Thesis (M.S.)--University of Wisconsin--Madison, 1967. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (M.S.)--University of Wisconsin--Madison, 1966. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (doctoral)--München, 1982.

No description available.

No description available.

Thesis (Ph. D.)--University of Queensland, 2001. / Privately bound. Includes bibliographical references.

No description available.

Encephalitis lethargica affected a large number of people in the pandemic in the early 1900s (von Economo, 1930). Histological and biochemical data suggest that autoimmune mechanisms play an important role in this disorder and recently serum anti-basal ganglia antibodies (ABGA) have been detected in affected sporadic cases associated with evidence of recent streptococcal infection (Dale et al., 2004a). ABGA are also associated with other neuropsychiatric disorders including Sydenhams chorea, paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, Tourettes syndrome and obsessive compulsive disorder. The precise frequency, presentation, disease course, treatment response and causes of these disorders are still unknown. As ABGA are strongly associated with recent streptococcal infection, these disorders represent a potentially good model for the study of molecular mimicry and autoimmunity. The present study focussed on various aspects of this group of disorders. Profiling of group A streptococcus isolates from both patients with postulated post-streptococcal disorders of the CNS and controls was done which highlighted differences in virulence factors like M protein and superantigens between the two groups. Also in the present study we demonstrated the pathogenicity of anti-neuronal antibodies found in patients in both an in vivo and in vitro setting. An animal model of the disorders was produced by passive transfer of antibodies from patients which resulted in symptoms reminiscent of diseases like encephalitis lethargica and dystonia. An active immunization animal model using GABHS proteins and recombinant proteins (putative autoantigens) was also developed. Furthermore, the autoantibodies from patients and animal models were analysed on both neuronal and non-neuronal cells where they demonstrated to have a functional effect on cytotoxicity, apoptosis, calcium flux and enolase activity. N-methyl D-aspartate glutamate receptor and voltage gated potassium channel have been recently been implicated in a 16 range of neurological disorders, hence we also tested the patient sera for antibodies against these receptors and found a group of patients to be positive. In summary, EL and other ABGA-associated disorders are still an emerging entity, with major implications for neuropsychiatry. As auto-antibody mediated diseases respond to immunomodulatory therapy, identifying and defining the pathogenesis of these disorders is important so that patients can be appropriately treated.

[Truncate abstract] Flaviviruses are small, positive-stranded RNA viruses belonging to the family Flaviviridae. Flavivirus infection in humans could cause diseases ranging from febrile illnesses to fatal encephalitis. Mice provide a useful small animal model to study flavivirus-induced encephalitis in humans since mice also develop encephalitis during flavivirus infection. Some strains of mice have been shown to be resistant to flavivirus challenge and this resistance is conferred by a single autosomal dominant gene, designated as Flvr. Recently, OAS1b gene has been identified to be a gene candidate for Flvr. Several congenic resistant mouse strains have been developed by introducing resistance genes from outbred or wild mice onto the genetic background of susceptible C3H mice. These new resistant strains that carry different allelic variants at the Flv locus include C3H/PRI-Flvr (RV), C3H.MOLD-Flvmr (MOLD) and C3H.M.domesticus-Flvr-like (DUB), the latter two being developed in the same laboratory in which the work described in this thesis was accomplished. Preliminary studies in this laboratory found that flavivirus resistant mice are vulnerable to certain flavivirus infections, particularly when challenged by intracerebral (i.c.) route. Intracerebral (i.c.) challenge with flaviviruses such as West Nile virus (WNV) Sarafend strain and Kunjin virus (KUNV) MRM16 strain were found to induce high mortality in flavivirus resistant mice while infection with Murray Valley encephalitis virus (MVEV) OR2 strain did not cause any apparent disease in the same mice. ... Thus, it can be concluded that CD8+ T cells exerted harmful effect to resistant DUB mice during KUNV i.c. infection by producing excessive IFN[gamma] that could be toxic, causing functional loss of the CNS cells. It was shown from in vitro studies that WNV had the highest tropism for macrophages and dendritic cells, followed by KUNV. MVEV however did not replicate well in these cells. This combined with the data from the in vivo studies indicates that macrophages might be involved in the pathogenesis of intraperitoneal (i.p.) infection of WNV but not KUNV and MVEV. The reason for this could be that the production of KUNV in macrophages may not be high enough to induce viraemia and subsequent fatal encephalitis in mice. In contrast, MVEV appears to use different mechanism or cells for virus dissemination. Although macrophages may not be involved in KUNV pathogenesis after i.p. infection, the fact that macrophages support KUNV replication in vitro may indicate the possibility that blood-borne macrophages were recruited to the brain where they can get infected with KUNV during i.c. infection and therefore could participate in KUNV pathogenesis in DUB mice. This study provides evidence for the first time on the detrimental effect of host antiviral immunity and inflammatory mediators during flavivirus i.c. infection in resistant mice. However, it also launches a new question on the selective cell tropism of KUNV versus MVEV responsible for inducing different pattern of immune responses and consequently leading to different outcomes of infection in resistant mice.

Thesis (M.S.)--University of Tennessee, Knoxville, 2003. / Title from title page screen (viewed Sept. 17, 2003). Thesis advisor: Reid R. Gerhardt. Document formatted into pages (viii, 67 p. : ill., maps, charts). Vita. Includes bibliographical references (p. 62-66).