tbuckley/cabot-search huggingface dataset:
Immunologic injury in measles virus infection. II. Suppression of immune injury through antigenic modulation.
Authors: B S Joseph, M B Oldstone
Journal: The Journal of Experimental Medicine (1975)

Upon the addition of antibody to measles virus, measles virus antigens expressed on the surface of infected cells can be modulated from the cell's membrane in vitro. Removal of measles virus antigens from the surface of cells occurs relatively rapidly and is accompanied by a parallel reduction in the ability of antibody and complement to lyse these cells. Modulation of surface viral antigens can occur in the absence of cap formation and is fully reversible once measles virus antibodies are removed from culture medium. Protracted exposure of acutely infected cells to measles virus antibodies results in a population of cells that exhibit normal cytomorphology and growth behavior. These cells continue to express measles virus antigens internally, but not at the cell surface, and are refractory to immune lysis. Once antiviral antibody is removed, measles virus antigens again appear on the cell surface, giant cell and syncytial formation occur, and cell death follows. These observations may explain the persistence of virus in spite of a vigorous host antiviral immune response in certain chronic infections of man.
Estimation of Cardiac Output from Precordial Dilution Curves in Patients with Cardiopulmonary Disease
Authors: BERNARD F. SCHREINER, FRANK W. LOVEJOY, PAUL N. YU, MRS. SURAN MAGRUDER, MRS. RUTH KNIGHT
Journal: Circulation Research (1959)

Comparison of flow rates measured from precordial dilution curves, simultaneous direct arterial dilution curves, and nearly simultaneous Fick determinations in 29 patients failed to indicate any difference in precision. Successive precordial determinations of flow rate were adequately reproducible. It is concluded that the precordial dilution method gives flow values comparable to those obtained by other, more laborious methods.
Chelation use and iron burden in North American and British thalassemia patients: a report from the Thalassemia Longitudinal Cohort
Authors: Janet L. Kwiatkowski, Hae-Young Kim, Alexis A. Thompson, Charles T. Quinn, Brigitta U. Mueller, Isaac Odame, Patricia J. Giardina, Elliott P. Vichinsky, Jeanne M. Boudreaux, Alan R. Cohen, John B. Porter, Thomas Coates, Nancy F. Olivieri, Ellis J. Neufeld
Journal: Blood (2012)
A Universal Strategy for Adoptive Immunotherapy of Cancer through Use of a Novel T-cell Antigen Receptor
Authors: Katarzyna Urbanska, Evripidis Lanitis, Mathilde Poussin, Rachel C. Lynn, Brian P. Gavin, Sander Kelderman, Jason Yu, Nathalie Scholler, Daniel J. Powell
Journal: Cancer Research (2012)

Abstract Adoptive immunotherapies composed of T cells engineered to express a chimeric antigen receptor (CAR) offer an attractive strategy for treatment of human cancer. However, CARs have a fixed antigen specificity such that only one tumor-associated antigen (TAA) can be targeted, limiting the efficacy that can be achieved because of heterogeneous TAA expression. For this reason, a more generalized and effective application of CAR therapy would benefit from the capability to produce large panels of CARs against many known TAAs. In this study, we show a novel strategy to extend the recognition specificity potential of a bioengineered lymphocyte population, allowing flexible approaches to redirect T cells against various TAAs. Our strategy employs a biotin-binding immune receptor (BBIR) composed of an extracellular-modified avidin linked to an intracellular T-cell signaling domain. BBIR T cells recognized and bound exclusively to cancer cells pretargeted with specific biotinylated molecules. The versatility afforded by BBIRs permitted sequential or simultaneous targeting of a combination of distinct antigens. Together, our findings show that a platform of universal T-cell specificity can significantly extend conventional CAR approaches, permitting the tailored generation of T cells of unlimited antigen specificity for improving the effectiveness of adoptive T-cell immunotherapies for cancer. Cancer Res; 72(7); 1844–52. ©2012 AACR.
Meta-Analysis of Magnetic Resonance Imaging in Detecting Residual Breast Cancer After Neoadjuvant Therapy
Authors: Michael L. Marinovich, Nehmat Houssami, Petra Macaskill, Francesco Sardanelli, Les Irwig, Eleftherios P. Mamounas, Gunter von Minckwitz, Meagan E. Brennan, Stefano Ciatto
Journal: JNCI Journal of the National Cancer Institute (2013)

It has been proposed that magnetic resonance imaging (MRI) be used to guide breast cancer surgery by differentiating residual tumor from pathologic complete response (pCR) after neoadjuvant chemotherapy. This meta-analysis examines MRI accuracy in detecting residual tumor, investigates variables potentially affecting MRI performance, and compares MRI with other tests.A systematic literature search was undertaken. Hierarchical summary receiver operating characteristic (HSROC) models were used to estimate (relative) diagnostic odds ratios ([R]DORs). Summary sensitivity (correct identification of residual tumor), specificity (correct identification of pCR), and areas under the SROC curves (AUCs) were derived. All statistical tests were two-sided.Forty-four studies (2050 patients) were included. The overall AUC of MRI was 0.88. Accuracy was lower for "standard" pCR definitions (referent category) than "less clearly described" (RDOR = 2.41, 95% confidence interval [CI] = 1.11 to 5.23) or "near-pCR" definitions (RDOR = 2.60, 95% CI = 0.73 to 9.24; P = .03.) Corresponding AUCs were 0.83, 0.90, and 0.91. Specificity was higher when negative MRI was defined as contrast enhancement less than or equal to normal tissue (0.83, 95% CI = 0.64 to 0.93) vs no enhancement (0.54, 95% CI = 0.39 to 0.69; P = .02), with comparable sensitivity (0.83, 95% CI = 0.69 to 0.91; vs 0.87, 95% CI = 0.80 to 0.92; P = .45). MRI had higher accuracy than mammography (P = .02); there was only weak evidence that MRI had higher accuracy than clinical examination (P = .10). No difference in MRI and ultrasound accuracy was found (P = .15).MRI accurately detects residual tumor after neoadjuvant chemotherapy. Accuracy was lower when pCR was more rigorously defined, and specificity was lower when test negativity thresholds were more stringent; these definitions require standardization. MRI is more accurate than mammography; however, studies comparing MRI and ultrasound are required.
Stroma-Initiated Hedgehog Signaling Takes Center Stage in B-Cell Lymphoma
Authors: Ralph K. Lindemann
Journal: Cancer Research (2008)

Abstract Hedgehog-mediated signaling has been shown to promote growth and dissemination of solid cancers, most prominently basal cell carcinomas and medulloblastoma. Recent findings indicate that hedgehog signals are also important for tumor growth in hematologic malignancies. Hedgehog ligands secreted by stromal cells could elicit Patched/Smoothened-mediated antiapoptotic signaling in mouse B-cell lymphomas. Inhibition of hedgehog signaling induced apoptosis in lymphoma cells and prolonged survival of lymphoma-bearing mice. Depletion of tumor cells proceeded in the absence of p53 via the mitochondrial apoptotic pathway. These and other recently published data on hedgehog inhibition in cancer cells and their implications will be discussed. [Cancer Res 2008;68(4):961–4]
Systematic Review: Anti–Epidermal Growth Factor Receptor Treatment Effect Modification by<i>KRAS</i>Mutations in Advanced Colorectal Cancer
Authors: Issa J. Dahabreh, Teruhiko Terasawa, Peter J. Castaldi, Thomas A. Trikalinos
Journal: Annals of Internal Medicine (2011)

Background: KRAS mutations have been extensively investigated as predictive biomarkers for treatment of advanced colorectal cancer with the anti–epidermal growth factor receptor (EGFR) antibodies cetuximab and panitumumab. Purpose: To summarize whether KRAS mutation status modifies effects of anti-EGFR–based treatments for patients with advanced colorectal cancer and whether KRAS status predicts clinical outcomes among such patients. Data Sources: MEDLINE and 2 curated genetics databases (through 24 March 2010) were searched for observational studies. MEDLINE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effects (through 1 September 2010) were searched for randomized, controlled trials. No search was restricted by language. Study Selection: Three reviewers screened titles and abstracts to identify published studies assessing KRAS mutations as predictors of overall and progression-free survival or treatment failure for patients who received anti-EGFR–based therapy for metastatic colorectal cancer. Data Extraction: Three investigators extracted data on population and study-design characteristics, including quality items, and on outcomes of interest. Random-effects meta-analyses were done on nonoverlapping studies. Data Synthesis: In 4 reanalyses of randomized trials of anti-EGFR–based therapy versus best supportive care or cytotoxic chemotherapy, no significant benefit was found for overall or progression-free survival from anti-EGFR–based treatment among KRAS-positive patients (hazard ratio [HR], 1.0). However, evidence favors anti-EGFR therapy among KRAS wild-type patients; the relative HR across KRAS-positive and wild-type patients was 1.30 (95% CI, 0.95 to 1.78) for overall survival and 2.22 (CI, 1.74 to 2.84) for progression-free survival by random-effects meta-analysis. In 13 cohorts of patients who received anti-EGFR antibodies, the summary HR for overall survival was 1.79 (CI, 1.48 to 2.17), with better survival in wild-type patients. The corresponding HR for progression-free survival was 2.11 (CI, 1.74 to 2.55 [16 cohorts]). In random-effects bivariate meta-analysis of 22 studies, the summary sensitivity of KRAS mutations for predicting lack of response was 0.49 (CI, 0.43 to 0.55), and summary specificity was 0.93 (CI, 0.87 to 0.97). Limitations: Limited evidence from randomized studies exists. Patient-level data are needed to assess modifiers of the mutation-by-treatment interaction. Publication bias could be a concern. Conclusion: KRAS mutations are consistently associated with reduced overall and progression-free survival and increased treatment failure rates among patients with advanced colorectal cancer treated with anti-EGFR antibodies. Primary Funding Source: Agency for Healthcare Research and Quality.
Recommended Patient-Reported Core Set of Symptoms to Measure in Adult Cancer Treatment Trials
Authors: B. B. Reeve, S. A. Mitchell, A. C. Dueck, E. Basch, D. Cella, C. M. Reilly, L. M. Minasian, A. M. Denicoff, A. M. O'Mara, M. J. Fisch, C. Chauhan, N. K. Aaronson, C. Coens, D. W. Bruner
Journal: JNCI Journal of the National Cancer Institute (2014)

The National Cancer Institute’s Symptom Management and Health-Related Quality of Life Steering Committee held a clinical trials planning meeting (September 2011) to identify a core symptom set to be assessed across oncology trials for the purposes of better understanding treatment efficacy and toxicity and to facilitate cross-study comparisons. We report the results of an evidence-synthesis and consensus-building effort that culminated in recommendations for core symptoms to be measured in adult cancer clinical trials that include a patient-reported outcome (PRO). We used a data-driven, consensus-building process. A panel of experts, including patient representatives, conducted a systematic review of the literature (2001–2011) and analyzed six large datasets. Results were reviewed at a multistakeholder meeting, and a final set was derived emphasizing symptom prevalence across diverse cancer populations, impact on health outcomes and quality of life, and attribution to either disease or anticancer treatment. We recommend that a core set of 12 symptoms—specifically fatigue, insomnia, pain, anorexia (appetite loss), dyspnea, cognitive problems, anxiety (includes worry), nausea, depression (includes sadness), sensory neuropathy, constipation, and diarrhea—be considered for inclusion in clinical trials where a PRO is measured. Inclusion of symptoms and other patient-reported endpoints should be well justified, hypothesis driven, and meaningful to patients. This core set will promote consistent assessment of common and clinically relevant disease- and treatment-related symptoms across cancer trials. As such, it provides a foundation to support data harmonization and continued efforts to enhance measurement of patient-centered outcomes in cancer clinical trials and observational studies.
Clinical Prevention of Sudden Cardiac Death by n-3 Polyunsaturated Fatty Acids and Mechanism of Prevention of Arrhythmias by n-3 Fish Oils
Authors: Alexander Leaf, Jing X. Kang, Yong-Fu Xiao, George E. Billman
Journal: Circulation (2003)

T his review will be limited specifically to the beneficial prevention by the n-3 polyunsaturated fatty acids (PUFAs) of arrhythmic deaths, including sudden cardiac death, which annually causes some 300 000 deaths in the United States and millions more worldwide.We will also show that the growing body of positive clinical studies is supported by what has been learned in animal and laboratory studies regarding the mechanism by which n-3 PUFAs prevent cardiac arrhythmias.
Expression of the multidrug resistance-associated protein (MRP) gene in primary non-small-cell lung cancer
Authors: K Nooter, F T Bosman, H Burger, K E van Wingerden, M J Flens, R J Scheper, R G Oostrum, A W Boersma, A van der Gaast, G Stoter
Journal: Annals of Oncology (1996)
Control of Cardiac Repolarization by Phosphoinositide 3-Kinase Signaling to Ion Channels
Authors: Lisa M. Ballou, Richard Z. Lin, Ira S. Cohen
Journal: Circulation Research (2014)

Upregulation of phosphoinositide 3-kinase (PI3K) signaling is a common alteration in human cancer, and numerous drugs that target this pathway have been developed for cancer treatment. However, recent studies have implicated inhibition of the PI3K signaling pathway as the cause of a drug-induced long-QT syndrome in which alterations in several ion currents contribute to arrhythmogenic drug activity. Surprisingly, some drugs that were thought to induce long-QT syndrome by direct block of the rapid delayed rectifier (IKr) also seem to inhibit PI3K signaling, an effect that may contribute to their arrhythmogenicity. The importance of PI3K in regulating cardiac repolarization is underscored by evidence that QT interval prolongation in diabetes mellitus also may result from changes in multiple currents because of decreased insulin activation of PI3K in the heart. How PI3K signaling regulates ion channels to control the cardiac action potential is poorly understood. Hence, this review summarizes what is known about the effect of PI3K and its downstream effectors, including Akt, on sodium, potassium, and calcium currents in cardiac myocytes. We also refer to some studies in noncardiac cells that provide insight into potential mechanisms of ion channel regulation by this signaling pathway in the heart. Drug development and safety could be improved with a better understanding of the mechanisms by which PI3K regulates cardiac ion channels and the extent to which PI3K inhibition contributes to arrhythmogenic susceptibility.
Predictors and outcomes of respiratory failure among hospitalized pneumonia patients with 2009 H1N1 influenza in Taiwan
Authors: Yu-San Chien, Chia-Ping Su, Huai-Te Tsai, Angela S. Huang, Chia-En Lien, Min-Nan Hung, Jen-Hsiang Chuang, Hsu-Sung Kuo, Shan-Chwen Chang
Journal: Journal of Infection (2009)
Prospective Study of Hyperglycemia and Cancer Risk
Authors: Pär Stattin, Ove Björ, Pietro Ferrari, Annekatrin Lukanova, Per Lenner, Bernt Lindahl, Göran Hallmans, Rudolf Kaaks
Journal: Diabetes Care (2007)

OBJECTIVE—To investigate whether hyperglycemia is associated with increased cancer risk. RESEARCH DESIGN AND METHODS—In the Västerbotten Intervention Project of northern Sweden, fasting and postload plasma glucose concentrations were available for 33,293 women and 31,304 men and 2,478 incident cases of cancer were identified. Relative risk (RR) of cancer for levels of fasting and postload glucose was calculated with the use of Poisson models, with adjustment for age, year of recruitment, fasting time, and smoking status. Repeated measurements 10 years after baseline in almost 10,000 subjects were used to correct RRs for random error in glucose measurements. RESULTS—Total cancer risk in women increased with rising plasma levels of fasting and postload glucose, up to an RR for the top versus bottom quartile of 1.26 (95% CI 1.09–1.47) (Ptrend &amp;lt;0.001) and 1.31 (1.12–1.52) (Ptrend = 0.001), respectively. Correction for random error in glucose measurements increased these risks up to 1.75 (1.32–2.36) and 1.63 (1.26–2.18), respectively. For men, corresponding uncorrected RR was 1.08 (0.92–1.27) (Ptrend = 0.25) and 0.98 (0.83–1.16) (Ptrend = 0.99), respectively. Risk of cancer of the pancreas, endometrium, urinary tract, and of malignant melanoma was statistically significantly associated with high fasting glucose with RRs of 2.49 (1.23–5.45) (Ptrend = 0.006), 1.86 (1.09–3.31) (Ptrend = 0.02), 1.69 (0.95–3.16) (Ptrend = 0.049), and 2.16 (1.14–4.35) (Ptrend = 0.01), respectively. Adjustment for BMI had no material effect on risk estimates. CONCLUSIONS—The association of hyperglycemia with total cancer risk in women and in women and men combined for several cancer sites, independently of obesity, provides further evidence for an association between abnormal glucose metabolism and cancer.
Variety of Roles for Molecular Genetics in Dealing With Cardiovascular Disease
Authors: Paul Cotton.
Journal: JAMA (1993)

GENETICS, one of medicine's leading hopes for advancement, is initiating what promises to be a slow assault on the leading killer, heart disease. More than 5% of all cataloged genes affect the heart in some way, notes Reed E. Pyeritz, MD, PhD, chair of human genetics at the Allegheny Singer Research Institute, Pittsburgh, Pa. So "hundreds of genes are likely to be important in the development and normal physiology of the cardiovascular system," says Pyeritz, who moderated a symposium on cardiovascular molecular genetics at the American Society of Human Genetics meeting in New Orleans, La. Most forms of heart disease appear to be multifactorial, with environmental risk factors as important, if not more so, than the initial conditions set down by genetics. But for rarer forms of heart disease, which have clear and concise genetic causes, the prospects for effective gene therapy seem good. <h3>Preliminary Success</h3> A human trial of
Time interval to conversion of interferon-γ release assay after exposure to tuberculosis
Authors: S.W. Lee, D.K. Oh, S.H. Lee, H.Y. Kang, C-T. Lee, J-J. Yim
Journal: European Respiratory Journal (2010)

The proper interval for repeating an interferon-γ release assay (IGRA) among tuberculosis contacts with initially negative results is unknown. The interval for IGRA conversion after exposure to patients with active pulmonary tuberculosis in an outbreak setting was evaluated. In a platoon of 32 soldiers, four active pulmonary tuberculosis patients, in addition to one index patient, were diagnosed during a contact investigation. For the other 27 contacts, a tuberculin skin test (TST) and QuantiFERON ® TB-Gold In-Tube (QFT-GIT) assay were performed. For soldiers with a negative result on the initial QFT-GIT assay, the test was repeated at 2, 4, 8, 14, 18 and 30 weeks until positive conversion occurred. When conversion was identified, the subject was treated for latent tuberculosis infection. Initially, 17 (63.0%) soldiers gave positive QFT-GIT results, whereas 21 (77.8%) showed positive TST results. Among 10 participants with initially negative QFT-GIT results, three showed conversion at 2 weeks, three at 4 weeks and three at 14 weeks. Conversion did not occur during the 30-week observation period in one contact. Based on the tuberculosis exposure time-points among the contacts, IGRA conversion generally occurred 4–7 weeks after exposure, although it could occur as late as 14–22 weeks after exposure.
Electrophoretic and Ultracentrifugal Analysis of Serum Lipoproteins of Normal, Nephrotic and Hypertensive Persons
Authors: LENA A. LEWIS, IRVINE H. PAGE
Journal: Circulation (1953)

Using a method of ultracentrifugation which brings out clearly the α and β lipoprotein components of serum, studies of normal, hypertensive and nephrotic human beings have been made. There are striking differences in distribution of lipoproteins among the different ages and sexes. During the stages of active atherogenesis in hypertensives and nephrotics, both the α and β lipoproteins and the lighter, higher molecular weight aggregates contribute importantly to the superabundance of plasma lipoproteins. The attribution of an exclusive atherogenesis to any one plasma fraction does not seem to us justified by these or other studies.
The role of PD-1 and PD-L1 in T-cell immune suppression in patients with hematological malignancies
Authors: Li Shi, Shaohua Chen, Lijian Yang, Yangqiu Li
Journal: Journal of Hematology & Oncology (2013)

Abstract T-cell activation and dysfunction relies on direct and modulated receptors. Based on their functional outcome, co-signaling molecules can be divided as co-stimulators and co-inhibitors, which positively and negatively control the priming, growth, differentiation and functional maturation of a T-cell response. We are beginning to understand the power of co-inhibitors in the context of lymphocyte homeostasis and the pathogenesis of leukemia, which involves several newly described co-inhibitory pathways, including the programmed death-1 (PD-1) and PD-1 ligand (PD-L1) pathway. The aim of this review is to summarize the PD-1 and PD-L1 biological functions and their alterative expression in hematological malignancies. The role of PD-1 and PD-L1 in T-cell immune suppression and the potential for immunotherapy via blocking PD-1 and PD-L1 in hematological malignancies are also reviewed.
Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein.
Authors: A D Watson, J A Berliner, S Y Hama, B N La Du, K F Faull, A M Fogelman, M Navab
Journal: Journal of Clinical Investigation (1995)

Our group has previously demonstrated that oxidized phospholipids in mildly oxidized LDL (MM-LDL) produced by oxidation with lipoxygenase, iron, or cocultures of artery wall cells increase monocyte-endothelial interactions and this sequence of events is blocked by HDL. To obtain further insight into the mechanism by which HDL abolishes the activity of MM-LDL we investigated the effect of the HDL-associated ester hydrolase paraoxonase (PON). Treatment of MM-LDL with purified PON significantly reduced the ability of MM-LDL to induce monocyte-endothelial interactions. Inactivation of PON by pretreating HDL with heat or EDTA reduced the ability of HDL to inhibit LDL modification. HPLC analysis of phospholipids isolated from MM-LDL before and after treatment with purified PON showed that the 270 nm absorbance of phospholipids was decreased, while no effect was observed on 235 nm absorbance. Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (Ox-PAPC) and specific fractions of Ox-PAPC isolated by HPLC induced the same monocyte-endothelial interactions as did MM-LDL. Biologically active and inactive HPLC fractions of Ox-PAPC were compared by fast atom bombardment-mass spectrometry which revealed that active fractions possessed ions with a mass to charge [correction of change] ratio greater than native PAPC by multiples of 16 D suggesting the addition of 3 and 4 oxygen atoms to PAPC. Comparison of Ox-PAPC by fast atom bombardment-mass spectrometry before and after PON treatment showed that PON destroyed these multi-oxygenated molecules found in biologically active fractions of Ox-PAPC. These results suggest that PON in HDL may protect against the induction of inflammatory responses in artery wall cells by destroying biologically active lipids in mildly oxidized LDL.