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Biomedical subjects

I MacIntyre

Publications and source records attributed to I MacIntyre.

At least 127 records · Page 7Linked to original sources
PubMed1984

Essential steps in the measurement of normal circulating levels of calcitonin.

Before interpreting the results of assays which claim to measure circulating levels, one must have full data on the sensitivity, the reproducibility and specificity of the methods and antisera used. Without this information figures are meaningless and may be regarded as fiction rather than science. Secondly, and of equal importance, one must have full details of those physiological and pharmacological factors which are known to affect the circulating levels. It is quite obvious to workers in the field that those laboratories which have paid attention to these matters, have achieved remarkable agreement in practice; those who have neglected these requirements have introduced quite unnecessary confusion in the literature.

Amino Acid Sequence↗
PubMed1983

Katacalcin: a new plasma calcium-lowering hormone.

A second potent plasma calcium-lowering peptide, katacalcin (PDN-21), flanks calcitonin within the human calcitonin precursor. Plasma katacalcin was present in 57 healthy volunteers. Concentrations were higher in males than in females and approximately equimolar with calcitonin. Plasma katacalcin doubled within 5 min of calcium infusion. Plasma katacalcin was markedly raised in 20 patients with medullary carcinoma of the thyroid. Measurement of plasma katacalcin concentrations may prove useful in the diagnosis and follow-up of this condition. Katacalcin, like calcitonin, may be involved in both plasma calcium regulation and skeletal maintenance and thus may prove useful in the treatment of bone disease.

Adolescent↗
PubMed1983

Regulation of calcium-regulating hormones by exogenous sex steroids in early postmenopause.

A major function of calcitonin in humans appears to be maintenance of the skeleton. There is a marked sex difference in circulating calcitonin levels: women have much lower levels. This has led to speculation that calcitonin lack may be one factor involved in the pathogenesis of postmenopausal bone loss. We have measured levels of calcitonin and the other major calcium-regulating hormones in healthy women during the early menopause, and studied the effects of reversing their oestrogen deficiency with natural and synthetic oestrogen. The major findings were that calcitonin levels were increased by oestrogen administration (P less than 0.02-less than 0.001) and that the levels of the bone-resorbing hormones, parathyroid hormone and 1,25 dihydroxyvitamin D, were not higher in postmenopausal than in premenopausal women. We suggest that loss of oestrogen at the menopause accelerates the natural age-related decline of calcitonin secretion, thus further decreasing the calcitonin levels. This leads to increased sensitivity of the skeleton to the actions of the bone-resorbing hormones. It seems likely that the well-known effect of oestrogen in preventing postmenopausal bone loss is achieved, at least in part, by enhancement of calcitonin secretion.

Adult↗
PubMed1983

Immunocytochemical localisation of katacalcin, a calcium-lowering hormone cleaved from the human calcitonin precursor.

Katacalcin is a newly discovered calcium-lowering hormone predicted from the nucleotide sequence of a cloned cDNA derived from human calcitonin mRNA. The aim of the study was to localise katacalcin by immunocytochemistry at both light and electron microscope levels. Antisera to synthetic katacalcin and calcitonin were used to investigate 8 cases of medullary thyroid carcinoma and 6 normal human thyroids (3 adult and 3 fetal). We have been able to demonstrate the co-localisation of these peptides in normal and neoplastic C-cells in all cases studied. Our results suggest that peptide sequences predicted by recombinant DNA technology can be localised using immunocytochemistry and that the combination of these techniques may have applications in diagnostic pathology.

Calcitonin↗
PubMed1983

Two distinct insulins in the guinea pig: the broad relevance of these findings to evolution of peptide hormones.

In this paper we use the published data of others as well as our own recent data to question the widespread assumption that the gene for guinea pig insulin mutated rapidly after the divergence of guinea pigs from the main line of rodent evolution. We suggest that instead guinea pigs may have two pairs of alleles, one for typical guinea pig insulin, which is expressed in its pancreatic beta cells, and the other for a more typical mammalian insulin (designated rat/pork-type insulin), which is expressed in extrapancreatic cells. Further, we suggest the possibility that both pairs of genes may be evolutionarily very ancient and highly conserved. We also review evidence that the concept of nonallelic evolution may also apply to other hormones, including vasopressin, calcitonin, and growth hormone.

Alleles↗
PubMed1983

Immunoreactive calcitonin production by a human promyelocytic leukemia cell line HL60.

Using a sensitive radioimmunoassay, we detected human immunoreactive calcitonin in cell extracts and in cell-exposed media of the HL60 cell line derived originally from a patient with acute promyelocytic leukemia. The cell extract was chromatographed on a reverse-phase high-pressure liquid chromatography system. Radioimmunoassay of the fractions showed that the immunoreactive calcitonin was heterogeneous but had peaks corresponding to those of synthetic human calcitonin monomer and its sulphoxide. We have previously shown that levels of immunoreactive calcitonin are elevated in the plasma of the majority of patients with acute and chronic myeloid leukemias. Our studies with the HL60 cell line add further support to the concept that leukemic cells can synthesize immunoreactive calcitonin "ectopically."

Animals↗
PubMed1982

Salmon calcitonin in lizard brain: a possible neuroendocrine transmitter.

Calcitonin is a polypeptide which until recently was thought to be concerned primarily with the control of body calcium. Recent studies carried out with radioimmunoassay have demonstrated the presence of this peptide in brain and we have carried out an immunohistochemical study showing the presence of high concentrations of calcitonin in the nerve varicosities and terminals of the hypothalamus and in particular the median eminence of the lizard Lacertus muralis. The distribution of this calcitonin, which cross-reacted with anti-salmon calcitonin, suggests that this polypeptide and/or its flanking peptides may function as a neuroendocrine neurotransmitter.

Animals↗
PubMed1982

Specific binding of 1,25-dihydroxycholecalciferol in human medullary thyroid carcinoma.

A specific 1,25-dihydroxycholecalciferol-binding protein has been detected in high-salt cytosols prepared from human medullary thyroid carcinomas. The binding protein had the same equilibrium dissociation constant (Kd = 0.17 +/- 0.05 nM; n = 4) and sedimentation coefficient on sucrose gradients (3.7S) as than seen in established vitamin D target tissues. This protein was not detected in normal thyroid cytosols, which may reflect the low proportion of C-cells within the gland.

Calcitriol↗
PubMed1982

Effect of rifampicin and isoniazid on vitamin D metabolism.

Rifampicin, 600 mg, and isoniazid, 300 mg daily for 14 days, reduced circulating levels of 25-hydroxy vitamin D (25-OHD) and 1 alpha, 25-dihydroxy vitamin D (1,25(OH)2D) by 34% (P less than 0.01) and 23% (P less than 0.05) in eight healthy subjects. This was accompanied by a rise in parathyroid hormone (PTH) of 57% (P less than 0.01), but not by a fall in serum calcium or phosphate levels. There was induction of endogenous cortisol oxidation in all subjects, but only in four fast acetylators was there a concomitant increase in antipyrine elimination. In the four slow acetylators antipyrine metabolism was inhibited after the first dose of the drugs. In nine tuberculous patients followed serially there was a fall in 25-OHD and 1,25 (OD)2D and a rise in PTH at the end of 1 mo (P less than 0.05). After 6 mo therapy 25-OHD concentration was further reduced (P less than 0.01), but there was no significant change in 1,25 (OH)2D or PTH levels. Combination treatment with rifampicin and isoniazid perturbs vitamin D metabolism, but less than might have been predicted from reports on each drug given alone. Nevertheless, tuberculous patients with already compromised calcium homeostasis receiving this combination of drugs should be carefully monitored.

Adult↗
PubMed1982

Bombesin: action on gut hormones and calcium in man.

Bombesin, a peptide with widespread biological actions, has been demonstrated in human tissues by immunological methods. To investigate its effect in man, synthetic bombesin was infused at low doses in six male volunteers. Bombesin at 2.4 pmol kg-1 min-1 produced significant rises in plasma insulin, glucagon, pancreatic polypeptide, gastrin, cholecystokinin, motilin, glucose-dependent insulinotropic polypeptide, neurotensin, enteroglucagon, vasoactive intestinal polypeptide, and serum calcium. In contrast, bombesin caused a profound fall in parathyroid hormone levels and reduced plasma glucose concentrations. A late rise in plasma calcitonin was also observed. Bombesin had no significant effect on the pituitary hormones, TSH, GH, PRL, or cortisol. No hormonal changes or alterations in calcium were noted during saline infusions. Bombesin has a marked stimulatory effect on gastrointestinal hormones, which is unique and opposite to the effect of somatostatin, a potent inhibitor of gut hormone release. Bombesin also influences calcium-regulating hormones, either directly or through its action on gut hormones. The bombesin concentrations achieved with the dosages used were low enough to indicate a possible physiological role for the endogenous peptide.

Adult↗
PubMed1982

Further evidence for calcitonin gene duplication: the identification of two different calcitonins in a fish, a reptile and two mammals.

In order to investigate the possibility of the simultaneous expression of two different calcitonin genes during evolution, we studied the nature of calcitonin in: eel pericardium, salamander branchial region, rat thyroid, ox thyroid, medullary carcinoma of the human thyroid and human thyrotoxic goitre. Sensitive and specific RIAs for human calcitonin (hCT) and salmon calcitonin (sCT) were used in combination with high pressure liquid chromatography (HPLC). We found that two different immunoreactive calcitonins resembling hCT and sCT exist in eels, salamanders and rats. The major form is i-sCT-like in eels and salamanders, while it is i-hCT-like in rats. Extracts of ox thyroid contained, in addition to the major artiodactyl-CT, an i-hCT-like material. The various human thyroid extracts studied, contained i-hCT but no i-sCT-like material. This study demonstrates the simultaneous expression of two different calcitonin genes in several species. Taken with the presence of molecules resembling sCT and hCT in birds, this further evidence is consistent with duplication of the calcitonin gene early in vertebrate evolution.

Animals↗
PubMed1982

Identification of both human and salmon calcitonin-like molecules in birds suggesting the existence of two calcitonin genes.

To investigate whether human calcitonin (hCT) is preserved during the evolution of vertebrates, we studied extracts of avian (pigeon and chicken) thyroid and ultimobranchial glands (UBG) which have previously been reported to contain salmon calcitonin (sCT)- like molecules. A sensitive and specific radioimmunoassay for hCT, employing two antisera reacting with different regions of the molecule, was used in combination with high performance liquid chromatography (HPLC). We found that extracts of thyroid and UBG from pigeons and chickens contain, in addition to an immunoreactive sCT-like molecule (which is the major immunoreactive form), an hCT-like molecule comprising from 0.4 to 3.75% of the calcitonin content. The extracts produced full displacement of 125I-labelled hCT from both antisera and gave a parallel displacement curve. With HPLC, we found an immunoreactive hCT peak which was 5 ml earlier than the insulin marker and an immunoreactive sCT peak which was 12 ml later than the insulin marker. These results demonstrate the presence of two calcitonins in birds, and suggest the existence of two genes with different degrees of expression.

Animals↗
PubMed1982

Role of prolactin in vitamin D metabolism and calcium absorption during lactation in the rat.

Intestinal calcium absorption and plasma levels of 1,25-dihydroxycholecalciferol (1,25(OH)2D3) were measured in lactating and non-lacting rats and the effects of bromocriptine and exogenous prolactin treatment were evaluated. In lacting rats calcium absorption and plasma levels of parathyroid hormone, 1,25(OH)2D3 and alkaline phosphatase activity were significantly increased. Bromocriptine treatment significantly reduced the enhanced calcium absorption and levels of plasma 1,25(OH)2D3 and alkaline phosphatase but had no significant effect on plasma levels of parathyroid hormone. Prolactin administered with bromocriptine to lactating animals prevented all the changes observed with bromocriptine treatment alone. It was concluded that the increased plasma levels of prolacting during lactation lead to high plasma levels of 1,25(OH)2D3 which are responsible for the enhanced intestinal calcium absorption.

Alkaline Phosphatase↗
PubMed1981

[Immunocytochemical detection in Stannius corpuscles of the eel (Anguilla anguilla L.) of a hormone similar to the mammalian parathyroid hormone].

In eels the parathyrin of the corpuscles of Stannius (PCS), mammalian parathyroid-like hormone, has been localized in the cytoplasm of all the cells in the corpuscles. This detection was done by indirect immunofluorescence with an antiserum anti 1-84 bovine parathormone. The specificity of the reaction was demonstrated by inhibition of the coloration obtained with the 1-84 bovine parathormone and the active fragment 1-34 of human parathormone. Variations of the cellular localization of the PCS or a complete depletion of the hormonal content were observed in eels made hypercalcaemic by calcium overloading.

Anguilla↗