G M Halliday

Neuroscience Research Australia, Sydney, New South Wales, Australia

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Publications (248)1094.41 Total impact

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    ABSTRACT: Imaging, cerebrospinal fluid (CSF) and blood-based biomarkers have the potential to improve the accuracy by which specific causes of dementia can be diagnosed in vivo, provide insights into the underlying pathophysiology, and may be used as inclusion criteria and outcome measures for clinical trials. While a number of imaging and CSF biomarkers are currently used for each of these purposes, this is an evolving field, with numerous potential biomarkers in varying stages of research and development. We review the currently available biomarkers for the three most common forms of neurodegenerative dementia, and give an overview of research techniques that may in due course make their way into the clinic.
    Journal of neurology, neurosurgery, and psychiatry. 09/2014;
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    ABSTRACT: BACKGROUND: Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder. METHODS: We did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with FTD and 9402 healthy controls. To reduce genetic heterogeneity, all participants were of European ancestry. In the discovery phase (samples from 2154 patients with FTD and 4308 controls), we did separate association analyses for each FTD subtype (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and FTD overlapping with motor neuron disease [FTD-MND]), followed by a meta-analysis of the entire dataset. We carried forward replication of the novel suggestive loci in an independent sample series (samples from 1372 patients and 5094 controls) and then did joint phase and brain expression and methylation quantitative trait loci analyses for the associated (p<5 × 10(-8)) single-nucleotide polymorphisms. FINDINGS: We identified novel associations exceeding the genome-wide significance threshold (p<5 × 10(-8)). Combined (joint) analyses of discovery and replication phases showed genome-wide significant association at 6p21.3, HLA locus (immune system), for rs9268877 (p=1·05 × 10(-8); odds ratio=1·204 [95% CI 1·11-1·30]), rs9268856 (p=5·51 × 10(-9); 0·809 [0·76-0·86]) and rs1980493 (p value=1·57 × 10(-8), 0·775 [0·69-0·86]) in the entire cohort. We also identified a potential novel locus at 11q14, encompassing RAB38/CTSC (the transcripts of which are related to lysosomal biology), for the behavioural FTD subtype for which joint analyses showed suggestive association for rs302668 (p=2·44 × 10(-7); 0·814 [0·71-0·92]). Analysis of expression and methylation quantitative trait loci data suggested that these loci might affect expression and methylation in cis. INTERPRETATION: Our findings suggest that immune system processes (link to 6p21.3) and possibly lysosomal and autophagy pathways (link to 11q14) are potentially involved in FTD. Our findings need to be replicated to better define the association of the newly identified loci with disease and to shed light on the pathomechanisms contributing to FTD
    The Lancet Neurology 07/2014; 3(7):686-99. · 23.92 Impact Factor
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    ABSTRACT: Hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72) have recently been linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis, and may be the most common genetic cause of both neurodegenerative diseases. Genetic variants at TMEM106B influence risk for the most common neuropathological subtype of FTLD, characterized by inclusions of TAR DNA-binding protein of 43 kDa (FTLD-TDP). Previous reports have shown that TMEM106B is a genetic modifier of FTLD-TDP caused by progranulin (GRN) mutations, with the major (risk) allele of rs1990622 associating with earlier age at onset of disease. Here, we report that rs1990622 genotype affects age at death in a single-site discovery cohort of FTLD patients with C9orf72 expansions (n = 14), with the major allele correlated with later age at death (p = 0.024). We replicate this modifier effect in a 30-site international neuropathological cohort of FTLD-TDP patients with C9orf72 expansions (n = 75), again finding that the major allele associates with later age at death (p = 0.016), as well as later age at onset (p = 0.019). In contrast, TMEM106B genotype does not affect age at onset or death in 241 FTLD-TDP cases negative for GRN mutations or C9orf72 expansions. Thus, TMEM106B is a genetic modifier of FTLD with C9orf72 expansions. Intriguingly, the genotype that confers increased risk for developing FTLD-TDP (major, or T, allele of rs1990622) is associated with later age at onset and death in C9orf72 expansion carriers, providing an example of sign epistasis in human neurodegenerative disease.
    Acta Neuropathologica 01/2014; · 9.73 Impact Factor
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    ABSTRACT: Background: Clinical heterogeneity in the development of levodopa-induced dyskinesias (LID) suggests endogenous factors play a significant role in determining their overall prevalence. Objective: We hypothesised that single nucleotide polymorphisms (SNPs) in specific genes may result in a clinical phenotype conducive to an increased risk of LID. Methods: We examined the influence of SNPs in the catechol-O-methyltransferase (COMT), monoamine oxidase A (MAO-A) and brain-derived neurotrophic factor (BDNF) genes on LID in a cohort of 285 pathologically confirmed Parkinson's disease patients, using data from their complete disease course. Results: Dyskinetic patients demonstrated younger age at disease onset (60.3 vs. 66.4 years, p < 0.0001), a longer disease duration (17.0 vs. 12.0 years, p < 0.0001) and a higher maximum daily levodopa equivalent dose (LED; 926.7 vs. 617.1 mg/day, p < 0.0001) than patients without dyskinesias. No individual SNP was found to influence prevalence or time to onset of dyskinesias, including after adjustment for known risk factors. We observed that patients carrying alleles conferring both high COMT activity and increased MAO-A mRNA expression received significantly higher maximum and mean daily LEDs than those with low enzyme activity/mRNA expression (max LED: 835 ± 445 vs. 508 ± 316 mg; p = 0.0056, mean LED: 601 ± 335 vs. 398 ± 260 mg; p = 0.025). Conclusions: Individual SNPs in BDNF, COMT and MAO-A genes did not influence prevalence or time to onset of dyskinesias in this cohort. The possibility that combined COMT and MAO-A genotype is a significant factor in determining an individual's lifetime levodopa exposure warrants further investigation.
    Neurodegenerative Diseases 09/2013; · 3.41 Impact Factor
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    ABSTRACT: Both fresh-frozen and formalin-fixed, paraffinembedded (FFPE) human brain tissues are invaluable resources for molecular genetic studies of central nervous system diseases, especially neurodegenerative disorders. To identify the optimal method for DNA extraction from human brain tissue, we compared methods on differently-processed tissues. Fragments of LRRK2 and MAPT (257 bp and 483 bp/245 bp) were amplified for evaluation. We found that for FFPE samples, the success rate of DNA extraction was greater when using a commercial kit than a laboratory-based method (successful DNA extraction from 76% versus 33% of samples). PCR amplicon size and storage period were key factors influencing the success rate of DNA extraction from FFPE samples. In the fresh-frozen samples, the DNA extraction success rate was 100% using either a commercial kit (QIAamp DNA Micro) or a laboratorybased method (sample boiling in 0.1 mol/L NaOH, followed by proteinase K digestion, and then DNA extraction using Chelex-100) regardless of PCR amplicon length or tissue storage time. Although the present results demonstrate that PCR-amplifiable genomic DNA can be extracted from both fresh-frozen and FFPE samples, fresh brain tissue is recommended for DNA extraction in future neuropathological studies.
    Neuroscience Bulletin 08/2013; · 1.37 Impact Factor
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    ABSTRACT: BACKGROUND AND AIMS: Tenuigenin (Ten) is a Chinese herbal extract with antioxidative and antiinflammatory effects on toxin-induced cell models of Parkinson's disease (PD); however, its effects on α-synuclein toxicity-based PD models remain unknown. α-synuclein hyperphosphorylation is a key event in PD pathogenesis and potential target of therapeutic interventions. We tested whether Ten alleviates α-synuclein-induced cytotoxicity via reducing kinases that phosphorylate α-synuclein. METHODS: SH-SY5Y cells transiently transfected with wild-type or A53T mutant α-synuclein were used to evaluate the effect of Ten on the levels of α-synuclein phosphorylation-related kinases. Cells treated with 10 μM Ten for 24 h were measured for viability (proliferation and apoptosis assays) and cellular proteins harvested and fractioned. The levels of total and phosphorylated α-synuclein and five associated kinases (polo-like kinase [PLK] 1-3, casein kinase [CK] 1-2) were evaluated by Western blotting. RESULTS: Overexpression of either wild-type or A53T mutant α-synuclein decreased cell viability and increased α-synuclein phosphorylation. Ten treatment-protected cells from this α-synuclein-induced toxicity and dramatically reduced α-synuclein phosphorylation and PLK3 (but not other kinase) levels. CONCLUSION: In α-synuclein cell model of PD, Ten is effective in attenuating α-synuclein-induced toxicity and α-synuclein phosphorylation probably via targeting PLK3, suggesting it could be an efficient therapeutic drug to treat α-synuclein-related neurodegeneration.
    CNS Neuroscience & Therapeutics 05/2013; · 4.46 Impact Factor
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    ABSTRACT: IMPORTANCE While mutations in glucocerebrosidase (GBA1) are associated with an increased risk for Parkinson disease (PD), it is important to establish whether such mutations are also a common risk factor for other Lewy body disorders. OBJECTIVE To establish whether GBA1 mutations are a risk factor for dementia with Lewy bodies (DLB). DESIGN We compared genotype data on patients and controls from 11 centers. Data concerning demographics, age at onset, disease duration, and clinical and pathological features were collected when available. We conducted pooled analyses using logistic regression to investigate GBA1 mutation carrier status as predicting DLB or PD with dementia status, using common control subjects as a reference group. Random-effects meta-analyses were conducted to account for additional heterogeneity. SETTING Eleven centers from sites around the world performing genotyping. PARTICIPANTS Seven hundred twenty-one cases met diagnostic criteria for DLB and 151 had PD with dementia. We compared these cases with 1962 controls from the same centers matched for age, sex, and ethnicity. MAIN OUTCOME MEASURES Frequency of GBA1 mutations in cases and controls. RESULTS We found a significant association between GBA1 mutation carrier status and DLB, with an odds ratio of 8.28 (95% CI, 4.78-14.88). The odds ratio for PD with dementia was 6.48 (95% CI, 2.53-15.37). The mean age at diagnosis of DLB was earlier in GBA1 mutation carriers than in noncarriers (63.5 vs 68.9 years; P < .001), with higher disease severity scores. CONCLUSIONS AND RELEVANCE Mutations in GBA1 are a significant risk factor for DLB. GBA1 mutations likely play an even larger role in the genetic etiology of DLB than in PD, providing insight into the role of glucocerebrosidase in Lewy body disease.
    JAMA neurology. 04/2013;
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    ABSTRACT: Disturbances in brain copper result in rare and severe neurological disorders and may play a role in the pathogenesis and progression of multiple neurodegenerative diseases. Our current understanding of mammalian brain copper transport is based on model systems outside the central nervous system and no data are available regarding copper transport systems in the human brain. To address this deficit, we quantified regional copper concentrations and examined the distribution and cellular localization of the copper transport proteins Copper transporter 1, Atox1, ATP7A, and ATP7B in multiple regions of the human brain using inductively coupled plasma-mass spectrometry, Western blot and immunohistochemistry. We identified significant relationships between copper transporter levels and brain copper concentrations, supporting a role for these proteins in copper transport in the human brain. Interestingly, the substantia nigra contained twice as much copper than that in other brain regions, suggesting an important role for copper in this brain region. Furthermore, ATP7A levels were significantly greater in the cerebellum, compared with other brain regions, supporting an important role for ATP7A in cerebellar neuronal health. This study provides novel data regarding copper regulation in the human brain, critical to understand the mechanisms by which brain copper levels can be altered, leading to neurological disease.
    Metallomics 10/2012; · 4.10 Impact Factor
  • Glenda Halliday
    Movement Disorders 10/2012; · 5.63 Impact Factor
  • S M Thanos, G M Halliday, D L Damian
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    ABSTRACT: The immune suppressive effects of topical photodynamic therapy (PDT) are potential contributors to treatment failure after PDT for nonmelanoma skin cancer. Nicotinamide (vitamin B(3) ) prevents immune suppression by ultraviolet radiation, but its effects on PDT-induced immunosuppression are unknown. To determine the effects of topical and oral nicotinamide on PDT-induced immunosuppression in humans. Twenty healthy Mantoux-positive volunteers received 5% nicotinamide lotion or vehicle to either side of the back daily for 3 days. Another group of 30 volunteers received 500 mg oral nicotinamide or placebo twice daily for 1 week in a randomized, double-blinded, crossover design. In each study, methylaminolaevulinate cream was applied to discrete areas on the back, followed by narrowband red light irradiation (37 J cm(-2) ) delivered at high (75 mW cm(-2) ) or low (15 mW cm(-2) ) irradiance rates. Adjacent, nonirradiated sites served as controls. Delayed-type hypersensitivity (Mantoux) reactions were assessed at treatment and control sites to determine immunosuppression. High irradiance rate PDT with vehicle or with placebo caused significant immunosuppression (equivalent to 48% and 50% immunosuppression, respectively; both P < 0·0001); topical and oral nicotinamide reduced this immunosuppression by 59% and 66%, respectively (both P < 0·0001). Low irradiance rate PDT was not significantly immunosuppressive in the topical nicotinamide study (15% immunosuppression, not significant), but caused 22% immunosuppression in the oral study (placebo arm; P = 0·006); nicotinamide reduced this immunosuppression by 69% (P = 0·045). While the clinical relevance of these findings is currently unknown, nicotinamide may provide an inexpensive means of preventing PDT-induced immune suppression and enhancing PDT cure rates.
    British Journal of Dermatology 06/2012; 167(3):631-6. · 3.76 Impact Factor
  • Amyotrophic Lateral Sclerosis. 2011; 12(Suppl. 1):35, Sydney, Australia; 11/2011
  • N. C. Delic, P. W. Sou, G. M. Halliday, J. G. Lyons
    Oral Oncology 07/2011; 47. · 2.70 Impact Factor
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    ABSTRACT: Background  Nonmelanoma skin cancer is caused by exposure to ultraviolet radiation within sunlight. Actinic keratoses (AKs) are benign precursor lesions that can develop into invasive squamous cell carcinoma (SCC). Little is known about the molecular events that lead to human skin cancer progression from benign to invasive. Objectives  To determine novel genes that may be involved in skin cancer progression based on data from an initial microarray screen of human skin cancers. Methods  The SWI/SNF chromatin remodelling ATPase subunit BRM was identified as being downregulated in SCC but not AK compared with normal skin in our microarray screen. Therefore reverse transcription-polymerase chain reaction, gene methylation and protein expression was used to study BRM and its alternative ATPase subunit BRG1 in a range of human skin cancers. Results  We found reduced levels of mRNA coding for BRM but not BRG1 in SCC. BRM mRNA levels in AK were similar to those in normal skin. Deregulation of BRM did not result from hypermethylation of CpG regions in the promoter of these genes. Both BRM and BRG1 protein was reduced by about 10-fold in 100% of SCC and basal cell carcinoma, but not in AK specimens examined. Conclusions  BRM protein may be decreased due to low levels of mRNA, while BRG1 protein loss appears to be post-translational. BRM and BRG1 may be novel tumour suppressor genes for human skin cancer. They appear to be involved after development of benign lesions, and are downregulated during progression towards invasion.
    British Journal of Dermatology 06/2011; 164(6):1221-7. · 3.76 Impact Factor
  • D L Damian, Y J Matthews, T A Phan, G M Halliday
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    ABSTRACT: The immune-suppressive effects of sunlight play a central role in skin carcinogenesis. Ultraviolet (UV) B radiation is highly immunosuppressive even at suberythemal doses, and longwave UVA is now also recognized to cause immunosuppression in humans. The relative contributions of UVA and UVB to immunosuppression by incidental daily sun exposure are, however, unclear. We previously determined wavelength dependencies for immunosuppression by UVB and UVA wavebands in humans. We now aimed to calculate relative and solar immune-suppressive effectiveness across the UVB and UVA spectra. We used the nickel model of recall contact hypersensitivity to determine UV immunosuppression dose responses and minimum immune suppression doses (MISDs) at 11 narrowbands from 289 to 392 nm. The relative immune-suppressive effectiveness of each narrowband was then determined as 1/MISD vs. wavelength. This curve was multiplied by the solar spectrum to show the relative immune-suppressive effectiveness of each waveband in sunlight. We found peaks of immune-suppressive effectiveness in the UVB waveband at 300 nm and in the UVA at 370 nm. Because of the far greater amount of longwave UVA in sunlight, the relative solar immune-suppressive effectiveness of UVA was threefold higher than that of UVB at doses equivalent to sun exposure from normal daily activities. Longwave UVA, which abuts the visible light spectrum and is less effectively filtered by sunscreens than UVB, is likely to be the largest contributor to immunosuppression resulting from incidental daily sun exposure.
    British Journal of Dermatology 03/2011; 164(3):657-9. · 3.76 Impact Factor
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    ABSTRACT: To determine whether neuropsychological measures differ between patients with idiopathic Parkinson's disease (PD) who acquire dementia within 10 years of disease onset versus those who acquire dementia later in the disease course, using data from the longitudinal Sydney Multicentre Study of PD. The Sydney Multicentre Study of PD is a cohort of 149 community-living de novo patients with idiopathic PD studied over a 20-year period. Detailed clinical and neuropsychological tests were administered at baseline and at 3, 5, 10, 15 and 20 years, and the dementia status was assessed at each time point. For the present study, the pattern of longitudinal neuropsychological measures was compared between PD patients with the onset of dementia in the middle (5-10 years, mid-stage PD dementia, N = 20) or late (>10 years, late-stage PD dementia, N = 10) disease stages using analysis of variance and multiple linear regression modelling, and the relationship between age and dementia onset assessed using survival statistics. Mid-stage PD dementia patients were differentiated from late-stage PD dementia patients by having greater deficits in vocabulary skills prior to and at dementia onset. The pattern of cognitive deficits following dementia onset are similar, and there is no difference in the age of dementia onset between the different PD groups. These data suggest that the evolution of dementia within PD occurs at around 70 years of age, regardless of the time of PD onset, and affects cognitive domains in a similar way, although patients with earlier-onset PD have a preserved linguistic ability prior to dementia onset.
    Journal of neurology, neurosurgery, and psychiatry 02/2011; 82(9):1033-7. · 4.87 Impact Factor
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    ABSTRACT: Neurogenesis, the birth of new neurons from precursors, continues throughout adulthood in the human subventricular zone and hippocampus. It is not known how levels of factors thought to regulate the proliferation of precursors change with age in human adult neurogenic areas. Purpose and Methods: The current project employed ELISAs to investigate changes in levels of putative proliferation-regulating factors in the healthy human subventricular zone and hippocampus throughout the adult lifespan (18 to 104 years). Results: Human hippocampal levels of the anti-proliferative transforming growth factor-β1 strongly increased with age (n=10, p=0.005), whilst human hippocampal and subventricular zone levels of the pro-proliferative basic fibroblast growth factor, epidermal growth factor, glial-derived neurotrophic factor, heparin binding epidermal growth factor, insulin-like growth factor-1, transforming growth factor-α and the anti-proliferative interleukin-1β and interleukin-6 did not change significantly with age. Levels of brain-derived neurotrophic factor, basic fibroblast growth factor and interleukin-1β were significantly higher in the hippocampus than in the subventricular zone and levels of glial-derived neurotrophic factor and transforming growth factor-α were significantly higher in the subventricular zone (p<0.005), suggesting that factors with predominant influences on neurogenesis differ between the two human adult neurogenic areas. Conclusion: These findings suggest regulation of the adult neurogenic environment in the human brain may differ over time from that in other species.
    Australian Neuroscience Society 31st Annual Meeting, Auckland, New Zealand; 01/2011
  • Australian Neuroscience Society 31st Annual Meeting, Auckland, New Zealand; 01/2011
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    ABSTRACT: Neuropathology of frontotemporal lobar degeneration is variable and relationship between the pathology and the clinical presentation remains uncertain. Abnormal deposits of hyperphosphorylated and ubiquitinated tau protein are present in 30% of cases, which include the classic presentation of Pick disease with argyrophilic, intraneuronal inclusions known as Pick bodies. This study aimed to improve sensitivity of clinicopathologic relations in cases with neuropathologically confirmed Pick disease and to identify clinical symptoms and signs predictive of disease progression. This was a retrospective analysis of 21 cases with a pathologic diagnosis of Pick disease and sufficient clinical information to establish early presenting clinical features from 2 specialist centers, representing 70% of all cases of Pick disease identified between 1998 and 2007 in these centers. At presentation, 13/21 cases (62%) were clinically diagnosed with behavioral variant frontotemporal dementia (bvFTD) and 8/21 (38%) with language variant frontotemporal dementia (lvFTD) including 2 with mixed syndromes. Patients with bvFTD died on average 5 years earlier than those with lvFTD (7 years vs 12 years after disease onset). Pathologically, fewer Pick bodies were present in the frontal and inferior temporal cortices of bvFTD than lvFTD cases. In contrast, both groups showed decreased neuronal density in the dentate gyrus with increasing disease duration. The pathologic course of the disease in FTLD cases with Pick bodies is not uniform and disease duration can be estimated based on early clinical features. These findings have relevance as treatment options, which are likely to be pathology specific, are developed.
    Neurology 01/2011; 76(3):253-9. · 8.30 Impact Factor
  • K L Double, S Reyes, E L Werry, G M Halliday
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    ABSTRACT: Neurodegenerative diseases exhibit varying and characteristic patterns of regional brain cell death, yet in each disorder there are distinct variations in the relative vulnerability of neurons within targeted brain regions. For example, in Parkinson's disease (PD) up to 90% of dopaminergic neurons of the ventral tier of the substantia nigra pars compacta are lost at post-mortem, while as few as 25% of dopaminergic neurons in the dorsal tier of this nucleus succumb to the disease process. To date the reasons underlying differential vulnerability of similar neurons within a defined cytoarchitectural region has received little attention. We suggest variations in protein distribution underlies this differential vulnerability. Within the substantia nigra pars compacta the more vulnerable neurons exhibit an increased expression of factors that may contribute to vulnerability (D(2) dopamine autoreceptors, GIRK-2 potassium channels, lactotransferrin and the dopamine transporter) while also expressing a relative lack of neuroprotective elements (dopamine vesicle transport protein and a number of trophic and growth factors). Differential distribution of key proteins expressed by individual cells within the same cytoarchitectural brain region may influence the severity and likelihood of common neurodegenerative mechanisms, such as protein aggregation, oxidative stress, neuroinflammation and apoptosis, and thus the eventual fate of individual cells in the disease process. An understanding of how variable protein expression can influence cell survival within the diseased human brain in a range of neurodegenerative disorders may provide avenues for the development of novel strategies to improve the survival of targeted neurons in vivo.
    Progress in Neurobiology 11/2010; 92(3):316-29. · 9.04 Impact Factor
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    ABSTRACT: Ultraviolet (UV) irradiation causes DNA damage in skin cells, immunosuppression and photocarcinogenesis. 1alpha,25-dihydroxyvitamin D3 (1,25D) reduces UV-induced DNA damage in the form of cyclobutane pyrimidine dimers (CPD) in human keratinocytes in culture and in mouse and human skin. UV-induced immunosuppression is also reduced in mice by 1,25D, in part due to the reduction in CPD and a reduction in interleukin (IL-6. The cis-locked analog, 1alpha,25-dihydroxylumisterol3 (JN), which has almost no transactivating activity, reduces UV-induced DNA damage, apoptosis and immunosuppression with similar potency to 1,25D, consistent with a non-genomic signalling mechanism. The mechanism of the reduction in DNA damage in the form of CPD is unclear. 1,25D doubles nuclear expression of p53 compared to UV alone, which suggests that 1,25D facilitates DNA repair. Yet expression of a key DNA repair gene, XPG is not affected by 1,25D. Chemical production of CPD has been described. Incubation of keratinocytes with a nitric oxide donor, SNP, induces CPD in the dark. We previously reported that 1,25D reduced UV-induced nitrite in keratinocytes, similar to aminoguanidine, an inhibitor of nitric oxide synthase. A reduction in reactive nitrogen species has been shown to facilitate DNA repair, but in view of these findings may also reduce CPD formation via a novel mechanism.
    The Journal of steroid biochemistry and molecular biology 07/2010; 121(1-2):164-8. · 3.98 Impact Factor

Publication Stats

9k Citations
1,094.41 Total Impact Points

Institutions

  • 2010–2012
    • Neuroscience Research Australia
      Sydney, New South Wales, Australia
    • Ruijin Hospital North
      Shanghai, Shanghai Shi, China
  • 1992–2011
    • Royal Prince Alfred Hospital
      • Division of Anatomical Pathology
      Camperdown, New South Wales, Australia
  • 1990–2011
    • University of Sydney
      • • Discipline in Dermatology
      • • School of Biological Sciences
      • • Bosch Institute
      • • Centre for Education and Research on Ageing
      • • Discipline of Biomedical Science
      Sydney, New South Wales, Australia
  • 1984–2011
    • University of New South Wales
      • • Prince of Wales Medical Research Institute
      • • Department of Anatomy
      Kensington, New South Wales, Australia
  • 1995–2008
    • Prince of Wales Hospital and Community Health Services
      • Department of Neurology
      Sydney, New South Wales, Australia
  • 2007
    • University of South Wales
      Понтиприте, Wales, United Kingdom
    • Universität des Saarlandes
      Saarbrücken, Saarland, Germany
  • 2004
    • Sydney Cancer Centre
      Camperdown, New South Wales, Australia
  • 2003
    • University of Cambridge
      • Neurology Unit
      Cambridge, ENG, United Kingdom
    • Royal North Shore Hospital
      Sydney, New South Wales, Australia
  • 1996–2002
    • Westmead Hospital
      • Department of Neurology
      Sydney, New South Wales, Australia
  • 2000
    • University of Queensland 
      • Queensland Centre for Schizophrenia Research
      Brisbane, Queensland, Australia
  • 1986–1992
    • University of Tasmania
      • School of Medicine
      Hobart Town, Tasmania, Australia
  • 1988
    • Flinders Medical Centre
      Tarndarnya, South Australia, Australia