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Biomedical subjects

J A Fischer

Publications and source records attributed to J A Fischer.

At least 145 records · Page 8Linked to original sources
PubMed1984

Salmon and human calcitonin-like peptides in man.

Calcitonin-like peptides have been identified in the serum of normal subjects and of medullary thyroid carcinoma (MTC) patients. Using specific homologous radioimmunoassays (RIA) in combination with reversed-phase high performance liquid chromatography and gel permeation chromatography under denaturing conditions, we have recognized major components which coeluted with human calcitonin-(1-32), PDN-21, a carboxyl-terminal flanking peptide derived from the calcitonin mRNA sequence, and salmon calcitonin-(1-32). An additional 12000 molecular weight peak possibly represents a human calcitonin-PDN-21 polyprotein. In both the human calcitonin-(1-32) (normal value less than 0.043 ngEq/ml; MTC 140 +/- 80 ngEq/ml, mean value +/- SEM) and the PDN-21 (normal value less than 0.050 ngEq/ml; MTC 33.6 +/- 16.5 ngEq/ml) RIAs, serum levels were increased in MTC patients. Circulating levels of the salmon calcitonin-like peptide were indistinguishable between normal subjects (0.038 +/- 0.006 ngEq/ml) and MTC patients (0.037 +/- 0.011 ngEq/ml).

Calcitonin↗
PubMed1984

Bone loss in premenopausal and postmenopausal women. A cross-sectional and longitudinal study using quantitative computed tomography.

Trabecular and total bone densities were determined by quantitative computed tomography in patients with untreated postmenopausal osteoporosis and in normal premenopausal and postmenopausal women. A special procedure was used for precise low-dose examinations of the distal end of the radius and the distal end of the tibia. The results indicate that the trabecular bone density of the peripheral skeleton is a reliable index of postmenopausal osteoporosis. In general, osteoporotic patients could be distinguished from patients with age-related bone loss based on differences in the magnitude of the decrease in trabecular bone density. Serial determinations of trabecular bone density in individual patients indicated that trabecular bone loss in postmenopausal osteoporotic patients shows a step-wise pattern in which phases of relative stability are followed by brief phases of bone loss. Quantitative computed-tomography measurements of bone density should provide a better understanding of the pathogenesis of postmenopausal osteoporosis and be useful in the assessment of different methods of treatment.

Adult↗
PubMed1983

Localization of salmon calcitonin binding sites in rat brain by autoradiography.

The regional distribution of [125I]salmon calcitonin (sCT) binding sites was examined in rat brain by receptor autoradiography. Dense specific labeling was recognized over the hypothalamus, preoptic and accumbent nuclei, amygdala, zona incerta, interpeduncular nucleus, periventricular gray and the reticular formation. Intermediate binding was seen over the arcuate and supramamillary nuclei and substantia nigra, and no binding in the neocortex, cerebellum, thalamus, basal ganglia and mamillary bodies. The well defined topographical distribution strongly indicates physiological roles for sCT in the mammalian brain.

Animals↗
PubMed1983

Potassium stimulates parathyroid hormone release in the absence of extracellular calcium.

Potassium-stimulated release of many hormones requires the presence of extracellular calcium. At variance with this mechanism, potassium-evoked parathyroid hormone (PTH) release from perifused dispersed bovine parathyroid cells also occurred in calcium-free medium containing 1 mM EGTA. Tetraethylammonium, which presumably suppresses the efflux of potassium from parathyroid cells, also stimulated PTH secretion. Removal of sodium did not suppress potassium-stimulated PTH secretion, but inhibited the release of the hormone evoked by calcium removal and by isoproterenol. Ouabain, on the other hand, suppressed the release of PTH evoked by calcium removal and by potassium, but not by isoproterenol. Unlike high potassium and removal of calcium, isoproterenol caused a parallel increase in cAMP release. In conclusion, PTH secretion is reversibly stimulated by potassium in the absence of extracellular calcium. Our findings suggest that potassium stimulates PTH secretion by a unique mechanism the nature of which remains to be elucidated.

Animals↗
PubMed1983

Pseudohypoparathyroidism: inheritance and expression of deficient receptor-cyclase coupling protein activity.

Pseudohypoparathyroidism, Type I (PSP-I) is a familial disorder characterized by secondary hyperparathyroidism, resistance of urinary cyclic adenosine-3', 5'-monophosphate (cAMP) excretion to exogenous parathyroid hormone (PTH), and by effects upon other hormones, including thyrotrophin (TSH) hyperresponsiveness to thyroliberin (TRH). In the present study, 12 PSP-I patients in five families exhibited partial deficiency of receptor-cyclase coupling protein (N protein) in blood cells, in association with the skeletal findings of Albright's hereditary osteodystrophy. In one father and six mothers of PSP-I patients, deficient N protein activity was associated with normal urinary cAMP responses to PTH. In this group of seven parents, five had Albright's osteodystrophy, two exhibited secondary hyperparathyroidism, and two had TSH hyperresponsiveness to TRH. In a sixth family with none of the features of Albright's osteodystrophy, N protein deficiency did not correlate with urinary cAMP responsiveness to PTH. In this kindred, one mother with N protein deficiency, but normal urinary cAMP responsiveness to PTH had raised serum levels of immunoreactive PTH. We conclude that in the majority of families with PSP-I the urinary cAMP response to PTH is an inadequate indicator of the genetic defect. In such families, deficiency of N activity more consistently points to metabolic defects, including secondary hyperparathyroidism and TSH hyperresponsiveness, even when urinary cAMP responses are normal.

Calcium↗
PubMed1983

Lack of rapid effects of cortisol on parathyroid hormone levels in cattle.

Experiments were performed to study plasma concentrations of parathyroid hormone in association with short-term changes of cortisol and dexamethasone. Parathyroid hormone was not significantly modified during 3-hour intravenous infusions of cortisol, leading to marked elevations (p less than 0.001) of plasma cortisol levels, and during intravenous administration of dexamethasone. Thus glucocorticoids, at least in cattle, apparently cause no short-term changes of plasma parathyroid hormone levels.

Animals↗
PubMed1983

Rapidity of plasma 1,25-dihydroxyvitamin D responses to hypo- and hypercalcemia in steers.

Experiments were designed to study the rapidity of changes in plasma 1,25-dihydroxyvitamin D [1,25-(OH)2D] levels in response to hypercalcemia and hypocalcemia induced by 10-h infusions of CaCl2 or EGTA in steers. In response to CaCl2 infusions, 1,25-(OH)2D was decreased within 4 h (P less than 0.05) and remained lower (P less than 0.05) than preinfusion concentrations for up to 14 h after termination of the infusions. PTH and inorganic phosphate (Pin) transiently decreased in response to the CaCl2 infusions, whereas total magnesium (Mg) continuously fell for up to 24 h after the start of the infusions. In response to infusions with EGTA, on the other hand, 1,25-(OH)2D continuously increased and was raised significantly (P less than 0.05) between 12 and 24 h after the start of the infusions. PTH increased within 2 h (P less than 0.05) and remained elevated (P less than 0.05) for up to 2 h after the end of the EGTA infusions, whereas Pin and Mg were not significantly changed. During and after 10-h control infusions of sodium chloride, the levels of 1,25-(OH)2D, PTH, Ca, Ca++, Pin, and Mg remained unaltered. In conclusion, plasma levels of 1,25-(OH)2D were lowered in response to hypercalcemia within 4 h and increased in response to hypocalcemia within 12 h. After termination of the infusions with CaCl2 or EGTA, levels of 1,25-(OH)2D remained decreased or elevated for at least 14 h, even though Ca, Ca++, and PTH levels were normalized. The slow changes in 1,25-(OH)2D contrast with the rapid responses of PTH to hyper- and hypocalcemia.

Animals↗
PubMed1983

Identification and characterization of calcitonin forms in plasma and urine of normal subjects and medullary carcinoma patients.

Different immunoreactive calcitonin (CT) forms were identified by a reversed phase high performance liquid chromatography gradient system in plasma and urine of normal subjects. The separated CT components were characterized by chemical and enzymatic methods and found to be identical in normal subjects and medullary thyroid carcinoma patients. Of seven major CT forms we identified monomeric human CT-(1-32), its sulfoxide form, and dimeric CT in plasma. The monomeric, but not the dimeric form, was also detected in urine. A predominant CT component in plasma with a molecular weight of about 12,000 may correspond to a biosynthetic precursor of the hormone.

Calcitonin↗
PubMed1983

Salmon and human calcitonin-like peptides coexist in the human thyroid and brain.

A salmon calcitonin-like material indistinguishable from synthetic salmon calcitonin-(1-32) on high performance liquid chromatography (HPLC) has been recognized in thyroid extracts of normal subjects and of patients with medullary carcinoma. The same peptide was detected in extracts of the periventricular mesencephalic region which included the periventricular dorsal thalamus, the subthalamus and the hypothalamus. Human calcitonin-(1-32)- and carboxyl-terminal adjacent peptide (CCAP)-like components were also found. The content of immunoreactive salmon calcitonin of the periventricular mesencephalic region (n = 6) and of normal thyroid glands (n = 6) was comparable (mean +/- SE, 0.34 +/- 0.17 ngeq/g wet tissue and 0.39 +/- 0.22 ngeq/g, respectively); and the levels were slightly, but not significantly higher in medullary thyroid carcinoma extracts (1.95 +/- 0.69 ngeq/g) (P less than 0.1). Immunoreactive human calcitonin and CCAP occurred in roughly equimolar concentrations. They were lowest in the periventricular mesencephalic region (0.26 +/- 0.09 ngeq/g and 0.46 +/- 0.10 ngeq/g, respectively), followed by normal thyroid glands (146 +/- 26 ngeq/g and 94 +/- 19 ngeq/g, respectively), and they were highest in medullary thyroid carcinoma tissue (680 +/- 372 mu geq/g and 144 +/- 125 mu geq/g, respectively).

Brain↗
PubMed1983

A new bioactive form of human calcitonin.

Distinct immunoreactive forms of calcitonin (CT), extracted with 2 M acetic acid from two pancreatic tumors, were characterized and identified by gel permeation chromatography and by reverse-phase high-performance liquid chromatography. The extracted CT forms were compared to CT obtained from medullary thyroid carcinoma and from normal thyroid glands, and were, furthermore, analyzed in a rat hypocalcemic bioassay. On gel filtration analysis, two broad peaks coeluting with synthetic human CT-(1-32) and extracted dimeric CT, respectively, were found in variable amounts. An acetonitrile gradient high-performance liquid chromatography system revealed two to three predominant CT peaks. Biologically active monomeric and dimeric CT and the biologically inactive sulfoxide form of human CT-(1-32) have been identified. Moreover, we have detected for the first time a new biologically active CT-like component which was most prominently recognized in a benign pancreatic tumor.

Aged↗
PubMed1982

Identity of calcitonin extracted from normal human thyroid glands with synthetic human calcitonin-(1-32).

Calcitonin in human thyroid glands obtained at autopsy from normal subjects were extracted with 2 M acetic acid. The extracts were additionally purified by adsorption to Sep-Pak C18 cartridges, and calcitonin was identified after gel filtration analysis, reverse-phase high-performance liquid chromatography (HPLC), thin-layer chromatography and isoelectric focusing. The purification steps were monitored by radioimmunoassay, and partially purified calcitonin was used for biological and physicochemical comparison with synthetic human calcitonin-(1-32) and its Met8-sulfoxide form. On gel filtration analysis a predominant peak coeluted with the synthetic hormone, and on HPLC two discrete peaks with the retention times of monomeric and dimeric human calcitonin were found. Thin-layer chromatography allowed the detection of two peaks with the Rf of human calcitonin-(1-32) and of its sulfoxide, respectively. The pI (7.9) of the predominant peaks of synthetic calcitonin were identical. Our findings provide strong evidence that the predominant forms of human calcitonin extracted from normal thyroid glands correspond to synthetic calcitonin-(1-32) and to dimeric calcitonin.

Calcitonin↗
PubMed1982

Potassium stimulates parathyroid hormone release from perifused parathyroid cells.

A method for perifusing dispersed bovine parathyroid cells is described. Using this approach, we have studied the effects of raised extracellular potassium and ouabain on calcium-regulated parathyroid hormone (PTH) secretion in vitro. Decreasing calcium from 1.5 to 0.5 mM stimulated PTH release within 5-10 min, and the increased secretory rate was maintained for the duration of the low calcium administration. High potassium (60 mM) promptly stimulated PTH secretion at 1.5 mM calcium. The effect of high potassium was more transient than that of low calcium. Raised potassium significantly enhanced the response to 0.5 mM calcium. Ouabain (10(-3) M) had no significant effect at 1.5 mM calcium, but depressed the secretory response to 0.5 mM calcium. In conclusion, the effect of raised potassium on parathyroid cells is qualitatively similar to its effect on other endocrine and exocrine systems.

Animals↗
PubMed1982

Dopamine does not affect parathyroid function in man.

There is conflicting evidence for a role of dopamine (DA) in modulating parathyroid gland function. DA stimulates parathormone (PTH) secretion in cattle in vivo and in vitro, but is without effect on dispersed human parathyroid cells from adenomatous and hyperplastic tissue. Therefore, we studied the PTH response to a 30-min infusion of DA (4 micrograms/kg . min) in five normal male volunteers. There was no change in the levels of PTH, as measured by RIA, although this infusion rate was effective in lowering PRL levels. During the infusion period, total calcium levels remained unchanged. We conclude that, unlike cattle, the parathyroid gland in humans is unresponsive to DA. Thus, the regulation of PTH secretion by biogenic amines has important species variation.

Adult↗
PubMed1982

Inhibition of cytochemical bioactivity of parathyroid hormone by plasma in pseudohypoparathyroidism type I.

Despite the high circulating levels of immunoreactive PTH in patients with pseudohypoparathyroidism type I (PSPI) the levels of bioactive PTH (bioPTH) have been found to be close to the normal range. To elucidate this dissociation, we have studied the recovery of the biological activity of bovine PTH added to the plasma of patients with either PSPI, or with hypoparathyroidism (PTX), primary hyperparathyroidism (HPT) or of normal subjects. In PSPI (n = 10) the recovery of biological activity was 5.6% +/- 3.6 (mean +/- SEM) whereas in PTX (n = 7), in HPT (n = 4) and in normal subjects (n = 8) it was 79% +/- 5, 75% +/- 9 and 68% +/- 4, respectively. In another PSPI patient, who had undergone total parathyroidectomy, bioPTH was undetectable but the recovery from the plasma of added PTH was 84%. Thus we have found inhibition of PTH bioactivity by plasma of PSPI patients which was absent after parathyroidectomy.

Animals↗