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Genghis H Lopez, Eunike C McGowan, Kelli A McGrath, Maria E Abaca-Cleopas, Elizna M Schoeman, Glenda M Millard, Helen O'Brien, Yew-Wah Liew, Robert L Flower, Catherine A Hyland
BACKGROUND: Blood donors whose red blood cells (RBCs) exhibit a partial RhD phenotype, lacking some D epitopes, present as D+ in routine screening. Such phenotypes can exhibit low-frequency antigens (LFAs) of clinical significance. The aim of this study was to describe the serologic and genetic profile for a blood donor with an apparent D+ phenotype carrying a variant RHD gene where D Exons 5 and 6 are replaced by RHCE Exon (5-6). STUDY DESIGN AND METHODS: Anti-D monoclonal antibodies were used to characterize the presentation of RhD epitopes on the RBCs...
September 2016: Transfusion
Fengqin Zhu, Tian Chen, Yeqiong Zhang, Haixia Sun, Hong Cao, Jianxi Lu, Linshan Zhao, Gang Li
More than 170 million individuals worldwide are infected with hepatitis C virus (HCV), and up to an estimated 30% of chronically infected individuals will go on to develop progressive liver disease. Despite the recent advances in antiviral treatment of HCV infection, it remains a major public health problem. Thus, development of an effective vaccine is urgently required. In this study, we constructed novel adeno-associated virus (AAV) vectors expressing the full-length NS3 or NS3/4 protein of HCV genotype 1b...
2015: PloS One
Lauren E Mays, Lili Wang, Jianping Lin, Peter Bell, Alison Crawford, E John Wherry, James M Wilson
Following gene transfer of adeno-associated virus 2/8 (AAV2/8) to the muscle, C57BL/6 mice show long-term expression of a nuclear-targeted LacZ (nLacZ) transgene with minimal immune activation. Here, we show that pre-exposure to AAV2/8 can also induce tolerance to the more immunogenic AAV2/rh32.33 vector, preventing otherwise robust T-cell activation and allowing stable transgene expression. Depletion and adoptive transfer studies showed that a suppressive factor was not sufficient to account for AAV2/8-induced tolerance, whereas further characterization of the T-cell population showed upregulation of the exhaustion markers PD1, 2B4, and LAG3...
January 2014: Molecular Therapy: the Journal of the American Society of Gene Therapy
Xueling Li, Hong Cao, Qiang Wang, Biao Di, Ming Wang, Jianxi Lu, Lijie Pan, Li Yang, Mingzhu Mei, Xingfei Pan, Gang Li, Lili Wang
The envelope protein of dengue virus is involved in host cell attachment for entry and induction of protective immunity. Current efforts are focused on producing a tetravalent vaccine by mixing four monovalent vaccine components. In this work, we developed a genetic vaccine based on a novel adeno-associated viral (AAV) vector expressing the carboxy-terminal truncated envelope protein (79E) of dengue virus. The expression of the recombinant 79E protein in HEK 293 cells was confirmed by Western blot. Vectors packaged with novel AAV capsids (AAV2/8 or AAV2/rh32...
September 2012: Microbes and Infection
Waldemar Rastawicki, Stanisław Kałuzewski, Natalia Rokosz
The ELISA were performed on polystyrene microtiter plates (Nunc, MaxiSorp) coated with LPS (2a antigen) at the final concentration of 10 microg/ml. The antigen was extracted from Klebsiella rhinoscleromatis Rh32 by the trichloroacetic acid and separated by ethanol (Boivin method). The antibodies against the LPS were detected by ELISA in serum samples collected from 65 patients suspected in clinical investigation for rhinoscleroma in Poland from 1970 to 2009. Additionally, the specificity of the antigen was tested using serum sample of immunized rabbit and 30 sera of patients from control group, with high level of antibodies to different bacterial pathogens...
2010: Medycyna Doświadczalna i Mikrobiologia
Lauren E Mays, James M Wilson
BACKGROUND: Adeno-associated virus (AAV) is an ideal gene therapy vector and is non-immunogenic in many small animal models. The stable gene expression commonly seen in murine models does not necessarily translate to nonhuman primates and higher-order species, highlighting the need for a better understanding of immune activation to these vectors. One capsid variant, AAVrh32.33, demonstrates a unique phenotype in murine muscle, reminiscent of what is often seen in higher-order species...
December 2009: Journal of Gene Medicine
Lauren E Mays, Luk H Vandenberghe, Ru Xiao, Peter Bell, Hyun-Joo Nam, Mavis Agbandje-McKenna, James M Wilson
The immunological sequelae of adeno-associated virus (AAV)-mediated gene transfer in vivo is quite complex. In murine models, most AAV capsids are associated with minimal or dysfunctional T cell responses to antigenic transgene products. In this study we compared T cell activation against AAV2/8 and AAV2/rh32.33 vectors expressing nuclear-targeted LacZ (nLacZ), GFP, or firefly luciferase in murine skeletal muscle. We show that, unlike AAV8, AAVrh32.33 yields qualitatively and quantitatively robust T cell responses to both the capsid and transgene product...
May 15, 2009: Journal of Immunology: Official Journal of the American Association of Immunologists
Roberto Calcedo, Luk H Vandenberghe, Guangping Gao, Jianping Lin, James M Wilson
Recombinant adeno-associated viruses (AAVs) have unique gene-transfer properties that speak to their potential as carriers for gene therapy or vaccine applications. However, the presence of neutralizing antibodies to AAV as a result of previous exposure can significantly limit effective gene transfer. In this study, we obtained 888 human serum samples from healthy volunteers in 10 countries around the world. Samples were assayed for neutralizing antibodies to AAV1, AAV2, AAV7, and AAV8, as well as to a novel, structurally distinct AAV vector, rh32...
February 1, 2009: Journal of Infectious Diseases
M Winkler
No abstract text is available yet for this article.
1987: Immunohematology
Connie M Westhoff, Jill R Storry, Phyllis Walker, Christine Lomas-Francis, Marion E Reid
BACKGROUND: The red blood cells (RBCs) of a patient, known to have the probable DC(W)(e)/D-- phenotype, typed as D(W)- and Rh32- but were unexpectedly agglutinated by an anti-D(W)/Rh32 serum. The reactivity suggested that the RBCs carried a novel antigen and that the molecular background of this DC(W)(e)/D-- phenotype might be different from those reported. The purpose of this study was to determine the molecular basis of the Rh phenotype. STUDY DESIGN AND METHODS: Samples were obtained for family studies...
July 2004: Transfusion
Marion E Reid, Jill R Storry, Laima Sausais, Edith Tossas, Maria Rios, Kim Hue-Roye, Elizabeth S Gloster, Scott T Miller, Carl Wolf, Christine Lomas-Francis
BACKGROUND: Some low-incidence antigens in the Rh blood group system (e.g., VS, Rh32, FPTT) are expressed by more than one Rh complex. We describe a new low-incidence antigen that is present on RBCs with the partial D phenotypes, DIIIa or DOL, on RN RBCs and on one example of STEM+S RBCs. STUDY DESIGN AND METHODS: Standard hemagglutination testing was performed with two sera that agglutinated DIIIa RBCs on our in-house antibody identification panel. DNA-based assays were performed on selected samples...
October 2003: Transfusion
France Noizat-Pirenne, Pierre-Yves Le Pennec, Isabelle Mouro, Anne-Marie Rouzaud, Geneviève Juszczak, Michèle Roussel, Pierre Lauroua, Claire Krause, Philippe Rouger, Jean-Pierre Cartron, Hélène Ansart-Pirenne
BACKGROUND: D(C)(e) and D(C)e haplotypes may be encountered in the white population. Few data are available on the molecular backgrounds responsible for depressed expression of C and e. STUDY DESIGN AND METHODS: Individuals of white origin carrying a D(C)(e) genotype resulting in depressed expression of C or both C and e were subdivided into two categories based on the RBC reactivity with the human sera Mol and Hor, which contain antibodies against low-frequency antigens of the Rh (RH) system and other non-Rh low-frequency antigens...
May 2002: Transfusion
C H Huang, Y Chen, M E Reid, Y Okubo
BACKGROUND: In a Moroccan family, the partial D phenotype DBT is defined by an RHD-CE-D gene in which exons 5 to 7 of RHD were replaced by those of RHCE. In this study, the molecular basis and inheritance of DBT in a Japanese family are described. STUDY DESIGN AND METHODS: A Japanese proposita exhibiting the DBT phenotype was analyzed by serologic methods and molecular techniques. The RH transcripts of the proposita were sequenced and compared with those of normal donors...
November 1999: Transfusion
M E Reid, L Sausais, C G Zaroulis, K Mohandas, G Coghlan, C Lomas-Francis
BACKGROUND AND OBJECTIVES: Anti-DW is a rare specificity that detects an antigen on DVa red blood cells (RBCs). Some anti-DW contain an inseparable component that cross-reacts weakly with RBCs expressing the low-incidence Rh antigen Rh32. RH32 is expressed by RBCs with either the R=Nor the DBT phenotype. CASE REPORT: We describe here an antibody found in the serum of 2 patients that reacts equally well with RBCs possessing either DVa, R=N, or DBT phenotypes. The reactivity for DW and Rh32 antigens could not be separated by adsorption onto and elution from DW+Rh32- or from DW-Rh32+ RBCs...
1998: Vox Sanguinis
M Wallace, C Lomas-Francis, E Beckers, M Bruce, G Campbell, S Chatfield, N Nagao, Y Okubo, A Opalka, M Overbeeke, M Scott, D Voak
Eight probands are described with a D phenotype in which a partial D antigen is associated with Rh32 antigen; three of these probands were investigated because of the anti-D in their serum. The partial D lacks epD1-epD5 and epD9 and some epD6/7 and only expresses epD8 and other parts of epD6/7. The strength of the partial D antigen varies between unrelated DBT individuals. The Rh32 antigen of the DBT cells is weaker than that of D(C)(e) cells. Tests on DBT, DFR and R0Har cells with anti-epD6/7 split these monoclonal anti-D into eight patterns of reaction...
September 1997: Transfusion Medicine
C Rouillac, P Gane, J Cartron, P Y Le Pennec, J P Cartron, Y Colin
The RH blood group locus is composed of two sequence-related genes, RHD and RHCE, encoding the D, Cc, and Ee antigens in common Rh-positive phenotypes. In this report, we have analyzed the molecular basis of Rh antigens expression in weak D (Du) and RN donors, in whom there is a severe reduction of the D and C/e antigens, respectively. Genomic and transcript analysis of three unrelated low-grade weak D (Du) variants indicated that the very low expression of the D antigen is not the result of rearrangement or mutation in the coding sequence of the RHO gone...
June 1, 1996: Blood
A R Orlina, P J Unger, P A Lacey
A case of severe hemolytic disease of the newborn due to anti-Rh32 (R = N) is described. The infant recovered without any evidence of neurologic defects, following one exchange transfusion and phototherapy. Using commercial antisera, very weak reactions with anti-Rh2(C) and apparently normal reactions with anti-Rh5(e) were found in the family members carrying the R = N gene complex. However titrations with individual antisera revealed a weakened expression of the Rh5(e) antigen, albeit to a lesser extent than the Rh2(C)...
October 1984: Revue Française de Transfusion et Immuno-hématologie
P Y Le Pennec, P Rouger, M T Klein, M Kornprobst, Y Brossard, B Boizard, C Salmon
The red cells (RBCs) and sera from 18 RN/RN persons were studied. The study confirmed the Rh type D+C+E-c-e+Cw-, which is characterized by an increased expression of the D antigen; a markedly decreased expression of the C and e antigens; the presence of a low-incidence antigen, Rh32; and the absence of a high-incidence antigen, Rh46, which is associated with an epitope recognized by a murine monoclonal antibody (MR432). Other Rh antigens of low and high incidence were investigated, and the presence of Rh17 and Rh44 on the RBCs was confirmed...
November 1989: Transfusion
P Y Le Pennec, P Rouger, M T Klein, C Salmon
The red blood cells and sera from 21 RN/RN individuals were studied. The study confirmed the Rh type D+C+E-c-e+, CW-, characterized by an increased expression of the D antigen, a markedly decreased expression of the C and e antigens, the presence of a low incidence antigen (Rh32) and the absence of a high incidence antigen (Rh46) associated with an epitope recognized by a murine monoclonal antibody (MR 432). Four individuals exposed to Rh46 cells by pregnancy and/or transfusion had an anti-Rh46 antibody. This antibody gave positive reactions with all red blood cells of common and rare Rh phenotype except Rh null, D--, D...
September 1989: Revue Française de Transfusion et D'hémobiologie
P D Issitt, N S Gutgsell, P A Martin, J R Forguson
A family is described in which the mother made anti-Rh32 as a result of pregnancy; her second liveborn child had hemolytic disease of the newborn and required an exchange transfusion. In investigating the family, it was found that the father's RN gene did not make rhi and that his second Rh gene made normal amounts of c and e but a reduced amount of f. In the two children of the couple, who inherited a normal r or Ro from their mother, the paternally derived RN encoded an amount of rhi that could be detected in direct typing tests...
January 1991: Transfusion
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