tbuckley/cabot-search huggingface dataset:
Tumoral and Immunologic Response After Vaccination of Melanoma Patients With an ALVAC Virus Encoding MAGE Antigens Recognized by T Cells
Authors: Nicolas van Baren, Marie-Claude Bonnet, Brigitte Dréno, Amir Khammari, Thierry Dorval, Sophie Piperno-Neumann, Danielle Liénard, Daniel Speiser, Marie Marchand, Vincent G. Brichard, Bernard Escudier, Sylvie Négrier, Pierre-Yves Dietrich, Dominique Maraninchi, Susanne Osanto, Ralf G. Meyer, Gerd Ritter, Philippe Moingeon, Jim Tartaglia, Pierre van der Bruggen, Pierre G. Coulie, Thierry Boon
Journal: Journal of Clinical Oncology (2005)

Purpose To evaluate the toxicity, antitumoral effectiveness, and immunogenicity of repeated vaccinations with ALVAC miniMAGE-1/3, a recombinant canarypox virus containing a minigene encoding antigenic peptides MAGE-3 168-176 and MAGE-1 161-169 , which are presented by HLA-A1 and B35 on tumor cells and can be recognized by cytolytic T lymphocytes (CTLs). Materials and Methods The vaccination schedule comprised four sequential injections of the recombinant virus, followed by three booster vaccinations with the MAGE-3 168-176 and MAGE-1 161-169 peptides. The vaccines were administered, both intradermally and subcutaneously, at 3-week intervals. Results Forty patients with advanced cancer were treated, including 37 melanoma patients. The vaccines were generally well tolerated with moderate adverse events, consisting mainly of transient inflammatory reactions at the virus injection sites. Among the 30 melanoma patients assessable for tumor response, a partial response was observed in one patient, and disease stabilization in two others. The remaining patients had progressive disease. Among the patients with stable or progressive disease, five showed evidence of tumor regression. A CTL response against the MAGE-3 vaccine antigen was detected in three of four patients with tumor regression, and in only one of 11 patients without regression. Conclusion Repeated vaccination with ALVAC miniMAGE-1/3 is associated with tumor regression and with a detectable CTL response in a minority of melanoma patients. There is a significant correlation between tumor regression and CTL response. The contribution of vaccine-induced CTL in the tumor regression process is discussed in view of the immunologic events that could be analyzed in detail in one patient.
Radioiodinated soluble canine fibrin. Preparation and evaluation as a thrombus localizing agent in the dog.
Authors: R E Coleman, S S Harwig, J F Harwig, L A Sherman, M J Welch
Journal: Circulation Research (1975)

To develop a thrombus localizing tracer which has characteristics superior to labeled fibrinogen for external detection, we evaluated radioiodinated soluble fibrin. Labeled soluble fibrin was prepared by clotting and dissolving radioiodinated (131I) canine fibrinogen under specified conditions. Biological clearance studies revealed rapid clearance of the labeled soluble fibrin from the blood with a half-life of 5 hours. The accumulation of labeled soluble fibrin and fibrinogen in induced venous thrombi, coronary artery thrombi, and the myocardium was compared in dogs. In venous thrombi, soluble fibrin and fibrinogen exhibited maximum thrombus-blood ratios when they were injected 4 hours after thrombus induction; the thrombus-blood ratio was greater for soluble fibrin than it was for fibrinogen when these agents were injected 4, 8, or 24 hours after thrombosis induction. In induced coronary artery thrombi, soluble fibrin and fibrinogen accumulated to the same extent. Since the blood clearance of soluble fibrin is faster than that of fibrinogen, a higher thrombus-blood ratio was obtained with soluble fibrin in coronary artery thrombi. The thrombus-infarcted myocardium, thrombus-normal myocardium, and infarcted myocardium-normal myocardium ratios obtained with soluble fibrin were slightly higher than those obtained with fibrinogen. Thus, soluble fibrin offers some advantages when it is compared with fibrinogen as a thrombus detecting agent.
Fluticasone in asthma
Authors: J. W HONOUR;
Journal: Thorax (2000)

The paper by Meijer et al 1 compares the effects of inhaled fluticasone propionate (2 mg and 0.5 mg daily) and oral steroids (prednisolone 30 mg daily) in patients with mild to moderate asthma. Many patients with severe asthma are dependent upon corticosteroids, although inhaled steroids can effectively replace oral prednisolone.2 The biological effects of oral versus inhaled steroids can be compared in terms of lung function, airway responsiveness, and blood eosinophil number and activity, but suppression … Dr H A M Kerstjens.
Methotrexate modulates the kinetics of adenosine in humans in vivo
Authors: N P Riksen
Journal: Annals of the Rheumatic Diseases (2005)

<b>Background:</b> Animal studies suggest that the anti-inflammatory effect of methotrexate (MTX) is mediated by increased adenosine concentrations. <b>Objective:</b> To assess the effect of MTX on the vasodilator effects of adenosine and the nucleoside uptake inhibitor, dipyridamole, in humans in vivo as a marker for changes in adenosine kinetics. <b>Methods:</b> Ten patients with active arthritis were treated with MTX (15 mg/week). Measurements were performed before and after 12 weeks of treatment. At these time points, the activity of adenosine deaminase was measured in isolated lymphocytes, and forearm blood flow (FBF) was determined by venous occlusion plethysmography during administration of adenosine and dipyridamole into the brachial artery. <b>Results:</b> The V<sub>max</sub> of adenosine deaminase in lymphocytes was reduced by MTX treatment (p<i>&lt;</i>0.05). MTX significantly enhanced vasodilator response to adenosine (0.5 and 1.5 μg/min/dl of forearm tissue; mean (SE) FBF ratio increased from 1.2 (0.2) to 1.4 (0.2) and 2.2 (0.2) ml/dl/min, respectively, before and from 1.3 (0.1) to 1.8 (0.2) and 3.2 (0.5) ml/dl/min during MTX treatment; p&lt;0.05). Also, dipyridamole-induced vasodilatation (30 and 100 μg/min/dl) was enhanced by MTX (FBF ratio increased from 1.2 (0.2) to 1.5 (0.3) and 1.8 (0.2), respectively, before and from 1.3 (0.1) to 1.8 (0.2) and 2.4 (0.4) during MTX treatment; p&lt;0.05). <b>Conclusions:</b> MTX treatment inhibits deamination of adenosine and potentiates adenosine-induced vasodilatation. Also dipyridamole-induced vasodilatation is enhanced by MTX treatment, suggesting an increased extracellular formation of adenosine. These effects on the adenosine kinetics in humans may contribute to the therapeutic efficacy of MTX.
Targeting of NAD Metabolism in Pancreatic Cancer Cells: Potential Novel Therapy for Pancreatic Tumors
Authors: Claudia C.S. Chini, Anatilde M. Gonzalez Guerrico, Veronica Nin, Juliana Camacho-Pereira, Carlos Escande, Maria Thereza Barbosa, Eduardo N. Chini
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Here, we describe a novel interplay between NAD synthesis and degradation involved in pancreatic tumor growth. Experimental Design: We used human pancreatic cancer cells, both in vitro (cell culture experiments) and in vivo (xenograft experiments), to demonstrate the role of NAD synthesis and degradation in tumor cell metabolism and growth. Results: We demonstrated that pharmacologic and genetic targeting of Nampt, the key enzyme in the NAD salvage synthesis pathway, inhibits cell growth and survival of pancreatic cancer cells. These changes were accompanied by a reduction of NAD levels, glycolytic flux, lactate production, mitochondrial function, and levels of ATP. The massive reduction in overall metabolic activity induced by Nampt inhibition was accompanied by a dramatic decrease in pancreatic tumor growth. The results of the mechanistic experiments showed that neither the NAD-dependent enzymes PARP-1 nor SIRT1 play a significant role on the effect of Nampt inhibition on pancreatic cancer cells. However, we identified a role for the NAD degradation pathway mediated by the NADase CD38 on the sensitivity to Nampt inhibition. The responsiveness to Nampt inhibition is modulated by the expression of CD38; low levels of this enzyme decrease the sensitivity to Nampt inhibition. In contrast, its overexpression decreased cell growth in vitro and in vivo, and further increased the sensitivity to Nampt inhibition. Conclusions: Our study demonstrates that NAD metabolism is essential for pancreatic cancer cell survival and proliferation and that targeting NAD synthesis via the Nampt pathway could lead to novel therapeutic treatments for pancreatic cancer. Clin Cancer Res; 20(1); 120–30. ©2013 AACR.
Pain and behavior
Authors: Howard Rachlin
Journal: Behavioral and Brain Sciences (1985)

Abstract There seem to be two kinds of pain: fundamental “sensory” pain, the intensity of which is a direct function of the intensity of various pain stimuli, and “psychological” pain, the intensity of which is highly modifiable by such factors as hypnotism, placebos, and the sociocultural setting in which the stimulus occurs. Physiological, cognitive, and behavioral theories of pain each have their own view of the nature of the two kinds of pain. According to physiological theory and cognitive theory, “psychological” pain and “sensory” pain are both internal processes, with the former influencing the latter as central processes influence peripheral processes. According to behavioral theory, “sensory” pain is a reflex (a respondent) while “psychological” pain is an instrumental act (an operant). Behavioral theory claims that neither kind of pain is an internal process — that both are overt behaviors. Although both physiological theory and cognitive theory agree with common sense that pain is internal, they disagree with commonsense intuitions at other points. They are no better at explaining the subjective experience of pain than is behavioral theory. They have not generated treatments for pain that are superior to those generated by behavioral theory. There is no basis for the frequent claim by antibehaviorist philosophers and psychologists that behaviorism, because it cannot explain pain, is less capable of explaining mental phenomena than physiology or cognition.
Structure and reactivity of small arteries in aging
Authors: P Moreau
Journal: Cardiovascular Research (1998)

Objective: Increased pulse pressure has been observed in aging subjects, but the impact on the structure and reactivity of small arteries has been scarcely evaluated. Methods: This study presents the modifications of vascular structure and function observed in female rats of 5, 18 and 32 months of age, and their relation to the prevailing hemodynamic status. Geometry and reactivity of perfused and pressurized basilar and mesenteric small arteries were analyzed in vitro using a video dimension analyzer. Results: Mean arterial pressure was similar in the three age groups, and only pulse pressure was increased in the oldest group. Media thickness and cross sectional area increased in basilar and mesenteric arteries of the oldest rats and these structural abnormalities were positively related to pulse pressure but not to mean, systolic or diastolic arterial pressure. Only minor changes of vascular reactivity were noted with age: there was a decreased contraction to angiotensin II in mesenteric arteries and an enhanced contraction to endothelin-1 in the basilar arteries. Conclusion: In conclusion, aging is associated with increased pulse pressure and hypertrophy of basilar and mesenteric resistance arteries, suggesting that this hemodynamic variable may influence cerebral and peripheral vascular structure in aging.
Socioeconomic Status and Childhood Asthma in Urban Minority Youths. The GALA II and SAGE II Studies
Authors: Neeta Thakur, Sam S. Oh, Elizabeth A. Nguyen, Melissa Martin, Lindsey A. Roth, Joshua Galanter, Christopher R. Gignoux, Celeste Eng, Adam Davis, Kelley Meade, Michael A. LeNoir, Pedro C. Avila, Harold J. Farber, Denise Serebrisky, Emerita Brigino-Buenaventura, William Rodriguez-Cintron, Rajesh Kumar, L. Keoki Williams, Kirsten Bibbins-Domingo, Shannon Thyne, Saunak Sen, Jose R. Rodriguez-Santana, Luisa N. Borrell, Esteban G. Burchard
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

The burden of asthma is highest among socioeconomically disadvantaged populations; however, its impact is differentially distributed among racial and ethnic groups.To assess the collective effect of maternal educational attainment, annual household income, and insurance type on childhood asthma among minority, urban youth.We included Mexican American (n = 485), other Latino (n = 217), and African American (n = 1,141) children (aged 8-21 yr) with and without asthma from the San Francisco Bay Area. An index was derived from maternal educational attainment, annual household income, and insurance type to assess the collective effect of socioeconomic status on predicting asthma. Logistic regression stratified by racial and ethnic group was used to estimate adjusted odds ratios (aOR) and their 95% confidence intervals (CI). We further examined whether acculturation explained the socioeconomic-asthma association in our Latino population.In the adjusted analyses, African American children had 23% greater odds of asthma with each decrease in the socioeconomic index (aOR, 1.23; 95% CI, 1.09-1.38). Conversely, Mexican American children have 17% reduced odds of asthma with each decrease in the socioeconomic index (aOR, 0.83; 95% CI, 0.72-0.96) and this relationship was not fully explained by acculturation. This association was not observed in the other Latino group.Socioeconomic status plays an important role in predicting asthma, but has different effects depending on race and ethnicity. Further steps are necessary to better understand the risk factors through which socioeconomic status could operate in these populations to prevent asthma.
Evolution of Function of a Fused Metazoan tRNA Synthetase
Authors: P. S. Ray, J. C. Sullivan, J. Jia, J. Francis, J. R. Finnerty, P. L. Fox
Journal: Molecular Biology and Evolution (2010)

The origin and evolution of multidomain proteins are driven by diverse processes including fusion/fission, domain shuffling, and alternative splicing. The 20 aminoacyl-tRNA synthetases (AARS) constitute an ancient conserved family of multidomain proteins. The glutamyl-prolyl tRNA synthetase (EPRS) of bilaterian animals is unique among AARSs, containing two functional enzymes catalyzing ligation of glutamate and proline to their cognate transfer RNAs (tRNAs). The ERS and PRS catalytic domains in multiple bilaterian taxa are linked by variable number of helix-turn-helix domains referred to as WHEP-TRS domains. In addition to its canonical aminoacylation activities, human EPRS exhibits a noncanonical function as an inflammation-responsive regulator of translation. Recently, we have shown that the WHEP domains direct this auxiliary function of human EPRS by interacting with an mRNA stem-loop element (interferon-gamma-activated inhibitor of translation [GAIT] element). Here, we show that EPRS is present in the cnidarian Nematostella vectensis, which pushes the origin of the fused protein back to the cnidarian-bilaterian ancestor, 50-75 My before the origin of the Bilateria. Remarkably, the Nematostella EPRS mRNA is alternatively spliced to yield three isoforms with variable number and sequence of WHEP domains and with distinct RNA-binding activities. Whereas one isoform containing a single WHEP domain binds tRNA, a second binds both tRNA and GAIT element RNA. However, the third isoform contains two WHEP domains and like the human ortholog binds specifically to GAIT element RNA. These results suggest that alternative splicing of WHEP domains in the EPRS gene of the cnidarian-bilaterian ancestor gave rise to a novel molecular function of EPRS conserved during metazoan evolution.
Human Immune Response to Active Immunization With Rauscher Leukemia Virus. I. Cell-Mediated and Cell-Associated Immunity2
Authors: E. M. Hersh, J. U. Gutterman, G. Mavligit, C. R. Gschwind, E. J. Freireich, P. H. Levine, E. J. Plata
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Human Immune Response to Active Immunization With Rauscher Leukemia Virus. I. Cell-Mediated and Cell-Associated Immunity Get access E. M. Hersh, E. M. Hersh Search for other works by this author on: Oxford Academic PubMed Google Scholar J. U. Gutterman, J. U. Gutterman Search for other works by this author on: Oxford Academic PubMed Google Scholar G. Mavligit, G. Mavligit Search for other works by this author on: Oxford Academic PubMed Google Scholar C. R. Gschwind, C. R. Gschwind Search for other works by this author on: Oxford Academic PubMed Google Scholar E. J. Freireich, E. J. Freireich Search for other works by this author on: Oxford Academic PubMed Google Scholar P. H. Levine, P. H. Levine Search for other works by this author on: Oxford Academic PubMed Google Scholar E. J. Plata E. J. Plata Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 53, Issue 2, August 1974, Pages 317–325, https://doi.org/10.1093/jnci/53.2.317 Published: 01 August 1974 Article history Received: 21 December 1973 Accepted: 23 April 1974 Published: 01 August 1974
A7.10 A combination of cellular biomarkers predicts clinical response to rituximab in rheumatoid arthritis
Authors: MH Stradner, J Fessler, C Dejaco, K Brickmann, WB Graninger, HP Brezinschek
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> Although B cell depletion with rituximab (RTX) is an effective treatment strategy in rheumatoid arthritis (RA) one third of patients does not achieve low disease activity after rituximab. We have previously reported that the frequency of circulating plasmablasts is a negative predictor of RTX response; however, additional biomarkers could be helpful to better tailor treatment strategies to RA patients. In the present study we investigated, whether other lymphocyte subsets or combinations thereof are useful predictors of a clinical response to RTX treatment. <h3>Material and methods</h3> RA patients receiving RTX for the first time were included in the Austrian rituximab registry. Clinical assessments, complete blood count and flow cytometry of lymphocyte subsets were obtained at baseline as well as at weeks 2 and 24 after RTX. Complete data was available for 48 patients. Logistic regression and receiving operating characteristic curve analyses were computed to analyse the predictive value of lymphocyte subsets for EULAR response and DAS ≤3.2 at week 24. <h3>Results</h3> Seventy-five percent of patients had a moderate or good EULAR response at week 24. Responders had lower total lymphocyte counts (TLC), T cells and CD4<sup>+</sup> T cells at baseline. Both, baseline TLC and baseline CD4<sup>+</sup>T cell independently predicted EULAR response. Furthermore, a combination of TLC and plasmablast frequency independently predicted achievement of low disease activity. Less than 7% of patients with high TLC or plasmablast frequency reached low disease activity. <h3>Conclusions</h3> In RA, patients with increased TLC or high plasmablast frequency are at high risk of failing therapy with RTX.
Genetic associations in peripheral joint osteoarthritis and spinal degenerative disease: a systematic review
Authors: J J Ryder, K Garrison, F Song, L Hooper, J Skinner, Y Loke, J Loughlin, J P T Higgins, A J MacGregor
Journal: Annals of the Rheumatic Diseases (2007)

We conducted a systematic review of genetic association studies for osteoarthritis of the peripheral joints (OA) and spinal degenerative disease (SDD). Electronic searches were carried out for any English language article reporting on a gene association study for either OA or SDD published up until the end of 2006. A team of seven reviewers used a standardised template to extract data in duplicate. In all, 90 studies fulfilled our inclusion criteria, reporting a total of 94 significant associations from 83 different genes. We found relatively few instances in which a specific gene-disease association had been analysed by more than one study, and there were 14 cases in which significant associations were replicated in independent studies (at joints associated with the AGC1, ASPN, COL9A2, COL9A3, COL11A2, ESR1, FZRB, HFE, IL1A, IL1RN, PTGS2 and VDR genes).logical and reporting problems were widespread, including failure to report full results, missing population details, multiple testing, and over-reliance on subgroup analysis. In summary, the complex phenotypes of OA and SDD may have made it difficult for researchers to focus their efforts. The field is dominated by isolated analyses of disparate potential associations, a problem that is amplified by the frequent analysis of different polymorphisms within individual genes. Flaws in study methodology and interpretation undoubtedly increase the risk of publication bias. Closer adherence to published recommendations (in particular those produced by HuGENet) will help to ensure that future studies are well-designed and build on current understanding, rather than simply adding to the growing bank of potential associations.
Clustered Mutations in HIV-1 Gag Are Consistently Required for Escape from Hla-B27–Restricted Cytotoxic T Lymphocyte Responses
Authors: Anthony D. Kelleher, Chad Long, Edward C. Holmes, Rachel L. Allen, Jamie Wilson, Christopher Conlon, Cassy Workman, Sunil Shaunak, Kara Olson, Philip Goulder, Christian Brander, Graham Ogg, John S. Sullivan, Wayne Dyer, Ian Jones, Andrew J. McMichael, Sarah Rowland-Jones, Rodney E. Phillips
Journal: The Journal of Experimental Medicine (2001)

The immune response to HIV-1 in patients who carry human histocompatibility leukocyte antigen (HLA)-B27 is characterized by an immunodominant response to an epitope in p24 gag (amino acids 263–272, KRWIILGLNK). Substitution of lysine (K) or glycine (G) for arginine (R) at HIV-1 gag residue 264 (R264K and R264G) results in epitopes that bind to HLA-B27 poorly. We have detected a R264K mutation in four patients carrying HLA-B27. In three of these patients the mutation occurred late, coinciding with disease progression. In another it occurred within 1 yr of infection and was associated with a virus of syncytium-inducing phenotype. In each case, R264K was tightly associated with a leucine to methionine change at residue 268. After the loss of the cytotoxic T lymphocyte (CTL) response to this epitope and in the presence of high viral load, reversion to wild-type sequence was observed. In a fifth patient, a R264G mutation was detected when HIV-1 disease progressed. Its occurrence was associated with a glutamic acid to aspartic acid mutation at residue 260. Phylogenetic analyses indicated that these substitutions emerged under natural selection rather than by genetic drift or linkage. Outgrowth of CTL escape viruses required high viral loads and additional, possibly compensatory, mutations in the gag protein.