TAL1 cooperates with PI3K/AKT pathway activation in T-cell acute lymphoblastic leukemia.

TAL1 is ectopically expressed in about 30% of T-cell acute lymphoblastic leukemia (T-ALL) due to chromosomal rearrangements leading to the STIL-TAL1 fusion genes or due to non-coding mutations leading to a de novo enhancer driving TAL1 expression. Analysis of sequence data from T-ALL cases demonstrates a significant association between TAL1 expression and activating mutations of the PI3K-AKT pathway. We investigated the oncogenic function of TAL1 and the possible cooperation with PI3K-AKT pathway activation using isogenic pro-T-cell cultures ex vivo and in vivo leukemia models.

Proximal tubular injury in Chinese herbs nephropathy: monitoring by neutral endopeptidase enzymuria.

Neutral endopeptidase (NEP) is a 94 kDa ectoenzyme of the proximal tubule brush border, physiologically released into the urine with apical membrane fragments. As proximal tubular atrophy was a histological hallmark of Chinese herbs nephropathy (CHN), this study firstly determined renal excretion of NEP in healthy control subjects (N = 31), in patients with CHN (N = 26) and in women having consumed Chinese herbs and whose renal function was normal but running the risk of developing CHN (N = 27). Another patient group consisted of female patients with glomerular diseases (N = 12).

Development and validation of new screening tests for nephrotoxic effects.

Within the framework of an European Commission-funded project, groups of industrial workers exposed to heavy metals (cadmium, mercury and lead) or solvents were studied together with corresponding control groups. Eighty-one measurements were carried out on urine and serum samples and the scientific results together with individual questionnaire information were entered into a central database. Data obtained was assessed centrally and individually in subsidiary studies.

Association between NAG-B and cadmium in urine with no evidence of a threshold.

Objectives: To explore the significance of the increase in urinary excretion of the lysosomal enzyme beta-N-acetylglucosaminidase (NAG) at low exposures to cadmium (Cd) that is frequently found in the absence of any other sign of renal dysfunction.

Methods: The activity was measured of the two main isoenzymes of NAG (NAG-A secreted by exocytosis and NAG-B released with cell membranes) in the urine of 49 male workers employed in a Cd smelter and of 20 age matched controls.

Results: An increased urinary excretion of low molecular weight proteins was noted only in subjects who excreted > 10 micrograms Cd/g creatinine.