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Thomas H. Price - One of the best experts on this subject based on the ideXlab platform.
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efficacy of transfusion with Granulocytes from g csf dexamethasone treated donors in neutropenic patients with infection
Blood, 2015Co-Authors: Thomas H. Price, Jeffrey Mccullough, Ronald G. Strauss, Michael Boeckh, Ryan W Harrison, Paul M Ness, Garrett W Nichols, Taye H HamzaAbstract:High-dose granulocyte transfusion therapy has been available for 20 years, yet its clinical efficacy has never been conclusively demonstrated. We report here the results of RING (Resolving Infection in Neutropenia with Granulocytes), a multicenter randomized controlled trial designed to address this question. Eligible subjects were those with neutropenia (absolute neutrophil count .99), and 49% and 41%, respectively, for subjects who received their assigned treatments (P = .64). Success rates for granulocyte and control arms did not differ within any infection type. In a post hoc analysis, subjects who received an average dose per transfusion of ≥0.6 × 10(9) Granulocytes per kilogram tended to have better outcomes than those receiving a lower dose. In conclusion, there was no overall effect of granulocyte transfusion on the primary outcome, but because enrollment was half that planned, power to detect a true beneficial effect was low. RING was registered at www.clinicaltrials.gov as #NCT00627393.
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Granulocyte transfusion in the G-CSF era.
International Journal of Hematology, 2002Co-Authors: Thomas H. PriceAbstract:Granulocyte transfusions have been used since the 1960s with varying degrees of clinical success in the treatment of infection in patients with neutropenia or inherited granulocyte disorders. A number of studies have indicated that efficacy may well be associated with the dose of Granulocytes delivered. Collection of Granulocytes using modern apheresis machines and corticosteroid administration yields approximately 20∼30×109 neutrophils, unlikely to be adequate for treating an established infection. The administration of G-CSF to healthy donors has resulted in average granulocyte yields up to 8×1010 cells. Normal or near normal blood neutrophil counts are often attained when these concentrates are transfused to neutropenic recipients, and these levels are sustained for up to 24 h. G-CSF-primed Granulocytes appear to be functionally normal by both in vitro and in vivo measurements. Adverse effects experienced by recipients are similar to those seen with traditional doses of Granulocytes. G-CSF administration to donors is well tolerated. Controlled clinical trials are needed to determine the therapeutic efficacy of G-CSF-primed granulocyte transfusions.
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Granulocyte transfusion in the G-CSF era.
International journal of hematology, 2002Co-Authors: Thomas H. PriceAbstract:Granulocyte transfusions have been used since the 1960s with varying degrees of clinical success in the treatment of infection in patients with neutropenia or inherited granulocyte disorders. A number of studies have indicated that efficacy may well be associated with the dose of Granulocytes delivered. Collection of Granulocytes using modern apheresis machines and corticosteroid administration yields approximately 20 to approximately 30 x 10(9) neutrophils, unlikely to be adequate for treating an established infection. The administration of G-CSF to healthy donors has resulted in average granulocyte yields up to 8 x 10(10) cells. Normal or near normal blood neutrophil counts are often attained when these concentrates are transfused to neutropenic recipients, and these levels are sustained for up to 24 h. G-CSF-primed Granulocytes appear to be functionally normal by both in vitro and in vivo measurements. Adverse effects experienced by recipients are similar to those seen with traditional doses of Granulocytes. G-CSF administration to donors is well tolerated. Controlled clinical trials are needed to determine the therapeutic efficacy of G-CSF-primed granulocyte transfusions.
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Granulocyte colony-stimulating factor-mobilized granulocyte concentrate transfusions
Current opinion in hematology, 1998Co-Authors: Thomas H. PriceAbstract:Granulocyte transfusion therapy has been used infrequently in the last 10 to 15 years, in large part because its efficacy in the treatment of infected neutropenic patients has not been impressive. This perceived lack of efficacy has been attributed primarily to the fact that the dose of Granulocytes obtainable with standard leukapheresis techniques has been inadequate. With the availability of recombinant granulocyte colony-stimulating factor (G-CSF) to stimulate neutrophilia in normal donors and increase the number of Granulocytes that can be collected, there is now renewed interest in this form of transfusion therapy. Recent studies have shown that stimulation with G-CSF, with or without corticosteroids, is well tolerated by normal donors and that granulocyte yields are increased three- to four-fold. Blood neutrophil counts in patients receiving these large cell doses rise substantially, often to normal or near normal levels, and commonly remain elevated for 24 hours or more. In vitro and in vivo measurements have shown that the functional capabilities of Granulocytes collected from G-CSF stimulated donors appear to be normal. Although early reports have been encouraging, the clinical efficacy of this new level of granulocyte transfusion therapy has been yet to be determined.
Christian Mueller-eckhardt - One of the best experts on this subject based on the ideXlab platform.
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Analysis of granulocyte‐reactive antibodies using an immunoassay based upon monoclonal‐antibody‐specific immobilization of granulocyte antigens
Transfusion Medicine, 1993Co-Authors: B. Kober, Volker Kiefel, Christian Mueller-eckhardtAbstract:Summary. To detect human granulocyte-reactive antibodies, a glycoprotein-specific enzyme immunoassay for platelet antibodies was adapted for the use of Granulocytes as target cells. Peripheral blood Granulocytes were simultaneously incubated with a monoclonal antibody (mAb) and the serum to be investigated. After solubilization, aliquots of the cell lysate were transferred to plastic tubes coated with goat anti-mouse antibodies. Following immobilization of the trimolecular (mAb-glycoprotein-human antibody) complex it was detected by addition of enzyme-labelled goat anti-human antibodies using a luminescence technique. This assay allowed identification of different granulocyte-reactive antibodies present in the same sample without the need for complicated absorption studies. Alloantibodies against HLA and the granulocyte-specific NA antigens as well as isoantibodies against the Fc-gamma-receptor III (FcRIII) were detectable using mAb-specific immobilization of granulocyte antigens (MAIGA). Binding of autoantibodies to the FcRIII and to the CD 11b/CD 18 complex could be shown.
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Influence of Granulocyte Antibodies on Granulocyte Function
Vox sanguinis, 1993Co-Authors: Juergen Bux, J. O. Dickmann, U. Stockert, Christian Mueller-eckhardtAbstract:The following substances were tested for their influence on granulocyte function: 8 sera that contained human granulocyte-specific alloantibodies against the antigens NA1, NA2 and NB1, two HLA antisera, and the monoclonal antibodies W6/32 and CLB-FcR-gran 1. The effects examined included spontaneous and directed migration, immune phagocytosis inhibition and the generation of oxygen radicals. Using the under-agarose technique, spontaneous migration of sensitized Granulocytes was normal. For all antibodies tested, the chemotactic index for N-fMLP, LTB4 and opsonized zymosan was greater than 1. Granulocyte immune phagocytosis of sensitized sheep red blood cells was strongly inhibited by all alloantisera and monoclonal antibodies. The generation of oxygen radicals after triggering the respiratory burst with sensitized sheep red blood cells was also strongly inhibited in the chemiluminescence assay. Immune phagocytosis and chemiluminescent response of Granulocytes lacking the corresponding antigen of the tested alloantibodies were not affected. Since sensitization of neutrophils with F(ab')2 fragments of the monoclonal antibodies W6/32 and CLB-FcR-gran 1 showed lower inhibition of generation of oxygen radicals after triggering, Fc-dependent interaction with the target cells seems to be necessary for inhibition. Our results suggest that binding of NA1-, NA2- or NB1-specific alloantibodies to Granulocytes not only causes neutropenia, but also impairs granulocyte function.
Yvon Berland - One of the best experts on this subject based on the ideXlab platform.
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Effect of uremia and hemodialysis on soluble L-selectin and leukocyte surface CD11b and L-selectin
American Journal of Kidney Diseases, 1998Co-Authors: Philippe Brunet, Françoise Dignat-george, José Sampol, Yvon BerlandAbstract:Abstract Leukocyte Mac-1 (CD11b/CD18) and L-selectin (CD62L) are implicated in leukocyte adhesion to endothelial cells. In this study, L-selectin and CD11b expression on leukocytes and soluble L-selectin (sL-selectin) serum levels were investigated in 17 nondialyzed patients with chronic renal failure (CRF), in 28 chronic hemodialysis patients before hemodialysis (basal state), and in 32 healthy subjects. These parameters were also monitored during hemodialysis with cuprophane and cellulose diacetate membranes in a crossover study in five patients. Granulocytes from CRF patients displayed lower expression of L-selectin and higher expression of CD11b than Granulocytes from healthy subjects. On the other hand, baseline expression of L-selectin and CD11b on leukocytes from hemodialysis patients did not differ from that of healthy subjects. In CRF and hemodialysis patients, sL-selectin levels were significantly lower than in healthy subjects. During hemodialysis, cuprophane membrane induced an upregulation of granulocyte CD11b, a decrease in granulocyte L-selectin, and an increase in sL-selectin serum levels. Conversely, cellulose diacetate caused only a transient increase in granulocyte CD11b and did not modify granulocyte L-selectin and sL-selectin serum levels. High CD11b and low L-selectin expression on Granulocytes in CRF patients suggests an activation state, which was not found in hemodialysis patients at the basal state. The lack of activation in hemodialysis patients could reflect the elimination of a uremic toxin by dialysis or a loss of granulocyte responsiveness because of the repetitive stimulation by hemodialysis treatment. The low serum levels of sL-selectin in CRF and hemodialysis patients also suggest granulocyte dysfunction. (Am J Kidney Dis 1998 Jan;31(1):67-73)
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Effect of uremia and hemodialysis on soluble L-selectin and leukocyte surface CD11b and L-selectin
American Journal of Kidney Diseases, 1998Co-Authors: Laetitia Dou, Philippe Brunet, Françoise Dignat-george, José Sampol, Yvon BerlandAbstract:Leukocyte Mac-1 (CD11b/CD18) and L-selectin (CD62L) are implicated in leukocyte adhesion to endothelial cells. In this study, L-selectin and CD11b expression on leukocytes and soluble L-selectin (sL-selectin) serum levels were investigated in 17 nondialyzed patients with chronic renal failure (CRF), in 28 chronic hemodialysis patients before hemodialysis (basal state), and in 32 healthy subjects. These parameters were also monitored during hemodialysis with cuprophane and cellulose diacetate membranes in a crossover study in five patients. Granulocytes from CRF patients displayed lower expression of L-selectin and higher expression of CD11b than Granulocytes from healthy subjects. On the other hand, baseline expression of L-selectin and CD11b on leukocytes from hemodialysis patients did not differ from that of healthy subjects. In CRF and hemodialysis patients, sL-selectin levels were significantly lower than in healthy subjects. During hemodialysis, cuprophane membrane induced an upregulation of granulocyte CD11b, a decrease in granulocyte L-selectin, and an increase in sL-selectin serum levels. Conversely, cellulose diacetate caused only a transient increase in granulocyte CD11b and did not modify granulocyte L-selectin and sL-selectin serum levels. High CD11b and low L-selectin expression on Granulocytes in CRF patients suggests an activation state, which was not found in hemodialysis patients at the basal state. The lack of activation in hemodialysis patients could reflect the elimination of a uremic toxin by dialysis or a loss of granulocyte responsiveness because of the repetitive stimulation by hemodialysis treatment. The low serum levels of sL-selectin in CRF and hemodialysis patients also suggest granulocyte dysfunction. (C) 1998 by the National Kidney Foundation, Inc.
Linsheng Song - One of the best experts on this subject based on the ideXlab platform.
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the Granulocytes are the main immunocompetent hemocytes in crassostrea gigas
Developmental and Comparative Immunology, 2017Co-Authors: Weilin Wang, Lingling Wang, Hao Chen, Zhaoqun Liu, Zhihao Jia, Limei Qiu, Linsheng SongAbstract:Hemocytes comprise diverse cell types with morphological and functional heterogeneity and play indispensable roles in immunological homeostasis of invertebrates. The morphological classification of different hemocytes in mollusk has been studied since the 1970's, yet the involvement of the different sub-populations in immune functions is far from clear. In the present study, three types of hemocytes were morphologically identified and separated as aGranulocytes, semi-Granulocytes and Granulocytes by flow cytometry and Percoll® density gradient centrifugation. The Granulocytes were characterized functionally as the main phagocytic and encapsulating population, while semi-Granulocytes and aGranulocytes exhibited low or no such capacities, respectively. Meanwhile, the lysosome activity and the productions of ROS and NO were all mainly concentrated in Granulocytes under both normal and immune-activated situations. Further, the mRNA transcripts of some immune related genes, including CgTLR, CgClathrin, CgATPeV, CgLysozyme, CgDefensin and CgIL-17, were mainly expressed in Granulocytes, lower in semi-Granulocytes and aGranulocytes. These results collectively suggested that the Granulocytes were the main immunocompetent hemocytes in oyster C. gigas, and a differentiation relationship among these three sub-population hemocytes was inferred based on the gradual changes in morphological, functional and molecular features.
Ronald G. Strauss - One of the best experts on this subject based on the ideXlab platform.
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efficacy of transfusion with Granulocytes from g csf dexamethasone treated donors in neutropenic patients with infection
Blood, 2015Co-Authors: Thomas H. Price, Jeffrey Mccullough, Ronald G. Strauss, Michael Boeckh, Ryan W Harrison, Paul M Ness, Garrett W Nichols, Taye H HamzaAbstract:High-dose granulocyte transfusion therapy has been available for 20 years, yet its clinical efficacy has never been conclusively demonstrated. We report here the results of RING (Resolving Infection in Neutropenia with Granulocytes), a multicenter randomized controlled trial designed to address this question. Eligible subjects were those with neutropenia (absolute neutrophil count .99), and 49% and 41%, respectively, for subjects who received their assigned treatments (P = .64). Success rates for granulocyte and control arms did not differ within any infection type. In a post hoc analysis, subjects who received an average dose per transfusion of ≥0.6 × 10(9) Granulocytes per kilogram tended to have better outcomes than those receiving a lower dose. In conclusion, there was no overall effect of granulocyte transfusion on the primary outcome, but because enrollment was half that planned, power to detect a true beneficial effect was low. RING was registered at www.clinicaltrials.gov as #NCT00627393.
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Granulocyte transfusion therapy.
Hematology oncology clinics of North America, 1994Co-Authors: Ronald G. StraussAbstract:Although the efficacy of therapeutic granulocyte transfusions as treatment for progressive infections in severely neutropenic patients is supported by the medical literature, this form of therapy is not widely accepted because it has been extremely difficult to transfuse an adequate dose of compatible Granulocytes. Recently, the possibility has been raised to greatly increase the number of Granulocytes collected by stimulating normal donors with recombinant granulocyte colony-stimulating factor. Accordingly, it is reasonable to reassess the possible role for granulocyte transfusions as therapy for progressive bacterial, yeast, and fungal infections.
