tbuckley/cabot-search huggingface dataset:
Abstract 314: Characterization of the Y83C Gab1 mutation in breast cancer
Authors: Marina Holgado-Madruga, Shawn Badal, Albert J. Wong
Journal: Cancer Research (2010)

Abstract Following addition of various growth factors and cytokines, the Gab1 docking protein is tyrosine phosphorylated, which then activates different signaling pathways. A screening of human breast cancers revealed a mutation in the Pleckstrin homology domain of Gab1, at the 83rd amino acid changing the tyrosine to a cysteine. To explore the impact of this mutation in human breast cancer, the mutation was overexpressed in the MDA-MB 468 cell line. Upon addition of EGF there was a significant higher increase in tyrosine phosphorylation of the mutant versus the wild type that correlated with an increased association with Shc, Shp2, Grb2 and p85. Pull down experiments with the GST/RBD (Ras binding domain of Raf) fusion protein detected higher activity levels of Ras in the mutant form in comparison with the wild type. Soft agar colony formation assays indicated a 2-3 fold increase in the number of colonies in the Y83C mutation with respect to the wt Gab1. The information understood from this study can help to characterize a mutant of Gab1 and this plays an important role in the context of personalized medicine by elucidating a specific target against tumors which express the mutation. 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 314.
Essentials of Medical Electricity
Journal: JAMA (1934)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Nitric Oxide Synthase Inhibitors Attenuate Ozone-induced Airway Inflammation in Guinea Pigs
Authors: HIROMASA INOUE, HISAMICHI AIZAWA, HIROYUKI NAKANO, KOICHIRO MATSUMOTO, KAZUYOSHI KUWANO, JAY A. NADEL, NOBUYUKI HARA
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Nitric oxide (NO) is increased in exhaled air of asthmatics. We hypothesized that endogenous NO contributes to airway inflammation and hyperresponsiveness, and that interleukin-8 (IL-8) might be involved in this mechanism. In human transformed bronchial epithelial cells in vitro, NO donors increased IL-8 production dose-dependently. In addition, tumor necrosis factor- α (TNF- α ) plus IL-1 β plus interferon- γ (IFN- γ ) increased IL-8 in culture supernatant of epithelial cells; the combination of NO synthase (NOS) inhibitors, aminoguanidine (AG) plus N G-nitro-l-arginine methyl ester (l-NAME) attenuated the cytokine-induced IL-8 production in epithelial cells. In guinea pigs in vivo, ozone exposure induced airway hyperresponsiveness to acetylcholine and increased neutrophils in bronchoalveolar lavage fluid (BALF), and these changes persisted for at least 5 h. Pretreatment with NOS inhibitors had no effect on airway hyperresponsiveness or neutrophil accumulation immediately after ozone, but significantly inhibited the changes 5 h after ozone. NOS inhibitors also attenuated the increases of nitrite/nitrate levels in BALF and the IL-8 mRNA expression in epithelial cells and in neutrophils in guinea pig airways 5 h after ozone. These results suggest that endogenous NO may play an important role in the persistent airway inflammation and hyperresponsiveness after ozone exposure, presumably partly through the upregulation of IL-8. Inoue H, Aizawa H, Nakano H, Matsumoto K, Kuwano K, Nadel JA, Hara N. Nitric oxide synthase inhibitors attenuate ozone-induced airway inflammation in guinea pigs: possible role of interleukin-8.
THU0311 What happens when etanercept is discontinued in “remission” in patients with juvenile idiopathic arthritis?:
Authors: G. Horneff, H.I. Hupppertz, I. Foeldvari, K. Minden
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Etanercept turned out to be highly effective in juvenile idiopathic arthritis. The aim of this study was to use the German Biker Registry data base to analyse the performance after discontinuation of Etanercept because of remission. <h3>Methods</h3> Requested reasons for discontinuation were inefficacy, intolerance, remission or other reasons. Judgement about decision for discontinuation or restart of treatment was not influenced by the registry. The course during follow up was analysed until restart of Etanercept treatment. <h3>Results</h3> 1499 patients (pts) recruited into the registry have been identified. 208 (13.9%) pts discontinued treatment with etanercept due to “remission” of their disease including patients of all JIA categories: enthesitis related arthritis 17/79 (17%), extended oligoarthritis 40/275 (14.5%), systemic JIA 18/130 (13.8%), RF - polyarthritis 62/472 (13.1%) but significantly less frequently patients with RF+ polyarthritis (9/154 (5.8%); p=0.003, χ<sup>2</sup>-test). Data of 476 follow ups were available in 166 pts for a median of 17 months (0-110 months). 100 (46%) were followed for at least 12 months, 47 (22%) for at least 24 months, 31 (14%) for at least 36 months. 71 (34%) Patients restarted treatment with Etanercept due to a relapse. Treatment was restarted in 5 pts in the first month, 18 in the first 3 months, 31 in the first 6 months and 47 in the first 12 months after discontinuation of Etanercept. Kaplan Meier analysis revealed a median Etanercept free survival time of 38.2 months. Etanercept free survival time is significantly influenced by the total treatment time with etanercept and ongoing treatment with methotrexate. Treatment with corticosteroids at the time of discontinuation of etanercept or disease duration before initiation of Etanercept were without significant input. At the time when Etanercept has been first discontinued due to “remission” 118 (62%) patients fulfilled the “Wallace” criteria for inactive disease. However, this had no effect on the median survival time until retreatment. <h3>Conclusions</h3> Discontinuation of a successful treatment with Etanercept occurred frequently in JIA patients. Compared to the total cohort, patients with enthesitis related arthritis more frequently and patients with RF+ polyarthritis less frequently discontinued due to “remission”. The median drug free survival time was influenced positively by treatment with methotrexate and negatively by a longer period of time to reach “remission”. Further observation of these pts will demonstrate the total rate of permanently discontinuation of antirheumatic drugs. <h3>Disclosure of Interest</h3> G. Horneff Grant/Research support from: Pfizer, Abbott, H. Hupppertz: None Declared, I. Foeldvari: None Declared, K. Minden: None Declared
Craniopharyngioma With High FDG Uptake
Authors: Tomoyuki Nagata, Toshibumi Kinoshita, Fumiko Kinoshita, Junta Moroi, Hajime Miyata
Journal: Clinical Nuclear Medicine (2011)

Craniopharyngiomas are slow-growing epithelial neoplasms in the suprasellar region. Fluorodeoxyglucose (FDG) accumulation in a craniopharyngioma has not been previously recognized. We report a case of a suprasellar craniopharyngioma with F-18 FDG positron emission tomography (PET) findings, which showed intense accumulation of FDG. Histologic examination revealed a papillary craniopharyngioma with no evidence of malignant features. Six months after excision, recurrence of the tumor was detected. FDG PET might be helpful in predicting the potential for early recurrence of craniopharyngioma. Nuclear medicine physicians should be aware that craniopharyngioma may be included in the differential diagnosis of suprasellar tumors with high FDG uptake.
Abstract 1297: SETD6-mediated deregulation of NF- κB signaling in 4-ABP-induced bladder carcinogenesis.
Authors: Neelam Mukherjee, Rita Ghosh
Journal: Cancer Research (2013)

Abstract Epidemiological data support an etiological role for chemicals from occupational exposure and cigarette smoke with increased risk of bladder cancer. However, epigenetic effects of these chemicals remain to be elucidated. Protein methyltransferases (PMTs) methylate protein lysine and arginine residues and play an important role in regulating gene transcription. Deregulation of SET-domain-containing PMTs has a crucial role in carcinogenesis. SETD6 has been shown to monomethylate RelA (a principal subunit of NF-κB at Lys310). Monomethylated RelA recruits GLP (G9A-like protein), a histone dimethyl transferase to the NF-κB target genes, which results in transcriptional repression. The role of SETD6 in bladder cancer is unknown. We used qPCR and immunoblotting to determine changes in SETD6 at the mRNA and protein level in bladder cancer cells relative to primary urothelial cells. We also found that knockdown of SETD6 significantly decreases the viability and proliferation of bladder cancer cells suggesting that SETD6 may function as an oncogene in bladder cancer. Furthermore, we also found that message and protein levels of SETD6 are induced in primary urothelial cells following treatment of 4-aminobiphenyl (4-ABP), an important constituent of cigarette smoke. Preliminary results indicate that induction may be mediated by 4-ABP-induced ROS. RelAK310Me1 level also increased with 4-ABP treatment showing the increase in SETD6 functional activity with 4-ABP exposure. We also found the decrease in expression of RelB, one of the target genes of RelA. Overall our results show that SETD6 may function as an oncogene in 4-ABP induced bladder cancer by deregulating transactivation property of RelA. These results show for the first time the relevance of PKMTs and epigenetic regulation of NF-κB in carcinogen induced bladder cancer. Supported by RO3 CA136058 (RG). Citation Format: Neelam Mukherjee, Rita Ghosh. SETD6-mediated deregulation of NF- κB signaling in 4-ABP-induced bladder carcinogenesis. [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 1297. doi:10.1158/1538-7445.AM2013-1297
AB0387 Amyloidosis can influence the qualithy of life in patients with rheumatoid arthritis during anti-TNFα treatment?
Authors: I.C. Filipescu, M. Andrei, L. Ghib, B. Stancu, C. Georgiu, C. Pamfil, M.M. Tamas, L. Damian, S.-P. Simon, L. Muntean, S. Rednic
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Quality of life of patients with rheumatoid arthritis (RA) and biological therapy can be influenced by several factors, not only the response to treatment. Amyloidosis can be one of this <h3>Objectives</h3> We investigated if the quality of life of patients with rheumatoid arthritis and various biological therapies is influenced by the existence of amyloidosis <h3>Methods</h3> We evaluated 113 RA patients (21 men and 92 women) with anti-TNF treatment between June and December 2011. We measured the patients' health-related quality of life using the health assessment questionnaire (HAQ) and visual analog scales for global estimate of status (VAS - GS). All patients were clinically and biologically evaluated. In some patients with HAQ&gt;1 we performed biopsy of abdominal fat to appreciate the existence of amyloidosis using special stain. <h3>Results</h3> The mean age was 53.2 years (range 21–73) and the mean disease duration was 172.9 months (range 18–476). The mean duration of biological treatment was 47.4 months (range 6-132). 32 patients have HAQ&gt;1 and the fat biopsy were performed at 16 of them. We found statistically significant differences between the 2 groups (with or without amyloidosis) and they were recorded between CRP value, VASpatient (p&lt;0.02) and ESR value (p&lt;0.04). We didn't find any significant difference between treatment duration, number of DMARDs, different anti-TNFα agents, swollen joints, DAS 28, sex, other comorbidities. <h3>Conclusions</h3> Amyloidosis is an entity that can influence the quality of life of patients with rheumatoid arthritis. We didn't found any significant correlation with type of biological treatment. Further studies will be necessary to complete this results <h3>Disclosure of Interest</h3> None Declared
SP0034 Ways to Approach Primary Raynaud's Phenomenon
Authors: A. Herrick
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Most patients presenting with Raynaud9s phenomenon have primary Raynaud9s phenomenon (PRP) which is common, especially in women. Estimates of prevalence of PRP vary widely: most studies report prevalence to be in the order of 5% in the general population, although some studies have found much higher prevalences. Athough PRP is a "benign" condition in that it does not progress to irreversible tissue damage, it can be associated with significant pain and disability in those severely affected. A key point is that in PRP, abnormalities in the digital vasculature are thought to be purely functional: structural vascular disease (as seen in systemic sclerosis) does not occur. Patients with PRP should have no features of an underlying disease and no abnormalities on examination: they should be antinuclear antibody (ANA) negative, and the full blood count, erythrocyte sedimentation rate (ESR), and nailfold capillaroscopy should all be normal. Therefore confronted with a patient with Raynaud9s phenomenon, the clinician must take a full history and perform a full examination (paying especial attention to the hands and peripheral pulses), looking for any clinical features suggestive of an underlying cause. The basic set of investigations comprises a full blood count, ESR, ANA and nailfold capillaroscopy. Many clinicians would also include a biochemical profile with thyroid function tests and (especially if symptoms are unilateral) a thoracic outlet radiograph to look for a cervical rib. All should be normal in the patient with PRP. Thermography, which measures surface temperature, can help to differentiate primary from secondary Raynaud9s phenomenon, but is available only in certain specialist centres. Most patients with PRP can be reassured and do not require drug treatment: in many patients symptoms improve spontaneously over the years. If drug treatment is required, a calcium channel blocker (sustained release) is generally the first choice, starting at low dosage and gradually increased as tolerated. If the maximum tolerated dose is ineffective, an alternative vasodilator should be tried, although the evidence base for other therapies is very weak. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6329
ICOSAPENT ETHYL (EICOSAPENTAENOIC ACID ETHYL ESTER) IN STATIN-TREATED PATIENTS WITH ELEVATED CARDIOVASCULAR RISK AND VERY HIGH TRIGLYCERIDE LEVELS: RESULTS FROM THE MARINE STUDY
Authors: Harold E. Bays, Sephy Philip, Sumita Chowdhury, Ralph Doyle, Rebecca A. Juliano
Journal: Journal of the American College of Cardiology (2016)
Abstract 1288: GLI2 is a significant determinant of HH-GLI pathway activaton in Ewing sarcoma
Authors: Laura Christensen, William A. May
Journal: Cancer Research (2012)

Abstract Ewing Sarcoma is an aggressive bone and soft tissue malignancy of children, adolescents and young adults. Non-canonical activation of the Hedgehog-GLI pathway by the Ewing specifc EWS/FLI1 transcription factor has been shown to mediate important aspects of tumor phenotype. While evidence regarding the role of EWS/FLI1 in direct activation has been published, no one has yet investigated the role of other pathway components in Ewing tumors. Physiologically, GLI2 is the principal transcriptional activator of GLI1 and substantial amounts of GLI2 can be demonstrated in Ewing tumors and cell lines. So we hypothesized that GLI2 may also function in Ewing cells to help to regulate GLI1 and Hedgehog-GLI pathway activaton. Since GLI2 can be targeted by pharmacologic means, understanding its role in Ewing tumors is of potential significance. We demonstrate that GLI2 is expressed at significant levels in Ewing tumors. Furthermore, we show by overexpression studies, that GLI2 overexpression augments expression of both GLI1 and other pathway targets in Ewing cell lines. By using shRNA, we also demonstrate that knockdown of GLI2 expression has the expected effect of diminishing GLI 1 expression in Ewing lines. Finally, we show that treatment with GLI inhibitors also diminishes GLI2 activation of GLI1. Overall, these data indicate that GLI2 in Ewing cells exists in an activator state in Ewing cells and that pharmacologic means of targeting GLI2 may be an effective strategy for targeted therapy. 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 1288. doi:1538-7445.AM2012-1288
Cardiac Ion Channels
Authors: Franklin H. Epstein, Arnold M. Katz
Journal: New England Journal of Medicine (1993)

The movement of ions across cardiac cell membranes generates the electrical potentials that activate the heart. Today's molecular biology is providing breathtaking new insights into the regulation of this electrical activity, which is the basis of electrocardiography. Whereas only a few years ago depolarization and repolarization of heart cells were attributed to changing membrane resistance, cardiac action potentials are now understood in terms of structural changes in the proteins that control ion fluxes across the plasma membrane.Ions cross hydrophobic lipid membranes by passing through regulated pores formed by members of an extended family of ion-channel proteins. The opening and . . .
Building a Robust 21st Century Chemical Testing Program at the U.S. Environmental Protection Agency: Recommendations for Strengthening Scientific Engagement
Authors: Jennifer McPartland, Heather C. Dantzker, Christopher J. Portier
Journal: Environmental Health Perspectives (2014)

Biological pathway-based chemical testing approaches are central to the National Research Council's vision for 21st century toxicity testing. Approaches such as high-throughput in vitro screening offer the potential to evaluate thousands of chemicals faster and cheaper than ever before and to reduce testing on laboratory animals. Collaborative scientific engagement is important in addressing scientific issues arising in new federal chemical testing programs and for achieving stakeholder support of their use.
AB0252 Mortality in Patients with Rheumatoid Arthritis: A Prospective Cohort Study over Two Years
Authors: J.S. Eun, N. Kim, C.H. Im, E.J. Nam, Y.M. Kang
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Rheumatoid arthritis (RA) patients have an increased risk of mortality, which has been partially attributed to higher cardiovascular mortality. <h3>Objectives</h3> To determine the mortality and their risk factors over 2 years of follow up in a cohort study. <h3>Methods</h3> A total of 406 RA patients and 209 age and sex-matched normal controls enrolled in the KNUH Atherosclerosis Risk in RA (KARRA) cohort was assessed according to a standardized protocol for two years. Demographic data, traditional CV risk factors, and clinical and laboratory variables relevant to disease activity were obtained. Erythrocyte sedimentation rate-area under the curve (ESR-AUC) overtime was calculated to assess the inflammatory burden. The carotid intima-media thickness (IMT) and plaques were measured using carotid artery ultrasound. <h3>Results</h3> Among RA patients, a total 10 deaths (1.25% per year) occurred during 2 years follow-up period while there were no deaths among the controls. Disease duration of RA until deaths was 32.3±34.0 years. Causes of death included infection (4 pneumonia and 2 septic shock), sudden cardiac death (1 patient), congestive heart failure (1 patient), and others (2 patients). Risk factors for mortality included age (alive vs. dead patients: 55±12.1 vs. 71±9.5, p&lt;0.001), functional class of RA (1.9±0.5 vs. 2.4±0.5, p&lt;0.001), modified Korean health assessment questionnaire (mKHAQ) (9.6±7.8 vs. 22.1±13.7, p&lt;0.05), DAS28 (3.3±4.5 vs. 4.6±1.3, p&lt;0.006), ESR (23.3±20.1 vs 64.3±38.2, p&lt;0.01), ESR-AUC (2,005±1,874 vs 4,106±1,649, p&lt;0.01), and carotid artery plaque number (0.7±1.3 vs 2.5±2.1, p&lt;0.05). After multivariate analysis, mKHAQ and ESR were found to be significantly associated with mortality (p&lt;0.01 and p&lt;0.05, respectively). mKHAQ and ESR cut-off points were made using a receiver-operating characteristic (ROC)-curve. Among the patients with mKHAQ &lt;19, no death occurred in patients with normal ESR, while 3 deaths in patients with abnormal ESR (Figure). Mortality was highest among patients with HAQ ≥19 and abnormal ESR (6 deaths among 41 patients, 14.6%). <h3>Conclusions</h3> These results suggest that functional outcome and inflammatory activity of RA have a critical prognostic impact and tight control of inflammation may improve survival in this population. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4620
A Comparison of Continuous Intravenous Epoprostenol (Prostacyclin) with Conventional Therapy for Primary Pulmonary Hypertension
Authors: Robyn J. Barst, Lewis J. Rubin, Walker A. Long, Michael D. McGoon, Stuart Rich, David B. Badesch, Bertron M. Groves, Victor F. Tapson, Robert C. Bourge, Bruce H. Brundage, Spencer K. Koerner, David Langleben, Cesar A. Keller, Srinivas Murali, Barry F. Uretsky, Linda M. Clayton, Maria M. Jöbsis, Shelmer D. Blackburn, Denise Shortino, James W. Crow
Journal: New England Journal of Medicine (1996)

Primary pulmonary hypertension is a progressive disease for which no treatment has been shown in a prospective, randomized trial to improve survival.
EFICACIA DEL FILTRADO DE SOLICITUDES DE COLONOSCOPIA AMBULATORIA PARA COMBATIR LA SOBREINDICACIÓN EN UN SISTEMA DE ACCESO ABIERTO
Authors: N Alcaide Suárez, P Díez Redondo, P Gil Simón, J Barrio, C De la Serna Higuera, R Atienza, MT Herranz, L Sancho del Val, A Caro-Patón, M Pérez-Miranda
Journal: Endoscopy (2010)

Objetivos: Evaluar la viabilidad de una estrategia de filtro de solicitudes de colonoscopia ambulatoria previa a la citación, identificando causas objetivas de sobreindicación.
422 LOCALIZATION OF MRP2 AT THE NUCLEAR ENVELOPE-ENDOPLASMIC RETICULUM COMPARTMENT OF HEPATOCYTES
Authors: R. Rosales, M.J. Monte, R.I.R. Macias, A.G. Blazquez, M.R. Romero, O. Briz, J.J.G. Marin
Journal: Journal of Hepatology (2012)