http://hdl.handle.net/2328/1588 2013-05-26T09:22:35Z 2013-05-26T09:22:35Z Appukuttan, Binoy McFarland, Trevor J Stempel, Andrew Kassem, Jean B Hartzell, Matthew Zhang, Yi Bond, Derek West, Kelsey Wilson, Reid Stout, Andrew Pan, Yuzhen Ilias, Hoda Robertson, Kathryn Klein, Michael L Wilson, David Smith, Justine R Stout, J Timothy http://hdl.handle.net/2328/26592 2013-05-13T02:10:14Z 2012-06-22T00:00:00Z

Title: The related transcriptional enhancer factor-1 isoform, TEAD4 216, can repress vascular endothelial growth factor expression in mammalian cells Authors: Appukuttan, Binoy; McFarland, Trevor J; Stempel, Andrew; Kassem, Jean B; Hartzell, Matthew; Zhang, Yi; Bond, Derek; West, Kelsey; Wilson, Reid; Stout, Andrew; Pan, Yuzhen; Ilias, Hoda; Robertson, Kathryn; Klein, Michael L; Wilson, David; Smith, Justine R; Stout, J Timothy Abstract: Increased cellular production of vascular endothelial growth factor (VEGF) is responsible for the development and progression of multiple cancers and other neovascular conditions, and therapies targeting post-translational VEGF products are used in the treatment of these diseases. Development of methods to control and modify the transcription of the VEGF gene is an alternative approach that may have therapeutic potential. We have previously shown that isoforms of the transcriptional enhancer factor 1-related (TEAD4) protein can enhance the production of VEGF. In this study we describe a new TEAD4 isoform, TEAD4 216, which represses VEGF promoter activity. The TEAD4 216 isoform inhibits human VEGF promoter activity and does not require the presence of the hypoxia responsive element (HRE), which is the sequence critical to hypoxia inducible factor (HIF)-mediated effects. The TEAD4 216 protein is localized to the cytoplasm, whereas the enhancer isoforms are found within the nucleus. The TEAD4 216 isoform can competitively repress the stimulatory activity of the TEAD4 434 and TEAD4 148 enhancers. Synthesis of the native VEGF 165 protein and cellular proliferation is suppressed by the TEAD4 216 isoform. Mutational analysis indicates that nuclear or cytoplasmic localization of any isoform determines whether it acts as an enhancer or repressor, respectively. The TEAD4 216 isoform appears to inhibit VEGF production independently of the HRE required activity by HIF, suggesting that this alternatively spliced isoform of TEAD4 may provide a novel approach to treat VEGF-dependent diseases.

2012-06-22T00:00:00Z Awadalla, Mona S Burdon, Kathryn Penelope Thapa, Suman S Hewitt, Alex W Craig, Jamie E http://hdl.handle.net/2328/26591 2013-05-13T02:10:16Z 2012-01-01T00:00:00Z

Title: A cross-ethnicity investigation of genes previously implicated in primary angle closure glaucoma Authors: Awadalla, Mona S; Burdon, Kathryn Penelope; Thapa, Suman S; Hewitt, Alex W; Craig, Jamie E Abstract: Purpose: To investigate the underlying genetic variation between candidate genes and primary angle closure glaucoma (PACG) in both Nepalese and Australian populations. Methods: A total of 213 patients with PACG (106 Nepalese and 107 Australian) and 492 age and sex matched controls (204 Nepalese and 288 Australian) were included in the current study. Three candidate genes were selected; methyltetrahydrofolate reductase (MTHFR), calcitonin receptor-like receptor gene (CALCRL), and membrane frizzled-related protein (MFRP). Tag single nucleotide polymorphisms (SNPs) were selected and genotyped to capture the majority of common variation across each locus. Allele and haplotype analyses were conducted using PLINK. Results: SNPs in the nanophthalmos gene MFRP were found to be nominally associated with PACG under the allelic model. Two SNPs were associated in the Australian cohort (rs948414; p=0.02 and rs36015759; p=0.02), and a single SNP in the Nepalese cohort (rs10790289; p=0.03), however these SNPs failed to remain significant after adjustment for sex and age. A haplotype at the CALCRL gene (AATACAGAT) was associated in the Australian cohort (corrected p-value= 0.024). No association was observed in either cohort for MTHFR. Conclusions: This study implicates genetic variation at the CALCRL gene in the pathogenesis of PACG in an Australian Caucasian cohort. Additionally, the MFRP gene shows tendency to be associated with PACG in both the Australian and Nepalese cohorts. Further investigation in a larger cohort is warranted to confirm these findings. No statistically significant associations were identified between MTHFR and PACG in either population.

2012-01-01T00:00:00Z Wang, Bob Z Siriwardana, Pradeep Taranath, Deepa A http://hdl.handle.net/2328/26590 2013-05-13T02:10:16Z 2012-01-01T00:00:00Z

Title: Macular hypoplasia in congenital disorder of glycosylation type 1a Authors: Wang, Bob Z; Siriwardana, Pradeep; Taranath, Deepa A Abstract: Congenital disorders of glycosylation are a rare group of metabolic disorders that can result in multiorgan disease. This article describes a novel finding of macular hypoplasia in congenital disorders of glycosylation type 1a.

2012-01-01T00:00:00Z Law, Siew W Lee, Andrew W Chen, Celia S http://hdl.handle.net/2328/26337 2013-05-13T02:09:01Z 2009-01-01T00:00:00Z

Title: Multiple sclerosis presenting with homonymous hemianopia Authors: Law, Siew W; Lee, Andrew W; Chen, Celia S Abstract: Ophthalmic manifestations are a prominent feature of multiple sclerosis (MS). Optic neuritis accounts for 18% of initial MS symptoms and 40–70% of all patients with MS have at least one episode of optic neuritis during their disease course. Eye movement abnormalities such as internuclear ophthalmoplegia are seen in over 50% of patients with MS. This case study describes a rare initial presentation of MS with ‘left eye blurred vision’ and examination findings of a complete left homonymous hemianopia. Although homonymous hemianopia is uncommon (0.5–3.5% of MS cases), this case highlights an important reminder that people with a field defect often complain of ‘blurred vision’ on the side of the defect.

2009-01-01T00:00:00Z