Pre-clinical studies suggest that granulocyte-colony stimulating factor (GCSF) holds promise for the treatment of ischaemic heart disease (IHD). However, its safety and efficacy in this setting, and in particular in patients with chronic refractory 'no-option' IHD, is unclear. Therefore, a clinical study was initiated in 20 such 'no-option' patients, with the aim of assessing the safety and efficacy of both G-CSF administration, and also, that of an intracoronary infusion of G-CSF mobilised CD133+ cells. The study involved initial baseline cardiac ischaemia assessment (symptom based questionnaire, exercise stress test (EST), nuclear Sestamibi (MIBI) and dobutamine stress echocardiographic (DSE) imaging). Stable 'no-option' IHD patients then received open-label G-CSF commencing at 10μg/kg s/c for five days, with an EST on days four and six (to facilitate myocardial cytokine generation and stem cell trafficking). After three months, cardiac ischaemia assessment and the same regimen of G-CSF and ESTs were repeated, but in addition, leukapheresis and then a randomised double-blinded intracoronary infusion of CD133+ or unselected cells were performed. Final cardiac ischaemia assessment was three months thereafter. Eighteen male and two female subjects (mean age 62.4) were enrolled. Eight events occurred that fulfilled pre-specified 'adverse event' criteria: four ischaemic (troponin positive) episodes, two episodes of transient thrombocytopaenia (one profound), one episode of gout and one unscheduled hospitalisation for exhaustion. Troponin was positive on 17 further occasions (all CK-MB negative), however, at these instances angina severity was identical to baseline. Importantly, no adverse event(s) resulted in any detectable long-term adverse sequelae for any subject. From baseline to final follow-up, the administration of two cycles of G-CSF was associated with statistically significant improvements in a range of subjective outcomes, including anginal symptoms, quality of life and EST performance (all p < 0.005). However, the objective MIBI and DSE scans showed only trends towards improvement (all p > 0.1). Compared to unselected cells, an intracoronary infusion of CD133+ cells did not improve either subjective or objective outcomes. In conclusion, administering G-CSF to patients with refractory 'no-option' IHD warrants careful monitoring, but may be performed with safety. A larger, randomised double-blind placebo-controlled trial of G-CSF in these patients appears warranted.

In the last decade, there has been renewed interest in the use of granulocyte transfusions to treat infections in individuals with compromised immune systems. However, granulocytes only remain functional for about a day after isolation and this short shelf life is a significant drawback. Cryopreservation would allow long term storage of granulocytes, but an effective cryopreservation method is currently unavailable. The following study was performed to provide membrane permeability values for multiple cryoprotectants in hopes of aiding the optimization of cryoprotectant addition and removal and minimizing the detrimental effects of the process. The granulocytes were separated from whole blood using centrifugation with Polymorphprep as the separating agent. The cellular membrane permeability values were then measured using a Beckman Coulter Counter Multisizer 3 under custom setup conditions. The cryoprotectants studied were glycerol, DMSO, ethylene glycol, and propylene glycol at the respective total concentrations of 1, 2, 2, 1 Osm/kg at temperatures of 4, 21, and 37 °C. The resulting membrane solute permeability values at 20 °C reference temperature for DMSO, ethylene glycol, glycerol, and propylene glycol were respectively 5.96, 7.84, 0.950, and 3.45 um/min and the Arrhenius activation energies were respectively 60.4, 58.7, 68.2, and 62.3 kJ/mol. The resulting hydraulic permeability values in the same order and temperature were 0.196, 0.189, 0.259, and 0.113 um/(atm min) and the Arrhenius activation energies were respectively 56.3, 60.7, 68.5, and 47.1 kJ/mol. It is anticipated that these permeability values will aid in the development of successful cryopreservation procedures for granulocytes. / Graduation date: 2013

Allergens are complex mixes of proteins and other compounds that have innate signaling capacity leading to Th2 inflammation. Understanding the role of each of these signals is essential to determining what separates allergens from innocuous proteins. Here, we examine two models for Th2 inflammation: infection with the helminth Trichinella spiralis and footpad immunization with papain, a cysteine protease structurally similar to proteases found in many common allergens including grass pollen and dust mites and helminth-secreted proteases secreted. Together, these studies highlight previously unappreciated effector roles of accessory cells during Th2 inflammation.

Pre-clinical studies suggest that granulocyte-colony stimulating factor (GCSF) holds promise for the treatment of ischaemic heart disease (IHD). However, its safety and efficacy in this setting, and in particular in patients with chronic refractory 'no-option' IHD, is unclear. Therefore, a clinical study was initiated in 20 such 'no-option' patients, with the aim of assessing the safety and efficacy of both G-CSF administration, and also, that of an intracoronary infusion of G-CSF mobilised CD133+ cells. The study involved initial baseline cardiac ischaemia assessment (symptom based questionnaire, exercise stress test (EST), nuclear Sestamibi (MIBI) and dobutamine stress echocardiographic (DSE) imaging). Stable 'no-option' IHD patients then received open-label G-CSF commencing at 10μg/kg s/c for five days, with an EST on days four and six (to facilitate myocardial cytokine generation and stem cell trafficking). After three months, cardiac ischaemia assessment and the same regimen of G-CSF and ESTs were repeated, but in addition, leukapheresis and then a randomised double-blinded intracoronary infusion of CD133+ or unselected cells were performed. Final cardiac ischaemia assessment was three months thereafter. Eighteen male and two female subjects (mean age 62.4) were enrolled. Eight events occurred that fulfilled pre-specified 'adverse event' criteria: four ischaemic (troponin positive) episodes, two episodes of transient thrombocytopaenia (one profound), one episode of gout and one unscheduled hospitalisation for exhaustion. Troponin was positive on 17 further occasions (all CK-MB negative), however, at these instances angina severity was identical to baseline. Importantly, no adverse event(s) resulted in any detectable long-term adverse sequelae for any subject. From baseline to final follow-up, the administration of two cycles of G-CSF was associated with statistically significant improvements in a range of subjective outcomes, including anginal symptoms, quality of life and EST performance (all p < 0.005). However, the objective MIBI and DSE scans showed only trends towards improvement (all p > 0.1). Compared to unselected cells, an intracoronary infusion of CD133+ cells did not improve either subjective or objective outcomes. In conclusion, administering G-CSF to patients with refractory 'no-option' IHD warrants careful monitoring, but may be performed with safety. A larger, randomised double-blind placebo-controlled trial of G-CSF in these patients appears warranted.

Amendments to thesis in pocket on back cover. / Copy of author's previously published article in pocket on back cover. / Bibliography: leaves 124-172. / viii, 172, [101] leaves, [22] leaves of plates : ill. (chiefly col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Studies the biological effects and leukaemic potential of h[beta]c mutants using murine models. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1999?

Errata posted inside back end-paper (leaf 250). / Bibliography: leaves 204-249. / xxiv, 250 leaves, [8] leaves of plates : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Investigates the nature of the seminal vesicle-derived trigger(s) that stimulate the granulocyte-macrophage colony-stimulating factor release from the murine uterine epithelium. / Thesis (Ph.D.)--University of Adelaide, Dept. of Obstetrics and Gynaecology, 1999

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 4 uppsatser.

Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1999? / Amendments to thesis in pocket on back cover. Copy of author's previously published article in pocket on back cover. Bibliography: leaves 124-172.

Thesis (M. Phil.)--University of Hong Kong, 2008. / Includes bibliographical references (leaf 119-147) Also available in print.

Thesis (M. Phil.)--University of Hong Kong, 2008. / Includes bibliographical references (leaf 119-147) Also available online.