Thesis (Ph. D.)--University of Wisconsin--Madison, 1970. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliography.

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Thesis--Copenhagen. / Bibliography: p. 127-134.

Thesis--Copenhagen. / Bibliography: p. 127-134.

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Thesis (M.S.)--University of Wisconsin--Madison, 1970. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

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Two novel B cell populations were characterized in peripheral blood of patients with common variable immunodeficiency and healthy controls were observed using flow cytometry in the study supported by the grant IGA MZ ČR NKT11414-3. These B cell populations were defined as CD19+ CD27- CD21+ CD38low CD24+ IgM+ FO I and CD19+ CD27- CD21+ CD38low CD24++ IgM++ cells. Since none of found populations has ever been described, the aim of this thesis was to characterize these populations with focus on analysis of variable regions of the heavy chains of immunoglobulins and genes coding proteins participating in the process of VHDHJH formation (Rag 1, Rag 2, and TdT) produced by cells of these populations. Flow cytometry, single cell sorting, single-cell RT-PCR, IgVH, Rag 1, Rag 2, and TdT specific PCR amplification and cycle sequencing were employed to perform the molecular analysis in individual B lymphocytes. Both populations in two patients with common variable immunodeficiency, two healthy controls, and in two patients with autoimmune diseases - rheumatoid arthritis and systemic lupus erythematosus (as the disease control) - were examined. Finally, the statistical analysis was used to evaluate the differences in expression of variable regions of the heavy chains of immunoglobulins and in Rag1 and 2, and...

Moklsiniame darbe tirtas chimerizmas vaikams po alogeninės kraujodaros kamieninių ląstelių transplantacijos. Tyrimas pradėtas Charité klinikose (Humboldto universitetas, Berlynas), kur chimerizmo tyrinėjimams pasirinkti recipientai, sergantys ūmia limfoblastine leukemija (ŪLL), Fanconi anemija (FA) ir adrenoleukodistrofija (ALD). Sergant šiomis ligomis nuoseklus chimerizmo stebėjimas ALP atliktas pirmą kartą. Darbas tęstas Vilniaus universitete, kuomet pirmą kartą buvo atlikti chimerizmo tyrinėjimai Lietuvoje transplantuotiems vaikams. Donoro ir recipiento ląstelėms atskirti naudoti polimorfiniai DNR žymenys, kurie tirti periferinio kraujo leukocituose (PKL) ir atskirose ląstelių populiacijose (ALP): CD3, CD19 ir CD34. Ląstelių frakcijoms atskirti naudotos imunomagnetinės dalelės. Atlikus chimerizmo analizę nutatyta, kad esant visiškam donoro chimerimui PKL, 74,4% ŪLL ir 66,7% ALD recipientų po mieloabliacinio kondicionavimo ląstelių populiacijose išlieka autologinė, aptinkama iki kelerių metų po transplantacijos. Po sumažinto intensyvumo kondicionavimo 45,5% FA recipientų autologinės kraujodaros pėdsakų nerandama nei PKL, nei ALP. FA ligoniams vystosi stabilus ilgalaikis mišrus chimerizmas, kuris susijęs su su ilgesniu išgyvenamumu po transplantacijos. Nustatėme, kad sergantiems FA galimybė išsivystyti mišriam chimerizmui yra 20 kartų didesnė perpylus kaulų čiulpus, nei periferinio kraujo kamienines ląsteles. / The doctoral thesis aimed to evaluate in a comparative way the benefit chimerism assessment in isolated cell populations (ICP) versus conventional monitoring in whole blood cells (WBC). The study was initiated in Pediatric Bone Marrow Transplant Service of Charité Children’s Hospital (Humboldt University, Berlin). Children suffered from: acute lymphoblastic leukemia (ALL), Fanconi anemia (FA) and adrenoleukodystrophy (ALD) were included into the study. Thereafter the doctoral thesis was accomplished at the Vilnius University where evaluation of the own experience of chimerism analysis in pediatric patients was performed. Chimerism was prospectively monitored in WBC and three cell subsets: CD3, CD19 and CD34. Cell populations were extracted from peripheral blood using immunomagnetic beads. Following polymorphisms of short tandem repeats between donor and recipient were compared. The analysis reveled that following myeloablative conditioning in patients with ALL and ALD analysis of ICP revealed persistent autologous hemopoiesis despite stable donor chimerism in WBC. In contrast after reduced intensity conditioning 45.5% of FA recipients had no evidence of autologous signals either in WBC, or in ICP. FA were found to develop stable long-lasting mixed chimerism associated with better overall survival. development of MC was related to the infusion of bone marrow but not to peripheral blood stem cells. Chimerism in ICP did no affected transplant outcome in any disease group.