Ph.D., Faculty of Health Sciences, University of the Witwatersrand, 2011 / Oesophageal squamous cell carcinoma (OSCC) has a high prevalence in the Asiatic belt and areas of Africa. In South Africa (SA), the incidence of this cancer in the Eastern Cape is one of the highest in the world. The molecular carcinogenesis of this disease remains unresolved. Single nucleotide polymorphism (SNP) array technology provides a high resolution technique to determine DNA copy number imbalances across the whole genome. DNA copy number changes can affect oncogenes and tumour suppressor genes, contributing to carcinogenesis. The aim of this study was to map common chromosomal break points previously identified in five SA OSCC cell lines by multi colour fluorescence in situ hybridisation (FISH) and to characterise copy number changes in these cell lines and OSCC patient’s specimens using SNP array technology. Genome wide copy number analysis was performed on the cell lines and 51 OSCC retrospective samples from the Eastern Cape region using Affymetrix® 500K SNP arrays. A number of genes were significantly affected by copy number changes across specimens. The copy number status of some of these candidate genes identified by arrays, were verified by (FISH) in a subset of the samples. Expression of the EPHA3, FGF3, FGF4, FGF19 and C-MYC candidate genes was assessed in the cell lines and four fresh samples. The common translocation break point previously detected in 5 cell lines involving chromosome 3p11.2 correlated with deletions affecting the EPHA3 gene in 4 of the 5 cell lines and was deleted in 74% of the OSCC cohort. EPHA3 is an ephrin A3 receptor tyrosine kinase that has been shown to have both oncogenic and tumour suppressor functionality. In addition, significant regions of amplification and deletion identified genes (CCND1, C-MYC, FHIT, SFRP1, SFRP2, FGF3, FGF4, FGF19, SMAD4, SMAD6 and FBXW7) involved in the Wnt, TGF-β and FGF. Deletion of the genes, WRN, ATM, RAD18 and XRCC4 involved in DNA repair pathways, may contribute to genetic instability that is characteristic of OSCC. This study has highlighted some molecular pathways that may contribute to better understanding carcinogenesis of OSCC in South Africa.

Excerpt: Tinnitus is the sensation of ringing, buzzing, whooshing or other sound in the ears or head without an external stimulus. You are not alone if you feel that your experience with tinnitus has changed you as a person. It can impair your ability to carry out basic activities, such as sleeping, relaxing, or enjoying a quiet peaceful location. It can influence the ability to interact with other people.

No description available.

No description available.

No description available.

Book Summary: This book was written for more than 50 million Americans who experience tinnitus - some 2 million disabled by it. Just some of the helpful ideas and simple treatment options in this book that readers can effectively accomplish at home include altering medications or changing diets, using sound therapy such as music, learning techniques for improving concentration through use of positive imagery, and improving sleep patterns by controlling middle-of-the-night thinking. The enormous advantages of this book over other titles on this topic come from the 17 renowned scientists who have contributed to this invaluable consumer resource, one that will make a difference in the lives of readers who suffer from this unfortunate malady.

No description available.

Cartilage Tissue Engineering. Joint pain and functional impairment due to cartilage damage from osteoarthritis and other means is a major source of disability for adults the world over. Cartilage is an avascular tissue with a very limited capacity for self repair. Current medical and surgical approaches to cartilage repair also have limited efficacy, and in all cases fail to completely restore a normal, healthy cartilage phenotype. Tissue engineering is a relatively new approach to cartilage repair that seeks to fabricate a replacement tissue, indistinguishable from healthy, native tissue. The basic idea of the tissue engineering approach is to seed tissue synthesizing cells into a shapeable, biocompatible/bioabsorbable scaffold that serves as a temporary extracellular matrix with a localized source of bioactive molecules to direct the development of new tissue. The challenge of tissue engineering is to identify cells, scaffolds, and growth conditions that will be optimal for tissue regeneration. The goal of the current studies was to evaluate one aspect of all three of the major components of cartilage tissue engineering: cell source, scaffolding material and preparation, and controlled growth factor delivery. We evaluated the chondrogenic potential of human nasal chondrocytes grown in calcium alginate in an in vivo culture system, the potential of computer-aided design and injection molding with calcium alginate to reliably reproduce complex geometries with high dimensional tolerances, and the potential for the controlled release of TGF-β1 from calcium alginate modified by the covalent addition of a recently discovered TGF-β binding peptide. We found that adult human nasal chondrocytes show significant chondrogenic potential when grown within an alginate scaffold. We also found that alginate is readily amenable to an injection molding process that utilizes precision made molds from computer-aided design and solid free form fabrication, allowing for the fabrication of tissue engineered constructs with very precise shape fidelity. Additionally, we found that calcium alginate could be reliably modified by the covalent addition of peptides, and that the addition of a newly discovered TGF-β binding peptide delayed the release of pre-loaded TGF-β1. Together these results show some of the encouraging prospects for cartilage tissue engineering. `Menière’s Syndrome.Menière’s syndrome is an inner ear disorder characterized by idiopathic endolymphatic hydrops with associated periodic tinnitus, vertigo, and progressive sensorineural hearing loss. It affects approximately 0.2% of the population, for whom it can be quite devastating. In addition to progressive hearing loss people with Menière’s syndrome are prone to sudden attacks of vertigo and tinnitus that are severe enough that they can lead to falls and potentially serious injury. People subject to frequent attacks are unable to drive, with obvious consequences on standard of living. In the current studies we evaluated the standard animal model of Menière’s syndrome by comparing cochlear turn specific hearing thresholds and the degree of hydrops in that turn. A positive correlation between these had previously been established in the study of human temporal bones from people with Menière’s syndrome, but had not been reported in the animal model. We also evaluated the potential of aminoguanidine, a relatively specific inhibitor of the inducible isoform of nitric oxide synthase, as a neuroprotective therapeutic agent for preservation of hearing in animals with surgically induced endolymphatic hydrops. We found, for the first time, a partial correlation between cochlear turn specific hydrops and hearing thresholds in the most commonly used animal model of Menière’s syndrome, helping to validate the utility of this animal model for future studies. We also found that aminoguanidine did indeed partially preserve hearing in animals with surgically induced Menière’s syndrome. This encouraging result appears to be the first report of a medical intervention protective against hearing loss in an animal model of Menière’s syndrome, and may help us to understand the etiology pathology seen in Menière’s syndrome.

The relation between discrimination of silent gaps and speech‐in‐noise perception was measured in 20 normal‐hearing listeners using speech‐shaped noise as both the gap markers and the noise source for speech testing. In the gap discrimination experiment, subjects compared silent gaps marked by 60 dB SPL 250‐ms noise bursts to standards of either 5, 10, 20, 50, 100, or 200 ms. The gap results were most similar to those reported by Abel [S. M. Abel, J. Acoust. Soc. Am. 52, 519–524 (1972)] as ΔT/T decreased non‐monotonically with increased gap length. In a second experiment, the California Consonant Test (CCT) was administered at 50 dB HL via CD in three conditions: quiet, +10 S/N, and 0 S/N. Results from both experiments were correlated and the association between ΔT/T and CCT scores was generally negative. Listeners who discriminated the gaps with greater acuity typically had higher speech scores. The relation was strongest for the smaller gap standards at each S/N, or when performance for any gap duration was compared to the CCT results obtained in quiet.

No description available.