tbuckley/cabot-search huggingface dataset:
Abstract 90: K63-linked JARID1B ubiquitination by TRAF6 contributes to aberrant elevation of JARID1B in prostate cancer
Authors: Wenfu Lu, Shenji Liu, Bo Li, Yingqiu Xie, Christine Adhiambo, Qing Yang, Billy R. Ballard, Keiichi I. Nakayama, Robert J. Matusik, Zhenbang Chen
Journal: Cancer Research (2015)

Abstract Aberrant elevation of JARID1B and histone H3 Lys4 trimethylations (H3K4me3) is frequently observed in many diseases including prostate cancer (PCa), yet the mechanisms on the regulations of JARID1B and H3K4me3 through epigenetic modifications still remain poorly understood. In this study we performed immunohistochemistry staining, immunofluorescence imaging, immunoprecipitation, shRNA and Western blotting analysis in mouse embryonic fibroblasts (MEFs), mouse models, and cultured human prostate cancer cells. As a result, we discovered that SKP2 modulates JARID1B and H3K4me3 levels in vitro in PTEN null prostate cancer cells and in vivo in Pten/Trp53 mouse models. We demonstrated that levels of SKP2, JARID1B and H3K4me3 are strikingly elevated in vitro and in vivo when both PTEN and P53 are inactivated. Importantly, SKP2 inactivation resulted in a reduction of cell growth, cell migration and malignant transformation of Pten/Trp53 double null MEFs, and further restrained prostate tumorigenesis of Pten/Trp53 mutant mice. Mechanistically, JARID1B is ubiquitinated by E3 ligase TRAF6 through the K63-linkage in prostate cancer cells. Interestingly, SKP2 contributes to JARID1B ubiquitination machinery as a non-E3 ligase regulator by decreasing TRAF6-mediated ubiquitination of JARID1B. SKP2 deficiency resulted in an increase of JARID1B ubiquitination and in turn a reduction of H3K4me3, and induced senescence through JARID1B accumulation in nucleoli of PCa cells and prostate tumors of mice. Furthermore, we showed that the aberrant levels of SKP2, JARID1B, and H3K4me3 are associated with malignant features of castration-resistant prostate cancer (CRPC) in mice. Overall, our findings reveal a novel network of SKP2- JARID1B, and targeting SKP2 and JARID1B may be a potential strategy for PCa control. Citation Format: Wenfu Lu, Shenji Liu, Bo Li, Yingqiu Xie, Christine Adhiambo, Qing Yang, Billy R. Ballard, Keiichi I. Nakayama, Robert J. Matusik, Zhenbang Chen. K63-linked JARID1B ubiquitination by TRAF6 contributes to aberrant elevation of JARID1B in prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 90. doi:10.1158/1538-7445.AM2015-90
Left Ventricular Isovolumic Flow Sequence During Sinus and Paced Rhythms
Authors: Partho P. Sengupta, Bijoy K. Khandheria, Josef Korinek, Arshad Jahangir, Shiro Yoshifuku, Ilija Milosevic, Marek Belohlavek
Journal: Journal of the American College of Cardiology (2007)
Abstract 9065: Na+/H+ Exchanger 1 Gene Regulates Migration of Human Pulmonary Artery Smooth Muscle Cells Under Hypoxia
Authors: Lunyin Yu, Charles A Hales
Journal: Circulation (2010)

Introduction: The Na+/H+ exchanger isoform 1 (NHE1) is ubiquitously expressed in many mammalian cell types, including pulmonary artery smooth muscle cell (PASMC). Our previous study has found that ...
Considerations of Long-term Pain Evaluation Post– Deep Brain Stimulation Surgery—Reply
Authors: Yu Jin Jung, Han-Joon Kim, Beom S. Jeon
Journal: JAMA Neurology (2015)

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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Neurology journal
Focus on modification of risk factors and patients' perception of lifestyle
Authors: G. Y H Lip, R. Balasubramaniam, A. Maurice, G. Beevers
Journal: BMJ (1995)

effects of intervention were lost in the background statistical noise.This study should not preclude a full integrated approach to the management of risk factors, including health education, dietary intervention, and drug treatment as it is necessary for the long term health of patients.
Medical students are positive about the future
Authors: R. Gauntlett
Journal: BMJ (1995)

EDITOR,—It is unfortunate that an editorial entitled “The inhumanity of medicine” should focus on medical students.1 Many would argue that students are in a better position than hardened professionals to spot inhumanities in established procedures and are more perceptive of insensitive behaviour towards patients. D J Weatherall seems to blame students and juniors for the situation in which they find themselves rather than the educational, political, and medical authorities. Can 15 year olds be held …
Involvement of polo-like-kinase 1 (Plk1) in prostate cancer: A novel target for treatment strategies
Authors: Shannon R. Reagan-Shaw, Moammir H. Aziz, Nihal Ahmad
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

3853 

Prostate Cancer (PCa) is one of the most common cancers in men. Each year ∼543,000 new cases are reported worldwide and the disease kills 200,000 (mostly older men) in developed countries. The existing treatment approaches and surgical intervention have not been able to effectively manage this dreaded cancer and, therefore, continuing efforts are ongoing to explore novel targets and strategies for the management of PCa. The activity of polo-like kinase-1 (Plk1) is found elevated in tissues and cells with a high mitotic index, including cancer cells. An increasing body of evidence suggests that the level of Plk1 expression has prognostic value for predicting outcomes in patients with some cancers. A close correlation between Plk1 expression and carcinogenesis has been documented. However, the role of Plk1 in PCa is not known. We propagated a hypothesis that Plk-1 plays a critical role in the development of PCa; and its inhibition will result in elimination of human PCa cells via a mitotic arrest followed by apoptosis (FASEB J; In Press). To define the role of Plk1 in PCa, we employed the technique of RNA silencing via small interference RNA (siRNA). First, employing a series of human prostate carcinoma cells and normal human prostate epithelial (PrEC) cells, we assessed Plk1 levels in PCa. Immunoblot analyses clearly showed a significant expression of Plk1 in LNCaP, DU145 and PC3 human PCa cells. Interestingly, Plk1 was not detectable in normal PrEC cells. Next, we transfected the PCa cells with Plk 1 siRNA, which resulted in significant (50 –72%) inhibition in Plk-1 protein in all PCa cells. The phenotype, proliferation, and cell cycle distribution of cells transfected with siRNAs were also monitored employing fluorescence microscopy and fluorescence-activated cell analysis. The PrEC cells were not affected by Plk1-siRNA treatment. Plk1-siRNA trasfection resulted in i) a 45-72% decrease in cell viability, and ii) significant induction of apoptosis (30%-50% in trasfected cells; vs 1%-4% in controls), at 24 hours post-transfection in PCa cells. As shown by the confocal microscopy, our data also demonstrated that Plk1-transfection of PCa cells resulted in i) mitotic arrest, ii) failure of cytokinesis, and iii) defects in centrosome integrity and maturation. Thus, our study suggested that i) Plk1 plays a critical role in the process of PCa development, and ii) gene therapeutic approaches aimed at Plk1 or the pharmacological inhibitors of Plk1 may be developed for the management of CaP.
Determining prognosis after acute myocardial infarction in the thrombolytic era
Authors: P. Lim, P. Shiels, G. A Beller
Journal: BMJ (1998)

Editor—Beller brings to readers’ attention the fact that routine invasive procedures after acute myocardial infarction offer no significant benefit over that offered by the routine practice of risk stratification with non-invasive methods.1 We are concerned, however, with the blanket statement that high risk patients should have early angioplasty or rescue angioplasty after failed thrombolysis. This technique should be used with caution. 

A meta-analysis by Ellis et al indicated a mortality of 10.6% after the procedure, either from the disease process or as a direct complication of the procedure.2 Furthermore, this procedure fails in 20% of cases and those failed cases have a mortality of 40%. Vigorous clinical assessment is therefore necessary before a patient is classified as being at high risk. Inadequate optimisation of supportive treatment often leads to signs such as hypotension and sinus tachycardia, which in turn predispose to further chest pain, interpreted as postinfarction angina even in the absence of electrocardiographic changes. Chest crepitations related to aging are often confused with those associated with pulmonary oedema. One prime example is inferior myocardial infarction with right ventricular extension. This is due to an occlusion of a dominant right coronary artery, which carries a relatively good prognosis. Suboptimal fluid replacement and the indiscriminate use of inotropic agents without prior careful assessment of left ventricular function with echocardiography and guidance by Swan-Ganz catheterisation lead to patients being classified as at high risk without having prior or incidental left coronary artery disease. 

The fact that rescue angioplasty for right coronary artery occlusion is associated with excessive complications3 should lead doctors to question whether this form of intervention is putting a patient’s life at risk, turning a relatively benign course into a fatal one.
Abstract P375: Vascular Age Versus Calendar Age as Surrogate for Atherosclerotic Burden and Cardiovascular Disease Risk
Authors: Sanne A Peters, Karlijn A Groenewegen, Hester M den Ruijter, Michiel L Bots
Journal: Circulation (2013)

Background Vascular age is the chronological age of an individual adjusted by their level of atherosclerosis. Vascular age can be used as understandable communication tool towards patients. It has been proposed that carotid intima-media thickness (CIMT) could be used to estimate the vascular age in individuals. The issue on how to best estimate vascular age remains an unanswered question and was evaluated in this study. Methods Data were used from the USE-IMT study collaboration, a global individual patient data meta-analysis including 14 population-based cohorts contributing data for 45 828 individuals. We used two methods to define vascular age. First, vascular age was the age at which a participant’s CIMT value would be at the 50th percentile of the age-and sex specific reference values of the healthy USE-IMT subpopulation (VA50). Second, vascular age was the age at which the estimated cardiovascular risk equals the risk of the observed CIMT value (VArisk). Results Mean (+/- standard deviation [SD]) chronological age, VA50, and VArisk were 58 (9), 63 (19), and 59 (7) years, respectively. VArisk was 0.24 yrs higher in women and 1.5 yrs higher in men than chronological age whereas VA50 was 4.4 yrs higher in women and 5.8 yrs higher in men than chronological age. After adjustment for traditional cardiovascular risk factors, a SD increase in VA50 and VArisk was associated with a 15% (95% confidence interval [CI]: 1.12; 1.19) and 22% (95% CI: 1.17; 1.28) higher risk of cardiovascular disease. For comparison, a SD increase in mean common CIMT increased the risk of cardiovascular disease with 15% (95% CI: 1.12; 1.19). Conclusion We presented two distinct measures a vascular age: VA50, and VArisk. VA50 is a straightforward translation of CIMT and is a measure of the age at which the average person would be expected to have a certain CIMT. In contrast, VArisk incorporates information about expected cardiovascular risk and is the chronological age of a person that conveys the same risk as the CIMT. VA50 and VArisk might provide a convenient transformation of CIMT to a scale that is more easily understood by patients and clinicians.
The Pathologic Basis of Q-Wave and Non-Q-Wave Myocardial Infarction
Authors: James C.C. Moon, Diego Perez De Arenaza, Andrew G. Elkington, Anil K. Taneja, Anna S. John, Duolao Wang, Rajesh Janardhanan, Roxy Senior, Avijit Lahiri, Philip A. Poole-Wilson, Dudley J. Pennell
Journal: Journal of the American College of Cardiology (2004)
Histone hypoacetylation and reduced expression of p21Waf1 in gastric carcinoma
Authors: Yoshitsugu Mitani, Naohide Oue, Tomohiro Kondo, Yasuhiro Oshimo, Hirofumi Nakayama, Masaru Sugiyama, Takenori Ishikawa, Wataru Yasui
Journal: Cancer Research (2004)

4170   Several lines of evidence indicate that histone acetylation plays an important role in transcriptional regulation. Inactive chromatin mediated by histone deacetylation is a critical component in silencing of tumor suppressor genes including p21waf1. However, alteration of histone acetylation status in human cancer tissues has not been well understood. In the present study, we studied the histone acetylation status of the p21waf1 gene by chromatin immunoprecipitation (ChIP) assay in 29 gastric carcinoma tissues and compared with levels of p21waf1 mRNA expression mea sured by real-time RT-PCR. Hypoacetylation of histone H3 in the promoter and coding region of the p21waf1 was detected in 18 (62%) and 16 (55%) of the 29 gastric carcinomas, respectively, while hypoacetylation of histone H4 in the promoter and coding region was detected in 21 (72%) and 24 (83%), respectively. Levels of p21waf1 mRNA in tumor tissues with histone H3 hypoacetylation of the promoter region were significantly lower than those in tumor tissues with histone H3 hyperacetylation. p53 mutation status was not associated with p21Waf1 mRNA expression levels and histone acetylation status in the promoter or coding region. The treatment of trichostatin A, a histone deacetylase inhibitor, up-regulated p21Waf1 protein expression in MKN-28, NKN-74, and KATO-III cells, while the levels of acetylation of histones H3 in the promoter region of p21waf1 was significantly enhanced. Dominant negative inhibition of p53 in MKN-74 cells significantly reduced p21Waf1 protein expression and histone H4 acetylation level of p21Waf1. Our study provides the first evidence that alteration of histone acetylation occurs in gastric carcinoma tissues and this leads to reduce p21waf1 expression in p53-independent manner.
A Randomized Trial of Diagnostic Techniques for Ventilator-Associated Pneumonia
Journal: New England Journal of Medicine (2006)

Critically ill patients who require mechanical ventilation are at risk for ventilator-associated pneumonia. Current data are conflicting as to the optimal diagnostic approach in patients who have suspected ventilator-associated pneumonia.In a multicenter trial, we randomly assigned immunocompetent adults who were receiving mechanical ventilation and who had suspected ventilator-associated pneumonia after 4 days in the intensive care unit (ICU) to undergo either bronchoalveolar lavage with quantitative culture of the bronchoalveolar-lavage fluid or endotracheal aspiration with nonquantitative culture of the aspirate. Patients known to be colonized or infected with pseudomonas species or methicillin-resistant Staphylococcus aureus were excluded. Empirical antibiotic therapy was initiated in all patients until culture results were available, at which point a protocol of targeted therapy was used for discontinuing or reducing the dose or number of antibiotics, or for resuming antibiotic therapy to treat a preenrollment condition if the culture was negative.We enrolled 740 patients in 28 ICUs in Canada and the United States. There was no significant difference in the primary outcome (28-day mortality rate) between the bronchoalveolar-lavage group and the endotracheal-aspiration group (18.9% and 18.4%, respectively; P=0.94). The bronchoalveolar-lavage group and the endotracheal-aspiration group also had similar rates of targeted therapy (74.2% and 74.6%, respectively; P=0.90), days alive without antibiotics (10.4+/-7.5 and 10.6+/-7.9, P=0.86), and maximum organ-dysfunction scores (mean [+/-SD], 8.3+/-3.6 and 8.6+/-4.0; P=0.26). The two groups did not differ significantly in the length of stay in the ICU or hospital.Two diagnostic strategies for ventilator-associated pneumonia--bronchoalveolar lavage with quantitative culture of the bronchoalveolar-lavage fluid and endotracheal aspiration with nonquantitative culture of the aspirate--are associated with similar clinical outcomes and similar overall use of antibiotics. (Current Controlled Trials number, ISRCTN51767272 [controlled-trials.com].).
P0258 : Tauroursodeoxycholic acid dampens oncogenic apoptosis induced by endoplasmic reticulum stress during hepatocarcinogen exposure
Authors: Y.-P. Vandewynckel, D. Laukens, L. Devisscher, A. Paridaens, E. Bogaerts, X. Verhelst, A. Van den Bussche, S. Raevens, C. Van Steenkiste, M. Van Troys, C. Ampe, B. Descamps, C. Vanhove, O. Govaere, L. Libbrecht, A. Geerts, H. Van Vlierberghe
Journal: Journal of Hepatology (2015)
Finland introduces rotavirus vaccine into the national vaccination programme in September 2009
Authors: H Nohynek, H Salo, M Renko, T Leino
Journal: Eurosurveillance (2009)

Supported by an economic evaluation, rotavirus vaccine is introduced into the national immunisation schedule in Finland. The vaccination programme has been estimated to be reasonably cost-effective. Given at the age of two, three and five months, the vaccine is expected to prevent annually in Finland among children under the age of five years approximately 2,000 rotavirus diarrhoea episodes needing hospitalisation, and over 10,000 outpatient visits. The impact of the programme will be evaluated in 2011 by repeating the economic analysis and carefully monitoring adverse events.
A Randomized Comparison of Sirolimus-Eluting Stent With Balloon Angioplasty in Patients With In-Stent Restenosis
Authors: Fernando Alfonso, Maria-José Pérez-Vizcayno, Rosana Hernandez, Armando Bethencourt, Vicens Martí, Jose R. López-Mínguez, Juan Angel, Ramón Mantilla, Cesar Morís, Angel Cequier, Manel Sabaté, Javier Escaned, Raúl Moreno, Camino Bañuelos, Alfonso Suárez, Carlos Macaya
Journal: Journal of the American College of Cardiology (2006)
A study of osteopontin as a plasma hypoxia marker in nasopharyngeal cancer
Authors: Edwin P. Hui, Fion L. Sung, Xiaorong Lin, Brigette By Ma, Cesar Sc Wong, Anthony Tc Chan
Journal: Cancer Research (2006)

4483    Background: Osteopontin (OPN) is a secreted phosphoglycoprotein that has been linked to tumor progression and survival in several solid tumors. Recent studies suggested that OPN secretion is induced by hypoxia, and its plasma level can serve as a surrogate marker for tumor hypoxia and treatment outcome in head and neck cancer patients. We investigated the response of OPN to in-vitro hypoxia in nasopharyngeal carcinoma (NPC) cell lines and also determined the plasma OPN levels in NPC patients and healthy subjects.  Methods:  Four human NPC cell lines (HK1, HONE-1, C666-1 and CNE-2) were treated with 0, 4, 8, 12, 16, 24 and 48 hours of hypoxia (0.1% oxygen) or normoxia. OPN secretion in the supernatant was measured by ELIZA assay. Cellular OPN protein concentration was detected by Western blotting. Plasma OPN levels in NPC patients and healthy controls were measured by ELIZA.  Results:  In HK1, HONE-1 and C666-1, OPN levels in the supernatant remained undetectable throughout the incubation periods either in normoxia or hypoxia. CNE-2 cells secreted OPN in both normoxia and hypoxia, but there was no significant induction by hypoxia. There was no induction of cellular OPN protein in CNE-2 after hypoxia incubation. The mean plasma level of OPN (± S.E.) was 512.1 ± 44.9 ng/ml in 12 consecutive, newly diagnosed NPC patients of various stages (AJCC stage I=1, II=4, III=4, IV=3), and 459.6 ± 34.8 ng/ml in 10 healthy volunteer subjects.  Conclusion:  Our result did not suggest a significant role for hypoxia induced secretion of OPN in NPC cell lines. Plasma OPN levels were elevated in newly diagnosed NPC patients but the range appeared to overlap with that of healthy control subjects. The exact cellular origin(s) and underlying causes of elevated plasma OPN in both health and disease states require further investigation. Acknowledgement: supported in part by a grant from the Research Grants Council of the Hong Kong Special Administrative Region (CUHK 4093/02M).
Prognostic Value of Fractional Flow Reserve
Authors: Nils P. Johnson, Gábor G. Tóth, Dejian Lai, Hongjian Zhu, Göksel Açar, Pierfrancesco Agostoni, Yolande Appelman, Fatih Arslan, Emanuele Barbato, Shao-Liang Chen, Luigi Di Serafino, Antonio J. Domínguez-Franco, Patrick Dupouy, Ali M. Esen, Özlem B. Esen, Michalis Hamilos, Kohichiro Iwasaki, Lisette O. Jensen, Manuel F. Jiménez-Navarro, Demosthenes G. Katritsis, Sinan A. Kocaman, Bon-Kwon Koo, Ramón López-Palop, Jeffrey D. Lorin, Louis H. Miller, Olivier Muller, Chang-Wook Nam, Niels Oud, Etienne Puymirat, Johannes Rieber, Gilles Rioufol, Josep Rodés-Cabau, Steven P. Sedlis, Yasuchika Takeishi, Pim A.L. Tonino, Eric Van Belle, Edoardo Verna, Gerald S. Werner, William F. Fearon, Nico H.J. Pijls, Bernard De Bruyne, K. Lance Gould
Journal: Journal of the American College of Cardiology (2014)

Fractional flow reserve (FFR) has become an established tool for guiding treatment, but its graded relationship to clinical outcomes as modulated by medical therapy versus revascularization remains unclear. The study hypothesized that FFR displays a continuous relationship between its numeric value and prognosis, such that lower FFR values confer a higher risk and therefore receive larger absolute benefits from revascularization. Meta-analysis of study- and patient-level data investigated prognosis after FFR measurement. An interaction term between FFR and revascularization status allowed for an outcomes-based threshold. A total of 9,173 (study-level) and 6,961 (patient-level) lesions were included with a median follow-up of 16 and 14 months, respectively. Clinical events increased as FFR decreased, and revascularization showed larger net benefit for lower baseline FFR values. Outcomes-derived FFR thresholds generally occurred around the range 0.75 to 0.80, although limited due to confounding by indication. FFR measured immediately after stenting also showed an inverse relationship with prognosis (hazard ratio: 0.86, 95% confidence interval: 0.80 to 0.93; p < 0.001). An FFR-assisted strategy led to revascularization roughly half as often as an anatomy-based strategy, but with 20% fewer adverse events and 10% better angina relief. FFR demonstrates a continuous and independent relationship with subsequent outcomes, modulated by medical therapy versus revascularization. Lesions with lower FFR values receive larger absolute benefits from revascularization. Measurement of FFR immediately after stenting also shows an inverse gradient of risk, likely from residual diffuse disease. An FFR-guided revascularization strategy significantly reduces events and increases freedom from angina with fewer procedures than an anatomy-based strategy.