43 research outputs found
Actions of Calcium on Smooth Muscle a
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72185/1/j.1749-6632.1988.tb33358.x.pd
Australian supervisors and recruits: Closing the gap in understanding each othersâ viewpoints
This study attempts to depict the shared meanings or collective schemas about the training of new recruits in organizations. Supervisors understood little about the new recruitsâ maps of the world, whereas new recruits had a greater understanding of their supervisorsâ points of view. The researchers investigated strategies that would close this gap in understanding and increase training effectiveness. Results from a 2-month pretest-posttest design demonstrated changes in the construings (ways of thinking about the world) in the groups regarding the 12 training activities. After the intervention, both groups perceived the training activities as being more conducive to understanding the othersâ points of view, with the supervisors making a moderate shift and the new recruits a smaller shift
Decoupling of normal CD40/interleukin-4 immunoglobulin heavy chain switch signal leads to genomic instability in SGH-MM5 and RPMI 8226 multiple myeloma cell lines
The processes mediating genomic instability and clonal evolution are obscure in multiple myeloma (MM). Acquisition of new chromosomal translocations into the switch region of the immunoglobulin heavy chain (IgH) gene (chromosome 14q32) in MM, often heralds transformation to more aggressive disease. Since the combined effects of CD40 plus interleukin-4 (IL-4) mediate IgH isotype class switch recombination (CSR), and this process involves DNA double strand break repair (DSBR), we hypothesized that CD40 and/or IL-4 activation of MM cells could induce abnormal DNA DSBR and lead to genomic instability and clonal evolution. In this study, we show that MM cell lines that are optimally triggered via CD40 and/or IL-4 demonstrate abnormal decoupling of IL-4 signal transduction from CD40. Specifically, CD40 alone was sufficient to trigger maximal growth of tumor cells. We further demonstrate that CD40 triggering induced both DNA DSBs as well as newly acquired karyotypic abnormalities in MM cell lines. Importantly, these observations were accompanied by induction of activation induced cytidine deaminase expression, but not gross apoptosis. These data support the role of abnormal CD40 signal transduction in mediating genomic instability, suggesting a role for the CD40 pathway and intermediates in myelomagenesis and clonal evolution in vivo