Thesis (Ph. D.)--Rutgers University, 2009. / "Graduate Program in Biochemistry." Includes bibliographical references (139-146).

Thesis (PhD.(Plant Science))-University of Pretoria, 2009. / Summary in English. Includes bibliographical references.

Thesis (Ph. D.)--University of Hong Kong, 1986.

Although several risk factors for severe influenza infection have been identified in previous studies, many patients having multiple risk factors only developed mild symptoms while many healthy young patients developed severe complications when infected with A(H1N1)pdm09. Thus, there are still undiscovered factors that affect the progression and severity of influenza. The early innate immune response may be critical in determining the disease progression. Non-neutralizing antibodies existed in the early stage of infection may contribute to the outcome of the disease. In this study, the association of disease severity with the titre and avidity of non-neutralizing antibodies in early stage of influenza infection was investigated. It has been shown that the titre of non-neutralizing antibody was higher in more severe patients in the early stage of infection. Higher antibody avidity was also found to be associated with more severe disease independently. These findings tend to support the view that antigenic drift leads to an excessive production of pro-inflammatory non-neutralizing antibodies in the patients and associated with severe outcome. Since patients with more severe disease tend to have a delayed clearance of the virus and allow more transmission, the antigenically shifted or drifted influenza virus may gradually become predominant in human population. This idea suggested that the predominance of influenza virus with NA-H275Y mutation in 2007-2008 was contributed by the co-existing, fitness restoring secondary adaptive mutation in HA. NA-H275Y was identified in previous studies to be the mutation encoding for the influenza virus to resist against oseltamivir but would also change the property of NA as a result of compromised viral fitness. Therefore, influenza virus carrying NA-H275Y is unlikely to emerge and spread in human population. However, NA-H275Y mutated strains of influenza virus emerged and spread globally in the influenza season of 2007-2008 and quickly become the predominant strain in 2008. Previous study found NA-R222Q and NA-V234M were the mutations responsible for restoring the viral fitness in oseltamivir resistant clinical isolates. Still, this cannot fully explain the predominance of the resistant strains over the susceptible strains. Therefore secondary adaptive mutation in HA was believed to be present and cause antigenic change to the resistant strains of influenza. In this study, mutual information analysis and HA structural analysis were conducted to screen out HA-A189T and HA-Y94H to be the candidates co-exist with NA-H275Y and possibly critical for antigenic changes. This study further suggested that HA-Y94H mutation leads to a change of antigenic property of the virus by examining the antigenicity and growth kinetics of the recombinant viruses carrying the selected HA mutations. HA-94 may be critical for determining both the receptor binding property and antigenic property of the virus. Review on the evolution of seasonal influenza viruses from 2005 to 2008 suggested that the emergence of HA-Y94H mutation may enhance the presence of NA-H275Y and helps the viruses carrying NA-H275Y to spread and dominate over the oseltamivir susceptible strains during 2007 and 2008. / published_or_final_version / Microbiology / Master / Master of Philosophy

There is no abstract available for this thesis. / Department of Biology

Enterococcus species are found in faeces of mammals, birds, insects, reptiles, but also soil, plants and water. These bacteria can also be isolated from animal products such as milk, cheese and meat. This study was aimed at isolating Enterococcus species from communal and commercial cattle faecal and water samples. A further objective was to determine the antibiotic resistance profiles of the isolates as well as some of the potential factors and mechanisms that could be responsible for their resistance to antibiotics. A total of 79 cattle faecal and water samples were collected from the communal and commercial farms. Sixty-five faecal samples were collected from commercial (33 healthy and 16 diarrhoeal cattle) and communal (16 healthy cattle) farms. Twelve water samples were collected from the commercial farms and 2 from the communal farm. From all the samples collected, 129 Enterococcus isolates were identified. Isolates, which included Enterococcus faecium (E. faecium), Enterococcus avium (E. avium), Enterococcus durans (E. durans) and Streptococcus bovis I (Sc. bovis !), were isolated from bovine faeces and water samples, while E. avium was only isolated from water at the communal farm. Furthermore, isolates from the healthy and diarrhoeal commercial cattle included E. faecium, E. avium, E. durans and Sc. bovis I. E. faecium and E. avium species were also isolated from the commercial farm cattle water sources. However, E. faecium was the predominant species in communal cattle faecal and water samples. On the other hand, E. avium was dominant in. commercial cattle faecal and water samples. Multiple antibiotic resistance (MAR) was observed in enterococci from all samples at both farm types. The predominant MAR phenotype that was prevalent in all enterococci species was GENSMX- NAL-NIT-KAN-STR All isolates showed an MAR index above 0.2 (water; 0.58 to 0.68 and faeces; 0.6 to l. 7). Cluster analysis based on antibiotic inhibition zone diameter data, resulted in dendrograms that showed a similar relationship of Enterococcus isolates from the two farms. Between 13% and 50% of Enterococcus isolates from cattle faeces and water samples from communal and commercial farms were resistant to vancomycin and oxytetracycline. In general, 11% of all the Enterococcus isolates from the cattle faeces was resistant to vancomycin. Thirty one per cent of the isolates from cattle water sources were resistant to both drugs. Vancomycin Resistant Enterococcus (VRE) genes conveying the vanC phenotype were obtained from E. durans and E. avium. This was an unexpected result. The tet A, tet Band tet C genes were not obtained from any of the Enterococcus species. Further studies on antibiotic resistance should be undertaken especially in rural areas, where farmers could be using over-the-counter medicines such as tetracycline even when it is not necessary. It was speculated in this study that there could be a development of potential reservoirs of antibiotic resistance in farmlands. In order to prevent the distribution of MAR organisms or their transferable resistance genes, a sensible use of antibiotics is necessary in veterinary medicine, animal husbandry and human medicine. / MSc. (Agriculture) North-West University, Mafikeng Campus, 2006

No description available.

A stock "parent" (S) strain of the mouse parasite Heligmosomoides polygyrus was exposed to increasing levels of ivermectin at the L4 stage for 15 generations. A Passage line was also developed from the parent strain parallel with the ivermectin selected line to control for the effects of rapid passage of the parasite from host to host during drug selection. A dose titration trial indicated 1.5 fold resistance had developed in the ivermectin selected strain at the 8th generation (IVM-8) both at the L4 and adult stage. A higher dose of drug was required to kill the L4 stage compared to the adults at generation 8. Additional selection pressure for 7 generations (IVM-15) did not change the resistance status of adult worms. The Passage strains (P-8 and P-15) remained susceptible to drug. The life history traits of the parent strain (S), the ivermectin selected (IVM-8 and IVM-15) and the Passage (P-8 and P-15) strains were then compared. Eight generations of selection with ivermectin (IVM-8) resulted in an increase in establishment 8 days post-infection (pi) but decreased egg output and worm burden over 4 months compared with strain S. However these effects were not seen after 15 generations of drug selection. The ivermectin selected strain (IVM-15) had similar establishment, egg production and worm burden as the parent strain (S). Establishment in strain P-8 was intermediate and not different from S or IVM-8 however 15 generations of passage (strain P-15) resulted in higher establishment and more rapid development to adult. This was also reflected in the net egg output and worm burden during the first month of infection. There were no differences in per capita fecundity among the five strains. Environmental pressure exerted by passage of H. polygyrus from host to host rather than ivermectin selection caused shifts in some life history traits of this nematode.

Thesis (MApSc(MedicalLaboratorySce))--University of South Australia, 2003.

Antimicrotubule drugs are used in the treatment of childhood neuroblastoma and acute lymphoblastic leukaemia (ALL). Resistance to these agents can be a major clinical problem and mechanisms mediating resistance are not fully understood. Previous studies have reported an association between the actin cytoskeleton and resistance to antimicrotubule drugs. Thus, the aim of this study was to investigate the role of the actin regulating proteins, LIM kinases (LIMK1 and LIMK2) in drug resistance. In addition, the role of ?? actin, a major actin isoform, in drug resistance was also examined. Chapter 1 reviewed the known mechanisms of antimicrotubule drug resistance and the interaction between the microtubules and actin cytoskeleton. The methodologies used in this study are described in chapter 2. LIMKs are known to regulate the actin cytoskeleton via phosphorylation of cofilin. Real Time RT PCR and western blotting was used in chapter 3 and showed that expression of LIMKs and their downstream target cofilin was altered in antimicrotubule resistant neuroblastoma and leukaemia cells. Moreover, altered LIMK expression was detected in in vivo derived vincristine resistant ALL xenografts and ALL clinical samples, further demonstrating that alterations in LIMKs and cofilin are associated with antimicrotubule drug resistance. Importantly, in chapter 4, gene silencing and drug treated clonogenic assays were performed to elucidate the functional role of LIMK1 and LIMK2 in drug response. Silencing of LIMK1 and/or LIMK2 increased sensitivity of neuroblastoma cells to microtubule targeting drugs and DNA damaging agents, suggesting that LIMKs may be useful targets to improve the efficacy of anticancer drugs. ??-Actin has been associated with drug resistance and chapter 5 used gene silencing and drug treated clonogenic assays to show that decreased ?? actin expression conferred resistance to anitmicrotubule drugs but not to DNA damaging agents. Microscopy and tubulin polymerisation assays showed that reduced ??-actin protects microtubules from paclitaxel induced polymerisation. This data supports a functional role for ?? actin in antimicrotubule drug action. In conclusion, this study showed that LIMKs and ?? actin mediate the action of antimicrotubule drugs and other anticancer agents, demonstrating that the actin cytoskeleton may serve as a useful drug target to improve the efficacy of anticancer drugs.