A5031110077- Lipid metabolism and biosynthesis
- Protein Kinase Regulation and GTPase Signaling
- Microbial Metabolic Engineering and Bioproduction
- Cardiac Ischemia and Reperfusion
- Lipid Membrane Structure and Behavior
- Cardiac Arrest and Resuscitation
- Sphingolipid Metabolism and Signaling
- Metabolomics and Mass Spectrometry Studies
- Long-Term Effects of COVID-19
- Protein Structure and Dynamics
- Peroxisome Proliferator-Activated Receptors
- Endoplasmic Reticulum Stress and Disease
- Metabolism and Genetic Disorders
- RNA and protein synthesis mechanisms
- Melanoma and MAPK Pathways
- Enzyme Catalysis and Immobilization
- Substance Abuse Treatment and Outcomes
- Diabetes Treatment and Management
- Plant biochemistry and biosynthesis
- Cellular transport and secretion
- Anesthesia and Neurotoxicity Research
- Geriatric Care and Nursing Homes
- Fatty Acid Research and Health
- Glycosylation and Glycoproteins Research
- Pancreatic function and diabetes
University College London
2015-2024
University College London Hospitals NHS Foundation Trust
2021-2024
Imperial College London
2022-2024
University of Leicester
2023
Glenfield Hospital
2023
University of Oxford
2023
University Hospitals of Leicester NHS Trust
2023
National Institute for Health Research
2023
NIHR Leicester Biomedical Research Centre
2023
Oxford Health NHS Foundation Trust
2023
Sphingosine inhibited protein kinase C activity and phorbol dibutyrate binding.When the mechanism of inhibition phorboi binding was investigated in vitro using Triton X-100 mixed micellar methods, sphingosine subject to surface dilution; 50% occurred when equimolar with sn-1,2-dioleoylgIy-cero1 (diCle:,) or 40% ph~phatidylserine (PS) present.Sphingosine modulated by Cas+ mole percent diCls:l PS a competitive inhibitor respect diClml, dibutyrate, Ca2+.Increasing levels markedly reduced...
A simple enzymatic method for the quantitation of mass sn-l,2-diacylglycerol (DAG) present in crude lipid extracts was developed to assess function DAGs as intracellular "second messengers" extracellular agents and oncogene products.The assay employed Escherichia coli DAG kinase which constituted approximately 15% membrane protein a plasmid-bearing strain defined mixed micellar conditions solubilize allow its quantitative conversion [82P]phosphatidic acid.The proportional with amount added...
Sphingolipid metabolism was examined in human promyelocytic leukemia HL-60 cells. Differentiation of cells with 1 alpha, 25-dihydroxyvitamin D3 (vitamin D3; 100 nM) accompanied by sphingomyelin turnover. Maximum turnover [3H]choline-labeled occurred 2 h following vitamin treatment, levels decreasing to 77 +/- 6% control and returning base-line 4 h. Ceramide phosphorylcholine were concomitantly generated. mass increased 55% at treatment returned The amount produced equaled the hydrolyzed,...
The treatment of HL-60 myelocytic leukemia cells with 1 alpha,25-dihydroxyvitamin D3 (1,25-(OH)2D3) resulted in the activation a neutral sphingomyelinase and sphingomyelin turnover (Okazaki, T., Bell, R., Hannun, Y. (1989) J. Biol. Chem. 264, 19076-19080). In this paper, effects 1,25-(OH)2D3 on product hydrolysis, ceramide, possible function ceramide as lipid mediator cell differentiation were investigated. Treatment time- dose-dependent increase mass levels. Ceramide levels peaked at 2 h...
A mixed micellar assay for protein kinase C was developed to investigate the specificity and stoichiometry of activation by phospholipids diacylglycerols. Triton X-100 micelles containing 8 mol % phosphatidylserine (PS) 2.5 sn-1,2-dioleoylglycerol (diC18:1) activated rat brain in presence Ca2+ same degree as sonicated PS/diC18:1 did standard assay. However, activity more responsive diC18:1 than At PS 100 microM Ca2+, stimulated maximally at 1 %. not activate until 3 then so cooperatively...
Results from a longitudinal experiment to curb drug use during junior high indicate that education programs based on social-influence model can prevent or reduce young adolescents' of cigarettes and marijuana. This multi-site involved the entire seventh-grade cohort 30 schools drawn eight urban, suburban, rural communities in California Oregon. Implemented between 1984 1986, curriculum's impact was assessed at 3-, 12-, 15-month follow-ups. The program, which had positive results for both...
Previous studies demonstrated that the cysteine-rich amino-terminal domain of Raf-1 kinase interacts selectively with phosphatidylserine (Ghosh, S., Xie, W. Q., Quest, A. F. G., Mabrouk, G. M., Strum, J. C., and Bell, R. M.(1994) Biol. Chem. 269, 10000-10007). Further analysis showed full-length bound to both phosphatidic acid (PA). Specifically, a carboxyl-terminal (RafC; residues 295-648 human Raf-1) interacted strongly acid. The binding RafC PA displayed positive cooperativity Hill...
Troponin elevation is common in hospitalized COVID-19 patients, but underlying aetiologies are ill-defined. We used multi-parametric cardiovascular magnetic resonance (CMR) to assess myocardial injury recovered patients.One hundred and forty-eight patients (64 ± 12 years, 70% male) with severe infection [all requiring hospital admission, 48 (32%) ventilatory support] troponin discharged from six hospitals underwent convalescent CMR (including adenosine stress perfusion if indicated) at...
Learning objectives▸ Define CIN and recognise this as a common serious complication in susceptible patients receiving intravascular contrast media.▸ Understand the possible pathological mechanisms underlying CIN.▸ Describe clinical periprocedural risk factors for perform assessment Appreciate established strategies used to prevent be aware of novel therapies.▸ Recognise onset manage appropriately.
BackgroundThe International Liaison Committee on Resuscitation has called for a randomised trial of delivery to cardiac arrest centre. We aimed assess whether expedited centre compared with current standard care following resuscitated reduces deaths.MethodsARREST is prospective, parallel, multicentre, open-label, superiority trial. Patients (aged ≥18 years) return spontaneous circulation out-of-hospital without ST elevation were randomly assigned (1:1) at the scene their by London Ambulance...
OBJECTIVES. Although several studies have reported short-term gains for drug-use prevention programs targeted at young adolescents, few assessed the long-term effects of such programs. Such information is essential judging how long benefits last. This paper reports results over a 6-year period multisite randomized trial that achieved reductions in drug use during junior high school years. METHODS. The 11-lesson curriculum, which was tested 30 schools eight highly diverse West Coast...
OBJECTIVES: To develop and test a standardized instrument, the purpose of which is to assess (1) whether skilled nursing facilities (SNFs) transfer residents emergency departments (ED) inappropriately, (2) are admitted hospitals (3) factors associated with inappropriate transfers. DESIGN: A structured implicit review (SIR) medical records. SETTING AND PARTICIPANTS: Using nested random sampling in eight community SNFs, we identified SNF hospital records 100 unscheduled transfers one 10...
The ability of exogenous sn-1 ,2-diacylglycerols and analogs to function as bioregulators protein kinase C in human platelets was investigated.The activation is indicated by specific phosphorylation a 40,000-dalton protein.Dihexanoylglycerol, dioctanoylglycerol (diCs), didecanoylglycerol, sn-1-oleoyl-2-acetylglycerol were active stimulating phosphorylation.Only trace elicited dibutyrylglycerol.Phosphorylation not induced diCs which an -H, -SH, or -C1 group replaced the free -OH, nor...
The effects of long-chain (sphingoid) bases on the phorbol ester-dependent differentiation HL-60 cells were investigated since these molecules are potent inhibitors protein kinase C (Hannun, Y. A., Loomis,
The neutrophil oxidative burst is characterized by increased ceIluIar 0 2 consumption due to the activation of a membrane-associated superoxide-generating NADPH-oxidase.The response triggered variety stimuli, including opsonized zymosan, formyl-methiony~leucinephenyl~anine (FMLP), arachidonate, short-chain diacylglycerols, and phorbol myristate acetate (PMA).We herein demonstrate that incubation cells with sphinganine or sphingosine blocks reverses these agonists.The inhibition reversible,...
A key event for Ras transformation involves the direct physical association between and Raf-1 kinase. This interaction promotes both Raf translocation to plasma membrane activation of kinase activity. Although substantial experimental evidence has demonstrated that residues 51-131 alone are sufficient binding, conflicting observations have suggested cysteine-rich domain (residues 139-184) may also be important with Ras. To clarify role in Ras-Raf we compared ability two distinct fragments...
Ischemic heart disease (IHD) is the leading cause of death worldwide. Novel cardioprotective strategies are therefore required to improve clinical outcomes in patients with IHD. Although a large number novel have been discovered research laboratory, their translation setting has largely disappointing. The reason for this failure can be attributed factors including inadequacy animal ischemia-reperfusion injury models used preclinical cardioprotection studies and inappropriate design execution...