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Biomedical subjects

C M Taylor

Publications and source records attributed to C M Taylor.

At least 181 records · Page 10Linked to original sources
PubMed1979

1,25-Dihydroxycholecalciferol in human serum and its relationship with other metabolites of vitamin D-3.

A competitive protein binding assay for 1,25-dihydroxycholecalciferol has been developed using the hormone's nuclear receptor protein from chick intestinal mucosa. This nuclear receptor protein can be stored at -70 degrees C for several months and bound and free hormone can be separated easily with dextran coated charcoal. Results obtained using this assay agree well with those reported by other groups of workers. Serum levels of other vitamin D-3 metabolites, namely 25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol have also been measured and are shown in relation to 1,25-(OH)2D3 levels.

Animals↗
PubMed1979

Highly specific binding of 1,25-dihydroxycholecalciferol in bone cytosol.

A method developed initially for the detection of high-affinity binding of glucocorticoids in the cytosol from foetal rat calvaria has been adapted for metabolites of vitamin D. Consistent displacement of [3H]1,25-dihydroxycholecalciferol ([3H]1,25(OH)2D3) by unlabelled 1,25(OH)2D3 was obtained with an apparent dissociation constant (Kd) of 2.3 x 10(-9) mol/l. The specificity of this binding was examined by competition experiments. Displacement of labelled 1,25(OH)2D3 by a 100-fold excess of unlabelled metabolites, expressing the fall with unlabelled 1,25(OH)2D3 as 100%, was as follows: 25-hydroxycholecalciferol (25(OH)D3), 61%; 24,25-dihydroxycholecalciferol, 29%; cholecalciferol, 3%. These are similar to results for the chick mucosa nuclear 1,25(OH)2D3 receptor. No displacement was obtained with corticosterone, testosterone, oestradiol or progesterone. When [3H]25(OH)D3 was used as ligand, a displacement curve with unlabelled 25(OH)D3 indicated only binding with a greater Kd (approximately 10(-7) mol/l). These data suggest a direct action of 1,25(OH)2D3 on bone which is similar to that of steroid hormones on their target tissues.

Animals↗
PubMed1979

The relationship between disturbed metabolism of vitamin D and bone disease in chronic renal failure.

Following the discovery that the kidney is involved in the metabolism of vitamin D, a causal relationship has been sought between defective production of 1,25-dihydroxy vitamin D3 and bone disease in chronic renal failure. This paper reviews some of the clinical evidence for and against such a relationship, and considers the possible role of other vitamin D metabolites in the pathophysiology of renal bone disease.

Bone Diseases↗
PubMed1978

The absence of 24,25-dihydroxycholecalciferol in anephric patients.

1. In subjects with normal renal function there was a strong positive correlation between serum concentrations of 25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol, as measured by competitive protein-binding assay. 2. The 24,25-dihydroxycholecalciferol concentration was about 7% of the prevailing 25-hydroxycholecalciferol concentration. 3. In contrast, sera from anephric patients contained very low or undetectable amounts of 24,25-dihydroxycholecalciferol even after the serum 25-hydroxycholecalciferol concentrations in these patients had been elevated by oral administration of 25-hydroxycholecalciferol. 4. In a further group of anephric patients, all having normal serum 25-hydroxycholecalciferol concentrations, no radioactively labelled 24,25-dihydroxycholecalciferol was formed from an injected pulse dose of [3H,14C]cholecalciferol. 5. These results indicate that in man the kidney is the major site of 24-hydroxylation of 25-hydroxycholecalciferol.

Adult↗
PubMed1977

1,25-dihydroxycholecalciferol in hypoparathyroidism.

8 patients with hypoparathyroidism have been treated successfully with 1,25-dihydroxycholecalciferol (0-25-1-0 mug/day) for 4-24 mo. Normal serum-calcium levels were restored in all patients, but half the patients required supplementary oral calcium. Treatment reduced serum-phosphorus in all patients, but values remained high in 3, and the renal-tubular reabsorption of phosphate returned to normal in only 2 of the 8 patients. A comparison is made with the effects of oral therapy with massive amounts of calcium salts. The data obtained are discussed in relation to the probable mode of therapeutic action of 1,25-dihydroxycholecalciferol.

Administration, Oral↗
PubMed1976

Metabolic fate of administered 1,25-dihydroxycholecalciferol in controls and in patients with hypoparathyroidism.

In four healthy controls and three patients with hypoparathyroidism serum-1,25-dihydroxycholecalciferol (1,25-D.H.C.C.) concentrations, after oral or intravenous administration, declined biphasically with a rapid-phase half-time of about 14 hours. Repeated oral doses of 1 mug 1,25-D.H.C.C. (2-4 nmol) produced serum concentrations well below the assayed normal range but were nevertheless effective in raising serum-calcium. It is suggested that orally administered 1,25-D.H.C.C. acts directly on the intestinal mucosal-cell nucleus to promote calcium absorption. 1,25-D.H.C.C. is more rapidly eliminated from the body than vitamin D, and it is predicted that any hypercalcaemia caused by 1,25-D.H.C.C. therapy should be of relatively short duration.

Administration, Oral↗
PubMed1976

Treatment of hypoparathyroidism with 1,25-dihydroxycholecalciferol.

Five patients with hypoparathyroidism (three post thyroidectomy and two idiopathic) were treated with synthetic 1,25-dihydroxycholecalciferol (1,25-(OH)2-D3) for up to 6 months. In each case daily oral administration of 1 microgram 1,25-(OH)2-D3, either alone or with additional calcium, raised ther serum calcium into the normal range. The serum phosphorus and the renal tubular reabsorption of phosphorus fell during treatment. None of these patients developed hypercalcaemia and no other complications of treatment have been recorded. 1,25-(OH)2D3 seems to represent a significant improvement over conventional methods for treating hypoparathyroidism.

Adult↗
PubMed1975

Vitamin D metabolism and parathyroid function in man.

1. The metabolism of an intravenous pulse dose of double-isotope-labelled cholecalciferol has been studied in control subjects with widely differing states of vitamin D nutrition and in patients with primary disorders of parathyroid function. 2. The formation of labelled 1,25-dihydroxy-cholecalciferol [1,25-(OH)2D3] and labelled 24,25-dihydroxycholecalciferol [24,25-(OH)2D3] has been related to the prevailing concentrations in serum of 25-hydroxycholecalciferol [25-(OH)D3], immunoreactive parathyroid hormonel, calcium and orthophosphate (Pi). 3. In control subjects with relative vitamin D deficiency [serum 25-(OH)2D3 was related inversely to the serum 25-(OH)D3 and serum calcium, and directly to serum immunoreactive parathyroid hormone. No formation of 1,25-(OH)2D3 was detectable to form labelled 24,25(OH)2D3 preferentially. 4. No control subject produced significant amounts of both labelled 1,25-(OH)2D3 and labelled 24,25-(OH)2D3 simultaneously. 5. All subjects with primary hyperparathyroidism produced significant amounts of labelled 1,25-(OH)2D3 and labelled 24,25-(OH)2D3 simultaneously; the renal turnover of 25-(OH)D3 was apparently greater than in nutritionally matched controls. Serum labelled 1,25-(OH)2D3 in this disease was not correlated with serum 25-(OH)D3, immunoreactive parathyroid hormone, calcium or Pi. Production of labelled 24,25-(OH)2D3 was inappropriately high for the prevailing nutritional state. 6. The indirectly estimated their concentration of 1,25-(OH)2D3 showed only a fourfold variation in control subjects (45-180 pmol/l), compatible with its having a regulated hormonal function. 7. The data suggest that the production of 1,25-(OH)2D3 from a pulse dose of cholecalciferol is normally regulated, directly or indirectly, by the parathyroid hormone.

Adult↗
PubMed1975

The effects of a diphosphonate and dietary calcium on the metabolism of vitamin D3 (cholecalciferol) in the chick.

1. Vitamin D-deficient chicks, maintained on a diet adequate in calcium and treated with ethane-1-hydroxy-1,1-diphosphonate for 2 days before a single oral dose of cholecalciferol (vitamin D3), converted the vitamin into 24,25-dihydroxycholecalciferol instead of into the normal metabolite 1,25-dihydroxycholecalciferol. 2. This inhibition of the renal 1-hydroxylase disappeared on withdrawal of the diphosphonate. 3. Kidneys from chicks given diphosphonate for 12 days converted 25-hydroxycholecalciferol into 24,25-dihydroxycholecalciferol on incubation in vitro. 4. The inhibition of the 1-hydroxylase was markedly accelerated by treating the birds with cholecalciferol. 5. No inhibition of renal 1-hydroxylation was observed in birds maintained on a diet low in calcium. 6. A possible mechanism producing this effect is discussed.

Animals↗