Malawi medical journal : the journal of Medical Association of Malawi, 2012
Cancer of the oesophagus is the 6th most common cancer in Malawi. Nationwide only three hospitals... more Cancer of the oesophagus is the 6th most common cancer in Malawi. Nationwide only three hospitals are able to perform oesophagectomies, and there is no radiotherapy or chemotherapy available. Owing to late presentation of the patients (sometimes in combination with co-morbidities such as HIV/AIDS or tuberculosis) the vast majority of patients are not suitable for surgery. Self-expanding metal stents (SEMS) of the oesophagus provide a suitable palliative option to improve the quality of life for patients. This project took a nationwide approach, raising funds for both technical equipment and training of endoscopists and nursing staff throughout Malawi.
The relative contribution of T cell receptor-versus CD28-mediated signals in co-stimulation of re... more The relative contribution of T cell receptor-versus CD28-mediated signals in co-stimulation of resting CD4 T cells is thought to influence their functional differentiation towards T helper (Th) 1 versus Th2 subsets. We have used a conventional and a mitogenic CD28-specific monoclonal antibody to assess the effect of polyclonal T cell activation through CD28 alone on CD4 subset differentiation. In vivo, mitogenic but not conventional anti-CD28 induces massive lymphocytosis, the Th2 cytokines interleukin (IL)-4 and IL-10, and Th2-dependent immunoglobulin isotypes, most notably IgE. In vitro, it is shown that mitogenic anti-CD28 primes for IL-4-dependent induction of IL-4 expression much more efficiently than conventional co-stimulation. At the molecular level, we show for the first time that the activation of the "Th2 promoting" transcription factor GATA-3 requires co-stimulation by CD28 and is also induced by mitogenic anti-CD28 alone. We suggest that CD28-dependent induction of GATA-3 in concert with other transcription factors, which are preferentially induced by strong CD28-signals, primes CD4 T cells for IL-4-dependent Th2 differentiaton.
Malawi medical journal : the journal of Medical Association of Malawi, 2012
Cancer of the oesophagus is the 6th most common cancer in Malawi. Nationwide only three hospitals... more Cancer of the oesophagus is the 6th most common cancer in Malawi. Nationwide only three hospitals are able to perform oesophagectomies, and there is no radiotherapy or chemotherapy available. Owing to late presentation of the patients (sometimes in combination with co-morbidities such as HIV/AIDS or tuberculosis) the vast majority of patients are not suitable for surgery. Self-expanding metal stents (SEMS) of the oesophagus provide a suitable palliative option to improve the quality of life for patients. This project took a nationwide approach, raising funds for both technical equipment and training of endoscopists and nursing staff throughout Malawi.
The relative contribution of T cell receptor-versus CD28-mediated signals in co-stimulation of re... more The relative contribution of T cell receptor-versus CD28-mediated signals in co-stimulation of resting CD4 T cells is thought to influence their functional differentiation towards T helper (Th) 1 versus Th2 subsets. We have used a conventional and a mitogenic CD28-specific monoclonal antibody to assess the effect of polyclonal T cell activation through CD28 alone on CD4 subset differentiation. In vivo, mitogenic but not conventional anti-CD28 induces massive lymphocytosis, the Th2 cytokines interleukin (IL)-4 and IL-10, and Th2-dependent immunoglobulin isotypes, most notably IgE. In vitro, it is shown that mitogenic anti-CD28 primes for IL-4-dependent induction of IL-4 expression much more efficiently than conventional co-stimulation. At the molecular level, we show for the first time that the activation of the "Th2 promoting" transcription factor GATA-3 requires co-stimulation by CD28 and is also induced by mitogenic anti-CD28 alone. We suggest that CD28-dependent induction of GATA-3 in concert with other transcription factors, which are preferentially induced by strong CD28-signals, primes CD4 T cells for IL-4-dependent Th2 differentiaton.
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