tbuckley/cabot-search huggingface dataset:
OP0060 Beta2GPI and TLR4 interaction on endothelial cells: A bridge between innate and adaptive immunity in APS
Authors: P.L. Meroni, E. Raschi, C. Chighizola, C. Grossi, N. Ronda, R. Gatti, M.O. Borghi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Beta2 glycoprotein I has been suggested as LPS scavenger protein and the complex b2GPI-LPS is uptaken by monocytes. <i>In vivo</i>/<i>in vitro</i> indirect data suggest the role of Toll Like Receptor (TLR) in aPL-mediated endothelial cell (EC) activation. Furthermore TLR4 has recently been suggested as a component of a multi-protein complex on the EC surface involved in beta2GPI/anti- beta2GPI antibody-induced signalling pathway. However, what is/are the molecule(s) eventually involved in this interaction is still an open question. <h3>Objectives</h3> To investigate the role of endothelial TLR4 in beta2GPI/anti- beta2GPI antibody interaction. <h3>Methods</h3> i) direct binding and internalization of beta2GPI was evaluated by confocal microscopy in living CHO/TLR4 cells; ii) anti- beta2GPI antibody binding and activation (as adhesion molecule up-regulation) were investigated in TLR4- and AnnexinA2-silenced HUVEC. Receptor expression was evaluated both at mRNA and protein level by real time RT-PCR and western blotting, respectively. <h3>Results</h3> incubation of living CHO/TLR4 cells, but not TLR4-negative CHO Mock cells, with beta2GPI-FITC resulted in a strong membrane signal shortly after the addition of the protein. After about 15 min the fluorescent signal was detected within the cytoplasm as granules, progressively more abundant in the following 20-30 min of observation, when membrane signal faded. Immunofluorescence studies on fixed cells showed the interaction between beta2GPI and TLR4 both on the cell membrane and in intracytoplasmic granules. beta2GPI/LPS complex induced EC activation evaluated as ELAM upregulation, while LPS alone or in combination with BSA had no effect. TLR4 and AnnexinA2 silencing significantly down-regulated mRNA and protein expression in HUVEC. Both <i>tlr4</i> and <i>annexinA2</i> siRNA transfection strongly inhibited anti-beta2GPI antibody binding to HUVEC. On the other hand aPL-induced ELAM/ICAM-1 up-regulation was significantly decreased in <i>tlr4</i> but not <i>annexinA2</i> silenced cells. This observation is in line with the fact that AnnexinA2 lacks an intracytoplasmic tail and needs co-receptors to induce cell signalling. No synergic effects were observed in tlr4 and annexinA2 simultaneously silenced HUVEC. <h3>Conclusions</h3> Our findings strongly support the binding of beta2GPI to TLR4 on EC offering the rationale for the TLR4 involvement in EC signalling and activation by aPL. At the same time, the interaction of beta2GPI with LPS and in turn with TLR4 may represent the molecular basis to explain the "two hit" theory in APS. <h3>Disclosure of Interest</h3> None Declared
S108 The Effect of an Interdisciplinary Rehabilitation Programme on Daily Physical Activity For Patients with Less Advanced COPD in a Primary Care Setting: A Systematic Review
Authors: G Leemans, K Ides, D Vissers, P Van Royen, W De Backer
Journal: Thorax (2012)

<h3>Introduction</h3> The natural course of COPD is characterised by progressive airflow limitation and complicated by the development of systemic consequences and co-morbidities. Daily physical inactivity (DPA) is believed to mediate those systemic consequences or co-morbidities. Recent research demonstrates that even in the early stages of COPD, DPA plays a role in developing systemic consequences and co-morbidities. Hence, interventions that enhance or maintain DPA in this population, such as pulmonary rehabilitation (PR), should be considered. Due to the low accessibility and high cost of PR in a specialised care setting, rehabilitation in primary care could be an added value for patients with less advanced COPD. related problems. Despite the widespread believe in the benefits of PR in a primary care setting, it remains unclear if such PR programmes are (cost) effective for patients with less advanced COPD <h3>Objective</h3> To evaluate data from clinical trials assessing the effect of PR in primary care for patients with less advanced COPD on DPA, exercise capacity (EC) and quality-of-life (QoL). <h3>Methods</h3> The electronic databases PEDro, CENTRAL, Pubmed and EMBASE were searched. Only randomised and controlled clinical trials were eligible for inclusion, provided they investigated the effects of interdisciplinary PR in primary care for patients with less advanced COPD (GOLD I-II). Independent data extraction was performed by two authors. Risk of bias was rated using the Cochrane Collaboration ‘Risk of bias’ tool. Primary outcome is the level of DPA, secondary outcomes are EC and QoL. <h3>Results</h3> Eight studies were found and methodological quality is displayed in table 1. One study objectively measured DPA by a pedometer and showed a significant improvement in DPA. EC was significantly improved in 7/8 studies. QoL is measured in all 8 studies, 3/8 had a significant improvement and two revealed to have clinical relevant effect on QoL. <h3>Conclusions</h3> PR in primary care for patients with less advanced COPD improves EC and QoL and could be beneficial in improving DPA. Since recent insights in the systemic burden of COPD and the role of DPA in this matter, future research must focus on the transfer of PR benefits to DPA, including a cost-effective analysis.
P186 Intrathoracic Lymph Node Tuberculosis - A Comprehensive Clinical Description
Authors: K. Kow, D. Connell, A. Singanayagam, D. A. Dafydd, H. Jarvis, M. O'Donoghue, M. Wickremasinghe, A. Lalvani, O. Kon
Journal: Thorax (2014)

<h3>Background</h3> Intrathoracic lymph node tuberculosis (ITLNTB) is an extra-pulmonary manifestation of tuberculosis (TB) and a predominant feature of primary TB in children. Historical literature supports the key role of lymph nodes in tuberculosis pathogenesis yet there is a paucity of literature describing ITLNTB in adults. <h3>Methods</h3> This study comprehensively reviewed the clinical, radiological and pathological features of ITLNTB from 2009–2012 at a busy urban tuberculosis clinic. <h3>Results</h3> 113 adult patients with ITLNTB were identified between 2009–2012. Patients were usually male, with a mean age of 41.5 ± 15.8 years and mostly from White, Black-African or Indian ethnic groups. 86% were non-UK born and most presented within 5–10 years of entering the country. 43% were asymptomatic. A subgroup of patients who were mycobacterial culture positive on endobronchial ultrasound sampling (EBUS) of intrathoracic lymph nodes were identified as patients with definite mycobacterial infection of the lymph nodes (n = 27). Comparisons between symptomatic and asymptomatic groups in the whole cohort and EBUS culture positive subgroup demonstrated significant associations between symptoms and disease dissemination (p = 0.0002 and p = 0.01 respectively); and symptoms and cytological response in the lymph nodes (p = 0.02 and p = 0.01 respectively), suggesting the presence of a spectrum of disease reflected in congruent clinical and pathological responses (Table 1). Comparisons between disease sites affected also showed a significant association between host response in the lymph nodes and disease dissemination (p = 0.006). The presence of radiological necrosis, number of affected nodal stations, and largest node size were significantly greater in symptomatic patients in the whole cohort; with a similar trend observed in the EBUS culture positive subgroup. In the EBUS culture positive subgroup, asymptomatic patients were identified significantly earlier following entry to the UK (p = 0.01). <h3>Discussion</h3> This study provides the first comprehensive clinical description of ITLNTB in adults. There is a spectrum of disease based on clinical severity, disease phenotype and diagnostic and radiological findings. Host response in the lymph nodes is reflected by both symptom manifestation and disease dissemination, implicating the lymph nodes in a critical role in the natural history of TB infection. Finally, a subclinical phenotype was identified, suggesting an early stage of disease progression in TB.
856 CLINICAL SIGNIFICANCE OF DRUG–DRUG-INTERACTIONS IN THE ERA OF DIRECT ACTING ANTIVIRAL AGENTS AGAINST HEPATITIS C – A REAL-WORLD EXPERIENCE
Authors: B. Maasoumy, K. Port, A.A. Markova, B. Calle Serrano, L. Sollik, M.P. Manns, M. Cornberg, H. Wedemeyer
Journal: Journal of Hepatology (2013)
Biliary and Liver Abscesses Demonstrated with Tc-99m DISIDA and Ga-67 Imaging
Authors: TZU-CHEN YEN, MING-FONG TSAI, KAI-YUAN TZEN
Journal: Clinical Nuclear Medicine (1998)

A 76-year-old woman with fever of unknown origin had a cholecystectomy 2 months earlier. Blood and pus cultures from percutaneous transhepatic drainage showed Staphylococcus aureus. Immediately after drainage, both Tc-99m DISIDA and Ga-67 imaging were performed. Tc-99m DISIDA cholescintigraphy showed stasis of radiotracer at the dome of the right hepatic lobe and in the biliary tree. The Ga-67 scan revealed multiple focal areas of increased radiotracer accumulation in both hepatic lobes. Under both drainage and antibiotic treatment, the patient was discharged in stable condition.
SP0012 Magnitude and Sites of Urate Crystal Deposits and Its Evaluation
Authors: N. Dalbeth
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Gout is a chronic disease of monosodium urate (MSU) crystal deposition. A variety of measurement techniques are used to assess the burden of MSU crystal deposition, including physical measurement and advanced imaging methods. Recent imaging studies, particularly using ultrasonography (US) and dual energy computed tomography (DECT), have demonstrated the extent and patterns of MSU crystal deposition in a way that is not appreciated by physical examination alone. In particular, the close proximity of MSU crystals with articular cartilage is clearly visualised as the double contour sign on US. The frequent involvement of tendons can also be visualised using these imaging techniques. The close relationship between structural joint disease and MSU crystals visualised by DECT provides further rationale for effective urate-lowering therapy in people with gout. <h3>Disclosure of Interest</h3> N. Dalbeth Consultant for: AstraZeneca, Takeda, Conflict with: Savient, Menorini <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6126
Genetic Susceptibility to Venous Thrombosis
Authors: Uri Seligsohn, Aharon Lubetsky
Journal: New England Journal of Medicine (2001)

The annual incidence of venous thrombosis, one of the leading causes of mortality and morbidity, increases from 1 per 100,000 during childhood to 1 per 100 in old age.1 In this article we will discuss conditions involving a genetic predisposition to venous thrombosis. The clinical relevance of this topic has increased with new evidence of the high prevalence of mutant genes that increase susceptibility to thrombosis.Of the three mechanisms of thrombosis defined by Virchow in the 19th century — vessel-wall injury, stasis, and “changes in the composition of blood” (hypercoagulability) — the last two predominate in venous thrombosis. Hypercoagulability . . .
FÍSTULA BILIAR COMPLEJA POST HEPATECTOMÍA: ¿ES EFECTIVO EL TRATAMIENTO ENDOSCÓPICO?
Authors: M Alburquerque Miranda, M Figa Francesch, J Figueras Felip, S Lopez Ben, M Pérez Contreras, F González-Huix Llado
Journal: Endoscopy (2013)

Introducción: Se desconoce si la CPRE es igualmente efectiva en fístulas biliares post hepatectomía (FBPH) y post colecistectomia (FBPC). Objetivo: Comparar la eficacia de la CPRE en FBPH vs. FBPC. Método: Período: Enero 2002 – octubre 2012. Registro prospectivo de pacientes con fístula biliar post quirúrgica (FBPQ) tratados por CPRE. Incluimos indicación y tipo de cirugía, características de las FBPQ: localización, débito y hallazgos asociados (estenosis, biloma/absceso, coledocolitiasis), tratamiento endoscópico y Resultados: Confirmamos cierre de fístula por CPRE y/o clínicamente. Para el análisis usamos el programa SPSS 15.0. Resultados: Entre 3785 CPREs hubo 67 FBPQ (1,7%): 51 FBPC y 16 FBPH. Edad: 64,79 ± 15 años. Mujeres: 20 (29,9%). En FBPC la indicación quirúrgica fue colelitiasis (100%); en FBPH fuerón: metastásis hepáticas 12 (75%), hidatidosis hepática: 2 (12,5%), traumatismo: 1 (6,25%) y cáncer de vesícula: 1 (6,25%). Muñón cístico y colédoco/hepático común fuerón localizaciones más frecuentes de las FBPC: 58,82 vs. 0,00% (p = 0,000) y 25,49 vs. 18,75% (p = 0,000), respectivamente. En FBPH, los conductos intrahepáticos primarios y secundarios fueron los más frecuentes: 31,25 vs. 5,88% (p = 0,000) y 37,5 vs. 5,88% (p = 0,000), respectivamente. En FBPC el éxito diagnóstico fue mayor que en FBPH: 96,08 vs. 87,5% (p = 0,000). No hubo diferencia significativa entre el débito. Estenosis (57,14 vs. 22%, p = 0,000) y biloma/absceso (87,5 vs. 26%, p = 0,000) se asociaron con mayor frecuencia a FBPH que coledocolitiasis (7,14 vs. 48%, p = 0,000). En tratamiento endoscópico, no hubo diferencias: papilotomía más colocación de prótesis fue el procedimiento más frecuente (Éxito técnico > 93%). La eficacia de la CPRE en FBPH fue mucho menor que en FBPC: 25 vs. 84,31%, p = 0,000. La tasa de complicaciones fue similar. Conclusiones: La eficacia de la CPRE en FBPH es mucho menor que en FBPC. Ello, relacionado con la mayor complejidad de las FBPH: frecuentemente intrahepáticas y asociadas a estenosis y biloma/abscesos.
Tc-99m Colloid and Ga-67 Imaging of Splenic Inflammatory Pseudotumor
Authors: Kazuyoshi Suga, Kimiko Miura, Norihiko Kume, Akiko Hara, Naofumi Matsunaga, Akira Tangoku, Masaaki Oka
Journal: Clinical Nuclear Medicine (1999)

Splenic inflammatory pseudotumor is extremely rare and may mimic splenic neoplasms, such as lymphomas or hamartomas, clinically and radiologically. A case of a surgically proved splenic inflammatory pseudotumor is presented in which Tc-99m colloid SPECT and Ga-67 scintigraphy characterized the changes in the spleen, but the findings of ultrasound and unenhanced CT and MRI were nonspecific. This report indicates the utility of radionuclide imaging for diagnosing splenic inflammatory pseudotumor.
Induction of Fetal Hemoglobin in the Presence of Increased 3-Hydroxybutyric Acid Associated with β-Ketothiolase Deficiency
Authors: Renzo Galanello, Antonio Cao, Nancy Olivieri
Journal: New England Journal of Medicine (1994)

To the Editor: Elevated levels of fetal hemoglobin may diminish the severity of the β-hemoglobinopathies sickle cell disease and β-thalassemia. In β-thalassemia, this effect is related to a reducti...
We need “healthy towns” across all of England
Authors: Michael Craig Watson, Sylvia Tilford
Journal: BMJ (2016)

We are pleased that an estimated 170 000 residents will be involved in a new healthy towns’ project because we believe that some of the country’s most urgent health challenges—such as mental health issues, obesity, and physical inactivity—can be influenced by positive changes to the environment.1 However, in terms of the current …
Cystatin F Ensures Eosinophil Survival by Regulating Granule Biogenesis
Authors: Stephen P. Matthews, Sarah J. McMillan, Jeff D. Colbert, Rachel A. Lawrence, Colin Watts
Journal: Immunity (2016)

Eosinophils are now recognized as multifunctional leukocytes that provide critical homeostatic signals to maintain other immune cells and aid tissue repair. Paradoxically, eosinophils also express an armory of granule-localized toxins and hydrolases believed to contribute to pathology in inflammatory disease. How eosinophils deliver their supporting functions while avoiding self-inflicted injury is poorly understood. We have demonstrated that cystatin F (CF) is a critical survival factor for eosinophils. Eosinophils from CF null mice had reduced lifespan, reduced granularity, and disturbed granule morphology. In vitro, cysteine protease inhibitors restored granularity, demonstrating that control of cysteine protease activity by CF is critical for normal eosinophil development. CF null mice showed reduced pulmonary pathology in a model of allergic lung inflammation but also reduced ability to combat infection by the nematode Brugia malayi. These data identify CF as a "cytoprotectant" that promotes eosinophil survival and function by ensuring granule integrity.Video AbstracteyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiI4NTlmMDA2OWJmNDM3NmI4ODlkMmNmZWYwMGY5N2M2OSIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjc4Nzc5NzcyfQ.FyI5iYs-7THdV3G06y00yQ_FptqdjUH6qF6guw2SSGZLG16ZTyf78WLdJJqCuNihwzfQgAezvy4cG0Z23B9zfSD_3UGW1m2HHStbKy_tLvT33HBtgvDAhfX4L_tmZKgifi0257ZiqeDE1ewn9joROoDK0yaYkmO0YH1RGHVTmgowhHsu_IsOIAhRnAjvXPATSuC2smDKNBG7gbJbuat24emvFMSvR2k9_1Hlg57G_Dadcn46qmelFImYoMiC-kUgTTzlc2WGd55zNcwbJBW46GCsOxGFFJxpR_QhxB1NywHPDvddiHYbqx8fTTB4D9I49DM0uJ_UBAWyIKpuB9Uhjg(mp4, (3.05 MB) Download video
Abstract 5228: Multi-modal <i>in vivo</i> imaging of breast cancer cells expressing dual reporters
Authors: Konnie Urban, Angel Ang, Chaincy Kuo, Kevin Francis, Raj Singh, Mark Roskey, Jae-Beom Kim
Journal: Cancer Research (2011)

Abstract We previously engineered tumor cell lines with bioluminescent markers and fluorescent proteins for whole animal imaging. In addition to conventional non-invasive tumor growth detection, these cells when harvested from animals can also be used to analyze cell-cell interactions by immunohistochemistry. Moreover, fluorescent cells can be isolated using fluorescent activated cell sorting (FACS) for gene expression profiling. In this study, we used a mouse mammary gland tumor cell line 4T1 that was labeled with firefly luciferase and tdTomato fluorescent protein (4T1-luc2-tdTomato). The generated cell line was tested for in vitro signal stability with respect to bioluminescence and fluorescence prior to injection into the animals. Tumor cells were implanted subcutaneously and monitored for tumor development by acquisition of bioluminescent and fluorescent images. In a separate study, 4T1-luc2-tdTomato cells were implanted orthotopically into mammary fat pads. Tumor growth was monitored and signals from the implantation sites were reconstructed into three dimensional images. In order to non-invasively detect bone metastases by 4T1-luc2-tdTomato cells, we applied both microCT and optical imaging. For this, an interchangeable imaging platform between an optical imager and microCT machine was developed. 4T1-luc2-tdTomato cells were injected into nu/nu mice by intracardiac injection. Bioluminescent imaging was performed immediately to verify the injection of cells into the left ventricle. Fluorescent signals were not detected, likely due to the small number of cells in the secondary tumor sites. Animals demonstrating substantial whole body bioluminescence were selected for further monitoring until post injection day 9. We found that bioluminescent signals were located in the knee joint regions. For these animals, bioluminescent and X-ray images were also taken without changing the positions of the animals using the interchangeable platform. Bioluminescent images in the knee joints were reconstructed using a diffused luminescence imaging tomography algorithm. These images were then co-registered with microCT images. The results showed that bioluminescent signals were colocalized within the joint area obtained by microCT. Moreover, high resolution images of the joints from these mice revealed bone erosion in the tibia induced by 4T1-luc2-tdTomato cells. These findings demonstrate that multimodal imaging can pinpoint the tumor lesions non-invasively. In addition, low dose microCT imaging can be used to acquire high resolution skeletal images longitudinally without inducing adverse effects on the animals. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5228. doi:10.1158/1538-7445.AM2011-5228
Bile Peritonitis Complicating Needle Biopsy of Liver
Authors: Davis T. Gallison, David Skinner
Journal: New England Journal of Medicine (1950)

ASPIRATION or punch needle biopsy of the liver is a recognized diagnostic procedure. In research in recent years, in an attempt to correlate liver function and histopathology, this method of obtaining biopsy material has become increasingly popular.That the procedure is not without some danger has been recognized by almost all groups, but the complications have been few enough so as not to dishearten the majority. The observation of Kinsell et al.1 that the blind approach to a highly vascular, bile-secreting, intraperitoneal organ can never be devoid of risk is indeed candid. Some groups, such as Mateer and his associates, . . .
Methemoglobinemia and Topical Pharyngeal Anesthesia
Authors: Franz C. Aepfelbacher, Patrick Breen, Warren J. Manning
Journal: New England Journal of Medicine (2003)

Cough and Bronchial Responsiveness in Firefighters at the World Trade Center Siteto the editor: Prezant and colleagues (Sept.12 issue) 1 describe cough and bronchial responsiveness in firefighters at the World Trade Center.They attribute the observed sinusitis, bronchial hyperreactivity, and bronchial responsiveness to dust inhalation.Although the dust had settled after six days, the peak incidence of disability occurred in late October and early November.This points to an illness with two phases, with World Trade Center cough representing a late-phase reaction.If this is to be an adequate explanation, we must account for sinusitis, bronchial hyperreactivity, and bronchial responsiveness among healthy firefighters exposed to the dust from the collapsed buildings.Aspergillus is known to cause allergic bronchopulmonary aspergillosis and allergic sinusitis.A well-known risk factor is building demolition. 2 The incubation period ranges between 36 hours and three months. 3 The thickening of the bronchial walls seen by Prezant and colleagues on computed tomography (CT) is compatible with this diagnosis. 4 The decrease in forced vital capacity (FVC) and forced expiratory volume in one second (FEV 1 ), with the stable FEV 1 /FVC ratio and normal carbon monoxide diffusing capacity, is also consistent with a diagnosis of pulmonary aspergillosis. 4 Findings on bronchoscopy, findings on examination of bronchoalveolar-lavage specimens, and specific IgE test results are not reported; these tests could have helped establish the diagnosis.Aspergillus-specific IgE should be sought in persons with World Trade Center cough, and polymerase-chain-reaction (PCR) analysis to detect aspergillus should be performed in available sputum or bronchoalveolar-lavage specimens.
FDG Positron Emission Tomographic Imaging of Thoracic Castleman’s Disease
Authors: Madhusudhan P Reddy, Michael M Graham
Journal: Clinical Nuclear Medicine (2003)

From the Departments of Radiology (Division of Nuclear Medicine), University of Iowa Hospitals and Clinics,† Iowa City, Iowa, and Rush Presbyterian St. Luke’s Medical Center,* Chicago, Illinois Received for publication September 27, 2001. Revision accepted October 7, 2002. Reprint requests: Michael M. Graham, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, Iowa 52242-1077. E-mail: [email protected]
State Bite Age Distribution of Breast Cancer Cases
Authors: B. F. Hankey
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article State Bite Age Distribution of Breast Cancer Cases Get access Benjamin F. Hankey, Sc.D. Benjamin F. Hankey, Sc.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 19, 5 October 1994, Page 1441, https://doi.org/10.1093/jnci/86.19.1441 Published: 05 October 1994