tbuckley/cabot-search huggingface dataset:
Abstract 5033: Stromal-derived conditioned media activates STAT3 via JAK2 and TYK2 and results in <i>de novo</i> resistance to Nilotinib
Authors: Rajesh R. Nair, Joel H. Tolentino, Raul F. Argilagos, Ling Zhang, Javier Pinilla-Ibarz, Lori A. Hazlehurst
Journal: Cancer Research (2011)

Abstract Complete eradication of CML has not been possible in patients because of the presence of minimal residual disease (MRD) in sanctuary sites like the bone marrow (BM). One of the reasons for MRD is the milieu of cytokines and growth factors present in the BM microenvironment, that contribute to BCR-ABL independent drug resistance in CML. For example, in the present study, we demonstrate the importance of STAT3-mediated drug resistance in the BM microenvironment by showing that conditioned media (CM) derived from both normal and patient-derived mesenchymal stem cells and osteoblasts leads to STAT3 phosphorylation (pSTAT3-Y705) and concomitant drug resistance to Nilotinib in CML cells. Inhibiting the activity or reducing the expression of JAK2 and TYK2 was necessary for sensitizing cells to Nilotinib in CM. Moreover, increased pSTAT3-Y705 levels were associated with increased STAT3 transcriptional activity and up-regulation of Mcl-1 and cyclin D1. Our study indicates that there is an inherent redundancy in CM-mediated STAT3 activation pathway because concomitant neutralization of two potent activators of STAT3, IL-6 and G-CSF, does not reverse CM-mediated protection against Nilotinib. Furthermore, utilizing a SCID-hu bone implant in vivo model, we show that K562 cells with reduced STAT3 showed significantly lower tumor burden, which could be attributed to not only the slower proliferation rate, but also to the observation that these cells underwent cell death in BM stromal derived CM. Finally, CD34+ cells from CML patients when exposed to CM showed an increase in STAT3 phosphorylation which correlated with the development of de novo resistance to Nilotinib-mediated cell death. Taken together our data indicate that STAT3 is an important target in CML and its direct inhibition, along with BCR-ABL inhibitors, will likely be the most effective therapeutic strategy for reversing resistance within the BM microenvironment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5033. doi:10.1158/1538-7445.AM2011-5033
Lysosomal hydrolases of the epidermis.
Authors: P.D. MIER, D.W.K. COTTON, JOSE J.M.A. HURK, M.M.H. JONCKHEER-VANNESTE
Journal: British Journal of Dermatology (1976)

The activity of twelve acid hydrolases has been measured in serial horizontal sections of cow snout epidermis. The majority of these enzymes showed a clear peak in the basal and lower spinous cell layers; acid phosphatase, however, was found mainly in the keratinizing zone. These findings suggest that two discrete populations of lysosomes may occur in epidermis. Those present in the lower layers possess a typical pattern of hydrolase activity and probably correspond to the 'orthodox' lysosomes observed by electron microscopy techniques, whereas those found in the keratinizing zone possess an unusual hydrolase profile and may correspond to the bodies identified morphologically as keratinosomes (Odland bodies, membrane-coating granules).
THE PATHOLOGY OF THE KIDNEY.SOME GENERAL CONSIDERATIONS.
Authors: W. T. COUNCILMAN
Journal: JAMA (1906)

There are few organs in the body in which both structure and circulation are so complex as in the kidney. There is some variation in the size of the kidneys, depending on the life of the individual. The increased exercise of function as in potators is accompanied by increased size. The congenital anomalies are chiefly those of position and do not especially influence either intimate structure or function. In the congenital absence of one kidney we find in the other practically the same tissue arrangement, but the amount is doubled. In no other secreting organ do we find such differentiation of structure as that represented by the glomeruli and tubules. It is possible to think of the tubules not only, as glandular secreting organs with a remarkable differentiation of epithelium in different parts, but as serving simply as the excretory ducts of the glomeruli. No other organ in the body
Follow-up Study of Lung-Cancer Suspects in a Mass Chest X-Ray Survey
Authors: Clarence L. Scamman
Journal: New England Journal of Medicine (1951)

THE purpose of this paper is to discuss that part of the recent Mass Chest X-ray Survey in the city of Boston that was concerned with revealing cancer of the lung. It is believed that this is the first such survey in which special procedures carried out by special staff workers have been followed to detect cancer.The mass survey was initiated by Dr. John H. Cauley, commissioner of the Department of Health of the City of Boston, because of the high incidence of tuberculosis in the city. The survey was in operation from September 15, 1949, to February 1, . . .
Nosocomial Transmission of Tuberculosis
Authors: Jordan B. Glaser
Journal: Annals of Internal Medicine (1995)

Letters1 October 1995Nosocomial Transmission of TuberculosisJordan B. Glaser, MD, Carol Bosholm, MD, and Dorothy Minucci, RNJordan B. Glaser, MDStaten Island University Hospital; Staten Island, NY 10305Search for more papers by this author, Carol Bosholm, MDStaten Island University Hospital; Staten Island, NY 10305Search for more papers by this author, and Dorothy Minucci, RNStaten Island University Hospital; Staten Island, NY 10305Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-7-199510010-00014 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:We read with interest the recent article by Maloney and colleagues [1]. We have detected a similar increase and decrease in cases of multidrug-resistant tuberculosis at our institution; however, our experience contrasts with those described in their group's recent and previous articles [2]. The annual multidrug-resistant tuberculosis rates at our institution were 0 of 7 cases (0%) in 1990, 2 of 17 (12%) in 1991, 11 of 24 (46%) in 1992, 4 of 28 (15%) in 1993, and 4 of 22 (18%) in 1994. A significant increase (P < 0.05) and decrease (P < 0.04) for trend ...References1. Maloney SA, Pearson ML, Gordon MT, Del Castillo R, Boyle JF, Jarvis WR. Efficacy of control measures in preventing nosocomial transmission of multidrug-resistant tuberculosis to patients and health care workers. Ann Intern Med. 1995; 122:90-5. Google Scholar2. Pearson ML, Jereb JA, Frieden TR, Crawford JT, Davis BJ, Dooley SW, et al. Nosocomial transmission of multidrug-resistant Mycobacterium tuberculosis. A risk to patients and health care workers. Ann Intern Med. 1992; 117:191-6. Google Scholar3. Mathur P, Sacks L, Auten G, Sall R, Levy C, Gordin F. Delayed diagnosis of pulmonary tuberculosis in city hospitals. Arch Intern Med. 1994; 154:306-10. Google Scholar4. Weis SE, Slocum PC, Blais FX, King B, Nunn M, Matney B, et al. The effect of directly observed therapy on the rates of drug resistance and relapse in tuberculosis. N Engl J Med. 1994; 330:1179-84. Google Scholar5. Glaser JB, Strange TJ, Rosati D. Heterosexual human immunodeficiency virus transmission among the middle class. Arch Intern Med. 1989; 149:645-9. Google Scholar Author, Article, and Disclosure InformationAffiliations: Staten Island University Hospital; Staten Island, NY 10305 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1995Volume 123, Issue 7Page: 551-552KeywordsAddictsDirectly observed therapyDrugsElderlyEthanolHeterosexualsMultidrug resistant tuberculosisNosocomial infectionsTuberculin Issue Published: 1 October 1995 CopyrightCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
CARDIAC MYOSIN-BINDING PROTEIN C PHOSPHORYLATION ENHANCES CARDIAC RELAXATION
Authors: Dhriti Mukhopadhyay, Yang Liu, Mohamed Abdalla, Himakarnika Alluri, Candice Thomas, Rajesh Kumar, Chad Warren, Patricia Powers, Kenneth Baker, Richard L. Moss, R. John Solaro, Carl Tong
Journal: Journal of the American College of Cardiology (2013)
Comparison of ICAM-1, HLA-DR, TLR2, and TNFR1 Expression in Response to Staphylococcus aureus and Pro-Inflammatory Cytokines between Primary Conjunctival Epithelial Cells and the Cell Line, IOBA-NHC
Authors: J.L. Stahl, E.B. Cook, N.P. Barney, F.M. Graziano
Journal: Journal of Allergy and Clinical Immunology (2007)
PROPHYLAXIS OF UTERINE CANCER.
Authors: W. W. GRANT
Journal: JAMA (1899)

Cancer of the body of the uterus, as a primary condition, and independent of the cervix, is not common. I assume that there can now be no discussion as to the proper treatment of uterine cancer, when the opportunity for early operation is presented. The field of preventive surgical disease is as interesting a study and imperative a duty as preventive medicine is to the general practitioner and sanitarian. Knowing the cause, we will in time discover and apply the remedy. In this day of perfected surgical technic and brilliant operative achievement, we are prone to overlook and underestimate the great work we can or may do, in preventing disease. In no respect can this interest us more than in reference to those diseases the inevitable tendency of which is to a fatal issue. A more complete operation for carcinoma is more certain of attainment and more satisfactory, if performed
Myocardial Perfusion Scintigraphy With Adenosine
Authors: Niels Brinkman, Petra Dibbets-Schneider, Arthur J. H. A. Scholte, Marcel P. M. Stokkel
Journal: Clinical Nuclear Medicine (2008)

Background: The aim of this study was to assess whether adenosine impairs left ventricular ejection fraction (LVEF) obtained with gated SPECT in patients with a normal myocardial perfusion scintigram. Materials and Methods: This prospective study included 160 consecutive patients with a normal myocardial perfusion scintigraphy (MPS), who were stressed with either exercise (n = 64) or with adenosine (n = 96). Student t-test or χ2 test was used to compare patient's characteristics and functional parameters. Linear regression analyses were used to assess which patient characteristics had an independent significant influence on LVEF. Results: Functional parameters at rest were not significantly different between the adenosine group and the exercise stress group. However at stress, these functional parameters were significantly different. LVEF in the adenosine group decreased by −2.5%, whereas in the exercise group LVEF increased by 2.2% (P = 0.001). Moreover, in 36.5% of the patients a decrease in the LVEF of more than 5% was observed in the group stressed with adenosine compared with 15.6% in the exercise group (P = 0.002). In regression analysis, adenosine (P = 0.001) was selected as an independent significant correlate of a decrease in LVEF. Conclusion: Adenosine seems to impair the LVEF obtained with gated SPECT in patients with a normal perfusion scintigram. Further evaluation is necessary to elucidate how adenosine exerts this effect and also, whether this finding has a prognostic value in patients with a normal perfusion scintigram.
Selective Estrogen Receptor Modulators
Authors: Jonna Frasor, Fabio Stossi, Jeanne M. Danes, Barry Komm, C. Richard Lyttle, Benita S. Katzenellenbogen
Journal: Cancer Research (2004)

Abstract Selective estrogen receptor modulators (SERMs) such as tamoxifen are effective in the treatment of many estrogen receptor-positive breast cancers and have also proven to be effective in the prevention of breast cancer in women at high risk for the disease. The comparative abilities of tamoxifen versus raloxifene in breast cancer prevention are currently being compared in the Study of Tamoxifen and Raloxifene trial. To better understand the actions of these compounds in breast cancer, we have examined their effects on the expression of ∼12,000 genes, using Affymetrix GeneChip microarrays, with quantitative PCR verification in many cases, categorizing their actions as agonist, antagonist, or partial agonist/antagonist. Analysis of gene stimulation and inhibition by the SERMs trans-hydroxytamoxifen (TOT) and raloxifene (Ral) or ICI 182,780 (ICI) and by estradiol (E2) in estrogen receptor-containing MCF-7 human breast cancer cells revealed that (a) TOT was the most E2-like of the three compounds, (b) all three compounds either partially or fully antagonized the action of E2 on most genes, with the order of antagonist activity being ICI &amp;gt; Ral &amp;gt; TOT, (c) TOT and Ral, but not ICI, displayed partial agonist/partial antagonist activity on a number of E2-regulated genes, (d) several stimulatory cell cycle-related genes were down-regulated exclusively by ICI, (e) the estrogen-like activity of Ral nearly always overlapped with that of TOT, indicating that Ral has little unique agonist activity different from that of TOT, and (f) some genes were specifically up-regulated by TOT but not Ral, ICI, or E2. Hence, gene expression profiling can discern fundamental differences among SERMs and provides insight into the distinct biologies of TOT, Ral, and ICI in breast cancer.
Prevalence and prognostic value of IDH1 and IDH2 mutations in childhood AML: a study of the AML–BFM and DCOG study groups
Authors: F Damm, F Thol, I Hollink, M Zimmermann, K Reinhardt, M M van den Heuvel-Eibrink, C M Zwaan, V de Haas, U Creutzig, J-H Klusmann, J Krauter, M Heuser, A Ganser, D Reinhardt, C Thiede
Journal: Leukemia (2011)
Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease
Authors: Gosia Trynka, Karen A Hunt, Nicholas A Bockett, Jihane Romanos, Vanisha Mistry, Agata Szperl, Sjoerd F Bakker, Maria Teresa Bardella, Leena Bhaw-Rosun, Gemma Castillejo, Emilio G de la Concha, Rodrigo Coutinho de Almeida, Kerith-Rae M Dias, Cleo C van Diemen, Patrick C A Dubois, Richard H Duerr, Sarah Edkins, Lude Franke, Karin Fransen, Javier Gutierrez, Graham A R Heap, Barbara Hrdlickova, Sarah Hunt, Leticia Plaza Izurieta, Valentina Izzo, Leo A B Joosten, Cordelia Langford, Maria Cristina Mazzilli, Charles A Mein, Vandana Midah, Mitja Mitrovic, Barbara Mora, Marinita Morelli, Sarah Nutland, Concepción Núñez, Suna Onengut-Gumuscu, Kerra Pearce, Mathieu Platteel, Isabel Polanco, Simon Potter, Carmen Ribes-Koninckx, Isis Ricaño-Ponce, Stephen S Rich, Anna Rybak, José Luis Santiago, Sabyasachi Senapati, Ajit Sood, Hania Szajewska, Riccardo Troncone, Jezabel Varadé, Chris Wallace, Victorien M Wolters, Alexandra Zhernakova, B K Thelma, Bozena Cukrowska, Elena Urcelay, Jose Ramon Bilbao, M Luisa Mearin, Donatella Barisani, Jeffrey C Barrett, Vincent Plagnol, Panos Deloukas, Cisca Wijmenga, David A van Heel
Journal: Nature Genetics (2011)
A taste of metal and a smell of burning flesh
Authors: Kieran Walsh
Journal: BMJ (2005)

I'd never heard a bomb before yesterday and what I remember most is not the boom but the whooshing sound afterwards. Friends from Northern Ireland tell me that the vacuum left by the explosion causes this. Then came a noise of showering glass and seats and people landing on the road. I was sitting at my desk looking forward to a day of editing and meetings and my initial thought was, “I'm going to have to cancel my 10 o'clock meeting.”

Everyone in BMJ Knowledge and in the BMJ walked down the stairs and out of the back of the building. Some people were crying but nobody panicked. When I got into the courtyard, I thought I'd better go out the front and see if I could help.

There …
IL-21 and CD40L signals from autologous T cells can induce antigen-independent proliferation of CLL cells
Authors: Maria Fernanda Pascutti, Margot Jak, Jacqueline M. Tromp, Ingrid A. M. Derks, Ester B. M. Remmerswaal, Rachel Thijssen, Martijn H. A. van Attekum, Gregor G. van Bochove, Dieuwertje M. Luijks, Steven T. Pals, René A. W. van Lier, Arnon P. Kater, Marinus H. J. van Oers, Eric Eldering
Journal: Blood (2013)
Treatment of Shigellosis: V. Comparison of Azithromycin and Ciprofloxacin: A Double-Blind, Randomized, Controlled Trial
Authors: Wasif Ali Khan
Journal: Annals of Internal Medicine (1997)

Background: Treatment of shigellosis is currently limited by the high prevalence of multidrug-resistant strains of Shigella. Objective: To determine the efficacy of azithromycin in the treatment of shigellosis. Design: Randomized, double-blind clinical trial. Setting: Diarrhea treatment center in Dhaka, Bangladesh. Patients: 70 men with shigellosis that had lasted 72 hours or less. Interventions: Patients stayed in the hospital for 6 days. Thirty-four patients were randomly assigned to receive 500 mg of azithromycin on study day 1, followed by 250 mg once daily for 4 days; 36 patients were assigned to receive 500 mg of ciprofloxacin every 12 hours for 5 days. Measurements: Clinical treatment failure was considered to have occurred if frank dysentery persisted for 72 hours after therapy began or if on study day 5 a patient had more than six stools, had any bloody-mucoid stools, had more than one watery stool, or had an oral body temperature exceeding 37.8 °C. Bacteriologic treatment failure was considered to have occurred if Shigella strains could be isolated from a stool sample after study day 2. Therapy was considered either clinically or bacteriologically successful in patients who completed therapy and did not meet criteria for failure. Results: Therapy was clinically successful in 28 (82%) patients who received azithromycin and 32 (89%) patients who received ciprofloxacin (difference, −7%[95% CI, −23% to 10%]). Therapy was bacteriologically successful in 32 (94%) patients receiving azithromycin and 36 (100%) patients receiving ciprofloxacin (difference, −6%[CI, −14% to 2%]). Peak serum concentrations of azithromycin were equal to the minimum inhibitory concentration (MIC) of the infecting Shigella strains, whereas serum concentrations of ciprofloxacin were 28 times the MIC. Stool concentrations of both drugs were more than 200 times the MIC. Conclusion: Azithromycin is effective in the treatment of moderate to severe shigellosis caused by multidrug-resistant Shigella strains.
Results of the International Study of the Implantable Pacemaker Cardioverter-Defibrillator
Authors: Douglas P. Zipes, Diana Roberts
Journal: Circulation (1995)

The purpose of the present report was to document clinical experience derived from the implantation of 2834 epicardial and endocardial cardioverter-defibrillators (ICDs) in 2807 patients who were followed for almost 1 year and to compare the results obtained with the two systems.Patients in the two groups had similar clinical characteristics. More than half of the patients had a total of almost 50,000 spontaneous ventricular tachyarrhythmias that were terminated with equal success (approximately 98%) by epicardial and endocardial ICDs. Lead dislodgement and pocket infection occurred more often with the endocardial than with the epicardial ICD, whereas perioperative mortality was higher with the epicardial ICD than with the endocardial ICD. Mortality from sudden cardiac death was 1.4% in the epicardial ICD group and 0.6% in the endocardial ICD group at 1 year (P = .069). Overall mortality at 1 year was 12.2% and 6.9% for the epicardial and endocardial groups, respectively (P < .001), reflecting the higher surgical mortality for the epicardial system.The endocardial ICD is as effective as the epicardial ICD but incurs lower perioperative mortality.
A1.83 Long-term effects of etanercept and certolizumab pegol treatment on vascular function and lipid parameters in rheumatoid arthritis and ankylosing spondylitis
Authors: Edit Végh, Andrea Váncsa, György Kerekes, Fruzsina Balázs, Lilla Pogácsás, Nóra Bodnár, Gabriella Szücs, Sándor Szántó, Zoltán Szekanecz
Journal: Annals of the Rheumatic Diseases (2014)

<h3>ABSTRACT</h3> Population estimates are commonly generated and used in conservation science. All estimates carry inherent uncertainty, but little attention has been given to when and how this uncertainty limits their use. This requires an understanding of the specific purposes for which population estimates are intended, an assessment of the level of uncertainty each purpose can tolerate, and information on current uncertainty. We conducted a review and meta-analysis for a widespread group of seabirds, the petrels, to better understand how and why population estimates are being used. Globally petrels are highly threatened, and aspects of their ecology make them difficult to survey, introducing high levels of uncertainty into population estimates. We found that by far the most common intended use of population estimates was to inform status and trend assessments, while less common uses were trialling methods to improve estimates, and assessing threat impacts and conservation outcomes. The mean coefficient of variation for published estimates was 0.17 (SD = 0.14), with no evidence that uncertainty has been reduced through time. As a consequence of this high uncertainty, when we simulated declines equivalent to thresholds commonly used to trigger management, only 5% of studies could detect significant differences between population estimates collected 10 years apart for populations declining at a rate of 30% over three generations. Reporting of uncertainty was variable with no dispersion statistics reported with 38% of population estimates and most not reporting key underlying parameters: nest numbers/density and nest occupancy. We also found no correlation between population estimates and either island size, body size or species threat status—potential predictors of uncertainty. <i>Synthesis and applications</i>—Key recommendations for managers are to be mindful of uncertainty in past population estimates if aiming to collect contemporary estimates for comparison, to report uncertainty clearly for new estimates, and to give careful consideration to whether a proposed estimate is likely to achieve the requisite level of certainty for the investment in its generation to be warranted. We recommend a practitioner-based Value of Information assessment to confirm where there is value in reducing uncertainty.