Leukemia cell signaling and signaling of non-malignant B-cells

Leukemia cell signaling Acute leukemia (AL) is the most common pediatric cancer. Approximately 90 - 100 children is diagnosed every year in the Czech Republic. Acute leukemia is a complex disease that is pathologically manifested at the DNA, mRNA, protein and cellular level. Leukemic cells aberrantly express molecules that are found in other cell types under physiological conditions and their functional involvement in leukemic cells is unknow. We found that aberrantly expressed CEACAM6 increases the expression and affinity of integrins, increases the phosphorylation of intracellular kinases Akt, p38MAPK and p44/42 MAPK and triggers apoptosis in B- cell precursor acute lymphoblastic leukemia cells. Adaptor molecule NTAL, aberrantly expressed in T-cell acute lymphoblastic leukemia, signals through intracellular kinase p44/42 MAPK and potentiates corticosteroid induced apoptosis. Current leukemia research is focused mainly on monitoring of mutations at the DNA level, however, the functional consequences of these changes on cellular machineries are not straightforward. Since proteome analysis can provide link between gene sequence and cellular physiology, proteomics will contribute to elucidate mechanism of disease, prognosis and response to treatment. Protein microarrays technology is of major..

Phylogenetic analyses.

<p>Phylogenetic tree for the HA gene (AA based) as well as the results on the genetic analyses of the NA gene, antigenic typing results and information on the time of sample collection of each virus; viruses in colour and framed by red rectangles indicate reference viruses; viruses in bold and with * indicate vaccinated influenza positive cases; viruses in red and bold indicate influenza B viruses with HA and NA from distinct influenza B lineages. (4A) detailed results of 59 influenza A(H1N1)pdm09 viruses, (4B) detailed results of 98 A(H3N2) viruses, and (4C) detailed results of 58 influenza B viruses.</p

Inclusion and exclusion criteria.

<p>Inclusion and exclusion criteria applied to the data set used for VE estimates.</p

Vaccine effectiveness estimates.

<p>Vaccine effectiveness estimates.</p

Participants Profile.

<p>Participants Profile.</p

The numbers of specimens with a positive RIDT result were determined within four intervals of cycle threshold (Ct) values: 20.3–27.1, 27.2–30.3, 30.5–34.8, 34.9–41.6 (quartiles of Ct values).

<p>The numbers of specimens with a positive RIDT result were determined within four intervals of cycle threshold (Ct) values: 20.3–27.1, 27.2–30.3, 30.5–34.8, 34.9–41.6 (quartiles of Ct values).</p

Performance of the QuickVue Influenza A+B rapid test in comparison with RT-PCR in the diagnosis of pandemic H1N1 (2009) virus infection.^a

a<p>confidence interval (CI).</p

Ct values of respiratory specimens in 119 patients with RT-PCR-confirmed pandemic influenza A H1N1 (2009) virus infections.

<p>Ct values are compared between patients who had positive (Ct median 28.44) and negative (Ct median 31.9) results in the QuickVue Influenza A+B rapid test (p<0.001). The box shows the median and interquartile range (box length). The whiskers represent minimum/maximum values. Individual values are presented as circles.</p

Inhibition of myristoylation by DDD85646 does not perturb CVB3 2C and VP1 colocalization.

<p>HeLa cells were infected with CVB3 (MOI of 5) in presence of 5 μM DDD85646 or DMSO (solvent control) and fixed and permeabilized with 0.5% saponin at 5 h p.i. Nuclei were visualized with DAPI (blue color). The location of VP1 was determined with a mouse monoclonal anti-enterovirus VP1 primary antibody and Alexa Fluor 488-conjugated secondary antibody (green color). 2C was probed in the same cells with an anti-CVB3 2C rabbit antibody and Alexa 555-conjugated secondary antibody (red color). Images were acquired by confocal immunofluorescence microscopy. Yellow regions in the merged images indicate colocalization. Scale bar 20 μm.</p

Ultrastructural changes of DDD85646- or control-treated HeLa cells infected with CVB3.

<p>(A) TEM image of a noninfected HeLa cell treated with 0.1% DMSO (solvent control). N, nucleus; Nm, nuclear membrane; M, mitochondria; ER, endoplasmic reticulum; MV, microvilli; Ch, chromatin. (B) TEM image of a noninfected HeLa cell treated with 5 μM DDD85646. (C) TEM image of a HeLa cell infected with CVB3 at an MOI of 10 in the presence of 0.1% DMSO (solvent control). The observed ultrastructural changes are typical for infection by this virus. DMV, double-membrane vesicle; MMV, multimembrane vesicle; Vb, virus bleb (an irregular virus-related aggregate); Ar, virus paracrystalline array. The black arrows indicate discontinuations of the nuclear envelope. Insets C1 to C3 are higher magnifications of the boxed regions. (D) TEM image of a HeLa cell infected with CVB3 at an MOI of 10 in the presence of 5 μM DDD85646. Virus blebs are present but no paracrystalline arrays are formed. Insets D1 and D2 are higher magnifications of the boxed regions.</p