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This thesis explores the complex web of social relations created by the use of donor insemination (DI) in Aotearoa/New Zealand. The experiences of pursuing parenthood and creating a family using this method of assisted conception are contextualised through attention to the practices of Donor Insemination Programmes and the discourses used by parents, their families and health professionals. Sociologists and other social scientists have drawn attention to the social and cultural consequences of the fragmentation of biological/genetic, gestational and social parenting that follows the use of third party gametes. This thesis explores the implications of these procreative arrangements for the meanings attached to cultural concepts such as 'kinship', 'family', and 'parenthood'. Variation in the way these families respond to issues associated with the use of donor sperm in the conception of a child is also highlighted. The thesis also explores the dominant discourse in the New Zealand context of children's 'right' to know their genetic origins, and how this is played out in the perceptions and actions of health professionals, parents of children conceived by DI and their kin. The research is exploratory and qualitative, drawing on semi-structured interviews with parents, grandparents, aunts and uncles of children conceived by DI, and with health professionals working in DI programmes. The inclusion of the perspectives of extended family members and health professionals constitutes a unique contribution to research on families with children conceived by DI. The secrecy, anonymity and confidentiality that have surrounded DI practices have long hindered the study of families with children conceived by DI. Despite a trend towards information-sharing in DI in New Zealand, the thesis shows that for these families, patterns of secrecy and disclosure are complex, variable and embedded in particular social and relational contexts.

The natural history for patients with de novo donor-specific antibodies (dnDSA) and the risk factors for its development have not been well defined. Furthermore, clinical and histologic correlation with serologic data is limited. We studied 315 consecutive renal transplants without pre-transplant donor-specific antibody (DSA), with a mean follow-up of 6.2 ± 2.9 years. Protocol (n = 215) and for cause (n = 163) biopsies were analyzed. Solid phase assays were used to screen for dnDSA post-transplant. A total of 47 out of 315 (15%) patients developed dnDSA at a mean of 4.6 ± 3.0 years post-transplant. Independent predictors of dnDSA were HLA-DRβ1 MM > 0 (OR 5.66, p < 0.006); and non-adherence (OR 8.75, p < 0.001); with a strong trend toward clinical rejection episodes preceding dnDSA (OR 1.57 per rejection episode, p=0.061). The median 10-year graft survival for those with dnDSA was lower than the No dnDSA group (57% vs. 96%, p < 0.0001). Pathology consistent with antibody-mediated injury occurred and progressed in patients with dnDSA in the absence of graft dysfunction. Furthermore, non-adherence and cellular rejection contributed to both dnDSA development and the risk of progression to graft loss. (Human leukocyte antigen) HLA epitope matching is a novel strategy that may minimize dnDSA development. HLAMatchmaker software was used to characterize epitope mismatches at 395 potential HLA-DR/DQ/DP conformational epitopes for a subset of 286 donor–recipient pairs in which samples were available for high-resolution HLA-typing. Epitope specificities were assigned using single antigen HLA bead analysis and correlated with known monoclonal alloantibody epitope targets. Locus-specific epitope mismatches were more numerous in patients who developed HLA-DR dnDSA alone (21.4 vs. 13.2, p<0.02) or HLA-DQ dnDSA alone (27.5 vs. 17.3, p<0.001). An optimal threshold for epitope mismatch (10 for HLA-DR, 17 for HLA-DQ) was defined that was associated with minimal development of Class II dnDSA using a receiver operating characteristic analysis. Applying these thresholds, 0% and 2.7% of patients developed dnDSA against HLA-DR and HLA-DQ, respectively, after a median of 6.9 years follow-up. Epitope specificity analysis revealed that 3 HLA-DR and 3 HLA-DQ epitopes were independent multivariate predictors of Class II dnDSA when mismatched between the donor and recipient. HLA-DR and DQ epitope matching outperforms traditional low-resolution antigen-based matching and has the potential to minimize the risk of de novo Class II DSA development, thereby improving long-term graft outcome.

Thesis (Ph.D.)--Bowling Green State University, 2007. / Document formatted into pages; contains xx, 166 p. : ill. Includes bibliographical references.

Thesis (Ph. D.)--University of Missouri-Columbia, 1998. / Typescript. Vita. Includes bibliographical references (leaves 327-343). Also available on the Internet.

Thesis (Ph. D.)--West Virginia University, 2000. / Title from document title page. Document formatted into pages; contains xvii, 289 p. : ill. Includes abstract. Includes bibliographical references.

Thesis (Ph. D.)--University of Missouri-Columbia, 1998. / Typescript. Vita. Includes bibliographical references (leaves 327-343). Also available on the Internet.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1982. / Typescript. Vita. Description based on print version record. Includes bibliographical references.

Hydrogen sulfide (H2S) is an essential small molecule in human physiology. Although quite toxic, H2S is produced endogenously and performs important regulatory functions in the cardiovascular, immune, nervous, and respiratory systems. Varied interactions with intracellular thiols, reactive oxidants, and protein transition-metal centers are highly dynamic and sensitive to fluctuations in redox homeostasis. Furthermore, H2S is implicated in a number of diseases such as cancer, neurodegeneration, and heart disease. Hence, exogenously delivered H2S as a therapeutic agent is an active area of intrigue and research. The complexity and interconnectivity of these processes has stimulated the development of advanced chemical tools with which to study biological H2S, including reaction-based fluorescent probes and slow-releasing H2S donors. Toward these goals, I present several significant advances in the fields of H2S detection and delivery. An azide reduction-based probe, MeRho-Az, provides a rapid >1,000-fold fluorescence response when treated with H2S. MeRho-Az is sufficiently sensitive to detect endogenous H2S in C6 cells and was used to image H2S in live zebrafish larvae using light sheet fluorescence microscopy, representing the first analyte-responsive experiments with this imaging technology. Using a ratiometric dual-fluorophore fragmentation strategy, NBD-Coum simultaneously detects, differentiates, and measures relative concentration ratios of H2S versus cysteine/homocysteine, two important metabolites in H2S biosynthesis. NBD-Coum was used to monitor changes in redox homeostasis in a simulated sulfur pool and is useful for studying H2S-thiol dynamics. The synthesis and amide-coupling conditions of ADT-NH2, a highly sought dithiolethione H2S donor, allow for hydrolytically stable, H2S-releasing non-steroidal anti-inflammatory drug hybrids. Finally, inspired by polysulfide-containing natural products, functionalized tetrasulfides are a new class of accessible, customizable, and versatile H2S donors with controllable H2S release rates. I hope that by using these investigative tools, chemists and biologists are able to refine our understanding of physiological H2S and exploit H2S activities in disease treatments.

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