Extended spectrum (3-lactamases (ESBLs) were characterized in Salmonella spp. isolates from a pediatric ward of a hospital in Durban. Forty one Salmonella spp. were subjected to serotyping, antibiotic susceptibility testing, E-Tests for ESBL detection, iso-electric focusing, polymerase chain reaction for detection of genes and sequencing. Isolates were screened for the presence of WaTEM, WaSHV, WaCTX-M, WaOXA , WaCMY, WaDHA and WaACC genes. The most common serotype was Salmonella Typhimurium. Isolates were multi-drug resistant with 100% susceptibility only to meropenem and ciprofloxacin. Tazobactam was the most effective inhibitor. Forty-one percent of the isolates were resistant to ceftriaxone, thus limiting therapeutic options for Salmonella infections.TEM-1 was the most predominant (3-lactamase found in 51% of isolates while SHV-12 found in 39 % was the most common ESBL. TEM-63 was evident in 29 %, TEM-116 in 10 % and TEM-131 was found in one isolate. The high ceftazidime MICs of isolates expressing only TEM-63 were indicative of R164S substitution which widens the binding cavity to accommodate the bulky side chains of oxyiminoaminothiazolyl cephalosporins. The identification of TEM-131 which differs from TEM-63 by 1 amino acid reiterates the evolutionary potential of the TEM-type plactamase. Other ESBLs identified included SHV-2, CTX-M-3, CTX-M-15 and CTX-M-37. CMY-2 and the OXA-1 p-lactamase were also detected. This is the first report of TEM-116, CTX-M-3, -15 and -37 in Salmonella spp. in South Africa. All isolates with nalidixic acid MICs > 48 ug/ml had the mutation D87N, or D87G in the QRDR of the gyrA gene. This study showed that Salmonella spp. may be multi-drug resistant with the propensity to harbour p-lactamases in unique combinations. The diversity of ESBLs and the co-expression of quinolone resistance suggests that their incidence in salmonellae needs to be monitored. / Thesis (Ph.D.)-University of KwaZulu-Natal, 2008.

Virus infection represents an intracellular invasion of host cells for the sole purpose of multiplication. Successful virus replication requires entry into tropic cells, usurping of the cellular machinery, and the production of progeny virions to initiate further rounds of infection. Establishment of the antiviral state in response to virus begins at the site of infection and requires the initiation of a preexisting signaling network designed to inhibit virus replication and aid in the establishment of this coordinated immune response. Integral components of this network include the IRF-3 and IRF-7 transcription factors that play essential roles in the cellular response to infection through virus induced phosphorylation by an unknown virus activated kinase. The objective of this research was to elucidate the viral antigen(s) required to induce the phosphorylation and subsequent activation of IRF-3 and IRF-7, to identify the molecular component(s) required in this activation process, and to decipher the mechanism(s) by which cellular recognition of virus infection initiates this antiviral response. We demonstrate that activation of this signaling network, following RNA virus infection, is dependent on viral entry, viral transcription, and viral translation and propose that the molecular requirements governing activation of IRF-3 and IRF-7 are the result of viral byproducts formed during the process of cytoplasmic RNA self replication; including both the formation of double stranded RNA and ribonucleoprotein complexes. Following cellular recognition of these motifs, signal transduction networks converge onto an IKK-related kinase structure composed of adaptor proteins bound to two kinase subunits, TBK-1 and IKKepsilon, which we propose to be essential components of the virus activated kinase. We demonstrate that TBK-1 or IKKepsilon activation results in the establishment of an antiviral state that renders cells non permissive to viral replic

No description available.

No description available.

Human immunodeficiency virus (HIV) infection is a worldwide epidemic where infected individuals usually develop acquired immunodeficiency syndrome (AIDS). HIV is primarily spread by sexual transmission across mucosal tissue where dendritic cells (DC) reside. DC regulate immune responses through their unique ability to capture antigen, migrate to lymphoid tissue, and activate naive T cells. In this Thesis, we have investigated whether HIV influences the migration of DC, thereby influencing their capacity to regulate immune function and facilitate transport of HIV to T cell rich lymphoid tissue. Transmigration assays demonstrated that the predominant HIV strain during primary infection, R5 HIV-1, was chemotactic for immature DC (iDC). Addition of soluble CD4 enhanced iDC migration to R5 HIV, presumably by binding to R5 HIV and altering the conformation to enhance binding to CCR5. Our results suggested that iDC migrated specifically to R5 and not X4 HIV gp120, through interactions between the extracellular loop-2 (ECL-2) domain of CCR5 with the V3 loop region of R5 gp120. iDC prepared from HIV-infected subjects were shown to have impaired chemotaxis to inflammatory chemokines compared with iDC from healthy individuals. Furthermore, the level of inhibition appeared to be proportional to the severity of disease progression in HIV infected subjects. Interestingly, chemotaxis of iDC from long-term non-progressor individuals was similar to normal individuals, whereas migration of iDC from typical progressors was greatly impaired. These differences did not appear to be related to the level of CCR5 expression or patient viral load. The protease inhibitor Indinavir used in antiretroviral therapy, limited DC trans-endothelial migration to chemokines, reduced DC-SIGN expression and increased CD83 on iDC. The results suggested that Indinavir inhibited proteases necessary for DC migration by adversely affecting interactions between DC-SIGN, VLA-4 and VLA-5 and ligands on the endothelium and underlying fibronectin matrix. A novel method has been successfully developed for amplifying rare HIV-specific CDS cells using DC transfected with HLA antigens matching HIV-infected subjects. This has enabled us to amplify HIV-specific CDS T cells by 10- to 60-fold. This may help us to clone and characterise HIV-specific CDS T cells from highly exposed persistently seronegative (HEPS) individuals. In summary, the results in this Thesis demonstrate that R5 HIV mimics chemokines to subvert the natural trafficking of DC. Indeed, we have shown that DC from typical progressors have severely impaired migration. This may have serious consequences on DC immunoregulation, compromising the immune function of these infected individuals.

No description available.

Little is known of the biology and importance of the ectomycorrhizal symbiosis in the Dipterocarpaceae. This project was undertaken: 1) to follow dynamics of mycorrhizal infection of dipterocarp seedlings at different sites in the forest, to characterise the major fungal associations involved; 2) to follow mycorrhizal infection of dipterocarp seedlings under laboratory conditions with different inoculum sources; 3) to determine whether dipterocarp ectomycorrhizas function in a manner similar to temperature ectomycorrhizas in the uptake of specific nutrients. Twenty-four different ectomycorrhizal types were described from roots of newly germinated seedlings, two to seven month-old seedlings and wildings of <i>Shorea leprosula</i> (Miq.), and approximately 20 year-old <i>S. acuminata</i> Dyer, <i>S. dasyphylla</i> Foxw., <i>S. leprosula</i> and <i>S. parvifolia</i> Dyer trees. Seventeen types were tentatively identified to family level. Vesicular-arbuscular mycorrhizas were not found. In the forest, some 14 day-old <i>S. leprosula</i> seedlings were already ectomycorrhizal but infection could be absent up to seven months after germination. The results implied that hyphal connections were important in early infection of seedlings in the vicinity of parent trees. Mycorrhizal infection of sequentially sampled two to seven month-old seedlings declined over the sampling period at two sites in Gombak, Selangor and one in Ulu Langat, Selangor. Five to six ectomycorrhizal types were dominant on seedlings at each site and a succession of types was observed on seedling roots. At final harvest, increased plant growth was significantly correlated with ectomycorrhizal infection only at one site in Gombak where infection by 'dominant' types exceeded 30%. Non-mycorrhizal seedlings of <i>S. acuminata, S. leprosula, Hopea helferi</i> and <i>H. odorata</i> were able to grow normally in sterile soil under non-competitive situations. Seedlings were able to form ectomycorrhizas even with inoculum present in grassland soils or with inoculum from different host species in the case of <i>H. helferi</i>. Increased phosphorus uptake by ectomycorrhizal seedlings of <i>S. acuminata, S. leprosula</i> and <i>H. odorata</i> was demonstrated.

HIV-positive men face multiple challenges when deciding whether or not to disclose their serostatus to sex partners. This survey design using repeated measures examined disclosure of HIV-positive serostatus to sex partners in an ethnically diverse population of men (N= 93) recruited from the community in O'ahu, Hawai'i. The framework guiding the research was Social Cognitive Theory (Bandura, 1987), with a specific focus on self-efficacy for disclosure decision-making and for negotiating safe sex. The aims of the research were to: 1) describe HIV serostatus disclosure to sex partners; 2) describe self-efficacy for disclosure to sex partners and self-efficacy for negotiating safer sex; 3) determine the relationships between demographic, HIV-illness, drug use history, self-efficacy and sex partner variables (relationship status, serostatus), and self-disclosure, and; 4) determine the relationships between demographic, HIV-illness, drug use history, self-efficacy, sex partner variables, self-disclosure, and condom use by the men in the sample. A convenience sample of HIV-seropositive men was enlisted through both active outreach and passive recruitment (posters and public advertisement). Survey responses were anonymous, as the subject matter being asked was sensitive in nature. Results reveal that self-disclosure to sex partners varied based on sex partner serostatus and relationship status, and was significantly influenced by perceived self-efficacy, by income, education, years since diagnosis and contextual factors including cocaine use before sex. Subjects were least likely to disclose to a sex partner whose serostatus was not discussed. An unknown partner serostatus was also significantly associated with less disclosure. The more committed the relationship, the greater the likelihood that a subject would self­ disclose. The longer the time since initial HIV diagnosis the more likely a subject was to disclose to sex partners. High self-efficacy scores were associated with self-disclosure, and with condom use. Cocaine use before sex was associated with less disclosure and less condom use. Self-disclosure was significantly associated with condom use as well. Although a causal relationship is not implied, self-disclosure practices did influence safe sex behavior. Implications for nursing and for future research are discussed.

Copy of author's previously published article on back end-paper. / Bibliography: leaves 105-158. / xii, 160, [58] leaves, [35] leaves of plates : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Studies the early events in the synthesis of HIV RNA and integration if viral DNA using a cell-to-cell transmission of infection model. / Thesis (Ph.D.)--University of Adelaide, Dept. of Microbiology & Immunology, 1998

Thesis (M. Med. Sc.)--University of Hong Kong, 2007.