A5062891142- Glioma Diagnosis and Treatment
- Neurological diseases and metabolism
- Prion Diseases and Protein Misfolding
- Mitochondrial Function and Pathology
- CNS Lymphoma Diagnosis and Treatment
- Alzheimer's disease research and treatments
- Traumatic Brain Injury and Neurovascular Disturbances
- Parkinson's Disease Mechanisms and Treatments
- Meningioma and schwannoma management
- Intracerebral and Subarachnoid Hemorrhage Research
- Metabolism and Genetic Disorders
- Peptidase Inhibition and Analysis
- Genetics and Neurodevelopmental Disorders
- Genetic Neurodegenerative Diseases
- MicroRNA in disease regulation
- Chromatin Remodeling and Cancer
- Sarcoidosis and Beryllium Toxicity Research
- Cancer Mechanisms and Therapy
- Amyotrophic Lateral Sclerosis Research
- Lymphoma Diagnosis and Treatment
- Neurofibromatosis and Schwannoma Cases
- Neurological disorders and treatments
- RNA regulation and disease
- Sarcoma Diagnosis and Treatment
- Infectious Diseases and Tuberculosis
Beaumont Hospital
2015-2024
Royal College of Surgeons in Ireland
2002-2023
Cambridge University Hospitals NHS Foundation Trust
2021
John Wiley & Sons (United States)
2020
Temple Street Children's University Hospital
2016
Neuromod (Ireland)
2015
St. James's Hospital
2015
University College London
2013
Ollscoil na Gaillimhe – University of Galway
2013
University of Oxford
2013
Abstract Blood-brain barrier (BBB) dysfunction is associated with worse epilepsy outcomes however the underlying molecular mechanisms of BBB remain to be elucidated. Tight junction proteins are important regulators integrity and in particular, tight protein claudin-5 most enriched brain endothelial cells regulates size-selectivity at BBB. Additionally, disruption expression has been implicated numerous disorders including schizophrenia, depression traumatic injury, yet its role not fully...
As both astrocytes and cytokines modulate the permeability of cerebral endothelial cells, transgenic animal models which overexpress cytokines, such as interleukin-6 (IL-6), may provide insight into neuropathological consequences increased BBB permeability. In this study, a GFAP-IL6 mouse model horseradish peroxidase (HRP) were used to investigate associated neuropathologic changes. cerebellum control mice, developed between postnatal days 7 14. never extensive breakdown was evident in high-...
Mutations in the gene encoding parkin (PARK2) are most common cause of autosomal recessive juvenile-onset and young-onset parkinsonism. The few available detailed neuropathologic reports suggest that homozygous compound heterozygous mutations characterized by severe substantia nigra pars compacta neuronal loss.
Size-selective and passive paracellular diffusion of amyloid-β across tight junctions the blood-brain barrier in Alzheimer’s disease.
Abstract We report two brothers from a non-consanguineous Irish family presenting with novel syndrome characterised by intellectual disability, facial dysmorphism, scoliosis and long QT. Their mother has milder phenotype including X-linked inheritance was suspected. Whole exome sequencing identified missense variant (c.128 A > C; p.Tyr43Ser) in NAA10 (X chromosome) as the cause of family’s disorder. Sanger confirmed that mutation arose de novo carrier mother. encodes catalytic subunit...
We characterized the role of structural variants, a largely unexplored type genetic variation, in two non-Alzheimer's dementias, namely Lewy body dementia (LBD) and frontotemporal (FTD)/amyotrophic lateral sclerosis (ALS). To do this, we applied an advanced variant calling pipeline (GATK-SV) to short-read whole-genome sequence data from 5,213 European-ancestry cases 4,132 controls. discovered, replicated, validated deletion
The contribution of somatic variants to epilepsy has recently been demonstrated, particularly in the etiology malformations cortical development. aim this study was determine diagnostic yield genes that have previously associated with a or germline model, ascertained from resected brain tissue patients multidrug-resistant focal epilepsy.
<b><i>Background:</i></b> Rapid-onset dystonia-parkinsonism (RDP) is an autosomal dominant disorder linked to chromosome 19q13 that characterized by sudden onset of primarily bulbar and upper limb dystonia with parkinsonism. <b><i>Methods:</i></b> The authors evaluated 12 individuals from three generations Irish family obtained detailed medical records on a deceased member. describe the clinical, psychiatric, genetic features affected individuals. <b><i>Results:</i></b> Five eight members...
Abstract Mutations in the Cu/Zn superoxide dismutase gene ( SOD‐1 ) are reported 20% of familial amyotrophic lateral sclerosis (ALS) cases, but no definite report a mutation “truly” sporadic case ALS has been proved. We present first novel patient with genetically proven ALS. This (H80A) is believed to alter zinc ligand binding, and its functional significance correlates well aggressive clinical course postmortem findings observed this patient.
Abstract The APOE locus is strongly associated with risk for developing Alzheimer’s disease and dementia Lewy bodies. In particular, the role of ε4 allele as a putative driver α-synuclein pathology topic intense debate. Here, we performed comprehensive evaluation in 2466 bodies cases versus 2928 neurologically healthy, aged controls. Using an APOE-stratified genome-wide association study approach, found that GBA patients without (P = 5.65 × 10−8, OR 3.21, 95% CI 2.11–4.88), but not 0.034,...
Abstract Background Patient-derived glioma stem-like cells (GSCs) have become the gold-standard in neuro-oncological research; however, it remains to be established whether loss of situ microenvironment affects clinically-predictive value this model. We implemented a GSC monolayer system investigate - vitro molecular correspondence and relationship between patient response temozolomide (TMZ). Methods DNA/RNA-sequencing was performed on 56 glioblastoma tissues 19 derived cultures. Sensitivity...
The common prion protein gene (PRNP) codon 129 polymorphism modifies the susceptibility to and phenotype of diseases. However, no truly representative normal population-based data, or data stratified according age gender are available on distribution this polymorphism.Allelic variation in three Finnish populations representing different groups, among Finnish, British Irish blood donors were examined.The PRNP genotype total sample was 49% for methionine-methionine (MM), 42% methionine-valine...
Haemangiomas of the vertebrae, usually regarded as having little or no consequence, may display aggressive features, including extension into extradural space, and cause significant neurological symptoms signs necessitating treatment. Extraosseous haemangiomas in an intradural extramedullary location are a rare entity. Here we review our radiologic pathologic experience osseous with primary haemangiomas. Magnetic resonance imaging plays pivotal role characterisation spinal haemangiomas,...
Abstract Here, we establish a CT-radiomics based method for application in invasive, orthotopic rodent brain tumour models. Twenty four NOD/SCID mice were implanted with U87R-Luc2 GBM cells and longitudinally imaged via contrast enhanced (CE-CT) imaging. Pyradiomics was employed to extract CT-radiomic features from the tumour-implanted hemisphere non-tumour-implanted of acquired CT-scans. Inter-correlated removed (Spearman correlation > 0.85) remaining underwent predictive analysis...
Abstract Background Breast cancer brain metastasis is a rising occurrence, necessitating better understanding of the mechanisms involved for effective management. metastases diverge notably from primary tumor, with gains in kinase and concomitant losses steroid signaling observed. In this study, we explored role receptor RET promoting breast provide rationale targeting receptor. Methods expression was characterized cohort patients metastatic tumors. functionality assessed using...
Familial diffuse Lewy body disease (DLBD) is rare and not yet associated with a defect in the synuclein gene. In differential diagnosis of parkinsonian syndromes, defects vertical gaze tend to be identified progressive supranuclear palsy. False-positive palsy can occur, have been reported DLBD, although so far pure pathological abnormalities substrate for has described.To report clinical findings 2 siblings relate distribution brainstem centers gaze.For several years, Irish experienced...
A retrospective analysis of 14 patients who presented with a progressively expanding mass lesion(s) shown at biopsy/autopsy to represent acute demyelination was carried out. The aims this study were determine the optimal neuropathological approach diagnosis and clinical evolution condition. Subsequent investigations outcome studies confirmed MS in 10 cases. Two had received an incorrect neuropathologic astrocytoma resulting cranial irradiation. Key histologic parameters establishing...
In ten male rats we inserted ceramic ‘drawing-pin’ implants in weight-bearing positions within the right proximal tibia. Two animals were killed 6 weeks after surgery and two more 14 surgery. The remaining six received intra-articular injections of either high-density polyethylene (4 rats) or saline (2 at 8, 10 12 These last injection. Histological examination bone-implant interface control showed appositional bone growth around implant both weeks. Polyethylene, but not saline, caused a...