Serum interleukin 2 receptor levels in childhood acute lymphoblastic leukemia

The clinical significance of interleukin 2 receptor (IL2R) concentrations in serum was determined for 344 children with newly diagnosed acute lymphoblastic leukemia (ALL). Serum levels of IL2R in patients (267 to 80,000 U/mL, median 2,007 U/mL) were significantly higher than normal control values (170 to 738 U/mL, median 347 U/mL) (P less than .0001). Measurements in cases of T cell ALL were lower than in the non-T, non-B cases (P = .02). Among the 264 patients with non-T, non-B ALL, but not in those with T cell disease, higher serum IL2R levels (greater than 2,000 U/mL) were associated with a poorer treatment outcome (P = .04). In a multivariate analysis, serum IL2R level contributed independent prognostic information beyond that conveyed by leukocyte count, race, and age (P = .04). One explanation for these results is that soluble IL2R competes with normal lymphocyte- integrated IL2R for the ligand and thus could suppress host antitumor immunity.     

tdic(9;12): a nonrandom chromosome abnormality in childhood B-cell precursor acute lymphoblastic leukemia: a Pediatric Oncology Group Study

In a review of 432 children with newly diagnosed acute lymphoblastic leukemia (ALL), we identified a new nonrandom translocation, tdic(9;12)(p1?1;p1?2), in the leukemic marrow cells of eight patients. Seven had hypodiploid karyotypes that lacked chromosomes 9 and 12 and contained a der(12), tdic(9;12); the eighth had a pseudodiploid karyotype with two normal 9 chromosomes, one normal 12 and the der(12), tdic(9;12). Abnormalities involving chromosomes other than 9 and 12 were noted in four of the eight patients. All cells with the tdic(9;12) expressed both the common ALL antigen and HLA-DR. Cytoplasmic immunoglobulin, a marker of pre-B ALL, was detected in one case with the tdic(9;12) but was absent in the other seven. Our results suggest that the tdic(9;12)(p1?1;p1?2) rearrangement is specifically associated with leukemic B cell precursors.     

Chronic pain beyond patienthood.

Forty nonconsumers (subjects with pain lasting for more than 1 year who had not consulted a doctor because of it during the preceding year) were compared with 46 chronic patients at a pain clinic. The mean duration of the nonconsumers' pain was twice as long as that of the patients'. Although their pain intensity, as assessed with pain diaries, did not differ, their estimated pain intensity was less than that of the pain patients; they took fewer analgesics, were less functionally impaired, made less use of coping strategies associated with poor adjustment, were less depressed, and expected less help from external resources. The "non-consumer attitude" appears to be independent of the duration of the pain complaints.     

Neuromuscular synaptic transmission in aged ganglioside-deficient mice

Gangliosides are sialylated glycosphingolipids that are present in high density on neuronal membranes, especially at synapses, where they are assumed to play functional or modulating roles. Mice lacking GM2/GD2-synthase express only the simple gangliosides GD3 and GM3 and develop progressive motor behaviour deficits upon ageing, apparently due to failing complex ganglioside-dependent maintenance and/or repair processes or, alternatively, toxic GM3/GD3 accumulation. We investigated the function of neuromuscular junctions (NMJs) of aged (>9 month-old) GM2/GD2-synthase null-mutant mice, because synaptic dysfunction might develop with age and could potentially contribute to the late-onset motor phenotype. In addition, we studied NMJs of old mice lacking GD3-synthase (expressing only O- and a-series gangliosides), which do not show an overt neurological phenotype but may develop subclinical synaptic deficits. Detailed electrophysiological analyses showed subtle changes in presynaptic neurotransmitter release. Acetylcholine release at 40 Hz nerve stimulation at aged GM2/GD2-synthase null-mutant NMJs ran down slightly more pronounced than at wild-type NMJs, and spontaneous acetylcholine release rate at GD3-synthase null-mutant NMJs was somewhat higher than at wild-type, selectively at 25 °C bath temperature. Interestingly, we observed faster kinetics of postsynaptic electrophysiological responses at aged GD3-synthase null-mutant NMJs, not previously seen by us at NMJs of young GD3-synthase null-mutants or other types of (aged or young) ganglioside-deficient mice. These kinetic changes might reflect a change in postsynaptic acetylcholine receptor behaviour. Our data indicate that it is highly unlikely that transmission failure at NMJs contributes to the progressive motor defects of aged GM2/GD2-synthase null-mutants and that, despite some kinetic changes of synaptic signals, neuromuscular transmission remains successful in aged GD3-synthase null-mutant mice. Apparently, mutual redundancy of the different gangliosides in supporting presynaptic function, as observed previously by us in young mice, remains adequate upon ageing or, alternatively, gangliosides have only relatively little direct impact on neuromuscular synaptic function, even in aged mice.