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Peng George Wang - One of the best experts on this subject based on the ideXlab platform.
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Production of human <B>BloodB> <B>GroupB> B antigen epitope conjugated protein in Escherichia coli and utilization of the adsorption <B>BloodB> <B>GroupB> B antiBody
Microbial Cell Factories, 2016Co-Authors: Wenjing Shang, Yafei Zhai, Zhongrui Ma, Gongjin Yang, Hou-cheng Zhang, Jiang Li, Yan Ding, Peng George WangAbstract:In the process of ABO-incompatiBle (ABOi) organ transplantation, removal of anti-A and/or B antiBodies from <B>BloodB> plasma is a promising method to overcome hyperacute rejection and allograft loss caused By the immune response Between anti-A and/or B antiBodies and the A and/or B antigens in the recipient. Although there are commercial columns to do this work, the application is still limited Because of the high production cost. In this study, the PglB glycosylation pathway from CampyloBacter jejuni was exploited to produce glycoprotein conjugated with Escherichia coli O86:B7 O-antigen, which Bears the <B>BloodB> <B>GroupB> B antigen epitope to aBsorB <B>BloodB> <B>GroupB> B antiBody in <B>BloodB>. The titers of <B>BloodB> <B>GroupB> B antiBody were reduced to a safe level without changing the clotting function of plasma after glycoprotein aBsorption of B antiBodies in the plasma. We developed a feasiBle strategy for the specific adsorption/removal of <B>BloodB> <B>GroupB> antiBodies. This method will Be useful in ABOi organ transplantation and universal <B>BloodB> transfusion.
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identification of a new α1 2 fucosyltransferase involved in o antigen Biosynthesis of escherichia coli o86 B7 and formation of h type 3 <B>BloodB> <B>GroupB> antigen
Biochemistry, 2008Co-Authors: Jie Shen, Jun Shao, Xianwei Liu, Christine S Chow, Peng George WangAbstract:Escherichia coli O86 possesses high human <B>BloodB> <B>GroupB> B activity Because of its O-antigen structure, sharing the human <B>BloodB> <B>GroupB> B epitope. In this study, the wBwK gene of E. coli O86:B7 was expressed and purified as the GST fusion protein. Thereafter, the wBwK gene was Biochemically identified to encode an α1,2-fucosyltransferase through radioactivity assays, as well as mass spectrometry and NMR spectroscopy. WBwK shows strict suBstrate specificity and only recognizes Galβ1,3GalNAcα-OR (T-antigen and derivatives) as the acceptor to generate the H-type 3 <B>BloodB> <B>GroupB> antigen. In contrast to other α1,2-fucosyltransferases, WBwK does not display activity toward the simple suBstrate Galβ-OMe. Comparison with another recently characterized α1,2-fucosyltransferase (WBsJ) of E. coli O128:B12 indicates a low level of amino acid identity Between them; however, they share a common acceptor suBstrate, Galβ1,3GalNAcα-OR. Domain swapping Between WBwK and WBsJ revealed that the smaller variaBle domains located in the...
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faBrication and application of carBohydrate microarray for analyzing human serum antiBody carBohydrate interaction
Applied Microbiology and Biotechnology, 2006Co-Authors: Gangliang Huang, Hanxing Zhang, Peng George WangAbstract:We introduced a strategy for preparing a carBohydrate microarray and demonstrated its utility for characterizing carBohydrate Binding and activities. We isolated the lipopolysaccharide (LPS) components from different Bacteria and explored the possiBility of immoBilizing these glycoconjugates on a high-Binding polystyrene plate. CarBohydrate-specific comBination was examined By oBserving the Binding of the <B>BloodB> <B>GroupB> B analogic LPS O-polysaccharide from Escherichia coli on the high-Binding polystyrene plate and anti-B from a Broad spectra antiBody of human <B>BloodB> serum. Strong Binding of antiBodies was screened, as it was evident that relative response value is two times higher than control. The hyBridization results indicated that this method is a reliaBle technique for the detection of human intestinal Bacteria and is expected to Be applied in diagnostics and seroepidemiology.
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escherichia coli o86 o antigen Biosynthetic gene cluster and stepwise enzymatic synthesis of human <B>BloodB> <B>GroupB> B antigen tetrasaccharide
Journal of the American Chemical Society, 2005Co-Authors: Jun Shao, Lizhi Zhu, Mamata Singh, Steven Lin, Kang Ryu, Jie Shen, Hongjie Guo, Qingjia Yao, And Allen C Bush, Peng George WangAbstract:Previous study showed that some Gram-negative Bacteria possess human <B>BloodB> <B>GroupB> activity. Among them, Escherichia coli O86 has high <B>BloodB> <B>GroupB> B activity and weak <B>BloodB> <B>GroupB> A activity. This is due to the cell surface O-antigen structure, which resemBles that of human <B>BloodB> <B>GroupB> B antigen. In this study, we sequenced the entire E. coli O86 antigen gene cluster and identified all the genes responsiBle for O-antigen Biosynthesis By sequence comparative analysis. The <B>BloodB> <B>GroupB> B-like antigen in E. coli O86 O-polysaccharide was synthesized By sequentially employing three glycosyltransferases identified in the gene cluster. More importantly, we identified a new Bacterial glycosyltransferase (WBnI) equivalent to human <B>BloodB> <B>GroupB> transferase B (GTB). The enzyme suBstrate specificity and stepwise enzymatic synthesis of <B>BloodB> <B>GroupB> B-like antigen revealed that the Biosynthetic pathway of B antigen is essentially the same in E. coli O86 as in humans. This new finding provides a model to study the specificity and structure relationship of <B>BloodB> <B>GroupB> transferases and supports the hypothesis of anti-<B>BloodB> <B>GroupB> antiBody production By Bacterial stimulation.
C F Bryan - One of the best experts on this subject based on the ideXlab platform.
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a2 a2 B to B renal transplantation past present and future directions
American Journal of Transplantation, 2016Co-Authors: C F Bryan, W S Cherikh, D A SesokpizziniAbstract:One component of the new national kidney allocation system (KAS) in the United States that was implemented on DecemBer 4, 2014, was the allocation of kidneys from A2 and A2 B (A, non-A1 and AB, non-A1 B) deceased donors into <B>BloodB> <B>GroupB> B candidates (A2 /A2 B → B). In so far as this is an important component of the new KAS that has the potential to further increase the access to transplantation for <B>BloodB> <B>GroupB> B candidates on the waiting list, most of whom are minority candidates, we will review the Body of evidence and historical perspectives that led to its inclusion in the new KAS. This review will also descriBe prospects for more widespread use of A2 /A2 B → B transplantation and a novel mechanism of humoral immunosuppression in B patients Before and after transplantation with an A2 or A2 B kidney.
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first report on the optn national variance allocation of a2 a2 B deceased donor kidneys to <B>BloodB> <B>GroupB> B increases minority transplantation
American Journal of Transplantation, 2015Co-Authors: Winfred W Williams, W S Cherikh, Carlton J Young, Pangyen Fan, Y Cheng, D A Distant, C F BryanAbstract:In 2002, the Organ Procurement and Transplantation Network (OPTN) Minority Affairs Committee (MAC) implemented a national, prospective, "variance of practice" to allow deceased donor, ABO <B>BloodB> <B>GroupB> incompatiBle, A2 antigen, kidney transplantation into <B>BloodB> <B>GroupB> B recipients; outcomes of this cohort were compared to ABO compatiBle recipients. The goal of the variance was to increase the numBer of transplants to B candidates without negatively impacting survival or compromising system equity. Only B recipients with low anti-A IgG titers (<1:8) were eligiBle to receive these kidneys. Across eight participating Donation Service Areas (DSA), there were 101 A2 /A2 B to B transplants through 12/31/11, of which the majority of the recipients (61%) were ethnic minorities. At 12, 24, and 36 months, Kaplan-Meier graft survival rates for the B recipients of A2 /A2 B kidneys were 95.0%, 90.6%, and 85.4%, respectively, comparaBle to outcomes for B recipients of B kidneys, 92.6%, 87.9%, and 82.5%, respectively (p-value = 0.48). Five DSAs increased the proportion of B transplants during 41 months postvariance, with a lesser proportional decrease in <B>BloodB> <B>GroupB> A transplants. The data support the proposition that this allocation algorithm may provide a roBust mechanism to increase access of <B>BloodB> <B>GroupB> B minority candidates to kidney transplantation.
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improving access to kidney transplantation without decreasing graft survival long term outcomes of <B>BloodB> <B>GroupB> a2 a2B deceased donor kidneys in B recipients
Transplantation, 2005Co-Authors: C F Bryan, Paul W Nelson, Charles F Shield, Daniel Murillo, Gilbert Ross, Franz T Winklhofer, Bradley A WaradyAbstract:Background. The transplantation of <B>BloodB> <B>GroupB> A 2 /A 2 B deceased donor kidneys into B recipients could improve access to transplantation for <B>BloodB> <B>GroupB> B recipients. However, this practice is controversial, and long-term data are lacking. This study analyzed the long-term outcomes of A 2 /A 2 B deceased donor kidneys transplanted into selected B recipients. Methods. We retrospectively assessed the outcomes (graft survival, transplant rates, and acute rejection) of deceased-donor kidneys using an allocation system that transplanted A 2 /A 2 B donors into B recipients with low anti-A <B>BloodB> <B>GroupB> antiBody titers Between 1994 and 2003. Patients received conventional immunosuppression without any specific antiBody reduction procedures. We further assessed the impact this system had on access to transplantation By <B>BloodB> <B>GroupB>. Results. Of 1,400 kidney transplants, 56 (4.0%) were A 2 /A 2 B to B recipients. The system reduced waiting time for all B recipients, even shorter than for <B>BloodB> <B>GroupB> A recipients (median waiting times of A 2 /A 2 B to B transplants=182 days vs. B to B transplants=297 days; and A to A=307 days). Although there was a trend toward increased acute rejection in A 2 /A 2 B to B transplants, the actuarial 7-year death censored graft survival was 72% for B recipients regardless of donor type. Conclusions. Transplanting A 2 /A 2 B deceased donor kidneys into B recipients leads to an equalization of waiting time Between <B>BloodB> <B>GroupB>s with similar patient and graft survival using conventional immunosuppression. This protocol could lead to more equal access to kidney transplantation in <B>BloodB> <B>GroupB> B recipients.
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increased access to transplantation for <B>BloodB> <B>GroupB> B cadaveric waiting list candidates By using a2 kidneys time for a new national system
American Journal of Transplantation, 2002Co-Authors: Paul W Nelson, Charles F Shield, Nicolas A Muruve, Daniel Murillo, Bradley A Warady, M I Aeder, C F BryanAbstract:Since <B>BloodB> <B>GroupB> B end-stage renal disease (ESRD) patients have less access to donor kidneys and a higher minority composition than any other <B>BloodB> <B>GroupB>, the United Network for Organ Sharing (UNOS) approved a voluntary national kidney allocation variance to allow organ procurement organizations (OPOs) to preferentially allocate A2 and A2B kidneys to B candidates. The Midwest Transplant Network OPO has preferentially allocated and transplanted kidneys from <B>BloodB> <B>GroupB> A2 and A2B donors to our <B>BloodB> <B>GroupB> B waiting list candidates for more than 7 years to increase access to kidneys for the B candidates on our OPO-wide waiting list. Between 1994 and 2000, a total of 121 <B>BloodB> <B>GroupB> B ESRD patients from our OPO-wide cadaveric kidney waiting list were transplanted. Thirty-four per cent (41/121) of those B candidates received either an A2 or an A2B kidney. One- and 5-year graft survival rates for the <B>GroupB> of B recipients of A2 or A2B kidneys were 91 and 85% (died with functioning graft [DWFG] censored), respectively, which were not significantly different from those of 91 and 80% for the 80 B recipients of B or O kidneys (Wilcoxon = 0.48; log-rank = 0.55). These data support the national trial for additional OPOs to voluntarily allocate A2 and A2B kidneys preferentially to B waiting list candidates, thus increasing access of <B>BloodB> <B>GroupB> B patients to renal transplantation.
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transplantation rate of the <B>BloodB> <B>GroupB> B waiting list is increased By using a2 and a2B kidneys
Transplantation, 1998Co-Authors: C F Bryan, Paul W Nelson, Charles F Shield, Bradley A Warady, M I Aeder, George E Pierce, Gilbert Ross, Alan M Luger, Thomas S Helling, J MartinezAbstract:Background. We have increased the transplantation rate for <B>BloodB> <B>GroupB> B cadaveric waiting list candidates By transplanting them with A 2 and A 2 B kidneys. Methods. Since 1991, five of the seven renal transplant programs in our organ procurement organization service area have preferentially transplanted <B>BloodB> <B>GroupB> A 2 and A 2 B cadaveric kidneys to B <B>BloodB> <B>GroupB> waiting list candidates with histories of low anti-A isoagglutinin titers. Results. Between 1991 and 1997, these five centers performed transplantations on 71 patients from the B cadaveric waiting list. Of those 71 patients, 29% (21 of 71) underwent transplantation with either A 2 (n=18) or A 2 B (n=3) cadaveric kidneys. In 1997 alone, 48% (11 of 23) of the B patient transplant recipients received A 2 or A 2 B kidneys. Conclusions. Transplantation of A 2 and A 2 B kidneys into B waiting list patients has successfully increased access of B patients to kidneys. Such an allocation algorithm implemented nationally may similarly increase the transplantation rate of B waiting list candidates.
Monica M. Palcic - One of the best experts on this subject based on the ideXlab platform.
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thermodynamic signature of suBstrates and suBstrate analogs Binding to human <B>BloodB> <B>GroupB> B galactosyltransferase from isothermal titration calorimetry experiments
Biopolymers, 2013Co-Authors: Nora Sindhuwinata, Eva Muñoz, Monica M. Palcic, Lena Lisbeth Grimm, Sophie Weisbach, Sabrina Zinn, Thomas PetersAbstract:It has Been oBserved earlier that human <B>BloodB> <B>GroupB> B galactosyltransferase (GTB) hydrolyzes its donor suBstrate UDP-Galactose (UDP-Gal) in the aBsence of acceptor suBstrate, and that this reaction is promoted By the presence of an acceptor suBstrate analog, α-L-Fuc-(1,2)-β-d-3-deoxy-Gal-O-octyl (3DD). This acceleration of enzymatic hydrolysis of UDP-Gal was traced Back to an increased affinity of GTB toward the donor suBstrate in the presence of 3DD. Herein, we present new thermodynamic data from isothermal titration calorimetry (ITC) on the Binding of donor and acceptor suBstrates and analogs to GTB. ITC data are supplemented By surface plasmon resonance and STD-NMR titration experiments. These new data validate mutual allosteric control of Binding of donor and acceptor suBstrates to GTB. It is of note that ITC experiments reveal significant differences in enthalpic and entropic contriButions to Binding of the natural donor suBstrate UDP-Gal, when compared with its analog UDP-Glucose (UDP-Glc). This may reflect different degrees of ordering of an internal loop (amino acids 176–194) and the C-terminus (amino acids 346–354), which close the Binding pocket on Binding of UDP-Gal or UDP-Glc. As Both ligands have rather similar dissociation constants KD and almost identical modes of Binding this finding is unexpected. Another surprising finding is that an acceptor analog, α-L-Fuc-(1,2)-β-d-3-amino-3-deoxy-Gal-O-octyl (3AD) as well as the constituent monosaccharide β-d-3-amino-3-deoxy-Gal-O-octyl (3AM) effectively inhiBit enzymatic hydrolysis of UDP-Gal. This is unexpected, too, Because in analogy to the effects of 3DD one would have predicted acceleration of enzymatic hydrolysis of UDP-Gal. It is difficult to explain these oBservations Based on structural data alone. Therefore, our results highlight that there is an urgent need of experimental studies into the dynamic properties of GTB. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 784–795, 2013.
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a nonionic inhiBitor with high specificity for the udp gal donor Binding site of human <B>BloodB> <B>GroupB> B galactosyltransferase design synthesis and characterization
Journal of Medicinal Chemistry, 2013Co-Authors: Katrin Schaefer, Nora Sindhuwinata, Thomas Peters, Monica M. Palcic, Thomas Hackl, Miriam P Kotzler, Felix C Niemeyer, Bernd MeyerAbstract:9-(5-O-α-d-Galactopyranosyl)-d-araBinityl-1,3,7-trihydropurine-2,6,8-trione (1) was designed and synthesized as a nonionic inhiBitor for the donor Binding site of human <B>BloodB> <B>GroupB> B galactosyltransferase (GTB). Enzymatic characterization showed 1 to Be extremely specific, as the highly homologous human N-acetylgalactosaminyltransferase (GTA) is not inhiBited. The Binding epitope of 1 demonstrates a high involvement of the araBinityl linker, whereas the galactose residue is only making contact to the protein via its C-2 site, which is very important for the discrimination Between galactose and N-acetylgalactosamine, the suBstrate transferred By GTA. The approach can generate highly specific glycosyltransferase inhiBitors.
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nmr Based exploration of the acceptor Binding site of human <B>BloodB> <B>GroupB> B galactosyltransferase with molecular fragments
Glycoconjugate Journal, 2010Co-Authors: Christoph Rademacher, Nora Sindhuwinata, Monica M. Palcic, Jens Landstrom, Goran Widmalm, Thomas PetersAbstract:A suBstantial Body of work has Been devoted to the design and synthesis of glycosyltransferase inhiBitors. A major oBstacle has always Been the demanding chemistry. Therefore, only few potent and selective inhiBitors are known to date. Glycosyltransferases possess two distinct Binding sites, one for the donor suBstrate, and one for the acceptor suBstrate. In many cases Binding to the donor site is well defined But data for acceptor Binding is sparse. In particular, acceptor Binding sites are often shallow, and in many cases the dimensions of the Binding pocket are not well defined. One approach to glycosyltransferase inhiBitors is to chemically link donor site and acceptor site ligands to generate high affinity Binders. Here, we descriBe a novel approach to identify acceptor site ligands from a fragment liBrary. We have chosen human <B>BloodB> <B>GroupB> B galactosyltransferase (GTB) as a Biologically important model target. The approach utilizes a comBination of STD NMR, spin-lock filtered NMR experiments and surface plasmon resonance measurements. Following this route we have identified molecular fragments from a fragment liBrary that Bind to the acceptor site of GTB with affinities of the order of a natural acceptor suBstrate. Unlike natural suBstrates these fragments allow for straightforward chemical modifications and, therefore will serve as scaffolds for potent GTB inhiBitors. In general, the approach descriBed is applicaBle to any glycosyltransferase and may assist in the development of novel glycosyltransferase inhiBitors.
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Binding of an acceptor suBstrate analog enhances the enzymatic activity of human <B>BloodB> <B>GroupB> B galactosyltransferase
Glycobiology, 2010Co-Authors: Nora Sindhuwinata, Eva Muñoz, Francisco Muñoz, Monica M. Palcic, Hannelore Peters, Thomas PetersAbstract:The hydrolysis of the donor suBstrate uridine diphosphate galactose (UDP-Gal) By human <B>BloodB> <B>GroupB> B galactosyltransferase (GTB) has Been followed By nuclear magnetic resonance in the presence and in the aBsence of an acceptor suBstrate analog. It is oBserved that the presence of the acceptor suBstrate analog promotes hydrolysis of UDP-Gal. SuBsequent analysis of the kinetics of the enzymatic hydrolysis suggests that this effect is due to an increased affinity of GTB for UDP-Gal in the presence of the acceptor analog. Isothermal titration calorimetry experiments suBstantiate this conclusion. As hydrolysis may Be understood as a glycosyl transfer reaction where water serves as universal acceptor, we suggest that in general the Binding of acceptor suBstrates to retaining glycosyltransferases modulates the rate of glycosyl transfer. In fact, this may point to a general mechanism used By retaining glycosyltransferases to discriminate acceptor suBstrates under physiological conditions.
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structural Basis for red cell phenotypic changes in newly identified naturally occurring suB<B>GroupB> mutants of the human <B>BloodB> <B>GroupB> B glycosyltransferase
Transfusion, 2007Co-Authors: Bahram Hosseinimaaf, Monica M. Palcic, Stephen V Evans, Mattias Persson, James A Letts, Elizabeth Smart, Pierreyves Lepennec, H Hustinx, Zhihon Zhao, Alan M ChesterAbstract:BACKGROUND: Four amino-acid-changing polymorphisms differentiate the <B>BloodB> <B>GroupB> A and B alleles. Multiple missense mutations are associated with weak expression of A and B antigens But the structural changes causing suB<B>GroupB>s have not Been studied. STUDY DESIGN AND METHODS: Individuals or families having serologically weak B antigen on their red cells were studied. Alleles were characterized By sequencing of exons 1 through 7 in the ABO gene. Single crystal X-ray diffraction, three-dimensional-structure molecular modeling, and enzyme kinetics showed the effects of the B allele mutations on the glycosyltransferases. RESULTS: Seven unrelated individuals with weak B phenotypes possessed seven different B alleles, five of which are new and result in suBstitution of highly conserved amino acids: M189V, I192T, F216I, D262N, and A268T. One of these (F216I) was due to a hyBrid allele resulting from recomBination Between B and O-1v alleles. The two other alleles were recently descriBed in other ethnic <B>GroupB>s and result in V175M and L232P. The first crystal-structure determination (A268T) of a suB<B>GroupB> glycosyltransferase and molecular modeling (F216I, D262N, L232P) indicated conformational changes in the enzyme that could explain the diminished enzyme activity. The effect of three mutations could not Be visualized since they occur in a disordered loop. CONCLUSION: The genetic Background for B-w phenotypes is very heterogeneous But usually arises through seemingly random missense mutations throughout the last ABO exon. The targeted amino acid residues, however, are well conserved during evolution. Based on analysis of the resulting structural changes in the glycosyltransferase, the mutations are likely to disrupt molecular Bonds of importance for enzymatic function. (Less)
Nathalie Ruvoenclouet - One of the best experts on this subject based on the ideXlab platform.
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influence of the comBined aBo fut2 and fut3 polymorphism on susceptiBility to norwalk virus attachment
The Journal of Infectious Diseases, 2005Co-Authors: Severine Marionneau, Nathalie Ruvoenclouet, Jacques Le Pendu, Nicolai V Bovin, Fabrice AiraudAbstract:4 Shemyakin Institute of Bioorganic Chemistry, Moscow, Russia The Binding of Norwalk virus (NV) recomBinant capsids was tested in a panel of saliva samples collected from 96 donors with different ABO, secretor, and Lewis phenotypes. As previously reported, Binding occurred specifically to saliva from secretors, regardless of their Lewis phenotype status. <B>BloodB> <B>GroupB> B saliva was poorly recognized, whereas Binding to <B>BloodB> <B>GroupB> O saliva was higher and Binding to <B>BloodB> <B>GroupB> A saliva was highest. Transfection of either <B>BloodB> <B>GroupB> A or B enzyme into H epitope-expressing cells showed that masking of H epitopes By the A and B antigens Blocked the attachment of NV capsids. The high level of Binding to <B>BloodB> <B>GroupB> A secretor saliva could Be explained By an optimal H type 1 ligand density, which was lower than that in <B>BloodB> <B>GroupB> O saliva and much higher than that in <B>BloodB> <B>GroupB> B saliva. Indeed, despite a higher ligand density, saliva from homozygotes with 2 functional FUT2 alleles was less strongly recognized than saliva from heterozygotes with 1 functional and 1 inactivated FUT2 allele. Partial fucosidase treatment of duodenal tissue sections and Binding to a synthetic proBe with varying densities of H type 1 trisaccharide indicated that optimal attachment occurred at medium ligand density.
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influence of the comBined aBo fut2 and fut3 polymorphism on susceptiBility to norwalk virus attachment
The Journal of Infectious Diseases, 2005Co-Authors: Severine Marionneau, Nathalie Ruvoenclouet, Jacques Le Pendu, Nicolai V Bovin, Fabrice AiraudAbstract:The Binding of Norwalk virus (NV) recomBinant capsids was tested in a panel of saliva samples collected from 96 donors with different ABO, secretor, and Lewis phenotypes. As previously reported, Binding occurred specifically to saliva from secretors, regardless of their Lewis phenotype status. <B>BloodB> <B>GroupB> B saliva was poorly recognized, whereas Binding to <B>BloodB> <B>GroupB> O saliva was higher and Binding to <B>BloodB> <B>GroupB> A saliva was highest. Transfection of either <B>BloodB> <B>GroupB> A or B enzyme into H epitope-expressing cells showed that masking of H epitopes By the A and B antigens Blocked the attachment of NV capsids. The high level of Binding to <B>BloodB> <B>GroupB> A secretor saliva could Be explained By an optimal H type 1 ligand density, which was lower than that in <B>BloodB> <B>GroupB> O saliva and much higher than that in <B>BloodB> <B>GroupB> B saliva. Indeed, despite a higher ligand density, saliva from homozygotes with 2 functional FUT2 alleles was less strongly recognized than saliva from heterozygotes with 1 functional and 1 inactivated FUT2 allele. Partial fucosidase treatment of duodenal tissue sections and Binding to a synthetic proBe with varying densities of H type 1 trisaccharide indicated that optimal attachment occurred at medium ligand density.
Bradley A Warady - One of the best experts on this subject based on the ideXlab platform.
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improving access to kidney transplantation without decreasing graft survival long term outcomes of <B>BloodB> <B>GroupB> a2 a2B deceased donor kidneys in B recipients
Transplantation, 2005Co-Authors: C F Bryan, Paul W Nelson, Charles F Shield, Daniel Murillo, Gilbert Ross, Franz T Winklhofer, Bradley A WaradyAbstract:Background. The transplantation of <B>BloodB> <B>GroupB> A 2 /A 2 B deceased donor kidneys into B recipients could improve access to transplantation for <B>BloodB> <B>GroupB> B recipients. However, this practice is controversial, and long-term data are lacking. This study analyzed the long-term outcomes of A 2 /A 2 B deceased donor kidneys transplanted into selected B recipients. Methods. We retrospectively assessed the outcomes (graft survival, transplant rates, and acute rejection) of deceased-donor kidneys using an allocation system that transplanted A 2 /A 2 B donors into B recipients with low anti-A <B>BloodB> <B>GroupB> antiBody titers Between 1994 and 2003. Patients received conventional immunosuppression without any specific antiBody reduction procedures. We further assessed the impact this system had on access to transplantation By <B>BloodB> <B>GroupB>. Results. Of 1,400 kidney transplants, 56 (4.0%) were A 2 /A 2 B to B recipients. The system reduced waiting time for all B recipients, even shorter than for <B>BloodB> <B>GroupB> A recipients (median waiting times of A 2 /A 2 B to B transplants=182 days vs. B to B transplants=297 days; and A to A=307 days). Although there was a trend toward increased acute rejection in A 2 /A 2 B to B transplants, the actuarial 7-year death censored graft survival was 72% for B recipients regardless of donor type. Conclusions. Transplanting A 2 /A 2 B deceased donor kidneys into B recipients leads to an equalization of waiting time Between <B>BloodB> <B>GroupB>s with similar patient and graft survival using conventional immunosuppression. This protocol could lead to more equal access to kidney transplantation in <B>BloodB> <B>GroupB> B recipients.
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increased access to transplantation for <B>BloodB> <B>GroupB> B cadaveric waiting list candidates By using a2 kidneys time for a new national system
American Journal of Transplantation, 2002Co-Authors: Paul W Nelson, Charles F Shield, Nicolas A Muruve, Daniel Murillo, Bradley A Warady, M I Aeder, C F BryanAbstract:Since <B>BloodB> <B>GroupB> B end-stage renal disease (ESRD) patients have less access to donor kidneys and a higher minority composition than any other <B>BloodB> <B>GroupB>, the United Network for Organ Sharing (UNOS) approved a voluntary national kidney allocation variance to allow organ procurement organizations (OPOs) to preferentially allocate A2 and A2B kidneys to B candidates. The Midwest Transplant Network OPO has preferentially allocated and transplanted kidneys from <B>BloodB> <B>GroupB> A2 and A2B donors to our <B>BloodB> <B>GroupB> B waiting list candidates for more than 7 years to increase access to kidneys for the B candidates on our OPO-wide waiting list. Between 1994 and 2000, a total of 121 <B>BloodB> <B>GroupB> B ESRD patients from our OPO-wide cadaveric kidney waiting list were transplanted. Thirty-four per cent (41/121) of those B candidates received either an A2 or an A2B kidney. One- and 5-year graft survival rates for the <B>GroupB> of B recipients of A2 or A2B kidneys were 91 and 85% (died with functioning graft [DWFG] censored), respectively, which were not significantly different from those of 91 and 80% for the 80 B recipients of B or O kidneys (Wilcoxon = 0.48; log-rank = 0.55). These data support the national trial for additional OPOs to voluntarily allocate A2 and A2B kidneys preferentially to B waiting list candidates, thus increasing access of <B>BloodB> <B>GroupB> B patients to renal transplantation.
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transplantation rate of the <B>BloodB> <B>GroupB> B waiting list is increased By using a2 and a2B kidneys
Transplantation, 1998Co-Authors: C F Bryan, Paul W Nelson, Charles F Shield, Bradley A Warady, M I Aeder, George E Pierce, Gilbert Ross, Alan M Luger, Thomas S Helling, J MartinezAbstract:Background. We have increased the transplantation rate for <B>BloodB> <B>GroupB> B cadaveric waiting list candidates By transplanting them with A 2 and A 2 B kidneys. Methods. Since 1991, five of the seven renal transplant programs in our organ procurement organization service area have preferentially transplanted <B>BloodB> <B>GroupB> A 2 and A 2 B cadaveric kidneys to B <B>BloodB> <B>GroupB> waiting list candidates with histories of low anti-A isoagglutinin titers. Results. Between 1991 and 1997, these five centers performed transplantations on 71 patients from the B cadaveric waiting list. Of those 71 patients, 29% (21 of 71) underwent transplantation with either A 2 (n=18) or A 2 B (n=3) cadaveric kidneys. In 1997 alone, 48% (11 of 23) of the B patient transplant recipients received A 2 or A 2 B kidneys. Conclusions. Transplantation of A 2 and A 2 B kidneys into B waiting list patients has successfully increased access of B patients to kidneys. Such an allocation algorithm implemented nationally may similarly increase the transplantation rate of B waiting list candidates.
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aBo mismatched renal transplantation in children a report of the north american pediatric renal transplant cooperative study naprtcs and the midwest organ Bank moB
Pediatric Transplantation, 1998Co-Authors: A V Osorio, C F Bryan, E K Sullivan, C F Shield, Bradley A WaradyAbstract:Successful ABO-mismatched renal transplantation (RT) (<B>BloodB> <B>GroupB> A2 donor to <B>BloodB> <B>GroupB> B or O recipient) has occurred in adults in the setting of a low titer ( or =1 acute rejection episodes, the initial episode occurring within the first 31 d post-transplant in 7 of them. Five grafts (45.4%) failed secondary to vascular thromBosis (1), acute rejection (2) and chronic rejection (2). The remaining grafts (54.5%) all functioned for >1000 d (range: 1023-3746 d). The pre-transplant anti-A titer was determined in 6 pts; in 4 it was low (2) and in 2 it was high (8). Graft survival in all But one of these patients (whose titer was 8 and who suffered a non-rejection-related vascular thromBosis) was > or =2 yr. In summary, ABO-mismatched RT in pediatric patients is an uncommon practice. However, the adult experience and our preliminary pediatric experience suggests that evaluation of recipient isoagglutinin levels in this setting may Be helpful in the selection of donor/recipient pairs in whom mismatched transplantation can Be successful.