Proefschrift--Amsterdam. / Summary in English. "Stellingen" leaf inserted. Includes bibliographical references (p. 121-122).

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.

Thesis (doctoral)--Lund University, 1992. / Added t.p. with thesis statement inserted.

Thesis (doctoral)--Lund University, 1992. / Added t.p. with thesis statement inserted.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1963. / Typescript. Vita. With this is bound: The J substance of cattle : VII. Production of immune anti-J in rabbits / A, G. Bednefoff, S.P. Datta and W.H. Stone. Reprinted from Journal of immunology, vol. 89, no. 3 (Sep. 1962), p. 408-413. Includes bibliographical references.

Os sistemas de grupos sanguíneos eritrocitários e plaquetários têm grande importância na medicina transfusional. Os serviços de hemoterapia têm investido cada vez mais em protocolos profiláticos à aloimunização contra antígenos eritrocitários, sendo o surgimento das plataformas de genotipagem em larga escala um avanço muito importante nesse âmbito. Este estudo tem por objetivo a padronização e a validação da plataforma OpenArray, por meio da técnica de microarranjos líquidos para genotipagem de antígenos eritrocitários e plaquetários em larga escala para futura implementação na rotina de doadores de sangue. Tal genotipagem permitirá a análise da frequência genotípica encontrada nos doadores de sangue da Fundação Pró-sangue/Hemocentro de São Paulo. Métodos: Foram analisadas 400 amostras de sangue total coletadas de doadores de sangue entre outubro e novembro de 2011. A genotipagem dos polimorfismos de troca de um nucleotídeo (Single nucleotide polymorphism - SNPs) que codifica os principais antígenos eritrocitários e plaquetários de relevância transfusional foi realizada utilizando a tecnologia OpenArray para as 400 amostras. Dessas, 242 também foram analisadas pela plataforma de genotipagem BLOODchip, em larga escala. Procedeu-se à comparação entre as técnicas em termos de acurácia, reprodutibilidade, número de resultados incorretos, número de resultados não amplificados ou indeterminados, possibilidade de customização dos ensaios, tempo total de duração da reação e número de amostras processadas por bateria. Foi também calculada a frequência genotípica dos SNPs e feita a comparação com dados prévios de literatura. Resultados e discussão: as amostras que foram testadas em ambas as plataformas apresentaram acurácia de 99,9% pela técnica OpenArray e 100% pela técnica BLOODchip, sendo os resultados discrepantes analisados por sequenciamento direto (técnica Sanger), confirmando os resultados obtidos pela genotipagem realizada no BLOODchip. Além disso, a técnica OpenArray apresentou maior número de resultados não amplificados ou indeterminados (no call), o que representa uma grande desvantagem do método, em decorrência da perda de insumos. Entretanto, a técnica OpenArray apresentou outras vantagens em relação ao BLOODchip, como a possibilidade de customização do ensaio, menor tempo para processamento das amostras, considerando a possibilidade de automatização total do processo e número de amostras testadas por bateria superior ao método comparativo. Os resultados da frequência alélica e genotípica dos polimorfismos analisados pelo método OpenArray foram comparados com as frequências encontradas na literatura, observando-se prevalência de doadores com perfil genotípico mais próximo da população caucasoide, porém, com a presença de alelos encontrados na população negra. Entretanto, esse perfil genotípico dos doadores predispõe à aloimunização de doentes falciformes, com perfil fenotípico negroide, reiterando a necessidade de transfusões com fenótipo compatível como profilaxia à aloimunização. / The erythrocyte and platelets blood groups are extremely important for transfusional medicine. Hemotherapy services have increasingly invested in prophylactic protocols for alloimmunization against erythrocyte antigens and the emergence of high-throuput genotyping platforms are a very prominent advance in this area. The aim of this study was to validate and to standardize the OpenArray platform, which is based on the microarray technolgy for the erythrocyte antigens genotyping on large scale, to further implementation in blood bank routine. This tecnique also allowed to asses the genotype frequencies in blood donors from Fundação Pró-sangue/Hemocentro de São Paulo. Method: We examined 400 blood donor samples collected from October to November 2011. The SNPs were detected using OpenArray technology. From the 400 blood samples, 272 were also tested using BLOODchip platform, to compare the results between both tecniques and evaluate the accuracy, reproducibility, number of incorrect results, failed samples, possibility of assays customization, duration of procedures, and number of samples that can be processed per batch. The genotype frequency of SNPs was also assesed and the findings were compared to previous studies. Results and Discussion: the OpenArray method showed accuracy of 99.9% and the BLOODchip of 100%. The inconsistent results were confirmed by Sanger Sequencing which showed that BLOODchip analysis was accurate. Besides, the OpenArray method showed a higher number of non-amplification or failed results (no call), which may be a major disavantage, due to reagent loss. However, the OpenArray platform showed other advantages when compared to BLOODchip such as the possibility of assay customization and full automation of the process, it was less time-consuming and allowed a higher number of samples per batch. The genotypic and allelic frequencies of each SNP tested in the blood donor population were calculated by the OpenArray method and the results were compared to reports from previous studies. We observed a prevalence of genotypic profiles closest to the Caucasian population, however, there was the presence of alleles found in the black population as well. This genotypic profile donors predispose to alloimmunization of sickle cell patients, with negroid phenotypic profile, reiterating the need for compatible phenotype transfusions and prophylaxis to alloimmunization.

Thesis (DPhil (Biomedical Science))--Cape Peninsula University of Technology, 2019. / Knowledge of population vulnerabilities to infectious diseases is key in managing many public health problems and for mapping appropriate strategies for prevention or intervention. A number of genes associated with resistance to HIV infection, such as the double deletion of 32 base pairs in the CCR5 gene , have been described and potentially account for lower HIV infections in some populations. The magnitude of the HIV pandemic in Sub-Saharan Africa warrants an investigation of the peculiar genetic factors that may have exacerbated its spread. An understanding of the genetic factors that are involved may aid in the development of specific strategies for prevention such as vaccine development, genetic counselling as well as gene therapy. The aim of this project was therefore to study the relationship between blood groups and HIV-infection in Botswana. HIV infection in Africa has not been linked to particular blood groups. The project was undertaken in two phases from December 2012 to December 2017. In the first phase, 346 subjects of known HIV status (negative or positive) were phenotyped for 23 erythrocyte antigens via standard scientific procedures. A Chi-square analysis was used to determine those antigens associated with increased or reduced risk of HIV infection. In the second phase, 120 samples were phenotyped for the protective blood group (RhC) and the risk-associated groups (Lub and P1). The samples were also characterized according to their laboratory results for viral load, lymphocyte sub-populations, complete blood count and blood chemistry, including total cholesterol. Some of the samples were also assessed for erythrocyte-associated viral RNA. Generally, the prevalence of the blood groups in the general population in Botswana did not differ with the known prevalence for Africans broadly. Three novel findings were established. First, the blood group Rh(C) was associated with a 40% risk reduction for HIV infection. Immunologically, carriage of the C antigen was associated with a more robust cell-mediated immunity as evidenced by enhanced cytotoxic T cell counts. Moreover, this antigen occurred with a frequency lower than 30% in all countries where HIV prevalence was high. There was therefore an inverse relationship between Rh(C) frequency and HIV prevalence. An examination of reports from previous studies revealed that the pattern was consistent in Africa, Europe, Asia, South America and Caribbean countries. It appears that the population frequency of this antigen explains, at least in part, a genetic factor that puts some African populations at higher risk for HIV infection. These results are novel in that Rh antigens have not been previously associated with immunity in any reports. Novel findings regarding the P1 blood group was its association with a double risk for HIV infection. While the plasma viral load did not differ between P1-positive and P1-negative subjects, P1-positive erythrocyte lysate yielded more viral RNA than P1-negative cells, implying more intracellular HIV RNA. Intra-erythrocytic viral RNA was detected even in patients with an undetectable plasma viral load. Glycosphingolipids, of which P1 is an example, have been documented to promote viral fusion to cells independent of CD4 receptors or other ligands. In at least one report, the presence of sphingolipids in lipid rafts was considered to be sufficient for viral fusion. The presence of viral RNA even in erythrocyte lysates corroborates this phenomenon and potentially explains the double risk of HIV infection observed. The occurrence of HIV RNA in erythrocyte lysate is a novel finding that suggests a new viral reservoir. Apparently, P1 has a high frequency among Africans and low in other races.

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Thesis (M.S.)--University of Michigan, 1986.

Thesis (Ph. D.)--Rijksuniversiteit te Leiden, 1964.