tbuckley/cabot-search huggingface dataset:
Abstract LB-55: UTX epigenetically regulates epithelial-mesenchymal transition-associated breast cancer stem cell properties independently of EZH2
Authors: Hee-Joo Choi, Ji-Hye Park, Mi-Kyung Park, Chang-Hoon Lee, Jeong-Yeon Lee, Gu Kong
Journal: Cancer Research (2014)

Abstract UTX is a histone H3 lysine 27 (H3K27) demethylase that can antagonize a histone methyltransferase EZH2. Although H3K27 trimethylation by EZH2 has been involved in cancer-related biological processes including tumorigenesis, invasion, and stemness, the role of UTX in cancer progression has not been identified yet. In this study, we demonstrated an EZH2-independent tumor suppressive function of UTX in breast cancer. We found that loss of UTX enhanced self-renewal and tumorigenicity of breast cancer stem cells (CSCs) and also promoted CSC-associated epithelial-mesenchymal transition (EMT) through upregulating EMT-transcription factors (EMT-TFs), Snail, ZEB1 and ZEB2. Moreover, UTX positively regulated E-cadherin, a key marker of EMT, via these EMT-TFs. Notably, we identified that UTX facilitated epigenetic silencing of EMT-TFs by cooperating with c-Myc and various epigenetic modulators independently of EZH2. In the promoter regions of EMT-TFs, the levels of histone H3K4 methylation and H3 acetylation were inhibited by UTX. We also found that UTX formed a transcriptional repressive complex with LSD1, HDAC1, and DNMT1 for recruiting them to the promoters of EMT-TFs, while loss of UTX led to recruitment of c-Myc and p300 transcriptional active complex to these promoters. These effects were dependent on c-Myc, as UTX knockdown-induced epigenetic alterations of EMT-TFs and breast cancer stemness were reversed by siRNA-mediated c-Myc repression. Taken together, these data indicated that UTX negatively regulates EMT-induced breast CSCs by epigenetically repressing EMT-TFs independently of H3K27 methylation, suggesting a novel tumor suppressive role of UTX in breast cancer. Citation Format: Hee-Joo Choi, Ji-Hye Park, Mi-Kyung Park, Chang-Hoon Lee, Jeong-Yeon Lee, Gu Kong. UTX epigenetically regulates epithelial-mesenchymal transition-associated breast cancer stem cell properties independently of EZH2. [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 LB-55. doi:10.1158/1538-7445.AM2014-LB-55
Metabolism of estradiol in liver cell culture. Differential responses of C-2 and C-16 oxidations to drugs and other chemicals that induce selective species of cytochrome P-450.
Authors: J Schneider, S Sassa, A Kappas
Journal: Journal of Clinical Investigation (1983)

The oxidative metabolism of estradiol (the natural estrogen 2,3,5(10)-estratriene-3,17 beta-diol) at positions C-2 and C-16 was examined in primary cultures of chick embryo liver cells using estradiol which was labeled with 3H specifically at either the C-2 or C-16 position as the substrate. Oxidation of estradiol by the cultured liver cells was assessed by the release of 3H which accumulated as 3H2O in the culture medium; both C-2 and C-16 oxidative reactions were detectable in the liver cell cultures by this technique. When incubated with a concentration of estradiol substrate close to the Michaelis constant (Km), approximately 45.8 pmol [2-3H]estradiol and 5.0 pmol [16-3H]estradiol/mg protein per minute underwent oxidative metabolism in untreated cells. Total amounts of oxidized product formation after 2 h of incubation were 28 and 5 pmol/mg protein for C-2 and C-16 oxidation, respectively. Treatment of cultures with phenobarbital or 2-propyl-2-isopropylacetamide significantly increased oxidation at C-16 (1.9-fold and 2.6-fold greater than control values, respectively), whereas no significant change in C-16 oxidation was observed after treatment of the cultures with 3-methylcholanthrene, benzo[a]pyrene, or benz[a]anthracene. The latter chemicals, however, were found to increase the extent of oxidation at C-2 significantly (i.e., 1.5-2.2-fold increases over control values). The increase in C-2 oxidation after treatment of cultures with phenobarbital or 2-propyl-2-isopropylacetamide was significantly less than that observed for oxidation at C-16. The apparent Km values for these oxidations in control cultures were 23.5 and 30.3 microM for C-2 and C-16 oxidation, respectively; corresponding maximum velocity (Vmax) values were 119 and 11.7 pmol/mg protein per minute, respectively. These data indicate that the C-2 and C-16 oxidations of estradiol take place in cultured avian hepatocytes and that the extent of metabolism at these positions on the hormone molecule can be altered by chemicals, such as drugs and polycyclic aromatic hydrocarbons, which induce distinctive species of cytochrome P-450 in the liver.
Accelerated Cellular Uptake and Metabolism of L-Thyroxine during Acute Salmonella typhimurium Sepsis
Authors: Frederick R. DeRubertis, Kenneth A. Woeber
Journal: Journal of Clinical Investigation (1973)

The effects of acute Salmonella typhimurium sepsis on the kinetics of peripheral L-thyroxine (T(4)) distribution and metabolism and on serum total and free T(4) concentrations were studied in rhesus monkeys inoculated i.v. with either heat-killed or viable organisms. The rate of disappearance of labeled T(4) from serum was increased within 8 h after inoculation of monkeys with either heat-killed or viable Salmonella. The effects of the heat-killed organisms were transient and no longer evident by 16 h postinoculation. The monkeys inoculated with the viable Salmonella experienced a 2-3 day febrile, septic illness that was accompanied by an increase in the absolute rate of T(4) disposal. In the infected monkeys, serum total T(4) and endogenously labeled protein-bound iodine concentrations fell significantly during the period of acute sepsis and then rose during convalescence to values that exceeded the preinoculation values, suggesting that thyroidal secretion of hormone had increased in response to a primary depletion of the peripheral hormonal pool. Total cellular and hepatic uptakes of T(4) were enhanced by 4 h after inoculation of monkeys with either heat-killed or viable Salmonella, but the increase in total cellular uptake persisted for 24 h only in the monkeys inoculated with the viable organisms. These alterations in T(4) kinetics could neither be correlated with changes in the binding of T(4) in plasma nor attributed to an increase in vascular permeability. Moreover, they could not be ascribed to an in vitro product of bacterial growth, suggesting that the presence of the organisms themselves was required. An acceleration of T(4) disappearance was also observed during Escherichia coli and Diplococcus pucumoniae bacteremias. Our findings are consistent with a primary increase in the cellular uptake and metabolism of T(4) during bacterial sepsis, possibly related to phagocytic cell function in the host.
Foxp-Mediated Suppression of N-Cadherin Regulates Neuroepithelial Character and Progenitor Maintenance in the CNS
Authors: David L. Rousso, Caroline Alayne Pearson, Zachary B. Gaber, Amaya Miquelajauregui, Shanru Li, Carlos Portera-Cailliau, Edward E. Morrisey, Bennett G. Novitch
Journal: Neuron (2012)
Book: Virus: The Co-Discoverer of HIV Tracks Its Rampage and Charts the Future
Authors: J. Collazos
Journal: BMJ (2000)

Luc Montagnier, Stephen Sartarelli (translator) W W Norton, £18.95, pp 224 ISBN 0 393 03923 4 Rating: ![Graphic][1]</img> ![Graphic][2]</img> HIV has generated a huge amount of literature in the relatively short period of time since AIDS was first described. Investigators quickly discovered the aetiological agent of this new and deadly disease, established its main genotypic determinants, and found an effective treatment—an amazing record in the field of virology. … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif
Diffuse Bone Marrow Uptake on Whole-Body F-18 Fluorodeoxyglucose Positron Emission Tomography in a Patient Taking Recombinant Erythropoietin
Authors: Todd M. Blodgett, Jennifer T. Ames, Frank S. Torok, Barry M. McCook, Carolyn C. Meltzer
Journal: Clinical Nuclear Medicine (2004)

F-18 fluorodeoxyglucose (FDG)–positron emission tomography (PET) is used extensively in oncology to diagnose, stage, and restage patients with various malignancies. Many patients treated for malignancies develop neutropenia secondary to marrow suppressive chemotherapy and are subsequently treated with synthetic hematopoietic growth factors (HGF), both granulocyte–macrophage colony-stimulating factor (GM-CSF) and granulocyte–colony-stimulating factor (G-CSF). Patients taking HGF can present a diagnostic challenge for those interpreting PET because they can demonstrate diffuse marrow uptake on FDG-PET scans, mimicking diffuse bone marrow metastases. It has not been reported whether bone marrow uptake is affected on PET scans in patients taking erythropoietin, the erythroid-specific cell-line stimulator. We report a case of extensive diffuse bone marrow uptake in a 77-year-old man with a history of colon cancer who began taking erythropoietin 3 weeks before his PET scan. This case demonstrates the need to consider erythropoietin in the differential diagnosis of possible etiologies causing diffuse bone marrow uptake on PET scans.
The future of microarray technology: networking the genome search
Authors: C. D'Ambrosio, L. Gatta, S. Bonini
Journal: Allergy (2005)

In recent years microarray technology has been increasingly used in both basic and clinical research, providing substantial information for a better understanding of genome‐environment interactions responsible for diseases, as well as for their diagnosis and treatment. However, in genomic research using microarray technology there are several unresolved issues, including scientific, ethical and legal issues. Networks of excellence like GA 2 LEN may represent the best approach for teaching, cost reduction, data repositories, and functional studies implementation.
TODAY — A Stark Glimpse of Tomorrow
Authors: David B. Allen
Journal: New England Journal of Medicine (2012)

Caloric intake that exceeds energy expended and its consequences, particularly development of type 2 diabetes mellitus, is emblematic of a climate change for modern medicine — a phenomenon so complex, embedded in culture and economics, and intertwined with conflicts between individual freedom and societal health that solutions are difficult to envision. Chronic caloric surplus (rather than obesity itself) is a central cause of epidemic type 2 diabetes,1 but differences in response to energy excess,24 disproportionately present among disadvantaged youth, increase susceptibility to type 2 diabetes in early life. Indeed, the percentage of type 2 diabetes in cases of new-onset . . .
Diagnosing cancer of the pancreas.
Authors: J N Thompson
Journal: BMJ (1990)

Single molecule imaging in live cells enables the study of protein interactions and dynamics as they participate in signaling processes. When combined with fluorophores that stochastically transition between fluorescent and reversible dark states, as in super-resolution localization imaging, labeled molecules can be visualized in single cells over time. This improvement in sampling enables the study of extended cellular responses at the resolution of single molecule localization. This chapter provides optimized experimental and analytical methods used to quantify protein interactions and dynamics within the membranes of adhered live cells. Importantly, the use of pair-correlation functions resolved in both space and time allows researchers to probe interactions between proteins on biologically relevant distance and time-scales, even though fluorescence localization methods typically require long times to assemble well-sampled reconstructed images. We describe an application of this approach to measure protein interactions in B cell receptor signaling and include sample analysis code for post-processing of imaging data. These methods are quantitative, sensitive, and broadly applicable to a range of signaling systems.
IMPROVED SURVIVAL IN PATIENTS WITH DIASTOLIC HEART FAILURE DISCHARGED ON BETA-BLOCKER AND ACE INHIBITORS
Authors: Kevin Shah, Niraj Parekh, Paul Clopton, Inderjit Anand, Robert Christenson, Lori Daniels, Salvatore Di Somma, Geros Filippatos, James McCord, Christian Mueller, Sean-Xavier Neath, Richard Nowak, W. Frank Peacock, Piotr Ponikowski, Stefan Anker, Alan Maisel
Journal: Journal of the American College of Cardiology (2013)
Lack of involvement of the Fas system in ankylosing spondylitis
Authors: D WENDLING
Journal: Annals of the Rheumatic Diseases (2000)

Apoptosis or programmed cell death is one of the regulation mechanisms of cell homeostasis.

Fas is a transmembrane receptor protein which transmits a cell death signal when cross linked with an antibody or with its physiological ligand—Fas ligand (Fas L).1 Fas and Fas L have a pivotal role in regulating lymphocyte apoptosis and maintaining lymphocyte homeostasis.

Soluble forms of Fas and Fas L may be detectable and measured in the serum,2 and may reflect the activation of this pathway. Moreover, soluble forms of Fas regulate Fas/Fas L mediated apoptosis.3 Raised levels of soluble Fas (sFas) have been shown in various chronic inflammatory rheumatic diseases, systemic lupus erythematosus, Sjogren's syndrome,1 4 5 and in the synovial fluid of rheumatoid arthritis.6 These diseases are autoimmune diseases …
Effect of Follow-Up of Women With Gestational Diabetes on the Ratio of IDDM to NIDDM in Pregnancy
Authors: Norman A Beischer, Peter Wein, Mary T Sheedy, Richard M Dargaville
Journal: Diabetes Care (1996)

OBJECTIVE We wished to test the hypothesis that the diagnosis of diabetes in women with previous gestational diabetes in our follow-up program had altered the ratio of IDDM to NIDDM in our pregnant population. RESEARCH DESIGN AND METHODS We identified all pregnancies managed at the Mercy Hospital for Women in Melbourne, Australia, from 1971 to 1994 that were complicated by prepregnancy diabetes. In these 374 pregnancies, we identified those women who had previously been diagnosed with gestational diabetes mellitus (GDM). The changing prevalences over time of prepregnancy IDDM and NIDDM, as well as the contribution to both of these conditions made by women who had previously had GDM, were calculated. RESULTS Over the period of the study, there was an increase in the prevalence of IDDM from 0.15 to 0.44% (χ2 for trend, P &amp;lt; 0.00001) and NIDDM from 0.03 to 0.11% (χ2 for trend, P = 0.0001). The proportion of all women with diabetes with NIDDM did not change significantly (16.7–20%). There was a progressive increase in the proportion of women with NIDDM who had had GDM (from 8.3 to 39.1%), but the trend was not statistically significant (P = 0.059). Women with NIDDM were more likely (20 of 64, 31.3%) to have had gestational diabetes in the past than women with IDDM (12 of 310, 3.9%, odds ratio 11.3, 95% CI 5.16–24.7, P &amp;lt; 0.0001). CONCLUSIONS Despite finding relatively young women to have NIDDM, our GDM follow-up clinic has not yet altered significantly the ratio of IDDM to NIDDM in pregnancy.
Determinants of ventricular tachycardia in patients with ventricular aneurysms: results of intraoperative epicardial and endocardial mapping.
Authors: I Wiener, B Mindich, R Pitchon
Journal: Circulation (1982)

We performed epicardial and endocardial mapping in 11 patients with ventricular aneurysms; six had chronic, recurrent ventricular tachycardia and five had no ventricular arrhythmias more severe than isolated ventricular premature complexes. Forty to 66 epicardial and 16-40 endocardial points were recorded during stable sinus rhythm in each patient. Local electrograms were evaluated as to timing and presence of fragmentation (duration greater than 50 msec, amplitude less than 1 mV, absence of discrete intrinsicoid deflection). Activation of the epicardial surface of the aneurysm was abnormal in all patients, and extended beyond completion of the QRS in three patients in the arrhythmia group and two in the nonarrhythmia group (NS). Activation of the epicardial border zone was normal in all patients. Electrograms from the endocardial surface of the aneurysm were abnormally fragmented in all patients and the mean duration of activation was not different between patients with and without arrhythmias (85.5 +/- 14.1 vs 96.2 +/- 13.8 msec, NS). However, in patients with ventricular tachycardia, electrograms from 33-58.3% (mean 45.5 +/- 8.8%) of the endocardial border zone showed fragmentation, compared with 0-16.7% (mean 4.9 +/- 7.4%) of the endocardial border zone in patients without arrhythmias (p less than 0.05). Fragmentation was always along the septal border of the aneurysm. The mean duration of the most prolonged endocardial border zone electrogram was 97.5 +/- 17.0 msec in ventricular tachycardia patients and 67.0 +/- 27.1 msec in patients without arrhythmia (p less than 0.05). Five of six ventricular tachycardia patients had electrical activity in the endocardial border zone extending beyond the end of the QRS, compared with one of five patients without ventricular tachycardia (p less than 0.05). We conclude that fragmented electrical activity is present in all patients with ventricular aneurysms, but the extent and severity of fragmentation in the endocardial border zone is greatest in patients with recurrent ventricular tachycardia.
Immunology in Medicine: A Comprehensive Guide to Clinical Immunology
Authors: Roberto Kretschmer
Journal: JAMA (1984)

England has produced several firstrate textbooks of immunology, and some have even reached the status of classics. Most noteworthy, however, is that the different groups writing these texts have successfully avoided overlapping their respective, welldefined audiences. As stated by the editors, this book is specifically aimed at a frequently overlooked audience: the physician active in other fields, too busy to stay informed in areas, such as immunology, that infiltrate virtually all aspects of modern medicine in a most pervasive fashion. It is a common experience that after a stimulating conference on immunology delivered to such an audience, somebody invariably comes up with the legitimate question: "Where can I read about all this?" The answer is not easy: a book too simple will certainly alienate the solicitant; a book too specialized (there are many of these), conversely, will probably not be read beyond the initial pages. Holborow and Reeves' book seems
Differentiation of <i>Malassezia</i> species: selectivity of Cremophor EL, castor oil and ricinoleic acid for <i>M. furfur</i>
Authors: P. MAYSER, P. HAZE, C. PAPAVASSILIS, M. PICKEL, K. GRUENDER, E. GUÉHO
Journal: British Journal of Dermatology (1997)

In recent years, the genus Malassezia has been reclassified based on molecular data. In addition to M. furfur, M. pachydermatis and M. sympodialis, four new species, M. globosa, M. obtusa, M. restricta and M. slooffiiae, have been described. However, apart from their lipid dependence, little is known about the metabolism and nutritional requirements of all the seven species. Further to recent studies, 10 hydrophilic emulsifiers (HLB > 10) were examined in an agar diffusion test to determine their growth-promoting effect on reference strains of the different Malassezia species. Polyethylene glycol (PEG) 7 glyceryl monoalcanoate (Cetiol HE). PEG-glyceryl stearate (Tagat S2) and macrogol-50 stearate (Myrj 53) were metabolized by all strains, while PEG-35 castor oil (Cremophor EL) was metabolized only by M. furfur. The latter observation is due to a different metabolism of castor oil and its main component, ricinoleic acid (12-hydroxy oleic acid), which may also give an insight into the pathogenesis of diseases that are associated with Malassezia spp. As hydroxy fatty acids are important in maintaining the epidermal structure and function, their metabolism specifically by M. furfur might clarify some clinical aspects of pityriasis versicolor. Apart from this speculation, use of Cremophor EL, with splitting of esculin as an additional key character, improves the distinction of the species M. furfur, M. slooffiae and M. sympodialis.
World Trade Center Cough — A Lingering Legacy and a Cautionary Tale
Authors: Paul D Scanlon
Journal: New England Journal of Medicine (2002)

One year has passed since the terrorist attacks in New York and at the Pentagon. As we struggle to address important issues related to the health consequences of warfare and terrorism, a simple question has arisen: Did working on the rescue and recovery operation at the World Trade Center have an effect on health? In this issue of the Journal, Prezant and colleagues report on their findings among New York City firefighters exposed to the early environmental conditions during and after the collapse of the World Trade Center on September 11, 2001.1 Prezant et al. recognized in the days after . . .
Short-term effects of expiration under positive pressure in patients with acute exacerbation of chronic obstructive pulmonary disease and mild acidosis requiring non-invasive positive pressure ventilation
Authors: Andrea Bellone, Liliana Spagnolatti, Monica Massobrio, Elena Bellei, Rossana Vinciguerra, Andrea Barbieri, Emilio Iori, Stefano Bendinelli, Stefano Nava
Journal: Intensive Care Medicine (2002)
Gym users and abuse of prescription drugs
Authors: J. S Baker
Journal: Journal of the Royal Society of Medicine (2006)

Better research for better healthcareThe ill-fated TGN1412 phase I study and Prince Charles versus the medical establishment over complementary therapies recently pushed evidence-based medicine and clinical trials into prominence.For a society with poor vocabulary about probability, risk and uncertainty, and which increasingly blurs boundaries between well and ill, moving the debates forward, and in unity, will be tough.Prince Charles called for orthodox medicine to learn from alternative, telling the World Health Assembly in Geneva 'The proper mix of proven complementary, traditional and modern remedies, which emphasizes the active participation of the patient, can help to create a powerful healing force in the world'.Which begs the question 'What's the proof?'.In parallel, 13 eminent doctors wrote to acute and primary care trusts urging them to review practices with regard to 'ways in which unproven or disproved treatments are being encouraged for general use in the NHS'. 1 About half of all general practitioners refer patients to alternative practitioners, and should stop if it is pointless.As clinical scientist Leslie Rose said, the letter was to 'instill equal vigour in gathering evidence for every treatment prescribed to NHS patients', adding that a business plan for refurbishing the Royal London Homoeopathic Hospitalwhich cost £20m to set up-put no emphasis on evidence.£20m can buy a lot of what works, and such support begs questions about government consistency in calling for hard evidence for healthcare.The hospital's Dr Peter Fisher described the letter as an attempt to introduce 'medical apartheid' into the National Health Service, and Terry Cullen, of the British Complementary Medicine Association, said: 'There is so much anecdotal evidence that thousands of people gain benefit from using complementary medicines.We shouldn't dismiss that'.He is right: which is where a major problem arisesconfusing treating illness with 'gaining benefit', and indeed anecdote with evidence.The World Health Organization defines health as 'a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity'. 2. But the NHS has enough to do without being charged-in both senses-with creating this nirvana.Hoards of sensible, bright people swear by various blends of snake oil for multiple malaises, from back pain to itchy skin to mild melancholy.And maybe it is more powerful.But we need hard evidence that we can cure cancer, bypass a heart or silence schizophrenic voices with homeopathy, reiki, reflexology or aromatherapy.That is not to say they