Colin Brown

University College London, Londinium, England, United Kingdom

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Publications (7)16.09 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: A serious constraint in the investigation of the human platelet antigen (HPA) status of potential neonatal alloimmune thrombocytopenia (NAIT) cases is the limited amount of DNA available from the neonates. Whole genome amplification (WGA) of these DNA samples could overcome this problem, but requires validation to ensure that it is sufficiently sensitive and accurate before its application in a clinical diagnostic setting. This study has validated the use of WGA DNA for HPA-1, -2, -3, -4, -5, and -15 genotyping with a panel of six controls and 13 previously HPA-typed samples from neonates together with parental DNA, using a 5'-nuclease (TaqMan) assay. WGA was performed using titrated amounts of genomic and WGA DNA template. HPA typing was performed on genomic and amplified DNA using a 5'-nuclease assay or polymerase chain reaction with sequence-specific primers (PCR-SSP). WGA DNA yields were in the suggested range of 400x to 800x, as assessed by spectrophotometry and gel analysis, and did not require further purification. HPA genotyping showed 100 percent concordance when using down to 5 ng of genomic or WGA template. This study demonstrates that WGA can be used for HPA typing using PCR-SSP or plate-based 5'-nuclease assays. The use of WGA for HPA typing in clinical samples from NAIT patients was validated with 100 percent concordance, and it is suggested that this technology can be used for other analyses where DNA amounts are limited.
    Transfusion 02/2009; 49(5):953-8. · 3.53 Impact Factor
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    ABSTRACT: In endemic areas, a small proportion of individuals infected with dengue virus develop dengue hemorrhagic fever (DHF) suggesting that there may be host specific resistance factors playing an important role. This work describes the frequency of HLA class I and class II alleles in patients with dengue and the relationship with the clinical manifestations of the disease. The analysis of the frequency of HLA specificities in the dengue patients revealed reduced frequencies of B*15, B*49, DRB1*02 and DRB1*03 and increased frequencies of B*57 and DRB1*15 compared with controls. When the patients were grouped and compared according to disease severity, an association with enhanced susceptibility to dengue fever (DF) in patients with B*57, an association with reduced susceptibility to DHF in patients with A*03, and an association with enhanced susceptibility to DHF in patients with B*40 was observed. Although the associations revealed in this study come from a very small case-control population and that after correction for multiple testing only the association with DRB1*15 is maintained, the data suggest that the HLA alleles can possibly play a role in the susceptibility and/or resistance to dengue virus infection and development of DHF.ResumenEn áreas endémicas, una pequeña proporción de individuos infectados con el virus dengue desarrollan la fiebre hemorrágica del dengue (FHD), sugiriendo la existencia de factores de resistencia que pudiesen estar jugando un papel importante en el huésped. Este trabajo describe la frecuencia de alelos HLA clase I y II en pacientes con dengue y su relación con las manifestaciones clínicas de la enfermedad. El análisis de la frecuencia de especificidades HLA en los pacientes con dengue mostró frecuencias disminuidas de los alelos B*15, B*49, DRB1*02 y DRB1*03 y frecuencias incrementadas de los alelos B*57 y DRB1*15 comparado con los controles. Cuando los pacientes fueron agrupados y comparados de acuerdo a la severidad de la enfermedad, se observó una susceptibilidad incrementada a la fiebre del dengue clásico (FD) en pacientes con B*57, una susceptibilidad disminuida al desarrollo de la FHD en pacientes A*03 y una susceptibilidad incrementada al desarrollo de la FHD en pacientes con B*40. Aunque las asociaciones observadas proceden de un estudio poblacional caso-control relativamente pequeño y que después de la corrección por múltiples comparaciones se mantuvo únicamente la asociación con DRB1*15, los datos confirman que posiblemente los alelos HLA pueden jugar un papel en la susceptibilidad y/o resistencia a la infección por virus dengue y al desarrollo de la FHD.
    Inmunología. 01/2009; 28(2):96–100.
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    ABSTRACT: Transfusion related acute lung injury (TRALI) is one of the complications of blood transfusion and can result in major morbidity or mortality. The diagnosis depends upon the application of strict clinical criteria defining acute lung injury (ALI) and a temporal relationship to blood transfusion. We present the clinical and immunogenetic findings of 96 suspected TRALI cases investigated between 1996 and 2004. During this time period the national haemovigilance scheme (UK) defined TRALI as a reaction occurring either during or within 24 h of blood transfusion. Using clinical, laboratory and post mortem evidence, 64/96 cases could be defined as TRALI in our series. Sensitive techniques were employed to screen for HLA class I, class II and granulocyte specific antibodies in donor serum. Donor derived antibodies were detected in 58/64 (90%) of cases. Recipient derived DNA or cells were not always available but incompatibility was confirmed by the presence of the cognate antigen on recipient leucocytes or by crossmatching in 47/64 (73%) of cases. Cases referred prior to 2001 were not tested for HLA class II antibodies. By applying strict clinical criteria and using sensitive techniques a white blood cell antibody mediated immunological pathophysiology can be implicated in the majority TRALI cases.
    Hematology (Amsterdam, Netherlands) 11/2007; 12(5):461-9. · 1.33 Impact Factor
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    ABSTRACT: Umbilical cord blood (UCB) is an important source of hematopoietic stem cells for transplantation. Although UCB is often collected from unrelated donors, directed umbilical cord blood (DCB) from sibling donors also provides an important source of UCB for transplantation. This report summarizes the experience in collection, testing, storage, and transplantation of DCB units by the National Blood Service for England and North Wales over 10 years. Eligibility for collection was based on an existing sibling suffering from a disease that may be treated by stem cell transplantation or a family history that could result in the birth of a sibling with a disease that could be treated by stem cell transplantation. Collections were made on the provision that the sibling's clinician was willing to financially support the collection and to take responsibility for medical review of the mother and potential recipient. Given the high investment in UCB banking and the introduction of new regulations and mandatory licensing under the European Union Tissues and Cells Directive and those proposed in the U.S., this report details the procedures that we have used for DCB donations, the outcome data where donations have been used for transplantation, and it provides some timely recommendations for best practices. Disclosure of potential conflicts of interest is found at the end of this article.
    Stem Cells 09/2007; 25(8):2087-93. · 7.70 Impact Factor
  • Nay Win, Colin Brown, Cristina Navarrete
    Transfusion 05/2003; 43(4):545-6. · 3.53 Impact Factor
  • Human Immunology - HUM IMMUNOL. 01/2003; 64(10).
  • Human Immunology - HUM IMMUNOL. 01/2003; 64(10).