Different types of FC γ -receptors are involved in anti-Lewis Y antibody induced effector functions in vitro

Stimulation of monocytes by interaction of monoclonal antibodies (mAbs) with Fc gamma receptors (FcγRs) results in the activation of various monocyte effector functions. In the present investigation we show that the anti-Lewis Y (LeY) anti-tumour mAb ABL 364 and its mouse/human IgG1 chimaera induce both antibody-dependent cellular cytotoxicity (ADCC) and the release of tumour necrosis factor α (TNF-α) during mixed culture of monocytes with LeY+SKBR5 breast cancer cells in vitro. Although anti-LeY mAb-mediated TNF-α release paralleled ADCC activity, cytokine release required a higher concentration of sensitizing mAb than the induction of cytolysis. The determination of the FcγR classes involved in the induction of the distinct effector functions showed that anti-LeY mAb-induced cytolysis was triggered by interaction between anti-LeY mAbs and FcγRI. In contrast, mAb-induced TNF-α release mainly depended on the activation of monocyte FcγRII. Neutralization of TNF-α showed no influence on monocyte ADCC activity towards SKBR5 target cells. Our data indicate an independent regulation of anti-LeY mAb induced effector functions of ADCC and TNF-α release which seemed to be triggered by activation of different types of FcγR. © 2000 Cancer Research Campaig

Training attentional control and working memory – is younger, better?

Authors have argued that various forms of interventions may be more effective in younger children. Is cognitive training also more effective, the earlier the training is applied? We review evidence suggesting that functional neural networks, including those subserving attentional control, may be more unspecialised and undifferentiated earlier in development. We also discuss evidence suggesting that certain skills such as attentional control may be important as ‘hub’ cognitive domains, gating the subsequent acquisition of skills in other areas. Both of these factors suggest that attentional training administered to younger individuals ought to be relatively more effective in improving cognitive functioning across domains. We evaluate studies that have administered forms of cognitive training targeting various subcomponents of attention and the closely related domain of working memory, and we contrast their reported transfer to distal cognitive domains as a function of the age of the participants. Although negative findings continue to be common in this literature we find that cognitive training applied to younger individuals tends to lead to significantly more widespread transfer of training effects. We conclude that future work in this area should concentrate on understanding early intensive training, and discuss a number of practical steps that might help to achieve this aim