Bibliography: leaves 209-254. / viii, 254, [39] leaves, [17] leaves of plates : ill. 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Attempts to construct an evolutionary overview of the regulation of surfactant secretion among the vertebrates. A detailed whole animal and in vitro study of the factors that control surfactant secretion and function in the central Australian agamid lizard Pogona vitticeps was undertaken. Type II pneumocytes were also isolated and cultured from Australian lungfish, North American bullfrogs and fat-tailed dunnarts. / Thesis (Ph.D.)--University of Adelaide, Dept. of Physiology, 1999

Pulmonary surfactant is a complex mixture of lipids and proteins that lowers surface tension, increases lung compliance, and prevents the adhesion of respiratory surfaces and pulmonary oedema. Pressure can have an enormous impact on respiratory function, by mechanically compressing tissues, increasing gas tension resulting in increased gas absorption and by increasing dissolved gas tensions during diving, resulting in the formation of bubbles in the blood and tissues. The lungs of diving mammals have a huge range of morphological adaptations to enable them to endure the extremely high pressures associated with deep diving. Here, I hypothesise that surfactant will also be modified, to complement the morphological changes and enable more efficient lung function during diving. Molecular adaptations to diving were examined in surfactant protein C (SP-C) using phylogenetic analyses. The composition and function of pulmonary surfactant from several species of diving mammals was examined using biochemical assays, mass spectrometry and captive bubble surfactometry. The development of surfactant in one species of diving mammal (California sea lion), and the control of surfactant secretion using chemical and mechanical stimuli were also determined. Diving mammals showed modifications to SP-C, which are likely to lead to stronger binding to the monolayer, thereby increasing its fluidity. Phospholipid molecular species concentrations were altered to increase the concentration of more fluid species. There was also an increase in the percentage of alkyl molecular species, which may increase the stability of the monolayer during compression and facilitate rapid respreading. Levels of SP-B were much lower in the diving species, and cholesterol was inversely proportional to the maximum dive depth of the three species. Surface activity of surfactant from diving mammals was very poor compared to surfactant from terrestrial mammals. The newborn California sea lion surfactant was similar to terrestrial mammal surfactant, suggesting that these animals develop the diving-type of surfactant after they first enter the water. The isolated cells of California sea lions also showed a similar response to neuro-hormonal stimulation as terrestrial mammals, but were insensitive to pressure. These findings showed diving mammal surfactant to have a primarily anti-adhesive function that develops after the first entry into the water, with a surfactant monolayer, which would be better suited to repeated collapse and respreading. / Thesis (Ph.D.)--School of Earth and Environmental Sciences, 2005.

Thesis (M.Sc.)--University of Adelaide, Department of Environmental Biology, 2001. / Includes bibliographical references.

Thesis supervisor: Madeline A. Shea. Includes bibliographical references (p. 195-206).

Bibliography: leaves 209-254. Attempts to construct an evolutionary overview of the regulation of surfactant secretion among the vertebrates. A detailed whole animal and in vitro study of the factors that control surfactant secretion and function in the central Australian agamid lizard Pogona vitticeps was undertaken. Type II pneumocytes were also isolated and cultured from Australian lungfish, North American bullfrogs and fat-tailed dunnarts.

No description available.

"March 2001". Bibliography: leaves 193-238. Relates changes in the development of the pulmonary surfactant system in response to birth strategy, lung morphology and phylogeny in order to determine the extent of conservation in this process, by quantifying the total of phsospholipid, disaturated phospholipid and cholesterol in the lung washings of embryonic and hatchling chickens, oviparous bearded dragons and viviparous sleepy lizards, snapping turtles and green sea turtles throughout the final stages of incubation and gestation. Finds that the pattern of development of pulmonary surfactant lipids is consistent with that of mammals.

Includes bibliographical references.

The fetal lung undergoes extensive physiological and biochemical maturation prior to birth in preparation for its postnatal function as an organ for gas exchange. Pulmonary surfactant, a substance that reduces surface tension and prevents alveolar collapse, is produced by type II pneumocytes within the lung. Reduced ability to produce surfactant leads to neonatal respiratory distress syndrome. Synthesis of the phospholipid component of surfactant, phosphatidylcholine (PC), is stimulated by fibroblast-pneumocyte factor (FPF), a protein expressed by fibroblast cells within the fetal lung. Although its function is well known, the identity of this important protein has remained a mystery. Recent research has suggested that FPF may be neuregulin-1, a growth factor found in many tissues during development. Enhanced synthesis of PC (and therefore detection of FPF) is measured using a tissue culture-based method. Primary cultures of lung fibroblasts and type II pneumocytes are prepared, and fibroblast-conditioned medium (FCM) is exposed to the type II cells. Resultant PC synthesis is measured using radioisotope-labeled PC-precursor and a chloroform-based lipid extraction method. Initial results using this method were very inconsistent, so a study was undertaken to determine which parts of the method could be contributing to this inconsistency. Cell density of type II cultures (measured in μg DNA.plate-1) was shown to have a significant effect on results. Treatment of fibroblasts with 100 nM dexamethasone and exposure of type II cultures to the resultant FCM caused a mean 9.17% increase in PC synthesis, but when only type II cultures with a cell density below 25 μg DNA.plate-1 were analyzed, this value increased to 17.56%. Type II cultures with cell density above this threshold value showed a mean increase in synthesis of only 3.39%. The consistent application of [3H]-choline chloride also had a significant effect on results. Experiments utilizing phorbol 12-myristate 13-acetate to stimulate fibroblasts were very inconsistent. The mean activity of the initial [3H]-choline chloride solution prepared for these experiments was found to be 2.04 μCi.mL-1, compared to a mean of 4.79 μCi.mL-1 for all other experiments. Observations from this section of the study led to considerable revision of the method used to measure PC synthesis. Quadrupolar ion trap mass spectrometry (MS) was used to analyze FCM and determine if neuregulin-1 (NRG1) could be FPF. A mass spectrum was obtained for recombinant NRG1, with predominant ions of 1068, 1142 and 1246 m/z. All three of these ions were also detected in both control and dexamethasone-treated FCM. Partial fragmentation of 1068 m/z of NRG1 was achieved using MS2, and generated a base peak of 1047 m/z. This fragmentation was also observed in 1068 m/z from FCM. LC/MS was utilized to quantify NRG1 in FCM, using a standard curve generated using recombinant NRG1. Control FCM had a NRG1 concentration of 19.85 μg.mL-1, while the concentration in dexamethasone treated FCM was 41.59 μg.mL-1. FCM which had given no positive response to dexamethasone when tested using the indirect cultured cell system had a control NRG1 concentration of 20.85 μg.mL-1, and a dexamethasone treated concentration of 22.84 μg.mL-1. These values were not significantly different from the control value for FCM in those fibroblast cultures that had generated a positive response to dexamethasone. Results of this section of the study have provided strong evidence that NRG1 is a major component of FPF, and a review of the NRG1 signaling pathway further supports this conclusion. Insulin-like growth factors (IGFs) are functionally related to neuregulins and are known to be important in fetal development. The effect of IGF-II on synthesis of surfactant PC and its subsequent secretion from type II pneumocytes was studied. In terms of PC synthesis, IGF-II was tested at concentrations of 0.4, 0.6 and 0.8 μM. The mean increase in synthesis was found to be 6.00, 6.15 and 6.91%, respectively. These values were not significantly different from control values. Secretion of PC was tested over the concentration range of 0.1 to 1.6 μM, with no significant effect observed. Possible inhibition by IGF-II was also studied, using the known stimulants of secretion, neuromedin C and isoproterenol. No significant effect on the enhanced level of secretion was observed when IGF-II was added with either secretagogue. Lack of an appropriate receptor and/or the possibility that cultured cells may not exactly mimic the situation in vivo are probably the reasons IGF-II has no effect on either synthesis or secretion.

"March 2001". / Bibliography: leaves 193-238. / vii, 238 leaves : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Relates changes in the development of the pulmonary surfactant system in response to birth strategy, lung morphology and phylogeny in order to determine the extent of conservation in this process, by quantifying the total of phsospholipid, disaturated phospholipid and cholesterol in the lung washings of embryonic and hatchling chickens, oviparous bearded dragons and viviparous sleepy lizards, snapping turtles and green sea turtles throughout the final stages of incubation and gestation. Finds that the pattern of development of pulmonary surfactant lipids is consistent with that of mammals. / Thesis (Ph.D.)--University of Adelaide, Dept. of Physiology, 2001