A5030932011- Tuberculosis Research and Epidemiology
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Mycobacterium research and diagnosis
- Long-Term Effects of COVID-19
- COVID-19 Clinical Research Studies
- Medical Imaging and Pathology Studies
- Infectious Diseases and Tuberculosis
- Sarcoidosis and Beryllium Toxicity Research
- Occupational and environmental lung diseases
- Pneumonia and Respiratory Infections
- COVID-19 and Mental Health
- Intensive Care Unit Cognitive Disorders
- Microbial metabolism and enzyme function
- COVID-19 and healthcare impacts
- Respiratory and Cough-Related Research
- Pneumocystis jirovecii pneumonia detection and treatment
- Diagnosis and treatment of tuberculosis
- Pulmonary Hypertension Research and Treatments
- Respiratory viral infections research
- Immune responses and vaccinations
- Immunodeficiency and Autoimmune Disorders
- Parasites and Host Interactions
- Immune Cell Function and Interaction
- Asthma and respiratory diseases
- Immune Response and Inflammation
University Hospital Southampton NHS Foundation Trust
2016-2025
NIHR Southampton Biomedical Research Centre
2017-2024
University of Southampton
2014-2024
University of Oxford
2023-2024
Restore America's Estuaries
2023
University Hospitals of Leicester NHS Trust
2023
National Institute for Health Research
2016-2023
NIHR Leicester Biomedical Research Centre
2022-2023
University of Leicester
2022-2023
Oxford University Hospitals NHS Trust
2023
Sarcoidosis is a highly variable, systemic granulomatous disease of hitherto unknown aetiology. The GenPhenReSa (Genotype-Phenotype Relationship in Sarcoidosis) project represents European multicentre study to investigate the influence genotype on phenotypes sarcoidosis.The baseline phenotype module comprised 2163 Caucasian patients with sarcoidosis who were phenotyped at 31 centres according standardised protocol.From this module, we found that acute onset mainly female, young and Scadding...
ObjectivesWe report the largest clinical experience using tigecycline-containing regimens for salvage treatment of patients with Mycobacterium abscessus and chelonae.
Abstract Idiopathic pulmonary fibrosis (IPF), the prototypic progressive fibrotic interstitial lung disease, is thought to be a consequence of repetitive micro-injuries an ageing, susceptible alveolar epithelium. Ageing risk factor for IPF and incidence has been demonstrated increase with age. Decreased (macro)autophagy age reported extensively in variety systems diseases, including IPF. However, it undetermined whether role faulty autophagy causal or coincidental context Here, we report...
Matrix stiffening with downstream activation of mechanosensitive pathways is strongly implicated in progressive fibrosis; however, pathologic changes extracellular matrix (ECM) that initiate mechano-homeostasis dysregulation are not defined human disease. By integrated multiscale biomechanical and biological analyses idiopathic pulmonary fibrosis lung tissue, we identify increased tissue stiffness a function dysregulated post-translational collagen cross-linking rather than any concentration...
The contribution of epithelial–mesenchymal transition (EMT) to human lung fibrogenesis is controversial. Here we provide evidence that ZEB1-mediated EMT in alveolar epithelial type II (ATII) cells contributes the development fibrosis by paracrine signalling underlying fibroblasts. Activation EGFR–RAS–ERK ATII induced via ZEB1. had extremely low extracellular matrix gene expression even after induction EMT, however conditioned media from undergoing RAS-induced augmented TGFβ-induced...
Extracellular matrix (ECM) stiffening with downstream activation of mechanosensitive pathways is strongly implicated in fibrosis. We previously reported that altered collagen nanoarchitecture a key determinant pathogenetic ECM structure-function human fibrosis (Jones et al., 2018). Here, through tissue, bioinformatic and ex vivo studies we provide evidence hypoxia-inducible factor (HIF) pathway critical for this process regardless the oxygen status (pseudohypoxia). Whilst TGFβ increased rate...
Sarcoid-like reaction is an immunological that can affect lymph nodes and organs but does not meet the diagnostic criteria for systemic sarcoidosis. Anti-CD20 auto-antibodies have been reported to be responsible such reactions. There are several associations between Chronic lymphocytic leukaemia (CLL), Amyotrophic lateral sclerosis (ALS) reactions (SLR). We report a case of ALS developing in patient with treated CLL drug related SLR one day after exposure Venetoclax Rituximab. A 60-year-old...
In idiopathic pulmonary fibrosis (IPF), the fibroblast focus is a key histological feature representing active fibroproliferation. On standard 2D pathologic examination, foci are considered small, distinct lesions, although they have been proposed to form highly interconnected reticulum as leading edge of "wave" fibrosis. Here, we characterized morphology and interrelationships in 3D using an integrated micro-CT methodology. 3D, were morphologically complex structures, with large variations...
Cell biology differs between traditional cell culture and 3-dimensional (3-D) systems, is modulated by the extracellular matrix. Experimentation in 3-D presents challenges, especially with virulent pathogens. Mycobacterium tuberculosis (Mtb) kills more humans than any other infection characterised a spatially organised immune response matrix remodelling. We developed system incorporating mycobacteria, primary human blood mononuclear cells collagen-alginate to dissect host-pathogen...
Results from 3,263 QuantiFERON-TB Gold in-tube (QFT-GIT) assays were analyzed to determine the impact of age on test performance. The proportion indeterminate results was significantly higher in pediatric and elderly (9.1% 7.4%, respectively) than adult (2.6%; chi-square test, P < 0.0001) patients. A detailed analysis QFT-GIT assay is presented.
// Franco Conforti 1,2,* , Elizabeth R. Davies Claire J. Calderwood 1 Thomas H. Thatcher 3 Mark G. Jones 1,2 David E. Smart Sumeet Mahajan 4 Aiman Alzetani 5 Tom Havelock 2,5 Toby M. Maher 6,7 Philip L. Molyneaux Andrew Thorley 7 Teresa D. Tetley Jane A. Warner 1,2,4 Graham Packham 8 A. Ganesan 9 Paul Skipp Benjamin Marshall Luca Richeldi 1,2,5 Patricia Sime Katherine M.A. O'Reilly 2,10,11 and Donna The Brooke Laboratory, Clinical Experimental Sciences, University of Southampton Faculty...
Objectively structured clinical examinations (OSCEs) are a stressful experience for many health care students and professionals in training. Mock OSCEs have been shown to be beneficial student OSCE preparation. However, due their expense administrative burden may only get few opportunities partake these. To address this gap preparation series of regularly run totally peer led multi-role practice (PrOSCEs) was developed. Fifteen PrOSCEs were over five-months. A total 32 second year medical...
Significance Tuberculosis is a major global pandemic responsible for more deaths than any other infectious disease, yet no effective vaccine exists. Here, we demonstrate CD1b expression within human tuberculous granulomas, supporting role lipid antigen presentation in host immunity to infection. presents mycolates, the dominant Mycobacterium tuberculosis (Mtb) cell wall class and key virulence factors, αβ T cells. We reveal that mycolate tail moieties, distal head group, are antigenic...
BACKGROUND. Tuberculosis (TB) kills more people than any other infection, and new diagnostic tests to identify active cases are required. We aimed discover verify novel markers for TB in nondepleted plasma.
Tuberculosis (TB) is a persistent global pandemic, and standard treatment for it has not changed 30 years. Mycobacterium tuberculosis (Mtb) undergone prolonged coevolution with humans, patients can control Mtb even after extensive infection, demonstrating the fine balance between protective pathological host responses within infected granulomas. We hypothesized that whole transcriptome analysis of human TB granulomas isolated by laser capture microdissection could identify therapeutic...
Idiopathic pulmonary fibrosis (IPF) is the prototypic progressive fibrotic lung disease with a median survival of 2 to 4 years. Injury and/or dysfunction alveolar epithelium strongly implicated in IPF initiation, but factors that determine whether progresses rather than normal tissue repair occurs remain poorly understood. We previously demonstrated zinc finger E-box-binding homeobox 1-mediated epithelial-mesenchymal transition human epithelial type II (ATII) cells augments transforming...
Significance T cells autoreactive to cluster of differentiation 1c (CD1c) are abundant in human blood but lipid antigens recognized by these remained poorly understood. A new 2.4-Å structure CD1c and computational simulations thereof indicated substantial conformational plasticity with ligand-induced formation an F′ roof G′ portal, as well the potential present acylated sterols. Confirming predictions we demonstrated loading biophysical interaction CD1c–lipid complexes self-reactive T-cell...
Abstract Idiopathic pulmonary fibrosis (IPF) is a chronic scarring disease in which aging, environmental exposure(s) and genetic susceptibility have been implicated pathogenesis, however, the causes mechanisms of progressive fibrotic cascade are still poorly understood. As epithelial–mesenchymal interactions essential for normal wound healing, through human 2D 3D vitro studies, we tested hypothesis that IPF fibroblasts (IPFFs) dysregulate alveolar epithelial homeostasis. Conditioned media...
A 53-year-old man presented acutely to the Accident and Emergency department with a 2-day history of progressive odynophagia shortness breath. The patient had stridor at rest acute epiglottitis was suspected. transferred urgently theatre for intubation but due severely oedematous airway, this unsuccessful emergency tracheotomy performed by ENT team. Throughout admission only positive microbiological sample nasopharyngeal swab SARS-CoV-2 infection. In absence other microbiology, it is highly...
Abstract Background The long-term consequences of COVID-19 remain unclear. There is concern a proportion patients will progress to develop pulmonary fibrosis. We aimed assess the temporal change in CXR infiltrates cohort following hospitalisation for COVID-19. Methods conducted single-centre prospective study admitted University Hospital Southampton with confirmed SARS-CoV2 infection between 20th March and 3rd June 2020. Patients were approached standard-of-care follow-up 12-weeks after...
Interactions between mononuclear cells, vascular endothelium, fibroblasts, and cytokines during the inflammatory reaction within a granuloma have potential to contribute progression fibrosis.Biopsy specimens of six tuberculous eight sarcoidosis skin lesions were examined by immunohistochemistry seek evidence for presence fibrotic reactions in human granulomatous disease. Additionally, understand how T cell mediated delayed type hypersensitivity reaction--a component chronic...