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Degree awarded by the University of Adelaide. / 223 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (M.D. 1971)--Stanford University School of Medicine California, Dept. of Medicine, 1970

1v. (various paging) ; / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (D.Sc.)--University of Adelaide, Dept. of Microbiology, 1976

Thesis (Ph. D.)--University of Chicago. / From the Memorial Institute for Infectious Diseases, Chicago. Includes bibliographical references. Also available on the Internet.

Twenty-four crossbred steer calves (235 + 6 kg initial BW) were weaned, adapted to a growing diet, trained to use Calan feeders and assigned to one of four treatments in a 2 x 2 factorial arrangement as follows: (1) no transit stress and saline injection, (2) no transit stress and trace mineral and vitamin E (TM/VitE) injections, (3) transit stress and saline injection and (4) transit stress and TM/VitE injection. TM/VitE injections consisted of MultiminTM to provide 0.3, 0.6, 0.15 and 0.6 mg of Cu, Mn, Se, and Zn/kg BW, respectively, and Vita ETM to provide 9 IU of VitE/kg BW on d 0 and 21 of the study. On d 24, transit-stressed steers were subjected to a three-d, 2000-km, transportation period. During the 56-d experiment, liver and serum samples were assayed to assess trace mineral status, antibody titers to keyhole limpet hemocyanin (KLH) measured to assess humoral immunity and phytohemagglutinin(PHA)- and ovalbumin(OVA)-induced skin swelling and lymphocyte proliferation measured to assess cellular immunity. TM/VitE-injected steers grew slower (P < 0.05) over the first 24 d of the experiment and tended (P = 0.10) to grow slower after transit. TM/VitE injections increased (P < 0.05) liver Cu and Zn concentrations 135 and 21 % by d 30, respectively. TM/VitE-injected steers had increased (P < 0.05) serum Cu on d 24 and 26, but decreased (P < 0.05) serum Zn and whole blood Se compared to saline-injected steers on d 24 and 56. TM/VitE injections increased serum α-tocopherol concentrations. TM/VitE injections did not affect humoral immunity, but decreased (P < 0.05) skin-swelling responses to PHA on d 21, and decreased (P < 0.05) lymphocyte proliferation to OVA and KLH. Transit-stressed steers had higher (P < 0.05) serum Cu on d 26, and higher (P < 0.05) liver Cu concentrations on d 56 than non-transit-stressed steers. Transit stress did not affect serum Zn or whole blood Se concentrations. Injections of TM/VitE increased Cu, Zn and vitamin E, but not Se status. The TM/VitE treatment suppressed growth and cellular immune function suggesting that levels of trace minerals used in this study were too high.

Although induction of innate immune responses during viral infection is essential, it can cause acute inflammation and lead to devastating results. The deleterious effect of innate immune responses has been demonstrated in gene therapy where administration of a replication deficient adenoviral vector (Ad) caused fatality during a clinical trial. Despite recent advances in our understanding of the innate immunity, there is a lack of understanding on how different cell types interact to mount inflammatory responses, which may play an important role in regulating immune responses in vivo. In this study, we investigated the interaction between macrophages and epithelial cells, the two major cell types capable of sensing and responding to viral infection in the airway, in induction of inflammatory responses against replication deficient Ads. We show in Chapter 2 that Ad infection of the macrophage-epithelial cell co-culture resulted in synergistic induction of inflammatory responses. Ad infection of the co-culture compared to macrophages alone resulted in higher cytotoxicity and induction of significantly higher levels of inflammatory mediators including pro-inflammatory cytokines, chemokines, nitric oxide, and reactive oxygen species. We found that these synergistic responses require macrophages and epithelial cells to be in close proximity suggesting that a novel mechanism regulates the inflammatory responses. In Chapter 3, we studied whether ATP plays a role in regulating inflammatory responses during acute Ad infection. Using the co-culture system, we found that ATP signaling through P2X7 receptor (P2X7R) is critical as inhibition or deficiency of P2X7R resulted in reduced inflammatory responses. We demonstrate that ATP-P2X7R signaling regulates inflammasome activation and IL-1β secretion. Furthermore, intranasal administration of Ad resulted in high mortality in mice but inhibition of ATP-P2X7R signaling enhanced survival and reduced inflammatory responses. These results suggest that ATP released by the infected cells plays an important role in regulating inflammatory responses during acute viral infection.

This research determined the influence of dietary vitamin E levels on the growth, body composition and various health indices of juvenile Epinephelus malabaricus. Five experimental diets were formulated by adding all-rac-a-tocopherol in 0, 200, 400, 1000 and 3000mg/kg feed to the basal feed that used casein as the sole protein source. The juveniles, having an average weight of 30g, were cultivated in an indoor closed recirculation system, with 6 fishes in each tank, and 3 tanks for each experimental feed. After the 17-week feeding trial, weight gain of the fish (170-250%) was not significantly affected by the vitamin E treatments. The supplemental level of vitamin E was positively related to the lipid levels in liver, but was negatively related to the protein levels in liver. Total w-3 HUFA of polar lipids in body muscle were decreased with the increasing supply of vitamin E. It was observed on the 11th week and beyond that the fish fed with the vitamin-free diet were prone to fail in taking in feed particles although their responses to feeding were of no difference to the supplemental groups. But once the supplemental levels of vitamin E were higher than 400mg/kg no difference in feeding failure was detected, indicating deficiency of vitamin E detrimentally affected fish feeding. Plasma AST activities in the 0 and 3000mg/kg groups were significantly higher than those of the other groups. Histological sections of fish liver indicated that liver cells in low vitamin E groups showed signs of vacuolization. TBARS (thiobarbituric acid reactive substances) decreased with the increasing vitamin E levels in the feed. Vitamin E showed limited enhancement on the immune parameters studied. Except that agglutination titter was significantly higher in fish fed the high vitamin E diet (3000mg/kg) and serum lysozyme and erythrocyte SOD showed highest activity in 200 and 400mg/kg groups, intracellular super oxide anion of macrophages and serum alternative complement pathway activities were not significantly affected by vitamin E supplementation.

Twenty-four crossbred steer calves (235 + 6 kg initial BW) were weaned, adapted to a growing diet, trained to use Calan feeders and assigned to one of four treatments in a 2 x 2 factorial arrangement as follows: (1) no transit stress and saline injection, (2) no transit stress and trace mineral and vitamin E (TM/VitE) injections, (3) transit stress and saline injection and (4) transit stress and TM/VitE injection. TM/VitE injections consisted of MultiminTM to provide 0.3, 0.6, 0.15 and 0.6 mg of Cu, Mn, Se, and Zn/kg BW, respectively, and Vita ETM to provide 9 IU of VitE/kg BW on d 0 and 21 of the study. On d 24, transit-stressed steers were subjected to a three-d, 2000-km, transportation period. During the 56-d experiment, liver and serum samples were assayed to assess trace mineral status, antibody titers to keyhole limpet hemocyanin (KLH) measured to assess humoral immunity and phytohemagglutinin(PHA)- and ovalbumin(OVA)-induced skin swelling and lymphocyte proliferation measured to assess cellular immunity. TM/VitE-injected steers grew slower (P < 0.05) over the first 24 d of the experiment and tended (P = 0.10) to grow slower after transit. TM/VitE injections increased (P < 0.05) liver Cu and Zn concentrations 135 and 21 % by d 30, respectively. TM/VitE-injected steers had increased (P < 0.05) serum Cu on d 24 and 26, but decreased (P < 0.05) serum Zn and whole blood Se compared to saline-injected steers on d 24 and 56. TM/VitE injections increased serum &#945;-tocopherol concentrations. TM/VitE injections did not affect humoral immunity, but decreased (P < 0.05) skin-swelling responses to PHA on d 21, and decreased (P < 0.05) lymphocyte proliferation to OVA and KLH. Transit-stressed steers had higher (P < 0.05) serum Cu on d 26, and higher (P < 0.05) liver Cu concentrations on d 56 than non-transit-stressed steers. Transit stress did not affect serum Zn or whole blood Se concentrations. Injections of TM/VitE increased Cu, Zn and vitamin E, but not Se status. The TM/VitE treatment suppressed growth and cellular immune function suggesting that levels of trace minerals used in this study were too high.

Dissertation : Sciences : Chicago : 1907. / From the Memorial Institute for Infectious Diseases, Chicago. Notes bibliographiques.