A5087997438- Atomic and Subatomic Physics Research
- Surgical site infection prevention
- RNA Interference and Gene Delivery
- Retinal and Optic Conditions
- Cancer Research and Treatments
- Retinal Development and Disorders
- Surgical Sutures and Adhesives
- Autophagy in Disease and Therapy
- Pleural and Pulmonary Diseases
- Cell death mechanisms and regulation
- Thermal Regulation in Medicine
- Advanced MRI Techniques and Applications
- Infant Nutrition and Health
- Cancer-related Molecular Pathways
- Wound Healing and Treatments
- Endoplasmic Reticulum Stress and Disease
- Social and Educational Sciences
- RNA modifications and cancer
- Reconstructive Surgery and Microvascular Techniques
- Nitric Oxide and Endothelin Effects
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Retinal Diseases and Treatments
- Urological Disorders and Treatments
- Prion Diseases and Protein Misfolding
Sheffield Teaching Hospitals NHS Foundation Trust
2023-2024
University of Sheffield
2023
Canadian Respiratory Research Network
2023
Sandwell & West Birmingham Hospitals NHS Trust
2021
Lund University
2004-2015
Skåne University Hospital
2014-2015
Singapore Immunology Network
2009
Institute of Laboratory Animal Science
2004-2005
Czech Academy of Sciences, Institute of Microbiology
2002
We studied the effect on skin papillomas of topical application a complex alpha-lactalbumin and oleic acid (often referred to as human made lethal tumor cells [HAMLET]) establish proof principle that alpha-lactalbumin-oleic kills transformed but not healthy, differentiated cells.Forty patients with cutaneous were resistant conventional treatment enrolled in randomized, placebo-controlled, double-blind study, which or saline placebo was applied daily for three weeks change volume each lesion...
Abstract Pronounced immune escape by the SARS-CoV-2 Omicron variant has resulted in many individuals possessing hybrid immunity, generated through a combination of vaccination and infection. Concerns have been raised that omicron breakthrough infections triple-vaccinated result poor induction omicron-specific prior infection is associated with dampening. Taking broad comprehensive approach, we characterize mucosal blood immunity to spike non-spike antigens following BA.1/BA.2 triple...
Abstract Malignant brain tumors present a major therapeutic challenge because no selective or efficient treatment is available. Here, we demonstrate that intratumoral administration of human α-lactalbumin made lethal to tumor cells (HAMLET) prolongs survival in glioblastoma (GBM) xenograft model, by induction cell apoptosis. HAMLET protein-lipid complex formed from when the protein changes its tertiary conformation and binds oleic acid as cofactor. induces apoptosis wide range vitro, but...
Mucosal Toll-like receptors (TLRs) respond to pathogens, but remain inert the indigenous flora, suggesting that TLRs can receive pathogen-specific signals. For example, TLR4 signalling is activated in CD14-negative epithelial cells by P-fimbriated, uropathogenic Escherichia coli, not lipopolysaccharide. The fimbriae use glycosphingolipids as recognition and there release of ceramide, which membrane-anchoring domain receptors. In this study, ceramide was identified a agonist putative...
Negative pressure wound therapy (NPWT) results in 2 types of tissue deformation, macrodeformation (ie, contraction) and microdeformation the interaction dressing on a microscopic level). These effects have been delineated for one type filler, foam, but not gauze. The mechanical deformation initiates signaling cascade which ultimately leads to healing. aim present study was examine effect gauze foam macro- during treatment with negative pressure. An vivo porcine peripheral model used. NPWT...
Abstract We studied if bladder cancers respond to HAMLET (human α‐lactalbumin made lethal tumor cells) establish intravesical application might be used selectively remove cancer cells in vivo . Patients with nonmuscle invasive transitional cell carcinomas were included. Nine patients received 5 daily instillations of (25 mg/ml) during the week before scheduled surgery. stimulated a rapid increase shedding into urine, daily, days instillation. The effect was specific for HAMLET, as...
Microvascular abnormalities and impaired gas transfer have been observed in patients with COVID-19. The progression of pulmonary changes these remains unclear.
Abstract HAMLET ( h uman α ‐lactalbumin m ade le thal to t umor cells) is a complex of human α‐lactalbumin and oleic acid (C18:1:9 cis) that kills tumor cells by an apoptosis‐like mechanism. Previous studies have shown conformational change required form from α‐lactalbumin, partially unfolded conformation maintained in the complex. This study examined if unfolding sufficient induce cell death. We used bovine Ca 2+ site mutant D87A, which unable bind , thus remains regardless solvent...
HAMLET is a folding variant of human α-lactalbumin in an active complex with oleic acid. selectively enters tumor cells, accumulates their nuclei and induces apoptosis-like cell death. This study examined the interactions nuclear constituents identified histones as targets. was found to bind histone H3 strongly lesser extent H4 H2B. The specificity these confirmed using BIAcore technology chromatin assembly assays. In vivo co-localized perturbed structure; associated insoluble fraction...
Objective: Vacuum-assisted closure (VAC) is a recently introduced method for the treatment of poststernotomy mediastinitis. The aim was to examine effects VAC negative pressure on peristernal soft tissue blood flow after internal mammary artery harvesting. Methods: Microvascular measured using laser Doppler velocimetry in porcine sternotomy wound model. effect edge investigated right side, where intact, and left had been removed. Results: Before removal artery, similar edges, 2.5 cm from (27...
HAMLET, a complex of partially unfolded alpha-lactalbumin and oleic acid, kills wide range tumor cells. Here we propose that HAMLET causes macroautophagy in cells this contributes to their death. Cell death was accompanied by mitochondrial damage reduction the level active mTOR triggered extensive cytoplasmic vacuolization formation double-membrane-enclosed vesicles typical macroautophagy. In addition, caused change from uniform (LC3-I) granular (LC3-II) staining LC3-GFP-transfected...
Proteasomes control the level of endogenous unfolded proteins by degrading them in proteolytic core. Insufficient degradation due to altered protein structure or proteasome inhibition may trigger cell death. This study examined response HAMLET, a partially protein-lipid complex, which is internalized tumor cells and triggers death.HAMLET bound directly isolated 20S proteasomes vitro significant co-localization HAMLET was detected confocal microscopy. interaction confirmed...
For the modified Hughes procedure, a tarsoconjunctival flap from upper eyelid is used to reconstruct large, full-thickness, lower defects. The conjunctival pedicle divided once vascularization deemed be adequate. importance of maintaining ensure adequate perfusion graft has been questioned. purpose study was investigate microvascular blood flow, oxygenation, and survival in an experimental porcine model procedure.The procedure performed 9 pigs. Microvascular flow measured by laser Doppler...