A5101916175- Cervical Cancer and HPV Research
- Prion Diseases and Protein Misfolding
- Virus-based gene therapy research
- Genital Health and Disease
- Reproductive tract infections research
- Receptor Mechanisms and Signaling
- Estrogen and related hormone effects
- Viral gastroenteritis research and epidemiology
- Molecular Biology Techniques and Applications
- Viral Infections and Immunology Research
- Microfluidic and Capillary Electrophoresis Applications
- Biosensors and Analytical Detection
- Flood Risk Assessment and Management
- Pharmacological Effects and Assays
- Neuropeptides and Animal Physiology
- Hepatitis B Virus Studies
- Genetics, Aging, and Longevity in Model Organisms
- Cancer, Hypoxia, and Metabolism
- Cancer Research and Treatments
- Environmental Toxicology and Ecotoxicology
- Microfluidic and Bio-sensing Technologies
- Underground infrastructure and sustainability
- Herpesvirus Infections and Treatments
- Cytomegalovirus and herpesvirus research
- Biochemical and Molecular Research
The Francis Crick Institute
2023
University of Tasmania
2023
AstraZeneca (United Kingdom)
2010-2019
Highways England
2016-2019
King University
2016-2018
NHS Grampian
2018
Loughborough University
1999-2014
Manchester Royal Infirmary
2000-2013
University of Manchester
1972-2011
Royal Manchester Children's Hospital
2006-2009
The platelet P2T receptor plays a major role in aggregation, and its antagonists are predicted to have significant therapeutic potential as antithrombotic agents. We explored analogues of adenosine triphosphate (ATP), which is weak, nonselective but competitive antagonist. Modification the polyphosphate side chain prevent breakdown agonist diphosphate (ADP) substitution adenine moiety enhance affinity selectivity for led identification 10e (AR-C67085MX), having an IC50 2.5 nM against...
To evaluate the effectiveness of human papillomavirus (HPV) testing in primary cervical screening. This was a cross-sectional study from recruitment phase prospective randomised trial. Women were screened for HPV addition to routine cytology testing. Greater Manchester, attendees at NHS Cervical Screening Programme. In all, 24 510 women aged 20-64 with liquid-based (LBC) and entry. Type-specific prevalence rates are presented relation age as well cytological histological findings had...
The prevalence of cervical human papillomavirus increases with increasing numbers sexual partners, leaving the impression that this infection is acquired only as a result high risk behaviour. Using longitudinal data from 242 women who had one partner, we found acquiring was 46% (95% CI 28–64) at three years after first intercourse and median time to detection months.
Human papillomavirus (HPV) infection causes cervical cancer and premalignant dysplasia. Type-specific HPV prevalence data provide a basis for assessing the impact of vaccination programmes on cytology. We report high-risk (HR-HPV) type-specific in relation to cytology 24 510 women (age range: 20–64; mean age 40.2 years) recruited into ARTISTIC trial, which is being conducted within routine NHS Cervical Screening Programme Greater Manchester. The most common HR-HPV types were HPV16, 18, 31,...
Rapid detection of viral contamination remains a pressing issue in various fields related to human health including clinical diagnostics, the monitoring food-borne pathogens, biological warfare agents as well clearance studies for biopharmaceutical products. The majority currently available assays virus are expensive, time-consuming, and labor-intensive. In present work we report creation novel micro total analysis system (µTAS) capable continuously with high sensitivity selectivity....
Knowledge of the prevalence type-specific human papillomavirus (HPV) infections is necessary to predict expected, and monitor actual, impact HPV immunisation design effective screening strategies for vaccinated populations.Residual specimens cervical cytology (N=4719), CIN3/CGIN cancer biopsies (N=1515) were obtained from sites throughout England, anonymised tested DNA using Linear Array typing system (Roche).The 16 and/or 18 (with or without another high-risk (HR) type) was 76% in squamous...
Abstract Background and Objectives: To identify if any process steps used in plasma fractionation may have a capability of removing agents human transmissible spongiform encephalopathy (TSE). Materials Methods: Sixteen were investigated separately by adding preparation hamster adapted scrapie 263K to the starting material at each step determining distribution into resultant fractions protease‐K‐resistant (abnormal) prion protein Western blot analysis. Results: A number operations found...
To identify if any process steps used in plasma fractionation may have a capability of removing agents human transmissible spongiform encephalopathy (TSE).Sixteen were investigated separately by adding preparation hamster adapted scrapie 263K to the starting material at each step and determining distribution into resultant fractions protease-K-resistant (abnormal) prion protein Western blot analysis.A number operations found remove abnormal limit detection assay. These cold ethanol...
A novel estrogen receptor down-regulator, 7-hydroxycoumarin (5, SS5020), has been reported with antitumor effects against chemically induced mammary tumors. Here, we report on our own investigation of 7-hydroxycoumarins as potential selective down-regulators, which led us to the discovery potent down-regulating antagonists, such 33. Subsequent optimization and removal 7-hydroxy group coumarin 59, had increased potency improved rat bioavailability relative SS5020.
We present data on the use of Hybrid Capture 2 (HC2) test for detection high-risk human papillomavirus (HR HPV) with different thresholds positivity within a primary screening setting and as method triage low-grade cytology. In ARTISTIC population-based trial, 18,386 women were screened by cytology HPV. Cervical intraepithelial neoplasia lesions grade two higher (CIN2+ lesions) identified 453 30 months an abnormal baseline sample. When relative light unit/cutoff (RLU/Co) ratio > or = 1 was...
A series of tetrahydroisoquinoline phenols was modified to give an estrogen receptor downregulator-antagonist profile. Optimization around the core, alkyl side chain, and pendant aryl ring resulted in compounds with subnanomolar levels potency. The phenol functionality shown be required achieve highly potent compounds, but unusually this compatible obtaining high oral bioavailabilities rat.
Herein, we report the identification and synthesis of a series tricyclic indazoles as novel class selective estrogen receptor degrader antagonists. Replacement phenol, present in our previously reported tetrahydroisoquinoline scaffold, with an indazole group led to removal reactive metabolite signal vitro glutathione trapping assay. Further optimization, guided by X-ray crystal structures NMR conformational work, varied alkyl side chain pendant aryl resulted compounds low turnover human...
A new chromatographic step for the selective binding of abnormal prion protein (PrP(Sc)) was developed, and optimization PrP(Sc) capture achieved by to an affinity ligand attached synthetic resin particles. This implemented into manufacturing process solvent/detergent (S/D)-treated biopharmaceutical quality plasma Octaplas further improve safety margin in terms risk variant Creutzfeldt-Jakob disease (vCJD) transmission.Intermediates final container material, spiked with hamster brain-derived...
GPR120 agonists have therapeutic potential for the treatment of diabetes, but few selective been reported. We identified an indazole-6-phenylcyclopropylcarboxylic acid series and conducted SAR studies to optimize potency. Furthermore, we a (S,S)-cyclopropylcarboxylic structural motif which gave selectivity against GPR40. Good oral exposure was obtained with some compounds displaying unexpected high CNS penetration. Increased MDCK efflux utilized identify such as 33 lower penetration,...
A series of dibasic des-hydroxy β2 receptor agonists has been prepared and evaluated for potential as inhaled ultralong acting bronchodilators. Determination activities at the human β-adrenoreceptors demonstrated a highly potent selective that were progressed to further study in guinea pig histamine-induced bronchoconstriction model. Following assessment by onset studies tracheal rings bronchial contracted with methacholine (guinea pigs) or carbachol (humans), duration action pigs after...