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S J Marx

Publications and source records attributed to S J Marx.

At least 163 records · Page 9Linked to original sources
PubMed1983

Urinary calcium excretion in familial hypocalciuric hypercalcemia. Persistence of relative hypocalciuria after induction of hypoparathyroidism.

Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant trait comprising hypercalcemia, hypophosphatemia, parathyroid hyperplasia, and unusually low renal clearance of calcium. We evaluated the role of parathyroid hormone in the relative hypocalciuria of FHH and characterized the renal transport of calcium in this disorder using three previously hypercalcemic FHH patients with surgical hypoparathyroidism and three controls with surgical hypoparathyroidism. Intravenous infusion of calcium chloride in two patients with FHH and in three controls increased serum calcium from a mean basal of 5.0 to a mean peak of 6.8 meq/liter in two FHH patients and from 4.2 to 5.7 in three control subjects. Urinary calcium in a third FHH patient was studied without calcium infusion during recovery from hypercalcemia of vitamin D intoxication. At all serum concentrations of calcium, calcium clearance was lower in FHH than in controls; at base-line serum calcium, the ratio of calcium clearance to inulin clearance (C(Ca)/C(IN)) in FHH subjects was 32% of that in controls and decreased to 19% during hypercalcemia. Calcium infusion increased the ratio of sodium clearance to inulin clearance in controls from a base line of 0.020 to 0.053 at peak concentrations of calcium in serum, but did not affect this parameter in FHH (0.017 at base-line serum calcium vs. 0.019 at peak). When calcium infusion studies were performed (in two patients with FHH and one control) during administration of acetazolamide, a drug whose principal renal action causes inhibition of proximal transport of solute, C(Ca)/C(IN) in the patients with FHH was 29 and 7% of that of the control at base-line and peak serum calcium, respectively. In contrast, ethacrynic acid, a diuretic that acts in the ascending limb of the loop of Henle, increased C(Ca)/C(IN) more in the FHH patients than in the control subject; C(Ca)/C(IN) was 65% at base-line and 47% at peak serum calcium, compared with that of the control subject. The greater calciuric response to ethacrynic acid than to acetazolamide or calcium infusion alone in FHH indicates that a major renal locus of abnormal calcium transport in this disorder may be the ascending limb of the loop of Henle.Decreased clearance of calcium in patients with FHH and hypoparathyroidism when compared with hypoparathyroid controls indicates that relative hypocalciuria in FHH is not dependent on hyperparathyroidism. Since the parathyroid glands in FHH are not appropriately suppressed by calcium, this implies that FHH represents a disorder of abnormal transport of, and/or response to, extracellular calcium in at least two organs, parathyroid gland and kidney.

Adolescent↗
PubMed1983

Binding of radioiodinated bovine parathyroid hormone-(1-84) to canine renal cortical membranes.

Binding of PTH to purified canine renal cortical membranes was investigated using biologically active radioiodinated bovine PTH-(1-84) [bPTH-(1-84)] as radioligand. PTH-(1-84) is thought to be the major circulating form of bioactive PTH, but oxidative inactivation upon iodination has prevented its use as a radioligand probe of PTH receptors. We have labeled PTH-(1-84) by a microelectrolytic constant current method to a high specific activity (180-220 muCi/micrograms), corresponding to an average ratio of 1 mol 125I/mol peptide. Affinity purification on chick renal membranes consistently improved the radioligand-binding properties, with a 6-fold increase in fraction specifically bound. Analysis of equilibrium (180 min at 15 C) competition curves showed two classes of binding sites for bPTH-(1-84). A high affinity binding site appeared to be coupled to activation of adenylate cyclase and exhibited affinity varying between 1.9 and 4.3 X 10(8) M-1. The affinity of this site for bPTH was decreased more than 50% by the nonhydrolyzable analog of GTP, guanyl-5'-yl-imidodiphosphate. A low affinity binding site also was detected (Ka = 0.6-6.2 X 10(6) M-1), and its affinity for bPTH was modulated by the concentration of magnesium. The high affinity sites exhibited hormonal specificity and guanine nucleotide dependency characteristic of peptide hormone receptors, while the low affinity sites did not. Analysis by polyacrylamide gel electrophoresis or high pressure liquid chromatography of the radioligand incubated with or released from purified canine renal cortical membranes revealed a single peak of radioactivity that comigrated with [125I]iodo-bPTH-(1-84). It appears from these studies that cleavage of amino-terminal to residue 43 ([125I]tyrosine) was not required for binding or release of hormone. These experiments indicate that radioiodinated bPTH-(1-84) is a useful probe for further characterization of PTH receptors in kidney and other organs.

Adenylyl Cyclases↗
PubMed1983

Rickets and alopecia with resistance to 1,25-dihydroxyvitamin D: two different clinical courses with two different cellular defects.

UNLABELLED: Two unrelated patients, aged 22 months and 31 months, with alopecia and rickets resistant to 1,25-dihydroxyvitamin D (1,25-(OH)2D] (vitamin D-dependency type II) presented with similar biochemical and radiologic features. They were treated with large doses of vitamin D3 derivatives [25-hydroxyvitamin D3 (25-(OH)D3), 1,25-(OH)2D3, and 1 alpha-hydroxyvitamin D3] for 28 months and 6 yr, respectively. In both patients, serum 1,25-(OH)2D levels remained high (approximately 10- to 100-fold normal) during the different therapeutic regimens. Circulating 1,25-(OH)2D and 24,25-dihydroxyvitamin D levels at various stages of the disease suggested in these children disturbances in the regulation of 25-hydroxyvitamin D (25(OH)D) 1 alpha- and 24-hydroxylase systems. In one child, all therapeutic trials were unsuccessful. Studies of her cultured skin fibroblasts showed low capacity (10% normal) for saturable (presumably receptor mediated) nuclear uptake of tritiated 1,25-(OH)2D3; the uptake process of nucleus associated 1,25-(OH)2D3 was normal in apparent affinity for 1,25-(OH)2D3 and in sedimentation velocity of nucleus-associated hormone. In the second child, correction of biochemical abnormalities, healing of rickets, and catch-up growth were obtained during similar therapeutic trials up to the age of 6 yr when a relapse occurred. This relapse has persisted for 2 yr in spite of similar or higher circulating concentrations of 25-(OH)D and 1,25-(OH)2D than those obtained previously when she was responsive to therapy. In her cultured skin fibroblasts, saturable high affinity nuclear uptake of 1,25(OH)2D was unmeasurable. IN CONCLUSION: 1) distinct patterns of clinical response can occur in patients with the syndrome of vitamin D-dependency type II, and can be associated with differing abnormalities in interaction of 1,25-(OH)2D3 with cultured skin fibroblasts; 2) aggravation of the resistance to 1,25-(OH)2D3 may occur during long term therapy in some patients.

24,25-Dihydroxyvitamin D 3↗
PubMed1983

Hereditary resistance to 1,25-dihydroxyvitamin D: defective function of receptors for 1,25-dihydroxyvitamin D in cells cultured from bone.

UNLABELLED: The syndrome of rickets, alopecia, hypocalcemia, and high circulating levels of 1,25-dihydroxyvitamin D (1,25-(OH)2D) apparently is caused by resistance of target tissues to 1,25-(OH)2D. To evaluate this, we cultured cells from explants of long bone of one patient with this syndrome and from a control without any preexisting disorder of mineral metabolism. The cultured cells showed morphological features of fibroblasts but contained alkaline phosphatase activity without detectable acid phosphatase activity, indicating an osteoblastic origin for some or all of the cultured cells. Receptors for 1,25-(OH)2D were assessed by three methods: high affinity uptake of hormone in nuclei of dispersed cells, high affinity binding in hypertonic extracts (herein termed cytosol) from cells, and sedimentation velocity of bound [3H]1,25-(OH)2D3 in extracts of cell nuclei. With cells cultured from bone of the normal control, receptors for 1,25-(OH)2D exhibited properties indistinguishable from those found with cultured skin fibroblasts. With cells cultured from bone of the patient with resistance to 1,25-(OH)2D, high affinity uptake of 1,25-(OH)2D into nuclei was unmeasurable, but high affinity binding of hormone with cytosol was normal; these abnormal findings also were indistinguishable from abnormal findings obtained with fibroblasts cultured from skin of that patient. IN CONCLUSION: 1) Cells cultured from explants of human bone showed morphological features of fibroblasts but retained a marker enzyme characteristic of osteoblasts. Significant admixture of osteoblast-like cells with fibroblasts was possible. 2) Cells cultured from bone of a patient with familial resistance to 1,25-(OH)2D exhibit a defect in vitamin D metabolism, indistinguishable from the defect observed with cells cultured from skin of the same patient.

Acid Phosphatase↗
PubMed1982

An association between neonatal severe primary hyperparathyroidism and familial hypocalciuric hypercalcemia in three kindreds.

Four cases of neonatal severe primary hyperparathyroidism occurred in three families; familial hypocalciuric hypercalcemia was present in each kindred. The diagnosis of familial hypocalciuric hypercalcemia was based on the following features; hypercalcemia in many relatives (eight to 16 per kindred), without other features of the multiple endocrine neoplasia syndromes; recognition of hypercalcemia before the age of 10 in one to three relatives; hypocalciuric hypercalcemia in all relatives tested (five to 14 per kindred); and abnormal serum calcium levels despite parathyroidectomy in all additional relatives (one to five per kindred) undergoing this operation. The association of two uncommon syndromes (neonatal severe primary hyperparathyroidism and familial hypocalciuric hypercalcemia) in these kindreds suggests that the two syndromes share a common genetic cause within each kindred.

Adolescent↗
PubMed1982

Deferred parathyroid autografts with cryopreserved tissue after reoperative parathyroid surgery.

Between August 1975 and March 1981, 12 patients underwent forearm parathyroid autotransplantation with cryopreserved tissue following reoperative parathyroid surgery. Tissue had been cryopreserved two to 18 months. Follow-up ranged from four to 66 months (median, 18 months) following autotransplantation. All patients required calcium supplementation as a condition for autografting; six patients were no longer receiving calcium supplementation at most recent follow-up and in one patient the dosage was being tapered. The presence of a parathyroid hormone gradient of 2 : 1 or greater correlated well with freedom from calcium supplementation. Of seven patients with preautograft and postautograft urinary cyclic adenosine monophosphate (cAMP) determinations, three with increases following transplantation did not require calcium, three without increases continued to require calcium, and the patient whose dosage was being tapered had increased urinary cAMP levels.

Freezing↗
PubMed1982

Radiographic findings in recurrent parathyroid carcinoma.

Seven cases of recurrent parathyroid carcinoma were reviewed. Subperiosteal resorption was seen in 6, pulmonary nodules in 4, renal calculi in 5, brown tumors in 5, and pancreatic calcification in 1. Angiography was performed in 5 patients, showing 1 definite and 2 probable cervical recurrences, 1 mediastinal lesion, and 1 case of possible bone metastases. Venous sampling for parathyroid hormone was carried out in 4 patients and suggested residual disease in 2; in addition, there were 1 false and 1 true negative. CT was performed in 4 patients and was useful in delineating metastatic pulmonary nodules, cervical recurrence, and hepatic metastases. The radiographic approach to recurrent parathyroid carcinoma and the use of CT and angiography are discussed.

Adult↗
PubMed1982

Deficiency of hormone receptor-adenylate cyclase coupling protein: basis for hormone resistance in pseudohypoparathyroidism.

Pseudohypoparathyroidism is an inherited disorder associated with resistance to the action of several hormones, including parathyroid hormone, thyroid-stimulating hormone, follicle-stimulating hormone, and luteinizing hormone. The disorders described under this designation are heterogeneous in regard to the underlying genetic defects, the phenotypic manifestation, and the severity of the defects in hormone action. The majority of affected individuals who also have the characteristic skeletal changes (heredity osteodystrophy) have a defect in the guanine nucleotide regulatory protein (G protein) that is essential for coupling certain cell-surface hormone receptors to the adenylate cyclase system. This defect is probably the cause for resistance to the action of multiple hormones. In the remaining patients the cause for hormone resistance has not been identified.

Adenylyl Cyclases↗
PubMed1982

Human chorionic gonadotropin subunit measurement in primary hyperparathyroidism.

The concentration of subunits of hCG (hCG alpha and hCG beta) was determined in plasma or serum from 70 patients with primary hyperparathyroidism (1 degrees HPT). Two of three patients with parathyroid carcinoma showed elevation in plasma concentrations of both subunits, which fell after surgical removal of the tumor. An extract prepared from the tumor of 1 of these patients contained the subunits in high concentrations, whereas in extracts similarly prepared from tissues removed from 7 patients with benign 1 degrees HPT, the subunits were not detectable or were present in much lower concentrations. In 42 cases of benign 1 degrees HPT, samples from veins containing a 10-fold gradient of parathyroid hormone obtained during selective venous catheterization and peripheral samples from the same patients were analyzed for hCG subunits. Only 1 patient demonstrated a mild elevation of hCG alpha in parathyroid venous effluent alone that may have represented subunit release by apparently benign parathyroid tissue. Thirty patients with multiple endocrine neoplasia type I were tested; 8 evidenced clinically active islet cell tumors, and 6 of these 8 showed high circulating concentrations of hCG alpha (and hCG beta in 1 case). Patients in the multiple endocrine neoplasia type I group with 1 degrees HPT or pituitary tumors, but no evident pancreatic islet disease, did not show elevations in subunit concentrations. Thus, in patients with 1 degrees HPT, determination of subunits of hCG may be helpful in making the diagnosis of parathyroid carcinoma or in screening for associated (and probably malignant) pancreatic islet disease.

Adenoma, Islet Cell↗
PubMed1982

Assessment of techniques for preoperative parathyroid gland localization in patients undergoing reoperation for hyperparathyroidism.

Persistent and recurrent hyperparathyroidism after previous unsuccessful surgery is a major problem for the patient and the physician. We have prospectively evaluated the ability of cine-esophagography, computed tomography, selective venous sampling for parathyroid hormone, and selective arteriography to preoperatively detect parathyroid tissue in 75 patients undergoing reoperation. The invasive studies were routinely and safely applied to all patients in an effort to determine their value. In 55% of studies performed, preoperative localization by selective venous sampling was consistent with the subsequent operative findings. Selective arteriography correctly localized abnormal parathyroid tissue in 49% of studies performed but was more specific than selective venous sampling. Cine-esophagography was not of help in localization but did demonstrate abnormalities of swallowing attributed to prior surgery. Computed tomography correctly localized 11% of patients studied.

Adolescent↗
PubMed1982

In vitro studies of parathyroid hormone release: effect of cimetidine.

We studied parathyroid hormone (PTH) release from cell suspensions of fresh and cryopreserved human parathyroid tissue. A sensitive PTH assay with midregion specificity and adaptation of "micro" methods of cell plating permitted conservation of tissue (200 microliters aliquots) and high reproducibility (5 to 10 aliquots per experimental condition). Viability of cells in suspension was confirmed by increased PTH release with increased incubation, increased incorporation of tritiated leucine with increased incubation, and incorporation of tritiated leucine following experimental incubation. Because of conflicting reports regarding the in vivo effect of cimetidine on PTH release, we incubated cells from both adenomatous and hyperplastic glands at 0, 10(-4)M, 10(-5)M, and 10(-6)M cimetidine (10(-5)M is therapeutic) and at 0.25, 1 to 1.2, and 2 mM Ca++. Despite occasional statistically significant (P = 0.05) differences in PTH release with and without cimetidine, therapeutic levels of cimetidine had no consistent effect on PTH release from pathologic parathyroid tissue in vitro.

Calcium↗
PubMed1981

The parathyroid glands in familial hypocalciuric hypercalcemia.

We analyzed, by light microscopy, specimens obtained at parathyroid surgery from 18 members of eight kindreds with familial hypocalciuric hypercalcemia. For comparison, similar analyses were performed with normal parathyroid glands (surgical or postmortem specimens) and with glands from patients with typical primary parathyroid hyperplasia. The average parathyroid parenchymal area in familial hypocalciuric hypercalcemia was 300 per cent of that in normal subjects (0.049 versus 0.15 sq. cm., p less than 0.0005) but significantly less than that in typical primary parathyroid hyperplasia. Thirteen of the 18 subjects with familial hypocalciuric hypercalcemia had one or more enlarged glands. Enlarged parenchymal areas were noted at all ages in familial hypocalciuric hypercalcemia, but there was a spectrum of histologic findings among the glands in each case, within most families, and between families. Mild parathyroid hyperplasia was a feature in most patients with familial hypocalciuric hypercalcemia who had undergone neck surgery. Simple quantitative analyses were useful in identifying parathyroid hyperplasia in the group with familial hypocalciuric hypercalcemia.

Adolescent↗