No abstract

The noninteractive module was more effective in promoting knowledge acquisition. Residents successfully demonstrated knowledge retention with completion of either module. The modules were insufficient to change clinical practice.

Sphingosine I-phosphate (SIP), lysophosphatidic acid (LPA) and phosphatidic acid (PA) bind to Gi/o-protein coupled receptors (GPCRs) to stimulate the p42/p44 mitogen-activated protein kinase (p42/p44 MAPK) pathway human embyronic kidney 293 (HEK293) cells. The bioavailability of these agonists at their receptors may be limited by a family of lipid phosphate phosphatases (LPP1, la, 2 and 3) which catalyse the dephosphorylation of these phosphorylated lipids. However, this study shows that although the stimulation of p42/p44 MAPK by SlP, LPA and PA was substantially reduced in cells transfected with LPPI, l a and 2, this was correlated with reduced basal intracellular phosphatidic acid and not ecto-LPP activity. Additionally, LPPl, l a and 2 also inhibited the stimulation of p42/p44 MAPK by thrombin, a peptide GPCR agonist that is not an LPP substrate. Since the LPPs had no effect on the stimulation of p42/p44 MAPK by other agents that d o not use G-proteins to signal, such as serum factors and phorbol ester, these findings suggest that LPPl, l a and 2 may function to perturb GPCR signalling per se. This may involve inhibition of receptor-mediated endocytosis, which is often required for GPCR internalisation and p42/p44 MAPK activation.We previously demonstrated that the signalling molecule arachidonic acid (AA), induced inhibition of cell growth and apoptosis in bcr-abl transformed leukemia cell line, H7.A54.bcr/abl and haematopoietic progenitor cells from patients with chronic myeloid leukemia (Cancer Res. 59:5047, 1999). The cell-type specificity of AA associated antiproliferative activities was investigated. Dosedependent inhibition of cell growth was detected on incubation of H7.A54.bcr/abl, HL-60 (human promyelocytic leukemia), JURKAT (human acute T-cell leukemia) and U937 (human histiocytic lymphoma) cell lines with 10-100pM AA. AA (100pM,72h) inhibited growth of H7.A54.bcr/abl, HL-60, JURKAT and U937 cell lines by 98%,53%,68%,20% respectively. In contrast, 10-100pM AA had no effect on RPMI 7666 (human normal lymphoblast)cell growth. AA effects on two kinases implicated in leukemic cell apoptosis: P38 mitogen activated protein kinase, p38-MAPK and c-jun amino-terminal kinase UNK) were investigated. J N K activation was detected in H7.A54 cells incubated with 10-lOOpM AA. J N K was also activated by AA in JURKAT, U937, RPMI 7666 cells but not in HL-60 cells. Additionally, AA activated p38-MAPK in H7.A54 bcr/abl, HL-60, U937 cells but not JURKAT and RPI 7666 cells. These results suggest inhibition of cell growth and activation of p38-MAPK and J N K by AA is type-specific. Moreover, leukemic cells were more sensitive to AA inhibitorv effects than normal cells.36 Vavl is required for platelet aggregation to threshold concentrations of Glycoprotein VI agonist, independent of phospholipase C and RacThe GDP/GTP exchange factor Vavl has been shown to have an important role in T-cell receptor signalling, a pathway that has similar components to that of the collagen receptor, Glycoprotein VI (GPVI), in platelets. In t...