tbuckley/cabot-search huggingface dataset:
SAT0181 Prognosis of MPO-ANCA-Positive Interstitial Pneumonia Patients Following Active Treatment
Authors: T. Shoda, T. Takeuchi, T. Kotani, K. Nagai, D. Wakura, K. Isoda, S. Yoshida, K. Hata, S. Makino, T. Hanafusa
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Chest CT scan of patients with MPO-ANCA positive interstitial pneumonia often identifies a UIP pattern. This condition shows UIP-dominant pathological features, accompanied by characteristics differing from idiopathic pulmonary fibrosis such as poor fibroblastic foci. If these pathological differences are taken into account, the prognosis may differ between MPO-ANCA-positive interstitial pneumonia and idiopathic pulmonary fibrosis patients. (1) <h3>Objectives</h3> The prognosis was investigated in patients with MPO-ANCA-positive interstitial pneumonia having received immunosuppressive therapy beginning soon after disease onset. <h3>Methods</h3> Of the patients with microscopic polyangiitis admitted to our hospital between 2001 and 2012, MPO-ANCA-positive patients complicated by interstitial pneumonia (MPA-ILD) were enrolled in this study, in accordance with the EMEA Classification (2007). The clinical data, prognosis, and other variables were investigated in these patients. <h3>Results</h3> There were 32 cases of MPA-ILD (14 males and 18 females), with a mean age of 71.8 years (range: 48-87). The data at the start of treatment were: MPO-ANCA 379±486 EU, KL-6 692±551 U/ml, Aa-DO2 33.6±58, %FVC 80.9±18%, %DLco/VA 61.5±19%, and RV/TLC 42.0±8.4%. Chest CT scan at the start of treatment revealed a UIP pattern in 25 cases and a non-UIP pattern in 7 cases. All patients received treatment with PSL, combined with immunosuppressors in 29 cases (CY in 11 cases) and apheresis in 6 cases. After treatment, the MPO-ANCA level was below the detectable limit in most cases. On analysis of the prognosis, 5 patients died (from exacerbation of interstitial pneumonia in 1 case, infection + alveolar bleeding in 1 case, pulmonary hypertension in 1 case, and sudden death in 2 cases), with the median survival period being 124.6 months and the 5-year- survival rate being 85.5%. Following treatment, the ground glass opacity on chest CT disappeared, and the cyst tended to grow slightly. <h3>Conclusions</h3> The prognosis of MPA-ILD patients was favorable, suggesting that is better than that of usual idiopathic pulmonary fibrosis patients. When immunosuppressive therapy at sufficiently high dose levels, started soon after disease onset, was continued, MPO-ANCA became negative and remained so thereafter. We suggest that the prognosis of MPA-ILD patients may be improved if immunosuppressive therapy is applied more effectively. <h3>References</h3> Tanaka T, Otani K, Egashira R, Fukuoka J, et al: Interstitial pneumonia associated with MPO-ANCA: clinicopathological features of nine patients. Respir Med. 2012; 106: 1765-70. <h3>Disclosure of Interest</h3> None Declared
Case 19-2015
Authors: David M. Dudzinski, Anand M. Prabhakar, Leon M. Ptaszek, Gus J. Vlahakes
Journal: New England Journal of Medicine (2015)

A 71-year-old man presented with sudden chest pain, diaphoresis, shortness of breath, and hypotension. An electrocardiogram showed new ST-segment elevations. Ten days earlier, an implantable cardioverter–defibrillator had been placed. Diagnostic procedures were performed.
Abstract 2588: Targeting overexpressed PLK1 and Aurora kinases in childhood medulloblastoma
Authors: Martin I. Holst, Ellen Westerhout, Marcel Kool, Huib Caron, Rogier Versteeg, Steve Clifford, Stefan Rutkowski, Torsten Pietsch
Journal: Cancer Research (2011)

Abstract The European research project Kids Cancer Kinome (KCK) is focusing on the investigation of aggressive childhood cancers. The competence of nine research centers is combined to explore the human protein kinase family in different highly malignant pediatric tumors (medulloblastoma, Ewing sarcoma, osteosarcoma, rhabdomyosarcoma, neuroblastoma, ALL) to validate novel drug targets and develop novel therapeutic options. Medulloblastomas belong to the most frequent malignant brain tumors in children and represent about 20% of all pediatric CNS cancers. Analyzing mRNA expression profiles (Affymetrix microarrays) we discovered a series of kinases considerably overexpressed in primary medulloblastoma tumors samples and medulloblastoma cell lines compared to non-neoplastic tissues. We found a significant mRNA overexpression of PLk1 and Aurora kinases A and B in medulloblastoma tumor samples and cell lines. For further investigation we selected these kinases which are all involved in cell cycle control. Defects in the process of cell division are believed to be associated with tumorigenesis. Using the small molecules inhibitors ZM447439 and VX680 for Aurora kinases and BI2536 and GW843682 for PLK1 inhibition we evaluated the effects on medulloblastoma cell proliferation and apoptosis. Incubation of medulloblastoma cells with the inhibitors for 72h resulted in a concentration dependent decrease of the proliferative activity as measured by MTS proliferation assays and an increased apoptosis determined by Caspase-Glo 3/7 assay. In a second approach, we transduced cell lines with lentiviral particles carrying shRNA targeting PLK1 or Aurora kinases A and B. The specific downregulation of the kinases mediated by the lentiviral shRNA was confirmed by Western blotting and had a negative effect on the viability of the medulloblastoma cells. We observed that the effect of PLK1 inhibition on the proliferation of the medulloblastoma cell lines was more effective compared to the aurora kinases. In conclusion, these data suggest that the inhibition of PLK1 or Aurora kinases may represent a promising approach for novel targeted strategies in the treatment of medulloblastoma. http://www.kidscancerkinome.org 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 2588. doi:10.1158/1538-7445.AM2011-2588
PTU-113 Osteopontin is involved in chronic HBV infection and enhances HBV replication and HBSAG secretion
Authors: S Phillips, J Coombes, S Mistry, R Williams, W Syn, S Chokshi
Journal: Gut (2015)

<h3>Introduction</h3> Hepatitis B virus (HBV) requires host cellular machinery such as cyclophilins to support its ongoing propagation (Phillips <i><i>et al</i></i>, Gastroenterology 2014) these host proteins represent ideal candidates for therapeutic interventions as they are generally expected to have a lower frequency of drug-resistance and antiviral efficacy across genotypes. We have also recently described a role for the host protein Osteopontin (OPN), a pro-fibrogenic downstream effector of the Hedgehog pathway, in enhancing HCV replication (Choi <i><i>et al</i></i>, Clinical Sciences 2014). Whilst increased levels of blood OPN have similarly been reported in chronic Hepatitis B (CHB), its role in viral replication remains unknown. This study aimed to evaluate the role of OPN in HBV replication, HBsAg secretion and HBV-driven liver injury. <h3>Method</h3> Stably (HepG2215), transiently (HUH-7) transfected and infected (HepaRG) cell lines, producing full HBV virions and HBsAg particles were cultured over 72 h in the presence/absence of several concentrations of recombinant OPN (recOPN). In addition, secreted OPN was neutralised using OPN-specific aptamers. Cells and supernatants were harvested at baseline, 24, 48 and 72 h. Intracellular OPN mRNA and HBV-DNA levels were quantitated by Real-Time qPCR. HBsAg levels were measured by ELISA. OPN levels were also measured by ELISA in cell culture supernatants and in sera of controls and HBeAg (+) CHB patients who were either treatment naive or treated with potent antiviral agents. In addition, expression of OPN was assessed in explanted livers from healthy and HBV-cirrhotic patients. <h3>Results</h3> Serum levels and intrahepatic expression of OPN were significantly increased in CHB patients compared to controls (up to 7 fold; p &lt; 0.05). <i>In vitro</i>, mRNA and protein levels of OPN were highly correlated with intracellular HBV-DNA (r = 0.858; p &lt; 0.001/r = 0.997; p = 0.003), secreted HBV-DNA (r = 0.968; p &lt; 0.001/r = 0.818; p = 0.047) and secreted HBsAg (r = 0.738; p = 0.001/r = 0.89; p = 0.018). The relationship between OPN and HBV replication was further confirmed following treatment with recOPN which showed a significant increase in intracellular and secreted HBV-DNA by an additional 1.3 Log10 copies/mL and amplified HBsAg secretion rates by 2 fold. <h3>Conclusion</h3> These data confirm that OPN is upregulated in the blood and livers of CHB patients. We also show that OPN directly augments HBV replication, thus identifying a novel therapeutic target. <h3>Disclosure of interest</h3> None Declared.
PWE-156 Durham Metrics To Evaluate Effectiveness Of A New Care Pathway For Patients With Advance Stage Liver Disease (asld)
Authors: S Saksena, L Hammal, C Lancaster, M Hewett
Journal: Gut (2014)

<h3>Introduction</h3> Patients with chronic liver disease have several unplanned admissions during their disease trajectory.<sup>1</sup> We undertook a service improvement initiative to develop a new care pathway for patients with ASLD. <h3>Methods</h3> Six month pilot of 20 ASLD patients, (≥ 2admissions in last 12 months/’would you be surprised question’ with 6–12 mths prognosis/Childs C). Team of hepatologist, community matron, hepatology nurse specialist and service improvement facilitator developed ‘Durham Metrics’: quantitative and qualitative metrics (Figure) to evaluate ASLD pathway, on best practice,<sup>2</sup> further refined with focussed discussion with stakehoders. <h3>Results</h3> The metrics demonstrated that patient expereince pre-pilot was poor with multiple unplanned admissions and/or long waits, preferred place of death was not discussed; care was not co-ordinated, and quality of life was often poor as a result. All post-pilot metrics reported significant improvements. Use of alternative community services, and shared care plans led to improved efficiency. 83% achieved their preferred place of care and death contrast to nil pre pilot. <h3>Conclusion</h3> Key metrics of performance are essential to evaluate service improvement project. The project metrics designed for this project were able to capture changes initiated by pathway however more data and time is needed to draw statistically valid conclusions. <h3>References</h3> National End of Life Care Intelligence Network 2012 Deciding Right Liver Quest <h3>Disclosure of Interest</h3> None Declared.
Lymphoscintigraphy Revealed Abnormal Lymphatic Drainage in Chyloperitoneum
Authors: Mana Yoshimura
Journal: Clinical Nuclear Medicine (2011)

Lymphoscintigraphy using 99mTc-human serum albumin delineates patterns of lymphatic drainage, is fast and nontraumatic, and has no known adverse effects. We set out to differentiate chyloperitoneum from fluid of unknown origin which had collected in the abdomen using lymphoscintigraphy. Anterior and posterior whole-body lymphoscintigraphic images were acquired 10, 30, 60, and 90 minutes after subcutaneous injection of 37 MBq 99mTc-human serum albumin into the first and second interdigital spaces of both feet, using a large field-of-view gamma camera fitted with a low-energy, high-resolution collimator.
Abstract LB-519: Chemotaxis of acute promyelocytic leukemia cells toward CXCL12 is involved in ATRA syndrome and the requirement of chemotherapy during Induction therapy with ATRA
Authors: Akihiko Gotoh, Yasuo Aota, Keisuke Miyazawa, Masahiro Kizaki, Kazuma Ohyashiki
Journal: Cancer Research (2012)

Abstract We previously reported that treatment of acute promyelocytic leukemia (APL) cells with all-trans retinoic acid (ATRA) in vitro increases the directed migration towards CXCL12. Here we report the clinical significance of this phenomenon. Bone marrow cells were corrected from 13 de-novo APL patients after obtaining informed consent. Flow-cytometric analysis revealed that all cases expressed CXCR4, the receptor of CXCL12. The CXCR4 expression was enhanced after 24 hour treatment with ATRA in vitro. Chemotaxis analysis using Boyden chamber demonstrated that the directed migration towards CXCL12 increased 1.03 to 4.16 (median 1.65) times in ATRA-treated APL cells as compared to non-treated cells. Four out of 13 APL patients developed ATRA syndrome during induction therapy with ATRA. The chemotaxis towards CXCL12 was enhanced in these four patients (p&amp;lt;0.01). Six cases required chemotherapy with IDR and Ara-C during induction therapy with ATRA. The significant increase in chemotaxis toward CXCL12 was also observed in these patients as compared with those who achieved CR by the induction therapy with ATRA alone (p&amp;lt;0.01). Interestingly, the ability of chemotaxis of APL cells appeared to be more well correlated with the occurrence of ATRA syndrome and the requirement of additional chemotherapy during ATRA treatment as compared with other well known predictable factors such as the APL cell number or white blood cell number in the peripheral blood, and the expression level of CXCR4. To investigate the possible mechanism of the chemotaxis, we used APL cell lines such as ATRA-sensitive NB4 cells and ATRA-resistant UF-1 cells as well as primary APL cells. An inhibitory antibody against CXCR4 and pertussis toxin effectively suppressed chemotaxis of APL cells toward CXCL12. Chemotaxis assay using selective signaling inhibitors demonstrated that activation of phospholipase C but not MAP kinase was strongly involved in the directed migration towards CXCL12 in APL cells. Additionally, the Akt-PI3-kinse pathway was partly participated in this chemotaxis. These results suggest that chemotaxis ability of APL cells toward CXCL12 is involved in the pathogenesis of ATRA syndrome and the requirement of chemotherapy during induction therapy with ATRA. Furthermore, specific signal targeted-therapy might contribute to prevent ATRA syndrome and/or avid administration of excessive chemotherapeutic agents. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-519. doi:1538-7445.AM2012-LB-519
THU0458 MPV and RDW: Subclinical Inflammation Markers in Attack-Free Familial Mediterranean Fever (FMF) Patients
Authors: G. Y. Cetin, O. Gul, F. Kesici-Metin, I. Gokalp, M. Sayarlioglu
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Mean platelet volume (MPV) and red cell distribution width (RDW), as a marker of inflammation, have an important role in several chronic inflammatory disorders like familial Mediterranean fever (FMF). Many studies have shown that subclinical low grade inflammation persisted during attack free periods in FMF patients. We aimed to investigate whether RDW and MPV values differ between patients with FMF during attack free periods and healthy controls. <h3>Methods</h3> In this study, 89 patients (Male/Female: 30/59, mean age:31,8±10) with FMF during attack-free periods and 30 age, sex-matched healthy controls (Male/Female:10/20, mean age:31,4±5,7) were enrolled. Erythrocyte sedimentation rate, C-reactive protein, white blood cell count, platelet count, hemoglobin, MPV and RDW levels were retrospectively recorded. The patients were evaluated in accordance with Tel-Hashomer Severity Scoring which includes six elements, including diseases onset age, dose of colchicum, number of involved sites in one attack and during the course of the disease, and the presence of pleuritic and erysipelas-like erythema. <h3>Results</h3> Mean age, male/female ratio and the mean levels of hemoglobin, white blood cell count were similar in two groups. RDW, platelet counts were significantly higher and MPV was significantly lower and in patients with FMF group (%15,59±1,6 vs %12,9±0,8 p&lt;0,001, 289±78,2 K/uL vs 245,63±55,7 K/uL p=0,005 and 7,9±1 fL vs 9,4±0,9 fL p&lt;0,001 respectively ). In attack-free FMF group negative correlation has been found between the MPV and RDW values (p&lt;0,001, r=-0,40). <h3>Conclusions</h3> Our results suggest that low MPV and high RDW levels may provide additional information about persisted subclinical inflammation in FMF patients during attack-free periods. <h3>Disclosure of Interest</h3> None Declared
AB0057 Influence of PVA coated nanoparticles on survival and functionality of human immune cells
Authors: C. Strehl, T. Gaber, M. Wagegg, M. Jakstadt, M. Hahne, S. Schellmann, B. Esche-Szostak, G. Coullerez, H. Hoffmann, G.-R. Burmester, F. Buttgereit
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Nanotechnology has developed into a key technology of the 21st century. Over the recent years, the number of nanotechnical products has received an enormous boost. More and more efforts are being done to use this technology in human medicine for diagnostic and therapeutic purposes. Therefore, crucial questions concern the safety aspects. The focus of our work here was to identify possible effects of nanoparticles on human immune cell function. <h3>Objectives</h3> We analysed clinical relevant interactions between PVA coated nanoparticles (spions) and human immune cells. <h3>Methods</h3> 100μl of whole blood obtained from patients with rheumatoid arthritis (RA) or healthy donors were incubated with 100μl serum free RPMI 1640. Functionalised spions were added at varying concentrations, and cells were incubated for 24h. After lysis of erythrocytes, cells were stained for apoptosis and necrosis using Annexin V and 7AAD, respectively. Samples were analysed by flow cytometry. As a second approach, PBMCs were isolated from blood samples of healthy donors and RA patients, and CD4 positive T cells were separated via MACS-Sort. T cells were incubated with/without PHA and/or with/without PVA spions at different concentrations. Activation (CD25 expression) of cells was analysed by flow cytometry. Functionality was determined via proliferation measurements of CFSE (carboxyfluorescein diacetatesuccinimidyl ester) labeled T cells after 72h under normoxic (5% CO<sub>2</sub> and 18% O<sub>2</sub>) or hypoxic (5% CO2 and &lt;1% O<sub>2</sub>) conditions by flow cytometry. <h3>Results</h3> Altogether, blood samples from 18 healthy donors and 19 patients suffering from RA were analysed for induction of apoptosis and necrosis in different cell types. The results on cell survival did not demonstrate any short-term general toxicity of PVA spions at concentrations less than 1000μg/ml on the several different blood cell subsets examined. Furthermore, T cells were isolated from 14 healthy donors and 9 RA patients for functional analysis. There is no influence of PVA spions on T cell activation and proliferation at concentrations less than 1000μg/ml. <h3>Conclusions</h3> PVA coated nanoparticles at concentrations up to 1000μg/ml (i) do not increase the frequencies of apoptotic or necrotic human immune and (ii) do not impair crucial functional activities of human T cells such as activation and proliferation. <h3>Disclosure of Interest</h3> None Declared
THU0287 Glycosylation of vitamin D binding protein reduced in juvenile idiopathic arthritis patients at risk of disease extension
Authors: D.S. Gibson, S. Finnegan, G. Manning, M. Duncan, S. Pennington, T. Moore, M. Rooney
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Juvenile idiopathic arthritis (JIA) comprises a poorly understood group of chronic, childhood onset, autoimmune diseases with variable clinical outcomes. <h3>Objectives</h3> We investigated whether profiling of the synovial fluid (SF) proteome by a fluorescent dye based, two-dimensional gel (DIGE) approach could distinguish the subset of patients in whom inflammation extends to affect a large number of joints, early in the disease process. The post-translational modifications to candidate protein markers were verified by a novel deglycosylation strategy. <h3>Methods</h3> SF samples from 57 patients were obtained around time of initial diagnosis of JIA. At 1 year from inclusion patients were categorized according to ILAR criteria as oligoarticular arthritis (n=26), extended oligoarticular (n=8) and polyarticular disease (n=18). SF samples were labeled with Cy dyes and separated by two-dimensional electrophoresis. Multivariate analyses were used to isolate a panel of proteins which distinguish patient subgroups. Proteins were identified using MALDI-TOF mass spectrometry with vitamin D binding protein (VDBP) expression and siaylation further verified by immunohistochemistry, ELISA test and immunoprecipitation. Candidate biomarkers were compared to conventional inflammation measure C-reactive protein (CRP). Sialic acid residues were enzymatically cleaved from immunopurified SF VDBP, enriched by hydrophilic interaction liquid chromatography (HILIC) and analysed by mass spectrometry. <h3>Results</h3> Hierarchical clustering based on the expression levels of a set of 23 proteins segregated the extended-to-be oligoarticular from the oligoarticular patients. A cleaved isoform of VDBP, spot 873, is present at significantly reduced levels in the SF of oligoarticular patients at risk of disease extension, relative to other subgroups (p&lt;0.05). Conversely total levels of vitamin D binding protein are elevated in plasma and ROC curves indicate an improved diagnostic sensitivity to detect patients at risk of disease extension, over both spot 873 and CRP levels. Sialysed forms of intact immunopurified VDBP were more prevalent in persistent oligoarticular patient synovial fluids. <h3>Conclusions</h3> The data indicate that a subset of the synovial fluid proteome may be used to stratify patients to determine risk of disease extension. Reduced conversion of VDBP to a macrophage activation factor may represent a novel pathway contributing to increased risk of disease extension in JIA patients. <h3>Disclosure of Interest</h3> None Declared