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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
21

Studies of Eosinophil Cationic Protein (ECP) in vivo and in vitro : Impact of Genetic and Posttranslational Modifications / Studier av Eosinophil Cationic Protein (ECP) in vivo och in vitro : Effekter av genetiska och posttranslationella modifieringar

Eriksson, Jenny January 2007 (has links)
<p>Eosinophil granulocytes are tissue dwelling leukocytes that are implicated in host defence, particularly against helminthic parasites; they also participate in most inflammatory disorders. Although eosinophils have important roles in host defence mechanisms, their actions can also be harmful to the host as in the allergic inflammation where lung epithelium is destructed due to the release of toxic granule proteins. </p><p>The focus of the present thesis work has been to characterize the molecular and functional heterogeneity of the granule protein Eosinophil Cationic Protein (ECP). We investigated a coding ECP gene polymorphism (arg97thr) in an African population endemically exposed to the <i>Schistosoma mansoni</i> parasite and found a correlation between ECP genotype and disease manifestations; ECP<sup>97arg</sup> was more effective in terms of host defence against the parasite, but was also correlated to development of liver fibrosis in infected subjects. </p><p>We purified ECP<sup>97arg</sup> and ECP<sup>97thr</sup> from healthy blood donors and showed that they differ in their cytotoxic activities; ECP<sup>97arg</sup> was cytotoxic whereas ECP<sup>97thr</sup> was non-cytotoxic. They did not differ in terms of RNase activity or in their ability to stimulate fibroblast-mediated collagen gel contraction. </p><p>We developed a new SELDI-TOF MS assay to enable the study of the structure of ECP in more detail and showed that ECP is produced in several glycosylated forms, and that the degree of glycosylation determines the cytotoxic activity. Enzymatic deglycosylation significantly enhanced the cytotoxic activity of highly glycosylated ECP-variants.</p><p>To summarize, in this thesis we demonstrated that the cytotoxic activity of ECP is dependent on both a gene polymorphism and post-translational modifications, and that the cytotoxic activity is distinct from other functions of ECP. We speculate that ECP is synthesised in heavily glycosylated variants as a means to protect the host from its harmful effects and that ECP is activated by deglycosylation when required at the site of inflammation.</p>
22

Mechanisms of granule protein mobiliation in blood eosinophils

Karawajczyk, Malgorzata January 2000 (has links)
Serum levels of eosinophil granule proteins namely ECP, EPO and EPX, which are stored in the matrix of specific granules, were shown to correlate with the course of disease in disorders involving eosinophils. The concentration of eosinophil proteins in serum is the result of their release in vivo and ex vivo during the sampling procedure. Generally, eosinophils release the content of their specific granules in three ways: exocytosis, piecemeal degranulation (PM) or cytolysis. Which of them is operating in circulating eosinophils has not yet been defined. The aim of this thesis was to study the mechanisms of granule protein release from blood eosinophils in respect of protein subcellular localization and cell ultrastructure. In patients with bacterial infections, serum levels of ECP but not EPO increased, while in patients with viral infections both proteins remained within the range of healthy controls. G-CSF is a cytokine involved in the response mechanism to bacterial but not viral infections. Administration of G-CSF to healthy subjects induced an elevation of eosinophil numbers and a preferential increase of serum EPX and ECP in comparison to EPO. The model of PM consists of the stepwise transportation of specific granule contents from the granules towards the plasma membrane. We observed that administration of G-CSF to healthy subjects and the allergen exposure of allergic subjects during the pollen season, caused changes in the ultrastructure of eosinophil specific granules such as loosening of the matrix, granule matrix lucency and ragged losses of their core. Similar alterations of morphology had been previously described for eosinophils undergoing PM. ECP, EPX and EPO were localized not only in the specific granules but also in extra-granular compartments as shown both by immuno electron microscopy and subcelular fractionations, An extra-granular EPX compartment was present in healthy as well as in allergic and in hypereosinophilic subjects, and there were no significant differences in its size between the groups. The size of the extra-granular compartments of ECP and EPO was increased in allergics during the season, and these compartments were clearly separate from that of EPX. Results of this show the differential mobilization ofgranule proteins in blood stream eosinophils serum and indicates PM as its mechanism.
23

Studies of Eosinophil Cationic Protein (ECP) in vivo and in vitro : Impact of Genetic and Posttranslational Modifications / Studier av Eosinophil Cationic Protein (ECP) in vivo och in vitro : Effekter av genetiska och posttranslationella modifieringar

Eriksson, Jenny January 2007 (has links)
Eosinophil granulocytes are tissue dwelling leukocytes that are implicated in host defence, particularly against helminthic parasites; they also participate in most inflammatory disorders. Although eosinophils have important roles in host defence mechanisms, their actions can also be harmful to the host as in the allergic inflammation where lung epithelium is destructed due to the release of toxic granule proteins. The focus of the present thesis work has been to characterize the molecular and functional heterogeneity of the granule protein Eosinophil Cationic Protein (ECP). We investigated a coding ECP gene polymorphism (arg97thr) in an African population endemically exposed to the Schistosoma mansoni parasite and found a correlation between ECP genotype and disease manifestations; ECP97arg was more effective in terms of host defence against the parasite, but was also correlated to development of liver fibrosis in infected subjects. We purified ECP97arg and ECP97thr from healthy blood donors and showed that they differ in their cytotoxic activities; ECP97arg was cytotoxic whereas ECP97thr was non-cytotoxic. They did not differ in terms of RNase activity or in their ability to stimulate fibroblast-mediated collagen gel contraction. We developed a new SELDI-TOF MS assay to enable the study of the structure of ECP in more detail and showed that ECP is produced in several glycosylated forms, and that the degree of glycosylation determines the cytotoxic activity. Enzymatic deglycosylation significantly enhanced the cytotoxic activity of highly glycosylated ECP-variants. To summarize, in this thesis we demonstrated that the cytotoxic activity of ECP is dependent on both a gene polymorphism and post-translational modifications, and that the cytotoxic activity is distinct from other functions of ECP. We speculate that ECP is synthesised in heavily glycosylated variants as a means to protect the host from its harmful effects and that ECP is activated by deglycosylation when required at the site of inflammation.
24

Clinical and Experimental Studies on Inflammatory Bowel Disease with special emphasis on Collagenous Colitis

Wagner, Michael January 2010 (has links)
This thesis describes studies in patients with inflammatory bowel disease (IBD) and collagenous colitis (CC). We investigated mucosal eosinophil and neutrophil granulocytes and T-cells involved in the inflammatory processes and aimed at determining whether these processes are reflected in the faecal (F) contents of specific proteins secreted by cells in the intestinal mucosa. Thus, we measured eosinophil cationic protein (ECP) and eosinophil protein X (EPX) and the neutrophil derived myeloperoxidase (MPO) and calprotectin (C); and in addition, chromogranin A (CgA), Chromogranin B (CgB) and secretoneurin (SN), derived from EEC cells and cells in the enteric nervous system. We found that a normalised FC level can serve as a surrogate marker for successful treatment in patients with IBD, but persistently high FC levels need further evaluation (study I). Furthermore, FC and F-MPO appear to relate better than F-EPX to treatment outcome in IBD. We evaluated F-ECP, F-EPX, F-MPO and FC as markers of disease activity and treatment outcome in patients with CC (study III) and concluded that F-ECP was the best discriminator of detecting active CC. Normalised F-ECP and F-EPX could serve as markers of successful treatment. We showed that the inflammation in CC is characterised by activated eosinophils, but that there is no neutrophil activity (study II). T-cells have a lower grade of activity in active CC than in control subjects. During budesonide treatment the normal activation of eosinophils and T-cells is restored, with concomitant clinical remission. The findings in studies II and III indicate that the eosinophils have an essential role in the pathophysiology of CC. Markedly higher values of F-CgA, F-CgB and F-SN were found in patients with CC than in those with IBD and controls (study IV) indicating a crucial role for the intestinal neuro-endocrine system in the pathogenesis of collagenous colitis.
25

A plan-do-check-act framework for WEEE and RoHS : a model for implementing WEEE and RoHS by integrating eco-design factors and activities into business operation and strategy.

El-Gomla, Randa A.M. January 2011 (has links)
Eco-design is relatively new and fast growing field of research due to its vital importance to the manufacturing industry and its related environmental issues such as reducing waste, and CO2 emission. A major EU programme relating to the environment is the waste of Electrical and Electronic Equipment (WEEE) directive. The (WEEE) directive specifies ten categories and a voltage range which is up to 1.000 volts AC or 1.500volts DC. The developed framework came for the implementation of Eco-design principles that helps to take into account the adaption of the (WEEE) directive and the restriction of hazard substances (RoHS) used in electrical and electronic equipments. As a result of identify gaps and needs such as a lack of a comprehensive Eco-design framework and the need to integrate it to the normal business operation. In this research the PDCA framework for Eco-design and WEEE directive will be discussed. The framework will encompass all of the Eco-design¿s implementation and integration factors and activities such as WEEE and RoHS directives, Eco-design management, Environmental legislations, Eco-design tools and considerations. The literature review covers the topic of Eco-design¿s related issues, and WEEE and RoHS directives rules. Based on comprehensive questionnaire survey of Eco-design, WEEE and RoHS issues and activities among a sample of environmentally aware companies, statistical analysis is carried out using SPSS software. Then the findings of the survey triangulated with the findings of the literature review formed the basis of the design and implementation plan of the proposed framework
26

Development and improvement of methods for characterization of HPLC stationary phases

Undin, Torgny January 2011 (has links)
High Performance Liquid Chromatography (HPLC) is a widely used tech-nique both for detecting and purifying substances in academy and in the industry. In order to facilitate the use of, and knowledge in HPLC, character-ization of stationary phases is of utmost importance. Tailor made characteri-zation methods and workflows are steadily increasing the speed and accura-cy in which new separation systems and methods are developed. In the field fundamental separation science and of preparative chromatography there is always the need for faster and more accurate methods of adsorption isotherm determination. Some of that demand are met with the steadily increase of computational power, but the practical aspects on models and methods must also be further developed. These nonlinear characterization methods will not only give models capable of describing the adsorption isotherm but also actual values of local adsorption energies and monolayer saturation capacity of an individual interaction sites etc.The studies presented in this thesis use modern alkali stable stationary phas-es as a model phase, which will give an insight in hybrid materials and their separation mechanism. This thesis will include an update and expansion in using the Elution by Characteristic Points (ECP) method for determination of adsorption isotherms. The precision is even further increased due to the ability to use slope data as well as an increase in usability by assigning a set of guidance rules to be applied when determine adsorption isotherms having inflection points. This thesis will further provide the reader with information about stationary phase characterization and the power of using existing tech-niques; combine them with each other, and also what the expansion of meth-ods can revile in terms of precision and increased usability. A more holistic view of what benefits that comes with combining a non-linear characteriza-tion of a stationary phase with more common linear characterization meth-ods are presented.

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