tbuckley/cabot-search huggingface dataset:
Abstract 3044: Cancer associated fibroblasts-derived HGF regulates cancer stem cell-like properties in hepatocellular carcinoma
Authors: Yuen Ting Lau, Jessica Lo, Irene Oi Lin Ng, Terence Kin Wah Lee
Journal: Cancer Research (2014)

Abstract Cancer stem cells (CSCs) play pivotal roles in tumor growth and therapeutic response; hence it is of fundamental importance to understand how CSCs is regulated inside the tumor mass. Similar to the regulation of normal stem cells by their ‘niche’, CSCs are also regulated by cells within the tumor microenvironment. Although most cases of HCC develop within a background of cirrhosis in which liver tissue is enriched in activated myofibroblasts, the role of cancer associated fibroblasts (CAFs) on liver CSCs within the tumor microenvironment has not yet studied. In order to achieve the goal of developing an effective therapy for HCC by specifically eliminating liver CSCs, we aim to dissect the cross-talks between HCC cells and CAFs. To study this, CAFs from fresh HCC tissues was successfully isolated, cultured and characterized by α-SMA immunoreactivity. Conditioned medium from CAFs enriched the populations of liver CSCs as reflected by an increased ability of self-renewal, chemoresistance, invasiveness and expression of stemness-associated genes and markers CD44 and CD47; and its CSC- stimulating effect was further enhanced when CAFs was stimulated with the conditioned medium of HCC cells. Using cytokine antibody array, hepatocyte growth factor (HGF) was found to be preferentially secreted by CAFs and increased upon stimulation by HCC cells. To verify whether the effect of CAFs on regulation of liver CSCs is due to HGF, the effect of recombinant HGF on regulation of liver CSCs was examined. Recombinant HGF at the physiological levels of CAFs (2ng/mL and 10ng/mL) promoted stem-like properties of HCC cells, and the effect of CAFs on CSC properties was alleviated with addition of HGF neutralizing antibody and c-met inhibitor (PHA665-752). In a cohort of HCC patient’s samples, HGF expression was significantly correlated with α-SMA (p=0.0003), suggesting the paracrine effect of CAFs on HCC cells. Further experiments showed that HCC cells induced proliferation and migration of CAFs to tumor-associated stroma; and CAFs in turn secretes HGF to regulate the CSC plasticity by activating NF-κB-mediated EMT transition. This study potentially dissects the signaling cross-talks between HCC cells and CAFs within the tumor microenvironment which may potentially open a new avenue to develop targeted therapy against this deadly disease. Citation Format: Yuen Ting Lau, Jessica Lo, Irene Oi Lin Ng, Terence Kin Wah Lee. Cancer associated fibroblasts-derived HGF regulates cancer stem cell-like properties in hepatocellular carcinoma. [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 3044. doi:10.1158/1538-7445.AM2014-3044
Prevalence and Risk Factors of Dry Eye Disease in Japan: Koumi Study
Authors: Miki Uchino, Yuji Nishiwaki, Takehiro Michikawa, Kazuhiro Shirakawa, Erika Kuwahara, Mutsuko Yamada, Murat Dogru, Debra A. Schaumberg, Tetsuya Kawakita, Toru Takebayashi, Kazuo Tsubota
Journal: Ophthalmology (2011)
The Indirect Psychological Costs of Cognitive Enhancement
Authors: Nadira Faulmüller, Hannah Maslen, Filippo Santoni de Sio
Journal: The American Journal of Bioethics (2013)

One of the main goals of the debate on the “new” cognitive enhancement substances like Ritalin and Adderall is to develop an appropriate policy regarding their regulation. In order to suggest such a policy, Veljko Dubljevic (2013) compares these enhancers to well-known drugs in their relative potential for harm. Implicit in his argument is the assumption that the new cognitive enhancers are not relevantly different in kind from other substances like alcohol or the “old” enhancer caffeine. We argue that, in being perceived negatively by the public, the new cognitive enhancers are psychologicallydifferent from other well-known drugs. Further, this negative social perception might generate indirect  psychological costs for users. These costs should be factored in to any risk–benefit analysis informing the regulation of the use of the new cognitive enhancement substances.
Immunoregulatory effects of alpha-interferon. Effects on in-vitro antibody synthesis by lymphocytes from patients with rheumatoid arthritis.
Authors: B K Pelton, A M Denman
Journal: Annals of the Rheumatic Diseases (1985)

The immunosuppressive effects of alpha-interferon (IFN) on the in-vitro synthesis of specific anti-influenza virus antibody by lymphocytes from 20 healthy donors were compared with those from 12 patients with rheumatoid arthritis. No differences were observed between the two groups. IFN suppressed the induction of in-vitro antibody synthesis by lymphocytes from rheumatoid donors but did not affect antibody synthesis once this had been initiated. Furthermore, the IFN-mediated suppression of antibody synthesised by rheumatoid lymphocytes could also be reversed by B cell helper supernatant. These findings make it unlikely that alpha-IFN affects established B cell responses characteristic of the rheumatic diseases.
Prescriptions for Peace in a Nuclear Age
Authors: George D. Lundberg
Journal: JAMA (1985)

The ethical basis for the current position of the American Medical Association (AMA) on nuclear war stems from its first Code of Medical Ethics that was adopted at the May 1846 meeting shortly after its founding. The Code contained the following provision that remained basically unchanged until 1957: "As good citizens, it is the duty of physicians to be ever vigilant for the welfare of the community, and to bear their part in sustaining its institutions and burdens." The current (1980) "Principles of Medical Ethics" of the AMA states in its preamble, "As a member of this profession, a physician must recognize responsibility not only to patients, but also to society, to other health professionals and to self." Paragraph VII of the Code states, "A physician shall recognize a responsibility to participate in activities contributing to an improved community." It was upon this backdrop that the House of Delegates of
Where Is the Evidence That the Resurgence of Nomograms Is Harmful?
Authors: David A. Grimes
Journal: Annals of Internal Medicine (2009)

Letters17 February 2009Where Is the Evidence That the Resurgence of Nomograms Is Harmful?David A. Grimes, MDDavid A. Grimes, MDFrom Family Health International, Research Triangle Park, NC 27709.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-150-4-200902170-00017 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Dr. Zwillich writes that my criticism of the “nomogram epidemic” was “fundamentally unsubstantiated.” Moreover, he suggests that use of computers “numbs” physicians. I infer that he would prefer to return to the days of slide rules for physics problems and pencil-and-paper arithmetic for completing income tax returns. When slide rules were used, mistakes by a factor of 10 were easy to make because the placement of the decimal could be unclear. This does not happen with a calculator. Although the utility of electronic versus hand calculations may be a testable hypothesis, some benefits of technology are self-evident (1).... Reference1. Smith GC, Pell JP. Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of randomised controlled trials. BMJ. 2003;327:1459-61. [PMID: 14684649] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAuthors: David A. Grimes, MDAffiliations: From Family Health International, Research Triangle Park, NC 27709.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe Nomogram Epidemic: Resurgence of a Medical Relic David A. Grimes Where Is the Evidence That the Resurgence of Nomograms Is Harmful? Samuel H. Zwillich Metrics Cited byUsing Nomograms to Reduce Harm from Clinical Calculations 17 February 2009Volume 150, Issue 4Page: 282KeywordsComputersConflicts of interestTaxes ePublished: 17 February 2009 Issue Published: 17 February 2009 Copyright & PermissionsCopyright © 2009 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Balloon angioplasty for acute myocardial infarction. Was it buried alive?
Authors: B Meier
Journal: Circulation (1990)

In the setting of acute myocardial infarction, balloon angioplasty was initially used as a com- plementary measure in patients with failure or incomplete success of intracoronary thrombolysis with streptokinase.1'2Later, it was recommended for the prevention of reocclusion after successful throm- bolysis if a significant stenosis remained.3-6Its supe- riority compared with intracoronary streptokinase therapy was proved in a randomized trial,7 and it quickly became the preferred and primary treatment in many centers equipped for emergency coronary angiography and angioplasty.8-10Then the renais- sance of intravenous fibrinolysis, triggered by the advent of clot-specific fibrinolytic agents, laid it to an See p 1910 early rest.When large-scale randomized trials11,12 invalidated smaller studies advocating a combined approach,13-15 acute infarction angioplasty seemed buried for good, much to the relief of spouses of interventional cardiologists and directors of nonprofit hospitals with facilities for interventional cardiology.Currently, however, it is slipping back in through the rear door under the alias of rescue angioplasty,16 looking for subgroups of patients treated by intrave- nous fibrinolysis who are in need of a mechanical procedure.The article by Kahn et al17 in this issue of Circula- tion is the latest in a series published by these researchers on emergency balloon angioplasty for acute myocardial infarction unassociated with fi- brinolysis.The series started with the original report introducing this concept8 and culminated in a flurry of recent publications campaigning for the resurrec- tion of acute infarction angioplasty.18-21Though there are definitely supporters of this therapy,22-24 others are rather skeptical.25As with all new treatment modalities and indications, one has to prove that primary coronary angioplasty for treatment of evolving infarction is safe
Antisense-mediated exon skipping to correct IL-12Rβ1 deficiency in T cells
Authors: Esther van de Vosse, Els M. Verhard, Roelof A. de Paus, Gerard J. Platenburg, Judith C. T. van Deutekom, Annemieke Aartsma-Rus, Jaap T. van Dissel
Journal: Blood (2009)
Careers in academic general practice
Authors: S. Hilton
Journal: BMJ (1995)

EDITOR,—Although an occupant of the corner so clearly fought for by Aly Rashid and colleagues in their recommendations on the need to increase general practitioners' contribution to teaching and research,1 I am concerned that those in other corners will view their paper as a polemic, or at best a case of special pleading. Historically, general practice has been service dominated. The opportunity for rapid attainment of principal status (compared with consultant status) has made acquiring research experience in junior academic posts unattractive financially. With respect to teaching, however, the vocational training …
A study of the comparative efficacy of diflucortolone valerate 0.3% ointment and clobetasol propionate 0.05% oontment
Authors: H. WENDT, C.J. MCGGLESTONE†, R.A. WISEMANI
Journal: British Journal of Dermatology (1978)

Three hundred and fifty-four patients with symmetrical dermatoses took part in a multicentre, double-blind, half-side study in order to compare the efficacy of a new topical steroid, diflucortolone valerate 0.3% (Nerisone Forte) against that of an established, potent topical steroid, clobetasol propionate 0.05% (Dermovate). The assessment of overall response, as judged by the physicians preference for one side or another, showed no difference between the two compounds. However, when the results were examined by separate diagnostic category the number of preferences was greater for diflucortolone valerate 0.3% in eczema, and for clobetasol propionate 0.05% in psoriasis, although neither of these differences reached levels of statistical significance. The graded assessments of response indicated that both compounds were highly effective, potent, topical steroids. Eighty-one percent of patients showed marked improvement or heating with diflucortolone valerate 0.3% and 84% showed marked improvement or healing with clobetasol propionate 0.05%. This difference was not statistically significant. Analysis of response, either by diagnosis or grade of severity, showed no statistically significant differences between the two compounds. No significant differences in the incidence of severity of side-effects were observed. It was concluded that the two compounds were of equal clinical efficacy.
Pathologie und Klinik; Band XIV. Lungenemphesem; Morphologie, Pathogenese und funktionelle Bedeutung
Authors: Robert W. Carton
Journal: JAMA (1964)

Dr. Hartung's monograph reviews the pathology, pathogenesis, and pathophysiology of pulmonary emphysema. No full-dress review of this type has appeared since that of Loeschcke, published in 1928. The section on pathology is thorough and valuable; it incorporates the contributions made by the study of thick whole-lung sections over the past ten years. The position of the pathological lesion as the unifying concept in emphysema is made clear. The section on pathogenesis is equally thorough, and no major idea now current is overlooked. A number of unproved assertions are, however, advanced (eg, the bulk of clinical emphysema is classified as secondary to anatomically demonstrable "bronchostenotic" mechanisms, a point still in serious dispute). Dr. Hartung's own development of physiological measurements of the cadaver lung is interesting. His methods deserve wider imitation and trial. The chief glory of this book, however, and the one which should make it indispensable for active workers in
New Metabolizable Immunologic Adjuvant for Human Use
Authors: Robert E. Weibel, Allen F. Woodhour, Joseph Stokes, Don P. Metzgar, Maurice R. Hilleman
Journal: New England Journal of Medicine (1967)

PREVIOUS reports by our group1 2 3 4 5 6 described the development and clinical evaluation of a new immunologic adjuvant, named adjuvant 65, which was applied to influenza-virus vaccine. The adjuvant preparation consisted of a water-in-peanut-oil emulsion of the aqueous vaccine employing mannide mono-oleate (Arlacel A) as emulsifier and aluminum monostearate as stabilizer. A detailed analytic review of all the available data on adjuvants and adjuvant 65 has been reported elsewhere.7 The desirability for maximal purity of antigens included in adjuvant formulations led to the development of a highly purified aqueous influenza-virus vaccine that has been tested both as aqueous material and incorporated into . . .
Neutrophil Sequestration and Pulmonary Dysfunction in a Canine Model of Open Heart Surgery With Cardiopulmonary Bypass
Authors: William J. Dreyer, Lloyd H. Michael, Ellen E. Millman, Kurt L. Berens, Robert S. Geske
Journal: Circulation (1995)

Background Previous studies documented an inflammatory reaction to cardiopulmonary bypass with neutrophil (PMN) sequestration in the lungs, contributing to microvascular injury and postoperative pulmonary dysfunction. This study explored the hypothesis that the β 2 integrin CD18, a leukocyte adhesion molecule, mediates this response. Methods and Results Fifteen adult, mixed-breed dogs underwent 90 minutes of cardiopulmonary bypass with 3 hours of subsequent recovery. Seven additional dogs were treated before cardiopulmonary bypass with a 1-mg/kg IV bolus of R15.7 IgG, a monoclonal antibody to CD18. Both groups were compared with 5 sham bypass control dogs. Bypassed dogs demonstrated an increased number of PMNs sequestered in the lungs 3 hours after bypass compared with sham bypass control dogs (1466±75 versus 516±43 PMN/mm 2 alveolar surface area, mean±SEM, P &lt;.001). Also, when PMNs from bypass dogs were compared with those from sham dogs, they produced more H 2 O 2 (305±45 versus 144±48 amol H 2 O 2 per phagocyte per 20 minutes, P &lt;.05). Bypass dogs had significantly decreased arterial oxygenation 3 hours after the procedure compared with shams (457±20 versus 246±49 mm Hg, P &lt;.05), and they had a significantly increased lung wet-to-dry weight ratio (5.38±0.14 versus 4.54±0.15, P =.003), demonstrating a significant increase in lung water. R15.7 markedly attenuated pulmonary PMN accumulation in bypass dogs (412±73 PMN/mm 2 , P &lt;.001) and significantly inhibited PMN production of H 2 O 2 (146±18 amol H 2 O 2 per phagocyte per 20 minutes, P &lt;.05) Bypass dogs pretreated with R15.7 also had improved oxygenation (445±28 mm Hg, P &lt;.05) and tended to have less lung water accumulation after bypass (4.99±0.20). Conclusions Pulmonary dysfunction after cardiopulmonary bypass is caused, at least in part, by a neutrophil-mediated, CD18-dependent mechanism.
Intermittent low dose prednisolone is safe in rheumatoid arthritis
Authors: P. C Gotzsche, H. K. Johansen
Journal: BMJ (1998)

<h3>ABSTRACT</h3> <h3>Background</h3> Evidence from animal studies suggests that greater reductions in post-stroke motor impairment can be attained with significantly higher doses and intensities of therapy focused on movement quality. These studies also indicate a dose-timing interaction, with more pronounced effects if high-intensity therapy is delivered in the acute/subacute, rather than chronic, post-stroke period. <h3>Objective</h3> To compare two approaches of delivering high-intensity, high-dose upper limb therapy in patients with subacute stroke: a novel exploratory neuro-animation therapy (NAT), and modified conventional occupational therapy (COT). <h3>Methods</h3> Twenty-four patients were randomized to NAT or COT and underwent 30 sessions of 60 minutes time-on-task in addition to standard care. The primary outcome was the Fugl-Meyer Upper Extremity motor score (FM-UE). Secondary outcomes included: Action Research Arm Test (ARAT), grip strength, Stroke Impact Scale (SIS) hand domain, and upper-limb kinematics. Outcomes were assessed at baseline, and days 3, 90, and 180 post-training. Both groups were compared to a matched historical cohort (HC), which received only 30 minutes of upper limb therapy per day. <h3>Results</h3> There were no significant between-group differences in FM-UE change or any of the secondary outcomes at any timepoint. Both high-dose groups showed greater recovery on the ARAT (7.3 ±2.9 pts, p=0.011), but not the FM-UE (1.4 ±2.6 pts, p =0.564) when compared to the HC. <h3>Conclusions</h3> Two forms of high-dose intensive upper limb therapy produced greater activity but not impairment improvements compared with regular care. Neuroanimation may offer a new enjoyable, efficient and scalable way to deliver increased upper limb therapy. Clinicaltrials.gov registration NCT02292251
Slow Infusion of Vinca Alkaloids in Idiopathic Thrombocytopenic Purpura
Authors: A. MANOHARAN
Journal: Annals of Internal Medicine (1984)

Letters and Corrections1 June 1984Slow Infusion of Vinca Alkaloids in Idiopathic Thrombocytopenic PurpuraA. MANOHARAN, M.D.A. MANOHARAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-100-6-921_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I read with interest the article by Ahn and coworkers (1) on slow infusion of vinca alkaloids in the treatment of idiopathic thrombocytopenic purpura, which reported good to excellent responses in 17 of 24 patients. In the past 2 years I have treated 5 women with slow infusions of vincristine at a standard dose of 2 mg given over a 4-hour period at weekly intervals for 4 weeks. Two patients responded with sustained increases in platelet counts, for 4 months and 20 months, respectively. There were no untoward clinical or laboratory side effects associated with vincristine therapy....References1. AHNHARRINGTONMYLVAGANAMALLENPALL YWRLL. Slow infusion of vinca alkaloids in the treatment of idiopathic thrombocytopenic purpura. Ann Intern Med. 1984;100:192-6. LinkGoogle Scholar2. AHNHARRINGTONSEELMAN YWR. Vincristine therapy of idiopathic and secondary thrombocytopenias. N Engl J Med 1974;291:376-80. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: A. MANOHARAN, M.D.Affiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1984Volume 100, Issue 6Page: 921-921KeywordsAlkaloidsClinical laboratoriesIdiopathic thrombocytopenic purpuraPlateletsResearch laboratories ePublished: 1 December 2008 Issue Published: 1 June 1984 PDF downloadLoading ...
Abstract 3603: Development of novel small molecule PIM kinase inhibitors
Authors: Carmen M. Baldino, Justin Caserta, Chee-Seng Lee, Yvonne Flanders, Stephane Dumas, Jixian Li, Chunping Xu, Jinying Ning, Taiping Chen, Yiyou Chen
Journal: Cancer Research (2011)

Abstract The PIM family of serine/threonine kinases, regulated by cytokines and growth factors, is over-expressed in multiple cancer types, including prostate tumors and hematologic malignancies. Recent reports of PIM kinase inhibitors have been implicated with anti-tumor growth activity in cancer cells and xenograft models, thus providing evidence that PIM kinases are attractive targets for anticancer drug development. Jasco Pharmaceuticals has developed a proprietary focused screening library of small molecules designed to inhibit PIM kinase activity. Kinase panel screening of the focused set identified nanomolar inhibitors from a novel chemical series. To further characterize the compounds, Jasco Pharma has established a research partnership with Crown BioScience for access to its cancer cell line and human primary tumor (HuPrime) xenograft models. The initial efforts of this partnership involved the identification of cancer cell lines which express high levels of PIM kinases for anti-proliferation studies and MOA exploration. Medicinal chemistry optimization provided a cluster of compounds with low single-digit micromolar anti-proliferation activity. These improved compounds have been demonstrated to act through a PIM driven mechanism of action, decreasing the levels of the proto-oncogene c-myc and the phosphorylation of the proteins BAD and 4E-BP1. In order to select the compounds with better in vivo drug activity, we performed in vivo PK followed by plasma protein binding assay (PPB) and drug-drug interaction (DDI) analysis instead of the whole series of in vitro ADME property assays. Four compounds were picked up for in vivo efficacy study according to their potency, in vivo pk characteristics, results of PPB and DDI. Preliminary results indicated that one compound had significant anti-tumor activity in MV-4-11 tumor models. 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 3603. doi:10.1158/1538-7445.AM2011-3603