Evidence for a role of RUNX1 as recombinase cofactor for TCRß rearrangements and pathological deletions in ETV6-RUNX1 ALL.

T-cell receptor gene beta (TCRß) gene rearrangement represents a complex, tightly regulated molecular mechanism involving excision, deletion and recombination of DNA during T-cell development. RUNX1, a well-known transcription factor for T-cell differentiation, has recently been described to act in addition as a recombinase cofactor for TCRδ gene rearrangements. In this work we employed a RUNX1 knock-out mouse model and demonstrate by deep TCRß sequencing, immunostaining and chromatin immunoprecipitation that RUNX1 binds to the initiation site of TCRß rearrangement and its homozygous inactivation induces severe structural changes of the rearranged TCRß gene, whereas heterozygous inactivation has almost no impact. To compare the mouse model results to the situation in Acute Lymphoblastic Leukemia (ALL) we analyzed TCRß gene rearrangements in T-ALL samples harboring heterozygous Runx1 mutations. Comparable to the Runx1+/- mouse model, heterozygous Runx1 mutations in T-ALL patients displayed no detectable impact on TCRß rearrangements. Furthermore, we reanalyzed published sequence data from recurrent deletion borders of ALL patients carrying an ETV6-RUNX1 translocation. RUNX1 motifs were significantly overrepresented at the deletion ends arguing for a role of RUNX1 in the deletion mechanism. Collectively, our data imply a role of RUNX1 as recombinase cofactor for both physiological and aberrant deletions.

[Ultrasound diagnosis of Meckel-Gruber syndrome at 13 weeks of gestation in families at risk--a case report and literature review]. / Ultrazvukova diagnoza na sindroma Meckel-Gruber v 13 g.s. pri riskovo semeistvo--predstaviane na sluchai i pregled na literaturata.

Meckel-Gruber syndrome (MGS) is a lethal, rare, autosomal recessive condition manifested by clinical and genetical heterogenicity. The syndrome is characterized by the triad: occipital meningo-encephalocele, cystic displastic kidneys and postaxial polidactyly. The diagnosis is suspected by ultrasound and in families at risk of reccurrence of the syndrome it is made in the late first trimester of pregnancy. We present a patient with a previous pregnancy terminated in the second trimester because of ultrasound features for MGS, in whom a correct transvaginal ultrasound diagnosis of the same syndrome was made in 13 w.g. of the present pregnancy.

Foam separation of DNA and proteins from solutions.

Foam separation on BSA-DNA (bovine serum albumine/deoxyribonucleic acid) and Lysozyme-DNA systems is performed. The separation of the total protein from DNA is evaluated for dissociated chromatin solution. Foam separation for the same systems is done also by a new method of creating a pressure gradient in the Plateau-Gibbs borders in the foam and obtaining a "dry" foam. It is shown that the effectiveness of the foam separation can be improved significantly by the application of the latter method. Some factors (pH, initial concentration of the solution, expansion factor of the foam) influencing the separation of proteins from DNA in the foam and in the residual solution are studied as well.

Study on the prostaglandin antagonistic activity of aligeron and piracetam.

The interaction of aligeron and piracetam with the effects of prostaglandin F2 alpha (PGF2 alpha) E2 (PGE2) was studied using in vitro and in vivo tests for evaluation of PG antagonistic activity. Aligeron was found to be a non-selective PG antagonist in isolated guinea-pig stomach smooth muscle preparations. It antagonized the PGF2 alpha and PGE2-induced fall in blood pressure in cats prevented diarrhoea induced by PGF2 alpha in mice, inhibited rat paw oedema induced by PGE2 in rats, but did not modify the PGF2 alpha induced bronchoconstriction in guinea-pigs. Piracetam did not antagonize the smooth muscle contractile effects of PGF2 alpha and PGE2 and in the in vivo tests it inhibited only the rat paw oedema induced by PGE2. It is concluded that aligeron is active in vitro and in vivo as an antagonist of some of the actions of PGs studied. Its effect in vitro lacks selectivity and is probably due to interference with the action of Ca2+. The probable clinical implication of these results will be discussed. Piracetam can not be considered a PG antagonist.