Thesis (Ph.D.)--University of Texas at Dallas, 2008. / Includes vita. Includes bibliographical references.

Thesis (Ph.D.)--Drexel University, 2008. / Includes abstract and vita. Includes bibliographical references (leaves 152-157).

Thesis (Ph.D.)--Drexel University, 2009. / Includes abstract and vita. Includes bibliographical references (leaves 98-101).

Thesis (PhD)--Montana State University--Bozeman, 2009. / Typescript. Chairperson, Graduate Committee: C. Martin Lawrence. Includes bibliographical references (leaves 101-112).

Thesis (Ph. D.)--Drexel University, 2004. / Includes abstract and vita. Includes bibliographical references (leaves 106-117).

Thesis (M.S.)--West Virginia University, 2004. / Title from document title page. Document formatted into pages; contains v, 54 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 34-36).

Thesis (M.S.)--University of Wisconsin--Madison, 1947. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaf 45).

Ανοσολογική διαταραχή η οποία οδηγεί σε καταστολή της αιμοποίησης μέσω υπερπαραγωγής μυελοκατασταλτικών κυτταροκινών από ενεργοποιημένα Τ λεμφοκύτταρα θεωρείται ότι παίζει καθοριστικό ρόλο στην παθογένεια της επίκτητης απλαστικής αναιμίας (ΑΑ). Μελετήσαμε αρρώστους με επίκτητη απλαστική αναιμία ως προς τα ανοσοφαινοτυπικά χαρακτηριστικά των λεμφοκυττάρων του περιφερικού αίματος και του μυελού των οστών με τη μέθοδο της κυτταρομετρίας ροής. Λεμφοπενία, κυρίως των CD4+ T λεμφοκυττάρων, παρατηρήθηκε σε ασθενείς με ενεργό νόσο όσο και σε ασθενείς σε αιματολογική ύφεση σε σχέση με φυσιολογικούς μάρτυρες. Επίσης, στατιστικά υψηλότερο ποσοστό ενεργοποιημένων CD4+ και CD8+ λεμφοκυττάρων ανιχνεύθηκε τόσο σε ασθενείς με ενεργό νόσο όσο και σε ασθενείς που βρίσκονται σε ύφεση. Επίσης, ανιχνεύθηκαν οι ενδοκυτταροπλασματικές κυτταροκίνες της τύπου-1 (IFNγ, IL-2) και τύπου-2 (IL-4, IL-10) ανοσολογικής απόκρισης στα CD4+ και CD8+ λεμφοκύτταρα πριν και μετά την in vitro ενεργοποίηση σε ασθενείς με ΑΑ καθώς και σε φυσιολογικούς μάρτυρες. Ασθενείς νεοδιαγνωσθέντες ή ανθεκτικοί (ενεργός νόσος) είχαν στην χωρίς ενεργοποίηση μελέτη, στατιστικά μεγαλύτερο ποσοστό CD4+ και CD8+ που παρήγαγαν IFNγ και IL-2, ενώ η παραγωγή IL-4 και IL-10 δεν διέφερε από τους φυσιολογικούς μάρτυρες. Οι ασθενείς σε αιματολογική ύφεση, παρουσίαζαν επίσης αυξημένο ποσοστό CD4+ και CD8+ λεμφοκυττάρων που παρήγαγε IFN-γ, ενώ ήταν επίσης αυξημένο των ποσοστό των CD4+ και CD8+ κυττάρων που παρήγαγαν IL-4 και IL-10. Σε ασθενείς με ενεργό νόσο, η ισορροπία μεταξύ των τύπου-1/τύπου-2 κυτταροκινών, όπως αυτή εκφράζεται από τον λόγο IFNγ/IL-4, δείχνει πόλωση προς μια τύπου-1 ανοσολογική απόκριση. Σε ασθενείς σε αιματολογική ύφεση, παρόλη την επίσης παρατηρούμενη αυξημένη παραγωγή INF-γ από τα λεμφοκύτταρα στην χωρίς διέγερση μελέτη, η ισορροπία του λόγου τύπου-1/τύπου-2 επανέρχεται στα επίπεδα των φυσιολογικών μαρτύρων. Η πόλωση των CD4+ κυττάρων προς μια τύπου-1 ανοσολογική απόκριση μπορεί να είναι απαραίτητη για την παθογένεια της ΑΑ, οδηγώντας σε ενεργοποίηση των κυτταροτοξικών CD8+ κυττάρων και στην καταστροφή των αρχέγονων αιμοποιητικών κυττάρων. Σ’ ένα μικρό ποσοστό ασθενών με ΑΑ σε αιματολογική ύφεση μετά από ανοσοκατασταλτική θεραπεία, αναπτύσεται δευτεροπαθής κλωνική διαταραχή, όπως παροξυντική νυχτερινή αιμοσφαιρινουρία ή καρυοτυπική ανωμαλία. Οι ασθενείς με φυσιολογικό καρυότυπο παρουσίαζαν μια πιο έντονη ανοσολογική απόκριση τύπου 1 σε σύγκριση με τους φυσιολογικούς μάρτυρες και τους ασθενείς με κλωνική διαταραχή. Πιθανά μια εμμένουσα και διαρκής ανοσολογική αντίδραση τύπου 1 σε ένα ποσοστό ασθενών με ΑΑ σε ύφεση μετά από επιτυχή ανοσοθεραπεία ενισχύει την ανοσολογική επιτήρηση και προστατεύει αυτούς τους ασθενείς από την εμφάνιση ενός παθολογικού κλώνου. Αρκετές μελέτες έχουν δείξει αυξημένη απόπτωση στο μυελό των ασθενών με ΑΑ και έχουν πιθανολογήσει πως παίζει σημαντικό ρόλο στην πρόκληση της μυελικής απλασίας. Η ρύθμιση της αυξημένης απόπτωσης των αρχέγονων προγονικών αιμοποιητικών κυττάρων στην απλαστική αναιμία (ΑΑ) παραμένει ασαφής. Η παρουσία της απόπτωσης στο μυελό των οστών διερευνήθηκε με ανάλυση κυτταρομετρίας ροής με ποσοτικό προσδιορισμό της επιφανειακής έκφρασης του Fas υποδοχέα και των αποπτωτικών Annexin+/PI- BMMNC και CD34+ κυττάρων. Παρατηρήθηκε σημαντική αύξηση του Fas υποδοχέα (MAb/cell) στα CD34+ κύτταρα τόσο στους ασθενείς με ενεργό νόσο όσο και σ’ αυτούς σε ύφεση, σε σύγκριση με τους μάρτυρες. Ο αριθμός των CD34+/Annexin+/PI- κυττάρων είναι σημαντικά αυξημένος τόσο σε ασθενείς με ενεργό νόσο όσο και σε ασθενείς σε ύφεση, σε σύγκριση με τους μάρτυρες. Συμπερασματικά, μια ανοσολογική αντίδραση τύπου-1 κυριαρχεί στα λεμφοκύτταρα των ασθενών με απλαστική αναιμία, ιδίως σ’ αυτούς με ενεργό νόσο. Η αντίδραση αυτή συσχετίζεται θετικά με το ποσοστό απόπτωσης των CD34+ κυττάρων του μυελού των οστών. / Immune dysfunction, which leads to suppression of haemopoiesis through cytokines secreted by activated T lymphocytes, is considered to play a key role in the pathogenesis of acquired aplastic anaemia (AAA). The peripheral blood lymphocyte subpopulations were calculated by flow cytometry. Lymphopenia, mainly of CD4+ subset, was observed in both patients with active disease and in patients in remission. There was also a significant increase in activated CD4+ and CD8+ T cells in active disease but also in remission. We also studied the intracytoplasmic cytokines of type-1 and type-2 immune responses in CD4+ and CD8+ cells before and after in vitro activation in AAA patients and controls. Untreated or refractory patients had a significantly higher proportion of unstimulated CD4+ and CD8+ cells that produced IFNg and IL-2, while the production of IL-4 and IL-10 did not differ from that of controls. In patients in remission, the proportion of IFN-γ-producing unstimulated CD4+ and CD8+ cells was also increased with a parallel increased production of IL-4 and IL-10. In newly diagnosed or refractory patients, the balance of type-1 /type-2 cytokines, as it has been shown by the ratio of IFNγ/IL-4, shows a polarization towards type-1 response. In patients in remission, despite the increased INF-γ production by unstimulated T cells, the balance returns to that of controls. Polarization of CD4+ cells towards a type-1 response may be essential for the pathogenesis of AAA, leading to activation of cytotoxic CD8+ cells and stem cell destruction. A small proportion of patients with AAA in hematologic remission after immunosuppressive therapy develop a secondary clonal abnormality (e.g. paroxysmal nocturnal hemoglobinuria, karyotypic abnormality). A significantly higher proportion of unstimulated CD4+ cells produced IL-2 and IFNγ in patients with a normal karyotype. The balance between IFNγ/IL-4 is normalized in unstimulated CD4+ cells of AA patients with an abnormal clone, whereas in patients with normal karyotype this ratio remains significantly higher compared to the group with clonal abnormality. According to the above data, the possibility exists that an ongoing type-1 reaction, especially in CD4+ cells in a cohort of AA patients after successful immunotherapy “protects” these patients from the emergence of an abnormal clone. Increased apoptosis is a possible pathogenetic mechanism for the damage of hematopoietic stem cells in aplastic anemia (AA), but the regulation of apoptotic machinery remains unclear. We examined the presence of apoptosis in the marrow cells with flow cytometry (FC) analysis. Bone marrow was obtained from aplastic anemia patients and healthy volunteers of similar age. The AA patients had active disease (untreated or refractory) or complete or partial hematological remission long after immunosuppressive therapy was discontinuated. Two-or three-color FC analysis was used for quantitative measurement of cell surface expression of Apo-1/Fas receptor in CD34+ cells and Annexin+/PI- total BMMNC and CD34+ cells. Two-color FC analysis revealed a significant increase in Fas expression CD34+ in active disease patients as well as in patients in remission compared to controls. CD34+/Annexin+/PI- cells are significantly increased in both active disease and in remission patients compared to controls. In conclusion, a type-1 immune response dominates in aplastic anemia patients, especially in patients with active disease. This polarization of lymphocytes correlates with increased apoptosis in CD34+ bone marrow cells.

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Ciências da Saúde, 2006. / Submitted by Thaíza da Silva Santos (thaiza28@hotmail.com) on 2009-09-25T01:11:12Z No. of bitstreams: 1 2006_Maria das Graças Guedes de França.pdf: 2027149 bytes, checksum: d7d89e0c4592a10c8e84789abc692bf3 (MD5) / Approved for entry into archive by Gomes Neide(nagomes2005@gmail.com) on 2010-07-13T20:28:29Z (GMT) No. of bitstreams: 1 2006_Maria das Graças Guedes de França.pdf: 2027149 bytes, checksum: d7d89e0c4592a10c8e84789abc692bf3 (MD5) / Made available in DSpace on 2010-07-13T20:28:29Z (GMT). No. of bitstreams: 1 2006_Maria das Graças Guedes de França.pdf: 2027149 bytes, checksum: d7d89e0c4592a10c8e84789abc692bf3 (MD5) Previous issue date: 2006 / As anemias nutricionais resultam da carência simples ou combinada de nutrientes como ferro, o acido fólico e a vitamina B12, podendo também ser causadas por outros fatores mais raros como a deficiência de piridoxina, riboflavina e proteína. Apesar de muitos nutrientes e co-fatores estarem envolvidos na manutenção da síntese normal de hemoglobina, a deficiência de ferro é a causa mais comum de anemia carencial no mundo, constituindo-se a carência nutricional de maior abrangência, afetando principalmente as crianças e as gestantes dos países em desenvolvimento. Com a realização deste trabalho, objetivou-se conhecer a prevalência de anemia ferropriva em adolescentes moradores da comunidade “Vila Princesa” – Lixão da cidade de Porto Velho – RO. A metodologia utilizada neste trabalho foi do tipo transversal descritivo e envolveu 48 adolescentes na faixa etária de 12 a 18 anos, de ambos os sexos. A coleta dos dados foi realizada por meio do emprego de questionário semi-estruturado, após os responsáveis terem assinado o Termo de Consentimento Livre e Esclarecido. Coletou-se dados referentes às condições sócio-econômica e ambiental, alimentares, sanitárias, aos níveis de hemoglobina e ao índice de massa corpórea – IMC. Verificou-se que 20 (42,55%) dos adolescentes de ambos os sexos apresentaram níveis de hemoglobina, inferior ao preconizado pela OMS, que considera anêmicos as adolescentes com níveis inferiores a <12 g/dl, e os adolescentes <12,5 g/dl. Dos 60,41% sujeitos que realizaram exame parasitológico de fezes (Método de Hoffan), 65,41% apresentaram parasitose intestinal (helmintos e/ou protozoários). Identificou-se 87,50% de adolescentes considerados eutróficos. Concluiu-se que a prevalência de anemia ferropriva e parasitose na comunidade estudada é elevada. Em relação às condições socioeconômicas dos adolescentes, verificou-se que esses indivíduos estão em completa vulnerabilidade e exclusão social. __________________________________________________________________________________________ ABSTRACT / The nutritional anemia results from the simple or combined deficiency of nutrients as iron, folic acid and vitamin B12, although is may caused also for others kind of factors such as pyridoxine, riboflavin and protein deficiency. Although several nutrients and co-factors have been involved in the normal synthesis of the hemoglobin, the iron deficiency is the most common cause of lack anemia in the world, constituting in the nutritional lack of major prevalence, affecting especially the children and pregnant of the developing countries. The objective of this study is to know the prevalence of iron deficiency in adolescent living en the community “Vila Princesa “ - the garbage dump in the city of Porto Velho - Rondônia (Brazil). The methodology used in this work was of the transverse kind and involved forty eight adolescent between the ages of 12 and 18 of both genders. The collection of data has been realized through a semi structured questionnare, after the Inform Consent Term has been signed by them. Data has been collected referring to the social – economic, environmental, food and, sanitary conditions, as well as levels of hemoglobin and mass corporal indicatior (IMC). It has been verified that 42.55% of adolescents of both sexes presented level of low hemoglobin preconised by the WHO which consider levels lower than < 12 g/dl and 12.5 g/dl as anemic levels in female and male adolescents, respectively. From 60,41% subjects of that realized parasitological exams (Hoffman method), 65.41% presented intestinal parasitosis (helminthes and/or protozoa). It has been identified that 87.50 % of adolescent were considered eutrophic. It has been concluded that the prevalence of iron deficiency anemia and parasitosis in the studied community is high . In relation the social economic conditions of the adolescents it has been verified that these individuals are in complete vulnerability and social exclusion.

O vírus da anemia das galinhas – CAV (chicken anemia virus) está presente em praticamente todos os países com produção avícola investigados, inclusive no Brasil. O CAV causa a doença chamada de anemia infecciosa das galinhas em aves jovens, que se caracteriza por anemia, aplasia de medula óssea, retardo no crescimento, mortalidade variável (2 a 20%), atrofia de órgãos linfóides e imunodepressão. O controle da anemia infecciosa das galinhas é baseado na transferência de imunidade passiva das matrizes à progênie. A transferência de anticorpos maternos via ovo em nível suficiente é uma forma de prevenir a transmissão vertical do vírus, reduzindo assim a ocorrência de surtos da doença. Este trabalho teve como objetivo comparar o desempenho entre frangos nascidos positivos e negativos para a presença de anticorpos contra o CAV. Para isso, foram utilizados dois lotes de matrizes pesadas, sendo um vacinado e o outro não. Com a progênie obtida dessas matrizes de ambos os lotes, foram constituídos três tratamentos com 50 fêmeas e 50 machos cada: T1 - pintos oriundos de matrizes vacinadas com títulos protetores; T2 - pintos oriundos de matrizes não vacinadas com títulos médios e; T3 - pintos oriundos de matrizes não vacinadas e negativas ou com títulos baixos. Todos os tratamentos permaneceram em regime de criação intensiva usual por 47 dias em 5 propriedades diferentes, portanto o experimento teve 5 repetições. Os dados analisados foram o peso inicial e final, conversão alimentar e mortalidade. Como resultado, foi observado que não houve diferença significativa (p>0,05) no peso final entre os tratamentos com relação as fêmeas. Já, nos machos, os frangos negativos (T3) foram significativamente (p<0,05) mais pesados que os frangos positivos (T1 e T2). Não houve diferença significativa (p>0,05) entre os tratamentos em relação à mortalidade e a conversão alimentar. A análise do soro e histologia do timo determinaram a não ocorrência do desafio durante o período de criação dos frangos. A vacinação das matrizes contra o CAV não gerou títulos de anticorpos superiores aos obtidos nas matrizes não vacinadas e infectadas naturalmente. Este estudo indicou que a presença de anticorpos contra o CAV em frangos de corte, seja através da vacinação ou da infecção natural das matrizes, não gerou uma progênie com melhor desempenho nas condições de criação testadas.