Thesis (M.S.)--Ball State University, 2009. / Title from PDF t.p. (viewed on June 08, 2010). Includes bibliographical references (p. 39-42).

Thesis (M. Phil.)--University of Hong Kong, 2005. / Title proper from title frame. Also available in printed format.

Systemic Lupus Erythematosus (SLE) is an autoimmune disease with chronic inflammation affecting multiple organ systems, as well as accelerated atherosclerosis as a major complication. Prior studies by our lab have shown beneficial effects of PPARgamma agonists towards preventing SLE in two different mouse models: the well-established lupus mouse model, MRL.lpr, and the gld.apoE^-/- model of accelerated lupus and atherosclerosis. Retinaldehyde is a retinoic acid precursor that has recently been shown to inhibit PPARgamma signaling in adipose tissue. We proposed that abnormal accumulation of retinaldehyde in lupus promotes autoimmunity by inhibition of PPARgamma signaling. We measured the serum retinaldehyde levels in both lupus mouse models using reversed-phase high-performance liquid chromatography. We also examined the mRNA expressions of genes involved in retinaldehyde metabolism and PPARgamma signaling in white adipose tissues using real-time quantitative PCR. We observed a higher level of circulating retinaldehyde in the MRL.lpr mouse model on a chow diet. The circulating retinaldehyde levels in both .gld.apoE^-/- and C57 increased when maintained on a high-cholesterol Western diet. Within visceral and subcuntaneous adipose tissue, we saw several changes to expression of the genes responsible for retinaldehyde synthesis and catabolism, however further study is required to definitively assess the role of these genes. Importantly, the expression levels of genes involved in PPARgamma signaling decreased in the subcutaneous fat of gld.apoE^-/- mice on a Western diet. Our data suggest that retinaldehyde may play a role in SLE pathogenesis and could be a potential therapeutic target for SLE.

OBJECTIVE: Atherosclerotic disease progression is mediated in part, by immunological mechanisms. In recent years, interest has increased towards the prospect of modulating these immune mechanisms through vaccination to ameliorate the course of disease. Patients with lupus are at a significantly higher risk for accelerated atherosclerosis and related complications. The goal of this study was to assess the outcome of immunization in mouse models of lupus, and lupus with accelerated atherosclerosis. MATERIALS/METHODS: Atherosclerosis-prone apoE^-/- mice and autoimmune gld mice were previously crossed to generate the gld.apoE^-/- mouse. Mice were treated with an apoB-100-derived vaccine, Alum (adjuvant control), or PBS control. The antibody response was determined by quantifying the amount of circulating anti-apoB100. Serum triglyceride and cholesterol levels were analyzed. Kidney tissue from gld and gld.apoE^-/- mice was processed and histologically analyzed, using glomerular tuft size as a measure of renal disease and by extension, autoimmune disease severity. Results: Immunization led to a pronounced initial antibody response that was decreased by the endpoint of the study. No significant differences in serum triglyceride or cholesterol were observed regardless of treatment. Similarly, no significant differences were observed in glomerular tuft size. Conclusion: The data suggests that immunization with an apoB-100- derived vaccine neither improves nor worsens autoimmune disease severity in the gld.apoE^-/- mouse model. It also appears that immunization is tolerated in the autoimmune background. While further study is necessary to determine the efficacy of immunization in reducing atherosclerotic disease in this model, this may be a possible therapy to lower incidence of atherosclerosis in lupus patients.

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No description available.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by loss of immune tolerance and the production of auto-antibodies which target various nuclear components. There is a 9:1 women to men ratio among lupus patients, indicating differing mechanisms of lupus pathogenesis between the sexes. Although lupus patients may develop many different manifestations, lupus nephritis (LN) remains to be one of the most devastating manifestations and an indicator of poor prognosis. Although both sexes develop LN, the nephritis in males often develops more rapidly and is more severe. Necrotic cell death is a characteristic of lupus nephritis and contributes to the exacerbation of the inflammatory immune response within the glomeruli. Previously our laboratory found that absence or pharmacological inhibition of Poly [ADP-ribose] polymerase 1 (PARP-1), an enzyme involved in necrotic cell death, results in milder nephritis, reduced necrotic lesions, and higher survival rates only among males. Although RIPK3-mediated necrosis was a likely candidate for inducing necrosis during female LN, murine models of glomerulonephritis revealed that the development of LN occurs independently of RIPK3. In addition, during LN, there is no crosstalk between the RIPK3- and PARP-1 mediated pathways to induce necrotic cell death. The sex bias in SLE indicates sex hormones may play a role in pathogenesis. Interestingly, estrogen receptor alpha (ERα) in the renal tissue is highly expressed and the renal specific estrogen-induced gene activation is second only to that of reproductive organs. The absence of estrogen receptor alpha protects female mice from developing nephritis, despite the presence of immune complexes in the kidneys and production of pro-inflammatory cytokines. Analysis of gene expression changes during LN progression indicate the protection seen in ERKO females may be due to alterations in metabolic pathways, including PPAR and retinol metabolism. These results demonstrate the complexity of lupus nephritis. Despite the presence of necrosis in LN, this manifestation occurs in a RIPK3-independent manner, which leaves the pathway responsible for necrosis in female kidneys to still be investigated. In addition, lupus nephritis occurs in an ER-dependent manner in females, demonstrating the significant impacts sex-hormone environments play in the pathogenesis of immune-mediated nephropathies. / Biomedical Sciences

Wigging Out, a memoir, chronicles my first chemotherapy treatment which began in 2008 for the autoimmune disease Lupus. The primary focus is on how identity is affected by disability. Each symptom of my disease and side effect from my medications prompted a reevaluation of my identity as I felt a change both in myself and in the way others perceived me. In order to maintain a sense of control, I tried several techniques to pass and cover my disabled status, including the use of prosthetic hair pieces. Ultimately, the use of prosthetics made accepting my situation more difficult as it encouraged holding onto a former identity rather than creating a new one. It was not until I stopped using prosthetics as a form of denial and instead adopted them as part of a new identity that I was finally able to achieve the confidence necessary to fight for my life. / by Jeanette Moffa. / Thesis (M.F.A.)--Florida Atlantic University, 201?. / Includes bibliography. / Mode of access: World Wide Web. / System requirements: Adobe Reader.

published_or_final_version / Medicine / Master / Master of Research in Medicine

 Neuropsychiatric systemic erythematosus (NPSLE) is a complicated complication of systemic erythematosus (SLE). Asian patients are associated with high prevalence of systemic disease and mortality It increases patients’ morbidity and mortality (Samanta et al., 1991). But the detailed pathology and pathogenesis are still remained unclear. Our study’s purpose is to use advanced functional imaging method, including diffusion tensor imaging (DTI) and magnetic resonance spectroscopy imaging (MRSI) to detect intracranial volumetry, functional and other metabolite changes in NPSLE patients. We recruited 3 age-matched female groups, one patient group with NPSLE (20 patients), one patient group with SLE (20 patients) and one control group (15 normal controls). Each patient was applied to structural 3D-T1 and axial T2, DTI and MRSI. Whole brain volumetry and hippocampus volumetry were analyzed by FSL and MARINA software from T1 images. White matter hyperintensity was calculated manually. Whole brain FA and other indices were collected. Regional FA was also collected and was collected with MRS over corpus callosum slice. The result showed no significant whole brain atrophy in NPSLE patients and SLE patients compared with controls. But with segmentation of grey matter, white matter and CSF, NPSLE patients showed significant decrease volume from SLE patients in white matter. Left hippocampus showed significant decreased volume in white matter and grey matter compared with control, while right hippocampus showed significant decreased volume in white matter. No other significant difference was found between NPSLE vs SLE and SLE vs controls. Whole brain FA was significantly decreased in NPSLE compared to SLE and controls, but not significantly different between SLE and controls. MD, λ∥ and λ⊥ were significantly increased in NPSLE and SLE compared with controls, but not significantly different between SLE and controls. White matter hyperintensity score was consistent with MD, λ∥ and λ⊥ results, showed significantly higher scores in two patients groups compared to controls. Regional FA, involving frontal lobes and corpus callosum, periventricular regions adjacent to centrum semiovale and posterior lateral temporal lobe, confirmed the regional FA decrease showed in whole brain FA statistical color map and NPSLE patients’ regional FA decrease correlated with MRS metabolic changes. N-acetyl aspartate (NAA)/ Creatine (Cr), the marker of neurons, decreased significantly in NPSLE patients compared with SLE and controls. Choline (Cho)/Cr showed significant increase of tendency of significant increase in NPSLE and SLE patients in some ROIs compared with controls. Our finding suggested that, although the whole brain atrophy is not obvious in NPSLE, the hippocampus and white matter suffered atrophy in NPSLE patients. These atrophy in white matter of whole brain and hippocampus combined with functional imaging results of DTI and MRS, indicated that NPSLE endured more severe axonal damage than SLE, which might be due to a variety of lesions, such as demyelination, microangiopathy, large vessel thrombosis, cytokine, etc. Varying ratio of NAA/Cr and Cho/Cr may be associated with the severity of axonal damage, probably due to demyelination in the background of inflammatory/ischemic/vasculitic changes. / published_or_final_version / Diagnostic Radiology / Master / Master of Philosophy