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Biomedical subjects

N H Bell

Publications and source records attributed to N H Bell.

15 recordsLinked to original sources
PubMed1979

Hypercalcemic and hypocalcemic disorders: diagnosis and treatment.

Current concepts concerning the mechanisms, diagnosis and means of treatment of a number of the major causes of hypercalcemia and hypocalcemia are reviewed. In particular, the role of abnormalities in metabolism of vitamin D including (1) excessive hepatic production of 25-hydroxyvitamin D (vitamin D intoxication), (2) increased production of 1 alpha, 25-dihydroxyvitamin D (hyperparathyroidism and sarcoidosis), (3) impaired production of 1 alpha, 25-dihydroxyvitamin D (hypoparathyroidism, renal failure, vitamin-D-dependent rickets type I, pseudohypoparathyroidism) and (4) resistance to 1 alpha, 25-dihydroxyvitamin D; the use of vitamin D and its metabolites therapeutically is discussed.

Humans↗
PubMed1979

Evidence that increased circulating 1 alpha, 25-dihydroxyvitamin D is the probable cause for abnormal calcium metabolism in sarcoidosis.

Mean plasma 1(alpha),25-dihydroxyvitamin D[1(alpha),25(OH)(2)D] was significantly increased and serum parathyroid hormone was suppressed in three patients with sarcoidosis and hypercalcemia. Prednisone lowered the mean plasma 1(alpha),25(OH)(2)D to normal range and corrected the hypercalcemia. To elucidate the mechanism for the increased sensitivity to vitamin D in this disorder, the effects of orally-administered vitamin D(2) were determined in seven normal subjects, four patients with sarcoidosis and normal calcium metabolism and three patients with sarcoidosis and a history of hypercalcemia who were normocalcemic when studied. Serum and urinary calcium, serum 25-hydroxyvitamin D (25-OHD), plasma 1(alpha),25(OH)(2)D and, in some studies, calcium balance were measured. Vitamin D(2), 250 mug a day for 12 d, produced little, if any, change in mean plasma 1(alpha),25(OH)(2)D and in urinary calcium in the normals and in the patients with normal calcium metabolism. In contrast, vitamin D(2) produced increases in plasma 1(alpha),25(OH)(2)D from concentrations which were within the normal range (20-55 pg/ml) to abnormal values and increased urinary calcium in two patients with abnormal calcium metabolism. In an abbreviated study in the third patient, vitamin D(2), 250 mug a day for 4 d, also increased plasma 1(alpha),25(OH)(2)D abnormally from a normal value. There was a highly significant correlation between plasma 1(alpha),25(OH)(2)D and urinary calcium. Serum 25-OHD and serum calcium remained within the normal range in all subjects and patients. These findings provide evidence that the defect in calcium metabolism in sarcoidosis probably results from impaired regulation of the production and(or) degradation of 1(alpha),25(OH)(2)D. Prednisone may act to correct the abnormal calcium metabolism by reducing circulating 1(alpha),25(OH)(2)D.

Adult↗
PubMed1978

Vitamin-D-dependent rickets type II. Resistance of target organs to 1,25-dihydroxyvitamin D.

Studies were done to determine the cause for hypocalcemia, secondary hyperparathyroidism, osteomalacia and osteitis fibrosa cystica in a 22-year-old black woman. The patient had normal serum 25-hydroxyvitamin D (14 ng per milliliter) and markedly elevated serum 1,25-dihydroxyvitamin D (137 pg per milliliter). Vitamin D3, 4000 units per day for four weeks, increased the serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D to as high as 29 and 297 pg per milliliter, respectively, and corrected the hypocalcemia and secondary hyperparathyroidism. The results suggest that the disorder results from impaired end-organ response to 1,25-dihydroxyvitamin D. We propose that the entity be called vitamin-D-dependent rickets Type II.

Adult↗
PubMed1978

A bioassay capable of measuring 1 picogram of 1,25-dihydroxyvitamin D3.

Fetal rat bones in organ culture constitute a sensitive system for assay of the vitamin D metabolite, 1 alpha,25-dihydroxyvitamin D3. Significant bone resorption is obtained with as little as 2 pg 1,25-dihydroxyvitamin D3 after 48 h of culture and with 1 pg after 64 h of culture. In the current study, organ cultures of fetal rat bone are used as a bioassay for 1,25-dihydroxyvitamin D i normal human plasma, which was prepared for assay by extraction with dichloromethane, chromatography on Sephadex LH-20, and purification on silicic acid by high pressure liquid chromatography. The concentration of 1 alpha,25-dihydroxyvitamin D3 in normal adult human plasma was 24.8 +/- 2.0 pg/ml (n = 19) by this assay.

Animals↗
PubMed1976

On the lipolytic action of parathyroid hormone in man.

An investigation was carried out to determine whether bovine PTH stimulates lipolysis in human fat tissue, whether this action is mediated by cyclic adenosine 3', 5'-monophosphate and whether the N-terminal 1-34 peptide of bovine PTH is responsible for the lipolytic effect. Studies were also performed to determine if parathyroid extract (PTE) produces lipolysis in normal subjects and in patients with pseudohypoparathyroidism in whom there is a defect in the adenylate system in response to PTH in the renal cortex and presumably in the skeletal system as well. It was found that highly purified bovine PTH in the concentration range between 10(-9) M and 10(-5) M stimulated lipolysis in vitro by human fat in a dose-dependent manner. Significant increases in glycerol production were observed at concentrations of PTH as low as 10(-9) M and maximal increases were seen at 10(-6) M. The hormone significantly increased the concentration of cyclic adenosine 3' ,5'-monophosphate in fat tissue. The synthetic N-terminal 1-34 peptide of bovine PTH was as effective as the native hormone in stimulating glycerol production at a concentration of 10(-9) M-10(-6) M. PTE, 100 mU per kg per min for 30 min given intravenously, produced transient increases in the concentration of plasma free fatty acid in each of eight normal subjects, three patients with hypoparathyroidism and eight patients with pseudohypoparathyroidism. Purified bovine PTH also increased plasma free fatty acid in each of two normal subjects. It is concluded that PTH stimulates lipolysis in human subcutaneous fat, that this action of the hormone is mediated through cyclic adenosine 3', 5'-monophosphate and that the N-terminal 1-34 peptide portion of the hormone is responsible for this lipolytic action. Further, PTE stimulates lipolysis in vivo in man. There appears to be no defect in the adenylate cyclase system in the fat cell in response to PTH in patients with pseudohypoparathyroidism.

Adipose Tissue↗
PubMed1976

Demonstration that cyclic adenosine 3',5'-monophosphate mediates the lipolytic action of parathyroid hormone.

Studies were carried out with rat epididymal fat pads first to compare the effects of the synthetic N-terminal 1-34 peptide of bovine parathyroid hormone and of the native hormone to determine whether this portion of the molecule is responsible for the lipolytic action of the hormone and second to determine whether this biologic action of parathyroid hormone is mediated by cyclic adenosine 3',5'-monophosphate. The N-terminal polypeptide was as effective as the native hormone in stimulating lipolysis in the concentration range between 10(-8) M and 10(-6) M. Parathyroid hormone stimulated lipolysis by isolated fat cells. The concentration of cyclic adenosine 3',5'-monophosphate in the fat pads was significantly increased by the hormone (10(-6)M). Lipolytic stimulation by parathyroid hormone (10(-6)M) was diminished by insulin (100 muU/ml) and prostaglandin E1 (1 mug/ml), both of which are known inhibitors of lipolysis. The findings indicate that the amino-terminal 1-34 peptide portion of parathyroid hormone is responsible for the lipolytic action and that this effect is mediated through cyclic adenosine 3',5'-monophosphate.

Adipose Tissue↗
PubMed1976

Acquired resistance to parathyroid hormone.

Studies are presented in a patient with pseudohypoparathyroidism who showed a partial response to parathyroid extract. Resistance to the extract was observed after its short-term administration for the gourth time. Serum from the patient contained antibodies of the gamma G globulin class which bound 125I-labelled bovine parathyroid hormone. Prior incubation of parathyroid hormone with the serum prevented the activation in vitro of adenylate cyclase from pork renal cortex. The antibodies were directed primarily toward the C-terminal portion of the molecule. Thus, clinical resistance to parathyroid hormone is attributed to specific antibodies.

Adenylyl Cyclases↗
PubMed1975

Solubilization of calcitonin-responsive renal cortical adenylate cyclase.

Purification of pork renal cortex membranes yielded a particulate adenylate cyclase retaining good sensitivity to stimulation by parathyroid hormone and glucagon and a modest but significant response to porcine calcitonin. Treatment of this partially purified membrane fraction with 0.5% Lubrol PX and 5 mM NaF released adenylate cyclase activity into a fraction which was not sedimented by centrifugation for 20 min at 37,000 X g or for 2 hours at 100,000 X g and passed through a Millipore filter (0.22 mum pore). This solubilized adenylate cyclase was stimulated by porcine calcitonin and NaF but not by parathyroid hormone or glucagon. On gel filtration (Sephadex G-200) in the presence of 1mM dithiothreitol and 5mM NaF, the major portion of the adenylate cyclase activity eluted with the void volume of the column and showed 2.0-fold stimulation with 10 muM calcitonin. Binding of 125I-labeled porcine calcitonin was demonstrated in the 37,000 X g and the 100,000 X g supernatants. From 74 to 86% of the observed binding could be blocked by the addition of unlabeled porcine calcitonin to the reaction mixture. Addition of salmon calcitonin, parathyroid hormone, or glucagon blocked only 12 to 18% of the binding. The dose-response curves for inhibition of binding of iodinated calcitonin by unlabeled calcitonin and the activation of adenylate cyclase by the hormone each showed 50% maximal effect at a concentration between 4.5 and 8 muM porcine calcitonin and maximal effect at a concentration between 33 and 66 muM porcine calcitonin.

Adenylyl Cyclases↗