Abstract not available

Addenda and corrigenda are tipped-in & numbered leaves 281-282. / Copies of author's previously published articles are inserted back end paper. / Bibliography: leaves 222-279. / xiv, 282 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Studies were performed in the Langendorff-perfused isolated rat heart, using a paradigm in which atrial distension was prevented. The release of natriuretic peptides and endothelin-1, along with cardiac function was monitored during periods of transient ischaemia or hypoxia. Additional studies were performed in patients undergoing cardiac catheterization. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1999?

Addenda and corrigenda are tipped-in & numbered leaves 281-282. Copies of author's previously published articles are inserted back end paper. Bibliography: leaves 222-279. Studies were performed in the Langendorff-perfused isolated rat heart, using a paradigm in which atrial distension was prevented. The release of natriuretic peptides and endothelin-1, along with cardiac function was monitored during periods of transient ischaemia or hypoxia. Additional studies were performed in patients undergoing cardiac catheterization.

M.Sc. (Biochemistry) / Peptides have become useful therapeutic and targeting molecules in the treatment of various diseases. In nano-medicine, gold nanoparticles (AuNPs) are potential carrier systems of various targeting and therapeutic molecules including peptides. This study investigated the ability of 14 nm AuNPs as intracellular carriers of therapeutic and targeting peptides by assessing the toxic effects of these peptides when conjugated to AuNPs, on U937 monocyte-derived macrophages. These peptides include the proapoptotic peptide (klaklak)2, the targeting Glucose-Regulated Protein 78 (GRP-78) binding peptide and the carrier Trans-Activating Transcriptional (TAT) cell penetrating peptide (CPP). These peptides were conjugated to the AuNPs via poly(ethylene glycol) (PEG) polymers. The size, morphology, aggregation state and surface charge of citrate-stabilized, PEGylated, as well as peptide-conjugated PEG-AuNPs were determined using Transmission Electron Microscopy (TEM), Ultraviolet-Visible Spectroscopy (UV-vis), Dynamic Light Scattering (DLS) and Zeta Potential (ζ-Potential). Intracellular uptake of the tested AuNPs was investigated using the Cytoviva® dark-field hyperspectral imaging system. The toxicity was assessed using the conventional toxicity assay systems including adenosine triphosphate (ATP) and lactate dehydrogenase (LDH) assays, as well as the impedance based technology, xCELLigence real time cell analysis (RTCA) single plate (SP) system. The genotoxicity was investigated with the alkaline comet assay and the mechanisms of toxicity were investigated using western blotting through the ability of the AuNPs to activate the oxidative stress pathways, namely, the nuclear factor erythroid 2-related factor 2 (Nrf2) and factor kappa B (Nf-κB) pathways. Characterisation of the AuNPs revealed that the physicochemical properties of the particles were altered when suspended in culture medium. All the AuNPs tested have shown increase in size through aggregation. Although they all kept their negative charge, this charge was increased, with the greatest increase in charge shown for PEGylated AuNPs (OHPEG-AuNPs). Intracellular uptake was confirmed with 14 nm citrate stabilized AuNPs, TAT and GRP PEG-AuNPs. Some degree of uptake was also observed with (klaklak)2 PEG-AuNPs but not with OHPEG-AuNPs which was generally inaccessible to cells.

Sixty-two newborn Holstein-Friesian calves were used to study the role of colostrokinin, serum cortisol, and serum thyroxine in the absorption of maternal immunoglobulin. Calves were removed from their dams prior to suckling and assigned one of four rations: colostrum, whole milk, milk plus colostral immunoglobulin, and milk plus immunoglobulin plus colostrokinin. Calves were fed their assigned ration either at birth or after twelve hours inanition. All calves were fed pooled colostrum at 24 hours postpartum. Blood samples were collected at seventeen times during the first 32 hours postpartum. Calves were born with high cortisol concentrations (88 ng/ml) which decreased (P < .05) within two hours postfeeding. Serum cortisol levels increased (P < .05) between two and three hours after calves ingested a colostral source of immunoglobulin. Time of initial feeding had no effect on the cortisol surge. No such increase was observed in neonates consuming an immunoglobulin-free milk ration. These results demonstrate that the immunoglobulin fraction of colostrum is responsible for initiating an increase in cortisol secretion by the adrenal cortex. Within four hours postpartum, serum thyroxine concentrations increased (P < .05) at least 50% in all treatment groups regardless of whether the calves were fed or fasted. After peaking at 18 μg/dL, the serum thyroxine concentrations fell gradually throughout the duration of the collection period. Colostrokinin exhibited a biphasic effect on serum immunoglobulin concentrations which was dependent on the initial time of feeding. Calves exposed to colostrokinin in 0 hour feedings had serum immunoglobulin G concentrations significantly higher (P < .05) after 16 hours postpartum than animals not fed colostrokinin. Fasted calves, exposed to colostrokinin at 12 hours postpartum, had no increase in serum immunoglobulin G concentrations following a colostrum feeding at 24 hours postpartum. Fasted calves fed a ration not containing colostrokinin exhibited a two-fold increase in serum immunoglobulin G concentrations after the 24 hour colostrum feeding. Colostrokinin did not have an immediate effect on serum immunoglobulin G concentrations, but required an approximate twelve hour period to manifest its regulatory function. The presence or absence of colostrokinin in the experimental rations did not have any effect on the cortisol or thyroxine profiles. The variable serum immunoglobulin G profiles suggest that colostrokinin is involved in the acquisition of passive immunity by the calf, but colostrokinin may have more than one physiological role.

Photosynthetic organisms exhibit a variety of responses to changes in light intensity, including differential biosynthesis of chlorophyll-protein complexes. Cultures of Rhodobacter capsulatus grown anaerobically with a low intensity of light (2 W/m²) contained about four times as much B800-850 light harvesting complex as cells grown under high light intensity (140 W/m²). The mRNA transcripts encoding B800-850 beta and alpha peptides were analyzed by Northern blot, S1 nuclease protection and capping with guanylyl transferase. It was found that the steady-state levels of B800-850 mRNAs in high light-grown cultures was about four times as great as in cells grown under low light intensity. Therefore the lesser amounts of mature B800-850 peptide gene products found in cells grown with high light intensity were the result of a posttranscriptional regulatory process. It was also found that there were two polycistronic messages encoding the B800-850 peptides. These messages shared a common 3' terminus but differed in their 5' end segments as a result of transcription initiation at two discrete sites. Moreover the half life of B800-850 mRNAs was about 10 minutes in cells grown with high light and approximately 19 minutes in low light-grown cultures. Transcriptional and translational fusions were constructed between the B800-850 transcription initiation region (from this point on referred to as the puc transcription initiation region; see Fig. 1) and the Escherichia coli lacZ gene. From these studies it was concluded that the rates of transcription initiation of the puc (B800-850) genes was higher in cells grown with high light illumination than in low light-grown cultures, and that the relative amount of B800-850 complexes under these conditions was controlled by a translational or a posttranslational mechanism. The translational and transcriptional fusions were also used for examination of oxygen regulated expression of the puc genes. / Science, Faculty of / Microbiology and Immunology, Department of / Graduate