Thesis (M.D.)--University of Adelaide, Dept. of Paediatrics, 1991. / Includes bibliographical references (leaves 287-310).

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 104-120).

Orientador: Iracema de Mattos Paranhos Calderon / Coorientador: Adenilda Cristina Honório França / Banca: Yuri Karen Sinzato / Banca: Debora Cristina Damasceno Meirelles dos Santos / Banca: Mahmi Fujimori / Banca: Mara Sandra Hoshida / Resumo: Durante a gravidez, a hiperglicemia materna altera a expressão e a transferência de células imunorregulatórias e de imunoglobulinas e o perfil de citocinas na interface materno-fetal. Avaliar, em gestações complicadas por hiperglicemia, a expressão de células NK e o perfil de citocinas no sangue, materno e do cordão umbilical, e na placenta (artigo 1); quantificar a produção de anticorpos e a passagem de IgG total, e respectivas subclasses, via receptor FcRn (artigo 2). MÉTODO - Foram avaliadas 120 gestantes, distribuídas nos grupos: não-diabético (ND; N = 30), hiperglicemia gestacional leve (HGL; N = 30), diabetes mellitus gestacional (DMG; N = 30) e diabetes mellitus tipo 2 (DM2; N = 30). Técnicas de citometria de fluxo foram utilizadas para análise de células e citocinas e, de ELISA, para avaliação das concentrações de IgG total e subclasses. A transferência placentária de anticorpos totais, e respectivas subclasses, foi definida pela relação [(concentrações no sangue de cordão umbilical/sangue materno) x 100]. Na análise estatística foram realizadas análises de variância (ANOVA), seguida pelo teste de Tukey, e de correlação de Pearson, com p < 0,05. No sangue materno dos grupos hiperglicêmicos, as células NK CD16+CD56- aumentaram, enquanto que CD16+CD56+ foi menor no grupo DMG. No sangue do cordão do grupo DM2 mostrou uma maior proporção de células CD16+CD56- e CD16-CD56+. As camadas extravilosas da placenta dos grupos DMG e DM2 most... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: - During pregnancy, the immune response associated with diabetes alters the expression and the transfer of immune cells, including regulatory, immunoglobulins and the profile of cytokines in the maternal-fetal interface. To evaluate the expression of NK cells, and the profile of cytokines in maternal blood, umbilical cord and placenta, quantify the production of antibodies, as well as, the passage of IgG and subclasses, via receptors FcRn in pregnancies complicated by diabetes or hyperglycemia.Wereessed 120 pregnant women, distributed as non-diabetic (ND; n=30), Mild Gestational Hyperglycemia (MGH; n=30), Gestational Diabetes Mellitus (GDM; n=30) and type 2 Diabetes Mellitus (DM2; N=30). The cells and cytokines were evaluated by flow cytometry. The concentrations of total IgG and subclasses were analyzed by ELISA. Placental transfer of the total and subclasses antibodies were defined in each assay by the ratio [(cord concentrations/maternal concentrations) x 100]. In the statistical analysis we used analysis of variance (ANOVA), followed by Tukey test, and Pearson's linear correlation, with p < 0.05. RESULTS - In the maternal blood from the hyperglycemic groups, the CD16+CD56− NK cells increased, whereas that of CD16+CD56+ decreased in GDM group. Cord blood from DM2 showed a higher proportion of CD16+CD56− and CD16−CD56+. The placental extravillous layer of GDM and DM2 showed an increase of CD16+CD56− cells and, irrespective of region, the proportion of CD16−CD56+ cells was higher in MGH and GDM and lower in DM2. IL-2 was lower in maternal blood and IFN-���� higher in maternal and cord blood from the GDM group. IL-17 was higher in maternal and cord blood from the DM-2 group. The placental extravillous layer of the MGH showed high levels of IL-4, IL-6, IL-10, IL- 17, and IFN-���� and low levels of IL-1���� and IL-8, whereas the placental villous layer... (Complete abstract click electronic access below) / Doutor

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Although research has linked central nervous system activity with changes in immunoresponsivity, research on the possible role of the central nervous system in altering a specific class of antibody is lacking. This study was an investigation of the possible relationship between anterior or medial hypothalamic functions on Immunoglobulin G. concentrations in rat serum. Thirty-six male albino rats were randomly assigned to three groups of equal size. Animals within the anterior hypothalamic group received bilateral electrode implants in the anterior hypothalamus while animals in the medial hypothalamic group received electrode implants within the ventromedial area of the hypothalamus. A control group received bilateral electrode implants within the lateral hypothalamus. Electrical brain stimulation was administered to animals in both experimental groups. Control animals spent a comparable time in an operant chamber but did not receive electrical brain stimulation. Following brain stimulation of animals within the experimental groups, Immunoglobulin G. concentrations were determined for all groups 3, 6, 12, and 24 hours post-stimulation sessions.

Madariaga virus (MADV) has recently been associated with severe human disease in Panama, where the closely related Venezuelan equine encephalitis virus (VEEV) also circulates. In June 2017, a fatal MADV infection was confirmed in a community of Darien Province. We conducted a cross-sectional outbreak investigation with human and mosquito collections in July 2017, where sera were tested for alphavirus antibodies and viral RNA. In addition, by applying a catalytic, force-of-infection (FOI) statistical model to two serosurveys from Darien Province in 2012 and 2017, we investigated whether endemic or epidemic alphavirus transmission occurred historically. In 2017, MADV and VEEV IgM seroprevalences were 1.6% and 4.4%, respectively; IgG antibody prevalences were MADV: 13.2%, VEEV: 16.8%, Una virus (UNAV): 16.0%, and Mayaro virus: 1.1%. Active viral circulation was not detected. Evidence of MADV and UNAV infection was found near households, raising questions about its vectors and enzootic transmission cycles. Insomnia was associated withMADVand VEEV infections, depression symptoms were associated with MADV, and dizziness with VEEV and UNAV. Force-of-infection analyses suggest endemic alphavirus transmission historically, with recent increased human exposure to MADV and VEEV in Aruza and Mercadeo, respectively. The lack of additional neurological cases suggests that severe MADV and VEEV infections occur only rarely. Our results indicate that over the past five decades, alphavirus infections have occurred at low levels in eastern Panama, but that MADV and VEEV infections have recently increased-potentially during the past decade. Endemic infections and outbreaks of MADV and VEEV appear to differ spatially in some locations of eastern Panama. / National Institute for Health Research / Revisión por pares

Glycosylation is among the most common post-translational protein modifications. Glycans are complex carbohydrates attached to the surface of many proteins, but are rarely extensively studied in a high-throughput manner. However, there is an increasing evidence of their involvement in various physiological processes and diseases. Glycosylation of Immunglobulin G was shown to be important in adaptive immunity, where it can act as a "safety switch" for different types of the immune response. Although the main enzymes of the glycosylation pathway are known, little is understood about how this template-independent process is regulated to result in a faithful synthesis of a specific glycoform. This question was previously addressed using genome-wide association studies (GWAS) and 9 loci were identified as being significantly associated with IgG N-glycosylation. Only 4 of these loci were the known glycosylation enzymes. An additional five loci were discovered by applying a newly developed multivariate GWAS method on the same dataset. Here, by performing a GWAS on 77 IgG N-glycan traits measured by ultra-performance liquid chromatography in more than 8000 samples from four European cohorts the number of genome-wide significant (p? ≤ 2.4 x 10−9) loci increased to 27, 15 of which are novel, with 6 additional loci being suggestively associated (p? ≤ 2.4 x 10−8). To assess which of the genes from the associated loci are more likely to be regulating IgG glycosylation, different gene prioritising strategies were employed. For 7 loci evidence of a non-synonymous amino acid change was found, two of which were predicted to be deleterious. Evidence of regulation through changes in gene expression levels in B-cells, the cell lineage responsible for production of IgG, was found for 4 genes, with an additional 11 genes exhibiting the same evidence with expression in peripheral blood or other immune cells. For the remaining loci the most likely candidate gene was proposed based on co-expression with genes from the enriched gene-sets or based on a physical proximity to the variant with the strongest association. To narrow down the most important loci for a functional follow-up, the omics nature of this data was used to compare glycome-wide SNP effects and suggest how newly discovered loci form a functional network that regulates the established members of the glycosylation pathway. The potential role of IgG glycosylation in various complex traits and diseases was explored by assessing the pleiotropy of the associated SNPs. The inflation of SNPs related to autoimmune, digestive and neurological diseases was observed in glycosylation SNPs. To assess whether IgG N-glycosylation is likely to share the same causal variant as the identified pleiotropic traits and diseases, regional association patterns were compared using summary data based Mendelian Randomisation analyses. This work demonstrates that an increased sample size empowered the identification of novel loci, enabling further insights into the molecular mechanisms underlying protein glycosylation and its relationship with complex human diseases. It also shows that such analyses of omic traits can assist in creating a functional network of the identified loci, prioritising the most important genes and allowing a more focused approach to future experimental functional follow-up.

Bibliography: leaves 287-310 / 311 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (M.D.)--University of Adelaide, Dept. of Paediatrics, 1991

Spinal cord injury (SCI) is a devastating condition that causes its victims to experience functional deficits. Inflammation plays a complex role in the progression of SCI. While some inflammatory cells attenuate further damage to the spinal cord tissue, other inflammatory mediators exacerbate the damage. Attenuating the detrimental aspects of inflammation after SCI is an attractive neuroprotective strategy that could potentially lead to significant functional improvement. In this regard, intravenous immunoglobulin G (IgG), which has many proposed immuno-modulatory mechanisms, is a potential treatment candidate. In this study, we investigated the neuroprotective properties of IgG by examining its effects after SCI at the molecular, cellular, and neurobehavioral levels. We observed that IgG treatment after SCI is associated with significant reduction in pro-inflammatory mediators and significant improvement in neurobehavioral recovery compared to the control. The results of the study suggest that IgG could potentially be used as an immuno-modulatory therapy for SCI.

Spinal cord injury (SCI) is a devastating condition that causes its victims to experience functional deficits. Inflammation plays a complex role in the progression of SCI. While some inflammatory cells attenuate further damage to the spinal cord tissue, other inflammatory mediators exacerbate the damage. Attenuating the detrimental aspects of inflammation after SCI is an attractive neuroprotective strategy that could potentially lead to significant functional improvement. In this regard, intravenous immunoglobulin G (IgG), which has many proposed immuno-modulatory mechanisms, is a potential treatment candidate. In this study, we investigated the neuroprotective properties of IgG by examining its effects after SCI at the molecular, cellular, and neurobehavioral levels. We observed that IgG treatment after SCI is associated with significant reduction in pro-inflammatory mediators and significant improvement in neurobehavioral recovery compared to the control. The results of the study suggest that IgG could potentially be used as an immuno-modulatory therapy for SCI.