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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.
1

Transcriptomic approach to understanding and characterising disease pathogenesis in sarcoidosis

Kendrick, Yvonne Rene January 2017 (has links)
Sarcoidosis is a multisystem immunological disorder, centred on the dysregulation of T cell activity, macrophage activation and granuloma formation. Most pulmonary sarcoidosis patients have a good prognosis, but up to 20% can go on to develop lung fibrosis. Previous research in sarcoidosis has generally focused on sarcoidosis as a single disease entity, whereas this thesis has focused on the importance of phenotypical characterisation, in particular active fibrotic pulmonary disease, and the standardisation of measuring disease activity. I first developed a scoring system to measure disease activity based on typical findings on high resolution CT scanning (CTAS). I then identified a set of readily available blood markers and a chest radiographic score as a surrogate for the CT activity score, which enables the physician to easily assess the level of disease activity in the clinic setting (SCAS). Using a transcriptomic approach, I used the activity score to identify the immunological pathways and individual genes correlating directly with increasing activity, both at the site of disease and in the periphery. Enrichment of immune response and defense response gene sets, particularly in BAL cell samples, were observed as disease activity increased, with CCR2, TREM2, and CCL18 featuring as prominent genes involved in the propagation of activity. CXCL9 and CXCL10 were identified as peripheral markers of active disease reflecting the activity in various compartments. In addition, after phenotyping patients with active disease into those with and without fibrosis, differential gene expression showed enrichment of immune related gene sets in the fibrotic cohort, and highlighted the roles of several significantly upregulated genes including CCL19, CCR7, CXCR3, CCR2, ADAMDEC1 and MMP12 in the pathogenesis of fibrotic sarcoidosis. Finally, enrichment of an IPF signature derived from differential expression to sarcoidosis, was observed in the fibrotic sarcoidosis cohort. This information may lend itself to further therapeutic treatments options already used in other fibrotic lung conditions in this interesting and understudied phenotype.
2

Factors contributing to the maintenance and activation of corynebacterial pseudotuberculosis in the laboratory mouse

Bruce, David Lorne January 1969 (has links)
Corynebacterial pseudotuberculosis, a murine disease caused by Corynebacterium kutscheri, occasionally developed in numbers of the departmental strain of random-bred Swiss white mice 3 to 5 weeks following intraperitoneal injection of the Rauscher leukemia virus. Virulent C. kutscheri, extremely difficult to isolate from apparently healthy animals, was frequently cultured from the organs of animals presenting symptoms of the Rauscher disease without active pseudotuberculosis. Representative groups of the departmental strain showed uniformly high resistance to intravenous injection of virulent C. kutscheri in comparison to imported pathogen-free strains, yet succumbed to pseudotuberculosis in large numbers following cortisone treatment; therefore the entire colony was assumed to be latently infected by this organism. Two strains of C. kutscheri were isolated and compared to strains ATCC 15677 and ATCC 15678. The latter strain, a presumed non-pathogenic variant of the former, was compared by cell wall sugar and deoxyribonucleic acid base analysis to the pathogenic strain. It was not possible by these methods to find support for the variant hypothesis. Transfer of the latent state from the departmental strain to a pathogen free strain of mice was attempted by injection of homogenates of visceral organs, but transfer of latency was not successfully demonstrated. The sera of latently infected mice stimulated in vivo phagocytosis of C. kutscheri by mouse peritoneal macrophage, but it was not possible to demonstrate circulating C. kutscheri specific antibody in non-immunized animals. Immunized normal mice of all strains developed high titers of specific circulating antibody following injections of either heat killed C. kutscheri cells or virulent organisms in numbers too low to initiate infection. Circulating antibody was demonstrated by passive bacterial hemagglutination and by indirect fluorescent antibody staining. When immunization was attempted during early Rauscher disease, C. kutscheri antibody production was inhibited. Clearance studies with labeled C. kutscheri showed that the organism is cleared with exceptional rapidity by the reticuloendothelial system of latently infected mice, pathogen free mice and mice with early Rauscher disease. The clearance constant decreased slightly in the above order. / Science, Faculty of / Microbiology and Immunology, Department of / Graduate
3

The ultrastructural features of developing epithelioid cell granulomas in man

Sheffield, Edward Alexander January 1990 (has links)
No description available.
4

Lung functions studies in diagnostics and follow-up of pulmonary sarcoidosis

Brådvik, Ingela. January 1994 (has links)
Thesis (doctoral)--Lund University, 1994. / Added t.p. with thesis statement inserted.
5

Lung functions studies in diagnostics and follow-up of pulmonary sarcoidosis

Brådvik, Ingela. January 1994 (has links)
Thesis (doctoral)--Lund University, 1994. / Added t.p. with thesis statement inserted.
6

Orofacial granulomatosis : clinical and immunological studies

Gibson, John January 1998 (has links)
No description available.
7

Apoptosis in chronic inflammation, with specific reference to airway disease /

Müller, Malin, January 2006 (has links)
Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.
8

Biological Factors in the Etiology of Pulmonary Sarcoidosis

Schouten, Janine R. Unknown Date
No description available.
9

Cytokines and tuberculosis : an investigation of tuberculous lung tissue and a comparison with sarcoidosis

Bezuidenhout, Juanita 12 1900 (has links)
Thesis (PhD (Pathology. Anatgomical Pathology))--University of Stellenbosch, 2005. / The formation of granulomas at the site of antigen presentation in both tuberculosis and sarcoidosis is an essential component of host immunity for controlling inflammation. Granuloma formation is a complex process that also requires recruitment and activation of lymphocytes and macrophages to the site of infection and arrangement into a granuloma. It is dependant on the activation of especially IFNγ secreting CD4+ T cells, resulting in a Th1 profile. However, it is suggested that a persistently high IFNγ is responsible for the damage caused by granulomatous disease and that moderating cytokines, resulting in a Th0 profile, are necessary to down-regulate the IFNγ response to more appropriate levels later in the disease process, after the antigen has been effectively contained. I propose that: “Cytokine profiles determine clinical and histopathological phenotypes of disease. This thesis tests the hypothesis that it will be reflected by cytokine expression profiles in granulomas in different forms of tuberculosis and in sarcoidosis.” To examine this, biopsy tissue was obtained from patients with pulmonary cavitary tuberculosis, pleural tuberculosis in HIV sero-negative and sero-positive patients, and sarcoidosis. The diagnosis of tuberculosis or sarcoidosis was confirmed, granulomas were characterised as necrotic or non-necrotic, sarcoidosis cases were graded histologically and in situ hybridisation was performed for IL-12-, IFNγ-, TNFα- and IL-4-mRNA. In all patients with pleural tuberculosis, a Th0 profile was noted, while necrotic granulomas were more evident in HIV positive than HIV negative patients. There was a clear association between TNFα and necrosis in tuberculous granulomas that may be ascribed to the increased apoptotic activity of TNFα. An increase in IFNγ correlated with an increase in necrosis, supporting the theory that high IFNγ levels later in disease is detrimental. This effect may be enhanced by a strong presence of TNFα positive cells. An increase in both Th1 and Th2 cytokine mRNA in HIV positive patients supports the theory that an overproduction of cytokines may be a mechanism to compensate for the failure of another immune effector mechanism. Findings in pulmonary tuberculosis were similar to those in pleural tuberculosis. In all sarcoidosis cases the presence of a very strong Th1 and TNFα, but no Th0 response was confirmed. None of the differences in either the histological grading, or the clinical outcome of patients were reflected in the cytokine profile. It is possible that this profile does not reflect the histological grade of disease or that it may reflect various stages of disease. These findings support the theory that a strong Th1 presence later in disease, in conjunction with TNFα may induce fibrosis, as most of these cases showed signs of at least focal fibrosis. Numerous aspects, including a T helper response are involved in granulomatous inflammation. The earlier dogma of good, beneficial (Th1) versus evil, detrimental (Th2), is an oversimplification of a very complex process. It is clear that the effect of a cytokine depends at least partially on the stage of disease. The balance between the various cytokines, and the levels of these cytokines contribute to their role in resolution or disease progression. An early, pure Th1 response may be beneficial if effectively clearing the granuloma-inducing antigen. At this stage, a Th2 presence will be harmful as clearing of the antigen will not be as effective. In chronic disease where failure to remove the antigen results in progression of granulomas with subsequent necrosis and/or fibrosis, a proinflammatory Th1 response may be detrimental and minimising of this effect is needed. An overly strong presence of the various cytokines may also be detrimental, while lower levels will be beneficial.
10

Expression Profiling Elucidates a Molecular Gene Signature for Pulmonary Hypertension in Sarcoidosis

Singla, Sunit, Zhou, Tong, Javaid, Kamran, Abbasi, Taimur, Casanova, Nancy, Zhang, Wei, Ma, Shwu-Fan, Wade, Michael S., Noth, Imre, Sweiss, Nadera J., Garcia, Joe G. N., Machado, Roberto F. 12 1900 (has links)
Pulmonary hypertension (PH), when it complicates sarcoidosis, carries a poor prognosis, in part because it is difficult to detect early in patients with worsening respiratory symptoms. Pathogenesis of sarcoidosis occurs via incompletely characterized mechanisms that are distinct from the mechanisms of pulmonary vascular remodeling well known to occur in conjunction with other chronic lung diseases. To address the need for a biomarker to aid in early detection as well as the gap in knowledge regarding the mechanisms of PH in sarcoidosis, we used genome-wide peripheral blood gene expression analysis and identified an 18-gene signature capable of distinguishing sarcoidosis patients with PH (n = 8), sarcoidosis patients without PH (n = 17), and healthy controls (n = 45). The discriminative accuracy of this 18-gene signature was 100% in separating sarcoidosis patients with PH from those without it. If validated in a large replicate cohort, this signature could potentially be used as a diagnostic molecular biomarker for sarcoidosis-associated PH.

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