tbuckley/cabot-search huggingface dataset:
Phase III Randomized Study Comparing Docetaxel Plus Trastuzumab With Vinorelbine Plus Trastuzumab As First-Line Therapy of Metastatic or Locally Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: The HERNATA Study
Authors: Michael Andersson, Elisabeth Lidbrink, Karsten Bjerre, Erik Wist, Kristin Enevoldsen, Anders B. Jensen, Per Karlsson, Ulla B. Tange, Peter G. Sørensen, Susanne Møller, Jonas Bergh, Sven T. Langkjer
Journal: Journal of Clinical Oncology (2010)

To evaluate docetaxel or vinorelbine, both with trastuzumab, as first-line therapy of human epidermal growth factor receptor 2-positive advanced breast cancer.Patients naive to chemotherapy for advanced disease were randomly assigned to docetaxel 100 mg/m(2) day 1 or vinorelbine 30 to 35 mg/m(2) on days 1 and 8, both combined with trastuzumab (8-mg/kg loading dose and 6-mg/kg maintenance dose) on day 1 every 3 weeks. The primary end point was time to progression (TTP).A total of 143 patients were randomly allocated to docetaxel, and 141 patients were assigned to vinorelbine. The median TTP for docetaxel and vinorelbine respectively was 12.4 months versus 15.3 months (hazard ratio [HR] = 0.94; 95% CI, 0.71 to 1.25; P = .67), median overall survival was 35.7 months versus 38.8 months (HR = 1.01; 95% CI, 0.71 to 1.42; P = .98), and the 1-year survival rate was 88% in both arms. Median time to treatment failure for study chemotherapy was 5.6 months versus 7.7 months (HR = 0.50; 95% CI, 0.38 to 0.64; P < .0001). The investigator-assessed overall response rate among 241 patients with measurable disease were 59.3% in both arms. More patients in the docetaxel arm discontinued therapy due to toxicity (P < .001). Significantly more treatment-related grade 3 to 4 febrile neutropenia (36.0% v 10.1%), leucopenia (40.3% v 21.0%), infection 25.1% v 13.0%), fever (4.3% v 0%), neuropathy (30.9% v 3.6%), nail changes (7.9% v 0.7%), and edema (6.5% v 0%) were reported with docetaxel.The study failed to demonstrate superiority of any drug in terms of efficacy, but the vinorelbine combination had significantly fewer adverse effects and should be considered as an alternative first-line option.
CELLULAR DIFFERENTIATION OF THE IMMUNE SYSTEM OF MICE
Authors: G. M. Shearer, G. Cudkowicz
Journal: The Journal of Experimental Medicine (1969)

Marrow cell suspensions of unprimed donor mice have been transplanted into X-irradiated syngeneic hosts. 5–46 days later, bone cavities and spleens contained regenerated cells of the immune system which required interaction with thymocytes (from intact donors) and antigen (SRBC) to form antigen-sensitive units (ASU) and to generate mature immunocytes. These cells were capable of differentiating either into direct or indirect hemolytic plaque-forming cells (PFC). The precursors of PFC regenerated earlier than the other cell type necessary for immunocompetence, the antigen-reactive cell (ARC). The latter was not found until 10 or more days after transplantation. Availability of ARC was inferred from PFC responses elicited by grafted mice challenged with SRBC at varying intervals. In a second series of experiments, graded numbers of marrow cells (ranging from 107 to 5 x 107) were transplanted with 5 x 107 or 108 thymocytes into irradiated mice, and SRBC were given 18 hr later. After 9–12 days the recipient spleens contained all or some of the following immunocytes: direct and indirect PFC, and hemagglutinating cluster-forming cells. The frequency of each immune response varied independently of the others, but in relation to the number of marrow cells grafted. This was interpreted to indicate that ASU formed in irradiated mice by interaction of marrow and thymus cells were similar to those of intact mice. In particular, they were specialized for the molecular class (IgM or IgG) and function (lysis or agglutination) of the antibody to be secreted by their descendent immunocytes. Hence, class-differentiation appeared to be conferred upon ASU by their marrow-derived components.
Lymphomatoid contact dermatitis caused by isopropyl-diphenylenediamine: Two cases
Authors: Vincent Marlière a, Marie Beylot-Barry a, Marie-Sylvie Doutre a, Michel Furioli a, Béatrice Vergier b, Pierre Dubus b, Jean-Philippe Merlio b, Claire Beylot a
Journal: Journal of Allergy and Clinical Immunology (1998)
Is IL-6 both a cytokine and a neurotrophic factor?
Authors: J A Wagner
Journal: The Journal of Experimental Medicine (1996)

The article by Hirota et al. (pp. 2627-2634) provides interesting evidence for the action of Interleukin-6 (IL-6) in the nervous system, but is it appropriate to consider IL-6 a neurotrophic factor; and, if so, what does this mean? The last decade has seen the discovery of a large number of neurotrophic and neural differentiation factors in both the peripheral and central nervous system. Examples of peptides with interesting activities in the nervous system include BDNF, NT-3, CNTF, GDNF, bFGF, aFGF, IL-3, IL-2, LIF, and others. The molecular characterization of growth factors has led to the realization that these peptides can play different roles in the nervous system and that they can also play important roles in many other
Lipoprotein Particles and Incident Type 2 Diabetes in the Multi-Ethnic Study of Atherosclerosis
Authors: Rachel H. Mackey, Samia Mora, Alain G. Bertoni, Christina L. Wassel, Mercedes R. Carnethon, Christopher T. Sibley, David C. Goff
Journal: Diabetes Care (2015)

OBJECTIVE In the Multi-Ethnic Study of Atherosclerosis (MESA), we evaluated associations of baseline levels of a lipoprotein-based insulin resistance (IR) index (LP-IR), IR-related lipoprotein particles, mean particle sizes, and lipids, with incident type 2 diabetes, independent of confounders, glucose, insulin, and HOMA-IR. RESEARCH DESIGN AND METHODS Among 5,314 adults aged 45–84 years without baseline diabetes or cardiovascular disease, 656 cases of diabetes were identified during a mean follow-up of 7.7 years. Lipoprotein particle concentrations, size, and LP-IR were determined by nuclear magnetic resonance spectroscopy of stored baseline plasma. Potential effect modification, by race/ethnicity, sex, baseline use of lipid-lowering medications or hormone therapy, or glucose strata (&amp;lt;90, 90–99, and ≥100 mg/dL), was also evaluated. RESULTS Higher levels of LP-IR, large VLDL particles (VLDL-P), small LDL particles, triglycerides (TG), and TG–to–HDL cholesterol (HDL-C) ratio and lower levels of large HDL particles, smaller HDL and LDL size, and larger VLDL size were significantly associated with incident diabetes adjusted for confounders and glucose or insulin. These also were similar by race/ethnicity, sex, and treatment group. Associations were similar for LP-IR, large VLDL-P, mean VLDL size, TG, and TG–to–HDL-C ratio; they persisted for LP-IR, large VLDL-P, or mean VLDL size adjusted for HOMA-IR or TG–to–HDL-C ratio and glucose but not for the TG–to–HDL-C ratio adjusted for LP-IR or for HOMA-IR or insulin if adjusted for LP-IR and glucose. CONCLUSIONS Among ethnically diverse men and women, LP-IR, large VLDL-P, large VLDL size, TG, and TG–to–HDL-C ratio were associated with incident diabetes independent of established risk factors, glucose, insulin, or HOMA-IR, as well as the use of lipid-lowering medications or hormone therapy.
Ligation of OX40 (CD134) regulates graft-versus-host disease (GVHD) and graft rejection in allogeneic bone marrow transplant recipients
Authors: Bruce R. Blazar, Arlene H. Sharpe, Andy I. Chen, Angela Panoskaltsis-Mortari, Christopher Lees, Hisaya Akiba, Hideo Yagita, Nigel Killeen, Patricia A. Taylor
Journal: Blood (2003)
Epstein-Barr virus-associated post-transplant lympho-proliferative disease of donor origin in liver transplant recipients
Authors: Mario Strazzabosco, Barbara Corneo, Rosa Maria Iemmolo, Chiara Menin, Giorgio Gerunda, Laura Bonaldi, Roberto Merenda, Daniele Neri, Alessandro Poletti, Marco Montagna, Annarosa Del Mistro, Alvise Maffei Faccioli, Emma D'Andrea
Journal: Journal of Hepatology (1997)
Mediation by NF-κB of cytokine induced expression of intercellular adhesion molecule 1 (ICAM-1) in an intestinal epithelial cell line, a process blocked by proteasome inhibitors
Authors: C Jobin, C Hellerbrand, L L Licato, D A Brenner, R B Sartor
Journal: Gut (1998)

Background/aims —The gene promoter for the intercellular adhesion molecule ICAM-1 possesses binding sites for several transcriptional factors, including nuclear factor κB (NF-κB). The role of NF-κB in ICAM-1 gene regulation was therefore examined by using different proteasome inhibitors in tumour necrosis factor α (TNF-α) stimulated IEC-6 rat intestinal epithelial cells. Methods —ICAM-1 expression was analysed by enzyme linked immunosorbent assay (ELISA), reverse transcriptase polymerase chain reaction, and immunohistochemistry. Steady state levels of cytoplasmic IκB protein were evaluated by western blot, and nuclear translocation of NF-κB was determined by electrophoretic mobility shift assay and immunofluorescence staining. Cell adhesion was assayed by measuring the binding of fluorescence labelled MOLT-4 cells. Results —TNF-α induced ICAM-1 mRNA and protein expression in IEC-6 cells, which was followed by increased adhesion of MOLT-4 lymphocytes. Blocking TNF-α induced IκBα degradation with proteasome inhibitors reduced TNF-α induced NF-κB activation and ICAM-1 gene induction and notably decreased MOLT-4 cell adhesion without affecting Jun N-terminal kinase (JNK/SAPK) activity or de novo protein synthesis. Conclusion —TNF-α induction of ICAM-1 expression is mediated by the transcription factor NF-κB and can be inhibited by blocking IκBα degradation. Thus the IκB/NF-κB system is a promising target for pharmacological modulation of the expression of adhesion molecules and other inflammatory genes in the intestine.
Transmembrane Protein 18 Enhances the Tropism of Neural Stem Cells for Glioma Cells
Authors: Jaana Jurvansuu, Ying Zhao, Doreen S.Y. Leung, Jerome Boulaire, Yuan Hong Yu, Sohail Ahmed, Shu Wang
Journal: Cancer Research (2008)

Abstract The failure of current glioma therapies is mainly due to the ability of the tumor cells to invade extensively the surrounding healthy brain tissue, hence escaping localized treatments. Neural stem cells (NSC) are able to home in on tumor foci at sites distant from the main tumor mass, possibly enabling treatment of scattered glioma clusters. To make the strategy more effective, we performed a cDNA expression library screening to identify the candidate genes that once overexpressed would enhance the tropism of NSCs for gliomas. Here, we show that a previously unannotated gene, the one encoding transmembrane protein 18 (TMEM18), is one such gene. Overexpression of TMEM18 was seen in the current study to provide NSCs and neural precursors an increased migration capacity toward glioblastoma cells in vitro and in the rat brain. Functional inactivation of the TMEM18 gene resulted in almost complete loss of the migration activity of these cells. Thus, TMEM18 is a novel cell migration modulator. Overexpression of this protein could be favorably used in NSC-based glioma therapy. [Cancer Res 2008;68(12):4614–22]
Prolonged Grief Disorder: Psychometric Validation of Criteria Proposed for DSM-V and ICD-11
Authors: Holly G. Prigerson, Mardi J. Horowitz, Selby C. Jacobs, Colin M. Parkes, Mihaela Aslan, Karl Goodkin, Beverley Raphael, Samuel J. Marwit, Camille Wortman, Robert A. Neimeyer, George Bonanno, Susan D. Block, David Kissane, Paul Boelen, Andreas Maercker, Brett T. Litz, Jeffrey G. Johnson, Michael B. First, Paul K. Maciejewski
Journal: PLoS Medicine (2009)

Bereavement is a universal experience, and its association with excess morbidity and mortality is well established. Nevertheless, grief becomes a serious health concern for a relative few. For such individuals, intense grief persists, is distressing and disabling, and may meet criteria as a distinct mental disorder. At present, grief is not recognized as a mental disorder in the DSM-IV or ICD-10. The goal of this study was to determine the psychometric validity of criteria for prolonged grief disorder (PGD) to enhance the detection and potential treatment of bereaved individuals at heightened risk of persistent distress and dysfunction.
Contexts and functions of retrieval
Authors: Eugene Winograd
Journal: Behavioral and Brain Sciences (1996)

Abstract Koriat &amp; Goldsmith provide an excellent analysis of the flexibility of retrieval processes and how they are situationally dependent. I agree with their emphasis on functional considerations and argue that the traditional laboratory experiment motivates the subject to be accurate. However, I disagree with their strong claim that the quantity–accuracy distinction implies an essential discontinuity between traditional and naturalistic approaches to the study of memory.
AMP-activated protein kinase suppresses urate crystal-induced inflammation and transduces colchicine effects in macrophages
Authors: Yun Wang, Benoit Viollet, Robert Terkeltaub, Ru Liu-Bryan
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objective</h3> AMP-activated protein kinase (AMPK) is metabolic biosensor with anti-inflammatory activities. Gout is commonly associated with excesses in soluble urate and in nutrition, both of which suppress tissue AMPK activity. Gout is driven by macrophage-mediated inflammation transduced partly by NLRP3 inflammasome activation and interleukin (IL)-1β release. Hence, we tested the hypothesis that AMPK activation limits monosodium urate (MSU) crystal-induced inflammation. <h3>Methods</h3> We studied bone marrow-derived macrophages (BMDMs) from AMPKα1 knockout and wild-type mice, and assessed the selective AMPK pharmacological activator A-769662 and a low concentration (10 nM) of colchicine. We examined phosphorylation (activation) of AMPKα Thr172, NLRP3 mRNA expression, and caspase-1 cleavage and IL-1β maturation using western blot and quantitative RT-PCR approaches. We also assessed subcutaneous murine air pouch inflammatory responses to MSU crystals in vivo. <h3>Results</h3> MSU crystals suppressed phosphorylation of AMPKα in BMDMs. Knockout of AMPKα1 enhanced, and, conversely, A-769662-inhibited MSU crystal-induced inflammatory responses including IL-1β and CXCL1 release in vitro and in vivo. A-769662 promoted AMPK-dependent macrophage anti-inflammatory M2 polarisation and inhibited NLRP3 gene expression, activation of caspase-1 and IL-1β. Colchicine, at low concentration (10 nM) achieved in gout flare prophylaxis dosing, promoted phosphorylation of AMPKα and macrophage M2 polarisation, and reduced activation of caspase-1 and release of IL-1β and CXCL1 by MSU crystals in BMDMs in vitro. <h3>Conclusions</h3> AMPK activity limits MSU crystal inflammation in vitro and in vivo, and transduces multiple anti-inflammatory effects of colchicine in macrophages. Targeting increased and sustained AMPK activation in inflammatory cells merits further investigation for enhancing efficacy of prophylaxis and treatment of gouty inflammation.
American Heart Association Guide for Improving Cardiovascular Health at the Community Level, 2013 Update
Authors: Thomas A. Pearson, Latha P. Palaniappan, Nancy T. Artinian, Mercedes R. Carnethon, Michael H. Criqui, Stephen R. Daniels, Gregg C. Fonarow, Stephen P. Fortmann, Barry A. Franklin, James M. Galloway, David C. Goff, Gregory W. Heath, Ariel T. Holland Frank, Penny M. Kris-Etherton, Darwin R. Labarthe, Joanne M. Murabito, Ralph L. Sacco, Comilla Sasson, Melanie B. Turner
Journal: Circulation (2013)
Evolutionary Relationships of Apusomonads Inferred from Taxon-Rich Analyses of 6 Nuclear Encoded Genes
Authors: Eunsoo Kim, Alastair G. B. Simpson, Linda E. Graham
Journal: Molecular Biology and Evolution (2006)

The phylogenetic relationships of the biflagellate protist group Apusomonadidae have been unclear despite the availability of some molecular data. We analyzed sequences from 6 nuclear encoded genes—small-subunit rRNA, large-subunit rRNA, α-tubulin, β-tubulin, actin, and heat shock protein 90—to infer the phylogenetic position of Apusomonas proboscidea Aléxéieff 1924. To increase the taxon richness of the study, we also obtained new sequences from representatives of several other major eukaryotic groups: Chrysochromulina sp. National Institute for Environmental Studies 1333 (Haptophyta), Cyanophora paradoxa (Glaucophyta), Goniomonas truncata (Cryptophyceae), Leucocryptos marina (Kathablepharidae), Mesostigma viride (Streptophyta, Viridiplantae), Peridinium limbatum (Alveolata), Pterosperma cristatum (Prasinophytae, Viridiplantae), Synura sphagnicola (Stramenopiles), and Thaumatomonas sp. (Rhizaria). In most individual gene phylogenies, Apusomonas branched close to either of the 2 related taxa—Opisthokonta (including animals, fungi, and choanoflagellates) or Amoebozoa. Combined analyses of all 4 protein-coding genes or all 6 studied genes strongly supported the hypothesis that Apusomonadidae is closely related to Opisthokonta (or to all other eukaryotic groups except Opisthokonta, depending on the position of the eukaryotic root). Alternative hypotheses were rejected in approximately unbiased tests at the 5% level. However, the strong phylogenetic signal supporting a specific affiliation between Apusomonadidae and Opisthokonta largely originated from the α-tubulin data. If α-tubulin is not considered, topologies in which Apusomonadidae is sister to Opisthokonta or is sister to Amoebozoa were more or less equally supported. One current model for deep eukaryotic evolution holds that eukaryotes are divided into primary "unikont" and "bikont" clades and are descended from a "uniflagellate" common ancestor. Together with other information, our data suggest instead that unikonts (=Opisthokonta and Amoebozoa) are not strictly monophyletic and are descended from biflagellate ancestors.
Effects of Notch Signaling on Regulation of Myeloid Cell Differentiation in Cancer
Authors: Pingyan Cheng, Vinit Kumar, Hao Liu, Je-In Youn, Mayer Fishman, Simon Sherman, Dmitry Gabrilovich
Journal: Cancer Research (2013)

Abstract Functionally altered myeloid cells play an important role in immune suppression in cancer, in angiogenesis, and in tumor cells' invasion and metastases. Here, we report that inhibition of Notch signaling in hematopoietic progenitor cells (HPC), myeloid-derived suppressor cells (MDSC), and dendritic cells is directly involved in abnormal myeloid cell differentiation in cancer. Inhibition of Notch signaling was caused by the disruption of the interaction between Notch receptor and transcriptional repressor CSL, which is normally required for efficient transcription of target genes. This disruption was the result of serine phosphorylation of Notch. We demonstrated that increased activity of casein kinase 2 (CK2) observed in HPC and in MDSC could be responsible for the phosphorylation of Notch and downregulation of Notch signaling. Inhibition of CK2 by siRNA or by pharmacological inhibitor restored Notch signaling in myeloid cells and substantially improved their differentiation, both in vitro and in vivo. This study demonstrates a novel mechanism regulation of Notch signaling in cancer. This may suggest a new perspective for pharmacological regulation of differentiation of myeloid cells in cancer. Cancer Res; 74(1); 141–52. ©2013 AACR.
Orocaecal transit time in health and disease.
Authors: I T Gilmore
Journal: Gut (1990)

Leading articleOrocaecal transit time in health and disease Few gastroenterologists would underrate the importance of gastrointestinal motility in the pathogenesis ofgut symptoms, particularly as the majority of clinic patients have functional symptoms.While there have been genuine advances in the understanding of the neurohumoral control mechanisms of gut motility, clinical applications have been limited.Gastro- enterologists have therefore shown great interest in simple
A5.1 Abnormal Calcium Influx in T and B Lymphocytes from Systemic Lupus Erythematosus Patients is Related to STIM-1 Over-Expression
Authors: Yves Renaudineau, Olivier Mignen, Tinhinane Fali, Miguel Burgos, Divi Cornec, Sandrine Jousse, Alain Saraux, Jacques-Olivier Pers
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> Recently described, the molecule STIM1 (stromal interaction molecule 1) acts as a key mediator of calcium influx by controlling cell proliferation after antigen stimulation, Erk phosphorylation, cytokine production and apoptosis. Although STIM1 mutations have been associated with severe immunodeficiency, no study has focused on the STIM1 molecule in autoimmune diseases. <h3>Materials and Methods</h3> T and B lymphocytes, purified by negative selection from peripheral blood of patients with systemic lupus erythematosus (SLE, n = 11), rheumatoid arthritis (RA, n = 7), primary Sjögren’s syndrome (pSS, n = 11) and healthy controls (HC, n = 12) were tested by flow cytometry and Western blotting to determine the expression of STIM1. Video microscopy using specific probes has been used to assess intracellular calcium levels. <h3>Results</h3> T cells from peripheral blood of HC express more STIM1 molecules (mean fluorescence intensity (MFI) 3.42 ± 0.13) than B cells (MFI 2.18 ± 0.20, P &lt; 0.01). In B lymphocyte subpopulations, the expression of STIM1 is 2 times higher in CD24<sup>high</sup>CD38<sup>high</sup> transitional B cells (MFI 4.83 ± 0.63) compared with CD24<sup>low</sup>CD38<sup>low</sup> mature B cells (MFI 2.47 ± 0.15, P &lt; 0.01) and CD24<sup>high</sup>CD38<sup>low</sup> memory B cells (MFI 3.64 ± 0.42, P &lt; 0.05). The expression of STIM1 in T and B lymphocytes from patients with RA and pSS was similar to HC. An highest calcium influx and a constitutive Erk phosphorylation characterise T and B cells from SLE patients when compared with HC and disease controls. As suspected, STIM1 is over-expressed in SLE, when compared with HC and this expression is similar between T cells (MFI 8.70 ± 0.87) and B cells (MFI 9.00 ± 1.08). Within B cell subsets, STIM1 expression is 3.4 fold highest in transitional SLE B cells (MFI: 16.25 ± 2.18, <i>P</i> &lt; 0.001) than in transitional HC B cells and 2.3 fold highest than in mature SLE B cells (MFI: 7.1 ± 1.53) and memory SLE B cells (MFI: 9.51 ± 2.01). Western blotting results confirm the highest expression of STIM1 in SLE. Transient transfection of STIM1-targeting siRNAs was shown to restore the calcium influx and decrease Erk phosphorylation. Of particular note, the associations of CpG/anti-IgM Ab and CpG/anti-CD40 Ab are effective to induce STIM1 expression. Finally, STIM1 level was not correlated with the SLE disease activity index (SLEDAI) and autoantibodies (ANA, anti-dsDNA, anti-SSA/Ro). <h3>Conclusions</h3> These results suggest that the differential expression of STIM1 may be an important factor in the process of lymphocyte self-reactivity in SLE, which opens new pathophysiological and therapeutic perspectives.