Search PubMed⌕ Search

Biomedical subjects

A S Brickman

Publications and source records attributed to A S Brickman.

At least 37 records · Page 2Linked to original sources
PubMed1986

Altered red cell sodium transport in hypoparathyroidism: relation to serum calcium.

We studied Na transport in red blood cells (RBC) from six patients with hypoparathyroidism (HYPO; 3 postsurgical and 3 idiopathic) and 13 normal subjects. In HYPO, the effect of treatment-induced increases in serum Ca2+ on RBC Na transport also was examined. Na efflux mediated by the ouabain-sensitive Na,K pump and furosemide-sensitive Na,K cotransport (CoT) was examined by flux methodology in RBCs Na loaded to 5 levels of intracellular Na (Nai; 5-90 mM/liter cells) by the p-chloromercuribenzene method. The pump-mediated Na efflux was similar in untreated HYPO patients and normal subjects. Correction of hypocalcemia by vitamin D and oral calcium produced a mean increase in serum Ca2+ from 6.62 +/- 0.23 (+/- SEM) to 8.73 +/- 0.32 mg/dl. In HYPO patients treated with vitamin D and oral calcium, an increasing serum Ca2+ level was associated with significant (P less than 0.01) reductions in pump activity. Further, there was an inverse correlation (r = 0.813; P less than 0.001) between serum Ca2+ and pump-mediated Na efflux rate. RBC Na efflux through the CoT pathway was markedly reduced (P less than 0.05-0.01) in HYPO patients compared to normal subjects at all levels of Nai. Treatment-induced increases in serum Ca2+ had no effect on the reduced RBC CoT function in HYPO. Thus, changes in ambient serum Ca2+ can modulate the activity of the RBC Na,K pump in HYPO, with increases in Ca2+ inhibiting pump function. The markedly decreased RBC CoT activity was not related to associated hypertension or altered renal function and may represent a primary phenomenon in HYPO. These alterations in RBC Na transport may account for the higher Na, in RBCs of HYPO patients.

Adult↗
PubMed1986

Responses to glucagon infusion in pseudohypoparathyroidism.

Single or graded doses of glucagon (Eli Lilly) were given to patients with pseudohypoparathyroidism (PsHP) type I to examine the possible presence of hormone resistance. The doses of glucagon ranged from 0.25-15 micrograms/kg. The following individuals were studied: 13 normal subjects, 5 patients with low erythrocyte N-protein activity (PsHP type Ia), and 7 patients with normal erythrocyte N-protein activity (PsHP type Ib). Two additional patients with treated primary hypothyroidism who were relatives of a patient with PsHP type Ib were also studied. The patients with PsHP type Ia had blunted plasma cAMP responses to all glucagon doses. In contrast, the patients with PsHP type Ib had normal cAMP responses to glucagon infusion. However, the 2 relatives of the patient with PsHP type Ib had clearly decreased cAMP responses to glucagon infusion; both had normal renal responses to PTH and were clinically and biochemically euthyroid at the time of study. Glucose responses to glucagon were normal in both PsHP groups; the glucose response per unit cAMP response was slightly, but not significantly, enhanced in PsHP type Ia patients. Glucagon resistance appears to be a common finding in patients with PsHP type Ia, but not in those with PsHP type Ib. However, the observation of reduced glucagon responsivity in association with familial hypothyroidism in a kindred with PsHP type Ib suggests the possibility that this disorder may also cause disturbances in several hormone systems.

Adolescent↗
PubMed1985

Hypercalcemia in rats bearing growth hormone- and prolactin-secreting transplantable pituitary tumors.

We evaluated the effects of chronic massive elevations of serum GH and PRL on calcium metabolism in rats bearing the MStT/W15 and 7315a transplantable pituitary tumors. MStT/W15 tumor rats manifest elevated serum GH and PRL levels, hypercalcemia, hypercalciuria, and elevated serum levels of PTH and 1,25-dihydroxyvitamin D. The hypercalcemia was not reversed by dexamethasone or propranolol treatment, but was ameliorated by starvation. Parathyroidectomy produced hypocalcemia in the MStT/W15 tumor rats, confirming the parathyroid dependence of the hypercalcemia. The 7315a tumor produced a milder degree of hypercalcemia, along with elevated serum levels of PRL, ACTH, and corticosterone; serum GH was normal. In high concentrations, PRL and/or GH may stimulate the secretion of PTH as well as enhance dietary calcium absorption, in part through the mediation of 1,25-dihydroxyvitamin D.

Animals↗
PubMed1985

Normal free fatty acid response to isoproterenol in pseudohypoparathyroidism.

The lipolytic response to isoproterenol infusion was examined in seven normal subjects and six patients with pseudohypoparathyroidism type I [two had deficiency of the hormone receptor-cyclase coupling protein (N-protein) and four did not]. Despite blunted plasma cAMP responses to isoproterenol in both subgroups of pseudohypoparathyroidism patients, the serum FFA responses were normal. We conclude that changes in plasma cAMP do not reflect the adequacy of the lipolytic response to isoproterenol.

Adult↗
PubMed1983

Preliminary trials with 24,25-dihydroxyvitamin D3 in dialysis osteomalacia.

Fifteen patients with dialysis osteomalacia were treated with 24,25-dihydroxyvitamin D3 in dosages up to 10 micrograms per day for two to 24 months. All had previously had no improvement during treatment with calcitriol but had been remarkably susceptible to hypercalcemia. When 24,25-dihydroxyvitamin D3 was given with either calcitriol or dihydrotachysterol, serum calcium levels were significantly lower than during treatment with calcitriol or dihydrotachysterol alone. Eight of nine patients who received combined therapy with 24,25-dihydroxyvitamin D3 and calcitriol for longer than two months had clinical improvement; six patients underwent repeated bone biopsy and showed evidence of improved bone mineralization. Patients who received 24,25-dihydroxyvitamin D3 alone did not improve clinically. Since 24,25-dihydroxyvitamin D3 appears to improve calcium homeostasis and bone mineralization in some patients with severe dialysis osteomalacia when administered with 1-hydroxylated vitamin D metabolites, further controlled studies are warranted.

24,25-Dihydroxyvitamin D 3↗
PubMed1983

Blunted plasma cyclic adenosine monophosphate response to isoproterenol in pseudohypoparathyroidism.

Plasma cAMP, serum glucose, and cardiovascular responses to isoproterenol infusion were examined in seven normal subjects and seven patients with pseudohypoparathyroidism (PHP), type I (three with deficiency of the hormone receptor-cyclase coupling protein (N-protein) and four who were N-protein replete). Although plasma cAMP responses were blunted in both subgroups of PHP patients, the cardiovascular and glucose responses to isoproterenol were normal. We conclude that the blunted plasma cAMP response to isoproterenol in PHP does not depend on deficient N-protein coupling of adenylate cyclase to the beta-adrenergic receptor and that the cardiovascular and glucose responses to isoproterenol are not reflected in changes in plasma cAMP.

Adult↗
PubMed1983

Pre-oedipal development of the superego.

The literature pertaining to the development of early superego precursors is reviewed. This development is traced through the oral, anal, and phallic levels of psychosexual development. Additional attention is paid to such significant theoretical issues as the 'auditive sphere' and the shifting nature of ideal types. Ego ideal and superego are treated as an integrated system comprised of cognitive, affective, and behavioural components. A sequential developmental scheme is proposed for understanding the evolution of superego primordia.

Child, Preschool↗
PubMed1982

Hypercalcemia in association with a Leydig cell tumor in the rat: a model for tumor-induced hypercalcemia in man.

The etiology of tumor-induced hypercalcemia was investigated in a transplantable Leydig cell tumor of the Fischer rat. In this model, serum calcium rose from a baseline of 10.4 +/0 0.3 mg/dl to 12.5 + 0.4 mg/dl at day 10 and 16.4 +/- 1.3 mg/dl (p less than 0.001) at day 13 post transplant. Urinary calcium also increased from 1.52 +/- 0.17 mg/d to 3.52 + 0.72 mg/d (Day 12, p less than 0.01). Serum phosphate decreased from a baseline of 7.5 +/- 0.3 mg/dl to 5.5 +/- 0.6 mg/dl at day 13 (p less than 0.05). At day 13 serum immunoreactive parathyroid hormone levels fell 76% from baseline (p less than 0.01). Calcitonin increased from 59 +/- 2 pg/ml to 88 +/- 9 pg/ml (p less than 0.02). The plasma prostaglandin E metabolite, 13,14-dihydro-15-keto-PGE2 increased from 407 +/- 103 pg/ml to 647 +/-62 pg/ml (p less than 0.05) and the active Vit D compound 1,25(OH)2D increased from 94.8 +/- 5.2 pg/ml to 162.3 +/- 11.8 pg/ml (p less than 0.01). Urinary cyclic AMP did not decrease in parallel with the parathyroid hormone level and, in fact, increased from 146 +/- 3 nmol/d to 172 +/- 27 nmol/d (NS). Administration of the cyclooxygenase inhibitor indomethacin (20 mg/Kg/d) or hydrocortisone (50 mg/Kg/d) did not prevent the development of hypercalcemia. This model is similar to many patients with humoral hypercalcemia of malignancy who demonstrate suppression of parathyroid hormone with elevated urinary cyclic AMP excretion and may prove useful in the understanding of the responsible mechanisms.

Animals↗
PubMed1982

Platelets of pseudohypoparathyroid patients: evidence that distinct receptor-cyclase coupling proteins mediate stimulation and inhibition of adenylate cyclase.

We studied platelets of patients with the genetic disorder pseudohypoparathyroidism (PHP) to test whether the nucleotide-binding proteins mediating stimulation of adenylate cyclase (termed N(s)) are identical to those mediating inhibition of cyclase (termed N(i)). Functional responses to hormones that work through stimulation of adenylate cyclase are blunted in PHP patients. The erythrocytes of many of these patients (PHP-Ia) have previously been shown to have decreased N(s) activity whereas those of other PHP patients (PHP-Ib) have normal N(s) activity. We find that this decreased N(s) activity (measured by the ability to restore adenylate cyclase activity to membranes prepared from S49 cyc(-) cells) also occurs in the platelets of PHP-Ia but not of PHP-Ib patients. Platelets from both groups of patients accumulate less cAMP in response to prostacyclin than do platelets from control subjects. In contrast to the decreased N(s) function in patients with PHP-Ia, we find that N(i) function in platelets is similar in these patients and control subjects in several types of experiments: (i) epinephrine-mediated inhibition of prostacyclin-stimulated cAMP production in intact platelets; (ii) the affinity of platelet alpha(2)-adrenergic receptors for epinephrine, as determined by competition for [(3)H]yohimbine binding; (iii) the decrease in receptor affinity for epinephrine produced by Na(+) and GTP; and (iv) the concentration dependence of GTP for decreasing the affinity of these receptors for epinephrine. Because N(i) is expressed normally in platelets from patients that are genetically deficient in N(s), we conclude that N(s) and N(i) are likely to be distinct gene products.

Adenylyl Cyclases↗
PubMed1982

Bone aluminum and histomorphometric features of renal osteodystrophy.

To evaluate the relationship between aluminum and the characteristics of bone disease in uremia, bone aluminum content and quantitative histomorphometric analysis of bone were evaluated in bone biopsies from 59 uremic patients undergoing maintenance hemodialysis. Biopsies were classified as showing 1) pure osteomalacia (OM) in 23 cases, 2) osteitis fibrosa (OF) in 13, 3) mixed in 7, and 4) mild lesions in 16. There were no significant differences in levels of serum calcium or alkaline phosphatase between the groups, but serum phosphorus levels were slightly higher in those with OF. Serum immunoreactive parathyroid hormone levels were greater in the patients with OF and mixed lesions than in patients with OM or mild lesions (P less than 0.01). Bone aluminum exceeded normal in all groups (P less than 0.01), with values of 175 +/- 18 mg/kg dry wt in OM patients, 46 +/- 7 of OF patients, 81 +/- 29 in mixed subjects, and 67 +/- 7 in patients with mild lesions. Bone aluminum was significantly higher in the OM patients than in any other group (P less than 0.01); also, bone aluminum correlated with the quantitative measure of unmineralized osteoid in OM (r = 0.67; P less than 0.001); no correlations existed for the other groups. There were inverse correlations between bone aluminum and the serum immunoreactive parathyroid hormone (r = -0.35; P less than 0.01) and resorbing surface on biopsy (r = -0.44; P less than 0.001). Bone aluminum correlated with the duration of hemodialysis in patients with OF with mixed and mild lesions (r = 0.49); no relation was seen in OM patients, and bone aluminum was higher for the duration of dialysis, suggesting that aluminum may accumulate more rapidly in OM subjects. These findings are consistent with but do not prove the hypothesis that aluminum plays a pathogenic role in dialysis osteomalacia; the mechanism by which aluminum accumulates remains unknown.

Aluminum↗
PubMed1982

Deficient activity of receptor-cyclase coupling protein is transformed lymphoblasts of patients with pseudohypoparathyroidism, type I.

Erythrocytes of many patients with pseudohypoparathyroidism, type 1 (PHP-I) exhibit quantitatively reduced activity of the N protein, the guanine nucleotide-binding regulatory component of adenylate cyclase. We have designated this group of patients PHP-Ia to distinguish them from PHP-Ib patients, in whom erythrocyte N activity is quantitatively normal. In virus-transformed lymphoblasts of three normal, three PHP-Ia, and two PHP-Ib subjects, we compared N and adenylate cyclase activities, as well as cAMP accumulation and susceptibility to radiolabeling in the presence of [32P]NAD and cholera toxin. In comparison to normal lymphoblasts, N activities were reduced by approximately 50% in lymphoblasts of the PHP-Ia patients, but were not reduced in lymphoblasts from the PHP-Ib patients. Toxin-catalyzed radiolabeling of the 42,000 molecular weight subunit of the N protein was also reduced in lymphoblasts of the PHP-Ia patients. These results are consistent with the hypothesis that N deficiency is generalized in tissues of PHP-Ia patients. Deficient lymphoblast N activity in PHP-Ia was not associated with decreases in adenylate cyclase activity or cAMP accumulation, probably because these activities involve many potential regulable cellular components in addition to the N protein.

Adenylyl Cyclases↗
PubMed1982

Circadian blood pressure and renin, aldosterone, cortisol, and prolactin levels in hypertensive pseudohypoparathyroid patients.

We investigated the relation between 24-h recumbent blood pressure levels and secretory patterns of PRA, aldosterone, cortisol, and PRL in four hypertensive pesudohypoparathyroid (PsHP) males and nine age- and weight-matched males with essential hypertension. Although both groups had PRA and aldosterone circadian rhythms, the variability and concentrations of these hormones over 24 h were considerably less in PsHP patients. Plasma cortisol concentrations demonstrated a well defined circadian rhythm in both groups, with no discernable differences between the PsHP patients and the patients with essential hypertension. All patients with essential hypertension had circadian rhythms of PRL secretion, but the PsHP patients failed to demonstrate a circadian variation in PRL secretion. These results suggest that factors other than those investigated in this study are responsible for the maintenance of elevated blood pressures in PsHP patients. The absence of circadian secretion of PRL may be related to altered dopaminergic control mechanisms in PsHP patients.

Adult↗
PubMed1981

Pseudohypoparathyroidism: inheritance of deficient receptor-cyclase coupling activity.

Pseudohypoparathyroidism, type I (PHP-I) is an inherited disorder of primary resistance to multiple hormones that work by stimulating adenylate cyclase. In an attempt to clarify the mode of inheritance of PHP-I, we measured the activity of the N protein, a receptor-cyclase coupling component, in erythrocyte membranes. Erythrocyte N-protein activity was reduced by approximately 50% in erythrocytes of 15 PHP-I patients and was normal in 19 of their clinically normal first degree relatives. Reduced N-protein activity and the PHP-I phenotype in these families exhibited both dominant and recessive patterns of inheritance. This suggests that at least two distinct genetic loci are involved in inheritance of N-protein deficiency. In two additional families, dominant inheritance of the PHP-I phenotype was associated with normal activities of erythrocyte N protein. Thus, it appears that mutation of at least one additional genetic locus, not involving the N protein, can produce PHP-I.

Adenylyl Cyclases↗
PubMed1981

Altered dopaminergic modulation of prolactin and aldosterone secretion in pseudohypoparathyroidism.

It has previously been demonstrated in our laboratory that patients with pseudohypoparathyroidism (PsHP) have impaired PRL responses to TRH and chlorpromazine. We have also observed that these patients have low basal plasma renin activity (PRA) and decreased aldosterone responses to upright posture and isometric handgrip exercise. Since inhibitory dopaminergic modulation of PRL and aldosterone is well established, we have examined whether PsHP is associated with altered dopaminergic inhibition of PRL and aldosterone secretion. To investigate this possibility, we compared the plasma PRL, aldosterone, and PRA responses to the dopamine antagonist metoclopramide (MCP; 10 mg iv) in seven normocalcemic PsHP patients and twelve normal controls. These patients were on no medications except calcium and vitamin D for 2 weeks; they were maintained on a diet containing 50 meq of sodium and 80 meq of potassium for 5 days. Although basal PRL levels were similar in the two groups of subjects, the maximal incremental PRL response in PsHP patients (38.7 +/- 12.6 ng/ml) was less (P less than 0.01) than in normal subjects (61.6 +/- 9.6 ng/ml). Basal supine plasma aldosterone was less (P less than 0.01) in PsHP patients (8.0 +/- 1.1 ng/dl) than in normal subjects (13.4 +/- 2.1 ng/dl). Maximum incremental aldosterone response to MCP (8.7 +/- 1.9 ng/dl) in PsHP patients was also less (P less than 0.01) than in normal subjects (13.4 +/- 2.1 ng/dl). Basal supine PRA was lower (P less than 0.05) in PsHP patients (1.3 +/- 0.3 ng/ml.h) than in normal subjects (2.8 +/- 0.4 ng/ml.h). However, the PRA responses to MCP were similar in both groups. Tonic dopaminergic inhibition of PRL and aldosterone secretion, but not renin secretion, appears to be less pronounced in PsHP patients. This is the first disease state in which reduced aldosterone responses to dopamine antoganism have been observed. Decreased PRL and aldosterone responses to MCP may reflect decreased ambient dopamine levels and/or a reduction in dopamine receptor number or binding affinity.

Adult↗
PubMed1981

Fibroblast defect in pseudohypoparathyroidism, type I: reduced activity of receptor-cyclase coupling protein.

Erythrocytes of many patients with pseudohypoparathyroidism, type I (PHP-I), exhibit reduced activity of the N protein, a guanine nucleotide-binding regulatory component of hormone-sensitive adenylate cyclase. We compared N and adenylate cyclase activities and the accumulation of cAMP in fibroblasts propagated from skin biopsies of six normal subjects and seven PHP-I patients. N activities were reduced by approximately 40% in fibroblasts as well as erythrocytes of five PHP-I patients. N activities in fibroblasts from two PHP-I patients with normal erythrocyte N activities were within the normal range. These results are consistent with the hypothesis that N deficiency is generalized in tissues of most PHP-I patients and is the primary defect responsible for their resistance to metabolic effects of hormones that work by stimulating adenylate cyclase. Fibroblast N deficiency was not associated with decreases in hormone-stimulated adenylate cyclase or cAMP accumulation in fibroblasts, probably because these activities involve many potentially regulable cellular components in addition to the N protein.

Adenylyl Cyclases↗