A5090516984- Toxic Organic Pollutants Impact
- Synthesis and Catalytic Reactions
- Chemical Reaction Mechanisms
- Carcinogens and Genotoxicity Assessment
- Effects and risks of endocrine disrupting chemicals
- Neuroendocrine regulation and behavior
- Asymmetric Synthesis and Catalysis
- Analytical Chemistry and Chromatography
- Pesticide Exposure and Toxicity
- Tryptophan and brain disorders
- Bipolar Disorder and Treatment
- Cannabis and Cannabinoid Research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Organophosphorus compounds synthesis
- Protease and Inhibitor Mechanisms
- Catalytic C–H Functionalization Methods
- NF-κB Signaling Pathways
- Cyclopropane Reaction Mechanisms
- Peptidase Inhibition and Analysis
- Skin and Cellular Biology Research
- Neuroscience of respiration and sleep
- Asymmetric Hydrogenation and Catalysis
- Stress Responses and Cortisol
- Adolescent and Pediatric Healthcare
- Histone Deacetylase Inhibitors Research
Age UK
2021-2024
GlaxoSmithKline (United Kingdom)
2013-2023
GlaxoSmithKline (Brazil)
2020
GlaxoSmithKline (India)
2019
UK Research and Innovation
2019
University of East Anglia
2009-2015
John Innes Centre
2009
Norwich Research Park
2009
Loughborough University
2007-2008
Cardiff University
2003
From March 1974 through July 1975, 76 (56%) of 133 persons who had worked at a pesticide plant that produced Kepone, chlorinated hydrocarbon insecticide, contracted previously unrecognized clinical illness characterized by nervousness, tremor, weight loss, opsoclonus, pleuritic and joint pain, oligospermia. Illness incidence rates for production workers (64%) were significantly higher than nonproduction personnel (16%). The mean blood Kepone level with was 2.53 ppm those without disease 0.60...
Blood lead levels were determined on a random sample of persons in all age groups living near lead-emitting smelter El Paso, Texas. A blood level greater than or equal to 40 mug per 100 ml, which was considered indicative undue absorption, found 53 cent the children one nine years old within 1.6 km and 18 those from 6.6 km; beyond that distance older lower. Children first with ml exposed 3.1 times as much dust there lower values (6447 vs 2067 ppm). There also airborne exposure (8 10 cubic...
Journal Article METABOLIC CONSEQUENCES OF EXPOSURE TO POLYCHLORINATED BIPHENYLS (PCB) IN SEWAGE SLUDGE Get access EDWARD L. BAKER, JR., JR. 1Bureau of Epidemiology, Center for Disease ControlAtlanta, GA Search other works by this author on: Oxford Academic PubMed Google Scholar PHILIP J. LANDRIGAN, LANDRIGAN 2 Reprint requests to Dr. Landrigan. CHARLES GLUECK, GLUECK 3Lipid Research Center, University Cincinnati Medical CenterCincinnati, OH MATTHEW M. ZACK, JOHN A. LIDDLE, LIDDLE 4Bureau...
Tetrachlorodibenzodioxin was identified as the apparent cause of an outbreak poisoning in humans, horses, and other animals. Exposure related to spraying contaminated waste oil on riding arenas for dust control. The contamination resulted from improper disposal a toxic industrial waste. pathologic effects chemical identification tetrachlorodibenzodioxin are described.
Abstract We describe epidemiological and laboratory investigation of a poisoning outbreak that involved three riding arenas killed fiftyseven horses, five colts, numerous other animals. The was traced to the spraying with salvage oil contaminated tetrachlorodibenzodioxin, trichlorophenol, polychlorinated biphenyls. contamination resulted from improper disposal toxic industrial waste. In tissues horses available for study, most prominent lesion centrilobular fibrosis liver arose in wall...
A six-stage stereoselective synthesis of indanyl-7-(3'-pyridyl)-(3R,6R,7R)-2,5-diketopiperazines oxytocin antagonists from indene is described. SAR studies involving mono- and disubstitution in the 3'-pyridyl ring variation 3-isobutyl group gave potent compounds (pK(i) > 9.0) with good aqueous solubility. Evaluation pharmacokinetic profile rat, dog, cynomolgus monkey those derivatives low human intrinsic clearance 2',6'-dimethyl-3'-pyridyl R-sec-butyl morpholine amide Epelsiban (69), a...
Article29 January 2021Open Access Transparent process Development of a small molecule that corrects misfolding and increases secretion Z α1-antitrypsin David A Lomas Corresponding Author [email protected] orcid.org/0000-0003-2339-6979 UCL Respiratory, Rayne Institute, University College London, UK Search for more papers by this author James Irving orcid.org/0000-0003-3204-6356 Christopher Arico-Muendel GlaxoSmithKline, Cambridge, MA, USA Svetlana Belyanskaya Andrew Brewster Stevenage, Murray...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHigh-resolution gas chromatographic high-resolution mass spectrometric analysis of human adipose tissue for 2,3,7,8-tetrachlorodibenzo-p-dioxinDonald G. Patterson, James S. Holler, Chester R. Lapeza, Louis Alexander, Donald F. Groce, Ralph C. O'Connor, Jay. Smith, John A. Liddle, and Larry L. NeedhamCite this: Anal. Chem. 1986, 58, 4, 705–713Publication Date (Print):April 1, 1986Publication History Published online1 May 2002Published inissue 1...
Three branched-chain hydroxy acids not previously reported in other bacteria were found extracts from saponified whole cells of Pseudomonas maltophilia. On the basis evidence mass spectrometry, infrared spectroscopy, and gas chromatographic procedures, they identified as 2-hydroxy-9-methyldecanoic acid, 3-hydroxy-9-methyldecanoic 3-hydroxy-11-methyldodecanoic acid. These appeared to be tightly bound cellular components since extracted lyophilized with a chloroform-methanol (3:1) mixture.
Optimization of KDM6B (JMJD3) HTS hit 12 led to the identification 3-((furan-2-ylmethyl)amino)pyridine-4-carboxylic acid 34 and 3-(((3-methylthiophen-2-yl)methyl)amino)pyridine-4-carboxylic 39 that are inhibitors KDM4 (JMJD2) family histone lysine demethylases. Compounds possess activity, IC50 ≤ 100 nM, in biochemical (RFMS) assays with ≥ 50-fold selectivity against activity a mechanistic KDM4C cell imaging assay (IC50 = 6-8 μM). also potent KDM5C (JARID1C) (RFMS 100-125 nM).
Endoplasmic reticulum aminopeptidase 1 (ERAP1) is an intracellular enzyme that optimizes the peptide cargo of major histocompatibility class I (MHC-I) molecules and regulates adaptive immunity. It has unusual substrate selectivity for length sequence, resulting in poorly understood effects on cellular immunopeptidome. To understand selection by ERAP1, we solved 2 crystal structures with bound transition-state pseudopeptide analogs at 1.68 Å 1.72 Å. Both peptides have their N terminus active...
Kynurenine monooxygenase (KMO) blockade protects against multiple organ failure caused by acute pancreatitis (AP), but the link between KMO and systemic inflammation has eluded discovery until now. Here, we show that product 3-hydroxykynurenine primes innate immune signaling to exacerbate during experimental AP. We find a tissue-specific role for KMO, where mice lacking Kmo solely in hepatocytes have elevated plasma levels prime inflammatory gene transcription. 3-Hydroxykynurenine synergizes...
In a preliminary study, 12 male and female weanling Sherman strain rats were given single dose of 1000 mg polybrominated biphenyls (PBBs) FireMaster FF1 Lot 7042 kg/body weight as 5% solution in corn oil. Three three One day after dosing PBB blood levels ranged from 78 to 162 ppm 42 days later they 1.1 2.99 ppm. The liver was the only organ with pathological changes. long-term recovery study groups 20 rats, 2 months old, 0 or PBBs/kg body peanut Five per group killed 2, 6, 10, 14 had...
Abstract Kynurenine-3-monooxygenase (KMO) is a key FAD-dependent enzyme of tryptophan metabolism. In animal models, KMO inhibition has shown benefit in neurodegenerative diseases such as Huntington’s and Alzheimer’s. Most recently it been identified target for acute pancreatitis multiple organ dysfunction syndrome (AP-MODS); devastating inflammatory condition with mortality rate excess 20%. Here we report dissect the molecular mechanism action three classes inhibitors differentiated binding...
ER aminopeptidase 1 (ERAP1) is an intracellular enzyme that generates antigenic peptides and emerging target for cancer immunotherapy the control of autoimmunity. ERAP1 inhibitors described previously active site are limited in selectivity, minimizing their clinical potential. To address this, we targeted regulatory using a high-throughput screen discovered small molecule hit highly selective ERAP1....
Journal Article Interlaboratory Comparison for Results of Analyses Polybrominated Biphenyls in Human Serum Get access Virlyn W. Burse, Burse Toxicology Branch, Clinical Chemistry Division, Bureau Laboratories, Center Disease Control, Public Health Service, U.S. Department Health, Education, and Welfare, Atlanta, GA 30333 Search other works by this author on: Oxford Academic PubMed Google Scholar Larry L. Needham, Needham John A. Liddle, Liddle David D. Bayse, Bayse Harold Price Michigan...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSimultaneous esterification of carboxyl and hydroxyl groups with alcohols heptafluorobutyric anhydride for analysis by gas chromatographyJohn B. Brooks, Cynthia C. Alley, John A. LiddleCite this: Anal. Chem. 1974, 46, 13, 1930–1934Publication Date (Print):November 1, 1974Publication History Published online1 May 2002Published inissue 1 November 1974https://pubs.acs.org/doi/10.1021/ac60349a040https://doi.org/10.1021/ac60349a040research-articleACS...
Kynurenine 3-monooxygenase (KMO) is a therapeutically important target on the eukaryotic tryptophan catabolic pathway, where it converts L-kynurenine (Kyn) to 3-hydroxykynurenine (3-HK). We have cloned and expressed human form of this membrane protein as full-length GST-fusion in recombinant baculovirus expression system. An enriched preparation was used for directed screen approximately 78,000 compounds using RapidFire mass spectrometry (RF-MS) assay. The platform provides an automated...