Gene transfer and expression of exogenous genetic information coding for an immunogenic protein in antigen presenting cells (APCs) can promote an immune response. This was investigated by retroviral transfer of a marker gene into CD34+ derived APCs.To achieve long term expression of a specific transgene in APCs, G-CSF mobilized peripheral blood CD34+ cell populations were retrovirally transduced with the bacterial nlsLacZ, a marker gene used here as a model, in the presence of IL-3, IL-6, GM-CSF and SCF prior to being induced to differentiate into dendritic and macrophage cells by GM-CSF and TNF-a.Addition of IL-4 was found to induce dendritic differentiation preferentially by inhibiting proliferation and differentiation of the macrophage lineage. As assessed by X-Gal staining, LacZ gene expression was observed in cells from both the dendritic lineage (CD1a+/CD14-) which still exhibits the highest immunostimulatory activity in mixed lymphocyte reaction and from the macrophage lineage (CD1a-/ CD14+).This study sets out the possibility of transducing dendritic and macrophage progenitors present in the CD34+ cell population and in using a marker gene such as nlsLacZ to study gene expression in antigen presenting cell compartments.
Abstract Background: Severe overcrowding of emergency departments (EDs) affects the quality of healthcare. One factor of overcrowding is precariousness, but it has rarely been considered a key factor in designing interventions to improve ED care. Health mediation (HM) aims to facilitate access to rights, prevention, and care for the most vulnerable persons and to raise awareness among healthcare providers about obstacles in accessing healthcare. The primary aim of this study was to determine whether HM intervention for frequent users of EDs (FUED) living in precarious conditions could reduce the readmission rate at 90 days. Methods : Between February 2019 and May 2022, we enrolled and interviewed 726 FUED in four EDs of southeastern France in this randomised controlled trial. The HM intervention started in the ED and lasted 90 days. The outcome was measured in the ED information systems. Statistical methods included an intention-to-treat analysis and a per-protocol analysis. Comparisons were adjusted for gender, age, ED, and health mediator. Results : 46% of patients reported attending the ED because they felt their life was in danger, and 42% had been referred to the ED by the emergency medical dispatch centre or their GP; 40% of patients were considered to be in a serious condition by ED physicians. The proportion of patients who were readmitted at 90 days was high but did not differ between the control and the HM intervention groups (31.7% vs 36.3, p=0.23). There was no significant difference in any of the secondary outcome measures between the control and HM intervention groups. Per-protocol analysis also showed no significant difference for the primary and secondary endpoints. Conclusions: Although health mediation seemed to be a promising solution at the end of our qualitative study, this randomised controlled trial did not show that it was effective in reducing the use of emergency services by FUED living in precarious conditions. Interventions should screen these patients and aim to accurately identify their social, psychosocial and medical needs, involve ED staff and train them on the issue of precariousness, with a view to long-term health empowerment. Trial registration : registered on clinicaltrials.gov as NCT03660215 on 4 th September 2018
Severe overcrowding of emergency departments (EDs) affects the quality of healthcare. One factor of overcrowding is precariousness, but it has rarely been considered a key factor in designing interventions to improve ED care. Health mediation (HM) aims to facilitate access to rights, prevention, and care for the most vulnerable persons and to raise awareness among healthcare providers about obstacles in accessing healthcare. The primary aim was to determine whether HM intervention for frequent users of EDs (FUED) living in precarious conditions could reduce the readmission rate at 90 days.