A5065152738- Transplantation: Methods and Outcomes
- Organ Transplantation Techniques and Outcomes
- Pulmonary Hypertension Research and Treatments
- Renal Transplantation Outcomes and Treatments
- Cytokine Signaling Pathways and Interactions
- Cardiac Imaging and Diagnostics
- Cardiovascular Function and Risk Factors
- Traumatic Brain Injury and Neurovascular Disturbances
- Cell Adhesion Molecules Research
- Congenital Heart Disease Studies
- Organ Donation and Transplantation
- Chemokine receptors and signaling
- Synthesis and Biological Evaluation
- Cardiovascular Issues in Pregnancy
- Ovarian cancer diagnosis and treatment
- Cerebrovascular and Carotid Artery Diseases
- Acute Ischemic Stroke Management
- Advanced MRI Techniques and Applications
- Adenosine and Purinergic Signaling
- Electron Spin Resonance Studies
- Mechanical Circulatory Support Devices
- Cardiac Arrest and Resuscitation
- Trauma Management and Diagnosis
- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
University Hospitals Birmingham NHS Foundation Trust
2007-2024
University of Sheffield
2016-2024
University of California, San Francisco
2021-2024
Queen Elizabeth Hospital Birmingham
2009-2023
Alberta Hospital Edmonton
2013-2022
Prince Charles Hospital
2021
University of South Carolina
2020
University of Chicago
2020
University of Notre Dame
2020
Royal Hallamshire Hospital
2010-2019
Abstract Constitutive expression of the inflammatory cytokine tumor necrosis factor-α (TNF-α) is characteristic malignant ovarian surface epithelium. We investigated hypothesis that this autocrine action TNF-α generates and sustains a network other mediators promote peritoneal cancer growth spread. When compared with two cell lines did not make TNF-α, constitutive production was associated greater release chemokines CCL2 CXCL12, cytokines interleukin-6 (IL-6) macrophage migration-inhibitory...
Abstract Purpose: We investigated whether inhibition of interleukin 6 (IL-6) has therapeutic activity in ovarian cancer via abrogation a tumor-promoting cytokine network. Experimental Design: combined preclinical and silico experiments with phase 2 clinical trial the anti-IL-6 antibody siltuximab patients platinum-resistant cancer. Results: Automated immunohistochemistry on tissue microarrays from 221 cases showed that intensity IL-6 staining malignant cells significantly associated poor...
Abstract The cytokine IL6 has a number of tumor-promoting activities in human and experimental cancers, but its potential as an angiogenic agent not been fully investigated. Here, we show that can directly induce vessel sprouting the ex vivo aortic ring model, well endothelial cell proliferation migration, with similar potency to VEGF. However, IL6-stimulated sprouts had defective pericyte coverage compared VEGF-stimulated vessels. mechanism action on pericytes involved stimulation Notch...
Abstract Purpose: In high-grade serous ovarian cancer (HGSOC), higher densities of both B cells and the CD8+ T-cell infiltrate were associated with a better prognosis. However, precise role in antitumor response remains unknown. As peritoneal metastases are often responsible for relapse, our aim was to characterize immune HGSOC metastases. Experimental Design: Unmatched pre post-chemotherapy studied. B-cell localization assessed by immunostaining. Their cytokines chemokines measured...
<h3>OBJECTIVES</h3> To determine the incidence, treatment, and outcome of Guillain-Barré syndrome in south east England. <h3>METHODS</h3> Patients presenting with confirmed between 1 July 1993 30 June 1994 were recruited via a voluntary reporting scheme coordinated by British Neurological Surveillance Unit, hospital activity data collected from acute admitting hospitals within South East West Thames Regional Health Authorities, death certificates, contemporary research study <i>Campylobacter...
Elevated expression of the chemokine receptor CCR4 in tumors is associated with poor prognosis several cancers. Here, we have determined that was highly expressed human renal cell carcinoma (RCC) biopsies and observed abnormal levels ligands RCC patient plasma. An antagonistic anti-CCR4 antibody had antitumor activity RENCA mouse model RCC. inhibition did not reduce proportion infiltrating leukocytes tumor microenvironment but altered phenotype myeloid cells, increased NK Th1 cytokine...
Abstract Human CD93 (known as C1qRp) has been shown to be a phagocytic receptor involved in the vitro C1q-dependent enhancement of phagocytosis. However, binding C1q and its function remain controversial. In this study, we have generated CD93-deficient mice (CD93−/−) investigate biological role(s). The CD93−/− were viable showed no gross abnormalities their development. Thioglycolate-elicited peritoneal macrophages deficient similar complement- FcγR-dependent uptake RBC wild-type when plated...
AimsThe aim of this study was to assess the haemodynamic effects tri-iodothyronine (T3) and methylprednisolone in potential heart donors.
Abstract Neutrophil elastase (NE) remains a controversial player in the process of leukocyte transmigration and much this controversy stems from conflicting reports on effects NE inhibitors. The availability NE-deficient mice (NE−/−) provides clean elegant tool for study migration vivo. In study, NE−/− were used to investigate role through cremasteric venules, as observed by intravital microscopy, induced locally administered cytokines IL-1β TNF-α particulate stimulus, zymosan. Although no...
Using high‐pressure liquid chromatography, we have quantitated the theophylline metabolites in 24‐hr urines of 15 patients a clinical ward who had been receiving 800 or 1,200 mg aminophylline /24 hr divided oral doses. Mean values for theophylline‐derived urine products were as follows: unchanged theophylline, 7.7 ± 6.1%; 3‐methylxanthine, 36.2 7.3%; 1,3‐dimethyluric acid, 39.6 4.5%; and 1‐methyluric 16.5 3.3%. These data are consistent with those earlier reported metabolism man other...
Adenosine receptors on the surface of coronary myocytes initiate relaxation, but events subsequent to receptor occupancy are uncertain. We assayed vasoactivity receptor-selective adenosine analogs in open chest dogs test hypothesis that is an adenylate cyclase stimulatory (Ra) receptor. The potency order was: ethyl adenosine-5'-uronamide greater than cyclopropyl 2-chloroadenosine N6-[R(-)-1-phenyl-2-propyl] (R-PIA) N6-cyclohexyladenosine S-PIA. Such a hierarchy activity resembles Ra thyroid...
Objective. To determine whether low-dose ciclosporin was a more effective corticosteroid-sparing agent than AZA in patients with SLE.
A cDNA clone, BET1 (for basal endosperm transfer layer), was isolated from a bank prepared 10-days after pollination (DAP) maize mRNA. mRNA shown to encode 7-kD cell wall polypeptide. Both the and protein were restricted in their distribution layer not expressed elsewhere plant. expression commenced at 9 DAP, reached maximum between 12 16 declined DAP. The initial accumulation of polypeptide plateau by DAP thereafter, becoming undetectable 20 antibody raised against reacted with number...
The protein encoded by the Opaque-2 (O2) gene is a transcription factor, translated from an mRNA that possesses unusually long 5' leader sequence containing three upstream open reading frames (uORFs). efficiency of translation O2 has been tested in vivo transient assay which level activation b32 promoter, natural target protein, measured. We show uORF-less alleles possess higher transactivation value than wild-type allele and reduction due to uORFs cis-dominant effect. data presented...
Brain stem death can elicit a potentially manipulable cardiotoxic proinflammatory cytokine response. We investigated the prevalence of this response, impact donor management with tri-iodothyronine (T3) and methylprednisolone (MP) administration, relationship biomarkers to organ function transplant suitability.In prospective randomized double-blinded factorially designed study T3 MP therapy, we measured serum levels interleukin-1 -6 (IL-1 IL-6), tumor necrosis factor-alpha (TNF-alpha),...
Abstract High‐grade serous ovarian cancer (HGSC) disseminates early and extensively throughout the peritoneal space, causing multiple lesions that are a major clinical problem. The aim of this study was to investigate cellular composition tumour deposits in patient biopsies their evolution mouse models using immunohistochemistry, intravital microscopy, confocal 3D modelling. Tumour from omentum HGSC patients contained prominent leukocyte infiltrate CD3 + T cells CD68 macrophages, with...
Summary The maize cob presents an excellent opportunity to screen visually for mutations affecting assimilate partitioning in the developing kernel. We have identified a defective kernel mutant termed rgf1 , reduced grain filling with final weight 30% of wild type. In contrast most endosperm mutants, shows gene dosage‐dependent expression endosperm. kernels possess small incompletely papery pericarp, but embryo development is unaffected and seeds are viable. mutation conditions pedicel...
Abstract The final stage in the migration of leukocytes to sites inflammation involves movement through endothelial cell layer and perivascular basement membrane. Both platelet-endothelial adhesion molecule-1 (PECAM-1/CD31) integrin αvβ3 have been implicated this process, vitro studies identified as a heterotypic ligand for PECAM-1. In present study we addressed roles these molecules by investigating comparing effects PECAM-1 blockade on leukocyte vivo. For purpose examined neutralizing Abs...
The demand for lung transplantation vastly exceeds the availability of donor organs. This translates into long waiting times and high list mortality. We set out to examine factors influencing patient outcomes from time listing in UK, examining differences by characteristics, disease category transplant centre.Data were obtained UK Transplant Registry held NHS Blood adult lung-only registrations between 1January 2004 31 March 2014. Pretransplant post-transplant evaluated against category,...
The measurement of extravascular lung water could aid the assessment and guide management potential donors following brain death. We therefore sought to validate a single indicator thermodilution index (EVLWI-T) using gravimetry assess impact clinical correlates elevated EVLWI-T in transplant recipients. In prospective study, we measured serial haemodynamic oxygenation data 60 donors. To measurement, vivo EVLWI gravimetric ex (EVLWI-G) donor lungs rejected for Holcroft Trunkey modification...
Background: Lung transplantation is a therapeutic option for patients with end-stage lung disease and survival benefit has been described in alpha-1-antitrypsin deficiency (A1ATD). The aims of the current study were to determine health benefits UK A1ATD compared carefully matched non-transplant patients.Methods: Patients PiZZ (alpha-1-antitrypsin deficiency) genotype who had undergone between 1996 2011 identified from registry. physiology, status pre- post-transplant using patients.Results:...