tbuckley/cabot-search huggingface dataset:
Abstract 561: Role of nucleolin in activation of NF-κB signaling with Tip≤, a carcinogenic factor of <i>H. pylori</i>
Authors: Tatsuro Watanabe, Kazuya Hirano, Masatoshi Beppu, Kensei Yamaguchi, Atsushi Takahashi, Hirota Fujiki, Masami Suganuma
Journal: Cancer Research (2012)

Abstract TNF-α inducing protein (Tip≤), a carcinogenic factor secreted from H. pylori, enters the cell through binding to nucleolin, a receptor of Tip≤ on the cell surface. Internalized Tip≤ induces NF-κB activation and TNF-α gene expression and finally induces tumor promotion in the stomach. Nucleolin is a major protein in nucleoli, but significant amounts of nucleolin localize on the cell surface of several gastric cancer cell lines. We investigate the relationship between induction of both NF-κB activation and TNF-α gene expression and the presence of nucleolin, the latter of which acts as a shuttling protein of various molecules, such as Tip≤, lactoferrin and AS1411, from cell surface to cytosol or nuclei. Lactoferrin, iron-binding glycoprotein with 80 kDa, shows anti-cancer activity and preventive activity of H. pylori infection. AS1411 is a nucleolin targeted DNA aptamer associated with a potent anti-cancer activity. First, we studied the effects of lactoferrin, AS1411, and anti-NUC295 (an antibody recognizing cell surface nucleolin) on Tip≤ incorporation into the cells and Tip≤-induced TNF-α gene expression. Pretreatment of mouse gastric cancer cells (MGT-40) with lactoferrin significantly inhibited the incorporation of Tip≤ and Tip≤-induced TNF-α gene expression. However, pretreatment with AS1411 enhanced the incorporation of Tip≤, and inhibited Tip≤-induced TNF-α gene expression. It is of interest to note that Anti-NUC295 enhanced both the incorporation of Tip≤ and Tip≤-induced TNF-α gene expression. These results suggest that both lactoferrin and AS1411 inhibit tumor promoting activity of Tip≤ mediated through inhibition of NF-κB signaling. Thus we think that nucleolin acts as not only a shuttling protein but also a direct regulator of NF-κB signaling. We discuss how lactoferrin and AS1411 inhibit NF-κB activation induced by Tip≤-nucleolin complex, and how nucleolin regulates the NF-κB signaling pathway. 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 561. doi:1538-7445.AM2012-561
390 NEW INTRAHEPATIC qPCR ASSAY DISSECTS THE DIFFERENT ANTIVIRAL EFFECTS INDUCED BY INTERFERON OR ENTECAVIR IN HDV INFECTED HUMAN-CHIMERIC uPA-SCID MICE
Authors: M. Lütgehetmann, K. Giersch, M. Homs, M. Helbig, T. Volz, L. Allweiss, A.W. Lohse, M. Buti, J. Petersen, M. Dandri
Journal: Journal of Hepatology (2013)
Fostering Responsible Data Sharing through Standards
Authors: Rebecca Kush, Michel Goldman
Journal: New England Journal of Medicine (2014)

cerns about causal interpretations remain.Randomized studies embedded in routine care that assess patient outcomes by means of electronic medical record databases are cost-effective and reduce residual imbalances in patient characteristics at the start of a study.The Patient Centered Outcomes Research Institute recently launched a major initiative to build a nationwide network of health care systems that will use their infrastructure for such pragmatic randomized trials.Ultimately, a key to success in learning from big health care data will be to remain focused on our ultimate goal: gaining ac-tionable insights into the best ways to treat the patients in the care system that generated the data.If we work backward from this goal, agreeing on the right analytic methods and the necessary data will be manageable steps, and together we'll be able to negotiate the critical issues of data privacy and standardization.Dr. Schneeweiss reports serving as a consultant to WHISCON and to Aetion, a software manufacturer in which he also owns shares.No other potential conflict of interest relevant to this article was reported.
AB0723 Evaluation of MRI Changes in Patients with Ankylosing Spondylitis and their Correlation with Clinical and Functional Impairment at Different Disease Duration
Authors: S. Kovalenko, G. Protsenko, V. Kachur, K. Ivanova
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease. Magnetic resonance imaging (MRI) is currently used not only to facilitate early diagnosis of the AS, but also to monitor the course of inflammation. <h3>Objectives</h3> To evaluate the differences in clinical and functional impairment for different duration of the disease in AS patients with and without of active inflammation on MRI. <h3>Methods</h3> Study involved 40 people (males) with AS and disease duration &lt;10 years and &gt;10 years. The patients were divided into two groups: Group I – patients without inflammation on MRI or with postinflammatory changes (20 people), Group II – patients with inflammation on MRI (20 people). All evaluation parameters: 10-point assessment of mobility of the spine in the cervical (neck rotation), thoracic (lateral flexion), lumbar parts (modified Schober test), indexes BASMI, BASDAI. All patients underwent MRI of sacroiliac joints and the spine. <h3>Results</h3> Between groups 1 (without inflammation on MRI) and 2 (with inflammation on MRI) were obtained following differences: index BASDAI: &lt;10 years disease duration: 4,10±1,0 vs 4,03±0,48; &gt;10 years of disease duration: 2,36±0,40 vs 3,92±0,35 (p&lt;0,05). Mobility in the cervical parts of spine: &lt;10 years disease duration: 2,75±0,47 vs 5,22±0,52 (p&lt;0,05); &gt;10 years disease duration: 7,49±0,46 vs 7,40±0,35. Mobility in the thoracic parts of spine: &lt;10 years disease duration: 3,50±0,28 vs 6,22±0,72 (p&lt;0,05); &gt;10 years disease duration: 8,50±0,39 vs 8,60±0,65. Mobility in the lumbar parts of spine: &lt;10 years disease duration: 5,75±0,25 vs 8,55±0,50 (p&lt;0,05); &gt;10 years disease duration: 9,81±0,34 vs 9,40±0,55. Index BASMI: &lt;10 years disease duration: 2,60±0,41 vs 4,38±0,38 (p&lt;0,05); &gt;10 years disease duration: 6,06±0,25 vs 5,92±0,41. <h3>Conclusions</h3> In patients with active inflammation on MRI mobility impairments were significantly higher in all parts of the spine in the early stages of the disease (up to 10 years AS duration), and disease activity was significantly higher than in patients without osteitis at disease duration over 10 years. This indicates a lower quality of life for patients with active inflammation on MRI as on the early so on the late stages of the disease. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2663
Amelioration of Diabetes Mellitus by an Insulinoma
Authors: Robert D. Gittler, Gary Zucker, Robert Eisinger, Norman Stoller
Journal: New England Journal of Medicine (1958)

' I 'HE occurrence of a functioning islet-cell tumor -1- of the pancreas in a patient with diabetes mellitus is an exceedingly rare phenomenon. We have recently studied a patient who demonstrated a gradual amelioration of diabetes over a period of nine years that finally culminated in frank episodes of spontaneous hypoglycemia. Laparotomy revealed a large islet-cell tumor of the pancreas. Excision of the neoplasm afforded complete relief of the hypoglycemia and re-emergence of the diabetic state. The preoperative diagnosis of an insulinoma was complicated by the coexistence of diffuse liver disease.Case ReportN.J., a 67-year-old Hebrew man, entered . . .
OP0027 Hand Osteoarthritis (OA) and the Associations to Mortality and Cardiovascular Events - Data from the Framingham Study
Authors: I. K. Haugen, V. Ramachandran, D. Misra, T. Neogi, J. Niu, T. Yang, Y. Zhang, D. T. Felson
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> OA may be influenced by a metabolic phenotype, which may increase risk of cardiovascular (CV) disease. Hand OA is especially likely to be related to metabolic as opposed to mechanical causes. Previous studies have suggested conflicting associations between hand OA and mortality and there has been no exploration of hand OA and specific types of CV disease, which may have different etiologies. <h3>Objectives</h3> To study whether hand OA is associated with increased mortality and cardiovascular events in a population-based cohort. <h3>Methods</h3> We included participants from the Framingham Heart Study, whose CV events and deaths were adjudicated and subtyped by a panel of cardiologists/neurologists. Subjects were 50-75 years, without rheumatoid arthritis and with available information enabling classification of radiographic (≥1 hand joints with Kellgren Lawrence grade (KLG)&gt;2 without pain) and symptomatic hand OA (≥1 hand joints with KLG≥2 and pain in the same joint). Incident CV events (coronary heart disease, congestive heart failure and/or atherothrombotic brain infarction) were defined among subjects that were free of such events at baseline. We examined whether symptomatic and radiographic hand OA were associated with mortality and incident CV events using Cox proportional hazards models adjusting for age, sex, cohort, body mass index, blood glucose, lipid profile, blood pressure, medication use (lipid-lowering, antihypertensive, antidiabetics, NSAIDs and aspirin), smoking and alcohol (for mortality: also previous cardiovascular events and cancer). We also adjusted for the number of joints in the lower limb with pain as a potential marker for OA related physical inactivity. <h3>Results</h3> For analyses on mortality, we included 1348 participants (53.8% women) with mean (SD) age of 62.2 (8.2) years at the time of hand OA assessment, of whom 540 (40.1%) and 186 (13.8%) had radiographic and symptomatic hand OA, respectively. Median (interquartile range) time to death or censoring was 191 (172, 203) months. There was no association between hand OA and mortality (table). Although we did not find a significant relation to incident CV events overall, we found a significant association between symptomatic hand OA and coronary heart disease (table). The association remained after additional adjustment for pain in the lower limb (HR 2.00, 95% CI 0.96-4-15). <h3>Conclusions</h3> Symptomatic hand OA was associated with an increased risk of coronary heart disease events, which remained after adjusting for metabolic factors at baseline as well as pain in the lower limb. The association was non-significant for radiographic hand OA, suggesting an effect of pain, which may be a possible marker of inflammation. <h3>Disclosure of Interest</h3> None Declared
Most unwanted.
Authors: B E Fisher
Journal: Environmental Health Perspectives (1999)

Persistent organic pollutants (POPs) can travel thousands of miles, accumulate in the food chain, and persist in the environment, taking as long as centuries to degrade. POPs are known to play a role in birth defects, cancer, immune system dysfunction, and reproductive problems in wildlife. While the effects of POPs on human health are unclear, many researchers believe that long-term exposure contributes to increasing rates of birth defects, fertility problems, greater susceptibility to disease, diminished intelligence, and certain cancers. Twelve POPs have been identified by the United Nations Environment Programme as requiring urgent regulatory attention. They include the pesticides aldrin, chlordane, DDT, dieldrin, endrin, heptachlor, hexachlorobenzene, mirex, and toxaphene. Of the remaining three POPs, polychlorinated biphenyls are industrial products (used in electrical transformers), and dioxins and furans are unintentional by-products of industrial processes.
The Natural History of Congestive Heart Failure: The Framingham Study
Authors: Patrick A. McKee, William P. Castelli, Patricia M. McNamara, William B. Kannel
Journal: New England Journal of Medicine (1971)

The natural history of congestive heart failure was studied over a 16-year period in 5192 persons initially free of the disease. Over this period, overt evidence of congestive heart failure developed in 142 persons. In almost every five-year age group, from 30 to 62 years, the incidence rate was greater for men than for women. Although the usual etiologic precursors were found, the dominant one was clearly hypertension, which preceded failure in 75 per cent of the cases. Coronary heart disease was noted at an earlier examination in 39 per cent, but in 29 per cent of the cases it was accompanied by hypertension. Precursive rheumatic heart disease, noted in 21 per cent of cases of congestive heart failure, was accompanied by hypertension in 11 per cent. Despite modern management, congestive heart failure proved to be extremely lethal. The probability of dying within five years from onset of congestive heart failure was 62 per cent for men and 42 per cent for women.
THU0435 Detection of synovitis, bone erosions, and bone marrow oedema in patients with inflammatory hand pain - a comparison of low field MRI and high field MRI:
Authors: M.S. Saltzherr, J.J. Luime, B.J. Ejbjerg, M. Østergaard, P.G. Conaghan, R. Ouwendijk, J.M. Hazes, G.S. Muradin
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To compare a 0.2T extremity MRI to a 1.5T conventional MRI for detecting patients with synovitis, bone erosions and bone marrow oedema (BME) among patients presenting with inflammatory hand pain. <h3>Methods</h3> Consecutively referred primary care patients participating in REACH<sup>1</sup> with unexplained inflammatory hand pain &lt;12 months had assessment of the wrist and MCP joints of the most painful hand on a 0.2T extremity MRI and a 1.5T conventional MRI. Both imaging procedures were performed using contrast and followed the recommendations of the OMERACT Rheumatoid Arthritis MRI Score (RAMRIS). The examinations were scored independently and in random time order by two musculoskeletal radiologists for synovitis, erosions and BME using the RAMRIS. A patient with synovitis was defined as ≥1 joint with a synovitis score ≥2, a patient with erosions was defined as ≥1 bone with an erosion score ≥2, and a patient with BME was defined as ≥1 bone with a BME score ≥1. We used cut-off points of 2 for synovitis and erosions, because grade 1 synovitis and erosions are often present in healthy controls.<sup>2-3</sup> Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for the 0.2T MRI with the 1.5T scanner as reference standard. Kappa values were calculated to determine inter-reader agreement in detecting patients with pathology. <h3>Results</h3> 24 out of 40 patients presented with clinically swollen joints, while the remaining 16 patients had only painful joints. The 1.5T MRI detected 20 patients with synovitis, 19 patients with erosions, and 17 patients with BME. The sensitivity, specificity PPV and NPV of the 0.2T MRI are shown in the table. Inter-reader agreement for the proposed case definitions for the 0.2T and the 1.5T MRI respectively, were: 0.50 and 0.75 for scoring synovitis, 0.23 and 0.53 for scoring erosions, and 0.15 and 0.17 for scoring BME. <h3>Conclusions</h3> 0.2T MRI is as sensitive as 1.5T MRI in detecting patients with synovitis and erosions, but had only moderate specificity, and lacks sensitivity for BME. Inter-reader reliability of 0.2T was moderate for synovitis, fair for erosions and low for BME. <h3>References</h3> Alves et al. Ann Rheum Dis 2011;70(9):1645. Ejbjerg et al. Arthritis Rheum 2004;50(4):1097. Palosaari et al. Scand J Rheumatol 2009;38(6):450. <h3>Disclosure of Interest</h3> None Declared
AB0421 Cutaneous involvement in systemic lupus erythematosus.a latenttraitanalysis
Authors: N. Molano-González, J. L. Pérez-Fernández, J. Amaya-Amaya, R. D. Mantilla, A. Rojas-Villarraga, J.-M. Anaya
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Cutaneous involvement is one of the most frequent manifestations of systemic lupus erythematosus (SLE); however ethnicity may influence its prevalence and clinical expression. <h3>Objectives</h3> We aimed to evaluate its prevalence and associated factors in a non-Caucasian population. <h3>Methods</h3> Data from a cohort of 310 patients with SLE (ACR 1997 update) who were seen at a single clinical center were analyzed. The cutaneous involvement latent trait (CILT) was constructed using item response theory and two-parameter logistic model (1) which involved the following variables: photosensitivity, oral ulcers, malar rash, discoid lupus, subacute lupus and urticary. CILT was included as dependent variable in a lineal regression model, adjusted for gender and age at onset. <h3>Results</h3> Cutaneous involvement was observed in 88% (n=273) of patients, and was associated with familial autoimmunity (β=0.44, p=0.001), renal involvement (β=0.34, p=0.042), serositis (β=0.32, p=0.009) and immunological criteria (β=0.20, p=0.035). On the other hand, inverse relationship with age at onset (β=-0.01, p=0.027) and leukopenia (β=-0.23, p=0.03) was found. Some interactions were also observed. Among these, patients with polyautoimmunity tended to have a lower CILT than those with lupus arthropathy. <h3>Conclusions</h3> Cutaneous involvement is a common manifestation in our SLE population. Found associations and interactions can help distinguish patients at risk and guide early interventions. Latent trait analysis may be an instrumental tool for the study of subphenotypes in SLE and other autoimmune diseases. <h3>References</h3> Rizopoulos, D. (2006) ltm: An R package for latent variable modeling and item response theory analyses. Journal of Statistical Software, 17(5), 1–25. <h3>Disclosure of Interest</h3> None Declared
Use of MMTV-Neu/P53 KO Transgenic Mice To Screen for Potential Chemopreventive Agents.
Authors: C. Grubbs, M. Juliana, A. Bode, K. Iwata, M. Ruppert, R. Lubet
Journal: Cancer Research (2009)

Abstract The MMTV-Neu transgenic model of mammary cancer was developed almost 20 years ago in which the mice develop Neu over-expressing ER- mammary cancers. Since human ER- Neu over-expressing mammary cancers often also have mutations in P53, a heterozygous KO of P53 was incorporated into the model. We used this model to examine a wide variety of potential chemopreventive agents. The agents were administered to virgin female MMTV-Neu/P53 KO mice beginning when they were 60 days of age. Initiation of treatment with the agents was later than that typically employed by other investigators (e.g., 35 days of age). Mice were monitored until 360 days of age. In agreement with Brown and colleagues (e.g., Cancer Research 62, 6376-6380, 2002), it was found that both RXR agonists (Targretin, UAB-30) and EGFR 1 and/or 2 inhibitors (Tarceva, Lapatinib) were highly effective in preventing the development of these cancers. We also observed that a wide variety of agents were ineffective; including Atorvastatin, rosiglitazone (a PPAR gamma agonist), SAHA (an HDAC inhibitor), and a soy isoflavones mixture. In separate studies, mice bearing small palpable mammary tumors were treated for five days with these various agents, and examined for alterations in potential biomarkers; including proliferation. As previously shown by our lab in an ER+ rat model of mammary cancer, effective agents (e.g., Iressa and Targretin) strongly inhibited cancer cell proliferation, whereas ineffective agents failed to significantly inhibit proliferation. Thus, such a short-term assay might be employed to predict potential chemopreventive compounds. Short-term treatment with the EGFR inhibitors also decreased levels of expression of phosphorylated EGFR and downstream proteins; e.g., AKT/ERK. Thus, this model is useful in identifying agents that will prevent the development of human breast cancers that over-express Neu. This is important since Neu over-expressing ER- cancers have a relatively poor prognosis, and Neu over-expressing ER+ tumors are relatively unresponsive to standard hormonal therapies (e.g., tamoxifen and aromatase inhibitors). Supported by NCI contract HHSN261200433001C. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1042.
A PHASE 1 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTIPLE ASCENDING DOSE STUDY TO EVALUATE SAFETY, TOLERABILITY AND PHARMACOKINETICS OF THE LIVER-SELECTIVE TR-BETA AGONIST VK2809 (MB07811) IN HYPERCHOLESTEROLEMIC SUBJECTS
Authors: Brian Lian, Rochelle Hanley, Steve Schoenfeld
Journal: Journal of the American College of Cardiology (2016)
FRI0489 Haemophilic artropathy: from sonographic scoring to histopathological modifications
Authors: D. Melchiorre, L. Ibba-Manneschi, A. F. Milia, E. Romano, M. Manetti, S. G. S. Guiducci, S. Linari, M. Morfini, M. Innocenti, M. Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Haemophilic arthropathy (HA) may involve mainly the larger joints (target joint) presenting a spontaneous bleeding, haemarthrosis. Repeated bleeding episodes lead to synovitis implying synovial changes, cartilage and bone damages resulting in disability. The mechanisms and pathways of blood-induced damage in cartilage and bone are still not completely clear. Ultrasonography (US) is helpful to detect bone and cartilage alterations and synovitis. Power Doppler US (PDUS) may identify bleeding also in asymptomatic joints and is able to show different entity of haemarthrosis. <h3>Objectives</h3> To investigate the expression tissue of molecules involved in bone remodelling (RANK/RANKL/OPG system) in synovial tissue from haemophilic patients (HP) with severe HA scored by sonographic score (US score). <h3>Methods</h3> Synovial biopsies from 20 patients with HA and from 16 osteoarthritic (OA) patients, obtained during arthroplasty of the knee, were routinally processed for light microscopy. The severity of HA was evaluated according to a) US score, based on a semiquantitative method (score ranging from 0-21 with cut off&gt;5), b) the World Federation of Haemophilia orthopaedic joint scale (WFH) and c) radiographic Petterson method. Synovial sections were stained with haematoxylin and eosin to evaluate pathological changes. The expression of RANK/RANK-L/OPG, involved in bone remodelling, was examined by immunohistochemistry. Moreover, levels of soluble RANKL and OPG in serum from 67 patients with HA and 30 healthy controls were measured by ELISA assay. <h3>Results</h3> The mean sonographic score in HA patients &gt;5 was 11. The mean WFH clinical score was 39.5 point (range:12-57). The mean Pettersson score was 10.4 points (range: 6-12). Microscopically the synovium from patients with HA showed a large amount of intra- and extracellular haemosiderinic deposits. The lining layer showed mild proliferation and in the sublining area the vessels were characterized by thickened wall, due to a local and chronic inflammatory stimuli. A lower expression of OPG was found in HA synovium compared to OA. RANK and RANK-L positivity was strongly expressed in the lining and sublining both in HA and OA synovial tissue. Serum levels of sRANKL and OPG resulted lower than in controls. <h3>Conclusions</h3> In HA synovial tissue, the elevation of RANK/RANKL and the reduction of OPG suggests an osteoclastic activation. Tissue expression of OPG correlates with serum level of this protein in HP and with severity of HA by US score. <h3>Disclosure of Interest</h3> None Declared