The fusion of TEL and ABL in human acute lymphoblastic leukaemia is a rare event

We have recently identified a common ALL patient which harboured a chromosomal fusion between the TEL gene on chromosome 12 and the ABL gene on chromosome 9. We designed an RT-PCR assay to screen 186 adult ALL and 30 childhood ALL patients for this novel translocation. We were unable to identify any additional cases with a TEL/ABL fusion product.     

EFFECTS OF GROWTH HORMONE ON PROTEIN METABOLISM Acute Changes in Plasma Amino Acids in Growth Retarded Patients with and without Growth Hormone Deficiency

Abstract 39 patients with growth retardation were investigated: 21 (group H) were suffering from GH deficiency and 18 (group N) had no endocrine disease except for two adequately treated patients with mild hypothyroidism. Analysis of 15 plasma amino acid concentrations was carried out before and 1 and 2 hours after intravenous HGH injection at a dosage of 2 mg per m². Except for one amino acid no significant difference between mean pre-treatment amino acid values was observed in the two groups of patients. In group H there was a highly significant decrease in plasma concentration of 14 amino acids already 1 hour after HGH injection and of all 15 amino acids after 2 hours. This response of plasma amino acids to HGH was less pronounced in group N. For 5 amino acids a moderate correlation was found in group H between acute metabolic response to HGH and growth response to long-term HGH treatment. Our results following HGH injection may reflect increased plasma amino acid transfer into cells due to HGH.     

Early motor repertoire is related to level of self-mobility in children with cerebral palsy at school age

Aim  To determine the predictive value of the early motor repertoire for the level of self-mobility in children with cerebral palsy (CP) at school age.
Method  Video recordings were made at 11 to 17 weeks post-term of 37 preterm infants (20 males, 17 females) who later developed CP. The early motor repertoire was assessed by obtaining a motor optimality score. At 6 to 12 years, children were classified according to the Gross Motor Function Classification System (GMFCS).
Results  Of 37 children (mean gestational age 29.1wks, SD 1.9; mean birthweight 1273g, SD 324), nine had unilateral and 28 had bilateral spastic CP. Twelve children were in GMFCS level I, three level II, 10 level III, four level IV, and eight level V. The absence of the age-adequate motor repertoire, a cramped motor repertoire, an abnormal kicking pattern, and a non-flat supine posture were associated with lower levels of self-mobility (χ² for trend test, p <0.05). Predictive for a low level of self-mobility was a cramped motor repertoire/non-flat supine posture (positive predictive values [PPV] 100%, negative predictive values [NPV] 54%). Predictive for a high level of self-mobility was a non-cramped repertoire/flat supine posture (PPV 80%, NPV 74%).
Interpretation  Several aspects of the motor repertoire at 11 to 17 weeks post-term predicted the degree of functional limitations in children with CP at school age.     

Biotransformation of the Fungicide Chlorthalonil by Glutathione Conjugation

The biotransformation of the nephrotoxic fungicide chlorthalonil(2,4,5,6-tetrachloroisophthalonitril) has been studied in therat and in rat liver subcellular fractions. In rat liver cytosol,chlorthalonil was rapidly transformed to 4,6-bis(glutathion-S-yl)-2,5-dichloroisophthalonitrilin the presence of glutathione in a reaction catalysed by glutathioneS-transferases. 4-{Glutathion-S-yl)-2,5,6-trichloroisiphthalonitrilwas observed as an intermediate in the glutathione-dependentbiotransformation of chlorthalonil. In the bile of rats dosedwith chlorthalonil (0.18 mmol/kg, orally) 4,6-bis(glutathion-S-yl)-2,5-dichloroisophthalonitrilwas recovered as a minor metabolite. In rats, chlorthalonilwas transformed to 4,6-bis(N-acetyl-cystein-S-yl)2,5-dichloroisophthalonitril.This metabolite was excreted in small amounts in the urine ofrats dosed orally with chlorthalonil (0.66 and 2.64 mmol/kg).In all experiments, a major part of the dose was recovered asunchanged chlorthalonil in feces. Oral administration of chlorthalonil(0.66 and 2.64 mmol/kg) resulted in a slight increase in theurinary excretion of -glutamyltranspeptidase, indicative ofnephrotoxicity. Other parameters indicative for renal proximaltubular damage (urinary glucose and protein excretion) werenot changed by acute chlorthalonil administration. Very minorrenal lesions were observed in chlorthalonil-dosed animals byhistopathological examination.     

Radioligand binding characteristics of β2–adrenoceptors of cultured melanoma cells

The existence of beta-adrenoceptors on intact cells of the human malignant melanoma cell line A-375 was investigated using the binding properties of the tritiated radioligand (-)-[3H]CGP-12177, a hydrophilic non-selective beta-adrenoceptor antagonist. Displacement experiments of the radioligand from its binding site were performed with antagonists and agonists to determine the beta-adrenoceptor subtype selectivity. The binding of (-)-[3H]CGP-12177 was saturable, of high affinity (KD = 0.025 nmol/l, n = 12) and was rapid and readily reversible. The maximal number of binding sites (Bmax) was 33.5 +/- 1.9 fmol/10(7) cells or 2018 +/- 114 receptors per cell. beta-adrenoceptor antagonists inhibited binding of the radioligand with monophasic displacement curves. IC50 values were (nmol/l): propranolol (non-selective) 2.82, alprenolol (non-selective) 2.0, ICI 118,551 (beta 2-selective) 3.5 and bisoprolol (beta 1-selective) 2200. Agonists inhibited binding in the order of potency of isoprenaline greater than adrenaline greater than noradrenaline. It is concluded that cells of the melanoma cell line A-375 contain a homogeneous population of beta 2-adrenoceptors.     

Cell lines of human germinal cancer

Three new established human germ cell tumour lines, H 12.1, H 12.5 and H 12.7, are described. Cytogenetic and growth characteristics, morphology, histology, and tumour marker and steroid hormone production in vitro and/or in vivo revealed properties commonly found in other germ cell tumour lines and in patients with these tumours. In vitro oestrone and oestradiol were produced by the H 12 lines and four other lines (833 KE, 1156 Q, 1428 A and 2102 EP) under high and low density (differentiation inducing) conditions. AFP was produced by one line and beta-hCG by six of seven lines under low density conditions. The pattern of oestrogen production suggests that these hormones could be useful in AFP and beta-hCG negative patients. Differentiated elements of somatic and extraembryonic character, observed in tumours of H 12.1 and H 12.7, underline the value of these lines in the study of differentiation and other germ cell tumour related questions.