Pregnancy-specific glycoprotein function, conservation and receptor investigation

Pregnancy-specific glycoproteins (PSGs) are highly glycosylated secreted proteins encoded by multi-gene families in some placental mammals. They are carcinoembryonic antigen (CEA) family and immunoglobulin (Ig) superfamily members. PSGs are immunomodulatory, and have been demonstrated to possess antiplatelet and pro-angiogenic properties. Low serum levels of these proteins have been correlated with adverse pregnancy outcomes. Objectives: Main research goals of this thesis were: 1). To attempt to replicate previously reported cytokine responses to PSG-treatment of immune cells and subsequently to investigate functionally important amino acids within PSG1. 2). To determine whether candidate receptor, integrin αvβ3, was a binding partner for PSG1 and to investigate whether PSG1 possessed functionality in a leukocyte-endothelial interaction assay. 3). To determine whether proteins generated from recently identified putative PSG genes in the horse shared functional properties with PSGs from other species. Outcomes: 1). Sequential domain deletion of PSG1 as well as mutation of conserved residues within the PSG1 Ndomain did not affect PSG1-induced TGF-β1. The investigated response was subsequently found to be the result of latent TGF-β1 contaminating the recombinant protein. Protein further purified by SEC to remove this showed no induction of TGF-β1. The most N-terminal glycosylation site was demonstrated to have an important role in PSG N domain secretion. PSG1 attenuated LPS-induced IL-6 and TNF-α. Investigations into signalling underpinning this proved inconclusive. 2). Integrin αvβ3 was identified as a novel PSG1 receptor mediating an as yet unknown function. Preliminary investigations into a role for PSGs as inhibitors of leukocyte endothelial interactions showed no effect by PSG1. 3). Horse PSG protein, CEACAM49, was shown to be similarly contaminated by latent TGF-β1 particle and once removed did not demonstrate TGF-β1 release. Interestingly horse PSG did show anti-platelet properties through inhibition of the plateletfibrinogen interaction as previously published for mouse and human PSGs.

An exploration through interview and drawings of the experiences of patients diagnosed with oral cancer across their cancer trajectory

Background: The treatment of oral cancer is complex and lengthy. Curative treatment implies a combination of surgery, radiotherapy and chemotherapy. The main goal of treatment is to guarantee long-term tumour free survival with as little functional and cosmetic damage. Despite progress in developing these strategies, cancers of the oral cavity continue to have high mortality rates that have not improved dramatically over the past ten years. Aim: The aim of this study was to uniquely explore the dynamic changes in the physical, psychological, social and existential experiences of newly diagnosed patients with oral cancer at two points across their cancer illness trajectory i.e. at the time of diagnosis and at the end of treatment. Methodology: A qualitative prospective longitudinal design was employed. Non-probability purposive sampling allowed the recruitment of 10 participants. The principal data collection method used was a digital audio taped semi-structured interview along with drawings produced by the participants. Analysis: Data was analysed using latent content analyses. Summary: Three ‘dynamic’ themes, physical, psychosocial and existential experiences were revealed that interact and influence each other in a complex and compound whole. These experiences are present at different degrees and throughout the entire trajectory of care. Patients have a number of specific concerns and challenges that cannot be compartmentalised into unitary or discrete aspects of their daily lives. Conclusion & Implications: An understanding of the patient’s experience of their illness at all stages of the disease trajectory, is essential to inform service providers’ decision making if the delivery of care is to be client centred. Dynamic and fluctuating changes in the patient’s personal experience of the cancer journey require dynamic, energetic and timely input from health care professionals.

Eleanor Roosevelt: supporting Zion, denying Palestine

Eleanor Roosevelt, as a renowned humanitarian, portrayed an inconsistency by supporting Zionist ambitions for a national homeland in Palestine while simultaneously ignoring the rights of the indigenous Palestinians. Because of this dichotomy, this dissertation explores her attitudes, her disposition and her position in light of the conflict in the region. It conveys how her particular character traits interplayed with the cultural influences prevalent in mid-century America and encouraged her empathy with the plight of European Jews after the Holocaust. As she evolved politically, initially under the tutelage of Franklin Roosevelt and latterly as a UN delegate, she outgrew the anti-Semitism of the period to become a committed Zionist. Judging the Palestinians as ‘primitives’ incapable of self-government and heartened by Jewish development, she supported the partition of Palestine in November 1947. After the 1948 Arab-Israeli war the 800,000 Palestinian refugees encamped in neighbouring Arab states threatened to destabilise the region. Her solution was to discourage repatriation and to re-settle them in Iraq – a plan that directly contravened the principles of the December 1948 Universal Declaration of Human Rights proclaimed by the UN committee she had chaired. No detailed work has been conducted on these aspects of Eleanor Roosevelt’s life; this dissertation reveals a complex person rather than a model of ‘humanitarianism’, and one whose activities cannot be so simply categorised. In the eight chapters that follow, her own thoughts are disclosed through her ‘My Day’ newspaper column, through letters to friends and to members of the public that petitioned her, through a scrutiny of her articles, books and autobiography. This information was attained as a result of archival research in the US and in The Netherlands and was considered against an extensive range of secondary literature. During the Cold War, to offset Soviet incursion, Eleanor Roosevelt promoted Jewish usurpation of Palestinian lands with equanimity in order that an industrious Western-style democracy would bring stability to the region. These events facilitated the exposure of a latent Orientalism and an imperialistic lien that fostered paternalism in a woman new to the nuances of international diplomacy.