tbuckley/cabot-search huggingface dataset:
Low Natural Killer (NK) Cell Counts and Functionality Are Associated With Molecular Relapse After Imatinib Discontinuation In Patients (pts) With Chronic Phase (CP)-Chronic Myeloid Leukemia (CML) With Undetectable BCR-ABL Transcripts For At Least 2 Years: Preliminary Results From Immunostim, On Behalf Of STIM Investigators
Authors: Nicolas Dulphy, Guylaine Henry, Ing., Joelle Guilhot, Francois Guilhot, Franck E. Nicolini, Laurence Legros, Philippe Rousselot, Francois-Xavier Mahon, Antoine Toubert
Journal: Blood (2013)
A paper-based invasion assay: Assessing chemotaxis of cancer cells in gradients of oxygen
Authors: Bobak Mosadegh, Matthew R. Lockett, Kyaw Thu Minn, Karen A. Simon, Karl Gilbert, Shawn Hillier, David Newsome, Howard Li, Amy B. Hall, Diane M. Boucher, Brenda K. Eustace, George M. Whitesides
Journal: Biomaterials (2015)
Polymorphisms of the<i>VDR</i>gene are associated with presence of solar keratoses on the skin
Authors: M.A. Carless, T. Kraska, N. Lintell, R.E. Neale, A.C. Green, L.R. Griffiths
Journal: British Journal of Dermatology (2008)

Vitamin D has a range of biological effects including antiproliferative functions that are mediated through its receptors, encoded by the VDR gene.We investigated polymorphisms within the VDR gene for association with solar keratosis (SK), a biomarker for skin cancer, and examined interactions with skin phenotype.Among participants of the community-based Nambour Skin Cancer Study, we genotyped 190 people with SKs and 190 without for ApaI, TaqI and FokI polymorphisms.We found a significant difference in genotype frequencies of the TaqI polymorphism between affected and unaffected populations (P = 0.008). The TT/tt genotype group was associated with a twofold increase in odds of being affected by one or more SK. Individuals with fair skin and the TT/tt genotype had about a sevenfold increase, whereas fair-skinned people with the Tt genotype had a fourfold increase in odds of being affected by SK. Individuals with the TT/tt genotype who were prone to burn and not tan on acute sun exposure had about a sixfold increase in odds of SK. Fair-skinned people with VDR-Apa AA/aa genotypes had about an eightfold increase in odds of being affected by SK compared with a fivefold increase in individuals with the Aa genotype and fair skin.The trend for homozygote genotypes to increase the odds of SK suggests that intermediate VDR activity is important in protection or that the heterodimer formed by a heterozygous genotype may have an altered binding potential. Overall, these analyses indicate that VDR may be important in SK development.
Relationship of Stimulation Frequency to Automaticity in the Canine Purkinje Fiber during Ouabain Administration
Authors: PERRY M. HOGAN, STEPHEN M. WITTENBERG, FRANCIS J. KLOCKE
Journal: Circulation Research (1973)

Spontaneously beating Purkinje-papillary preparations stimulated transiently at 60-180 beats/min exhibited typical overdrive suppression of spontaneous rate in normal Tyrode's solution. When superfused with ouabain (2 x 10 -7 g/ml), the same preparations showed a progressive diminution of overdrive suppression and, ultimately, an acceleration of spontaneous rate in the immediate postoverdrive period. Usual effects of stimulation frequency on electrogenic activity associated with automaticity in the Purkinje fiber were altered significantly during the administration of ouabain. With ouabain, rapid stimulation reduced the maximum diastolic potential and the threshold potential by approximately the same amount and increased the rate of diastolic depolarization. During overdrive, the minimum diastolic potential decreased as a function of maximum diastolic potential, rate of diastolic depolarization, and cycle length. The magnitude of all effects increased directly with the stimulation frequency and the exposure time. At any given time, frequency-induced changes were quickly reversible on return to a lower frequency. However, a single early depolarization during recovery transiently reevoked changes in diastolic depolarization similar to those seen during rapid drive. The increase in the rate of diastolic depolarization appears to be the major change responsible for frequency-dependent enhanced automaticity. The effects observed during transient rapid stimulation resemble the electrophysiological alterations responsible for the final toxic effects of ouabain but occur well before any glycoside-induced change in the spontaneous rate. These effects appear to explain the frequency-dependent acceleration of ventricular pacemakers and the phenomenon of repetitive ventricular response previously described in intact animals during digitalization.
Receptor for Advanced-Glycation End Products
Authors: Loredana G. Bucciarelli, Michiyo Kaneko, Radha Ananthakrishnan, Evis Harja, Larisse K. Lee, Yuying C. Hwang, Shulamit Lerner, Soliman Bakr, Qing Li, Yan Lu, Fei Song, Wu Qu, Teodoro Gomez, Yu Shan Zou, Shi Fang Yan, Ann Marie Schmidt, Ravichandran Ramasamy
Journal: Circulation (2006)

Background— The beneficial effects of reperfusion therapies have been limited by the amount of ischemic damage that occurs before reperfusion. To enable development of interventions to reduce cell injury, our research has focused on understanding mechanisms involved in cardiac cell death after ischemia/reperfusion (I/R) injury. In this context, our laboratory has been investigating the role of the receptor for advanced-glycation end products (RAGE) in myocardial I/R injury. Methods and Results— In this study we tested the hypothesis that RAGE is a key modulator of I/R injury in the myocardium. In ischemic rat hearts, expression of RAGE and its ligands was significantly enhanced. Pretreatment of rats with sRAGE, a decoy soluble part of RAGE receptor, reduced ischemic injury and improved functional recovery of myocardium. To specifically dissect the impact of RAGE, hearts from homozygous RAGE-null mice were isolated, perfused, and subjected to I/R. RAGE-null mice were strikingly protected from the adverse impact of I/R injury in the heart, as indicated by decreased release of LDH, improved functional recovery, and increased adenosine triphosphate (ATP). In rats and mice, activation of the RAGE axis was associated with increases in inducible nitric oxide synthase expression and levels of nitric oxide, cyclic guanosine monophosphate (cGMP), and nitrotyrosine. Conclusions— These findings demonstrate novel and key roles for RAGE in I/R injury in the heart. The findings also demonstrate that the interaction of RAGE with advanced-glycation end products affects myocardial energy metabolism and function during I/R.
The Evolutionary History of Quorum-Sensing Systems in Bacteria
Authors: Emmanuelle Lerat, Nancy A. Moran
Journal: Molecular Biology and Evolution (2004)

Communication among bacterial cells through quorum-sensing (QS) systems is used to regulate ecologically and medically important traits, including virulence to hosts. QS is widespread in bacteria; it has been demonstrated experimentally in diverse phylogenetic groups, and homologs to the implicated genes have been discovered in a large proportion of sequenced bacterial genomes. The widespread distribution of the underlying gene families (LuxI/R and LuxS) raises the questions of how often QS genes have been transferred among bacterial lineages and the extent to which genes in the same QS system exchange partners or coevolve. Phylogenetic analyses of the relevant gene families show that the genes annotated as LuxI/R inducer and receptor elements comprise two families with virtually no homology between them and with one family restricted to the gamma-Proteobacteria and the other more widely distributed. Within bacterial phyla, trees for the LuxS and the two LuxI/R families show broad agreement with the ribosomal RNA tree, suggesting that these systems have been continually present during the evolution of groups such as the Proteobacteria and the Firmicutes. However, lateral transfer can be inferred for some genes (e.g., from Firmicutes to some distantly related lineages for LuxS). In general, the inducer/receptor elements in the LuxI/R systems have evolved together with little exchange of partners, although loss or replacement of partners has occurred in several lineages of gamma-Proteobacteria, the group for which sampling is most intensive in current databases. For instance, in Pseudomonas aeruginosa, a transferred QS system has been incorporated into the pathway of a native one. Gene phylogenies for the main LuxI/R family in Pseudomonas species imply a complex history of lateral transfer, ancestral duplication, and gene loss within the genus.
The T Cell Receptor/CD3 Complex: A Dynamic Protein Ensemble
Authors: H Clevers, B Alarcon, T Wileman, C Terhorst
Journal: Annual Review of Immunology (1988)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Analysis and Stability of Retinol in Plasma2
Authors: Yei-Mei Peng, Min-Jian Xu, David S. Alberts
Journal: JNCI Journal of the National Cancer Institute (1987)

A simple, precise, and specific high-performance liquid chromatography (HPLC) method was developed for the simultaneous measurement of retinol (ROH), 13-cis-retinoic acid (13-cRA), and 4-oxo-13-cRA. The average recovery of ROH from serum or plasma was 95%, and the precision of the assay was less than 5%. With this HPLC method, a series of studies was carried out to evaluate the stability of ROH in various matrices. ROH was stable under our HPLC assay conditions as well as in plasma- and in serum-enriched culture media; however, ROH was not stable in aqueous matrices. Serum or heparinized plasma may be routinely used for measurement of ROH concentrations, providing EDTA, oxalate, and citrate are not used as anticoagulants. Because of ROH stability, blood samples can be kept on ice in the dark for at least 24 hours prior to separation of plasma. In addition, plasma samples containing ROH can be stored for up to 1 year at −20°C without loss of stability.
Survival after adding capecitabine and trastuzumab to neoadjuvant anthracycline-taxane-based chemotherapy for primary breast cancer (GBG 40—GeparQuattro)
Authors: G. von Minckwitz, M. Rezai, P.A. Fasching, J. Huober, H. Tesch, I. Bauerfeind, J. Hilfrich, H. Eidtmann, B. Gerber, C. Hanusch, J.U. Blohmer, S.D. Costa, C. Jackisch, S. Paepke, A. Schneeweiss, S. Kümmel, C. Denkert, K. Mehta, S. Loibl, M. Untch
Journal: Annals of Oncology (2013)
Autophagy Is Critical for Pancreatic Tumor Growth and Progression in Tumors with p53 Alterations
Authors: Annan Yang, N.V. Rajeshkumar, Xiaoxu Wang, Shinichi Yabuuchi, Brian M. Alexander, Gerald C. Chu, Daniel D. Von Hoff, Anirban Maitra, Alec C. Kimmelman
Journal: Cancer Discovery (2014)

Pancreatic ductal adenocarcinoma is refractory to available therapies. We have previously shown that these tumors have elevated autophagy and that inhibition of autophagy leads to decreased tumor growth. Using an autochthonous model of pancreatic cancer driven by oncogenic Kras and the stochastic LOH of Trp53, we demonstrate that although genetic ablation of autophagy in the pancreas leads to increased tumor initiation, these premalignant lesions are impaired in their ability to progress to invasive cancer, leading to prolonged survival. In addition, mouse pancreatic cancer cell lines with differing p53 status are all sensitive to pharmacologic and genetic inhibition of autophagy. Finally, a mouse preclinical trial using cohorts of genetically characterized patient-derived xenografts treated with hydroxychloroquine showed responses across the collection of tumors. Together, our data support the critical role of autophagy in pancreatic cancer and show that inhibition of autophagy may have clinical utility in the treatment of these cancers, independent of p53 status.Recently, a mouse model with embryonic homozygous Trp53 deletion showed paradoxical effects of autophagy inhibition. We used a mouse model with Trp53 LOH (similar to human tumors), tumor cell lines, and patient-derived xenografts to show that p53 status does not affect response to autophagy inhibition. These findings have important implications on ongoing clinical trials.
PRODUCTION OF ATHEROMATOSIS IN THE AORTA OF THE BIRD BY THE ADMINISTRATION OF DIETHYLSTILBESTROL
Authors: I. L. Chaikoff, Stuart Lindsay, F. W. Lorenz, C. Entenman
Journal: The Journal of Experimental Medicine (1948)

A new experimental procedure for the production of arteriosclerosis in the bird is described. The subcutaneous implantation of diethylstilbestrol by means of which a sustained increase in the concentration of cholesterol, phospholipid, and neutral fat can be readily established, is shown to induce atherosclerosis of the aorta. The atherosclerosis has been compared with that artificially induced in the bird by the prolonged feeding of cholesterol and also with that occurring spontaneously. The stilbestrol-induced lesion more closely resembled the spontaneously occurring one in the bird than did that produced by cholesterol feeding. But all 3 lesions were fundamentally similar, differing only in the amounts and proportions of the various lipid constituents present. The concentrations of cholesterol in plasma of the stilbestrol-treated and cholesterol-fed birds were of the same order. Yet cholesterol constituted a greater proportion of the lipids deposited in the arterial wall of the cholesterol-fed than in that of the stilbestrol-treated birds. This finding suggests that the cholesterol content of the vascular lesion depends not only on the absolute concentration of cholesterol in plasma, but also on the proportion of cholesterol to other lipid constituents in plasma.
Tacrolimus ointment 0·1% in pityriasis alba: an open-label, randomized, placebo-controlled study
Authors: D. Rigopoulos, S. Gregoriou, C. Charissi, G. Kontochristopoulos, D. Kalogeromitros, S. Georgala
Journal: British Journal of Dermatology (2006)

Pityriasis alba (PA) is a frequent reason for dermatological consultation because of its chronic course, tendency to relapse and aesthetic impact.In view of its strong association with atopic dermatitis, the objective of this open-label study was to assess the efficacy and safety of tacrolimus ointment in the treatment of PA compared with the efficacy of moisturizers.The study population consisted of 60 individuals of phototype III or IV according to Fitzpatrick's classification, aged 6-21 years. Patients were randomly assigned to one of two groups. Subjects in group A were instructed to apply tacrolimus ointment 0.1% twice daily, 12 h apart, on all hypopigmented macules. Standard moisturizers with SPF 20 sunscreen were used on all lesions applied at least 30 min apart from the tacrolimus ointment. Subjects in group B used solely the same moisturizers with sunscreen. Hypopigmented areas were evaluated at baseline and weeks 0, 3, 6 and 9 by investigators for scaling, hypopigmentation and pruritus on a scale of 0-3. Patient satisfaction was also recorded on a scale of 0-3. All adverse effects were recorded.A statistically significant improvement through time, in hypopigmentation, pruritus and scaling was observed in both groups during the course of 9 weeks. Hypopigmentation resolved from a baseline score of 2.38+/-0.64 to 1.15+/-0.54 at week 3, 0.46+/-0.51 at week 6 and 0.00+/-0.00 at week 9 for the group applying tacrolimus ointment 0.1%. The difference in improvement between the two groups was statistically significant on all three assessments for hypopigmentation (P<0.001), and for pruritus on week 6 and 9 assessments (P<0.05). Three patients (11.5%) in the tacrolimus group reported a mild transient sensation of burning. All patients in the tacrolimus group reported they were completely satisfied or just satisfied with the treatment compared with only 50% of patients using the placebo.Tacrolimus ointment 0.1% appears to be an effective and safe treatment for PA.
Azithromycin treatment failure in macrolide-resistant Mycoplasma pneumoniae pneumonia
Authors: K. K. W. To, K.-H. Chan, Y.-F. Fung, K.-Y. Yuen, P.-L. Ho
Journal: European Respiratory Journal (2010)

<h3>Background</h3> Mental health disorders are viewed as a global concern requiring globally led approaches to address them. Since the publication of the 2007 <i>Lancet</i> series on global mental health (GMH), the term has become widespread. Over the last two decades, GMH has become increasingly affiliated with policy reform, academic courses, funding bodies and research. However, it is not always obvious how those working in the field of GMH are using the term, resulting in a lack of clarity. Therefore, work is needed to synthesise the current understanding(s) of GMH to help characterise its meaning. <h3>Aim</h3> To synthesise the literature and identify the different ways GMH is understood. <h3>Method</h3> A conceptual review, using a systematic search and a content analysis, was conducted to develop a conceptual framework of the different conceptual understandings of GMH. <h3>Results</h3> We developed a conceptual framework of four understandings of GMH. These understandings of GMH are as follows: an area of research generating findings to establish a GMH evidence-base; implementation of research into practice; improving the mental health environment; learning from and supporting low-and-middle-income countries (LMICs). <h3>Conclusion</h3> Our review proposes a simple framework, clarifying the key characteristics of the GMH landscape. The findings highlight the diversity of usage of the term in the literature, as well as present the wide scope that comprises the field of GMH. Referring to this framework may help those engaged with GMH to be more specific with which aspect of the field they are concerned with.
Effect of upper airway obstruction in acute stroke on functional outcome at 6 months
Authors: P M Turkington
Journal: Thorax (2004)

<b>Background:</b> The aim of this study was to determine whether upper airway obstruction occurring within the first 24 hours of stroke onset has an effect on outcome following stroke at 6 months. Traditional definitions used for obstructive sleep apnoea (OSA) are arbitrary and may not apply in the acute stroke setting, so a further aim of the study was to redefine respiratory events and to assess their impact on outcome. <b>Methods:</b> 120 patients with acute stroke underwent a sleep study within 24 hours of onset to determine the severity of upper airway obstruction (respiratory disturbance index, RDI-total study). Stroke severity (Scandinavian Stroke Scale, SSS) and disability (Barthel score) were also recorded. Each patient was subsequently followed up at 6 months to determine morbidity and mortality. <b>Results:</b> Death was independently associated with SSS (OR (95% CI) 0.92 (0.88 to 0.95), p&lt;0.00001) and RDI-total study (OR (95% CI) 1.07 (1.03 to 1.12), p&lt;0.01). The Barthel index was independently predicted by SSS (p = 0.0001; <i>r</i> = 0.259; 95% CI 0.191 to 0.327) and minimum oxygen saturation during the night (p = 0.037; <i>r</i> = 0.16; 95% CI 0.006 to 0.184). The mean length of the respiratory event most significantly associated with death at 6 months was 15 seconds (sensitivity 0.625, specificity 0.525) using ROC curve analysis. <b>Conclusion:</b> The severity of upper airway obstruction appears to be associated with a worse functional outcome following stroke, increasing the likelihood of death and dependency. Longer respiratory events appear to have a greater effect. These data suggest that long term outcome might be improved by reducing upper airway obstruction in acute stroke.
Identifying and Targeting <i>ROS1</i> Gene Fusions in Non–Small Cell Lung Cancer
Authors: Kurtis D. Davies, Anh T. Le, Mariana F. Theodoro, Margaret C. Skokan, Dara L. Aisner, Eamon M. Berge, Luigi M. Terracciano, Federico Cappuzzo, Matteo Incarbone, Massimo Roncalli, Marco Alloisio, Armando Santoro, D. Ross Camidge, Marileila Varella-Garcia, Robert C. Doebele
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Oncogenic gene fusions involving the 3′ region of ROS1 kinase have been identified in various human cancers. In this study, we sought to characterize ROS1 fusion genes in non–small cell lung cancer (NSCLC) and establish the fusion proteins as drug targets. Experimental Design: An NSCLC tissue microarray (TMA) panel containing 447 samples was screened for ROS1 rearrangement by FISH. This assay was also used to screen patients with NSCLC. In positive samples, the identity of the fusion partner was determined through inverse PCR and reverse transcriptase PCR. In addition, the clinical efficacy of ROS1 inhibition was assessed by treating a ROS1-positive patient with crizotinib. The HCC78 cell line, which expresses the SLC34A2–ROS1 fusion, was treated with kinase inhibitors that have activity against ROS1. The effects of ROS1 inhibition on proliferation, cell-cycle progression, and cell signaling pathways were analyzed by MTS assay, flow cytometry, and Western blotting. Results: In the TMA panel, 5 of 428 (1.2%) evaluable samples were found to be positive for ROS1 rearrangement. In addition, 1 of 48 patients tested positive for rearrangement, and this patient showed tumor shrinkage upon treatment with crizotinib. The patient and one TMA sample displayed expression of the recently identified SDC4–ROS1 fusion, whereas two TMA samples expressed the CD74–ROS1 fusion and two others expressed the SLC34A2–ROS1 fusion. In HCC78 cells, treatment with ROS1 inhibitors was antiproliferative and downregulated signaling pathways that are critical for growth and survival. Conclusions: ROS1 inhibition may be an effective treatment strategy for the subset of patients with NSCLC whose tumors express ROS1 fusion genes. Clin Cancer Res; 18(17); 4570–9. ©2012 AACR.
Association between pathological and MRI findings in multiple sclerosis
Authors: Massimo Filippi, Maria A Rocca, Frederik Barkhof, Wolfgang Brück, Jacqueline T Chen, Giancarlo Comi, Gabriele DeLuca, Nicola De Stefano, Bradley J Erickson, Nikos Evangelou, Franz Fazekas, Jeroen JG Geurts, Claudia Lucchinetti, David H Miller, Daniel Pelletier, Bogdan F Gh Popescu, Hans Lassmann
Journal: The Lancet Neurology (2012)
THE EFFECT OF NITROGEN MUSTARDS ON ENZYMES AND TISSUE METABOLISM
Authors: E. S. Guzman Barron, Grant R. Bartlett, Zelma Baker Miller
Journal: The Journal of Experimental Medicine (1948)

Nitrogen mustards are powerful inhibitors for choline oxidase, acetylcholine esterase, and choline acetylase, half-inhibition of the first enzyme being produced with concentrations around 1 x 10–6 M; i.e., ten times less than the LD50 values. Acetylcholine esterase and choline acetylase required higher concentrations. This inhibition seems to be due to the structural similarity of the ethylenimonium derivatives with choline and acetylcholine. A list of enzyme systems inhibited by nitrogen mustards is given.
Constipation and recurrent abdominal distension in a 39-year-old woman with irritable bowel syndrome
Authors: Seth Sweetser, Archana S Rao, Lawrence A Szarka
Journal: Gut (2011)

A 39-year-old woman with a previous diagnosis of irritable bowel syndrome presented with progressively worsening episodes of marked abdominal distension and difficulties with defecation. She had a long history of constipation and had tried a variety of laxatives with an unsatisfactory response. Recent colonoscopy was unremarkable. Physical exam revealed a protuberant abdomen with tympany and high-pitched bowel sounds. Inspection of the anus …