Fractionated total-body irradiation and high-dose etoposide as a preparatory regimen for bone marrow transplantation for 94 patients with chronic myelogenous leukemia in chronic phase

Ninety-four consecutive patients with chronic myelogenous leukemia in first clinical chronic phase, median age of 34.0 years (range, 6.8 to 52.4 years), with a histocompatible sibling donor, were treated with fractionated total body irradiation (1,320 cGy) and high-dose etoposide (60 mg/kg) followed by allogeneic bone marrow transplantation (BMT). The median time from diagnosis to BMT was 7.0 months (range, 2.3 to 72.0 months). Sixty patients were treated before BMT with hydroxyurea alone, four patients with busulfan alone, one patient with interferon alone, and the other 29 patients were treated with various combinations of these drugs. Cumulative probabilities of overall survival, event- free survival, and relapse at 5 years were 73%, 64%, and 14%, respectively. The median follow-up time for surviving patients was 38 months, ranging from 12 to 88 months. By stepwise Cox regression analysis, significant prognostic variables were age at transplant, acute graft-versus-host disease > or = grade II, cytomegalovirus- associated interstitial pneumonitis, and years from diagnosis to BMT.     

Chronic myelocytic leukemia: eosinophils involved in the malignant clone

Chronic myelocytic leukemia (CML) is a clonal disorder involving neutrophil, monocyte, erythrocyte, and platelet precursors. In order to determine if the eosinophils are also involved in the leukemic clone, we purified the eosinophils from a woman heterozygous for the common electrophoretic variants of the G6PD gene. Only type B enzyme was demonstrable in the eosinophils, neutrophils, and red cells, but both A and B enzymes were found in the fibroblasts. The data provide evidence that the eosinophil is involved in the malignant clone.     

Decreased pain response in mice following cortex-specific knockout of the N-methyl-d-aspartate NR1 subunit

Studies have shown that N-methyl-d-aspartate (NMDA) receptors play a critical role in pain processing at different levels of the central nervous system. In this study, we used cortex-specific NR1 knockout mice (C57BL/6 strain) to elucidate the role of cortical NMDA receptors in pain processes. On post-natal day 20, paw withdrawal latency (PWL) to a noxious thermal stimulus was measured in male and female knockout (KO), control (Ctrl), and C57BL/6 (C57) mice. Twenty-four hours later, the same mice were tested in the formalin-pain assay (20 μl of 5% formalin injected into one hind-paw). The results show that KO mice (both male and female) have significantly reduced pain responses during both early and late phases of formalin test, as compared with Ctrl and C57 mice (p < 0.01). By contrast, no differences among groups were found in PWL to a noxious thermal stimulus. Taken together, these results demonstrate dissociation in the role of cortical NMDA receptors in mediating different types of pain.     

A gradient in the duration of the G1 phase in the murine neocortical proliferative epithelium

Neuronogenesis in the neocortical pseudostratified ventricular epithelium (PVE) is initiated rostrolaterally and progresses caudo- medially as development progresses. Here we have measured the cytokinetic parameters and the fractional neuronal output parameter, Q, of laterally located early-maturing regions over the principal embryonic days (E12-E15) of neocortical neuronogenesis in the mouse. These measures are compared with ones previously made of a medial, late- maturing portion of the PVE. Laterally, as medially, the duration of the neuronogenetic interval is 6 days and comprises 11 integer cell cycles. Also, in both lateral and medial areas the length of G1 phase (TG1) increases nearly 4-fold and is the only cell cycle parameter to change. Q progresses essentially identically laterally and medially with respect to the succession of integer cell cycles. Most importantly, from E12 to E13 there is a steeply declining lateral to medial gradient in TG1. The gradient is due both to the lateral to medial graded stage of neuronogenesis and to the stepwise increase in TG1 with each integer cycle during the neuronogenetic interval. To our knowledge this gradient in TG1 of the cerebral PVE is the first cell biological gradient to be demonstrated experimentally in such an extensive proliferative epithelial sheet. We suggest that this gradient in TG1 is the cellular mechanism for positionally encoding a protomap of the neocortex within the PVE.