tbuckley/cabot-search huggingface dataset:
A loose-fit coculture of activated keratinocytes and dendritic cell-related cells for prediction of sensitizing potential
Authors: M. Schreiner, M. Peiser, D. Briechle, R. Stahlmann, T. Zuberbier, R. Wanner
Journal: Allergy (2007)

Protection against contact allergy begins with the collection of reliable data about the sensitizing potential of chemicals. Today, the local lymph node assay (LLNA) in mice is widely used to identify sensitizing substances. For several reasons, an in vitro assay could be preferable to animal experiments. We propose an in vitro test for the detection of a sensitizing potential of a chemical composed of a single layer of human nondifferentiating keratinocytes and of allogenic floating monocytes which are cocultured in serum‐free medium in the presence of a cytokine cocktail. Within days, the coculture develops to an allergen‐ sensitive system consisting of activated keratinocytes and of mobile dendritic cell‐related cells (DC‐related cell). The sensitizing potential can be determined by analyzing the expression of the dendritic cell maturation marker CD86. For the model contact allergens tested so far [trinitrobenzenesulfonic acid (TNBS), phenylendiamine, and 4‐aminoacetanilide], the strength of the reaction was in concordance with results from the LLNA. Sensitivity of the assay allowed testing at concentrations without general cytotoxicity. Thus, a differentiation between allergens and irritants was possible. Regarding cytokine secretion, the assay distinguished between the allergen TNBS and the Toll‐like receptor ligand lipopolysaccharide. The coculture can be set up from cryopreserved cells. The assay is easy to perform and reproducible. Donor‐variance is negligible. This in vitro assay based on a loose‐fit coculture is a reasonable approach to screen for the sensitizing potential of xenobiotics and might partially replace the LLNA and other animal tests.
Truncated thioredoxin (Trx80) induces differentiation of human CD14+ monocytes into a novel cell type (TAMs) via activation of the MAP kinases p38, ERK, and JNK
Authors: Klas Pekkari, Mohammad Taghi Goodarzi, Annika Scheynius, Arne Holmgren, Javier Avila-Cariño
Journal: Blood (2004)
Reporting Clinical Trial Results
Authors: C. David Naylor
Journal: Annals of Internal Medicine (1993)

Letters1 July 1993Reporting Clinical Trial ResultsC. David Naylor, MD, DPhil and Erluo Chen, MD, MPHC. David Naylor, MD, DPhilSunnybrook Health Science Center and the Institute for Clinical Evaluative Sciences; North York, Ontario, Canada M4N 3M5 and Erluo Chen, MD, MPHSunnybrook Health Science Center and the Institute for Clinical Evaluative Sciences; North York, Ontario, Canada M4N 3M5Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-119-1-199307010-00026 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We thank Dr. Avins for his interest and cautionary comments. Assuming the stability of the relative risk reductions demonstrated in trials such as the Helsinki Heart Study [1], a cumulative increase in coronary events would indeed reduce the number of patients who must be treated to prevent one event (the number needed to treat). In highlighting the potential merits of long-term investments in prevention, however, one cannot overlook the continuing effort of treatment in relation to deferred yields. Such situations run counter to innate time preferencesour natural tendency to want benefits as soon as possible while deferring burdensome ...References1. Frick MH, Elo O, Haapa K, Heinonen OP, Heinsalmi P, Helo P, et al. Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med. 1987; 317:1237-45. Google Scholar2. Detsky AS, Naglie IG. A clinician's guide to cost-effectiveness analysis. Ann Intern Med. 1990; 113:147-54. Google Scholar3. Naylor CD, Chen E, Strauss B. Measured enthusiasm: does the method of reporting trial results alter perceptions of therapeutic effectiveness? Ann Intern Med. 1992; 117:916-21. Google Scholar Author, Article, and Disclosure InformationAffiliations: Sunnybrook Health Science Center and the Institute for Clinical Evaluative Sciences; North York, Ontario, Canada M4N 3M5 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCommunicating the Benefits of Chronic Preventive Therapy 1 July 1993Volume 119, Issue 1Page: 93-94KeywordsAbsolute risk reductionAcute myocardial infarctionClinical trial reportingDrugsForecastingHeartLongitudinal studiesMotivationRelative riskSurgery ePublished: 15 August 2000 Issue Published: 1 July 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Scintigraphic Recognition of Papillary Muscles and Papillary Muscle Ischemia
Authors: J C MILLIN, S M KIM, C H PARK, C M INTENZO
Journal: Clinical Nuclear Medicine (1993)

During stress thallium imaging, papillary muscles (anterolateral and posteromedial) appear scintigraphically as focal regions of enhanced activity in sites corresponding to their anatomic position. In the normal case, enhancement after exercise is greater than or equal to enhancement at rest. With papillary muscle ischemia, the involved papillary muscle demonstrates more enhanced activity at rest than at postexercise. This pattern change with papillary muscle ischemia was observed in four patients. Three cases demonstrated complete reversal of those ischemic changes after angioplasty and the remaining case failed to show any significant improvement after angioplasty.
Commentary: Public access to surveillance data
Authors: J. Williams
Journal: BMJ (1996)

Sentiweb would perhaps be easier to understand if the underlying Sentinel system was more fully described.1 This system was set up in 1984 jointly by the French Department of Health, and the French National Institute of Health and Medical Research to improve surveillance of communicable diseases. There are about 500 sentinel general practitioners distributed around France. At least once a week they feed an agreed simple set of information relating to the eight diseases under surveillance across the telephone network, often using the videotex Minitel terminal freely available to all telephone users, to a national database. Associated …
Omega 3 fatty acids and cardiovascular disease
Authors: Matthew D Barber
Journal: BMJ (2004)

Editor—Concern about depletion of fish stocks will not be addressed by supplementing animal feed with fish oil, as suggested by Din et al,1 because this requires the harvesting of wild fish to provide the fish oil. Fish farming does not provide a solution as farmed fish contains fewer omega 3 fatty acids, this being dependent on what they are fed—usually wild caught fish products.2​2




Figure 1



Marine algae: source of omega 3 fatty acids

Credit: SINCLAIR STAMMERS/SPL




The original source of the long chain omega 3 fatty acids found in fish is, however, the chloroplasts of marine algae and phytoplankton at the bottom of the food chain.3 In the marine environment polyunsaturated fatty acids may provide the degree of desaturation needed to keep cell membranes fluid in cold water. Rather than genetically modifying terrestrial plants to produce eicosapentaenoic and docosahexanoic acid, marine algae can be cultured industrially to provide the “fish” oil while leaving the fish alone.4

If cod liver oil is used as a source of fish oil it is important to remember that this contains a comparatively high concentration of vitamin A, producing a risk of toxicity.5
A novel allergen-adjuvant conjugate suitable for specific immunotherapy of respiratory allergy
Authors: Lucia Filì, Alessandra Vultaggio, Elisa Cardilicchia, Cinzia Manuelli, Andrea Casini, Francesca Nencini, Laura Maggi, Sara Pratesi, Giulia Petroni, Francesca Boscaro, Antonio Guarna, Ernesto G. Occhiato, Sergio Romagnani, Enrico Maggi, Paola Parronchi
Journal: Journal of Allergy and Clinical Immunology (2013)
Cutaneous side-effects of transdermal iontophoresis with and without surfactant pretreatment: a single-blinded, randomized controlled trial
Authors: G.L. Li, T.J. Van Steeg, H. Putter, J. Van Der Spek, S. Pavel, M. Danhof, J.A. Bouwstra
Journal: British Journal of Dermatology (2005)

Background Iontophoresis, a method that facilitates drug transport across skin by an external electrical field, offers the possibility for long-term transdermal delivery of compounds in a well-controlled manner. In general, the literature supports the contention that iontophoresis is a safe procedure. However, there are important medical issues concerning the epidermal and dermal effects of iontophoresis that have not been extensively investigated. Specific and strictly controlled studies on the dermal effect of iontophoresis are scarce. Objectives The aim of this study was to investigate the cutaneous side-effects of transdermal iontophoresis application in healthy human volunteers. Methods This was a single-blinded, randomized and parallel design study. In one group (n = 12) subjects were treated nonocclusively with a surfactant formulation followed by iontophoresis (3-h application at a current density of 250 µA cm−2). In another group (n = 12) iontophoresis alone was performed. No drug was included in these studies. The corresponding passive treatments served as controls. Noninvasive methods including sensation record, transepidermal water loss (TEWL), skin colour and the visual scoring were used to assess cutaneous effects. Results Tingling and itching were commonly experienced in the first 30 min of the current application. Iontophoresis in combination with the pretreatment induced significant increases in TEWL values and in skin redness, and resulted in slight to mild erythema and oedema compared with the control. Compared with the iontophoresis alone, the presence of surfactant pretreatment caused slightly more skin irritation (erythema and oedema) but did not further disturb the skin barrier function. Conclusions The transdermal iontophoresis challenges the skin barrier function and induces transient mild skin irritation, but does not cause any permanent damage to the skin when applied for 3 h at a current density of 0·25 mA cm−2.
Long-Term Effects of Traffic-Related Air Pollution on Mortality in a Dutch Cohort (NLCS-AIR Study)
Authors: Rob Beelen, Gerard Hoek, Piet A. van den Brandt, R. Alexandra Goldbohm, Paul Fischer, Leo J. Schouten, Michael Jerrett, Edward Hughes, Ben Armstrong, Bert Brunekreef
Journal: Environmental Health Perspectives (2007)

Several studies have found an effect on mortality of between-city contrasts in long-term exposure to air pollution. The effect of within-city contrasts is still poorly understood.We studied the association between long-term exposure to traffic-related air pollution and mortality in a Dutch cohort.We used data from an ongoing cohort study on diet and cancer with 120,852 subjects who were followed from 1987 to 1996. Exposure to black smoke (BS), nitrogen dioxide, sulfur dioxide, and particulate matter < or = 2.5 microm (PM(2.5)), as well as various exposure variables related to traffic, were estimated at the home address. We conducted Cox analyses in the full cohort adjusting for age, sex, smoking, and area-level socioeconomic status.Traffic intensity on the nearest road was independently associated with mortality. Relative risks (95% confidence intervals) for a 10-microg/m(3) increase in BS concentrations (difference between 5th and 95th percentile) were 1.05 (1.00-1.11) for natural cause, 1.04 (0.95-1.13) for cardiovascular, 1.22 (0.99-1.50) for respiratory, 1.03 (0.88-1.20) for lung cancer, and 1.04 (0.97-1.12) for mortality other than cardiovascular, respiratory, or lung cancer. Results were similar for NO(2) and PM(2.5), but no associations were found for SO(2).Traffic-related air pollution and several traffic exposure variables were associated with mortality in the full cohort. Relative risks were generally small. Associations between natural-cause and respiratory mortality were statistically significant for NO(2) and BS. These results add to the evidence that long-term exposure to ambient air pollution is associated with increased mortality.
Deep Molecular Response in Chronic Myeloid Leukemia: The New Goal of Therapy?
Authors: François-Xavier Mahon, Gabriel Etienne
Journal: Clinical Cancer Research (2013)

Chronic myeloid leukemia (CML) is caused by formation of the BCR-ABL1 fusion protein. Tyrosine kinase inhibitors (TKI) that target BCR-ABL1 are now the standard of care for patients with CML. Molecular monitoring of residual BCR-ABL1 mRNA transcripts, typically performed using real-time quantitative PCR, has improved treatment management, particularly for patients with CML in chronic phase. Major molecular response (MMR; i.e., a ≥3-log reduction in BCR-ABL1 transcript levels) is used in current treatment guidelines to assess prognosis. Recent evidence suggests that deeper molecular responses (≥4-log reductions in BCR-ABL1 transcript levels), particularly when attained early during treatment, may have even better correlation with long-term outcomes, including survival and disease progression. Furthermore, achieving deep molecular response is a requirement for entering trials evaluating treatment-free remission (TFR). In this review, we discuss the evolving definition of minimal residual disease and the various levels of molecular response under evaluation in current clinical studies. In addition, the available clinical data on achieving MMR and deeper levels of molecular response with TKI therapy, the prognostic value of deep molecular response, and factors that may predict a patient's ability to achieve and sustain a deep molecular response on TKI therapy are also discussed. Available data from TFR studies are addressed. We discuss current knowledge of the ideal conditions for attempting treatment discontinuation, factors predictive of molecular relapse, when TKI therapy should be restarted, and which therapeutic strategies (when administered in the first-line setting and beyond) are expected to best enable successful TFR.
Metabolic interactions between metals and metalloids.
Authors: O A Levander
Journal: Environmental Health Perspectives (1978)

The experimental evidence obtained with laboratory animals which shows that the toxicities of lead, cadmium, and mercury can be increased by deficiencies of certain essential nutrients such as calcium, iron, zinc, and selenium is briefly reviewed. An idealized theoretical model which indicates the possible influence of multiple nutritional deficiencies on the toxicity of a heavy metal is presented. It is suggested that multiple marginal nutritional deficiencies may be of importance in determining the response of humans to the toxic effects of various heavy metal pollutants.
Saxagliptin and Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus
Authors: Benjamin M. Scirica, Deepak L. Bhatt, Eugene Braunwald, P. Gabriel Steg, Jaime Davidson, Boaz Hirshberg, Peter Ohman, Robert Frederich, Stephen D. Wiviott, Elaine B. Hoffman, Matthew A. Cavender, Jacob A. Udell, Nihar R. Desai, Ofri Mosenzon, Darren K. McGuire, Kausik K. Ray, Lawrence A. Leiter, Itamar Raz
Journal: New England Journal of Medicine (2013)

The cardiovascular safety and efficacy of many current antihyperglycemic agents, including saxagliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, are unclear.We randomly assigned 16,492 patients with type 2 diabetes who had a history of, or were at risk for, cardiovascular events to receive saxagliptin or placebo and followed them for a median of 2.1 years. Physicians were permitted to adjust other medications, including antihyperglycemic agents. The primary end point was a composite of cardiovascular death, myocardial infarction, or ischemic stroke.A primary end-point event occurred in 613 patients in the saxagliptin group and in 609 patients in the placebo group (7.3% and 7.2%, respectively, according to 2-year Kaplan-Meier estimates; hazard ratio with saxagliptin, 1.00; 95% confidence interval [CI], 0.89 to 1.12; P=0.99 for superiority; P<0.001 for noninferiority); the results were similar in the "on-treatment" analysis (hazard ratio, 1.03; 95% CI, 0.91 to 1.17). The major secondary end point of a composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization, or heart failure occurred in 1059 patients in the saxagliptin group and in 1034 patients in the placebo group (12.8% and 12.4%, respectively, according to 2-year Kaplan-Meier estimates; hazard ratio, 1.02; 95% CI, 0.94 to 1.11; P=0.66). More patients in the saxagliptin group than in the placebo group were hospitalized for heart failure (3.5% vs. 2.8%; hazard ratio, 1.27; 95% CI, 1.07 to 1.51; P=0.007). Rates of adjudicated cases of acute and chronic pancreatitis were similar in the two groups (acute pancreatitis, 0.3% in the saxagliptin group and 0.2% in the placebo group; chronic pancreatitis, <0.1% and 0.1% in the two groups, respectively).DPP-4 inhibition with saxagliptin did not increase or decrease the rate of ischemic events, though the rate of hospitalization for heart failure was increased. Although saxagliptin improves glycemic control, other approaches are necessary to reduce cardiovascular risk in patients with diabetes. (Funded by AstraZeneca and Bristol-Myers Squibb; SAVOR-TIMI 53 ClinicalTrials.gov number, NCT01107886.).
Incidence of systemic lupus erythematosus among 255 patients with uveitis of unknown origin
Authors: J Jimenez-Alonso
Journal: Annals of the Rheumatic Diseases (2002)

Anterior and intermediate uveitis are inflammatory processes of diverse causes, including among others, infections, trauma, lymphoproliferative disorders, and ischaemia.The remainder are considered to have an immune pathogenesis with an autoimmune component.For example, uveitis is a common manifestation of spondyloarthropathy (SpA), a related group of disorders, with common clinical, biological, genetic, and therapeutic characteristics. 1 Within the SpA group of diseases, considerable overlap between the different disease entities can occur-for example, during the course of ankylosing spondylitis, 40% of the patients will develop acute anterior uveitis (AUU). 2 In addition, in patients with AUU, SpA is the most commonly identified systemic disease. 3 Moreover, as is true for other diseases within the SpA group, subclinical gut inflammation has been found in patients with AUU. 4 5 From a therapeutic perspective, the management of patients with AAU is targeted at stopping the inflammatory process, in the shortest time possible, as otherwise it might result in irreversible damage leading to impaired visual acuity.Most attacks can be managed by topical steroids and mydriatic agents; in severe episodes of iritis periocular injection of corticosteroids may be beneficial.Occasionally, oral administration of steroids is necessary, sometimes in combination with immunosuppressive agents.However, in some patients the uveitis appears to be treatment resistant; in others, the use of steroids is restricted owing to a lack of response, intolerance, or side effects.The beneficial effects of tumour necrosis factor α (TNFα) blockade with infliximab (Remicade) are well established in Crohn's disease and, more recently, open and placebo controlled studies indicated a significant improvement of articular symptoms of this treatment in patients with SpA. [6]7][8] Considering the disease overlap within the SpA group and the promising therapeutic results of TNFα blockade in this group of diseases, we suggested that this treatment might possibly provide a clinical benefit in SpA related uveitis.Here, we report the effect of TNFα blockade with infliximab on chronic treatment resistant uveitis in a patient with SpA.. . . .
Differential induction of functional B1-bradykinin receptors along the rat nephron in endotoxin induced inflammation
Authors: Maria E. Marin-Castaño, Joost P. Schanstra, Françoise Praddaude, João B. Pesquero, Jean-Louis Ader, Jean-Pierre Girolami, Jean-Loup Bascands
Journal: Kidney International (1998)
Obesity Drug Renews Toxicity Debate
Authors: Rebecca Voelker
Journal: JAMA (1994)

THE DISPUTE has been going on for decades: What criteria should researchers and regulators use to judge whether compounds with therapeutic potential are, in reality, neurotoxic? If the controversy is settled in the near future, it may be thanks to dexfenfluramine, an amphetamine derivative now being evaluated by the Food and Drug Administration (FDA) as an appetite suppressant. Interneuron Pharmaceuticals Inc, Lexington, Mass, which sponsored dexfenfluramine's new drug application with the FDA, calls it an antiobesity drug. The stakes for dexfenfluramine's approval are high. Given the increase in overweight Americans and the nation's obsession with being thin, new weight control medications that are effective and nonaddicting face an immense commercial market. One FDA official says dexfenfluramine has been referred to as "the $5-billion drug." There's just one catch. A handful of researchers have published animal studies that they say raise a red flag. They say that their data show evidence
A Phase II Study of Oxaliplatin, Pemetrexed, and Bevacizumab in Previously Treated Advanced Non-small Cell Lung Cancer
Authors: Rebecca Suk Heist, Panos Fidias, Mark Huberman, Blair Ardman, Lecia V. Sequist, Jennifer S. Temel, Thomas J. Lynch
Journal: Journal of Thoracic Oncology (2008)
Redox modifier genes in amyotrophic lateral sclerosis in mice
Authors: Jennifer J. Marden, Maged M. Harraz, Aislinn J. Williams, Kathryn Nelson, Meihui Luo, Henry Paulson, John F. Engelhardt
Journal: Journal of Clinical Investigation (2007)

Amyotrophic lateral sclerosis (ALS), one of the most common adult-onset neurodegenerative diseases, has no known cure. Enhanced redox stress and inflammation have been associated with the pathoprogression of ALS through a poorly defined mechanism. Here we determined that dysregulated redox stress in ALS mice caused by NADPH oxidases Nox1 and Nox2 significantly influenced the progression of motor neuron disease caused by mutant SOD1(G93A) expression. Deletion of either Nox gene significantly slowed disease progression and improved survival. However, 50% survival rates were enhanced significantly more by Nox2 deletion than by Nox1 deletion. Interestingly, female ALS mice containing only 1 active X-linked Nox1 or Nox2 gene also had significantly delayed disease onset, but showed normal disease progression rates. Nox activity in spinal cords from Nox2 heterozygous female ALS mice was approximately 50% that of WT female ALS mice, suggesting that random X-inactivation was not influenced by Nox2 gene deletion. Hence, chimerism with respect to Nox-expressing cells in the spinal cord significantly delayed onset of motor neuron disease in ALS. These studies define what we believe to be new modifier gene targets for treatment of ALS.