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G D Aurbach

Publications and source records attributed to G D Aurbach.

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

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↗
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↗
PubMed1979

Inhibition of adenosine 3',5'-monophosphate accumulation and parathyroid hormone release by sodium nitroprusside.

Sodium nitroprusside effected a significant reduction in intracellular cAMP accumulation and parathyroid hormone release in dispersed bovine parathyroid cells. The inhibition was apparent at 3 x 10-4 M and maximal at 10-2 M nitroprusside. The effect was rapid and reversible and could be demonstrated in both the presence and absence of stimulating agonists [i.e. (-)isoproterenol, dopamine, and cholera toxin]. The inhibition was additive with that previously described for alpha-adrenergic agonists and prostaglandin F2 alpha and was not affected by phentolamine, suggesting that nitroprusside does not act through the inhibitory receptors previously described in this system. The nitroprusside effect on cAMP accumulation and parathyroid hormone release was present at virtually all concentrations of extracellular calcium tested; 2mM EGTA failed to prevent the inhibition. While extracellular calcium may play some role in this inhibition, it is not required for demonstration of the effect.

Animals↗
PubMed1979

Separation of a guanine nucleotide regulatory unit from the adenylate cyclase complex with GTP affinity chromatography.

We studied the relationship between guanine nucleotide binding proteins and adenylate cyclase activity of solubilized turkey erythrocyte membranes with GTP affinity chromatography. Solubilized adenylate cyclase from untreated membranes or membranes pretreated with GMP only (GMP prep) responded poorly to GTP or Gpp(NH)p but were markedly stimulated by fluoride. The solubilized enzyme from membranes pretreated with isoproterenol+GMP (ISO+GMP prep) did not respond to GTP but was markedly stimulated by Gpp(NH)p. Fluoride-stimulated activity of the ISO+GMP prep was reduced by comparison with the GMP prep but could be increased significantly by addition of GTP. GTP hexane agarose (GTP linked to matrix via morpholine derivative of ribose) failed to interact specifically with either the GMP or ISO+GMP prep. Incubation of ISO+GMP prep with GTP-gamma-agarose (GTP linked to matrix via terminal phosphate) reduced the Gpp(NH)p response and the GTP-dependent fraction of the fluoride response. GTP-gamma-agarose did not reduce the fluoride response of the GMP prep. Following incubation with ISO+GMP prep, GTP-gamma-agarose beads were eluted with buffer containing Gpp(NH)p. The eluate had only slight intrinsic adenylate cyclase activity but was able to increase significantly the activity of GTP-gamma-agarose-treated ISO+GMP prep as well as untreated GMP prep. An eluate from GTP-gamma-agarose beads incubated with GMP prep did not possess activity. Our results suggest that the guanine nucleotide-regulatory unit is reversibly associated with the adenylate cyclase complex of turkey erythrocyte membranes.

Adenylyl Cyclases↗
PubMed1978

Hypercalcemia with suppressed parathyroid hormone in Burkitt's lymphoma.

Two patients with Burkitt's lymphoma presented with severe hypercalcemia, a previously unreported complication of this tumor. Roentgenograms and radionuclide scans showed multiple osteolytic lesions in both patients. Plasma parathyroid hormone (PTH) was undetectable during the hypercalcemia phase. Chemotherapy was followed by rapid tumor lysis, hyperphosphatemia, phosphaturia and hypocalcemia. The hypocalcemic phase persisted for two weeks despite rapid normalization of serum phosphorus and renal function. Measurement of urinary cyclic AMP, an index of PTH action, indicated that parathyroid function had been suppressed by the hypercalcemia and remained suppressed for almost one week despite marked hypocalcemia.

Adult↗
PubMed1978

Role of anions in parathyroid hormone release from dispersed bovine parathyroid cells.

It is known that permeant anions are required for the release of epinephrine from isolated chromaffin granules and of serotonin from intact platelets. We have now investigated the role of anions in the release of a polypeptide hormone, parathyroid hormone, from dispersed bovine parathyroid cells. The release is inhibited 60%-80% by decreasing either [Cl-] or [OH-] and 60%-70% by replacement of NaCl with the impermeant anion isethionate. By contrast, substitution of various monovalent cations in the medium had no effect on the release. Disodium 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonate (SITS) and probenecid, which are known to block anion transport in the erythrocyte, also cause a dose-dependent 90%-100% inhibition of release. Moreover, kinetic analysis of inhibition by probenecid suggests that it is competitive with respect to either OH- or Cl-. These results suggest that anions and the anion transport system may play a role in exocytosis of a polypeptide hormone. The proton ionophore carbonyl cyanide p-trifluoromethoxyphenylhydrazone was was also found to block hormone release, and the possibility is discussed of a "chemosmotic" mechanism for exocytosis in this system similar to that previously postulated for chromaffin granules and platelets.

Animals↗
PubMed1978

Human parathyroid cryopreservation: in vitro testing of function by parathyroid hormone release.

The functional viability of cryopreserved human parathyroid tissue was assessed by determining suppressibility of parathyroid hormone release by evaluation of ambient calcium concentration. Parathyroid hormone release from dispersed human parathyroid cells prepared from both fresh tissue and tissue cryopreserved for up to 200 days was suppressed 0-90% in response to four-fold increases in calcium concentration. In the tissue that demonstrated suppression precryopreservation, the suppression curve was similar in form postcryopreservation. The ability to retain functional integrity within human parathyroid cells by cryopreservation, allows preservation for periods of time probably sufficient to determine the presence of the aparathyroid state, and allows for subsequent successful parathyroid autotransplantation. This technique has particular applicability to patients reoperated upon for persistent hyperparathyroidism where the remaining amount of normal parathyroid tissue is obscure or unknown.

Calcium↗