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Biomedical subjects

J A Fischer

Publications and source records attributed to J A Fischer.

At least 163 records · Page 9Linked to original sources
PubMed1982

Effects of somatostatin on parathyroid hormone levels and on responses of parathyroid hormone to beta-adrenergic agonists and hypocalcaemia.

Experiments were designed to study the effect of exogenous somatostatin (S) on basal levels or parathyroid hormone (PTH) and on PTH responses to isoproterenol (ISO), adrenaline (A) or ethyleneglycol-bis (beta-aminoethylether) N,N'-tetraacetate (EGTA) in cattle. During S infusions (6.11 nmol injected iv as a bolus and 0.82 nmol/kg/min infused iv for 30 or 60 min) plasma levels of PTH and calcium (Ca) did not change, whereas concentrations of immunoreactive insulin (IRI) decreased significantly (P less than 0.01). In response to ISO (0.09 nmol/kg/min) or EGTA (5.6 mumol/kg/min, depressing plasma Ca by 0.27 nmol/l) PTH levels were similarly increased (P less than 0.05) both in the absence and presence of S. On the other hand, S suppressed IRI responses to ISO. During 60-min infusions of EGTA (3.15 mumol/kg/min) plasma Ca fell to significantly lower levels (P less than 0.01) during simultaneous infusions of S than in the absence of exogenous S, while the magnitude of PTH responses was similar. The results do not support a role of somatostatin on basal PTH levels and on PTH responses to beta-adrenergic agonists or hypocalcaemia under conditions, in which S markedly lowers IRI levels and IRI responses to ISO. However, S apparently reduces Ca mobilisation during abrupt hypocalcaemia.

Adrenergic beta-Agonists↗
PubMed1982

Effects of alpha-adrenergic stimulation and blockade on parathyroid hormone responses to beta-adrenergic agonists in cattle.

Experiments were designed to investigate the effect of alpha-adrenergic stimulation on parathyroid hormone (PTH) responses to isoproterenol (ISO). In addition, PTH responses to adrenaline (A) and hypocalcaemia were studied with and without alpha-adrenergic blockade by phentolamine. Infusions of phenylephrine (a 'pure' alpha-adrenergic agonist) did not modify basal PTH levels and PTH responses to ISO infusions, whereas the heart rate response to ISO was reduced (P less than 0.05). The results demonstrate that alpha-adrenergic stimulation by phenylephrine does not reduce PTH responses to beta-adrenergic agonists. In response to phentolamine the heart rate increased and plasma levels of Ca and Ca++ decreased. Plasma PTH concentrations were slightly but not significantly raised and PTH responses to adrenaline (P less than 0.05), but not to hypocalcaemia, were enhanced. The potentiation of PTH responses to A in the presence of phentolamine may have ben due to inhibiton of alpha-adrenergic properties of A. It may have been also, in part, the consequence of the hypocalcaemia, which is known to augment PTH responses to A.

Adrenergic alpha-Agonists↗
PubMed1981

[The differential diagnosis of hypercalcitoninism].

Plasma levels of calcitonin (CT) are highest in patients with medullary thyroid carcinoma (MTC). Plasma CT is also raised in some patients with carcinoma such as that of the breast, the lung or the pancreas, and in pheochromocytoma. It must be kept in mind, however, that plasma CT can be similarly raised in patients with renal failure, non-tumoral pulmonary disease or acute pancreatitis. In hypercalcemia patients with primary hyperparathyroidism the plasma CT is normal or only marginally elevated. It is speculated that the raised levels in pregnant and lactating women and in new-born infants prevent excessive bone destruction at times of greater physiological need for calcium. Larger molecular weight forms than monomeric CT (1--32) are circulating at least in plasma of patients with calcitonin-producing tumors and in renal insufficiency. The biological function of these larger molecular weight forms is not yet known. The discrepancies among the results of different laboratories can in part be explained by the immunoheterogeneity of the hormone and the different antigenic recognition sites of the antisera used. The measurement of plasma CT levels is nevertheless important for the diagnosis of MTC and may prove useful in some patients with malignant tumors unrelated to the C-cells of the thyroid gland. CT-radioimmunoassay may be improved by using antibodies specific to the different forms of circulating calcitonin.

Adult↗
PubMed1981

Calcitonin: regional distribution of the hormone and its binding sites in the human brain and pituitary.

Immunoreactive calcitonin (CT), indistinguishable from human CT-(1-32) and its sulfoxide, has been identified in extracts of the hypothalamus, the pituitary, and the thyroid obtained from human subjects at autopsy. DCT concentrations were highest in a region encompassing the posterior hypothalamus, the median eminence, and the pituitary; intermediate in the substantia nigra, the anterior hypothalamus, the globus pallidus, and the inferior colliculus; and low in the caudate nucleus, the hippocampus, the amygdala, and the cerebral and cerebellar cortices. Specific CT binding measured with 125I-labeled salmon CT was highest in homogenates of the posterior hypothalamus and the median eminence, shown to contain the highest concentrations of endogenous CT in the brain; CT binding was less than 12% of hypothalamic binding in all of the other regions of the brain examined and was negligible in the pituitary. Half-maximal binding was achieved with 0.1 nM nonradioactive salmon CT-(1-32), and the binding was directed to structural or conformational sites, or both, in the COOH-terminal half of salmon CT. The rank order of the inhibition of the binding by CT from different species and analogues of the human hormone was the same as in receptors on a human lymphoid cell line (Moran, J., Hunziker, W. & Fischer, J. A. (1978) Proc. Natl. Acad. Sci. USA 75, 3984-3988). The functional role of CT and of its binding sites in the brain remains to be elucidated.

Binding Sites↗
PubMed1981

Suppression of secondary hyperparathyroidism by propranolol in renal failure patients.

Renal osteodystrophy in part due to secondary hyperparathyroidism, is one of the major unresolved problems affecting patients on chronic hemodialysis. In addition, evidence has shown that parathyroid hormone (PTH) is toxic to other organ systems besides bone. The results of a prospective study on the effect of propranolol in reducing PTH levels in chronic renal failure patients on hemodialysis are reported. Propranolol administration reduced PTH levels by over 50-75%. The levels of calcium, phosphorus, alkaline phosphatase and hematocrit were variable, but patients with severe derangements in these measurements also seemed to benefit from propranolol. It should now be determined by larger and longer studies whether these biochemical improvements can be translated into clinical benefits.

Alkaline Phosphatase↗
PubMed1981

Suppressive effects of 24,25-dihydroxycholecalciferol on bone resorption induced by acute bilateral nephrectomy in rats.

The possible suppressive effects of 24,25-dihydroxycholecalciferol on secondary hyperparathyroidism and increased bone resorption were investigated in adult rats raised on a diet normal in calcium, phosphorus, and vitamin D, and subjected to acute bilateral nephrectomy. The animals had received subcutaneous radiocalcium 4 wk before the experiment. 5 h after nephrectomy an increase in serum total calcium, (45)Ca-specific activity, citrate, phosphorus, and magnesium concentrations were observed. Serum immunoreactive parathyroid hormone increased, while serum calcitonin decreased. The osteoclast count in the tibial metaphyses was augmented. The biochemical and histological changes observed were partly parathyroid hormone and calcitonin independent, as they also occurred in parathyroidectomized hypocalcemic rats. Pretreatment with 650 pmol of 24,25-dihydroxycholecalciferol 16 h before nephrectomy prevented bone calcium mobilization and diminished the rise in serum total calcium and citrate both in parathyroid-intact and in parathyroidectomized animals. In parathyroid-intact rats, serum immunoreactive parathyroid hormone and calcitonin remained normal in spite of the fall in serum-ionized calcium, and the number of osteoclasts did not increase. In parathyroidectomized rats, 24,25-dihydroxycholecalciferol did not prevent the postnephrectomy rise in the osteoclast count. This latter observation suggests that this metabolite exerts its effect on bone either by acting on cells other than osteoclasts, i.e., the osteocytes, or by inhibiting cell activity. At equimolar dosage 1,25-dihydroxycholecalciferol had a potent stimulatory effect on bone resorption. This effect of 1,25-dihydroxycholecalciferol was partly blocked by the simultaneous administration of 24,25-dihydroxycholecalciferol. The potential clinical significance of these observations remains to be determined.

24,25-Dihydroxyvitamin D 3↗
PubMed1981

Calcium-regulated biosynthesis of the parathyroid secretory protein, proparathyroid hormone, and parathyroid hormone in dispersed bovine parathyroid cells.

Dispersed bovine parathyroid cells were incubated in vitro with 3H-labeled amino acids for 30--120 min. Analysis of cell extracts by sodium dodecyl sulfate-urea-polyacrylamide gel electrophoresis revealed a calcium-regulated incorporation of 3H-labeled amino acids into three major peaks, one with a molecular weight (Mr) of 70,000 and two peaks in the 10,000 Mr region, and a minor 5,000 Mr peak. Furthermore, [3H]mannose was incorporated into the 70,000 Mr peak, which corresponds to the parathyroid secretory protein (PSP) recognized as a glycoprotein. The two peaks in the 10,000 Mr region had the electrophoretic mobility of [3H]bovine proparathyroid hormone (ProPTH) and [3H]bovine PTH (1--84), respectively. Immunoreactive PTH was only detected in a peak comigrating with [3H]PTH-(1--84). The nonimmunoreactive 5,000 Mr peptide was not further identified. The incorporation of radioactive amino acids into PSP, ProPTH, PTH-(1--84), and the 5000-daltons peptide was inversely related to the calcium concentration in the incubation medium. The incorporation of radioactive mannose into PSP was also greater at low extracellular calcium concentrations. Our findings provide evidence for an inverse relationship between the extracellular calcium concentration and the formation of PSP, ProPTH, PTH-(1--84), and a yet to be identified 5000-dalton peptide in dispersed bovine parathyroid cells.

Amino Acids↗
PubMed1981

Dissociation of parathyroid hormone bioactivity and immunoreactivity in pseudohypoparathyroidism type I.

Circulating levels of parathyroid hormone (PTH) in six patients with pseudohypoparathyroidism type I (PSPI) have been measured by two immunoassays and by cytochemical bioassay and compared with measurements in normal subjects and patients with clinically defined hyper- and hypoparathyroidism. In all PSPI patients, the levels of immunoreactive PTH were in the hyperparathyroid range, whereas the bioactive levels were either in the normal or close to the normal range. In one patient from whom the dihydrotachysterol therapy was withdrawn, both immunoreactive and bioactive PTH concentrations increased. The finding that the PTH measured by RIA in these PSPI patients may have reduced biological activity may explain some of the clinical findings of hypoparathyroidism in this syndrome.

Adult↗
PubMed1981

Parathyroid hormone response to hypocalcaemia following hypercalcaemia.

Experiments were designed to study the ability of calcium infusions to suppress parathyroid hormone (PTH) responses to hypocalcaemia, induced by iv infusions of ethylene-glycol-bis(beta-aminoethylether)N,N'-tetraacetate (EGTA). When plasma calcium (Ca) was raised for 60 min to levels higher then 2.6 mmol/l, PTH responses to a subsequent fall of Ca due to EGTA infusions for 7 min were significantly reduced (P < 0.02) or abolished when compared to PTH responses during 7-min EGTA infusions in normocalcaemic animals. CaCl2 infusions lasting for 10 min only, however, did not cause a significant reduction of PTH responses to subsequent 7-min EGTA infusions. The results demonstrate, that raised Ca reduced PTH available for immediate release. This effect was time-dependent, since it was only seen, when CaCl2 was infused for more than 10 min prior to the administration of EGTA.

Animals↗
PubMed1980

Calcium-dependent, parathyroid hormone-independent regulation of 1,25-dihydroxyvitamin D.

The increase of plasma 1,25-dihydroxyvitamin D (1,25(OH)2D) in response to Ca restriction has been suggested to be essentially mediated by parathyroid hormone (PTH). In this study, we have assessed the influence of variations in calcium intake on plasma 1,25(OH)2D in pair-fed sham-operated (sham) and in hypocalcemic hypoparathyroid rats after thyroparathyroidectomy (TPTX). In sham rats, plasma 1,25(OH)2D increased from 189 +/- 16 to 486 +/- 41 pM when dietary calcium was inreased from 1.2% Ca to 0.2% Ca. This increase was associated with an increase in plasma PTH level. In TPTX rats, plasma 1,25(OH)2D increased from 112 +/- 9 to 332 +/- 36 pM when dietary calcium was decreased. In this case, the increase was not associated with a rise in plasma PTH level nor with an increase in urinary cyclic AMP. When TPTX rats were infused chronically with PTH (60 U/day), plasma 1,25(OH)2D was 62 +/- 9 pM when the 1.2% Ca diet was given and 281 +/- 45 pM with the 0.2% Ca diet. These reults confirm that the thyroparathyroid glands influence plasma 1,25(OH)2D but they also provide evidence for a PTH-independent response of plasma 1,25(OH)2D to Ca restriction.

Animals↗
PubMed1980

Parathyroid hormone response to dopamine in cattle.

The effects of dopaminergic agonists on plasma levels of parathyroid hormone (PTH) have been studied in cattle. PTH increased within minutes in a dose-dependent manner during intravenous infusions of dopamine (DA) or epinine. Bromocriptine, in amounts that lowered plasma prolactin, inconsistently elevated PTH. Pimozide suppressed PTH responses to DA, whereas propranolol, phentolamine, phenylephrine, and atropine were ineffective. Plasma calcium and magnesium remained unaltered during DA and epinine infusions. Therefore DA appears to stimulate PTH secretion directly. After prolonged DA infusions, the secretion of PTH became resistant to both the administration of DA and isoproterenol, whereas the parathyroid glands remained responsive to a hypocalcemia. On the other hand, calcium suppressed PTH responses to DA. The results suggest that DA, beta-adrenergic agonists, and low calcium stimulate PTH secretion by separate but closely related mechanisms. Based on biochemical and histochemical observations on DA occurring in high amounts in bovine parathyroid glands, it is conceivable that this amine might stimulate PTH secretion at the level of the gland.

Animals↗
PubMed1980

Perinatal parathyroid hormone, vitamin D metabolites, and calcitonin in man.

Plasma levels of calcium and of parathyroid hormone (PTH) were comparable in the mothers at delivery and in nonpregnant controls; magnesium was decreased (P < 0.001) in maternal blood; and phosphate (P < 0.001), 1,25-dihydroxyvitamin D (1,25(OH)2D) (P < 0.001), and calcitonin (CT) (P < 0.01) were raised. Cord levels of calcium (P < 0.01), magnesium (P < 0.05), and CT (P < 0.01) were higher, and PTH (P < 0.01) was lower than in the maternal blood. Levels of 25(OH)D, 1,25(OH)2D, and 24,25(OH)2D lower in fetal than in maternal blood (P < 0.01) and significant linear correlations between the vitamin D metabolites examined in mothers and neonates (P < 0.001) are consistent with a diffusion barrier across the placenta and/or different affinities of binding proteins. Plasma levels of 25(OH)D and 24,25(OH)2D were significantly related (P < 0.01), suggesting precursor product type, relationships. Levels of 1,25(OH)2D higher in arterial than in venous umbilical blood (P = 0.06, sign test; P < 0.005, paired t test) suggest that the fetus participates in the synthesis of 1,25(OH)2D. Maternal PTH was significantly related to the arteriovenous difference of 1,25(OH)2D levels (P < 0.01) in cord blood, and it possibly enhances the synthesis of 1,25(OH)2D during the final stage of fetal development.

Adolescent↗
PubMed1980

1,25-Dihydroxycholecalciferol in dialysed patients with clinically asymptomatic renal osteodystrophy. A controlled study.

Clinically asymptomatic patients undergoing hemodialysis and with histologically proven renal osteodystrophy were treated with 1,25-dihydroxycholecalciferol (1,25[OH]2D3) or with placebo for 9-37 weeks. Serum concentrations of total calcium were frequently increased when the ionized calcium was raised into the normal range. Serum magnesium was in the upper normal range due to the presence of magnesium in the aluminum hydroxide used to lower the hyperphosphatemia, which was difficult to control. Basal serum parathyroid hormone (PTH) levels were increased and seven times higher when measured with a radioimmunoassay recognizing mainly COOH-terminal fragments of human PTH-(1-84) (C-terminal assay) as compared to another assay measuring predominantly intact PTH-(1-84) (N-terminal assay). During treatment with 1,25 (OH)2D3, serum PTH returned towards the normal range with increasing calcium levels. Mean PTH concentrations decreased significantly by 34% (p less than 0.05) when measured with the N-terminal assay and by only 14% (p greater than 0.1) in the C-terminal assay. Serum alkaline phosphatase activity and the mineral content of the forearm estimated by photon absorptiometry remained unchanged.

Adult↗
PubMed1980

Influence of 1,25 dihydroxycholecalciferol on sexual dysfunction and related endocrine parameters in patiens on maintenance hemodialysis.

It has been postulated that hyperparahyroidism is in part responsible for sexual dysfunction in dialyzed patients and that this could improved by 1,25(Oh)2D3. In a single blind study patients on maintenance hemodialysis were treated after a control period with 1,25 (OH)2D3 and with placebo in random order. Sexual performance was assessed with a detailed semistructured psychiatric interview protocol in 14 and several endocrine parameters were analyzed in 15 patients. Under control conditions sexual function was disturbed in 11/14 patients. Plasma testosterone was moderately decreased in men, PRL and PTH levels were distinctly elevated in both sexes. 1,25(OH)2D3 raised serum calcium levels significantly from 9.6 to10.6 mg/100 ml ( P < 0.01) and lowered PTh from 1.39 to 0.82 ng/ml ( P < 0.01). However, no improvement in sexual function (such as libido, frequency of intercourse or masturbation) was found, and apart from a slight rise of testosterone in men and moderate fall of PRl in men and women endocrine parameters remained unchanged. It is concluded that in spite of an improvement of secondary hyperparathyroidism, treatment with 1,25(OH)2D3 for 2 to 4 months was of no value in improving sexual dysfunction in these hemodialysis patients.

Adult↗
PubMed1979

[Diagnosis of primary hyperparathyroidism and differential diagnosis of hypercalcemia].

The leading symptom in patients with primary hyperparathyroidism (pHPT) is renal lithiasis and not osteopathy. The most abundant circulating forms of parathyroid hormone in pHPT represent COOH-terminal fragments with molecular weights ranging from 4000 to 7000. Radioimmunnoassays making use of antibodies directed to CCOH-terminal parts of human parathyroid hormone are therefore suitable in distinguishing patients with pHPT from control subjects and patients with hypercalcemia unrelated to hyperfunctioning parathyroid glands.

Autoantibodies↗