tbuckley/cabot-search huggingface dataset:
PTU-019 A Comparison of Two Colonoscope withdrawal Techniques: Interim Analysis of a Randomised Cross over Study: Abstract PTU-019 Table 1
Authors: A J Ball, S S Johal, S A Riley
Journal: Gut (2013)

<h3>Introduction</h3> Many endoscopists withdraw the colonoscope with the patient in a single position (left lateral or supine), while others advocate position change. A previous study in a small group of patients suggested position change is beneficial in the transverse and left colon. We have compared colonoscope withdrawal in the supine position with position change. <h3>Methods</h3> A randomised cross-over study compared colonoscope withdrawal in the supine position with position change (caecum to hepatic flexure in the left lateral position, transverse colon in the supine position and the hepatic flexure and descending colon in the right lateral position). Colonic segments were precisely defined using biopsy sites as markers, aided by a Scopeguide imager. Segments were cleansed and examined for at least 2 minutes during which air was insufflated to distend the colon. After each segment was examined the colonoscope was reinserted and the same segment was re-examined in the alternative position. Luminal distension was rated on a validated 5 point scale, ranging from 1 = completely collapsed to 5 = maximal distension. Ordinal and categorical data were compared with the Mann Whitney U test and Fisher’s exact test respectively. <h3>Results</h3> This is an interim analysis of 65 patients (mean age 62, 38 male). 30 patients were initially examined in the supine position and 35 patients with position change. Distension scores were higher in the right colon when examined in the left lateral position (mean = 3.9 vs. 3.5 p = &lt; 0.001), and in the left colon when examined in the right lateral position (4.4 vs. 3.6, p = &lt; 0.001) (see table 1). The proportion of patients with scores of 4–5 (adequate) were higher in the right colon when examined in the left lateral position (42/65 vs. 27/65, p = 0.014) and in the left colon when examined in the right lateral position (59/65 vs. 34/65, p = &lt; 0.001). There was no significant carry-over effect in any of the examined segments. <h3>Conclusion</h3> Position change improves suboptimal distension of the right and left colon. Further analysis of this study will clarify whether position change also improves polyp detection. <h3>Disclosure of Interest</h3> None Declared <h3>References</h3> East JE <i>et al.</i> Position changes improve visibility during colonoscope withdrawal: a randomised, blinded, crossover trial. <i>Gastrointest Endosc.</i><i></i> Feb 2007; 65(2):263–269. East JE <i>et al.</i> Dynamic patient position changes during colonoscope withdrawal increase adenoma detection: a randomised, crossover trial. <i>Gastrointest Endosc.</i><i></i> Mar 2011; 73(3):456–463.
Abstract 361: Large scale virtual screening to identify novel inhibitors of Fyn as potential drugs for cancer treatment
Authors: Madhusoodanan Mottamal, Jong-Eun Kim, Nam Joo Kang, Ki Won Lee, Carlos P. Sosa, Ann M. Bode, Zigang Dong
Journal: Cancer Research (2010)

Abstract Protein kinases are involved in a number of signaling cascades and they are considered as one of the major classes of potential drug targets. Overexpression of protein kinases is often found in many human cancers. Fyn, a member of the Src family of tyrosine kinases, plays a critical role in T-cell receptor signaling, brain function, and cell adhesion-mediated signaling. More importantly, Fyn has oncogenic potential and is involved in carcinogenesis processes, including skin cancer development. These properties make Fyn an ideal molecular target for chemoprevention of skin cancer and other diseases. Molecular docking-based virtual screening has become an important tool in the drug discovery process, and it significantly reduces the number of possible chemical compounds to be investigated. In the present study, we carried out virtual screening of chemical databases to find potential inhibitors of Fyn by targeting the ATP-binding pocket. Because binding of ATP to a protein kinase is essential for the phosphotransferase activity of kinases, the ATP-binding pocket is often considered as the first potentially effective target of most inhibitor screens. Potential Fyn kinase activity inhibitors were identified based on the docking score and selected compounds were subjected to in vitro and cellular assays. The in vitro kinase assay has resulted in the identification of a compound with strong (&amp;lt;50 nM) inhibition of Fyn kinase activity. The same compound was found to suppress UVB-induced Fyn kinase activity in JB6 P+ cells. The inhibitor also suppressed UVB-induced cyclooxygenase-2 expression in JB6 P+ cells, indicating its involvement in skin carcinogenesis. Thus, by using virtual screening, we have identified a potential drug candidate to prevent UVB-induced skin cancer. Studies are in progress to validate our observations in vivo. 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 361.
Abstract 2005: Modulation of tumor suppressor gene DNA-methylation by quercetin and dietary indoles
Authors: Temesgen Samuel, Khalda Fadlalla, Teshome Yehualaeshet, Timothy Turner
Journal: Cancer Research (2011)

Abstract Epidemiological and preclinical research provide strong evidence for the anticancer properties of bioactive dietary compounds abundantly found in fruits, vegetables and other fiber-rich food stuff. However, the mechanisms by which nutritional intake of such dietary compounds prevent oncogenesis is largely unknown. We hypothesize that synergistic activities of different dietary compounds through epigenetic mechanisms underlie some of the chemopreventive functions of the dietary compounds. We undertook a preliminary study to examine the effects of Quercetin, Indole-3-Carbinol (I3C) and diindolylmethane (DIM) on promoter methylation profiles of selected genes known to be suppressed by methylation in colorectal cancer. Quercetin is a polyphenolic flavonoid, while I3C and DIM are dietary indoles, DIM being a derivative of I3C. The genes queried in this study were p16INK4a, E-cadherin (CDH1), and IGFBP7. p16INK4a is a cell cycle regulator silenced in up to 40-50% of colorectal carcinomas. E-cadherin is a tumor suppressor and metastasis regulator protein the loss of which promotes wnt-signaling, which is dysregulated in the majority of colorectal cancers. IGFBP7 has recently been identified as a p53-responsive gene frequently silenced in colorectal and gastric cancers. In this study, RKO colorectal cancer cells were treated with the three dietary compounds, vehicle (DMSO), or the demethylating compound 5-azacytidine. DNA was harvested and bisulfite converted. Methylation of the gene promoters was examined by methylation-specific PCR using primer sets that amplify only methylated DNA. Gel electrophoresis and Real-time PCR were used to assess the relative abundance of methylated DNA in control and treated samples. Preliminary results show that the dietary compounds can reverse the methylated-promoter phenotype, with the indole compounds having higher potency compared to quercetin especially in demethylating the CDH1 gene promoter. Further experiments will elucidate the molecular mechanisms through which the compounds modulate gene methylation. 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 2005. doi:10.1158/1538-7445.AM2011-2005
Abstract 5126: Development of a high throughput quantitative phosphoproteomic method to study trastuzumab resistance
Authors: Alaina P. Boyer, Sophie Alvarez, Michael Boyne, Leslie Hicks, Ron Bose
Journal: Cancer Research (2011)

Abstract Her2 is a receptor tyrosine kinase that is overexpressed in approximately 20-30% of human breast cancers and affects clinical prognosis and outcome of these cancers. Treatment of Her2-positive breast cancer with the monoclonal antibody, trastuzumab, has improved the outcomes and prognosis for patients with this breast cancer subtype. However, development of resistance to trastuzumab is a major clinical problem in metastatic Her2-positive breast cancer. Many of the known mechanisms of trastuzumab resistance cause changes in protein phosphorylation patterns and therefore we have employed quantitative phosphoproteomics to further study trastuzumab resistance. Quantitative phosphoproteomics is a powerful method to comparatively identify phosphorylated proteins between different samples. Using electrospray tandem-mass spectrometry coupled with immunoaffinity purification and titanium dioxide (TiO2) phosphoenrichment, we wanted to identify differentially phosphorylated proteins in a pair of trastuzumab sensitive and resistant cells. We used stable isotope labeling of amino acids in cell culture (SILAC) to obtain quantitative information on the proteins identified by mass spectrometry. We have obtained quantitative data on two trastuzumab sensitive and resistant pairs of Her2 overexpressing human breast cancer cell lines (BT474 and SKBR3). 275 proteins were identified in the phosphoenriched fraction from the SKBR3 pair with 83 proteins reporting a ratio. 769 proteins were identified in the phosphoenriched fraction from the BT474 pair with 683 proteins reporting a ratio. Treatment of the trastuzumab resistant cells with Her2 siRNA drastically resulted in cell death indicating the sustained dependence of these cells on Her2 despite the resistance to Her2 targeted therapy. RNAi experiments, in combination with trastuzumab exposure, of candidate proteins expressing an increase in phosphorylation will be tested further to determine if trastuzumab resistance can be reversed. 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 5126. doi:10.1158/1538-7445.AM2011-5126
S77 Compartmentalisation of surface Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) in Ventilator-Associated Pneumonia (VAP)
Authors: V. Grover, P. Kelleher, D. Henderson, N. Soni, S. Singh
Journal: Thorax (2010)

<h3>Introduction</h3> Biomarkers have been investigated in order to speed up diagnosis of VAP, a common condition in ICU patients. TREM-1 is a protein involved in amplification of immune responses to bacterial and fungal infection and exists as soluble and surface forms.<sup>1 2</sup> The diagnostic value of soluble TREM-1 in broncho-alveolar lavage fluid (BALF) in VAP is controversial.3 Therefore the utility of surface TREM-1 for diagnosing VAP in a two-compartment model (BALF and blood) was investigated. <h3>Methodology</h3> Paired blood and BALF were obtained in consenting patients in the following groups: (1) Ventilated patients with VAP diagnosed on semi-quantitative microbiology and Clinical Pulmonary Infection Score (CPIS); (2) Ventilated patients without sepsis; (3) Day-case bronchoscopy patients without evidence of infection. Flow cytometry was performed on cell pellets derived from simultaneous BALF and blood samples. Surface TREM-1, CD11b (immune cell activation marker) and L-selectin (immune cell migration marker) levels were measured on monocytes and neutrophils. At the same time an inflammatory cytokine panel (comprising IL-1β, IL-6, IL-8 and soluble TREM-1) was measured by ELISA in the paired blood and BALF samples. <h3>Results</h3> Expression of TREM-1 and CD11b on monocytes were significantly elevated in BALF samples obtained from the VAP patient group. There was no change in blood surface TREM-1 and CD11b levels between the different patient groups. The BALF/blood ratio of monocytic TREM-1 increased the discrimination between the VAP and non-VAP groups (Abstract S77 Figure 1). Soluble TREM-1 levels were not significantly different between the groups. There was no difference in peripheral blood white cell count, CRP, expression of CD11b, L-selectin and inflammatory cytokines between VAP and disease controls. <h3>Conclusion</h3> The BALF/blood ratio of monocytic surface TREM-1 discriminates between the VAP and non-VAP groups. Measurement of surface TREM-1 using a two-compartment index may have utility in diagnosing VAP.
Abstract 5449: Histone deacetylase inhibitor treatment in B-cell non-Hodgkin's lymphoma - effect of <i>ex vivo</i> treatment on primary patient samples
Authors: Torsten H. Nielsen, Luca A. Petruccelli, Monica C. Dobocan, Filippa Petterson, Tina P. Haliotis, Sarit Assouline, Koren K. Mann, Wilson H. Miller
Journal: Cancer Research (2010)

Abstract The use of histone deacetylase inhibitors (HDACis) is approved in cutaneous T-cell lymphoma, but the efficacy in other lymphomas, particularly B-cell Non-Hodgkin's lymphoma (B-NHL), remains to be established. To investigate the hypothesis that HDACis have anti-neoplastic effects in B-NHL, we have tested a series of primary B-NHL patient samples for response to the two HDACis Vorinostat (SAHA) and Panobinostat (LBH589). Lymph node biopsies from patients with B-NHL were obtained with patient consent. A single-cell suspension was prepared and mononuclear cells isolated by Ficoll gradient separation. Lymphocytes were treated with clinically achievable doses of SAHA (2.5 μM, 5 μM and 7 μM) and LBH589 (10 nM, 25 nM and 50 nM) ex vivo for 48 hours. Treatment effect was evaluated by assays of cell viability (trypan blue staining and Cell TiterGlo luminescence assay) and cell death (propidium iodide staining analyzed by flow cytometric quantification of the sub-G0 cell population). Expression of acetylated histone H4, Bcl-2 and BCL6 was evaluated by western blot. To date, 16 patient samples, covering a wide variety of B-NHL, have been analyzed. Diagnoses include: follicular lymphoma (n=7), diffuse large B-cell lymphoma (n=5), mantle cell lymphoma (n=1), nodal marginal zone lymphoma (n=1), hairy cell leukemia (n=1) and small lymphocytic lymphoma/chronic lymphocytic leukemia (n=1). Fifteen out of 16 patient samples analyzed showed moderate to high sensitivity to one or both HDACis tested at the given concentrations. Overall, the effects of SAHA and LBH589 were comparable. Western blots of lymphocytes treated with both types of HDACi showed increased acetylation of histone H4 compared to untreated cells. No change in Bcl-2 expression was seen (n=2) and no expression of BCL6 was detected in the samples tested for this (n=2). Based on the data outlined herein, B-NHL is sensitive to the growth inhibitory effects of HDACis at clinically achievable doses. Building upon this pilot study, we are developing cell line models of B-NHL in order to characterize the mechanism of action of HDACis in B-NHL, including combination therapy with currently used agents such as Rituximab. A phase 2 clinical trial of LBH589 in diffuse large B-cell lymphoma, including an arm evaluating combination therapy with Rituximab, is also planned. 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 5449.
ISOLATED CORONARY VASCULITIS AS A CAUSE OF ACUTE MYOCARDIAL INFARCTION: A DIAGNOSTIC DILEMMA
Authors: Menhel Kinno, Njambi Mathenge, Monali Patel, Osama Niazi, Ra'Ad Tashman, Seth Justin Lichtenstein, Umair Tariq, Yulanka Castro Dominguez, Venkata Subbarao Boppana, Qaisra Saeed
Journal: Journal of the American College of Cardiology (2016)
THU0282 Immunoadsorption in Lupus Nephritis: Three Different High Affinity Columns are Equally Effective in Inducing Remission
Authors: P. Biesenbach, K. Derfler, J. Smolen, G. Stummvoll
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Pathogenic autoantibodies and immune complexes are a hallmark of SLE and are effectively removed by immunoadsorption (IAS). We previously reported that IAS performed with columns using sheep IgG as ligand (Ig-Therasorb®) reduces proteinuria and global disease activity in highly active renal SLE (Ref.1). Meanwhile, three different IAS columns using different adsorbing ligands are in use for lupus patients. <h3>Objectives</h3> We now attempted to answer the question if one column should be preferred in the treatment of active, refractory lupus nephritis. <h3>Methods</h3> All patients with histologically proven lupus nephritis undergoing IAS (n=26) were included to analyze the effects of IAS during induction therapy (≤3 months) on renal outcome and global disease activity. Patients were grouped according to the IAS column used: IgG-group (sheep IgG, Ig-Therasorb®, n=16), ProtA-group (staphylococcal protein A, Immunosorba®, n=5), and Gam-group (synthetic peptid Gam146, Globaffin®, n=5). Patients underwent IAS therapy when cyclophosphamide or MMF therapy was not effective or contraindicated; characteristics are given in the table. As described, we used response criteria R20 and R50, defined as a reduction by 20% or 50% in at least 2 of the 3 main outcome parameters proteinuria, SLEDAI and pre-treatment anti-dsDNA levels (Ref 1). <h3>Results</h3> In all 3 groups, IASsignificantly lowered serum levels of IgG, IgM, and anti-dsDNA-abs. Proteinuria significantly decreased in all groups, with a reduction by 48% in IgG versus 67% in ProtA and 64% in Gam groups, respectively (p=n.s.), while serum-creatinine decreased accordingly (table). All groups presented with comparably high disease activity scores (SLEDAI) and achieved a significant reduction within one month. After 3 months, all groups showed good responses with a R20 in &gt;80% and a R50 in &gt;60% of patients. No severe adverse event (allergic reaction, critical hypotension) occurred. Infections were distributed equally among the 3 groups with one infection per patient year necessitating antibiotics. <h3>Conclusions</h3> IAS reduces proteinuria and global disease activity in refractory lupus nephritis and improves renal function. All three columns performed well in induction therapy with slightly, albeit not significantly better response rates for ProtA and Gam columns. Our findings on efficacy of different columns may facilitate future attempts for randomized controlled trials on IAS in lupus nephritis <h3>References</h3> Stummvoll et al;IgG immunoadsorption reduces SLE activity and proteinuria: a long term observational study. ARD Juli 2005 <h3>Disclosure of Interest</h3> None Declared
The Free Achilles Reflex in Hypothyroidism and Hyperthyroidism
Authors: John D. Lawson
Journal: New England Journal of Medicine (1958)

FOR many years clinicians have noted a correlation between the level of thyroid function and the speed of tendon reflexes. As early as 1924 Chaney, at the Mayo Clinic, attempted to quantitate the slowing of the Achilles reflex in myxedema.1 Although his observations were subsequently proved to be valid, his recording methods were too cumbersome for the average clinician in office practice.Since Chaney's original work several investigators have studied the Achilles reflex in hypothyroidism2 3 4 5 and hyperthyroidism,4 and the biceps reflex has been studied in myxedema.6 Several textbooks have also called attention to the diagnostic importance of the Achilles reflex . . .
THU0016 Investigation of RA genetic susceptibility loci contribution to response outcomes following conventional DMARD treatment in early RA
Authors: M.D. Morgan, S. Twigg, E.M.A. Hensor, P.G. Conaghan, J. Worthington, P. Emery, J.H. Barrett, A.W. Morgan
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The first-line treatment of rheumatoid arthritis (RA) involves the introduction of one or more disease-modifying anti-rheumatic drugs (DMARDs), such as methotrexate (MTX) or more historically sulphasalazine (SSA). Many patients only achieve a partial response to these therapies, ultimately requiring biological therapy. There are currently no predictive biomarkers that are sufficiently robust to inform treatment decisions in routine clinical practice. <h3>Objectives</h3> To investigate RA genetic susceptibility variants in the context of treatment outcomes in the initial 6 months of conventional DMARD therapy in RA. <h3>Methods</h3> Clinical data from early RA patients recruited into a multi-centre observational cohort were used, consisting of matched clinical and genotyping data on 608 patients with 6 month follow-up. A multivariate analysis of each of 41 single nucleotide polymorphisms (SNPs) across 34 genomic loci previously associated with susceptibility to RA were investigated for association with primary and secondary treatment outcomes; the primary outcome of improvement in DAS28 (ΔDAS28; baseline DAS28 minus 6month DAS28) after adjustment for baseline DAS28 and baseline HAQ, and the secondary outcome of achieving a low-disease activity state at 6 months (DAS28≤3.2) adjusted for baseline HAQ only. A threshold for nominal association was set at p&lt;0.05, with a Bonferroni adjusted p&lt;1.47×10<sup>-3</sup> for 34 tests based on the number of loci tested for association. <h3>Results</h3> The 608 patients with 6 month follow-up data included in this analysis had a mean age at baseline of 59.4 years (SD 12.9), mean symptom duration of 8.59 months (SD 9.6), (70.7%) were female, 70.8% were seropositive for RF and/or ACPA (RF 70.5%, ACPA 61.4%) and 38.7% achieved a low disease activity state (DAS28≤3.2 at 6months). No differences were observed in treatment outcomes between patients on MTX or SSA (ΔDAS28 p=0.858, DAS28≤3.2 p=0.728). SNPs mapping to the <i>FCGR2A</i>, <i>TRAF1/C5</i> and <i>UBASH3A</i> loci (rs12746613, rs10760130 and rs3788013 respectively) showed nominal association with ΔDAS28 at 6months follow up (p=0.028, p=0.035, p=0.034, respectively). Two SNPs were found to show nominal association with DAS28≤3.2 at 6months at the <i>STAT4</i> (rs10181656) and <i>UBASH3A</i> (rs3788013) loci (p=0.004 and p=0.045, respectively). No SNPs were found to be associated with treatment outcomes at the Bonferroni adjusted threshold. <h3>Conclusions</h3> Genetic variants associated with modulating susceptibility to RA may also have a role in determining treatment outcomes in early RA patients following conventional DMARD treatment. Replication studies in comparable populations are needed in order to interpret these findings robustly. <h3>Disclosure of Interest</h3> None Declared
Double-Stranded RNA Stimulates TLR3-Dependent Upregulation of IL-33 Transcript and Protein in Pulmonary Microvascular Endothelial Cells
Authors: Akio Matsuda, Maiko Sugie, Tetsuo Shoda, Kyoko Futamura, Hirohisa Saito, Kenji Matsumoto
Journal: Journal of Allergy and Clinical Immunology (2015)