tbuckley/cabot-search huggingface dataset:
Class A scavenger receptors regulate tolerance against apoptotic cells, and autoantibodies against these receptors are predictive of systemic lupus
Authors: Fredrik Wermeling, Yunying Chen, Timo Pikkarainen, Annika Scheynius, Ola Winqvist, Shozo Izui, Jeffrey V. Ravetch, Karl Tryggvason, Mikael C.I. Karlsson
Journal: The Journal of Experimental Medicine (2007)

Apoptotic cells are considered to be a major source for autoantigens in autoimmune diseases such as systemic lupus erythematosus (SLE). In agreement with this, defective clearance of apoptotic cells has been shown to increase disease susceptibility. Still, little is known about how apoptotic cell–derived self-antigens activate autoreactive B cells and where this takes place. In this study, we find that apoptotic cells are taken up by specific scavenger receptors expressed on macrophages in the splenic marginal zone and that mice deficient in these receptors have a lower threshold for autoantibody responses. Furthermore, antibodies against scavenger receptors are found before the onset of clinical symptoms in SLE-prone mice, and they are also found in diagnosed SLE patients. Our findings describe a novel mechanism where autoantibodies toward scavenger receptors can alter the response to apoptotic cells, affect tolerance, and thus promote disease progression. Because the autoantibodies can be detected before onset of disease in mice, they could have predictive value as early indicators of SLE.
GLOB-1: a prospective randomised clinical phase III trial comparing vinorelbine–cisplatin with vinorelbine–ifosfamide–cisplatin in metastatic non-small-cell lung cancer patients
Authors: P.J. Souquet, E.H. Tan, J. Rodrigues Pereira, R. Van Klaveren, A. Price, U. Gatzemeier, M. Jaworski, J.P. Burillon, D. Aubert
Journal: Annals of Oncology (2002)
Long non-coding RNA HOTAIR, a c-Myc activated driver of malignancy, negatively regulates miRNA-130a in gallbladder cancer
Authors: Ming-zhe Ma, Chun-xiao Li, Yan Zhang, Ming-zhe Weng, Ming-di Zhang, Yi-yu Qin, Wei Gong, Zhi-wei Quan
Journal: Molecular Cancer (2014)

Protein coding genes account for only about 2% of the human genome, whereas the vast majority of transcripts are non-coding RNAs including long non-coding RNAs. A growing volume of literature has proposed that lncRNAs are important players in cancer. HOTAIR was previously shown to be an oncogene and negative prognostic factor in a variety of cancers. However, the factors that contribute to its upregulation and the interaction between HOTAIR and miRNAs are largely unknown. A computational screen of HOTAIR promoter was conducted to search for transcription-factor-binding sites. HOTAIR promoter activities were examined by luciferase reporter assay. The function of the c-Myc binding site in the HOTAIR promoter region was tested by a promoter assay with nucleotide substitutions in the putative E-box. The association of c-Myc with the HOTAIR promoter in vivo was confirmed by chromatin immunoprecipitation assay and Electrophoretic mobility shift assay. A search for miRNAs with complementary base paring with HOTAIR was performed utilizing online software program. Gain and loss of function approaches were employed to investigate the expression changes of HOTAIR or miRNA-130a. The expression levels of HOTAIR, c-Myc and miRNA-130a were examined in 65 matched pairs of gallbladder cancer tissues. The effects of HOTAIR and miRNA-130a on gallbladder cancer cell invasion and proliferation was tested using in vitro cell invasion and flow cytometric assays. We demonstrate that HOTAIR is a direct target of c-Myc through interaction with putative c-Myc target response element (RE) in the upstream region of HOTAIR in gallbladder cancer cells. A positive correlation between c-Myc and HOTAIR mRNA levels was observed in gallbladder cancer tissues. We predicted that HOTAIR harbors a miRNA-130a binding site. Our data showed that this binding site is vital for the regulation of miRNA-130a by HOTAIR. Moreover, a negative correlation between HOTAIR and miRNA-130a was observed in gallbladder cancer tissues. Finally, we demonstrate that the oncogenic activity of HOTAIR is in part through its negative regulation of miRNA-130a. Together, these results suggest that HOTAIR is a c-Myc-activated driver of malignancy, which acts in part through repression of miRNA-130a.
High prevalence of the H1069Q mutation in East German patients with Wilson disease: rapid detection of mutations by limited sequencing and phenotype–genotype analysis
Authors: Karel Caca, Peter Ferenci, Hans-Jürgen Kühn, Claudia Polli, Helmut Willgerodt, Bernhard Kunath, Wieland Hermann, Joachim Mössner, Frieder Berr
Journal: Journal of Hepatology (2001)
Using a gluten oral food challenge protocol to improve diagnosis of wheat-dependent exercise-induced anaphylaxis
Authors: Knut Brockow, Daniel Kneissl, Luzia Valentini, Otto Zelger, Martine Grosber, Claudia Kugler, Martina Werich, Ulf Darsow, Hiroaki Matsuo, Eishin Morita, Johannes Ring
Journal: Journal of Allergy and Clinical Immunology (2014)
A randomised comparative trial of infusional ECisF versus conventional FEC as adjuvant chemotherapy in early breast cancer: the TRAFIC trial
Authors: B. Sirohi, R. A'Hern, G. Coombes, J.M. Bliss, T. Hickish, T. Perren, M. Crawford, M. O'Brien, T. Iveson, S. Ebbs, A. Skene, R. Laing, I.E. Smith
Journal: Annals of Oncology (2010)

The epirubicin with cisplatin and infusional 5-fluorouracil (5-FU) (ECisF) regimen was found to be highly active in the treatment of metastatic breast cancer and as neoadjuvant therapy. The UK TRAFIC (trial of adjuvant 5-FU infusional chemotherapy) trial (CRUK/95/007) compared this schedule with 5-FU, epirubicin and cyclophosphamide (FEC60) as adjuvant therapy in patients with early breast cancer.In this multicentre, open-label, phase III randomised controlled trial, 349 women were randomly assigned to receive i.v. ECisF [epirubicin 60 mg/m(2), day 1, cisplatin 60 mg/m(2), day 1 and 5-FU 200 mg/m(2) by daily 24-h infusion (n = 172)] or FEC [5-FU 600 mg/m(2), day 1, epirubicin 60 mg/m(2), day 1 and cyclophosphamide 600 mg/m(2), day 1 (n = 177)]. Both treatments were delivered every 3 weeks for six cycles. The primary end point was relapse-free interval (RFI). TRAFIC is registered as an International Standard Randomised Controlled Trial (ISRCTN 83324925).All randomised patients were included in the intent-to-treat population. With a median follow-up of 112 months, there was no significant difference in RFI between the treatment groups [hazard ratio 0.84 (95% confidence interval 0.60-1.19); P = 0.33]. Toxic effects were more frequent in patients allocated to ECisF.While limited by size, TRAFIC has long follow-up. No evidence of a clinically worthwhile benefit for the infusional treatment compared with standard treatment was observed which would justify further investigation or widespread use.
Group 2 innate lymphoid cells and <scp>CD</scp>4<sup>+</sup> T cells cooperate to mediate type 2 immune response in mice
Authors: L. Y. Drake, K. Iijima, H. Kita
Journal: Allergy (2014)

Abstract Background Innate lymphoid cells ( ILC s) play important roles in innate immunity and tissue remodeling via production of various cytokines and growth factors. Group 2 ILC s ( ILC 2s) were recently shown to mediate the immune pathology of asthma even without adaptive immunity. However, little is known about possible interactions between ILC 2s and other immune cells. We sought to investigate the capacity of ILC 2s to regulate effector functions of T cells. Methods We isolated ILC 2s from the lungs of naïve mice. We cultured CD 4 + T cells with ILC 2s in vitro and examined the functions of these cell types. The mechanisms were investigated using blocking antibodies and cells isolated from cytokine‐deficient mice. For the in vivo study, we adoptively transferred ILC 2s and CD 4 + T cells into Il7ra −/− mice and subsequently exposed the mice to ovalbumin and a cysteine protease. Results Lung ILC 2s enhanced CD 4 + T‐cell proliferation and promoted production of type 2 cytokines in vitro . The interaction between ILC 2s and CD 4 + T cells involved costimulatory molecule OX 40L and cytokine IL ‐4, which was mainly derived from ILC 2s. Adoptive transfer of both ILC 2 and CD 4 + T‐cell populations, but not each population alone, into Il7ra −/− mice resulted in induction of a robust antigen‐specific type 2 cytokine response and airway inflammation. Conclusion Lung ILC 2s function to promote adaptive immunity in addition to their established roles in innate immunity. This novel function of ILC 2s needs to be taken into account when considering the pathophysiology of asthma and other allergic airway diseases.
Prevention of Dialysis Catheter Malfunction with Recombinant Tissue Plasminogen Activator
Authors: Brenda R. Hemmelgarn, Louise M. Moist, Charmaine E. Lok, Marcello Tonelli, Braden J. Manns, Rachel M. Holden, Martine LeBlanc, Peter Faris, Paul Barre, Jianguo Zhang, Nairne Scott-Douglas
Journal: New England Journal of Medicine (2011)

The effectiveness of various solutions instilled into the central venous catheter lumens after each hemodialysis session (catheter locking solutions) to decrease the risk of catheter malfunction and bacteremia in patients undergoing hemodialysis is unknown.We randomly assigned 225 patients undergoing long-term hemodialysis in whom a central venous catheter had been newly inserted to a catheter-locking regimen of heparin (5000 U per milliliter) three times per week or recombinant tissue plasminogen activator (rt-PA) (1 mg in each lumen) substituted for heparin at the midweek session (with heparin used in the other two sessions). The primary outcome was catheter malfunction, and the secondary outcome was catheter-related bacteremia. The treatment period was 6 months; treatment assignments were concealed from the patients, investigators, and trial personnel.A catheter malfunction occurred in 40 of the 115 patients assigned to heparin only (34.8%) and 22 of the 110 patients assigned to rt-PA (20.0%)--an increase in the risk of catheter malfunction by a factor of almost 2 among patients treated with heparin only as compared with those treated with rt-PA once weekly (hazard ratio, 1.91; 95% confidence interval [CI], 1.13 to 3.22; P = 0.02). Catheter-related bacteremia occurred in 15 patients (13.0%) assigned to heparin only, as compared with 5 (4.5%) assigned to rt-PA (corresponding to 1.37 and 0.40 episodes per 1000 patient-days in the heparin and rt-PA groups, respectively; P = 0.02). The risk of bacteremia from any cause was higher in the heparin group than in the rt-PA group by a factor of 3 (hazard ratio, 3.30; 95% CI, 1.18 to 9.22; P = 0.02). The risk of adverse events, including bleeding, was similar in the two groups.The use of rt-PA instead of heparin once weekly, as compared with the use of heparin three times a week, as a locking solution for central venous catheters significantly reduced the incidence of catheter malfunction and bacteremia. (Current Controlled Trials number, ISRCTN35253449.).
Terlipressin vs. Somatostatin in bleeding esophageal varices: A controlled, double-blind study
Authors: Siegfried Walker, Heinz-Peter Kreichgauer, Christian J. Bode
Journal: Hepatology (1992)

Fifty episodes of bleeding from esophageal or gastric varices in 33 patients with cirrhosis were randomized to treatment with either intravenous terlipressin (2 mg initially and 1 mg every 4 hr for 24 hr together with bolus injection and continuous infusion of placebo) or with somatostatin (250 μg as a bolus and continuous infusion of 250 μg/hr somatostatin for 24 hr and placebo injections). Standard therapy with transfusions, fluid and electrolyte correction and lactulose was administered in both groups. In the terlipressin group, 22 of 25 bleeding episodes (88%) were initially stopped by the vasoactive drugs, and in the somatostatin group 19 of 25 bleeding episodes (76%) were initially stopped by the vasoactive drugs. Two of the three bleeding episodes not arrested by terlipressin and five of the six bleeding episodes not arrested by somatostatin were controlled by balloon tamponade. In one patient in each group variceal bleeding initially could not be stopped, and the patients died. The failure rate of the vasoactive treatment alone, including rebleeding episodes within the study period, was 20% in the terlipressin group and 32% in the somatostatin group. The control rate, including balloon tamponade, was 96% in both groups. The hospital mortality rate was 16% (4 of 25) in the terlipressin group and 24% (6 of 25) in the somatostatin group. Blood transfusions, use of balloon tamponade and duration of bleeding did not differ significantly. This interim analysis of the ongoing study indicates that a large proportion of bleeding episodes from esophageal and fundic varices can be stopped initially (82%) and definitively controlled (74%) by vasoactive drugs alone. Differences in the effectiveness of terlipressin and somatostatin were not observed. (Hepatology 1992;15:1023–1030).
Dietary iron supplementation: a proinflammatory attack on the intestine?
Authors: Guenter Weiss
Journal: Gut (2014)

Iron deficiency is a global health problem affecting likewise two billion people, and this condition is more prevalent in developing than in industrialised countries. Specifically, in childhood, iron deficiency and subsequent iron deficiency anaemia are considered to negatively affect the development of children causing growth and mental retardation.1 This is due to the fact that iron is essential for oxygen transport as being the central molecule in haemoglobin and referred to the metal's function as an essential compound of many vital enzymes in mitochondrial respiration, metabolism, hormone synthesis and DNA replication. In order to prevent the negative consequences of iron deficiency on children's development, several controlled clinical trials were initiated to study the effects of dietary fortification with iron and other micronutrients on children's health mostly in rural sites of developing countries where such nutrients are scarce and where iron deficiency is highly prevalent. However, the results of these studies were staggering because iron supplementation resulted in a significant increase of infection related mortality, mostly related to malaria and invasive bacterial infections or increased morbidity due to diarrhoea.2 ,3 The mechanisms underlying these observations remained elusive thus far but may be linked to two major …
Acupuncture: An Evidence-Based Review of the Clinical Literature
Authors: David J. Mayer
Journal: Annual Review of Medicine (2000)

This chapter reviews the experimental literature on the effects of acupuncture treatment. The review covers the 14 medical conditions for which the National Institutes of Health Acupuncture Consensus Development Panel (NIHCDP) concluded that acupuncture either is effective (2 conditions) or may be useful (12 conditions). My conclusions partially support those of the NIHCDP. There is evidence that acupuncture is effective for the treatment of postoperative and chemotherapyinduced nausea and vomiting. Also, some data indicate that acupuncture may be useful for headache, low back pain, alcohol dependence, and paralysis resulting from stroke (4 of the 12 conditions for which the NIHCDP found that acupuncture may be useful). For most of the remaining conditions, there is little evidence that acupuncture is either effective or ineffective. It is recommended that workers in the field design double blind, sham controlled trials using adequate acupuncture treatment regimens, with specific hypotheses, and sample sizes sufficient to allow both positive and negative conclusions.
Sequence relationship of retrotransposable elements R1 and R2 within and between divergent insect species.
Authors: W D Burke, D G Eickbush, Y Xiong, J Jakubczak, T H Eickbush
Journal: Molecular Biology and Evolution (1993)

R1 and R2 are retrotransposable elements that integrate at specific sites in the 28S ribosomal RNA (rRNA) genes of Bombyx mori and Drosophila melanogaster. We have previously shown that most insect species contain insertions in their 28S genes at the R1 and/or R2 site. We have sequenced the 3' half of R1 and R2 elements from three additional insect species: the fungus gnat, Sciara coprophila (Diptera); the Japanese beetle, Popillia japonica (Colleoptera); and the parasitic wasp, Nasonia vitripennis (Hymenoptera). The elements were obtained by screening lambda phage genomic clones containing rDNA units and by a polymerase chain reaction approach using degenerate primers to conserved sequences in the reverse-transcriptase domain, in combination with a second primer to the 28S gene 3' of the insertion site. Comparisons of the sequences of R1 and R2 from four insect orders suggest that the organization of their open-reading frames has been conserved and is therefore likely to be similar throughout insects. This sequence analysis also indicates that, except for 5' truncations generated during the retrotransposition process itself, most elements have not accumulated mutations that would make them inactive. Popillia japonica and N. vitripennis differed from previously described species, in that (a) P. japonica contained multiple families of R2 and (b) N. vitripennis contained multiple families of R1. Nucleotide sequence identity between these different families is low. Amino acid sequence identity of their open-reading frames averaged only 41% for the R2 families of P. japonica and 35% for the R1 families of N. vitripennis. The presence of multiple highly divergent families of elements within a species suggests either that each insertion family is able to maintain its copy number without eliminating the other families in its competition for a limited number of 28S genes or that there has been extensive horizontal transfer of R1 and R2 elements between insect species.
Pregnancy-associated breast cancer is as chemosensitive as non-pregnancy-associated breast cancer in the neoadjuvant setting
Authors: R. Rouzier, G. Werkoff, C. Uzan, O. Mir, J. Gligorov, L. Selleret, F. Goffinet, F. Goldwasser, J.M. Treluyer, S. Uzan, S. Delaloge
Journal: Annals of Oncology (2011)
Internally Recurring Hippocampal Sequences as a Population Template of Spatiotemporal Information
Authors: Vincent Villette, Arnaud Malvache, Thomas Tressard, Nathalie Dupuy, Rosa Cossart
Journal: Neuron (2015)

The hippocampus is essential for spatiotemporal cognition. Sequences of neuronal activation provide a substrate for this fundamental function. At the behavioral timescale, these sequences have been shown to occur either in the presence of successive external landmarks or through internal mechanisms within an episodic memory task. In both cases, activity is externally constrained by the organization of the task and by the size of the environment explored. Therefore, it remains unknown whether hippocampal activity can self-organize into a default mode in the absence of any external memory demand or spatiotemporal boundary. Here we show that, in the presence of self-motion cues, a population code integrating distance naturally emerges in the hippocampus in the form of recurring sequences. These internal dynamics clamp spontaneous travel since run distance distributes into integer multiples of the span of these sequences. These sequences may thus guide navigation when external landmarks are reduced.
Reintroduction of Oxaliplatin Is Associated With Improved Survival in Advanced Colorectal Cancer
Authors: Aimery de Gramont, Marc Buyse, Jose Cortinas Abrahantes, Tomasz Burzykowski, Emmanuel Quinaux, Andres Cervantes, Arie Figer, Gérard Lledo, Michel Flesch, Laurent Mineur, Elisabeth Carola, Pierre-Luc Etienne, Fernando Rivera, Isabel Chirivella, Nathalie Perez-Staub, Christophe Louvet, Thierry André, Isabelle Tabah-Fisch, Christophe Tournigand
Journal: Journal of Clinical Oncology (2007)

In the OPTIMOX1 trial, previously untreated patients with advanced colorectal cancer were randomly assigned to two different schedules of leucovorin, fluorouracil, and oxaliplatin that were administered until progression in the control arm or in a stop-and-go fashion in the experimental arm. The randomly assigned treatment groups did not differ significantly in terms of response rate, progression-free survival, and overall survival (OS). However, the impact of oxaliplatin reintroduction on OS was potentially masked by the fact that a large number of patients did not receive the planned oxaliplatin reintroduction or received oxaliplatin after second-line therapy in both treatment groups.A Cox model was fitted with all significant baseline factors plus time-dependent variables reflecting tumor progression, reintroduction of oxaliplatin, and use of second-line irinotecan. A shared frailty model was fitted with all significant baseline factors plus the number of lines of chemotherapy received by the patient and the percentage of patients with oxaliplatin reintroduction in the center. An adjusted hazard ratio (HR) was calculated for three reintroduction classes (1% to 20%, 21% to 40%, and > 40%), using centers with no reintroduction (0%) as the reference group.Oxaliplatin reintroduction had an independent and significant impact on OS (HR = 0.56, P = .009). The percentage of patients with oxaliplatin reintroductions also had a significant impact on OS. Centers in which more than 40% of the patients were reintroduced had an adjusted HR for OS of 0.59 compared with centers in which no patient was reintroduced.Oxaliplatin reintroduction is associated with improved survival in patients with advanced colorectal cancer.
Functional suppression of Kcnq1 leads to early sodium channel remodelling and cardiac conduction system dysmorphogenesis
Authors: Angel J. de la Rosa, Jorge N. Domínguez, David Sedmera, Bara Sankova, Leif Hove-Madsen, Diego Franco, Amelia E. Aránega
Journal: Cardiovascular Research (2013)

Ion channel remodelling and ventricular conduction system (VCS) alterations play relevant roles in the generation of cardiac arrhythmias, but the interaction between ion channel remodelling and cardiac conduction system dysfunctions in an arrhythmogenic context remain unexplored. We have used a transgenic mouse line previously characterized as an animal model of Long QT Syndrome (LQTS) to analyse ion channel remodelling and VCS configuration. Reverse transcriptase-PCR and immunohistochemistry analysis showed early cardiac sodium channel upregulation at embryonic stages prior to the onset of Kv potassium channel remodelling, and cardiac hypertrophy at foetal stages. In line with these findings, patch-clamp assays demonstrated changes in sodium current density and a slowing of recovery from inactivation. Functional analysis by optical mapping revealed an immature ventricular activation pattern as well as an increase in the total left ventricle activation time in foetal transgenic hearts. Morphological analysis of LQTS transgenic mice in a Cx40GFP/+background demonstrated VCS dysmorphogenesis during heart development. Our data demonstrate early sodium channel remodelling secondary to IKs blockage in a mouse model of LQTS leading to morphological and functional anomalies in the developing VCS and cardiac hypertrophy. These results provide new insights into the mechanisms underlying foetal and neonatal cardiac electrophysiological disorders, which might help understand how molecular, functional, and morphological alterations are linked to clinical pathologies such as cardiac congenital anomalies, arrhythmias, and perinatal sudden death.