tbuckley/cabot-search huggingface dataset:
Abstract 4167: Target mRNA analysis for miR-125a-5p in cervical carcinoma cells.
Authors: Natalia Martinez Acuna, Maria L. Benitez Hess, Luis M. Alvarez Salas
Journal: Cancer Research (2013)

Abstract It has been firmly established that high-risk human papillomavirus (HPV) infection is associated with the appearance and persistence of anogenital dysplasia. However, only a small fraction of HPV-infected patients ever develop cervical cancer. Therefore, other factors must contribute for the development of a malignant phenotype in HPV-infected cells. Aberrant microRNA (miRNA) expression is nowadays recognized as a key factor for the development of several pathologies including cancer. Several studies on the miR-125a-5p function have suggested a tumor suppressor role in diverse cell types. Our previous results shown that miR-125a-5p induced cell-cycle arrest, proliferation inhibition and apoptosis in cervical carcinoma cells. Nevertheless, miR-125a-5p role and mRNA targets in cervical cancer are not fully established in cervical cancer. RT-qPCR analysis of miR-125a-5p expression showed differential expression on immortal and tumor cervical cell lines suggesting a role in malignant progression. To probe for possible miR-125a-5p targets we performed in silico analyses using several miRNA target analysis tools and validated the results with a panel of cervical immortal and tumor cell lines. The bio-informatics analysis showed Mark1, bcl-2 and vEGF genes as possible targets for miR-125a-5p. Further RT-qPCR and immunoblot analysis indicated an inverse correlation of miR125a-5p and MARK1 expression in tumor lines but not in immortal lines irrespective of the HPV content. Interestingly, transfection of a pre-miR-125a-5p mimic in C33-A cells (lacking HPV and with low endogenous miR-125a-5p levels), resulted in specific down-regulation of MARK1 and VEGF. Therefore, we suggest a potential role for miR-125a-5p in cervical carcinogenesis through the regulation of MARK1. Citation Format: Natalia Martinez Acuna, Maria L. Benitez Hess, Luis M. Alvarez Salas. Target mRNA analysis for miR-125a-5p in cervical carcinoma 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 4167. doi:10.1158/1538-7445.AM2013-4167
Endoscopic findings of intestinal Behçet’s disease complicated with toxic megacolon
Authors: Y. Umehara, M. Kudo, M. Kawasaki
Journal: Endoscopy (2010)

A 73-year-old woman was admitted to our hospital because of diarrhea and inveterate oral ulcers. Upon admission, her body temperature was 38.2 °C. The abdominal examination revealed mild tenderness without guarding. Initial blood tests revealed a white blood cell count of 10 500/µL, hemoglobin level of 7.8 g/dL, C-reactive protein level of 21.7 mg/dL, and positivity for HLA-B52. The day after admission, massive bloody stools appeared. Colonoscopy of the descending colon revealed punched-out ulcers scattered throughout the rectum up to the descending colon ([Fig. 1 a]). While genital ulcers appeared after admission, skin lesions and eye inflammation were not detected. The patient was consequently diagnosed as having intestinal Behçet’s disease. She was treated with mesalazine (3 g/day) but her condition worsened gradually, and therefore intravenous prednisolone pulse therapy (1000 mg/day) was performed. However, bloody stools continued to appear. Second-look colonoscopy detected deep longitudinal ulcers in the transverse colon that exposed the muscular layer ([Fig. 1 b]). The patient was treated with infliximab (5 mg/kg) but complained 3 days later of severe abdominal pain and showed guarding in the left lower abdominal area. Computed tomography revealed a dilated transverse colon and perforation of the sigmoid colon with free air ([Fig. 1 c, d]). Consequently, the patient underwent surgery ([Fig. 2]), but unfortunately she died of disseminated intravascular coagulation after surgery.
Infection by Human Immunodeficiency Virus — CD4 is Not Enough
Authors: J A Levy
Journal: New England Journal of Medicine (1996)

The interaction between the human immunodeficiency virus (HIV) and its cellular target once seemed fairly simple: the virus attached to the CD4 molecule on the cell surface, entered the cell, and began its replicative cycle.1 However, in the past few years, research has turned up surprising evidence that the virus can bind to cells by means of receptors other than CD4. These alternative receptors include galactosylceramide on brain and bowel cells and, when the virus has formed a complex with antibody, Fc receptors. Binding through Fc receptors can actually enhance viral infection.1 Recent studies of the early events in HIV . . .
PTH-180 Small Bowel Ultrasound and Video Capsule Endoscopy: Complimentary Investigations to Diagnose Small Bowel Crohn’S Disease
Authors: M J McDonnell, R Beable, A Higginson, M A Quine, D S Pearl
Journal: Gut (2013)

<h3>Introduction</h3> Crohn’s disease affecting the small intestine requires accurate localization, assessment and follow up, to direct and monitor therapy. Video capsule endoscopy (VCE) has an established role in small bowel Crohn’s evaluation; however, use is limited by procedure costs and risks of capsule retention. Small bowel ultrasound (SB USS) with doppler is a rapid, inexpensive, dynamic and non-invasive method for assessing activity of Crohn’s disease. We present the largest published comparative UK dataset of SB USS and capsule endoscopy in Crohn’s disease. <h3>Methods</h3> A 5 year retrospective analysis from 2008–2012 was carried out. Patients investigated for suspected small bowel Crohn’s disease with SB USS and VCE were included, if one examination occurred within 12 month of the others. VCE findings were graded as mild (apthous ulcers only), moderate (apthous ulcers with mucosal distortion) or severe (apthous ulcers with mucosal distortion and strictures/stenosis). SB USS was graded positive or negative for small bowel Crohn’s disease. Both assessments were single operator. Results were expressed as sensitivity, specificity, positive and negative predictive value (PPV and NPV) of SB USS compared with VCE for detection of small bowel Crohn’s. Sub-analysis of SB USS findings for VCE-defined severity of small bowel Crohn’s disease was carried out. <h3>Results</h3> 500 VCE procedures were reviewed, of which 61 fulfilled the inclusion criteria. 19 patients had SB Crohn’s on VCE; this was detected in 5 patients by SB USS (sensitivity 26%). 42 patients had no evidence of SB Crohn’s on VCE; none of these had SB USS findings (specificity 100%). 56 patients had a negative SB USS, of these 14 VCE studies had findings compatible with Crohn’s disease (NPV 75%). All patients with positive findings of Crohn’s disease on SB USS had evidence of SB Crohn’s on VCE (PPV 100%). Sub-analysis for Crohn’s severity was carried out; of 11 VCE patients with moderate to severe Crohn’s disease, 5 patients had a positive SB USS (sensitivity 45%), however of 8 patients with mild Crohn’s on VCE, no patients had a positive SB USS. <h3>Conclusion</h3> SB USS has excellent positive predictive value (100%) and specificity (100%) for detection of SB Crohn’s disease. All detected cases were moderate or severe identifying cases at higher risk of capsule retention. Sensitivity of SB USS is 26% rising to 45% in VCE proven moderate or severe disease. It follows that a positive expert SB USS in the context of suspected small bowel Crohn’s is a definitive radiological result, on which therapy can be commenced. However, a negative SB USS should be followed by VCE or magnetic resonance enterography (MRE) if clinical suspicion remains. <h3>Disclosure of Interest</h3> None Declared.
OP0186 Analysis of Anti Porphyromonas Gingivalis (PG) Antibodies in a Large Cohort of Patients with an Early Arthritis (ESPOIR)
Authors: R. Seror, S. Legall, M. Bonnaure-Mallet, T. Schaeverbeke, A. Cantagrel, X. Mariette
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Chronic Porphyromonas Gingivalis (PG) infection is associated with parodonditis and the later is associated with rheumatism arthritis (RA). PG contains a bacterial deiminase able to citrullinate bacterial and human antigens. Thus it is logical to suspect an association with chronic PG infection and anti-CCP + RA. <h3>Objectives</h3> To investigate a possible link between PG infection and RA antibody profile and structural damage. <h3>Methods</h3> For assessing chronic PG infection we look at serum anti PG antibodies (titers were log-transformed) at baseline in the ESPOIR cohort consisting of 813 patients with early arthritis (more than 6 weeks and less than 6 months) not treated with steroid or DMARD. RA was defined according to ACR/EULAR 2010 criteria or ACR 1987 criteria. RA patients were divided between anti-CCP+ and -. Sex and age-matched control were also studied. <h3>Results</h3> Among the 812 patients included in the ESPOIR cohort, 694 (78% female, mean age 48.5±12.3, mean DAS28 5.3±1.2) had RA according to ACR/EULAR 2010 criteria and 641 according to ACR 1987 criteria. Whatever the used criteria set, the level of anti-PG antibodies did not significantly differ between RA and non-RA patients. Likewise, the mean level of anti-PG antibodies in the 694 RA patients did not differ from that of 70 healthy controls (1.53±0.50 vs 1.47±0.43; p=0.20). The mean level of anti-PG antibody did not differ between anti-CCP positive and negative RA patients (1.48±0.43 vs 1.46±0.43; p=0.63), and did not correlate with anti-CCP levels. Anti-PG antibody level did not correlate with DAS28 (rho=-0.01; p=0.76) or other parameters of disease activity or serum level of inflammatory cytokines (IL.6, IL1b, INFg or TNFa). Anti-PG antibody levels were higher in the 361 never smoker patients compared to the 333 ever smokers (1.51±0.42 vs 1.43±0.43; p=0.01). In sensitivity analyses, significantly more never smoker had high anti-PG level (&gt;mean+2SD of healthy controls) than ever smoker (35.7% vs 27.6%; p=0.02). There was a trend for a higher frequency of baseline erosive change (mSharp score ≥1) in patients with high anti-PG levels compared to those with low levels (46.7% vs 32.4%; p=0.008). But the level of anti- PG antibodies was neither associated with baseline modified Sharp score (mSharp) nor with structural progression (defined by a &gt;1 point increase of mSharp). <h3>Conclusions</h3> Like in a much smaller study recently published, we could not detect in this large cohort of patients with early arthritis any association between anti PG antibodies with RA or anti CCP+ RA. However, we found an association between anti-PG levels and baseline erosive change in never smokers patients, suggesting a possible association in this population not exposed to this major pathogen. <h3>Disclosure of Interest</h3> None Declared
Abstract 5402: Pre-clinical treatment of adrenal cortical carcinoma with a combination of small molecule inhibitors to IGF-1R and mTOR
Authors: Lauren Frome, Kathy Ignatoski
Journal: Cancer Research (2010)

Abstract Adrenocortical carcinoma (ACC) is a rare, aggressive cancer of the adrenal cortex. The five-year survival rate is 10-20% due to late diagnosis and lack of effective systemic therapy. The only treatment options available are surgical resection and chemotherapy in the form of mitotane; however, up to 95% of patients are not responsive to treatment, so new therapies are needed. Research has shown that the mitogenic hormone insulin-like growth factor 2 (IGF-2) is overexpressed in 93% of sporadic cases of ACC. IGF-2 binds to the receptor tyrosine kinase IGF receptor 1 (IGF-1R). Inhibition of IGF-1R has been shown to be effective against ACC in animal studies using IGF-1R targeted therapies. The major IGF-1R signaling pathway is phosphotidylinositol-3′-kinase (PI3′K), which activates AKT leading to the activation of mTOR, the mammalian target of rapamycin. Recent research has shown that mTOR may be a viable target for inhibition to treat tumors. Work in our lab has shown that a combination of mTOR inhibition by rapamycin and IGF1-R inhibition by either PQ401 or NVP-AEW54 at sub optimal doses blocks proliferation of human ACC H295R cells compared to application of either drug alone. Further investigation will be conducted in a mouse model system to determine the effects of the mTOR inhibitor everlimus (RAD001) alone and in combination with IGF1-R inhibitor OSI-906 to determine possible synergistic effects of the drugs that can be clinically applicable to treat ACC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5402.
End-Tidal Carbon Dioxide and Outcome of Out-of-Hospital Cardiac Arrest
Authors: Robert L. Levine, Marvin A. Wayne, Charles C. Miller
Journal: New England Journal of Medicine (1997)

Survival after cardiac arrest occurring outside the hospital averages less than 3 percent. Unfortunately, the outcome of prolonged resuscitative attempts cannot be predicted. End-tidal carbon dioxide levels reflect cardiac output during cardiopulmonary resuscitation. We prospectively determined whether death could be predicted by monitoring end-tidal carbon dioxide during resuscitation after cardiac arrest.We performed a prospective observational study in 150 consecutive victims of cardiac arrest outside the hospital who had electrical activity but no pulse. The patients were intubated and evaluated by mainstream end-tidal carbon dioxide monitoring. Our hypothesis was that an end-tidal carbon dioxide level of 10 mm Hg or less after 20 minutes of standard advanced cardiac life support would predict death.There was no difference in the mean age or initial end-tidal carbon dioxide level between patients who survived to hospital admission (survivors) and those who did not (nonsurvivors). After 20 minutes of advanced cardiac life support, end-tidal carbon dioxide (+/-SD) averaged 4.4+/-2.9 mm Hg in nonsurvivors and 32.8+/-7.4 mm Hg in survivors (P< 0.001). A 20-minute end-tidal carbon dioxide value of 10 mm Hg or less successfully discriminated between the 35 patients who survived to hospital admission and the 115 nonsurvivors. When a 20-minute end-tidal carbon dioxide value of 10 mm Hg or less was used as a screening test to predict death, the sensitivity, specificity, positive predictive value, and negative predictive value were all 100 percent.An end-tidal carbon dioxide level of 10 mm Hg or less measured 20 minutes after the initiation of advanced cardiac life support accurately predicts death in patients with cardiac arrest associated with electrical activity but no pulse. Cardiopulmonary resuscitation may reasonably be terminated in such patients.
SC-36 * RECIPROCAL INTERACTION OF PGE2 AND WNT SIGNALING REGULATES CANCER STEM CELLS IN GLIOBLASTOMA
Authors: M. Wu, L. Nusrat, A. Celebre, M. Bredel, J. Karamchandani, C. Morshead, S. Das
Journal: Neuro-Oncology (2014)

The concept of oncogene addiction presupposes that cancer cells require certain dominant oncogenic signals for growth and survival. A profound implication of this hypothesis is that antagonizing this crucial pathway should have significant effects on cancer cells, while sparing normal cells that are not similarly addicted. Clinically, the recognition of oncogenes to which a cancer is addicted could have profound resonance for targeted cancer therapy. The Wnt signaling pathway has recently been described to be constitutively activated in a subgroup of glioblastomas. Here, we performed a systematic review of high-throughput screens of CSC and physiologic stem cell systems to identify possible mediators of the stem cell phenotype in glioblastoma. Of the agents identified in multiple screens, we chose to study indomethacin, a chemical inhibitor of cyclooxygenase-2, because of the well described role of COX-2 in stem cell maintenance and of prostaglandin E2 (PGE2) in glioma biology. We then found COX-2 to be expressed in glioma stem cells (GSCs), but not in normal adult neural stem cells. Activation of COX-2 signaling in vitro resulted in increased GSC proliferation, while antagonism of COX-2 using indomethacin or siRNA inhibits GSC proliferation and self-renewal. PGE2 further directs GSCs activation through its aberrant activation of the Wnt/β-catenin pathway, which then induces COX-2 expression. Blockade of the reciprocal PGE2/β-catenin signaling cycle results in inhibition of GSC proliferation, and loss of markers of stem-ness. In vivo, concurrent administration of the COX-2 antagonist, celecoxib, and the Wnt inhibitor, LGK974, enhanced the activity of temozolomide in a mouse glioblastoma xenograft model, through its antagonism of CSCs. Our findings demonstrate a central role for COX-2 and Wnt signaling in maintenance of the CSC phenotype in glioblastoma, and suggest that disruption of their reciprocal interaction has therapeutic potential in glioblastoma.
Mumps Meningoencephalitis with Low Cerebrospinal-Fluid Glucose, Prolonged Pleocytosis and Elevation of Protein
Authors: Catherine M. Wilfert
Journal: New England Journal of Medicine (1969)

Four patients with mumps meningoencephalitis had prolonged lowering of the cerebrospinal-fluid glucose. Retrospective study of 45 other cases of mumps meningoencephalitis revealed 10 additional patients with at least one glucose value of less than 40 mg per 100 ml. Pleocytosis persisted for as long as five weeks; increases in pleocytosis and in protein content of the cerebrospinal fluid during the hospital course were frequently recorded. A consideration of known mechanisms that might be responsible for hypoglycorrhachia in mumps meningoencephalitis fails to account satisfactorily for the phenomenon.
SAT0040 Prevalence and Predictors for Sustained Remission in Rheumatoid Arthritis
Authors: Y.-K. Sung, K. Yoshida, F. H. Prince, M. L. Frits, J.-Y. Choe, H.-S. Lee, J. Lee, S. Lee, D.-H. Yoo, S. M. Helfgott, N. A. Shadick, M. E. Weinblatt, S.-C. Bae, D. H. Solomon
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Disease progression of RA is unpredictable and recurrence occurs frequently even in patients in remission. Since patients with short term remission are more likely to experience radiographic structural progression compared with those achieving long-term remission, sustained remission is likely to improve patient outcomes and quality of life. Therefore, understanding the prevalence and predictors of sustained remission in typical clinical settings is important for physicians and patients to plan treatment strategies. <h3>Objectives</h3> In this study, we aimed to investigate the prevalence of sustained remission in established RA patients and to identify the predictors for sustained remission. <h3>Methods</h3> The study cohort consisted of subjects with RA from the Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS) and the Korean Observational Study Network for Arthritis (KORONA). We analyzed subjects with remission in 2009 with 2 years of annual follow-up. Remission was assessed according to the Disease Activity Score 28 (DAS28-CRP) and sustained remission was defined as three consecutive annual visits with remission 2009-2011. Predictors for sustained remission were identified by multivariate logistic regression analysis. <h3>Results</h3> A total of 465 subjects with remission in 2009 were analyzed, and sustained remission was achieved by 53 of 92 (57.5%) in BRASS and by 198 of 373 (53.1%) in KORONA. In multivariate analyses, baseline predictors of sustained remission were: disease duration less than 5 years [odds ratio (OR) 1.96, 95% confidence interval (95% CI) 1.08-3.58], Modified Health Assessment Questionnaire (MHAQ) score of 0 (OR 1.80, 95% CI 1.18-2.74), and non-use of oral glucocorticoid (OR 1.58, 95% CI 1.01-2.47). <h3>Conclusions</h3> More than half of RA subjects in remission in 2009 remained in remission through 2011. Short disease duration, no disability, and non-use of oral glucocorticoid at baseline were associated with sustained remission. <h3>Acknowledgements</h3> This study had no specific support. However, BRASS is supported by grants from Crescendo Biosciences, Medimmune, and Briston Myers Squib. KORONA receives support from the Korea Healthcare technology R&amp;D Project, Ministry for Health and Welfare, Republic of Korea (A102065). <h3>Disclosure of Interest</h3> None Declared
AB1254 Subclinical atherosclerosis in patients with psoriatic arthritis evaluated by “ultrasonic biopsy”
Authors: F. Teixeira, D. Peixoto, M. Bogas, C. Afonso, D. Araújo
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Increased cardiovascular morbility and mortality has been observed in several inflammatory rheumatic diseases, namely, rheumatoid arthritis and systemic lupus erythematosus The chronic inflammatory state in these diseases may contribute to accelerated atherosclerosis. ``Ultrasonic biopsy" (U-B) is a described noninvasive screening technique to detect early atherosclerotic plaques and arterial wall changes. <h3>Objectives</h3> To evaluate the prevalence of subclinical atherosclerosis in patients with Psoriatic Arthritis, examining carotid and femoral arteries and to identify early clinical and biologic markers for these changes in this population. <h3>Methods</h3> Consecutive PsA patients who fulfilled the CASPAR criteria who were followed at our Rheumatology departmentbwere recruited. Traditional risk factors, biological inflammatory parameters and disease activity scores were checked. We studied 69 patients (39 women and 30 men), with a median age of 53 years (range 23-80yr) and a median disease duration of 96 months (range 18-552months). All patients underwent U-B study of left and right carotid (CA) and femoral artery (FA). The UB features were classified and scored as follows: Class A, normal (score 0); Class B, interface disruption (score 2); class C, intima-media (I-M) granulation (score 4); Class D, plaque without hemodynamic disturbance (score 6); Class E, stenotic plaque (score 8); and Class F, plaque with symptoms (score 10). <h3>Results</h3> Thirty-three (49%)of the 69 patients had at least a lesion in 1 of the 4 vessels tested (Classe C, D e F), these, 12 (36%) had lesion in 4 vessels. The AF was involved in 27 patients but the CA in only 20 patients. The presence of carotid plaque(classes D-F) correlated significantly with disease duration, LDL and triglyceride levels. Diabetes and hypertension were associated with the presence of plaques (classes D-F). Mean C-reactive protein washigher in classes D-F compared to the class A-B. <h3>Conclusions</h3> This study evaluates both carotid and femoral arteries in psoriatic arthritis patients looking for subclinical atherosclerosis. The results Our study demonstrates show that patients with PsA may have an increased prevalence of subclinical atherosclerosis. Femoral artery evaluation should be performed and complement the more frequent carotid study as it may show additional information about the atherosclerotic state of the patient. Special attention and strict control of atherosclerotic risk factors in patients with PsA is warranted to prevent future cardiovascular events. <h3>Disclosure of Interest</h3> None Declared
Replacement of percutaneous endoscopic gastrostomy: pierce to replace
Authors: Amadeu Nunes, Armando Peixoto, Guilherme Macedo
Journal: Endoscopy (2014)

A 69-year-old man underwent placement of a conventional percutaneous endoscopic gastrostomy (PEG) device in 2011 for dysphagia due to neurological impairment. The device was replaced 2 years later with one that had a balloon filled with saline solution as its internal retention mechanism. In January 2014, another balloon PEG replacement was scheduled. However, it was not possible to aspirate the saline solution and remove the internal bolster through the gastrostomy tract.