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S J Marx

Publications and source records attributed to S J Marx.

At least 19 recordsLinked to original sources
PubMed1992

Allelic loss from chromosome 11 in parathyroid tumors.

Parathyroid tumors may occur in a sporadic fashion or, more rarely, as part of a familial syndrome (such as familial multiple endocrine neoplasia type I). The MENI gene has been mapped by linkage analysis to chromosome 11 at band q11-q13, and presumably acts as a tumor suppressor gene. In the present study, which is an extension of our previous studies, we examined 41 parathyroid tumors from patients with familial multiple endocrine neoplasia type I and 61 sporadic parathyroid tumors with markers on chromosome 11, to assess the extent of allelic loss in those tumors. Twenty-four of the MENI-associated tumors (58%) and 16 of the sporadic parathyroid tumors (26%) displayed allelic loss from chromosome 11. The region of overlap of the allelic losses in the MENI-associated tumors enables us to place the MENI gene between PGA centromerically and INT2 telomerically, a region spanning about 7.5 cM. Taken together with locus ordering by linkage analysis, this clearly localizes the MENI gene telomeric to the PGA locus. Our inability to detect allelic loss on chromosome 11 in some parathyroid tumors suggests the existence of other genes involved in the development and/or progression of this subgroup of presumably monoclonal tumors; or that localized events involving the 11q tumor suppressor gene have occurred in some parathyroid tumors whose detection is beyond the sensitivity of our analysis; or that at least some of the specimens analyzed were in fact primarily hyperplastic parathyroid tissue.

Adenoma↗
PubMed1992

Rapid effects of insulin on cyclic GMP location in an intact protozoan.

We studied rapid changes in location of cyclic GMP in Tetrahymena pyriformis. Insulin caused cGMP localization in cilia and near the plasma membrane (0.5-1 min). Later (1-5 min) cGMP localization was diffuse in cytoplasm with perinuclear accentuation. Inactive insulin analogs did not elicit these changes.

1-Methyl-3-isobutylxanthine↗
PubMed1992

Results of a multidisciplinary strategy for management of mediastinal parathyroid adenoma as a cause of persistent primary hyperparathyroidism.

Persistent primary hyperparathyroidism due to mediastinal parathyroid adenoma was effectively treated by either angiographic ablation or median sternotomy in this study of 49 patients managed at the National Institutes of Health since 1977. Each patient presented here with symptomatic persistent primary hyperparathyroidism after failed initial surgical procedures done at other institutions. Each patient underwent extensive parathyroid localization procedures, including selective angiography, and most had a parathyroid adenoma localized to the mediastinum. Angiographic ablation, the deliberate injection of large doses of contrast material into the artery that selectively perfuses the adenoma, was initially successful in 22 of 30 procedures (73%) in 27 patients. Long-term control of persistent primary hyperparathyroidism was achieved in 17 of 27 patients (63%) by angiographic ablation. Each unsuccessful ablation could be easily salvaged by surgical resection. Surgical resection of the parathyroid adenoma by median sternotomy achieved immediate success in 24 of 24 procedures (p2 less than 0.02 versus ablation), and long-term cure in 23 of 23 evaluable patients (p2 less than 0.001 versus ablation). However, ablation did have benefits for the patients in whom it was successfully performed. It was associated with a significantly shorter hospital stay (median, 6 days versus 9 days for sternotomy, p2 less than 0.003), much less pain, and easier recuperation. Complications of each procedure were transient and similar in both groups. Operative resection is the most effective single means to eradicate mediastinal parathyroid adenoma; however, angiographic ablation can provide similar long-term control of hyperparathyroidism in 63% of patients with less pain and shorter convalescence than that seen in patients after median sternotomy. Our results suggest that angiographic ablation should be attempted as the initial procedure for patients with persistent primary hyperparathyroidism caused by an angiographically identified mediastinal parathyroid adenoma. Operation can be reserved for those who fail ablation.

Adenoma↗
PubMed1991

Rapid accumulation of cyclic GMP near activated vitamin D receptors.

The mechanisms of early calcitriol (1 alpha,25-dihydroxycholecalciferol) effects, including its receptor activation process as well as its "nongenomic" effects, are poorly understood. Calcitriol causes a rapid accumulation of cGMP, dependent on the presence of normal vitamin D receptors (VDRs). We recently developed an immunocytology method based on rapid microwave fixation suitable to detect the locations of agonist-induced intracellular cGMP accumulation. With the same technique we found that calcitriol induces stepwise and rapid reorganization of VDRs. Here we used this technique to study the subcellular compartmentalization of cGMP accumulation after exposure of cells to various steroid-related agonists and to study the spatial relationship between cGMP accumulation and VDRs. Calcitriol (10 nM) within 15 sec caused clumping of VDRs and accumulation of cGMP around VDR clumps; thereafter (up to 5 min), the cGMP accumulation surrounded VDRs throughout their stepwise reorganization. In fibroblasts from subjects with mutations affecting VDR function, we found disruptions of the calcitriol-induced patterns of cGMP accumulation analogous to the disruptions of VDR reorganization. The colocalization of cGMP accumulation with reorganizing VDRs at early moments after calcitriol addition indicates transduction of the cGMP increase by VDRs inside the cell, rather than by components in the plasma membrane. Other steroid-related agonists caused compartmentalized and sequential changes in cGMP accumulation that seemed specific for each class of agonist. Our findings suggest that compartmentalized cGMP accumulation is an early and common step during activation of steroid-related receptors.

Animals↗
PubMed1991

Etiologies of parathyroid gland dysfunction in primary hyperparathyroidism.

Primary hyperparathyroidism is caused by defects in the parathyroid gland. Investigations have implicated three interesting genes whose mutation can cause primary hyperparathyroidism. Familial hypocalciuric hypercalcemia is believed to be an atypical form of primary hyperparathyroidism with an inherited defect in calcium recognition expressed not only in all parathyroid chief cells (thus a polyclonal defect) but in some renal tubular cells as well. In typical primary hyperparathyroidism a monoclonal parathyroid tumor is usually the central cause. Either of two apparently different genes on the long arm of chromosome 11 has been implicated in development of a parathyroid tumor clone. One gene (D11S287) was shown to have undergone a rearrangement with the parathyroid hormone gene on the short arm of the same chromosome (pericentromeric inversion) in a small fraction of tumors; the D11S287 locus may encode a growth stimulator. Another gene, the locus for familial multiple endocrine neoplasia type 1 (FEMEN1), is likely to encode a growth inhibitor. Inactivation of this gene or another nearby gene by somatic mutation has been indirectly implicated in one-quarter of sporadic parathyroid adenomas and in more than half of parathyroid tumors in FMEN1. In conclusion, studies have suggested three different mechanisms for parathyroid gland dysfunction in primary hyperparathyroidism: (1) a defect in calcium recognition, (2) a monoclonal tumor from overexpression of a growth stimulator, or (3) a monoclonal tumor from inactivation of a growth inhibitor.

Adenoma↗
PubMed1991

Heterogeneous size of the parathyroid glands in familial multiple endocrine neoplasia type 1.

OBJECTIVE: We wished to determine whether there was size heterogeneity of the parathyroid glands in patients with familial multiple endocrine neoplasia type 1 (FMEN1) and primary hyperparathyroidism. DESIGN: At the National Institutes of Health we performed a retrospective analysis of parathyroid gland volume either from initial or repeat parathyroid exploration. PATIENTS: We studied subjects with FMEN1 and primary hyperparathyroidism. MEASUREMENTS: The parathyroid gland volume was estimated from recorded orthogonal diameters. Volume could also be estimated conservatively in many glands for which one or more diameters were not recorded. Reproducibility of volume measurements was tested with a series of clay gland models. Indices of variability (among glands at an operation or among replicate measurements of a clay model) were the ratio of maximum volume/minimum volume and the average standard deviation of the log volume. RESULTS: The most complete data were from eight initial operations with three dimensions recorded for all four glands. Volume heterogeneity was indicated by the average ratio of 9.6 for the maximum/minimum gland volume within an operation. The size heterogeneity was even greater among other subgroups. For example, the average ratio of maximum/minimum gland volume within an operation was 17 among five initial operations with four glands removed, but lacking measurements of three dimensions for some glands. Little of this size heterogeneity could be attributed to measurement error since eight replicate measurements on a model gland yielded a maximum/minimum volume ratio of 1.45. CONCLUSIONS: There is a wide heterogeneity in size of the parathyroid glands in the patients with FMEN1 and primary hyperparathyroidism.

Humans↗
PubMed1991

Overexpression of the human vitamin D3 receptor in mammalian cells using recombinant adenovirus vectors.

The human vitamin D3 receptor (hVDR) cDNA was cloned into the E1 region of the adenovirus genome to generate recombinant viruses which were used to infect 293 (adenovirus-transformed human fetal kidney) cells. High salt extracts from cells infected with the recombinant viruses were subjected to immunoblot analysis using a monoclonal antibody to chicken VDR and were shown to contain large quantities of a protein of approximately 50 kDa with a migration identical to that of the hVDR in T47D (human mammary adenocarcinoma) cells. Scatchard analysis showed that the infected cells express approximately 100-fold more receptor than T47D cells and that this receptor binds 1,25-dihydroxyvitamin D3 with high affinity. The overexpressed hVDR also binds to DNA-cellulose and is eluted with a KCl concentration similar to that determined for fully active endogenous VDR. Nuclear extracts from cells infected with the hVDR-expressing adenoviruses contain an activity that specifically binds an oligonucleotide with sequences from the rat osteocalcin vitamin D3 response element, as determined by gel mobility shift. This interaction can be inhibited by the presence of an anti-VDR antibody, but not by nonspecific immunoglobulins. We conclude, therefore, that the overexpressed receptor has the ligand- and DNA-binding characteristics defined for endogenous VDR and that adenoviruses can be used to efficiently express large quantities of functional hVDR in a human cell line. Finally, a second binding activity, specific for the vitamin D response element, but distinct from the VDR, has been identified in extracts from uninfected cells.

Adenoviruses, Human↗
PubMed1979

Autotransplantation of cryopreserved parathyroid tissue in man.

Human cryopreserved parathyroid autografts have been performed in six patients following reoperative parathyroid surgery. All patients were rendered hypoparathyroid by their most recent reoperation. Parathyroid tissue was successfully autotransplanted after as long as eighteen months of cryopreservation. Viability and expected in vivo function of cryopreserved parathyroid tissue may be predicted by in vitro testing of parathyroid hormone secretion in response to varying ambient calcium concentration. Parathyroid cryopreservation with subsequent autotransplantation is a practical solution to the problem of permanent hypoparathyroidism that may follow multiple surgical procedures for persistent hyperparathyroidism.

Calcium↗
PubMed1979

Angiographic ablation of parathyroid adenomas.

Six mediastinal parathyroid adenomas were stained by infusing contrast agent through a catheter wedged in the feeding artery. Adenomas in the first three cases were stained unintentionally with small volumes of dilute contrast media and hypercalcemia recurred within 3 to 6 months. In the next three patients, adenomas were deliberately stained with larger doses of concentrated contrast media and these patients have remained normocalcemic from 2 to 18 months following staining. The permanency of parathyroid ablation following deliberate staining with contrast media has not been established.

Adenoma↗
PubMed1978

Experimental cryopreservation and autotransplantation of parathyroid glands: technique and demonstration of function.

A canine model for cryopreservation and autotransplantation of parathyroid glands was developed as a prototype for cryopreservation of human parathyroid glands; Each of 18 dogs had two parathyroids removed, sectioned, and cooled at a controlled rate to -80 degrees in media containing 10% dimethylsulfoxide and 10% autologous serum. After storage for two months at -196 degrees the tissue was thawed and implanted in muscle; the remaining two parathyroid glands were removed from the neck. Function was assessed by monitoring serum calcium levels and measuring parathyroid hormone levels in venous effluent from the graft beds. Autograft function was demonstrated in ten of 18 dogs; graft failure occurred in four dogs. In the remaining four dogs, function could not be evaluated because of accessory parathyroid tissue. Parathyroid tissue cryopreserved for nine months was documented to function in six of seven dogs. Histologic study of the cryopreserved, autografted tissue showed normal parathyroid architecture.

Animals↗
PubMed1978

Dermatoglyphic and radiographic findings in a mother and daughter with pseudohypoparathyroidism.

The dermatoglyphic features of a mother and daughter with pseudohypoparathyroidism were compared with those of 19 other reported PHP cases and with findings typical of 45,X Turner syndrome. Our observations included large patterns with a predominance of whorls, unusual accidental patterns on the third fingers, elevated total and absolute finger ridge counts, extralimital digital triradii, intermediately placed axial triradii, and a single complete transverse palmar crease. With barium-coated hand radiographs, the positions of the palmar digital triradii were compared with those of the underlying metacarpal and carpal bones. Normally, the fourth digital triradii (c) are superficial to the epiphyseal region of the proximal phalanx, near the fourth M-P joint. In our cases, the c triradii were distal to the proximal phalanx, near the fourth M-P joint. In our cases, the c triradii were distal to the M-P joint, adjacent to the diaphysis of the proximal phalanx. These findings, related to post-natal differences in growth potential of osseous structures and overlying dermal ridge tissues in this disease, may also be relevant to other syndromes with abnormal development of the hand. The need for further delineation of PHP dermatoglyphics and comparison of findings with data from Turner syndrome and normals is stressed.

Adult↗