tbuckley/cabot-search huggingface dataset:
Abstract BS2-1: Collective invasion in breast cancer is led by specialized cancer cells with basal gene expression
Authors: Andrew J Ewald
Journal: Cancer Research (2015)

Abstract Metastasis is the major driver of mortality and morbidity from breast cancer. Unfortunately, there are very few therapies that are effective in the metastatic setting. The overall hypothesis guiding our work is that a deeper biological understanding of the cellular and molecular mechanisms driving metastatic progression would facilitate the development of novel therapeutic concepts. A major barrier to achieving this goal is that the essential cellular steps occur deep within the body over a period of months to years. To overcome this barrier, we developed a novel organoid invasion assay that enables us to prospectively identify the most invasive cells within primary breast tumors. We initially explanted organoids from advanced tumors derived from the MMTV-PyMT transgenic mouse model of luminal B breast cancer. Surprisingly, we discovered that the cells that lead invasion into the extracellular matrix express basal epithelial genes, such as keratin-14, p63, and P-cadherin, both in 3D culture and in vivo. We next demonstrated that the cells leading invasion in mouse models of Her2 overexpressing (MMTV-Neu) and basal breast cancer (C3(1)-Tag) also expressed basal epithelial markers. We then adapted our organoid invasion assay to study primary human breast tumors in real-time and found that keratin-14+ cells lead collective invasion across diverse molecular subtypes of breast cancer, both in 3D culture and in vivo. With these correlations firmly established, we returned to the MMTV-PyMT mouse model to dissect the mechanisms underlying collective invasion. Using a keratin-14 reporter line we revealed that the basal invasion program can be induced in luminal phenotype cancer cells and that these newly keratin-14+ cells can lead collective invasion. We then identified shRNA constructs to knockdown keratin-14 and demonstrated that it is required for collective invasion in 3D culture and in vivo. Our current work focuses on using next generation sequencing to identify targetable genes required for the invasive process and using in vivo lineage analysis to study the relationship between collective invasion and distant metastasis. Citation Format: Andrew J Ewald. Collective invasion in breast cancer is led by specialized cancer cells with basal gene expression [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr BS2-1.
My most unfortunate mistake: The heights of folly
Authors: J. C R Bowling
Journal: BMJ (2003)

My house jobs had finished, and I had just arrived in Huaraz, northern Peru, for a trek around Mount Huascaran with Andy, my fellow senior house officer and flatmate from medical school.

After 72 hours of acclimatisation at an altitude of 3500 m, we set off for the five day adventure. As dawn broke, we started to ascend, my only symptom being a mild headache. After four hours of climbing the near vertical mountain footpath, the headache had matured into a persistent thump with each heartbeat. Further water and painkillers weren't having much effect. My pace had slowed, much to my annoyance, and we were still some distance from the first pass at a height of 4900 m. My shortness of breath …
Abstract 3939: Delineation of the ATM-Snail pathway in the DNA damage response
Authors: Rebecca J. Boohaker, Joshua Fried, Xiaoli Cui, Bo Xu
Journal: Cancer Research (2014)

Abstract To cope with constant challenges toward the fidelity of genome by DNA damaging insults (both endogenous and exogenous), activation of the DNA damage response (DDR) is an essential step in preventing genomic instability. Studies of mammalian mechanisms have revealed that there are comprehensive, coordinated pathways that, when activated, serve to regulate the DDR. Recently, we have shown that hyperactive DDR mediated by the Ataxia-Telangiectasia Mutated (ATM) kinase is linked to activation of the Zinc finger protein SNAI1 (Snail). Activated Snail in metastasis is well-characterized by its role as transcriptional repressor of E-cadherin thereby inducing an epithelial-to-mesenchymal transition (EMT). Here we report that, in response to DNA damage, activation of the ATM-Snail pathway, mediated by Snail Serine 100 phosphorylation, also contributes to the regulation of the cellular sensitivity to ionizing radiation. Expression of a hyperactive Snail led to radioresistance. More interestingly, the Serine 100 to Glutamic Acid mutant variant of Snail displayed an enhanced invasion index after low dose radiation, independent of survival. Functional genomics and proteomics studies revealed downstream targets and interacting partners of Snail in the DDR. Together, we highlight the functional significance of the ATM-Snail pathway in the DDR. Citation Format: Rebecca J. Boohaker, Joshua Fried, Xiaoli Cui, Bo Xu. Delineation of the ATM-Snail pathway in the DNA damage response. [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 3939. doi:10.1158/1538-7445.AM2014-3939
Abstract 18006: Safety of Novel Oral Anticoagulants Compared with Uninterrupted Warfarin for Catheter Ablation of Atrial Fibrillation
Authors: John Lindsley, Heather Armbruster, Michael Moranville, Mohammadali Habibi, Irfan Khurram, David D Spragg, Ronald D Berger, Hugh Calkins, Joseph E Marine
Journal: Circulation (2014)

OBJECTIVE: The purpose of this study is to evaluate the frequency of hemorrhagic and thrombotic events as well as peri-procedural management strategies associated with the use of novel oral anticoagulants (NOACs: dabigatran, rivaroxaban, and apixaban) compared to warfarin as anticoagulation therapy for AF ablation. METHODS: This was a retrospective cohort study from a prospective AF ablation registry maintained at a large, academic medical center. All patients undergoing AF ablation between 1/31/2012 and 12/31/13 with pre- and post-procedure anticoagulation were included. RESULTS: The cohort included 374 patients (mean age 62 +/- 10 years, 74% male). Warfarin was used for 173 cases, dabigatran for 123 cases, rivaroxaban for 61 cases, and apixaban for 17 cases. The overall hemorrhagic/thrombotic complication rate was 14.2 % (major hemorrhage 2.7%, minor hemorrhage 11%, thrombotic stroke 0.5%). There was no significant difference in the frequency of major hemorrhage or thrombotic events associated with the ...
Treatment of Cognitive Deficits in Genetic Disorders
Authors: Thijs van der Vaart, Iris E. Overwater, Rianne Oostenbrink, Henriëtte A. Moll, Ype Elgersma
Journal: JAMA Neurology (2015)

Knowing the underlying etiology of intellectual disability in genetic disorders holds great promise for developing targeted treatments. Although successful preclinical studies and many positive clinical studies have been reported, it is unclear how many purported therapies have become established treatments. The quality of the clinical trials may be an important determinant for achieving clinical impact.To evaluate clinical impact, strengths, and weaknesses of clinical trials of diet or drug treatments to improve cognitive function in patients with a genetic disorder.MEDLINE, EMBASE, PsycINFO, and Cochrane databases were searched from inception date to January 26, 2014, for clinical trials with cognitive outcomes in patients with genetic disorders. Outcome measures of randomized clinical trials (RCTs) were compared between trial registries and reports, and trials were evaluated for the quality of design using the Jadad score and Consolidated Standards of Reporting Trials (CONSORT) criteria.We identified 169 trial reports of 80 treatments for 32 genetic disorders. Seventy-five trials (44.4%) reported potential efficacy, of which only 2 therapies are now established treatments, namely, dietary restriction for phenylketonuria and miglustat for Niemann-Pick disease type C. The median sample size for RCTs was 25 (range, 2-537). Only 30 of 107 RCTs (28.0%) had acceptable Jadad scores exceeding 3. Reporting of key CONSORT items was poor. Reported outcome measures matched preregistered outcome measures in trial registries in only 5 of 107 RCTs (4.7%).The number of trials in the field of cognitive genetic disorders is rapidly growing, but clinical impact has been limited because few drugs have become established treatments and the benefit of most drugs remains unclear. Most trials have small sample sizes and low quality of design. Predefinition of outcome measures, improved trial reporting and design, and international collaboration to increase recruitment are needed to unequivocally determine efficacy of drugs identified in preclinical research.
A memorable patient: The inflating lady
Authors: S. Almond
Journal: BMJ (1998)

Some four years ago, as a novice medical registrar, I was awoken at 3 00 am by a panic stricken senior house officer who told me that an elderly woman had been admitted to the accident and emergency department in anaphylactic shock, presumably from a dressing on a trivial back injury. The patient had had adrenaline, steroids, antihistamine, and nebulisers but remained ill. Of particular worry was her worsening facial and neck oedema, which I was told was endangering her airway. …
Intact Microtubules Are Required for Ad-Vector Induction of Chemokine Genes in Epithelial Cells
Authors: Daniel A. Muruve, Lindsay R. White
Journal: Molecular Therapy (2004)

Upon entry in epithelial cells, adenovirus vectors (Ad-vectors) activate a cascade of signaling pathways including p38 MAPK (p38) and extracellular-signal regulated kinase (ERK). These signaling events occur within minutes and are triggered directly by the viral capsid. The activation of signaling by Ad-vectors leads to the expression of chemokine inflammatory genes such as IP-10. Shortly following internalization, Ad-vectors interact with microtubules that are required to mediate viral translocation to the nucleus. To better understand the role of microtubules in Ad vector induced signaling and chemokine gene expression, epithelial cells (REC) were treated with the microtubule depolymerizing reagent nocodazole (20mM). Nocodazole substantially reduced transduction of REC cells by a first generation Ad-vector, Adβgal, as determined by β-galactosidase expression 24 hours post-transduction. Vector internalization into REC however was unaffected as measured by flow cytometry confirming that microtubules were required to mediate nuclear translocation of Ad-vectors. To determine the effect of microtubule depolymerization on the induction of chemokine mRNA expression, RANTES and IP-10 gene expression was determined at 6 hours following transduction with Adβgal. Compared to untreated cells, nocodazole blocked the Adβgal induction of RANTES and IP-10 expression. Phosphorylated ERK or p38 was increased by nocodazole in the absence of Ad-vector transduction, a response that was not changed following the addition of Adβgal. Although indirect, this finding suggests that p38 and ERK signaling is linked to microtubules and is required but not sufficient to induce the expression of IP-10 and RANTES. In contrast, experiments with the microtubule-stabilizing agent, paclitaxel, did not affect Adβgal transduction of REC cells. Furthermore, Adβgal induction of p38/ERK phosphorylation and IP-10/RANTES gene expression was unchanged following paclitaxel suggesting that microtubule treadmilling or dynamic instability was not required for Ad-vector induction of host immune responses. These preliminary data suggest that intact microtubules are required for the Ad-vector induction of host inflammatory genes in epithelial cells. Understanding the biology of Ad-vector induced intracellular signaling will contribute significantly to the development of novel recombinant vectors for gene therapy.
THE TREATMENT OF PNEUMONIA
Authors: Rufus Cole
Journal: Annals of Internal Medicine (1936)

Article1 July 1936THE TREATMENT OF PNEUMONIARUFUS COLE, M.D.RUFUS COLE, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-10-1-1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThirty years ago Dr. Osler wrote, "Pneumonia is a self-limited disease, which can neither be aborted nor cut short by any means at our command." When I went to the Rockefeller Institute shortly afterwards, I said to myself, "Here, at least, is a wide open field. This is the most serious acute infectious disease with which physicians have to deal. Is it possible that nothing can be done to decrease the frightful mortality due to this malady? At any rate, we can attempt to obey St. Paul's injunction, 'Prove all things, hold fast that which is good.'" From that time... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, N. Y.*Read at the Detroit meeting of the American College of Physicians, March 5, 1936.From the Hospital of the Rockefeller Institute for Medical Research, New York. Nextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byLow-Dose Radiotherapy for Late-Stage COVID-19 Pneumonia?The Nature and Treatment of Pneumococcal PneumoniaDie PneumonienSerum treatment of pneumonia in childhoodMedical Diathermy in PneumoniaThe New York State Program for the Control of Pneumococcus Pneumonia 1 July 1936Volume 10, Issue 1Page: 1-12KeywordsInfectious diseasesMortalityPneumonia ePublished: 1 December 2008 Issue Published: 1 July 1936 PDF downloadLoading ...
Cooperation between COA6 and SCO2 in COX2 Maturation during Cytochrome c Oxidase Assembly Links Two Mitochondrial Cardiomyopathies
Authors: David Pacheu-Grau, Bettina Bareth, Jan Dudek, Lisa Juris, F.-Nora Vögtle, Mirjam Wissel, Scot C. Leary, Sven Dennerlein, Peter Rehling, Markus Deckers
Journal: Cell Metabolism (2015)
Virtual Colonoscopy—Reply
Authors: Perry J. Pickhardt, Joseph Ferrucci, Steve Halligan, Stuart Taylor, David Burling, Ronald M. Summers, Ingmar Bitter, Nicholas Petrick, Peter B. Cotton, Douglas Rex, David J. Vining, Benoit Pineau
Journal: JAMA (2004)

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More Evidence That the Use of Venous Thromboembolism Rates as Hospital Quality Measures May Be Off the Mark
Authors: Christian de Virgilio, Jerry J. Kim
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Abstract 19557: Novel Stress Signaling JNK Regulates Pro-arrhythmic Molecular CaMKIIδ Activity and Expression in Aged Human Atrium
Authors: Xiaomin Wu, Weiwei Zhao, Elena Corrillo, Weizhe Chen, Jiajie Yan, Donald M Bers, Seth L Robia, Xun Ai
Journal: Circulation (2014)

The c-Jun N terminal kinase (JNK) is an important member of the MAP kinases family, activated in response to stress and implicated in the development of cardiovascular diseases (CVDs). We have previously shown that JNK plays a pivotal role in development of atrial arrhythmia in aged hearts. However, the underlying mechanism remains incompletely understood. Accumulating evidence suggests that CaMKIIδ is another critical kinase in the development of arrhythmias and CVDs. In human atrial tissue, we discovered that enhanced phosphorylation of JNK (JNK-P) was associated with an increased ratio of phosphorylation of CaMKIIδ Thr286 (CaMKII-P) to total CaMKIIδ (immunoblotting assay) with increasing age (19-82yrs; n=12), while the level of CaMKIIδ mRNA expression (qPCR) was also up-regulated. To further characterize the JNK-CaMKIIδ relationship, we used a unique HL1 atrial myocyte line. CaMKIIδ activation status was assessed using a specific CaMKIIδ-P antibody (immunoblotting assay) and a CaMKIIδ biosensor camui (FRET imaging assay). We found that atrial myocytes treated with JNK activator anisomysin (24hrs) exhibited significantly increased CaMKIIδ-P (56% vs sham controls; p&lt;0.01; n=4,4) that was associated with markedly elevated JNK-P. In JNK activated live HL-1 myocytes, the activation of CaMKII (ratio of CFP to YFP fluorescence (FCFP/FYFP)) was increased by 35% (vs sham controls; p&lt;0.05; n=4,4 monolayers). This suggests that JNK activation caused enhanced CaMKII activation in atrial myocytes. Overexpression of inactivated JNK2 (dominant negative; JNK2dn) attenuated JNK-induced CaMKIIδ activation (both CaMKII-P and camui FRET assays). Moreover, we found that the amount of CaMKIIδ protein and mRNA expressions in JNK-activated myocytes was up-regulated by 103% and 75%, respectively (p&lt;0.05; n=3,3). Finally, overexpressed JNK2dn markedly suppressed JNK-induced CaMKIIδ up-regulation at both protein and mRNA levels (n=4,4). In conclusion, we report here for the first time that the novel stress signaling JNK regulates not only activity but also expression of the pro-arrhythmic signaling molecular CaMKIIδ in aged atrium. Modulation of JNK signaling could be a novel therapeutic approach to prevent and treat arrhythmias and CVDs in the elderly.
Therapy of Transplanted Lymphomas 2
Authors: Donna L. Vredevoe, Esther F. Hays
Journal: JNCI Journal of the National Cancer Institute (1976)

Allogeneic cells or cell products containing murine leukemia virus were effective in curtailing growth of a transplanted CBA lymphoma, which was originally induced by Gross virus and then maintained by syngeneic cell passage. All allogeneic cells or products effective in therapy of this lymphoma expressed virus as tested by the XC cell in vitro infectivity assay. Some of the materials also expressed virus as assayed by oncogenicity in vivo. A therapeutic effect was not demonstrated with allogeneic cells or cell products laking these virus activities. Syngeneic lymphoma cells were ineffective. Protected animals did not develop lymphoma when rechallenged several months later. Mechanisms for this therapy with virus were proposed.
Abstract 19949: Attainment of Lipid Levels in Patients at High Cardiovascular Risk: Results from a U.S. Managed Care Population Study
Authors: Dylan Steen, Irfan Khan, Laura K Becker, Katherine M Gorcyca, JoAnne Foody
Journal: Circulation (2014)

Background: Current, generalizable data on low density lipoprotein cholesterol (LDL-C) and non-high density lipoprotein cholesterol (non-HDL-C) as well as triglyceride (TG) levels are necessary to guide health policy decisions, guideline recommendations and treatment innovation. While LDL-C and non-HDL-C are established targets, TG elevations of 150-500 mg/dL and &gt;500 mg/dL can contribute to CV disease and pancreatitis risk, respectively. We evaluated attainment of these lipid measures in a large, managed care population in the US. Methods: The analysis included patients from the Optum Research Database meeting the following criteria: a valid lipid profile measurement in 2012 (i.e. “index date”); ≥20 years of age; continuous enrollment for≥ 2 years; and ≥1 high risk CV condition. Each patient was categorized into a mutually-exclusive category in the following hierarchy: acute coronary syndrome (ACS) within 12 months; stable coronary heart disease (CHD); ischemic stroke; peripheral arterial disease (PAD); and diabetes mellitus. Patients covered by a prescription on the index date or within 30 days were considered to be on treatment. Results: In total, 217,516 patients met the inclusion criteria. Median (Q1 to Q3) age was 61 (53 to 70) years, 51.6% were male, 10.7% were treated with intensive statins, 34.8% with less-intensive statins and 5.8% with nonstatin lipid-modifying therapy. Median LDL-C was 92 (72 to 116) mg/dL, non-HDL-C was 118 (96 to 145) mg/dL and TG was 120 (85 to 169) mg/dL in the overall cohort. The frequency of lipid level achievement is displayed by hierarchical disease state (TABLE). Conclusions: This study is the largest analysis of LDL-C, non-HDL-C and TG levels in a contemporary US managed care high risk population. Statins were underutilized, reflected by inadequate achievement of optimal LDL-C and non-HDL-C levels. While very high TG levels were infrequent, more optimal TG level were only achieved in about two-thirds of the population.
Boy on the Rocks
Authors: M. Therese Southgate
Journal: JAMA (1999)

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