Thesis (Ph.D.)--University of Florida, 2004. / Typescript. Title from title page of source document. Document formatted into pages; contains 234 pages. Includes Vita. Includes bibliographical references.

Thesis (M.S.)--University of Florida, 2005. / Title from title page of source document. Document formatted into pages; contains 80 pages. Includes vita. Includes bibliographical references.

The progressive growth of tumors in human cancer patients and experimental animals has frequently been associated with a generalized depression of immunological responsiveness. Suppressor cells have been implicated as mediators of tumor-associated immunosuppression, but the identities of the cells causing suppression and the mechanisms by which they act have been unclear. The object of this thesis was thus to determine: if suppressor cells capable of non specifically suppressing immune responses were present in anergic mice bearing methylcholanthrene-induced sarcomas; the cell types responsible for suppression; and the mechanisms by which suppression occurs. The spleens of mice with large tumors were found to contain two distinct populations of non specific suppressor cells. One population inhibited the proliferative responses of normal lymphocytes to the T cell mitogen, Concanavalin A (Con A) and the B cell mitogen, lipopolysaccharide (LPS). These cells also inhibited the generation of antibody forming cells by normal lymphoid cells stimulated in vitro with the T cell dependent antigen, sheep red blood cells (SRBC) and the T cell independent antigen, dinitrophenylated-lipopolysaccharide (DNP-LPS). These suppressor cells appeared to be from the macrophage/monocyte line since they adhered to plastic and nylon wool, were removed by carbonyl iron and magnet, and were inactivated by carragheenan treatment, but were not removed by anti-Thy-1 or anti-mouse immunoglobulin sera plus complement. They were among the less dense spleen cells since they were retained in the light fraction after centrifugation on hypaque-ficoll of specific gravity 1.08 and did not appear to require cell division in order to suppress- since mitomycin C treatment did not inactivate them. Cell-cell contact appeared to be essential for suppression. The second population of suppressor cells, which pelleted to the bottom of a hypaque-ficoll gradient, inhibited only the generation of plaque forming cells to the T cell dependent antigen, SRBC. These cells appeared to be T cells since they were non adherent to plastic or nylon wool, were not removed by carbonyl iron and magnet, but were removed by anti-Thy-1 serum plus complement. Cell division was necessary since suppressive activity was totally removed by mitomycin C treatment. Suppression by this cell type appeared to be mediated by a soluble factor with a molecular weight of about 3,500 to 12,000. / Science, Faculty of / Microbiology and Immunology, Department of / Graduate

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A Thesis submitted to the Faculty of Health Sciences, University of Witwatersrand, in fulfilment of the requirements for the degree of Doctor of philosophy. Johannesburg, 2017. / Pancreatic cancer (PDAC) is a deadly type of cancer with almost an equal amount of new cases and deaths observed yearly. It accounts for about 7% of cancer related deaths worldwide with less than 5% of PDAC patients living up to 5 years. The lack of specific and sensitive diagnostic tests is strongly responsible for this poor statistic. The discovery of differentially expressed genes and proteins associated with PDAC is crucial to elucidating this condition and may lead to biomarker finding and further understanding of the disease. This in turn may lead to improved diagnostic tests for early diagnosis. The aim of this study was to identify novel potential biomarkers for PDAC. [No abstract provided. Information taken from summary] / MT2017

Brain tumours are the second most common malignancy in childhood and account for approximately 20% of all childhood cancers. Children diagnosed with a primary brain tumour are at risk of significant morbidity. Measurement of quality of life (QOL) and health status (HS) are important in quantifying morbidity and identifying strategies to provide relevant support for patients. We aimed to: (1) Measure QOL and HS, using the PedsQL and HUI3 in children with brain tumours one, six and twelve months after diagnosis. (2) Compare QOL and HS with “normal” matched controls, and assess the relationship between parent- and self-report QOL and HS. (3) Identify determinants of overall QOL one year after diagnosis. A total of 45 patients and 43 controls were recruited to the study, with 37 patients and 42 controls and 27 patients and 31 controls eligible for comparison of QOL using parent-report and self-report PedsQL respectively. Thirty-five patients were eligible for analysis of determinants of parent-report and 26 for self-report QOL one year after diagnosis. There were 29 patients and 29 controls, and 21 patients and 22 controls eligible for comparison of HS between patients and controls using the parent-report and selfreport HUI3 respectively, one year after diagnosis. In addition, 29 and 21 patients were eligible for analysis of determinants of parent- and self-reported HS one year after diagnosis. Children with a primary brain tumour have significantly lower QOL/ HS in the first year after diagnosis than normal controls. QOL/ HS improved significantly over time, most notably in the six months after diagnosis. For patients, agreement between parent- and self-report was variable, with greater agreement for the more observable (physical), compared with less observable (psychosocial) domains. Agreement between parent- and self-report was better using the HUI3 than the PedsQL. Parents of patients rated their children's HRQL lower than their child did, while for controls this was reversed. Selective attention one month after diagnosis and infratentorial tumour site are most important in predicting both parent- and self-report overall QOL at 1 year after diagnosis. Larger multi-centre, prospective studies are needed to confirm these findings. Cognitive remediation and/ or pharmacological intervention, particularly aimed at children with infratentorial tumours may improve attention and subsequently QOL, and both merit further investigation. THE CLIC SARGENT BRAIN TUMOUR STUDY The study on QOL and its determinants as reported in this thesis was undertaken as part of a prospective longitudinal multidisciplinary study led by Dr Peta Sharples (Consultant Paediatric Neurologist) and Dr Stephen Lowis (Consultant Paediatric Oncologist), with support from Dr Renee McCarter (Consultant Neuropsychologist), Professor Mike Stevens (Professor of Paediatric Oncology), Dr Andrew Curran (Senior Registrar in Paediatric Neurology), Dr Linda Hunt (Senior Lecturer in Medical Statistics) and Mr Robert Shortman (Assistant Psychologist). The overall aim of the study was to investigate, in detail, the effects of childhood brain tumour on the child and family. More specifically, it was intended to investigate the effect of primary brain tumours on cognitive, neurological, behavioural and functional outcome by comparing children presenting with CNS tumours with matched normal controls. In addition, the study sought to assess the effect of the diagnosis and treatment on the primary carer’s emotional status, family functioning and other family variables. Assessments were to be undertaken at an early stage (within 1 month of diagnosis) and at 6 and 12 months thereafter with the intention that the findings would define the early rehabilitation needs and rate of recovery of this patient population. In collaboration with supervisors, particularly Dr. Sharples, the author of this thesis, after reviewing the literature on QOS in children diagnosed and treated for a primary intracranial tumour made the decision to use QOL as the primary outcome measure and dependent variable. During the study, the importance of assessment of the relationship between parent- and child-reported QOL using both the PedsQL and HUI3 became clear, and self- report HUI3, in addition to the PedsQL, was incorporated into the study and became an important theme of two of the papers submitted in support of the author’s thesis and the thesis itself. In addition to the contribution to the direction of the study, as mentioned above, the PhD applicant’s role in the study were (1) to recruit all patients and controls; (2) to collect, score and enter data relating to quality of life, behavioural/emotional functioning, neurological and physical outcome and family structure and function in patients, controls and their families; (3) to undertake preliminary data analysis for presentation at local, national and international meetings, and publication of results in the form of the four papers submitted in support of the PhD, Integrated Format; (4) to collate the data and divide it for publication in its current form; (5) to write and act as corresponding author for the four papers submitted in support of the PhD. Details of collection, handling and statistical analysis of data are covered below. For the purpose of this manuscript, only data used in the papers submitted in support of the author’s PhD are referred to, not other data arising from study.

A dissertation presented in fulfillment of part of the requirements for the degree of Master of Medicine (Pathology) in the Faculty of Medicine, University of the Witwatersrand, Johannesburg, November, 1966. / WHSLYP2017

Submitted a requirements for the degree of Master of Medicine in the branch of Community Health (Occupational Medicine). It has not been used, either wholly or partially, for any other degree or examination at this or any other university. / Introduction This is the first study in South Africa to look for an association between breast cancer and occupations in black women. Breast cancer is one of the commonest forms of malignancy experienced by women in South Africa and its incidence is increasing (1). Approximately six million women work in South Africa, some of these women are likely to be exposed to carcinogenic agents during their daily working lives. Many occupational carcinogens to the breast have been described and there is some evidence suggesting that many more synthetic chemicals used in different industries may also have carcinogenic properties that have not fully been explored as yet (2). This study plans to identify occupations that place black women at risk of breast cancer in the South African context. Thereafter, it will assess if there is an association between shift work (a known carcinogen to the breast) and breast cancer in black women in South Africa. The findings of the study could be of particular significance to the local context, given that women are entering the workforce in increasing numbers possibly putting more women at risk. Aims The aims of the study are to identify occupations that possibly increase the risk of breast cancer in South Africa, and to specifically assess if there is an association between shift work and breast cancer in black South African women. Objectives To determine whether there are associations between different occupations and breast cancer in black women by calculating the odds ratios (ORs) for breast cancer in different occupations in South Africa. To examine the association between shift work and breast cancer in black women adjusting for variables that may confound the association. Methods The study is an unmatched case-control study using secondary data from the existing Johannesburg Cancer Case Control Study (JCCS) database. The JCCS study is a large ongoing study that recruits black male and female cancer patients with all types of cancers receiving treatment at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH), a tertiary hospital in Johannesburg. All women patients recruited from 1 January 2001 to 31 December 2009 were included in the analysis. This included 1 903 cases and 3 990 controls. An expert group was set up to estimate the likelihood of occupational engagement in shift work for the existing occupational groupings present in the JCCS database. These occupations were classified into: a) high probability of shift work; b) possibility of shift work and c) unlikely to do shift work. ORs were estimated using logistic regression. Those who had never worked were the reference category. Bivariate analysis was then carried out to estimate ORs between individual occupations and breast cancer and later to estimate ORs between the likelihood of involvement in shift work and breast cancer. Multivariate logistic regression followed a forward stepwise approach and all the possible confounders present in the JCCS database were considered. These included age, smoking, drinking alcohol, age at first menarche, parity, age at menopause, use of oral contraception and retroviral status. Results With regards to occupation, the bivariate analyses showed significant ORs for breast cancer in the occupational categories of health, education, social services, retail, hospitality, construction, food, textile and manufacturing, with the highest OR in education (OR 2.33, 95% CI: 1.44 – 3.78) and social service (OR 2.39, 95% CI: 1.24 – 4.58) followed by office workers (OR 2.17, 95% CI: 1.47-3.20) and health workers (OR 2.01, 95% CI: 1.33-3.04). Agriculture (OR 0.55, 95% CI: 0.32 – 0.94) and domestic workers (OR 0.96, 95% CI: 0.75 – 1.22) had ORs under one. Following the adjustments for possible confounders, no statistically significant ORs were found between specific occupations and breast cancer. However, manufacturing had the highest OR (OR 1.44, 95% CI: 0.42- 4.94), followed by office workers (OR 1.44 95% CI: 0.31- 5.94) and health workers (OR 1.31, 95% CI: 0.36-4.76) as compared to the never worked group. In the bivariate analyses there was an association between a possibility of doing shift workers and breast cancer (OR 1.66, 95% CI: 1.41-1.97). Similarly, women who had a high likelihood of participating in shift work had an elevated odds ratio for the disease (OR 1.76, 95% CI: 1.44-2.15). After adjusting for confounders in the multivariate model the ORs for both shift work groups were increased with women who possibly did shift work having an OR of 2.18 (95% CI: 1.34- 3.56) and those who had a high likelihood of carrying out shift work having an OR of 2.13 (95% CI: 1.26- 3.61). Conclusions The bivariate analyses identified elevated ORs for breast cancer in some occupations but in multivariate analyses no statistically significant OR were found. Nevertheless ORs>1 were found for the occupational categories of manufacturing, office and health workers. This study reports a strong association of breast cancer and shift work, which is supported by the literature. However shift work still remains necessary for the functioning of many industries. Many gaps still exist, however, and this study has tried to address one of the neglected areas of occupational risks for breast cancer development.