A5102915371- Organ Transplantation Techniques and Outcomes
- Transplantation: Methods and Outcomes
- Renal Transplantation Outcomes and Treatments
- Effects and risks of endocrine disrupting chemicals
- Liver Disease and Transplantation
- Organ Donation and Transplantation
- Radiation Effects and Dosimetry
- Estrogen and related hormone effects
- Carcinogens and Genotoxicity Assessment
- Organ and Tissue Transplantation Research
- Animal Virus Infections Studies
- Cancer Risks and Factors
- Bone Tissue Engineering Materials
- Effects of Radiation Exposure
- 3D Printing in Biomedical Research
- Advanced MRI Techniques and Applications
- Acute Kidney Injury Research
- Cancer-related Molecular Pathways
- Lanthanide and Transition Metal Complexes
- MRI in cancer diagnosis
- Anatomy and Medical Technology
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Proteoglycans and glycosaminoglycans research
- Mechanical Circulatory Support Devices
- Hemoglobin structure and function
Manchester Academic Health Science Centre
2017-2023
University of Manchester
2014-2023
Manchester University NHS Foundation Trust
2017-2022
Centre for Inflammation Research
2014-2020
Wythenshawe Hospital
2017-2019
Tufts Medical Center
1993
Brookhaven National Laboratory
1980-1985
Associated Universities, Inc.
1981
Activated platelets and stimulated endothelial cells express P-selectin, an integral membrane protein receptor that binds monocytes neutrophils. P-selectin mediates adhesion to glycoproteins with carbohydrate structures containing sialyl-Lewis X. Since many carcinoma also these are known interact platelets, we asked whether may mediate this interaction. Both small cell lung cancer neuroblastoma lines bound activated interaction was blocked inhibitory anti-P-selectin antibodies by...
This paper examines the relationship between feeding a diet rich in protease inhibitors and reduction of mammary cancer induced by x-irradiation Sprague-Dawley rats. Of total 145 irradiated animals, 44% 45 rats fed raw soybean containing high concentration inhibitor developed tumors as compared to 74% 50 casein no inhibitor. Animals Purina rat chow which contained low levels exhibited 70% tumor incidence. No spontaneous neoplasms were found any non-irradiated animals on whereas about 10%...
Passenger leukocyte transfer from the donor lung to recipient is intrinsically involved in acute rejection. Direct presentation of alloantigen expressed on leukocytes recognized by T cells, promoting cellular We utilized ex vivo perfusion (EVLP) study passenger migration lungs into and evaluate effects depletion prior transplantation. For this purpose, female pigs received male left either following 3 h EVLP or retrieved using standard protocols. Recipients were monitored for 24 sequential...
In Brief Background Lung transplantation is limited by a scarcity of suitable donors resulting in high waiting list mortality. Ex vivo lung perfusion (EVLP) allows the evaluation and reconditioning marginal donor lungs for use transplantation. This study aimed to compare clinical outcome patients transplanted with organs means EVLP standard transplant cohort through multicenter open trial. Methods Group 1 (n = 9) included using reconditioned lungs. 2 46) consisted date-matched acceptable The...
Ex vivo normothermic perfusion offers an alternative method of organ preservation, allowing donor kidneys to be reanimated and evaluated prior transplantation. Beyond it can used characterize the immunological contribution kidney in isolation. Furthermore, has potential as immunomodulatory strategy manipulate transplantation.Explanted porcine underwent 6 hours perfusion. Sequential perfusate samples were collected leukocytes characterized via flow cytometry. An inflammatory profile was...
Attempts to improve limb preservation for transplantation using ex vivo perfusion have yielded promising results. However, metabolic acidosis, aberrant perfusate biochemistry and significant perfusion-induced oedema are reported universally. Optimizing protocols is therefore essential maintaining tissue health.A randomized, two-stage open preclinical trial design was used determine the optimal temperature mean arterial pressure machine perfusion. Conditions compared were: normothermic at 70...
Introduction: Many donor organs contain significant leukocyte reservoirs which upon transplantation activate recipient leukocytes to initiate acute rejection. We aimed assess whether ex vivo heart perfusion promotes immunodepletion and alters the inflammatory status of organ prior transplantation. Methods: Isolated porcine hearts underwent hypothermic, cardioplegic for 8 hours. Leukocyte populations were quantified in left ventricle samples by flow cytometry. Cell-free DNA, cytokines...
Mammary tumorigenesis was studied in female ACi rats after treatment with X-irradiation or neutron-irradiation, without diethylstilbestrol (DES) treatment. The mortality-corrected cumulative tumor rate based on all mammary neoplasms and the incidence first only have been derived. In non-DES-treated animals, at relatively high radiation doses studied, dose-effect relationships were consistent relative biological effectiveness (RBE) values slightly excess of 10. DES-treated definite findings...
Primary graft dysfunction and allograft rejection represent major caveats to successful lung transplantation. Reducing inflammation in donor lungs before transplantation may improve outcomes. Evidence exists that ex vivo perfusion (EVLP) can alter the environment, although mechanisms remain unclear. This study aimed characterize inflammatory signaling profile of following standard EVLP transplant delineate immediate impact on recipient circulation.Female pigs (n = 12) were randomized undergo...
Kidney transplantation is the best renal-replacement option for most patients with end-stage renal disease. Normothermic machine preservation (NMP) of kidney has been studied extensively during last two decades and implemented in clinical trials. Biomarker research led to success identifying molecules diagnostic, predictive therapeutic properties chronic However, perfusate biomarkers potential mechanisms NMP have not identified yet. Twelve discarded human kidneys ( n = 7 DBD, 5 DCD)...
One compressed 20-mg pellet containing cholesterol only or mixed with 0.98, 1.6, 2.6, 3.9 mg of diethylstilbestrol (DES) was implanted into each 203 female F344 rats. Two days later, half the animals in group were exposed to 150 R X-rays, and other sham irradiated. The rats maintained until 350 post implantation. Mortality increased higher doses DES, without X-rays. DES at all dose levels, produced pituitary tumors pyometritis. Only that received both X-rays had mammary adenocarcinomas (AC)....
Background. Ex vivo lung perfusion (EVLP) is used to evaluate and recondition extended criteria donor lungs for transplantation. Interleukin-1β (IL-1β) has been identified as a prognostic indicator of nonrecovery during EVLP. This may be an effect inflammasome activation or cellular necrosis following donation graft preservation. Delineating the mechanism IL-1β release required. Methods. The inactive intracellular precursor molecule, pro-IL-1β, was characterized along with pro-IL-1β...
Investigators have proposed that cardiovascular magnetic resonance (CMR) should restrictions similar to those of ionizing imaging techniques. We aimed investigate the acute effect 1.5 T CMR on leucocyte DNA integrity, cell counts, and function in vitro, a large cohort patients vivo.In vitro study: peripheral blood mononuclear cells (PBMCs) were isolated from healthy volunteers, histone H2AX phosphorylation (γ-H2AX) expression, functional parameters quantified using flow cytometry under...
There has been significant progress in the development of ex vivo machine perfusion for nonischemic preservation donor organs. However, several complications remain, including logistics using human blood graft oxygenation and hemolysis occurring as a result mechanical technology. Recently, hemoglobin-based oxygen carriers, originally developed use substitutes, have studied an alternative to red cell–based perfusates. Although research this field is somewhat limited, findings are promising....
Background. Donor kidneys contain a large reservoir of passenger leucocytes that contribute to acute rejection via direct alloantigen presentation and pro-inflammatory cytokine secretion. However, the early contribution these cells following revascularization has not previously been described. We performed secondary, high-volume preservation flush cold storage characterize inflammatory donor kidney upon reperfusion. Methods. Porcine were retrieved using protocol analogous current UK clinical...
Introduction The current protocol for vascularized composite allograft (VCA) preservation involves cold static storage on ice. This severely limits times of the graft and is associated with several deleterious processes that augment ischaemia reperfusion injury acute rejection. As a result there major drive to develop ex-vivo perfusion (EVP) protocols can improve preservation. Critical parameters successful EVP include temperature circulating perfusate mean arterial pressure have yet be...
Recent experimental evidence suggests normothermic machine perfusion of the vascularized composite allograft results in improved preservation compared to static cold storage, with less reperfusion injury immediate post-operative period. However, metabolic acidosis is a common feature perfusion, primarily due inability process by-products. We evaluated impact combined limb-kidney on markers and inflammation porcine model.Ten paired pig forelimbs were used for this study, grouped as either...
Normothermic machine perfusion (NMP) offers a superior alternative to hypothermic preservation but is currently time limited. Extending this could electivise transplantation and enable physiologic assessments of functionality. Porcine kidneys were retrieved, stored on ice for 3.5 hours before being placed onto NMP circuit 12 hours. Hemodynamics, biochemistry, urine output assessed. After hours, scored using the clinical assessment score. Biopsies collected histological assessment. Kidneys...
Ischemia-reperfusion injury (IRI) is a significant complication in kidney transplantation, often affecting the viability and function of organs. Normothermic machine perfusion (NMP) technique used to improve condition organs prior transplantation. In this study, we show that incorporating antioxidant poly(propylene sulfide) nanoparticles (PPS-NPs) during cold-storage NMP significantly enhances its efficacy reducing IRI upon porcine We found by scavenging reactive oxygen species, PPS-NPs...