Suppression of Smad-1 mRNA expression level by Smad-2 likely control dichotomy of NF-κB and Smads mediated activation.

The aim of this study was to find out how NF-κB and Smad-mediated signaling influenced the expression of astrogliogenic versus neurogenic markers of brain development in U4C cells which were either enriched (Tg Jak-1) or deprived in Jak-1 molecule (Jak-1 KO). Genetically modified U4C cells were transfected with NF-kB reporter plasmid in order to follow its activation when cells were cotransfected with different combinations of Smads constructs. In wild type cells no significant activation of NF-κB was observed while genetically modified cells exhibited somewhat different pattern of NF-κB activation depending on the Smad constructs combination used. The absence of NF-κB activation in Jak-1 transgenic cells transfected with Smad-1 plus Smad-3 was accompanied by the appearance of apoptotic cells as revealed by DAPI staining. Smad-1 expression was undetectable in Jak-1 transgenic cells and was downregulated in wild type cells upon transfection with Smad-2. The absence of p65 nuclear translocation in Smad-2 transfected cells and the presence of Smad-4 in nucleus of the same cells indicates dichotomy in NF-κB and Smads mediated signaling pathways. The significance of this study is that helps to elucidate the point of collaboration among three different signaling pathways - Jak-1 mediated cytokine signaling, NF-κB and Smads mediated pathways.

Alternative splicing of p53 and p73: the novel p53 splice variant p53delta is an independent prognostic marker in ovarian cancer.

Similar to p73, the tumor suppressor gene p53 is subject to alternative splicing. Besides p53DeltaE6 and p53beta, we identified p53zeta, p53delta and p53varepsilon, arising from alternative splicing of exon 6 and intron 9, respectively. p53 splice variants were present in 18 of 34 ovarian cancer cell lines (52.9%) and 134 of 245 primary ovarian cancers (54.7%). p53delta expression was associated with impaired response to primary platinum-based chemotherapy (P=0.032). Also, p53delta expression constituted an independent prognostic marker for recurrence-free and overall survival (hazard ratio 1.854, 95% confidence interval 1.121-3.065, P=0.016; and hazard ratio 1.937, 95% confidence interval 1.177-3.186, P=0.009, respectively). p53beta expression was associated with adverse clinicopathologic markers, that is, serous and poorly differentiated cancers (P=0.002 and P=0.008, respectively), and correlated with worse recurrence-free survival in patients exhibiting functionally active p53 (P=0.049). DeltaN'p73 constituted the main N-terminally truncated p73 isoform and was preferentially found in ovarian cancer cell lines showing functionally active p53, supporting our hypothesis that N-terminally truncated p73 isoforms can alleviate the selection pressure for p53 mutations by the inhibition of p53 protein function.

[Exposure to benzene and hematologic changes in workers at the Ina-Oki Drnisplast factory in Drnis]. / Izlozenost benzenu i hematoloske promjene u radnica u tvornici "Ina-Oki Drnisplast" u Drnisu.

In the summer of 1984 workers in the "INA-OKI Drnisplast" factory frequently complained about headaches, weight loss and irregular menstrual cycles. According to the factory engineers that might have been due to an altered composition of the paints and glues that were used in the manufacturing process that year. Those had been found to lack specifications of chemical composition. Experts from the Institute for the Safety at Work from Zagreb were called in to perform measurements of organic solvents content in the workroom air. Benzene concentrations were found to be up to five times higher than the maximum permissible levels, those of toluene up to three times and of cyclohexane up to ten times higher. The polluted part of the factory was closed down, changes were introduced into the working process (use of paints was stopped, only glues without benzene content were allowed and proper ventilation was installed) and all the workers, twenty in all, received medical treatment. After three months the working process was resumed. In 1989 all the twenty workers underwent a control medical examination. All showed signs of recovery, both objective and subjective. Their blood tests values were within normal range. All the workers continued working, save one who retired in 1988 upon recommendation of a disability commission. The cause of disablement was occupational disease--benzene poisoning. On the basis of this experience emphasis is placed on the importance, in working with benzene, of complying with the Legislation on working capacity assessment for jobs requiring special working conditions and with the Safety at work act.