tbuckley/cabot-search huggingface dataset:
AB0101 Impact on Bone Destruction by LILRA3: A High Risk Susceptible Gene in Rheumatoid Arthritis
Authors: M. Liu, Y. Du, Y. Zou, H. Liu, J. Guo, Z. Li
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Leukocyte immunoglobulin-like receptor A3 (LILRA3) is a putatively secreted protein belongs to the leukocyte immunoglobulin-like receptor (LILR) family. Our previous study provided the first evidence that the functional LILRA3 was a novel genetic risk for rheumatoid arthritis (RA) in Chinese Han population. <h3>Objectives</h3> we undertake this study to investigate the role of LILRA3 on bone destruction in RA patients. <h3>Methods</h3> i) The expression of LILRA3 in serum and synovial fluid from patients with RA, OA, and health controls were measured by using ELISA. Bone destruction was scored using modified Sharp-vander Heijde score (SHS) on hands. ii) RAW264.7 cells and peripheral blood mononuclear cells (PBMCs) from RA,OA patients and health controls were cultured in the medium containing different concentration of recombinant LILRA3 protein in the presence or absence of Receptor Activator for Nuclear Factor-κ B Ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Osteoclasts were identified by tartrate-resistant acid phosphatase (TRAP) staining. Bone resorption activity of osteoclasts was determined by bone slices stained with toluidine blue, iii) PBMCs from patients with RA, OA and health controls were transfected with LILRA3 plasmid or control vector. The expression of osteoclasts related genes, including TRAP, CTSK, MMP-9 was measured by q-PCR array and Western Blotting method. MAPK and NF–κB signaling pathway activation levels were detected by Western Blotting method. One-way analysis of variance was used to detect the differences between the group means. <h3>Results</h3> Compared with health controls, the expression of LILRA3 in RA and OA serum was high and LILRA3 was specifically express in synovial fluid with RA patients. The serum level of LILRA3 in RA patients was positively correlated with bone damage. We demonstrated that LILRA3 can promote bone damage independently or synergy with RANKL in RAW264.7 cells through MAPK and NF–κB signaling pathway. Furthermore, we proved that LILRA3 can induce the differentiation of osteoclasts in the presence of RANKL and M-CSF both in vitro and in a transfect system in PBMCs with RA,OA patients and health controls. <h3>Conclusions</h3> Our data indicate that LILRA3 can promote done destruction through MAPK and NF–κB signaling pathway. These findings may give us some clues for the study on the pathogenesis of RA. <h3>Disclosure of Interest</h3> None declared
Identification and characterization of riproximin, a new type II ribosome-inactivating protein with potent anticancer activity, from aqueous Ximenia americana extracts used by African traditional medicine
Authors: Cristina Voss, Ergül Eyol, Martin R. Berger
Journal: Cancer Research (2006)

1919  Xanthoceras sorbifolia Bunge (Sapindaceae) is found in the Inner Mongolia region of China. The plant has been used as folk medicine for various diseases. To determine its effect on anti-tumor activity, cancer cell lines derived from 12 different human organs were exposed to the plant extract and their growth properties analyzed with MTT assay. Among the cells studied, OVCAR-3 (derived from ovarian carcinoma) cells were found to be the most sensitive for growth inhibition. The active ingredient was then purified with two times C18 column chromatography. Six active compounds were identified. The IC50 value of the purified products is approximately 1.5 - 4.5 ug/ml. Their chemical structures were determined with NMR (H, C13, HMQC, HMBC, NOESY, HOHAHA) and MS (MALDI-TOF) spectroscopy analysis. These compounds are: Xanifolia-Y1: 3-O-[β-D-galactopyranosyl-(1→2)]-α-L-arabinofuranosyl-(1→3)-β-D-glucuronopyranosyl-21-O-(3,4-diangeloyl)-α-L-rhamnophyranosyl-22-O-acetyl-3β,16α, 21β, 22α, 28-pentahydroxyolean-12-ene. Xanifolia-Y2: 3-O-[β-D-glucopyranosyl-(1→2)]-α-L-arabinofuranosyl-(1→3)-β-D-glucuronopyranosyl-21,22-O-diangeloyl-3β, 15α, 16α, 21β, 22α, 24β, 28-heptahydroxyolean-12-ene. Xanifolia-Y3: 3-O-[β-D-galactopyranosyl-(1→2)]-α-L-arabinofuranosyl-(1→3)-β-D-glucuronopyranosyl-21,22-O-diangeloyl-3β, 15α, 16α, 21β, 22α, 28-hexahydroxyolean-12-ene. Xanifolia-Y8: 3-O-[β-glucopyranosyl (1→2)]-α-arabinofuranosyl (1→3)-β-glucuronopyranosyl-21, 22-O-diangeloyl-3β, 16α, 21β, 22α, 24β, 28-hexahydroxyolean-12-ene. Xanifolia-Y9: 3-O-[β-galactopyranosyl (1→2)]-α-arabinofuranosyl (1→3)-β-glucuronopyranosyl-21-O-(3,4-diangeloyl)-α-rhamnopyranosyl-28-O-acetyl-3β, 16α, 21β, 22α, 28-pentahydroxyolean-12-ene. Xanifoli-Y10: 3-O-[β-galactopyranosyl (1→2)]-α-arabinofuranosyl (1→3)-β-glucuronopyranosyl-21, 22-O-diangeloyl-3β, 16α, 21β, 22α, 28-pentahydroxyolean-12-ene. These active compounds belong to a family of oleanene triterpenoidal saponin. Four of them (Xanifolia Y2, Y3, Y8 and Y10) have a trisaccharide chain attached at C3 of the aglycone and two angeloyl groups are acylated at C21 and C22. Other two (Xanifolia Y1 and Y9) have a trisaccharide chain at C-3 and a monosaccharide at C21 where two angeloyl groups are acylated at C3 and C4 positions. A common feature among these compounds is the presence of the diangeloyl group. To study the structure-function relationship, a compound with a similar structure toY3 but with only one angeloyl group at C22 was investigated. It was found that it has 1/10 of the Y3 activity. Removal of both angeloyl groups from C21 and C22 of Y3 completely abolishes its activity. Results indicate that diangeloyl groups in these compounds are important for anti-tumor activity.
THU0464 Osteoporosis, Not Osteoarthritis, Could Predict The Occurrence of Sarcopenia in The Near Future: A 4-Year Follow-up of The Road Study
Authors: N. Yoshimura, S. Muraki, H. Oka, S. Tanaka, H. Kawaguchi, K. Nakamura, T. Akune
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Objectives</h3> The present 4-year follow-up study of the general population was conducted to clarify whether the presence of musculoskeletal diseases, such as, osteoporosis (OP), knee osteoarthritis (KOA), and lumbar spondylosis (LS) could predict the occurrence of sarcopenia (SP) in the near future. <h3>Methods</h3> The second survey of the Research on Osteoarthritis/Osteoporosis Against Disability (ROAD) study, a large-scale population-based cohort study, was conducted between 2008 and 2010. We enrolled 1,099 participants (aged ≥60 years; 377 men and 722 women) from the second survey of the ROAD study who had completed assessments of handgrip strength, gait speed, skeletal muscle mass by using bioimpedance analysis, and bone mineral density by using dual X-ray absorptiometry. The third survey was conducted between 2012 and 2013. Of the 1,099 individuals who were enrolled from the second survey, 767 (69.8%; 253 men and 514 women) had completed assessments identical to those in the second survey. SP was defined as per the algorithm of the Asian Working Group for Sarcopenia, while OP at the lumbar spine L2–4 and/or femoral neck was defined according to the World Health Organization criteria. KOA and LS were diagnosed as grade 3 or higher of the Kellgren-Lawrence scale. <h3>Results</h3> Among the 767 subjects who completed both the second and third surveys of the ROAD study, the prevalence rates of OP, KOA, and LS in the second survey were 20.5% (men, 3.6%; women, 28.9%), 32.7% (men, 23.1%; women, 37.4%), and 49.8% (men, 46.0%; women, 51.7%), respectively. The cumulative incidence of SP during the 4-year period between the second and third surveys was 2.0%/yr (men, 2.2%/yr; women, 1.9%/yr). After adjustment for confounding factors such as age (yr), gender (0: men, 1: women), regional differences (0: mountainous area, 1: coastal area), and body build (0: normal; body mass index (BMI) ≥18.5 and ≤27.5 kg/m<sup>2</sup>, 1: emaciation; BMI &lt;18.5 kg/m<sup>2</sup>, 2: obesity; BMI &gt;27.5 kg/m<sup>2</sup>), a logistic regression analysis using the occurrence of SP as the objective variable and the presence of OP as the explanatory variable indicated that the presence of OP was significantly associated with the occurrence of SP (odds ratio, 2.51; 95% confidence interval, 1.23–5.11; <i>p</i> =0.011). By contrast, the presence of KOA, and LS was not significantly associated with the occurrence of SP (KOA: 1.32, 0.72–2.41, <i>p</i> =0.369; LS: 1.08, 0.60–1.94, <i>p</i> =0.792). <h3>Conclusions</h3> This prospective study suggests that the presence of OP could predict the incidence of SP in the near future, but KOA and LS could not. Treatment of OP might reduce the risk not only of osteoporotic fracture but also of SP. <h3>Disclosure of Interest</h3> None declared
SAT0561 Finger Joint Cartilage Evaluated by Ultrasound and X-ray in Rheumatoid Arthritis and Control Joints
Authors: T. Ogura, A. Hirata, N. Hayashi, H. Ito, S. Takenaka, K. Mizushina, Y. Fujisawa, M. Imamura, R. Kujime, S. Nakahashi, N. Yamashita, H. Kameda
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Joint destruction in RA includes both bone and cartilage lesions. By X-ray examination, cartilage destruction is evaluated as a joint space narrowing (JSN). However, joint space narrowing is not a direct evaluation of cartilage. <h3>Objectives</h3> The aim of the study was to examine the finger joint cartilage by ultrasound (US) imaging and to compare it with JSN score in relation to clinical relevance. <h3>Methods</h3> We enrolled 27 RA patients in low disease activity or clinical remission (DAS28-CRP &lt;2.7) and 21 healthy controls in this study. The cartilage thickness (CT) of metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of 2nd to 5th fingers was bilaterally visualized and measured from a dorsal view, with approximately 90 degrees flexion. In addition, JSN of finger were scored by van der Heijde- modified Sharp method. <h3>Results</h3> In patients with RA, CT in MCP joints ranged from 0.0 to 0.8 mm (median 0.4 mm), and CT in PIP ranged from 0.0 to 0.4mm (median 0.2mm), respectively. The sum of total CT from 8 fingers ranged from 2.7 to 6.8 mm (median 4.7 mm), and there was a significant difference in CT, but not in JSN score, between male and female patients (5.6 versus 4.6, respectively, p=0.005). Healthy controls had the sum of total CT significantly thicker as compared with RA (p≤0.001). Importantly, CT was well correlated with JSN (r=-0.696, p&lt;0.001). Although CT was not correlated with age, disease duration, DAS28-CRP, functional disability score, positivity of rheumatoid factor and anti-CCP-antibody, CT was reduced in RA patients with elevated serum matrix metalloproteinase-3 (MMP-3) values compared with those with normal MMP-3 (3.9 versus 5.0, p=0.015). <h3>Conclusions</h3> The US method of direct visualization and quantification of cartilage in MCP and PIP joints can be valid and useful in RA, and our results may support the importance of MMP-3 in the pathophysiology of cartilage destruction. <h3>Disclosure of Interest</h3> None declared
Concomitant Systemic and Neuro-Meningeal Non-Hodgkin’s Lymphoma: The Role of Consolidation with Intensive Chemotherapy and Autologous Stem Cell Transplantation. a Retrospective Study of 65 Cases
Authors: Gandhi Damaj, Sarah Ivanoff, Diane Coso, Loic Ysebaert, Sylvain Choquet, Caroline Houillier, Wajed Abarah, Zora Marjanovic, Reda Garidi, Momar Diouf, anne Claire Gac, Jehan Dupuis, Franck Morschhauseur, Herve Ghesquieres, Carole Soussain
Journal: Blood (2014)
PTH-012 ERCP Training – Achieving Better Outcomes for Patients and Trainees through A New Training Guide
Authors: BR Chinnathurai, L Dwyer, R Saleem, N Stern, S Hood, R Sturgess
Journal: Gut (2016)

<h3>Introduction</h3> It is acknowledged that ERCP is challenging to train both for the trainers and the trainees. Recent evidence has suggested that a much longer period of focused training is required to achieve competence, particularly cannulation of the native ampulla.<sup>1</sup> There is also significant variability in training and performance. Unlike other endoscopic interventions, such as colonoscopy there is a lack of coherent strategy to guide training. The traditional model is unstructured and intuitive, largely conforming to the notion of ‘start the trial at the incisors and continue until failure’ at which point the trainers take over the scope to complete the procedure. Our model identifies a range of individual skills that can be developed in a structured manner. <h3>Methods</h3> Our model in practice, was borne of multiple informal focus groups involving experienced and training ERCPists, both in service and in training courses. <h3>Results</h3> Our model of graded progression in ERCP training takes into account the broadly agreed complexity of the each skill set in a deconstructed ERCP.We allocate skills to 4 different domains of increasing complexity, which requires increasing dexterity and cognitive awareness from the endoscopist. In each procedure the trainee would have the opportunity to gain exposure to aspects of ERCP that is appropriate to the stage/level of training, gradually moving along a spectrum of skills of increasing complexity, associated with higher risk of complications. Such a graded progression ensures that the trainee is set up to learn each increasing complex skill with appropriate level of preparedness, enabling smoother progression in training. Trainees are assessed every 10 ERCP for progression. An example of an ERCPist at early stage of training (Pic A) is as shown below. <h3>Conclusion</h3> Our training guide could be a component of much needed structure to drive streamlined ERCP training in UK. Adoption of the guide or similar will enable enhanced continuity in training when trainees move between training centres, from initiation to independence. <h3>Reference</h3> 1 Verma D, <i>et al</i>. Establishing a true assessment of endoscopic competence in ERCP during training and beyond: a single-operator learning curve for deep biliary cannulation in patients with native papillary anatomy. <i>Gastrointest Endosc</i>. 2007. <h3>Disclosure of Interest</h3> None Declared
Aberrant Pax5 Production with Deletion of Exon 8 in Childhood B-Lineage Acute Lymphoblastic Leukemia.
Authors: Eiichi Ishii, Yujiro Sadakane, Masafumi Zaitsu, Masanori Nishi, Kanji Sugita, Shuki Mizutani, Akinobu Matsuzaki, Eizaburo Sueoka, Yuhei Hamasaki
Journal: Blood (2006)
PTH-103 Clinician Confidence in Stratifying Risk in Primary Biliary Cirrhosis - A UK-PBC Survey
Authors: M Corrigan, L Vale, D Coughlan, D Jones, G Hirschfield
Journal: Gut (2016)

<h3>Introduction</h3> Primary biliary cirrhosis or Primary biliary cholangitis (PBC) has only one licensed therapy, ursodeoxycholic acid (UDCA). Assessment of biochemical response to UDCA allows identification of patients who are at high risk of disease progression and would be suitable for trials and emerging therapies. The aim of this survey was to determine current understanding of UDCA response criteria amongst clinicians practicing in the UK. <h3>Methods</h3> An online survey of clinical practice was created by UK-PBC and distributed to clinicians via the British Society of Gastroenterology (BSG) and British Association for the Study of the Liver (BASL) mailing list and newsletters. The survey was carried out between April and June 2015. Questions covered diagnosis and management of the condition with four questions specifically covering UDCA response assessment. Statistical analysis was performed using GraphPad software. Chi squared testing as used to compare groups. <h3>Results</h3> A total of 206 responses were received. Respondents came from a variety of clinical backgrounds – consultant in a tertiary hospital – 14 (7%), consultant hepatologists in non tertiary centres – 32 (15.5%), consultant gastroenterologists – 75 (36.4%), trainees – 78 (37.9%), others including specialist nurses – 7 (3.4%). Whilst 90% of respondents reported routine use of UDCA in clinical practice, only 20% reported that they always assessed UDCA response once the patient had been on treatment for 12 months. 50% never formally assessed treatment response. Looking at rates of assessment of UDCA response between specialist groups: 64% of gastroenterologists and 47% of trainees never assessed response compared to 25% of non-tertiary hepatologists and 14% of tertiary hepatologists. The number of patients seen appeared to affect rates of UDCA response assessment: 64% of those who saw fewer than 10 patients per year never assessed response compared to 10% of those who saw more than 50 patients per year. 40% of respondents reported themselves to be "<i>not at all confident" </i>in assessing response with 58% stating they were unaware of response criteria and 27% were unsure of the best criteria to use. <h3>Conclusion</h3> The majority of patients with PBC are managed by non-specialists outside of tertiary centres many of whom see low volumes of patients with this condition. The application of emerging therapies for patients with PBC requires appropriate use of risk stratification tools in routine clinical practice. Our results demonstrate gaps in knowledge and confidence amongst non-specialists. Implementing a stratified approach to management requires these gaps to be addressed. <h3>Disclosure of Interest</h3> None Declared
GATA1 Changes DNA-Binding Fashion in a Binding-Site-Specific Manner and Alters Transcriptional Activity during Erythropoiesis
Authors: Atsushi Hasegawa, Hiroshi Kaneko, Daishi Ishihara, Masahiro Nakamura, Akira Watanabe, Cecelia D Trainor, Yamamoto Masayuki, Ritsuko Shimizu
Journal: Blood (2015)
A Prospective Study on the Feasibility of Related and Unrelated Donor Search and Hematopoietic Cell Transplantation for Adults with Acute Leukemia at 31 European Transplant Centers
Authors: Vanderson Rocha, Mutlu Arat, Vladimir Koza, Norbet C Gorin, Augustin Ferrant, Kerstin Schäfer-Eckart, Freja Ebeling, Giuseppe Milone, Paolo de Fabritiis, Leo Verdonck, Alberto Bosi, Jordi Esteve, Bernardino Allione, Johan Maertens, Attilio Olivieri, Chiara Pilatrino, Andree-Laure Herr-Bellon, Fernando Pinto, Celso Arrais, Samir Nabhan, Gerard Socié, Giorgio Dini, Eliane Gluckman, Emmanuelle Polge, Myriam Labopin
Journal: Blood (2008)
OP0242 Selective Deletion of Fap Expressing Cells Attenuates Synovial Inflammation and Protects against Inflammatory Bone Changes
Authors: A.P. Croft, J. Campos, M. MacKenzie, A. Filer, D. Fearon, G. Desanti, F. Barone, C. Buckley
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Despite their role as key effector cells driving synovial inflammation and joint damage, fibroblast like synoviocytes (FLS) have yet to be targeted therapeutically. Fibroblast activation protein (FAP) is a cell surface serine protease, known to be expressed at a low level in resting FLS but up-regulated during inflammation (1). Genetic deletion of FAP has been shown to protect against cartilage damage despite no protective effect on inflammation or bone erosion (2). The pathogenic role of FLS expressing FAP is currently unknown. <h3>Objectives</h3> To determine the role of FAP expressing FLS in a murine model of autoantibody mediated inflammatory arthritis. <h3>Methods</h3> We utilized a transgenic mouse in which FAP expressing cells were conditionally ablated (FAP-DTR) by administration of diphtheria toxin (3) in either in a prophylactic or therapeutic regime. Inflammatory polyarthritis was induced by the passive transfer of K/BxN serum into naïve mice. Mice were scored for clinical signs of arthritis and flow cytometry of digested synovial tissue was performed to determine the expression of fibroblast subsets. In addition, MicroCT was performed on hind-limbs of mice 15 days following induction of arthritis to evaluate inflammatory bone changes. <h3>Results</h3> We found that FAP expression in the human synovium predicts disease persistence in patients with early synovitis.FAP was dynamically expressed by FLS during inflammatory arthritis and defined a population of activated fibroblasts that co-express the lining layer marker Podoplanin (gp38). Therapeutic deletion of FAP+ cells during either the induction or peak phases of inflammatory arthritis significantly attenuated synovial inflammation leading to a reduction in the clinical severity of arthritis reduced inflammatory cell infiltration and protection against inflammatory bone changes as measured by micro CT. In contrast, prophylactic deletion of FAP expressing cells led to a delayed onset of inflammatory arthritis, but did not impact on subsequent clinical severity. <h3>Conclusions</h3> These data support a pathogenic role for FAP expressing FLS in inflammatory arthritis and provide a rationale for the selective targeting of FAP+ fibroblasts as a novel therapeutic approach. <h3>References</h3> Bauer et al. Arthritis Res Ther 2006:8(6):R171 Wäldele et al. Arthritis Res Ther. 2015:20;17:12. Kraman et al. Science. 2010:5;330(6005):827–30. <h3>Acknowledgement</h3> This woirk was supported by an individual Wellcome Trust Postdoctoral Clinical Research Fellowship awarded to APC. <h3>Disclosure of Interest</h3> None declared
Conditional Knockout of Sfpi1 in Post GC B and Plasma Cells Induces B Cell Lymphoma and Plasma Cell Neoplasm
Authors: Shinya Endo, Hiromichi Yuki, Yoshihiro Komohara, Shikiko Ueno, Nao Nishimura, Niina Ueno, Hiro Tatetsu, Motohiro Takeya, Hiroyuki Hata, Seiji Okada, Daniel G. Tenen, Hiroaki Mitsuya, Yutaka Okuno
Journal: Blood (2014)
LP39 : Implications of baseline HCVRNA level and intrapatient viral load variability on OBV/PTV/R + DSV 12-week treatment outcomes
Authors: R.S. Brown, M. Puoti, C. Cooper, D.L. Wyles, T.E. Sepe, R.G. Nahass, M. King, E. Coakley, B.H. McGovern, J.J. Feld
Journal: Journal of Hepatology (2015)
NIMG-76HIGH INCIDENCE OF ABERRANT PARAMAGNETIC SIGNALS ON MRI OF ADULT PATIENTS SURVIVING TWO OR MORE YEARS AFTER BRAIN IRRADIATION THAT SIGNIFIES RADIATION-INDUCED LATE EFFECTS
Authors: Shlomit Yust-Katz, Edna Inbar, Dror Limon, Tali Siegal
Journal: Neuro-Oncology (2015)

BACKGROUND: Late complications of cerebral radiation therapy involve vascular injury that may lead to development of cavernous malformation (CM), telangiectasias and damage to vascular walls. Radiation-induced CM is a recognized late complication in children but its incidence in adult patients is unknown. Typically, blood products, iron deposition and calcifications which accompany vascular injury/malformation create paramagnetic/diamagnetic effects on MRI. OBJECTIVE: To retrospectively investigate frequency of MRI paramagnetic lesions in adult patients surviving >2 years after cranial irradiation. METHODS: We reviewed MRI studies of 60 patients followed for > 2 years after radiotherapy. Studies that did not have either susceptibility weighted images or gradient echo sequence or blood oxygenation level dependant imaging sequences were excluded from the study. Lesions inside the tumor volume were not considered. RESULTS: 34 studies fulfilled the inclusion criteria. The underlying pathology requiring radiotherapy included glial tumors (20), lymphoma (4), and others. The median age at time of radiotherapy was 44 years (range 20 -71). Aberrant paramagnetic/diamagnetic lesions were found in 22 (65%) patients. The size of the lesions ranged between 1-9 mm. The number of lesions varied: 10 patients had 1-5 lesions, 5 had 6-10 and 7 had >10 lesions. In one case the finding was associated with venous anomaly. Most lesions were within the radiation field and none of the patients had related symptomatology. The median interval between radiation and the study MRI was 6 years (range 2-29). No statistical difference was found in patients' age or in the interval from radiation between those who developed signal abnormality and those who did not. CONCLUSIONS: MRI paramagnetic/diamagnetic signal aberrations, consistent with CM and/or calcifications, are common findings which signify late effects of radiotherapy in adult brain tumor patients surviving >2 years after treatment. These lesions are benign and do not require intervention.