Search PubMed⌕ Search

Biomedical subjects

S Iacobelli

Publications and source records attributed to S Iacobelli.

At least 127 records · Page 7Linked to original sources
PubMed1981

Glucocorticoid receptor determinations in leukemia patients using cytosol and whole-cell assays.

Parallel determinations of glucocorticoid receptors in the cells of patients with various forms of leukemia were made by two assay methods, one using cell-free cytosolic extracts and the other using whole-cell preparations. Both assays revealed saturable binding of triamcinolone acetonide in all cases. The mean equilibrium dissociation constant for the interaction of triamcinolone acetonide with the cytoplasmic receptor at 2 degrees was 9.45 +/- 6.33 (S.D.) nM while that for the whole-cell binding at 37 degrees was 6.13 +/- 3.25 nM, suggesting an increase in receptor affinity at physiological temperatures. Competition experiments with various unlabeled steroids revealed a higher degree of glucocorticoid specificity at 37 degrees in whole-cell suspensions than at 2 degrees in cytosol. In a comparative analysis of 41 leukemic cell specimens, it was found that determinations carried out by whole-cell assay, calculated as number of sites per cell correlated well with those performed by cytosol assay, calculated as fmol/mg protein, independent of the type of leukemia. However, for cells with low receptor content, the two assay methods were more difficult to compare. In agreement with previous reports, the cytosol assay consistently underestimated the number of receptors with respect to the whole-cell assay, particularly in cases of lymphatic leukemia. Furthermore, the underestimation decreased for increasing levels of total cellular receptor. These results suggest that, in addition to possible defects in the cytoplasm-to-nucleus translocation process, the acceptor-binding capacity of the nucleus may also represent one of the factors which determines the levels of assayable cytoplasmic receptors. Moreover, they indicate that the two assay methods furnish nonequivalent information.

Cytosol↗
PubMed1980

Clinical implications of glucocorticoid receptor studies in childhood acute lymphoblastic leukemia.

We have performed in parallel, in 19 children with acute lymphoblastic leukemia, a quantitative determination of glucocorticoid levels, in vitro steroid induced inhibition of nucleic acid precursors, and a short-term clinical trial of corticosteroids alone, before the treatment was given, which included corticosteroids and other drugs. From our results it appears that high glucocorticoid receptor levels in acute lymphoblastic leukemia of children do not guarantee a clinical response to corticosteroids. On the other hand, glucocorticoid receptors may turn out to be of value in predicting a poor response to corticosteroids only if their levels are considerably low.

Adolescent↗
PubMed1979

Binding of (3H)R5020 to progesterone receptor and serum contaminants in human endometrium.

The binding of [3H]R5020 to cytosol from human endometrium was utilized to evaluate the concentration of progesterone receptor by means of agar gel electrophoresis, using D-norgestrel as cold competitor. It was observed that radioligand binds predominantly to the receptor, and that serum contaminants such as albumin and corticosteroid-binding globulin do not interfere in the assay procedure.

Binding, Competitive↗
PubMed1979

Levels of estrogen and progesterone receptor in human endometrium during the menstrual cycle.

Receptors for estrogens and progesterone have been assayed in 24 samples of normal human endometria at different phases of the menstrual cycle. In the proliferative endometrium the concentration of estrogen binding sites was significantly higher than that of progesterone receptor while, in the secretive endometrium, the concentration of estrogen receptor was low, compared to that of progesterone receptor. The highest concentration of both receptors was observed during the periovulatory period. From the correlation observed between estrogen and progesterone receptors and the levels of the respective steroids in the plasma, it is suggested that the levels of plasma estradiol or its own tissue receptor determine the synthesis of progesterone receptors in the periovulatory period.

Cytosol↗
PubMed1978

Glucocorticoid receptors in human fetal lung.

A specific dexamethasone binding protein of human fetal lung is described. Characterization of the receptor by sucrose density gradient centrifugation showed a sedimentation coefficient of approximately 7S (low ionic strength) and 4S (high ionic strength). Competition studies showed high specificity for glucocorticoids since binding of radioactive dexamethasone was inhibited by cortisol and corticosterone but not by testosterone and 17 beta-estradiol. Uptake of radioactive steroid by isolated lung nuclei required the presence of cytosol and was temperature dependent. The KCl-extractable nuclear complex sedimented at approximately 5S. Thus the dexamethasone binding components of the human fetal lung have properties similar to those described for steroid receptors present in target tissues. The concentration of receptor remained fairly constant between 15 and 28 weeks of gestation.

Binding, Competitive↗
PubMed1978

Glucocorticoid-binding components in human thymus hyperplasia.

Preliminary experiments on thymocyte suspensions derived from human thymus hyperplasia indicated the presence of specific cytoplasmic receptors binding [3H]-dexamethasone with high affinity and specificity. The receptor was rapidly transferred into the nuclei at 28 degrees but not at 2 degrees. With cell-free preparations and ion-exchange cellulose-impregnated paper filters, thymus cytosol bound [3H]dexamethasone with a dissociation constant of 4.3 x 10(-9) M; the concentration of receptor sites was 9.6 x 10(-14) mole/mg cytosol protein. Cytosol contained binding components that sedimented at approximately 7S and 3.6S (low ionic strength) and at 4S (high ionic strength). Competition studies showed high specificity for glucocorticoids since binding of labeled dexamethasone was inhibited in the presence of 10(-6) M beta-methasone, prednisolone acetate, dexamethasone, corticosterone, cortisol, and cortisone. 17beta-Estradiol, testosterone, and dihydrotestosterone at 10(-6) M did not inhibit specific binding of [3H]dexamethasone. Thus, the dexamethasone-binding components of the human thymus hyperplasia had properties similar to those described for steroid hormone receptors present in target tissues.

Cell Nucleus↗
PubMed1974

Phosphoprotein phosphatase activity associated with estrogen-induced protein in rat uterus.

Estrogen-induced protein was purified from rat uteri and assayed for several enzymatic activities involved in the metabolism and action of cyclic nucleotides. No adenylate and guanylate cyclase (EC 4.6.1.1 and 4.6.1.2, respectively), protein kinase (EC 2.7.1.33), and cyclic nucleotide binding activities could be demonstrated in three independent preparations of the protein. However, all three preparations exhibited significant phosphoprotein phosphatase activity (EC 3.1.3.16) on phosphorylated protamine and histones F1. This activity is optimal at neutral pH, inhibited by Zn(++), and unaffected by cyclic AMP or cyclic GMP.

Adenylyl Cyclases↗