tbuckley/cabot-search huggingface dataset:
FRI0265 The effect of mycophenolate mofetil on disease development in the gld.apoe-/- mouse model of accelerated atherosclerosis and systemic lupus erythematosus
Authors: C. Richez, P. Duffau, I. Rifkin, T. Aprahamian
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is characterized by autoantibody production and inflammatory disease involving multiple organs. Premature atherosclerosis is a common complication of SLE and results in substantial morbidity and mortality from cardiovascular disease (CVD). The reasons for the premature atherosclerosis in SLE are incompletely understood, although chronic inflammation is thought to play an important role. There is currently no known preventative treatment of premature atherosclerosis in SLE. Mycophenolate mofetil (MMF) is an immunosuppressive agent that is commonly used for treatment of patients with SLE. Findings suggest a potential role for MMF in the treatment of atherosclerosis. <h3>Objectives</h3> To determine if MMF is effective in the treatment of lupus-associated atherosclerosis, including premature atherosclerosis development. <h3>Methods</h3> We treated <i>gld.apoE<sup>-/-</sup></i> mice, a model of SLE and atherosclerosis, with MMF. We maintained seven-week old <i>gld.apoE<sup>-/-</sup></i> mice on a high cholesterol Western diet with or without MMF. We studied atherosclerosis and lupus development as previously described. <h3>Results</h3> After 12 weeks on diet, mice receiving MMF showed decreased atherosclerotic lesion area compared to the control group. A significant decrease in aortic root atherosclerotic lesion area (revealed by staining with Oil red O) was observed in the MMF-treated mice compared to control (p = 0.02). MMF treatment also improved the lupus phenotype, indicated by a significant decrease circulating autoantibody levels (p = 0,001), splenomegaly (<i>p</i> &lt; 0.05) and lymphadenopathy (<i>p =</i> 0.001) size, and ameliorating lupus nephritis (glomerular tuft size, <i>p =</i> 0.002 and cell count, <i>p =</i> 0.004) associated with this model. <h3>Conclusions</h3> This data suggests that the effects of MMF on the immune system may not only be beneficial for lupus, but also for inflammation driving atherosclerosis. A more extensive analysis of atherosclerosis and SLE in these MMF-treated <i>gld.apoE<sup>-/-</sup></i> mice will need to be performed to fully determine how MMF impacts the accelerated atherosclerosis of our lupus mouse model and potentially bring a better understanding of the link between atherogenesis and autoimmune disease. <b>References:</b> Aprahamian T, Rifkin I, Bonegio R, Hugel B, Freyssinet JM, et al. (2004) Impaired clearance of apoptotic cells promotes synergy between atherogenesis and autoimmune disease. J Exp Med 199: 1121-1131. <b>Disclosure of Interest</b>: C. Richez Speakers bureau: Roche, P. Duffau: None Declared, I. Rifkin: None Declared, T. Aprahamian: None Declared
FRI0137 Measurement of Lateral Spinal Flexion and Schober is Sufficient to BE Informed about Spinal Mobility in Patients with Ankylosing Spondylitis: 12-Year OASIS Results
Authors: S. Ramiro, R. Landewé, D. van der Heijde, C. Stolwijk, M. Dougados, F. van den Bosch, A. van Tubergen
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> We have shown that spinal mobility gets impaired in a fixed order in ankylosing spondylitis (AS), with the highest impairment in lumbar spine. <h3>Objectives</h3> To investigate whether assessing few measures could capture full information on impairment in spinal mobility, which would be useful for clinical practice. <h3>Methods</h3> Patients from the Outcome in AS International Study (OASIS) were followed-up for 12 years in which spinal mobility was regularly measured (see Table). From a previous study in normal subjects (1), percentile curves (2.5th to 97.5th) were obtained for each of the spinal mobility measures (SMMs) (Figure). We added 4 parallel curves representing z-scores of 2.5, 3, 3.5 and 4 respectively (helplines a to d) to be able to plot impaired measures. Each of the SMMs was defined as impaired if the measurement fell below help-line a (first cutoff below normal subjects). The number of observations and of patients using baseline observation only with at least one SMM impaired was calculated. Of those, the proportion of observations or of patients, respectively, with each of the SMMs impaired was calculated. Furthermore, we investigated in how many cases would impairment in spinal mobility be missed if only a fixed number of SMMs was assessed. <h3>Results</h3> A total of 216 patients were included (70% males, mean (SD) age 44 (13) years, mean symptom duration 21 (12) years and 85% HLA-B27 positive). Impairment in spinal mobility was present in 1111 (78%) out of 1422 observations and in 161 (79%) out of the 203 patients with a complete baseline assessment. From the observations (and also patients) with at least one impaired SMM, in 83% (86% of the patients) lateral spinal flexion (LSF) was impaired, followed by Schober in 63% of them (58% of the patients). In one quarter of the observations, 1 SMM was impaired, in 32% 2 SMMs and in 18% 3 SMMs. At a patient-level, 1 SMM was impaired in 30% of the patients, 2 SMMs in 33% and 3 SMMs in 17%. If only LSF was measured, 17% of the observations (14% of the patients) with impairment in SMM would be missed. If additionally Schober was also measured, only 9% of the observations (and also of patients) would be missed (Table). <h3>Conclusions</h3> Impairment in spinal mobility can be investigated by assessing only 2 SMMs. We hereby recommend that measurement of LSF and Schober is sufficient to be informed about impairment in spinal mobility in patients with AS. Only if these are impaired it is important to assess additional measures. <h3>References</h3> Ramiro et al. A&amp;R 64(12):4173-4174 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2678
PTH-100 Psychological Morbidity and Provision of Psychological Support in the Inflammatory Bowel Disease Clinic
Authors: S Mankodi, E Cronin, K Greveson, T Shepherd, E Despott, M Jaboli, G Erian, M Hamilton, C Murray
Journal: Gut (2013)

<h3>Introduction</h3> Inflammatory bowel disease (IBD) can have a significant impact on physical, psychological and social wellbeing. We aimed to survey the impact of IBD on our patients’ lives and their perceptions of psychological support use and availability. <h3>Methods</h3> Inflammatory bowel disease (IBD) can have a significant impact on physical, psychological and social wellbeing. We aimed to survey the impact of IBD on our patients’ lives and their perceptions of psychological support use and availability. <h3>Results</h3> 6 patients were excluded as they had not completed the questionnaire. 94 patients were included (43 male, 51 female, average age 42 years, range 17–76). 46 had a diagnosis of Crohn’s disease, 41 ulcerative colitis and 7 indeterminate colitis. Average disease duration for these patients was 15 years (range 1–51 years). Over the past 6 months 20 had symptoms constantly, 16 often, 17 occasionally, 10 sometimes, 13 rarely and 18 never. The average SIBDQ score was 48 (range 21–70). The average HAD score was 12.6 (range 0–33). When separated into HAD A (anxiety) and HAD D (depression) scores were 8.1 (range 0–18) and 4.8 (range 0–15) on average respectively, a score of 8 to 10 for either subscale being suggestive of the presence of the respective state. They were also asked which services they had previously used as forms of support. Of the 86 patients who answered this portion of the questionnaire, 13 (15%) said they had previously had counselling or psychological input, and 32 (37%) said they would like counselling or psychological input in the future if it was available. <h3>Conclusion</h3> Our survey suggests there may be a higher rate of anxiety in patients with IBD, and that over a third of our patients would like access to psychological and counselling services if they were available. Psychological support is important to patients with IBD and should be incorporated into their management. <h3>Disclosure of Interest</h3> None Declared.
Focal Nodular Hyperplasia of the Liver
Authors: N Shuke, D Yoshikawa, Y Saito, J Sato, Y Ishikawa, H Yoshida, S Kino, N Miyokawa, T Aburano
Journal: Clinical Nuclear Medicine (1999)

A 26-year-old woman, who had occasionally received an estrogen preparation for dysmenorrhea, was hospitalized for closer evaluation of a large hepatic mass detected incidentally by abdominal ultrasonography. To characterize the mass, liver imaging was performed using three imaging agents: Tc-99m phytate as a radiocolloid, Tc-99m pyridoxyl-5-methyl tryptophan (PMT) as a hepatobiliary agent, and Tc-99m DTPA galactosyl human serum albumin (GSA) as a radiolabeled neoglycoalbumin for the asialoglycoprotein receptor. Tc-99m PMT and Tc-99m GSA accumulated in the mass in a manner similar to the uptake in the normal liver parenchyma. On the other hand, Tc-99m phytate showed less accumulation than the other two agents did. Based on these findings, the diagnosis of focal nodular hyperplasia of the liver was strongly suggested. The mass was resected, and pathologic analysis confirmed the diagnosis of focal nodular hyperplasia.
Gastric Volvulus Detected With Iodine-131 Whole-Body Imaging
Authors: RYAN J. ZUCKER, YONG C. BRADLEY, MORAKINYO O. TONEY, ROBERT S. BRIDWELL
Journal: Clinical Nuclear Medicine (2000)

Organoaxial gastric volvulus was detected on a I-131 whole-body scan in a 79-year-old man with thyroid cancer with metastatic disease within his lower cervical and upper thoracic spine. He had recently undergone thyroidectomy, debulking of his metastatic disease, and many I-131 treatments. During an additional I-131 ablation, an abnormal appearance of the stomach was noted. This was thought to represent a gastric volvulus. An upper gastrointestinal study later confirmed the possible diagnosis. This is the first report of organoaxial gastric volvulus detected on a I-131 whole-body scan.
P448 THE ROLE OF METABOLIC SYNDROME AND ITS COMPONENTS IN SHORT TERM DECOMPENSATION RISK IN PATIENTS WITH CIRRHOSIS
Authors: B. Procopet, O. Farcau, D. Crisan, H. Stefanescu, M. Balagel, D. Feier, C. Radu, M. Grigorescu
Journal: Journal of Hepatology (2014)
Abstract LB-149: Sustained activity of the mTOR pathway is required for DNA damage-induced up-regulation of RRM2 in cancer cells.
Authors: Changxian Shen, Peter J. Houghton
Journal: Cancer Research (2013)

Abstract Balanced deoxyribonucleotides (dNTPs) are essential for the accurate and efficient replication and repair DNA synthesis. Increased or imbalanced dNTP pool leads to a mutator phenotype, while decreased dNTP level impairs DNA replication and repair, and hence cell survival. Ribonucleotide reductase (RNR) is the rate-limiting enzyme for the production of dNTPs from ribonucleotides and is under tight control during cell cycle and in response to stress. Increase of RNR is required for yeast cells to survive DNA damage and replication stress. However, the regulation and function of RNR in response to DNA damage remains unclear and controversial in mammalian cells. We report here that the mTOR pathway controls both RRM1 and RRM2 but not p53R2. mTOR signaling is required for mitomycin C (MMC) induced up-regulation of RRM2 in rhabdomyosarcoma Rh30 cells. Pharmacological inhibition of mTOR kinase with AZD8055 or mTORC1 inhibitor rapamycin resulted in the decrease of both RRM1 and RRM2, but not p53R2. 4E-BP1 and 4E-BP2 double knockout mouse embryonic fibroblast cells (4E-BP1/2-/- MEF) showed increased basal expression of RRM1 and RRM2, indicating that mTORC1 controls RRM1 and RRM2 via cap-dependent protein translation. In addition, pharmacological inhibition of either mTORC2-Akt signaling or CDK4/6 led to decrease of the mRNAs of RRM1 and RRM2, accompanied with the suppression of pRb-S780 signaling, suggesting that mTORC2-Akt signaling controls the gene transcription of RRM1 and RRM2 via regulating G1 cyclin-dependent kinases (CDK4/6). Both rapamycin and AZD8055 impaired the induction of endogenous RRM2 by MMC, but not ectopically expressed RRM2, which is not controlled by mTOR signaling. Our data demonstrate that mTOR controls both the protein translation and gene transcription of RRM1 and RRM2. DNA damage induced up-regulation of RRM2 depends on sustained mTOR signaling, suggesting that control of RNR by mTOR signaling may be one of the mechanisms by which cell growth-promoting signaling pathways enhance the survival and genome instability of cancer cells under constant DNA replication and damage induced stress. Supported by UPHS award CA77776. Citation Format: Changxian Shen, Peter J. Houghton. Sustained activity of the mTOR pathway is required for DNA damage-induced up-regulation of RRM2 in cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-149. doi:10.1158/1538-7445.AM2013-LB-149
PREVALENCE OF DIFFERENT POLYP TYPES IN MSI AND MSS AGE AND GENDER MATCHED COHORTS OF COLORECTAL CANCER RESECTIONS
Authors: D Gibbons, A Rogers, C H Ng, R Geraghty, E Rhinehart, J Hyland, R P O'Connell, D Winter, H Mulcahy, G Doherty, D O'Donoghue, D Fennelly, K Sheahan
Journal: Gut (2013)

<h3>Introduction</h3> The sessile serrated pathway has gained increased recognition in recent years. Up to 30% of of colorectal tumours are thought to arise in this manner but its significance remains to be elucidated. <h3>Aims/Background</h3> This study sought to establish the prevalence and significance of the sessile serrated pathway in curative resections for colorectal carcinoma. <h3>Method</h3> All colorectal carcinomas resected with curative intent, with immunohistochemical characterization of microsatellite status at diagnosis, over an eight year period were identified. 1415 colectomy specimens were identified of which 126 had microsatellite instability (MSI). An age and gender matched MSS cohort was generated. A careful gross examination described and sampled all polyps. All polyps were reviewed, enumerated and classified as SSA (sessile serrated adenoma), adenoma or hyperplastic. Appendiceal polyps were excluded. Mean numbers of polyps, total and subtypes were compared in the MSI and MSS groups. A two tailed t-test was used to test for significance. <h3>Results</h3> 57% of MSI cases and 50% of MSS cases had polyps in the resection. In the MSI group there were 5 SSAs, 92 adenomas and 37 hyperplastic polyps (totalling 134). In the MSS group there were 0 SSAs, 62 adenomas and 23 hyperplastic polyps (totalling 95). There were no significant differences in numbers of adenomas, hyperplastic polyps or total polyps in both groups. However there were significantly more SSAs in the MSI group (p=0.0239). <h3>Conclusion</h3> Although absolute numbers are low, the finding of an SSA in a cancer colectomy specimen is a strong indicator that the carcinoma will display microsatellite instablity (MSI).
CS-31 * A NOVEL YAP-DRIVEN MIGRATION AND INVASION SIGNALING PATHWAY PREDICTS POOR OUTCOME IN GLIOBLASTOMA
Authors: S. R. Shah, N. D. Tippens, J. Park, A. Mohyeldin, G. Vela, A. Levchenko, A. Quinones-Hinojosa
Journal: Neuro-Oncology (2014)

One of the hallmarks of tumor malignancy is the ability of cells to not only locally invade its surrounding parenchyma but also distally metastasize. Aggressive tumors such as glioblastoma (GBM) often display a collective sheet of migrating cells which may eventually disseminate and migrate in a single cell manner. By integrating extracellular cues and intracellular signaling, cell polarization and the persistence and speed of locomotion is tightly governed. Given the diverse inputs that may modulate this intricate cell migration pathway, it is of interest to identify critical modulators of this network. Yes-associated protein (YAP), a transcriptional regulator, has been suggested to potentiate migration, invasion, and metastasis; however, it is not known how or whether YAP expression and activity can regulate the molecular networks controlling cell migration and invasion, and whether this function of YAP may be consequential to the progression of aggressive cancers. We thus explored mechanisms of YAP-mediated migration and invasion in normal cells as well as cancer cells where YAP is hyperactive (p < 0.05). We found that YAP plays a pivotal role in regulation of this complex migratory and invasive behavior through a novel small Rho-GTPase-dependent signaling mechanism. As with GBM, metastatic cancers often evade detection because individual cells spread from the primary bulk tumor; thus, making complete resection and treatment virtually impossible. Congruent with our in vitro studies, our murine intracranial xenograft model argue the role of YAP in driving invasive tumor growth (p < 0.05). Moreover, we demonstrate that these YAP-driven cell dispersal mechanisms confer poor patient prognosis in the TCGA and REMBRANDT GBM databases (p < 0.05). Thus, our findings provide new insights into the biology of aggressive cancers with particular prognostic relevance of this YAP-driven pro-motility cascade in glioblastoma. In addition, our studies suggest these YAP-dependent mechanisms are evolutionary conserved during development and regeneration and co-opted by pathological diseases.
Abstract 4714: Vemurafenib reverses immunosuppression by myeloid derived suppressor cells.
Authors: Bastian Schilling, Antje Sucker, Klaus Griewank, Fang Zhao, Benjamin Weide, Andre Görgens, Bernd Giebel, Dirk Schadendorf, Annette Paschen
Journal: Cancer Research (2013)

Abstract Purpose: To evaluate the impact of Vemurafenib on myeloid derived suppressor cell (MDSC) populations in patients with advanced melanoma. Experimental Design: Ex vivo MDSCs were obtained from PBMCs of late stage melanoma patients treated with Vemurafenib as well as healthy controls. The frequency and phenotype of MDSCs was determined by flow cytometry. MDSC populations were characterized for their suppressive function on autologous T cells in CFSE proliferation assays. Additionally, conditioned medium of a melanoma cell line treated with Vemurafenib or not was studied for its effect on MDSCs in vitro. Results: In comparison to healthy donors, patient PBMCs showed an increased frequency of CD14+HLA-DR−/low monocytic MDSCs (moMDSCs) and of a previously unrecognized population of CD14−CD66b+Arginase1+ granulocytic MDSCs (grMDSCs). In vitro, both populations suppressed autologous T-cell proliferation. Vemurafenib treatment of melanoma patients reduced the frequency of both moMDSCs and grMDSCs. Accordingly, conditioned medium from Vemurafenib treated melanoma cells was less active in inducing moMDSCs in vitro. Conclusion: Patients with advanced melanoma show increased levels of moMDSCs, as well as a population of CD14−CD66b+Arginase1+ grMDSCs. Both MDSCs are distinct populations capable of suppressing autologous T-cell responses independently of each other. In vitro as well as in vivo, Vemurafenib inhibits the generation of human moMDSCs. Thus, Vemurafenib decreases immunosuppression in patients with advanced melanoma, indicating its potential as a part of future immunotherapies. Citation Format: Bastian Schilling, Antje Sucker, Klaus Griewank, Fang Zhao, Benjamin Weide, Andre Görgens, Bernd Giebel, Dirk Schadendorf, Annette Paschen. Vemurafenib reverses immunosuppression by myeloid derived suppressor cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4714. doi:10.1158/1538-7445.AM2013-4714
Case 2-1998
Authors: Daniel H. O'Leary, Suzanne de la Monte
Journal: New England Journal of Medicine (1998)

Presentation of CaseA 50-year-old right-handed woman was admitted to the hospital with worsening headache and a left abducent-nerve palsy.The patient had been well until six weeks earlier, when she began to have diffuse headaches that fluctuated in intensity, became increasingly severe, and were soon accompanied by neck pain and stiffness. Changing her position for sleeping and taking nonsteroidal antiinflammatory drugs and oxycodone–acetaminophen provided no relief.Ten days before admission, the patient noticed blurred vision on looking ahead or to the right and horizontal diplopia on looking to the left. She could read only when looking downward. Magnetic resonance . . .
Total atrioventricular block in burn unit patients: a matter of iodine toxicity
Authors: Fiona Tromp, Eric Hoste, Kirsten Colpaert, Sofie Gevaert, Els Vandecasteele, Alain Verstraete, Annemieke Dhondt, Stan Monstrey, Johan Decruyenaere, Jo Dewaele
Journal: Intensive Care Medicine (2009)
Satisfaction Highest Among Patients Told the Truth
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Satisfaction Highest Among Patients Told the Truth Get access Cori Vanchieri Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 16, August 1993, Page 1280, https://doi.org/10.1093/jnci/85.16.1280 Published: 01 August 1993
O109 ALL ORAL FIXED-DOSE COMBINATION SOFOSBUVIR/LEDIPASVIR WITH OR WITHOUT RIBAVIRIN FOR 12 OR 24 WEEKS IN TREATMENT-EXPERIENCED GENOTYPE 1 HCV-INFECTED PATIENTS: THE PHASE 3 ION-2 STUDY
Authors: N. Afdhal, R.K. Reddy, P. Pockros, A.M. Di Bisceglie, S. Arora, J.C. Yang, H. Dvory-Sobol, Y. Zhu, P.S. Pang, W.T. Symonds, J.G. McHutchison, M.S. Sulkowski, P. Kwo
Journal: Journal of Hepatology (2014)
Endoscopic mucosal ablation: a novel technique for a giant nonampullary duodenal adenoma
Authors: Z. Tsiamoulos, S. Peake, L. Bourikas, B. Saunders
Journal: Endoscopy (2013)

Piecemeal endoscopic mucosal resection (p-EMR) for large sessile or flat duodenal polyps results in a high incidence of bleeding [1]. A novel injection and ablation technique, endoscopic mucosal ablation (EMA), was used to eradicate a benign sporadic nonampullary duodenal adenomatous polyp. EMA comprises two conventional modalities: submucosal fluid injection followed by high power argon plasma coagulation (APC) tissue ablation ([Fig. 1]). The fluid-filled submucosal cushion absorbs thermal energy and protects the underlying thin duodenal muscle layer: providing a heat-sink effect [2] [3]. The entire mucosal layer progressively "melts" with lateral propagation of the thermal energy within the duodenal submucosal layer giving a macroscopic appearance of a honeycomb ([Fig. 2]) [4].