Dissertations / Theses on the topic 'Blood cells'
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Guo, Quan. "Deformability based sorting of red blood cells and white blood cells using microfluidic ratchets." Thesis, University of British Columbia, 2016. http://hdl.handle.net/2429/59592.
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There are many situations in medicine and biology where it is desirable to sort cells in a heterogeneous sample based on their mechanical deformability, which can potentially serve as a proxy for morphology or pathology. This biophysical characteristic is particularly relevant for cells in the circulatory system, such as red blood cells and white blood cells, because deformability determines the capacity for these cells to transit through the microvasculature. Since deformability is such a fundamental characteristics of blood cells, deviations in normal cell deformability can contribute to a range of pathological conditions, such as microvascular occlusion, tissue necrosis and organ failure, observed in diseases such as malaria caused by Plasmodium falciparum. A commonly employed approach for deformability-based cell sorting is microfiltration. However, this method suffers from cell clogging at the filter microstructures, leading to reduced selectivity and device malfunction.
This dissertation presents an improved microfiltration strategy performed using the microfluidic ratchet mechanism, which relies on the deformation of individual cells through micrometer-scale tapered constrictions. Deforming single cells through such constrictions requires directionally asymmetrical forces, which enables oscillatory flow to create a ratcheting transport that depends on cell size and deformability. Simultaneously, oscillatory flow continuously agitates the cells to limit the contact time with the filter microstructure to prevent clogging and adsorption.
This work demonstrates the utility of the ratchet mechanism for cell sorting by developing a microfluidic device to sort red blood cells based on deformability. The device is used to separate Plasmodium falciparum infected red blood cells from uninfected cells. The method was shown to dramatically improve the sensitivity of malaria diagnosis performed using both microscopy and rapid diagnostic tests by converting samples with difficult-to-detect parasitemia (<0.01%) into samples with easily detectable parasitemia (>0.1%). This work further demonstrates the utility of the microfluidic ratchet mechanism by developing a microfluidic device to isolate and sort leukocytes directly from whole blood. The method is capable of separating leukocytes from whole blood with 100% purity (i.e. no contaminant erythrocytes) and <2% leukocytes loss. Furthermore, the approach demonstrates the potential to phenotypically sort leukocytes to enrich for granulocytes and lymphocytes subpopulations.Applied Science, Faculty of
Mechanical Engineering, Department of
Graduate
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Goddard, Nicola. "Manufacture of red blood cells from stem cells." Thesis, Heriot-Watt University, 2017. http://hdl.handle.net/10399/3271.
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Although the current system of blood transfusion is relatively safe and established within the UK, periodic shortages of certain blood groups and residual risks of emerging transfusion transmitted infections (TTIs) make an industrial manufacture process for the generation of red blood cells more desirable. The generation of red blood cells from human embryonic stem cells has been completed in vitro but the major challenge lies in making the process highly scalable and economically viable. Initially human embryonic and induced pluripotent stem cells were trialled for use on the project however these were found to be inconsistent, a major issue in cellular therapies. They were replaced with CD34+ cord blood stem cells which are morphologically and physiologically divergent. In order to assess their suitability for a GMP-complaint manufacturing process an ultra-scale down (microfluidic) approach was taken to assess the cells’ reactions to the changeable physical environment associated with scale-up procedures. Cellular responses to hypoxia and shear stress were evaluated at successive time-points in the step-wise haematopoietic differentiation process and recommendations made for optimum scale-up conditions. Conversely further challenges in the manufacture of red blood cells from stem cells were uncovered regarding the differences between stem cell derived red blood cells and their adult equivalents.
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Kuck, Jan L. "Mechanotransduction in red blood cells." Thesis, Griffith University, 2023. http://hdl.handle.net/10072/421118.
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Red blood cells (RBC), the oxygen-carriers within blood, eject their nuclei and other organelles to optimise cellular mechanics for gas exchange in capillary networks. Lack of organelles, however, strictly limits circulatory longevity of these cells, due to the inability to repair damaged cellular components. Given the turnover of RBC, the cell population within blood is inherently heterogenous, comprising RBC across the whole spectrum of in vivo age. Moreover, surrender of translational capacity restricts cellular signalling within RBC to modifications of existing proteins and/or flux of ions through membrane-embedded channels,
rather than alterations in protein expression.
The traversal of the cardiovascular system for the purpose of gas exchange exposes RBC to varying mechanical forces. Exposure to mechanical force physically deforms the RBC membrane, which, upon cessation of force exposure, readopts its native bi-concave disc chape. Novel observations support that these mechanical forces also activate biochemical pathways that may acutely and transiently alter RBC mechanics. The molecular machinery facilitating these mechanotransduction processes in RBC, however, is largely undescribed.
The aim of the present body of work was thus to elucidate i. mechanotransductive pathways in mature, enucleated RBC; ii. the contribution of mechanically-activated signalling to the regulation of RBC mechanics; and iii. the impact of sub-populations of RBC with abnormal mechanical properties on blood fluid behaviour.
The salient findings of the present dissertation support the presence of a relevant post-translational signalling network in circulating, enucleated RBC, some of which is sensitive to activation by mechanical forces. The cation channel Piezo1 appears to be a central mechanism of ‘force sensing’ in these cells. That is, opening of Piezo1 in response to mechanical force facilitates influx of calciumions, which regulate RBC mechanics via diverse mechanisms, including acute shifts in cell volume, selective removal of susceptible cells within a given RBC population, and initiation of nitric oxide production.
Collectively, the herein presented results enhance the current understanding of fundamental RBC physiology by elucidating hitherto unrecognised signalling pathways. Given the demonstrated relevance of these processes to the regulation of RBC mechanical properties, which determine blood fluid properties and effective gas exchange, components of mechanically-activated signalling in these cells may provide novel therapeutic targets. Moreover, adverse complications arising in scenarios where blood is exposed to mechanical forces far exceeding those investigated here, for example during transit of mechanical circulatory support devices or dialysis machines, may be linked to overactivation of mechanically-sensitive signalling.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Health Sci & Soc Wrk
Griffith Health
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Shuib, Anis Suhaila. "Investigation of blood cells migration in large stenosed artery." Thesis, University of Edinburgh, 2012. http://hdl.handle.net/1842/6265.
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Atherosclerosis is one of the main diseases responsible for the high global mortality rate involving heart and blood vessel disorders. The build-up of fatty materials in the inner wall of the human artery prevents sufficient oxygen and nutrients reaching the organs of the body. Atherosclerosis is a chronic, long term condition, which develops and progresses over time; however, the disease does not present any symptoms until an advanced stage is reached, which results in potential permanent debility and sometimes sudden death. This thesis is concerned with the progression of atherosclerosis in an artery with mild stenosis that has resulted in a 30% reduction in its diameter. To this end, data on the low wall shear stress has been correlated with the atherosclerotic prone region. In a stenosed artery, this region corresponds to the separation zone that is formed distal to the lumen reduction. Atherosclerosis is a complex phenomenon, and not only involves wall shear stress, but also cellular interactions. Previous research has shown that even in the absence of wall biological effects, the blood cell distribution is strongly influenced by the hydrodynamics of the fluid. The mechanisms of blood cell distribution and the dynamic behaviour of the blood flow were investigated by developing a physical model of the stenosed artery, and by using particles to represent the presence of the blood cells. Particle Image Velocimetry system was employed and the size of particles were the 10μm and 20μm. The flow field was characterised and the particle distribution was measured. The characteristics of steady flow in the stenosed artery at Reynolds numbers of 250 and 320 revealed the importance of fluid inertia and the shear gradient distal to stenosis. Unequal distribution of the particles modelling the blood cells was observed, as more particles occupied the recirculation zones than the high shear region and central jet. The particle migration was found to depend on the particle size, particle concentration and fluid flow rates. The results suggested that the presence of similar effects in the real human arterial system may be significant to the progression of atherosclerotic plaques. At lower Reynolds number of 130, a particle depleted layer was observed at the wall region. In physiological flow the cell free layer will prevent the transport of oxygen and nitrogen oxide (NO) to the muscle tissues. A numerical method was used to simulate the flow characteristics measured in the experiment. The numerical results revealed the importance of the hydrodynamic mechanism of particle migration. Drag and lift forces were found to affect the residence time of particles in the recirculation region. The findings of this work have suggested that for a complex geometry like a large stenosed artery at physiological flow rates, hydrodynamic forces are important in cell migration in the flow separation zone. Even without biological forces, the cells migrate to the low wall shear stress region. For computational dynamics studies, this study has demonstrated the need for higher-order modelling at the cellular level in order to establish the particle migration mechanisms.
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Sethia, Pavan P. "Development and Commercialization of Menstrual Blood Stem Cells Banking." Case Western Reserve University School of Graduate Studies / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1303759438.
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Drake, Mary. "Characterisation of mononuclear cells in peripheral blood stem cell harvests." Thesis, Queen's University Belfast, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.287206.
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Drew, Clare G. "Membrane transport in red blood cells." Thesis, University of Oxford, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.275332.
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Lee, F. Y. "The effects of CAMPATH on cord blood and peripheral blood cells." Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1463448/.
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CAMPATH-1H is administered prior to haematopoietic stem cell transplantation (HSCT) to reduce risks of graft versus host disease (GvHD) by targeting CD52 antigens on T cells, resulting in their depletion. CAMPATH-1H is routinely used in HSCT using haematopoietic stem cells (HSC) from peripheral blood (PB) and bone marrow but not cord blood (CB). Data regarding in vivo and in vitro effects of CAMPATH-1H on immune cells is limited to PB T and B cells. Thus, we sought to determine whether a direct correlation between CD52 density and the depleting effects of CAMPATH-1H exists with fresh and frozen, resting and activated, PB and CB cells. CD52 expression was generally higher in resting CB than PB T cell subsets and B cells although CD52 levels were higher in PB natural killer cells. Furthermore, CAMPATH-1H depleted resting cells more effectively than activated cells with minimal or no necrosis. Higher percentages of apoptosis were noted in naïve CD4 and CD8 T cells with wild type/wild type genotype for caspase-8 (CASP8) gene promoter compared to donors with a single or double deletions, suggesting the potential contribution of CASP8 promoter polymorphism on sensitivity to the drug. CD52 was absent on HSC but upregulated during differentiation, implying that residual CAMPATH-1H could potentially impact on HSC differentiation by depleting CD52 expressing progenitors. This study provides evidence that low dose of CAMPATH-1H may be effective for cell depletion and prevent GvHD whilst allowing cell differentiation. Although the impacts of CAMPATH-1H on viability and differentiation of CB and PB cells were comparable, the use of CAMPATH-1H pre-CBT may not be ideal as it may further delay immune recovery and increase infection incidences. Therefore, this project provides a better understanding of CAMPATH-1H effects at the cellular and molecular level, with potential for clinical translation to achieve effective GvHD modulation while preserving GvL.
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Gibaud, Etienne. "Numerical simulation of red blood cells flowing in a blood analyzer." Thesis, Montpellier, 2015. http://www.theses.fr/2015MONTS135/document.
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L'objectif de cette thèse est d'améliorer la compréhension des phénomènes jouant un rôle dans la mesure effectuée dans un analyseur sanguin, en particulier le comptage et la mesure de volumétrie d'une population de globules rouges reposant sur l'effet Coulter. Des simulations numériques sont effectuées dans le but de prédire la dynamique des globules rouges dans les zones de mesure et pour reproduire la mesure électrique associée, servant au comptage et à la volumétrie des cellules. Ces simulations sont effectuées à l'intérieur de configurations industrielles d'analyseur sanguin, en utilisant un outil numérique développé à l'IMAG, le solveur YALES2BIO. En utilisant la méthode des frontières immergées avec suivi de front, un modèle de particule déformable est introduit, celui-ci prend en compte le contraste de viscosité ainsi que les effets mécaniques de la courbure et de l'élasticité sur la membrane. Le solveur est validé grâce à de nombreux cas tests parcourant différents régimes et effets physiques. L'écoulement fluide dans cette géométrie d'analyseur sanguin est caractérisée par un fort gradient de vitesse axial dans la direction de l'écoulement, impliquant la présence d'un écoulement extensionnel au niveau du micro-orifice, là où a lieu la mesure. La dynamique des globules rouges est étudiée par des simulations numériques pour différentes conditions initiales, telles que sa position ou son orientation. Il est observé que les globules rouges vont se réorienter selon l'axe principal de l'analyseur sanguin dans tous les cas. Pour comprendre le phénomène, des modèles analytiques sont adaptés au cas des écoulements extensionnels et reproduisent correctement les tendances de réorientation.Cette thèse présente également la reproduction de la mesure électrique utilisée pour le comptage et la mesure de la distribution des volumes de globules rouges. De nombreuses simulations de la dynamique des globules rouges sont effectuées et utilisées pour générer l'impulsion électrique correspondant au passage du globule rouge dans le micro-orifice. Les amplitudes d'impulsions électriques résultantes permettent la caractérisation de la réponse électrique en fonction des paramètres initiaux de la simulation par une approche statistique. Un algorithme de Monte-Carlo est utilisé pour la quantification des erreurs de mesure liées à l'orientation et la position des globules rouges dans le micro-orifice. Ceci permet la génération d'une distribution de volume mesurée pour une population de globules rouges bien définie et la caractérisation des erreurs de mesure associéesThe aim of this thesis is to improve the understanding of the phenomena involved in the measurement performed in a blood analyzer, namely the counting and sizing of red blood cells based on the Coulter effect. Numerical simulations are performed to predict the dynamics of red blood cells in the measurement regions, and to reproduce the associated electrical measurement used to count and size the cells. These numerical simulations are performed in industrial configurations using a numerical tool developed at IMAG, the YALES2BIO solver. Using the Front-Tracking Immersed Boundary Method, a deformable particle model for the red blood cell is introduced which takes the viscosity contrast as well as the mechanical effects of the curvature and elasticity on the membrane into account. The solver is validated against several test cases spreading over a large range of regimes and physical effects.The velocity field in the blood analyzer geometry is found to consist of an intense axial velocity gradient in the direction of the flow, resulting in a extensional flow at the micro-orifice, where the measurement is performed. The dynamics of the red blood cells is studied with numerical simulations with different initial conditions, such as its position or orientation. They are found to reorient along the main axis of the blood analyzer in all cases. In order to understand the phenomenon, analytical models are adapted to the case of extensional flows and are found to reproduce the observed trends.This thesis also presents the reproduction of the electrical measurement used to count red blood cells and measure their volume distribution. Numerous dynamics simulations are performed and used to generate the electrical pulse corresponding to the passage of a red blood cell inside the micro-orifice. The resulting electrical pulse amplitudes are used to characterize the electrical response depending on the initial parameters of the simulation by means of a statistical approach. A Monte-Carlo algorithm helps quantifying the errors on the measurement of cell depending on its orientation and position inside the micro-orifice. This allows the generation of a measured volume distribution of a well defined red blood cell population and the characterization of the associated measurement errors
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Yuan, Yifan. "Enhancing Blood Outgrowth Endothelial Cells for Optimal Coating of Blood Contacting Surfaces." Thesis, Université d'Ottawa / University of Ottawa, 2017. http://hdl.handle.net/10393/36837.
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Implantable cardiovascular biomaterials have been widely applied in multiple cardiovascular disorders such as coronary artery disease, heart failure, and abdominal aortic aneurysms. However the failure modes of cardiovascular biomaterials are not uncommon, which is mainly due to the complications on blood-contacting surfaces such as thrombosis, calcification, and inflammation. Endothelium locates the inner surface of vessel lumen and is a critical regulator of vascular homeostasis. However, a readily available functional autologous source of endothelium has been hard to achieve. Human blood outgrowth endothelial cells (BOECs), cultured from peripheral blood mononuclear cells are proliferative and express endothelial protein profiles and as such are a very promising novel cell source for cardiovascular biomaterials coating. Endothelial nitric oxide synthase (eNOS) is an important regulator of vascular homeostasis and loss of eNOS activity is a hallmark of endothelial dysfunction. My data demonstrated that BOECs express markedly lower eNOS protein, mRNA as well as activity levels when compared to mature endothelial cells (ECs). My first project was to use transient transfection methods along with minicircle DNA to enhance eNOS expression levels in BOECs. Two promoters were tested in BOECs, the CMV promoter (pMini-CMV-eNOS) and the EF1α promoter (pMini-EF1α-eNOS). Transfection with pMini-CMV-eNOS achieved 24.8 ± 5.1 times more eNOS expression when compared to null transfected cells at 24 hours, a marked improvement over that achieved with conventional PVAX plasmid (10.2 ± 4.7 fold increase) or pMini-EF1α-eNOS (8.2 ± 1.2 fold increase both compared to null transfected control). pMini-CMV-eNOS mediated overexpression improved cell migration and network formation. When cultured on Osteopontin (OPN) coated surfaces, transient transfection with plasmid eNOS in BOECs can markedly enhance cell spreading and adhesion to ECM modified surfaces. These results suggest that eNOS expression in BOECs is suboptimal and BOECs may be functionally improved by techniques to enhance expression of this critical homeostatic regulator.
Extracellular matrix (ECM) proteins have been shown to negatively regulate eNOS expression and NO production in mature ECs. In addition, the deposition of Col IV and Col I in BOECs is higher compared to that in mature ECs. Thus, I have proposed that the lower eNOS expression/activity in BOECs compared to mature ECs is due to higher ECM deposition. When grown on fibronectin, type I collagen, type IV collagen and laminin, significantly decreased eNOS protein in HUVECs were found compared to cells on polystyrene. Interestingly, when cultured on polystyrene, BOECs express significantly more extracellular matrix (ECM) proteins especially type I collagen compared to mature ECs. Blocking collagen synthesis significantly enhanced eNOS expression in BOECs (1.77 ± 0.41 fold increase). My results suggest that the regulation of eNOS in BOECs and mature ECs is similar and the reduced eNOS level in BOECs may be due to their increased collagen production.
ECM proteins regulate intracellular signaling transduction primarily through integrin signaling associated with focal adhesion complexes. I have proposed that ECM proteins regulation on eNOS signaling in BOECs and mature ECs is through integrin and integrin-associated proteins. Matrix mediated eNOS downregulation was blocked by β1 integrin siRNA and focal adhesion kinase siRNA transfection in both BOECs and HUVECs. In addition, inhibitors of actin polymerization (e.g. ROCK inhibitors and cytochalasin D) block the effect of ECM on eNOS signaling. Taken together, my results suggest that ECM proteins regulate eNOS expression via a β1 integrin/FAK/actin polymerization dependent mechanism.
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Wolf, A. S. "Natural killer cell responses to Plasmodium falciparum-infected red blood cells." Thesis, London School of Hygiene and Tropical Medicine (University of London), 2017. http://researchonline.lshtm.ac.uk/3449324/.
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NK cells are known to respond in vitro to P. falciparum-infected red blood cells (iRBCs), although responses are highly heterogeneous between donors. Although their role during malaria infection is not fully understood, they may play a role in cytokine production during early infection, and furthermore may interact with and kill iRBCs. The work described in this thesis examines the role of NK cell receptors in determining the functional outcomes of NK cell activation by iRBCs, focusing on NK cell responses to exogenous cytokines and the phenotypic and functional profiles of NK cells from malaria naive (LSHTM) and malaria exposed (Ugandan) subjects. In a model of early activation of NK cells by accessory cell-derived cytokines, I have shown a key role for IL-18 in mediating NK cell responses during both primary and secondary immune responses as IL-18 synergises with cytokines from the common gamma chain family. NK cells from LSHTM donors showed low background expression of IFN- and CD25, but responded to iRBCs by secretion of IFN-, which was potentiated by exogenous IL-15. By contrast, NK cells from Ugandan donors showed higher background CD25 expression and signs of in vivo/ex vivo preactivation and enhanced responsiveness to IL-15, but did not make any appreciable response to iRBCs. Potential explanations for these findings are explored and discussed. KIR genotype and KIR expression also varied between LSHTM and Ugandan donors. Specifically, expansions of KIR2DL1+ CD57+ NKG2C+ NK cell populations (possibly driven by human cytomegalovirus (HCMV) infection) were observed in the Ugandan donors. Conversely, percentages of KIR2DL3+ and 2DS4+ NK cells were higher among LSHTM donors, indicating that HLA genotype or allelic KIR polymorphisms may influence KIR expression. Finally, the formation of NK-iRBC conjugates, which may be a precursor to NK cellmediated killing of iRBCs, was observed in cells from nearly all donors, but did not correlate with other functional responses. Analysis of KIR expression and NK cell functional responses indicated that donors expressing inhibitory KIR2DL5 had reduced numbers of conjugates. Further experiments indicated that KIR2DL5 might be specifically upregulated after incubation with iRBCs, and that individuals carrying a normally non-expressed KIR2DL5 gene may be able to express this gene under certain circumstances. This tentatively suggests a role for KIR2DL5 during NK cell responses to malaria infection, and suggests a possible function for a common but frequently non-expressed gene. In summary, my work suggests that NK cell responses are strongly influenced by cytokine receptor and KIR expression, which in turn depend on NK cell maturation status. KIR expression patterns may in part explain differential NK responses to iRBCs between LSHTM and Ugandan donors. I also propose a possible role for KIR2DL5 in malaria infection, and a reason for the low expression of this gene in African populations.
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Rübsaamen, Katharina. "Lipidomic analysis of circulating human blood cells." kostenfrei, 2010. http://epub.uni-regensburg.de/13246/.
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Atkins, Chad Garry. "Raman spectroscopy of transfusable red blood cells." Thesis, University of British Columbia, 2016. http://hdl.handle.net/2429/59728.
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Blood banking is an essential aspect of modern healthcare. When red blood cells (RBCs) are stored, they degrade over time as a result of various chemical and biological processes leading to an accumulation of waste products and oxidative damage, among others. Significant growth in the application of Raman spectroscopy (RS) to biomedical problems has made it a feasible tool for investigating biochemical changes associated with storage of RBCs. It was hypothesized that RS could be used to monitor in situ, non-destructively and non-invasively, certain structural and compositional changes associated with these ageing effects as they occur in storage bags. The presence of a relationship between these changes and the viability of RBCs would have substantial implications for the health care industry.
Preliminary results demonstrated the oxygenation state of hemoglobin in stored RBCs changed in a manner that was donor-dependent and that closely tracked the morphological index, a qualitative metric for evaluating cell quality. Investigations of the storage-solution supernatant revealed that lactate, a metabolic waste product, accumulated at different rates in stored bags and displayed more rapid accumulation in units from male donors than units from female donors.
It was shown that spatially offset Raman spectroscopy (SORS) could measure stored RBC biochemistry through the plastic bag. Spectra collected with SORS compared well with previously-obtained conventional Raman spectra. Thus, information about the contents of a stored unit could be obtained without breaching its sterility. These outcomes provided proof-of-concept for the development of a SORS-based instrument to measure storage bag contents in a rapid and non-invasive manner.
The results reported in this thesis fall into two distinct categories. Regarding the observed data, the substantial inter-donor variability and gender and age effects have significant implications for the design of clinical trials, the collection and administration of donated blood, and clinical use. Regarding instrumentation, obtaining chemical information from stored RBCs using RS will enable new research directions for the field of transfusion medicine and obtaining this information in situ from storage bags will have utility for quality control in a blood bank or hospital setting.Science, Faculty of
Graduate
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Khan, Asif Iqbal. "Potassium transport in human red blood cells." Thesis, University of Oxford, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.342545.
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Williams, Helen. "Interactions between extracellular Hsp72 and blood cells." Thesis, University of Chester, 2010. http://hdl.handle.net/10034/277691.
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In recent years, compelling evidence has accumulated suggesting heat shock proteins (HSPs) which are generally believed to be localised and functioning mainly within eukaryotic cells as cyto-protective molecular chaperones, are also localised in the extracellular milieu. Depending on their localisation, on the cell surface (membrance-bound or embedded), or in the peripheral circulation, extracellular HSPs may induce apoptotic cell death, or in contrast protect cells from cell damage and/or cell death when exposed to cellular stress, or may even elicit a stimulatory effect on the innate immune response including cell activiation and cytokine secretion. Hence, the localisation of intracellular and extracellular HSPs appears to be critical in determining their roles in terms of stimulating cell death, cyto-protection, or immune activiation under normal physiological conditions and following exposure to stress stimuli. This thesis describes the intracellular expression, up-regulation, and cell surface localisation of endogenous HSPs: HSP27, Hsp60, Hsp72 and Hsp90 by flow cytometry, florescence microscopy and Western blotting, under control conditions and in response to environmental stress using in vitro and ex vivo models with the intention of determining their physiological roles. The ability of extracellularly administered HSPs (Hsp70 and Hsp72) to protect cultured U937 cells in vitro or peripheral primary human leukogytes or erythrocytes ex vivo from various stress stimuli was demonstrated and was found to be dependent on surface binding and/or internalisation via scavenger receptors (SRs) or phosphatidylserine (PS), which could be blocked by receptor specific ligands. Extracellular HSPs were also shown to be able to stimulate an immune response through the induction of U937 monocyte differentiation into macrophages as evidenced through the up-regulation of the surface receptors: CD36, SR-A1 and CD91 analysed by flow cytometry. These proteins were able to stimulate TNF-x and IL-10 production and secretion by U937 macrophages, shown by ELISA, and chemotatic properties were demonstrated using Boyden chambers. The cyto-protective and immune regulatory effects of extracellular HSPs have potential therapeutic value as treatments in a wide variety of clinical situations.
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Hale, John P. "The thermal fluctuations of red blood cells." Thesis, University of Exeter, 2009. http://hdl.handle.net/10036/92613.
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In this thesis, we describe the development of a new technique for determination of the mechanical properties of the red blood cell membrane from measurement of its thermal fluctuations. Experimentally, the shape fluctuations of the equatorial contours of red blood cells are recorded using fast phase-contrast video microscopy, from which the Fourier fluctuation spectrum is obtained and analysed. The experimentally obtained fluctuation spectra are interpreted using a coarse grained particle dynamics simulation which models the thermal fluctuations of an elastic mesh endowed with bending and shear elasticity, and constant volume and surface area. We demonstrate that the simulation correctly describes the mean shape of the red cell as well as the membrane thermal fluctuations. Comparison between theory and experiment leads to physically sound values for the relevant membrane elastic moduli and helps distinguish between the contributions of the lipid bilayer and the membrane skeleton. We extend this technique to investigate the mechanical response of red blood cells to oxidative stress. We show that it is possible to discriminate between the actions of different oxidising agents from their distinctive effects on the membrane thermal fluctuation spectrum. This allows comparative measures of the membrane material properties to be extracted using an approximate analytical model thus discriminating between the effects of each oxidising agent on different structural components of the membrane. This technique was also applied to investigate the response of the red blood cell to oxidative stress under simulated hyperglycemic conditions characteristic for disease states such as diabetes. We established that the membrane elasticity of glycated cells deteriorate much fasted under administration of hydrogen peroxide, which may be related to the observed microvascular complications in diabetes, characterised by disproportionately high levels of reactive oxidative species. We demonstrate that metformin, one of the most widely prescribed anti-diabetic drugs, has an ameliorative effect on the membrane mechanical properties, which is probably due to its anti-glycating effects. The technique provides a reproducible means to assess the effects of reactive oxidative species on the red blood cell membrane mechanical properties and distinguish between effects on the protein membrane skeleton and the lipid bilayer. This makes the new method of potential value in monitoring the effects of drug induced changes hence assessing progress of treatment in terms of the antioxidant or anti-glycation properties of administered drugs in diabetes or other conditions characterised by high levels of oxidative stress.
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Brooks, C. F. "Antigen presenting cells in human peripheral blood." Thesis, University of Manchester, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.234349.
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Silva, Carolina Sousa. "Protemic characterization of peripheral blood mononuclear cells." Master's thesis, Universidade de Aveiro, 2015. http://hdl.handle.net/10773/15872.
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Mestrado em Biotecnologia - Biotecnologia MolecularPeripheral blood mononuclear cells (PBMCs) play quite diverse and important roles in monitoring immune homeostasis. Thus, these subset of blood cells may provide access to potential physiological relevant biomolecules, namely proteins. For this reason, PBMCs represent a promising biological sample in scientific research, particularly as a source of potential biological markers discovery of the most diverse diseases. Prior studies of proteomic characterization of PBMCs from healthy individuals lack either the identification of a large number of proteins or its quantification in a way that is compatible with the search of potential biomarker candidates. Therefore, this study aimed to provide a comprehensive PBMCs proteome characterisation as well as to create a SWATH library. It was also evaluated if by using the BD Vacutainer® CPT™ tubes for PBMCs isolation, it would be possible to identify a larger number of immunologically relevant proteins in comparison to plasma samples. The enrichment test assay revealed that it is possible to identify more immune-related proteins from isolated PBMCs than from plasma. Moreover, the majority of the quantified proteins with an “immune system” GO term assigned is present in higher amounts in PBMCs samples. 2D LC-MS/MS proved to be the best approach to use in qualitative analysis of PBMCs and in the construction of a SWATH library, since it resulted in an increase of both identified and quantified proteins (66.3% and 16.9%, respectively) in comparison to 1D LC-MS/MS. A total of 2071 proteins were identified and it was possible to quantify 922 different proteins among six distinct samples. From these proteins, 445 were commom between all individuals. In conclusion, this work provides a comprehensive PBMCs proteome dataset that will be useful in further studies that focus on the search for potential biological markers of various pathologies in these cells. Additionally, SWATH-MS proved to be a reproducible and effective acquisition method to quantify PBMCs proteins.
As células mononucleares do sangue (CMS) desempenham diversos e importantes papéis na monitorização da homeostasia do sistema imunitário. Assim sendo, esta subpopulação de células sanguíneas pode providenciar acesso a potenciais biomoléculas relevantes a nível fisiológico, nomeadamente proteínas. Por esta razão, as CMS representam uma amostra biológica promissora na investigação científica, particularmente na descoberta de potenciais marcadores biológicos de diversas doenças. Estudos anteriores de caracterização proteómica das CMS de indivíduos saudáveis falharam quer na identificação de um grande número de proteínas, quer na sua quantificação, de forma compatível com a pesquisa de potenciais biomarcadores. Portanto, este estudo teve como objectivo providenciar uma caracterização proteómica abrangente, bem como a criação de uma biblioteca SWATH. Foi igualmente avaliado se usando tubos CPT™ disponíveis na BD Vacutainer® para o isolamento das CMS, seria possível identificar um maior número de proteínas imunologicamente relevantes comparativamente a amostras de plasma. O teste de enriquecimento revelou que é possível identificar mais proteínas associadas ao sistema imunitário em CMS isoladas do que em amostras de plasma. Também se verificou que a maioria das proteínas quantificadas com ontologia genética “sistema imunitário” estão presentes em maior quantidade nas amostras de CMS. 2D LC-MS/MS mostrou ser a melhor abordagem na análise qualitativa das CMS e na elaboração da biblioteca SWATH, uma vez que o número de proteínas identificadas e quantificadas apresentou um aumento de 66,3% e 16,9%, respectivamente, comparativamente à 1D LC-MS/MS. No total foram identificadas 2071 proteínas e foi possível quantificar 922 proteínas diferentes em seis amostras distintas. Destas, 445 proteínas eram comuns a todos os indivíduos. Em conclusão, este trabalho disponibiliza um amplo conjunto de dados do proteoma das CMS que será útil a estudos futuros que pretendam centrar-se na pesquisa de potenciais marcadores biológicos, nas CMS, das mais diversas patologias. Além disso, comprovou-se que o método de aquisição SWATH-MS é reprodutível e eficaz na quantificação das proteínas das CMS.
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Craig, Jenny I. O. "Peripheral blood stem cells in haematological malignancies." Thesis, University of Edinburgh, 1991. http://hdl.handle.net/1842/19651.
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Autologous bone marrow transplantation is used successfully as intensive therapy for patients with haematological malignancies and other solid tumours. Peripheral blood contains haematopoietic progenitors whose levels are greatly increased during very early remission after treatment for acute leukaemia or after high dose chemotherapy schedules. These circulating progenitors have been harvested by leucapheresis and used as an alternative to bone marrow as salvage after myeloablative treatments. Peripheral blood stem cells (PBSC) appear to have several advantages over bone marrow including rapid haematopoietic reconstitution after transplantation, the ability to collect PBSC without a general anaesthetic and in the presence of bone marrow abnormalities and the possibility of minimal tumour contamination. My aims were 1) to establish the response of PBSC, measured by the CFU-GM assay, to standard chemotherapy regimes with particular reference to patients with lymphoma, 2) to assess our ability to harvest these progenitors by leukapheresis when numbers were raised and 3) to determine tumour infiltration in PBSC harvests using Southern blotting techniques. Circulating CFU-GM were studied sequentially in 64 patients (40 female, 24 male) 24 non-Hodgkin's lymphoma (NHL), 22 Hodgkin's disease (HD), 9 acute myeloid leukaemia (AML), 5 acute lymphoblastic leukaemia (ALL) and 4 myeloma. Three patients with NHL receiving ALL type therapy showed a mean increase in CFU-GM 15.6 fold over normal values occurring on day 21. Eighteen received CHOP based regimes and demonstrated a 6.2 fold rise between days 15-28. PEEC increased progenitors 43 fold, however CVP and VAD only raised CFU-GM by 2.9 and 2.4 fold respectively. In those patients wth HD a 14.5 fold increase in PBSC was induced in the 4 patients treated with HOPE-bleo. ABVD and MOPP raised peak values to 2.8 and 3.5 times normal and ChlVPP produced a 2.9 fold increase. In the lymphoma group as a whole, standard chemotherapy failed to mobilise PBSC in 15% of patients. Significantly lower peak CFU-GM were found in those who had received previous chemotherapy or who had marrow involvement with disease.
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Pishesha, Novalia. "Engineered red blood cells and their applications." Thesis, Massachusetts Institute of Technology, 2018. https://hdl.handle.net/1721.1/122831.
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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biological Engineering, 2018Cataloged from PDF version of thesis.
Includes bibliographical references.
The humble red blood cell (RBC) is the most abundant cell in the human body. Every second, a normal adult generates some 2.5 million RBCs, which subsequently circulate through the blood vessels for a lifespan of 50 or 120 days in mouse and human, respectively. RBCs are also unique in that they are completely enucleated once fully mature. These two characteristics exist as distinct assets for cellular therapy applications utilizing RBCs as a platform, enabling long-lasting availability in vivo and the ability to genetically modify precursor cells without worry of the terminally differentiated progeny carrying any foreign genetic material. The first part of this thesis is devoted to the establishment of methodologies that allow for the covalent attachment of both natural and synthetic cargoes to the surface of red blood cells without compromising its biological properties. This system employs genetic engineering and sortase A, a bacterial transpeptidases.
We show that this strategy is able to efficiently engineer both mature mouse and human RBCs in a site-specific and covalent manner. The next portion of this work describes how these established methodologies can be mixed and matched according to the diverse needs of engineered RBC applications. We provide a proof of concept that utilizes engineered RBCs to prolong prophylactic protection against deadly toxins. By expressing chimeric proteins of single domain antibodies (VHHs) against botulinum neurotoxin A (BoNT/A) with RBC-specific proteins, we demonstrated that mouse RBCs expressing anti-BoNT/A VHHs can provide resistance up to 10,000 times the lethal dose (LD₅₀) of BoNT/A. We validate this finding by repeating our results in a human RBC culture system that we have improved to achieve 90% enucleation, illustrating the broad translatability of our strategy for therapeutic applications.
Finally, drawing upon knowledge that the body clears 2.5 millions RBCs every second to maintain homeostasis, we use sortase to attach disease-associated autoantigens to genetically engineered and to unmodified red blood cells (RBCs). Such modified RBCs masquerade with these autoantigens as their own, and hijack the non-inflammatory nature of the RBC clearance pathway to promote tolerance to their carried payload. We show that this blunts the immune contribution of major subsets of immune effector cells (B cells, CD4+ and CD8+ T cells) in an antigen-specific manner. Transfusion of RBCs expressing self-antigen epitopes alleviates and even prevents signs of disease in an experimental system for autoimmune encephalomyelitis, and also maintains normoglycemia in a mouse model of type 1 diabetes, highlighting the potential of engineered RBCs for treating autoimmune diseases.
Taken together, the results of applying our engineered RBCs in areas of both acute infectious and toxic agents, as well as for longer-term chronic and autoimmune diseases, hint at the tremendous potential of this system, and we have only begun to scratch the surface.
by Novalia Pishesha.
Ph. D.
Ph.D. Massachusetts Institute of Technology, Department of Biological Engineering
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Egawa, Haruto. "Peripheral blood mononuclear cells in early pregnancy promote invasion of human choriocarcinoma cell line, BeWo cells." Kyoto University, 2004. http://hdl.handle.net/2433/147458.
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Birkenmeier, Gerd, Nasr Y. A. Hemdan, Susanne Kurz, Marina Bigl, Philipp Pieroh, Tewodros Debebe, Martin Buchold, Rene Thieme, Gunnar Wichmann, and Faramarz Dehghani. "Ethyl pyruvate combats human leukemia cells but spares normal blood cells." Universitätsbibliothek Leipzig, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-213853.
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Ethyl pyruvate, a known ROS scavenger and anti-inflammatory drug was found to combat leukemia cells. Tumor cell killing was achieved by concerted action of necrosis/apoptosis induction, ATP depletion, and inhibition of glycolytic and para-glycolytic enzymes. Ethyl lactate was less harmful to leukemia cells but was found to arrest cell cycle in the G0/G1 phase. Both, ethyl pyruvate and ethyl lactate were identified as new inhibitors of GSK-3β. Despite the strong effect of ethyl pyruvate on leukemia cells, human cognate blood cells were only marginally affected. The data were compiled by immune blotting, flow cytometry,
enzyme activity assay and gene array analysis. Our results inform new mechanisms of ethyl pyruvate-induced cell death, offering thereby a new treatment regime with a high therapeutic window for leukemic tumors.
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Stroobach, Mark. "Effects of Red Blood Cell Aggregation on Microparticle Margination in Human Blood." Thesis, Université d'Ottawa / University of Ottawa, 2017. http://hdl.handle.net/10393/36989.
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Margination is the migration of particles in a channel towards the outer walls of the channel. In blood microcirculation, studying the margination of microparticles is important to understand platelet migration and the kinetics of drug delivery. Many new topics in drug delivery research examine the slow release of drugs through micro particles, such as micelles. The margination of such drug carriers is related to tissue absorption and, consequently, to the efficiency of drug delivery. We hypothesized that the intensity of red blood cell (RBC) aggregation will change the level of margination in a cylindrical channel. RBC aggregation is the reversible process of RBCs clumping together over time, under low fluid shear rate. A higher level of aggregation means that this clumping occurs more quickly.
The goal of this thesis is to design an experiment that measures the level margination of microparticles and the effect that RBC aggregation has on margination, in a controlled in vitro environment. Fluorescent microparticles were added to human blood preparations. The aggregation properties of the blood preparation were modulated by the addition of a macromolecule (Dextran 500). The blood preparations were injected into PDMS microfluidic devices that were modified to have circular channels in order to better mimic the geometry of physiological microcirculation.
We designed a circular microchannel that worked to capture the marginating microparticles and it was found that the level of margination of the microparticles increased with an increase in aggregation of the RBCs. This increase in margination was especially sensitive to aggregation levels in the range of physiological aggregation levels of whole blood, suggesting that aggregation plays an important role in margination in vivo.
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Lester, Elizabeth Ann. "Consequences of biomaterial activation of blood cells on endothelial cell proinflammatory phenotype." Thesis, Georgia Institute of Technology, 2001. http://hdl.handle.net/1853/11869.
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Alnabhan, R. M. "Study of the activation of peripheral blood and cord blood natural killer cells." Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1460319/.
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Background: Natural killer (NK) cells are cytotoxic effectors providing a first line of defence against viruses and tumours. NK cells can be isolated from peripheral blood (PB) or cord blood (CB) for cancer immunotherapy. However, it was shown by our group and others, that CB NK cells express higher NKG2A and less killer immunoglobulin like receptors (KIRs) than PB NK cells indicating an immature phenotype. Also, CB NK cells require high doses of interleukin (IL)-2 for proliferation and activation. It was also shown that resting CB NK cells are poorly cytotoxic and produce less IFN-γ than PB NK cells after stimulation with IL-2. Hypothesis and aims: CB NK cells have an immature phenotype and could mediate different role in neonatal immunity than adult PB NK cells. Hence, the aim of this study was to explore whether differential mechanisms of activation exist between PB and CB NK cells. Methods: PB samples from healthy volunteers and CB samples were obtained with prior written consent and ethical approval from Anthony Nolan. Purified PB and CB NK cells were stimulated with cytokines including IL-2, IL-12, IL-15, IL-18, individually or in combination. Thereafter, comparative analysis was performed on their phenotype, signalling, proliferation, cytotoxicity, cytokine secretion and chemotaxis post-cytokine stimulation. Results: My results show that CB NK cells responded less to IL-2 activation than PB NK cells, which correlated with lower levels of IL-2 receptors and decreased phosphorylation of STAT5 pathway. CB NK cells activated with IL-15+IL-2 showed enhanced cytotoxicity while activation with IL-15+IL-18 promoted maximal proliferation, higher IFN-γ and TNF-α secretion. In contrast, optimal activation of PB NK cells was achieved by IL-2 stimulation. Interestingly, CB NK cells secreted substantial IL-8 concentrations following cytokine stimulation. IL-12 or IL-18 stimulation induced L- selectin expression on CB NK cells and promoted NK cell migration towards chemokines that induce homing to lymph nodes. I also generated long-lived memory- like NK cells from PB and CB using cytokines whereby IL-12+IL-15+IL-18 pre- activation led to substantial IFN-! production. Conclusions: CB NK cells are fully functional upon activation with IL-15+IL-2 or IL-15+IL-18 rather than IL-2 thereby providing a basis for activation of NK cells derived from different sources that may be utilised for future NK cell-based therapeutic purposes. In addition, CB NK cell cytokine secretion profile is suggestive for a role of neonatal NK cells in providing protective immunity against bacterial infections.
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Gao, Hua. "Microluidic Sorting of Blood Cells by Negative Selection." University of Cincinnati / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1479816171280535.
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Cytlak, Urszula Malgorzata. "Phosphatidylserine exposure in red blood cells from patients with sickle cell disease." Thesis, University of Cambridge, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708601.
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Karsten, Elisabeth. "Red blood cells: the immune system’s hidden regulator, investigation into the role of red blood cells in inflammatory cytokine signalling." Thesis, The University of Sydney, 2016. http://hdl.handle.net/2123/16929.
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Red blood cells are the most abundant cell type in mammals, although, they are mostly described as inert carriers of haemoglobin that function only in gas exchange and transport. Evidence is now mounting that these enucleate cells are more complex than previously understood. Studies have reported that red blood cells from healthy individuals regulate immune cell activity and maturation, but red blood cells from inflammatory disease cohorts are dysfunctional. Red blood cells are known to bind a small number of chemokines and have been described as a sink for these molecules, and the loss of this activity is correlated with disease progression. This results of this thesis support a broader role for red blood cells in regulating inflammation by acting as a cytokine buffer and modulating cell activity. The aims and hypotheses of this thesis were founded on the discovery that red blood cells are a major reservoir for the pro-inflammatory cytokine, macrophage migration inhibitory factor (MIF); in fact, they contribute 1000-fold more per millilitre than plasma. Red blood cells were also identified to be a major reservoir of 30 additional cytokines, chemokines, and growth factors. Further investigation showed that red blood cells bind and release significant quantities of these proteins, a function that can be modulated by other cells and by enzyme inhibitors. Incubating red blood cells with a cancer cell line (A549 cells) resulted in the significant increase of eight pro-tumorigenic cytokines in the red blood cell lysates. These primed red blood cells altered the activity of lymphocytes by stimulating the proliferation of T cells compared to controls, and promoted the expression of cell activation markers. This study supports the hypothesis that red blood cells act as a buffer for cytokines through binding and release, and that alterations in red blood cells from cell-to-cell interactions affects the activity of T cells. This thesis proposes that red blood cells have multiple functions and the results have implications for the study of inflammation, the role of red blood cells in diagnostics, and on the development of red blood cell derived therapeutics.
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Schütte, Judith. "Analysis of regulatory networks in blood stem/progenitor cells." Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648631.
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Liu, Enmei. "The development of cord blood monocyte-derived dendritic cells /." Hong Kong : University of Hong Kong, 2002. http://sunzi.lib.hku.hk/hkuto/record.jsp?B24520901.
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Ho, Christopher Siaw Kang. "Blood dendritic cells in surgery and breast cancer /." [St. Lucia, Qld.], 2002. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe18162.pdf.
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Poon, Steven Sui-Sang. "Algorithms for detecting and segmenting nucleated blood cells." Thesis, University of British Columbia, 1989. http://hdl.handle.net/2429/27989.
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The analysis of the different types of cells in blood is routinely used in today's medical practice to give an indication of a person's state of health. Many imaging systems and algorithms have been developed over the last 30 years in an attempt to automate this process. Some of these systems can now distinguish the difference between normal and abnormal cells but the differentiation among the various types of abnormal cells is still undergoing active research.
A new system, the Cell Analyzer Imaging System, has been developed to acquire and process images from a microscope. In this work, some new algorithms have been developed using this system to detect and segment nucleated cells in Wright's stained blood smears for classification and sub-classification of the normal and abnormal cell types. The initial steps are to obtain high quality images by greatly reducing noise as well as by correcting distortions, aberrations and shading effects present in the acquired images. Spectral information from the images is then utilized to detect and segment nucleated cells from the rest of the scene (non-nucleated cells and background). All nucleated cells as well as those which are just touching are selected and separated into individual cells. The resulting single cells are further segmented into the regions of nucleus and cytoplasm. Simple features are then extracted from the segmented cells and these features are compared to determine if any clustering of a particular class of cell exists. Results show that these algorithms can detect, segment and classify
different types of normal and abnormal nucleated blood cells. The major
errors in segmentation accounts for approximately 6% of the cells analyzed.Applied Science, Faculty of
Electrical and Computer Engineering, Department of
Graduate
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Dekkers, David Walterus Cornelis. "Studies on transbilayer lipid movement in blood cells." Maastricht : Maastricht : Universiteit Maastricht ; University Library, Maastricht University [Host], 2001. http://arno.unimaas.nl/show.cgi?fid=7089.
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Lo, Yuk-Ming Dennis. "Genetic analysis of fetal cells in maternal blood." Thesis, University of Oxford, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.359448.
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Al-Malki, Aysha Ibrahim. "Detection of endothelial cells in whole blood donations." Thesis, University of Sheffield, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.531130.
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Kooshesh, Fatemeh. "Measurement of the deformability of red blood cells." Thesis, Cardiff University, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.235606.
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Holme, E. R. "C3b receptors (CR1) on peripheral human blood cells." Thesis, University of Glasgow, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.381473.
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Emery, Martin F. "Some technetium complexes for labelling red blood cells." Thesis, University of Southampton, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.328262.
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Mills, John Philip Ph D. Massachusetts Institute of Technology. "Deformability of Plasmodium falciparum parasitized red blood cells." Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/42972.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2007.Includes bibliographical references (p. 99-103).
The biophysical properties of the human red blood cell (RBC) permit large deformations required for passage through narrow capillaries and spleen sinusoids. Several pathologic conditions alter RBC deformability that can result in abnormal circulation behavior. In the present work, altered RBC deformability caused by invading Plasmodium falciparum parasites, which are responsible for the disease malaria, is evaluated. P. falciparum parasitized RBCs (pRBCs) display decreased deformability and novel cytoadherence properties, and sequester in the microcirculation. Parasite-exported proteins that interact with the pRBC membrane are identified as the cause for these alterations. It is postulated that sequestration of pRBCs is responsible for severe cases malaria. Previous studies of pRBC deformability could not characterize deformability over all parasite intra-erythrocytic developmental stages due to experimental limitations. In the present work, a technique based on optical tweezers is developed to permit testing of pRBC deformability over all intra-erythrocytic stages. Optical tweezers can measure the force versus displacement response of a single RBC in uniaxial tension. The membrane shear modulus, which is a major factor in determining overall RBC deformability, can be interpreted based on the single RBC force versus displacement response.
(cont.) Initial tests with optical tweezers conducted on healthy RBCs demonstrate that shear modulus values were consistent with accepted values from standard techniques. Next, deformability of P. falciparum pRBCs was measured at all intra-erythrocytic parasite developmental stages. Deformability is found to decrease ten-fold during parasitization, which is three to four times greater than previously estimated. Finally, optical tweezers experiments are combined with targeted gene disruption techniques to measure the effect of a single parasite-exported protein on pRBC deformability. It is shown that Ring-infected Erythrocyte Surface Antigen (RESA), a membrane binding parasite-exported protein, plays a major role in reducing deformability of pRBCs at the early stages of intra-erythrocytic parasite development. Furthermore, the effect of RESA ondeformability is more pronounced at febrile temperature, which early stage pRBCs can be exposed to during a malaria attack, than at normal body temperature.
by John Philip Mills.
Ph.D.
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Lentini, Tim. "Monocytes and dendritic cells in human peripheral blood." Thesis, Boston University, 2013. https://hdl.handle.net/2144/21204.
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Thesis (M.A.) PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.Inflammatory myeloid dendritic cells (DCs) are critical in the pathogenesis and maintenance of psoriasis vulgaris, a chronic inflammatory skin disease of unknown etiology. New ways to define these cells, and their precursors, may allow us to better understand their role in inflammation. Immunohistochemistry was performed on frozen tissue sections of normal and psoriasis biopsies to examine the dermal expression of potential markers of inflammatory DCs, namely CLEC9A, CD103, SlanDC, and TREM-1. The allostimulatory capacity of DC subsets (of SlanDC+ and CD1c+) was compared in a mixed leukocyte assay (MLR). Potential precursors of inflammatory DCs were FACS-sorted for transcriptomic profiling and functional assays. CLEC9A, CD103, and SlanDC did not prove useful in uniquely identifying myeloid dendritic cells in normal skin, and inflammatory dendritic cells in inflammation. TREM-1 was highly upregulated in psoriasis lesional skin as compared to non-lesional, and its activation may be critical in the maintenance of inflammation. Contrary to published findings, CD1c+ DCs possessed a higher allo-stimulatory capacity than SlanDCs, and induced greater IL-17 in T cells. TREM-1 may provide a novel therapeutic target for psoriasis treatment. The six circulating monocyte and dendritic cell populations in human peripheral blood were obtained via FACS sorting, and their genomic profiles will be examined. By comparing the genomic profiles of the six circulating monocyte and dendritic cell populations in human blood, and examining their allo- and autostimulatory capacities in a peptidoglycan (PGN) stimulated in vitro model of inflammation, the source of these inflammatory dendritic cells can be identified, and provide future targets of therapy for this psoriasis.
2031-01-01
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Balanant, Marie-Anne. "Experimental studies of red blood cells during storage." Thesis, Queensland University of Technology, 2018. https://eprints.qut.edu.au/119221/1/Marie-Anne_Balanant_Thesis.pdf.
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This project used mechanical testing and imaging techniques to understand how red blood cells age in an in vitro environment, and identified markers of red blood cell product quality. The damage caused to the cells by cold storage could lead to a reduced transfusion efficiency and potential improvements to current storage protocols were proposed as a result of this research.
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Barrett, Laura. "Microfluidic blood fractionation and lysis towards analysis of cytokine levels in red blood cells." Thesis, KTH, Skolan för elektroteknik och datavetenskap (EECS), 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-266109.
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In the process of blood analysis, for biomarker detection, blood plasma or serumis analyzed, while Red blood cells (RBCs) are usually considered waste. A recentstudy has found that cytokine concentrations in RBC lysate are on average 12-fold higher than in plasma. Microfluidic devices for the extraction of plasma fromwhole blood and containers of dried blood spots have already been developed.They o↵er a small tool size, low required sample volume, and low productioncost, which makes them suitable for point-of-care applications.In this thesis, an approach of isolating and lysing RBCs in a commercial bloodfilter using a microfluidic device was investigated. The design is based on a previouslydeveloped microfluidic device for plasma extraction. It was used for plasmaextraction, washing, and RBC lysing with RBC lysis bu↵er. The device’s functionalitywas examined, and the output lysate analyzed through measurements ofhemoglobin concentration, optical microscopy and an Elisa test of the cytokineIL-3.The results show that 48% of the devices were subject to one of two problems.One was slow filling of the capillary channel, and the other was the lysate beingvisibly clear. These problems were attributed to blood cells obstructing the filtersand increasing flow resistance. The device lysate viewed through an optical microscopewas shown to contain a significant amount of blood cells in some cases,suggesting that cells were passing through the filters. The mean lysis efficiency ofthe devices was determined to be 20%, which with the Elisa test results, suggeststhat there is low rates of mixing between the RBCs and the lysate within the filtermatrix. In conclusion, the tested method of isolating and lysing RBCs needs tobe improved in terms of reliability and efficiency. It was shown to work in someof the cases, and so shows promise for future development.Röda blodkroppar (RB) ses vanligtvis som avfall vid blodmatningar av biomarköreri plasma eller serum. Men en ny studie har funnit att koncentrationerna av cytokiner i lyserade RB är i snitt 12 gånger högre än i plasma. Mikrofluidiska apparater som extraherar plasma från helblod har redan utvecklats. Deras fördelarär att de är små, använder små provvolymer och är billiga att producera. Detta gör dem lampliga for patientnara analyser, eller s.k. point-of-care-användning.I det här arbetet prövas en metod för att isolera och lysera RB i ett kommersiellt blodfilter, med hjälp av en mikrofluidisk apparat. Designen av apparaten är baserad på en mikrofluidisk apparat som utvecklats för plasmaextrahering. Den används för plasmaextraktion, tvätt och lysering med lyseringsbu↵ert. Appa-ratens funktionalitet undersöktes, och RB-lysatet analyserades med mätningar avhemoglobinvärden, ljusmikroskopi och en Elisa-mätning av cytokinet IL-3.Resultaten visar att 48 % av apparaterna hade något av två problem. Det ena problemet var att den kapillära kanalen fylldes långsamt, och det andra var att lysatet var till synes ofärgat. Dessa problem tillskrivs att blodceller blockerar filtren och ökar flödesmotståndet. I ljusmikroskop visade sig lysatet från apparaten i vissa fall innehålla stora mängder blodceller. Detta tyder på att celler passerat igenom filtret. Medelvärdet av lyseringse↵ektiviteten i apparaterna visades vara 20 %. Tillsammans med Elisa-resultaten tyder detta på att vätskan i filtret blandas i otillräcklig utsträckning. Sammanfattningsvis behöver metoden för att isolera och lysera RB förbättras gällande tillförlitlighet och e↵ektivitet. Den visadesig fungera i vissa fall och är därför lovande för framtida utveckling.
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Pinzon-Charry, Alberto. "Characterisation of blood dendritic cells in patients with cancer /." [St. Lucia, Qld.], 2005. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe18933.pdf.
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劉恩梅 and Enmei Liu. "The development of cord blood monocyte-derived dendritic cells." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2002. http://hub.hku.hk/bib/B3124340X.
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Latham, Nicholas. "Second Generation Cardiac Cell Therapy: Combining Cardiac Stem Cells and Circulating Angiogenic Cells for the Treatment of Ischemic Heart Disease." Thèse, Université d'Ottawa / University of Ottawa, 2013. http://hdl.handle.net/10393/24293.
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Blood-derived circulatory angiogenic cells (CACs) and resident cardiac stem cells (CSCs) have both been shown to improve cardiac function after myocardial infarction (MI) but the superiority of either cell type has long been an area of speculation with no definitive head-to-head trial. In this study, we compared the paracrine profile of human CACs and CSCs, alone or in combination. We characterized the therapeutic ability of these cells to salvage myocardial function in an immunodeficient mouse model of MI by transplanting these cells as both single and dual cell therapies seven days after experimental anterior wall MI. CACs and CSCs demonstrated unique paracrine repertoires with equivalent effects on angiogenesis, stem cell migration and myocardial repair. Combination therapy with both cell types synergistically improves post infarct myocardial function greater than either therapy alone. This synergy is likely mediated by the complementary paracrine signatures that promote revascularization and the growth of new myocardium.
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Alférez, Baquero Edwin Santiago. "Methodology for automatic classification of atypical lymphoid cells from peripheral blood cell images." Doctoral thesis, Universitat Politècnica de Catalunya, 2015. http://hdl.handle.net/10803/308328.
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Morphological analysis is the starting point for the diagnostic approach of more than 80% of the hematological diseases. However, the morphological differentiation among different types of abnormal lymphoid cells in peripheral blood is a difficult task, which requires high experience and skill. Objective values do not exist to define cytological variables, which sometimes results in doubts on the correct cell classification in the daily hospital routine. Automated systems exist which are able to get an automatic preclassification of the normal blood cells, but fail in the automatic recognition of the abnormal lymphoid cells.
The general objective of this thesis is to develop a complete methodology to automatically recognize images of normal and reactive lymphocytes, and several types of neoplastic lymphoid cells circulating in peripheral blood in some mature B-cell neoplasms using digital image processing methods. This objective follows two directions: (1) with engineering and mathematical background, transversal methodologies and software tools are developed; and (2) with a view towards the clinical laboratory diagnosis, a system prototype is built and validated, whose input is a set of pathological cell images from individual patients, and whose output is the automatic classification in one of the groups of the different pathologies included in the system.
This thesis is the evolution of various works, starting with a discrimination between normal lymphocytes and two types of neoplastic lymphoid cells, and ending with the design of a system for the automatic recognition of normal lymphocytes and five types of neoplastic lymphoid cells.
All this work involves the development of a robust segmentation methodology using color clustering, which is able to separate three regions of interest: cell, nucleus and peripheral zone around the cell. A complete lymphoid cell description is developed by extracting features related to size, shape, texture and color. To reduce the complexity of the process, a feature selection is performed using information theory. Then, several classifiers are implemented to automatically recognize different types of lymphoid cells. The best classification results are achieved using support vector machines with radial basis function kernel.
The methodology developed, which combines medical, engineering and mathematical backgrounds, is the first step to design a practical hematological diagnosis support tool in the near future.Los análisis morfológicos son el punto de partida para la orientación diagnóstica en más del 80% de las enfermedades hematológicas. Sin embargo, la clasificación morfológica entre diferentes tipos de células linfoides anormales en la sangre es una tarea difícil que requiere gran experiencia y habilidad. No existen valores objetivos para definir variables citológicas, lo que en ocasiones genera dudas en la correcta clasificación de las células en la práctica diaria en un laboratorio clínico. Existen sistemas automáticos que realizan una preclasificación automática de las células sanguíneas, pero no son capaces de diferenciar automáticamente las células linfoides anormales. El objetivo general de esta tesis es el desarrollo de una metodología completa para el reconocimiento automático de imágenes de linfocitos normales y reactivos, y de varios tipos de células linfoides neoplásicas circulantes en sangre periférica en algunos tipos de neoplasias linfoides B maduras, usando métodos de procesamiento digital de imágenes. Este objetivo sigue dos direcciones: (1) con una orientación propia de la ingeniería y la matemática de soporte, se desarrollan las metodologías transversales y las herramientas de software para su implementación; y (2) con un enfoque orientado al diagnóstico desde el laboratorio clínico, se construye y se valida un prototipo de un sistema cuya entrada es un conjunto de imágenes de células patológicas de pacientes analizados de forma individual, obtenidas mediante microscopía y cámara digital, y cuya salida es la clasificación automática en uno de los grupos de las distintas patologías incluidas en el sistema. Esta tesis es el resultado de la evolución de varios trabajos, comenzando con una discriminación entre linfocitos normales y dos tipos de células linfoides neoplásicas, y terminando con el diseño de un sistema para el reconocimiento automático de linfocitos normales y reactivos, y cinco tipos de células linfoides neoplásicas. Todo este trabajo involucra el desarrollo de una metodología de segmentación robusta usando agrupamiento por color, la cual es capaz de separar tres regiones de interés: la célula, el núcleo y la zona externa alrededor de la célula. Se desarrolla una descripción completa de la célula linfoide mediante la extracción de descriptores relacionados con el tamaño, la forma, la textura y el color. Para reducir la complejidad del proceso, se realiza una selección de descriptores usando teoría de la información. Posteriormente, se implementan varios clasificadores para reconocer automáticamente diferentes tipos de células linfoides. Los mejores resultados de clasificación se logran utilizando máquinas de soporte vectorial con núcleo de base radial. La metodología desarrollada, que combina conocimientos médicos, matemáticos y de ingeniería, es el primer paso para el diseño de una herramienta práctica de soporte al diagnóstico hematológico en un futuro cercano.
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van, Veen Hendrik Theun. "Continuous proliferation and simultaneous maturation of haematopoietic stem cells into blood cell lineages." Thesis, University of Liverpool, 2014. http://livrepository.liverpool.ac.uk/2004970/.
Full textAbstract:
For decades, research has been focussed on finding a way to produce artificial blood as a resolution for the insufficient amount of blood components provided by donation and to provide a more transportable alternative with a longer shelf life. Red blood cells (RBCs) are the most common cell type in blood and are responsible for oxygen transport throughout the human body. It is therefore extremely important to find an alternative oxygen carrier whether these are tissue engineered RBCs or a chemically defined oxygen delivery system The study conducted for this thesis was part of a larger project called Redontap, and was aimed to develop a bioreactor for the manufacture of RBCs. During this research to produce RBCs from adult stem cells in vitro, the main goal was to upscale haematopoietic and erythroid cultures. Understanding the biological signals and their temporal magnitude involved in the division, maturation and migration of the CD34+ haematopoietic stem cells (HSCs) and their differentiated progeny would allow for a controlled continuous production of mature blood cells. The differentiation of HSCs into different blood cell types occurs within different bone marrow niches and so mimicry of the erythrocyte niche is likely to result in maximisation of the rate of red blood cell development. Published research provides evidence that peripheral blood mononuclear cells (PBMCs), including CD34- cells, will be advantageous for erythroid maturation. For this thesis, CD34+ cells were expanded within a population of PBMCs on a stromal layer to recreate a niche-like environment. This approach was also utilised with umbilical cord blood isolated MNCs (UBMCs) to compare HSC expansion potential and subsequently efficiency in erythroid maturation was analysed. Whereas the cell output was limited, differentiated cells proved positive for a range of RBC surface markers and haemoglobin content. As part of the aim for upscaling cell culture by translating static cultures to bioreactor processes, bioreactors with volumes varying between 250mL-3L were analysed for cell retention and viability to achieve high cell densities whilst refreshing culture medium, monitoring culture parameters (e.g. pH, dissolved oxygen), and introducing an hypoxia environment for mimicking the in vivo stem cell niche. In general, this research was focussed on improving dynamic culture conditions for generating higher numbers of cultured erythrocytes than so far has been achieved.
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Brand, Verena Beatrice. "Programmed cell death in Plasmodium infected normal and sickle trait red blood cells." [S.l. : s.n.], 2007.
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Evans, David. "The genetics of blood cell concentrations /." St. Lucia, Qld, 2003. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe17511.pdf.
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James, Francine O. "The rhythmic expression of circadian clock genes in human peripheral blood mononuclear cells : investigating the functional clock in circulating white blood cells." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=103024.
Full textAbstract:
The rhythmic expression of an autoregulatory loop of circadian clock genes underlies the intrinsic circadian rhythmicity in the central circadian pacemaker of the suprachiasmatic nucleus (SCN). Clock genes are also known to be rhythmically expressed outside the SCN and outside the brain. While these peripheral circadian oscillators are functional, their expression is chiefly coordinated by the central circadian pacemaker of the SCN. This thesis presents the first evidence of a functional circadian oscillator in human peripheral blood mononuclear cells (PBMCs). Measuring levels of RNA transcripts in PBMCs sampled throughout specific behavioural protocols permitted the characterization of these peripheral circadian oscillators in humans. The expression of clock genes HPER1, HPER2, and HPER3 peaks early after the time of typical awakening and demonstrates a significant circadian rhythmicity in PBMCs sampled from healthy young men that persists in time isolation and under the constant behavioural conditions of a constant routine (CR). The functional circadian oscillator in human PBMCs is also observable in the presence of the sleep/wake cycle. Using frequent sampling over 72 hours, it was determined that the patterns of HPER1 and HPER2 expression are comparable when sampled in the presence of a habitual sleep/wake cycle or during a CR. The expression of HBMAL1 in PBMCs was more variable under different behavioural conditions. The pattern of light and darkness exposure including bright light during night shifts, shielding from morning light and sleep in darkened quarters can induce adaptive phase delays in the endogenous circadian rhythms of cortisol secretion in night shift workers. In the presence of such a light intervention, the cortisol rhythm in night shift workers re-assumes an appropriate temporal alignment with the shifted sleep/wake schedule and cortisol levels peak near the shifted time of awakening. Following nine days of simulated night shift work, HPER1 and HPER2 expression in PBMCs is aligned to the shifted sleep/wake schedule of a typical night shift worker in the presence of a comparable light/darkness intervention. This thesis will consider the implications of a functional clock in human white blood cells in light of the demonstration of a functional and shiftable circadian oscillator in human PBMCs.