ABSTRACT
The combination of neurodevelopmental regression and adrenal insufficiency should alert practitioners or emergency room physicians about ALD. Although still unproven, early medical intervention with either gene therapy or bone marrow transplantation may offer more promise to these patients.
Subject(s)
Adrenoleukodystrophy/diagnosis , Adrenoleukodystrophy/psychology , Bone Marrow Transplantation , Erucic Acids/therapeutic use , Learning Disabilities/etiology , Triolein/therapeutic use , Adrenoleukodystrophy/therapy , Brain/pathology , Child , Diagnosis, Differential , Dietary Fats, Unsaturated/therapeutic use , Drug Combinations , Humans , Learning , Magnetic Resonance Imaging , Male , Neuropsychological Tests , Physical ExaminationABSTRACT
In eukaryotic cells oxysterols inhibit cholesterol biosynthesis and cell growth. A potent oxysterol, 25-hydroxycholesterol, was used to investigate the biological effects of oxysterols on three clonal lines of either glucocorticoid-sensitive or -resistant CEM cells, human leukemic T-lymphocytes. In addition, the glucocorticoid sensitivity of an oxysterol-resistant CEM cell line was tested. Oxysterols blocked growth and caused the lysis of cells regardless of their glucocorticoid response. All cells studied herein possessed an oxysterol binding protein with high affinity for 25-hydroxycholesterol. For all clones grown in serum-free medium, the half-maximal cytolytic concentration of 25-hydroxycholesterol (20-40 nM) correlated with its affinity (Kd = approximately 31 nM) for this oxysterol binding protein. Both cholesterol and mevalonate reversed 25-hydroxycholesterol cytotoxicity; 3-6 microM cholesterol or 0.1 mM mevalonate decreased 60 nM 25-hydroxycholesterol cytotoxicity by 50%. This cholesterol or mevalonate reversal appeared possible even after several days of 60 nM oxysterol treatment. The protective effect of cholesterol could be overcome by increasing 25-hydroxycholesterol concentrations. Cholesterol and mevalonate did not prevent glucocorticoid-mediated lymphocytolysis. Furthermore, the oxysterol-resistant line was sensitive to dexamethasone lysis. These data support the hypothesis that oxysterols and glucocorticoids act independently to block the growth of human leukemic lymphoblasts.
Subject(s)
Apoptosis/drug effects , Cell Death/drug effects , Glucocorticoids/pharmacology , Hydroxycholesterols/pharmacology , Receptors, Steroid/metabolism , Cholesterol/metabolism , Cholesterol/pharmacology , Female , Glucocorticoids/metabolism , Growth Inhibitors , Humans , In Vitro Techniques , Mevalonic Acid/pharmacology , Tumor Cells, CulturedABSTRACT
Associated with some plant viruses are small satellite RNA's that depend on the plant virus to provide protective coat protein and presumably at least some of the proteins necessary for satellite RNA replication. Multimeric forms of the satellite RNA of tobacco ringspot virus are probable in vivo precursors of the monomeric satellite RNA. Evidence is presented for the in vitro autolytic processing of dimeric and trimeric forms of this satellite RNA. The reaction generates biologically active monomeric satellite RNA, apparently is reversible to form dimeric RNA from monomeric RNA, and does not require an enzyme for its catalysis.
