tbuckley/cabot-search huggingface dataset:
Abstract 3573: The novel FASN inhibitor UCMG028 overcomes resistance to trastuzumab and lapatinib
Authors: Teresa Puig, Daniel Gómez, Ander Urruticoechea, Sílvia Cufí, Carlos Turrado, Helena Aguilar, Òscar Campuzano, Ramon Brugada, María Luz López-Rodríguez, Ramon Colomer
Journal: Cancer Research (2010)

Abstract The vast majority of Her-2 positive advanced breast cancer patients develop resistance to trastuzumab based therapies within the first year of treatment. We have shown that inhibition of Fatty Acid Synthase (FASN) activity, an enzyme overexpressed and hiperactivated in breast carcinoma, shows marked synergic anticancer activity combined with anti-HER drugs. To examine the molecular mechanisms of acquired resistance to HER2, we have generated clones of FASN+ and HER2+ cell lines (AU565 and SK-Br3) resistant to trastuzumab (TTZ) and lapatinib (LAP) for longer than 9 months, and have evaluated the anticancer effect of UCMG028. We further characterized the effect of UCM028 in a mice model of HER2+ xenograft (BT474). TTZ and LAP-resistant cells displayed an increased sensitivity to UCMG028 compared to previously known FASN inhibitors (C75 and EGCG). Gene expression profiling of LAP and TTZ-resistant cells showed a significant differential expression in different sets of genes involved on cell cycle pathways. Mice BT474 xenografts showed tumor regression after long-term exposure to UCMG028. Preliminary toxicity data showed no weight loss, and histological studies (H&amp;E, Masson's Tricromic, Sudan Black B and Picrosirius Red Stains) showed no structural myocardial abnormalities in treated mice with UCMG028-treated mice. Thus, UCMG028 is an effective anticancer treatment for HER2 + breast cancer and its activity remains unchanged in TTZ and LAP resistant cells. Taken together, these data suggest that FASN activity inhibition by UCMG028 could be a new therapeutic strategy in HER2 + breast cancer with potential to overcome resistance to standard anti-HER2 therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3573.
Comparison of manual and automated cell counts in EDTA preserved synovial fluids. Storage has little influence on the results
Authors: M. Salinas, J. Rosas, J. Iborra, H. Manero, E. Pascual
Journal: Annals of the Rheumatic Diseases (1997)

To determine the precision and agreement of synovial fluid (SF) cell counts done manually and with automated counters, and to determine the degree of variability of the counts in SF samples, kept in the tubes used for routine white blood cell (WBC) counts--which use liquid EDTA as anticoagulant--at 24 and 48 hours at 4 degrees C, and at room temperature.To determine precision, cell counts were repeated 10 times--both manually and by an automated counter--in a SF sample of low, medium, and high cellularity. The variances were calculated to determine the interobserver variation in two manual (M1,M2) and two automated cell counts (C1,C2). The agreement between a manual (M1) and automated counter (C1) results, was analysed by the Bland and Altman method and the difference against the mean of the two methods was plotted. Then, the mean difference between the two methods was estimated and the standard deviation of the difference. To determine the effects of storage, SF samples were kept in a refrigerator at 4 degrees C, and at room temperature; cell counts were done manually (M1) and automatically (C1) at 24 and 48 hours and the changes analysed by the Bland and Altman method. The variances were compared using an F test.(1) Precision. With the manual technique, the coefficients of variation were 27.9%, 14%, and 10.7% when used for counting the SF with low (270), medium (6200), and high cellularities (25,000). With the automated technique the coefficients of variation were 20%, 3.4%, and 2.9% in the same SF samples. In the fluids of medium and high cellularity, the variances of the automated cell counts were significatively lower (F test, p < 0.002) than those of the manual counts. (2) Interobserver variation. The variance between C1 and C2 (25 SF) was significatively lower (F test, p < 0.002) than that of the manual counts (41 SF). (3) Agreement between the two techniques (100 SF). For cellularities above 2000 cells/mm3, the manual method gave results between +10% to -34% of the results obtained by the coulter. For cellularities below 2000 cells/mm3, manual cell counts were between +60 to -1280 cells/mm3 of those obtained by the automated counter. (4) Influence of storage. The coulter counts of SF samples preserved at 4 degrees C showed less variance (F test, p < 0.05) than the manual counts. The worst results were obtained in manual counts of SF samples kept at room temperature; these samples at 48 hours showed a variation between -47% to 42% of the initial results.Automated cell count of the SF offers advantages: it gives higher precision and consumes less time. The stability of the samples preserved in the EDTA tubes used for routine WBC counts is of additional interest, because if delay cannot be avoided, the results of the WBC counts are still accurate at 24 and even at 48 hours, at least for clinical purposes.
Mission Management: A New Synthesis
Authors: Jack Ende
Journal: Annals of Internal Medicine (1999)

Medical Writings: Book Notes6 July 1999Mission Management: A New SynthesisJack Ende, MDJack Ende, MDUniversity of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. (Ende)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-131-1-199907060-00036 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Volume 2. Rubin ER, ed. 408 pages. Washington, DC: Assoc of American Health Centers; 1998. $30.00. ISBN 1879694123. Order phone 202-265-9600.Field of medicine: Health care management and medical education.Format: Softcover book.Audience: Leaders of academic medical centers and faculty responsible for strategic planning for education, research, and clinical programs.Purpose: To highlight critical issues, emerging initiatives, and new perspectives that should be considered by educators, administrators, and policymakers as they prepare their organizations for the next century.Content: Divided into three sections, the book presents 18 background papers prepared by leaders of academic health centers, health policy institutes, ... Author, Article, and Disclosure InformationAffiliations: University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. (Ende) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 6 July 1999Volume 131, Issue 1Page: 80KeywordsComputer softwareGlobal healthHealth careHealth care sectorHealth economicsMedical education ePublished: 15 August 2000 Issue Published: 6 July 1999 Copyright & PermissionsCopyright © 1999 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Opposing Effects Mediated by the Chemokine Receptor CXCR2 on Myocardial Ischemia-Reperfusion Injury
Authors: Sima T. Tarzami, Wenfeng Miao, Kartik Mani, Lillie Lopez, Stephen M. Factor, Joan W. Berman, Richard N. Kitsis
Journal: Circulation (2003)

The timely reperfusion of ischemic myocardium limits infarction, but components of reperfusion, such as inflammation, may be injurious. The chemokine receptor CXCR2 mediates neutrophil chemotaxis. CXCR2 activation also inhibits hypoxia-induced death of isolated cardiac myocytes. This study assesses whether CXCR2 mediates protection in the intact heart and, if so, the magnitude of this protection relative to CXCR2-mediated chemotaxis of potentially damaging inflammatory cells.After ischemia-reperfusion in vivo, CXCR2-/- mice exhibited infarcts that were 50.5% smaller (P<0.05) with 44.3% fewer inflammatory cells (P<0.05) than wild type mice. These data suggest that in this model, CXCR2-mediated chemotaxis may be important in myocardial cell death. To isolate the role of CXCR2 specifically on blood cells, adoptive transfer experiments were performed. After ischemia-reperfusion, infarcts were 53.4% smaller (P<0.05) and contained 65.0% fewer inflammatory cells (P<0.05) in lethally irradiated wild type mice reconstituted with CXCR2-/- compared with wild type bone marrow. Thus, CXCR2 on blood cells is important in myocardial damage, most likely because of CXCR2-mediated chemotaxis. To unmask whether CXCR2 mediates direct myocardial protection in the intact heart, wild type and CXCR2-/- hearts were studied in the absence of blood using Langendorff preparations. In this case, infarcts were 19.7% larger in CXCR2-/- than wild type hearts (P<0.05), revealing a novel CXCR2-mediated cardioprotective effect.CXCR2 exerts opposing effects on myocardial viability during ischemia-reperfusion with recruitment of damaging inflammatory cells predominant over direct tissue protection.
THE DIRECT COMPARATIVE DIFFRACTION METHOD OF DEMONSTRATING MEGALOCYTOSIS
Authors: J. H. Malloy
Journal: BMJ (1930)

Haemoglobin 68 per cent.Lymphocytes ... 66% 1221 Colour index 1.0 Endothelials ... 16% 296 White blood cells 1,850 Eosinophils ... 1% Mast cells ... 1% Size of red cells, 7.81 microns.Marelh 3rd.Red blood cells 3,910,000 Polymorphs ... 12% 264 Haemoglobin 72 per cenit.. Lymphocytes ... 80..1760 Colourl index 0.92 Endotlielials ... 8%b White blood cells 2,200 Red cells almost normal in appearance and by Eve's lialometer 7.48 mnicrons (normal).It will be seen-that thirouighout there was a veery grave aniaemia with a, high colour index, reaehing oIn Januairy 5th the figure -1;a.The white couilit in the miiost serious part of thie ililness wi-Ias very loii-, and the total p)ol-umorplh count
Reactive Oxygen Species-Induced Actin Glutathionylation Controls Actin Dynamics in Neutrophils
Authors: Jiro Sakai, Jingyu Li, Kulandayan K. Subramanian, Subhanjan Mondal, Besnik Bajrami, Hidenori Hattori, Yonghui Jia, Bryan C. Dickinson, Jia Zhong, Keqiang Ye, Christopher J. Chang, Ye-Shih Ho, Jun Zhou, Hongbo R. Luo
Journal: Immunity (2012)
The Role of Anger in Adherence to Highly Active Antiretroviral Treatment in Patients Infected with HIV
Authors: Paolo Leombruni, Secondo Fassino, Luca Lavagnino, Giancarlo Orofino, Pierluigi Morosini, Angelo Picardi
Journal: Psychotherapy and Psychosomatics (2009)

Adherence to highly active antiretroviral treatment (HAART) is critical to long-term treatment success in patients infected with human immunodeficiency virus (HIV). However, the relationship between psychological variables and medication adherence is still poorly understood. The aim of this study was to investigate how anger dimensions in subjects with HIV affect adherence to antiretroviral drugs.One hundred and thirty outpatients with HIV who were nondepressed and receiving HAART were administered the State-Trait Anger Inventory and a compliance self-report questionnaire. They also underwent clinical laboratory tests aimed at investigating immune function and disease stage.Forty-three patients (33%) reported suboptimal adherence. Full compliance with HAART was related to higher age, lower HIV RNA level, lower trait anger, lower outside-directed anger and greater anger control. In a multiple regression analysis, low trait anger (p = 0.02) and high anger control (p = 0.03) were significantly associated with full adherence to HAART.Anger dimensions are linked with, and may affect, adherence to HAART. A better understanding of the psychological determinants of compliance might allow for the identification of patients who are at higher risk of nonadherence. To sustain adherence to HAART, these patients may benefit from increased clinical attention or intervention.
A "Long Indel" Model For Evolutionary Sequence Alignment
Authors: I. Miklos
Journal: Molecular Biology and Evolution (2003)

We present a new probabilistic model of sequence evolution, allowing indels of arbitrary length, and give sequence alignment algorithms for our model. Previously implemented evolutionary models have allowed (at most) single-residue indels or have introduced artifacts such as the existence of indivisible "fragments." We compare our algorithm to these previous methods by applying it to the structural homology dataset HOMSTRAD, evaluating the accuracy of (1) alignments and (2) evolutionary time estimates. With our method, it is possible (for the first time) to integrate probabilistic sequence alignment, with reliability indicators and arbitrary gap penalties, in the same framework as phylogenetic reconstruction. Our alignment algorithm requires that we evaluate the likelihood of any specific path of mutation events in a continuous-time Markov model, with the event times integrated out. To this effect, we introduce a "trajectory likelihood" algorithm (Appendix A). We anticipate that this algorithm will be useful in more general contexts, such as Markov Chain Monte Carlo simulations.
Why Health Care Is Going Home
Authors: Steven H. Landers
Journal: New England Journal of Medicine (2010)

In Albuquerque, New Mexico, and Buffalo, New York,1 acutely ill patients have been sent out of the emergency department for hospital-like care at home. In Baton Rouge, Louisiana, and Little Rock, Arkansas, home health agencies provide chronic care management services, emphasizing care coordination and support for patients' management of their own conditions. In San Diego, California, physicians arrive at patients' homes with a new version of the black bag that includes a mobile x-ray machine and a device that can perform more than 20 laboratory tests at the point of care. Several engineering and electronics companies have developed products for . . .
THE USE OF SURFACE ANESTHESIA IN THE TREATMENT OF PAINFUL MOTION
Authors: HANS KRAUS
Journal: JAMA (1941)

This paper describes a method of treatment for impaired function when pain is the factor responsible for the loss of motion or power. The treatment is the application of a surface anesthetic (ethyl chloride spray) combined with active motion. <h3>DEVELOPMENT OF THE TREATMENT</h3> In 1933 a gymnastic teacher—Heinz Kowalsky— suggested that treatment of sprains and pulled muscles by immobilization was not satisfactory to active sportsmen. He said that professional sportsmen had found by experience that immediate active motion after any such injury provided the quickest cure. He further told me that he usually advised his pupils to rub their injured joints with alcohol and expose them to live steam for a time. Numbness of the joint was said to result, and active motion was started as soon as this numbness set in. The result of this treatment was said to be satisfactory and superior to treatment by immobilization. I tried
Less than 2% of food aid is spent on interventions to reduce malnutrition in children
Authors: M. Day
Journal: BMJ (2009)

World leaders will be condemning millions of children to death or permanent handicap from malnutrition unless they radically alter their policies and priorities for dealing with famine ridden countries, a leading medical charity has warned.

Medecins Sans Frontieres made the attack ahead of this month’s world food summit in Rome. 

Daniel Berman, chairman of the charity’s campaign on access to essential medicines, said that rich nations were about to make a “colossal mistake” by investing in long term agriculture programmes at the expense of urgent measures to target food aid at the hungriest children.

He warned that recent policy statements emerging from the G8 and G20 summits indicated that flawed …
Management of difficult and severe eczema in childhood
Authors: M. A. McAleer, C. Flohr, A. D. Irvine
Journal: BMJ (2012)

The antitumor immune response activated by IL-12, especially by a combination of cyclophosphamide and IL-12 (Cy+IL-12), is clinically significant in certain experimental tumor models, in that a number of well-established (10–20 mm in diameter) s.c. tumors are completely eradicated. Furthermore, Cy+IL-12 treatment is also able to eradicate well-established grossly detectable experimental lung metastases and advanced ascites tumors. Despite the dramatic antitumor effects seen in some tumor models, Cy+IL-12 fails to induce regression of other established tumors. Characterization of tumor immunogenicity shows that all tumors responding to IL-12 and Cy+IL-12 treatments are immunogenic tumors, in that an antitumor immune response is detectable in tumor-bearing hosts upon tumor establishment. In contrast, none of the nonimmunogenic tumor responds to IL-12 and Cy+IL-12 treatments. Analysis of cellular requirements for successful tumor rejection through an adoptive cell transfer approach reveals that the presence of tumor-sensitized, but not naive, T cells is essential for tumor rejection by IL-12 and Cy+IL-12. Transfer of these tumor-sensitized T cells must be conducted before, but not after, IL-12 treatment in order for tumor rejection to occur. The requirement of sensitized T cells is also tumor specific. In mice bearing immunogenic tumors, the presence of pre-existing tumor-sensitized T cells is demonstrated by adoptive cell transfer experiments using purified spleen T cells from these mice. Results from our study show that Cy+IL-12-based immunotherapy of cancer may be highly effective and that pre-existing tumor-sensitized T cells are essential for the success of the therapy.
Paclitaxel coating reduces in-stent restenosis: a serial volumetric intravascular ultrasound analysis
Authors: Myeong-Ki Hong, Gary S. Mintz, Seong-Wook Park, Jae-Joong Kim, None Cheol Whan Lee, Neal E. Fearnot, William D. Vorhees, Neil J. Weissman, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2002)
Effects of clopidogrel-aspirin combination versus aspirin alone on platelet aggregation and major receptor expression in patients with heart failure: For the plavix use for treatment of congestive heart failure (PLUTO-CHF) trial
Authors: Victor L. Serebruany, Alex I. Malinin, Scott D. Jerome, David R. Lowry, Athol W. Morgan, David C. Sane, Christopher M. O'Connor
Journal: Journal of the American College of Cardiology (2003)
127 PHOSPHODIESTERASE POLYMORPHISMS MAY BE ASSOCIATED WITH BASELINE THYROID STIMULATING HORMONE (TSH) AND PEGINTERFERON TREATMENT INDUCED HYPOTHYROIDISM IN PATIENTS WITH CHRONIC HEPATITIS C
Authors: P.J. Clark, A.J. Thompson, M. Zhu, D. Ge, K. Shianna, H.L. Tillmann, K. Patel, T. Urban, A. Singh, M. Sulkowski, N. Afdhal, I. Jacobson, R. Esteban, F. Poordad, E. Lawitz, J. McCone, M.L. Shiffman, G. Galler, W.M. Lee, R. Reindollar, J. King, P. Kwo, R. Ghalib, B. Freilich, L. Nyberg, S. Noviello, N. Bopari, K. Koury, L.D. Pedicone, C. Brass, J.K. Albrecht, D. Goldstein, J.G. McHutchison, A.J. Muir
Journal: Journal of Hepatology (2011)
Letter: Epidemic neuromyasthenia.
Authors: M J Dillon, W C Marshall, J A Dudgeon, A J Steigman
Journal: BMJ (1974)

tinue to use celphaloridine as a local applica- tion in the proiphylaxis of potentially con- taminated wounds.We are indebted to Glaxo Research Ltd. for the supply of cephaloridine (Ceporin) and Aspro-Nicholas Ltd. for the gentamicin (Genticin).-Weare, etc.,
Fetal Pancreas Transplantation for Treatment of IDDM Patients
Authors: Kevin J Lafferty, Liming Hao
Journal: Diabetes Care (1993)

The debate concerning use of fetal tissue in a clinical setting is relevant to the treatment of diabetes; the ban on clinical use of fetal tissue remains in force. Specifically, this issue raises questions about what has been and what can be done in the use of HFP tissue for treatment of the IDDM patient. The possibility of using such tissue was first raised by Lazarow et al. in the 1973 Banting Lecture (1). Since that time there has been much progress in our understanding of the allograft response and in studies of the growth and differentiation of the HFP. In this report, we review developments in this area and consider their implications in the current political climate.
Hepatic Adenomata With Type 1 Glycogen Storage Disease
Authors: R. Rodney Howell, Roger E. Stevenson, Yoram Ben-Menachem, Robert L. Phyliky, D. H. Berry
Journal: JAMA (1976)

In older patients with glucose-6-phosphatase deficiency adenomatous nodules develop within the liver parenchyma. Investigation of eight such patients, age 3 to 28 years, using radioisotopic scans, has demonstrated areas of depressed isotope uptake in the liver in all except the one preteenaged child. Three patients were further studied with hepatic angiograms and liver biopsy specimens. A diffuse nodularity, more widespread than apparent on isotopic scans, was demonstrated on angiograms. Although initial histologic study in each case showed adenomatous tissue without evidence of neoplasm, the development of hepatocellular carcinoma in one of our patients and in others from the literature suggests that the nodules may be premalignant.
Abstract 4585: Expression of fibroblast growth factor-9 is associated with poor prognosis of resected non-small cell lung cancer patients
Authors: keiko ohgino, Kenzo Soejima, Daisuke Arai, Kota Ishioka, Takashi Sato, Hideki Terai, Shinnosuke Ikemura, Satoshi Yoda, Junko Hamamoto, Katsuhiko Naoki, Tomoko Betsuyaku
Journal: Cancer Research (2012)

Abstract Background: Fibroblast growth factor (FGF)-9 is a member of the FGF family, which modulates cell proliferation, differentiation and motility. Recent studies show that activation of FGF signals including FGF-9 is associated with pathogenesis of several cancers, however its clinicopathological and biological significance in non-small cell lung cancer (NSCLC) is unclear. The purpose of this study is to clarify the characteristics of FGF-9-expressing NSCLC. Methods: We evaluated expression of FGF-9 in completely resected NSCLC and corresponding non-tumorous lung samples using cDNA microarray combining with quantitative RT-PCR for confirmation, and compared with clinical pathological parameters and survival. We also evaluated altered gene expression patterns between FGF-9-high and -low NSCLCs. Results: The expression of FGF-9 increased compared with the corresponding non-cancerous lung tissues in 13 (13.2%) of 98 NSCLCs. Histologically, 10 out of 13 FGF9-high NSCLC were adenocarcinoma, while none of them were squamous cell carcinoma. The relationship between FGF-9 expression and sex, smoking history or clinical stage was not observed. On the other hand, postoperative recurrence rates and 3-year survival rates were 40% vs. 21% and 54% vs. 92% (p=0.002) for FGF9-high vs. -low NSCLC patients, respectively. The overall survival rate was also significantly worse in FGF9-high NSCLC (p=0.023). The specific gene expression pattern of FGF-9-high NSCLC will be also presented. Conclusion: Our data indicate that FGF-9 may be a novel unfavorable prognostic indicator and a candidate for therapeutic targets of NSCLC. 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 4585. doi:1538-7445.AM2012-4585
Chronic Supraventricular Tachycardia
Authors: Paul C. Gillette
Journal: JAMA (1985)

Two cases of congestive cardiomyopathy were proved to be due to chronic atrial automatic-focus tachycardia. Surgical elimination of the tachycardia resulted in normalization of cardiac function in both cases. We suggest that patients with congestive cardiomyopathy be carefully screened for supraventricular tachycardia. Patients with chronic supraventricular tachycardia should be treated aggressively to prevent myocardial dysfunction. (<i>JAMA</i>1985;253:391-392)