Regulation of IL-2 expression by transcription factor BACH2 in umbilical cord blood CD4+ T cells.

On activation, umbilical cord blood (UCB) CD4(+) T cells demonstrate reduced expression of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), whereas maintaining equivalent interleukin-2 (IL-2) levels, as compared with adult peripheral blood (PB) CD4(+) T cells. Nuclear factor of activated T cells (NFAT1) protein, a transcription factor known to regulate the expression of IL-2, TNF-alpha and IFN-gamma, is reduced in resting and activated UCB CD4(+) T cells. In contrast, expression of Broad-complex-Tramtrack-Bric-a-Brac and Cap'n'collar homology 1 bZip transcription factor 2 (BACH2) was shown by gene array analyses to be increased in UCB CD4(+) T cells and was validated by qRT-PCR. Using chromatin immunoprecipitation, BACH2 was shown binding to the human IL-2 proximal promoter. Knockdown experiments of BACH2 by transient transfection of UCB CD4(+) T cells with BACH2 siRNA resulted in significant reductions in stimulated IL-2 production. Decreased IL-2 gene transcription in UCB CD4(+) T cells transfected with BACH2 siRNA was confirmed by a human IL-2 luciferase assay. In summary, BACH2 maintains IL-2 expression in UCB CD4(+) T cells at levels equivalent to adult PB CD4(+) T cells despite reduced NFAT1 protein expression. Thus, BACH2 expression is necessary to maintain IL-2 production when NFAT1 protein is reduced, potentially impacting UCB graft CD4(+) T-cell allogeneic responses.

[The origin of the Wilno Obstetric and Gynaecological Clinic and its roots, which reach as far back as the 18th century]. / Poczatki Kliniki Polozniczo-Ginekologicznej Uniwersytetu Stefana Batorego w Wilnie i jej korzenie siegajace wieku XVIII.

Studies carried out in libraries and archives in Wilno, Cracow, Warsaw and Gdánsk raven how the clinic of obstetrics and gynaecology was created in Wilno, describe the first years activity, and the persons who had the greatest influence on its creation and position. This clinic, which was organized by Tadeusz Burdzinski and developed by Wladyslaw Jakowicki in cooperation with Waclaw Zaleski, functioned in the years 1922-1939. In its scarcely 17 years of existence this clinic had a marked presence among the Polish clinics of obstetrics and gynaecology in the Second Republic (II RP). In the author's opinion this fact can be traced back to the roots of obstetrics and gynaecology in the university in Wilno, which reach as far as the 18th century and the person of Mikolaj Regnier. For the first half of the 19th century the gynaecologists and obstetrics of Wilno includes Andrzej Matusewicz and Mikolaj Mianowski carried out their scientific activities outside the University for nearly 80 years. It seems that this activity, which lead to numerous publications, is the platform upon which rests continuous scientific tradition of obstetrics and gynaecology in Wilno and lets us see to present clinic in the University of Stefan Batory - in 21st surely century - as her heiress of that tradition.

QSAR studies of antiviral agents using molecular similarity analysis and structure-activity maps.

Quantitative structure-activity relationships (QSAR) were developed for nucleoside analogs with anti-HIV activity. These compounds were investigated to determine the correlation of structure and toxicity/activity using molecular similarity analysis and structure-activity maps. A multiple-formula approach was used to perform quantitative molecular similarity analysis (QMSA) and QSAR study. Molecular descriptors such as number of atoms and bonds of a molecule (NAB), maximum common substructure (MaCS), and molecular similarity index (MSI) were used in our structure-activity relationship study. The MaCS of two molecules is defined as the substructure with the greatest NAB value common to both molecules. The MSI of two molecules X and Y is defined as MSI(X,Y) = [MaCS(X,Y)/NAB(X)] x [MaCS(X,Y)/NAB(Y)]. MaCS and MSI quantify the similarity between two molecular structures. Structure-activity maps (structure-toxicity map and structure-antiviral map) and QMSA were used to determine the site and type of modification for reduced toxicity and improved activity of new compounds.