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Biomedical subjects

A Griekspoor

Publications and source records attributed to A Griekspoor.

10 recordsLinked to original sources
PubMed2002

Herpes viral proteins manipulating the peptide transporter TAP.

The peptide transporter associated with antigen processing (TAP) is crucial for class I-restricted antigen presentation because it transfers cytosolic peptides into the endoplasmic reticulum (ER) lumen for class I binding. It is therefore not surprising that TAP is targeted for inactivation by many viruses. Herpesviruses have been very successful in designing various proteins that inactivate TAP. We summarise current knowledge on the class I antigen presentation pathway and the function, structure and action of TAP and its viral inhibitors.

Animals↗
PubMed2001

Refugees.

Explore the source record for details and available documents.

Altruism↗
PubMed2001

Regulation of MHC class II antigen presentation by sorting of recycling HLA-DM/DO and class II within the multivesicular body.

MHC class II molecules bind antigenic peptides in the late endosomal/lysosomal MHC class II compartments (MIIC) before cell surface presentation. The class II modulatory molecules HLA-DM and HLA-DO mainly localize to the MIICs. Here we show that DM/DO complexes continuously recycle between the plasma membrane and the lysosomal MIICs. Like DMbeta and the class II-associated invariant chain, the DObeta cytoplasmic tail contains potential lysosomal targeting signals. The DObeta signals, however, are not essential for internalization of the DM/DO complex from the plasma membrane or targeting to the MIICs. Instead, the DObeta tail determines the distribution of both DM/DO and class II within the multivesicular MIIC by preferentially localizing them to the limiting membrane and, in lesser amounts, to the internal membranes. This distribution augments the efficiency of class II antigenic peptide loading by affecting the efficacy of lateral interaction between DM/DO and class II molecules. Sorting of DM/DO and class II molecules to specific localizations within the MIIC represents a novel way of regulating MHC class II Ag presentation.

Amino Acid Motifs↗
PubMed2000

What to do with HLA-DO?

Antigenic peptide binding to MHC class II molecules in the endocytic pathway occurs via a multifactorial process that requires the support of a specialized lysosomal chaperone called HLA-DM. DM shows both in primary amino acid sequence and quaternary structure a high homology to both MHC class I and class II molecules. Like the peptide presenting class II molecules, DM is expressed in all professional antigen presenting cells. DM catalyzes the dissociation of peptides that do not bind stably to the class II peptide-binding groove, thereby leading to the preferential presentation of stably binding antigenic peptides. The recently discovered HLA-DO molecule is mainly expressed in B cells and associates with DM, thereby markedly affecting DM function. Like DM, the genes encoding the HLA-DO heterodimer lie within the MHC class II region and exhibit strong homology to classical class II molecules. This review evaluates the unique effects of DO on DM-mediated antigen presentation by MHC class II molecules and discusses the possible physiological relevance for the B cell-specific expression of DO and its function.

Animals↗
PubMed1999

Cost-effectiveness analysis of humanitarian relief interventions: visceral leishmaniasis treatment in the Sudan.

Spending by aid agencies on emergencies has quadrupled over the last decade, to over US$6 billion. To date, cost-effectiveness has seldom been considered in the prioritization and evaluation of emergency interventions. The sheer volume of resources spent on humanitarian aid and the chronicity of many humanitarian interventions call for more attention to be paid to the issue of 'value for money'. In this paper we present data from a major humanitarian crisis, an epidemic of visceral leishmaniasis (VL) in war-torn Sudan. The special circumstances provided us, in retrospect, with unusually accurate data on excess mortality, costs of the intervention and its effects, thus allowing us to express cost-effectiveness as the cost per Disability Adjusted Life Year (DALY) averted. The cost-effectiveness ratio, of US$18.40 per DALY (uncertainty range between US$13.53 and US$27.63), places the treatment of VL in Sudan among health interventions considered 'very good value for money' (interventions of less than US$25 per DALY). We discuss the usefulness of this analysis to the internal management of the VL programme, the procurement of funds for the programme, and more generally, to priority setting in humanitarian relief interventions. We feel that in evaluations of emergency interventions attempts could be made more often to perform cost-effectiveness analyses, including the use of DALYs, provided that the outcomes of these analyses are seen in the broad context of the emergency situation and its consequences on the affected population. This paper provides a first contribution to what is hoped to become an international database of cost-effectiveness studies of health interventions during relief operations, which use a comparable measure of health outcome such as the DALY.

Altruism↗
PubMedDate not supplied

Enhancing the quality of humanitarian assistance: taking stock and future initiatives.

During the last five years, the debate on the performance of humanitarian assistance has intensified. The motivation to "do better" has come both from within the humanitarian agencies as well as from pressure exerted by the donors and the media. Paradoxically, until now, the voice of those who are to benefit from this assistance has not been heard. This paper is an overview of the most important initiatives to increase the quality of humanitarian assistance. The introduction of the logical framework and the increasing body of knowledge made available through guidelines have improved project management by measuring process and outcomes. Increasingly, evaluations are used to give account and to learn from experiences. But, current evaluation practice must develop in a wider variety of approaches more appropriate to create change of the operations in the field. Some agencies oppose new developments like the Sphere and the Humanitarian Accountability Projects, arguing that standards and regulation would undermine necessary flexibility to adjust responses to the local context, or be a threat to their independence. Nonetheless, standards are considered to be a prerequisite as reference to assess performance. Furthermore, it is hoped that a new breakthrough will be achieved by improved accountability towards beneficiaries. An option to address some of the gaps in the current quality assessment tools was to widen the perspective on performance from projects to the organisations behind them. Quality management models may provide the required framework, and they also can be used to embed current initiatives by organisations. Humanitarian organisations may want to develop forms of self-regulation rather than waiting for accreditation by donors. Another area in which progress is needed is a system-wide approach to performance. At this level, the influence of political actors, donors, national governments, and other representatives of the parties in a conflict also should be assessed. It is their legal obligation to protect the basic right to assistance of persons affected by disasters, as enshrined in international law.

Altruism↗