tbuckley/cabot-search huggingface dataset:
Single Cell Assay for Molecular Diagnostics and Medicine: Monitoring Intracellular Concentrations of Macromolecules by Two-photon Fluorescence Lifetime Imaging
Authors: Artem Pliss, Xiao Peng, Lixin Liu, Andrey Kuzmin, Yan Wang, Junle Qu, Yuee Li, Paras N Prasad
Journal: Theranostics (2015)

Molecular organization of a cell is dynamically transformed along the course of cellular physiological processes, pathologic developments or derived from interactions with drugs.The capability to measure and monitor concentrations of macromolecules in a single cell would greatly enhance studies of cellular processes in heterogeneous populations.In this communication, we introduce and experimentally validate a bio-analytical single-cell assay, wherein the overall concentration of macromolecules is estimated in specific subcellular domains, such as structure-function compartments of the cell nucleus as well as in nucleoplasm.We describe quantitative mapping of local biomolecular concentrations, either intrinsic relating to the functional and physiological state of a cell, or altered by a therapeutic drug action, using two-photon excited fluorescence lifetime imaging (FLIM).The proposed assay utilizes a correlation between the fluorescence lifetime of fluorophore and the refractive index of its microenvironment varying due to changes in the concentrations of macromolecules, mainly proteins.Two-photon excitation in Near-Infra Red biological transparency window reduced the photo-toxicity in live cells, as compared with a conventional single-photon approach.Using this new assay, we estimated average concentrations of proteins in the compartments of nuclear speckles and in the nucleoplasm at ~150 mg/ml, and in the nucleolus at ~284 mg/ml.Furthermore, we show a profound influence of pharmaceutical inhibitors of RNA synthesis on intracellular protein density.The approach proposed here will significantly advance theranostics, and studies of drug-cell interactions at the single-cell level, aiding development of personal molecular medicine.
Dissociation in aging Holocaust survivors
Authors: R Yehuda, A Elkin, K Binder-Brynes, B Kahana, S M Southwick, J Schmeidler, E L Giller
Journal: American Journal of Psychiatry (1996)

This study explored relationships among dissociation, trauma, and posttraumatic stress disorder (PTSD) in elderly Holocaust survivors with and without PTSD and in a demographically comparable group of nontraumatized subjects.Holocaust survivors with PTSD (N = 35) and without PTSD (N = 25) who had been recruited from the community and a comparison group (N = 16) were studied. Dissociation was evaluated with the Dissociative Experiences Scale. Past cumulative trauma and recent stress were evaluated with the Antonovsky Life Crises Scale and the Elderly Care Research Center Recent Life Events Scale, respectively. PTSD symptoms were assessed with the Clinician-Administered PTSD Scale.The Holocaust survivors with PTSD showed significantly higher levels of current dissociative experiences than did the other groups. However, the extent of dissociation was substantially less than that which has been observed in other trauma survivors with PTSD. Dissociative Experiences Scale scores were significantly associated with PTSD symptom severity, but the relation between Dissociative Experiences Scale scores and exposure to trauma was not significant.Possible explanations for this finding include the age of the survivors, the length of time since the traumatic event, and possible unique features of the Holocaust survivor population. Nevertheless, the findings call into question the current notion that PTSD and dissociative experiences represent the same phenomenon. The findings suggest that the relationships among dissociation, trauma, and PTSD can be further clarified by longitudinal studies of trauma survivors.
Hybrid origin of Japanese mice "Mus musculus molossinus": evidence from restriction analysis of mitochondrial DNA.
Authors: H Yonekawa, K Moriwaki, O Gotoh, N Miyashita, Y Matsushima, L M Shi, W S Cho, X L Zhen, Y Tagashira
Journal: Molecular Biology and Evolution (1988)

The Japanese mouse, Mus musculus molossinus, has long been considered an independent subspecies of the house mouse. A survey of restriction-site haplotypes of mitochondrial DNA (mtDNA) showed that Japanese mice have two main maternal lineages. The most common haplotype is closely related to the mtDNA of the European subspecies M. m. musculus. The other common haplotype and two minor ones are closely related to each other and to the mtDNA of an Asiatic subspecies, M. m. castaneus. Two other rare variants are probably the result of recent contamination by European M. m. domesticus. The musculus type of mtDNA is found in the southern two-thirds of Japan, whereas the common castaneus type is found in the northern third and the minor variants are found sporadically throughout Japan. The castaneus mtDNA lineage had a few minor variants, whereas the musculus lineage was completely monomorphic. By contrast, the native population of M. m. castaneus and the Chinese and Korean musculus populations were highly polymorphic. These results suggest that M. m. molossinus is a hybrid between ancestral colonies, possibly very small, of M. m. musculus and M. m. castaneus, rather than an independent subspecies.
Ectopic Beats Before CRT and Patient Outcomes
Authors: John Gorcsan, Jeanne E. Poole
Journal: Journal of the American College of Cardiology (2014)

The benefit of cardiac resynchronization therapy (CRT) for most heart failure (HF) patients with low ejection fraction (EF) and widened QRS is undisputed. Mortality and HF hospitalization are reduced, and multiple measures of cardiac function are improved. It remains of clinical importance that
Preliminary results of a phase II study of high-dose radiation therapy and neoadjuvant plus concomitant 5-fluorouracil with CDDP chemotherapy for patients with anal canal cancer: A French cooperative study
Authors: D. Peiffert, J.-F. Seitz, P. Rougier, E. François, F. Cvitkovic, X. Mirabel, S. Nasca, M. Ducreux, J.M. Hannoun-Levi, A. Lusinchi, E. Debrigode, T. Conroy, J.P. Pignon, J.P. Gérard
Journal: Annals of Oncology (1997)
Activation-Induced Cytidine Deaminase Expression in Human B Cell Precursors Is Essential for Central B Cell Tolerance
Authors: Tineke Cantaert, Jean-Nicolas Schickel, Jason M. Bannock, Yen-Shing Ng, Christopher Massad, Tyler Oe, Renee Wu, Aubert Lavoie, Jolan E. Walter, Luigi D. Notarangelo, Waleed Al-Herz, Sara Sebnem Kilic, Hans D. Ochs, Shigeaki Nonoyama, Anne Durandy, Eric Meffre
Journal: Immunity (2015)
Functional IL-17R in glioma stem cells: potential role in tumor progression and therapeutic implications
Authors: Prahlad Parajuli, Rohit Anand, Chandramouli Mandalaparty, Raviteja Suryadevara, Preethi Sriranga, Sharon Michelhaugh, Archana Thakur, Lawrence G Lum, Chaya Brodie, Sandeep Mittal
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Interleukin 17 (IL-17) is one of the most potent inflammatory cytokines and has been strongly implicated in inflammatory autoimmune disorders like rheumatoid arthritis and multiple sclerosis. However, the role of IL-17 in tumor progression is quite controversial and the underlying
Primary Gene Structure and Expression Studies of Rodent Paracellin-1
Authors: Stefanie Weber, Karl P. Schlingmann, Melanie Peters, Lene Niemann Nejsum, Søren Nielsen, Hartmut Engel, Karl-Heinz Grzeschik, Hannsjörg W. Seyberth, Hermann-Joseph Gröne, Rolf Nüsing, Martin Konrad
Journal: Journal of the American Society of Nephrology (2001)

ABSTRACT. The novel member of the claudin multigene family, paracellin-1/claudin-16, encoded by the gene PCLN1, is a renal tight junction protein that is involved in the paracellular transport of magnesium and calcium in the thick ascending limb of Henle's loop. Mutations in human PCLN1 are associated with familial hypomagnesemia with hypercalciuria and nephrocalcinosis, an autosomal recessive disease that is characterized by severe renal magnesium and calcium loss. The complete coding sequences of mouse and rat Pcln1 and the murine genomic structure are here presented. Full-length cDNAs are 939 and 1514 bp in length in mouse and rat, respectively, encoding a putative open-reading frame of 235 amino acids in both species with 99% identity. Exon-intron analysis of the human and mouse genes revealed a 100% homology of coding exon lengths and splice-site loci. By radiation hybrid mapping, the murine Pcln1 gene was assigned directly to marker D16Mit133 on mouse chromosome 16 (syntenic to a locus on human chromosome 3q27, which harbors the human PCLN1 gene). Mouse multiple-tissue Northern blot showed Pcln1 expression exclusively in the kidney. The expression profile along the nephron was analyzed by reverse transcriptase-PCR on microdissected nephron segments and immunohistochemistry of rat kidney. Paracellin-1 expression was restricted to distal tubular segments including the thick ascending limb of Henle's loop, the distal tubule, and the collecting duct. The identification and characterization of the rodent Pcln1 genes provide the basis for further studies of paracellin-1 function in suitable animal models.
Why a GME Squeeze Is Unlikely
Authors: Fitzhugh Mullan, Edward Salsberg, Katie Weider
Journal: New England Journal of Medicine (2015)

Interview with Dr. Fitzhugh Mullan on trends in the numbers of U.S. medical school graduates and GME positions. (06:42)Download Increases in numbers of medical students and a cap on Medicare-funded residency positions have sparked fear that some U.S. medical graduates won't be able to practice medicine. But the trends suggest that there will be ample slots for U.S. graduates over the next decade.
Inequalities in Alcohol-Related Mortality in 17 European Countries: A Retrospective Analysis of Mortality Registers
Authors: Johan P. Mackenbach, Ivana Kulhánová, Matthias Bopp, Carme Borrell, Patrick Deboosere, Katalin Kovács, Caspar W. N. Looman, Mall Leinsalu, Pia Mäkelä, Pekka Martikainen, Gwenn Menvielle, Maica Rodríguez-Sanz, Jitka Rychtaříková, Rianne de Gelder
Journal: PLoS Medicine (2015)

Socioeconomic inequalities in alcohol-related mortality have been documented in several European countries, but it is unknown whether the magnitude of these inequalities differs between countries and whether these inequalities increase or decrease over time.We collected and harmonized data on mortality from four alcohol-related causes (alcoholic psychosis, dependence, and abuse; alcoholic cardiomyopathy; alcoholic liver cirrhosis; and accidental poisoning by alcohol) by age, sex, education level, and occupational class in 20 European populations from 17 different countries, both for a recent period and for previous points in time, using data from mortality registers. Mortality was age-standardized using the European Standard Population, and measures for both relative and absolute inequality between low and high socioeconomic groups (as measured by educational level and occupational class) were calculated. Rates of alcohol-related mortality are higher in lower educational and occupational groups in all countries. Both relative and absolute inequalities are largest in Eastern Europe, and Finland and Denmark also have very large absolute inequalities in alcohol-related mortality. For example, for educational inequality among Finnish men, the relative index of inequality is 3.6 (95% CI 3.3-4.0) and the slope index of inequality is 112.5 (95% CI 106.2-118.8) deaths per 100,000 person-years. Over time, the relative inequality in alcohol-related mortality has increased in many countries, but the main change is a strong rise of absolute inequality in several countries in Eastern Europe (Hungary, Lithuania, Estonia) and Northern Europe (Finland, Denmark) because of a rapid rise in alcohol-related mortality in lower socioeconomic groups. In some of these countries, alcohol-related causes now account for 10% or more of the socioeconomic inequality in total mortality. Because our study relies on routinely collected underlying causes of death, it is likely that our results underestimate the true extent of the problem.Alcohol-related conditions play an important role in generating inequalities in total mortality in many European countries. Countering increases in alcohol-related mortality in lower socioeconomic groups is essential for reducing inequalities in mortality. Studies of why such increases have not occurred in countries like France, Switzerland, Spain, and Italy can help in developing evidence-based policies in other European countries.
Local immunotherapy with ONCOS-102 shapes harmful tumor associated CD68+ macrophages to become beneficial cells that correlate with increased overall survival
Authors: Sari Pesonen, Johan Lundin, Nina Linder, Riku Turkki, Ari Ristimäki, Timo Joensuu, Kalevi Kairemo, Kaarina Partanen, Tuomo Alanko, Elke Jäger, Julia Karbach, Claudia Wahle, Akseli Hemminki, Charlotta Backman, Mikael von Euler, Tiina Hakonen, Tuuli Ranki, Antti Vuolanto, Magnus Jäderberg, Dmitry Zamarin
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts With the increasing excitement around new immunotherapeutic approaches, there has been a shift in the way viral cancer therapy is regarded from providing mainly oncolysis towards being a cancer immunotherapy. Adenoviruses have a unique ability to prime and boost immune responses.
Foxp3<sup>+</sup> cells are running the show in patients with surgically resected nonsmall cell lung cancer
Authors: Nathalie Chaput, Aurelien Marabelle
Journal: European Respiratory Journal (2015)

Foxp3 microlocalisation dictates prognosis in NSCLC; CD8+ T-cells may influence prognosis in Treg-infiltrated tumours <http://ow.ly/T9PwJ> Tumor lymphocyte infiltrates (TILs) have a significant impact on multiple cancers prognosis, but the diversity of TILs and the methodological challenges to analyse TIL infiltrates in a reliable manner render difficult the interpretation of data explaining that to date TIL infiltration is not used in daily clinical practice.
Screen detection of ductal carcinoma in situ and subsequent incidence of invasive interval breast cancers: a retrospective population-based study
Authors: Stephen W Duffy, Amanda Dibden, Dimitrios Michalopoulos, Judith Offman, Dharmishta Parmar, Jacquie Jenkins, Beverley Collins, Tony Robson, Suzanne Scorfield, Kathryn Green, Clare Hall, Xiao-Hui Liao, Michael Ryan, Fiona Johnson, Guy Stevens, Olive Kearins, Sarah Sellars, Julietta Patnick
Journal: The Lancet Oncology (2015)

The value of screen detection and treatment of ductal carcinoma in situ (DCIS) is a matter of controversy. At present, the extent to which the diagnosis and treatment of DCIS could prevent the occurrence of invasive breast cancer in the future is not clear. We sought to estimate the association between detection of DCIS at screening and invasive interval cancers subsequent to the relevant screen.
Prévalence des infections nosocomiales dans deux hôpitaux de Lettonie
Authors: U Dumpis, A Balode, D Vīgante, I Narbute, R Valinteliene, V Pïrags, A Martinsons, I Vingre
Journal: Eurosurveillance (2003)

Une premiere enquete de prevalence du taux d'infections nosocomiales (IN) a ete menee dans deux hopitaux de Lettonie. Au moment de l'enquete, 17,5% des patients (226/1291) presentaient des signes d'infection ou etaient deja traites pour une infection. Le taux de prevalence global etait de 5,6% pour les IN (72/1291) et 12,7% (164/1291) pour les infections communautaires. L'infection des plaies operatoires etaient l'IN la plus courante (62%), suivie des infections des voies respiratoires (IVR) (7,5%) et des infections urinaires (6,4%). Le taux d'IN augmentait avec l'âge des patients, et etait plus eleve dans les unites de soins intensifs et les services de chirurgie, ainsi que chez les patients sous perfusion ou avec une sonde urinaire. L'investigation microbiologique a montre des resultats positifs chez 29% des patients presentant une IN. Un traitement antibiotique a ete administre a 22,3% des patients hospitalises (288/1291) et la cefazoline prescrite pour 62% d'entre eux (182/288).
Identification of novel CSF biomarkers for neurodegeneration and their validation by a high-throughput multiplexed targeted proteomic assay
Authors: Wendy E. Heywood, Daniela Galimberti, Emily Bliss, Ernestas Sirka, Ross W. Paterson, Nadia K. Magdalinou, Miryam Carecchio, Emma Reid, Amanda Heslegrave, Chiara Fenoglio, Elio Scarpini, Jonathan M. Schott, Nick C. Fox, John Hardy, Kailash Bahtia, Simon Heales, Neil J. Sebire, Henrik Zetterburg, Kevin Mills
Journal: Molecular Neurodegeneration (2015)

Currently there are no effective treatments for many neurodegenerative diseases. Reliable biomarkers for identifying and stratifying these diseases will be important in the development of future novel therapies. Lewy Body Dementia (LBD) is considered an under diagnosed form of dementia for which markers are needed to discriminate LBD from other forms of dementia such as Alzheimer's Disease (AD). This work describes a Label-Free proteomic profiling analysis of cerebral spinal fluid (CSF) from non-neurodegenerative controls and patients with LBD. Using this technology we identified several potential novel markers for LBD. These were then combined with other biomarkers from previously published studies, to create a 10 min multiplexed targeted and translational MRM-LC-MS/MS assay. This test was used to validate our new assay in a larger cohort of samples including controls and the other neurodegenerative conditions of Alzheimer's and Parkinson's disease (PD).Thirty eight proteins showed significantly (p < 0.05) altered expression in LBD CSF by proteomic profiling. The targeted MRM-LC-MS/MS assay revealed 4 proteins that were specific for the identification of AD from LBD: ectonucleotide pyrophosphatase/phosphodiesterase 2 (p < 0.0001), lysosome-associated membrane protein 1 (p < 0.0001), pro-orexin (p < 0.0017) and transthyretin (p < 0.0001). Nineteen proteins were elevated significantly in both AD and LBD versus the control group of which 4 proteins are novel (malate dehydrogenase 1, serum amyloid A4, GM2-activator protein, and prosaposin). Protein-DJ1 was only elevated significantly in the PD group and not in either LBD or AD samples. Correlations with Alzheimer-associated amyloid β-42 levels, determined by ELISA, were observed for transthyretin, GM2 activator protein and IGF2 in the AD disease group (r(2) ≥ 0.39, p ≤ 0.012). Cystatin C, ubiquitin and osteopontin showed a strong significant linear relationship (r(2) ≥ 0.4, p ≤ 0.03) with phosphorylated-tau levels in all groups, whilst malate dehydrogenase and apolipoprotein E demonstrated a linear relationship with phosphorylated-tau and total-tau levels in only AD and LBD disease groups.Using proteomics we have identified several potential and novel markers of neurodegeneration and subsequently validated them using a rapid, multiplexed mass spectral test. This targeted proteomic platform can measure common markers of neurodegeneration that correlate with existing diagnostic makers as well as some that have potential to show changes between AD from LBD.
Comparison of Cell Lysis Mediated by LFB-R603 with That Mediated by Ofatumumab Against Cells Expressing Low Levels of CD20,
Authors: Anne Bellon, Alain Sadoun, Karine Grivel, Maxime Moulard, Frederique Brune, Jean-Francois Prost, Margarita Salcedo
Journal: Blood (2011)
An Anti-EGFR IgA That Displays Improved Pharmacokinetics and Myeloid Effector Cell Engagement <i>In Vivo</i>
Authors: Stefan Lohse, Saskia Meyer, Laura A.P.M. Meulenbroek, J.H. Marco Jansen, Maaike Nederend, Anna Kretschmer, Katja Klausz, Uwe Möginger, Stefanie Derer, Thies Rösner, Christian Kellner, Denis Schewe, Peter Sondermann, Sanjay Tiwari, Daniel Kolarich, Matthias Peipp, Jeanette H.W. Leusen, Thomas Valerius
Journal: Cancer Research (2015)

Antibodies of IgA isotype effectively engage myeloid effector cells for cancer immunotherapy. Here, we describe preclinical studies with an Fc engineered IgA2m(1) antibody containing the variable regions of the EGFR antibody cetuximab. Compared with wild-type IgA2m(1), the engineered molecule lacked two N-glycosylation sites (N166 and N337), two free cysteines (C311 and C472), and contained a stabilized heavy and light chain linkage (P221R mutation). This novel molecule displayed improved production rates and biochemical properties compared with wild-type IgA. In vitro, Fab- and Fc-mediated effector functions, such as inhibition of ligand binding, receptor modulation, and engagement of myeloid effector cells for antibody-dependent cell-mediated cytotoxicity, were similar between wild-type and engineered IgA2. The engineered antibody displayed lower levels of terminal galactosylation leading to reduced asialoglycoprotein-receptor binding and to improved pharmacokinetic properties. In a long-term in vivo model against EGFR-positive cancer cells, improved serum half-life translated into higher efficacy of the engineered molecule, which required myeloid cells expressing human FcαRI for its full efficacy. However, Fab-mediated effector functions contributed to the in vivo efficacy because the novel IgA antibody demonstrated therapeutic activity also in non-FcαRI transgenic mice. Together, these results demonstrate that engineering of an IgA antibody can significantly improve its pharmacokinetics and its therapeutic efficacy to inhibit tumor growth in vivo.
The treatment of neuroblastoma.
Authors: J V Simone
Journal: Journal of Clinical Oncology (1984)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1984.2.7.717 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 6737017 The treatment of neuroblastoma. J V SimonexJ V SimoneSearch for articles by this author https://doi.org/10.1200/JCO.1984.2.7.717 PDF "The treatment of neuroblastoma.." Journal of Clinical Oncology, 2(7), pp. 717–718© 1984 by American Society of Clinical Oncology