tbuckley/cabot-search huggingface dataset:
Abstract 2813: Modulation of Signal Transducer and Activator of Transcription 3 by emodin through the induction of a phosphatase leads to the suppression of HCC growth in orthotopic mouse model
Authors: Muthu K. Shanmugam, Tina H. Ong, Rajendran Peramaiyan, Aruljothi Subramaniam, Kam M. Hui, Gautam Sethi
Journal: Cancer Research (2012)

Abstract Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and the third cause of global cancer mortality. Activation of signal transducer and activator of transcription 3 (STAT3) is commonly encountered in tumor cells and is a critical mediator of oncogenic signaling in HCC and controls the expression of several genes involved in proliferation, survival, metastasis and angiogenesis. Current drug-targeted therapies, besides being expensive, are associated with serious side effects and morbidity. Thus, novel agents that can suppress STAT3 activation have potential for both prevention and treatment of HCC. In this study, we tested an agent, emodin, a quinone, for its ability to suppress STAT3 activation in HCC cells and in nude mice model along with prospectively testing the hypothesis of STAT3 inhibition in a virtual predictive functional proteomics tumor pathway technology platform. We present evidence that emodin can inhibit both constitutive and inducible STAT3 activation in HCC cells. The suppression was mediated through the inhibition of activation of upstream kinases c-Src, and Janus-activated kinase-2. Vanadate treatment reversed the emodin induced down-regulation of STAT3 activation, suggesting the involvement of SHP1. Indeed, we found that emodin induced the expression of tyrosine phosphatase SHP1 and deletion of SHP1 by small interfering RNA abolished emodin ability to inhibit STAT3 activation and provide new evidence on the critical role of SHP1 in mechanism of action of emodin. Emodin inhibited proliferation, and produced a synergistic apoptotic effects in the presence of paclitaxel and doxorubicin in HCC cells. When administered i.p., emodin inhibited the growth of human HCC orthotopic tumors in male athymic nu/nu mice. In conclusion, results from experimental and predictive studies suggest that emodin exerts its anti-proliferative and pro-apoptotic effects through suppression of STAT3 signaling cascade in HCC both in vitro and in vivo. 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 2813. doi:1538-7445.AM2012-2813
SAT0065 Alpha-enolase facilitates migration of fibroblast-like synoviocytes in rheumatoid arthritis
Authors: K. Shin, J.A. Park, S. Bae, J.S. Kang, Y.W. Song
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Alpha-enolase (ENO1) is a multifunctional glycolytic enzyme ubiquitously expressed in the cytoplasm. Citrullinated ENO1 is reported to be a candidate autoantigen in rheumatoid arthritis (RA), yet its specific biologic function remains unknown. Histologic analysis indicates that ENO1 is expressed in fibroblast-like synoviocytes (FLS), monocytes, and endothelial cells in the synovium. In pro-inflammatory conditions, ENO1 is translocated to the cell surface where it activates plasminogen. Its expression in monocytes mediates migration of the cells into inflamed lung tissues in animal models. <h3>Objectives</h3> Our aim was to investigate the role of surface-expressed ENO1 in RA FLS, the key constituent of pannus in RA synovium. <h3>Methods</h3> FLS from RA synovial tissues were isolated and cultured <i>in vitro</i>. ENO1 expression on the cell surface was assessed by confocal microscopy. Cell surface-expressed ENO1 was treated with a mouse anti-human ENO1-stimulating monoclonal antibodyas well as an isotype control. Scratch test of cultured FLS and transwell experiments under platelet-derived growth factor (PDGF) were performed to assess FLS migration. Cytoskeletal rearrangement was analyzed after staining FLS with an anti-fillagrin antibody. Fluo-4 fluorophore was used for calcium-flux assays directly on discs plated with FLS. <h3>Results</h3> Cell surface ENO1 expression was low in (5∼6 passages) cultured FLSunder normal condtions. However, overnight TNF-alpha (as low as 0.1ng/ml)treatment induced ENO1 translocation to the cell surface, which peaked at 24 hours (figure). Stimulation of cell surface-expressed ENO1 induced faster repopulation of FLS in the scratch test assay, and increased PDGF-induced transwell migration. Cytoplasmic actin filament rearrangement in FLS was markedly enhanced with ENO1 stimulation. Moreover, ENO1 stimulation induced a positive calcium flux response in FLS under intravital confocal microscopy. <h3>Conclusions</h3> Translocation of cytoplasmic ENO1 to the cell surface in RA FLS is potentiated by TNF-alpha. Our results indicate that ENO1 can contribute to migration of RA FLS, especially under the pro-inflammatory milieu as in the RA synovium. <h3>Disclosure of Interest</h3> None Declared
Recurrent Hematuria and Focal Nephritis
Authors: Thomas F. Ferris, Phllip Gorden, Michael Kashgarian, Franklin H. Epstein
Journal: New England Journal of Medicine (1967)

MICROSCOPIC hematuria of renal origin associated with repeated episodes of gross hematuria is often considered to indicate the continued activity of chronic progressive glomerulonephritis. Several studies have shown that during the natural history of chronic glomerulonephritis, episodes of gross hematuria can follow upper-respiratory-tract infections, usually streptococcal but occasionally of nonstreptococcal etiology.1 Although in chronic poststreptococcal glomerulonephritis these episodes of gross hematuria are usually associated with edema, worsening of the hypertension and evidence of a reduction in glomerular filtration rate, they are said to cause a permanent reduction in renal function only rarely.1 Nevertheless, the persistence of repeated episodes of hematuria . . .
Pyloric-Sphincter Dysfunction in Patients with Gastric Ulcer
Authors: Robert S. Fisher, Sidney Cohen
Journal: New England Journal of Medicine (1973)

Abstract To determine whether alterations of pyloric-sphincter pressure are involved in the increased duodenogastric reflux in patients with gastric ulcer, pyloric-sphincter pressure was measured in 10 patients, both while their ulcer was active and after healing. Basal pressures in the patients with gastric ulcers did not differ from those in normal persons. Although pyloric pressure increased in normal subjects during either endogenous release or exogenous administration of secretin and cholecystokinin, patients with gastric ulcer showed no response. In normal subjects, during duodenal acidification, duodenogastric reflux significantly diminished as pyloric pressure increased, but not in patients with gastric ulcer. After healing of the ulcer, the pyloric sphincter still showed no response to hormonal stimulation. These studies suggest that in patients with gastric ulcer, pyloric-sphincter dysfunction is responsible for increased duodenogastric reflux.
Pedal Pulses Disappearing with Exercise
Authors: James A. DeWeese
Journal: New England Journal of Medicine (1960)

THE association of intermittent claudication with obstructive atherosclerosis is well recognized. However, the presence of readily palpable pedal pulses easily deters one from considering atherosclerosis and arterial occlusion as the cause of claudication. Actually, significant partial to complete obstruction of an artery may be associated with palpable distal pulses. Exercise to the point of claudication causes these pulses to disappear, with a gradual return with rest, whereas normally the peripheral pulses remain unchanged or increase with exercise. Although this phenomenon has been reported1 2 3 its value in screening patients with symptoms suggestive of intermittent claudication has not been generally recognized.Thirteen . . .
ClearPath-assisted underwater endoscopic mucosal resection of a laterally spreading tumor of the colon
Authors: Gabriele Curcio, Antonino Granata, Neville Azzopardi, Patrizia Sanna, Luca Barresi, Ilaria Tarantino, Mario Traina
Journal: Endoscopy (2014)

A 50-year-old gentleman with a 4 cm laterally spreading tumor of the sigmoid colon was referred to our institute for endoscopic resection. Biopsy of this lesion confirmed the presence of an adenomatous polyp with high-grade dysplasia. Based on the size and histology of the polyp, and in view of its location in the sigmoid colon, we opted to carry out underwater endoscopic mucosal resection (UEMR) [1]. This procedure was carried out with a high-definition narrowband endoscope (GIF-H190; Olympus Medical, Center Valley, PA, USA) equipped with a ClearPath cleaning device (Easy-Glide Ltd., Kfar Truman, Israel) to facilitate water irrigation and aspiration during the procedure. With the help of the ClearPath, the colon was rapidly irrigated with water, allowing piecemeal UEMR. All the polyp fragments, regardless of size, were aspirated through the ClearPath suction channel into the central suction canister ([Fig. 1], [Fig. 2]). The patient tolerated the procedure well with no adverse events recorded in the following days.
Improving Value in Medicare with an SGR Fix
Authors: Gail R. Wilensky
Journal: New England Journal of Medicine (2013)

Interview with Dr. Gail Wilensky on proposed legislation to replace Medicare's physician-payment formula. (11:52)Download Congressional attention is being directed toward developing an alternative Medicare reimbursement system that rewards physicians who improve the quality and efficiency of care, rather than trying to fix the sustainable growth rate formula.
Abstract 2154: Simultaneous analysis of cell death mechanisms and oxidative stress using live cell fluorescence microscopy
Authors: Michelle Yan, Scott T. Clarke, Bhaskar S. Mandavilli, Shih-Jung Huang, Upinder Singh, Michael S. Janes, Nicholas J. Dolman
Journal: Cancer Research (2011)

Abstract Reactive oxygen species (ROS) can directly damage DNA, proteins and lipids, while increased oxidative stress has been reported to be associated with apoptotic and autophagic cell death. Importantly, increased oxidative stress and dysregulation of cell death mechanisms have been linked with cancer development. To better understand the connection between increased oxidative stress and cell death pathways, it is important to be able to monitor both of these events simultaneously in the same cell and amongst mixed populations of cells. The goal of this study was to utilize multi-parametric fluorescence microscopy to examine the temporal progression of oxidative stress relative to cell death. By using a fluorogenic caspase substrate in combination with a near infrared fluorescent probe for ROS, we observed that increased oxidative stress was followed by activation of caspase-3/7 after induction by several agonists. We examined the effect of various agonists in both primary cells as well as cancer cell lines. Loss of mitochondrial membrane potential, nuclear condensation, and cell proliferation were also measured to establish a more comprehensive assessment of the cellular response to stress in these models. By simultaneously examining multiple parameters over time, we were able to define the temporal progression of apoptosis relative to the onset of oxidative stress. Furthermore, we were able to characterize the mechanism of cell death by discriminating between cells which were apoptotic (active caspase-3/7), autophagic (LC3B-positive autophagosomes), or both. This multi-parametric approach provided detailed spatial information at the cellular level so that correlations and temporal resolution could be determined between oxidative stress and cell death mechanisms. 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 2154. doi:10.1158/1538-7445.AM2011-2154
A9.01 Characterisation of extracellular histidyl-trnasynthethase in myositis
Authors: C Fernandes-Cerqueira, A Sohrabian, I Albrecht, A Notarnicola, E Ossipova, J Lengqvist, M Fathi, GJ Pruijn, J Grunewald, J Rönnelid, IE Lundberg, PJ Jakobsson
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Histidyl-transfer RNA synthetase (HisRS) is a major autoantigen in myositis with lung involvement. Simultaneous presence of anti-HisRS and anti-Ro52 antibodies has been demonstrated in patients with myositis. We investigated the presence of HisRS&nbsp;in extracellular compartments such as plasma, sera and bronchoalveolar lavage (BAL). In addition, the occurrence of anti-HisRS antibody isotypes as well as other auto-reactivities was evaluated in BAL and sera from patients with myositis. <h3>Materials and methods</h3> HisRS was measured in sera, plasma and BAL from myositis (anti-HisRS antibody positive, anti-Jo1+ and negative, anti-Jo1-), sarcoidosis, rheumatoid arthritis (RA) patients and healthy controls (HC) by dot-blot, western-blot, immunoprecipitation and mass spectrometry. The presence in BAL and sera of anti-Jo1 isotypes and autoantibodies to other reactivities was analysed by ELISA and addressable laser bead immunoassay. <h3>Results</h3> HisRS was detected in sera, plasma and BAL fluid of patients with myositis, sarcoidosis and RA and in&nbsp;HC. HisRS systemic levels were elevated in anti-Jo1+ myositis in comparison to anti-Jo1- myositis, sarcoidosis, RA or HC sera. In HC BAL HisRS was detected in significant levels. Experiments demonstrated the presence of a factor in BAL with high binding capacity for HisRS and HisRS&nbsp;complexed with anti-HisRS-N-terminal antibody. Immune complexes (IC) containing HisRS and C1q were not the binding factor. However, several anti-HisRS&nbsp;isotypes (anti-Jo1 IgG, IgM and IgA) as well as anti-Ro52IgG were identified in both BAL and sera. Furthermore, a positive correlation between the presence of anti-Jo1 IgG and anti-Ro52IgG in BAL was identified. <h3>Conclusions</h3> HisRS was detected both in blood and BAL fluid. The identification of extracellular HisRS, anti-HisRSisotypes and anti-Ro52 in myositis BAL may provide additional clues for the development of autoimmunity in the lungs.
Commentary: Emerging Concepts of Regulation
Authors: Sheldon W. Samuels
Journal: Environmental Health Perspectives (1975)

There are several concepts emerging in the field of environmental regulation that need discussion and clarification. First, in the private sector, my organization has been pressing for competition between agencies in the public sector as a key strategy to check the integrity of the environmental police force. Second, in the public sector, Marvin Schneiderman, Marcus Key and others in HEW have sold many of us on the broad concept of socially acceptable risk in environmental regulation. Third, among professional groups, there is the perennial soul-searching about the role in regulation of the scientist in the employ of industry, the universities, and government. (Essentially the existence or nonexistence of Brodeur's industrial-medical complex) Let me take the last concept first because it provides the setting for the rest of what I have to say. Yesterday Dr. Eckhardt was honest. He put the presence of an industrial-medical complex in its best light. His explication of its ideology was lucid: a clear endorsement of the corporate scientist as an advocate for the marketplace of commerce in the marketplace of ideas, shifting the burden of the environmental problem from the control of toxic substances to changing the habits of the general population. Whether this ideology will prevail is a key question in the years ahead. I gather from the disturbed and loud silence his presentation evoked-as well as comments after the session-
243 A REPRODUCIBLE, CLINICALLY-RELEVANT, INTENSIVELY-MANAGED, PIG MODEL OF ACUTE LIVER FAILURE FOR TESTING OF THERAPIES AIMED TO PROLONG SURVIVAL
Authors: K. Lee, C. Palacios Jimenez, H. Alibhai, Y.-M. Chang, P. Leckie, S. Priestnall, R. Mookerjee, R. Jalan, N. Davies
Journal: Journal of Hepatology (2012)
OUTCOMES OF THE ABSORB BIORESORBABLE VASCULAR SCAFFOLD IN VERY SMALL AND NOT VERY SMALL CORONARY ARTERIES: THE ABSORB III RANDOMIZED TRIAL
Authors: Gregg W. Stone, Stephen Ellis, Charles Simonton, David Metzger, Ronald Caputo, David Rizik, Paul S. Teirstein, Jeffrey Popma, Jennifer Jones-McMeans, Zhen Zhang, Dean Kereiakes
Journal: Journal of the American College of Cardiology (2016)
Paracentesis for successful treatment of tension pneumoperitoneum related to endoscopic submucosal dissection
Authors: K. Fu, T. Ishikawa, T. Yamamoto, Y. Kaji
Journal: Endoscopy (2009)

A 78-year-old man underwent total colonoscopy because of positive fecal occult blood test. Two lateral spreading tumors (LST), approximately 35 mm and 40 mm in size, were detected in the cecum and transverse colon, respectively. Both lesions were endoscopically diagnosed as adenoma or focal cancer in adenoma, and therefore considered good candidates for endoscopic resection.
White matter compromise predicts poor intellectual outcome in survivors of pediatric low-grade glioma
Authors: Fang Liu, Nadia Scantlebury, Uri Tabori, Eric Bouffet, Suzanne Laughlin, Douglas Strother, Dina McConnell, Juliette Hukin, Chris Fryer, Marie-Eve Brière, Isabelle Montour-Proulx, Daniel Keene, Frank Wang, Donald J Mabbott
Journal: Neuro-Oncology (2014)

While the impact of cranial radiation on white matter following treatment for pediatric brain tumor has been the focus of many recent studies, the effect of treatment in the absence of radiation has received little attention. The relations between white matter and cognitive outcome have not been explored in patients who have undergone radiation-free treatment. As most patients treated without cranial radiation survive long after their diagnosis, it is critical to identify factors that may impact structural and neurocognitive outcomes. Using diffusion tensor imaging, we examined white matter structure in 32 patients with pediatric low-grade glioma (PLGG) (19 with subtentorial location and 13 with supratentorial location) and 32 healthy participants. Indices of intellectual functioning were also evaluated. Radiation was not used to treat this cohort, aged 8–19 years. We detected evidence of deficits in IQ and compromised supra- and subtentorial white matter in patients relative to healthy children (P < .05). Compromise of supratentorial white matter mediated the impact of treatment for PLGG on IQ. Greater white matter compromise was observed in patients who presented without multiple symptoms, were treated with biopsy/no surgery, had positive neurofibromatosis 1 status, were younger age at diagnosis, and whose parents had lower levels of education (P < .05). Our findings provide evidence of increased risk of intellectual and white matter compromise in patients treated for PLGG without radiation. We identify a neural origin of cognitive deficit useful for predicting outcome and mitigating long-term adverse effects in pediatric brain tumor patients treated without cranial radiation.
The American Health Security Act -- A Single-Payer Proposal
Authors: Paul D. Wellstone, Ellen R. Shaffer
Journal: New England Journal of Medicine (1993)

Almost 30 years after the nation's last brush with comprehensive health care reform, the prospect of fundamental change once again seems almost palpable. As in 1965, policy analysts, interest groups, and the public are debating the nature and extent of reform. This time, however, it is imperative that we adopt a solution that will successfully control costs, while improving access and quality. The American Health Security Act of 1993 (S. 491), which one of us (Senator Wellstone) introduced into the Senate, proposes such a solution, through a publicly accountable single-payer system -- in our opinion, the best way to control . . .
A Comparison of Ceftriaxone and Cefuroxime for the Treatment of Bacterial Meningitis in Children
Authors: Urs B. Schaad, Susanne Suter, Athos Gianella-Borradori, Juerg Pfenninger, Raymond Auckenthaler, Otto Bernath, Jean-Jacques Cheseaux, Joanna Wedgwood
Journal: New England Journal of Medicine (1990)

To compare ceftriaxone with cefuroxime for the treatment of meningitis, we conducted a study in which 106 children with acute bacterial meningitis were randomly assigned to receive either ceftriaxone (100 mg per kilogram of body weight per day, administered intravenously once daily; n = 53) or cefuroxime (240 mg per kilogram per day, administered intravenously in four equal doses; n = 53). The mean age of the children was 3 years (range, 42 days to 16 years), and the characteristics of the two treatment groups were comparable at admission. Excluded from the study were eight other children who died within 48 hours of admission.
Clinical Role of Three-dimensional Endoscopic Ultrasonography for Estimating the Depth of Early Colorectal Cancer Invasion
Authors: K Kobayashi, M Kida, S Haruki, K Yokoyama, M Sada, T Katsumata, K Saigenji
Journal: Endoscopy (2006)

Objective: EUS has been established to be useful for estimating the depth of early colorectal cancer (CRC) invasion. With conventional equipment, the ability to image lesions can depend on tumor site or macroscopic type. We examined whether 3-dimensional (3-D) EUS can overcome imaging difficulties associated with conventional EUS.
PH 1 Study of PI3KMTOR Inhibitors PF-04691502 or PF-05212384 + MEK Inhibitor PD-0325901 or Irinotecan in Advanced Cancer
Authors: C. Britten, Z. Wainberg, J. Tabernero, M.A. Maqueda, S. Leong, C. Sessa, R. Millham, T. Hirohashi, L.L. Siu, I. Brana
Journal: Annals of Oncology (2013)
SP0058 Where does RA start - the joint or lymphoid tissues?
Authors: L. van Baarsen
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease of unknown etiology. To ultimately cure or prevent this chronic disease, it is critical to understand the earliest changes in the immune system that cause RA. Recent work has shown that systemic autoimmunity precedes cellular inflammation in the synovium of RA patients. Animal models have suggested that changes in the lymph nodes may precede those in the synovial tissue. To provide insight into the immunological mechanisms involved in the pathogenesis of RA, most research has been focused on the target tissue of arthritis, the synovium. We now developed a method to obtain lymph node biopsies under local anaesthesia in autoantibody positive individuals at risk of developing RA, early arthritis patients and healthy controls. During this presentation our latest findings on synovial tissue as well as lymph node tissue changes during the pre-clinical and the earliest phase of arthritis will be discussed. <i>Funding: the Dutch Arthritis Association, the Netherlands Organization for Health Research and Development (ZonMw), Smart Mix and Innovative Medicines Initiative BeTheCure.</i> <h3>Disclosure of Interest</h3> None Declared