Browsing by Author "Abdul-Rasool, Sahar"
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Item Autosomal recessive congenital cataract in captive-bred vervet monkeys (Chlorocebus aethiops)(Wiley, 2018) Magwebu, Zandisiwe E.; Abdul-Rasool, Sahar; Seier, Jurgen V.; Chauke, Chesa G.BACKGROUND: The aim of the study was to evaluate the genetic predisposition of congenital cataract in a colony of captive-bred vervet monkeys. METHODS: Four congenital cataract genes: glucosaminyl (N-acetyl) transferase 2 (GCNT2), heat shock transcription factor 4 (HSF4), crystallin alpha A (CRYAA) and lens intrinsic membrane protein-2 (LIM2) were screened, sequenced and analysed for possible genetic variants in 36 monkeys. Gene expression was also evaluated in these genes. RESULTS: Fifteen sequence variants were identified in the coding regions of three genes (GCNT2, HSF4 and CRYAA). Of these variations, only three were missense mutations (M258V, V16I and S24N) and identified in the GCNT2 transcripts A, B and C, respectively, which resulted in a downregulated gene expression. CONCLUSION: Although the three missense mutations in GCNT2 have a benign effect, a possibility exists that the candidate genes (GCNT2, HSF4 and CRYAA) might harbour mutations that are responsible for total congenital cataract.Item Genomic instability in South African breast cancer patients(2013) Langa, Bridget Cebisile; Abdul-Rasool, Sahar; Hiss, DonavonBreast cancer (BC) is one of the most common malignancies in women. Death results from treatment failure and metastatic disease. Thousands of lives might be saved if it was possible to detect and eliminate occult metastatic cells before they become clinically evident. Therefore, there is a critical need to identify new markers to improve treatment options for these patients. Genomic instability is the earliest indication of breast cancer and the use of genomic methodologies is a progress towards early detection and treatment, through the identification of biomarkers that can be translated into novel therapy targets. The interferon regulatory factor-1(IRF-1) gene, localized on chromosome 5q31.1, is believed to act as a tumor suppressor gene in breast cancer. The IRF-1 was found to be inactivated by single nucleotide polymorphism (SNP) in breast cancer suggesting that the loss of its function might be critical to the development of the disease. The phosphatidylinositol 3-kinase (PIK3) signaling pathway mediates key cellular functions and alterations of genes in this pathway, including PIK3CA, serine-threonine protein kinases (AKT1and AKT2), phosphatase and tensin homolog (PTEN), fibroblast growth factor receptor 2 (FGFR2) and ERBB2, whose expression have been demonstrated to be altered in breast cancer patients. In addition, these genes are linked to treatment resistance. vi In this study, we have investigated allelic loss of IRF-1 gene in primary tumors obtained from patients undergoing mastectomy at Groote Schuur hospital (Cape Town, South Africa). These samples were then further analyzed for the DNA copy number changes of specific genes involved in the PIK3/AKT signaling pathway. Statistical analysis has been performed in order to correlate genomic findings with clinical-histopathological and follow up information from the patients and to establish whether these genes can predict prognosis. Our data analysis has indicated that 46 cases (45.5%) out of 101 cases were informative for the IRF-1 dinucleotide marker used for LOH analysis (Figure 3.1). LOH was detected in 23 of these informative cases (23/46; 50%). No statistical significance was found between LOH at the IRF-1 locus and age (≤50 years or >50 years) (P value = 1.0000) and earlier stage (Stages I and II) (P value= 0.4982) based on Fisher’s exact test. Patients presented a high level of DNA copy number changes in genes involved in the PIK3/AKT pathway. The most frequent changes were observed in the PIK3CA and PTEN genes. PIK3CA presented high copy number in 36.8% of the cases. PTEN was observed with low copy number in 47.5% of the cases. This dissertation shows the effectiveness of genomic methodologies as means for the detection of early breast cancer progression in South African women. The PIK 3/AKT genes can validate the usefulness of breast cancer therapies.Item The synergistic and neuroprotective effects of alcohol–antioxidant treatment on blood–brain barrier endothelial cells(Wiley-Blackwell, 2020) Fisher, David W.; Thomas, Kelly Angelique; Abdul-Rasool, SaharBackground: Alcohol (EtOH) is reported to adversely affect one of the most crucial roles of the blood–brain barrier (BBB), the regulation of its permeability, thereby compromising the stability of the homeostatic environment of the brain. The central component of the BBB, endothelial cells (ECs), regulates BBB transcellular transport, while their paracellular pathways are made virtually impermeable by molecular structures called tight junctions (TJs). These TJs are composed of proteins, such as claudin-5, a protein involved in the regulation of paracellular permeability and of key interest in this study. Methods and Results: The working hypothesis of this study postulated that the high levels of antioxidants (AOs) in the fermented Aspalathus linearis (Rooibos; Rf) tincture may protect the ECs of the BBB against oxidative stress induced by EtOH exposure. Cells were exposed for 24 hours to selected concentrations of EtOH (25 and 100 mM), Rf (containing an antioxidant equivalence of 1.9 nM Aspalathin), and cotreatments of EtOH and Rf. Cell viability, live cell number, and toxicity were analyzed using the trypan blue exclusion assay. RT-qPCR was implemented to quantify claudin-5 transcription. In addition, permeability (Transepithelial Electrical Resistance) of bEnd5 monolayers was measured. The experimental timeline for the above-mentioned parameters was 24 and 48 hours. Conclusions: Our study showed that simultaneous exposure of Rf and EtOH was able to negate the effects of EtOH on cell viability and cell proliferation, but was not able to reverse or reduce the effects of EtOH on claudin-5 transcription and paracellular permeability. Furthermore, a novel finding in this study suggests that very low concentrations of AOs in tinctures such as Rooibos tea could profoundly alter the redox status of brain ECs.Item Understanding human coronavirus HCoV-NL63(Bentham Science, 2010) Abdul-Rasool, Sahar; Fielding, Burtram C.Even though coronavirus infection of humans is not normally associated with severe diseases, the identification of the coronavirus responsible for the outbreak of severe acute respiratory syndrome showed that highly pathogenic coronaviruses can enter the human population. Shortly thereafter, in Holland in 2004, another novel human coronavirus (HCoV-NL63) was isolated from a seven-month old infant suffering from respiratory symptoms. This virus has subsequently been identified in various countries, indicating a worldwide distribution. HCoV-NL63 has been shown to infect mainly children and the immunocommpromised, who presented with either mild upper respiratory symptoms (cough, fever and rhinorrhoea) or more serious lower respiratory tract involvement such as bronchiolitis and croup, which was observed mainly in younger children. In fact, HCoV-NL63 is the aetiological agent for up to 10% of all respiratory diseases. This review summarizes recent findings of human coronavirus HCoV-NL63 infections, including isolation and identification, phylogeny and taxonomy, genome structure and transcriptional regulation, transmission and pathogenesis, and detection and diagnosis.