A5023921657- Muscle Physiology and Disorders
- Nuclear Structure and Function
- melanin and skin pigmentation
- Extracellular vesicles in disease
- Mitochondrial Function and Pathology
- Neurogenetic and Muscular Disorders Research
- Endoplasmic Reticulum Stress and Disease
- Biochemical Analysis and Sensing Techniques
- Cardiomyopathy and Myosin Studies
- Advanced Sensor and Energy Harvesting Materials
- Inflammatory Myopathies and Dermatomyositis
- Metabolism and Genetic Disorders
- RNA Interference and Gene Delivery
- Adipose Tissue and Metabolism
- Diet and metabolism studies
- Tissue Engineering and Regenerative Medicine
- Biotin and Related Studies
- Virus-based gene therapy research
- Cellular transport and secretion
- Telomeres, Telomerase, and Senescence
- Genetic Neurodegenerative Diseases
- Muscle activation and electromyography studies
- Myasthenia Gravis and Thymoma
- RNA regulation and disease
- Connective tissue disorders research
University College London
2016-2025
National Hospital for Neurology and Neurosurgery
2018-2025
National Institute for Health Research
2025
Boston Children's Museum
2024
Boston Children's Hospital
2024
Great Ormond Street Hospital
2011-2021
Great Ormond Street Hospital for Children NHS Foundation Trust
2021
Imperial College London
2007
Western General Hospital
1990-1998
University of Edinburgh
1998
We have determined the exon structure of mouse tyrosinase-related protein-1 (TRP-1) gene. The gene is only 15kb in length, but contains seven introns, contrast to tyrosinase which almost 100kb long with four Introns. Only two introns are located homologous positions both genes. Intron I TRP-1 has three alternative 5′ splice sites clustered within 21 bp, all same 3′ site. V a very unusual site, dinucleotide GC rather than conventional GT. show that as little 370bp 5′-f)anking DNA sufficient...
Abstract The mouse brown locus encodes a putative membrane-bound metalloenzyme, tyrosinase-related protein-1 (TRP-1). We have examined the effect on mRNA expression of number mutant alleles. common null allele, brown, produces wild-type levels TRP-1 mRNA, which is nonfunctional. Another recessive cordovan-Harwell, has an intermediate, dark-brown phenotype and only very low presumably normal mRNA. Two dominant alleles appear to act by killing melanocyte in they are expressed. One them, Light,...
Abstract During the last decade, multiple clinical trials for Duchenne muscular dystrophy (DMD) have focused on induction of dystrophin expression using different strategies. Many these reported a clear increase in protein following treatment. However, low levels induced raised questions its functionality. In our present study, an unbiased, high-throughput digital image analysis platform, we assessed markers regeneration and associated via immunofluorescent whole muscle sections 25 DMD boys...
TRAPPC11, a subunit of the transport protein particle (TRAPP) complex, is important for complex integrity and anterograde membrane from endoplasmic reticulum (ER) to ER-Golgi intermediate compartment. Several individuals with TRAPPC11 mutations have been reported muscle weakness other features including brain, liver, skeletal eye involvement. A detailed analysis brain pathology will further our understanding presentation aetiology disease.We describe five cases early-onset TRAPPC11-related...
Clinical trials using strategies aimed at inducing dystrophin expression in Duchenne muscular dystrophy (DMD) are underway or advanced planning stage, including splice switching antisense oligonucleotides (AON), drugs to induce read-through of nonsense mutations and viral mediated gene therapy. In all these strategies, different proteins, often internally deleted, produced, similar those found patients with the milder DMD allelic variant, Becker (BMD). The primary biological endpoint is...
To characterize a long-term model of recovery from critical illness, with particular emphasis on cardiorespiratory, metabolic, and muscle function.Randomized controlled animal study.University research laboratory.Male Wistar rats.Intraperitoneal injection the fungal cell wall constituent, zymosan or n-saline.Following intervention, rats were followed for up to 2 weeks. Animals peritonitis reached clinical biochemical nadir day 2. Initial reductions seen in body weight, total protein fat,...
Journal Article Evidence for distinguishable transcripts of the putative testis determining gene (ZFY) and mapping homologous cDNA sequences to chromosomes X,Y 9 Get access N.A. Affara, Affara * To whom correspondence should be addressed Search other works by this author on: Oxford Academic PubMed Google Scholar D. Chambers, Chambers J. O'Brien, O'Brien S.S.M. Habeebu, Habeebu M. Kalaitsidaki, Kalaitsidaki 2Duncan Guthrie Institute Medical Genetics, Royal Hospital For Sick Children....
Abstract Background Somatic α‐synuclein ( SNCA ) copy number variants (CNVs, specifically gains) occur in multiple system atrophy (MSA) and Parkinson's disease brains. Objective The aim was to compare somatic CNVs MSA subtypes (striatonigral degeneration [SND] olivopontocerebellar [OPCA]) correlate with inclusions. Methods We combined fluorescent situ hybridization immunofluorescence for some cases oligodendrocyte marker tubulin polymerization promoting protein (TPPP). Results analyzed one...
Pompe disease is a lysosomal storage disorder caused by malfunctions of the acid alpha-glucosidase (GAA) enzyme with consequent toxic accumulation glycogen in cells. Muscle wasting and hypertrophic cardiomyopathy are most common clinical signs that can lead to cardiac respiratory failure within first year age more severe infantile forms. Currently available treatments have significant limitations not curative, highlighting need for development alternative therapies. In this study, we...
Abstract Duchenne muscular dystrophy (DMD) is an incurable disease caused by out-of-frame DMD gene deletions while in frame lead to the milder Becker (BMD). In last decade several antisense oligonucleotides drugs have been developed induce a partially functional internally deleted dystrophin, similar that produced BMD, and expected ameliorate course. The pattern of dystrophin expression functionality dystrophinopathy patients variable due multiple factors, such as molecular its distribution....
Abstract The primary molecular endpoint for many Duchenne muscular dystrophy (DMD) clinical trials is the induction, or increase in production, of dystrophin protein striated muscle. For accurate analysis, it essential to have reliable, robust and objective quantification methodologies capable detecting subtle changes expression. In this work, we present further development optimisation an automated, digital, high-throughput script quantitative analysis multiplexed immunofluorescent (IF)...
Abstract Disclosure: D.M. Chambers: None. Y. Chan: M.K. Crocker: Patient SH is a now 17-year-old female treated for generalized congenital lipodystrophy with course complicated by severe hypertriglyceridemia, type 2 diabetes mellitus, hypertension, hepatosteatosis, and intermittent menstrual irregularity. She had been managed successfully metreleptin years, but in 2022-2023, she developed repeated episodes of pancreatitis (4 times over 14-month period) secondary to hypertriglyceridemia...
Mutations in the dystrophin gene (DMD) cause severe muscle-wasting disease Duchenne Muscular Dystrophy (DMD). Additionally, there is a high incidence of intellectual disability and neurobehavioural comorbidities individuals with DMD. Similar behavioural abnormalities are found mdx dystrophic mouse models. Unlike muscle, several isoforms expressed human brain, but detailed map regional cellular localisation missing. This crucial understanding neuropathology DMD individuals, for evaluating...
Abstract The novel combination of disseminated primary endometrial adenocarcinoma and a symptomatic pituitary metastasis presenting as apoplexy is described for the first time. Pituitary an unusual manifestation metastatic disease. more common clinical features metastases approach to their management are discussed. usefulness magnetic resonance imaging in assessing base skull emphasised.
Background Patients with multiple injuries or sepsis requiring intensive care treatment invariably develop a catabolic state resultant loss of lean body mass, for which there are currently no effective treatments. Recovery can take months and mortality is high. We hypothesise that the orexigenic anti-inflammatory gastric hormone, ghrelin may attenuate mass following critical illness improve recovery. Methods Male Wistar rats received an intraperitoneal injection fungal cell wall derivative...
It has been suggested that variations found in colour vision upon repeated testing may be due to fluctuations the plasma glucose level, but results of studies date are conflicting. Therefore, aim this study was investigate whether a short-term increase concentration had an influence on patients with non insulin-dependent diabetes mellitus (NIDDM) (n = 16). The and levels were monitored every 30 min for total period 4 h during three test conditions: two when increased by administration...
Abnormal expansion of trinucleotide repeats (TRs) has now been implicated in the pathogenesis at least nine human genetic disorders, particularly those which anticipation and/or fragile sites have demonstrated. Anticipation, phenomenon increasing severity phenotype successive generations, never seen species other than man. Nevertheless, animal models for dynamic mutation TRs would be extremely valuable. We screened a mouse brain cDNA library an attempt to identify clones representing each 10...