Clinical application of autologous technetium-99m-labelled eosinophils to detect focal eosinophilic inflammation in the lung.

This is the final version of the article. It first appeared from the BMJ Group via http://dx.doi.org/10.1136/thoraxjnl-2015-207156The detection of focal eosinophilic inflammation by non-invasive means may aid the diagnosis and follow-up of a variety of pulmonary pathologies. All current methods of detection involve invasive sampling, which may be contraindicated or too high-risk to be performed safely. The use of injected autologous technetium-99m (Tc-99m)-labelled eosinophils coupled to single-photon emission computed tomography (SPECT) has been demonstrated to localise eosinophilic inflammation in the lungs of a patient with antineutrophil cytoplasmic antibody-positive vasculitis. Here, we report on the utility of this technique to detect active eosinophilic inflammation in a patient with focal lung inflammation where a biopsy was contraindicated.The authors thank all the staff at the Department of Nuclear Medicine at Addenbrooke’s Hospital and the Wellcome Trust Clinical Research Facility, Cambridge; Cambridge Biomedical Research Centre Core Biochemistry Assay Laboratory; and the National Institute for Health Research, through the Comprehensive Clinical Research Network. This work was supported by Asthma-UK [08/11], the Medical Research Council [grant number MR/J00345X/1], the Wellcome Trust [grant number 098351/Z/12/Z], and Cambridge NIHR Biomedical Research Centre. Written informed consent was obtained in accordance with the Declaration of Helsinki. The study was approved by Cambridgeshire Research Ethics Committee (09/H0308/119) and the Administration of Radioactive Substances Advisory Committee of the United Kingdom (83/3130/25000)

A holistic approach to network security in OGSA-based grid systems

Grid computing technologies facilitate complex scientific collaborations between globally dispersed parties, which make use of heterogeneous technologies and computing systems. However, in recent years the commercial sector has developed a growing interest in Grid technologies. Prominent Grid researchers have predicted Grids will grow into the commercial mainstream, even though its origins were in scientific research. This is much the same way as the Internet started as a vehicle for research collaboration between universities and government institutions, and grew into a technology with large commercial applications. Grids facilitate complex trust relationships between globally dispersed business partners, research groups, and non-profit organizations. Almost any dispersed “virtual organization” willing to share computing resources can make use of Grid technologies. Grid computing facilitates the networking of shared services; the inter-connection of a potentially unlimited number of computing resources within a “Grid” is possible. Grid technologies leverage a range of open standards and technologies to provide interoperability between heterogeneous computing systems. Newer Grids build on key capabilities of Web-Service technologies to provide easy and dynamic publishing and discovery of Grid resources. Due to the inter-organisational nature of Grid systems, there is a need to provide adequate security to Grid users and to Grid resources. This research proposes a framework, using a specific brokered pattern, which addresses several common Grid security challenges, which include: Providing secure and consistent cross-site Authentication and Authorization; Single-sign on capabilities to Grid users; Abstract iii; Underlying platform and runtime security, and; Grid network communications and messaging security. These Grid security challenges can be viewed as comprising two (proposed) logical layers of a Grid. These layers are: a Common Grid Layer (higher level Grid interactions), and a Local Resource Layer (Lower level technology security concerns). This research is concerned with providing a generic and holistic security framework to secure both layers. This research makes extensive use of STRIDE - an acronym for Microsoft approach to addressing security threats - as part of a holistic Grid security framework. STRIDE and key Grid related standards, such as Open Grid Service Architecture (OGSA), Web-Service Resource Framework (WS-RF), and the Globus Toolkit are used to formulate the proposed framework

Lesson of the month: novel method to quantify neutrophil uptake in early lung cancer using SPECT-CT

Neutrophils play an important role in the lung tumour microenvironment. We hypothesised that radiolabelled neutrophils coupled to single-photon emission CT (SPECT) may non-invasively quantify neutrophil uptake in tumours from patients with non-small cell lung cancer. We demonstrated increased uptake of radiolabelled neutrophils from the blood into tumours compared with non-specific uptake using radiolabelled transferrin. Moreover, indium-111-neutrophil activity in the tumour biopsies also correlated with myeloperoxidase (MPO)-positive neutrophils. Our data support the utility of imaging with In-111-labelled neutrophils and SPECT-CT to quantify neutrophil uptake in lung cancer

In vivo imaging reveals increased eosinophil uptake in the lungs of obese asthmatic patients.

To The Editor: Eosinophils play an important pathogenic role in pulmonary and systemic conditions including eosinophilic asthma and eosinophilic granulomatosis with polyangiitis.1,2 While progress has been made in understanding the mechanisms responsible for the activation of these cells, existing biomarkers of eosinophilic inflammation are indirect and/or invasive and do not always correlate with tissue eosinophilia. Hence, there is a need to develop non-invasive biomarkers of tissue eosinophilia. We have previously demonstrated the capacity of SPECT (single photon emission computed tomography) to quantify neutrophil uptake into the lungs of COPD patients.3 We sought to determine whether this methodology could be used to quantify eosinophil kinetics and pulmonary uptake, which may differ amongst diseases characterized by eosinophilic inflammation. In particular, the role of the eosinophil in asthma with obesity, a distinct asthma endotype associated with increased severity,4 is controversial. We hypothesized that injection of radiolabeled eosinophils, coupled with SPECT/CT, would reveal changes in eosinophil kinetics in patients compared to healthy volunteers.This work was supported by Asthma UK [08/11], the Medical Research Council [grant number MR/J00345X/1], the Wellcome Trust [grant number 098351/Z/12/Z], Cambridge NIHR Biomedical Research Centre, Wellcome Trust Senior Fellowship (to CEB) [grant number WT082265], AirPROM 7th EU Framework grant and Leicester NIHR Biomedical Research Centre

Suppression of Eosinophil Integrins Prevents Remodeling of Airway Smooth Muscle in Asthma

Background: Airway smooth muscle (ASM) remodeling is an important component of the structural changes to airways seen in asthma. Eosinophils are the prominent inflammatory cells in asthma, and there is some evidence that they contribute to ASM remodeling via released mediators and direct contact through integrin-ligand interactions. Eosinophils express several types of outer membrane integrin, which are responsible for cell-cell and cell-extracellular matrix interactions. In our previous study we demonstrated that asthmatic eosinophils show increased adhesion to ASM cells and it may be important factor contributing to ASM remodeling in asthma. According to these findings, in the present study we investigated the effects of suppression of eosinophil integrin on eosinophil-induced ASM remodeling in asthma. Materials and Methods: Individual combined cell cultures of immortalized human ASM cells and eosinophils from peripheral blood of 22 asthmatic patients and 17 healthy controls were prepared. Eosinophil adhesion was evaluated using eosinophil peroxidase activity assay. Genes expression levels in ASM cells and eosinophils were measured using quantitative real-time PCR. ASM cell proliferation was measured using alamarBlue® solution. Eosinophil integrins were blocked by incubating with Arg-Gly-Asp-Ser peptide. Results: Eosinophils from the asthma group showed increased outer membrane α4β1 and αMβ2 integrin expression, increased adhesion to ASM cells, and overexpression of TGF-β1 compared with eosinophils from the healthy control group. Blockade of eosinophil RGD-binding integrins by Arg-Gly-Asp-Ser peptide significantly reduced adhesion of eosinophils to ASM cells in both groups. Integrin-blocking decreased the effects of eosinophils on TGF-β1, WNT-5a, and extracellular matrix protein gene expression in ASM cells and ASM cell proliferation in both groups. These effects were more pronounced in the asthma group compared with the control group. Conclusion: Suppression of eosinophil-ASM interaction via RGD-binding integrins attenuates eosinophil-induced ASM remodeling in asthma. Trial Registration: ClinicalTrials.gov Identifier: NCT02648074

Lesson of the month: novel method to quantify neutrophil uptake in early lung cancer using SPECT-CT

Neutrophils play an important role in the lung tumour microenvironment. We hypothesised that radiolabelled neutrophils coupled to single-photon emission CT (SPECT) may non-invasively quantify neutrophil uptake in tumours from patients with non-small cell lung cancer. We demonstrated increased uptake of radiolabelled neutrophils from the blood into tumours compared with non-specific uptake using radiolabelled transferrin. Moreover, indium-111-neutrophil activity in the tumour biopsies also correlated with myeloperoxidase (MPO)-positive neutrophils. Our data support the utility of imaging with In-111-labelled neutrophils and SPECT-CT to quantify neutrophil uptake in lung cancer