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Biomedical subjects

S J Marx

Publications and source records attributed to S J Marx.

At least 181 records · Page 10Linked to original sources
PubMed1981

Nuclear uptake of 1,25-dihydroxy[3H]cholecalciferol in dispersed fibroblasts cultured from normal human skin.

Because of the relative inaccessibility of known calciferol target tissues (i.e., intestine and bone), we examined fibroblasts derived from normal human skin and grown in tissue culture as a means of evaluating the interaction of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] and its effector system. When dispersed, intact cells were used, nuclear uptake of 1,25-dihydroxy[23,24(n)3-H]cholecalciferol [1,25(OH)2[3H]D3) was temperature-dependent, optimal at 45 min at 37 degrees C, and saturable. In competition experiments with other calciferols, the 1,25(OH)2[3H]D3 uptake showed specificity indistinguishable from that reported for 1,25(OH)2D3 receptors from calciferol target tissues. Analysis of 1,25(OH)2[3H]D3 nuclear uptake in fibroblast strains from six normal adults (four male, two female) yielded an average binding capacity (R0) of 10,600 +/- 2,000 (SEM) nuclear sites per cell and an apparent dissociation contant (Kd) of 0.50 +/- 0.07 (SEM) x 10(-9) M. Donor sex, donor age, or anatomic site of origin of the cell line did not affect the characteristics of uptake. Similar nuclear uptake was demonstrable with cultured MCF-7 cells (derived from human breast cancer) when assayed in the same fashion. When hypertonic extracts of nuclei obtained from skin fibroblasts incubated with 1,25(OH)2[3H]D3 were subjected to centrifugation on sucrose gradients, a single peak of radioactivity sedimented at approximately 3 S; when excess 1,25(OH)2D3 was coincubated during the cellular uptake phase, this 3S peak was not observed. Molybdate was an essential buffer component for receptor stabilization during cell fractionation and sedimentation analysis. In summary, by using fibroblasts cultured from normal human skin, we have identified a process of nuclear uptake of 1,25(OH)2[3H]D3 with the affinity, saturability, and specificity characteristics of a steroid hormone--receptor interaction. This method should be useful in studying 1,25(OH)2D3 recept physiology in cells from normal persons as well as in cells from patients who have disorders in the responsiveness of calciferol target tissues.

Biological Transport↗
PubMed1981

Results of reoperation for persistent and recurrent hyperparathyroidism.

Between August 1975 and January 1981, 106 patients thought to have persistent or recurrent hyperparathyroidism underwent a total of 108 parathyroid re-explorations at the National Institutes of Health. These 106 patients had a total of 175 previous operations for hyperparathyroidism (156 cervical and 19 mediastinal). Nephrolithiasis (54% of patients) and bone disease (24% o patients) were the predominant symptoms. Arteriographic examination and selective venous sampling provided highly accurate localizing results in 33% of the patients, and were of some help in 64%. The final diagnoses after reoperation and re-evaluation were: single-gland disease in 58 patients, primary nonfamilial hyperplasia in 19 patients, familial hyperplasia in three patients, multiple endocrine neoplasia (MEN) Type I in ten patients, MEN Type II in two, parathyroid carcinoma in four patients, secondary hyperplasia in three patients, and familial hypocalciuric hypercalcemia (FHH) in two patients. The diagnosis was in doubt in five patients. In the 95 patients with unequivocal hyperparathyroidism, not due to parathyroid carcinoma, surgery eliminated hypercalcemia in 91 (96%). Two patients died after operation, one of disseminated candidiasis, and one patient, with an immunodeficiency, of sepsis. Five patients developed temporary, and one permanent, recurrent nerve damage; 41% of the patients were hypocalcemic, at the time of discharge from the hospital.

Adenoma↗
PubMed1981

Failure of ablation of a mediastinal parathyroid adenoma by repeated contrast staining.

In a patient with primary hyperparathyroidism an attempt was made to ablate a middle mediastinal parathyroid gland by forceful staining with radiographic contrast material. The gland was stained on two separate occasions, two weeks apart. Both times the serum calcium level temporarily fell to the normal range but reverted to abnormal levels. The patient ultimately required surgery for correction of hypercalcemia. The mechanism of staining and possible reasons for failure as well as potential complications are discussed.

Adenoma↗
PubMed1981

The detection of mediastinal parathyroid glands by computed tomography, selective arteriography, and venous sampling: an analysis of 17 cases.

Computed tomography (CT) scans were reviewed in 19 cases of proved mediastinal parathyroid glands. Glands were detected in five of 17 cases (29%) with adequate scans; four of six (67%) anterior mediastinal glands larger than 2 cm were visible. The smallest lesion demonstrated by CT ws 1.6 cm. In the same series, selective arteriography was positive in 10 of 15 cases (67%), with the smallest lesion measuring 0.5 cm. Venous sampling was performed in 15 patients, and a thymic sample obtained in 10; a twofold step-up of parathyroid hormone in thymic veins was noted in eight of 15 cases (53%), but was not localizing, as samples in other veins were elevated in all but one case. Angiography appears more sensitive than second-generation CT for detecting mediastinal glands. However, CT is very useful in patients with previous failed explorations. Scanning must include contiguous sections extending several centimeters below the carina, in order to encompass low-lying mediastinal glands.

Adenoma↗
PubMed1981

Maximal urine-concentrating ability: familial hypocalciuric hypercalcemia versus typical primary hyperparathyroidism.

Impairment of urine-concentrating ability is common in persons with chronic hypercalcemia. We assessed urine-concentrating ability in 40 patients with typical primary hyperparathyroidism and 10 patients with familial hypocalciuric hypercalcemia, a disorder resembling typical primary hyperparathyroidism but lacking some of its clinical complications. Urine-concentrating ability was determined during a dehydration test of 18-22 h. The two patient groups were comparable with respect to serum calcium concentration and creatinine clearance. In the group with familial hypocalciuric hypercalcemia, the duration of hypercalcemia was probably greater, because it commences during infancy; the urinary excretion rate for calcium was lower [6.6 +/- 5.4 (mean +/- 1 SD) vs. 14.8 +/- 7.5 meq/day; P less than 0.005]. Patients with familial hypocalciuric hypercalcemia showed higher maximal urinary osmolality (800 +/- 150 vs. 664 +/- 130 mosmol/kg; P less than 0.0005). Among the patients with typical primary hyperparathyroidism, there was a negative association between maximal urinary osmolality and urinary cAMP (r = -0.40; P less than 0.05), but there was no significant relation between maximal urinary osmolality and the urinary excretion rate for calcium. Among 18 patients retested within 1 month after surgical correction of typical primary hyperparathyroidism, urine-concentrating ability did not improve. In patients with typical primary hyperparathyroidism, impairment in urine-concentrating ability reflects features of the chronic disease state, as it is not rapidly reversible by correction of that state. However, in patients with familial hypocalciuric hypercalcemia, longstanding hypercalcemia is not associated with obvious impairment of urine-concentrating ability. Complete or partial freedom from impairment of urine-concentrating ability and from calcareous renal disease are expressions of the generally mild course in familial hypocalciuric hypercalcemia.

Calcium↗
PubMed1981

Parathyroid imaging after intraarterial injections of [75Se]selenomethionine.

Thirteen patients with persistent hyperparathyroidism after unsuccessful neck surgery were given up to 250 microCi [75Se]selenomethionine intraarterially during parathyroid arteriography, gamma-Camera images of the neck and mediastinum localized abnormal parathyroids in four of five patients receiving complete injections, despite very small glands or unsuccessful arteriograms in some of the patients. Correctly localizing images were obtained in three patients receiving incomplete injections. However, images in five of eight of the remaining patients receiving incomplete injections showed areas of false positive uptake, and there was no way preoperatively to distinguish these from the true positive studies. We conclude that intraarterial injection of radioselenomethionine is a simple supplementary procedure in patients undergoing arteriography that may, with proper technique, be useful in identifying small foci of abnormal parathyroid tissue.

Humans↗
PubMed1981

Radioimmunoassay for the middle region of human parathyroid hormone: studies with a radioiodinated synthetic peptide.

We radioiodinated a synthetic fragment representing residues 44-68 from the middle region of human parathyroid hormone (hPTH). At least 90% of the purified [125I]-hPTH-(44-68) was able to bind to anti-hPTH serum. Antibody-bound [125I]hPTH-(44-68) could be rapidly and efficiently separated from nonbound radioligand by dextran-coated charcoal. [125I]hPTH-(44-68) was not degraded after a 72-h incubation in undiluted plasma at 7 C, and it was stable for many weeks at -20 C in a 1% albumin buffer. [125I]hPTH-(44-68) was used to develop midregion specific PTH RIAs. The immunoreactive PTH concentration in plasma was above the upper limit of the normal range in 39 of 43 patients with primary hyperparathyroidism. Values from the midregion assay and an established carboxy-terminus assay correlated using peripheral plasma from 17 patients with primary hyperparathyroidism (r = 0.84; P less than 0.0001) or using parathyroid gland venous effluent plasma from the same 17 patients (r = 0.79; P less than 0.0005). Gel filtration analysis of peripheral plasma from 2 patients with primary hyperparathyroidism and azotemia suggested peptides possessing midregion immunoreactivity but deficient in carboxyterminus immunoreactivity. Similar peptides were present at higher concentrations in parathyroid gland venous effluent plasma than in peripheral plasma, indicating release from the parathyroid gland. In conclusion, [125I]hPTH-(44-68) had properties favorable for the development of RIAs reactive solely with the midregion of PTH. Fragments secreted in vivo by two human parathyroid glands were reactive in midregion assays but nonreactive in a carboxy-terminus assay.

Chemical Phenomena↗
PubMed1981

ABO(H) cell surface antigens in parathyroid adenoma and hyperplasia.

Forty-three cases of primary hyperparathyroidism were studied with the specific red cell adherence test (SRCA) to determine the presence or absence of ABO(H) cell surface antigens on abnormal parathyroid tissue. Of the 27 patients with the clinicopathologic diagnosis (CPD) of adenoma, 24 (89%) had lost the ABO(H) cell surface antigen of the abnormal gland. Among the 15 patients with the CPD of hyperplasia, the parathyroid tissue from three (20%) had lost its red cell antigen. In one patient, a metastasis from a parathyroid carcinoma had lost the ABO surface antigen. Several patients in whom conflicting SRCA and CPD were obtained had factors that raised doubts as to the validity of their CPD. The SRCA is a simple test that may aid in the difficult differentiation between parathyroid adenoma and hyperplasia.

ABO Blood-Group System↗
PubMed1980

Adenosine 3',5'-monophosphate response to parathyroid hormone: familial hypocalciuric hypercalcemia versus typical primary hyperparathyroidism.

We investigated cAMP metabolism during and after a 15-min infusion of parathyroid hormone (PTH) in 7 normals, 13 patients with typical primary hyperparathyroidism (1HPT), and 6 patients with familial hypocalciuric hypercalcemia (FHH). Nephrogenous urinary cAMP excretion rate reached a peak during the first or second 30 min urine collection interval after the start of the PTH infusion in all subjects. cAMP concentration in plasma reached a peak within 5--20 min of the start of the infusion and then decreased with an initial half-time of 15 min. The peak value of nephrogenous urinary cAMP excretion rate was lower in the group with 1HPT than in the group with FHH or in normals (119 vs, 275 vs. 204 nmol/100 ml glomerular filtrate; P less than 0.0 5 for both comparisons). Similarly, the peak value of plasma cAMP concentration was less in 1HPT subjects than in FHH patients or in normals (11.1 vs. 17.1 vs. 16.6 nmol/100 ml, respectively; P less than 0.05 for both comparisons). For purposes of diagnostic classification, the two hypercalcemia groups could be more completely separated by the values of either the renal calcium to creatinine clearance ratio or the plasma PTH concentration than by the values of inidices of cAMP response to PTH. The differences in cAMP response to PTH between FHH and 1HPT patients could be secondary to differences in circulating PTH concentrations (these are lower in subjects with FHH) or could reflect a renal lesion more closely related to the underlying etiology of FHH.

Cyclic AMP↗
PubMed1980

Normal intrauterine development of the fetus of a woman receiving extraordinarily high doses of 1,25-dihydroxyvitamin D3.

We monitored the course of pregnancy in a 28-yr-old patient with hereditary insensitivity to 1,25-dihydroxyvitamin D (1,25-(OH)2D). During pregnancy, she received 1,24-(OH)2D3 in doses of 17--36 micrograms/day (usual dose for hypocalcemia, 0.25--1.0 microgram/day). We separately measured 25-hydroxyvitamin D3 (25OHD3), 25OHD2, 1,25-(OH)2D3, and 1,25-(OH)2D2 to assess contributions to total 1.25-(OH)2D from endogenous biosynthesis (1 alpha-hydroxylation of 25OHD2 or 25OHD3) vs. contributions from exogenously administered 1.25-(OH)2D3. Serum concentrations of 1,25-(OH)2D were extraordinarily high throughout gestation. The evaluations of total 1,25-(OH)2D in maternal plasma reflected large amounts from both 1 alpha-hydroxylation of 25OHD and oral intake of 1,25-(OH)2D3. At parturition, the calcium concentration was 9.6 mg/dl in maternal serum and 10.2 mg/dl in cord serum. The concentration of total 1,25-(OH)2D in cord serum was high (470 pg/ml; normal mean for placental venous serum, 19 pg/ml); most derived from transplacental passage of maternal 1,25-(OH)2D3 and not from fetoplacental biosynthesis. The child manifested mild hypercalcemia in the first 2 days of life, indicating that the 1,25-(OH)2D3 measured in cord serum was active in vivo. The child showed no somatic features of the syndrome of elfin facies and supravalvular aortic stenosis. We conclude that an extraordinarily high concentration of 1.25-(OH)2D in maternal serum throughout gestation was not apparently toxic to the fetoplacental unit, though the maternal metabolite entered the fetal circulation.

Adolescent↗