3. Electronic Theses and Dissertations (ETDs) - All submissions
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Item A study of natural killer cells(1984) Herman, Marian JeanThese studies involved the isolation of populations of peripheral blood leukocytes enriched for large granular lymphocytes (LGL), cells thought to be responsible for natural killer activity. It was found that the degree of cytotoxicity of LGLs could be modulated by various substances, namely, PLC/PRF/5 cell supernatants, interferon, certain monosaccharides and prostaglandin E2. This modulation appears to be due, at least in part, to the regulation of interleukin-1 (TL-) production by LGLs. LGLs are able to produce TL- in response, not only to LPS and Staphlococcus aureus hut also to a variety of NK sensitive target cells. The degree of sensitivity of these cells, to NK lysis, correlates with their ability to stimulate TL-1 production by LGLs„ The observed decrease in cytotoxic activity of LGLs from patients with advanced malignant disease can be ascribed to a defect in TL-1 production by these LGLs, an effect which can be partially corrected by in vitro interferon treatment. Treatment of target cells with IL-1 increased cytotoxicity of cancer patients LGLs to normal levels. This effect r v , appears to he a result, of increased hi ruling of LGLs to the target cells. It is postulated, therefore, that LGLs, coming into contact with K562 cells, produce II.-l which acts on the target cells enhancing their ability to bind further LGLs and thereby increasing the cytotoxicity of the latter.Item Iron and Malaria(1997-02-07) Van Zyl, Robyn L.Malaria is one of the most devastating infections found in man and the resurgence of drug resistance has prompted the search for novel chemotherapeutic strategies. Clinical observations have exposed the susceptibility of malaria parasites to iron deficiency, thus the metabolism of iron in parasitized erythrocytes could be a potential antimalarial target. In in vitro experiments, the parasites accumulated approximately four times more non-transferrin-bound iron than diferric transferrin. Both forms were accumulated in a concentration- and time-dependent manner, with more iron being associated with the trophozoite stage than the ring stage. The ferric iron chelating agent, desferrioxamine inhibited the uptake of transferrin and non-transferrin-bound iron in a concentration dependent manner. 2,2’-Bipyridyl, a ferrous iron chelating agent also inhibited the uptake of non-transferrin-bound iron, but did not affect the uptake of diferric transferrin. This indicated that the parasite does not accumulate diferric transferrin by transferrin-receptor mediated endocytosis, but rather by a non-specific endocytotic pathway. A large quantity of the accumulated iron was associated with the parasite haemozoin. Desferrioxamine effectively reduced the amount of iron associated with the haemozoin, whilst 2,2’-bipyridyl did not, which indicates that the haemozoin-associated iron is in the ferric state. The parasitized erythrocytes were more susceptible to haemolysis by the haemozoin subunits than the uninfected erythrocytes. The presence of chloroquine and 2,2’-bipyridyl potentiated the haemolysis induced by the subunits, whilst desferrioxamine protected the parasitized erythrocytes. The plasma chelating agents and aminocarboxylate compounds were not as effective in inhibiting parasite growth, as desferrithiocin, bathophenanthroline, desferrioxamine and 2,2’-bipyridyl which avidly chelate iron. The additive interaction between the latter two agents and chloroquine, quinine and pyrimethamine, completely eliminated the malaria infection. As did the combination of two lipophilic ferrous or two hydrophilic ferric iron chelating agents, as well as the combination of a hydrophilic ferric and lipophilic ferrous iron chelating agent. Whilst the combination of hydrophilic ferric and hydrophilic ferrous iron chelating agents antagonised each others antimalarial actions. Variables such as inoculum size, extracellular pH, cation supplementation and stage dependency, all affected the antimalarial activity of the iron chelating agents. Thus, the unique pathways involved in the iron metabolism of P. falciparum-infected erythrocytes, could be potential targets for new antimalarial drugs, which are membrane permeable and avidly chelate iron.Item The in vitro activity of antimicrobial agents alone and in combination against clinical isolates of gram-positive bacteria.(1993) Van den Berg, AlanAnalysis of organisms involved in hospital infections has shown that Gram-positive bacteria have assumed an increasingly important role. Examples that have been recognised as important pathogens are staphylococci , enterococci, streptococci, Corynebacterium jeikeium and Leuconostoc species. Methicillin resistance in staphylococci has become a major problem in certain hospitals. Viridans streptococci continue to be the most frequent cause of native valve endocarditis. Leuconostoc species are being increasingly isolated from blood cuIture specimens. strains of Gram-positive bacteria have become resistant to specific antibiotics; e.g. staphylococci to methicillin, enterococci to ampicillin, and viridans streptococci to penicillin. JK corynebacteria are sensitive only to vancomycin and resistant to other antimicrobials normally used for treating infection caused by Gram-positive bacteria. In this study various combinations of antimicrobials against 35 clinical isolates of Gram-positive bacteria obtained from three hospitals in the Johannesburg area (Johannesburg, Hillbrow, and Baragwanath) from 1987- 1988 were investigated. The MIC / MBC results conformed to others described in worldwide studies. Results when different methodologies for determining synergy were used, varied. This emphasizes the need for standardization, especially with regard to the time-kill studies. Most antimicrobial combinations demonstrated tested against Leuconostoc species synergy using the checkerboard method, but these results were not confirmed by time-kill procedures, which showed mainly indifference. Synergy was also obtained when gentamicin plus ciprofloxacin was combined Corynebacterium jeikeium. Because of increasing resistance and the fact that Gram- positive bacteria cause serious infections, various and new combinations of antimicrobials need to be tested before treating these infections. Parts of this dissertation have been presented at the following congresses: 10th Annual Congress of the Society of Medical. Laboratory Technologists of South Africal Sun city 1989 75th Anniversary Congress of Pathology Johannesburg 1990 11th Annual Congress of the Society of Medical Laboratory Technologists of South Africa, Durban 1991Item Hepatitis B virus serology : eight years of laboratory data in retrospect(1993-10-26) Sim, John. Gray. MalcolmAn analysis of 39,774 specimen records of diagnostic screening for hepatitis B virus (HBV), consisting of HBV surface antigen (HBsAg), antibody to surface antigen (anti- HBs) and antibody to HBV core antigen (anti-HBc) was performed. Specimens representative of all possible result combinations for these primary markers were found in the dataset and were investigated further by studying the distribution of extended marker frequencies within the groups defined by the primary marker combinations in an attempt to reconcile the patterns observed with standard profiles of HBV serology. The extended markers consisted of HBV e antigen (HBeAg), antibody to HBeAg (anti- HBe) and anti-HBc IgM. Unusual patterns of serological results which were identified were investigated further for the presence of HBsAg/anti-HBs immune complexing by acid dissociation techniques, and for the low level HBV chronic carrier state by polymerase chain reaction (PCR) amplification of HBV DNA. Results obtained indicated that immune complexing was not a common occurrence in the groups investigated, while preliminary findings in patients with isolated anti-HBc positivity demonstrated a 6.5% low level HBV carrier rate in this groupItem The defectiveness of the subgroup F adenoviruses in vitro(1992-08-17) Tiemessen., Caroline. T.A distinguishing feature of the human subgroup F adenoviruses, types 40 and 41, is their inability to replicate in cells that permit efficient growth of other adenoviruses. This study was conducted to determine the basis of the viral defect(s) responsible for poor growth in vitroItem Growth regulation by heparin in the vascular wall(1983-06-10) Karnovsky, Morris, JohnVascular smooth muscle proliferation follows upon endothelial injury, and is thought to be an early component in the pathogenesis of atherosclerosis, and a possible noxious consequence of vascular surgery. We have shown that heparin suppresses vascular smooth muscle proliferation iri vivo and in vitro. The inhibitory effect is specific for heparin, and not other anions, and is not related to the antithrombin III binding activity of heparin. It is dependent on the size of the molecule, (hexasaccharidees or smaller being ineffective), and O-sulfation, but not N-sulfationItem Investigation of the immune-modulatory effects of erythromycin(1986-06-20) Fernandes, Antonio, CelestinoThe Literature Review covers the immunosuppressive and immunopotentiating properties of antibiotics on the immune system and the effects these could have on the resolution of an infection. The possible pathogenic mechanisms of C. albicans are also reviewed in this section. The experimental section shows that pre-treatment of mice with erythromycin increases the mean survival time following intraperitoneal inoculation of C. albicans. It was shown that erythromycin enhanced lymphocyte transformation and PMNL migration in both in-vivo and in-vitro situations. These enhanced immunological components probably caused improved survival times in the aforementioned animal experiments. To investigate the effects of oral administration of erythromycin on in-vivo PMNL migration in adult volunteers a new quantitative test which could only be applied to humans was developed and is described in detail. Using this method preliminary data were obtained which show that erythromycin increases PMNL migration in-vivo.Item The role of ferritin in iron absorption(1967-01) Torrance, J. D.Although reports of the medicinal use of iron date back to ancient times it was not until the present century that the many functions of iron in the body were studied. Once started, the investigation received impetus from the seriousness of iron deficiency anaemia, a major cause of ill health throughout the world. The introduction of radio-isotope tracer techniques in 1939 greatly facilitated investigation of absorption, excretion and the metabolic pathways of iron. The tremendous amount of work already carried out has led to a fairly comprehensive knowledge of the various aspects of iron metabolism. Nevertheless, there remain wide gaps in the overall picture. InItem An in vivo and in vitro study of some luminal and cellular factors influencing iron absorption(1966-03) Jacobs, PeterAlthough the various factors which influence the absorption of iron from the gastrointestinal tract have been extensively investigated, there still remains uncertainty concerning several basic aspects of this process