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Biomedical subjects

Z Farfel

Publications and source records attributed to Z Farfel.

107 records · Page 6Linked to original sources
PubMed1981

Human mutation affecting hormone-sensitive adenylate cyclase.

Hormone-sensitive adenylate cyclase contains a recently discovered protein component that is required for stimulation of cyclic AMP synthesis by hormones and guanine nucleotides. We measured this protein in erythrocyte membranes of ten patients with pseudohypoparathyroidism (PHP), using assays of its biochemical activity and of its susceptibility to radiolabeling in the presence of 32P-NAD and cholera toxin. By both assays, the protein was reduced by 50% in erythrocytes of 4 PHP patients, as compared with normal and hypoparathyroid subjects. These 4 subjects, in contrast to the 6 PHP patients (5 in one family) whose erythrocytes contained apparently normal amounts of the cyclase component, exhibited the full spectrum of skeletal abnormalities found in PHP. We conclude that partial deficiency of the guanine nucleotide regulatory protein is a biochemical marker for a subset of PHP patients. If present in other tissues, this deficiency could explain the resistance of target organs in PHP to parathormone and other hormones that work via cyclic AMP.

Adenylyl Cyclases↗
PubMed1980

Defect of receptor-cyclase coupling protein in pseudohypoparathyroidism.

Hormone-sensitive adenylate cyclase contains a recently discovered protein component that is required for stimulation of cyclic AMP synthesis by hormones and guanine nucleotides; the component presumably couples the membrane receptor to the cyclase. We studied this protein (termed "N") in erythrocyte membranes of patients with pseudohypoparathyroidism, using assays of the protein's biochemical activity and of its susceptibility to radiolabeling in the presence of [32P]NAD and cholera toxin. By both assays, the protein's activity was reduced by 40 to 50 per cent in erythrocytes of five of 10 patients with Type I pseudohypoparathyroidism as compared with those of normal and hypoparathyroid subjects and one patient with Type II pseudohypoparathyroidism. If activity of the N protein is reduced in other tissues, this deficiency could cause the resistance of target organs in pseudohypoparathyroidism to parathyroid hormone and other hormones that work via cyclic AMP. Erythrocytes of five patients with Type I pseudohypoparathyroidism, all in one family, showed no defect in activity of the N protein; the biochemical defect of this family remains undefined.

Adenylyl Cyclases↗
PubMed1980

Deficient activity of receptor-cyclase coupling protein in platelets of patients with pseudohypoparathyroidism.

Erythrocytes of patients with pseudohypoparathyroidism exhibit decreased activity of a membrane protein that is required for functional coupling of hormone receptors and catalytic adenylate cyclase. We observed decreased activity of this coupling protein in platelet extracts obtained from two pseudohypoparathyroid subjects, as compared with those of four normal control subjects. These findings support the hypothesis that generalized deficiency of this coupling protein is the primary biochemical defect of pseydohypoparathyroidism.

Adenylyl Cyclases↗
PubMed1979

A transient increase in amino acid transport modulated by insulin in differentiating muscle cells.

During synchronous differentiation of embryonic chick muscle cells in cultures, the Na-dependent uptake of an amino acid analog, alpha-amino isobutyric acid (AIB) undergoes in abrupt, transient increase. The increase in AIB uptake is concomitant with the rapid fusion of mononucleated myoblasts, and precedes the accumulation of muscle-specific proteins. Subsequently, Na-dependent AIB transport diminishes markedly during postfusional differentiation of myotubes. The rate of AIB uptake is increased by insulin both before and after myoblast fusion. This stimulation by insulin is restricted to the Na-dependent component of total AIB uptake but is apparently not the result of insulin-mediated increase in the trans-membrane Na gradient.

Aminoisobutyric Acids↗
PubMed1978

Proximal renal tubular acidosis: association with familial normaldosteronemic hyperpotassemia and hypertension.

Further investigation of a family with normaldosteronemic hyperpotassemia and low-renin hypertension showed seven members from three generations, who ranged in age from 4 to 56 years, to be affected. Results of earlier studies had established a normally functioning renin-aldosterone system and normal renal handling of potassium. Constant, albeit mild and asymptomatic, metabolic acidosis in all those affected prompted bicarbonate loading in both the propositus and his brother, which revealed a maximal renal tubular excretory capacity for bicarbonate reabsorption at serum levels of 18 mmole/liter and proved proximal renal tubular acidosis (PRTA). Further, a linear increase in urinary fractional potassium excretion accompanied that of bicarbonate in both, as in normal individuals. Dextrose-insulin infusion in the brother failed to reduce hyperpotassemia. These data support the hypothesis that a generalized cell membrane defect that specifically impedes potassium influx (as opposed to an isolated renal tubular defect) underlies this autosomal dominant disorder.

Acidosis, Renal Tubular↗
PubMed1978

Presence of insulin-renin-aldosterone-potassium interrelationship in normal subjects, disrupted in chronic hemodialysis patients.

The factors regulating aldosterone secretion in normals and in patients on chronic hemodialysis were studied by the determination of the circadian rhythm of plasma aldosterone, renin, cortisol, insulin, potassium, sodium, and glucose. Four normal volunteers and eight normotensive patients on regular dialysis treatment (RDT) were studied during prolonged recumbency on low sodium diet. A definite circadian rhythm for renin could not be demonstrated in RDT patients. The significant simple and multiple correlation coefficients found in normal subjects suggest that insulin participates in the regulation of aldosterone together with the other known factors: ACTH, renin, and potassium. In chronic renal failure, however, when basal conditions were maintained during prolonged recumbency, the correlations of insulin and renin with aldosterone were not found, suggesting that in this condition aldosterone secretion is controlled by ACTH and potassium. As a direct influence of insulin on aldosterone could not be demonstrated by multiple variance analysis, it seems that insulin is related to aldosterone indirectly through renin and/or potassium. The presence of significant correlations between insulin-potassium and potassium-aldosterone in RDT patients, without a significant insulin-aldosterone correlation, suggest that in the normals insulin participates in aldosterone regulation through renin secretion and not through potassium. A correlation between potassium and renin was not found in normals or in RDT patients.

Adult↗
PubMed1978

Familial hyperpotassemia and hypertension accompanied by normal plasma aldosterone levels: possible hereditary cell membrane defect.

Hypertension and hyperpotassemia that were accompanied by normal plasma aldosterone and low renin levels and were responsive to chlorothiazide administration were found in a 29-year-old patient and two decades later in his 21-year-old son. Their renal function is normal, including response to sodium sulfate, mannitol, and aldosterone infusions. Adrenal insufficiency was excluded. The renin-aldosterone system was proved intact by physiological and pharmacologic stress and angiotensin-II infusion. Also normal were values for blood counts, blood volumes, and erythrocyte and exchangeable body potassium. The postulation of a defective cell membrane impeding potassium influx is supported by the failure of glucose and insulin infusions to substantially reduce hyperpotassemia. In the context of a hereditary disorder (the pedigree, compatible with autosomal dominant inheritance, includes five affected in two generations), hypertension is a second phenotypic character of a single defective pleiotropic gene although its pathogenesis remains unclear.

Adult↗