tbuckley/cabot-search huggingface dataset:
553 RISK FACTORS ASSOCIATED WITH HEPATITIS A VIRUS (HAV) AND ALCOHOL RELATED LIVER DISEASE SEVERITY - A MOLECULAR DIAGNOSIS BASED STUDY FROM NORTHEAST INDIA
Authors: M. Bose, S. Bose, A.K. Saikia, B. Baruah, S. Medhi, A. Sarma, M. Deka
Journal: Journal of Hepatology (2012)
A7.15 <i>in vitro</i>silencing of HNRNP-A2/B1 in synovial fibroblasts reveals involvement in regulation of several signal transduction pathways
Authors: A Fischer, S Herman, K von Dalwigk, H Kiener, G Steiner
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> The heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 is involved in post-transcriptional regulation of gene expression. It has been shown to be highly upregulated in synovial tissue of patients with rheumatoid arthritis (RA). In addition, autoantibodies and T cells directed against hnRNP-A2/B1 can be found in RA patients. Recently, it was shown that silencing of hnRNP-A2/B1 in two animal models of RA, namely Collagen-induced arthritis and K/BxN serum transfer arthritis, led to reduction of arthritis severity.<sup>1</sup> To further elucidate the role of hnRNP-A2/B1 in RA, we sought of analysing the signalling pathways affected by silencing of hnRNP-A2/B1 in human fibroblast-like synoviocytes (FLS). <h3>Materials and methods</h3> siRNA-mediated silencing of hnRNP-A2/B1 in FLS was achieved by lipofectamine-based transfection. After three days, successful reduction of hnRNP-A2/B1 expression was analysed by real-time quantitative polymerase chain reaction (RT-qPCR). The role of hnRNP-A2/B1 in FLS was investigated by activating cells with TNF-α. Proteome Profiler Arrays were used to analyse cytokine production and phosphorylation of various signal transduction molecules. Interleukin (IL) -6 and IL-8 secretion was assayed using enzyme-linked immunosorption assay (ELISA). <h3>Results</h3> Silencing of hnRNP-A2/B1 led to a reduction of phosphorylation of AKT and mammalian target of rapamycin (mTOR) in TNF-α stimulated cells and a slight reduction in phosphorylation of p70 S6 kinase, which is a downstream signalling component of mTOR. Moreover, down-regulation of hnRNP-A2/B1 led to reduced levels of phosphorylated MAPK14 (p38α), and a reduction of MSK2 phosphoryl&nbsp;ation. Analysis of supernatants revealed reduced levels of CCL5 (RANTES), CXCL10 (IP-10), CCL20 (MIP-3α) and Serpine E1, but increased levels of ICAM-1. In addition, reduced secretion of Dickkopf-1 (DKK-1) or IGFBP-3 could be detected in silenced cells. Surprisingly, secretion of IL-6 and IL-8 was slightly increased in hnRNP-A2/B1 silenced FLS. <h3>Conclusions</h3> hnRNP-A2/B1 seems to play an important role in regulation of several signalling pathways, mainly the mTOR pathway, which is involved in translation and cell growth. Further analyses will be needed to fully understand the role of hnRNP-A2/B1 in signalling pathways operative in FLS and other inflammatory cell types involved in the pathogenesis of RA. <h3>Reference</h3> Herman S, <i>et al</i>. Inhibition of Inflammation and Bone Erosion by RNA Interference-Mediated Silencing of Heterogeneous Nuclear RNP A2/B1 in Two Experimental Models of Rheumatoid Arthritis. Arthritis Rheumatol 2005;67:2536–46
Giant Intracranial Aneurysm
Authors: Vishesh Kumar, Christopher S Ogilvy
Journal: New England Journal of Medicine (2011)

A 56-year-old woman with hypertension underwent an evaluation for recurrent syncope. On physical examination, the blood pressure and heart rate were normal, with no observed bradycardia or pauses on telemetry, and the respiratory rate and oxygen saturation were normal. The funduscopic examination was normal, with no signs of papilledema. Computed tomographic (CT) angiography of the head showed a partially thrombosed giant paraclinoid aneurysm of the left internal carotid artery, measuring 5 cm in diameter (Panels A and B, arrows). Six years earlier, an aneurysm of the left internal carotid artery (2.2 cm by 1.3 cm) had been diagnosed, but the . . .
O81 COST-EFFECTIVENESS OF NON-INVASIVE LIVER FIBROSIS TESTS FOR TREATMENT DECISIONS IN PATIENTS WITH CHRONIC HEPATITIS C: SYSTEMATIC REVIEW AND ECONOMIC EVALUATION
Authors: E. Tsochatzis, C. Crossan, L. Longworth, K. Gurusamy, M. Rodriguez-Peralvarez, K. Mantzoukis, J. O'Brien, E. Thalassinos, V. Papastergiou, A. Noel-Storr, B. Davidson, A. Burroughs
Journal: Journal of Hepatology (2014)
Nurse endoscopists: the unsung Florence Nightingales
Authors: M. Thoufeeq
Journal: Endoscopy (2013)

The article by van Putten et al. was read with interest [1]. Nurse endoscopists contribute enormously at their place of work on a daily basis. The British Society of Gastroenterology supports the provision of nurse endoscopists. In 2007, the Healthcare Commission reported that 85 % of acute trusts in England employed nurse endoscopists.
A2.33 Citrullinated self antigen-specific blood B cells carry cross-reactive immunoglobulins with effector potential
Authors: PJ Titcombe, K Amara, LO Barsness, N Zhang, A Krishnamurthy, A Shmagel, M Hansson, L Israelsson, P Sahlström, L Giacobbe, AI Catrina, EC Gillespie, L Klareskog, EJ Peterson, V Malmström, DL Mueller
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Presence of autoantibodies targeting citrullinated proteins (ACPA) and clinical response from anti-CD20 Rituximab therapy indicate a critical role for B cells in rheumatoid arthritis (RA). Due to the difficulty of reliably tracking rare B cells with a defined specificity, the composition of the autoreactive B cell repertoire contributing to ACPA<sup>+</sup> RA has not been analysed. We previously developed a tetramer enrichment strategy for capturing autoreactive B cells. We now employ cyclic citrullinated peptide (CCP) tetramers for cloning and expressing citrulline-specific immunoglobulin (Ig) from single blood B cells in RA. <h3>Materials and methods</h3> We analysed B cells specific for two previously described CCP, which are citrullinated epitopes from human filaggrin (Cfc1) and alpha-enolase (CEP-1). Antigen-specific B cells were detected by flow cytometry – with fluorescent CCP tetramer for citrulline-specific capture and non-citrullinated peptide decoy tetramer for distinguishing B cells that bind irrelevant epitopes on the tetramer complex. Tetramers were subsequently used to sort single B cells from RA patient (n = 3) blood. Reverse transcription-PCR generated Ig cDNA from the cells. Ig was amplified, cloned, and expressed as monoclonal antibody (mAb). <h3>Results</h3> Single B cells sorted by either CCP tetramer (Cfc1 or CEP-1) from RA patients' peripheral blood have highly mutated Ig sequences and show preferential use of the VH4 gene family. When expressed as mAb, 9 of 25 tetramer-sorted clones demonstrated high reactivity towards the targeted CCP epitope, as opposed to 0 of 21 randomly selected memory B cells isolated from the same patient samples. All of the highly citrulline-specific clones further exhibited cross-reactivity to citrullinated epitopes from other proteins and unique binding patterns to these autoantigens on peptide array. The mAb generated from tetramer-selected cells also induced osteoclastogenesis and bone erosion <i><i>in vitro</i></i>. <h3>Conclusions</h3> Single B cells selected by CCP tetramers have highly mutated Ig sequences and receptors with citrulline-specific reactivity. Efficient isolation of mAb clones from the autoreactive B cell repertoire by this strategy will be used to better understand the pathogenesis of autoimmunity. By re-engineering the expressed Ig Fc domain towards blocking or immunosuppressive functions, mAb with defined disease-associated specificities could also offer intriguing possibilities in targeted therapeutic design for RA and other conditions.
A7.5 Combined Analysis of Epigenetic and Transcriptional Profiles in Different Immune Cells Identifies Hot Spots of Gene Regulation by DNA Methylation
Authors: Marc Bonin, Stephan Flemming, Stefan Günther, Andreas Grützkau, Thomas Häupl
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> Methylation of DNA may contribute to the regulation of gene expression. Chip technology enables to analyse for methylation of CpG sites but requires a pre-selection of potential hot spots. Such a selection of sites is represented on the HumanMethylation450 array (Illumina). In order to test these CpG sites for possible functional effects, gene expression and DNA methylation were investigated between different immune cell types. <h3>Materials and Methods</h3> Cells from 4 healthy donors were sorted by FACS technology for naive and memory T-cells (CD4m, CD4n, CD8m, Cd8n), B-cells (CD19m, CD19n), NK-cells (CD56), monocytes (CD14), and granulocytes (CD15). Genome-wide DNA methylation was assessed using the Illumina HumanMethylation450 BeadChip platform. Analysis of data was performed using Genome-Studio (Illumina). Gene expression data were collected from Affymetrix HG-U133P transcriptomes analysed in the BioRetis database. Mapping of CpG sites with genes was performed using the ensemble genome assembly GRCh37 genomic location map. <h3>Results</h3> The number of differentially expressed genes or methylated CpG sites were highest between very different cell types like CD14 monocytes and CD4 T-cells (4624 genes; 19261 sites) and lower between naive and memory cells of the same lymphocyte subtype (CD4: 638 genes; 9412 sites). There was a tendency towards more methylation in naive (CD4n: 5433 sites ≈2694 genes) compared to memory cells (CD4m: 3979 sites ≈2258 genes). Overlap of differential expression with corresponding changes in methylation was found in only 629 (279) of 1951 increased (2673 decreased) expressed genes for CD14 versus CD4 comparison and 57 (53) of 332 (306) genes for CD4m versus CD4n cells. Of all CpG sites annotated to these identified genes, only about 10% were concordant with expression. These CpG site were within or immediately upstream of the annotated start of the gene with a maximum distance of ≈1500 nucleotides, indicating that overlap with the promoter site is most likely. A common sequence motif around these CpG sites was not immediately detectable but requires more detailed analysis. <h3>Conclusions</h3> Microarray based comparative analysis of transcriptional and epigenetic differences suggests a detailed picture of methylation associated gene regulation and enables to generate an epigenetic map of relevant CpG site for genes expressed and regulated in immune cell types. As many of the microarray based suspected CpG sites of a defined gene did not match with differential gene expression, epigenetic profiling with microarrays has to be interpreted carefully.
ED-24 * GANGLIOGLIOMAS IN CHILDREN- THE MD ANDERSON CANCER CENTER EXPERIENCE
Authors: S. Patil, W. Zaky, M. Park, D. Liu, S. Khatua
Journal: Neuro-Oncology (2014)

BACKGROUND: Ganglioglioma (GG) are rare mixed glial-neuronal neoplasms of the central nervous system. METHODS: Retrospective review of 57 patients below 21 years diagnosed with GG at MD Anderson Cancer Center, Houston from 1992 to 2012 was performed. Patient demographics, clinical history, radiological features and treatment data were collected and analyzed. Kaplan-Meier and Cox-regression analysis were used to assess disease progression free survival (PFS) and symptom free survival (SFS) time after surgery. RESULTS: Median follow-up period was 6.08 years with mean age at presentation as 10.89 years. 3 patients had tumor recurrence after gross total resection (GTR) and 16 patients had sub-total resection (STR). Patients with GTR had a longer PFS time compared to patients with STR (5-year PFS 89% vs. 13%; p < 0.0001). Tumor type (cystic versus mixed cystic/solid) and location (supra-tentorial vs. infra-tentorial) of tumors correlated significantly with prolonged PFS (p = 0.014, p < 0.0001). Children 14 years or older were noted to have longer PFS than younger ages (p = 0.0053). Both PFS and SFS worsened with the adjuvant therapy use (p = <0.0001, p = 0.0027). 2 of the 4 patients had malignant transformation following radiation therapy. One patient was diagnosed with grade IV anaplastic GG and 4 patients died due to progressive tumor. Based on multivariate analyses, PFS and SFS correlated significantly with the surgery type (GTR vs. STR; HR = 0.185, p = 0.0262) and adjuvant therapy (Yes vs. No; HR = 0.222, p = 0.044). CONCLUSION: We present one of the largest retrospective reviews of pediatric gangliogliomas. High incidence of malignant transformation (15.38%) following radiation was noted in STR tumors. Extent of surgery, adjuvant treatment, location and radiological feature of the tumor correlated significantly with PFS, whereas age and adjuvant treatment with SFS. Larger prospective studies are warranted to better understand the molecular signature including targetable mutations of this rare tumor, and evaluate the need and define an optimal adjuvant therapy.
PTU-084 Prevention Of Opportunistic Infections In Patients On Biological Agents For Management Of Inflammatory Bowel Disease
Authors: H Gordon, A Steel
Journal: Gut (2014)

<h3>Introduction</h3> Patients with inflammatory bowel disease are at increased risk of infection; this is especially true of the 20% on biological agents. ECCO guidelines recommend the following vaccines: Influenza (annual), Pneumococcal, Hepatitis B, Varicella, HPV (women under 26). The guidelines also highlight the need to exclude latent TB; local policy is to perform an interferon gamma release assay. Within the UK vaccination services are provided by primary care. <h3>Methods</h3> The measures taken to prevent opportunistic infection in patients prescribed anti-TNFs for IBD at Chelsea and Westminster Hospital in 2013 were audited against the ECCO OI Guidelines. The following were retrieved from electronic records: age, sex, anti TNF prescribed, pneumococcal antibodies, hepatitis B core and surface antibodies, varicella IgG, Elispot®. Attempts were made to retrieve vaccination history from General Practice. <h3>Results</h3> 60 patients were prescribed infliximab and 15 patients were prescribed adalimumab. 46 GPs were able to provide vaccination history. Influenza: 50% (23/46) patients received vaccination against influenza within the past year. Pneumococcus: 55% (47/85) patients demonstrated immunity. 6% (5/85) were not immune and the remainder were not tested. The vaccination history of 26 patients who were not immune or not tested was retrieved. 27% (7/26) had since been vaccinated. Hepatitis B: No patients were core Ab positive. Surface Ab levels demonstrated immunity in 7% (6/85). 53% (45/85) were not immune, and the remainder were not tested. Vaccination history of 44 patients who were not immune or not tested was retrieved. Of these, 25% (11/44) had since been vaccinated. HPV: 4 patients were women under 26 years old. 25% (1/4) had confirmed HPV vaccination. Varicella: 21% (18/85) patients demonstrated immunity to varicella. 2% 2/85 were not immune. Elispot: 65% (55/85) patients had a nonreactive assay. 1% (1/85) had a positive result and the remainder were not tested. <h3>Conclusion</h3> The standards set out by ECCO to protect patients from opportunistic infection are not being met. Problems obtaining accurate vaccination history from GP records include incorrect surgery details, lack of availability of staff able to review records and incomplete records. HPV vaccination usually takes place at school and is not routinely recorded by primary care. Potential service improvements include provision of vaccines at clinic, improved patient education regarding the importance of vaccination and a check list to review bloods at first anti-TNF prescription. <h3>Reference</h3> Rahier JF, Ben-Horin S, Chowers Y, Conlon C, De Munter P, D’Haens G, Domènech E, Eliakim R, Eser A, Frater J, <i>et al</i>. European evidence-based Consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. <i>J Crohns Colitis</i> 2009;3:47–91 <h3>Disclosure of Interest</h3> None Declared.
Evidence that thalidomide is effective in recurrent bleeding from watermelon stomach associated with liver cirrhosis
Authors: Stephan Moser, Alexander Tischer, Asia Karpi, Michael Schleicher, Susanne Stavjanik, Michael Gschwantler
Journal: Endoscopy (2014)

Thalidomide has been shown to be effective in preventing bleeding from gastrointestinal vascular malformations that have not responded to endoscopic therapy [1] [2]. However, the efficacy of thalidomide in patients with watermelon stomach associated with liver cirrhosis has not yet been adequately studied and no long-term results have been published [3].
Abstract 2737: The MUC1 membrane-bound mucin is an actor in renal tumor progression
Authors: Audrey Bouillez, Viviane Gnemmi, Caroline Butruille, Bélinda Ringot, Brigitte Hémon, Isabelle van Seuningen, Laurent Zini, Xavier Leroy, Sébastien Aubert, Michael Perrais
Journal: Cancer Research (2011)

Abstract MUC1, an O-glycoprotein membrane-bound mucin, is overexpressed in clear-cell carcinomas (cRCC) with correlation to two prognostic factors, tumor-node metastasis stage and nuclear Fürhman grade. Previously (Aubert et al, Cancer Res 2009), we have shown that MUC1 was significantly overexpressed in metastatic cRCC vs non-metastatic cRCC and MUC1 is a target gene of HIF-1 transcription factor which is a part of the hypoxia pathway, the main renal carcinogenetic pathway. To better understand the roles of MUC1 in cRCC, we used two renal cell lines expressing MUC1 (Caki-2) or not (ACHN cells). Caki-2 cells were stably transfected with shRNA targeting MUC1 and ACHN cells with an expressing vector containing MUC1 cDNA. Flow cytometry assay and confocal microscopy showed a homogenous membrane expression of MUC1 but also in the nucleus. In vitro studies underlined MUC1 role in the invasion, migration and anchorage-independent growth. In contrast, MUC1 had no role in proliferation and clonogenicity. Cellular agreggation test showed that MUC1 expression is associated with a decrease of cell-cell interactions. Phospho-JNK and phospho-p38 levels were higher in MUC1 expressing cells. Transcriptomic analysis results performed on 44K Agilent Microarrays suggest that MUC1 is a candidate in chemoresistance. Subcutaneous xenograft will be also performed. Our results show that MUC1 plays a role in biological properties of renal cancer cells suggesting the important function for this mucin in tumor progression and confirms its potential as a therapeutic target in this type of cancer. 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 2737. doi:10.1158/1538-7445.AM2011-2737
Case 34-2004
Authors: Douglas M. Dahl, Peter R. Mueller, Robert H. Young
Journal: New England Journal of Medicine (2004)

A 45-year-old man had right flank pain associated with hematuria. Computed tomographic scanning without enhancement disclosed a nonobstructing stone in the right kidney. After a second episode 11 months later, the stone was still present, and there was new dilatation of the right renal pelvis. The physicians discuss how this patient was evaluated and treated.
Abstract P1-11-22: Bisphosphonates and Pathologic Complete Response to Neoadjuvant Chemotherapy in Patients with Breast Cancer
Authors: M Chavez-Mac Gregor, EN Brown, X Lei, L Hsu, F Meric-Bernstam, J Litton, EA Mittendorf, V Valero, GN Hortobagyi, AM. Gonzalez-Angulo
Journal: Cancer Research (2010)

Abstract Purpose: Several studies have suggested that bisphosphonates have antitumor effects and that their use may have a potential benefit on recurrence and survival in patients with primary breast cancer. In a retrospective study, we sought to evaluate whether the use of bisphosphonates increased the rates of pathological complete response (pCR) in breast cancer patients receiving taxane and anthracycline-based neoadjuvant chemotherapy. Methods: We identified from our database 1449 breast cancer patients receiving taxane and anthracycline-based neoadjuvant chemotherapy between 1995 and 2007 at M.D. Anderson Cancer Center. Among the entire cohort, we identified by chart review those patients that while receiving chemotherapy also received bisphosphonates for a different indication (osteopenia or osteoporosis). Primary outcome was the proportion of patients achieving a pCR. Groups were compared using the chi-squared test. A multivariable logistic regression model was fit to examine the relationship between the use of bisphosphonates and pCR. An exploratory survival analysis using the Kaplan-Meier method was performed; groups were compared using the log-rank test. Results: From the 1449 patients included, 39 (2.7%) received bisphosphonates at the time of neoadjuvant chemotherapy.66.7% received alendronate, 28.2% risedronate and 5.1% ibandronate. Those receiving bisphosphonates were older (P&amp;lt;.001) and less likely to be obese (P=.04). The pCR rate was 26% in the bisphosphonate group and 16% in the non- bisphosphonate group (P=.11). After adjusting for potential confounding variables, patients treated with bisphosphonates tended to have higher rates of pCR (OR 2.16 95% CI 0.89-5.25); however the difference did not reach statistical significance. With a median follow up of 55 months (3-145) there were 412 recurrences and 359 deaths. There were no differences on 5-year PFS (71% vs 80%; P=.28) or 5-year OS (77% vs 82%; P=.42) between the two groups. Conclusions: In this cohort of patients, the concurrent use of bisphosphonates at the time of neoadjuvant chemotherapy was not associated with significant increased rates of pCR. The observed estimates suggest a positive effect; however, it is possible that the small proportion of patients receiving bisphosphonates affected the power to detect a statistically significant difference. To fully test the hypothesis, additional, well-powered prospective studies to evaluate the potential use of bisphosphonates as antitumor agents used in the neoadjuvant setting are warranted. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-11-22.