tbuckley/cabot-search huggingface dataset:
Abstract 602: Silencing BRG1 in human cancers
Authors: David R. Reisman, Sarah Gramling, Tracy Wright
Journal: Cancer Research (2011)

Abstract BRG1 is a novel tumor suppressor that serves as the major catalytic subunit of the SWI/SNF complex. Because this complex is central to the function of a number of transcription factors and key cellular proteins and it is required for a plethora of signal transduction pathways, its loss can have devastating effects on cellular function. We know that BRG1 is not only lost in lung cancer but also in a variety of tumor types: between 10-40%. Hence, the loss of this protein plays an important role in cancer development and progression. In cell lines, it has been well document that BRG1 is mutated or altered in the vast majority of cell lines, but in primary lung cancer mutations are not found. Our analysis has led us to believe that BRG1 is epigenetically silenced like its homolog BRM. Hence, it may be possible to restore its expression in cancer cells. The loss of BRG1 impacts the sensitivity to Cisplatin by making cells more sensitive to the DNA damaging effects of this agent. Similarly, this loss also impacts sensitivity to EGFR inhibitors by making cells more resistant. Hence, the loss of BRG1 can help to explain the reciprocal sensitivity to these drugs seen in cancers. Hence, the BRG1 protein can play the role of a biomarker for chemotherapy sensitivity as well as being a potential target for therapy. Further research will reveal how this gene can best be integrated into clinical practice. 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 602. doi:10.1158/1538-7445.AM2011-602
Abstract 3376: Mirk/Dyrk1B modulates the development of chemoresistance in human ovarian cancer.
Authors: Jingchun Gao, Ji Li, Heli Gao, Jianxin Tian, Yunyi Lv, Zhihai Yang, Qiuping Zhang, Fandou Kong, Jian Pang, Hongwei Guan, Hong Shi
Journal: Cancer Research (2013)

Abstract Ovarian cancer is one of the leading causes of cancer death in women and chemoresistance is a major obstacle that need to be overcome in the treatment of ovarian cancer patients. Our previous study along with others have found that the serine/threonine kinase Mirk/Dyrk1B is overexpressed in a wide spectrum of cell lines and clinical specimens of ovarian cancer. It has been known that Mirk/Dyrk1B regulates cell survival and sensitivity to conventional chemotherapeutics, and it also contributes to G0 arrest by destabilization of cyclin D1 and stabilization of p27kip1in ovarian cancer cells. We therefore hypothesize that Mirk/Dyrk1B may be associated with cancer ‘stem cell-like’ sustaining cells and chemoresistance formation. In this study, the mRNA and protein expressions of Mirk/Dyrk1B and the side population (SP) cells in the human ovarian cancer SKOV3, OVCAR5, and A2780S cells were measured during cisplatin resistance development. In addition, the protein expressions of ALDH1, Nanog, Ki-67, and Mirk/Dyrk1B were examined in the clinical specimens obtained from the patients with high-grade serous ovarian cancer before and after neoadjuvant chemotherapy, respectively. It was found that drug resistance formation was accompanied by a significant increase in the mRNA and protein expressions of Mirk/Dyrk1B as well as proportion of SP cells in all ovarian cancer cell strains, which was annulled after knockdown of Mirk/Dyrk1B by shRNA. Moreover, the protein expressions of ALDH1, Nanog, and Mirk/Dyrk1B were up-regulated and ki-67 was down-regulated in the specimens after neodajuvant chemotherapy. Our result confirms the important contribution of Mirk/Dyrk1B-dependent mechanisms into the development of chemoresistance of human ovarian cancer. Citation Format: Jingchun Gao, Ji Li, Heli Gao, Jianxin Tian, Yunyi Lv, Zhihai Yang, Qiuping Zhang, Fandou Kong, Jian Pang, Hongwei Guan, Hong Shi. Mirk/Dyrk1B modulates the development of chemoresistance in human ovarian cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3376. doi:10.1158/1538-7445.AM2013-3376 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Quantitative Magnetic Resonance Imaging Analysis of Neovasculature Volume in Carotid Atherosclerotic Plaque
Authors: William Kerwin, Andrew Hooker, Mary Spilker, Paolo Vicini, Marina Ferguson, Thomas Hatsukami, Chun Yuan
Journal: Circulation (2003)

Background— Neovasculature within atherosclerotic plaques is believed to be associated with infiltration of inflammatory cells and plaque destabilization. The aim of the present investigation was to determine whether the amount of neovasculature present in advanced carotid plaques can be noninvasively measured by dynamic, contrast-enhanced MRI. Methods and Results— A total of 20 consecutive patients scheduled for carotid endarterectomy were recruited to participate in an MRI study. Images were obtained at 15-second intervals, and a gadolinium contrast agent was injected coincident with the second of 10 images in the sequence. The resulting image intensity within the plaque was tracked over time, and a kinetic model was used to estimate the fractional blood volume. For validation, matched sections from subsequent endarterectomy were stained with ULEX and CD-31 antibody to highlight microvessels. Finally, all microvessels within the matched sections were identified, and their total area was computed as a fraction of the plaque area. Results were obtained from 16 participants, which showed fractional blood volumes ranging from 2% to 41%. These levels were significantly higher than the histological measurements of fractional vascular area. Nevertheless, the 2 measurements were highly correlated, with a correlation coefficient of 0.80 ( P &lt;0.001). Conclusions— Dynamic contrast-enhanced MRI provides an indication of the extent of neovasculature within carotid atherosclerotic plaque. MRI therefore provides a means for prospectively studying the link between neovasculature and plaque vulnerability.
Dramaturgical study of meetings between general practitioners and representatives of pharmaceutical companies Commentary: dramaturgical model gives valuable insight
Authors: M. Somerset, M. Weiss, T. Fahey, R. Mears
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objectives:</b> To examine the interaction between general practitioners and pharmaceutical company representatives. <b>Design:</b> Qualitative study of 13 consecutive meetings between general practitioner and pharmaceutical representatives. A dramaturgical model was used to inform analysis of the transcribed verbal interactions. <b>Setting:</b> Practice in south west England. <b>Participants:</b> 13 pharmaceutical company representatives and one general practitioner. <b>Results:</b> The encounters were acted out in six scenes. Scene 1 was initiated by the pharmaceutical representative, who acknowledged the relative status of the two players. Scene 2 provided the opportunity for the representative to check the general practitioner9s knowledge about the product. Scene 3 was used to propose clinical and cost benefits associated with the product. During scene 4, the general practitioner took centre stage and challenged aspects of this information. Scene 5 involved a recovery strategy as the representative fought to regain equilibrium. In the final scene, the representative tried to ensure future contacts. <b>Conclusion:</b> Encounters between general practitioners and pharmaceutical representatives follow a consistent format that is implicitly understood by each player. It is naive to suppose that pharmaceutical representatives are passive resources for drug information. General practitioners might benefit from someone who can provide unbiased information about prescribing in a manner that is supportive and sympathetic to the demands of practice. <h3>What is already known on this topic</h3> Pharmaceutical representatives influence physicians9 prescribing in ways that are often unacknowledged by the physicians themselves Meetings with pharmaceutical representatives are associated with increased prescribing costs and less rational prescribing <h3>What this study adds</h3> Meetings between pharmaceutical representatives and general practitioners follow a consistent format that is implicitly understood by each player General practitioners may cooperate because representatives make them feel valued
A multicenter trial of the prophylactic effect of ketotifen, theophylline, and placebo in atopic asthma
Authors: D.G. Tinkelman, B.A. Moss, S.C. Bukantz, A.L. Sheffer, J.H. Dobken, S. Chodosh, B.M. Cohen, R.R. Rosenthal, I. Rappaport, C.E. Buckley, E.L Chusid, A.J. Deutsch, G.A. Settipane, R.B.P. Burns
Journal: Journal of Allergy and Clinical Immunology (1985)
Osteoarthritis: New Insights
Authors: Thomas E. Lindow
Journal: Annals of Internal Medicine (2002)

Letters1 January 2002Osteoarthritis: New InsightsThomas E. Lindow, MDThomas E. Lindow, MDTucson, AZ 85712Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-136-1-200201010-00015 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The authors of the Systemic and Topical Treatments section in part 2 of the National Institutes of Health conference on osteoarthritis (1) did not provide a fair assessment of glucosamine and chondroitin compared with their assessment of the cyclooxygenase (COX)-2 inhibitors. Seeing that one of the three authors is sponsored by the manufacturer of the COX-2 inhibitor rofecoxib, one cannot help but suspect that market-share competition may have had something to do with the bias.The authors state, “Of note, most (if not all) trials [of glucosamine and chondroitin] were sponsored by a manufacturer of the product.” ...References1. Hochberg MC, McAlindon T, Felson DT. Systemic and topical treatments. In: Felson DT, conference chair. Osteoarthritis: new insights. Part 2: treatment approaches. Ann Intern Med. 2000; 133:726-9. [PMID: 11074906] Google Scholar Author, Article, and Disclosure InformationAffiliations: Tucson, AZ 85712 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoOsteoarthritis: New Insights. Part 2: Treatment Approaches Conference Chair: David T. Felson , Conference Organizer: Reva C. Lawrence , Discussants: Marc C. Hochberg , Timothy McAlindon , Paul A. Dieppe , Marian A. Minor , Steven N. Blair , Brian M. Berman , James F. Fries , Morris Weinberger , Kate R. Lorig , Joshua J. Jacobs , and Victor Goldberg Osteoarthritis: New Insights David D. Waddell Osteoarthritis: New Insights Paul J. Rosch Osteoarthritis: New Insights Robert H. Palmer Osteoarthritis: New Insights David T. Felson and Timothy McAlindon Metrics 1 January 2002Volume 136, Issue 1Page: 86KeywordsChondroitinCyclooxygenase 2DisclosureDrug safetyDrugsOsteoarthritisSafety ePublished: 1 January 2002 Issue Published: 1 January 2002 Copyright & PermissionsCopyright © 2002 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Is selection responsible for the low level of variation in the last intron of the ZFY locus?
Authors: J. Jaruzelska, E. Zietkiewicz, D. Labuda
Journal: Molecular Biology and Evolution (1999)

DNA variability was investigated in the last intron of the Y-chromosome-specific zinc finger gene, ZFY, and its X homolog on Xp21.3, ZFX. No polymorphisms were found in the 676-bp ZFY segment in a sample of 205 world-wide-distributed Y chromosomes, other than a solitary nucleotide variant in one individual (nucleotide diversity pi = 0.0014%). In contrast, 10 segregating sites (pi = 0.082%) were identified within 1,089 bp of the ZFX sequence in a sample of 336 X chromosomes. Four of these polymorphisms, which contributed most of the diversity, were located within an Alu insert disrupting the ZFY-ZFX homology (pi Alu = 0.24%). The diversity in the homologous portion of the ZFX intron, although higher than that in ZFY, was lower than that found in genomic segments believed to evolve neutrally; interspecies divergence in both segments was also reduced. Although this suggests that the evolution of both ZFY and ZFX homologs may not be entirely neutral, both Tajima and HKA tests did not reject neutrality. The lack of statistical significance may be attributed to a lack of power in these tests (the low divergence and variability values reduce the power of the HKA and Tajima tests, respectively); furthermore, Homo sapiens has recently undergone a rapid population growth, and selection is more difficult to detect in an expanding population. Therefore, the failure to reject neutrality does not necessarily indicate the absence of selection. In this context, the phylogenetic argument was given more weight in out interpretations. The high level of sequence identity in ZFY and ZFX segments, in spite of their separation 80-130 MYA, reflects a lower mutation rate as compared with other segments believed to undergo unconstrained evolution. Thus, the possibility of weak selection contributing to the low level of nucleotide diversity in the last ZFY intron cannot be excluded and should be kept in mind in the population genetics studies based on Y chromosome variability.
Treatment of Primary Hyperparathyroidism
Authors: Robert D. Utiger
Journal: New England Journal of Medicine (1999)

Hypercalcemia, and subsequently primary hyperparathyroidism, is discovered in two ways. Most commonly, hypercalcemia is discovered when serum calcium is measured as a screening test or in patients who have fatigue, weakness, or other symptoms of physical or neuropsychological disability. Much less often, it is discovered when serum calcium is measured in patients with nephrolithiasis or osteopenia, the two main complications of hyperparathyroidism. Unless the cause of the hypercalcemia is obvious — for example, the patient has cancer or is taking large doses of vitamin D — the next step is measurement of serum parathyroid hormone. A high or even inappropriately . . .
Dyssynchronous Breathing during Arm but Not Leg Exercise in Patients with Chronic Airflow Obstruction
Authors: Bartolome R. Celli, John Rassulo, Barry J. Make
Journal: New England Journal of Medicine (1986)

Some patients with chronic airflow obstruction experience dyspnea with mild arm exercise but not with more-intense leg exercise. To investigate why these patients have limited endurance during arm exertion, we studied ventilatory responses to exercise with unsupported arms in 12 patients with chronic airflow obstruction (mean [±SD] forced expiratory volume in one second, 0.68±0.28 liters). Unloaded leg cycling was also studied for comparison. In the five patients who had the most severe airflow obstruction, arm exercise was limited by dyspnea after 3.3±0.7 minutes, and dyssynchronous thoracoabdominal breathing developed. In the other seven patients, arm exercise was limited by the sensation of muscle fatigue after 6.1±2.0 minutes (P<0.05), and dyssynchronous breathing did not occur. None of the 12 patients had dyssynchronous breathing during unloaded leg cycling. Maximal transdiaphragmatic pressure, a measure of diaphragmatic fatigue, declined similarly after arm and leg exercise in both groups. During unsupported arm work, the accessory muscles of inspiration help position the torso and arms. We hypothesize that the extra demand placed on these muscles during arm exertion leads to early fatigue, an increased load on the diaphragm, and dyssynchronous thoracoabdominal inspirations. This sequence may contribute to dyspnea and limited endurance during upper-extremity exercise. (N Engl J Med 1986; 314: 1485–90.)
NHS agrees 7% price reduction for prescription drugs for next five years
Authors: Susan Mayor
Journal: BMJ (2004)

The NHS has agreed a 7% reduction in price for the purchase of branded prescription drugs by the NHS, after negotiations with the Association of the British Pharmaceutical Industry.

The deal has been agreed as part of the pharmaceutical price regulation scheme, a voluntary agreement between the association and the four health departments in England, Scotland, Wales, and Northern Ireland that limits the price of branded, prescription only drugs prescribed on the NHS.

It allows drug companies complete freedom to set the price of new drugs launched in the UK market but sets a target rate of return on capital, and allowances for expenditure on research and …
THE LEVELS AND CELLULAR ORIGINS OF PROCOAGULANT MICROPARTICLES WITHIN THE CULPRIT CORONARY ARTERY OF PATIENTS WITH ACUTE MYOCARDIAL INFARCTION
Authors: Pil-Ki Min, Sung-Yu Hong, Hee-Sun Mun, Sung-Joo Lee, Jong Kwan Park, Jong-Youn Kim, Byoung Kwon Lee, Bum-Kee Hong, Se-Joong Rim, Kwang-Hoe Chung, Hyuck Moon Kwon, Hyun Seung Kim
Journal: Journal of the American College of Cardiology (2010)
NKG2D ligand expression in AML increases in response to HDAC inhibitor valproic acid and contributes to allorecognition by NK-cell lines with single KIR-HLA class I specificities
Authors: Stefan Diermayr, Heike Himmelreich, Bojana Durovic, Arina Mathys-Schneeberger, Uwe Siegler, Ulrich Langenkamp, Jan Hofsteenge, Alois Gratwohl, André Tichelli, Monika Paluszewska, Wieslaw Wiktor-Jedrzejczak, Christian P. Kalberer, Aleksandra Wodnar-Filipowicz
Journal: Blood (2007)
Relaxin Improves Renal Function and Histology in Aging Munich Wistar Rats
Authors: Lee A. Danielson, Angela Welford, Alexis Harris
Journal: Journal of the American Society of Nephrology (2006)

Administration of recombinant human relaxin (rhRLX) to conscious, chronically instrumented rats increases GFR and effective renal plasma flow (ERPF) and decreases effective renal vascular resistance (ERVR) with no significant change in mean arterial pressure. The Munich Wistar albino rat shows progressive chronic nephrosis with age and therefore was used to determine the functional and histologic consequences of rhRLX on matrix remodeling in the kidney of older rats. RLX-infused rats showed increased GFR and ERPF with decreased ERVR. Furthermore, in a double-blinded examination, the renal histology showed a significant decrease in glomerular and tubular collagen deposition in the rhRLX-infused aged rats. During short-term rhRLX administration (24 h), gelatinase activity was found to be essential for renal vasodilation and hyperfiltration. Surprisingly, after 20 d, improved renal function was insensitive to the inhibition of gelatinase activity, suggesting that collagen degradation in these rats had permanently altered the matrix of the renal vasculature. In conclusion, long-term administration of rhRLX improves renal function and ameliorates renal pathology in an aging rat model. The biphasic action of rhRLX on the kidney indicates that, acutely, the vessels dilate, causing increased filtration and renal blood flow with decreased vascular resistance as a result of upregulation of gelatinase activity. Subsequently, the renal vessels undergo alteration in supporting matrix, showing increased blood supply even in the face of acute matrix metalloproteinase inhibition, most likely as a result of the inhibitory properties of RLX on collagen production or increased collagen breakdown.
Role of cholinesterase inhibitors in dementia care: Memory clinics and cholinesterase inhibitors have their place
Authors: David J Jolley, Susan M Benbow
Journal: BMJ (2006)

A prescription for better prescribing Medical education is a continuumEditor-The editorial by Aronson et al raises important concerns about the preparedness of newly qualified doctors to prescribe safely and effectively, but fails to provide evidence to support the claims that are made. 1 Importantly, the authors assume that the number of curricular hours equates to learning.The General Medical Council issues and regularly updates requirements for the content and outcomes of undergraduate medical education and the first foundation year.We deliberately do not tell medical schools how many hours must be spent on a particular subject: it is the acquisition of our learning objectives that is important.Medical education is a continuum.With respect to prescribing, as with so many other areas of medical education, we expect principles to be learnt and understood at medical school and then put into practice, under supervision, during the F1 year.Our requirements are laid out clearly in Tomorrow's Doctors and The New Doctor and include very clear expectations about the quality and extent of knowledge about the safe and effective use of drugs.Despite the strength of views expressed in the editorial, the authors have not presented robust and generally applicable evidence to show serious inadequacies in the learning of clinical pharmacology in the undergraduate medical curriculum.We look forward, however, to engaging with all interested parties to clarify the issues surrounding this very important subject.
Visualization of the Stomach on Rhenium-186 HEDP Imaging After Therapy for Metastasized Prostate Carcinoma
Authors: FREDERIC DE WINTER, BOUDEWŸN BRANS, CHRISTOPHE VAN DE WIELE, RUDY ANDRE DIERCKX
Journal: Clinical Nuclear Medicine (1999)

Post-therapeutic rhenium-186 HEDP scintigraphy revealed unexpected tracer uptake in the stomach of a 69-year-old man with prostate carcinoma. Because serum calcium and phosphate values were normal and bone scintigraphy showed no abnormal soft tissue uptake, microcalcifications in the stomach are unlikely to explain the abnormal tracer uptake. More likely, because visualization of the stomach is usually a result of trapping of free pertechnetate and because both rhenium and technetium are group VII metals, this finding was attributed to trapping of free perrhenate.
Differential expression of a human endogenous retrovirus E transmembrane envelope glycoprotein in normal, psoriatic and atopic dermatitis human skin
Authors: D. Bessis, J.P. Moles, N. Basset-Seguin, A. Tesniere, C. Arpin, J.J. Guilhou
Journal: British Journal of Dermatology (2004)

Psoriasis is a common inflammatory skin disease characterized by uncontrolled proliferation of keratinocytes and recruitment of T lymphocytes into the skin. The possible role of human endogenous retroviruses (HERVs) in the induction of psoriasis has been suggested, based upon the previous observations of retrovirus-like particles in psoriasis from skin lesional plaques, urine and stimulated lymphocytes.To investigate the expression of HERV-E transmembrane envelope glycoprotein (HERV-E env) in normal, psoriatic and atopic human skin, and to examine the influence of ultraviolet (UV) B irradiation on HERV-E env expression in normal human epidermal keratinocytes.The analysis was performed on both skin biopsies and organotypic skin cultures using immunofluorescence and Western immunoblotting. UVB irradiation (312 nm) of cultured normal human keratinocytes was performed using a dose of 30 mJ cm(-2).Positive staining was observed in most of the psoriatic and atopic skin samples, whereas only 15% of the normal skin samples were faintly positive. In addition, the pattern of expression of HERV-E env differed markedly in psoriasis vs. atopy. By Western blotting analysis, two main proteins of 54 and 57 kDa were detected in extracts of normal skin, normal keratinocyte cultures and reconstructed epidermis from psoriatic and normal punch biopsies. An increased level of expression of these proteins was noted in extracts from psoriatic vs. normal reconstructed epidermis. The overexpression of the 57-kDa protein in normal human cultured keratinocytes was dramatically reduced by UVB irradiation.These data suggest for the first time that HERV-E env is expressed in normal and pathological human skin. Further studies are now required to elucidate the role of such viral proteins in the pathogenesis of psoriasis.