- Renal Transplantation Outcomes and Treatments
- Transplantation: Methods and Outcomes
- T-cell and B-cell Immunology
- Organ Transplantation Techniques and Outcomes
- Synthesis and Biological Evaluation
- Cytomegalovirus and herpesvirus research
- Immune Cell Function and Interaction
- Nicotinic Acetylcholine Receptors Study
- Skin and Cellular Biology Research
- Smoking Behavior and Cessation
- American Constitutional Law and Politics
- Immune Response and Inflammation
- Adipose Tissue and Metabolism
- Click Chemistry and Applications
- Pluripotent Stem Cells Research
- Viral-associated cancers and disorders
- Immunotherapy and Immune Responses
- Heme Oxygenase-1 and Carbon Monoxide
- Crystallization and Solubility Studies
- Viral Infections and Immunology Research
- Diabetes and associated disorders
- X-ray Diffraction in Crystallography
- Lymphoma Diagnosis and Treatment
- Diabetes Management and Research
- Chemical Synthesis and Analysis
Scottish National Blood Transfusion Service
2014-2024
Edinburgh Royal Infirmary
2014-2023
University of Liverpool
2023
Royal Victoria Hospital
2022
University of Ulster
2022
University of Dundee
2021
Medical Research Council
2021
Newcastle University
1972-2020
Newcastle upon Tyne Hospital
2004-2020
Cancer Research UK
2020
SUMMARY Interleukin‐10 (IL‐10) has been described as an anti‐inflammatory cytokine and B‐cell proliferation factor implicated in autoimmunity, tumorigenesis transplantation tolerance. We have identified three single base pair substitutions the IL‐10 gene promoter investigated whether this polymorphism correlates with protein production vitro.
Transforming growth factor (TGF)-beta1 is a profibrogenetic cytokine that has been implicated in the development of fibrosis transplanted tissues. In this study, we have analyzed genetic regulation TGF-beta1 production lung transplant recipients.A polymerase chain reaction-single-stranded conformational polymorphism technique was used to detect polymorphisms gene from genomic DNA. Polymorphisms were shown correlate with vitro by stimulated lymphocytes. A single-specific oligonucleotide probe...
Eight men volunteers each smoked a single cirgarette containing 14C-nicotine and gave arterial blood samples during for 50 minutes after smoking. The maximum concentration of nicotine in the ranged from 31 to 41 mug/l four regular cigarette smokers who inhaled. Two non-smokers achieved levels 2 4 mug/l. On separate occasion two inhalers received 1 mg. 10 divided doses injected intravenously. In both cases peak concentrations bore similar relationship intravenous dose, as did retained
Background. Allograft rejection is mediated by cytokines. As polymorphism in cytokine genes can result interindividual differences production, we hypothesize that some patients may have an increased risk of rejection. Methods. We related polymorphisms influence production the tumor necrosis factor (TNF)-A and interleukin (IL)-10 to early graft 115 heart transplant recipients. Results. Certain combinations TNF-A IL-10 gene are associated with Five 19 who had high levels typed as TNF-α/low...
Summary Epstein‐Barr virus ( EBV ) is associated with several malignancies, including post‐transplant lymphoproliferative disorder PTLD ). Conventional treatments for are often successful, but risk organ rejection and cause significant side effects. ‐specific cytotoxic T lymphocytes CTL s) generated in vitro from peripheral blood provide an alternative treatment modality few effects, autologous s difficult to use clinical practice. Here we report the establishment operation of a bank derived...
Purines and related heterocycles substituted at C-2 with 4′-sulfamoylanilino C-6 a variety of groups have been synthesized the aim achieving selectivity binding to CDK2 over CDK1. 6-Substituents that favor competitive inhibition ATP site were identified typically exhibited 10–80-fold greater compared Most impressive was 4-((6-([1,1′-biphenyl]-3-yl)-9H-purin-2-yl)amino) benzenesulfonamide (73) high potency toward (IC50 0.044 μM) but ∼2000-fold less active CDK1 86 μM). This compound is...
Abstract Although autologous induced pluripotent stem cells (iPSCs) can potentially be useful for treating patients without immune rejection, in reality it will extremely expensive and labor-intensive to make iPSCs realize personalized medicine. An alternative approach is use of human leukocyte antigen (HLA) haplotype homozygous donors provide HLA matched iPSC products significant numbers patients. To establish a haplobank iPSCs, we repurposed the cord blood bank by screening ∼4,200 high...
Summary paragraph An outbreak of acute hepatitis unknown aetiology in children was first reported Scotland April 2022. 1 Cases aged <16 years have since been identified 35 countries. 2 Here we report a detailed investigation 9 early cases and 58 control subjects. Using next-generation sequencing real-time PCR, adeno-associated virus (AAV2), detected the plasma 9/9 liver 4/4 patients but 0/13 sera/plasma age-matched healthy controls, 0/12 with adenovirus (HAdV) infection normal function...
Abstract Cytokine gene polymorphisms affecting cytokine production may influence rejection and graft‐versus‐host disease following solid organ haemopoietic stem cell (HSC) transplantation, respectively. Polymorphisms in the regulatory regions of several genes have been described; for example, tumour necrosis factor‐α (TNF‐α) has a G/A substitution at position −308, interleukin‐2 (IL‐2) T/G −330 interleukin‐10 (IL‐10) substitutions positions −1082(G/A), −819(C/T) −592(C/A). Microsatellites...
The cytokine TNF-α has been implicated in the pathogenesis of both acute and chronic transplant rejection. Levels are known to vary a normal population, leading speculation that high responders may be at greater risk Particular TNF region polymorphic markers have associated with increased levels biallelic polymorphism identified position –308 promoter contribute significantly interindividual variation healthy persons. We describe here new association between locus gene production heart...
We have detected two novel single nucleotide polymorphisms in the IL-2 gene, at positions -330 and +166 relative to transcription start site. The change occurs within leader peptide does not affect amino acid sequence. polymorphism has common alleles, making it an ideal marker for genetic association studies.
The metabolism of [2'-(14)C]nicotine given as an intravenous injection in small doses to anaesthetized and unanaesthetized cats has been studied. A method is described for the quantitative determination [(14)C]nicotine [(14)C]cotinine tissues body fluids. Nanogram amounts these compounds have detected. After a single dose 40mug. [(14)C]nicotine/kg., 55% injected radioactivity was excreted urine within 24hr., but only 1% this unchanged nicotine. [(14)C]Nicotine metabolized extremely rapidly,...
COVID-19 disease caused by the SARS-CoV-2 virus is characterized dysregulation of effector T cells and accumulation exhausted cells. cell responses to viruses can be corrected adoptive cellular therapy using donor-derived virus-specific One approach establishment banks HLA-typed for rapid deployment patients. Here we show that SARS-CoV-2–exposed blood donations contain CD4 CD8 memory which recognize spike, nucleocapsid membrane antigens. Peptides these antigens used isolate in a...
The outcome of 81 adult aplastic anaemia patients who had successful cytogenetics at diagnosis and received immunosuppressive therapy was evaluated. Ten an abnormal karyotype, six which a trisomy. Four five evaluable with trisomy responded. One patient monosomy 7 achieved complete response later developed haemolytic paroxysmal nocturnal haemoglobinuria but no recurrence 7. None the non-numerical karyotypic abnormality No significant differences in survival or clonal disorders were observed...