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Biomedical subjects

M D Gross

Publications and source records attributed to M D Gross.

At least 145 records · Page 8Linked to original sources
PubMed1989

Lipoprotein incorporation enhances radioiodinated cholesteryl ester uptake into steroid hormone-secreting tissues.

This study was undertaken to determine whether incorporation of radioiodinated cholesterol derivatives into plasma lipoproteins prior to administration to animals could lead to improvements in adrenal localization of radioactivity. Rat high density lipoproteins (HDL) were labeled with [125I]cholesteryl iopanoate, a nonhydrolyzable ester of cholesterol. No enhancement in adrenal uptake of radioactivity was noted at 30 min following administration of the HDL preparation to control rats when compared with [125I]NP-59. However, when animals were made hypolipidemic by treatment with either 4-APP or ethinyl estradiol, the adrenal radioactivity after i.v. administration of the HDL preparation was found to be over 15 times greater than that achieved with [125I]NP-59. Scans of hypolipidemic rats taken at 30 min correlated well with the tissue distribution results.

Adrenal Cortex↗
PubMed1988

Distinguishing benign from malignant euadrenal masses.

STUDY OBJECTIVE: To determine the efficacy of 131I-6-beta-iodomethylnorcholesterol (NP-59) adrenal scintigraphy in distinguishing benign from malignant euadrenal masses. DESIGN: Case series of patients with incidentally discovered unilateral, euadrenal masses. SETTING: Referral-based nuclear medicine clinics at university and affiliated Veterans Administration medical centers. PATIENTS: Consecutive sample of 119 euadrenal patients with unilateral adrenal masses discovered on computed tomographic (CT) scans for reasons other than suspected adrenal disease. INTERVENTIONS: Adrenal scintiscans done using 1 mCi of NP-59 intravenously, and gamma camera imaging 5 to 7 days later. MEASUREMENTS AND MAIN RESULTS: Mean lesion diameter was 3.3 +/- 1.9 cm (SD) (95% CI: 2.9 to 3.6 cm). In 76 patients, NP-59 uptake lateralized to the abnormal adrenal seen on CT scans (concordant imaging), and in all of these patients, a diagnosis of adenoma was made by needle-aspiration biopsy, adrenalectomy, or extended follow-up with repeat CT scans that were unchanged at 6 months or later. Twenty-six patients had absent or markedly reduced NP-59 uptake in the glands identified as abnormal on CT scans (discordant imaging). These adrenal masses proved to be metastatic malignancies in 19 patients, primary adrenal neoplasms other than adenoma in 4, and adrenal cysts in 3. Bilateral, symmetric accumulation of NP-59 was seen in 17 patients, in whom the adrenal masses were shown to be metastatic malignancies in 2, and adenomas in 6 (the lesions in these cases being 2 cm or less in diameter), and lesions not truly involving the adrenal in the rest (periadrenal metastases in 4 and pseudoadrenal masses in 5). Sensitivity was 76% (26 of 34 patients; CI, 58% to 88%); specificity, 100% (85 of 85 patients; CI, 95% to 100%), and accuracy, 93% (111 of 119 patients: CI, 88% to 98%). CONCLUSIONS: Functional NP-59 scintigraphy can be used to accurately and noninvasively characterize many euadrenal masses; concordance of CT and NP-59 scans can be used to exclude the presence of a malignancy or other space-occupying adrenal lesion.

19-Iodocholesterol↗
PubMed1988

Expression in Escherichia coli of full-length and mutant rat brain calbindin D28. Comparison with the purified native protein.

Studies of vitamin D-dependent 28-kilodalton calcium binding protein (calbindin D28) have been hindered by difficulties in purifying large amounts of the protein. In order to overcome this problem, we cloned and expressed a full-length rat brain calbindin D28 cDNA. In addition, we isolated and purified to homogeneity, native rat brain calbindin D28. The isolated native protein has an apparent molecular mass of 27 kDa and properties similar to those of the well-characterized chicken calbindin D28. It has an acidic isoelectric point (approximately 4.5), a high affinity for calcium, and an amino terminus blocked to Edman degradation. The properties of the native and the recombinant proteins were examined by gel electrophoresis, isoelectric focusing, protein sequencing, amino acid composition analysis, and calcium binding assays. We demonstrated that: (i) the authentic and the full-length recombinant proteins have similar molecular weights and isoelectric points; (ii) the proteins have the same amino acid composition; (iii) the proteins bind calcium in a similar manner; (iv) the absence of a blocking NH2-terminal group in the recombinant protein does not appreciably influence the binding of calcium. To further examine the calcium binding properties of this protein, we constructed deletion mutants lacking one or both of the two putative degenerated calcium binding sites (EF hand regions). These deletions resulted in smaller proteins that still bound calcium. The ability to express and purify calbindin D28 and mutants thereof should allow the systematic elucidation of structure-function relationships in this class of calcium binding proteins.

Amino Acid Sequence↗
PubMed1988

Adrenal localization in the adrenocorticotropic hormone-independent Cushing syndrome.

STUDY OBJECTIVE: To assess the efficacy of 131I-6-beta-iodomethylnorcholesterol scintigraphy in the adrenocorticotropic hormone-independent Cushing syndrome and to compare this with computed tomography. DESIGN: Retrospective analysis of case series from 1977 to 1987. SETTING: Referral to the Division of Nuclear Medicine at a tertiary-care university medical center. PATIENTS: Twenty-four patients with a pathologically-confirmed diagnosis of the adrenocorticotropic hormone-independent Cushing syndrome had 131I-6-beta-iodomethylnorcholesterol scintigraphy and, in most cases, computed tomography. MEASUREMENTS AND MAIN RESULTS: Using 131I-6-beta-iodomethylnorcholesterol scintigraphy, adenomas were accurately seen as focal, unilateral tracer uptake in 14 of 14 patients. In carcinoma, the classic scintigraphic pattern of bilateral nonvisualization was observed in 3 of 4 patients, with ipsilateral uptake of tracer in 1 patient with a histologically well-differentiated malignancy. Computed tomography done during the same interval depicted abnormal adrenals in all cases of adenoma and carcinoma. In cortical nodular hyperplasia, however, computed tomography identified abnormal pairs of adrenals in only one of four cases studied, whereas scintigraphy showed typical patterns of bilateral increased uptake in all of the cases. CONCLUSION: 131I-6-beta-iodomethylnorcholesterol scintigraphy accurately shows the location and nature of adrenal dysfunction in the adrenocorticotropic hormone-independent Cushing syndrome and may be particularly useful in identifying the bilateral adrenal involvement in cortical nodular hyperplasia.

19-Iodocholesterol↗
PubMed1988

Radionuclide determination of the relationship between left ventricular contractile state and ejection fraction.

To determine whether the relationship between various measures of left ventricular (LV) contractile state and ejection fraction (EF) is linear in man, we studied 30 patients during right atrial pacing over a range of loading conditions. With the use of micromanometer LV pressures and radionuclide LV volumes, pressure-volume (P-V) loops were generated for each loading condition. Then isochronal, instantaneous P-V data points were obtained by linear regression analysis to attain the maximum slope (Emax) of these time-varying isochrones. Other measures of LV end systole were also used to calculate end-systolic P-V relations in a similar fashion, and indirect P-V relations were obtained from the linear regression analysis of brachial artery peak pressure vs minimum LV volume data points. When the slopes of these LV contractile measures were compared to the radionuclide LV EFs, the linear correlation coefficients ranged from 0.53 to 0.67. After natural log transformation of the LV contractile state and EF data, the correlation coefficients for the polynomial curve fits ranged from 0.80 to 0.88. When the correlation coefficients for the polynomial curve fits of the natural log transformed data were compared to those for the linear regression analyses of the raw data, significant improvements were evident (p less than 0.05). Thus the relationship between various measures of LV contractile state and EF obtained with radionuclide angiography is best approximated by a complex, curvilinear relationship that is due, in part, to the wide range of LV contractile states within the relatively narrow normal range of LV ejection fractions.

Adult↗
PubMed1988

Multiple forms of rat kidney L-arginine:glycine amidinotransferase.

The relative amount of L-arginine:glycine amidinotransferase (transamidinase) protein in kidneys from rats fed a complete purified diet with and without the addition of creatine and/or glycine was determined by a monoclonal antibody-immunosorbent inhibition assay. Kidneys from the creatine-fed rats had 10% of the transamidinase activities and 78% of the monoclonal antibody immunoreactive transamidinase protein as kidneys from the control rats. An excellent correlation between transamidinase activities and protein was reported previously when the amounts of enzyme protein were determined by immunotitration with polyclonal antibodies. One possible explanation for the contrasting results was that multiple forms of transamidinase are present in rat kidneys. If so, the monoclonal antibody may have recognized forms of the enzyme that were not decreased in amounts commensurate with the decrease in enzyme activities as a result of creatine feeding. Evidence is presented in this report that multiple forms of transamidinase are present in rat kidneys. The distribution of the isoelectric points of the individual forms of transamidinase in kidneys of the control rats appeared to be dissimilar from that in the creatine-fed rats. Therefore, an alteration in the distribution of the individual forms of the enzyme may be a factor in the alteration of transamidinase activities in creatine-fed rats.

Amidinotransferases↗
PubMed1988

Adrenal masses in oncologic patients: functional and morphologic evaluation.

The role of adrenocortical scintigraphy in the evaluation of unilateral adrenal masses detected with computed tomography (CT) in 28 oncologic patients with normal adrenal function was studied prospectively with the use of NP-59 (iodine-131-6-iodomethyl-19-norcholesterol). The diagnosis was proved by means of percutaneous fine-needle aspiration cytologic examination in 20 patients, surgical biopsy in one, and clinical and CT follow-up in seven. In 14 of the 28 patients, there was increased uptake of the NP-59 on the side of the adrenal mass detected at CT (concordant uptake). Thirteen of the 14 masses with concordant uptake were greater than 2 cm in diameter, and one was 1.5 cm; all were found to be adenomas. In 11 of 28 patients there was decreased uptake on the side of the mass detected at CT (discordant uptake). None of these 11 masses were adenomas; nine were metastases and two were adrenal cysts. Uptake was indeterminate (symmetric) in three patients, two of whom had adrenal adenomas and one an adrenal metastasis; each mass with indeterminate uptake was less than 2 cm in diameter.

Adosterol↗
PubMed1988

Scintigraphic localization of ovarian dysfunction.

To assess the potential role of scintigraphy in the evaluation of clinically and biochemically suspect ovarian hyperandrogenism (HA), dexamethasone suppression 131I-6 beta-iodomethyl-19-norcholesterol (NP-59) scans were performed to characterize ovarian function in nine patients. Pelvic ultrasound and/or computed tomography (CT) identified anatomic abnormalities in the adnexal region in six women in whom there was discernible pelvic accumulation(s) of NP-59. In the remaining three patients testosterone levels were normal or only slightly elevated and the NP-59 scan did not demonstrate abnormal adrenal or pelvic uptake. CT and/or ultrasound studies failed to demonstrate an abnormality in the pelvis suggesting excessive peripheral conversion or abnormal end organ sensitivity of androgen precursors as potential etiologies of their HA. In three women with androgen secreting lipoid tumors of the ovary, unilateral, pelvic NP-59 activity was noted; these tumors were subsequently resected. Two women with bilateral pelvic NP-59 uptake were later shown to have hyperthecosis with markedly asymmetric and enlarged ovaries. In one woman the extent of asymmetric NP-59 uptake was anticipated by the asymmetry of ovarian vein androgen levels at selective venous catheterization. In another woman with markedly asymmetric polycystic ovary disease, intense focal uptake of NP-59 localized to the side of the anatomically abnormal, enlarged ovary. Thus, our preliminary study reviews our experience to date and suggests that NP-59 scintigraphy may be used to localize both tumorous and nontumorous ovarian dysfunction in states of HA and virilization.

Adosterol↗
PubMed1988

Assessment of the radionuclide angiographic left ventricular maximum time-varying elastance calculation in man.

This investigation was designed to determine whether left ventricular (LV) maximum time-varying elastance (Emax) calculations obtained using equilibrium radionuclide angiography (RNA) were comparable to those obtained using biplane contrast cineangiography (CINE), and whether simple, indirect P-V relations might provide reasonable, alternative estimates of Emax. Accordingly, we studied 19 patients with simultaneous high-fidelity micromanometer LV and fluid brachial artery (Ba) pressure recordings, CINE, and RNA under control conditions and during methoxamine and nitroprusside infusions. Emax was defined for CINE and RNA as the maximum slope of the linear relation of isochronal, instantaneous P-V data points obtained from each of the three loading conditions. The indirect P-V relations were similarly obtained from Ba peak (P) pressure versus minimum RNA LV volume (BaP/minV) and Ba dicrotic notch (di) pressure versus minimum RNA LV volume (Badi/minV) data points. The mean heart rates and LV (+)dP/dtmax values were minimally altered during the three loading conditions. The isochronal Emax values ranged from 1.40 to 6.73 mmHg/ml (mean 4.13 +/- 1.99 s.d. mmHg/ml) for CINE and from 1.48 to 7.25 (mean 4.35 +/- 1.81 mmHg/ml) for RNA (p = N.S.). Similarly, the unstressed volumes ranged from -10 to 80 ml (mean 30 +/- 23 ml) for CINE and from -8 to 77 ml (29 +/- 21 ml) for RNA (p = N.S.). The individual, isochronal Emax values by RNA correlated with those by CINE (r = 0.86). In 14 of the 19 patients, the BaP/minV and Badi/minV relations correlated with the isochronal Emax values calculated by RNA (r = 0.83 and 0.82, respectively), and these relations also correlated with the Emax values calculated by CINE (r = 0.82 and 0.78, respectively). The slope and V0 values for the BaP/minV and Badi/minV relations underestimated those for Emax by RNA and CINE (p less than 0.01 and p less than 0.05, respectively, for both). Thus, the isochronal Emax values calculated using RNA are comparable to those obtained using CINE in man. Moreover, indirect P-V relations underestimate these Emax values, but they are linearly related with the isochronal Emax values calculated by RNA and CINE. Consequently, these indirect P-V relations may provide a more simple, alternative estimate of LV contractile function in man.

Adult↗
PubMed1987

Atrial natriuretic hormone secretion in patients with renal failure.

To study the effects of volume overload and renal failure on plasma levels of immunoreactive atrial natriuretic hormone (IR-ANH), we measured levels of this hormone in normal subjects, in patients with advanced chronic renal failure (CRF) with and without clinically evident volume overload, and in patients with end-stage renal disease (ESRD) treated with chronic hemodialysis. The levels were 13 +/- 2 pmol/l in normal volunteers, 77 +/- 24 pmol/l in patients with CRF without volume overload, and 219 +/- 50 pmol/l in patients with CRF and clinically evident volume overload (analysis of variance, p less than 0.001, alpha = 0.05 compared to normals). In patients with ESRD, the levels of IR-ANH were 145 +/- 46 pmol/l before dialysis and decreased to 87 +/- 31 after dialysis (p less than 0.025). No correlation was found between the decrease in IR-ANH levels and the decrease in weight during dialysis. A significant positive correlation was found between the IR-ANH levels and blood urea nitrogen in patients with CRF (r = 0.658, p less than 0.01). Volume overload appears to be the most important stimulatory factor for ANH secretion in renal failure patients but other mechanisms, especially a decrease in metabolic clearance, may also contribute to elevated plasma levels. The increased secretion of ANH in patients with renal failure may be an important adaptive response to volume overload and hypertension.

Adult↗
PubMed1987

Observations on the binding of lanthanides and calcium to vitamin D-dependent chick intestinal calcium-binding protein. Implications regarding calcium-binding protein function.

The binding of calcium and terbium to purified chick vitamin D-dependent intestinal calcium-binding protein was studied by terbium fluorescence, circular dichroism, and intrinsic protein fluorescence techniques. Calcium-binding protein bound, with high affinity, at least 3 mol of terbium/mol of protein; numerous low affinity terbium-binding sites were also noted. The three highest affinity sites were resolved into one very high affinity site (site A) and two other sites (sites B and C) with slightly lower affinity. Resonance energy transfer from tryptophan residues to terbium occurred only with site A. This site was filled before sites B and C. Competition experiments in which calcium was used to displace terbium bound to the protein showed that larger amounts of calcium were needed to displace terbium from site A than from sites B and C. Energy transfer from terbium to holmium indicated that the terbium-binding sites (B and C) were located close to each other (about 7-12 A) but were distant (greater than 12 A) from site A. The addition of EDTA to calcium-binding protein resulted in a 25% decrease in intrinsic protein fluorescence, suggesting a conformational change in the protein. The titration of EDTA-treated calcium-binding protein with calcium resulted in recovery of intrinsic protein fluorescence. A reversible calcium-dependent change in the ellipticity of calcium-binding protein in circular dichroism experiments was also seen. These observed properties suggest that vitamin D-dependent chick intestinal calcium-binding protein behaves in a manner similar to other well-known calcium-binding regulatory proteins.

Animals↗
PubMed1987

Radiochemistry, biochemistry, and kinetics of 131I-metaiodobenzylguanidine (MIBG) and 123I-MIBG: clinical implications of the use of 123I-MIBG.

Metaiodobenzylguanidine (MIBG) is actively concentrated in adrenergic neuroendocrine tissues and tumors by an active, energy- and sodium-dependent, high-affinity, saturable mechanism. This has proved successful, when labeled with 131-I or 123-I, in scintigraphically depicting pheochromocytomas and neuroblastomas. For imaging purposes 123-I has multiple advantages over 131-I; the gamma ray energy is ideal for modern instruments, the decay by electron capture limits the particulate emissions, and the short half-life reduces the radiation burden. It is thus possible to use doses of 123-I-MIBG 20 times as large as doses of 131-I-MIBG with equivalent absorbed radiation doses. Disadvantages of 123-I include the cost and difficulties in the regular delivery of this short-lived radionuclide. For most imaging purposes 123-I-MIBG is the optimal agent if logistical problems in its supply can be overcome.

3-Iodobenzylguanidine↗
PubMed1987

Clonidine-induced suppression of plasma catecholamines in states of adrenal medulla hyperfunction.

To assess adrenal medulla activity in states of hyperfunction, a single 0.3 mg oral dose of clonidine hydrochloride (Catapres) was given to twelve patients with varying evidence of familial adrenal medullary hyperplasia and pheochromocytomas from kindreds with Multiple Endocrine Neoplasia type 2 syndrome (MEN-2), seven patients with sporadic pheochromocytomas and six normal subjects. Mean arterial blood pressure and plasma norepinephrine (NE) levels were lower than baseline values 2 h after clonidine in the normal subjects. Plasma epinephrine (E) rose in one normal but fell in the remainder after clonidine administration. In sporadic pheochromocytoma patients, E fell slightly in 4 and NE fell in 3 while mean arterial blood pressure was not significantly lower than baseline values in 7 patients 2 h after clonidine. In MEN-2, mean arterial blood pressure fell and there was a variable response of plasma E and NE to clonidine, which appears to be related to the presence of detectable anatomic (CT scan) and functional (131I-mlBG scintigraphy) abnormalities of the adrenal medulla. These findings are thus compatible with the spectrum of adrenal medulla dysfunction and the presumed development of pheochromocytoma in this syndrome.

Adolescent↗
PubMed1987

Iodine-131 MIBG scintigraphy of neuroendocrine tumors other than pheochromocytoma and neuroblastoma.

Metaiodobenzylguanidine (MIBG) locates most pheochromocytomas and neuroblastomas. The tracer is concentrated in intracellular storage vesicles by an active process. Many other neuroendocrine tumors of the amine precursor uptake and decarboxylation (APUD) series have hormonal storage vesicles and, thus, the potential to take up [131I]MIBG. A variety of neuroendocrine tumors in 57 patients were studied 1, 2, and 3 days after 0.5 mCi [131I]MIBG. Views from skull to pelvis were obtained. Results of MIBG scans were compared with all available imaging modalities (including plain radiography, liver scan, ultrasound, computed tomography, and angiography) and surgical exploration. The neuroendocrine nature of the tumor was determined by histology, immunohistochemistry, electron microscopy, and the assay of appropriate biogenic amines and peptide hormones. Results were (positive/total cases): carcinoids (four of ten), nonsecreting paragangliomas (three of three), sporadic medullary carcinomas of the thyroid (MCT) (one of five), familial MCT (one of 26), chemodectomas (two of five), oat cell carcinomas (zero of four), choriocarcinoma (one of one), atypical schwannoma (with storage granules) (one of one), Merkel cell skin cancer (one of one), islet cell carcinoma (zero of one). We conclude that a wide range of neuroendocrine tumors show [131I]MIBG uptake; tumors other than pheochromocytomas and neuroblastomas are less often seen scintigraphically, but in certain cases (e.g., carcinoid and nonsecreting paragangliomas) scintigraphy may be useful in depicting the extent and location of disease and may indicate therapeutic potential. Iodine-131 MIBG shows promise in the diagnosis and staging of tumors of varied types.

3-Iodobenzylguanidine↗
PubMed1987

Hepatobiliary imaging to demonstrate drainage patterns in a patient with an indwelling hepatic catheter.

The presence of normal biliary flow was established in a patient with an indwelling hepatic catheter placed to drain an intrahepatic cyst cavity with the use of sequential hepatobiliary scintiscans. In the initial study drainage was demonstrated from the indwelling catheter; when the catheter was clamped, drainage was observed in the native biliary system. Serial biliary scintigraphy not only confirmed the patency of the hepatobiliary system, but served as a guide in the removal of the intrahepatic catheter.

Catheters, Indwelling↗
PubMed1987

Functional and scintigraphic evaluation of the silent adrenal mass.

Seven patients with unilateral and one patient with bilateral and asymmetric (R greater than L) incidentally discovered adrenal mass abnormalities depicted by computed tomography (CT) were studied by 131I-6 beta-iodomethyl-19-norcholesterol (NP-59) scintigraphy. There was marked lateralization of NP-59 uptake to the side of the mass lesion in the seven patients with unilateral masses and prominent asymmetric, (R greater than L) bilateral uptake in the patient with bilateral masses despite the fact that there were no obvious abnormalities of adrenocortical or adrenomedullary function as determined from peripheral blood and 24-hr urinary hormone measurements. Simultaneous bilateral adrenal vein catheterization (AVC) was employed to measure the levels of hormone effluent from the adrenal cortex and medulla and in all instances the cortisol concentrations were greatest from the side of the mass lesion in those patients with unilateral masses and from the larger of the two adrenals in the patient with bilateral adrenal masses. Thus, there was congruence between the anatomic (CT) and functional (NP-59 scintigraphy and AVC) investigations that depicted asymmetry of the adrenal glands which were not associated with abnormalities of overall adrenal function or hypothalamic-pituitary-adrenal axis integrity.

Adosterol↗