ABSTRACT
Glucocorticoid receptors were quantified in circulating lymphoblasts from a child with relapsed acute lymphocytic leukemia refractory to multiple glucocorticoid containing drug regimens. The number of receptor sites in this patient's lymphoblasts was found to be similar to the number of receptor sites in lymphoblasts from a group of newly diagnosed children with acute lymphocytic leukemia. This patient differs from previous reported cases of relapsed acute lymphocytic leukemia in that all previous relapsed patients with normal receptor numbers obtained complete remissions when glucocorticoid containing treatment regimens were employed.
Subject(s)
Antineoplastic Agents/administration & dosage , Glucocorticoids/administration & dosage , Leukemia, Lymphoid/drug therapy , Receptors, Glucocorticoid/analysis , Receptors, Steroid/analysis , Child , Drug Resistance , Drug Therapy, Combination , Female , Humans , Leukemia, Lymphoid/analysisABSTRACT
Glucocorticoid receptor sites were measured in lymphoblasts of six patients with childhood acute lymphocytic leukemia in relapse who were resistant to glucocorticoid therapy and compared to the number of receptor sites found in the lymphoblasts of 12 patients with acute lymphocytic leukemia who achieved initial complete remissions on glucocorticoid-containing chemotherapy regimens. Resistant patients as a group were found to have lower receptor site levels. This data supports the hypothesis that reduction in the number of receptor sites per cell is one mechanism by which cells become resistant to glucocorticoids. However, the clinical usefulness of these measurements to prospectively select glucocorticoid-resistant patients appears limited because four of the six resistant patients had measurements within one standard deviation of the mean for the 12 patients who achieved remission.
Subject(s)
Leukemia, Lymphoid/analysis , Lymphocytes/analysis , Receptors, Glucocorticoid/analysis , Receptors, Steroid/analysis , Adolescent , Bone Marrow/analysis , Child , Child, Preschool , Drug Resistance , Humans , Leukemia, Lymphoid/blood , Prednisone/pharmacology , Prednisone/therapeutic useABSTRACT
Non-pregnant and pregnant rats of known gestational age were killed at intervals and their uterine cervices were excised and digested with papain. Glycosaminoglycans thus extracted were separated by cellulose acetate electrophoresis and stained with Alcian Blue. Glycosaminoglycans were identified by comparison with standards and by serial degradation with chondroitin ABC lyase, butyl nitrite and leech hyaluronidase. Dermatan sulphate, hyaluronic acid and heparan sulphate were identified and quantitative determined by densitometry. The overall concentration of glycosaminoglycans changed little during pregnancy. A 3-fold total increase in uronic acid paralleled the increase in cervical weight. Hyaluronate content, however, increased 17-fold, and rose from 6% of total glycosaminoglycans in the non-pregnant state to 33% at term. Furthermore, the ratio of hyaluronate to hydroxyproline increased 10-fold. These changes are consistent with an accumulation of hyaluronate in the interstices between collagen fibres, resulting in the softening of this tissue that is seen in late pregnancy.
