Thesis (Ph. D.)--Oregon State University, 2007. / Printout. Includes bibliographical references. Also available on the World Wide Web.

Thesis (MHSc--Health Science) -- AUT University, 2008. / Includes bibliographical references. Also held in print (ix, 144 leaves ; 30 cm.) in the Archive at the City Campus (T 613.954 WAE)

Thesis (Ph. D.)--University of Washington, 1996. / Vita. Includes bibliographical references (leaves [83]-96).

Thèse (M.Sc.)--Université Laval, 2004. / Bibliogr.: f. 62-76. Publié aussi en version électronique.

Abstract Chlamydia pneumoniae is a common, widespread pathogen that causes acute and chronic infections. Serological diagnosis of C. pneumoniae infection is primarily based on the microimmunofluorescence (MIF) method, but only a fourfold IgG antibody increase between paired sera and the presence of IgM antibodies have generally been accepted as markers of acute infection. At the present, no commonly accepted, reliable serological or other methods for the diagnosis of chronic C. pneumoniae infection exist. We evaluated C. pneumoniae specific serological tests in different populations, followed the kinetics of C. pneumoniae antibodies in multiple sera obtained from the same individuals, compared anti-human IgA FITC conjugates in MIF test and evaluated C. pneumoniae specific antibody tests before and after coronary events in case-control pairs matched for the time point of serum sampling, place of residence, and treatment. We showed that reinfection or reactivation is needed for the persistence of elevated IgG and IgA antibody levels. In chronic infections and upon reactivation, chronic processes may be better diagnosable based on IgA persistence than IgG levels because of the rapid disappearance of IgA levels after seroconversions. The cycle of reinfection and reactivation seems to be faster than previously thought in crowded conditions, such as in military service, since we recorded several antibody changes between the arrival and departure sera of military recruits during 6-month service. The presence of antibodies does not provide protection from reinfection. Commercial anti-human IgA conjugates act differently in MIF tests, and there is marked variation in their ability to detect IgA antibodies. The EIA test used here overestimated the prevalence and persistence of IgA antibodies when compared to MIF. The best compability between MIF and EIA antibody levels was seen in the participants with high titers. Only high IgA MIF titers to C. pneumoniae at the baseline predicted future coronary events. In the present study, seroconversions both in the participants who developed a coronary event and in the controls were detected by MIF and EIA, but mostly in different persons. Seroconversion suggesting reinfection or reactivation of persistent infection may have a role in accelerating chronic processes, because the participants with MIF seroconversion between consecutive sera had a slightly higher risk for coronary events than the controls. EIA seroconversions were more common in the controls than in the cases before the coronary event. The difference in the kinetics of EIA and MIF antibodies warrants future research and supports the use of the MIF method as a golden standard in the measurement of C. pneumoniae IgG and IgA antibody levels and seroconversions. In their diagnostic practice, laboratories should use, compare, and validate more C. pneumoniae IgA antibody tests in addition to IgG tests. Unspecific findings in C. pneumoniae EIA tests require re-estimation and a new way to interpret the results. Chlamydia experts should speak for MIF and rethink the meaning of IgA antibodies and recommendations in the diagnosis of C. pneumoniae infections.

Diss. (sammanfattning) Linköping : Univ., 2004. / Härtill 5 uppsatser.

Genomic analysis is a new approach for the characterization and investigation of novel genes, gene clusters, the function of uncharacterized proteins, and genetic diversity in microorganisms. These approaches are important for the study of chlamydiae, a system in which several genomes have been sequenced but in which techniques for genetic manipulation are not available. The objective of this thesis is to combine computer-based analysis of chiamydial inclusion membrane proteins (Incs) with cellular and molecular biological analysis of the bacteria. Three different experimental lines of investigation were examined, focusing on Incs of C. trachomatis and C. pneumoniae. Chlamydiae are obligate intracellular bacteria that develop within a nonacidified membrane bound vacuole termed an inclusion. Putative Inc proteins of C. trachomatis and C. pneumoniae were identified from genomic analysis and a unique structural motif. Selected putative Inc proteins are shown to localize to the inclusion membrane. Chiamydia trachomatis variants with unusual multiple-lobed, nonfusogenic, inclusion were identified from a large scale serotyping study. Fluorescence microscopy showed that IncA, a chiamydial protein localized to the inclusion membrane, was undetectable on non-fusogenic inclusions of these variants. Sequence analysis of incA from non-fusogenic variant isolates revealed a defective incA in most of the variants. Some variants lack not only IncA on the inclusion membrane but also CT223p, an additional Inc protein. However, no correlation between the absence of CT223p and distinctive inclusion phenotype was identified. Nucleotide sequence analysis revealed sequence variations of C. trachomatis incA and CT223 in some variant and wild type isolates. Comparative analyses of the three recently published C. pneumoniae genomes have led to the identification of a novel gene cluster named the CPn1O54 gene family. Each member of this family encodes a polypeptide with a hydrophobic domain characteristic of proteins localized to the inclusion membrane. These studies provided evidence that gene variation might occur within this single collection of paralogous genes. Collectively, the variability within this gene family may modulate either phase or antigenic variation, and subsequent physiologic diversity, within a C. pneumoniae population. These studies demonstrate the genetic diversity of Inc proteins and candidate Inc proteins, within and among the different chiamydial species. This work sets the stage for further investigations of the structure and function of this set of proteins that are likely critical to chlamydial intracellular growth. / Graduation date: 2003

Diss. (sammanfattning) Stockholm : Karol inst., 2004. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karol inst., 2004. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. Inst., 2002. / Härtill 4 uppsatser.