Medical Sciences Commons^™

Delivering Genetic Education And Genetic Counseling For Rare Diseases In Rural Brazil, A.X. Acosta, K Abe-Sandes, R Giugliani, Alan H. Bittles

Research outputs 2013

Brazil is the largest country in Latin America, with an ethnically diverse, Portuguese-speaking and predominantly Roman Catholic population of some 194 million. Universal health care is provided under the Federal Unified Health System (Sistema Único de Saúde) but, as in many other middle and low income countries, access to medical genetics services is limited in rural and remote regions of the country. Since there is no formally recognized Genetic Counseling profession, genetic counseling is provided by physicians, trained either in medical genetics or a related clinical discipline. A comprehensive medical genetics program has been established in Monte Santo, an inland …

Retinal Vascular Biomarkers For Early Detection And Monitoring Of Alzheimer's Disease, Shawn Frost, Yogi Kanagasingam, Hamid Sohrabi, J Vignarajan, P Bourgeat, Olivier Salvado, Victor Villemagne, Christopher Rowe, S Lance Macaulay, Cassandra Szoeke, Kathryn A. Ellis, David Ames, Colin L. Masters, Stephanie Rainey-Smith, Ralph N. Martins

Research outputs 2013

The earliest detectable change in Alzheimer's disease (AD) is the buildup of amyloid plaque in the brain. Early detection of AD, prior to irreversible neurological damage, is important for the efficacy of current interventions as well as for the development of new treatments. Although PiB-PET imaging and CSF amyloid are the gold standards for early AD diagnosis, there are practical limitations for population screening. AD-related pathology occurs primarily in the brain, but some of the hallmarks of the disease have also been shown to occur in other tissues, including the retina, which is more accessible for imaging. Retinal vascular changes …

Multiplex Biomarkers In Blood, Veer Bala Bala Gupta, Ramani Sundaram, Ralph N. Martins

Research outputs 2013

Advances in the field of blood biomarker discovery will help in identifying Alzheimer's disease in its preclinical stage, allowing treatment to be initiated before irreversible damage occurs. This review discusses some recent past and current approaches being taken by researchers in the field. Individual blood biomarkers have been unsuccessful in defining the disease pathology, progression and thus diagnosis. This directs to the need for discovering a multiplex panel of blood biomarkers as a promising approach with high sensitivity and specificity for early diagnosis. However, it is a great challenge to standardize a worldwide blood biomarker panel due to the innate …

The Characterisation Of Pax3 Expressant Cells In Adult Peripheral Nerve [Journal Article], Judith Blake, Melanie Ziman

Research outputs 2013

Pax3 has numerous integral functions in embryonic tissue morphogenesis and knowledge of its complex function in cells of adult tissue continues to unfold. Across a variety of adult tissue lineages, the role of Pax3 is principally linked to maintenance of the tissue’s resident stem/progenitor cell population. In adult peripheral nerves, Pax3 is reported to be expressed in nonmyelinating Schwann cells, however, little is known about the purpose of this expression. Based on the evidence of the role of Pax3 in other adult tissue stem and progenitor cells, it was hypothesised that the cells in adult peripheral nerve that express Pax3 …

Biomarkers Of Disease : Concentrations In The Serum Of Women During Natural And Stimulated Ovarian Cycles And During Early Pregnancy, Melissa Stemp

Theses: Doctorates and Masters

Molecular biomarkers are chemical signatures that all cell types possess. They are used in medicine to evaluate both normal biological events and pathogenic processes. A series of biomarkers associated with cancer of the breast, ovaries and other parts of the female reproductive tract and the monitoring of pregnancy were measured in disease‐free women. The biomarkers measured were prostate specific antigen (PSA), CA125, CA15‐3, CA72‐4, and pregnancy associated plasma protein‐a (PAPP‐A). The patterns of change during natural and stimulated ovarian cycles and early pregnancy were investigated to determine if these biomarkers could reflect normal events relating to ovulation and implantation/placentation. In …

Discovery Of New Biomarkers Of Mild Cognitive Impairment And Alzheimer's Disease Risk In Buccal Cells Using Laser Scanning Cytometry, Maxime Francois

Theses: Doctorates and Masters

Previous studies have shown that mild cognitive impairment (MCI) may reflect the early stages of more pronounced neurodegenerative disorders such as Alzheimer’s disease (AD). In clinical practice, patients with AD are not usually identified until the disease has progressed to a stage when primary prevention is no longer possible. Therefore there is a need for a minimally invasive and inexpensive diagnostic to identify those who exhibit cellular pathology indicative of MCI and AD risk so that they can be prioritised for primary prevention. Human buccal cells are accessible in a minimally invasive manner, and exhibit cytological and nuclear morphologies that …

Pax3 Expression, Protein Modifications And Downstream Target Gene Profiling In Melanocytes And Melanoma Cells, Danielle Bartlett

Theses: Doctorates and Masters

PAX3 is a transcription factor. It plays a major role in the development of melanocytes in the embryo. As a result of alternative splicing, the gene gives rise to eight different transcripts which encode proteins that have differing structures and are therefore likely to activate different downstream target genes. The presence of post-translational modifications has also been shown to alter the functions of the proteins.

PAX3 regulates the maintenance of undifferentiated melanoblasts and mediates pathways involved in proliferation, migration and survival. It has been shown to be expressed in melanoblasts, adult melanocytes, naevi and in most melanoma cells. This implies …

Protocol For A Randomized Controlled Trial Evaluating The Effect Of Physical Activity On Delaying The Progression Of White Matter Changes On Mri In Older Adults With Memory Complaints And Mild Cognitive Impairment: The Aibl Active Trial, E V Cyarto, N T Lautenschlager, P M Desmond, D Ames, C Szoeke, O Salvado, Matthew Sharman, Kathryn A Ellis, P M Phal, C L Masters, C C Rowe, Ralph Martins, Kay L Cox

Research outputs 2012

Background: Older adults free of dementia but with subjective memory complaints (SMC) or mild cognitive impairment (MCI) are considered at increased risk of cognitive decline. Vascular risk factors (VRF), including hypertension, heart disease, smoking, hypercholesterolemia and lack of physical activity (PA) have been identified as modifiable risk factors contributing to cognitive decline, and white matter hyperintensities (WMH) are associated with VRF, SMC and cognitive impairment. Findings from a growing number of clinical trials with older adults are providing strong evidence for the benefits of physical activity for maintaining cognitive function, but few studies are investigating these benefits in high-risk populations. …

Evidence For A Non-Genomic Action Of Testosterone In Skeletal Muscle Which May Improve Athletic Performance: Implications For The Female Athlete, J R Dent, D K Fletcher, Michael Mcguigan

Research outputs 2012

This review will focus on the proposed second mode of testosterone action (now termed non-genomic) that appears to occur independently of the traditional transcriptional mechanism in mammalian skeletal muscle cells which may enhance skeletal muscle contractile properties. This mechanism of testosterone action differs from the traditional pathway, originating at the cell membrane, having a rapid onset of action, requiring second messengers to execute its effects and is insensitive to inhibitors of traditional androgen receptor action, transcription and protein synthesis. Importantly, unlike the traditional action of testosterone in skeletal muscle, this non-genomic pathway is shown to have a direct acute effect …

Profiling Plasma Peptides For The Identification Of Potential Ageing Biomarkers In Chinese Han Adults, Jiapeng Lu, Yuqing Huang, Youxin Wang, Yan Li, Youjun Zhang, Jingjing Wu, Feifei Zhao, Shijiao Meng, Xinwei Yu, Qingwei Ma, Manshu Song, Naibai Chang, Alan H. Bittles, Wei Wang

Research outputs 2012

Advancing age is associated with cardiovascular disease, diabetes mellitus and cancer, and shows significant inter-individual variability. To identify ageing-related biomarkers we performed a proteomic analysis on 1890 Chinese Han individuals, 1136 males and 754 females, aged 18 to 82 years, using weak cation exchange magnetic bead based MALDI-TOF-MS analysis. The study identified 44 peptides which varied in concentration in different age groups. In particular, apolipoprotein A-I (ApoA1) concentration gradually increased between 18 to 50 years of age, the levels of fibrinogen alpha (FGA) decreased over the same age span, while albumin (ALB) was significantly degraded in middle-aged individuals. In addition, …

Multiple Γ-Secretase Product Peptides Are Coordinately Increased In Concentration In The Cerebrospinal Fluid Of A Subpopulation Of Sporadic Alzheimer's Disease Subjects, Saori Hata, Miyako Taniguchi, Yi Piao, Takeshi Ikeuchi, Anne Fagan, David Holtzman, Randall Bateman, Hamid Sohrabi, Ralph Martins, Sam Gandy, Katsuya Urakami, Toshiharu Suzuki

Research outputs 2012

Background: Alcadeinα (Alcα) is a neuronal membrane protein that colocalizes with the Alzheimer's amyloid-β precursor protein (APP). Successive cleavage of APP by β- and γ-secretases generates the aggregatable amyloid-β peptide (Aβ), while cleavage of APP or Alcα by α- and γ-secretases generates non-aggregatable p3 or p3-Alcα peptides. Aβ and p3-Alcα can be recovered from human cerebrospinal fluid (CSF). We have previously reported alternative processing of APP and Alcα in the CSF of some patients with sporadic mild cognitive impairment (MCI) and AD (SAD). Results: Using the sandwich enzyme-linked immunosorbent assay (ELISA) system that detects total p3-Alcα, we determined levels of …

Investigating The Impact Of Cd147 And Its Expression On Neurodegenaration And Alzheimer's Disease (Ad), Limbikani J. Kanyenda

Theses: Doctorates and Masters

CD147, also known as basigin, extracellular matrix metalloproteinase inducer, neurothelin, tumour cell-derived collagenase stimulatory factor, M6, HT7, OX47 or gp42, is a transmembrane glycoprotein of the immunoglobulin super-family. It is expressed in many neuronal and non-neuronal tissues with high expression in the hippocampus, pre-frontal cortex, thyroid, heart, early erythroid, amygdala and placenta. This protein is involved in various cellular and biological functions such as lymphocyte migration and maturation, tissue repair, cancer progression, T and B lymphocyte activation and induction of extracellular matrix metalloproteinase. The CD147 protein interacts with with cyclophilin A, cyclophilin B, sterol carrier protein, caveolin-1 and integrins, and …

Associatioin Of Plasma Aβ Peptides With Blood Pressure In The Elderly, Jean-Charles Lambert, Jean Dallongeville, Kathryn A. Ellis, Susanna Schraen-Maschke, James Lui, Simon Laws, Julie Dumont, Florence Richard, Dominque Cottel, Claudine Berr, David Ames, Colin L. Masters, Christopher C. Rowe, Cassandra Szoeke, Christophe Tzourio, Jean-Francois Dartigues, Luc Buee, Ralph Martins, Philippe Amouyel

Research outputs 2011

Background Aß peptides are often considered as catabolic by-products of the amyloid ß protein precursor (APP), with unknown physiological functions. However, several biological properties have been tentatively attributed to these peptides, including a role in vasomotion. We assess whether plasma Aß peptide levels might be associated with systolic and diastolic blood pressure values (SBP and DBP, respectively). Methodology/Principal Findings Plasma Aß1-40 and Aß1-42 levels were measured using an xMAP-based assay in 1,972 individuals (none of whom were taking antihypertensive drugs) from 3 independent studies: the French population-based 3C and MONA-LISA (Lille) studies (n = 627 and n = 769, respectively) …

Internet Use And Its Impact On Secondary School Students In Chiang Mai, Thailand, Kesaraporn Wanajak

Theses: Doctorates and Masters

Internet addiction (IA) is a relatively new field of academic inquiry. Empirical studies suggest that IA, like other well researched addictive behaviours, has an effect on many aspects of a person‟s life, including academic/work performance, relationships, and physical and mental health (Goldberg, 1996; Young, 1996, 1998). Evidence of IA has been suggested by the findings that some Internet users spend increasingly longer periods of time online and experience withdrawal symptoms when offline. Those preoccupied with Internet-related activities may neglect exercise, family and social activities (Kim et al., 2010; Nalwa & Anand, 2003; Seo, Kang, & Yom, 2009; S. Yang & …

Yeast As A Model For Studying Aβ Aggregation, Toxicity And Clearance, Prashant R. Bharadwaj

Theses: Doctorates and Masters

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder of the central nervous system, characterised by acute memory loss and behavioural symptoms. The AD brain is characterized by the presence of senile amyloid plaques associated with degenerating neurites and inflammatory processes. The major protein component of these amyloid deposits is the amyloid beta (Aβ) protein. The Aβ protein is a 40 or 42 amino acid cleavage product of APP (Amyloid Precursor Protein) which is produced in low levels in the normal ageing brain. Although senile amyloid plaques is the major pathological hallmark of AD brains, accumulating evidence has been presented to …

Impact Of Static Stretch And Muscular Contractions On Force Production Within The Human Triceps Surae Muscle-Tendon Complex, Anthony D. Kay

Theses: Doctorates and Masters

Pre-performance routines commonly include stretching and intense muscular contractions in an attempt to optimise muscular performance and reduce injury risk. However, the isolated and combined effects of stretching and muscle contractions on neuromuscular performance are not well described. The aims of this research were to examine the effects of acute static stretch and intense muscular contractions on force production of the human plantarflexors and to examine possible mechanical and neuromuscular mechanisms underpinning any changes. Techniques including isokinetic dynamometry, electromyography (EMG), sonography and motion analysis were used in three studies on recreationally active human volunteers (n=20). In the first study, three …

Metabolomic Investigation Of A New Rat Model Of Autosomal Recessive Polycystic Kidney Disease, Hayley White

Theses : Honours

Metabolomics is complementary to genomics, transcriptomics and proteomics; however, it has the capacity to reflect the activities of the organism at a functional level. Metabolomics can therefore be used as a diagnostic tool by identifying the up- or down-regulation of metabolites in the cell, tissue, plasma, serum or urine. Specifically, these are, but are not limited to, identifying biomarkers of disease, monitoring drug treatments, and monitoring surgical procedures such as organ transplant. Autosomal recessive polycystic kidney disease (ARPKD) makes up 5-8% of patients requiring kidney dialysis and/or transplantation and of these, an estimated 50% of patients progress to end-stage renal …

Genetic Counselling And Testing For Inherited Gene Mutations In Newly Diagnosed Patients With Breast Cancer: A Review Of The Existing Literature And A Proposed Research Agenda, Bettina Meiser, Kathy Tucker, Michael Friedlander, Kristine Barlow-Stewart, Elizabeth Lobb, Christobel Saunders, Gillian Mitchell

Research outputs pre 2011

Many women newly diagnosed with breast cancer and with a strong family history of breast cancer are referred to a family cancer service for genetic counselling and for consideration of genetic testing for germline mutations in cancer predisposition genes following completion of their cancer treatment. However, there is growing evidence that mutation status may influence treatment recommendations, and that there may be benefits in having 'treatment-focused genetic counselling and testing' available shortly after cancer diagnosis. This article reviews the literature that could inform the development of treatment-focused genetic counselling and testing, including: the rationale for genetic testing to aid with …

A Luteinizing Hormone Receptor Intronic Variant Is Significantly Associated With Decreased Risk Of Alzheimer's Disease In Males Carrying An Apolipoprotein E Epsilon 4 Allele, Ryan J. Haasl, M Reza Ahmadi, Sivan Vadakkadath Meethal, Carey E. Gleason, Sterling C. Johnson, Sanjay Asthana, Richard L. Bowen, Craig S. Atwood

Research outputs pre 2011

Genetic and biochemical studies support the apolipoprotein E (APOE) ε4 allele as a major risk factor for late-onset Alzheimer's disease (AD), though ~50% of AD patients do not carry the allele. APOE transports cholesterol for luteinizing hormone (LH)-regulated steroidogenesis, and both LH and neurosteroids have been implicated in the etiology of AD. Since polymorphisms of LH beta-subunit (LHB) and its receptor (LHCGR) have not been tested for their association with AD, we scored AD and age-matched control samples for APOE genotype and 14 polymorphisms of LHB and LHCGR. Thirteen gene-gene interactions between the …

The Evaluation Of Midazolam On Head Injured Patients In The Prehospital Setting, Dragana Klinac

Theses: Doctorates and Masters

Midazolam (Hypnovel ®) is the only sedating agent used by paramedics at St John Ambulance Service W.A. in the management of many conditions including seizure activities, antisocial or uncontrollable behaviours, back pain incidents and head injuries. Midazolam, with a rapid absorption, fast onset of action and short duration on neurological activity, has been accepted as a safe and effective agent in prehospital treatment since the late-1990s. Often, if a patient is not complying with treatment or is uncontrollable or aggressive, paramedics are required to sedate the individual. This study primarily examines the use of midazolam for the sedation of unmanageable …

The Effect Of Antioxidant Supplementation On Human Sperm Cryopreservation, Katrina E. Taylor

Theses : Honours

Semen cryopreservation has an important role in assisted reproductive technology however, the cooling, freezing and thawing processes often result in a significant loss of sperm motility, viability and nuclear integrity. The destructive effects of cryopreservation are significantly exacerbated in samples exhibiting low sperm number and poor morphological characteristics. Recent research into infertility has focused on the correlation between excessive oxidation and subfertility, in particular radical induced lipid peroxidation within the phospholipid bilayer of the spermatozoon plasma membrane and the promotion of cellular damage as a result of antioxidant insufficiency. The aim of this study was to evaluate the effect of …

Analysis Of Expression Patterns Of Scl And Pax7 In The Mouse Brain For Potential Concomitant Function Within The Mesencephalon, Julie Stampalia

Theses : Honours

Investigation of the cascade of events that leads to brain formation during embryogenesis allows an understanding of the processes involved that may well be applicable to future neurodegenerative therapies. Two genes at work during embryonic neurogenesis in a brain region called the superior colliculus are Scl, a member of the basic helix-loop-helix factor transcription factor family and Pax7, a paired box transcription factor containing a homeobox dornain. The superior coiliculus forms part of the visual system in mammals and in sepmate studies both the Scl and Pax7 genes have been shown to be present in this region of the mouse …

Molecular Genetic Investigation Of Autosomal Dominant Hemifacial Microsomia, Rebecca Watt

Theses: Doctorates and Masters

The overall purpose of this project was to explore the underlying pathogenesis of Hemifacial microsomia (HFM), investigate treatment and management options identify likely candidate genes and screen candidate genes for mutation(s) causing the form of HFM segregating on chromosome 11 in a West Australian family. Hemifacial microsomia is a congenital malformation arising from the derivatives of the first and second branchial arches. It is both clinically and genetically heterogeneous and can occur sporadically or segregate within families in an autosomal fashion. HFM is characterised by significant undergrowth to one side of the face and is a common birth defect with …

Target Selection For Antisense Oligonucleotide Induced Exon Skipping In The Dystrophin Gene, Stephen J. Errington

Theses: Doctorates and Masters

Duchene Muscular Dystrophy (DMD), and the milder allelic Becker muscular dystrophy (EMD), are X-linked recessive muscle wasting disorders characterised by mutations in the dystrophin gene. DMD occurs at a frequency of approximately 1 in 3500 male newborns and life expectancy is typically less than 30 years. Due to progressive muscle wasting, affected boys are restricted to a wheelchair by the age of 12 years. The most common cause of death is pneumonia, compounded by cardiac involvement. Mutations that disrupt the dystrophin reading frame, or prevent the synthesis of either terminus, preclude the synthesis of a fully functional dystrophin. The subsequent …

Good Life In The Balance: A Cross-National Study Of Dutch And Australian Disability Perspectives On Euthanasia And Physician-Assisted Suicide, Erik A. Leipoldt

Theses: Doctorates and Masters

This is a cross-national qualitative study with the purpose of obtaining perspectives held by people with quadriplegia and leading figures in disability movements in the Netherlands and Australia on the issues of euthanasia and physician-assisted suicide (EPAS). A disability voice is not prominent in public debate on EPAS in Australia or the Netherlands, even though people with disabilities are often thought to be vulnerable in relation to EPAS policies. Disability perspectives are potentially valuable in illuminating issues in relation to euthanasia and physician-assisted suicide, because issues of dependence, independence, and individual autonomy play important roles in relation to both EPAS …

The Effect Of Moderate +Gz Force On The Cervical Spine Bone Mineral Density In Raaf Pc-9 Pilots, Meghan C. Grant

Theses : Honours

Previous research on exercise and bone mineral density (BMD) has established that increases in BMD are site specific, responding to unusual strain and particularly to high magnitude loading. The positive Gz forces generated during high performance flying provide all three variables. Naumann, Bennell and Wark (2000) investigated the effects of moderate gravitational force on the BMD of fighter pilots. The pilots in this study had significant increases in BMD and bone mineral content (BMC) for the thoracic spine, pelvis and total body. However, it is now suspected that the cervical spine, which was unable to be analysed at that time …

Molecular Genetic Investigation Of Autosomal Dominant Muscular Dystrophy, Christopher Meredith

Theses: Doctorates and Masters

This thesis contributes to the Human Genome Project by adding detail to the physical and genetic maps of the human genome, and by identifying a strong candidate gene for a form of distal myopathy. Genomic clones for the human skeletal muscle genes slow troponin (TNN/1), alpha actin (ACTA1), and (3-tropomyosin (TPM2) were isolated for use in the fluorescent in situ hybridisation localisation of these genes on the cytogenetic map of the human genome. The localisation of these genes made them potential candidates for inherited skeletal muscle diseases, including the muscular dystrophies investigated here. Microsatellite, VNTR and RFLP markers were used …

Genetic Variation And Disease In The Roma (Gypsies), David J. Gresham

Theses: Doctorates and Masters

The Roma (Gypsies) are a European people composed of a mosaic of culturally heterogeneous populations. Linguistic analyses point to their origins in the Indian subcontinent. Cultural diversity in extant Romani populations suggests that they are descended from a mixture of Indian populations. Previous population genetic studies of the Roma have supported this claim by demonstrating the genetic heterogeneity of Romani populations. More recently, medical genetic research has detected identical founder mutations in separated Romani populations, which provides evidence of their relatedness. In this thesis, the genetic heritage of the Roma and its significance for genetic disease and research is investigated. …

Molecular Investigations In The Role Of The Galk1 Gene In Galactokinase Deficiency, Michael L. Hunter

Theses : Honours

Galactokinase deficiency is an autosomal-recessive inborn error of galactose metabolism whose major clinical manifestation is the development of cataracts during the first months of life. This metabolic disorder is caused by defects in the first enzyme of the Leloir pathway, galactokinase, encoded by the gene GALK1 on chromosome 17q24. Despite the identification of a number of conserved domains in GALK1, understanding of the functional significance of these regions and the molecular basis of the disorder is limited. This is largely due to the rarity of the disease and the fact that the small number of GALK1 mutations identified to-date are …

A Linkage Study Of Autism Using Multipoint Sib-Pair Analysis, Tamara Rogers

Theses: Doctorates and Masters

Autism is a severe developmental disorder that was first described by Kanner in 1943. It is characterised by four major criteria: marked social deficits, delay in language development, a restricted range of stereotyped repetitive behaviours and onset of the disease within the first three years of life. The last decade of research has provided support for a strong genetic basis in the aetiology of autism. Firstly, a number of genetic conditions, such as fragile X syndrome, chromosome 15 anomalies and tuberous sclerosis, have been associated with autism. Secondly, family studies have demonstrated that the recurrence risk for autism among siblings …