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School of Pharmacy : Sasson Shlomo

Researchers

 Last updated June 2021 - School of Pharmacy

List of Publications

(1) Robinson EL, da Costa Gomes CP, Potočnjak I, Hellemans J, Betsou F, de Gonzalo-Calvo D, et al. A year in the life of the EU-CardioRNA COST action: CA17129 catalysing transcriptomics research in cardiovascular disease. Non-coding RNA 2020;6(2).

(2) Maulucci G, Cohen O, Daniel B, Ferreri C, Sasson S. The combination of whole cell lipidomics analysis and single cell confocal imaging of fluidity and micropolarity provides insight into stress-induced lipid turnover in subcellular organelles of pancreatic beta cells. Molecules 2019;24(20).

(3) Parchem K, Sasson S, Ferreri C, Bartoszek A. Qualitative analysis of phospholipids and their oxidised derivatives–used techniques and examples of their applications related to lipidomic research and food analysis. Free Radic Res 2019;53(sup1):1068-1100.

(4) Xepapadaki E, Maulucci G, Constantinou C, Karavia EA, Zvintzou E, Daniel B, et al. Impact of apolipoprotein A1- or lecithin:cholesterol acyltransferase-deficiency on white adipose tissue metabolic activity and glucose homeostasis in mice. Biochim Biophys Acta Mol Basis Dis 2019;1865(6):1351-1360.

(5) Early experiences in 4D quantitative analysis of insulin granules in living beta-cells. Proceedings - 2018 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2018; 2019.

(6) da Costa Gomes CP, Ágg B, Andova A, Arslan S, Baker A, Barteková M, et al. Catalyzing transcriptomics research in cardiovascular disease: The CardioRNA COST action CA17129. Non-coding RNA 2019;5(2).

(7) Uchida K, Shibata T, Toyokuni S, Daniel B, Zarkovic K, Zarkovic N, et al. Development of a novel monoclonal antibody against 4-hydroxy-2E,6Z-dodecadienal (4-HDDE)-protein adducts: Immunochemical application in quantitative and qualitative analyses of lipid peroxidation in vitro and ex vivo. Free Radic Biol Med 2018;124:12-20.

(8) Maulucci G, Di Giacinto F, De Angelis C, Cohen O, Daniel B, Ferreri C, et al. Real time quantitative analysis of lipid storage and lipolysis pathways by confocal spectral imaging of intracellular micropolarity. Biochim Biophys Acta Mol Cell Biol Lipids 2018;1863(7):783-793.

(9) Egea J, Fabregat I, Frapart YM, Ghezzi P, Görlach A, Kietzmann T, et al. Corrigendum to “European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS)” (Redox Biol. (2017) 13 (94–162)(S2213231717303373)(10.1016/j.redox.2017.05.007)). Redox Biol 2018;14:694-696.

(10) Rozentul N, Avrahami Y, Shubely M, Levy L, Munder A, Cohen G, et al. A Novel Phenylchromane Derivative Increases the Rate of Glucose Uptake in L6 Myotubes and Augments Insulin Secretion from Pancreatic Beta-Cells by Activating AMPK. Pharm Res 2017;34(12):2873-2890.

(11) Sasson S. Nutrient overload, lipid peroxidation and pancreatic beta cell function. Free Radic Biol Med 2017;111:102-109.

(12) Shamni O, Cohen G, Gruzman A, Zaid H, Klip A, Cerasi E, et al. Supportive data on the regulation of GLUT4 activity by 3-O-methyl-D-glucose. Data Brief 2017;14:329-336.

(13) Shamni O, Cohen G, Gruzman A, Zaid H, Klip A, Cerasi E, et al. Regulation of GLUT4 activity in myotubes by 3-O-methyl-D-glucose. Biochim Biophys Acta Biomembr 2017;1859(10):1900-1910.

(14) Egea J, Fabregat I, Frapart YM, Ghezzi P, Görlach A, Kietzmann T, et al. European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS). Redox Biol 2017;13:94-162.

(15) Sasson S. 4-Hydroxyalkenal-activated PPARδ mediates hormetic interactions in diabetes. Biochimie 2017;136:85-89.

(16) Shefer-Weinberg D, Sasson S, Schwartz B, Argov-Argaman N, Tirosh O. Deleterious effect of n-3 polyunsaturated fatty acids in non-alcoholic steatohepatitis in the fat-1 mouse model. Clin Nutr Exp 2017;12:37-49.

(17) Maulucci G, Cohen O, Daniel B, Sansone A, Petropoulou PI, Filou S, et al. Fatty acid-related modulations of membrane fluidity in cells: detection and implications. Free Radic Res 2016;50:S40-S50.

(18) Maulucci G, Daniel B, Cohen O, Avrahami Y, Sasson S. Hormetic and regulatory effects of lipid peroxidation mediators in pancreatic beta cells. Mol Asp Med 2016;49:49-77.

(19) Karavia EA, Hatziri A, Kalogeropoulou C, Papachristou NI, Xepapadaki E, Constantinou C, et al. Deficiency in apolipoprotein A-I ablates the pharmacological effects of metformin on plasma glucose homeostasis and hepatic lipid deposition. Eur J Pharmacol 2015;766:76-85.

(20) Stancu CS, Carnuta MG, Sanda GM, Toma L, Deleanu M, Niculescu LS, et al. Hyperlipidemia-induced hepatic and small intestine ER stress and decreased paraoxonase 1 expression and activity is associated with HDL dysfunction in Syrian hamsters. Mol Nutr Food Res 2015;59(11):2293-2302.

(21) Manea A, Manea S-, Todirita A, Albulescu IC, Raicu M, Sasson S, et al. High-glucose-increased expression and activation of NADPH oxidase in human vascular smooth muscle cells is mediated by 4-hydroxynonenal-activated PPARα and PPARβ/δ. Cell Tissue Res 2015;361(2):593-604.

(22) Manea S-, Constantin A, Manda G, Sasson S, Manea A. Regulation of Nox enzymes expression in vascular pathophysiology: Focusing on transcription factors and epigenetic mechanisms. Redox Biol 2015;5:358-366.

(23) Riahi Y, Kaiser N, Cohen G, Abd-Elrahman I, Blum G, Shapira OM, et al. Foam cell-derived 4-hydroxynonenal induces endothelial cell senescence in a TXNIP-dependent manner. J Cell Mol Med 2015;19(8):1887-1899.

(24) Cohen G, Shamni O, Avrahami Y, Cohen O, Broner EC, Filippov-Levy N, et al. Beta cell response to nutrient overload involves phospholipid remodelling and lipid peroxidation. Diabetologia 2015;58(6):1333-1343.

(25) Kahremany S, Livne A, Gruzman A, Senderowitz H, Sasson S. Activation of PPARδ: From computer modelling to biological effects. Br J Pharmacol 2015;172(3):754-770.

(26) Pasternak L, Meltzer-Mats E, Babai-Shani G, Cohen G, Viskind O, Eckel J, et al. Benzothiazole derivatives augment glucose uptake in skeletal muscle cells and stimulate insulin secretion from pancreatic β-cells via ampk activation. Chem Commun 2014;50(76):11222-11225.

(27) Cohen G, Riahi Y, Sunda V, Deplano S, Chatgilialoglu C, Ferreri C, et al. Signaling properties of 4-hydroxyalkenals formed by lipid peroxidation in diabetes. Free Radic Biol Med 2013;65:978-987.

(28) Jaganjac M, Tirosh O, Cohen G, Sasson S, Zarkovic N. Reactive aldehydes-second messengers of free radicals in diabetes mellitus. Free Radic Res 2013;47(S1):39-48.

(29) Meltzer-Mats E, Babai-Shani G, Pasternak L, Uritsky N, Getter T, Viskind O, et al. Synthesis and mechanism of hypoglycemic activity of benzothiazole derivatives. J Med Chem 2013;56(13):5335-5350.

(30) Kapitulnik J, Benaim C, Sasson S. Endothelial cells derived from the blood-brain barrier and islets of Langerhans differ in their response to the effects of bilirubin on oxidative stress under hyperglycemic conditions. Front Pharmacol 2012;3 JUL.

(31) Gruzman A, Elgart A, Viskind O, Billauer H, Dotan S, Cohen G, et al. Antihyperglycaemic activity of 2,4:3,5-dibenzylidene-D-xylose-diethyl dithioacetal in diabetic mice. J Cell Mol Med 2012;16(3):593-603.

(32) Cohen G, Riahi Y, Shamni O, Guichardant M, Chatgilialoglu C, Ferreri C, et al. Role of lipid peroxidation and PPAR-δ in amplifying glucose-stimulated insulin secretion. Diabetes 2011;60(11):2830-2842.

(33) Cohen G, Riahi Y, Sasson S. Lipid peroxidation of poly-unsaturated fatty acids in normal and obese adipose tissues. Arch Physiol Biochem 2011;117(3):131-139.

(34) Notides AC, Sasson S, Callison S. An allosteric regulatory mechanism for estrogen receptor activation. Molecular Mechanism of Steroid Hormone Action: Recent Advances; 2011. p. 173-198.

(35) Lamers D, Schlich R, Greulich S, Sasson S, Sell H, Eckel J. Oleic acid and adipokines synergize in inducing proliferation and inflammatory signalling in human vascular smooth muscle cells. J Cell Mol Med 2011;15(5):1177-1188.

(36) Riahi Y, Cohen G, Shamni O, Sasson S. Signaling and cytotoxic functions of 4-hydroxyalkenals. Am J Physiol Endocrinol Metab 2010;299(6):E879-E886.

(37) Negre-Salvayre A, Auge N, Ayala V, Basaga H, Boada J, Brenke R, et al. Pathological aspects of lipid peroxidation. Free Radic Res 2010;44(10):1125-1171.

(38) Riahi Y, Sin-Malia Y, Cohen G, Alpert E, Gruzman A, Eckel J, et al. The natural protective mechanism against hyperglycemia in vascular endothelial cells: Roles of the lipid peroxidation product 4-hydroxydodecadienal and peroxisome proliferator-activated receptor δ. Diabetes 2010;59(4):808-818.

(39) Gruzman A, Babai G, Sasson S. Adenosine monophosphate-activated protein kinase (AMPK) as a new target for antidiabetic drugs: A review on metabolic, pharmacological and chemical considerations. Rev Diabetic Stud 2009;6(1):13-36.

(40) Gruzman A, Shamni O, Yakir MB, Sandovski D, Elgart A, Alpert E, et al. Novel D-xylose derivatives stimulate muscle glucose uptake by activating AMP-activated protein kinase α. J Med Chem 2008;51(24):8096-8108.

(41) Cohen G, Riahi Y, Alpert E, Gruzman A, Sasson S. The roles of hyperglycaemia and oxidative stress in the rise and collapse of the natural protective mechanism against vascular endothelial cell dysfunction in diabetes. Arch Physiol Biochem 2007;113(4-5):259-267.

(42) Alpert E, Gruzman A, Tennenbaum T, Sasson S. Selective cyclooxygenase-2 inhibitors stimulate glucose transport in L6 myotubes in a protein kinase Cδ-dependent manner. Biochem Pharmacol 2007;73(3):368-377.

(43) Vahsen S, Rakowski K, Ledwig D, Dietze-Schroeder D, Swifka J, Sasson S, et al. Altered GLUT4 translocation in skeletal muscle of 12/15-lipoxygenase knockout mice. Horm Metab Res 2006;38(6):391-396.

(44) Sasson S, Eckel J. Disparate effects of 12-lipoxygenase and 12-hydroxyeicosatetraenoic acid in vascular endothelial and smooth muscle cells and in cardiomyocytes. Arch Physiol Biochem 2006;112(2):119-129.

(45) Alpert E, Gruzman A, Lardi-Studler B, Cohen G, Reich R, Sasson S. Cyclooxygenase-2 (PTGS2) inhibitors augment the rate of hexose transport in L6 myotubes in an insulin-and AMPKα-independent manner. Diabetologia 2006;49(3):562-570.

(46) Ben-Yakir M, Gruzman A, Alpert E, Sasson S. Glucose transport regulators. Curr Med Chem : Immunol , Endocr Metab Agents 2005;5(6):519-527.

(47) Totary-Jain H, Naveh-Many T, Riahi Y, Kaiser N, Eckel J, Sasson S. Calreticulin destabilizes glucose transporter-1 mRNA in vascular endothelial and smooth muscle cells under high-glucose conditions. Circ Res 2005;97(10):1001-1008.

(48) Alpert E, Gruzman A, Riahi Y, Blejter R, Aharoni P, Weisinger G, et al. Delayed autoregulation of glucose transport in vascular endothelial cells. Diabetologia 2005;48(4):752-755.

(49) Alpert E, Altman H, Totary H, Gruzman A, Barnea D, Barash V, et al. 4-Hydroxy tempol-induced impairment of mitochondrial function and augmentation of glucose transport in vascular endothelial and smooth muscle cells. Biochem Pharmacol 2004;67(10):1985-1995.

(50) Gruzman A, Hidmi A, Katzhendler J, Haj-Yehie A, Sasson S. Synthesis and characterization of new and potent α-lipoic acid derivatives. Bioorg Med Chem 2004;12(5):1183-1190.

(51) Krimsky M, Yedgar S, Aptekar L, Schwob O, Goshen G, Gruzman A, et al. Amelioration of TNBS-induced colon inflammation in rats by phospholipase A2 inhibitor. Am J Physiol Gastrointest Liver Physiol 2003;285(3 48-3):G586-G592.

(52) Noyman I, Marikovsky M, Sasson S, Stark AH, Bernath K, Seger R, et al. Hyperglycemia reduces nitric oxide synthase and glycogen synthase activity in endothelial cells. Nitric Oxide Biol Chem 2002;7(3):187-193.

(53) Alpert E, Gruzman A, Totary H, Kaiser N, Reich R, Sasson S. A natural protective mechanism against hyperglycaemia in vascular endothelial and smooth-muscle cells: Role of glucose and 12-hydroxyeicosatetraenoic acid. Biochem J 2002;362(2):413-422.

(54) Dransfeld O, Rakatzi I, Sasson S, Eckel J. Eicosanoids and the regulation of cardiac glucose transport. Ann New York Acad Sci 2002;967:208-216.

(55) Dransfeld O, Rakatzi I, Sasson S, Gruzman A, Schmitt M, Häussinger D, et al. Eicosanoids participate in the regulation of cardiac glucose transport by contribution to a rearrangement of actin cytoskeletal elements. Biochem J 2001;359(1):47-54.

(56) Kaye AM, Spatz M, Waisman A, Sasson S, Tamir S, Vaya J, et al. Paradoxical interactions among estrogen receptors, estrogens and SERMS: Mutual annihilation and synergy. J Steroid Biochem Mol Biol 2001;76(1-5):85-93.

(57) Sasson S, Davarashvili A, Reich R. Role of lipoxygenase in the regulation of glucose transport in aortic vascular cells. Adv Exp Med Biol 2000;469:377-383.

(58) Von Der Crone S, Deppe C, Barthel A, Sasson S, Joost H-, Schürmann A. Glucose deprivation induces Akt-dependent synthesis and incorporation of GLUT1, but not of GLUT4, into the plasma membrane of 3T3-L1 adipocytes. Eur J Cell Biol 2000;79(12):943-949.

(59) Dransfeld O, Uphues I, Sasson S, Schürmann A, Joost H-, Eckel J. Regulation of subcellular distribution of GLUT4 in cardiomyocytes: Rab4A reduces basal glucose transport and augments insulin responsiveness. Exp Clin Endocrinol Diabetes 2000;108(1):26-36.

(60) Yudt MR, Vorojeikina D, Zhong L, Skafar DF, Sasson S, Gasiewicz TA, et al. Function of estrogen receptor tyrosine 537 in hormone binding, DNA binding, and transactivation. Biochemistry 1999;38(43):14146-14156.

(61) Buchs AE, Sasson S, Joost HG, Cerasi E. Characterization of GLUT5 domains responsible for fructose transport. Endocrinology 1998;139(3):827-831.

(62) Dimitriadis G, Leighton B, Parry-Billings M, Sasson S, Young M, Krause U, et al. Effects of glucocorticoid excess on the sensitivity of glucose transport and metabolism to insulin in rat skeletal muscle. Biochem J 1997;321(3):707-712.

(63) Sasson S, Kaiser N, Dan-Goor M, Oron R, Koren S, Wertheimer E, et al. Substrate autoregulation of glucose transport: Hexose 6-phosphate mediates the cellular distribution of glucose transporters. Diabetologia 1997;40(1):30-39.

(64) Sasson S, Kredy-Farahan L, Kaiser N, Reich R. Bovine vascular cells and extracellular matrix interactions: Dual effect of hyperglycemia. Exp Clin Endocrinol Diabetes 1997;105(SUPPL. 3):54-56.

(65) Dan-Goor M, Sasson S, Davarashvili A, Almagor M. Expression of glucose transporter and glucose uptake in human oocytes and preimplantation embryos. Hum Reprod 1997;12(11):2508-2510.

(66) Melamed M, Castaño E, Notides AC, Sasson S. Molecular and kinetic basis for the mixed agonist/antagonist activity of estriol. Mol Endocrinol 1997;11(12):1868-1878.

(67) Arnold SF, Melamed M, Vorojeikina DP, Notides AC, Sasson S. Estradiol-binding mechanism and binding capacity of the human estrogen receptor is regulated by tyrosine phosphorylation. Mol Endocrinol 1997;11(1):48-53.

(68) Cerasi E, Sasson S. Glucotoxicity at the level of glucose transporters: a toxicologic or physiological phenomenon? Journ Annu Diabetol Hotel Dieu 1996:111-119.

(69) Melamed M, Arnold SF, Notides AC, Sasson S. Kinetic analysis of the interaction of human estrogen receptor with an estrogen response element. J Steroid Biochem Mol Biol 1996;57(3-4):153-159.

(70) Sasson S, Gorowits N, Joost HG, King GL, Cerasi E, Kaiser N. Regulation by metformin of the hexose transport system in vascular endothelial and smooth muscle cells. Br J Pharmacol 1996;117(6):1318-1324.

(71) Youngren JF, Maddux BA, Sasson S, Sbraccia P, Tapscott EB, Swanson MS, et al. Skeletal muscle content of membrane glycoprotein PC-1 in obesity: Relationship to muscle glucose transport. Diabetes 1996;45(10):1324-1328.

(72) Maddux BA, Sbraccia P, Kumakura S, Sasson S, Youngren J, Fisher A, et al. Membrane glycoprotein PC-1 and insulin resistance in non-insulin-dependent diabetes mellitus. Nature 1995;373(6513):448-451.

(73) Weil-Maslansky E, Gutman Y, Sasson S. Insulin activates furosemide-sensitive K+ and Cl- uptake system in BC3H1 cells. AM J PHYSIOL CELL PHYSIOL 1994;267(4 37-4):C932-C939.

(74) Sasson S, Oron R, Cerasi E. Enzymatic assay of 2-deoxyglucose 6-phosphate for assessing hexose uptake rates in cultured cells. Anal Biochem 1993;215(2):309-311.

(75) Sasson S, Ashhab Y, Melloul D, Cerasi E. Autoregulation of glucose transport: Effects of glucose on glucose transporter expression and cellular location in muscle. ADV EXP MED BIOL 1993;334:113-127.

(76) Kaiser N, Sasson S, Feener EP, Boukobza-Vardi N, Higashi S, Moller DE, et al. Differential regulation of glucose transport and transporters by glucose in vascular endothelial and smooth muscle cells. Diabetes 1993;42(1):80-89.

(77) Bond JP, Sasson S, Notides AC. The binding of estrogen and estrogen antagonists to the estrogen receptor. Arch Biochem Biophys 1992;296(2):583-591.

(78) Cerasi E, Sasson S. Autoregulation of carbohydrate recovery in the muscle. Journ Annu Diabetol Hotel Dieu 1992:23-36.

(79) Greco-Perotto R, Wertheimer E, Jeanrenaud B, Cerasi E, Sasson S. Glucose regulates its transport in L8 myocytes by modulating cellular trafficking of the transporter GLUT-1. Biochem J 1992;286(1):157-163.

(80) Sasson S. Equilibrium binding analysis of estrogen agonists and antagonists: relation to the activation of the estrogen receptor. Pathol Biol 1991;39(1):59-69.

(81) Weil E, Sasson S, Gutman Y. Mechanism of insulin-induced activation of Na+-K+-ATPase in isolated rat soleus muscle. AM J PHYSIOL CELL PHYSIOL 1991;261(2 30-2):C224-C230.

(82) Wertheimer E, Sasson S, Cerasi E, Ben-Neriah Y. The ubiquitous glucose transporter GLUT-1 belongs to the glucose-regulated protein family of stress-inducible proteins. Proc Natl Acad Sci U S A 1991;88(6):2525-2529.

(83) Sasson S, Kunievsky B, Nathan C, Ceras E. On the role of 5-hydroxytryptamine in the peripheral action of fenfluramine: studies with the isolated rat soleus muscle. Biochem Pharmacol 1990;39(5):965-968.

(84) Wertheimer E, Sasson S, Cerasi E. Regulation of hexose transport in L8 myocytes by glucose: Possible sites of interaction. J Cell Physiol 1990;143(2):330-336.

(85) The clinical significance of insulin resistance in NIDDM: Studies with continuous subcutaneous insulin infusion. Frontiers of diabetes research: current trends in non-insulin-dependent diabetes mellitus: proceedings of the Symposium on NIDDM: research and clinical frontiers in diabetes. ICS859; 1989.

(86) Sasson S, Kunievsky B, Nathan C, Cerasi E. Failure of fenfluramine to affect basal and insulin-stimulated hexose transport in rat skeletal muscle. Biochem Pharmacol 1989;38(16):2655-2661.

(87) Sasson S, Katzenellenbooen JA. Reversible, positive cooperative interaction of 11β-chloromethyl-[3H]estradiol-17β with the calf uterine estrogen receptor. J Steroid Biochem 1989;33(5):859-865.

(88) Sasson S, Notides AC. The effects of dimethylformamide on the interaction of the estrogen receptor with estradiol. J Steroid Biochem 1988;29(5):491-495.

(89) Sasson S, Notides AC. Mechanism of the estrogen receptor interaction with 4-hydroxytamoxifen. Mol Endocrinol 1988;2(4):307-312.

(90) Amir S, Sasson S, Kaiser N, Meyerovitch J, Shechter Y. Polymyxin B is an inhibitor of insulin-induced hypoglycemia in the whole animal model. Studies on the mode of inhibitory action. J Biol Chem 1987;262(14):6663-6667.

(91) Sasson S, Edelson D, Cerasi E. In vitro autoregulation of glucose utilization in rat soleus muscle. Diabetes 1987;36(9):1041-1046.

(92) Sasson S, Cerasi E. Substrate regulation of the glucose transport system in rat skeletal muscle. Characterization and kinetic analysis in isolated soleus muscle and skeletal muscle cells in culture. J Biol Chem 1986;261(36):16827-16833.

(93) Mayer M, Finci Z, Chaouat M, Sasson S. Plasminogen activator activity in differentiating rat myoblasts. Mol Cell Biochem 1986;69(2):147-154.

(94) Sasson S, Notides AC. Inability of [3H]estriol to induce maximal cooperativity of the estrogen receptor. J Steroid Biochem 1984;20(4 PART 2):1027-1032.

(95) Sasson S, Notides AC. The estriol-induced inhibition of the estrogen receptor's positive cooperativity. J Steroid Biochem 1984;20(4 PART 2):1021-1026.

(96) Sasson S, Notides AC. Estriol and estrone interaction with the estrogen receptor. II. Estriol and estrone-induced inhibition of the cooperative binding of [3H]estradiol to the estrogen receptor. J Biol Chem 1983;258(13):8118-8122.

(97) Sasson S, Notides AC. Estriol and estrone interaction with the estrogen receptor. I. Temperature-induced modulation of the cooperative binding of [3H]estriol and [3H]estrone to the estrogen receptor. J Biol Chem 1983;258(13):8113-8117.

(98) Sasson S, Notides AC. The inhibition of the estrogen receptor's positive cooperative [3H]estradiol binding by the antagonist, clomiphene. J Biol Chem 1982;257(19):11540-11545.

(99) Sasson S, Mayer M. Antiglucocorticoid activity of androgens in rat thymus lymphocytes. Endocrinology 1981;108(3):760-766.

(100) Sasson S, Mayer M. Resistance to androgen in murine lymphosarcoma lines resistant or sensitive to glucocorticoid hormone. Br J Cancer 1981;44(1):127-128.

(101) Sasson S, Mayer M. Effect of androgenic steroids on rat thymus and thymocytes in suspension. J Steroid Biochem 1981;14(6):509-517.