523 research outputs found
Fourth international workshop on haploidentical transplants, Naples, Italy, July 8-10, 2004
No full textAbstract: Many patients with high-risk hematological malignancies or with incurable inborn errors do not have an HLA-matched sibling and cannot find an HLA-matched donor for an allogeneic hematopoietic stem cell transplantation (SCT). Transplantation strategies using mismatched haploidentical family donors have been an important development. Although the procedure has saved patients from certain death, it is still beset by major problems like life-threatening infections-due to profound immunodeficiency following T-cell depletion and to disease relapse. At every International Workshop on Haploidentical Transplants, new data are presented, showing how scientists are attempting to improve the outcomes of mismatched transplants while reducing the severity of complications. The fourth Workshop continues in this tradition of presenting ground-breaking research. It opened with presentations of the current results with unrelated volunteer and umbilical cord blood transplants and proceeded to a session with the results of haploidentical transplants in the world with series of patients with high-risk acute leukemia, ranging in number from well over 100 in Perugia, Italy, and 80 in Haifa, Israel, to smaller groups in Europe and the United States. The session on graft engineering presented the latest results in the search for the optimal graft. The graft-vs.-leukemia effect in the haploidentical transplant was discussed in depth. Subsequently, attention focussed on one of the major problems in haploidentical transplant, that is, the delay in immunological recovery. The Workshop closed with presentations on tolerance induction that was followed by the results of ongoing registration studies being performed by the Italian GIMEMA group and the European Bone Marrow Transplant group
Improving laboratory diagnosis of von Willebrand Disease
No full textAbstract: In von Willebrand disease (VWD), the most common inherited bleeding disorder, patients have a quantitative or qualitative defect of von Willebrand factor (VWF). VWD is widely misdiagnosed because both its diagnosis and classification involve several pitfalls. The complexity and heterogeneity of VWF, (pre)analytical variables, limited repertoire of laboratory tests, intra-individual variation, complex interpretation of results and lack of expertise contribute to the diagnostic challenge. To provide the reader of the general knowledge on VWD, background information regarding biosynthesis, structure and function of VWF and epidemiology, classification, diagnosis and treatment of the disease is provided. Subsequently, the various published articles are presented. Recent developments in VWD diagnosis and classification are highlighted. All available laboratory tests are described, including their mechanisms and pitfalls, and are reviewed whether they are able to improve the VWD characterization. Two new automated VWF:GPIb binding activity assays, HemosIL VWF:RCo (ISTH nomenclature VWF:GPIbR) and INNOVANCE VWF Ac (ISTH nomenclature VWF:GPIbM), are compared in an extensively typed VWD population to evaluate whether they are more able to clearly distinguish type 1 and 2 VWD by using the VWF:GPIb binding activity / VWF antigen ratio, and also whether they are able to improve the quality of diagnosis and subtyping of VWD within this VWD cohort. The semi-automatic Hydragel von Willebrand Factor multimer technique, after correlation with the "gold standard" method for VWD diagnosis, is standardized and quantified by the establishment of reference intervals. Finally, we discuss the cross-sectional studies in VWD which were set up in collaboration with the Czech Republic and Slovakia (University Hospital Brno and Bratislava, F.D. Roosevelt Hospital Bansk\ue1 Bystrica). These studies aim to improve the understanding of the VWD epidemiology and laboratory phenotype/genotype correlation. Pitfalls in VWD diagnosis and classification are also highlighted in these studies. Based on all our findings from this thesis, it is emphasized that for the most accurate and complete VWD diagnosis/classification, an extensive test panel, analyzing different aspects of VWF, is required. Methodologies with the best balance between accessibility and accuracy are recommended, with automated testing being preferred above more manual methods. However, the currently available diagnostic tests are not infallible, which means that often unreliable results can lead to a misdiagnosis. The VWD cohort studies provide unique information on the laboratory phenotype-genotype relationship in VWD, and on the presence of certain causal mutations in a specific geographic region, which invite comparisons with other regions
Interleukin-13 as a master regulator of alternative microglia/macrophage activation : modulation of allograft- and pathology-associated immune responses
No full textBreaching the barrier-targeting dendritic cell migration in the treatment of multiple sclerosis
No full textOptimizing dendritic cells for cancer vaccination through introduction of ribonucleic acid for neo-expression of the tumor-associated antigen "receptor for hyaluronic acid-mediated motility" and the cytokine interferon-\u3b1
No full textAbstract: abstract not availabl
Towards a \u201cnegative\u201d cellular vaccine for the treatment of multiple sclerosis : counteracting epitope spreading for long-lasting tolerance induction using mRNA-electroporated tolerogenic dendritic cells
No full textAbstract: abstract not availabl
Absence of a directly causative role for human herpesvirus 7 in human lymphoma and a review of human herpesvirus 6 in human malignancy
No full textIn search of a (new) viral etiological agent, we screened 64 lymph node samples from Hodgkin's disease (HD) and 43 samples (32 lymph node and 11 skin biopsies) from non-Hodgkin's lymphoma (NHL) for human herpesvirus 7 (HHV-7). Twenty-nine control samples were tested as well, including 17 with benign lymphadenopathy. None of the samples tested positive by Southern blot hybridization using HHV-7-specific probes, We conclude that there is no major HHV-7 load in human lymphoma and that HHV-7 is not likely to be directly involved in its etiology. This is in contrast to a small minority of human lymphoproliferative diseases in which HHV-6 can be found at high copy number, but in which an etiological role is still uncertain
Murine induced pluripotent stem cell‐derived neuroimmune cell culture models emphasize opposite immune-effector functions of interleukin 13-primed microglia and macrophages in terms of neuroimmune toxicity
No full textCellular models of induced pluripotent stem cell (iPSC)‐derived microglia and macrophages are an emerging toolbox to investigate neuroinflammation in vitro. We previously demonstrated that murine iPSC‐microglia and iPSC‐macrophages display phenotypical activation properties highly comparable to microglia and macrophages in vivo. Here we extended the characterization of iPSC‐microglia and iPSC‐macrophages with the analysis of their transcriptome profile. Next, these cellular models were employed to evaluate neuroimmune toxicity in vitro and to investigate the immune‐modulatory properties of interleukin 13 (IL13), a cytokine known for its ability to protect against neuroinflammation‐induced pathology by modulating microglia and macrophage activation. iPSC‐microglia and iPSC‐macrophages, in co‐culture with astrocyte‐committed neural stem cells (NSC), were (pre)treated with IL13 and stimulated with lipopolysaccharide (LPS) and interferon γ (IFNγ), to assess how IL13 modulates their inflammatory response. Additionally, the use of luciferase‐expressing NSC (Luc‐NSC) allowed real‐time monitoring of immune‐mediated neurotoxicity. Despite the known anti‐inflammatory properties of IL13, iPSC‐microglia primed with IL13 before LPS + IFNγ stimulation significantly increased NO secretion. This was associated with a marked reduction of the luminescence signal produced by Luc‐NSC. Interestingly, we observed that IL13 signaling has a divergent functional outcome in microglia as compared to macrophages, as for the latter no major alterations in NO release and Luc‐NSC viability were observed upon IL13 (pre)treatment. Finally, the striking IL13‐induced upregulation of NO secretion by microglia under pro‐inflammatory conditions was confirmed in vivo, where intracerebral delivery of IL13 increased inducible nitric oxide synthase mRNA expression. Concluding, we applied iPSC‐derived neuroimmune cell culture models to identify distinct neuroimmune (toxicity) responses of microglia and macrophages to IL13‐based immune modulation
The effect of apoptotic cells on virus-specific immune responses detected using IFN-gamma ELISPOT
No full textInterferon (IFN)-gamma ELISPOT can be used to monitor the magnitude of virus-specific cellular immune responses in vaccine trials. Often, IFN-gamma ELISPOT is performed with cryopreserved peripheral blood mononuclear cells (PBMC). However, it has not been well defined yet to what extent diminished cell viability of PBMC following cryopreseivation affects IFN-gamma responses in ELISPOT. Therefore, we assessed the influence of apoptotic cells on the number of spot-forming cells (SFC) in IFN-gamma ELISPOT using a gradient of UV-irradiated apoptotic PBMC and viral antigens derived from varicella zoster virus (VZV) and cytomegalovirus (CMV). No SFC were observed when UV-irradiated apoptotic cells were stimulated with VZV or CMV antigens. Moreover, presence of apoptotic cells among viable T cells hampered the detection of SFC following stimulation with VZV or CMV cell lysates, but not with CMVpp65 peptide pool. Statistical analysis showed that mainly late apoptotic cells, staining both Annexin V and 7-amino-actinomycin D (7-AAD), were associated with a decreased number of SFC. In conclusion, it is recommended to use highly viable thawed PBMC for the detection of virus-specific cellular immune responses by IFN-gamma ELISPOT, since the detection of CMV- and VZV-specific T cell responses stimulated by cell lysates was significantly impeded by the presence of apoptotic cells. (C) 2010 Elsevier B.V. All rights reserved
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