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Current problems and future directions of transfusion-induced alloimmunization : summary of an NHLBI working group

In April 2010, a working group sponsored by the National Heart, Lung, and Blood Institute was assembled to identify research strategies to improve our understanding of alloimmunization caused by the transfusion of allogeneic blood components and to evaluate potential approaches to both reduce its occurrence and manage its effects. Significant sequelae of alloimmunization were discussed and identif

Recent progress in understanding the pathogenesis of immune thrombocytopenia

PURPOSE OF REVIEW: Immune thrombocytopenia (ITP) is a bleeding disorder in which both antibody and cell-mediated autoimmune responses are directed against an individual's own platelets and/or megakaryocytes, leading to either enhanced platelet destruction and/or reduced platelet production, respectively. The cause of this platelet-specific autoimmunity remains unknown, but there has been a constan

Recipient T lymphocytes modulate the severity of antibody-mediated transfusion-related acute lung injury

Transfusion-related acute lung injury (TRALI) is a serious complication of transfusion and has been ranked as one of the leading causes of transfusion-related fatalities. Nonetheless, many details of the immunopathogenesis of TRALI, particularly with respect to recipient factors are unknown. We used a murine model of antibody-mediated TRALI in an attempt to understand the role that recipient lymph

Transfusion of antibody-opsonized red blood cells results in a shift in the immune response from the red blood cell to the antibody in a murine model

BACKGROUND: It is well known that infusion of immunoglobulin (Ig)G-coated cells results in an inhibited antigen-specific humoral immune response compared to the cells themselves, a phenomenon termed antibody-mediated immune suppression (AMIS). Although this AMIS effect has been well described with many different types of cells as well as vaccines and insoluble antigens, the mechanisms behind this

Animal models of immune thrombocytopenia (ITP)

With regards to research animal models related to immune thrombocytopenia (ITP), there is an extensive literature of over 300 publications published since 1959. It appears that many of these models either confirm what has been found in human ITP or, in some instances, are the first to describe a phenomenon related to ITP that is still of relevance today in human medicine. These models will undoubt

Future research in ITP : an ICIS consensus

While much has been learned about the basic immunology and clinical characteristics of immune thrombocytopenia, many important questions remain with regard to pathogenesis, disease progression, identification of novel therapeutic targets and approaches, and clinical trials that rationalize and optimize use of existing therapies. The answers to these questions are likely to impact our understanding

Platelets and innate immunity

Although platelets are best known as primary mediators of hemostasis, this function intimately associates them with inflammatory processes, and it has been increasingly recognized that platelets play an active role in both innate and adaptive immunity. For example, platelet adhesive interactions with leukocytes and endothelial cells via P-selectin can lead to several pro-inflammatory events, inclu

A murine model of severe immune thrombocytopenia is induced by antibody- and CD8+ T cell-mediated responses that are differentially sensitive to therapy

Immune thrombocytopenia (ITP) is a bleeding disorder characterized by antibody-opsonized platelets being prematurely destroyed in the spleen, although some patients with ITP may have a cell-mediated form of thrombocytopenia. Although several animal models of ITP have been developed, few mimic primary chronic ITP nor have any shown cell-mediated platelet destruction. To create this type of model, s

Infections, antigen-presenting cells, T cells, and immune tolerance : their role in the pathogenesis of immune thrombocytopenia

In the last 20 years, many publications have shed new light on the complex immunopathogenesis of immune thrombocytopenic purpura. They are associated with 3 interrelated areas of environmental autoimmunity, for example, infectious influences, antigen-presenting cell (APC) function, and T-cell abnormalities, particularly tolerance induction. This article highlights the recent literature and argues

Processed platelet HPA1a peptides au naturel

An understanding of how helper T cells are activated to drive blood group immune responses will help to explain the immunogenicity of antigens such as HPA-1a. In this issue of Blood, Anani Sarab and colleagues identify the naturally processed HPA1a peptides recognized by T cells and set the stage for peptide-based therapies in NAIT.(1).

Transfusion-related immunomodulation by platelets is dependent on their expression of MHC Class I molecules and is independent of white cells

BACKGROUND: Transfusion-related immunomodulation (TRIM) has been correlated with the presence of white cells (WBCs) in blood transfusions, but the role of components such as platelets (PLTs) in mediating TRIM has not been extensively examined. We designed a murine PLT transfusion model to study whether leukoreduced PLTs mediate TRIM effects.STUDY DESIGN AND METHODS: CBA recipient mice were adminis

Evaluation of platelet gel characteristics using thrombin produced by the thrombin processing device : a comparative study

PURPOSE: Autologous platelet gels can be prepared using the patient's own platelet-rich plasma and thrombin produced by the Thrombin Processing Device (Thermogenesis Corp, Rancho Cordova, CA). As the Thrombin Processing Device thrombin contains a residual amount of ethanol, the purpose of this study was to investigate the effect of the Thrombin Processing Device thrombin on growth factor release f

Bipolar Monte Carlo simulation of hot carriers in III-N LEDs

We perform fully bipolar Monte Carlo simulations of electrons and holes in III-Nitride multi-quantum well light-emitting diodes (LEDs) to investigate the effects of hot carriers. Our results show how accounting for hot carriers affects the current-voltage characteristics and device efficiency. We also discuss the effects of bandstructure details on the simulation results. Further simulations with

Diffusion-driven current transport to near-surface nanostructures

Diffusion-driven current transport (DDCT) has recently been proposed as a new way to organize the current injection in nanoscale optoelectronic devices. The very recent first proof-of-principle experiments have also shown that DDCT works as predicted theoretically. In this work we perform simulations on DDCT-based III-Nitride devices and demonstrate how the optimization of DDCT differs significant

Subspace detectors for multichannel signals

In this paper a multichannel subspace detector is proposed based on a separable spatio-temporal linear model. The generalized likelihood ratio test (GLRT) for this model is derived for the case of coloured Gaussian noise and known temporal and covariance matrices. Simulation results support the theory and illustrate the benefits of the spatio-temporal detector versus channel-by-channel detectors f

Relationships between negotiators : A neglected topic in the study of negotiation

Negotiation can be seen as a dynamic social process. Perspectives emphasizing the social context and dynamics of negotiations have been largely neglected in the negotiation literature. This article addresses the question of why social relations have received such scant attention, reviews the existing literature on negotiation as a social process, and spells out some ingredients of a social context