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Biomedical subjects

I MacIntyre

Publications and source records attributed to I MacIntyre.

At least 145 records · Page 8Linked to original sources
PubMed1981

The construction and partial characterization of plasmids containing complementary DNA sequences to human calcitonin precursor polyprotein.

(1) Total poly(A)-containing RNA isolated from human thyroid medullary carcinoma tissue was shown to direct the synthesis in the wheat germ cell-free system of a major (Mr 21000) and several minor forms of human calcitonin precursor polyproteins. Evidence for processing of these precursor(s) by the wheat germ cell-free system is also presented. (2) A small complementary DNA (cDNA) plasmid library has been constructed in the PstI site of the plasmid pAT153, using total human thyroid medullary carcinoma poly(A)-containing RNA as the starting material. (3) Plasmids containing abundant cDNA sequences were selected by hybridization in situ, and two of these (ph T-B3 and phT-B6) were characterized by hybridization--translation and restriction analysis. Each was shown to contain human calcitonin precursor polyprotein cDNA sequences. (4) RNA blotting techniques demonstrate that the human calcitonin precursor polyprotein is encoded within a mRNA containing 1000 bases. (5) The results demonstrate that human calcitonin is synthesized as a precursor polyprotein.

Calcitonin↗
PubMed1981

Interrelations of calcium-regulating hormones during normal pregnancy.

Profound changes in calcium metabolism occur during pregnancy. The mother has to make available extra calcium for fetal requirements while ensuring that her plasma and bone calcium concentrations are satisfactorily maintained. In a cross-sectional study plasma concentrations of the major calcium-regulating hormones--namely, calcitonin, parathyroid hormone, 25-hydroxyvitamin D (25-OHD), and 1,25-dihydroxyvitamin D (1,25-(OH)2D)--were measured to establish their interrelations during normal pregnancy. The major changes observed were increases in the circulating concentrations of 1,25-(OH)2D and calcitonin. Concentrations of parathyroid hormone and 25-OHD remained within the normal range. The increased concentrations of 1,25-(OH)2D enable the increased physiological need for calcium to be met by enhancing intestinal absorption of this element. The simultaneous rise in calcitonin opposes the bone-resorbing activities of 1,25-(OH)2D, thereby protecting the integrity of the maternal skeleton. Maternal calcium homeostasis is thus maintained yet the requirements of the fetus are fulfilled.

25-Hydroxyvitamin D 2↗
PubMed1981

Immunoreactive calcitonin in the central nervous system of the pigeon.

To determine whether calcitonin (CT) is present in avian central nervous system (CNS), as it has been recently found in the CNS of other species, we studied extracts of pigeon (Columbia livia) brain by immunochemical methods. A sensitive and specific radioimmunoassay for salmon CT was used together with gel filtration and high performance liquid chromatography (HPLC). Extracts of hypothalamus contained 31.5 +/- 9.65 ng/g wet weight as salmon CT-like immunoreactivity while extracts of midbrain and brain stem contained 17.0 +/- 5.00 and 2.85 +/- 2.1 ng/g wet weight respectively. Extracts of whole pituitary gland, other areas of the CNS and vazrious peripheral tissues were below the detection limits of our assay, but salmon CT-like immunoreactivity was present in ultimobranchial gland (UBG), thyroid gland and lung tissue extracts. On Sephadex G-50 chromatography extracts of hypothalamic, midbrain, UBG and thyroid gland gave an immunoreactive peak which co-eluted with synthetic salmon CT. However, on HPLC the material in pigeon hypothalamus, midbrain, UBG and thyroid gland eluted in an identical manner when compared to each other but the major peak was 2 ml after that of synthetic salmon CT. These results clearly show that a salmon CT-like immunoreactive molecule is present in pigeon hypothalamus and midbrain, in addition to its main locations in the UBG and thyroid gland.

Animals↗
PubMed1981

Regulation of vitamin D metabolism by calcium and phosphate ions in isolated renal tubules.

The acute and long-term effects of Ca2+ and Pi on vitamin D metabolism were studied in vitro with isolated renal tubules from vitamin D-deficient and vitamin D-supplemented chicks. Ca2+ depletion, achieved by isolating renal tubules in Ca2+-free buffers, led to suppression of 1 alpha-hydroxylase activity. Re-introduction of Ca2+ during incubation caused an acute stimulation of this enzyme. This stimulatory effect of Ca2+ was prevented by prior treatment of Ca2+-depleted renal tubules for 6 h with 1,25-dihydroxycholecalciferol. Ca2+ and Pi produced marked acute affects on 1 alpha-hydroxylase activity, which persisted for the whole 8 h experimental period, in Ca2+-depleted renal tubules from vitamin D-deficient chicks. The effects of either ion were influenced by the concentration of the other. However, the effects of these ions could not be reproduced in either Ca2+-depleted renal tubules from vitamin D-supplemented chicks or in renal tubules from vitamin D-deficient chicks, isolated in Ca2+-containing buffers. Isolation of renal tubules from vitamin D-supplemented chicks in Ca2+-containing buffers and subsequent incubation for 8 h in the presence of increased [Ca2+] led to a modest but statistically significant suppression of 1 alpha-hydroxylase and stimulation of 24-hydroxylase activity. It is concluded that the acute effects of Ca2+ and Pi on 1 alpha-hydroxylase activity of Ca2+-depleted renal tubules from vitamin D-deficient chicks are not regulatory but the results of the experimental conditions. In contrast the long-term effects of Ca2+ on both hydroxylases of renal tubules from vitamin D-supplemented chicks may be of physiological significance.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1981

Calcitonin and the calcium-regulating hormones in postmenopausal women: effect of oestrogens.

In man, the major function of calcitonin appears to be prevention of excessive or unwanted bone resorption. There is a striking sex difference in circulating levels, with a relative deficiency in women. Calcitonin secretion in young adults is increased by oestrogens and therefore long periods of oestrogen lack, such as after the menopause, may be associated with a more pronounced calcitonin deficiency. This exaggerated deficiency could be an important factor in the pathogenesis of postmenopausal bone loss, especially since the latter may be due to excessive bone resorption. In a study of the effects of oestrogen treatment on circulating levels of calcitonin, parathyroid hormone, and vitamin-D metabolites in postmenopausal women, the most striking change was a sharp rise in plasma-calcitonin. Oestrogens prevent postmenopausal bone loss, and it is suggested that this effect could be mediated, at least in part, through control of calcitonin secretion. Calcitonin may prove effective in the prevention of postmenopausal bone loss, and it is suggested that this effect could be mediated, at least in part, through control of calcitonin secretion. Calcitonin may prove effective in the prevention of postmenopausal bone loss. Its place in the treatment of postmenopausal osteoporosis warrants further evaluation.

Aged↗
PubMed1981

Stimulation of 1,25-dihydroxycholecalciferol production by prolactin and related peptides in intact renal cell preparations in vitro.

Ovine prolactin stimulated the 1 alpha-hydroxylase activity in isolated renal tubules and especially in primary kidney cell cultures, both prepared from vitamin D-deficient chicks. In primary chick kidney cell cultures, treated for 48 h with 1,25-dihydroxycholecalciferol (to induce the 24-hydroxylase activity) ovine prolactin, after a 1 h incubation period, stimulated the 1 alpha-hydroxylase activity without affecting the 24-hydroxylase activity. Similar results were obtained with related peptide hormones such as human growth hormone, chicken growth hormone, and human placental lactogen. These observations are discussed in relation to the possible role of these peptide hormones as modulators of 1,25-dihydroxycholecalciferol production in physiological situations of calcium stress, such as pregnancy, lactation, growth in mammals and egg laying in birds.

Animals↗
PubMed1981

Effect of isoniazid on vitamin D metabolism and hepatic monooxygenase activity.

isoniazid, 300 mg daily for 14 days, reduced serum calcium and phosphate levels (P less than 0.001) in eight healthy subjects. After a single dose of isoniazid the concentration of 1 alpha-,25-dihydroxyvitamin D, the most active metabolite of vitamin D, fell by 47% (P less than 0.01) and was reduced throughout the study. Levels of 25-hydroxyvitamin D, the major circulating form of the vitamin, declined in all subjects and to below normal range in six (P less than 0.01). Parathyroid hormone levels rose by 36% (P less than 0.01) in response to the relative hypocalcemia produced. Isoniazid inhibited hepatic mixed-function oxidase activity, as evidenced by a reduction in antipyrine and cortisol oxidation, and a similar inhibition of the hepatic 25-hydroxylase and renal 1 alpha-hydroxylase would explain the reduction in the corresponding vitamin D metabolites. This perturbation of vitamin D metabolism differs from the vitamin D wasting effects after rifampicin. Patients with tuberculosis treated with isoniazid and rifampicin may show changes similar to those shown here in calcium and phosphate homeostasis and thus may be at risk of developing metabolic bone disorders.

Acetylation↗
PubMed1981

Sipple syndrome: marked variability of the disease within a family and implications for management.

Familial medullary carcinoma of the thyroid gland is often associated with phaeochromocytoma; this condition is known as Sipple syndrome. The rate of progression of the disease and the degree of malignancy of the medullary carcinoma may vary from family to family. Thus the nature and behaviour of this disease in any particular family influences the management of the thyroid carcinoma component. The authors measured plasma calcitonin and plasma catecholamines in 21 members of a family with Sipple syndrome. In one branch of this family 5 out of 7 members have so far been affected, 4 with metastases or recurrence of the carcinoma and 2 with development of phaeochromocytomas. In contrast, of the 14 members in the other 4 family branches, only 4 have had pathologically elevated plasma calcitonin concentrations following alcohol provocation, probably representing C-cell hyperplasia or very early neoplasia and apparently not progressing. None has evidence of phaeochromocytoma. This family demonstrates a striking variability in the natural history of Sipple syndrome which, despite increasing discovery of more families with medullary thyroid carcinoma, has not been previously reported. In the light of this finding, a reappraisal of the management of the thyroidal component of this disease is necessary. It appears that radical neck surgery may be needed to prevent recurrence of the disease.

Adrenal Gland Neoplasms↗
PubMed1981

Immunochemical characterization and distribution of calcitonin in the lizard.

Immunological and chromatographic methods were used to investigate the distribution of calcitonin (CT) in various tissues of Lacerta muralis, a common wall lizard. Salmon CT-like immunoreactivity was found in high concentration in extracts of ultimobranchial gland (UBG) and in significant amounts in lung and brain extracts, but not in other tissues (oesophagus, stomach, duodenum, liver, skin, muscle and thyroid). Serial dilution of UBG, lung and brain extracts gave parallel displacement curves to that of synthetic salmon CT (sCT), but no reactivity was found in the human CT assay. On Sephadex G-50, UBG, lung and brain extracts contained an sCT-like immunoreactive peak which co-eluted with synthetic sCT. However, on high performance liquid chromatography (HPLC) the sCT-like peak in UB, lung and brain extracts eluted 2 ml later than synthetic sCT. This paper describes the first immunochemical characterization of CT in the UBG of the lizard, demonstrates the distribution of extra-ultimobranchial CT and throws some light on the evolution of the calcitonins.

Animals↗
PubMed1980

Role of pituitary hormones in regulating renal vitamin D metabolism in man.

Studies in animals and tissue culture have shown the importance of prolactin and growth hormone in regulating renal 1 alpha-hydroxylase activity and plasma concentrations of 1,25-dihydroxycholecalciferol (1,25(OH)2D3). Evidence for a similar role for these hormones in man was sought by using a radioreceptor assay to measure plasma 1,25(OH)2D3 concentrations in 20 normal subjects, 12 patients receiving dialysis, 11 patients with primary hyperparathyroidism, 10 pregnant women, seven women with prolactinoma, and 14 patients with acromegaly. Circulating 1,25(OH)2D3 concentrations were appreciably raised in the patients with primary hyperparathyroidism and the pregnant women (P less than 0.001), slightly but significantly increased in the patients with prolactinoma (P less than 0.05), and greatly raised in those with acromegaly (P less than 0.001). These results suggest that prolactin and growth hormone are important regulators of renal vitamin D metabolism in the physiological conditions of pregnancy, lactation, and growth in man.

Acromegaly↗