tbuckley/cabot-search huggingface dataset:
Abstract 1014: Targeting cancer stem cells by a Notch2/Notch3 cross-reactive antibody inhibits tumor growth and delays tumor recurrence in pancreatic cancer
Authors: Marcus M. Fischer, Wan-Ching Yen, Min Wang, Ann M. Kapoun, Aaron Sato, John Lewicki, Austin Gurney, Timothy Hoey
Journal: Cancer Research (2012)

Abstract Pancreatic cancer is a devastating disease with very poor prognosis and few treatment options. The Notch pathway has been implicated in the development of pancreatic cancer, and in particular both Notch2 and Notch3 are known to be important in this disease. In this report, we examined the in vivo efficacy of an antibody that was initially identified by binding to Notch2 and was subsequently shown to block signaling of both human and mouse Notch2 and Notch3. Utilizing a panel of minimally-passaged, patient-derived, pancreatic adenocarcinoma xenograft tumors, we performed in vivo growth inhibition and tumorigenicity studies with the Notch2/3 antibody alone or combined with the standard-of-care chemotherapeutic gemcitabine. We demonstrated that the Notch2/3 antibody was active as a single agent, and when combined with gemcitabine, the combination therapy resulted in improved efficacy over that of gemcitabine alone. Utilizing an in vivo limiting dilution tumorigenicity assay, we found that the cancer stem cell (CSC) frequency was increased by gemcitabine as a single agent, but significantly decreased by the combination of anti-Notch2/3 and gemcitabine. Analysis of cell surface markers associated with pancreatic cancer stem cells indicated that gemcitabine treatment results in an increase in the percentage of CSCs, while the Notch2/3 antibody significantly reduced the CSC population. Utilizing this pancreatic cancer xenograft model, we analyzed the ability of the Notch 2/3 antibody to delay tumor recurrence following gemcitabine induced tumor regression. While gemcitabine-treated tumors re-grew rapidly following treatment termination, the ability of tumors to recur was significantly delayed by the Notch2/3 antibody suggesting that the delay in tumor recurrence is in part due to the Notch2/3 antibody-mediated decrease in CSC frequency. Gene set enrichment analysis in tumors that responded to anti-Notch2/3 revealed that various stem cell gene sets were up-regulated in tumors treated by gemcitabine alone, but down-regulated by the combination of anti-Notch2/3 and gemcitabine. Findings from this study suggest that antagonists of Notch signaling may act as chemotherapeutic-sensitizing agents by interfering with CSC self renewal pathways and thereby enhancing the cytotoxic effects of chemotherapy on CSCs. 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 1014. doi:1538-7445.AM2012-1014
Queries and Minor Notes: Then and Now
Authors: Jay N. Cohn
Journal: JAMA (1984)

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
Neutrophil-generated free radicals: possible mechanisms of injury in adult respiratory distress syndrome.
Authors: J M McCord, B Gao, J Leff, S C Flores
Journal: Environmental Health Perspectives (1994)

The acute lung injury resulting from adult respiratory distress syndrome (ARDS) is thought to be largely mediated by activated neutrophils. Because activated neutrophils produce the superoxide radical, which is both bacterial and cytotoxic to host cells, this oxygen-derived free radical is likely responsible for at least part of the neutrophil-mediated lung injury. In a rat model of ARDS resulting from intratracheal instillation of interleukin-1, recombinant human manganous superoxide dismutase significantly decreased lung leak. One detrimental action of proteases released by adherent neutrophils may be the degradation of extracellular superoxide dismutase (ECSOD), which normally binds to the heparan sulfate on the surface the endothelium. We found that rabbit ECSOD incubated with either trypsin or activated neutrophils loses affinity for heparin. Furthermore, soluble ECSOD is elevated in the serum of patients with ARDS, consistent with this hypothesis.
Surrogacy to be reviewed in United Kingdom
Authors: J. Warden
Journal: BMJ (1997)

The government has announced an independent review of surrogacy law in the United Kingdom after controversy in several cases. In the most recent case the potential surrogate mother decided that she wished to keep the baby.

The review will cover the scope of surrogacy law; whether payments to surrogate mothers, including expenses, should continue to be allowed; and whether there is a …
Malpractice Insurance-Reply
Authors: Donald P. Wilcox
Journal: JAMA (1975)

<h3>In Reply.—</h3> In making his decision as to which person(s) and/or institutions(s) should be properly named as defendants in a professional liability suit, the one essential element that the plaintiff's attorney must properly evaluate is whether or not, for each possible defendant, negligence can be proved. The fact that a possible defendant has substantial assets, ie, insurance, will usually be persuasive in the decision regarding which possible defendants should be named in a suit when it is expected that the negligence of this defendant in this instance can be successfully demonstrated in court. Of course, if the court subsequently finds that this defendant was not negligent, his assets are not available to compensate the plaintiff for any damages he may allege.
Scene in Print: Is That All?
Authors: GEORGE A. ULETT
Journal: Annals of Internal Medicine (1973)

Comments and Corrections1 March 1973Scene in Print: Is That All?GEORGE A. ULETTGEORGE A. ULETTSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-78-3-463_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn the last few years, characterized as these have been by protest, demonstrations, and a demand for increased consumer participation, all governments have been placed under greater-than-usual pressures; and what has resulted is rich thesis material for students of social psychology.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 March 1973Volume 78, Issue 3Page: 463-463KeywordsSocial psychology ePublished: 1 December 2008 Issue Published: 1 March 1973 PDF downloadLoading ...
Differential Criticism of the Spinal Cord.
Authors: Stewart Leroy McCurdy
Journal: JAMA (1891)

<h3>To the Editor:</h3> —Nearly three-fourths of a century ago Longet, by very careful experimental research, concluded that sensory impressions were conducted solely by the posterior column of the spinal cord to the brain, and in his day this theory was generally accepted. Soon after Longet, or in 1823, Bellingeri demonstrated by experiments on living animals that sensory impressions were conducted to the brain through the gray matter of the cord exclusively. Flint, in his text-book, p. 678, makes the following inquiries: 1. Does or does not the white substance of the posterior column of the cord conduct sensory impressions to the brain? 2. Does the entire substance of the cord act as a conductor of sensibility? 3. Does both the gray matter of the cord and the white substance of the posterior column act as conductors, or does either one act to the exclusion of the other? "These questions," he
Tissue-specific analysis of chromatin state identifies temporal signatures of enhancer activity during embryonic development
Authors: Stefan Bonn, Robert P Zinzen, Charles Girardot, E Hilary Gustafson, Alexis Perez-Gonzalez, Nicolas Delhomme, Yad Ghavi-Helm, Bartek Wilczyński, Andrew Riddell, Eileen E M Furlong
Journal: Nature Genetics (2012)
Meta-Analysis: Chronic Disease Self-Management Programs for Older Adults
Authors: Joshua Chodosh, Sally C. Morton, Walter Mojica, Margaret Maglione, Marika J. Suttorp, Lara Hilton, Shannon Rhodes, Paul Shekelle
Journal: Annals of Internal Medicine (2005)

Although enthusiasm is growing for self-management programs for chronic conditions, there are conflicting data regarding their effectiveness and no agreement on their essential components.To assess the effectiveness and essential components of self-management programs for hypertension, osteoarthritis, and diabetes mellitus.The authors searched multiple sources dated through September 2004, including the Cochrane Library, MEDLINE, PsycINFO, and Nursing and Allied Health databases, and bibliographies of 87 previous reviews.Randomized trials that compared outcomes of self-management interventions with a control or with usual care for diabetes mellitus, osteoarthritis, or hypertension; outcomes included hemoglobin A1c level, fasting blood glucose level, weight, blood pressure, pain, or function.Two reviewers independently identified trials and extracted data regarding whether the intervention used tailored adjustments to meet individual patient needs, a group setting, feedback, and psychological services, and whether the intervention was provided by the patient's usual physician.Of 780 studies screened, 53 studies contributed data to the random-effects meta-analysis (26 diabetes studies, 14 osteoarthritis studies, and 13 hypertension studies). Self-management interventions led to a statistically and clinically significant pooled effect size of -0.36 (95% CI, -0.52 to -0.21) for hemoglobin A1c, equivalent to a reduction in hemoglobin A1c level of about 0.81%. Self-management interventions decreased systolic blood pressure by 5 mm Hg (effect size, -0.39 [CI, -0.51 to -0.28]) and decreased diastolic blood pressure by 4.3 mm Hg (effect size, -0.51 [CI, -0.73 to -0.30]). Pooled effects of self-management interventions were statistically significant but clinically trivial for pain and function outcomes for osteoarthritis. No consistent results supported any of the 5 characteristics examined as essential for program success.Studies had variable quality, and possible publication bias was evident.Self-management programs for diabetes mellitus and hypertension probably produce clinically important benefits. The elements of the programs most responsible for benefits cannot be determined from existing data, and this inhibits specification of optimally effective or cost-effective programs. Osteoarthritis self-management programs do not appear to have clinically beneficial effects on pain or function.
Iliopsoas bursitis in rheumatoid arthritis: an unusual cause of leg oedema.
Authors: M J Ford, A G Martynoga, G Nuki
Journal: BMJ (1981)

Conversion: SI to traditional units-Potassium: 1 mmol/l= 1 mEq/l.Glucose: 1 mmol/l 18 mg/100 ml.Bicarbonate: 1 mmol/l= 1 mEq/l.Hydrogen ion: 1 nmol/l=O l ng/lOOml.
Tapping the Ventricles
Authors: W. W. Keen
Journal: BMJ (1891)

Clinical trials contribute to the improvement of health through testing potentially efficacious interventions (e.g. vaccines, drugs, devices, and even behavioural strategies) among selected population segments to provide evidence to support health policy and practice. There are indisputable health benefits, not only to the communities directly involved in the trials but also to the wider population affected by the health problems in question. On the other hand, regardless of the results of the trials, it is assumed that there are immediate benefits disseminated to the whole population of reference resulting from training, resources, services quality, and improvement and local knowledge. Particularly for low-income countries, this assumption is often taken for granted, as the implementation of clinical trials is usually accompanied by infrastructure development, institutional capacity building, and improved standards of care. The actual direct benefit to health and health care delivery, its sustainability, and more importantly, the communities9 perceptions of those benefits are seldom measured, because clinical trials often miss the opportunity to evaluate communities9 acceptability of the potential intervention, and the extent to which their needs and priorities are met through the trials. Formative research, which must be conducted in advance and during trial implementation, is a valuable approach to address such questions and to recommend appropriate ways of conducting the trials so as to gain optimal synergies with communities9 expectations while balancing those with the intended improvement of health. The Manhiça Health research centre takes such approach when implementing complex interventions involving large segments of the population and health services catchment areas, such as entire districts and provinces. This talk focuses on lessons learnt from engaging the community in three different interventions, namely the Malaria Elimination Program in Magude District, the Community Level Interventions for Pre-eclampsia in Maputo and Gaza Provinces, and the Cause of Death Determination using Minimally Invasive Autopsies in Manhiça District, all in Southern Mozambique.
Managing antibiotic associated diarrhoea
Authors: F. Barbut
Journal: BMJ (2002)

<h3>Background</h3> There is increasing evidence to suggest many elite athletes fail to recognise and report symptoms of exercise-induced bronchoconstriction (EIB), supporting the contention that athletes should be screened routinely for EIB. <h3>Purpose</h3> To screen elite British athletes for EIB using eucapnic voluntary hyperpnoea (EVH). <h3>Methods</h3> 228 elite athletes provided written informed consent and completed an EVH challenge with maximal flow volume loops measured at baseline and 3, 5, 10 and 15 min following EVH. A fall of 10% in forced expiratory volume in 1 s (FEV<sub>1</sub>) from baseline was deemed positive. Two-way analysis of variance was conducted to compare FEV<sub>1</sub> at baseline and maximal change following EVH between EVH-positive and EVH-negative athletes who did and did not report a previous diagnosis of EIB. Significance was assumed if p≤0.05. <h3>Results</h3> Following the EVH challenge 78 athletes (34%) demonstrated EVH positive. 57 out of the 78 (73%) athletes who demonstrated EVH positive did not have a previous diagnosis of EIB. 30 athletes reported a previous diagnosis of asthma, nine (30%) of whom demonstrated EVH negative. There was no significant difference between the magnitude of the fall in FEV<sub>1</sub> between athletes who reported a previous diagnosis of EIB and demonstrated EVH positive, and those with no previous diagnosis of EIB who demonstrated EVH positive (mean±SD; −21.6±16.1% vs −17.1±9.7%; p=0.07). <h3>Conclusion</h3> The high proportion of previously undiagnosed athletes who demonstrated EVH positive suggests that elite athletes should be screened routinely for EIB using a suitable bronchoprovocation challenge.
Effects of duration of ventricular fibrillation and heart massage on haemodynamic responses after defibrillation in dogs
Authors: R. H GEUZE, J. D. VENTE
Journal: Cardiovascular Research (1983)

The purpose of this study was to investigate the effects of duration of ventricular fibrillation (VF), and of closed chest manual cardiac massage during VF on the recovery of the circulation. 24 open chest episodes and 50 closed chest episodes were studied. Longer duration of VF resulted in slower recovery. The critical recovery time was 60 to 90 s, beyond which no recovery occurred spontaneously. Heart massage improved recovery in nearly all cases. This indicates that the favourable effect of heart massage is not only confined to carotid flow to the brain but also that it has a favourable effect on the contractility of the heart, probably by the generation of coronary flow. Changes in coronary flow during spontaneous recovery were similar to those in reactive hyperaemia. The maximum mean coronary flow during recovery was 1.7 to 6 times the steady state values. When the duration of VF was longer than 60 s the recovery of the circulation was often worsened by a pronounced transient bradycardia, occasional ventricular tachycardia or frequent ventricular premature excitations.
Thrombolytic Therapy for Elderly Patients With Myocardial Infarction
Authors: Roberto Bernabei, Giuseppe Zuccalà, Pierugo Carbonin
Journal: JAMA (1997)

Both the article by Dr Krumholz and colleagues<sup>1</sup>and the Editorial by Drs Gurwitz and Goldberg<sup>2</sup>point out that thrombolytic therapy in older patients with myocardial infarction is not yet routinely used in medical practice. Thus, clinical decisions in this setting often are not evidence based; rather, the decision not to administer thrombolytic therapy is mainly driven by physicians' personal opinions, almost never clearly stated. Appropriate choices of treatment for older patients—and even better outcomes—will probably only be achieved when comprehensive geriatric assessment (CGA) becomes part of routine treatment of cardiac disorders. Indeed, patients with heart disease are those who mainly benefit from CGA.<sup>2</sup>In a recent editorial, Parmley has recommended that cardiologists practice geriatric assessment when dealing with "frail" elderly patients.<sup>3</sup> The findings by Krumholz et al highlight the necessity to update evaluation methods in geriatric cardiology. In this study,for example, an older patient's confusion was
Risk factors for patellar tendinopathy in volleyball players: a cross-sectional study
Authors: H van der Worp, M van Ark, J Zwerver, I van den Akker-Scheek
Journal: British Journal of Sports Medicine (2011)

Background Patellar tendinopathy (PT) has a multifactorial etiology, and many possible risk factors have been described in the literature. Findings are conflicting though, and most research is conducted on elite athletes. Objective Aim of the current study is to determine risk factors for PT in a large representative sample of volleyball players. Design Cross-sectional study using an online questionnaire. Setting Volleyball players of all playing levels. Participants All volleyball players between ages 18 and 35 years from the Dutch Volleyball Association were invited to complete the questionnaire (n=7750). 1561 volleyball players completed the questionnaire. Assessment of risk factors The following independent variables were collected: Gender, age, body mass index, waist-to-hip ratio, years playing volleyball, hours of training during the last week, number of games during the last month, average hours of other sports per week, training increase compared to last year, playing surface, playing level and playing position. Main outcome measurements Presence of symptomatic tendinopathy was the dependent variable. Results Being male (OR=2.1) and playing at the national level (OR=2.1) were risk factors for PT in volleyball players. Also players that play as outside hitter (OR=2.3) or middle blocker/hitter (OR=2.8) are at a greater risk for PT than those who play as setter. Conclusions Several potential risk factors for PT were identified. Volleyball players that play as outside hitter or middle block/hitter have the highest odds for PT. Therefore, changing playing position to libero/opposite hitter or setter may be an option in volleyball players with PT.
An Attempt at the Assessment of Myocardial Contractility from Phonocardiographically Measured Time Components of Ventricular Contraction in Patients with Prosthetic Aortic Valves
Authors: W. BECK, V. SCHRIRE
Journal: Circulation (1968)

The phonocardiographically recorded time interval between the first heart sound and the mid-ejection point is a rough guide to the time interval between the onset and the peak ventricular pressure in patients with the University of Cape Town aortic valve prosthesis. This time interval is insensitive to changes in stroke volume and aortic pressure produced by variations in ventricular filling and may be used to show changes in contractility in any one patient. In a group of 42 patients with 64 postoperative phonocardiograms, mid-ejection time varied between 140 and 250 msec. A strong negative correlation with heart rate, and a strong positive correlation with the width of the QRS complex were present without any significant correlation with heart size or with other estimates of left ventricular function. It is suggested that in the abnormal myocardium, ventricular asynchrony may seriously interfere with the velocity of the ventricular contraction invalidating the assessment of contractile element velocity from the velocity components of the ventricular pressure pulse.
AN EXPERIMENTAL STUDY OF MULTIPLE SCLEROSIS
Authors: JOSEPH COLLINS
Journal: JAMA (1923)

I. CLINICAL HISTORY AND GENERAL DISCUSSION  By Joseph Collins, M.D.  Hysteria and disseminated sclerosis are the nervous diseases of mystery. They are half sisters who reveal their relationship in the way they carry on. The greatest master of modern neurology courted them so assiduously that his name is indissolubly linked with both of them. He did not succeed in making them yield the secret of their being, and his successors have not succeeded. Now that syphilis is being forced into the category of curable diseases, and now that there is hope that we shall be able soon to shape and control by serum and antitoxin diseases caused by cocci and bacilli, hysteria and disseminated sclerosis are the two diseases of the nervous system on which the physician and bacteriologist may concentrate their exploratory urge.  An instructive lesson may be learned from the history of disseminated sclerosis in this