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No description available.

No description available.

No description available.

No description available.

Beta-Thalassaemia-Major is a life-long genetic haemoglobin disorder where patients require intensive treatment regimens to stay alive, including frequent blood transfusions and daily chelation therapy. Adherence to chelation therapy is vitally important to prevent organ damage and potential death. Little research has been conducted into the psychosocial correlates of chelation adherence representing a significant gap in the literature. Information concerning psychosocial factors is important when considering potential interventions to improve adherence and improve health outcomes. The present study aimed to address this gap in the literature by investigating correlates of chelation adherence on a daily (episodic) basis as well as on a generic (global) basis. Using constructs suggested by the Health Action Process Approach, the study hypotheses were that situational self-efficacy and positive outcome expectancies would differentiate episodes of adherence and non-adherence. A secondary hypothesis was that lower levels of depression and perceptions of severe illness consequences would be associated with higher global adherence. Thirty-seven participants with Beta-Thalassaemia Major were recruited for the study, 31 of whom completed the episodic part of the study and all who completed the global parts of the study. A structured interview was used to obtain accounts of adherent and non-adherent episodes including behavioural situational variables as well as psychological situational variables (e.g. self-efficacy, mood and outcome expectancies). Validated questionnaires were used to assess depression, anxiety and illness perceptions and their relationship with adherence. Bivariate analyses revealed that a number of behavioural situational variables were associated with adherence episodes as well as ratings of self-efficacy and outcome expectancies. Conditional logistic regression analysis revealed that positive outcome expectancies and higher self-efficacy together Significantly predicted adherent episodes, however, only self-efficacy independently predicted adherent episodes. No associations between global adherence and depression, anxiety and illness perceptions were found. The findings are discussed in relation to general adherence literature as well as to chelation adherence specifically. Theoretical and practice implications are explored.

Congenital dyserythropoietic anaemia type 1 (CDA I) is an autosomal recessive disorder of erythropoiesis characterized by a clinical picture of anaemia secondary to ineffective erythropoiesis, haemolysis and striking morphology of erythroid precursors (inteternuclear chromatin bridges, spongy heterochromatin, invaginations of nuclear membrane) and erythrocytes (macrocytosis, anisocytosis, basophilic stippling) in the bone marrow and peripheral blood smears, respectively. The aim of this work was to 1) collect patients and characterize this rare disease, 2) understand the genetics of CDA I using linkage analysis, 3) identify the CDAN1 gene mutations and finally 4) to study the molecular perturbations which lead to dyserythropoiesis.

Fanconi anaemia (FA) is a hereditary, heterogeneous disease that is characterized by chromosomal instability, hypersensitivity to DNA cross-linking agents and cancer. Fifteen FA genes are identified, mutations in any of which are known to cause FA: FANCA, B, C, DI, D2, E, F, G, I, J, L, M, N, 0, and P. Cell lines defective for any FA gene show cellular and cytogenetic hypersensitivity to DNA inter-strand cross-linking agents such as mitomycin C (MMC). The FA proteins function through several complexes in a poorly defined, intricate phosphorylation-ubiquitination DNA repair network (the FA-BRCA pathway) that mediates the removal of inter-strand cross-links (ICL). ICL removal requires the action several different repair activities including cross-link unhooking, translesion synthesis and subsequent repair of the double-strand break (DSB) formed by homologous recombination. Critical for ICL repair is the FA core complex (comprising A, B, C, E, F, G, L and M proteins) that is essential for the mono- ubiquitination of FANCD2 and FANCI and formation of the ID complex. FANCG, one component of the FA core complex, is involved in at least two further distinct protein complexes that likely have independent functional roles to the core complex. The G-ERCC-XPF complex (FANCG-XPF-ERCCI) is required for inter-strand cross link (ICL) unhooking. The G-BRCA2 complex (FANCDIIBRCA2-FANCD2-FANCG-XRCC3) is hypothesised to be involved in modulating some aspect of homologous recombination repair (HRR). The aim of this study is to characterise the roles ofFANCG and the G-BRCA2 complex in ICL and DSB repair. MMC and phleomycin, that induces DNA strand breaks, were utilized to evaluate the efficiency of the HRR pathway in Chinese hamster ovary FANCG mutant cells (NM3) and human FANCA (GM6914) and F ANCD2 (PD20) fibroblasts. Drug hypersensitivity, chromosomal instability and HRR were evaluated using growth inhibition and clonal survival assays, metaphase analysis and a plasmid based HRR reporter assay respectively. Cell lines unable to form the G-BRCA2 complex are hypersensitive to phleomycin (in addition to MMC) and exhibit elevated chromosomal aberrations and reduced levels of HRR. This implicates the G-BRCA2 complex in the repair of both indirectly and directly induced DSB. Cell lines able to form the G-BRCA2 complex (such as FANCA-deficient cells) exhibit little or no hypersensitivity to phleomycin. The study also provides evidence that FANCD2 that is not mono-ubiquitinated has biological activity, specifically in the G-BRCA2 protein complex. The study provides important new insights into the molecular defects associated with FA and the role of the FA proteins in ICL and DSB repair.

No description available.

No description available.