tbuckley/cabot-search huggingface dataset:
Abstract 3679: Inhibition of LSD1 disrupts global EWS/ETS transcriptional function in Ewing sarcoma
Authors: Emily Rose Theisen, Savita Sankar, Jared Bearss, Timothy Mulvihill, Venkataswamy Sorna, Sunil Sharma, Stephen L. Lessnick
Journal: Cancer Research (2014)

Abstract Ewing sarcoma is an aggressive pediatric bone tumor characterized by an absolute reliance on the transcriptional activity of the EWS/ETS family of transcription factor fusion oncoproteins. The most common fusion is EWS/FLI, present in 85-95% of cases, though less common fusions include EWS/ERG, EWS/ETV1, EWS/ETV4 and EWS/FEV. EWS/FLI utilizes lysine-specific demethylase 1 (LSD1) as member of the NuRD complex to mediate transcriptional repression of critical tumor suppressors in Ewing sarcoma. LSD1 overexpression has been observed in clinical samples from Ewing sarcoma patients and small molecule blockade of LSD1 using tranylcypromine has been suggested as a therapeutic approach for Ewing sarcoma. We therefore evaluated the effects of LSD1 inhibition with the small molecule inhibitor, HCI-2509, in both in vitro and in vivo models of Ewing sarcoma. HCI-2509 is an LSD1 inhibitor with a Ki of ∼30 nM and multiple Ewing sarcoma cell lines show IC50s in cell viability assays from 500 nM-1 μM. Using RNA-seq, we show that HCI-2509 dramatically reverses both the up- and downregulated transcriptional profiles of both EWS/FLI and EWS/ERG accompanied by the induction of apoptosis and disruption of oncogenic phenotypes modulated by EWS/FLI. We further developed a 9-gene panel based on the RNA-seq data to assess the transcriptional phenotype of HCI-2509 in additional cell lines and showed that it HCI-2509 disrupted both EWS/FLI-activated and -repressed genes similarly across the tested Ewing sarcoma cell lines. HCI-2509 impaired transformation of Ewing sarcoma cell lines in colony forming assays with IC50s from from 25 nM-1 μM. Notably, HCI-2509 displayed single-agent efficacy in multiple xenograft models. We investigated the PK/PD relationship using tumor histone H3K4 and H3K9 methylation. Taken together, these data suggest that epigenetic modulation through LSD1 inhibition may be a therapeutic strategy for Ewing sarcoma, and highlight a critical dual role for LSD1 in the oncogenic transcriptional activity of EWS/ETS proteins. Citation Format: Emily Rose Theisen, Savita Sankar, Jared Bearss, Timothy Mulvihill, Venkataswamy Sorna, Sunil Sharma, Stephen L. Lessnick. Inhibition of LSD1 disrupts global EWS/ETS transcriptional function in Ewing sarcoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3679. doi:10.1158/1538-7445.AM2014-3679
Repositioning self regulation
Authors: R. Smith
Journal: BMJ (1998)

The British government is to take the power to change in one parliamentary move the legislation governing professional regulatory bodies, including the General Medical Council. At the moment changes require modification of the governing acts by a new act of parliament on each occasion, which involves the full parliamentary procedure of multiple readings and committee stages. Is this proposal to make future changes through an order in parliament simply a tidying up exercise or is it an ominous signal on self regulation?

The government insists that its proposals are benign. Parliamentary time is at a premium. It is thus hard to find time to modify the acts …
Abstract 19854: A National Perspective of Weekend- Effect on Mortality and Adverse Outcomes in Patients with Intracerebral Hemorrhage
Authors: Achint Patel, Girish Nadkarni, Neil Patel, Sopan Lahewala, Sudharani Busani, Shantanu Solanki, Grishma Dhaduk, Chirag Bambhroliya, Abhimanyu Mahajan, Priya Simoes, Ioannis Konstantinidis, Yogesh Gujarati, Alexandre M Benjo, Vishal Jani, Apurva Badheka, Syed I Hussain
Journal: Circulation (2014)

Introduction: Management of intracerebral hemorrhage (ICH) requires urgent diagnostic and therapeutic procedures, which may not be uniformly available throughout the week. We attempt to define a "weekend effect" for ICH, which has not yet been fully established in this patient population. Hypothesis: We aimed to evaluate whether outcomes differ with respect to the day of admission in patients admitted with ICH. Methods: We reviewed the Healthcare Cost and Utilization Project’s Nationwide Inpatient Sample (NIS) database from 2000 to 2011 for ICH using ICD 9-CM codes. NIS represents 20% of all US hospital pts and weighted numbers represent national estimates.We defined primary outcome as mortality and adverse outcome(composite of in-hospital mortality &amp; discharge other than home). We utilized chi-square test for univariable analysis for categorical variables and generated hierarchical multilevel regression models to determine independent predictors of mortality and adverse outcome. Results: We included 161017 patients (weighted n=788641) with ICH, out of which 42996(weighted n= 210592) were admitted on weekend. After adjusting for confounders (demographics, Deyo’s modification of charlson’s co-morbidity index, admission type (elective or emergent), hospital region, hospital teaching status, hospital ICH volume and primary payer), the weekend admissions were still associated with 10 % higher mortality (OR 1.10, 95% CI 1.07-1.16, P=0.001) and 20% higher adverse outcome (OR 1.12, 95% CI 1.09-1.16, p=0.001). Conclusions: Thus, admission for ICH on the weekend was a significant and independent predictor of increased in hospital mortality and adverse outcomes as compared to weekday admission. The reasons for this are likely manifold and warrant further investigation both from a quantitative and qualitative standpoint.
Risks of Epilepsy During Pregnancy
Authors: Jacqueline A. French, Kimford Meador
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
The hepatocellular expression of a carbohydrate antigen ‘sialyl Lewis X’ in chronic hepatitis
Authors: Yoshio Okada, Ryoji Usumoto, Mitsuru Muguruma, Toshinari Shimoe, Takayuki Sunayama, Gotaro Yamada, Kazuhide Yamamoto, Takahiro Yamabuki, Takao Tsuji
Journal: Journal of Hepatology (1990)
Variable content of von Willebrand factor mutant monomer drives the phenotypic variability in a family with von Willebrand disease
Authors: Junmei Chen, Jesse D. Hinckley, Sandra Haberichter, Paula Jacobi, Robert Montgomery, Veronica H. Flood, Randall Wong, Gianluca Interlandi, Dominic W. Chung, José A. López, Jorge Di Paola
Journal: Blood (2015)
Abstract 16830: Effects of Exercise Training on Coronary Endothelial Function in Pre-diabetic, Adipose Patients with Coronary Heart Disease
Authors: Ephraim B Beck, Sandra Erbs, Felix Woitek, Robert Hollriegel, Volker Adams, Matthias Bluher, Michael Stumvoll, Gerhard C Schuler, Axel Linke
Journal: Circulation (2010)

Certain fat-tissue-derived adipokines are thought to contribute to endothelial dysfunction, which is a predictor of future cardiovasvular events. The aim of our study was to elucidate the association between obesity and endothelial function in pre-diabetic patients with coronary heart disease (CHD) and to investigate the influence of exercise training (ET) in these patients.   Methods:  62 patients with CHD (age ≤ 75 years), obesity (BMI > 26kg/m 2 ) and impaired glucose tolerance were randomized to 4 weeks of ET (in-hospital basis, 4 times a day for 30 min on a bicycle and rowing ergometer) or sedentary lifestyle (C). At begin and after 4 weeks changes in vascular diameter in response to intracoronary infusion of acetylcholine (7.2 μg/ minute), adenosine 2.4 mg/ minute and nitroglycerin (200 μg as an intracoronary bolus) was assessed by quantitative coronary angiography. Intracoronary average peak blood flow velocity (APV) was measured by Doppler velocimetry. Coronary blood flow (CBF) [ml/ minute] and coronary flow reserve (CFR) [x-fold increase in APV after adenosine infusion compared to saline] were calculated. The number of circulating CD 34 +  stem cells and CD34/KDR +  endothelial progenitor cells (EPC) were quantified by FACS.   Results:  Exercise training was associated with a reduction in BMI by -0.6±0.1 kg/m 2  (p +  stem cells by 30% and the amount of CD34/KDR +  EPC by 72% (p   Conclusion:  In obese patients with CHD having an impaired glucose tolerance, ET leads to a reduction in body weight and improves endothelium-dependend vasodilation both in epicardial coronary vessels and resistance vessels. This might be partially a result of an augmented number of circulating stem and progenitor cells.
148. The Altered Binding Properties of Sleeping Beauty Transposase Hyperactive Mutants May Explain Their Enhanced Efficacy
Authors: Julie Park, Stephen R. Yant, Mark A. Kay
Journal: Molecular Therapy (2004)

Top of pageAbstract
The Sleeping Beauty (SB) transposon system has been shown as an effective vector to mediate stable, long-term gene transfer. We have previously identified SB hyperactive mutants through an alanine scan of the DNA binding region of the transposase. In total, 96 single-substitution mutants were generated and those individual missense mutations leading to increased activity were combined to generate four hyperactive Sleeping Beauty (HSB) mutants. In this study, we have begun to delve into the mechanism behind the increased activity of these mutants by comparing the four HSB mutants and wild-type transposase for their ability to bind the DNA-recognition sites. Truncated (N123) derivatives of wild-type and hyperactive SB proteins were generated by in vitro transcription/translation and tested for their ability to bind to oligos corresponding to transposase binding sites in an electrophoretic mobility shift assay. Each SB transposon inverted repeat contains two transposase binding sites, an outer binding site (OBS) adjacent to the transposon boundary and an inner binding site (IBS) internally situated about 165bp from the OBS. We found that there was no change in the binding affinities of the hyperactive mutants versus wild-type for the IBS but that binding to the OBS was increased 2–4 fold. Our results in conjunction with previous work, where it was shown that simply increasing the binding affinity of the transposase at the transposon terminal end causes the abolishment of transposition (Cui et al, J Mol Biol, 1221–1235; 2002), suggest that the mechanisms underlying hyperactivity may be due to an enhanced ability of these mutants to form an active synaptic complex and we are in the process of investigating this possibility. We are also examining all of the single-substitution mutants to determine which individual residues contribute to increased binding affinity. Through these experiments we hope to gain additional insight into the mechanisms involved in transposase function which, in turn, will lead to further enhancement of SB as a tool for gene transfer.
Reforming the Russian health service Otherwise it might be convenient Urgent aid, chronic penalties Professional law breakers Training general practitioners in St Petersburg Training general practitioners in Gatchina
Authors: P. D Toon, T. Vilks, K. Schlachter, V. Vinokur, N N Gurin, C V Logunov, N U Baranova
Journal: BMJ (1998)

# Reforming the Russian health service {#article-title-2}

Health service reform is an important part of the growth of democracy in Russia, and several Western groups have been helping the Russians tackle this huge task. Since 1992, general practitioners in the United Kingdom and medical teachers at the Medical Academy of Postgraduate Studies in St Petersburg have been sharing knowledge on medical education and primary health care. In this article, Dr Peter Toon, the UK coordinator, and Russian doctors involved in the partnership describe Russian health care and attempts at its reform from different perspectives.

# Otherwise it might be convenient {#article-title-3}

The Russian health service is vast. Primary care takes place, not in cosy domestic surgeries, but in polyclinics that feel like small district general hospitals without inpatients. Hospitals are correspondingly massive, often with a thousand or two thousand beds. Many were built in that architecturally depressing period that gave Britain the tower blocks we are now replacing. Unfortunately, Russia has no money for new buildings and little for maintenance, so they crumble gently away.



Russian health care is burdened by its massive inhuman scale and a heavy authoritarian bureaucracy



The Russian health service is specialist led. District physicians based in polyclinics, each responsible for 2000 patients in a neat geographical patch (patient choice has yet to reach Russia) look after primary care. They do little other than treat viral illnesses, issue medical certificates, and refer about half the patients they see to specialist colleagues. Half the doctors in polyclinics are specialists, and since patients have direct access to them, district physicians are often bypassed altogether.

As a Russian colleague put it, the service is “obese.” There are long hospital stays, large numbers of specialists seeing too few patients, and a heavy authoritarian bureaucracy, since every doctor's work is checked by a superior. As in the United States and France, politicians—but not the health …
Occupational Health: Recognizing and Preventing Work-Related Disease.
Authors: Barry S. Levy, David H. Wegman
Journal: Annals of Internal Medicine (1983)

A multidisciplinary approach to the practice of occupational medicine. It is an introductory text that puts into context the complex medical, political, social, and economic issues involved in diagnosing and preventing work-related illness. The text covers: approaches to recognizing and preventing occupational disease, hazardous workplace exposures, occupational diseases by organ system. The new edition has been completely updated and revised. The contents have been reorganized and tightened so that some of the more specialized sections from the previous edition are covered by a parent topic in a preceding section. A new chapter on shift work has been added. Contributors include primary care and specialist physicians; contributors from industry, government, industrial hygienists, safety and ergonomic experts, psychologists, economists, lawyers and sociologists.
Rapid Health Response, Assessment, and Surveillance After a Tsunami—Thailand, 2004-2005
Authors: Usa Prevention
Journal: JAMA (2005)

EARTHquake triggered a devastating tsunami that caused an estimated 225,000 deaths in eight countries (India, Indonesia, Malaysia, Maldives, Seychelles, Somalia, Sri Lanka, and Thailand) on two continents.In Thailand, six provinces (Krabi, Phang-Nga, Phuket, Ranong, Satun, and Trang) were impacted, including prominent international tourist destinations.The Thai Ministry of Public Health (MOPH) responded with rapid mobilization of local and nonlocal clinicians, public health practitioners, and medical supplies; assessment of health-care needs; identification of the dead, injured, and missing; and active surveillance of syndromic illness.The MOPH response was augmented by technical assistance from the Thai MOPH-U.S. CDC Collaboration (TUC) and the Armed Forces Research Institute of Medical Sciences (AFRIMS), with support from the office of the World Health Organization (WHO) representative to Thailand.This report summarizes these activities.The experiences in Thailand underscore the value of written and rehearsed disaster plans, capacity for rapid mobilization, local coordination of relief activities, and active public health surveillance. Rapid ResponseMOPH rapidly activated mass casualty plans and deployed personnel and resources to meet local health-care needs.
Convalescence, Historical and Practical.
Authors: J. H. Elliott
Journal: JAMA (1928)

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
Abstract 9015: Correlation between Spatial Repolarization and Peak-to-end of the T Wave on Transmural Left Ventricular and Body Surface Electrocardiographic Recordings
Authors: Daisuke Izumi, Masaomi Chinushi, Kenichi Iijima, Kanae Hasegawa, Akinori Sato, Hiroshi Furushima, Yoshifusa Aizawa
Journal: Circulation (2011)

Background. Previous studies showed that Tp-e is a marker of transmural dispersion of ventricular repolarization. Objectives. We studied the relationship between a) the interval between peak and end of the T wave (Tp-e) on local transmural electrograms (transmural Tp-e) or body surface ECG (surface Tp-e) and b) the intracardiac left ventricular (LV) repolarization during QT interval prolongation. Methods. Using a canine anthopleurin-A model, transmural LV electrograms were recorded via needle electrodes placed in the baso-anterior, mid-anterior, apico-anterior, baso-lateral, mid-lateral, and apico-lateral LV wall. Recovery time (RT) was calculated as an index of local repolarization at each transmural unipolar electrode. Results. RT was longer at the LV apex than that at the base, and longer in the lateral than in the anterior wall. A high correlation was found between transmural Tp-e and the transmural RT-dispersion (figure 1). On the other hand, surface Tp-e was correlated with total spatial LV RT-dispersion, though not with transmural RT-dispersion (figure 2). The slope of the linear correlation between surface Tp-e and total spatial LV RT-dispersion was 1.04 (P &lt; 0.001), whereas betwwen surface Tp-e and averaged transmural RT-dispersion was 0.25 (P &lt; 0.001). The shortest RT in the heart corresponded to the peak, whereas the longest RT coincided with the end of the T wave on the surface ECG. Conclusions. Surface Tp-e may overestimate the transmural dispersion of LV repolarization, and seems to express the special distribution of repolarization in the whole LV during iatrogenic QT interval prolongation.
Long-Term Hemodialysis. The Management of the Patient with Chronic Renal Failure.
Authors: Constantine L. Hampers, Eugene Schupak
Journal: Annals of Internal Medicine (1968)

In addition, it is too large and not designed to give the "core" of neuropathology taught in about 30 hours of instruction in a medical school.Moreover, it lacks teach- ing method in its approach.As descriptive neuropathology, it has great merit.This, along with its excellent reference source and its illustra- tions, should make it very useful as a reference text.
Fulminating septicaemia caused by Vibrio vulnificus
Authors: L. Serrano-Jaen, F. Vega-Lopez
Journal: British Journal of Dermatology (2000)

Journal Article Fulminating septicaemia caused by Vibrio vulnificus Get access L. Serrano‐Jaen, L. Serrano‐Jaen Department of Dermatology and Medical Mycology, Hospital de Especialidades ‘Dr Bernardo Sepúlveda’, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Avenida Cuauhtemoc 330, Colonia Doctores, 06725 Mexico, D.F., Mexico , Department of Dermatology, Middlesex Hospital, Mortimer Street, London W1N 8AA U.K. Search for other works by this author on: Oxford Academic Google Scholar F. Vega‐Lopez F. Vega‐Lopez Department of Dermatology and Medical Mycology, Hospital de Especialidades ‘Dr Bernardo Sepúlveda’, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Avenida Cuauhtemoc 330, Colonia Doctores, 06725 Mexico, D.F., Mexico , Department of Dermatology, Middlesex Hospital, Mortimer Street, London W1N 8AA U.K. Correspondence: F.Vega‐Lopez Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 142, Issue 2, 1 February 2000, Pages 386–387, https://doi.org/10.1046/j.1365-2133.2000.03322.x Published: 01 February 2000
Heparanase alters lipid raft composition in newly developed, highly brain-metastatic melanoma cells
Authors: Jane Reiland, Derek Kopecky, Yvonne Denkins, Doty Kempf, Madhuchhanda Roy, Dario Marchetti
Journal: Cancer Research (2006)

4376   Lipid rafts are membrane micro-domains containing cell signaling molecules which cause an increased cell migration, adhesion, invasion, and tumor metastasis upon their activation. Heparan sulfate proteoglycans (HSPG) are signaling macromolecules present on the cell-surface and in the surrounding extracellular matrix (ECM), and found in lipid rafts. Heparanase (HPSE-1) is a unique ECM degrada tive enzyme cleaving heparan sulfate glycosaminoglycan chains (HS GAG) which are attached to HSPG core proteins. Importantly, changes in HS GAG composition promote an altered cell signaling and biological behavior as well as a relocalization of certain HSPG, mainly cell-surface syndecan-1 (Synd-1). We have examined how HPSE-1 treatment of newly developed, highly brain-metastatic human melanoma cells (70W–SM3) affects lipid raft protein composition using Western blotting analyses of isolated lipid rafts. Our results show a HPSE-1 - mediated increase in phosphorylation of extracellular signal-regulated kinase (pERK) and focal adhesion kinase (pFAK) in lipid raft localization. Equally important, we have demonstrated that HPSE-1 affects lipid raft composition by decreasing Synd-1, therefore regulating HSPG mobility from the detergent-insoluble lipid raft of the cell into the medium. These findings are relevant because they provide  first-time  evidence that HPSE-1 is involved in a novel mechanism regulating cell signaling and tumorigenesis