tbuckley/cabot-search huggingface dataset:
P466Coronary vascular smooth muscle cell proteins in the hypercholesterolemic swine: plaque-related markers of accelerated atherogenesis
Authors: S Rocchiccioli, A Cecchettini, N Ucciferri, F Viglione, L Citti, O Parodi, MG Trivella, G Pelosi
Journal: Cardiovascular Research (2014)

Purpose: A major drawback in atherogenesis research is the difficulty of investigating early phase of disease in the clinical context. A high-cholesterol diet animal model of coronary artery disease was exploited in order to characterized by histomorphometry early stages of disease and to identify plaque-related markers of accelerated atherogenesis. The comparison of the secretomes from atherosclerotic and healthy coronaries led to the identification of differentially released proteins. Histology and immunohistology validated the proteomics results, allowing the tissue localization of interesting factors and correlating the released proteins with the lesion stage. Methods: Histological characterization of segmented main coronary arteries was performed in high cholesterol (HCD) and standard diet treated (SD) farm pigs and histomorphometry indexes (intimal thickness and lesion area wall percent) of all lesions were estimated. Right coronary artery (RCA) segments from HCD and SD animals were incubated for 24 hrs in serum-free medium. Released proteins were digested with trypsin and analysed by HPLC coupled with mass spectrometry. Immunohistology was performed for the most relevant differentially expressed proteins. Results: Atherosclerotic lesions (from fatty streaks to fibrofatty atheromas) of all 3 main coronary arteries have been observed in HCD group, with intimal thickening of 0,52±0,38 mm and lesion area of 40 ± 26%. Proteomics analysis of secreted factors identified 200 actively secreted proteins, of which, 10 were up-released as compared to SD and 6 were significantly related to morphometric indexes of ATS severity and burden. Among these, Chitinase-3-like protein 1 was validated by immunostaining. This last co-localizes with alpha-SM actin showing a distinctive tissue distribution that resulted significantly correlated to secretome expression both in early (fatty streaks) and atheromatous lesions. Conclusions: In the accelerated coronary atherogenesis swine model, tissue factors related to ATS stages and overall burden have been identified. These factors are strictly linked to VSMC phenotype changes and cell activation, thus they may be regarded as specific lesion-related molecules and are exploitable as potential biomarkers of atherosclerosis progression.
Side-by-side dual echoendoscope and ultrathin endoscopy to facilitate EUS-ERCP biliary rendezvous
Authors: T. Baron, M. Levy
Journal: Endoscopy (2012)

Endoscopic ultrasound (EUS)-guided biliary access is performed when standard endoscopic retrograde cholangiopancreatography (ERCP) techniques fail and for inaccessible papillae [1]. EUS rendezvous requires passage of the guide wire into the duodenum, with subsequent removal of the echoendoscope and insertion of a second endoscope to grasp the distal end of the wire. During echoendoscope withdrawal, the position of the guide wire is tenuous. We describe EUS rendezvous whereby passage of a small-caliber endoscope alongside the echoendoscope stabilizes the position of the guide wire.
AB0813 Increased FASCII thickness in inflammatory myopathies: An ultrasound study:
Authors: K. Bhansing, M. van Rosmalen, M. Vonk, S. Pillen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Inflammatory myopathies (IM) are a multisystem diseases characterized by inflammation of skeletal muscles and skin. The skeletal muscle fascia forms a part of the muscle. In this study we investigated if inflammation of the fascia is present in inflammatory myopathies and whether this can be detected by ultrasound. <h3>Objectives</h3> To assess fascia thickness of the deltoid and vastus lateralis (VL) muscles in healthy controls and IM patients. <h3>Methods</h3> Healthy controls (n=54) and IM patients (n=9), diagnosed according to the Bohan and Peter criteria, were included. All scans were made in the transverse plane, unilateral with the Zonare Zone ultrasound device with a broad band linear 12-5 MHz transducer. The deep and superficial fascia of the VL and the superficial fascia of the deltoid muscle were measured at standardized anatomically defined location corresponding to the largest diameter of the muscle belly. Fascia thickness was measured with electronic calipers using a 2x magnification. They were placed at a interval of 0.25 cm with a maximum of 12 per scan. Fascii thickness of the healthy controls was correlated to age, height, weight and sex using a spearman's rho correlation. Reference values were calculated. An unpaired Student's t-test was used to determine the difference between IM patients and controls. <h3>Results</h3> The median age of healthy controls was 52 years (range 22-87; 32 females) of IM patients 44 years (range 20-64; 5 females). The IM group consisted of n=5 dermatomyositis and n=4 polymyositis patients, the median disease duration was 3.3 years (range 1-23). The intraobserver ICC's were 0.6 (deltoid), 0.58 (superficial fascia VL) and 0.8 (deep fascia VL). Interobserver ICC's were 0.29, 0.49 and 0.86. Mean muscle fascia thickness in healthy controls was 0.54 mm of the deltoid muscle and 1.28 and 1.33 mm of the superficial and deep fascii of the vastus lateralis muscle respectively (table 1). There was a small but significant increase of the deep fascia thickness of the VL with increasing weight (r =0.38). Age, sex and height did not influence fascia thickness. Fascia thickness of the deltoid muscle was significantly increased in patients with IM (table 1). All patients had a deltoid fascia thickness above 2 SD. The fascii of the vastus lateralis muscle were not thickened in IM patients. <h3>Conclusions</h3> This study reveals evidence of fascia thickening in the deltoid muscle of IM patients, indicative of a concomitant fasciitis in this disease. Further studies including more muscles and comparison with muscle biopsy will elucidate the extent of involvement of the muscle fascia in myositis. <h3>Disclosure of Interest</h3> None Declared
Abstract 5672: A novel anti-cancer effect of hesperidin: reversion of epithelial mesenchymal transition in human prostate cancer cells
Authors: Yiu-Keung Lau
Journal: Cancer Research (2010)

Abstract Prostate cancer is the most common noncutaneous malignancy in men. About one third of prostate cancers invade surrounding tissues, and metastasize to distant organs at the time of diagnosis. Once prostate cancer metastasizes to distant organs, the disease is basically not curable. The median survival for men with metastatic prostate cancer is 1 to 3 years. Epithelial mesenchymal transition (EMT) is a process facilitating cancer cell invasion and metastasis. Hesperidin (3′-5,7-trihydroxy-4′-methoxyflavanone 7-rhamnoglucoside) is a flavonoid found abundantly in citrus fruits. It demonstrates anti-inflammatory, anti-oxidative, and anti-proliferative actions in various cancer types. Its effect on EMT of prostate cancer is not known. We therefore hypothesize that hesperidin inhibits the cell growth and EMT of prostate cancer cells. In our study, we use androgen-sensitive prostate cancer LNCaP cells, androgen-insensitive Du 145 and PC3 cells, and benign prostate BPH-1 cells. These cell lines are treated with increasing concentrations of hesperidin, from 10 µM to 200 µM. We first examine the effects of hesperidin on cell viability by MTT assays. Hesperidin inhibits all three prostate cancer cell viability in a dose dependent manner but it has no significant effects on that of normal prostate cells, BPH-1. We then examine whether hesperidin reverses EMT in these cells by investigating the migration ability and the expression of EMT marker. Hesperidin at 100 µM and 200 µM inhibits the cell migration ability of PC3 and LNCaP as showed by wound scratch assay. Next, we examine expression of E-cadherin, a molecular marker for EMT, by immunohistochemistry. Hesperidin at 100 µM significantly enhances the membranous expression of E-cadherin in LNCaP cells after 48 hours of treatment as compared to the control. There are no significant changes in androgen receptor (AR) protein level or PSA mRNA after hesperidin treatment suggestive that the effects of hesperidin on LNCaP cells are AR-independent. In conclusions, our data provide novel findings that hesperidin can induce the reversion of EMT in prostate cancer cells. Hesperidin may therefore be a potential chemopreventive agent in human prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5672.
Extreme Hemolysis and Red-Cell Distortion in Erythrocyte Pyruvate Kinase Deficiency
Authors: Frank A. Oski, David G. Nathan, Victor W. Sidel, Louis K. Diamond
Journal: New England Journal of Medicine (1964)

BIZARRE morphologic abnormalities of the erythrocytes are generally not considered a prominent feature of congenital nonspherocytic hemolytic anemias.1 , 2 We have observed a child with a severe congenital nonspherocytic hemolytic anemia associated with a deficiency of erythrocyte pyruvate kinase in whom morphologic abnormalities of the red cells were profound. The bizarre red-cell abnormality was in some respects similar to that observed in the syndrome of acanthocytosis associated with absence of serum beta-lipoprotein.3 Of additional interest was the finding that the mother of the patient was not only a heterozygote for the pyruvate kinase (PK) deficiency but was also a carrier of . . .
IMPACT OF ENHANCED EXTERNAL COUNTERPULSATION ON HEART FAILURE REHOSPITALIZATION AMONG PATIENTS WITH ISCHEMIC CARDIOMYOPATHY
Authors: Kristen Tecson, Marc Silver, Sonja Brune, Clay Cauthen, Michael D. Kwan, Jeffrey Schussler, Anupama Vasudaven, James A. Watts, Peter A. McCullough
Journal: Journal of the American College of Cardiology (2016)
DCE-MRI and dynamic FDG PET to monitor breast cancer response to neoadjuvant sunitinib in patients with locally-advanced breast cancer.
Authors: JM Specht, S Partridge, L Dunnwald, R Doot, E Schubert, B Kurland, J Gralow, H Linden, V Gadi, G Ellis, D Mankoff
Journal: Cancer Research (2009)

Abstract Abstract #6006 Background: We are enrolling patients with locally-advanced (LABC) or inflammatory breast cancer on a phase II trial of neoadjuvant sunitinib and metronomic chemotherapy. The addition of sunitinib is hypothesized to increase rate of pathologic complete response (pCR) via its effect on tumor vasculature. Measurement of FDG PET and MRI parameters of metabolism and blood flow (BF) after a one week run-in of sunitinib alone provides an opportunity to evaluate in vivo pharmacodynamics of sunitinib which may be predictive of response and provide insight into mechanism of sunitinib activity. Materials and Methods: Patients with HER2 negative LABC participated in an imaging trial with pre-therapy [18F]-FDG PET and DCE-MRI (T0) followed by a one-week run-in of sunitinib 37.5 mg orally daily with a second PET and MRI on day 7 (T1). FDG metabolic rate (MRFDG), transport (FDG K1) and MR indices of tumor perfusion (peak enhancement (PE), signal enhancement ratio (SER), and washout volume(WV)) were assessed. Results: Metabolism and perfusion parameters are available for the first 3 patients treated on this trial. All patients presented with grade 3, HER2 negative LABC. DCI-MRI (left) and PET images (right) pre-therapy (T0, top) and after one week sunitinib (T1, bottom) are illustrated in Figure 1. DCE-MRI studies show gray-scale images with color-coded regional perfusion (SER) superimposed; red indicates high levels of perfusion and blue lower levels. Three different responses were observed and expressed as percent change T0 to T1: patient 1 had no significant change in metabolism (MRFDG) or perfusion (K1,SER, PE); patient 2 showed a decline in perfusion with decreases in K1 (-55%), SER (-19%), PE (-10%), and WV (-56%), but minimal change in MRFDG (+ 5.9%); while patient 3 had marked declines in perfusion K1 (-41%), SER (-25%), WV (-78%) and MRFDG (-59%). Discussion: These early data demonstrate the ability to measure changes in tumor metabolism and blood flow by PET and MRI and illustrate heterogeneity in tumor response to sunitinib. As patients complete neoadjuvant chemotherapy (NC), metabolism and perfusion parameters from mid-therapy (T2) and end-therapy (T3) imaging will be evaluated in the context of pCR versus other with the goal of exploiting functional imaging parameters to predict response to NC and elucidate mechanism of response to sunitinib and metronomic chemotherapy. Supported by grant from NCCN, SI11.&amp;#x2028; &amp;#x2028; Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6006.
A6.11 Immunoclust based analysis of cytometric profiles reveals immunophenotypic changes in synovial fluid compared to peripheral blood cells in rheumatoid arthritis
Authors: T Sörensen, U Schulte-Wrede, S Hermann, A Grützkau, T Häupl
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Flow cytometry offers quantification of multidimensional characteristics at single cell level for millions of cells. Multiplex flow cytometry or mass cytometry enable to screen for dozens of antigens on a single cell. Conventional analysis of such data requires user defined gating and is time consuming. Using the new bioinformatics tools immunoClust for automated and user-independent analysis, we investigated the complexity of phenotypic changes of immune cells upon migration from peripheral blood (PB) to synovial fluid (SF) in rheumatoid arthritis (RA). <h3>Materials and methods</h3> Seven paired samples of PB and SF from RA patients were stained in 10 different antibody cocktails and data investigated by the newly developed immunoClust pipeline for sample specific populations and differences between PB and SF. Population clustering and comparative meta-clustering assume finite mixture models and use Expectation Maximisation (EM)-iterations with integrated classification likelihood (ICL) criterion to stabilise the number of reasonable clusters. For meta-clustering, a probability measure on Gaussian distributions was invented, which is based on the Bhattacharyya Coefficients. Meta-clusters were manually annotated and classified. The clustering tools of immunoClust are available as open source R-package in Bioconductor. <h3>Results</h3> Automated clustering with 46 different surface markers detected all major leukocyte subsets and several activation markers in PB and SF samples including neutrophils, eosinophils, T-cells and sub-populations, monocytes, B-cells, NK-cells and dendritic cells. The comparison revealed about 10 highly significant changes per staining cocktail. For example the percentage of monocytes/macrophages was doubled in SF and dominated by CD16<sup>+</sup> cells, the frequencies of effector/memory subpopulations of lymphocytes were increased and naïve T-cells and B-cells were almost completely absent. In addition several unexpected populations like CCR7+ monocytes were found in SF only. <h3>Conclusion</h3> In conclusion, the results give a reasonable starting point to face the next field of research for marker detection and prediction analysis. The data will be further exploited for changes in cell activation and differentiation in SF in order to screen for these populations also in PB. This approach is not only applicable to fluorescence-based flow data but could be also used for multi-parametric data sets generated by mass spectrometry-based cytometry (CyTOF).
M23 COPD exacerbations of longer duration worsens health related quality of life
Authors: GC Donaldson, AJ MacKay, R Singh, J Allinson, S Brill, JA Wedzicha
Journal: Thorax (2013)

<h3>Introduction</h3> Patient’s quality of life is related to the frequency of COPD exacerbations [Seemungal <i>et al</i> AJRCCM 1998: 157: 1418–1422]. There is increasing interest in reducing the duration of exacerbations but little evidence that this benefits patient’s quality of life. <h3>Methods</h3> We analysed data from 384 patients in the London COPD cohort collected between 1995 and 2012. Patients completed diary cards recording respiratory symptoms. Exacerbation onset was defined as the first of two days of 2 major symptoms (increased breathlessness, sputum volume or purulence) or 1 major and 1 minor symptom (cold, increased cough, increased wheeze, sore throat). Recovery was defined as the first of two symptom free days and exacerbation duration was defined as the period between onset and recovery.. Patients completed the St. George’s Respiratory Questionnaire (SGRQ) annually when clinically stable. To avoid bias with repeated measures, exacerbation recovery and SGRQ total scores were averaged. FEV<sub>1</sub>% predicted was measured at recruitment. <h3>Results</h3> The 384 COPD patients (246 male); mean age 68.6 years (SD8.4), FEV<sub>1</sub> % predicted 45.8% (16.6) and FEV<sub>1</sub>/FVC 45.8% (12.2) with 122 patients (32.1%) still smoking at recruitment. There were 3498 exacerbations (median annual rate = 2.13 (IQR 1.0–3.2)). The median exacerbation duration was 10 days (IQR 6–18). Exacerbation duration was not available for 350 (10.0%) exacerbations as no symptoms were recorded and for a further 109 (3.1%) where the patient continued to recorded symptoms post-exacerbation for 100 days or more. In a multiple linear regression model, total SGRQ score increased by 0.20 units/1 day increase in exacerbation duration (95% CI 0.008–0.39; p = 0.041) after allowance for FEV<sub>1</sub>% predicted and exacerbation frequency. The results suggest that halving the duration of 4 exacerbation events from 10 to 5 days will produce a 4 unit change in the total SGRQ score. <h3>Concluison</h3> Shorter exacerbations are associated will improved quality of life. More research is needed on acute interventions designed to ameliorate exacerbations.
HG-05 * DAAM2 PROMOTES TUMOR PROLIFERATION AND MIGRATION IN GLIOBLASTOMA
Authors: W. Zhu, H.-K. Lee, J. Loturco, C. Mohila, B. Deneen
Journal: Neuro-Oncology (2015)

Glioblastoma multiforme (GBM) is one of the most common and aggressively malignant high-grade gliomas in humans. GBM tumors as are comprised of astrocytes and oligodendrocytes. Genes involved in the development of these glial cells have been linked to GBM tumorigenesis. Considering tumorigenesis is currently viewed as a convergence of genetic mutation and developmental context, we want to understand how the mechanisms which govern glial cell fate decisions contribute to GBM formation. The Wnt signaling pathway, for example, has well defined functions in neural progenitor self-renewal during development. This function is dysregulated in several cancers, yet surprisingly poorly defined in GBM. Given our finding that Daam2 plays a key role in Wnt signaling in the developing and CNS, we hypothesize that Daam2 is a key component of the Wnt signaling pathway which is dis-regulated in GBM. Indeed, we found that Daam2 is highly expressed in human GBM samples. Subsequent analysis of Daam2 function in GBM reveals that it promotes tumor proliferation and migration both in vitro and in vivo. The way we approached gain and loss of function in vivo study is to use In Utero Electroporation (IUE) technology to target astro-glial lineages with oncogenes. The attributes of this model are rapid and efficient generation of GBM after three weeks. Currently, I am working to precisely define Daam2 molecular mechanism in tumor. It shows that Daam2 potentiates canonical Wnt signaling in GBM tumor cell lines. Moreover, we surprisingly find that Daam2 not only functions through Wnt signaling pathway in GBM, but also interacts with PI3K. These studies represent the first characterization of Daam2/Wnt signaling/ PI3K function in GBM.
AB0878 Heterotopic Ossifications after Cervical Fasciitis: about 26 Cases
Authors: H. Tran, T. Leturc, J.P. Blancal, J.-P. Guichard, R. Kania, T. Bardin, H.K. Ea
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Heterotopic ossifications are lamellar bone formations within soft tissues. They can occur after trauma, orthopedic surgery, neurologic injuries, burns, hematoma, necrosis or even spontaneously. They can have major functional consequences. Ossifications of head and neck have already been reported, but never after cervical fasciitis. We describe here 26 cases. <h3>Objectives</h3> To reported rare complication of cervical fasciitis <h3>Methods</h3> Retrospective study of cervical fasciitis occurring between January 2008 and May 2013, with post surgery CT scans. Tomography images have been read by a neuroradiologist with anatomic expertise of the cervical region. Features of infections (origin, microbiology), patient demographic and clinical data (age, sex, diabetes, immunodepression) and ossifications are described. <h3>Results</h3> Among 170 fasciitis cases, 98 had post surgery CT scan, 36 of which were performed more than 28 days after surgery. 26 cases of ossification were identified (6 women, 20 men). Mean age was 50.6±16.6 years. Comorbidities included hypertension (n=5), diabetes mellitus (n=3), ischemic cardiopathy (n=1), chronic bronchitis (n=2), allergy (n=3), dyslipidemia (n=4), neurovascular events (n=1), previous talus bone infection after fracture (n=1), and congenital deafness (n=1). 8 patients reported smoking, and one patient admitted regular important alcohol uptake. Origin of the infection was dental (n=9), sub-maxillary (n=5), parapharyngeal (n=1), peritonsillar (n=9), foreign body in piriform sinus (n=1), unknown (n=1). Mediastinitis was associated in 10 cases. Microbiology showed involvement mostly of streptococcus (n=18), staphylococcus aureus (n=2) and epidermidis (n=3), and anaerobic bacteriae (n=6). Seven patients had trismus. CT scan showed that bone formations lay within muscles, or in cervical fascias, along surgical detachment plans. <h3>Conclusions</h3> Heterotopic ossifications are unknown and probably underestimated complications of cervical fasciitis, that can entail important functional impairment. CT scan is a sensitive imaging tool and can be performed in the presence of trismus. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4788