A5077444123- Prion Diseases and Protein Misfolding
- Neurological diseases and metabolism
- Trace Elements in Health
- Connexins and lens biology
- Alcoholism and Thiamine Deficiency
- RNA regulation and disease
- Heat shock proteins research
- RNA Research and Splicing
- Amino Acid Enzymes and Metabolism
- Animal Genetics and Reproduction
- Folate and B Vitamins Research
- Bacteriophages and microbial interactions
- Monoclonal and Polyclonal Antibodies Research
- Autoimmune Neurological Disorders and Treatments
- Infectious Encephalopathies and Encephalitis
- Retinal Development and Disorders
- Biochemical effects in animals
- Electromagnetic Fields and Biological Effects
- Biochemical Acid Research Studies
- Biotin and Related Studies
- Fibroblast Growth Factor Research
- Molecular Biology Techniques and Applications
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Enzyme Structure and Function
- Spaceflight effects on biology
University of Edinburgh
2009-2018
Canadian Food Inspection Agency
2018
Western General Hospital
2007-2017
Edinburgh College
2017
Salford Royal NHS Foundation Trust
2014
University of Manchester
2014
John Radcliffe Hospital
2014
University of Oxford
2014
Tohoku University
2013
Southern General Hospital
2013
Current cerebrospinal fluid (CSF) tests for sporadic Creutzfeldt-Jakob disease (sCJD) are based on the detection of surrogate markers neuronal damage such as CSF 14-3-3, which not specific sCJD. A number prion protein conversion assays have been developed, including real time quaking-induced (RT-QuIC). The objective this study is to investigate whether RT-QuIC analysis could be used a diagnostic test in sCJD.An exploratory was undertaken that analyzed 108 samples from patients with...
Prion diseases are characterized by the presence of abnormal prion protein PrP Sc , which is believed to be generated conversion α-helical structure that predominates in normal isoform into a β-sheet resistant proteinase K (PK). In human diseases, two major types type 1 and 2, can distinguished based on difference electrophoretic migration PK-resistant core fragment. this study, sequencing was used identify PK cleavage sites 36 cases diseases. We demonstrated primary at residue 82 97 for 2...
All UK patients with bleeding disorders treated any UK-sourced pooled factor concentrates between 1980 and 2001 have been informed that they may be at an increased risk of infection variant Creutzfeldt-Jakob disease (vCJD). We describe a study to detect disease-associated, protease-resistant prion protein (PrP(res)) in 17 neurologically aymptomatic haemophilia considered vCJD. Materials from 11 autopsy seven biopsy cases were analysed for PrP(res). The tissues available each case variable,...
Real-time quaking-induced conversion (RT-QuIC) is an assay in which disease-associated prion protein (PrP) initiates a rapid conformational transition recombinant PrP (recPrP), resulting the formation of amyloid that can be monitored real time using dye thioflavin T. It therefore has potential advantages over analogous cell-free assays such as misfolding cyclic amplification (PMCA). The QuIC and related seeding have been developed largely rodent-passaged sheep scrapie strains. Given RT-QuIC...
Human-to-human transmission of Creutzfeldt-Jakob disease (CJD) has occurred through medical procedures resulting in iatrogenic CJD (iCJD). One the commonest causes iCJD was use human pituitary-derived growth hormone (hGH) to treat primary or secondary deficiency. As part a comprehensive tissue-based analysis largest cohort yet collected (35 cases) UK hGH-iCJD cases, we describe clinicopathological phenotype UK. In 33/35 cases with sufficient paraffin-embedded tissue for full pathological...
Abstract Human prion diseases can occur as an idiopathic disorder (sporadic Creutzfeldt–Jakob disease) or be acquired, is the case for variant disease. These disorders are characterized by accumulation of a protease‐resistant form host‐encoded protein termed PrP Sc in brains affected individuals. has been proposed to principal, if not sole, component infectious agent, with its central nervous system primary event leading neurodegeneration. A major question remains whether self‐propagating...
Prions are infectious agents that cause neurodegenerative diseases such as Creutzfeldt–Jakob disease (CJD). The absence of a human cell culture model replicates prions has hampered prion research for decades. In this paper, we show astrocytes derived from induced pluripotent stem cells (iPSCs) support the replication brain samples CJD patients. For experimental exposure to variant (vCJD), kinetics occur in protein codon 129 genotype–dependent manner, reflecting genotype-dependent...
Abstract α‐Crystallins share structural and functional properties with the stress protein hsp27. These polypeptides are expressed at low constitutive levels in many tissues including brain, αB‐crystallin hsp27 can accumulate central nervous system glia a variety of neurological conditions. We report here that heat shock exposure to transition metals result an increase steady state mRNA level primary cultures rat forebrain astrocytes. Both tumour necrosis factor‐α hypertonic conditions...
Demonstration of the abnormal form prion protein (PrP) in brain confirms diagnosis human disease (PrD). Using immunohistochemistry, we have compared ten monoclonal antibodies PrD subtypes including sporadic and variant Creutzfeldt‐Jakob (CJD), fatal familial insomnia, Alzheimer's (AD), control brains. CJD subgroups were determined using Western blot analysis for protease‐resistant PrP type combination with sequencing to determine genotype at methionine/valine polymorphism codon 129 gene....
Prion diseases are closely associated with the conversion of cellular prion protein (PrP C ) to an abnormal conformer Sc [Prusiner, S. B. (1998) Proc. Natl. Acad. Sci. USA 95, 13363–13383]. Monoclonal antibodies that bind epitopes comprising residues 96–104 and 133–158 PrP potently inhibit this process, presumably by preventing heterodimeric association , suggest these regions may be critical components –PrP replicative interface. We reasoned transplanting sequence corresponding into a...
Stimulation of human promyelocytic HL60 cells by a 60Hz magnetic field at normal growth temperatures results in heat shock factor 1 activation and element binding, sequence events that mediates the stress-induced transcription stress gene HSP70 increased synthesis response protein hsp70kD. Thus, mediating electromagnetic field–stimulated appear to be similar those reported for other physiological stresses (e.g., hyperthermia, heavy metals, oxidative stress) could well general mechanism...