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Arzanlou, Mahdi, Somayeh Mousavi, Mounes Bakhshi, Reza Khakvar, and Ali Bandehagh. "Inhibitory effects of antagonistic bacteria inhabiting the rhizosphere of the sugarbeet plants, on Cercospora beticola Sacc., the causal agent of Cercospora leaf spot disease on sugarbeet." Journal of Plant Protection Research 56, no. 1 (January 1, 2016): 6–14. http://dx.doi.org/10.1515/jppr-2016-0002.
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AbstractIn the present study, the antagonistic capability of bacterial agents inhabiting the rhizosphere of sugarbeet plants were evaluated against Cercospora beticola Sacc. under laboratory and greenhouse conditions. After preliminary screening using the dual culture method, 14 strains with higher antagonistic capability were selected for further inhibitory assays against C. beticola. Bacterial strains were identified based on the sequence data of the small subunit-rDNA (SSU-rDNA) gene. Based on the SSU sequence data, the identity of bacterial strains were determined as Bacillus (10 strains: RB1, RB2, RB3, RB4, RB5, RB6, RB7, RB8, RB9, RB10), Paenibacillus (two strains: RP1, RP2), Enterobacter (one strain: RE), and Pseudomonas (one strain: RPs). The results obtained in this study showed that in all of the assays (dual culture, volatile and non-volatile metabolites) bacterial antagonists significantly inhibited the growth of C. beticola compared to the control. Bacillus (RB2) showed the highest inhibition rate on C. beticola in all of the assays. Based on the results of the laboratory assays, three bacterial strains RB2 (Bacillus), RPs (Pseudomonas), and RE (Paenibacillus) were selected for greenhouse assays. The experiment was designed based on a completely randomised design (CRD) with the application of antagonists prior to, simultaneously, and after inoculation with C. beticola on sugarbeet leaves. The reduction in disease severity was evaluated seven days after inoculation. The results of greenhouse assays were consistent with the results of laboratory studies. The obtained results showed that bacterial antagonists significantly reduced the disease severity when compared to the control.
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Lievano, A., A. Bolden, and R. Horn. "Calcium channels in excitable cells: divergent genotypic and phenotypic expression of alpha 1-subunits." American Journal of Physiology-Cell Physiology 267, no. 2 (August 1, 1994): C411—C424. http://dx.doi.org/10.1152/ajpcell.1994.267.2.c411.
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The Ba2+ currents and mRNA levels of four members of the rat brain family of alpha 1-subunit Ca2+ channel genes were examined and compared in the rat cell lines GH3 and PC-12 and in the mouse lines NIE-115 and AtT-20. The RNA was measured with ribonuclease protection assays using probes derived from rat brain (rb) Ca2+ channel cDNAs (rbA, rbB, rbC, and rbD), and the Ba2+ currents were studied by whole cell patch-clamp recording. L-, N-, P-, and T-type currents were discriminated by the voltage dependence and pharmacological properties of Ba2+ currents. All cell lines expressed all four rat brain Ca2+ channel genes, except GH3 cells, which lacked rbB. The functional diversity of Ba2+ currents, however, was quite different among the cell lines. GH3 cells showed evidence of L- and T-type currents, undifferentiated PC-12 cells of L-type currents, AtT-20 cells of L-, N-, and P-type currents, and undifferentiated NIE-115 cells of a T-type current that was partially blocked by both nifedipine and BAY K 8644. Dimethyl sulfoxide-differentiated NIE-115 cells also had an L-type current. Differentiation of NIE-115 cells caused an increase in the levels of rbB, rbC, and rbD RNAs. Differentiation by nerve growth factor caused an increase in levels of all four genes in PC-12. Our data give further support for the assignment of rbA, rbB, and rbC/rbD gene products as components of P-, N-, and L-type Ca2+ channels, respectively.
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Martín-Cereceda, M., B. Pérez-Uz, S. Serrano, and A. Guinea. "An integrated approach to analyse biofilms of a full scale wastewater treatment plant." Water Science and Technology 46, no. 1-2 (July 1, 2002): 199–206. http://dx.doi.org/10.2166/wst.2002.0478.
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A rotating biological contactor (RBC) system operating in a full-scale wastewater treatment plant has been described by several approaches accounting for performance, composition and structure of biofilms in three stages through biological wastewater treatment (RBC1, RBC 2, RBC 3). RBC biofilms were effective in removing the BOD loading from 13 g BOD5 d−1 m−2 in RBC 1 to 6 g BOD5 d−1 m−2 in RBC 3. Analysis of biofilm composition showed: i) the volatile solids were similar in the three RBCs (0.6 g m−2 VS per g m−2 of TS); ii) the protozoan and metazoan biocenosis was mainly made up of ciliated protozoa, which were most abundant in RBC 2 (1.84 × 106 ciliates g−1 VS). Relationship between ciliate species and physical-chemical profile of the system by cluster analysis indicated that the species Acineria uncinata, Amphileptus punctatus, Cinetochilum margaritaceum and Holosticha mancoidea were associated with the best RBC performance; iii) the exopolymeric matrix of the three RBC biofilms was mainly constituted by proteins, although humic substances, polysaccharides, uronic acids and DNA were also found. Analysis of biofilm structure by confocal microscopy indicated changes in biofilm organisation with depth. Results have been brought together and a graphic representation of the composition and architecture of RBC biofilms is presented.
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Berling, C., C. Lacombe, J. C. Lelièvre, M. Allary, and J. Saint-Blancard. "The RBC morphological dependance of the RBC disaggregability." Biorheology 25, no. 5 (October 1, 1988): 791–98. http://dx.doi.org/10.3233/bir-1988-25506.
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Hess, John R. "RBC storage lesions." Blood 128, no. 12 (September 22, 2016): 1544–45. http://dx.doi.org/10.1182/blood-2016-08-729541.
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Said, Ahmed S., Philip C. Spinella, Mary E. Hartman, Katherine M. Steffen, Ronald Jackups, Richard Holubkov, Mike Wallendorf, and Allan Doctor. "RBC Distribution Width." Pediatric Critical Care Medicine 18, no. 2 (February 2017): 134–42. http://dx.doi.org/10.1097/pcc.0000000000001017.
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Parker, Robert I. "RBC Distribution Width." Pediatric Critical Care Medicine 18, no. 2 (February 2017): 193–94. http://dx.doi.org/10.1097/pcc.0000000000001033.
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Parker, Robert I. "RBC Transfusion Practices." Critical Care Medicine 41, no. 10 (October 2013): 2449–50. http://dx.doi.org/10.1097/ccm.0b013e3182963e69.
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Schonewille, Henk, Hans L. Haak, and Annette M. van Zijl. "RBC antibody persistence." Transfusion 40, no. 9 (September 2000): 1127–31. http://dx.doi.org/10.1046/j.1537-2995.2000.40091127.x.
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Girelli, G., P. De Fabritiis, G. Menichella, R. Serafini, M. L. Foddai, M. Di Carlo, A. D'Angiolino, and M. Migliaccio. "Multicomponent Collection: The Experience of Regione Lazio." International Journal of Artificial Organs 21, no. 6_suppl (May 1998): 23–25. http://dx.doi.org/10.1177/039139889802106s05.
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Five blood banks of Regione Lazio implemented a multicomponent collection program using apheresis technology. The automated collection of blood components included: red blood cell concentrate and fresh plasma (RBCP), plasma and platelet concentrate (P-PLT), red blood cell and platelet concentrates (RBC-PLT). 334 voluntary blood donors and 30 patients - as autologous donors- were involved. Apheresis collection of RBCP, P - PU, RBC - PLT yielded a standardized product (adequate volume, low residual leucocyte counts, adeguate hematocrit, low platelet contamination) was well tolerated by donors, was performed without technical problems. We conclude that multicomponent collection is a new feasible alternative to conventional whole blood collection.
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Mashuri, Mashuri, Achmad Zaini, Diana Rahmanisa, Muhammad Rifqi Alfiannoor, Muhammad Rosyhan Sanjaya, and Eko Suhartono. "NEW MOLECULAR MECHANISM OF CEFTAZIDIME-INDUCED HUMAN RED BLOOD CELL HEMOLYSIS THROUGH THE PHOTOHEMOLYSIS REACTION." Asian Journal of Pharmaceutical and Clinical Research 11, no. 15 (October 3, 2018): 47. http://dx.doi.org/10.22159/ajpcr.2018.v11s3.30029.
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Objective: The present study was undertaken to investigate the photohemolysis reaction through photosensitization reaction by ceftazidime as a photosensitizer in human red blood cell (RBC).Methods: In this present study, human erythrocytes have used a sample. The sample then divided into six groups consisting of Group 1 (T1) served a negative control which consists of erythrocytes and buffers phosphate with pH 6.8; Group 2 (T2) served as a positive control which consists erythrocytes and buffers phosphate with pH 6.8 and exposed to UV-light; and Group 3, 4, 5, and 6 (T3, T4, T5, and T6) served as an experimental group which consists of erythrocytes, buffer phosphate with pH 6.8, ceftazidime with concentration 10%, 20%, 30%, and 40%, respectively, and also exposed to UV-light. UV-light exposure was done in 2 h. After the treatment period, the level of hydrogen peroxide (H2O2), conjugated diene (CD), advanced oxidation protein products (AOPPs), and percentage of RBC hemolysis (RBCH) were measured.Results: The results of this present studies showed that ceftazidime significantly increases the levels of H2O2, CD, AOPPs, and percentage of RBCH during the UV radiation.Conclusion: The present study demonstrated that ceftazidime acts as a photosensitizer and induced the photohemolysis reaction in human RBC. Furthermore, the hemolysis of RBC seems through the protein damage than lipid damage.
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Hanhan, O., D. Orhon, Kh Krauth, and B. Günder. "Evaluation of denitrification potential of rotating biological contactors for treatment of municipal wastewater." Water Science and Technology 51, no. 11 (June 1, 2005): 131–39. http://dx.doi.org/10.2166/wst.2005.0399.
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In this study the effect of retention time and rotation speed in the denitrification process in two full-scale rotating biological contactors (RBC) which were operated parallel and fed with municipal wastewater is evaluated. Each rotating biological contactor was covered to prevent oxygen input. The discs were 40% submerged. On the axle of one of the rotating biological contactors lamellas were placed (RBC1). During the experiments the nitrate removal performance of the rotating biological contactor with lamellas was observed to be less than the other (RBC2) since the lamellas caused oxygen diffusion through their movement. The highest nitrate removal observed was 2.06 g/m2.d achieved by a contact time of 28.84 minutes and a recycle flow of 1 l/s. The rotation speed during this set had the constant value of 0.8 min−1. Nitrate removal efficiency on RBC1 was decreasing with increasing rotation speed. On the rotating biological contactor without lamellas no effect on denitrification could be determined within a speed range from 0.67 to 2.1 min−1. If operated in proper conditions denitrification on RBC is a very suitable alternative for nitrogen removal that can easily fulfil the nutrient limitations in coastal areas due to the rotating biological contactors economical benefits and uncomplicated handling.
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Arthur, Connie M., Nicole H. Smith, James C. Zimring, Jeanne E. Hendrickson, and Sean R. Stowell. "Storage-Induced Clearance Of RBCs Following Transfusion Occurs Independent Of RBC Age." Blood 122, no. 21 (November 15, 2013): 792. http://dx.doi.org/10.1182/blood.v122.21.792.792.
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Abstract Background During red blood cell (RBC) storage, changes occur that increase the clearance of RBCs following transfusion. RBCs also display unique age related changes that target them for removal in vivo, a process commonly termed RBC senescence. However, whether storage related changes simply reflect acceleration of the normal senescent programs that occur in vivo, or whether all RBCs display equal sensitivity to storage induced alterations that enhance clearance following transfusion remains unknown. As a result, we sought to determine whether enhanced RBC removal following storage simply reflects preferential clearance of older RBCs. Methods B6 mice expressing green fluorescent protein (GFP) under a H-2Kb promoter were injected with N-hydroxysulfosuccinimide biotin followed by evaluation of biotinylated RBCs at weekly time points post transfusion by staining RBCs with strepavidin and flow cytometric analysis. At approximately 1 or 35 days post-biotinylation, blood was harvested into citrate phosphate dextrose adenine (CPDA) and RBCs were immediately transfused or stored in CPDA for 21 days prior to transfusion. Prior to transfusion, the percent of RBCs that remained biotinylated was enumerated. Following transfusion, mice were bleed at 10 minutes, 1 hour or 2 hours followed by daily bleeds for 7 days and weekly thereafter and the ratio of biotin and GFP double positive to GFP single positive RBCs was examined by staining RBCs with strepavidin followed by flow cytometric analysis. Results Immediately after whole mouse biotinylation, nearly 100% of donor RBCs became strepavidin positive. The percent strepavidin positivity gradually decreased until approximately 20% of the total RBCs remained strepavidin positive 35 days post-biotinylation. RBCs harvested 35 days post biotinylation into CPDA and transfused immediately exhibited gradual clearance over time, such that very few transfused RBCs were detectable 40 days post transfusion. In contrast, the percent of transfused RBCs that remained biotin positive rapidly declined to undetectable levels within 7 days following transfusion. Transfused RBCs harvested only 1 day following biotinylation failed to display enhanced clearance during the same 7 day interval. In contrast, the percent of biotin positive RBCs remained unchanged during storage. In addition, transfusion of stored RBCs failed to result in selective clearance of biotin positive RBCs during the initial clearance phase, although biotin positive RBCs appeared to retain enhanced rates of removal following the initial phase of RBC removal. Conclusion Older RBCs appear to retain signals that result in preferential removal compared to younger RBCs following harvesting, processing and transfusion into a new recipient. Preferential clearance of older RBCs does not appear to reflect a biotinylation artifact, as newly biotinylated RBCs failed to display similar increases in RBC clearance. However, storage induced changes do not appear to result in selective removal of older RBCs, as biotinylated and non-biotinylated RBCs displayed significant removal during the initial phase of clearance following transfusion. Taken together, these results suggest that older RBCs retain senescent markers that results in enhanced clearance, but that RBC storage induces unique RBC changes that marks them for rapid clearance largely independent of RBC age. Disclosures: Zimring: Immucor Inc.: Research Funding; Terumo: Research Funding; Haemonetics: Consultancy; Cerus: Honoraria.
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Alfano, Kenneth M., Michael Tarasev, Steven Meines, and Gene Parunak. "An approach to measuring RBC haemolysis and profiling RBC mechanical fragility." Journal of Medical Engineering & Technology 40, no. 4 (March 23, 2016): 162–71. http://dx.doi.org/10.3109/03091902.2016.1153741.
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Grau, Marijke, Sebastian Pauly, Jamal Ali, Katja Walpurgis, Mario Thevis, Wilhelm Bloch, and Frank Suhr. "RBC-NOS-Dependent S-Nitrosylation of Cytoskeletal Proteins Improves RBC Deformability." PLoS ONE 8, no. 2 (February 12, 2013): e56759. http://dx.doi.org/10.1371/journal.pone.0056759.
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Zerra, Patricia E., Seema R. Patel, Connie M. Arthur, Kathryn R. Girard-Pierce, Ashley Bennett, and Sean R. Stowell. "Marginal Zone B Cells Regulate RBC Alloimmunization Toward Distinct RBC Alloantigens." Blood 128, no. 22 (December 2, 2016): 3847. http://dx.doi.org/10.1182/blood.v128.22.3847.3847.
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Abstract Background: While red blood cell (RBC) transfusion can be beneficial, exposure to allogeneic RBCs can result in the development of RBC alloantibodies that can make it difficult to obtain compatible RBCs for future transfusions. Aside from phenotype matching protocols, no strategy currently exists that is capable of preventing RBC alloimmunization following therapeutic transfusion. As RBC alloantigens represent diverse determinants capable of driving distinct immune pathways, common immunological nodes must be identified in order to successfully prevent RBC alloimmunization against a variety of different alloantigens. Recent results demonstrate that marginal zone (MZ) B cells mediate anti-KEL antibody formation in the complete absence of CD4 T cells. However, whether MZ B cells similarly regulate RBC alloantibody formation against other RBC alloantigens remains unknown. As a result, we examined the role of MZ B cells and CD4 T cells in the development of RBC alloantibodies following exposure to the HOD (hen egg lysozyme, ovalbumin and duffy) antigen. Methods: Each recipient was transfused with HOD or KEL RBCs following either MZ B cell or CD4 T cell depletion using a cocktail of MZ B cell (anti-CD11a and anti-CD49d) or anti-CD4 depleting antibody, 4 and 2 days prior to transfusion. Control groups received isotype control injections in parallel. MZ B cell deficient (CD19cre/+ X Notch2flx/flx) and CD4 T cell deficient (MHC class II knockout) recipients were also used to examine the role of MZ B cells and CD4 T cells, respectively. Serum collected on days 5 and 14 post-transfusion was evaluated for anti-HOD or anti-KEL antibodies by incubating HOD or KEL RBCs with serum, followed by detection of bound antibodies using anti-IgM and anti-IgG and subsequent flow cytometric analysis. Evaluation of antibody engagement and overall survival of HOD or KEL RBCs was accomplished by labeling RBCs with the lipophilic dye, DiI, prior to transfusion, followed by examination for bound antibody and RBC clearance on days 5 and 14 post-transfusion by flow cytometry. Results: Similar to the ability of MZ B cell depletion to reduce anti-KEL antibody formation following KEL RBC exposure, depletion of MZ B cells significantly reduced anti-HOD IgM and IgG antibodies following HOD RBC transfusion. In contrast, injection of recipients with isotype control antibodies in parallel failed to prevent alloantibody formation following HOD or KEL RBC transfusion. Similar results were obtained following HOD or KEL RBC transfusion into recipients genetically deficient in MZ B cells. In contrast, although MZ B cells were required for HOD and KEL RBC-alloantibody formation, manipulation of CD4 T cells differentially impacted the ability of each antigen to induce alloantibodies. While transfusion of HOD or KEL RBCs resulted in robust IgM alloantibodies in the absence of CD4 T cells, depletion or genetic elimination of CD4 T cells significantly inhibited anti-HOD IgG antibody formation, while failing to impact IgG anti-KEL antibody formation. Consistent with this, while manipulation of CD4 T cells protected HOD RBCs from antibody deposition and subsequent RBC clearance, this same approach failed to similarly protect KEL RBCs following transfusion. In contrast, depletion of MZ B cells not only prevented detectable alloantibody production, but also completely protected HOD or KEL RBCs from antibody deposition and subsequent RBC clearance. Conclusion: These results suggest that while MZ B cells mediate a robust IgM antibody response following either KEL or HOD antigen exposure, MZ B cells appear to possess the capacity to orchestrate unique downstream IgG responses through CD4 T cell dependent and independent pathways contingent on target alloantigen. As a result, while manipulation of CD4 T cells may prevent alloantibody formation against some antigens, targeting this immune population inadequately prevents RBC alloantibody formation against all RBC antigens. As chronic transfusion therapy exposes recipients to a wide variety of alloantigens, these results suggest that MZ B cells may represent a central initiating node that governs RBC alloimmunization against a variety of RBC alloantigens, and may therefore serve as a useful target in preventing alloantibody formation in chronically transfused individuals. Disclosures No relevant conflicts of interest to declare.
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Yasuda, Toshitaka, Akio Funakubo, Kenli Shimokasa, Shahriar Ahmed, Tetsuya Higami, Tsuyoshi Kawamura, and Yasuhiro Fukui. "ESTIMATION OF RED BLOOD CELL (RBC) DAMAGE BY MEASURING RBC AREA." ASAIO Journal 48, no. 2 (March 2002): 191. http://dx.doi.org/10.1097/00002480-200203000-00263.
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Li, Jun, Hao Wu, Bin Liu, Zhaoxi Fang, Shaozhong Zhang, and Jiong Shi. "RBC-CC: RBC-Based Cascade Caching Scheme for Content-Centric Networking." Journal of Network and Systems Management 25, no. 2 (September 19, 2016): 375–96. http://dx.doi.org/10.1007/s10922-016-9394-8.
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Conlan, Maureen G., Adonis Stassinopoulos, George Garratty, David Wages, Laurence Corash, Lindsey Wood, Steven R. Sloan, and Richard J. Labotka. "Antibody Formation to S-303-Treated RBCS in the Setting of Chronic RBC Transfusion." Blood 104, no. 11 (November 16, 2004): 382. http://dx.doi.org/10.1182/blood.v104.11.382.382.
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Abstract Background : S-303 treatment (200 μM S-303 and 2 mM glutathione) has been shown to inactivate viruses, bacteria, protozoa and leukocytes in RBC concentrates. S-303-treated RBCs (SRBC) have comparable in vitro parameters to untreated conventional RBCs (CRBC) over 42 days (d) of storage. Three Phase I trials in healthy human subjects showed recovery and life span of 35 d old autologous S-303 RBC were comparable to that for CRBC without detectable antibody (Ab) formation. During the course of a Phase III trial for patients (pts) in chronic transfusion (txn) programs receiving repeated SRBC txn, 2 pts developed asymptomatic anti-SRBC Ab, leading to trial termination. Methods : A randomized, controlled, double-blinded, crossover design, non-inferiority trial of SRBC in pts with thalassemia (thal) or sickle cell anemia (SSA) was conducted. Fifty pts were to receive a course (≥5 months or ≥6 txn) of SRBC or CRBC with crossover to the other arm. The frequency and number of RBC units per txn and target hemoglobin (Hb) were at physician discretion. The primary endpoint was Hb txed per kg body weight per d. Secondary endpoints were: time between txn, pre-txn Hb, number of RBC units txed, Ab formation, and adverse events (AEs). Routine DAT and IAT with RBC panels, and cross match with IAT to SRBC (and to the pre-S-303 treatment segment if positive to SRBC), were performed at trial sites prior to each txn. Following detection of positive cross match to SRBC in 2 pts, all pre-txn samples from all pts were tested by polyethylene glycol (PEG) SRBC cross match with IAT at a reference lab. Post study termination, pts had monthly follow-up (for up to 6 months) for AEs and repeated SRBC PEG cross match IAT. Results : The trial was terminated after 26 pts received ≥1 txn when 2 asymptomatic pts in the SRBC arm developed positive (+) pre-txn IAT cross matches with SRBC but not the same RBC unit pre-S-303 treatment (SRBC Ab). No pt completed the trial; 69% started the 1st period only and 31% crossed over to the 2nd period. 17 pts had ≥1 SRBC txn. Neither pt with (+) cross matches had clinical evidence of significantly reduced RBC survival. Hapten inhibition assays showed inhibition by S-303 derivatives but not glutathione used in the treatment process; a monocyte monolayer RBC phagocytic assay was negative with pt sera, suggesting these Ab were not likely clinically significant. Six-month follow-up of all txed pts did not reveal additional SRBC Ab or AEs. No Ab to SRBC were detected in a companion Phase III trial of SRBC txn for pts undergoing cardiac surgery supported with SRBC txn for up to 7 d. Conclusions : Two of 17 pts with exposure to SRBC in chronic txn programs developed Ab to SRBC after txn with SRBC. These Ab did not appear to result in decreased RBC survival (e.g., hemolysis), AEs, autoantibody formation, or Ab formation to RBC antigens. None of 74 pts txed with SRBC for up to 7 d to treat anemia of cardiac surgery developed SRBC Ab. A modified S-303 treatment process to reduce immunogenicity has been developed. Patients With Antibodies to S-303 RBC Patient 1 Patient 2 Age (yr) 3 13 Sex F M Diagnosis Thal SSA Time on study (d) 139 58 AEs Splenomegaly Pt. blood type AB+ A+ DAT/IAT (allo-Ab panel RBC) −/− −/− No. SRBC txn/units before (+) crossmatch 5/10 1/1 IAT reaction (LISS/PEG) against SRBC 2+/3+ 3+/2+ Titer of (+) sera against SRBC 2 8
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Ganguly, Kumkum, Tatiana Krasik, Khalil Bdeir, Douglas B. Cines, Vladimir R. Muzykantov, and JuanCarlos Murciano. "Conjugation of Plasminogen Activators to Carrier Erythrocytes Imparts New Biological Properties to Their Soluble Counterparts." Blood 104, no. 11 (November 16, 2004): 534. http://dx.doi.org/10.1182/blood.v104.11.534.534.
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Abstract Conjugation of plasminogen activators (PA) to carrier red blood cells (RBC) generates a new agent (RBC/PA), which selectively lyses nascent blood clots. In this work, we studied two types of RBC/PA conjugates, carrying Alteplase (tissue type plasminogen activator, tPA) or Reteplase (an engineered form of tPA, Ret). Compared to non-conjugated 125I-PA counterparts, both 125I-tPA and 125I-Ret coupled to 51Cr-RBC via biocompatible biotin-streptavidin cross-linker showed markedly prolonged circulation in rats and mice. Despite slightly faster blood clearance, RBC/tPA retained significantly higher fibrinolytic activity in circulation than RBC/Ret. In part, the higher fibrinolytic activity of RBC/tPA vs RBC/Ret in the circulation was due to its lessened susceptibility to plasma inhibitors. Analysis of amidolytic activity of RBC-coupled vs free tPA and Ret using chromogenic substrates in vitro revealed that coupling to RBC rendered Ret, but not tPA, insensitive to stimulation of fibrinolytic activity by fibrin. In vitro binding assay in cultural wells showed that RBC/tPA specifically binds to fibrin clot (6±0.2x104 RBC/tPA bound per well vs. 1±0.4x104 RBC/Ret or 7.3±0.6x103 naive RBC). RBC/tPA also bind specifically to immobilized fibrinogen and plasminogen (8±2x104 and 2±0.4x104 RBC/well), but not to non-cleavable plasminogen, collagen, fibronectin or thrombospondin (<1.1±0.3x103RBC/well). Neither RBC/Ret nor naïve RBC bind to these proteins (<1.1±0.2x103 RBC/well). Therefore, RBC/PA complexes display a considerable functional diversity, a result of interplay between the pharmacokinetic features offered by carrier RBC, individual features of a given PA and alterations of the latter caused by RBC coupling. In theory, this diversity may enhance flexibility and utility of potential applications of RBC/PA for thromboprophylaxis.
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Colin, FC, and SL Schrier. "Myosin content and distribution in human neonatal erythrocytes are different from adult erythrocytes." Blood 78, no. 11 (December 1, 1991): 3052–55. http://dx.doi.org/10.1182/blood.v78.11.3052.3052.
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Abstract Neonatal erythrocytes (N-RBC) are different from adult erythrocytes (A- RBC). N-RBC are larger, less deformable, and undergo enhanced spontaneous and drug-induced endocytosis. The reticulocyte population of N-RBC is also different, consisting primarily of the youngest (R1) reticulocytes that are motile and capable of receptor-mediated endocytosis. Processes such as motility could require a contractile system. Myosin, a contractile protein, was identified in both A-RBC and N-RBC. We proposed to compare myosin content and distribution in A-RBC and N-RBC by immunofluorescence and enzyme-linked immunosorbent assay (ELISA) using a monospecific polyclonal rabbit antimyosin. There was bright immunofluorescence on 44% of N-RBC with some heterogeneity contrasting with a barely detectable fluorescence on A-RBC. ELISA measurements showed that A-RBC had 4,315 myosin copies/RBC, whereas N- RBC had 10,855 copies/RBC (or 2.5 times as much). ELISA measurements of white ghosts showed that A-ghosts contained 1,250 copies of myosin/RBC (29% of total) whereas N-ghosts contained 3.4 times as much at 4,320 copies/RBC (39% of total). Therefore, N-RBC not only have more myosin, but the amount that is membrane-associated is disproportionately increased. It is proposed that such differences in amount and distribution of myosin could account for some of the unusual properties of neonatal RBC indicated.
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Colin, FC, and SL Schrier. "Myosin content and distribution in human neonatal erythrocytes are different from adult erythrocytes." Blood 78, no. 11 (December 1, 1991): 3052–55. http://dx.doi.org/10.1182/blood.v78.11.3052.bloodjournal78113052.
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Neonatal erythrocytes (N-RBC) are different from adult erythrocytes (A- RBC). N-RBC are larger, less deformable, and undergo enhanced spontaneous and drug-induced endocytosis. The reticulocyte population of N-RBC is also different, consisting primarily of the youngest (R1) reticulocytes that are motile and capable of receptor-mediated endocytosis. Processes such as motility could require a contractile system. Myosin, a contractile protein, was identified in both A-RBC and N-RBC. We proposed to compare myosin content and distribution in A-RBC and N-RBC by immunofluorescence and enzyme-linked immunosorbent assay (ELISA) using a monospecific polyclonal rabbit antimyosin. There was bright immunofluorescence on 44% of N-RBC with some heterogeneity contrasting with a barely detectable fluorescence on A-RBC. ELISA measurements showed that A-RBC had 4,315 myosin copies/RBC, whereas N- RBC had 10,855 copies/RBC (or 2.5 times as much). ELISA measurements of white ghosts showed that A-ghosts contained 1,250 copies of myosin/RBC (29% of total) whereas N-ghosts contained 3.4 times as much at 4,320 copies/RBC (39% of total). Therefore, N-RBC not only have more myosin, but the amount that is membrane-associated is disproportionately increased. It is proposed that such differences in amount and distribution of myosin could account for some of the unusual properties of neonatal RBC indicated.
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Tsan, M. F., D. Lawrence, and J. E. White. "Erythrocyte insufflation-induced protection against oxygen toxicity: role of cytokines." Journal of Applied Physiology 71, no. 5 (November 1, 1991): 1751–57. http://dx.doi.org/10.1152/jappl.1991.71.5.1751.
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We studied the pulmonary response of adult rats to erythrocyte (RBC) and RBC lysate insufflation to define the mechanism of RBC insufflation-induced protection against oxygen toxicity. Tracheal insufflation of 1 ml RBC (75%) or RBC lysate induced an intense pulmonary inflammatory response. Within 24 h of oxygen exposure, greater than 95% of insufflated RBCs was hemolyzed. The cell-free fraction of alveolar lavage fluids from RBC- or RBC lysate-insufflated rats had similar capacity in protecting endothelial cells against H2O2 cytotoxicity. However, RBC insufflation but not RBC lysate insufflation, protected rats against oxygen toxicity. There was marked erythrophagocytosis by alveolar macrophages of RBC-insufflated rats. Insufflation of RBCs, but not RBC lysate, resulted in production of tumor necrosis factor and interleukin 1, which could be recovered by bronchoalveolar lavages. When rats were insufflated with a combination of RBC lysate and cytokines at dosages within the range of cytokine levels achievable in alveolar lavage fluids by RBC insufflation, they became tolerant to oxygen. These results suggest that endogenously produced tumor necrosis factor and interleukin-1 as a result of RBC insufflation may play an important role in RBC insufflation-induced oxygen tolerance.
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Howard, R. J., G. Reuter, J. W. Barnwell, and R. Schauer. "Sialoglycoproteins and sialic acids ofPlasmodium knowlesischizont-infected erythrocytes and normal rhesus monkey erythrocytes." Parasitology 92, no. 3 (June 1986): 527–43. http://dx.doi.org/10.1017/s0031182000065422.
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SUMMARYThe effects of malaria infection on RBC sialic acids and sialoglycoproteins were studied with asexual blood-stage infections ofPlasmodium knowlesiin rhesus monkeys. Glycoprotein radio-isotope labelling methods were used to compare the sialoglycoproteins of normal RBC andP. knowlesischizont-infected RBC (SI-RBC). Tritiation of glycoproteins from SI-RBC with the standard sialidase + galactose oxidase/NaB3H4method or standard periodate/NaB3H4method was significantly decreased when compared to normal RBC. However, tritium uptake into glycoproteins was normal when SI-RBC were treated with 5-fold higher concentrations of both enzymes in the first labelling method, or with a 5-fold increase in the molar ratio of periodate to sialic acid in the second method. The mobility of tritiated host cell glycoproteins on SDS–polyacrylamide gels was identical for SI-RBC and normal RBC. New bands, possibly glycoproteins, of 230, 160, 90, 52, and 30 kDa were detected after labelling SI-RBC by the modified periodate/NaB3H4method. Sialic acid analysis of normal rhesus monkey RBC (62μg/1010RBC) revealed that 46% of the total sialic acid wasN-glycolylneuraminic acid, 33% wasN-acetyl-9-O-acetylneuraminic acid, and the remainderN-acetylneuraminic acid. SI-RBC collected either directly from infected monkeys or afterin vitroculture of ring-infected RBC in horse serum, had increased total sialic acid (126 or 115μg/1010RBC, respectively). The sialic acid content of infected RBC must increase during parasite development since RBC infected with ring-stageP. knowlesihad the same content as normal RBC. There was no significant difference in the ratio of the three sialic acids of SI-RBC and normal RBC. In contrast, the uninfected RBC from infected blood of different monkeys showed marked variation in sialic acid composition and generally had a lower sialic acid content than normal RBC.
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Zahid, Waleed M., and Jerzy J. Ganczarczyk. "Structure of RBC biofilms." Water Environment Research 66, no. 2 (March 1994): 100–106. http://dx.doi.org/10.2175/wer.66.2.2.
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Soupene, Eric, and Frans A. Kuypers. "Lysophospholipid Acylation in RBC." Blood 108, no. 11 (November 16, 2006): 1575. http://dx.doi.org/10.1182/blood.v108.11.1575.1575.
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Abstract The formation, distribution and utilization of acyl-CoA plays a crucial role in plasma membrane phospholipid turnover in red blood cells (RBC). Upon de-acylation of glycero-phospholipids (PL) via the action of phospholipase, re-acylation of the lysophospholipids (LPL) requires activity of two enzymes of the Lands pathway. Long-chain acyl-CoA synthetases (ACSL) activate fatty acids to acyl-CoA which are subsequently ligated to LPL by LysoPhosphoLipid Acyl Transferase (LPLAT) a family of enzymes with exclusive specificity for the polar group of LPL (phosphatidic acid, choline, serine and ethanolamine). We recently identified ACSL6 as the enzyme responsible for the activation of fatty acid in RBC. None of the family members of LPLAT have been identified in RBC to date. LPC, either generated in the RBC or taken up from plasma, is rapidly acylated by RBC suggesting an important role for Lysohosphatidylcholine-acyl transferase (LPCAT) in RBC. We report the identification and characterization of LPCAT, the enzyme that generates PC from LPC and acylCoA. We identified the RNA expression of LPCAT, an approximately 60kD protein, in reticulocytes, confirming proteomic studies suggesting the presence of this protein in adult RBC membranes.). It is a modular protein containing an acyltransferase domain at the amino-terminus, three predicted membrane spanning domains, and a putative calcium binding site at the C-terminus, distinguishing it from the lysophosphatidic acid acyltransferease (LPAAT). The putative LPCAT was expressed in E. coli. It was found in the E. coli membrane fraction, and was able to use oleoyl-CoA and LPC as substrates to generate PC. Lysophosphatidic acid (LPA) was not acylated by this protein. In contrast the previously identified LPAAT (1) expressed in E. coli, utilized LPA but not LPC, indicating LPL specificity of these enzymes. Radioactive fatty acid added to RBC is also incorporated in phosphatidyl ethanolamine (PE) and phosphatidyl serine (PS). Sequence analysis suggests that two other proteins present in the genome of mammals are homologues of LPCAT. We hypothesize that these putative acyltransferases are responsible for the acylation of lysophosphatidyl ethanolamine (LPE) and lysophosphatidyl serine (LPS). These proteins are essential to maintain a proper glycerophospholipid composition of the RBC membrane and thereby viability of the cells. A dysfunction of this system may underlie the observed differences in phospholipid molecular species composition in subpopulations of sickle cells contributing to sickle cell pathology. A complete description of these proteins involved in the maintenance of glycerophospholipid composition of RBC will aid to better understand the maintenance of plasma membrane lipid composition of all mammalian cells.
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Cheng, Michael, Norman Christ, Saumen Datta, Shinji Ejiri, Chulwoo Jung, Olaf Kaczmarek, Frithjof Karsch, et al. "The RBC-Bielefeld Collaboration." Nuclear Physics A 830, no. 1-4 (November 2009): 968c. http://dx.doi.org/10.1016/j.nuclphysa.2009.10.155.
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Gale, R. P., G. Barosi, T. Barbui, F. Cervantes, K. Dohner, B. Dupriez, V. Gupta, et al. "RBC-transfusion guidelines update." Leukemia Research 36, no. 5 (May 2012): 659–60. http://dx.doi.org/10.1016/j.leukres.2012.01.023.
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Hess, John R., Heather R. Hill, Cindy K. Oliver, Lloyd E. Lippert, Neeta Rugg, Amy D. Joines, Jennifer F. Gormas, P. Gayle Pratt, Edward B. Silverstein, and Tibor J. Greenwalt. "Twelve-week RBC storage." Transfusion 43, no. 7 (June 20, 2003): 867–72. http://dx.doi.org/10.1046/j.1537-2995.2003.00442.x.
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Tamm, Alexander, Martha Decker, Michael Hoskinson, Jonathan Abele, and Vimal Patel. "Heat-Damaged RBC Scan." Clinical Nuclear Medicine 40, no. 5 (May 2015): 453–54. http://dx.doi.org/10.1097/rlu.0000000000000701.
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Yoo, Justin, Connie Maridith Arthur, Patricia Zerra, Kathryn Girard-Pierce, Jeanne E. Hendrickson, and Sean R. Stowell. "Antigen Density Impacts RBC Survival and Antigen Modulation Following Incompatible RBC Transfusion." Blood 126, no. 23 (December 3, 2015): 2350. http://dx.doi.org/10.1182/blood.v126.23.2350.2350.
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Abstract Background: While chronic transfusion therapy can signficantly reduce morbidity and mortality in patients with hemoglonbinopathies, transfusion is not without risk. Differences in red blood cell (RBC) antigen distributions between donors and recipients can result in the development of RBC alloantibodies, which can make it difficult, if not impossible, to find compatible blood. As a result, heavily alloimmunized individuals experience greater morbidity and mortality than those who do not possess RBC-induced alloantibodies. While incompatible RBC transfusion can result in fatal hemolytic transfusion reactions (HTRs), these adverse events are not the invariable outcome of incompatible transfusion. Although a variety of factors likely contribute to the likilihood of developing a HTR following incompatible RBC transfusion, variability in the density of the donor antigen may contribute to different outcomes. Using a novel model that utilizes RBC donors with different levels of the KEL antigen, we sought to directly examine the impact of antigen density on RBC clearance following incompatible RBC transfusion. Methods: Wild type C57BL/6 mice (WT) were passively immunized with anti-KEL serum, generated following immunization of WT recipients with KEL RBCS, 2 hours prior to incompatible KEL RBC transfusion. RBC collected from previously generated KEL transgenic mice that express high (KELhi), intermediate (KELmed), and low (KELlo) levels of human KEL glycoprotein antigen, were labeled with chloromethylbenzamido 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI), while WT RBC were labeled with fluorescently distinct 3,3'-dihexadecyloxacarbocyanine perchlorate (DiO) to facilitate detection post-transfusion. Passively immunized recipient WT mice were transfused with labeled KEL RBC to WT RBC. Percent KEL RBC survival was measured using flow cytometric analysis at various time points post transfusion by comparing the DiI to DiO ratio. Bound antibody, complement and the KEL antigen were assessed by staining cells with anti-Ig, anti-C3 and anti-KEL followed by flow cytometric analysis. Results: Transfusion of RBCs expressing low, intermediate or high levels of the KEL antigen into non-immunized mice failed to result in any detectable alteration in RBC survival or KEL expression. However, transfusion of KELlo, KELmed and KELhi RBCs into anti-KEL immunized recipients resulted in differential clearance of each population, with KELhi experiencing the most clearance, followed by KELmed and KELlo. Similarly, the level of detectable C3 and bound antibody on KEL positive cells likewise correlated with the initial level of KEL antigen expression, with more C3 and IgG being detected on the surface of KELhi following transfusion into immunized recipients, than KELmed or KELlo. However, KELhi RBCs also experience the most significant alterations in KEL antigen levels following antibody engagement. Regardless of the KEL positive RBC transfused, each population developed a relatively rapid state of resistance to additional anti-KEL-mediated RBC removal. Conclusions: Our results indicate that lower antigen densities may be less efficient in not only facilitating rapid clearance of RBCs following incompatible transfusion, but also antibody-induced antigen modulation. While KELhi RBCs displayed the greatest degree of clearance and antigen modulation, each population developed resistance to antibody-mediate removal, suggesting that once RBC antigen levels fall below a certain threshold, clearance discontinues, regardless of the initial levels of antigen prior to incompatible transfusion. Taken together, these results suggest that antigen density may provide an additional feature of RBC transfusion that may impact the outcome of incompatible transfusion in heavily alloimmunized recipients. Disclosures No relevant conflicts of interest to declare.
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Pasini, Erica M., Hans U. Lutz, Matthias Mann, and Alan W. Thomas. "Red blood cell (RBC) membrane proteomics — Part I: Proteomics and RBC physiology." Journal of Proteomics 73, no. 3 (January 2010): 403–20. http://dx.doi.org/10.1016/j.jprot.2009.06.005.
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Stussi, Georg, Andreas Buser, and Andreas Holbro. "Red Blood Cells: Exchange, Transfuse, or Deplete." Transfusion Medicine and Hemotherapy 46, no. 6 (2019): 407–16. http://dx.doi.org/10.1159/000504144.
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Erythrocytapheresis, red blood cell (RBC) depletion, and RBC exchange transfusions are apheresis techniques used to rapidly lower the circulating RBC mass or to exchange the patient erythrocyte mass with donor RBC. Automated RBC exchange is performed using an apheresis device, while manual RBC exchange is based on sequential phlebotomies and isovolemic replacement. Compared to simple RBC transfusions, RBC exchange offers several advantages, e.g., a lower risk for iron accumulation and efficient control of pathological erythrocyte populations. Disadvantages are the higher costs of the procedure, the increased use of donor RBC, and the requirement of apheresis devices and trained hospital staff. The most frequent indication for RBC exchange is sickle cell disease (SCD). RBC exchange transfusions are standard treatment in SCD patients with a history of or a risk for acute stroke and are clinical options for other acute complications of SCD. The most common indication for RBC depletion is the removal of donor RBC from the bone marrow grafts in major ABO-incompatible allogeneic hematopoietic stem cell transplantation to avoid immediate hemolysis. Rare indications for RBC exchange are severe infections with intraerythrocytic pathogens such as malaria or babesiosis and severe erythrocytosis or hereditary hemochromatosis where the aim is to rapidly decrease RBC populations or the iron content. However, only few high-quality studies are available looking at the efficacy of RBC exchange in the different disease entities, and treatment is often based on low levels of evidence and should therefore be decided in close collaboration with a transfusion medicine specialist.
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Hosomi, Masaaki, Inamori Yuhei, Kazuo Matsushige, and Ryuichi Sudo. "Denitrification of Landfill Leachate by the Modified Rotating Biological Contactor (RBC)." Water Science and Technology 23, no. 7-9 (April 1, 1991): 1477–85. http://dx.doi.org/10.2166/wst.1991.0600.
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In order to remove high-strength nitrogen and organics in landfill leachate simultaneously, the modified RBC which was combined with the standard RBC and the anaerobic biofilter was proposed. The treatability for actual landfill leachate of the standard RBC and the modified RBC was evaluated. The capability of COD removal in the modified RBC is much greater than that in the standard RBC, although both RBCs showed a BOD removal rate of more than 95%. This suggested that the combination method of aerobic and anaerobic treatment was effective in reducing refractory organic compounds. The nitrogen removal in the modified RBC was about 90% compared to 50% in Che standard RBC. The modified RBC had the advantage of nitrogen removal because nitrification and denitrification proceeded efficiently, even if a carbon source was not added. The performance of the modified RBC was superior to that of the standard RBC in both BOD surface loading and BOD volumetric loading.
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Singhal, Deepak, Sophia Hague, David Roxby, L. Amilia Wee, Oi-Lin Lee, Romi Sinha, Rakchha Chhetri, et al. "RBC Alloimmunization Burden Is High in Regularly RBC-Transfused Myelodysplastic Syndrome (MDS) Patients: A Report from South Australian-MDS Registry." Blood 126, no. 23 (December 3, 2015): 3562. http://dx.doi.org/10.1182/blood.v126.23.3562.3562.
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Abstract Introduction: Anemia is one of the commonest presenting features of MDS and approximately 30-40% of patients require regular RBC-transfusion. RBC-transfusion dependency (RBC-TD) is a poor-prognostic factor independent of revised International Prognostic Scoring System (IPSS-R) (Hiwase et al ASH 2014). Although RBC transfusion increases the risk of alloimmunization, there is limited literature characterizing this risk in MDS patients as compared to other hematological disorders (such as thalassemia). Methods: This retrospective study assessed the alloimmunization rate in 784 MDS and AML (20-30% blasts) patients registered in the South Australian-MDS registry (SA-MDS registry) between 1991 and 2015. RBC-TD was defined as ≥1 unit of RBC transfused every eight weeks for four months according to WHO based Prognostic Scoring System. The cumulative incidence of RBC-alloimmunization was calculated using competing risk analysis (death being the competing risk). Factors associated with increased rate of RBC antibody formation were investigated by Cox regression analysis. Results: The median age of the 784 patients at diagnosis was 75 years with 66% males. The estimated median follow up time was 7.3 years. 70% of patients (549/784) were diagnosed with primary MDS, while the remaining patients were diagnosed with AML (20-30% blasts; n=57), CMML (n=91) or therapy-related myeloid neoplasm (T-MN; n=87). At last follow-up 30% patients were alive, 67% were deceased and 3% were lost to follow-up. During the study period, 658 (84%) patients required ≥1 unit of RBC transfusion and median RBC units transfused were 29 (range 0-708). The WPSS definition of RBC-TD was met in 47% (366/784 patients), while 36% (282/784) patients required intermittent RBC-transfusions (RBC-TI). During follow up, 83 (13%) patients formed 155 RBC-alloantibodies and 50% of these cases (42/83) developed >1 RBC-alloantibody. Autoantibodies were also detected in 31 cases, mainly in association with RBC-alloantibodies (n=27; complex alloimmunization) while 4 cases had only autoantibodies. Interestingly, in 19/27 of cases autoantibodies were detected only after alloimmunization. The pathophysiologic mechanism of this remains unclear. The most common alloantibody specificities were Rh (57%) and Kell (21%) (Table 1). The median interval between 1st RBC transfusion and antibody detection was 10 (0.2-225) months. In 9 cases (6 females) alloantibodies were detected prior to the 1st unit of RBC-transfused. The incidence of RBC alloimmunization reached a plateau at 16% by 100 units of RBC (Fig. 1A), however 80% of antibodies were detectable by 30-40 RBC units transfused. It indicates that most "responders" will form antibodies during the first 30-40 units of RBC transfused. Since most chronically transfused MDS patients do not form RBC alloantibodies it is important from a clinical and resource-utilization standpoint to identify who is at greatest risk of RBC alloimmunization. Multivariate analysis using Cox-regression model was performed. The only factor which was associated with significantly higher risk of RBC alloimmunization was RBC-TD (HR 2.52; p=0.0005). Age, sex, IPSS-R category and number of RBC units transfused did not independently predict alloimmunization rate. Using competing risk analysis, the cumulative incidence of RBC-alloimmunization was significantly higher in RBC-TD group compared to RBC-TI group (p=0.0004; Fig. 1B). Conclusion: RBC-alloimmunization is a substantial risk in MDS patients, especially in RBC-transfusion dependent cases. Extended phenotype matching (D,C,c,E,e and Kell) could have prevented alloantibody formation in 79% of alloimmunized MDS patients. Table 1. Specificity of 155 RBC-alloantibodies Table 1. Specificity of 155 RBC-alloantibodies Disclosures Yeung: Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.
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Srinivasan, Ramprasad, Danielle Coyle, Neil Batra, Victor Blanco, Wilson Tong, Mary B. Palascak, Robert S. Franco, et al. "Red Blood Cells As a Novel Mediator of Chronic Inflammation in Diet-Induced Obesity: Implications for Atherosclerosis." Blood 120, no. 21 (November 16, 2012): 3198. http://dx.doi.org/10.1182/blood.v120.21.3198.3198.
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Abstract Abstract 3198 Background: Red blood cell (RBC) extravasation contributes to the growth of atherosclerotic plaque, and is associated with plaque rupture. High Fat Diet (HFD) fuels systemic inflammation by promoting monocyte activation and their recruitment/transendothelial migration. RBC bind chemokines such as monocyte chemotactic protein-1 (MCP-1) via Duffy Antigen Receptor for Chemokines (DARC). While it was previously reported that HFD may impact RBC cholesterol content, very little is known about the impact – if any – of HFD on RBC function(s). Hence, we studied whether HFD affects biochemical and functional properties of RBC in ways potentially relevant to the progression of atherosclerosis. Methods and Results: Wild type (WT) C56BL6/J mice were fed either chow (10% total fat) or HFD (60% total fat) for 312 weeks. MCP-1 levels were measured in plasma before and after the release of DARC-bound MCP-1 by heparin. Released MCP-1 was 1.5 fold higher in HFD RBC (12 weeks on diet, n=3) compared to chow RBC. Levels of intracellular reactive oxygen species (ROS) were measured by DCFH fluorescence using flow cytometry, and were increased in HFD RBC (17 weeks on diet, n=3) by ∼1.2 fold compared to chow RBC (p<0.05). We also observed a 1.5 fold increase in external phosphatidylserine (PS) in HFD RBC (12 weeks on diet, n=3) as revealed by Annexin V binding (flow cytometry). In vitro erythrophagocytosis was assayed by incubating thioglycollate-induced peritoneal macrophages from WT mice with calcein-AM labeled RBC obtained from mice on HFD (12 weeks on diet, n=3) or chow. A ∼1.5 fold (p<0.05) increase in phagocytosis was observed for HFD RBC compared to chow RBC. When HFD RBC served as a source of chemoattractant(s), we observed a ∼1.4 fold (p<0.05) increase (compared to chow RBC) in the number of monocytes undergoing transendothelial migration in a Boyden chamber assay. Experiments performed on RBC from LDLr −/− mice fed either HFD or chow for 12 weeks (n=3), displayed the fold changes analogous to those observed in RBC from WT mice with respect to ROS levels, transendothelial monocyte migration, and PS externalization but a significant increase in RBC phagocytosis of ∼1.7 fold (p<0.05). The increased PS exposure was associated with an increase in splenic uptake of RBC: calcein-AM labeled packed RBC (chow or HFD) were injected retroorbitally into WT mice maintained on chow and after 24 hrs, peripheral blood was removed by cardiac perfusion, spleens harvested, embedded in OCT media, and 10 mm sections were analyzed using Image J software. Macrophages located predominantly in splenic sinuses engulfed ∼3 fold more HFD RBC (12 weeks on diet, n=3) compared to chow RBC (p<0.05). Microarray analysis was then performed on peritoneal macrophages derived from HFD mice that were incubated with either HFD RBC or chow RBC for 4 hrs (results validated by qRT-PCR). Interestingly, several chemokines such as Il-1b, Ccl3, and Cxcl2 were upregulated in HFD macrophages that engulfed HFD RBC compared to those that engulfed chow RBC (3 fold, 3 fold, and 12 fold, respectively). RBC deformability, a crucial characteristic enabling RBC to traverse through narrow capillaries/splenic sinuses, was measured using ektacytometry. Deformability expressed as elongation index was decreased in HFD RBC compared to chow RBC, especially at intermediate shear stress (2 – 20 Pa). Finally, when freshly harvested aortic segments were incubated with packed RBC (HFD or chow), washed, and exposed to pre-labeled fluorescent WT murine macrophages, there was an enhancement of macrophage adhesion to the luminal endothelium when HFD RBC were used (∼3 fold, p<0.05). Conclusions: We here show that HFD elicits an increase in surface levels of MCP-1 in RBC, which is associated with an enhanced macrophage adhesion to the intact vascular endothelium and increased transendothelial migration in vitro. Further, HFD increases ROS levels and PS externalization in RBC, and HFD RBC exhibit an enhanced splenic uptake in vivo. These effects of HFD on circulating RBC are likely to promote chronic inflammation, rendering RBC a heretofore unknown contributor to local as well as systemic changes that lead to atherosclerosis. Disclosures: No relevant conflicts of interest to declare.
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Baskurt, Oguz K., Robert A. Farley, and Herbert J. Meiselman. "Erythrocyte aggregation tendency and cellular properties in horse, human, and rat: a comparative study." American Journal of Physiology-Heart and Circulatory Physiology 273, no. 6 (December 1, 1997): H2604—H2612. http://dx.doi.org/10.1152/ajpheart.1997.273.6.h2604.
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Horse blood has a higher tendency to form red blood cell (RBC) aggregates compared with human blood, with this enhanced aggregation previously attributed to differences in plasma factors. Our results confirm this observation and further indicate that washed horse RBC also have a significantly higher aggregation tendency in dextran 70 solutions (i.e., horse RBC have a higher “aggregability”). In contrast, the aggregation tendency of rat RBC, both in autologous plasma and in dextran 70, is significantly less compared with human and horse RBC. Other rheological findings for horse and rat RBC include smaller changes in RBC deformation indexes over the same shear stress range and a lower RBC shape recovery time constant. Rat RBC also had higher two-phase aqueous polymer partition coefficients, suggesting a higher surface charge. Membrane protein analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed marked differences: 1) band 4.2 protein was lacking in horse RBC membranes, and 2) carbohydrate groups have different distributions in human, rat, and horse RBC, as indicated by different patterns in periodic acid-Schiff-stained protein bands. Our results clearly indicate significant differences in RBC aggregability among the three species and indicate that cellular factors contribute importantly to these differences. Furthermore, they suggest that systematic studies of blood and RBC from different species should provide insight into the mechanism(s) of RBC aggregation.
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Zhou, Zhichao, Aida Collado, Changyan Sun, Yahor Tratsiakovich, Ali Mahdi, Hanna Winter, Ekaterina Chernogubova, et al. "Downregulation of Erythrocyte miR-210 Induces Endothelial Dysfunction in Type 2 Diabetes." Diabetes 71, no. 2 (November 9, 2021): 285–97. http://dx.doi.org/10.2337/db21-0093.
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Red blood cells (RBC) act as mediators of vascular injury in type 2 diabetes mellitus (T2DM). miR-210 plays a protective role in cardiovascular homeostasis and is decreased in whole blood of T2DM mice. We hypothesized that downregulation of RBC miR-210 induces endothelial dysfunction in T2DM. RBC were coincubated with arteries and endothelial cells ex vivo and transfused in vivo to identify the role of miR-210 and its target protein tyrosine phosphatase 1B (PTP1B) in endothelial dysfunction. RBC from patients with T2DM and diabetic rodents induced endothelial dysfunction ex vivo and in vivo. miR-210 levels were lower in human RBC from patients with T2DM (T2DM RBC) than in RBC from healthy subjects. Transfection of miR-210 in human T2DM RBC rescued endothelial function, whereas miR-210 inhibition in healthy subjects RBC or RBC from miR-210 knockout mice impaired endothelial function. Human T2DM RBC decreased miR-210 expression in endothelial cells. miR-210 expression in carotid artery plaques was lower in T2DM patients than in patients without diabetes. Endothelial dysfunction induced by downregulated RBC miR-210 involved PTP1B and reactive oxygen species. miR-210 mimic attenuated endothelial dysfunction induced by RBC via downregulating vascular PTP1B and oxidative stress in diabetic mice in vivo. These data reveal that the downregulation of RBC miR-210 is a novel mechanism driving the development of endothelial dysfunction in T2DM.
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Ficicioglu, Can, Christie Hussa, Paul R. Gallagher, Nina Thomas, and Claire Yager. "Monitoring of Biochemical Status in Children with Duarte Galactosemia: Utility of Galactose, Galactitol, Galactonate, and Galactose 1-Phosphate." Clinical Chemistry 56, no. 7 (July 1, 2010): 1177–82. http://dx.doi.org/10.1373/clinchem.2010.144097.
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Abstract Background: Duarte galactosemia (DG) is frequently detected in newborn-screening programs. DG patients do not manifest the symptoms of classic galactosemia, but whether they require dietary galactose restriction is controversial. We sought to assess the relationships of selected galactose metabolites (plasma galactose, plasma galactitol, erythrocyte (RBC) galactitol, RBC galactonate, and urine galactitol and galactonate) to RBC galactose 1-phosphate (Gal-1-P), dietary galactose intake, and neurodevelopmental/clinical outcomes in DG children. Methods: We studied 30 children 1–6 years of age who had DG galactosemia and were on a regular diet. All participants underwent a physical and ophthalmologic examination and a neurodevelopmental assessment. RBC galactitol, RBC galactonate, RBC Gal-1-P, plasma galactose, plasma galactonate, and urine galactitol and galactonate concentrations were measured. Results: RBC galactitol and galactonate concentrations were about 2 and 6 times higher, respectively, than control values. Plasma galactose and galactitol concentrations were also about twice the control values. The mean values for RBC Gal-1-P and urine galactitol were within the reference interval. We found a relationship between plasma and urine galactitol concentrations but no relationship between RBC galactose metabolites and urine galactitol. There was a significant relationship between galactose intake and RBC galactose metabolites, especially RBC galactitol (P < 0.0005) and RBC galactonate (P < 0.0005). Galactose intake was not related to the urine galactitol, plasma galactose, or plasma galactitol concentration. RBC galactitol, RBC galactonate, plasma galactose, plasma galactitol, and urine galactonate concentrations showed no relationship with clinical or developmental outcomes. Conclusions: DG children on a regular diet have RBC Gal-1-P concentrations within the reference interval but increased concentrations of other galactose metabolites, including RBC galactitol and RBC galactonate. These increased concentrations correlate with galactose intake and neither cause any developmental or clinical pathology during early childhood nor oblige a lactose-restricted diet.
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Hofstra, TC, VK Kalra, HJ Meiselman, and TD Coates. "Sickle erythrocytes adhere to polymorphonuclear neutrophils and activate the neutrophil respiratory burst." Blood 87, no. 10 (May 15, 1996): 4440–47. http://dx.doi.org/10.1182/blood.v87.10.4440.bloodjournal87104440.
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The vasoocclusive process in patients with sickle cell disease (SCD) is complex and involves interactions among sickle erythrocytes (SS-RBC), vascular endothelium, and plasma and cellular components. The role of neutrophils (PMN) in vasoocclusion has not been examined. Patients with SCD appear to have chronically activated PMN. Because the first step in PMN activation is particle recognition, we explored whether normal PMN recognize SS-RBC and whether this recognition results in PMN monolayers, significantly more SS-RBC adhered to the PMN than did normal erythrocytes (AA-RBC; P < .001). Preincubation of erythrocytes with autologous plasma significantly increased the adherence of SS-RBC to PMN but had no effect on AA-RBC (P < .001). When adhesion of density fractionated SS-RBC was performed, dense SS-RBC showed greater adherence to the PMN monolayers than did light SS-RBC (P < .001). To determine mechanisms of this adhesion, IgG and Arg-Gly-Asp-Ser (RGDS) receptor sites on PMN were saturated. IgG inhibited adherence of dense SS-RBC, whereas RGDS inhibited adherence in both fractions, although to a greater extent in the light fraction. We measured SS-RBC activation of PMN by incubating SS-RBC with 2′, 7′-Dichloro-fluroescin Diacetate (DCF)-labeled PMN. Incubation of PMN with SS-RBC resulted in a significant increase in fluorescence compared to AA-RBC. We show here that PMN recognize SS-RBC through multiple mechanisms and that this recognition results in activation of PMN. These findings contribute to the understanding of vasoocclusive crisis in patients with SCD and may have therapeutic implications.
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Colard, Martin, Michaël Dussiot, Anaïs Martinez, Carole Peyssonnaux, Patrick Mayeux, Fleur Samantha Benghiat, Pierre Buffet, Olivier Hermine, and Pascal Amireault. "Erythropoietin Downregulates Red Blood Cell Clearance in Mice." Blood 134, Supplement_1 (November 13, 2019): 3524. http://dx.doi.org/10.1182/blood-2019-126768.
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Purpose Equilibrium between red blood cells (RBC) production and clearance maintains an appropriate circulating RBC biomass. During anemia or hypoxia, a well-characterized hypoxia-dependent induction of erythropoietin (EPO) synthesis leads to an increase in RBC production. At the other extremity of the RBC lifespan, age-related modifications of RBC properties are expected to be recognized by the mononuclear phagocytic system (MPS) and trigger their clearance. We reasoned that, like RBC production, RBC clearance might be physiologically regulated by hypoxia and therefore that its downregulation could contribute to maintain an appropriate RBC biomass. A mouse model was used to explore specific hypotheses on potential regulatory mechanisms involved in RBC clearance. Material and methods Two steps in vivo biotinylation was used to evaluate the impact of EPO on 3 RBC subpopulations: a young subpopulation (<25 days at treatment initiation) representing the RBC produced, one of intermediate age (25-34 days at treatment initiation) which is neither produced nor eliminated, and an old one (> 34 days at treatment initiation) that is steadily cleared. A model of RBC banking (leucocyte depleted and stored in CPDA solution) was used to evaluate the clearance after transfusion of fluorescently-labeled storage-damaged RBC by flow cytometry. Different recipient models were used to evaluate the impact of specific parameters on RBC clearance including: phlebotomy-induced anemia, normobaric hypoxia, erythropoiesis-stimulating agent (ESA) treatment (darbepoietin), splenectomy, doxorubicin-induced inhibition of erythropoiesis and EPO neutralization (anti-EPO rabbit serum) either alone or in combination. Results Decreased clearance of the oldest subpopulation was observed 2 days after ESA treatment and before the increase in RBC production (7 days). After 20 days of treatment, an increased number of RBC from the oldest subpopulation was detected in circulation confirming that senescent RBC clearance is sensitive to EPO signaling. After transfusion, clearance of storage-damaged RBC is reduced by 30% in anemic recipients when compared to non-anemic recipients. RBC clearance is significantly reduced in hypoxic non-anemic recipients, as soon as 6 hours after the initiation of hypoxia, suggesting that hematocrit per se does not affect RBC clearance. In ESA-treated non-anemic non-hypoxic mice, RBC clearance is also reduced showing that EPO signaling is sufficient. To investigate the role of the spleen in this process, splenectomy was combined with the previous models. As expected, RBC clearance was reduced by 20% in splenectomized recipients. RBC clearance is however even more decreased when splenectomy is combined with anemia, hypoxia or ESA treatment compared to splenectomized or control mice, suggesting that EPO downregulation of RBC clearance is not restricted to the spleen. Erythropoiesis inhibition did not alter the anemia-induced downregulation of RBC clearance ruling out the possibility that an erythroid factor is involved in the process. Finally, neutralization of circulating EPO not only abolishes the reduction of RBC clearance observed in anemic recipients, but also increases RBC clearance in both anemic and non-anemic recipients. Taken together these results indicate that EPO regulates RBC clearance during anemia and in steady state (Figure). Conclusion RBC clearance is downregulated during anemia/hypoxia and EPO is sufficient and necessary to mediate this physiological function. RBC clearance downregulation preceded the increase in production rate induced by ESA treatment suggesting it is a very early physiological response to maintain oxygen supply during anemia. The lifespan of a circulating RBC is therefore adaptable and could be regulated by 2 factors: the RBC pro- and anti-phagocytic properties on one side and, on the other side, the MPS level of activity and sensitivity toward these RBC properties. In case of anemia or hypoxia, increased EPO level would act on the RBC itself, on the activity/sensitivity of the MPS or both to downregulate RBC clearance until the equilibrium between oxygen need and supply is restored. Future studies will evaluate if the pathological dysregulation of this mechanism participates in the pathogenesis of anemia or, modulate transfusion efficacy and burden in chronically transfused patients. Figure Disclosures Buffet: Zimmer Biomet: Research Funding. Hermine:Celgene: Research Funding; Novartis: Research Funding; AB science: Consultancy, Equity Ownership, Honoraria, Research Funding. Amireault:Zimmer Biomet: Research Funding.
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Fazili, Zia, Neelima Paladugula, Ming Zhang, and Christine M. Pfeiffer. "Folate Forms in RBC and Whole-Blood Lysates Appear Stable When Stored Frozen for 2 Years." Journal of Nutrition 151, no. 9 (June 5, 2021): 2852–60. http://dx.doi.org/10.1093/jn/nxab184.
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ABSTRACT Background The use of RBC lysate (RBC-Lys) eliminates the need for serum folate and hematocrit (Hct) measurement to calculate RBC folate. Information on the long-term frozen storage stability of RBC-Lys is missing. Objectives We aimed to assess the comparability of RBC folate forms in whole-blood lysate (WB-Lys) and RBC-Lys and the folate stability in both matrices. Methods We prepared conventional WB-Lys (1:11 dilution with 1% ascorbic acid) and RBC-Lys (1:11 dilution of washed and saline-diluted RBCs with 1% ascorbic acid) from EDTA blood (n = 60 adult donors) and stored lysates at −70°C until analysis at baseline (1 wk), 3, 6, 12, and 24 mo. Before analysis by HPLC–tandem MS, we incubated the WB-Lys (4 h at 37°C) and treated the RBC-Lys with human recombinant γ-glutamyl hydrolase for folate polyglutamate deconjugation. We analyzed RBC-Lys samples for hemoglobin (Hb) (same aliquot) to normalize for the preanalytical dilution; Hb-folate was converted to RBC folate for each folate form using the mean corpuscular Hb concentration. We analyzed Hct as well as folate forms in matching serum samples for traditional RBC folate calculation. We conducted descriptive data analyses (correlation, Bland–Altman plot, Deming regression). Results At baseline, results for RBC folate forms derived from WB-Lys compared with RBC-Lys samples showed excellent correlation (Pearson r ≥ 0.97). Mean ± SD concentrations compared well for total folate (WB-Lys: 886 ± 255 compared with RBC-Lys: 899 ± 271 nmol/L), 5-methyltetrahydrofolate (WB-Lys: 831 ± 258 compared with RBC-Lys: 843 ± 276 nmol/L), and nonmethyl folate (WB-Lys: 53.3 ± 74.4 compared with RBC-Lys: 52.9 ± 70.7 nmol/L), but were 17% higher in RBC-Lys for pyrazino-s-triazine derivative of 4α-hydroxy-5-CH3-H4folate (MeFox) (WB-Lys: 147 ± 44.1 compared with RBC-Lys: 172 ± 53.5 nmol/L). Frozen storage of WB-Lys and RBC-Lys samples for ≤24 mo showed ≤5%, ≤5%, ≤13%, and ≤11% change in total folate, 5-methyltetrahydrofolate, nonmethyl folate, and MeFox, respectively. Conclusions Erythrocyte folate forms appear to be stable in RBC-Lys samples stored frozen at −70°C for ≤2 y. The relatively small changes in folate concentrations over time were comparable between RBC-Lys and conventionally prepared WB-Lys samples.
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Ko, Myung S., Kate K. Xu, and Marilyn J. Telen. "Mechanism of Soluble Laminin-Mediated Enhancement of Sickle Red Cell Adhesion to Endothelial Cells." Blood 108, no. 11 (November 16, 2006): 1237. http://dx.doi.org/10.1182/blood.v108.11.1237.1237.
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Abstract We have previously shown that erythrocytes from patients homozygous for hemoglobin S (SS RBC) adhere to immobilized laminins −10,11 (α5 LAM) with high affinity through the B-CAM/LU receptor. SS RBC also avidly bind soluble LAM via B-CAM/LU. In addition, the interaction between endothelial cell (EC) integrin αVβ3 and erythrocyte ICAM4 is a significant contributor to the adhesion of SS RBC to EC. We have recently shown that soluble LAM, either purified or in plasma, enhances SS RBC adhesion to EC. We have now studied the mechanism by which soluble LAM enhances RBC adhesion to EC and the possible relationship between LAM-enhanced and ICAM-4 mediated adhesion of SS RBC. We tested the adhesion of SS RBC to EC under various potentially adhesion-blocking conditions to determine possible modes of interaction between SS RBC, LAM, SS RBC pre-incubated in LAM (SS RBC+LAM), and EC. We first studied whether blocking RBC-bound LAM with an anti-LAM antibody (Ab) could reduce the adhesion-enhancing effects of LAM. SS RBC were pre-incubated in 10 μg/mL soluble LAM for 1 hr at 37°C. After LAM incubation, SS RBC+LAM were washed and re-incubated for 1 hr in 4C7 mAb, an anti-LAM Ab, followed by washing. Adhesion of SS RBC+LAM incubated in 4C7 was compared to adhesion of SS RBC+LAM incubated with an irrelevant Ab and SS RBC not first incubated in LAM. SS RBC+LAM showed on average more than a two-fold increase in adhesion compared to SS RBC not incubated with LAM, at shear stresses of both 2 and 5 dynes/cm2 (n=3). In contrast, SS RBC+LAM incubated in Ab 4C7 showed < a 50% increase in adhesion compared to SS RBC not pre-incubated in LAM. However, due to variability in adhesion among patient samples, these differences were not significant. In order to determine the EC structure to which SS RBC+LAM might bind, we then incubated EC for 1 hr in an IgM Ab to dystroglycan, a putative LAM receptor on EC. SS RBC+LAM were tested for adhesion to untreated EC, EC treated with anti-dystroglycan, and EC treated with a control IgM. Treatment of EC with anti-dystroglycan decreased the adhesion of SS RBC+LAM by 39.1% and 50.1% at shear stresses of 2 and 5 dynes/cm2, respectively, while EC treated with control IgM showed insignificant decreases in adhesion of 3.3% and 6.6% at shear stresses of 2 and 5 dynes/cm2, respectively (n=3; p=.0013 at 2 dynes/cm2; p=.0175 at 5 dynes/cm2). These results suggest that enhancement of SS RBC adhesion in the presence of LAM is due to LAM interaction with an EC receptor, possibly dystroglycan. We then explored whether the adhesion enhancing effects of LAM could still be observed when the interaction between erythrocyte ICAM4 and EC αVβ3 was blocked. EC were pre-treated for 1 hr with 25 μg/mL of soluble recombinant (sr) ICAM4, in order to block αvβ3 binding sites. We found that pre-incubation of SS RBC in 10 μg/mL LAM failed to enhance RBC adhesion to sr-ICAM4 treated EC (p=.0276 at 2 dynes/cm2, n=3). Similar results were obtained with the 7E3 mAb directed against αVβ3. This suggests that blocking the interaction between ICAM4 and αVβ3 abolishes adhesion despite the presence of RBC-bound LAM. Therefore, we conclude that soluble LAM enhances SS RBC adhesion to EC, probably by providing secondary adhesive interactions that can be abrogated by anti-LAM as well as anti-dystroglycan antibodies. However, the contribution of LAM to SS RBC adhesion was negligible in the absence of interaction between ICAM4 and αVβ3. Thus, the mechanism by which LAM enhances SS RBC adhesion to EC appears to be a complex process, dependent on both the binding of RBC-bound LAM to EC as well as ICAM4 interaction with EC αVβ3.
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Stassinopoulos, Adonis, Mary Ann Schott, Grace M. Castro, and Lisa M. Turin. "Elimination of Immunoreactivity of Red Cells Treated with a Modified S-303 Pathogen Inactivation Process." Blood 104, no. 11 (November 16, 2004): 2703. http://dx.doi.org/10.1182/blood.v104.11.2703.2703.
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Abstract Background S-303 was developed to inactivate viruses, bacteria, protozoa, and leukocytes in red blood cell concentrates (RBC). S-303 is a modular FRALE compound (FRangible Anchor Linker Effector) designed to bind to nucleic acids with its Anchor, to react through its Effector, and to form cross-links. S-303 spontaneously decomposes to the non-reactive compound S-300 by hydrolysis of the Linker, to minimize protein adducts. Pathogen inactivation (PI) treatment utilized the co-addition of S-303 and unbuffered GSH to quench non-specific S-303 reactions. The treatment process was optimized to maintain RBC function and maximize PI. Pre-clinical dog and rabbit chronic transfusion studies with allogeneic S-303 RBC showed no detectable antibodies to S-303 RBC. In Phase 1 studies, transfusion of healthy subjects with autologous human S-303 RBC demonstrated acceptable post-transfusion recovery and life span. Repeated transfusion (n=5) of 28 healthy subjects with autologous S-303 RBC showed no detectable antibodies to S-303 RBC. In a Phase 3 trial evaluating chronic transfusion of allogeneic S-303 RBC to patients with thalassemia or sickle cell anemia, 2 of 26 patients developed low titer positive Indirect Antiglobulin Tests (IAT) to S-303 RBC (one of the 2 patients also had a direct reacting IgM agglutinin). For both patients Direct Antiglobulin Tests (DAT) were negative. However, pretreatment RBC from the same unit remained compatible. S-303-related Anchor derivatives inhibited the positive IAT. Following this observation, clinical trials of S-303 RBC were stopped, studies were initiated to define the immunologic response to S-303 RBC, and an improved S-303 treatment process was developed. Methods The original PI process utilized 200 μM S-303 and 2 mM unbuffered GSH. The process was modified to use 10-fold more neutralized GSH (20 mM) added to RBC 10 minutes prior to addition of S-303 (200μM). High titer anti-Anchor sera (RaS) were elicited by immunizing rabbits with a stable Anchor-KLH construct. A FACS assay to detect decoration of RBC with S-303 was developed using RaS and FITC goat anti-rabbit (GAR) IgG. IAT assays were performed with two methods: High titer RaS were tested with buffer gel cards (MTS), S-303 RBC suspended in low ionic strength solution (LISS) and GAR IgG. Reactive patient sera were tested with S-303 RBC and anti-IgG gel cards (MTS) Results S-303 RBC prepared with the original clinical process were positive for IAT by gel card for both the RaS (1:100) and for the patient sera (1:3). FACS analysis using RaS (1:100) with FITC GAR IgG (1:64) demonstrated a high level of labeling. Under the modified conditions (S-303m), S-303m RBC exhibited minimal labeling above background by FACS with RaS. Sera from the 2 patients with positive IAT against S-303 RBC were negative against S-303m RBC. In addition, high titer RaS were negative against S-303m RBC in IAT by gel card. Potent inactivation of bacteria in S303m RBC (S. epidermis, S. marcescens) and viruses (Vesicular stomatitis virus) was retained. Storage of S-303m RBC for 42 days exhibited hemolysis and K+ levels comparable to S303 RBC and higher ATP levels than S-303 RBC. Conclusions An improved PI process has been developed that significantly reduces RBC decoration by S-303 while maintaining PI and RBC in vitro function. The new process eliminated the positive IAT reactivity with sera from patients previously alloimmunized to S-303 RBC.
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Howard, R. J., D. C. Seeley, Vivien Kao, Margreat Wember, and R. Schauer. "Sialic acid analysis and tritium-labelling of sialoglycoproteins of mouse erythrocytes infected withPlasmodium berghei." Parasitology 92, no. 3 (June 1986): 545–57. http://dx.doi.org/10.1017/s0031182000065434.
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SUMMARYSchizont-infected red blood cells (SI-RBC) fromPlasmodium berghei-infected mice contain between 2 and 10 times as much sialic acid as uninfected RBC from the same blood (99–550 μg/1010RBC versus 33–65 μg/1010RBC). Total RBC samples from infected animals containing up to 63% ring- and trophozoite-infected cells had identical sialic acid contents to purified RBC samples (of < 3% parasitaemia) from the same blood (52–64 μg/1010RBC). We conclude that RBC containing immature parasites have the same sialic acid content as uninfected RBC from infected blood and that total cellular sialic acid increases during maturation to the schizont stage. Uninfected RBC from infected blood had 25–50% as much sialic acid as normal mouse RBC (33–65 μg/1010RBC versus 126 μg/1010RBC). There were no qualitative changes in RBC sialic acids, all RBC samples having 60–70%N-acetyl neuraminic acid, 30–40%N-acetyl-9-O-acetylneuraminic acid and 5–10%N-gly colylneuraminic acid. The quantitative changes we observed during infection must reflect changes in murine sialoglycoconjugates, as we have shown elsewhere that Plasmodia do not synthesize or contain sialic acids. Since the sialic acid composition of mouse serum glycoconjugates is quite different to that of the RBC fractions studied here, the quantitative data suggest that part of the sialic acids of the uninfected RBC has been transferred to SI-RBC. With higher molar ratios of periodate to substrate than generally used, we were able to radio-isotopically label normal murine sialoglycoproteins on SI-RBC and purified uninfected RBC from infected blood by the periodate/NaB3H4method. Several new proteins were then tritiated with SI-RBC but these proteins may be intracellular and could even lack sialie acid.
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Schroder, J. C., S. J. Hanna, R. L. Modini, A. L. Corrigan, S. M. Kreidenwies, A. M. Macdonald, K. J. Noone, L. M. Russell, W. R. Leaitch, and A. K. Bertram. "Size-resolved observations of refractory black carbon particles in cloud droplets at a marine boundary layer site." Atmospheric Chemistry and Physics 15, no. 3 (February 9, 2015): 1367–83. http://dx.doi.org/10.5194/acp-15-1367-2015.
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Abstract. Size-resolved observations of aerosol particles and cloud droplet residuals were studied at a marine boundary layer site (251 m a.m.s.l.) in La Jolla, San Diego, California, during 2012. A counterflow virtual impactor (CVI) was used as the inlet to sample cloud residuals while a total inlet was used to sample both cloud residuals and interstitial particles. Two cloud events totaling 10 h of in-cloud sampling were analyzed. Based on bulk aerosol particle concentrations, mass concentrations of refractory black carbon (rBC), and back trajectories, the two air masses sampled were classified as polluted marine air. Since the fraction of cloud droplets sampled by the CVI was less than 100%, the measured activated fractions of rBC should be considered as lower limits to the total fraction of rBC activated during the two cloud events. Size distributions of rBC and a coating analysis showed that sub-100 nm rBC cores with relatively thick coatings were incorporated into the cloud droplets (i.e., 95 nm rBC cores with median coating thicknesses of at least 65 nm were incorporated into the cloud droplets). Measurements also show that the coating volume fraction of rBC cores is relatively large for sub-100 nm rBC cores. For example, the median coating volume fraction of 95 nm rBC cores incorporated into cloud droplets was at least 0.9, a result that is consistent with κ-Köhler theory. Measurements of the total diameter of the rBC-containing particles (rBC core and coating) suggest that the total diameter of rBC-containing particles needed to be at least 165 nm to be incorporated into cloud droplets when the core rBC diameter is ≥ 85 nm. This result is consistent with previous work that has shown that particle diameter is important for activation of non-rBC particles. The activated fractions of rBC determined from the measurements ranged from 0.01 to 0.1 for core rBC diameters ranging from 70 to 220 nm. This type of data is useful for constraining models used for predicting rBC concentrations in the atmosphere.
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Barabino, GA, LV McIntire, SG Eskin, DA Sears, and M. Udden. "Endothelial cell interactions with sickle cell, sickle trait, mechanically injured, and normal erythrocytes under controlled flow." Blood 70, no. 1 (July 1, 1987): 152–57. http://dx.doi.org/10.1182/blood.v70.1.152.152.
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Abstract Increased adhesive forces between sickle erythrocytes and endothelial cells (EC) have been hypothesized to play a role in the initiation of vasoocclusion in sickle cell anemia. Erythrocyte/human umbilical vein EC interactions were studied under controlled flow conditions for normal (AA), homozygous sickle cell (SS), sickle cell trait (AS), mechanically injured normal, and “high-reticulocyte control” RBC by using video microscopy and digital image processing. The number of adherent RBC was determined at ten-minute intervals during a washout period. Results indicate that SS RBC were more adherent than AA RBC. Mechanically injured (sheared) AA RBC were also more adherent than control normal cells but less adherent than SS RBC. AS RBC did not differ significantly in their adhesive properties from normal RBC. Less- dense RBC were more adherent to EC than dense cells for normal, SS, and high-reticulocyte control RBC. The number of cells adherent at a given time during washout was a very strong function of wall shear rate. In addition, at all shear rates studied, the average velocity of individual SS RBC in the region near the EC surface was approximately half that of AA RBC at the same bulk volumetric flow rate through the flow chamber. These findings suggest that the increased adhesion of sickle RBC is at least partially related to the increased numbers of less-dense RBC present. Increased adherence of the less-dense cells to the EC lining vessel walls could contribute to microvascular occlusion by lengthening vascular transit times of other sickle cells.
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Barabino, GA, LV McIntire, SG Eskin, DA Sears, and M. Udden. "Endothelial cell interactions with sickle cell, sickle trait, mechanically injured, and normal erythrocytes under controlled flow." Blood 70, no. 1 (July 1, 1987): 152–57. http://dx.doi.org/10.1182/blood.v70.1.152.bloodjournal701152.
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Increased adhesive forces between sickle erythrocytes and endothelial cells (EC) have been hypothesized to play a role in the initiation of vasoocclusion in sickle cell anemia. Erythrocyte/human umbilical vein EC interactions were studied under controlled flow conditions for normal (AA), homozygous sickle cell (SS), sickle cell trait (AS), mechanically injured normal, and “high-reticulocyte control” RBC by using video microscopy and digital image processing. The number of adherent RBC was determined at ten-minute intervals during a washout period. Results indicate that SS RBC were more adherent than AA RBC. Mechanically injured (sheared) AA RBC were also more adherent than control normal cells but less adherent than SS RBC. AS RBC did not differ significantly in their adhesive properties from normal RBC. Less- dense RBC were more adherent to EC than dense cells for normal, SS, and high-reticulocyte control RBC. The number of cells adherent at a given time during washout was a very strong function of wall shear rate. In addition, at all shear rates studied, the average velocity of individual SS RBC in the region near the EC surface was approximately half that of AA RBC at the same bulk volumetric flow rate through the flow chamber. These findings suggest that the increased adhesion of sickle RBC is at least partially related to the increased numbers of less-dense RBC present. Increased adherence of the less-dense cells to the EC lining vessel walls could contribute to microvascular occlusion by lengthening vascular transit times of other sickle cells.
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Beerlage, Astrid, Joerg Halter, Sabine Gerull, Michael Medinger, Tanja Ruefli, Georg Stussi, Dominik Heim, et al. "Red Blood Cell Allo-Antibodies after Allogeneic Hematopoietic Stem Cell Transplantation." Blood 132, Supplement 1 (November 29, 2018): 2551. http://dx.doi.org/10.1182/blood-2018-99-116237.
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Abstract Introduction Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) may require red blood cell (RBC) transfusions. AB0 blood group barrier is the clinically most important RBC group in transfusion medicine and HSCT and patients always receive AB0 compatible RBC transfusions. Some patients however develop allo-antibodies against minor RBC antigens. To date there is only limited information about the specificity, immuniser and risk factors for the development of RBC allo-antibodies. In this retrospective single centre study we aimed to identify specificities, risk factors and clinical significance of the development of RBC allo-antibodies in HSCT patients. Methods In this study, we examined the occurrence of RBC alloantibodies in all consecutive patients treated with allogeneic HSCT at the University Hospital Basel between 1996 and 2017 receiving RBC transfusions. RBC and PLT components were all leukocyte depleted. As of 2012, all PLT components were pathogen reduced using the Intercept Blood system. AB0 and extended RBC typing of donor/ recipient pairs, the total number of RBC transfusions and their blood group typing (AB0 and extended RBC antigen typing when available) and the detection of RBC allo-antibodies were analysed and related to clinical outcome parameters. Results 1314 donor/ recipient pairs were analysed. 110 (13%) of patients developed RBC allo-antibodies, 66 patients (5%) prior to HSCT, and 103 (8%) developed the first RBC allo-antibody after HSCT. 8 patients (0.6%) with an RBC allo-antibody before HSCT developed further RBC allo-antibodies after HSCT. Most patients developed only one RBC allo-antibody but in single patients up to 6 antibodies could be detected. The median time between HSCT and the detection of the antibody was 61 days, corresponding to the phase of the most intensive immunosuppressive treatment. In 60% of the patients developing RBC allo-antibodies after HSCT, the antibody was neither directed against the stem cell donor nor the recipient. In these cases, immunization occurred most likely by RBC transfusion. Anti-Rhesus-group antibodies are the most common antibodies (57%). >10 RBC transfusions and the development of GvHD were risk factors for the development of antibodies. There was no significant difference in the occurrence of RBC allo-antibodies between donor type (related vs. unrelated), age or sex of the recipient. Only few patients showed significant haemolysis in the period of the detection of the antibody. The direct antiglobulin test (DAT) was positive in 66% of the cases. Haemolysis defined as an increase of bilirubin, LDH or reticulocytes and a haemoglobin drop of more than 10 g/l could only be reported in 6% of the cases with antibodies detected. The development of RBC allo-antibodies per se has no effect on the survival of patients (1y-survival 70±3% (without antibody) versus 68 ± 9%). However, evidence of haemolysis (even without drop of haemoglobin) in the context of allo-antibodies, is associated with significantly worse survival (1y- survival 75 ± 10% versus 42 ± 20%). Conclusion Allo-Antibodies after HSCT significantly contribute to the difficulties in transfusion management of these patients. Formation of RBC allo-antibodies is not frequent, but patients showing haemolysis after the development of an RBC allo-antibody show decreased survival. Most RBC allo-antibodies appear to be induced by RBC transfusion rather than by minor blood group mismatching between donor/ recipient pairs. Disclosures Heim: Novartis: Research Funding.
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George, Alex, Sebastian Koochaki, Suvarnamala Pushkaran, Narla Mohandas, Yi Zheng, Clinton H. Joiner, and Theodosia A. Kalfa. "Elevated Reactive Oxygen Species Production In Sickle Erythrocytes Is Modulated by a Pathway Involving Endothelin-1, TGFβ1, PKC, and Rac GTPases." Blood 116, no. 21 (November 19, 2010): 1634. http://dx.doi.org/10.1182/blood.v116.21.1634.1634.
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Abstract Abstract 1634 Chronic inflammation has emerged as an important pathogenic mechanism in sickle cell disease. One component of this inflammatory response is oxidant stress mediated by reactive oxygen species (ROS) generated by leukocytes, endothelial cells, plasma enzymes, and sickle erythrocytes. Sickle RBC ROS generation has been attributed to sickle hemoglobin auto-oxidation and Fenton chemistry reactions catalyzed by denatured heme moieties bound to the RBC membrane. The potential role of enzymatic mechanisms in ROS production in RBCs has not been fully explored. One candidate for enzyme-mediated ROS production in SS RBCs is NADPH oxidase, which is activated by the small Rho GTPases Rac1 and Rac2 in a variety of cell types (Hordijk P.L. Circ. Res. 2006; 98:453-462). Using flow cytometry with 5-(and 6-)-chloromethyl-2`,7`-dichlorodihydrofluorescein diacetate, a peroxide-sensitive probe, we determined that ROS generation is elevated in HbSS RBCs by 150–250% relative to that in HbAA RBCs. The NADPH oxidase NOX subunit homologs NOX1 and NOX5 were expressed in erythrocytes, and treatment of SS RBCs with the NADPH oxidase inhibitor diphenyleneiodonium (DPI) reduced ROS generation in a dose-dependent manner. Inhibition of PKC or Rac activity by the small molecule-inhibitors calphostin and NSC23766, respectively, also resulted in decreased ROS production in HbSS-RBCs in a dose-dependent fashion, while PKC activation by phorbol 12-myristate 13-acetate (PMA) increased ROS production. This effect of PMA could be inhibited by parallel treatment with NSC23766, implicating a PKC-Rac axis in erythrocyte ROS production. Enzymatic ROS production in sickle RBCs was dependent on the availability of free intracellular calcium, since it was inhibited by BAPTA-AM, a cell-permeable calcium chelator. Moreover, we found that ROS generation in SS RBCs was modulated by humoral factors. Incubation of AA RBCs in blood type-matched SS patient plasma resulted in increased ROS generation, while the incubation of SS RBCs in AA plasma decreased ROS production. Immunoblotting of AA and SS RBC membranes with specific antibodies revealed receptors for the inflammatory signaling molecules TGFβ1 and Endothelin-1 (ET-1), both of which are present in elevated levels in the plasma of patients with SCD. Incubation of AA RBCs with TGFβ1 or ET-1 resulted in increased Rac activation and increased ROS production in these treated cells. Our results suggest that ROS production in sickle RBCs is mediated by NADPH oxidase through Ca2+-regulated PKC and Rac signals, which in turn are modulated by plasma TGFβ1 and ET-1 via their receptors. ROS-mediated damage to RBC membrane components is known to contribute to erythrocyte deformation and fragility in sickle cell disease. Erythrocyte ROS generation, RBC lysis, vaso-occlusion, and the inflammatory response to tissue damage may therefore act in a positive feedback loop to drive the pathophysiology of sickle cell disease. These data may offer new therapeutic targets to counteract inflammation and RBC fragility and deformation in sickle cell disease. Disclosures: No relevant conflicts of interest to declare.