tbuckley/cabot-search huggingface dataset:
H-2Kb–Restricted CTL Epitopes from Mouse Heparanase Elicit an Antitumor Immune Response <i>In vivo</i>
Authors: Xu-Dong Tang, Yin Wan, Ling Chen, Ting Chen, Song-Tao Yu, Zhen Xiong, Dian-Chun Fang, Guang-Ping Liang, Shi-Ming Yang
Journal: Cancer Research (2008)

Abstract The identification of CTL epitopes from tumor antigens is very important for the development of peptide-based, cancer-specific immunotherapy. Heparanase is broadly expressed in various advanced tumors and can serve as a universal tumor-associated antigen. Although several epitopes of heparanase antigen are known in humans, the corresponding knowledge in mice is still rather limited. The present study was designed to predict and identify the CTL epitopes in the mouse heparanase protein. For this purpose, H-2Kb–restricted CTL epitopes were identified by using the following four-step procedure: (a) a computer-based epitope prediction from the amino acid sequence of mouse heparanase, (b) a peptide-binding assay to determine the affinity of the predicted epitopes with the H-2Kb molecule, (c) the testing of the induction of CTLs toward various carcinoma cells expressing heparanase antigens and H-2Kb, and (d) the induction of immunoprotection and immunotherapy in vivo. The results showed that, of the tested peptides, effectors induced by peptides of mouse heparanase at residue positions 398 to 405 (LSLLFKKL; mHpa398) and 519 to 526 (FSYGFFVI; mHpa519) lysed three kinds of carcinoma cells expressing both heparanase and H-2Kb (B16 melanoma cells, EL-4 lymphoma cells, and Lewis lung cancer cells). In vivo experiments indicated that mHpa398 and mHpa519 peptides offered the possibility of not only immunizing against tumors but also treating tumor-bearing hosts successfully. Our results suggest that the mHpa398 and mHpa519 peptides are novel H-2Kb–restricted CTL epitopes capable of inducing heparanase-specific CTLs in vitro and in vivo. These epitopes may serve as valuable tools for the preclinical evaluation of vaccination strategies. [Cancer Res 2008;68(5):1529–37]
In Vitro Studies on Mechanism of the “Eclipse” of Cell-Mediated Immunity in Mice Bearing Advanced Tumors2
Authors: Jung Koo Youn, Danielle Le François, Georges Barski
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article In Vitro Studies on Mechanism of the “Eclipse” of Cell-Mediated Immunity in Mice Bearing Advanced Tumors Get access Jung Koo Youn, Jung Koo Youn Tissue Culture and Virus Laboratory, Institut Gustave-Roussy; and Centre National de la Recherche Scientifique, 94- Villejuif, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Danielle Le François, Danielle Le François Tissue Culture and Virus Laboratory, Institut Gustave-Roussy; and Centre National de la Recherche Scientifique, 94- Villejuif, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Georges Barski Georges Barski Tissue Culture and Virus Laboratory, Institut Gustave-Roussy; and Centre National de la Recherche Scientifique, 94- Villejuif, France Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 50, Issue 4, April 1973, Pages 921–926, https://doi.org/10.1093/jnci/50.4.921 Published: 01 April 1973 Article history Received: 18 July 1972 Accepted: 10 October 1972 Published: 01 April 1973
PUVA treatment for psoriasis using metal halide quartz lamps
Authors: Lionel Fry
Journal: British Journal of Dermatology (1977)

Journal Article PUVA treatment for psoriasis using metal halide quartz lamps Get access Lionel Fry Lionel Fry St Mary's Hospital, London W2 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 96, Issue 3, 1 March 1977, Page 327, https://doi.org/10.1111/j.1365-2133.1977.tb06147.x Published: 01 March 1977
Mental Health Care Quality Under Managed Care in the United States: A View From the Health Employer Data and Information Set (HEDIS)
Authors: Benjamin G. Druss, Carolyn L. Miller, Robert A. Rosenheck, Sarah C. Shih, James E. Bost
Journal: American Journal of Psychiatry (2002)

This study examined the rates and correlates of mental health care performance measures in the Health Employer Data and Information Set (HEDIS).For all 384 health maintenance organizations (HMOs) participating in the HEDIS program of the National Committee for Quality Assurance during 1999, analyses examined the rates of compliance with five mental health care performance measures and their association with general medical care quality, public reporting, and HMO finances.The mean rate of mental health care performance was 48.0%, compared with 69.2% for non-mental-health care domains. In multivariate models adjusted for plan characteristics, scores for worse quality of non-mental-health domains, failure to report data publicly, and low medical-loss ratio (proportion of revenues spent on clinical care) all predicted poor mental health care performance.Better general medical care, transparency of reporting, and commitment of fiscal resources to clinical care predicted better mental health care performance for U.S. HMOs.
Apixaban versus aspirin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a predefined subgroup analysis from AVERROES, a randomised trial
Authors: Hans-Christoph Diener, John Eikelboom, Stuart J Connolly, Campbell D Joyner, Robert G Hart, Gregory YH Lip, Martin O'Donnell, Stefan H Hohnloser, Graeme J Hankey, Olga Shestakovska, Salim Yusuf
Journal: The Lancet Neurology (2012)
Myocardial perfusion in patients with permanent ventricular pacing and normal coronary arteries
Authors: Emmanuel I Skalidis, George E Kochiadakis, Sophia I Koukouraki, Stavros I Chrysostomakis, Nikolaos E Igoumenidis, Nikolaos S Karkavitsas, Panos E Vardas
Journal: Journal of the American College of Cardiology (2001)
Mapping collective behavior in the big-data era
Authors: R. Alexander Bentley, Michael J. O'Brien, William A. Brock
Journal: Behavioral and Brain Sciences (2014)

The behavioral sciences have flourished by studying how traditional and/or rational behavior has been governed throughout most of human history by relatively well-informed individual and social learning. In the online age, however, social phenomena can occur with unprecedented scale and unpredictability, and individuals have access to social connections never before possible. Similarly, behavioral scientists now have access to "big data" sets - those from Twitter and Facebook, for example - that did not exist a few years ago. Studies of human dynamics based on these data sets are novel and exciting but, if not placed in context, can foster the misconception that mass-scale online behavior is all we need to understand, for example, how humans make decisions. To overcome that misconception, we draw on the field of discrete-choice theory to create a multiscale comparative "map" that, like a principal-components representation, captures the essence of decision making along two axes: (1) an east-west dimension that represents the degree to which an agent makes a decision independently versus one that is socially influenced, and (2) a north-south dimension that represents the degree to which there is transparency in the payoffs and risks associated with the decisions agents make. We divide the map into quadrants, each of which features a signature behavioral pattern. When taken together, the map and its signatures provide an easily understood empirical framework for evaluating how modern collective behavior may be changing in the digital age, including whether behavior is becoming more individualistic, as people seek out exactly what they want, or more social, as people become more inextricably linked, even "herdlike," in their decision making. We believe the map will lead to many new testable hypotheses concerning human behavior as well as to similar applications throughout the social sciences.
Salivary cortisol levels are associated with outcomes of weight reduction therapy in obese Japanese patients
Authors: Akihiro Himeno, Noriko Satoh-Asahara, Takeshi Usui, Hiromichi Wada, Mayu Tochiya, Shigeo Kono, Nobuko Yamada-Goto, Goro Katsuura, Koji Hasegawa, Kazuwa Nakao, Akira Shimatsu
Journal: Metabolism (2011)
What Is Better for Older Patients With Acute Myeloid Leukemia?
Authors: Felicetto Ferrara, Pellegrino Musto
Journal: Journal of Clinical Oncology (2012)

recently published an article concerning the potential therapeutic advantage of decitabine com-pared with the so-called treatment choice (TC) in older patients with acute myeloid leukemia (AML).The article raises several points of interest, but in our opinion, it also raises some concerns.In this study, from a series of 632 patients who were initially assessed for eligibility, 485 of the patients were randomly assigned to receive either decitabine or TC.Notably, 147 patients (23%)
Parity and the risk of developing rheumatoid arthritis: results from the Swedish Epidemiological Investigation of Rheumatoid Arthritis study
Authors: Cecilia Orellana, Sara Wedrén, Henrik Källberg, Marie Holmqvist, Elizabeth W Karlson, Lars Alfredsson, Camilla Bengtsson
Journal: Annals of the Rheumatic Diseases (2013)

To study the impact of parity history on the risk of antibodies to citrullinated peptide antigens (ACPA) positive and ACPA-negative rheumatoid arthritis (RA), in different age-groups.Data from a population-based case-control study of female incident RA cases were analysed (2035 cases and 2911 controls, aged 18-70 years ). Parity history was assessed through a questionnaire. Parous women were compared with nulliparous, by calculating odds ratios (ORs) with 95% confidence interval (CI).Parity was associated with an increased risk of ACPA-negative RA in women aged 18-44 years (OR=2.1, 95% CI 1.4 to 3.2), but not in those aged 45-70 years (OR=0.9, 95% CI 0.7 to 1.3). Among young women, an increased risk of ACPA-negative RA was found in those who gave birth during the year of symptom onset (OR=2.6, 95% CI 1.4 to 4.8) and who were at a young age at first birth (<23) (OR=2.5, 95% CI 1.5 to 4.1). Parity and the postpartum period were not associated with ACPA-positive RA, but older age at first birth was weakly associated with a decreased risk.The increased risk of ACPA-negative RA in parous women of reproductive age seemed to be associated with an increased postpartum risk and with young age at first birth. Further research is needed to explore the biological mechanisms behind our findings.
THE ROLE OF NONLYMPHOID ACCESSORY CELLS IN THE IMMUNE RESPONSE TO DIFFERENT ANTIGENS
Authors: Ken Shortman, E. Diener, Pamela Russell, W. D. Armstrong
Journal: The Journal of Experimental Medicine (1970)

Tissue culture techniques were combined with cell separation procedures to investigate the cellular requirements for a response to antigen, leading to the production of antibody-forming cells. Mouse spleen was dissociated, and the cells were separated into various groups on the basis of density, size, and active adherence. The ability of fractions to initiate a response in vivo, on transfer to an irradiated recipient, was compared to the response in vitro; and this ability was correlated with the presence or absence of phagocytic cells. Two different antigens were studied, sheep erythrocytes (SRC) and polymerized bacterial flagellin (POL). Density distribution analysis of spleen showed a wide density range of cells responding to both antigens in vivo. The same fractions responded to POL in vitro as in vivo. By contrast, only the light density regions responded in vitro to SRC. Response occurred in regions of overlap between lymphocytes and phagocytic macrophages. Separation by active adherence on columns of large glass beads gave a preparation containing large, medium, and small lymphocytes but no detectable phagocytic macrophages and very low levels of phagocytic polymorphs. This lymphocyte preparation responded to both antigens in vivo. In vitro it gave a full response to POL, but no response to SRC. Addition of a small quantity of the adherent fraction, enriched for phagocytic cells, restored response to SRC. The use of strain-specific antisera in a mixed culture containing a C57 phagocytic fraction and CBA lymphocytes showed that the lymphocyte fraction contributed the precursors of the final antibody-forming cells. The accessory cells from C57 spleen banded in the light regions of the density gradient where phagocytic macrophages were found. Irradiated spleen cells also activated the lymphocyte preparation, suggesting that the irradiated host provided the accessory cells for the in vivo response to SRC. Small lymphocytes were purified from spleen by the small glass bead size filtration technique. This sample of small lymphocytes responded less well to POL than the total lymphocyte population, but it responded as well in vitro as in vivo. The small lymphocyte preparation responded in vivo to SRC but not in vitro. Addition of a small quantity of the phagocyte-rich fraction from adherence columns restored the in vitro response to SRC. The results indicated that phagocytic cells are not required in the initiation of an immune response to POL. By contrast some accessory cell, possibly a phagocytic macrophage, is required for a response to SRC. The basis for this marked difference is discussed.
Common Pattern of Evolution of Gene Expression Level and Protein Sequence in Drosophila
Authors: Sergey V. Nuzhdin, Marta L. Wayne, Kristy L. Harmon, Lauren M. McIntyre
Journal: Molecular Biology and Evolution (2004)

Sequence divergence scaled by variation within species has been used to infer the action of selection upon individual genes. Applying this approach to expression, we compared whole-genome whole-body RNA levels in 10 heterozygous Drosophila simulans genotypes and a pooled sample of 10 D. melanogaster lines using Affymetrix Genechip. For 972 genes expressed in D. melanogaster, the transcript level was below detection threshold in D. simulans, which may be explained either by sequence divergence between the primers on the chip and the mRNA transcripts or by down-regulation of these genes. Out of 6,707 genes that were expressed in both species, transcript level was significantly different between species for 534 genes (at P < 0.001). Genes whose expression is under stabilizing selection should exhibit reduced genetic variation within species and reduced divergence between species. Expression of genes under directional selection in D. simulans should be highly divergent from D. melanogaster, while showing low genetic variation in D. simulans. Finally, the genes with large variation within species but modest divergence between species are candidates for balancing selection. Rapidly diverging, low-polymorphism genes included those involved in reproduction (e.g., Mst 3Ba, 98Cb; Acps 26Aa, 63F; and sperm-specific dynein). Genes with high variation in transcript abundance within species included metallothionein and hairless, both hypothesized to be segregating in nature because of gene-by-environment interactions. Further, we compared expression divergence and DNA substitution rate in 195 genes. Synonymous substitution rate and expression divergences were uncorrelated, whereas there was a significant positive correlation between nonsynonymous substitution rate and expression divergence. We hypothesize that as a substantial fraction of nonsynonymous divergence has been shown to be adaptive, much of the observed expression divergence is likewise adaptive.
Proteome Analysis and Functional Expression Identify Mortalin as an Antiapoptotic Gene Induced by Elevation of [Na <sup>+</sup> ] <sub>i</sub> /[K <sup>+</sup> ] <sub>i</sub> Ratio in Cultured Vascular Smooth Muscle Cells
Authors: Sebastien Taurin, Volkan Seyrantepe, Sergei N. Orlov, Tammy-Lynn Tremblay, Pierre Thibault, Martin R. Bennett, Pavel Hamet, Alexey V. Pshezhetsky
Journal: Circulation Research (2002)

Apoptosis of vascular smooth muscle cells (VSMCs) plays an important role in remodeling of vessel walls, one of the major determinants of long-term blood pressure elevation and an independent risk factor for cardiovascular morbidity and mortality. Recently, we have found that apoptosis in cultured VSMCs can be inhibited by inversion of the intracellular [Na+]/[K+] ratio after the sustained blockage of the Na+,K+-ATPase by ouabain. To understand the mechanism of ouabain action, we analyzed subsets of hydrophilic and hydrophobic VSMC proteins from control and ouabain-treated cells by 2-dimensional electrophoresis. Ouabain treatment led to overexpression of numerous soluble and hydrophobic cellular proteins. Among proteins that showed the highest level of ouabain-induced expression, we identified mortalin (also known as GRP75 or PBP-74), a member of the heat shock protein 70 (HSP70) superfamily and a marker for cellular mortal and immortal phenotypes. Northern and Western blotting and immunocytochemistry all have confirmed that treatment of VSMCs with ouabain results in potent induction of mortalin expression. Transient transfection of cells with mortalin cDNA led to at least a 6-hour delay in the development of apoptosis after serum deprivation. The expression of tumor suppressor gene, p53, in mortalin-transfected cells was delayed to the same extent, and the expressed protein showed abnormal perinuclear distribution, suggesting that p53 is retained and inactivated by mortalin. Our studies therefore define a new [Na+]i/[K+]i-responsive signaling pathway that may play an important role in the regulation of programmed cell death in VSMCs.
Acute cutaneous T-cell lymphoma transformation during treatment with alemtuzumab
Authors: S. Faguer, F. Launay, L. Ysebaert, C. Mailhol, O. Estines-Chartier, L. Lamant, C. Paul
Journal: British Journal of Dermatology (2007)

Conflicts of interest: none declared. Sir, Alemtuzumab (Campath‐1) has newly been described as salvage treatment1, 2 in patients with advanced Sézary syndrome. CD52 is a peptide cell‐surface antigen expressed on normal and also malignant T and B lymphocytes.3 Alemtuzumab is a monoclonal anti‐CD52 antibody (IgG1). It is known to induce profound lymphocyte depletion mainly mediated by apoptosis or complement‐mediated cell lysis. Overall response rates of 38–55% (complete response in 0–32% of patients) have been observed in advanced T‐cell lymphoma, with a median time to treatment failure of 3–12 months.1, 2 Opportunistic infections, cardiac toxicity and neutropenia have been described during treatment with alemtuzumab.4 We report a 68‐year‐old patient diagnosed with cutaneous T‐cell lymphoma (CTCL) in May 2006. Clinical examination showed large erythematous plaques and a left temporal nodular lesion. Clonal T‐cell receptor Vβ22+ CD4+ CD7– CD26– circulating CTCL cells (3000 mm−3) were observed, with an elevated CD4+/CD8+ ratio of 15. Histological examination of the temporal lesion disclosed transformed mycosis fungoides. Immunostaining showed that malignant cells were positive for CD4 and CD52. The cells were negative for CD8 and < 10% were CD30+. Bone marrow biopsy and total‐body computed tomographic scan were normal. Staging according to the TNM classification was T4N0M0 B1. Cytomegalovirus (CMV) and Epstein–Barr virus (EBV) viral loads were negative. In August 2006, alemtuzumab 30 mg three times per week was started because of disease progression despite treatment with interferon alfa and psoralen and ultraviolet A radiation. The patient was also treated with valaciclovir, co‐trimoxazole and fluconazole as a recommended prophylaxis regimen.5 After the third subcutaneous injection, he presented with severe asthenia and high fever related to septicaemia (Pseudomonas aeruginosa and Staphylococcus aureus). In September 2006, after 3 weeks of alemtuzumab, CMV viraemia was detected (15 600 mL−1, 4·2 log), associated with fever but no organ involvement. Pre‐emptive treatment with intravenous ganciclovir was given for 7 days due to the increase of viral load associated with symptoms, then followed by prophylaxis with valganciclovir 450 mg daily. The fever resolved within 5 days and CMV viraemia became negative.
Tumors Acquire Inhibitor of Apoptosis Protein (IAP)-mediated Apoptosis Resistance through Altered Specificity of Cytosolic Proteolysis
Authors: Xu Hong, Lu Lei, Rickard Glas
Journal: The Journal of Experimental Medicine (2003)

Many tumors overexpress members of the inhibitor of apoptosis protein (IAP) family. IAPs contribute to tumor cell apoptosis resistance by the inhibition of caspases, and are degraded by the proteasome to allow further progression of apoptosis. Here we show that tumor cells can alter the specificity of cytosolic proteolysis in order to acquire apoptosis resistance, which promotes formation of rapidly growing tumors. Survival of tumor cells with low proteasomal activity can occur in the presence of high expression of Tri-peptidyl-peptidase II (TPP II), a large subtilisin-like peptidase that complements proteasomal activity. We find that this state leaves tumor cells unable of effectively degrading IAPs, and that cells in this state form rapidly growing tumors in vivo. We also find, in studies of apoptosis resistant cells derived from large in vivo tumors, that these have acquired an altered peptidase activity, with up-regulation of TPP II activity and decreased proteasomal activity. Importantly, we find that growth of subcutaneous tumors is limited by maintenance of the apoptosis resistant phenotype. The apoptosis resistant phenotype was reversed by increased expression of Smac/DIABLO, an antagonist of IAP molecules. Our data suggest a reversible mechanism in regulation of apoptosis resistance that drives tumor progression in vivo. These data are relevant in relation to the multitude of therapy-resistant clinical tumors that have increased levels of IAP molecules.
A melanoma helper peptide vaccine increases Th1 cytokine production by leukocytes in peripheral blood and immunized lymph nodes
Authors: Patrick M Dillon, Walter C Olson, Andrea Czarkowski, Gina R Petroni, Mark Smolkin, William W Grosh, Kimberly A Chianese-Bullock, Donna H Deacon, Craig L Slingluff
Journal: Journal for ImmunoTherapy of Cancer (2014)

Cancers produce soluble and cell-associated molecules that can suppress or alter antitumor immunity. Preclinical studies suggest the disease burden may alter the cytokine profile of helper T cell responses to cancer antigens. We studied cytokine production by helper T cells responding to vaccination with 6 melanoma helper peptides (6MHP) in blood and lymph nodes.Twenty-three patients with stage IIIB-IV melanoma received a 6MHP vaccine. Antigen-reactive T cells from blood and draining lymph nodes were cultured, exposed to antigen, and then supernatants (days 2 and 5) were assayed for Th1 and Th2 cytokines. Results from 4 time points were compared to pre-vaccine levels.Cytokine responses to vaccinating peptides were observed in 83% of patients. Th1 favoring responses were most common (17 of 19 responders). The most abundant cytokines produced were IFN-γ and IL-5 in the PBMC's. IL-2 responses predominated in cells obtained from draining lymph nodes in 2-day culture but not in 5-day cultures. Patients with clinically measurable disease produced similar levels of total cytokine and similar degree of Th1 polarization as patients with no evidence of disease (NED).The MHC class II-associated peptides used in this study induced helper T cells with a Th1-biased cytokine response in both PBMC and sentinel immunized nodes. Most patients can mount a Th1 dominant response to these peptides. Future studies are needed to test newer vaccine adjuvants in combination with these peptides.CDR0000378171, Clinicaltrials: NCT00089219.