Biomedical subjects

S Posen

Publications and source records attributed to S Posen.

At least 55 records · Page 3Linked to original sources

PubMed1988

Neuromuscular symptoms in elderly patients with hyperparathyroidism: improvement with parathyroid surgery.

In a consecutive series of 100 neck explorations for primary hyperparathyroidism, 42 patients were 60 years of age or older; in this group of elderly patients the surgical cure rate was 100%. These patients were reviewed retrospectively by means of a structure interview. Twenty-one patients had had preoperative neuromuscular symptoms that ranged from coma to subjective muscular weakness. These patients had significantly-higher preoperative serum calcium and parathyroid hormone levels than did 21 patients without neuromuscular symptoms (P = 0.003 and P = 0.046, respectively). Most of the neuromuscular symptoms improved in the postoperative period. In particular, 15 of 17 patients with muscle weakness reported a significant improvement, while 14 of 15 patients who suffered from fatigue and lethargy reported an improvement. An improvement also occurred in the level of day-to-day function in eight patients. While surgery for primary hyperparathyroidism generally is undertaken for a specific indication, such as severe hypercalcaemia or renal stones, it appears from this study that neuromuscular symptoms also may improve, particularly in elderly patients.

Adolescent↗

PubMed1988

Extracellular matrix modulates the function of human melanocytes but not melanoma cells.

Normal human epidermal melanocytes are attached to a basement membrane, a specialized form of extracellular matrix (ECM), located between the epithelium and underlying dermal tissues. To determine whether ECM influences pigmented cell behavior in vitro, human epidermal melanocytes and melanoma cells were cultured on uncoated or ECM-coated plastic culture surfaces, and a comparison was made between growth and function in the presence or absence of ECM. Melanocytes cultured on ECM-coated surfaces developed flatter and larger cell bodies and produced more melanin than melanocytes cultured on uncoated surfaces. In the presence of phorbol-myristate-acetate and cholera toxin, the rate of melanocyte replication was increased by ECM. In the absence of these mitogens, ECM significantly enhanced the adhesiveness of nonproliferating melanocytes. ECM had little or no effect on these parameters (morphology, tyrosinase activity, replication) in a pigmented human malignant melanoma cell line. These findings indicate that normal human epidermal pigment cells have the ability to recognize and respond to matrix signals, whereas this capacity appears to be absent in melanoma cells.

Cell Division↗

PubMed1988

Forearm mineral content in normal men: relationship to weight, height and plasma testosterone concentrations.

We measured forearm bone mineral content by single photon absorptiometry together with height, weight and the plasma concentrations of testosterone, free testosterone and sex steroid binding globulin in 66 normal Caucasian males aged 29-46 years. Multiple regression analysis suggests that bone mineral content in either the dominant or the nondominant arm is correlated with weight and sex steroid binding globulin (p less than 0.05 for both parameters). The partial negative correlation of bone mineral content (corrected for weight and sex steroid binding globulin) with plasma testosterone failed to reach statistical significance (p = 0.07). The parsimonious regression equation which best explained the bone mineral content measurements in the nondominant forearm in these men was bone mineral content = 29.1-0.374 (plasma testosterone) + 0.383 (weight) + 0.220 (sex steroid binding globulin) with an R2 value of 29.7%. A similar equation was generated for the dominant arm.

Adult↗

PubMed1988

Human melanoma cells: functional modulation by calciotropic hormones.

Four human melanoma cell lines were examined for their responsiveness to the hormones 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), calcitonin, and parathyroid hormone (1-34). Cells from each of the 4 lines contained high affinity binding sites for 1,25(OH)2D3. At high cell densities, binding of 1,25(OH)2D3 was diminished due to a decrease in receptor number with no apparent change in affinity. Preincubation with 1,25(OH)2D3 (10(-10) to 10(-8) M) increased tyrosinase activity 1.3- to 3.2-fold and 25-hydroxyvitamin D3-24-hydroxylase activity 1.4- to 10-fold. Human calcitonin (0.82 to 82.5 ng/well) raised the intracellular concentration of cyclic adenosine monophosphate 1.4- to 9.4-fold. Tyrosinase activity increased in response to calcitonin in 2 of the cell lines, decreased in the third, and showed no change in the fourth. Human parathyroid hormone (1-34) in concentrations of 1 to 10 ng/ml produced no significant changes in cyclic adenosine monophosphate accumulation, cell numbers, or tyrosinase activity in any of the cell lines. This study indicates that the phenotype of human melanoma cells can be modulated by the calciotropic hormones 1,25(OH)2D3 and calcitonin.

Calcitonin↗

PubMed1988

Human melanocytes as a target tissue for hormones: in vitro studies with 1 alpha-25, dihydroxyvitamin D3, alpha-melanocyte stimulating hormone, and beta-estradiol.

Clinical evidence exists which suggests that normal pigment cell (melanocyte) function is subject to hormonal influences, but the nature of these interactions at a cellular level is poorly understood. We have investigated the effects of the vitamin D-derived secosteroid hormone 1 alpha-25, dihydroxyvitamin D3 (1,25(OH)2D3), the pituitary-derived peptide alpha-melanocyte stimulating hormone (alpha-MSH), and the sex steroid beta-estradiol on melanocytes cultured from normal human foreskin. Human melanocytes specifically internalized 1,25(OH)2D3 with high affinity (Kd 0.5-0.8 nM). Incubation with 1,25(OH)2D3 (10(-9) M) for 48 h resulted in a 100% increase in 25-hydroxyvitamin D3-24-hydroxylase activity and a 50% increase in tyrosinase activity. There was no significant effect of 1,25(OH)2D3 on intracellular cyclic adenosine monophosphate (cAMP). In contrast to 1,25(OH)2D3, alpha-MSH at a concentration of 5 X 10(-7) M caused a sevenfold increase in intracellular cAMP after 12 min but only a modest increase (less than 20%) in melanocyte tyrosinase activity after 48 h. Incubation with beta-estradiol for 24 h caused a dose-dependent increase in tyrosinase activity. The maximal response varied from 145%-213% of basal activity depending on the donor source. These results indicate that melanocytes from normal human foreskin in culture have the capacity to respond directly to several hormones. They also suggest that these cells form a useful model to study the effect of various hormones on pigment cell function.

Calcitriol↗

PubMed1987

Is there a place for forearm osteodensitometry in clinical screening studies?

In order to evaluate forearm osteodensitometry for its potential to detect subjects with a low spinal mineral content and/or vertebral fractures, single-photon absorptiometry of the forearm and estimations of spinal mineral content by computed tomography were performed in 124 normal and abnormal subjects. Eighty-one per cent (22/27) of patients with vertebral crush fractures had a low spinal mineral content. In contrast, among 64 apparently normal individuals, six patients (four women, two men; 9.4%) had a low spinal mineral content. Forearm osteodensitometry showed a significant positive correlation with spinal mineral content. A forearm value in women in excess of 35 arbitrary units was associated with a spinal value of 75.1-mg equivalent dipotassium phosphate (K2HPO4) or above in 29/31 cases. A forearm value in women of 28.5 arbitrary units or lower was associated with a spinal value of 75-mg equivalent K2HPO4 or less in 20/24 subjects. While of no predictive value for the spine in patients with intermediate readings, forearm osteodensitometry is nevertheless considered a useful screening procedure for spinal osteoporosis.

Adult↗

PubMed1987

A 6-hour human parathyroid hormone (1-34) infusion protocol: studies in normal and hypoparathyroid subjects.

Parathyroid hormone (PTH)-resistant states are usually diagnosed by the failure of an acute PTH injection to elicit a rise in urinary cAMP and phosphate or, less commonly, by the failure of repeated PTH injections to raise serum calcium. We have established a 6 hour infusion of human PTH (1-34) which identifies PTH-resistant hypoparathyroid subjects on the basis of serum 1,25-dihydroxyvitamin D (1,25(OH)2D) and calcium responses. 1,25-Dihydroxyvitamin D levels increased by at least 58 pmol/liter and serum calcium by at least 0.1 mmol/liter in PTH-responsive hypoparathyroid subjects (n = 6), whereas in pseudohypoparathyroid subjects (n = 5) these levels rose by less than 22 pmol/liter and 0.06 mmol/liter respectively. The responsiveness of urinary phosphate excretion, expressed as the renal threshold phosphate concentration (TmPO4/GFR), to PTH also clearly separated the pseudohypoparathyroid patients from the other subjects. Differences in urinary calcium responses were observed though this parameter was less reliable in the identification of individual PTH-resistant or PTH-sensitive hypoparathyroid patients. Nephrogenous cAMP did not discriminate between groups when this protocol was used. This test has the potential to facilitate and extend the classification of PTH-resistant states.

Adult↗

PubMed1987

Interactions between 1,25-dihydroxyvitamin D3 and vitamin D2: effects of pharmacologic doses in normal individuals.

To determine whether the administration of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) affects the conversion of a pharmacologic dose of vitamin D2 to 25-hydroxyvitamin D (25OHD), 20 normal subjects received two separate doses of vitamin D2--one with and the other without the concomitant administration of 1,25(OH)2D3. Serum 1,25(OH)2D rose in response to 1,25(OH)2D3 administration and fell when vitamin D2 was given alone. Serum osteocalcin rose in response to 1,25(OH)2D3 administration. Serum 25OHD rose in response to vitamin D2 administration regardless of whether the subjects also received 1,25(OH)2D3. The data from this study in humans support the suggestion that the effects of 1,25(OH)2D3 on serum 25OHD concentrations are mediated through mechanisms other than impairment of production.

25-Hydroxyvitamin D 2↗

PubMed1986

Humoral hypercalcaemia of malignancy: report of two further patients with biochemical studies on tumour extracts.

Tumour extracts from two patients with humoral hypercalcaemia of malignancy contained material which stimulated adenylate cyclase in chick renal membranes and in rat osteosarcoma cells. Adenylate cyclase-stimulating activity in each system was inhibited by a specific parathyroid hormone (PTH) antagonist. Studies in two HPLC systems suggested that the adenylate cyclase-stimulating factors extracted from these tumours differed from each other and from synthetic human parathyroid hormone 1-34. The presence of similar PTH-like adenylate cyclase stimulating material(s) in oncogenic osteomalacia suggests that adenylate cyclase stimulating factor(s) may not be the direct or the sole cause of hypercalcaemia.

Adenylyl Cyclases↗

PubMed1986

Clinical experiences with human parathyroid hormone 1-34.

Human parathyroid hormone (PTH) 1-34 was given to nine normal subjects and to 10 patients with hypoparathyroidism. There were no side effects associated with the protocol employed. In normal subjects, five statistically significant changes occurred during the period of observation: plasma cyclic adenosine monophosphate (cAMP) rose by a factor of 3 (at 30 min), nephrogenous cyclic AMP rose approximately 40-fold (at 60 min), urinary phosphate rose by a factor of 2 (at 120 min), urine calcium levels fell by 50% between 60 and 120 min, and plasma prolactin rose by a factor of 1.4 (at 60 min). The cAMP responses were significantly blunted in five patients with chronic hypocalcemia, chronic hyperphosphatemia, and detectable serum immunoreactive PTH levels. On the basis of this test these patients were designated as suffering from pseudohypoparathyroidism. The acute phosphaturic and hypocalciuric responses were apparently intact in these five individuals. Human PTH 1-34 is likely to replace bovine material in the delineation of syndromes associated with PTH resistance.

Adult↗

PubMed1986

Epidermal growth factor causes hypocalcemia in sheep.

During iv infusions of epidermal growth factor into sheep, serum calcium concentrations fell, whereas serum magnesium and serum immunoreactive PTH levels increased. Urinary calcium and magnesium decreased significantly. The role of epidermal growth factor in calcium homeostasis is discussed.

Animals↗

PubMed1986

Serum osteocalcin concentrations in Paget's disease of bone.

Total body scintiscans, serum alkaline phosphatase estimations, and serum osteocalcin radioimmunoassays were performed in 49 consecutive patients with Paget's disease of bone. Eleven were receiving calcitonin (salmon synthetic) at the time of the study. The serum alkaline phosphatase activities were elevated in all but one patient, with the highest value almost 50 times the upper limit of the reference range. Serum osteocalcin concentrations were elevated in 53% of patients and normal in the rest. The highest serum osteocalcin value was 4.2 times the upper limit of the reference range. The correlation coefficient between the extent of skeletal involvement and serum osteocalcin level was .70, while that between skeletal involvement and serum alkaline phosphatase level was .55. In spite of the better correlation between bone scintiscans and serum osteocalcin level, osteocalcin measurements are diagnostically less useful than serum alkaline phosphatase estimations in patients with Paget's disease of bone.

Aged↗

PubMed1985

The effect of metabolic acidosis on vitamin D metabolites and bone histology in uremic rats.

Biochemical data and skeletal histomorphometric measurements are presented for normal rats and for two groups of rats rendered uremic by partial nephrectomy. In one of these groups chronic acidosis was induced by the oral administration of hydrochloric acid. Uremic animals had higher urine calcium excretion rates and lower serum concentrations of vitamin D metabolites than normal rats. Chronic acid loading of uremic rats resulted in hypercalcemia, elevated serum parathyroid hormone concentrations, and a significant loss of trabecular bone in addition to the above changes. greater osteoclast densities and higher resorption surfaces wee seen in the uremic acidotic animals than in the other two groups. The acidotic uremic state induced more potent changes in calcium metabolism and bone structure than uremia alone.

Acidosis↗

PubMed1985

Some problems associated with adenylate cyclase bioassays for parathyroid hormone.

A renal adenylate cyclase system was assessed for its suitability in the performance of parathyroid hormone (PTH) bioassays. Membrane preparations from 1 week old chicks were found to be more sensitive to PTH than material from humans, dogs or rats. Because of the presence of non-specific inhibitors and stimulators of adenylate cyclase in human serum, each serum sample was assayed in the presence and in the absence of a specific PTH inhibitor and the difference was used to calculate PTH activity. Calcium, an inhibitor of adenylate cyclase, was either removed from serum samples by pretreatment with Chelex resin or chelated during assay by means of EGTA. Human and bovine PTH (1-34) stimulated adenylate cyclase in this system to the same extent. The lower limit of detectability was 19.5 pg/ml (final concentration). The intra-assay coefficient of variation at a final concentration of 45 pg/ml was 18%. The index of precision was 0.08 +/- 0.04 (n = 7). When synthetic human PTH (1-34) was infused into three normal volunteers, the mean biological half-life of this material was found to be 3.2 min. PTH-like bioactivity could be routinely detected in sera from normal rats, while such activity was significantly decreased in rats subjected to thyroparathyroidectomy.

Adenylyl Cyclases↗

PubMed1985

An adenylate cyclase bioassay for parathyroid hormone: some clinical experiences.

An adenylate cyclase bioassay for parathyroid hormone (PTH) was evaluated in peripheral sera of ten normal subjects, 15 patients with various types of hypoparathyroidism, nine patients with malignancy-associated hypercalcaemia and 60 patients with primary or secondary hyperparathyroidism. The lower limit of detectability was 150 pg/ml in terms of synthetic human PTH (1-34). PTH-like bioactivity was not detected in normal subjects, in patients with surgical hypoparathyroidism, in patients with idiopathic hypoparathyroidism or in patients with malignancy-associated hypercalcaemia. Serum from one untreated pseudohypoparathyroid patient consistently contained PTH-like bioactivity. Bioactivity was detected in sera from 50% of patients with primary or secondary hyperparathyroidism. In two patients with secondary hyperparathyroidism calcium infusions suppressed this activity within 5 min. Both in primary and in secondary hyperparathyroidism there was a significant positive correlation between levels of PTH-like bioactivity, PTH immunoreactivity and the histological severity of the disease.

Adenylyl Cyclases↗

PubMed1985

Parathyroid hormone-like bioactivity in tumours from patients with oncogenic osteomalacia.

Extracts from the tumours of three patients with oncogenic osteomalacia stimulated renal adenylate cyclase in a parathyroid hormone (PTH) responsive system. The stimulation was suppressed by a specific PTH antagonist. These observations suggest that osteomalacia-producing tumours exert some of their effects through PTH-like material acting on PTH receptors.

Adenylyl Cyclases↗

PubMed1985

Bioactive parathyroid hormone in the rat: effects of calcium and calcitriol.

Bioactive PTH was measured in Wistar rats under a variety of experimental conditions. The mean activity in normal rat sera was 0.17 +/- 0.12 ng/ml (expressed in terms of bovine PTH 1-34). Sera from animals reared on a vitamin D deficient diet showed a mean value of 0.46 +/- 0.24 ng/ml (P less than 0.01), whereas sera from animals with 1,25-dihydroxyvitamin D (1,25(OH)2D) deficiency had a mean activity of 0.62 +/- 0.23 ng/ml (P less than 0.01). Dietary calcium deficiency also resulted in high serum PTH levels (0.71 +/- 0.34 ng/ml, P less than 0.01) in spite of marked elevations of serum 1,25(OH)2D concentrations in these animals. A significant negative correlation was noted between serum calcium and bioactive PTH. Calcium infusions into hypocalcemic, vitamin D-deficient rats caused a fall in serum bioactive PTH concentrations to a mean of 13% of control values within 10 min. Intraperitoneal administration of 1,25(OH)2D3 to hypocalcemic, 1,25(OH)2D-deficient rats did not suppress serum bioactive PTH concentrations after 30 or 60 min even though serum 1,25(OH)2D concentrations were greater than 900 pmol/liter in each animal at these time points. To our knowledge, this is the first study using PTH bioassays for physiological experiments in rats.

Adenylyl Cyclases↗

PubMed1985

Dialysis osteodystrophy. A study involving 94 patients.

Dynamic skeletal histomorphometry was performed in 94 unselected patients receiving maintenance dialysis for chronic renal failure. An attempt was made to correlate the results with the clinical, biochemical and radiological findings. Skeletal histology was abnormal in each case. Hyperparathyroidism was present as the only abnormality in 18 patients and osteomalacia in 26; 50 patients showed both abnormalities. Osteomalacia, in contrast to hyperparathyroidism, increased in prevalence and severity with the duration of dialysis and with bone aluminum content. The majority of patients had histological osteosclerosis. It was impossible to predict either the nature or the severity of the histological lesions on the basis of symptoms and physical signs or on the basis of most biochemical parameters (including serum concentrations of three vitamin D metabolites). Serum alkaline phosphatase values and serum immunoreactive parathyroid hormone (iPTH) concentrations were positively correlated with the severity of histological hyperparathyroidism. Subperiosteal erosions of the phalanges were associated with severe histological hyperparathyroidism in each case but this radiological sign was absent in 66% of patients with histological hyperparathyroidism. Radiological osteosclerosis was associated with severe histological osteomalacia in each case, but this radiological sign was absent in 87% of patients with histological osteomalacia. No other radiological sign proved a reliable guide to the underlying skeletal histology. In the majority of dialysis patients, a skeletal biopsy is required for an accurate diagnosis of the nature and severity of azotemic osteodystrophy.

Adolescent↗