Thesis (Ph. D.)--University of Virginia, 2001. / Includes bibliographical references (leaves 146-168). Also available online through Digital Dissertations.

Thesis (M. Phil.)--Hong Kong University of Science and Technology, 2003. / Includes bibliographical references (leaves 118-130). Also available in electronic version. Access restricted to campus users.

T -2 toxin is an immunosuppressive mycotoxin that has been conjoined with several symptoms and diseases as early as the turn of the century, but whose mechanisms of action are still being investigated. Accordingly, this study was an attempt to determine the cytotoxic effects of T -2 toxin on normal human lymphocytes in vitro, with particular emphasis on mitochondrial viability, cellular and nuclear morphology as well as the localisation of the subcellular sites of toxin interaction. The cytotoxicity of T -2 toxin was assessed with the use of a methylthiazol tetrazolium (MTT) assay. This assay targeted the succinate dehydrogenase activity of the lymphocytic mitochondria, over a range of concentrations of T-2 toxin at various incubation times. The morphology of treated lymphocytes was analysed with the use of transmission electron microscopy and the localisation of the toxin was accomplished via immunocytochemistry. DNA fragmentation studies formed an integral part of the analyses. The cytotoxicity assay indicated that not only was cell viability inversely proportional to both the dose and exposure time, but that the eftects of the different doses were only evident at prolonged incubation times (12-24 hours). The electron microscopy studies showed that T-2 toxin (1,56 ug/ml) induced apoptosis (cell suicide) in normal human lymphocytes. This was determined by the observation of chromatin condensation and nuclear disintegration within the toxin treated lymphocytes. Apoptosis seemed to occur independently of mitochondrial damage at 6 hours of exposure to T-2 toxin. The presence of polyribosomes within the treated lymphocytes indicated that protein synthesis was not inhibited. Anti-T-2 toxin conjugated gold label was present in all areas of damage, particularly within the nuclei of the T-2 toxin treated lymphocytes. The DNA fragmentation results showed that T-2 toxin induced fragmentation in lymphocytes, the extent of which was directly proportional to the exposure time. It appears that the early signs of T-2 toxin induced apoptosis in normal human lymphocytes can be determined by damage to the nucleus. / Thesis (M.Med.)-University of Natal, Durban, 1998.

The work presented here represents research done on mycotoxins and plant toxins by the author and his postgraduate students over a period from 1964 to date. The first phase, which ends at 1980, mainly addresses the biosynthesis of the aflatoxins. The involvement of anthraquinone derivatives in this process was investigated and the role of versicolorin A and its derivatives was partially elucidated. Novel active enzymes systems were derived from protoplasts and used in these studies. The period lasting from 1980 to 1992 concentrates on the occurrence of mycotoxins in agricultural commodities and effects on animals and their systems. Over 7000 samples were analysed using a multimycotoxin analytical method and a fungal screen. The most common mycotoxin found was aflatoxin B₁ and prevalent fungus was Fusarium moniliforme. Later work is indicating that fumonisin B₁ is the most commonly occurring mycotoxin. As this was only discovered in 1988, its presence was only looked from 1995 onwards. It was also found that rumen fluid could metabolise trichothecenes. During this period (1980-1992) further work on aflatoxin metabolism was done and a novel dehydrogenase involved in aflatoxin B₁ was isolated and characterised. An Elisa assay was developed for atractyloside, a toxin found in a plant (Callilepis laureola) used in tradition medicine. The site of atractyloside storage was found to be in the plant vacuole. The final period covers 1992 to the present, where the occurrence and effects of mycotoxins in human disease were studied. The major and most important finding is that fumonisin B₁ is present in the blood and tissues of many of the Black population examined in Kwazulu Natal. This includes, oesophageal cancer patients, eclamptic patients, school children and members of the rural population. A similar circumstance also appertains for the presence of aflatoxin B₁. It seems likely from these results that chronic mycotoxicoses are a common occurrence, particularly in the Black rural population and are not the sporadic rare event that is found in the first world countries. / Thesis (Ph.D.)-University of Natal, Pietermaritzburg, 1999.

ClC proteins encompass a large protein family consisting of both voltage-dependent chloride channels and chloride/proton exchangers that are found in both eukaryotes and prokaryotes. These proteins mediate Cl- flux across the plasma membrane or intracellular membranes of many cell types including neurons, epithelial cells, and skeletal muscle in mammals. Mutations in genes encoding these channels also contribute to several human diseases. The mechanism of ion conduction through ClC proteins is becoming better defined, largely due to the availability of a crystal structure of a bacterial ClC transporter. Because crystal structures only capture a snapshot a protein in a single conformation, however, the large conformational changes associated with channel opening and closing have remained largely undefined. In the cation channel field, ion conduction and conformational changes that occur during channel gating have been studied using peptide toxin inhibitors isolated from animal venoms. However, only one peptide toxin inhibitor of a chloride channel of known molecular identity has ever been identified. Georgia anion toxin 1 (GaTx1), inhibits the CFTR chloride channel, which is unrelated to ClC proteins on the levels of both three dimensional structure and primary sequence. Here, we describe the characterization of the inhibitory activity of Leiurus quinquestriatus hebraeus scorpion venom against the ClC-2 chloride channel. We found that the venom from this scorpion contains a peptide component that is capable of inhibiting the ClC-2 chloride channel. This component was isolated using standard chromatography techniques, and found that the active component is a 3.2 kDa peptide composed of 29 amino acids. We showed that the active toxin, Georgia anion toxin 2 (GaTx2), interacts with ClC-2 with an affinity in the picomolar range, and appears to slow channel opening. Finally, GaTx2 is not capable of inhibiting other members of the ClC protein family, other major chloride channels, or voltage-gated potassium channels. This toxin will provide a new tool for structure/function studies of ClC-2, and will hopefully serve as only the first toxin inhibitor available for this protein family.

Bibliography: leaves 252-267. / xvi, 267 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / These cyanobacteria are two freshwater phytoplankton which produce toxins, taint the taste and odour of potable water and form surface blooms. A technique was developed to assess cell metabolic activity and to determine the influence of light and nutrients on gas reside synthesis and bouyancy regulation in order to understand factors which favour their dominance, and thus how to control them. / Thesis (Ph.D.)--University of Adelaide, Dept. of Botany, 1998?

Some ill. mounted / Bibliography: leaves 145-160 / vii, 160, [58] leaves : ill. (some col.), maps ; 31 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Plant Pathology, 1985

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

Diss. (sammanfattning) Umeå : Univ., 2003. / Härtill 5 uppsatser.

Lic.-avh. (sammanfattning) Stockholm : Kungliga Tekniska högskolan., 2007. / Härtill 2 uppsatser.