A5078346633- Metabolism and Genetic Disorders
- Mitochondrial Function and Pathology
- Biochemical and Molecular Research
- Neonatal Health and Biochemistry
- Diet and metabolism studies
- Folate and B Vitamins Research
- Peroxisome Proliferator-Activated Receptors
- Muscle metabolism and nutrition
- Neurological and metabolic disorders
- Renal cell carcinoma treatment
- Diabetes and associated disorders
- Cancer, Hypoxia, and Metabolism
- Renal and related cancers
- Amino Acid Enzymes and Metabolism
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Mass Spectrometry Techniques and Applications
- Glycogen Storage Diseases and Myoclonus
- Neurogenetic and Muscular Disorders Research
- Uterine Myomas and Treatments
- Genomic variations and chromosomal abnormalities
- Adenosine and Purinergic Signaling
- Pediatric Hepatobiliary Diseases and Treatments
- Lipoproteins and Cardiovascular Health
- Genomics and Rare Diseases
- Infectious Encephalopathies and Encephalitis
Sheffield Children's NHS Foundation Trust
2007-2024
Sheffield Children's Hospital
2009-2022
Boston Children's Hospital
1997-2015
University of Sheffield
1993-2012
Addenbrooke's Hospital
1988
University of Cambridge
1982
Medical Research Council
1982
The nuclear-encoded Krebs cycle enzymes, fumarate hydratase (FH) and succinate dehydrogenase (SDHB, -C -D), act as tumour suppressors. Germline mutations in FH predispose individuals to leiomyomas renal cell cancer (HLRCC), whereas SDH cause paragangliomas phaeochromocytomas (HPGL). In this study, we have shown that FH-deficient cells tumours accumulate and, a lesser extent, succinate. SDH-deficient principally situ analyses showed these also over-expression of hypoxia-inducible factor 1α...
There are marked mitochondrial abnormalities in parkin-knock-out Drosophila and other model systems. The aim of our study was to determine function morphology parkin-mutant patients. We also investigated whether pharmacological rescue impaired may be possible human tissue.
Multiple acyl-CoA dehydrogenation deficiency (MADD) is a disorder of fatty acid, amino acid and choline metabolism that can result from defects in two flavoproteins, electron transfer flavoprotein (ETF) or ETF: ubiquinone oxidoreductase (ETF:QO). Some patients respond to pharmacological doses riboflavin. It unknown whether these have the flavoproteins themselves formation cofactor, FAD, We report 15 11 pedigrees. All index cases presented with encephalopathy muscle weakness combination...
1. Studies were carried out in vitro to examine the effects of phytate on solubility trace elements zinc, copper and manganese. Appropriate volumes a solution sodium added mineral achieve phytate: Zn values from 0: 1 45:1. In second series same for achieved by varying amount at fixed concentration. 2. both experiments > 85% was rendered insoluble pH 6.5 even lowest value phytate:Zn (5:1). The effect greater than Cu or Mn. 3. dietary study, rats offered semi-synthetic egg-albumin-based...
To investigate the clinical features of multiple cutaneous and uterine leiomyomatosis (MCUL) syndrome, including hereditary renal cell cancer syndrome.A case series patients with skin leiomyomas solicited via a circular letter to dermatologists.Research institute.A total 108 affected individuals, 46 probands 62 relatives.The proportion underlying fumarate hydratase (FH) mutations, penetrance FH clinicopathologic MCUL.Forty-one (89%) had evidence germline which were highly penetrant. All 26...
Childhood onset motor neuron diseases or neuronopathies are a clinically heterogeneous group of disorders. A particularly severe subgroup first described in 1894, and subsequently called Brown-Vialetto-Van Laere syndrome, is characterized by progressive pontobulbar palsy, sensorineural hearing loss respiratory insufficiency. There has been no treatment for this neurodegenerative disorder, which leads to failure usually death during childhood. We recently reported the identification SLC52A2,...
Mutations in the gene encoding Krebs cycle enzyme fumarate hydratase (FH) predispose to hereditary leiomyomatosis and renal cell cancer affected individuals. FH-associated neoplasia is characterized by defective mitochondrial function upregulation of transcriptional pathways mediated hypoxia-inducible factor (HIF), although whether what means these processes are linked has been disputed. We analysed HIF pathway Fh1−/− mouse embryonic fibroblasts (MEFs), FH-defective neoplastic tissues MEFs...
Aims Amyotrophic lateral sclerosis ( ALS ) and primary PLS are two syndromic variants within the motor neurone disease spectrum. As most cases sporadic SALS ), this limits availability of cellular models for investigating pathogenic mechanisms therapeutic targets. The aim study was to use gene expression profiling evaluate fibroblasts as , establish whether dysregulated biological processes recapitulate those seen in central nervous system elucidate pathways that distinguish clinically...
Abstract Primary systemic carnitine deficiency or uptake defect (OMIM 212140) is a potentially lethal, autosomal recessive disorder characterized by progressive infantile‐onset cardiomyopathy, weakness, and recurrent hypoglycemic hypoketotic encephalopathy, which highly responsive to L ‐carnitine therapy. Molecular analysis of the SLC22A5 ( OCTN2 ) gene, encoding high‐affinity transporter, was done in 11 affected individuals direct nucleotide sequencing polymerase chain reaction products...
Succinate dehydrogenase (SDH) is a crucial metabolic enzyme complex that involved in ATP production, playing roles both the tricarboxylic cycle and mitochondrial respiratory chain (complex II). Isolated II deficiency one of rarest oxidative phosphorylation disorders with mutations described three structural subunits assembly factors; just case attributed to recessively inherited SDHD mutations. We report pathological, biochemical, histochemical molecular genetic investigations male neonate...
Recent studies demonstrated a strong influence of rare genetic variants on several lipid-related traits. However, their impact free fatty acid (FFA) plasma concentrations, as well the role in general population, has not yet been thoroughly addressed. The adipose triglyceride lipase (ATGL) is encoded by PNPLA2 gene and catalyzes rate-limiting step lipolysis. It represents prominent candidate affecting FFA concentrations. We therefore screened full genomic region ATGL for mutations 1,473...
1. The increase in activation coefficient (stimulated: basal activity) of erythrocyte NAD(P)H 2 :glutathione oxidoreductase ( EC 16.4.2) and reduction hepatic flavin concentration which occurred riboflavin-deficient weanling rats were not markedly or consistently affected by differences the lipid diet nor total proportion saturated polyunsaturated fatty acids dietary lipid. 2. Their gain body-weight was, however, reduced when was increased from 30 to 200 g/kg liver: triglyceride content...