Browsing by Subject "Blood"
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Item Antibody Repertoires in Humanized NOD-scid-IL2Rγnull Mice and Human B Cells Reveals Human-Like Diversification and Tolerance Checkpoints in the Mouse(Public Library of Science, 2012-04-27) Ippolito, Gregory C.; Hoi, Kam Hon; Reddy, Sai T.; Carroll, Sean M.; Ge, Xin; Rogosch, Tobias; Zemlin, Michael; Shultz, Leonard D.; Ellington, Andrew D.; VanDenBerg, Carla L.; Georgiou, GeorgeImmunodeficient mice reconstituted with human hematopoietic stem cells enable the in vivo study of human hematopoiesis. In particular, NOD-scid-IL2Rγnull engrafted mice have been shown to have reasonable levels of T and B cell repopulation and can mount T-cell dependent responses; however, antigen-specific B-cell responses in this model are generally poor. We explored whether developmental defects in the immunoglobulin gene repertoire might be partly responsible for the low level of antibody responses in this model. Roche 454 sequencing was used to obtain over 685,000 reads from cDNA encoding immunoglobulin heavy (IGH) and light (IGK and IGL) genes isolated from immature, naïve, or total splenic B cells in engrafted NOD-scid-IL2Rγnull mice, and compared with over 940,000 reads from peripheral B cells of two healthy volunteers. We find that while naïve B-cell repertoires in humanized mice are chiefly indistinguishable from those in human blood B cells, and display highly correlated patterns of immunoglobulin gene segment use, the complementarity-determining region H3 (CDR-H3) repertoires are nevertheless extremely diverse and are specific for each individual. Despite this diversity, preferential DH-JH pairings repeatedly occur within the CDR-H3 interval that are strikingly similar across all repertoires examined, implying a genetic constraint imposed on repertoire generation. Moreover, CDR-H3 length, charged amino-acid content, and hydropathy are indistinguishable between humans and humanized mice, with no evidence of global autoimmune signatures. Importantly, however, a statistically greater usage of the inherently autoreactive IGHV4-34 and IGKV4-1 genes was observed in the newly formed immature B cells relative to naïve B or total splenic B cells in the humanized mice, a finding consistent with the deletion of autoreactive B cells in humans. Overall, our results provide evidence that key features of the primary repertoire are shaped by genetic factors intrinsic to human B cells and are principally unaltered by differences between mouse and human stromal microenvironments.Item Drawn in bloodlines : blood, pollution, identity, and vampires in Japanese society(2012-05) Miller, Benjamin Paul; Cather, Kirsten; Maclachlan, PatriciaThis thesis is an examination of the evolution of blood ideology, which is to say the use of blood as an organizing metaphor, in Japanese society. I begin with the development of blood as a substance of significant in the eighth century and trace its development into a metaphor for lineage in the Tokugawa period. I discuss in detail blood's conceptual and rhetorical utility throughout the post-Restoration period, first examining its role in establishing a national subjectivity in reference to both the native intellectual tradition of the National Learning and the foreign hegemony of race. I then discuss the rationalization of popular and national bloodlines under the auspices of the popular eugenics movement, and the National Eugenics Bill. Then, I discuss the racialization this conception of blood inflicted on the Tokugawa era Outcastes, and its persistent consequences. Through the incongruity of the Outcastes ability to "pass" despite popular expectations that their blood pollution was visibly demonstrative, I introduce the notion of blood anxiety. Next, I address the conceptual and rhetorical role blood played in articulating Japan's empire and imperial ambitions, focusing on the Theory of Common Descent and the Investigation of Global Policy with the Yamato Race as Nucleus report. I follow this discussion with a detailed examination of the postwar reconceptualization of national subjectivity, which demands native bloodlines and orthodox cultural expressions, and which effectively de-legitimized minority populations. As illustration of this point, I describe the impact of this new subjectivity on both the Zainichi and the Nikkeijin in lengthy case studies. Finally, I conclude this examination with a consideration of blood ideology's representation in popular culture. I argue that the subgenre of vampire media allegorizes many of the assumptions and anxieties surrounding blood that have developed since the Restoration, and demonstrates the imprint of blood ideology on contemporary society.Item A Microchip CD4 Counting Method for HIV Monitoring in Resource-Poor Settings(Public Library of Science, 2005-07-19) Rodriguez, William R; Christodoulides, Nicolaos; Floriano, Pierre N; Graham, Susan; Mohanty, Sanghamitra; Dixon, Meredith; Hsiang, Mina; Peter, Trevor; Zavahir, Shabnam; Thior, Ibou; Romanovicz, Dwight; Bernard, Bruce; Goodey, Adrian P; Walker, Bruce D; McDevitt, John TBackground -- More than 35 million people in developing countries are living with HIV infection. An enormous global effort is now underway to bring antiretroviral treatment to at least 3 million of those infected. While drug prices have dropped considerably, the cost and technical complexity of laboratory tests essential for the management of HIV disease, such as CD4 cell counts, remain prohibitive. New, simple, and affordable methods for measuring CD4 cells that can be implemented in resource-scarce settings are urgently needed. Methods and Findings -- Here we describe the development of a prototype for a simple, rapid, and affordable method for counting CD4 lymphocytes. Microliter volumes of blood without further sample preparation are stained with fluorescent antibodies, captured on a membrane within a miniaturized flow cell and imaged through microscope optics with the type of charge-coupled device developed for digital camera technology. An associated computer algorithm converts the raw digital image into absolute CD4 counts and CD4 percentages in real time. The accuracy of this prototype system was validated through testing in the United States and Botswana, and showed close agreement with standard flow cytometry (r = 0.95) over a range of absolute CD4 counts, and the ability to discriminate clinically relevant CD4 count thresholds with high sensitivity and specificity. Conclusion -- Advances in the adaptation of new technologies to biomedical detection systems, such as the one described here, promise to make complex diagnostics for HIV and other infectious diseases a practical global reality.