A5088297667- Immune Response and Inflammation
- Sepsis Diagnosis and Treatment
- Nosocomial Infections in ICU
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Lymphoma Diagnosis and Treatment
- Neonatal Respiratory Health Research
- Immune cells in cancer
- Pneumonia and Respiratory Infections
- Respiratory viral infections research
- Respiratory Support and Mechanisms
- Chronic Lymphocytic Leukemia Research
- Renal function and acid-base balance
- Blood groups and transfusion
- Genetics, Bioinformatics, and Biomedical Research
- Spaceflight effects on biology
- Erythrocyte Function and Pathophysiology
- Immune responses and vaccinations
- Viral-associated cancers and disorders
- Microbial Community Ecology and Physiology
- Intensive Care Unit Cognitive Disorders
- Social Media and Politics
- Cystic Fibrosis Research Advances
- Neutropenia and Cancer Infections
- Pediatric health and respiratory diseases
- Myeloproliferative Neoplasms: Diagnosis and Treatment
NIHR Queen Square Dementia Biomedical Research Unit
2024
University College London
2024
Newcastle University
2013-2023
University of California, Santa Cruz
2023
University of California, Riverside
2023
Health Education North West
2022
Health Education England
2022
European Astronaut Centre
2017-2019
University of Southampton
2014-2016
Wyle (United States)
2016
Group 2 innate lymphoid cells (ILC-2s) regulate immune responses to pathogens and maintain tissue homeostasis in response cytokines. Positive regulation of ILC-2s through ICOS has been recently elucidated. We demonstrate here that PD-1 is an important negative regulator KLRG1+ ILC-2 function both mice humans. Increase cell numbers was attributed intrinsic defect signaling, which resulted enhanced STAT5 activation. During Nippostrongylus brasiliensis infection, a significant expansion subsets...
Abstract The nasal epithelium is a plausible entry point for SARS-CoV-2, site of pathogenesis and transmission, may initiate the host response to SARS-CoV-2. Antiviral interferon (IFN) responses are critical outcome Yet little known about interaction between SARS-CoV-2 innate immunity in this tissue. Here we apply single-cell RNA sequencing proteomics primary cell model human differentiated at air-liquid interface. demonstrates widespread tropism epithelial types. dominated by type I III...
BackgroundVentilator-associated pneumonia is the most common intensive care unit (ICU)-acquired infection, yet accurate diagnosis remains difficult, leading to overuse of antibiotics. Low concentrations IL-1β and IL-8 in bronchoalveolar lavage fluid have been validated as effective markers for exclusion ventilator-associated pneumonia. The VAPrapid2 trial aimed determine whether measurement could effectively safely improve antibiotic stewardship patients with clinically suspected...
Neutrophils are the most abundant inflammatory cells at earliest stages of wound healing and play important roles in repair fibrosis. Formyl peptide receptor 1 (FPR-1) is abundantly expressed on neutrophils has been shown to regulate their function, yet importance FPR-1 fibrosis remains ill defined. FPR-1–deficient (fpr1–/–) mice were protected from bleomycin-induced pulmonary but developed renal hepatic normally. Mechanistically, we observed a failure effectively recruit lungs fpr1–/– mice,...
Significance GDF15, a hormone produced by wide variety of cells undergoing different types stress, acts on receptor in the brain where it transmits signals that are perceived organism as aversive. We now report an action whereby activates endocrine stress response and increases circulating levels principal glucocorticoid (a “stress” steroid). By studying mice genetically deficient we also demonstrate GDF15 is key signal through which damage due to toxic chemicals steroid response. currently...
Abstract Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, often neglected. In present study, we have shown that ARDS patients were hypoxemic monocytopenic within first 48 h ventilation. Monocytopenia was also observed in mouse models hypoxic lung injury, which hypoxemia drove suppression type I interferon signaling bone marrow....
PURPOSE To evaluate an intensive therapy regimen of high-dose etoposide and melphalan autologous bone marrow transplantation (ABMT) in advanced Hodgkin's disease; to determine possible prognostic factors that predict for long-term disease-free survival (DFS). PATIENTS AND METHODS Seventy-three patients with disease who had failed achieve remission front-line chemotherapy (n = 16) or relapsed 57) were treated 60 mg/kg 160 mg/m2 ABMT. Previous included mechlorethamine, vincristine,...
<h3>Background</h3> Excessive use of empirical antibiotics is common in critically ill patients. Rapid biomarker-based exclusion infection may improve antibiotic stewardship ventilator-acquired pneumonia (VAP). However, successful validation the usefulness potential markers this setting exceptionally rare. <h3>Objectives</h3> We sought to validate capacity for specific host inflammatory mediators exclude patients with suspected VAP. <h3>Methods</h3> A prospective, multicentre, study VAP was...
<h3>Rationale</h3> Platelets play an active role in the pathogenesis of acute respiratory distress syndrome (ARDS). Animal and observational studies have shown aspirin9s antiplatelet immunomodulatory effects may be beneficial ARDS. <h3>Objective</h3> To test hypothesis that aspirin reduces inflammation clinically relevant human models recapitulate pathophysiological mechanisms implicated development <h3>Methods</h3> Healthy volunteers were randomised to receive placebo or 75 1200 mg (1:1:1)...
Abstract Mononuclear phagocytes (MPs) including monocytes, macrophages and dendritic cells (DCs) are critical innate immune effectors initiators of the adaptive response. MPs present in alveolar airspace at steady state, however little is known about DC recruitment acute pulmonary inflammation. Here we use lipopolysaccharide inhalation to induce inflammation healthy volunteers examine impact on bronchoalveolar lavage fluid blood MP repertoire. Classical monocytes two subsets (DC2/3 DC5)...
Thirty-one patients with hairy-cell leukemia were treated 2'-deoxycoformycin (DCF) in a National Cancer Institute of Canada multicenter trial. The DCF was administered cycle (4mg/m2iv weekly × 3), which repeated every 8 weeks. Following Complete remission, consolidation done two further cycles DCF. Of 28 evaluable for response, 25 obtained complete remission; 3 had partial response. To date there has been only one relapse; the median time no thereapy 429.5 days (range 99–743days). Toxicity...
BackgroundExtended criteria donor lungs deemed unsuitable for immediate transplantation can be reconditioned using ex vivo lung perfusion (EVLP). Objective identification of which successfully and will function well post-operatively has not been established. This study assessed the predictive value markers inflammation tissue injury in undergoing EVLP as part DEVELOP-UK study.MethodsLongitudinal samples perfusate, bronchoalveolar lavage, from 42 human clinical assessments were analyzed...
Background Critically ill patients with impaired neutrophil phagocytosis have significantly increased risk of nosocomial infection. Granulocyte-macrophage colony-stimulating factor (GM-CSF) improves by neutrophils ex vivo. This study tested the hypothesis that GM-CSF in critically whom is known to be impaired. Methods was a multicentre, phase IIa randomised, placebo-controlled clinical trial. Using personalised medicine approach, only were included. Patients randomised 1:1 subcutaneous (3...
In order to limit the adverse effects of excessive inflammation, anti-inflammatory responses are stimulated at an early stage infection, but during sepsis these can lead deactivation immune cells including monocytes. addition, there is emerging evidence that up-regulation mitochondrial quality control mechanisms, biogenesis and mitophagy, important recovery from inflammation. We aimed describe relationship between compensatory triggered following exposure inflammatory stimulus in human...
<h2>Abstract</h2><h3>Introduction</h3> Tissue factor expression on monocytes is implicated in the pathophysiology of sepsis-induced coagulopathy. How tissue expressed by monocyte subsets (classical, intermediate and non-classical) unknown. <h3>Methods</h3> Monocytic surface was investigated during three conditions. Primary human microvascular endothelial cell co-cultures were used for <i>in vitro</i> studies. Volunteers received a bolus lipopolysaccharide (2 ng/kg) to induce endotoxemia....
PURPOSE To evaluate the efficacy of carmustine (BCNU), etoposide, cytarabine (Ara-C), and melphalan (mini-BEAM) as salvage therapy in patients with relapsed or refractory Hodgkin's disease who were potentially eligible to undergo intensive autologous bone marrow transplantation (ABMT). PATIENTS AND METHODS Forty-four after front-line combination chemotherapy referred for consideration ABMT treated mini-BEAM (BCNU 60 mg/m2 on day 1, etoposide 75 days 2 5, Ara-C 100 twice per 30 6) maximum...
Twenty-six patients were treated with chemotherapy following surgery for gastrointestinal non-Hodgkin's lymphoma (GI-NHL). The median age was 50 years (range, 20 to 76). primary site included stomach (16 patients), small bowel (seven), large (two), and mesenteric nodes (one). Following surgery, nine had macroscopic four microscopic residual disease, 13 felt have complete surgical resection. Thirteen stage I II. Sixteen COPP (cyclophosphamide, vincristine, procarbazine, prednisone), CHOP...
Patients with intermediate grade non‐Hodgkin's lymphoma (NHL) who relapse or fail to achieve a complete remission after anthracycline‐containing induction regimens have poor outcome conventional‐dose salvage treatment. This may be improved intensive therapy and autologous transplantation (ABMT) but even in patients proven chemotherapy‐sensitive disease, rates of up 60% are observed. Reliable powerful prognostic indicators needed identify appropriate for this expensive procedure those...
Critical illness is accompanied by the release of large amounts anaphylotoxin, C5a. C5a suppresses antimicrobial functions neutrophils which associated with adverse outcomes. The signaling pathways that mediate C5a-induced neutrophil dysfunction are incompletely understood. Healthy donor exposed to purified demonstrated a prolonged defect (7 hours) in phagocytosis Staphylococcus aureus. Phosphoproteomic profiling 2712 phosphoproteins identified persistent and selective impairment phagosomal...
The process of producing news has changed significantly due to the advent Web, which enabled increasing involvement citizens in production. This trend been given many names, including participatory journalism, produsage, and crowd-sourced but these terms are ambiguous have applied inconsistently, making comparison systems difficult. In particular, it is problematic distinguish levels citizen involvement, therefore extent production genuinely opened up. this paper we perform an analysis 32...
Rationale: Aspiration of infective subglottic secretions causes ventilator-associated pneumonia (VAP) in mechanically ventilated patients. Mechanisms underlying colonization critical illness have not been defined, limiting strategies for targeted prevention VAP.Objectives: To characterize host defense dysfunction patients the ICU; to determine whether mucin contributes neutrophil phagocytic impairment and bacterial growth.Methods: Prospective sampling (intubated four or more days), newly...
Abstract The COVID-19 pandemic, caused by SARS coronavirus 2 (SARS-CoV-2), has resulted in excess morbidity and mortality as well economic decline. To characterise the systemic host immune response to SARS-CoV-2, we performed single-cell RNA-sequencing coupled with analysis of cell surface proteins, providing molecular profiling over 800,000 peripheral blood mononuclear cells from a cohort 130 patients COVID-19. Our cohort, three UK centres, spans spectrum clinical presentations disease...