A5101628618- Cancer-related molecular mechanisms research
- Hormonal Regulation and Hypertension
- Molecular Biology Techniques and Applications
- Cancer Genomics and Diagnostics
- Monoclonal and Polyclonal Antibodies Research
- Ion Transport and Channel Regulation
- Plant Pathogenic Bacteria Studies
- Sexual Differentiation and Disorders
- RNA modifications and cancer
- Cystic Fibrosis Research Advances
- Plant-Microbe Interactions and Immunity
- Birth, Development, and Health
- Neurofibromatosis and Schwannoma Cases
- Prostate Cancer Treatment and Research
- Systemic Sclerosis and Related Diseases
- HER2/EGFR in Cancer Research
- Cancer-related Molecular Pathways
- Antibiotic Resistance in Bacteria
- Genetic Syndromes and Imprinting
- Neuroblastoma Research and Treatments
- Adrenal Hormones and Disorders
- Olfactory and Sensory Function Studies
- Hair Growth and Disorders
- Respiratory and Cough-Related Research
- RNA Research and Splicing
Saint Louis University
2025
Medical University of South Carolina
2013-2024
University of Inland Norway
2023
University College London
2022
University College London Hospitals NHS Foundation Trust
2022
William Harvey Research Institute
2018
Queen Mary University of London
2018
University of London
2018
Imperial College London
1998-2017
GlaxoSmithKline (United Kingdom)
2010-2017
The phenazine pigments pyocyanin and 1-hydroxyphenazine were resolved by high-pressure liquid chromatography from the sputum sol phase 9 of 13 patients with cystic fibrosis or bronchiectasis colonized Pseudomonas aeruginosa. concentrations measured each sufficient to inhibit ciliary beating in vitro contributed a significant proportion toxicity for respiratory epithelium.
Over the last two decades, we have extensively studied genetics of congenital adrenal hyperplasia caused by 21-hydroxylase deficiency (CAH) and performed 8,290 DNA analyses CYP21A2 gene on members 4,857 families at risk for CAH—the largest cohort CAH patients reported to date. Of studied, 1,507 had least one member affected with three known forms CAH, namely salt wasting, simple virilizing, or nonclassical CAH. Here, report genotype phenotype each patient, as well ethnic group country origin...
In the PATHWAY-2 study of resistant hypertension, spironolactone reduced blood pressure substantially more than conventional antihypertensive drugs. We did three substudies to assess mechanisms underlying this superiority and pathogenesis hypertension.PATHWAY-2 was a randomised, double-blind crossover trial done at 14 UK primary secondary care sites in 314 patients with hypertension. Patients were given 12 weeks once daily treatment each placebo, 25-50 mg, bisoprolol 5-10 doxazosin 4-8 mg...
Pseudomonas aeruginosa culture filtrates varied in their ability to slow human ciliary beat frequency (7-71%). This activity did not correlate with known virulence factors. However, a close correlation (r = 0.97) existed between slowing and pigment content. In prolonged culture, the increase correlated 0.94) accumulation. Gel filtration of lyophilized filtrate yielded single peak corresponding fraction. Pyocyanin extracted from an active strain, 1-hydroxyphenazine were purified by high...
Apparent mineralocorticoid excess (AME) is a genetic disorder causing pre- and postnatal growth failure, juvenile hypertension, hypokalemic metabolic alkalosis, hyporeninemic hypoaldosteronism due to deficiency of 11β-hydroxysteroid dehydrogenase type 2 enzyme activity (11βHSD2). The 11βHSD2 responsible for the conversion cortisol inactive metabolite cortisone therefore protects receptors from intoxication. Several homozygous mutations are associated with this potentially fatal disease. We...
African-Americans (AA) have increased prostate cancer risk and a greater mortality rate than European-Americans (EA). AA exhibit high prevalence of vitamin D deficiency. We examined the global transcriptome in EA, effect D3 supplementation.Twenty-seven male subjects (ten 17 EA), slated to undergo prostatectomy were enrolled study. Fourteen received (4000 IU daily) 13 placebo for 2 months prior surgery.AA show higher expression genes associated with immune response inflammation.Systems level...
1 Pyocyanin and related members of the phenazine family are produced by Pseudomonas aeruginosa have been associated with events pathophysiological importance. 2 its base hydrolysis product 1-hydroxyphenazine were purified to homogeneity reverse-phase high-pressure liquid chromatography. Their mass spectrometric behaviour was examined a view evaluating use high-resolution chromatography/mass spectrometry in studying phenazine-mediated effects man. 3 The molecular naturally derived pyocyanin...
Products of the bacterium Pseudomonas aeruginosa have been shown to slow beating human respiratory tract cilia in vitro. We tested effects two these compounds, pyocyanin and 1-hydroxyphenazine (given as a bolus dose dissolved 2 microliters Ringer solution), on tracheal mucus velocity radiolabeled erythrocytes anesthetized guinea pigs. 1-Hydroxyphenazine (200 ng) caused rapid slowing (maximum fall 47% at 20 min) with recovery by 1 h. The effect was slower onset, 600 ng causing 60% reduction 3...
Significance Apparent mineralocorticoid excess, a rare autosomal recessive disorder characterized by low renin hypertension, may display severe or mild phenotype in patients. The variability clinical presentation stems from different extents of impairment the 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) enzyme arising distinct mutations encoding gene. computational model HSD11B2 protein that we constructed here will be useful predicting disease severity for newly reported missense this
Abstract Resistance of breast cancer to human epidermal growth factor receptor 2 (HER2) inhibitors involves reprogramming the kinome through HER2/HER3 signaling via activation multiple tyrosine kinases and transcriptional upregulation. The heterogeneity induced prevents kinase targeting by a single inhibitor presents major challenge treatment therapeutically recalcitrant HER2-positive cancers (HER2+ BCs). As result, there is critical need for effective that attacks aberrant associated with...
Mucociliary clearance protects the respiratory epithelium against inhaled particles. There is in vitro evidence that some bacteria produce factors cause ciliary slowing, dyskinesia, and stasis. These changes may predominantly affect function alone or be associated with epithelial disruption cell death. Some act immediately, while others can take up to a number of days achieve effect. It postulated rapidly acting involved during bacterial colonization, allowing bacterium time (by slowing...
ETS factors have been shown to be dysregulated in breast cancer. control the expression of genes involved many biological processes, such as cellular proliferation, differentiation, and apoptosis. FLI1 is an protein aberrantly expressed retrovirus-induced hematological tumors, but limited attention has directed towards elucidating role epithelial-derived cancers. Using data mining, we show that loss associated with shorter survival more aggressive phenotypes Gain function studies indicate...
The chromosome 8p11-p12 amplicon is present in 12% to 15% of breast cancers, resulting an increase copy number and expression several chromatin modifiers these tumors, including KAT6A. Previous analyses SUM-52 cancer cells showed amplification overexpression KAT6A, subsequent RNAi screening identified KAT6A as a potential driving oncogene. histone acetyltransferase previously fusion partner with CREB binding protein acute myeloid leukemia. Knockdown cells, luminal cell line harboring the...
72 Background: Current treatment of metastatic hormone sensitive prostate cancer (mHSPC) includes androgen deprivation therapy (ADT) monotherapy or combination (ADT + docetaxel an receptor pathway inhibitor). However, no comparative studies have been conducted to assess the hospitalization rates and causes admission between two groups. We assessed different therapies determine adverse events improve selection in mHSPC. Methods: A nationwide retrospective study 6,651 US Veterans with de novo...
Reinforcement learning models are widely used in psychology and neuroscience to study cognitive processes underlying decision-making. However, accurately reliably estimating model parameters is often challenging due factors ubiquitous modeling, such as limited data, measurement noise, complexity, hindering the interpretation of these behavioral neural data. Here we evaluate whether deep method -- combining networks with modern optimization techniques can improve parameter estimation compared...
The presence of Pseudomonas aeruginosa in the sputum 191 patients with cystic fibrosis was significantly related (p less than 0.0001) to absence Staphylococcus aureus. Cross-streaking tests showed that 40 50 clinical strains P. produced substances inhibited growth S. When incorporated into agar plates, this antibacterial substance(s) 177 189 nine staphylococcal species, all 16 methicillin-resistant aureus and 27 39 six other gram-positive genera. did not inhibit 23 seven gram-negative genera...
The factors predisposing toward the development of pulmonary nontuberculous mycobacterial (pNTM) disease and influencing progression remain unclear. Impaired immune responses have been reported in individuals with pNTM disease, but data are limited inconsistent. In this study, we sought to use gene expression profiling examine host response disease. Microarray analysis whole-blood was performed on 25 subjects 27 uninfected control respiratory Gene results were compared phenotypic variables...
During clinical trials of a tumour necrosis factor (TNF)-R1 domain antibody (dAb™) antagonist (GSK1995057), infusion reactions consistent with cytokine release were observed in healthy subjects high levels novel, pre-existing human anti-VH (HAVH) autoantibody. In the presence HAVH autoantibodies, GSK1995057 induced vitro due to binding autoantibodies framework region dAb. The epitope on was characterized and dAbs reduced generated; pharmacological comparability determined in-vitro systems...