No description available.

No description available.

No description available.

The oral commensal Candida albicans is found in a majority of the human population. Defects in innate and cell-mediated immunity alter the status of the yeast from a commensal to an opportunistic pathogen. One of the most common clinical manifestations of this infection is oro-pharyngeal candidiasis. Previous studies have reported on the establishment of a chronic oro-pharyngeal infection in a mouse model. In this study, investigations were carried out on local and systemic immune responses against oral C. albicans infection using an IL-12p40 cytokine deficient knockout mouse model. Draining lymph nodes (LN) and oral tissues (OT) consisting of tongue, buccal mucosa and palate were isolated from naïve (Day 0) and infected (Day 6) IL-12p40 knockout and C57BL/6J wildtype mice and analysed using Affymetrix Mouse Genechip MOE430A. Quality control of the samples was carried out using hierarchical clustering. Clustering analysis showed how comparable the duplicates for each group were clustered together. Analysis of the data including data mining tool (DMT) and MAS5.0 was performed to generate reliable and manageable gene lists for the lymph nodes and oral tissues, and of highly expressed genes that could be verified using traditional molecular methods. Identification of differentially expressed genes using statistical (t-test and ANOVA with Benjamini-Hochberg correction, p<0.05) and non-statistical (Fold Change > 1.5) tools highlighted substantially greater numbers of differentially expressed genes in the knockout mice with respect to strain and/or disease. Further analysis of this data, limited to the immune response pathways, showed that CD4 antigen was downregulated in the infected knockout mice compared to the infected wildtype mice. The CD8α antigen was also down-regulated in the infected knockout mice compared to the infected wildtype mice. Within the oral tissues, genes expressing proteins such as β-defensin 4 and triggering receptor expressed on myeloid cells 1 (Trem1) were down-regulated in the infected knockout mice compared to the infected wildtype mice. The glycoprotein osteopontin was up-regulated in the oral tissues in the naïve knockout mice and to a lesser extent in the infected knockout mice. Confirmation of the microarray data was undertaken using real time quantitative reverse-transcription polymerase chain reaction qRT-PCR for the selected immune response genes in the lymph nodes and oral tissues. Real time qRT-PCR data confirmed the differential expression of nominated genes obtained from the microarray analysis.

A polyphasic study of the population diversity in a collection of Campylobacter jejuni isolates involved in human disease and from animal and environmental sources was undertaken. Isolates were characterised by phenotype, using heat stable antigen serotype, bacteriophage type and biotyping methods. Isolates were also genotyped by restriction fragment length polymorphism analysis of genomic DNA, using a 16S rRNA gene probe, a random-cloned DNA sequence probe, and of the flagellin A gene following amplification by the potymerase chain reaction. A diverse range of polyphasic strain profiles was seen amongst a population of C. jejuni isolates examined from sporadic human infections in the UK over a seven-month period. Associations between gene polymorphisms identified a number of prevalent genotypes and a cluster analysis of RFLP profiles identified a strong relationship between three of these prevalent genotypes. The association of these three genotypes with serogroup and phage-group markers was highly suggestive of clonality within this C. jejuni population. Three hunian pathogenic C. jejuni strains identified by this analysis could be recognised by association with specific Preston phage-groups. A retrospective survey indicated that these phage-groups were responsible for approximately 27% of sporadic cases of C. jejuni infection in the UK. The population diversity amongst sporadic human C. jejuni isolates remained consistent over a seven year period and these three phagegroups were a consistent feature of sporadic C. jejuni infections during this period. Each phage-group demonstrated a distinctly different seasonal distñbution suggesting that the epidemiology of these strains could be different. C. jejuni isolates from poultry samples were also diverse and a significant proportion of these isolates were indistinguishable from human C. jejuni isolates using the same polyphasic strain characteristics. Pathogenic human strains were found in contaminated environments but environmental populations largely contained stains which had not been seen amongst human isolates in this study. One of the strains identified in this study (R4:C8:11S4:flaA-26:PG55: BT6000) was demonstrated to have a global distribution and appears to have a host preference for cattle. In addition this strain was responsible for at least four milkborne outbreaks of (Ljejuni enteritis. Data from this study indicates that this strain may be responsible for up to 5 % of sporadic cases of human enteritis in the United Kingdom each year and that milking cows may be a reservoir for the organism.

No description available.

There is an on-going debate among health professionals, policy-makers and politicians, as to the optimal way of delivering sexual health services to young people. There is as yet, no consensus on their best patterns of organisation or configuration. This study uses qualitative and quantitative research methods, to explore both the views of young people accessing sexual health services, expressed through in-depth interview, and variations in client satisfaction with different characteristics of service delivery, expressed through completion of a questionnaire. The key research questions are:  How does young people’s satisfaction with sexual health services vary with the age-dedication of the service; that is, whether it serves young people only, or all ages?  How does young people’s satisfaction with sexual health services vary with the integration of the service; that is, whether family planning and genito-urinary services are offered separately, or together?  How does young people’s satisfaction with sexual health services vary with the location of the service; that is, in community or hospital based services? In the qualitative component, in-depth interviews were conducted with 25 young people recruited from a purposively selected sample of young people’s services. In the survey, a total sample of 1166 was achieved. Of these, 36% were attending an integrated contraceptive and STI service and 64% were attending a more traditional ‘separate’ service. 48% attended a service dedicated to young people and 52% an all-age service. 50% attended a hospital-based service and 50% a service located in the community. Of the total sample, 22% were male and 78% female. The analysis has been done not on a comparison of services in their entirety, but on a comparison of key features of their organisation, that is, whether they are provided separately as contraceptive and STI sessions or services, or whether these aspects of sexual health provision are integrated in sessions or services (integration); on whether they are run exclusively for young people or for all ages (dedication); and on whether they are located in the community or in a hospital setting (location). Recommendations are made for future service development and delivery and implications for policy are discussed.

Epithelial rest cells of Malassez (ERM) are small groups of epithelial cells within the periodontal ligament closely approximated to the radicular cementum surface. The cells have a high nuclear/cytoplasm ratio. In oblique sections of the periodontal ligament, the cell rests can be seen, not as isolated groups of cells but as a network, similar to a fish-net, surrounding the root. The function of the ERM is unknown and their participation in some dental pathological conditions is still controversial. Some new publications have described the isolation of ERM from human periodontal ligaments. To date no publications have described the expression of bone-related proteins by ERM. ERM were cultured and isolated from porcine periodontal ligaments (chapter 2). An immunohistochemical study was carried out in rat porcine and human periodontal sections using AE1/AE3 antibody. The expression of cytokeratins by ERM was demonstrated in all species (chapter 3). Characterization and identification of ERM was achieved by Transmission Electron Microscopy (TEM), immunohistochemistry and Western blot. The results demonstrated the epithelial nature of these cells obtained from the mid radicular third of porcine first deciduous molars (chapter 4). An in vitro study using a semi quantitated RT-PCR technique was carried out in four different types of porcine periodontal cells (GF, PDLF, ERM and alveolar bone cells). These cell types were compared for the expression of the bone related proteins osteopontin and bone sialoprotein. The strongest expression of osteopontin was for the ERM compared to alveolar bone cells, PDLF and GF. These results demonstrated for the first time the expression of osteopontin from cultured porcine ERM suggesting a possible role of these cells in cementogenesis (chapter 5). Finally, emdogain (EMD), an enamel matrix derivative protein, was utilized at different concentrations to stimulate periodontal ligament cells and determine its role in proliferation, attachment and by RT-PCR expression of osteopontin or bone sialoprotein in vitro (chapter6). EMD demonstrated proliferative and attachment responses in a dose dependent manner. EMD stimulated the expression of OPN m RNA by porcine ERM and alveolar bone cells. The results contribute to explaining the different regenerative events associated with EMD in periodontal regenerative therapy. The findings of this study contribute to a broader understanding of possible functions of the ERM and suggests a role for these cells in cementogenesis by their strong OPN expression.