tbuckley/cabot-search huggingface dataset:
Abstract 3825: Prognosis of esophageal adenocarcinoma is dependent on early G1 cyclin-dependent kinase activity
Authors: Amin Ismail, Santhoshi Bandla, Liana Toia, Zhongren Zhou, William E. Gooding, Marie Reveiller, Irina Kalatskaya, Lincoln Stein, Mary D'Souza, Virginia R. Litle, Jeffrey H. Peters, Arjun Pennathur, James D. Lucketich, Tony E. Godfrey
Journal: Cancer Research (2011)

Abstract Background: Chromosomal gain at 7q21 is a frequent event in esophageal adenocarcinoma (EAC). However, this event has not been mapped with fine resolution in a large EAC cohort and its associations with clinical endpoints and functional relevance are unclear. Methods: We used a cohort of 116 patients to fine map the 7q21 amplification using SNP microarrays. 7q21 amplification and its gene expression were explored for associations with patient survival. Effects of siRNA-mediated knockdown of CDK6, its homolog CDK4 and the CDK4/6 inhibitor PD-0332991 were studied in vitro. Results: 34.5% of tumors harbor 7q21 amplification which spans 17 genes with a focal amplicon of 6 genes. The amplification is associated with patient overall survival. Correlation of gene expression and survival identified CDK6 as the only gene in the core amplicon whose expression strongly associates with poor survival. In addition, the expression of CDK4, which is an unamplified homolog of CDK6, correlates with poor survival. The combined expression of both genes is a superior predictor of survival than either alone. siRNA-mediated knockdown of CDK4 and/or CDK6 suggests that they are required for proliferation of EAC cells and that their function is additive. PD-0332991 targets the kinase activity of both molecules and suppresses proliferation and anchorage-independence of EAC cells through activation of the pRB tumor suppressor pathway. Conclusion: We refined 7q21 amplification in EAC and demonstrate its association with poor survival. We suggest that CDK6 is the driver of the amplicon and that prognosis of EAC is dependent on its expression along with its homolog CDK4. Targeting these molecules may thus constitute a viable new therapy for EAC. 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 3825. doi:10.1158/1538-7445.AM2011-3825
Lewisham appeal will decide which local commissioners can veto reconfigurations
Authors: C. Dyer
Journal: BMJ (2013)

England’s health secretary, Jeremy Hunt, will argue in the Court of Appeal next month that if the High Court ruling stopping him downgrading services at Lewisham Hospital is upheld, local commissioning groups with a vested interest in the status quo will have a veto on NHS service reorganisation.

Mr Justice Silber ruled at the High Court in July that one of the tests for reconfiguration had not been met because commissioners in Lewisham, south east London, who commission 70% of services at the hospital, were hostile to the proposals.1 Hunt had argued that …
P197 ENDOCANNABINOIDS SUPPRESS CYTOKINE SECRETION IN HCV INFECTION
Authors: E. Patsenker, P. Sachse, J. Mattson, C. Lanz, V. Schneider, R. Brenneisen, A. de Gottardi, J.F. Dufour, F. Stickel, N. Semmo
Journal: Journal of Hepatology (2014)
LOW ENDOTHELIAL PROGENITOR CELL (CD34+/VEGFR2+) COUNT IS AN INDEPENDENT PREDICTOR OF PERIPHERAL ARTERIAL DISEASE
Authors: Salim Hayek, Ayman Samman Tahhan, Adithya Yadalam, James MacNamara, Mosaab Awad, Ibhar Al Mheid, Qunna LI, Edmund Waller, Arshed Quyyumi
Journal: Journal of the American College of Cardiology (2015)
Enhanced recruitment of genetically modified CX3CR1-positive human T cells into Fractalkine/CX3CL1 expressing tumors: importance of the chemokine gradient
Authors: Imran Siddiqui, Marco Erreni, Mandy van Brakel, Reno Debets, Paola Allavena
Journal: Journal for ImmunoTherapy of Cancer (2016)

<h3>Background</h3> Adoptive T-cell based immunotherapies constitute a promising approach to treat cancer, however, a major problem is to obtain effective and long-lasting anti-tumor responses. Lack of response may be due to insufficient trafficking of specific T cells to tumors. A key requirement for efficient migration of cytotoxic T cells is that they express chemokine receptors that match the chemokines produced by tumor or tumor-associated cells. <h3>Methods</h3> In this study, we investigated whether the in vivo tumor trafficking of activated T cells could be enhanced by the expression of the chemokine receptor CX3CR1. Two human colorectal cancer cell lines were used to set up a xenograft tumor model in immunodeficient mice; the NCI-H630, constitutively expressing the chemokine ligand CX3CL1 (Fractalkine), and the RKO cell line, transduced to express CX3CL1. <h3>Results</h3> Human primary T cells were transduced with the receptor CX3CR1-eGFP. Upon in vivo adoptive transfer of genetically modified CX3CR1-T cells in mice bearing NCI-H630 tumors, enhanced lymphocyte migration and tumor trafficking were observed, compared to mice receiving Mock-T cells, indicating improved homing ability towards ligand-expressing tumor cells. Furthermore, significant inhibition of tumor growth was found in mice receiving modified CX3CR1-T cells. In contrast, tumors formed by RKO cells transduced with the ligand (RKO-CX3CL1) were not affected, nor more infiltrated upon transfer of CX3CR1-T lymphocytes, likely because high levels of the chemokine were shed by tumor cells in the systemic circulation, thus nullifying the blood-tissue chemokine gradient. <h3>Conclusions</h3> This study demonstrates that ectopic expression of CX3CR1 enhanced the homing of adoptively transferred T cells towards CX3CL1-producing tumors, resulting in increased T cell infiltration in tumor tissues and decreased tumor growth. Our results also establish that a correct chemokine gradient between the systemic circulation and the tumor is an essential requirement in adoptive T-cell based immunotherapy to efficiently recruit T cell effectors at the correct sites.
CAPSULE ENDOSCOPY IN THE SOUTHERN TRUST-INITIAL EXPERIENCES
Authors: J B M Doyle, N McKee, S J Murphy
Journal: Gut (2013)

<h3>Introduction</h3> Capsule endoscopy (CE) has been utilised for &gt;10 years, commencing in the Southern Trust in 2010. We assessed our initial experiences with CE. <h3>Method</h3> Retrospective chart reviews of Southern Trust patients referred for CE. <h3>Results</h3> The first 31 cases were available. Twenty-one (68%) were undertaken assessing for suspected Crohn9s disease/stage existing Crohn9s disease, nine (29%) for obscure GI bleeding (OGIB) and one (3%) for assessing polyp formation in a patient with FAP. For OGIB patients, 6 (67%) had an OGD and Colonoscopy performed, 2 had no OGD, and one had no colonoscopy performed. Eleven patients (35%) had an abnormal CE. Of these, 6 (55%) showed findings consistent with Crohn9s disease. In 4 cases a new diagnosis was made, the other 2 cases helped guide treatment intensification with thiopurine/biologic therapy. Of the five remaining abnormal CE9s, 2 showed small bowel erythema of unclear significance. One showed duodenal erosions, one duodenal polyps, and one showed small bowel erosions which when biopsied was consistent with Cryptogenic-Multifocal-Ulcerating-Stenosing-Enteritis (CMUSE). Two referrals for enteroscopy were made following an abnormal CE. Twenty patients/(65%) had a normal CE. Nine/(45%) were discharged from clinic, five/(25%) had one final OPD review, two/(10%) were referred back to their referring Consultant, and four/(20%) had on-going review. <h3>Conclusion</h3> Overall, CE is a useful modality for diagnosis of small bowel disorders. It is useful in cases of diagnostic uncertainty regarding IBD, and guides treatment options. It leads to fewer follow up clinics, with 45% of patients with a normal CE being discharged, and 25% seen for one final clinic appointment.
Bilateral Alien Hand Syndrome in Cerebrovascular Disease
Authors: Justo Serrano-Vicente, Carmen Duran-Barquero, Lucia Garcia-Bernardo, Maria Luz Dominguez-Grande, Jose Rafael Infante-Torre, Juan Ignacio Rayo-Madrid
Journal: Clinical Nuclear Medicine (2014)

We report a 65-year-old man with a right cerebral infarction that occurred 15 years ago and a residual left hemiparesis that began with progressive contralateral hemiparesis. During the hospitalization, the patient developed a bilateral alien hand syndrome. Urgent CT, MR, CT angiography, and brain perfusion SPECT were performed that revealed an old right cerebral infarction and a new ischemic lesion in left parietal lobe and adjacent brain territories.
Scintigraphy of Popliteus Bursitis
Authors: KIRSTEN DUFFEY, HANS VAN DER WALL
Journal: Clinical Nuclear Medicine (2000)

A 16-year-old boy had pain in the lateral aspect of the right knee after he played two games of cricket. Examination revealed a tender firm mass along the posterolateral aspect of the right knee. Results of plain radiographs were normal. Bone scintigraphy showed hyperemia and increased uptake along the posterolateral margins of the right tibial plateau and across the fibula head. Ultrasound confirmed a fluid collection in the popliteus bursa and abnormal echogenicity from the popliteus tendon. Popliteus bursitis was diagnosed and treated by local anesthetic and corticosteroid injection into the bursa.
Targeting Src/Stat3 pathway in malignant melanoma
Authors: J. Homsi, J. Messina, C. Cubutt, S. Maunglay, L. Scalf, A. Komarla, H. Yu, R. Jove, A. Daud
Journal: Journal of Clinical Oncology (2006)

8025 Background: The Src/Stat 3 pathway has been implicated in the pathogenesis of several malignancies including melanoma. In the current study we evaluated the prevalence of Src and Stat3 activation in human melanoma and the effect of Src inhibitors alone or in combination with chemotherapeutic agents on melanoma cell lines. Methods: Activation of Src was measured by staining for Src-phosphotyrosine 416 (P-Src) and Stat3 by phosphotyrosine 705 Stat3 (P-Stat3). Immunohistochemistry was performed with anti-pStat3-Y705 and anti-pSrc-Y416 antibodies (Cell Signaling, Beverly, MA) on 3 melanoma subtypes. Staining of tumor cells for P-Stat3 was scored by percentage of stained cells as follows: 0 (no staining), 1 (1–25%), 2 (26–50%), 3 (&gt;50%), and intensity 0–3 (0: absent, 1: low, 2: moderate, and 3: high). The sum of these was the composite P-Stat3 score: 0 (0), 1 (1–2), 2 (3–4), and 3 (5–6). P-Src staining was scored by intensity. Melanoma cell lines, A-375, SK-Mel-5 and SK-Mel-28 were exposed to Src inhibitors, SKI-606, PD 180970 and BMS 354825 alone or in combination with standard chemotherapy agents and IC-50 was determined by MTT assay at 24 and 72 hours. Results: 35 biopsies were stained. Median age was 66 years (range 23–90); 60% were women. 48% of all melanoma stained express P-Src; all samples express pStat3. We found a positive correlation between P-Src and P-Stat3 (Spearman coefficient=0.346, p=0.042). 46% stained only for pStat3 and 6% did not stain for either P-Src or P-Stat3. Most positively stained biopsies stained weakly for P-Src and moderately or strongly for pStat3. Src inhibitors inhibited the proliferation of melanoma cell lines; furthermore Src inhibitor treatment synergized with platinum and topoisomerase I inhibitors but not temozolomide. Conclusions: 1) Immunohistochemistry shows variable expression of P-Src and P-Stat3 in human melanoma 2) All tumors staining for P-Src also stain for P-Stat3 and the strength of staining is significantly related. 3) This data may be useful in planning future clinical trials with Src inhibitors in melanoma. [Table: see text] [Table: see text]
SAT0078 Decreased peripheral CD3 zeta chain expression in patients with active rheumatoid arthritis can be restored by various biologic DMARDs and methotrexate
Authors: T. Kondo, K. Yoshimoto, K. Suzuki, H. Kameda, K. Amano, T. Takeuchi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> CD3 zeta chain (CD3 zeta) is a member of T cell antigen receptor CD3 complex and has crucial role in proximal signal transduction after peptide antigen recognition. CD3 deficiency and loss of immunoreceptor tyrosine-based activation motif (ITAM) domain in CD3 zeta can lead to autoimmune diseases in mice. Furthermore, previous reports including us have clearly shown that CD3 zeta expression was decreased in peripheral blood T cells from lupus patients. On the other hand, a few reports on CD3 zeta in rheumatoid arthritis (RA) were controversial and its role remains still unclear. <h3>Objectives</h3> Aim of this study is to investigate the role of CD3 zeta in RA. Especially, we focused on the effect on the expression of CD3 zeta by biologic DMARDs and methotrexate (MTX). <h3>Methods</h3> In this study, 33 patients who had visited to our division were diagnosed as the 2010 ACR-EULAR classification criteria for RA and 8 healthy subjects were enrolled. The patients' background, clinical and laboratory features were also evaluated. Peripheral blood T cells were obtained from the patients with RA at the point of start and 24 weeks after treatment. Protein expression of CD3 zeta was measured by immunoblot analysis by anti-CD3 specific monoclonal antibody. <h3>Results</h3> Mean age was 60.2 years old and 72.7% of patients were female. All of the patients had active diseases at the start of treatment. Disease activity score (DAS28-ESR) were 5.16±1.37 and simplified disease activity index (SDAI) was also high, 26.1±14.2 (Mean ± SD). Twenty-six patients were treated with biologic DMARDs (infliximab (IFX): 11 cases, tocilizumab (TCZ): 9, abatacept (ABT): 3, adalimumab (ADA): 2, and etanercept (ETN): 1). Residual 7 patients were treated with MTX alone for 24 weeks. The protein expression level of CD3 zeta was significantly decreased in 29/33 (87.9%) of RA patients as compared with that in healthy subjects (cutoff value were set as mean – 2SD in healthy subject). In average, 68% reduction of CD3 zeta were observed in RA patients (p&lt;0.05). Next, comparing to clinical indicators, DAS28-ESR, SDAI, and dose of concomitant steroid administration were not significantly correlating to CD3 zeta at the start. However, CD3 zeta expression after treatment is restored to nearly same level as healthy subjects in half of them. The recovery level of CD3 zeta did not correlated to DAS28-ESR directly. The recovery was observed in all treatment groups. Compared with agents, interestingly IFX treatment made 3.3 times as high recovery as MTX treatment. <h3>Conclusions</h3> Decreased peripheral CD3 zeta protein expression was observed in active RA patients. These effects can be restored by various biologic DMARDs and MTX. Such new insights on CD3 zeta may give a clue for discovery of fundamental pathogenesis on RA. <h3>Disclosure of Interest</h3> None Declared
Case 12-2014
Authors: Lawrence S. Friedman, Leigh H. Simmons, Rose H. Goldman, Aliyah R. Sohani
Journal: New England Journal of Medicine (2014)

A 59-year-old man was admitted to the hospital because of fatigue, abdominal pain, new anemia, arthralgias, abnormal liver function, and emotional lability. A peripheral-blood smear showed polychromasia and coarse basophilic stippling of erythrocytes.
A Cystic Fibrosis Mutation Associated with Mild Lung Disease
Authors: King-Han Gan, Henk J. Veeze, Ans van den Ouweland, Dicky Halley, Hans Scheffer, Annemieke van der Hout, Shelley E. Overbeek, Johan C. de Jongste, Willem Bakker, Harry Heijerman
Journal: New England Journal of Medicine (1995)

Cystic fibrosis is the most common lethal autosomal recessive disorder among whites. Among Dutch patients with cystic fibrosis, ΔF508 is the most common mutation and A455E the second most common mutation of the cystic fibrosis transmembrane conductance regulator gene on chromosome 7. A455E is associated with preserved pancreatic function and residual secretion of chloride across membranes. We investigated whether it is also associated with less severe pulmonary disease in patients with cystic fibrosis.
SP0200 What is New in Psoriatic Arthritis?
Authors: H. Burkhardt
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Recent advances in the field of genetics, immunology and molecular biology have improved our understanding of underlying disease mechanisms in psoriatic arthritis (PsA) implicating pathways of innate as well as adaptive immunity. Some of the incriminated pathogenic mechanisms such as cytokine actions associated with TH17-driven effector pathways have also been targeted by new therapeutic agents. Thus, pivotal phase III studies have demonstrated effectiveness of IL-12/IL-23 inhibition by ustekinumab leading to its approval for PsA treatment. Trial programs for additional biologics targeting either IL-17A directly such as the anti-cytokine antibodies secukinumab and ixekizumab or its respective receptor such as the anti-IL-17RA antibody brodalumab are ongoing with preliminary encouraging results. Moreover, the armentarium for PsA treatment has also broadend by the recent approval of the TNF-blocking agent certolizumab. In addition, new results from a large phase III trial program of the orally applicable small-molecule apremilast, a phosphodiesterase inhibitor, have demonstrated its safety and effectiveness in PsA and psoriatic skin disease. The achieved progress in PsA reflected by an increased number of available pharmacotherapeutic options is flanked by attempts to further improve treatment results by the adaptation of treat to target strategies. Respective recommendations have been recently published by an international task force of experts and are supported by data available from the TICOPA study in the UK showing that the use of early and intensive treatment in PsA in routine clinical care leads to an improved clinical and radiographic outcome <h3>Disclosure of Interest</h3> H. Burkhardt Grant/Research support from: Abbvie, Pfizer, Roche, Consultant for: Abbvie, BMS, Janssen-Cilag, Pfizer, UCB, Conflict with: Abbvie, BMS,Chugai, GSK, Pfizer, MSD, UCB <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6205
Proteomic analysis to identify the pathophysiological role of placental growth factor (Plgf) in hepatic stellate cell function and cirrhosis
Authors: Jordi Ribera, Sonia Tugues, Montserrat Pauta, Anja Geerts, Christophe Van Steenkiste, Isabelle Colle, Peter Carmeliet, Vicente Arroyo, Wladimiro Jiménez, Manuel Morales-Ruiz
Journal: Hepatology (2008)
PREVALENCE, INDICATIONS AND MANAGEMENT OF BALLOON UNCROSSABLE CHRONIC TOTAL OCCLUSIONS: INSIGHTS FROM A CONTEMPORARY MULTICENTER US REGISTRY
Authors: Judit Karacsonyi, Aris Karatasakis, Dimitrios Karmpaliotis, Khaldoon Alaswad, Robert Yeh, Farouc Jaffer, R. Michael Wyman, William Lombardi, Aaron Grantham, David Kandzari, Nicholas Lembo, Jeffrey Moses, Ajay Kirtane, Manish Parikh, Santiago Garcia, Anthony Doing, Mitul Patel, John Bahadorani, Erica Resendes, Barbara Anna Danek, Bavana Rangan, Imre Ungi, Craig Thompson, Subhash Banerjee, Emmanouil Brilakis
Journal: Journal of the American College of Cardiology (2016)
The Use of Phthalylsulfathiazole (Sulfathalidine) in Colonic Surgery
Authors: Robert Thomson, Ernest M. Daland
Journal: New England Journal of Medicine (1946)

IN 1941, Poth and Knotts1 introduced succinylsulfathiazole (sulfasuxidine) as an intestinal antiseptic and bacteriostatic agent. It has proved especially valuable as an adjunct to surgery of the large bowel, as well as in the treatment of certain medical conditions. A further improvement was made in this field with the discovery of phthalylsulfathiazole (sulfathalidine§) by Poth and Ross2 in 1943. This new drug has the advantage of having twice the bacteriostatic activity of succinylsulfathiazole but requiring only half to one third of its dosage. In addition, the drug has not given rise to any toxic reactions such as have occasionally . . .
SAT0393 The Effects of Coexisting Fibromyalgia on Disability of the Computer Users with Cumulative Trauma Disorders
Authors: Ö. Bozkurt Tuncer, H. Genc, H. R. Erdem, B. Nacir
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The effects of coexisting fibromyalgia syndrome (FS) on disability of computer users with cumulative trauma disorders (CTD) hasn't been studied previously. <h3>Objectives</h3> To evaluate the existence of FS in computer users with CTD and to investigate the effects of coexisting fibromyalgia on disability of computer users. <h3>Methods</h3> 150 computer users are included in the study. Computer users were classified as complainant group (CDT+) who have complaints concerning to neck, back and upper extremity and non-complainant group (CTD-) who have no complaint. 50 age, sex and body mass index matched non-computer user, healthy hospital stuff were recruited as the control group. All participants were asked to fill our questionnaire form including detailed risk factor query and physical examination. Pain assessment was made by visual analog scale. ACR 2010 classification criteria were used to identify patients with FS. Tender point (TP), control point (CP) and pressure pain threshold (PPT) measurements of all participants were made using Fischer's tissue compliancemeter and number of tender points (NTP), tender point score (TPS), control point score (CPS) and total myalgic score (TMS) were calculated. In order to measure the general disability levels of the participants, Quick DASH Score (QDS) was used, besides to measure their disability levels during work, Quick DASH Work Score (QDWS) was used. <h3>Results</h3> 104 (69%) of the computer users had CTD. The mean ages of the 104 participants with CTD (72 females and 32 males) was 31,1±6,2 years, of the 46 with non-CTD (28 females and 18 males) was 30,5±6,6 years and of the 50 controls (32 females and 18 males) was 31,9±5,8 years. The presence of FS in complainant group (n:42) was higher than the non-complainant group (n:5) and control group (n:0) (p&lt;0.05). The mean value of NTP was higher (p&lt;0.001) and the mean values of TPS, CPS and TMS were lower (p&lt;0.001) in the complainant group than non-complainant group and controls. The coexisting fibromyalgia increased the severity of pain, and levels of QDS and QDWS (p&lt;0.05-p&lt;0.001). Statistically significant correlations were found between increased NTP, decreased TPS, decreased tender point PPT, decreased TMS and high levels of both QDS and QDWS. <h3>Conclusions</h3> We found that coexisting fibromyalgia increased the disability levels of computer users with CTD. We believe that treatment of coexisting fibromyalgia is of great importance as well as recovery in the workplace conditions, ergonomic circumstances, depression and negative aspects in social life. <h3>Disclosure of Interest</h3> None Declared
Identification of verocytotoxin-producing Escherichia coli O117:H7 in men who have sex with men, England, November 2013 to August 2014
Authors: I Simms, V L Gilbart, L Byrne, C Jenkins, G  K Adak, G Hughes, P D Crook
Journal: Eurosurveillance (2014)

Between November 2013 and August 2014, nine cases of verocytotoxin-producing Escherichia coli O117:H7 VT1 were confirmed in adult men. Further investigation using semi-structured interviews revealed that eight cases were United Kingdom (UK)-born men who have sex with men (MSM) who had sexually acquired infection in the UK. Most were HIV-positive with high numbers of sexual partners. This behavioural profile resembles that associated with the recent rapid increase in other sexually acquired infections in MSM.
NONCONVULSIVE ELECTRIC STIMULATION THERAPY
Authors: LEO ALEXANDER
Journal: American Journal of Psychiatry (1950)

Convulsive treatment through frontal leads inhibits respiration temporarily; nonconvulsive treatment through frontal or temporopariental leads stimulates respiration. Convulsive treatment through frontal leads relieves depression but reduces awareness for memory content and may enhance anxiety, while nonconvulsive treatment through temporoparietal leads relieves anxiety and restores awareness for memory content, but may enhance depression. By using both, it is possible to avoid the "untreatable" residual after electroshock treatment.