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Cellular immune mechanisms in autoimmune thrombocytopenic purpura : An update

Autoimmune thrombocytopenic purpura (AITP) is a bleeding disorder in which autoantibodies are directed against an individual's own platelets, leading to enhanced clearance through Fc receptor (R)-mediated phagocytosis by macrophages residing in the reticuloendothelial system (RES), particularly in the spleen. The production of IgG autoantibodies is critically dependent on cellular immune mechanism

γ-globulins prepared from sera of multiparous women bind anti-HLA antibodies and inhibit an established in vivo human alloimmune response

It has previously been shown that sera from multiparous women have increased levels of anti-idiotypic antibodies specific for anti-HLA molecules. γ-Globulins prepared from these sera may be superior to commercial preparations of intravenous γ-globulin (IVIg) for inhibiting HLA alloimmunization. To test this, F(ab′)2 fragments prepared from either commercial IVIg or from the sera of men or multipar

Recipient antigen-processing pathways of allogeneic platelet antigens : essential mediators of immunity.

Clinical studies have convincingly demonstrated that WBC reduction of blood components can reduce the incidence of primary HLA antigen alloimmunization at least in patients with acute myeloid leukemia.1 However, despite receiving WBC‐reduced platelets, approximately 19 percent of acute myeloid leukemia patients still became alloimmunized.1 In addition, it is not known whether WBC reduction will pr

Anti-D (WinRho SD™) treatment of children with chronic autoimmune thrombocytopenic purpura stimulates transient cytokine/chemokine production

Intravenous anti-D is often used in the treatment of autoimmune thrombocytopenic purpura (AITP), but little is known about its mechanisms of action. To investigate anti-D's potential in vivo mechanism(s) of action, a small group (N = 7) of children with chronic AITP was studied. The children initially received either 25 or 50 μg/kg of WinRho-SD in a four-cycle cross-over trial, and peripheral bloo

IVIg inhibits reticuloendothelial system function and ameliorates murine passive-immune thrombocytopenia independent of anti-idiotype reactivity

Although the mechanism of action of intravenous immunoglobulin (IVIg) in treating antibody-dependent thrombocytopenia remains unclear, most studies have suggested that IVIg blocks the function of Fc receptors in the reticuloendothelial system (RES) and/or the protective effect may be due to the presence of variable region-reactive (anti-idiotype) antibodies within IVIg. We evaluated the effect of

Flow cytometric parameters for characterizing platelet activation by measuring P-selectin (CD62) expression : Theoretical consideration and evaluation in thrombin-treated platelet populations

Two flow cytometric parameters are generally used to quantify platelet activation as measured by P-selectin (CD62) expression: percentage and mean channel fluorescence of CD62-positive platelets (%+ and MCF+, respectively). We describe a method for calculation of indices of platelet activation for positive (IPA+) and total (IPA(Σ)) platelets, which reflect integrated amounts of CD62 expressed in t

White blood cell subsets in buffy coat-derived platelet concentrates : The effect of pre- and poststorage filtration

Background and Objectives: Our objective was to study the effect of storage time on the filtration of platelet concentrates (PCs). We compared the total number of white blood cells (WBC), as well as the distribution of WBC subsets, in units filtered before and after storage. Materials and Methods: Buffy coat-derived PCs were filtered either fresh or after 5 days of storage, and total WBC were enum

Unique processing pathways within recipient antigen-presenting cells determine IgG immunity against donor platelet MHC antigens

Recipient IgG immunity against leukoreduced donor platelets is dependent on indirect T-cell allorecognition and is suppressed in vivo by inhibitors (aminoguanidine, AMG) of inducible nitric oxide synthase (INOS). To examine recipient processing pathways of donor platelet antigens, enriched macrophages (antigenpresenting cells [APC]) from BALB/c (H-2(d)) mice were pulsed with allogeneic C57BL/6 (H-

Quantification of platelet activation status by analyzing P-selectin expression

Platelet activation status (PAS) is used for characterizing quality and function of platelets in various experimental and clinical settings. In this study, we created a set of platelet populations differing in PAS, using stimulation of platelets with thrombin in a wide range of concentrations, and analyzed a number of flow cytometric parameters, which characterize PAS by measuring P-selectin (CD62

Extreme leukoreduction of major histocompatibility complex class II positive B cells enhances allogeneic platelet immunity

In a murine model of platelet alloimmunization, we examined the definitive role that mononuclear cells (MC) have in modulating platelet immunity by using platelets from severe combined immunodeficient (SCID) mice. CB.17 (H-2(d)) SCID or BALB/c (H-2(d)) mouse platelets were transfused weekly into fully allogeneic CBA (H-2(k)) mice and antidonor antibodies measured by flow cytometry. MC levels in BA

Preanalytical requirements for flow cytometric evaluation of platelet activation : Choice of anticoagulant

Accurate assessment of in viva or in vitro platelet activation requires optimal preanalytical conditions to prevent artefactual in vitro activation of the platelets. The choice of anticoagulant is one of the critical preanalytical conditions as anticoagulants exert different effects on the activation of platelets ex vivo. We tested the effectiveness of Diatube-H (also known as CTAD; sodium citrate

Roadmap for valuing soil ecosystem services to inform multi-level decision-making in agriculture

Agricultural soils contribute to human welfare through their generation of manifold ecosystem services such as food security, water quality and climate regulation, but these are degraded by common farming practices. We have developed a roadmap for evaluating the contribution of both private- and public-good ecosystem services generated by agricultural soils to societal welfare. The approach consid

Clinical characteristics of subependymal giant cell astrocytoma in tuberous sclerosis complex

Background: This study evaluated the characteristics of subependymal giant cell astrocytoma (SEGA) in patients with tuberous sclerosis complex (TSC) entered into the TuberOus SClerosis registry to increase disease Awareness (TOSCA). Methods: The study was conducted at 170 sites across 31 countries. Data from patients of any age with a documented clinical visit for TSC in the 12 months preceding en

Kulturmiljöer i odlingslandskapet – hur kan de bevaras?

Kulturmiljöer som historiska byggnader, stenmurar, diken och alléer är värdefulla delar av vårt kulturarv. Om miljöerna ska bevaras krävs att ersättningen för skötsel av dem är så pass attraktiv att många väljer att ansluta sig. Förutom nivån på den ekonomiska ersättningen finns en rad faktorer som spelar roll för viljan att ansluta sig, och vissa av dessa kan stimuleras av så kallad nudging.Denna

Oxygen Therapy in Myocardial Infarction Patients With or Without Diabetes : A Predefined Subgroup Analysis From the DETO2X-AMI Trial

OBJECTIVE: To determine the effects of oxygen therapy in myocardial infarction (MI) patients with and without diabetes. RESEARCH DESIGN AND METHODS: In the Determination of the Role of Oxygen in Suspected Acute Myocardial Infarction (DETO2X-AMI) trial, 6,629 normoxemic patients with suspected MI were randomized to oxygen at 6 L/min for 6-12 h or ambient air. In this prespecified analysis involving

Comparison of conventional and Si-photomultiplier-based PET systems for image quality and diagnostic performance

BACKGROUND: A new generation of positron emission tomography with computed tomography (PET-CT) was recently introduced using silicon (Si) photomultiplier (PM)-based technology. Our aim was to compare the image quality and diagnostic performance of a SiPM-based PET-CT (Discovery MI; GE Healthcare, Milwaukee, WI, USA) with a time-of-flight PET-CT scanner with a conventional PM detector (Gemini TF; P

Immune effector monocyte–neutrophil cooperation induced by the primary tumor prevents metastatic progression of breast cancer

Metastatic behavior varies significantly among breast cancers. Mechanisms explaining why the majority of breast cancer patients never develop metastatic outgrowth are largely lacking but could underlie the development of novel immunotherapeutic target molecules. Here we show interplay between nonmetastatic primary breast cancer and innate immune response, acting together to control metastatic prog