tbuckley/cabot-search huggingface dataset:
Navigating the Challenge of Tumor Heterogeneity in Cancer Therapy
Authors: Clare Fedele, Richard W. Tothill, Grant A. McArthur
Journal: Cancer Discovery (2014)

Abstract Summary: The future of cancer treatment lies in personalized strategies designed to specifically target tumorigenic cell populations present in an individual. Although recent advances in directed therapies have greatly improved patient outcomes in some cancers, intuitive drug design is proving more difficult than expected owing largely to the complexity of human cancers. Intratumoral heterogeneity, the presence of multiple genotypically and/or phenotypically distinct cell subpopulations within a single tumor, is a likely cause of drug resistance. Advances in systems biology are helping to unravel the mysteries of cancer progression. In this issue of Cancer Discovery, Zhao and colleagues define a path for functional validation of computational modeling in the context of heterogeneous tumor populations and their potential for drug response and resistance. Cancer Discov; 4(2); 146–8. ©2014 AACR. See related article by Zhao et al., p. 166
Interleukin-10 induces a long-term antigen-specific anergic state in human CD4+ T cells.
Authors: H Groux, M Bigler, J E de Vries, M G Roncarolo
Journal: The Journal of Experimental Medicine (1996)

Human CD4+ T cells, activated by allogeneic monocytes in a primary mixed lymphocyte reaction in the presence of exogenous interleukin (IL) 10, specifically failed to proliferate after restimulation with the same alloantigens. A comparable state of T cell unresponsiveness could be induced by activation of CD4+ T cells by cross-linked anti-CD3 monoclonal antibodies (mAbs) in the presence of exogenous IL-10. The anergic T cells failed to produce IL-2, IL-5, IL-10, interferon gamma, tumor necrosis factor alpha, and granulocyte/macrophage colony-stimulating factor. The IL-10-induced anergic state was long-lasting. T cell anergy could not be reversed after restimulation of the cells with anti-CD3 and anti-CD28 mAbs, although CD3 and CD28 expression was normal. In addition, restimulation of anergized T cells with anti-CD3 mAbs induced normal Ca2+ fluxes and resulted in increased CD3, CD28, and class II major histocompatibility complex expression, indicating that calcineurin-mediated signaling occurs in these anergic cells. However, the expression of the IL-2 receptor alpha chain was not upregulated, which may account for the failure of exogenous IL-2 to reverse the anergic state. Interestingly, anergic T cells and their nonanergic counterparts showed comparable levels of proliferation and cytokine production after activation with phorbol myristate acetate and Ca2+ ionophore, indicating that a direct activation of a protein kinase C-dependent pathway can overcome the tolerizing effect of IL-10. Taken together, these data demonstrate that IL-10 induces T cell anergy and therefore may play an important role in the induction and maintenance of antigen-specific T cell tolerance.
Dodging the explanatory gap – or bridging it
Authors: Drew McDermott
Journal: Behavioral and Brain Sciences (2007)

Abstract Assuming our understanding of the brain continues to advance, we will at some point have a computational theory of how access consciousness works. Block's supposed additional kind of consciousness will not appear in this theory, and continued belief in it will be difficult to sustain. Appeals to “what it's like” to experience such-and-such will carry little weight when we cannot locate a subject for whom it might be like something.
Retinoic Acid Receptor β2 Hypermethylation
Authors: Reuben Lotan, Yair Lotan
Journal: Clinical Cancer Research (2004)

Cancer development involves multiple steps during which cells acquire unlimited replicative potential, autonomy in growth promoting signals, resistance to growth-suppressing signals and apoptosis, effective angiogenesis, and enhanced ability to invade and metastasize [(1)][1] . The acquisition of
Allowing Patients to Die: Practical, Ethical, and Religious Concerns
Authors: Marc J. Kahn, Cathy J. Lazarus, Donald P. Owens
Journal: Journal of Clinical Oncology (2003)

Article Tools ART OF ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.01.005 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12885824 Allowing Patients to Die: Practical, Ethical, and Religious Concerns Marc J. KahnxMarc J. KahnSearch for articles by this author , Cathy J. LazarusxCathy J. LazarusSearch for articles by this author , Donald P. OwensxDonald P. OwensSearch for articles by this author Show More From the Departments of Medicine and Psychiatry, Tulane University School of Medicine, New Orleans, LA. https://doi.org/10.1200/JCO.2003.01.005 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
Physicians' Conflicts in Patient Referrals
Authors: Rep Fortney H. (Pete) Stark
Journal: JAMA (1989)

Representative Stark, author of the Ethics in Patient Referrals Act (HR 939), argues for the need for federal oversight of the physician practice of referring patients to health facilities in which the physician has a financial interest. He takes issue with some of the conclusions reached by E. Haavi Morreim in her article in the same issue of JAMA on the problem of physician self referral. She proposes physician disclosure of interests, utilization review, quality assurance, and a judicially fashioned, common law remedy to discourage referral abuses. Stark argues that these approaches cannot effectively address the problem, and that the federal government, as an informed purchaser of health services through Medicare, should not pay for self referral.
Cost Effectiveness of Adjuvant Trastuzumab in Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer
Authors: Nicola Lucio Liberato, Monia Marchetti, Giovanni Barosi
Journal: Journal of Clinical Oncology (2007)

To evaluate the cost-effectiveness of 12-month adjuvant trastuzumab therapy in women with high-risk human epidermal growth factor receptor 2 (HER2) -positive early breast cancer.A Markov model tracked quarterly patients' transitions between five health states: disease free, local relapse, disease free after local relapse, metastatic disease, and death. Patients were allowed to incur symptomatic or asymptomatic transient cardiac dysfunction during trastuzumab administration. Probabilities were derived mainly from the combined report of the National Surgical Adjuvant Breast and Bowel Project B-31 and the North Central Cancer Treatment Group N9831 trials (95% node positive) and a meta-analysis by the Early Breast Cancer Trialists' Collaborative Group. Costs were estimated from the perspective of the Italian and US health care systems. The analysis was run during a 15-year time horizon. A 3% yearly discount rate was applied to both costs and life-years. Second-order Monte-Carlo and probabilistic sensitivity analyses were performed.Adjuvant trastuzumab increases life expectancy by 1.54 (1.18 discounted) quality-adjusted life-years (QALYs). At a cost of 675 euros and 767 dollars per weekly dose in the Italian and US setting, respectively, trastuzumab achieves its clinical benefit at a cost of 14,861 euros (95% CI, 3,917 euros to 44,028 euros) and 18,970 dollars (95% CI, 6,014 dollars to 45,621 dollars) per QALY saved. The incremental cost effectiveness was higher than 50,000 euros/QALY (or 60,000 dollars/QALY) at time horizons shorter than 7.8 years and for patients older than 76 years or with a 10-year risk of relapse lower than 15%. The results confirmed the cost effectiveness when simulating a Herceptin Adjuvant Trial (HERA) -like scenario at multiway sensitivity analysis.In a long-term horizon, adjuvant trastuzumab is a cost-effective therapy for patients with HER2-positive, high-risk, early breast cancer.
Controversial online “scorecard” shows complication rates of 17 000 US surgeons
Authors: Michael McCarthy
Journal: BMJ (2015)

An analysis of the complication rates of nearly 17 000 US surgeons regarding eight elective procedures has been posted on the internet in a searchable database that allows patients to look up and compare individual physicians.

The database, called Surgeon Scorecard, was created by the investigative journalism organization ProPublica. The website went online on 13 July.1

To create the database Olga Pierce and Marshall Allen, two ProPublica reporters, analyzed Medicare billing data over the five years from 2009 through to 2013, focusing on eight common elective surgeries: knee replacements; hip replacements; three types of spinal fusions, one in the neck and two in the lower back; gall bladder removals; prostate removals; and prostate resections. The scorecard ranks individual surgeons as having a low, medium, or high risk of complications.

In an article …
IgG and IgE Antibody Patterns after Immunotherapy with Monomethoxy Polyethyleneglycol Modified Honey Bee Venom
Authors: S. L. Nordvall, T. Uhlin, S. ÖHman, J. Björkander, H.‐J. Malling, B. Wheke, S. Dreborg, Å. Lanner, R. Einarsson
Journal: Allergy (1986)

Antibody responses to honey bee venom (HBV) were studied in 13 patients during a 4‐month course of immunotherapy with monomethoxy polyethyleneglycol (mPEG) modified venom. There was a rise of HBV‐specific IgG antibodies as measured by IgG‐RAST in all patients and a slight decrease of IgE antibody in most of them. The IgG‐antibody responses during mPEG‐HBV treatment as examined by crossed radio‐immunoelectrophoresis were directed to phospholipase A, hyaluronidase, acid phosphatase and to another allergen, antigen 1. Thus, despite a high degree of mPEG‐ modification of HBV, the immunogenicity of the most important HBV allergens was retained.
Problem-Oriented Medical Record
Authors: HAROLD D. CROSS
Journal: Annals of Internal Medicine (1973)

Comments and Corrections1 August 1973Problem-Oriented Medical RecordHAROLD D. CROSS, M.D., CHARLES S. BURGER, M.D., JOHN C. BJORN, M.D.HAROLD D. CROSS, M.D.Search for more papers by this author, CHARLES S. BURGER, M.D.Search for more papers by this author, JOHN C. BJORN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-79-2-278 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In his criticism (1) of the problem-oriented medical record (2, 3), Dr. Alvan Feinstein states that better use of the standard source-oriented medical record would suffice, yet he carefully limits his remarks to in-patients at medical centers and, to the best of our knowledge, does so without having used this record in an on-going study to test his hypotheses.Most people receiving medical care do not fall into that group. Many are cared for by several physicians—who may not have detailed chart rounds, may see...References1. FEINSTEIN A: The problems of the "problem-oriented medical record." Ann Intern Med 78:751-762, 1973 LinkGoogle Scholar2. WEED L: Medical Records, Medical Education, and Patient Care. The Problem-Oriented Record as a Basic Tool. Chicago, Yearbook Medical Publishers Inc., 1970 Google Scholar3. BJORNCROSS JH: Problem-Oriented Practice. Chicago, Modern Hospital Press, 1970 Google Scholar1. HurstWalker JH (eds.): The Problem-Oriented System. New York, Medcom, Inc., 1972, p. 23 Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Promis Clinic Hampden Highlands, Maine PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byA PROBLEM‐ORIENTATED OUTPATIENT RECORD 1 August 1973Volume 79, Issue 2Page: 278-279KeywordsChartsFalls Issue Published: 1 August 1973 PDF downloadLoading ...
Corpus gastritis is protective against reflux oesophagitis
Authors: H B El-Serag, A Sonnenberg, M M Jamal, J M Inadomi, L A Crooks, R M Feddersen
Journal: Gut (1999)

BACKGROUND Gastric acid is important in the pathogenesis of reflux oesophagitis. Acid production by the gastric corpus is reduced in corpus gastritis. AIMS To determine whether corpus gastritis protects against reflux oesophagitis. METHODS Patients presenting for elective oesophagogastroduodenoscopy were studied. Two biopsy specimens were taken from the antrum, corpus, and cardia and stained with haematoxylin/eosin and Diff-Quick II stains. The presence and severity of gastritis were graded according to a modified updated Sydney classification. RESULTS Of 302 patients, 154 had endoscopic signs of reflux oesophagitis. There was no difference between patients with and controls without oesophagitis in the overall infection rates with Helicobacter pylori . Acute or chronic corpus gastritis occurred less often in patients with than those without reflux oesophagitis. Compared with controls, corpus gastritis was less severe in patients with reflux oesophagitis. The presence of acute or chronic gastritis in the corpus was significantly correlated with either type of gastritis in other areas of the stomach. In a multivariate logistic regression, age, sex, smoking status, and the presence of chronic corpus gastritis all exerted a significant influence on the presence of reflux oesophagitis. Chronic corpus gastritis was associated with a 54% reduced risk for reflux oesophagitis. CONCLUSIONS While infection with H pylori alone may not affect the occurrence of reflux oesophagitis, the development of chronic corpus gastritis seems to be protective.
Expression of Interleukin 9 in the Lungs of Transgenic Mice Causes Airway Inflammation, Mast Cell Hyperplasia, and Bronchial Hyperresponsiveness
Authors: Ulla-Angela Temann, Gregory P. Geba, John A. Rankin, Richard A. Flavell
Journal: The Journal of Experimental Medicine (1998)

Interleukin (IL)-9, a pleiotropic cytokine produced by the Th2 subset of T lymphocytes has been proposed as product of a candidate gene responsible for asthma. Its wide range of biological functions on many cell types involved in the allergic immune response suggests a potentially important role in the complex pathogenesis of asthma. To investigate the contributions of IL-9 to airway inflammation and airway hyperresponsiveness in vivo, we created transgenic mice in which expression of the murine IL-9 cDNA was regulated by the rat Clara cell 10 protein promoter. Lung selective expression of IL-9 caused massive airway inflammation with eosinophils and lymphocytes as predominant infiltrating cell types. A striking finding was the presence of increased numbers of mast cells within the airway epithelium of IL-9–expressing mice. Other impressive pathologic changes in the airways were epithelial cell hypertrophy associated with accumulation of mucus-like material within nonciliated cells and increased subepithelial deposition of collagen. Physiologic evaluation of IL-9–expressing mice demonstrated normal baseline airway resistance and markedly increased airway hyperresponsiveness to inhaled methacholine. These findings strongly support an important role for IL-9 in the pathogenesis of asthma.
Comparison of contrast-enhanced magnetic resonance angiography and conventional pulmonary angiography for the diagnosis of pulmonary embolism: a prospective study
Authors: Matthijs Oudkerk, Edwin JR van Beek, Piotr Wielopolski, Peter MA van Ooijen, Elise MJ Brouwers-Kuyper, Alfons HH Bongaerts, Arie Berghout
Journal: The Lancet (2002)
Laparoscopic fundoplication is the treatment of choice for gastro-oesophageal reflux disease
Authors: L Lundell
Journal: Gut (2002)

Surgical treatment of gastro-oesophageal reflux disease (GORD) has previously been limited to chronic complicated reflux in patients with very longstanding severe symptoms. There is now an increasing tendency in many countries to utilise surgery in the earlier stages of the disease.1 This change in clinical practice is partly due to advances in surgical technique (laparoscopic approach) but paradoxically is also probably due to improvement in medical therapy.2,3 With the efficacy and availability of modern medical therapy, the focus, as well as the opportunities of therapy in GORD, have changed but also the recognition of the magnitude of the impairment in quality of life of GORD patients who are not adequately treated.4 This increased awareness may be the most pregnant cause of the suggested increase in prevalence of the disease in the adult population.

An important background factor for the significant but not eminent strategic decisions to be taken in the long term management of GORD patients is the fact that there are shortcomings and drawbacks with pharmacological maintenance therapy. GORD is a disease of a chronic nature where medical therapies are entirely targeting the control of acid reflux and not correcting the underlying motor abnormalities of the upper alimentary canal.5 Low dose proton pump inhibitor (PPI) therapy and full dose H2 receptor antagonists insufficiently interfere with food stimulated acid production and the latter also have a significant tachyphylaxis problem.6–8 A profound and sometimes prolonged acid rebound phenomenon is perhaps a greater problem after PPI therapy in Helicobacter pylori negative subjects than previously recognised. Furthermore, in patients with severe reflux disease, twice daily dosing of PPI is often necessary. In addition, there is sometimes insufficient control of volume reflux, nocturnal symptoms, and retrosternal pain. Acid breakthrough during the night has recently been recognised …
Gene Transfer of Connexin43 Mutants Attenuates Coupling in Cardiomyocytes
Authors: Eddy Kizana, Connie Y. Chang, Eugenio Cingolani, Genaro A. Ramirez-Correa, Rajesh B. Sekar, M. Roselle Abraham, Samantha L. Ginn, Leslie Tung, Ian E. Alexander, Eduardo Marbán
Journal: Circulation Research (2007)

Modification of electrical conduction would be a useful principle to recruit in preventing or treating certain arrhythmias, notably ventricular tachycardia (VT). Here we pursue a novel gene transfer approach to modulate electrical conduction by reducing gap junctional intercellular communication (GJIC) and hence potentially modify the arrhythmia substrate. The ultimate goal is to develop a nondestructive approach to uncouple zones of slow conduction by focal gene transfer. Lentiviral vectors encoding connexin43 (Cx43) internal loop mutants were produced and studied in vitro. Transduction of neonatal rat ventricular myocytes (NRVMs) revealed the expected subcellular localization of the mutant gene product. Fluorescent dye transfer studies showed a significant reduction of GJIC in NRVMs that had been genetically modified. Additionally, adjacent mutant gene-modified NRVMs displayed delayed calcium transients, indicative of electrical uncoupling. Multi-site optical mapping of action potential (AP) propagation in gene-modified NRVM monolayers revealed a 3-fold slowing of conduction velocity (CV) relative to nontransduced NRVMs. In conclusion, lentiviral vector-mediated gene transfer of Cx43 mutants reduced GJIC in NRVMs. Electrical charge transfer was also reduced as evidenced by delayed calcium transients in adjacent NRVMs and reduced CV in NRVM monolayers. These data validate a molecular tool that opens the prospect for gene transfer targeting gap junctions as an approach to modulate cardiac conduction.
Lymphocyte Adherence in Multiple Sclerosis
Authors: Paula Dore-Duffy, Robert B. Zurier
Journal: Journal of Clinical Investigation (1979)

Peripheral blood lymphocytes from multiple sclerosis (MS) patients form substantially greater numbers of rosettes with measles virus-infected human epithelial cells than do lymphocytes from healthy controls or from patients with other diseases. We have previously shown that prostaglandin E1-treated normal lymphocytes exhibit increased lymphocyte adherence, and thus behave like MS lymphocytes in this in vitro system. In this study we describe the effect of prostaglandin synthesis inhibition on lymphocyte adherence in both MS and control patients. Direct addition of aspirin or indomethacin to peripheral blood mononuclear cells from MS patients in vitro reduced lymphocyte adherence to control levels. Ingestion of therapeutic (anti-inflammatory) doses of aspirin (1 g, 4 times daily for 2 d) by MS patients resulted in reduction of lymphocyte adherence to levels seen in healthy controls. A single 325-mg dose of aspirin did not reduce lymphocyte adherence. A dose-dependent reduction in lymphocyte adherence was observed after single doses ranging from 650 mg to 1.3 g; duration of the effect was directly related to the aspirin dose. These observations indicate that treatment of MS patients with aspirin profoundly influences adherence of their lymphocytes to measles virus-infected cells and suggest that the altered cellular response, which results in increased lymphocyte adherence in MS patients, may be mediated by a prostaglandin-sensitive mechanism.
THE T CELL RECEPTOR: Critical Role of the Membrane Environment in Receptor Assembly and Function
Authors: Matthew E. Call, Kai W. Wucherpfennig
Journal: Annual Review of Immunology (2004)

Recent studies have demonstrated that cell membranes provide a unique environment for protein-protein and protein-lipid interactions that are critical for the assembly and function of the T cell receptor (TCR)-CD3 complex. Highly specific polar interactions among transmembrane (TM) domains that are uniquely favorable in the lipid environment organize the association of the three signaling dimers with the TCR. Each of these three assembly steps depends on the formation of a three-helix interface between one basic and two acidic residues in the membrane environment. The same polar TM residues that drive assembly also play a central role in quality control and export by directing the retention and degradation of free subunits and partial complexes, while membrane proximal cytoplasmic signals control recycling and degradation of surface receptors. Recent studies also suggest that interactions between the membrane and the cytoplasmic domains of CD3 proteins may be important for receptor triggering.
Racial and Ethnic Differences in Advanced-Stage Prostate Cancer: the Prostate Cancer Outcomes Study
Authors: R. M. Hoffman, F. D. Gilliland, J. W. Eley, L. C. Harlan, R. A. Stephenson, J. L. Stanford, P. C. Albertson, A. S. Hamilton, W. C. Hunt, A. L. Potosky
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: African-Americans have twice the risk of non-Hispanic whites for presenting with advanced-stage prostate cancer. To investigate the reasons for this difference, we evaluated the association between race/ethnicity and advanced-stage prostate cancer, adjusting for demographic, socioeconomic, clinical, and pathologic factors. Methods: A population-based cohort of 3173 men diagnosed with prostate cancer between October 1, 1994, and October 31, 1995, was analyzed. Medical record abstracts and self-administered survey questionnaires were used to obain information regarding race/ethnicity, age, marital status, insurance status, educational level, household income, employment status, comorbidity, urinary function, prostate-specific antigen level, tumor grade, and clinical stage. The odds ratio (OR) for advanced-stage prostate cancer was estimated with weighted logistic regression analysis. All P values were two-sided. Results: Clinically advanced-stage prostate cancers were detected more frequently in African-Americans (12.3%) and Hispanics (10.5%) than in non-Hispanic whites (6.3%). Socioeconomic, clinical, and pathologic factors each accounted for about 15% of the increased relative risk. After adjusting for all covariates, the risk remained statistically significantly increased for African-Americans (OR = 2.26; 95% confidence interval [CI] = 1.43 to 3.58) but not for Hispanics (OR = 1.23; 95% CI = 0.73 to 2.08). Conclusion: Traditional socioeconomic, clinical, and pathologic factors accounted for the increased relative risk for presenting with advanced-stage prostate cancer in Hispanic but not in African-American men.