The Experts below are selected from a list of 20619 Experts worldwide ranked by ideXlab platform
Jacques-olivier Pers - One of the best experts on this subject based on the ideXlab platform.
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membrane microdomain sphingolipids are required for anti cd20 induced death of chronic lymphocytic leukemia b cells
Haematologica, 2012Co-Authors: Mariam Hammadi, Pierre Youinou, Adrian Tempescul, Anne Bordron, Gabriel J Tobon, Christian Berthou, Jacques-olivier PersAbstract:BACKGROUND: Chronic lymphocytic leukemia remains incurable, despite the addition of rituximab to chemotherapy as an available means of treatment. The resistance of certain patients to this monoclonal Antibody prompted us to set up in vitro studies of another CD20-specific monoclonal Antibody, B1 (later termed tositumomab). We hypothesized that the membrane lipid organization of leukemic B cells might be instrumental in the cells' sensitivity to the B1 monoclonal Antibody. Design AND METHODS: B lymphocytes from 36 patients with chronic lymphocytic leukemia and 13 patients with non-Hodgkin's lymphoma were investigated for B1-triggered cell death. Membrane components, such as sphingomyelin and ganglioside M1, were investigated by flow cytometry, immunofluorescence and co-immunoprecipitation, together with the Csk-binding protein. RESULTS: Chronic lymphocytic leukemia patients segregated into two groups: B cells from one group were sensitive to B1, whereas those from the second group were not. Further results ascribed the resistance of these latter cases to a defective recruitment of Csk-binding protein, resulting in a lack of sphingomyelin and ganglioside M1 at the outer leaflet of the plasma membrane of their malignant B cells. Sphingolipids were indeed retained in the cytoplasm, because of lowered activity of P-glycoprotein. Supporting this mechanism, rifampicin, an inducer of P-glycoprotein, improved the activity of this transmembrane efflux pump, normalized the quantity of sphingomyelin within the membrane, and thereby restored the efficacy of the B1 monoclonal Antibody in the formerly B1-resistant cases of chronic lymphocytic leukemia. CONCLUSIONS: The lipid organization of membranes of B cells from patients with chronic lymphocytic leukemia differs from one patient to another. In practice, given the relevance of the membrane lipid distribution to the efficacy of biotherapies, this observation is of potential importance.
Annie W C Kung - One of the best experts on this subject based on the ideXlab platform.
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increased fetal abortion rate in autoimmune thyroid disease is related to circulating tpo autoantibodies in an autoimmune thyroiditis animal model
Fertility and Sterility, 2009Co-Authors: Yinlau Lee, Ks Lau, Weimin Liu, Wai Sum O, William S B Yeung, Annie W C KungAbstract:Objective To determine the fertility and abortion rates in a mouse model of autoimmune thyroiditis and its relationship with circulating anti–thyroid peroxidase (TPO) Antibody. Design Experimental animal study. Setting University research laboratory. Animal(s) C57bl/6 mice. Intervention(s) Female C57bl/6 mice immunized with recombinant mouse TPO (rmTPO) in complete Freund adjuvant (CFA) or glutathione-S-transferase (GST-CFA) were allowed to mate. The pregnant mice were killed on day 14 of pregnancy for assessment of fetal development. The effects of TPO Antibody on preimplantation embryo development and implantation rate were also studied. Main Outcome Measure(s) Litter size, resorption rate, preimplantation embryo development, and implantation rate. Result(s) All of the mice immunized with rmTPO-CFA possessed anti-TPO Antibody. They had reduced litter size and increased incidence of resorbed fetus compared with the control. Higher serum TSH levels, but not T 4 levels, were demonstrated after rmTPO-CFA immunization. Anti-TPO Antibody bound to preimplantation embryos. Treatment of the embryos with the Antibody marginally decreased the formation of 3/4-cell embryos but had no effect on the subsequent development and implantation compared with the nonimmune control sera. Conclusion(s) Autoimmune thyroiditis is associated with reduced fertility and higher incidence of fetal loss. The anti-TPO Antibody may affect post-implantation embryo development, leading to fetal loss.
Mariam Hammadi - One of the best experts on this subject based on the ideXlab platform.
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membrane microdomain sphingolipids are required for anti cd20 induced death of chronic lymphocytic leukemia b cells
Haematologica, 2012Co-Authors: Mariam Hammadi, Pierre Youinou, Adrian Tempescul, Anne Bordron, Gabriel J Tobon, Christian Berthou, Jacques-olivier PersAbstract:BACKGROUND: Chronic lymphocytic leukemia remains incurable, despite the addition of rituximab to chemotherapy as an available means of treatment. The resistance of certain patients to this monoclonal Antibody prompted us to set up in vitro studies of another CD20-specific monoclonal Antibody, B1 (later termed tositumomab). We hypothesized that the membrane lipid organization of leukemic B cells might be instrumental in the cells' sensitivity to the B1 monoclonal Antibody. Design AND METHODS: B lymphocytes from 36 patients with chronic lymphocytic leukemia and 13 patients with non-Hodgkin's lymphoma were investigated for B1-triggered cell death. Membrane components, such as sphingomyelin and ganglioside M1, were investigated by flow cytometry, immunofluorescence and co-immunoprecipitation, together with the Csk-binding protein. RESULTS: Chronic lymphocytic leukemia patients segregated into two groups: B cells from one group were sensitive to B1, whereas those from the second group were not. Further results ascribed the resistance of these latter cases to a defective recruitment of Csk-binding protein, resulting in a lack of sphingomyelin and ganglioside M1 at the outer leaflet of the plasma membrane of their malignant B cells. Sphingolipids were indeed retained in the cytoplasm, because of lowered activity of P-glycoprotein. Supporting this mechanism, rifampicin, an inducer of P-glycoprotein, improved the activity of this transmembrane efflux pump, normalized the quantity of sphingomyelin within the membrane, and thereby restored the efficacy of the B1 monoclonal Antibody in the formerly B1-resistant cases of chronic lymphocytic leukemia. CONCLUSIONS: The lipid organization of membranes of B cells from patients with chronic lymphocytic leukemia differs from one patient to another. In practice, given the relevance of the membrane lipid distribution to the efficacy of biotherapies, this observation is of potential importance.
Junho Chung - One of the best experts on this subject based on the ideXlab platform.
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application of bispecific Antibody against antigen and hapten for immunodetection and immunopurification
Experimental and Molecular Medicine, 2013Co-Authors: Hyori Kim, Sunyoung Park, Hwa Kyoung Lee, Junho ChungAbstract:We present a bispecific Antibody that recognizes an antigen and a hapten and can be applied to various biological assays, including immunoblotting and immunoprecipitation. In immunoblot analysis of serum, an anti-C5 × anti-cotinine bispecific tandem single-chain variable fragment (scFv)-Fc fusion protein and cotinine-conjugated horseradish peroxidase (HRP) generated a clean signal without the high background that was observed in a parallel experiment using HRP-conjugated goat anti-rabbit immunoglobulin G (Fc-specific) Antibody. In immunoprecipitation analysis of serum, use of the bispecific tandem scFv-Fc fusion protein and cotinine-crosslinked magnetic beads significantly reduced the amount of protein contaminants compared with a parallel experiment done with protein A agarose beads. In subsequent immunoblot analysis, use of cotinine–HRP as the secondary probe instead of HRP-conjugated goat anti-rabbit IgG (Fc-specific) Antibody successfully eliminated the band corresponding to the bispecific tandem scFv-Fc fusion protein. Using a two-headed Antibody Design, researchers in Korea have devised a sensitive tool for isolating and detecting proteins in experimental work. Scientists routinely use antibodies to recognize specific target molecules in complex mixtures like blood. However, many Antibody-based assays require a secondary ‘detection’ Antibody that recognizes the primary ‘capture’ Antibody, and these often generate signal-obscuring background noise. The two-headed', or bispecific, Antibody Design of Junho Chung's team at Seoul National University simplifies such assays. One end of their engineered bispecific Antibody binds the target of interest, while the other recognizes a tiny molecular flag called cotinine. In turn, cotinine can be attached to a bioluminescent reagent, for example, for far cleaner detection of Antibody-labeled target molecules than is possible with secondary antibodies. Importantly, this Design should prove applicable to most experimental targets and assays.
Takefumi Yamashita - One of the best experts on this subject based on the ideXlab platform.
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toward rational Antibody Design recent advancements in molecular dynamics simulations
International Immunology, 2018Co-Authors: Takefumi YamashitaAbstract:Because antibodies have become an important therapeutic tool, rational Antibody Design is a challenging issue involving various science and technology fields. From the computational aspect, many types of Design-assist methods have been developed, but their accuracy is not fully satisfactory. Because of recent advancements in computational power, molecular dynamics (MD) simulation has become a helpful tool to trace the motion of proteins and to characterize their properties. Thus, MD simulation has been applied to various systems involving antigen-Antibody complexes and has been shown to provide accurate insight into antigen-Antibody interactions and dynamics at an atomic resolution. Therefore, it is highly possible that MD simulation will play several roles complementing the conventional Antibody Design. In this review, we address several important features of MD simulation in the context of rational Antibody Design.