No description available.

In this study 12 acute myeloid leukaemia (AML) patients (3 in 1<SUP>st</SUP> complete remission (CR), 3 in 2<SUP>nd</SUP> CR, 3 in early relapse or partial remission and 3 in frank relapse) were treated with continuous infusion of recombinant Interleukin-2 (rIL-2). Adverse reactions among these patients were common. In all patients, there were evidence of lymphocyte activation with subsequent upregulation of the cellular cytotoxic functions following the infusion of rIL-2. Despite this, clinical response among patients treated with active disease remains disappointing, with only 1 patient achieving a 3<SUP>rd</SUP> complete remission after being treated in early 2<SUP>nd</SUP> relapse (marrow blast counts of 10%). The other patients had brief periods of stable disease but died eventually of disease progression. No conclusion however can be drawn from patients treated in complete remission due to the small number of patients entered into the study. In vitro studies were performed in a different cohort of AML patients, at presentation and during complete remission. In all the patients, both the Natural Killer (NK) and Lectin-Dependent Cellular Cytotoxicity (LDCC) activities were significantly reduced when compared to normal healthy controls. Patients in complete remission however had higher values than those studied during active diseases. These findings would suggest a strong rationale for the use of immunotherapy capable of upregulating the NK and LDCC activities, e.g. rIL-2. Further rationale for the use of immunotherapy has been drawn from the findings that leukaemia blast cells of AML are immunogenic, as evidenced by data of T cell activation in these patients and the presence of complement-fixing antibodies for autologous myeloblasts. More importantly no stimulation of the myeloblast proliferation by IL-2 was observed in any of the myeloblasts studied. All these findings would point to a good and safe rationale for the use of rIL-2 in AML patients.

Cyclosporin A immunosuppression following organ transplantation is associated with a reversible nephrotoxicity as manifested by elevations in serum urea and creatinine concentrations and urinary N-acetyl-B-D-glucosaminidase activities. The metabolism of Cyclosporin A is primarily via the hepatic cytochrome P-450 mono-oxygenase system with previous studies having demonstrated that the short term co-administration of phenobarbitone, an inducer of this enzyme system, ameliorates this nephrotoxicity in the non-renal allografted rat. Initial studies demonstrated that the induction of Cyclosporin A nephrotoxicity in the Lewis rat followed by the co-administration of phenobarbitone in the long term abolished nephrotoxicity in the female whilst alleviating it in the male animal. In addition Cyclosporin A hepatotoxicity was also abolished in female rats co-treated with phenobarbitone. A rat renal transplantation model was successfully developed to allow the study of Cyclosporin A nephrotoxicity in the renal allografted animal. Initial studies demonstrated a protective effect of phenobarbitone against Cyclosporin A nephrotoxicity within the first 14 days of treatment in female, but not male allografted animals. These studies also demonstrated a greater susceptibility of the male renal allografted and surgically intact rat to Cyclosporin A induced nephrotoxicity. The effect of ischaemia and sympathetic nervous system denervation were investigated using a series of Lewis syngeneic renal transplanted animals. Histological examination revealed Cyclosporin A induced renal damage to be more marked in non-transplanted than transplanted kidneys. The results are discussed in relation to cold and warm ischaemia and also to the role of the sympathetic nervous and renin-angiotensin-aldosterone systems in the potentiation of Cyclosporin A induced nephrotoxicity. The effect of long term phenobarbitone treatment on Cyclosporin A induced deteriorations in renal and hepatic function was determined using the Lewis syngeneic transplant model. The effect of intraoperative liver ischaemia and diethyl ether anaesthesia on hepatic function and their potentiation of Cyclosporin A hepatotoxicity is also considered. Finally the role of surgical stress and reduction of renal mass by unilateral nephrectomy, on Cyclosporin A nephrotoxicity was studied revealing a protective effect of unilateral nephrectomy against nephrotoxicity in the female animal. Previous studies have demonstrated that reduction in renal mass results in glomerulosclerosis with a progressive impairment of renal function. The protective effect of unilateral nephrectomy reported here is discussed in relation to a Cyclosporin A induced reduction in glomerular filtration rate and subsequent protection against glomerulosclerosis.

The treatment of end-stage renal disease (ESRD) by dialysis and transplantation (renal replacement therapy - RRT) imposes major social and economic burdens on the patient, the family and society. Data obtained from 2 Scottish and 4 European renal units indicate that non-renal comorbid illness significantly increased patient mortality. Furthermore, application of a simple risk stratification method based on age and comorbidity divided patients into groups which carried different survival rates. Multivariate analysis showed that even after adjustment for comorbidity and age, an apparent "centre effect" persisted which ranked the centres. A further study examined factors influencing early mortality on RRT. The method of risk stratification described can be used for comparative survival studies by national and international registries. The generic health status questionnaire (the SF-36) which has been validated in the UK was administered to patients receiving all 3 modalities of RRT and their health status compared with a large sample of the general population. Patients' quality of life was influenced by mode of treatment and like survival was also shown to relate to comorbidity. Further studies of the incidence and prevalence of chronic renal failure in Grampian showed that advancing age and comorbidity significantly influenced the decision by non-nephrologists to refer a patient to the renal service. The results of this study have manifest resource implications for the provision of renal services. A protocol for the use of erythroprotein in the Aberdeen renal unit was developed and implemented. Its efficacy was monitored by studying defined outcome measures. This study showed that formal implementation of the protocol led to an increase in the proportion of patients with haemoglobin concentrations in the acceptable range and a fall in the number of blood transfusions.

This thesis aims to place corneal allograft rejection in the context of general transplantation immunology, examine the role of lymphocyte subsets in the rejection process and consider the potential application of monoclonal antibody therapy in clinical corneal graft rejection. The literature relating to the current clinical practice of corneal grafting, with particular reference to corneal allograft rejection, is reviewed in chapter 1 to present the extent of the problem. Chapter 2 then reviews the mechanisms of allograft rejection from the literature of transplantation immunology, much of which has arisen from studies of kidney, heart, pancreatic islets and liver in animal models. The materials and methods are described in detail in chapter 3, and only the relevant experimental design is detailed in the Materials and Methods sections of the succeeding chapters. The experimental mouse model of transplanting corneal tissue into the renal subcapsular is evaluated in chapter 4, demonstrating that isografts survive indefinitely whereas allografts are rejected typically by 30 days. Pretransplant sensitisation decreased allograft survival time to 10 days. Immunohistochemistry demonstrated the presence of CD4⁺ and CD8⁺ lymphocytes and macrophages at the rejection site. Heterotopic corneal graft recipients were then treated with various monoclonal antibody regimes. Chapter 5 demonstrates that allograft survival can be increased by either anti-CD4 or anti-CD8 therapy, providing near total depletion of the respective lymphocyte subset is achieved. Xenograft rejection is shown to depend on mainly CD4⁺ lymphocytes in chapter 6, with no benefit being found of depleting the CD8⁺ subset in addition. A mild immunosuppressive effect of anti-Vβ8 monoclonal antibody is demonstrated and discussed in chapter 7. The final chapter discusses these results in the light of recent, related work in other transplant systems, and presents a case for a trial of intracameral pan-T-cell monoclonal antibody treatment.

No description available.

No description available.

Erratum is pasted on back end paper. / Bibliography: leaves 231-268. / xv, 268 leaves : ill. (chiefly col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / This thesis examines the expression of cell adhesion molecules on both endothelial cells (ECs) and circulating leukocytes, and investigates the role of these molecules in renal allograft rejection. The aims of the study are to establish an ovine model of renal allograft transplantation, to generate monoclonal antibodies (mAbs) against ovine endothelial cell adhesion molecules, to examine the efficacy of the mAbs in prolonging the survival of the sheep renal allografts and to study the kinetics of expression of cell adhesion molecules (CAMs) during cellular activation 'in vitro' and 'in vivo' during the onset of allograft rejection. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1996

vii, 228 leaves : ill. ; 28 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 Surgery, 1970

Photosynthetic activity of three seagrass species, Posidonia sinuosa Cambridge et Kuo, Posidonia australis Hook. f. and Halophila ovalis (R. Br.) Hook., growing in Cockburn Sound, Western Australia, was assessed using an underwater pulse amplitude modulated fluorometer (Diving-PAM). The study aimed to determine possible causes and the extent of stress to seagrasses during transplantation, so that rehabilitation efforts can be improved by reducing stress during the transplant process. Absorptance factors for each species were determined as 0.64 ± 0.04 for P. sinuosa, 0.59 ± 0.02 for P. australis and 0.55 ± 0.02 for H. ovalis, which were substantially lower than previously reported photosynthetic absorption factors. Transmittance, reflectance and non-photosynthetic absorptance of light diverted between 35-45% of irradiance from use in photosynthesis. An investigation of potential errors during measurement of rapid light curves (RLCs) reinforced the importance of ensuring that leaves remained stationary in the Universal Sample Holder. Any movement of seagrass leaves resulted in incorrect measurements of electron transport rates (ETR). A study on seasonal photosynthetic rates of each species found that maximum ETR (ETRmax) varied seasonally and among species. The highest ETRmax for each species occurred during summer, when ambient irradiances were at a maximum, and decreased during autumn. H. ovalis had the highest overall ETRmax in summer, followed by P. australis and P. sinuosa. Effective quantum yield(ΔF/Fm′)of each species varied seasonally, changing inversely with irradiance, which agrees with previously reported studies. ETRmax for each species also showed a diurnal pattern coincident with irradiance throughout the day. The ÄF/Fm for all species demonstrated a diurnal decrease in photosynthetic efficiency coincident with the midday irradiance maximum. Large natural variation in ETR was detected in all species, indicating that the effects of external stress on ETR may be difficult to detect. Two adjacent, physically separated seagrass meadows were examined to determine if apparent visual differences between the sites were reflected by measured physical and photosynthetic characteristics. ETR, leaf area index and sediment grain size differed between sites, but ΔF/Fm, canopy height, shoot density and epiphyte biomass did not, indicating a poor connection between physical and photosynthetic characteristics at these two meadows. Therefore caution should be used when attempting to visually assess the photosynthetic activity of a site based on physical characteristics. Changes in photosynthetic activity were monitored to determine seagrass stress during transplantation, and post-transplantation recovery. Two transplantation methods, sprigs and plugs, were examined, and photosynthetic activity was compared before, during and after transplantation. ETRmax of sprigs took one to two months to increase to the same level recorded at a control meadow, primarily due to desiccation stress suffered during transport. The ΔF/Fm′ decreased below 0.2 after transplantation, but fully recovered after three months. Survival of sprigs was reduced due to strong currents and heavy epiphytic fouling. The ETRmax of transplanted plugs (5, 10 and 15 cm diameter) took up to one week to recover to the same level recorded at a control meadow. Survival of plugs was reduced due to winter swells and storms. Since the leading human-controlled cause of transplant failure was desiccation stress, future transplanting efforts should endeavour to keep seagrasses submerged at all times during the transplanting process.