Philadelphia chromosome (Ph)-positive leukaemia cells express the chimeric bcr/abl oncoprotein, whose deregulated protein tyrosine kinase (PTK) activity antagonizes the induction of apoptosis by DNA damaging agents. Treatment of Ph-positive K562, TOM 1 and KCL-22 cells with etoposide for 2d induced cytosolic vacuolation, but not nuclear condensation or DNA fragmentation. The bcr/abl kinase-selective inhibitor herbimycin A increased the induction of nuclear apoptosis by etoposide or g-radiation. The concentration of herbimycin required to synergize with etoposide was similar to that required to decrease the level of tyrosine phosphorylated proteins or of the protein tyrosine kinase activity of anti-abl immune complexes in K562 cells. The ability of herbimycin A to sensitize K562, TOM 1 or KCL-22 cells to apoptosis induction correlated with its ability to decrease the cellular content of phosphotyrosyl proteins in these Philadelphia-positive lines. Enhancement of nuclear apoptosis by herbimycin was not attributable to downregulation of the bcl-2 or bcl-X L anti-apoptotic proteins. In contrast, herbimycin protected Philadelphianegative HL60 cells from apoptosis induction by etoposide and did not a ect killing of NC37 and CEM cells. The data suggest that the induction of apoptosis is blocked in cells expressing the bcr/abl oncoprotein and that herbimycin A increases induction of programmed cell death following DNA damage. Selective PTK inhibitors may therefore be of value in securing the genetic death of Ph-positive leukaemia cells.
Research has called for courses to be developed that provide preservice teachers opportunities to actively engage their pedagogies under construction in order to effectively translate their beliefs into sound instructional practice. This article presents research that examined how a service-learning writing tutoring program affected preservice teachers' pedagogy of writing instruction. Students enrolled in the course Teaching Writing in Elementary School spent an hour each week during a semester at a local community center working as writing tutors with elementary students. The service-learning experience represented a "third space" of interaction, where course requirements and children's needs converged. The preservice teachers experienced pedagogical dissonance as they experienced tension in "working the hyphen" between the service and the learning. A negotiation model emerged from the preservice teachers' experiences, which this article shares and explains through the description of three preservice teachers' experiences. Learning how to negotiate this tension may provide preservice teachers with the skills to work as third-space practitioners when faced with similar challenges as future educators.In the era of high-stakes testing and teacher accountability for students' performance on standardized writing assessments, classroom teachers face a challenging instructional environment. The classroom setting has become a space where teachers' professional pedagogy of writing instruction is continually influenced by institutionalized prepackaged curricula.Striving to meet their students' needs yet simultaneously attempting to complete the coverage of the curriculum, classroom teachers are positioned in a middle s p x e of constant negotiation. Rather than sink into defeatist thinking, some teachers, what English (2005) calls "third space" practitioners, strategize and shift to meet the needs of the situation. Such teachers negotiate an instructional third space that values students' needs and supports district and state standards. The concept of third space (Bhabha, 1994; English, 2005; Fine, 1994) can be understood as the place where multiple cultural ways of being, habits, and practices from different spaces or contexts are brought together Negotiating Pedagogy Development 95 in a shared context. No longer is one set of cultural practices superior to another. To sustain existence in this shared space, negotiation that leads to a unique and new context must occur (Bhabha, 1994). This study demonstrates how servicelearning offers a third space for preservice teachers to negotiate their pedagogical beliefs and instructional skills. To engage preservice teachers in constructing pedagogies of writing instruction, we designed a Teaching Writing in Elementary School course, which included a service-learning writing tutoring experience at a local community center. As the worlds of the university course and the community center interacted, they created a third space where the preservice teachers and children were the acto...
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