Clinical features and outcome in childhood T-cell leukemia-lymphoma according to stage of thymocyte differentiation: a Pediatric Oncology Group Study

The immunophenotypes of lymphoblasts from children with newly diagnosed T-cell acute lymphoid leukemia (T-ALL, n = 101) or T-cell non-Hodgkin lymphoma (T-NHL, n = 31) were analyzed to correlate stage of thymocyte differentiation with clinical features and outcome. The 67 boys and 34 girls with T-ALL were 1 month to 18 years old (median, 8 years) with leukocyte counts ranging from 2 to 810 x 10(9)/L (median, 55 x 10(9)/L). Eighteen of these patients were black, and 70 had a mediastinal mass. Twenty-six boys and five girls with a median age of 9 years (range, 1 to 20 years) had T-NHL. Seven of these patients were black, and 24 had a mediastinal mass. The distributions of thymocyte developmental stages (early [CD7+], intermediate [CD1+ and/or CD4+ and/or CD8+], and mature [CD3+]) in cases of T-ALL and T-NHL were significantly different: 34%, 43%, and 23% v 6%, 62%, and 32% (P = .02). A comparison of the patients' clinical features according to the maturational stage of thymocytes failed to disclose significant differences in the majority of characteristics studied. However, patients with mature-stage T-NHL, with or without the addition of subjects with mature-stage T-ALL, were less likely to have a mediastinal mass (P = .02 for both comparisons). Those with intermediate-stage T-cell malignancy (T-ALL and T-NHL combined) were the subgroup most likely to have a mediastinal mass (P = .01). Response to remission induction therapy was significantly worse in the T-ALL subgroup with an early-stage phenotype: a failure rate of 21% v 0% and 6% for the two more differentiated phenotypic subgroups (P = .007). Event-free survival was not affected by thymocyte maturational stage in cases of either T-ALL or T-NHL. Despite evidence of clinical heterogeneity among the maturational stages of T-cell malignancies in children, these developmental subdivisions do not appear to be critical determinants of outcome once remission is achieved. We conclude that such phenotypes need not be included in the stratification plans for clinical trials using common induction treatment.     

Catecholamine synthesis and metabolism in the central nervous system of mice lacking α2-adrenoceptor subtypes

Background and purpose:

This study investigates the role of α₂-adrenoceptor subtypes, α_2A, α_2B and α_2C, on catecholamine synthesis and catabolism in the central nervous system of mice.

Experimental approach:

Activities of the main catecholamine synthetic and catabolic enzymes were determined in whole brains obtained from α_2A-, α_2B- and α_2C-adrenoceptor knockout (KO) and C56Bl\7 wild-type (WT) mice.

Key results:

Although no significant differences were found in tyrosine hydroxylase activity and expression, brain tissue levels of 3,4-dihydroxyphenylalanine were threefold higher in α_2A- and α_2C-adrenoceptor KO mice. Brain tissue levels of dopamine and noradrenaline were significantly higher in α_2A and α_2CKOs compared with WT [WT: 2.8 ± 0.5, 1.1 ± 0.1; α_2AKO: 6.9 ± 0.7, 1.9 ± 0.1; α_2BKO: 2.3 ± 0.2, 1.0 ± 0.1; α_2CKO: 4.6 ± 0.8, 1.5 ± 0.2 nmol·(g tissue)⁻¹, for dopamine and noradrenaline respectively]. Aromatic L-amino acid decarboxylase activity was significantly higher in α_2A and α_2CKO [WT: 40 ± 1; α_2A: 77 ± 2; α_2B: 40 ± 1; α_2C: 50 ± 1, maximum velocity (V_max) in nmol·(mg protein)⁻¹·h⁻¹], but no significant differences were found in dopamine β-hydroxylase. Of the catabolic enzymes, catechol-O-methyltransferase enzyme activity was significantly higher in all three α₂KO mice [WT: 2.0 ± 0.0; α_2A: 2.4 ± 0.1; α_2B: 2.2 ± 0.0; α_2C: 2.2 ± 0.0 nmol·(mg protein)⁻¹·h⁻¹], but no significant differences were found in monoamine oxidase activity between all α₂KOs and WT mice.

Conclusions and implications:

In mouse brain, deletion of α_2A- or α_2C-adrenoceptors increased cerebral aromatic L-amino acid decarboxylase activity and catecholamine tissue levels. Deletion of any α₂-adrenoceptor subtypes resulted in increased activity of catechol-O-methyltransferase. Higher 3,4-dihydroxyphenylalanine tissue levels in α_2A and α_2CKO mice could be explained by increased 3,4-dihydroxyphenylalanine transport.     

MR fluoroscopy: initial clinical studies

Magnetic resonance (MR) fluoroscopy is a method for high-speed MR image acquisition with the goals of short acquisition time per image (500 msec or less), high image rate (10 images or more per second), and high-speed image reconstruction (150 msec or less from data acquisition to image display). The authors present their results with the first two goals in volunteers. MR fluoroscopic image data were acquired with a limited flip angle pulse sequence with reduced repetition times (TRs) and fewer phase encodings used per image. The sequence was applied continuously, and images were formed by updating one set of data with data from the most recently taken measurements. Sample head images were generated with TR/echo times as small as 11/5.5 msec and 48 phase encodings for a total acquisition time of about 500 msec. Images were acquired while the volunteer flexed his head. Artifacts from the motion became less evident on images as progressively shorter acquisition times were used.     

Tetralogy of Fallot: MR findings

Surgical treatment of patients with tetralogy of Fallot requires accurate definition of all anatomic structures, particularly the central pulmonary arteries. Magnetic resonance (MR) images of 22 patients with tetralogy of Fallot were studied to assess their usefulness in providing information regarding the spectrum of anatomic abnormalities in this condition. MR findings were compared with information obtained at catheterization (in 16 patients) and at surgery (in nine patients), both of which were performed within 3 months of MR imaging. Ventricular chamber enlargement and wall hypertrophy were clearly delineated in most of the 17 patients who were examined before definitive surgical repair, and ventricular septal defects were visualized in all 17. Palliative systemic-to-pulmonary shunts were visualized in 11 patients and could be evaluated for patency. Most important, the morphology and size of the right ventricular outflow tract and central pulmonary arteries could be accurately assessed. Pulmonary artery measurements obtained from MR images demonstrated excellent correlation with angiographic measurements. In six patients examined after complete surgical repair, MR images accurately reflected changes in pulmonary artery outflow tract morphology and complications, such as residual pulmonary artery stenosis and thrombosis. The findings suggest that MR imaging can complement or obviate catheterization in the evaluation of tetralogy of Fallot with regard to suitability for definitive surgical repair.     

Hematopoietic and fatty bone marrow distribution in the normal and ischemic hip: new observations with 1.5-T MR imaging

The conversion of hematopoietic to fatty marrow is known to correlate with physiologic decreases in intramedullary blood flow. To determine whether the chronology of conversion is altered in patients with hip ischemia, T1-weighted magnetic resonance (MR) images of the hips in 50 healthy people and 27 with documented avascular necrosis (AVN) were reviewed. The distribution of fatty (high-signal) versus hematopoietic (low-signal) marrow was noted with respect to age. All patients had fatty marrow in the femoral capital epiphysis and greater trochanter. Hematopoietic intertrochanteric marrow was seen in 95% (80 of 84) of femurs in control subjects less than 50 years old, but in only 12.5% (two of 16) of those in control subjects older than 50 years (P less than .005). Only 33% (19 of 57) of patients less than 50 years with AVN had predominantly hematopoietic intertrochanteric marrow (P less than .005). The early conversion to fatty marrow in most patients with AVN as depicted by MR imaging may be an effect of decreased vascularity of the proximal femur and may allow the identification of patients at increased risk for AVN.     

Detection of DNA adducts of acetaldehyde in peripheral white blood cells of alcohol abusers

The effect of alcohol drinking on the formation of DNA adducts of acetaldehyde, the primary oxidative metabolite of ethanol, was investigated in humans. DNA was isolated from granulocytes and lymphocytes from 24 alcoholic patients and 12 control subjects. DNA adduct levels were measured by 32P-postlabelling using reversed-phase HPLC with on-line detection of radioactivity. A large interindividual variation in adduct levels was observed. The average adduct levels in granulocyte and lymphocyte DNA from alcoholic patients were 3.4 +/- 3.8 and 2.1 +/- 0.8 adducts/10(7) nucleotides (n = 24), respectively. These levels were 13- and 7-fold higher than the corresponding levels in control subjects (P<0.001). The average adduct level in granulocyte DNA from alcoholic patients was 60% higher than in lymphocyte DNA (P<0.01). Our results, in conjunction with the genotoxicity of acetaldehyde, thus suggest the formation of DNA adducts of acetaldehyde as a plausible mechanism explaining the involvement of alcohol drinking in carcinogenesis.