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Role of the clinical immunology laboratory in disease monitoring

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World Journal of Immunology 2013年第2期3卷 18-30页

作者： john maher Department of Immunology Barnet and Chase Farm NHS Trust Barnet Hertfordshire EN5 3DJ United Kingdom King’s College London King’s Health Partners Integrated Cancer Centre Department of Research Oncology Guy’s Hospital Campus London SE1 9RT United Kingdom Department of Clinical Immunology and Allergy King’s College Hospital NHS Foundation Trust Denmark Hill London SE5 9RS United Kingdom

Immunological investigations provide useful informa-tion to guide diagnosis of several disorders. Many such tests are also commonly repeated at intervals, in an effort to facilitate disease monitoring. In general how-ever, immunology test results are often slow to alter. Furthermore, audit activity has indicated that repeated testing accounts for a substantial workload in many immunology services, which may waste resources and compromise the effcient completion of necessary tests. Consequently, the need and appropriate mini-mum interval between repeated testing requires critical evaluation. In this review, the clinical utility of repeat-ed performance of several common immunology inves-tigations has been evaluated, based upon published evidence. In some cases （ e.g. , paraprotein quantifca-tion, or measurement of anti-glomerular basement membrane antibodies）, repeated testing provides vital clinical information and can be justifed on a frequent and individualized basis. However, many other investi-gations provided by immunology services provide less valuable information when used to aid disease moni-toring rather than diagnosis. It is hoped that the data summarized here will facilitate a more evidence-based approach to repeated testing. Such information may also assist with the local implementation of demand management strategies based upon setting of mini-mum retesting intervals for these investigations.

关键词： Clinical immunology Immune monitoring Retest Test interval

Chimeric antigen receptors:On the road to realising their full potential

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World Journal of Immunology 2015年第3期5卷 86-94页

作者： May CI van Schalkwyk john maher Department of HIV Medicine Royal Free HospitalRoyal Free London NHS Foundation Trust CAR Mechanics Group Department of Research OncologyGuy’s Hospital CampusKing’s Health Partners Integrated Cancer CentreKing’s College London Department of Immunology Barnet HospitalRoyal Free London NHS Foundation Trust Department of Clinical Immunology and Allergy King’s College Hospital NHS Foundation Trust

Chimeric antigen receptors （CARs） are fusion molecules that may be genetically delivered ex-vivo to T-cells and other immune cell populations, thereby conferring specifcity for native target antigens found on the surface of tumour and other target cell types. Antigen recognition by CARs is neither restricted by nor dependent upon human leukocyte antigen antigen expression, favouring widespread use of this technology across transplantation barriers. Signalling is delivered by a designer endodomain that provides a tailored and target-dependent activation signal to polyclonal circulating T-cells. Recent clinical data emphasise the enormous promise of this emer-ging immunotherapeutic strategy for B-cell malignancy, notably acute lymphoblastic leukaemia. In that context, CARs are generally targeted against the ubiquitous B-cell antigen, CD19. However, CAR T-cell immunotherapy is limited by potential for severe ontarget toxicity, notably due to cytokine release syndrome. Furthermore, effcacy in the context of solid tumours remains unproven, owing in part to lack of availability of safe tumourspecific targets, inadequate CAR T-cell homing and hostility of the tumour microenvironment to immune effector deployment. Manufacture and commercial development encountered with more traditional drug products. Finally, there is increasing interest in the application of this technology to the treatment of non-malignant disease states, such as autoimmunity, chronic infection and in the suppression of allograft rejection. Here, we consider the background and direction of travel of this emerging and highly promising treatment for malignant and other disease types.

关键词： Adoptive T-cell immunotherapy Chimeric antigen receptor Genetic engineering Leukaemia Cancer

Potential of a fucoidan-rich Ascophyllum nodosum extract to reduce Salmonella shedding and improve gastrointestinal health in weaned pigs naturally infected with Salmonella

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Journal of Animal Science and Biotechnology 2022年第4期13卷 1193-1208页

作者： Brigkita Venardou john VO’Doherty Shane maher Marion TRyan Vivian Gath Rajeev Ravindran Claire Kiely Gaurav Rajauria Marco Garcia-Vaquero Torres Sweeney School of Veterinary Medicine University College DublinBelfield Dublin 4Ireland School of Agriculture and Food Science University College DublinBelfield Dublin 4Ireland.

Background:Dietary supplementation with a fucoidan-rich Ascophyllum nodosum extract(ANE),possessing an in vitro anti-Salmonella Typhimurium activity could be a promising on-farm strategy to control Salmonella infection in *** objectives of this study were to:1)evaluate the *** activity of ANE(containing 46.6%fucoidan,18.6%laminarin,10.7%mannitol,4.6%alginate)in vitro,and;2)compare the effects of dietary supplementation with ANE and Zinc oxide(ZnO)on growth performance,Salmonella shedding and selected gut parameters in naturally infected *** was established post-weaning(newly weaned pig experiment)and following regrouping of post-weaned pigs and experimental re-infection with ***(challenge experiment).Results:In the in vitro assay,increasing ANE concentrations led to a linear reduction in *** counts(P0.05).ANE supplementation decreased the Enterobacteriaceae counts compared to the *** counts were also reduced in the ZnO-residual group compared to the control(P<0.05).ANE supplementation decreased the expression of interleukin 22 and transforming growth factor beta 1 in the ileum compared to the control(P<0.05).Conclusions:ANE supplementation was associated with some beneficial changes in the composition of the colonic microbiota,Salmonella sh

关键词： Ascophyllum nodosum Gastrointestinal microbiota Inflammation Pig Salmonella Seaweed extract Zinc oxide

Resolution of Crohn's disease and complex regional pain syndrome following treatment of paratuberculosis

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World Journal of Gastroenterology 2015年第13期21卷 4048-4062页

作者： J Todd Kuenstner William Chamberlin Saleh A Naser Michael T Collins Coad Thomas Dow john M Aitken Stuart Weg Grzegorz Telega Kuruvilla john David Haas Torsten M Eckstein maher Kali Christine Welch Thomas Petrie Department of Pathology Charleston Area Medical CenterCharlestonWV 25304United States Department of Gastroenterology Mountain View Regional HospitalLas CrucesNM 88011United States Burnett School of Biomedical Sciences UCF College of MedicineOrlandoFL 32816United States Department of Pathobiological Sciences the University of Wisconsin School of Veterinary MedicineMadisonWI 53706United States 5 Damon Street Eau ClaireWI 54701United States Otakaro Pathways Ltd. 63 Bibiana StreetChristchurch 8011New Zealand Patients Medical Alternative Pain Management800 Second Avenue Suite 900New York CityNY 10017United States Children’s Hospital of Wisconsin 8915 W.Connell Ave.MilwaukeeWI 53226United States Department of Neurosciences Charleston Area Medical CenterCharlestonWV 25304United States Department of Chemistry University of CharlestonCharlestonWV 25304United States Department of Microbiology Colorado State UniversityImmunology and PathologyCO 80523United States CAMC Clinical Trials Center 3100 Mac Corkle Avenue S.E.Suite 806CharlestonWV 25304United States CAMC Clinical Trials Center CharlestonWV 25304United States AVIcure Bioscience LLC Superior Quartz ProductsBethlehemPA 18020United States

A cohort of family members with various chronic diseases including Crohn's disease, asthma, complex regional pain syndrome, hypothyroidism, type 1 diabetes mellitus, and lymphangiomatosis and/or evidence of infection by Mycobacterium avium subsp. paratuberculosis(MAP) are described in this series of case reports. MAP was cultured from the blood of three members affected by the first five diseases and there was accompanying elevated anti-MAP Ig G in two members. The patient affected by the sixth disease has a markedly elevated anti-MAP titer. The two patients affected by the first four diseases have been treated with a combination of anti-MAP antibiotics and ultraviolet blood irradiation therapy with resolution of the disease symptomatology and inability to culture MAP in post treatment blood samples. These case reports of patients with MAP infections provide supportive evidence of a pathogenic role of MAP in humans.

关键词： Crohn’s disease Complex regional pain syndrome Lym

Review of the role of abdominal imaging in irritable bowel syndrome

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World Journal of Radiology 2018年第11期10卷 143-149页

作者： Richard G Kavanagh john O'Grady Brian W Carey Owen J O'Connor Michael M maher Department of Radiology Cork University Hospital Department of Gastroenterology Cork University Hospital APC Microbiome Ireland University College Cork

The role of radiologic imaging in the investigation of irritable bowel syndrome(IBS) remains a subject of debate and there is some evidence, from recent studies of utilization of imaging in IBS, which focused on associated costs and radiation exposure, that imaging is being used relatively widely in these patients. This review aims to assess current best evidence to accurately define the role of radiologic imaging in IBS patients. Primary and secondary literature searches were performed. Evidence suggests that the lack of "red flag" or alarm features in IBS patients should reassure the clinician that the diagnosis of IBS is correct and United States and United Kingdom guidelines recommend no radiologic imaging for IBS patients if alarm features are not present. In patients presenting with IBS symptoms and alarm features, radiologic testing may be used to exclude an alternative diagnosis and the imaging modality should be chosen based on the most likely alternative diagnosis.

关键词： Abdominal imaging Rome criteria Irritable bowel syndrome

Impact of radiotherapy on the immune landscape in oesophageal adenocarcinoma

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World Journal of Gastroenterology 2022年第21期28卷 2302-2319页

作者： Noel E Donlon Maria Davern Fiona O'Connell Andrew Sheppard Aisling Heeran Anshul Bhardwaj Christine Butler Ravi Narayanasamy Claire Donohoe James J Phelan Niamh Lynam-Lennon Margaret R Dunne Stephen maher Jacintha O'Sullivan john V Reynolds Joanne Lysaght Department of Surgery Trinity Translational Medicine InstituteSt James HospitalDublin D08Ireland

BACKGROUND In the contemporary era of cancer immunotherapy,an abundance of clinical and translational studies have reported radiotherapy(RT)and immunotherapies as a viable option for immunomodulation of many cancer subtypes,with many related clinical trials *** locally advanced disease,chemotherapy or chemoradiotherapy followed by surgical excision of the tumour remain the principal treatment strategy in oesophageal adenocarcinoma(OAC),however,the use of the host immune system to improve anti-tumour immunity is rapidly garnering increased support in the curative *** To immunophenotype OAC patients’immune checkpoint(IC)expression with and without radiation and evaluate the effects of checkpoint blockade on cell *** In the contemporary era of cancer immunotherapy,an abundance of studies have demonstrated that combination RT and IC inhibitors(ICIs)are effective in the immunomodulation of many cancer subtypes,with many related clinical trials *** surgical excision and elimination of tumour cells by chemotherapy or chemoradiotherapy remains the gold standard approach in OAC,the propagation of anti-tumour immune responses is rapidly garnering increased support in the curative *** aim of this body of work was to immunophenotype OAC patients’IC expression with and without radiation and to establish the impact of checkpoint blockade on cell *** study was a hybrid combination of in vitro and ex vivo *** of serum immune proteins was performed by enzyme-linked immunosorbent *** cytometry staining was performed to evaluate IC expression for in vitro OAC cell lines and ex vivo OAC *** viability in the presence of radiation with and without IC blockade was assessed by a cell counting kit-8 *** We identified that conventional dosing and hypofractionated approaches resulted in increased IC expression(PD-1,PD-L1,TIM3,TIGIT)in vitro and ex vivo in *** were two distinct subco

关键词： Oesophageal Cancer Radiotherapy Immunotherapy Immunology Surgery Oncology

Potential of damage associated molecular patterns in synergising radiation and the immune response in oesophageal cancer

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World Journal of Gastrointestinal Oncology 2023年第8期15卷 1349-1365页

作者： Noel E Donlon Maria Davern Andrew Sheppard Fiona O'Connell Brendan Moran Timothy S Nugent Aisling Heeran James J Phelan Anshul Bhardwaj Christine Butler Narayanasamy Ravi Claire L Donohoe Niamh Lynam-Lennon Stephen maher john V Reynolds Joanne Lysaght Cancer Immunology and Immunotherapy Group Department of SurgeryTrinity Translational Medicine Institute and Trinity St James’s Cancer InstituteTrinity College DublinSt James’s HospitalDublin D08Ireland

BACKGROUND There is an intimate crosstalk between cancer formation,dissemination,treatment response and the host immune system,with inducing tumour cell death the ultimate therapeutic goal for most anti-cancer ***,inducing a purposeful synergistic response between conventional therapies and the immune system remains *** release of damage associated molecular patterns(DAMPs)is indicative of immunogenic cell death and propagation of established immune ***,there is a gap in the literature regarding the importance of DAMP expression in oesophageal adenocarcinoma(OAC)or by immune cells *** To investigate the effects of conventional therapies on DAMP expression and to determine whether OAC is an immunogenic *** We investigated the levels of immunogenic cell death-associated DAMPs,calreticulin(CRT)and HMGB1 using an OAC isogenic model of *** expression was also assessed directly using ex vivo cancer patient T cells(n=10)and within tumour biopsies(n=9)both pre and post-treatment with clinically relevant chemo(radio)*** Hypoxia in combination with nutrient deprivation significantly reduces DAMP expression by OAC cells in *** increased frequencies of T cell DAMP expression in OAC patients were observed following chemo-(radio)therapy,which was significantly higher in tumour tissue compared with peripheral *** with high expression of HMGB1 had a significantly better tumour regression grade(TRG 1-2)compared to low *** In conclusion,OAC expresses an immunogenic phenotype with two distinct subgroups of high and low DAMP expressors,which correlated with tumour regression grade and lymphatic *** also identifies DAMPs namely CRT and HMGB1 as potential promising biomarkers in predicting good pathological responses to conventional chemo(radio)therapies currently used in the multimodal management of locally advanced disease.

关键词： Damage associated molecular patterns HMGB1 Calreticulin Oesophageal adenocarcinoma T cells Radiation

New Energy Recovery Pilot Coke Oven Concept and Design

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New Energy Recovery Pilot Coke Oven Concept and Design

EMF Antenna Exposure on a Multilayer Human Head Simulation for Alzheimer Disease Treatments

第十届中国钢铁年会暨第六届宝钢学术年会

作者： Al-dojayli maher Wittich Kirby Quancl john Kruse Richard Brown Rick Cameron Ian Hatch Ltd. Canmet ENERGY/Natural Resources Canada Sun Coke Energy Inc. Arcelor Mittal

Interest in Heat Recovery Coke Oven（HRCO） usage and processes has increased due to their improved environmental performance and ability to use a wide range of metallurgical and non-coking coals. To better understand the HRCO process, the Canadian Carbonization Research Association（CCRA） embarked on a program to construct a pilot-scale HRCO. Hatch completed the design of this unique pilot oven needed to reproduce the industrial scale HRCO heating profile and coal charge, and to minimize coal heating edge effect. Different aspects of the pilot coke oven design concept are presented, including oven geometry and wall insulation design, heating strategy using electric heaters, structural buckstay and oven door designs. Several 2D and 3D thermal transient finite element analyses were carried out to calculate the temperature profile of the coal/coke bed and oven walls during coking, capturing the thermal nonlinear behavior of the coal and oven wall bricks and to size the coal bed insulation for minimum edge heating effect. The structural stability of the oven arches was achieved using a spring loaded buckstay for lateral support and expansion allowance. The pilot oven, referred to as the Energy Recovery Coke Oven（ERCO）, is being constructed at the Canmet ENERGY Laboratory in Ottawa, Canada.

关键词： energy recovery coke oven cokemaking pilot scale design buckstay

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Journal of Biomedical Science and Engineering 2022年第5期15卷 129-139页

作者： Felipe P. Perez Maryam Rahmani john Emberson Makenzie Weber Jorge Morisaki Farhan Amran Syazwani Bakri Akmal Halim Alston Dsouza Nurafifi Mohd Yusuff Amran Farhan James Maulucci maher Rizkalla Department of Medicine Division of General Internal Medicine and Geriatrics Indiana University School of Medicine Indianapolis IN USA Department of Electrical and Computer Engineering Indiana University-Purdue University Indianapolis IN USA Department of Bioengineering University of Illinois at Chicago Chicago IL USA

In this paper, we follow up with our preliminary biological studies that showed that Repeated electromagnetic field stimulation (REMFS) decreased the toxic amyloid-beta (Aβ) levels, which is considered to be the cause of Alzheimer’s disease (AD). The REMFS parameters of these exposures were a frequency of 64 MHz and a Specific absorption rate (SAR) of 0.4 to 0.9 W/Kg in primary human neuronal cultures. In this work, an electromagnetic field (EMF) model was simulated using high-frequency simulation system (HFSS/EMPro) software. Our goal was to achieve the EM parameters (EMF Frequency and SAR) required to decrease the toxic Aβ levels in our biological studies in a simulated human head. The simulations performed here will potentially lead to the successful development of an exposure system to treat Alzheimer’s disease patients. A popular VFH (very high frequency) patch microstrip antenna system was considered in the study. The selection was based on simple and easy construction and appropriateness to the VHF applications. The evaluation of the SAR and temperature distribution on the various head layers, including skin, fat, dura, the cerebrospinal (CSF), and grey matter, brain tissues, were determined for efficacy SAR and safety temperature increase on a simulated human head. Based on a current pulse of 1 A peak current fed to the antenna feeder, a maximum SAR of 0.6 W/Kg was achieved. A range of 0.4 to 0.6 SAR was observed over the various layers of the simulated human head. The initial design of the antenna indicated an antenna size in the order of 1 m in length and width, suggesting a stationary practical model for AD therapy. Future direction is given for wearable antenna and exposure system, featuring high efficiency and patient comfort.

关键词： EM Antenna Brain Tissues Simulation Alzheimer