with a decrease in plasma ionized calcium concentration. Prevention of the fall in plasma ionized calcium concentration by infusion of a calcium containing Ringer's solution prevented the increase in serum iPTH but the magnitude of the phosphaturia was not affected.

Animals↗