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https://www.readbyqxmd.com/read/28808818/first-in-human-study-of-the-epichaperome-inhibitor-pu-h71-clinical-results-and-metabolic-profile
#1
Giovanna Speranza, Larry Anderson, Alice P Chen, Khanh Do, Michelle Eugeni, Marcie Weil, Larry Rubinstein, Eva Majerova, Jerry Collins, Yvonne Horneffer, Lamin Juwara, Jennifer Zlott, Rachel Bishop, Barbara A Conley, Howard Streicher, Joseph Tomaszewski, James H Doroshow, Shivaani Kummar
Background Molecular chaperone targeting has shown promise as a therapeutic approach in human cancers of various histologies and genetic backgrounds. The purine-scaffold inhibitor PU-H71 (NSC 750424), selective for Hsp90 in epichaperome networks, has demonstrated antitumor activity in multiple preclinical cancer models. The present study was a first in-human trial of PU-H71 aimed at establishing its safety and tolerability and characterizing its pharmacokinetic (PK) profile on a weekly administration schedule in human subjects with solid tumors refractory to standard treatments...
August 12, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28808688/adaptive-mistranslation-accelerates-the-evolution-of-fluconazole-resistance-and-induces-major-genomic-and-gene-expression-alterations-in-candida-albicans
#2
Tobias Weil, Rodrigo Santamaría, Wanseon Lee, Johan Rung, Noemi Tocci, Darren Abbey, Ana R Bezerra, Laura Carreto, Gabriela R Moura, Mónica Bayés, Ivo G Gut, Attila Csikasz-Nagy, Duccio Cavalieri, Judith Berman, Manuel A S Santos
Regulated erroneous protein translation (adaptive mistranslation) increases proteome diversity and produces advantageous phenotypic variability in the human pathogen Candida albicans. It also increases fitness in the presence of fluconazole, but the underlying molecular mechanism is not understood. To address this question, we evolved hypermistranslating and wild-type strains in the absence and presence of fluconazole and compared their fluconazole tolerance and resistance trajectories during evolution. The data show that mistranslation increases tolerance and accelerates the acquisition of resistance to fluconazole...
July 2017: MSphere
https://www.readbyqxmd.com/read/28758712/spatiotemporally-controlled-release-of-rho-inhibiting-c3-toxin-from-a-protein-dna-hybrid-hydrogel-for-targeted-inhibition-of-osteoclast-formation-and-activity
#3
Jasmina Gačanin, Anna Kovtun, Stephan Fischer, Victoria Schwager, Johanna Quambusch, Seah Ling Kuan, Weina Liu, Felix Boldt, Chuang Li, Zhongqiang Yang, Dongsheng Liu, Yuzhou Wu, Tanja Weil, Holger Barth, Anita Ignatius
In osteoporosis, bone structure can be improved by the introduction of therapeutic molecules inhibiting bone resorption by osteoclasts. Here, biocompatible hydrogels represent an excellent option for the delivery of pharmacologically active molecules to the bone tissue because of their biodegradability, injectability, and manifold functionalization capacity. The present study reports the preparation of a multifunctional hybrid hydrogel from chemically modified human serum albumin and rationally designed DNA building blocks...
July 31, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28730418/total-and-free-cortisol-levels-during-1-%C3%AE-g-25-%C3%AE-g-and-250-%C3%AE-g-cosyntropin-stimulation-tests-compared-to-insulin-tolerance-test-results-of-a-randomized-prospective-pilot-study
#4
Seenia Peechakara, James Bena, Nigel J Clarke, Michael J McPhaul, Richard E Reitz, Robert J Weil, Pablo Recinos, Laurence Kennedy, Amir H Hamrahian
PURPOSE: The appropriate cosyntropin dose during cosyntropin stimulation tests remains uncertain. We conducted a prospective, randomized pilot study to compare 1 μg IV low dose cosyntropin test, 25 μg IM medium dose cosyntropin test, and 250 μg IM standard dose cosyntropin test to evaluate secondary adrenal insufficiency. Insulin tolerance test was used as the gold standard. METHOD: The study included patients with hypothalamic/pituitary disease (n  = 10) with at least one pituitary axis deficiency other than ACTH deficiency and controls (n  = 12)...
July 20, 2017: Endocrine
https://www.readbyqxmd.com/read/28679734/high-prevalence-of-myeloid-neoplasms-in-adults-with-non-langerhans-cell-histiocytosis
#5
Matthias Papo, Eli L Diamond, Fleur Cohen-Aubart, Jean-François Emile, Damien Roos-Weil, Nishant Gupta, Benjamin H Durham, Neval Ozkaya, Ahmet Dogan, Gary A Ulaner, Raajit Rampal, Jean-Emmanuel Kahn, Thomas Sené, Frédéric Charlotte, Baptiste Hervier, Caroline Besnard, Olivier A Bernard, Catherine Settegrana, Nathalie Droin, Zofia Hélias-Rodzewicz, Zahir Amoura, Omar Abdel-Wahab, Julien Haroche
Erdheim-Chester Disease (ECD) is a rare non-Langerhans Cell histiocytosis that most commonly affects adults and is driven by a high frequency of mutations in BRAF, MAP2K1, and kinases promoting MAP kinase signaling. Due to the relative rarity of ECD, key clinical features of the disease may not be well defined. Across a multi-institutional cohort of 189 patients with ECD and ECD overlapping with Langerhans Cell Histiocytosis (so-called Mixed Histiocytosis (MH)), we identified an unexpected and heretofore undescribed frequent occurrence of myeloid neoplasms amongst patients with ECD and MH...
July 5, 2017: Blood
https://www.readbyqxmd.com/read/28668503/spatial-analysis-of-leptospira-infection-in-muskrats-in-lower-saxony-germany-and-the-association-with-human-leptospirosis
#6
Jillian Hurd, Olaf Berke, Zvonimir Poljak, Martin Runge
Leptospirosis has been reported as an emerging zoonosis and the most widespread zoonotic disease in the world. Muskrats (Ondatra zibethicus) have been known to carry Leptospira serovars, which have been linked to Weil's disease - a serious and life threatening disease in humans. In this study, muskrats were sampled across 43 regions of Lower Saxony, Germany, during 2007 to 2009 and were tested for leptospirosis using Polymerase Chain Reaction (PCR). Circular and flexibly shaped spatial scan tests were applied and detected two leptospirosis clusters in Lower Saxony, Germany...
June 24, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28592676/life-or-death-disease-tolerant-coral-species-activate-autophagy-following-immune-challenge
#7
Lauren E Fuess, Jorge H Pinzón C, Ernesto Weil, Robert D Grinshpon, Laura D Mydlarz
Global climate change has increased the number and severity of stressors affecting species, yet not all species respond equally to these stressors. Organisms may employ cellular mechanisms such as apoptosis and autophagy in responding to stressful events. These two pathways are often mutually exclusive, dictating whether a cell adapts or dies. In order to examine differences in cellular response to stress, we compared the immune response of four coral species with a range of disease susceptibility. Using RNA-seq and novel pathway analysis, we were able to identify differences in response to immune stimulation between these species...
June 14, 2017: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/28567666/serum-protein-based-profiles-as-novel-biomarkers-for-the-diagnosis-of-alzheimer-s-disease
#8
Shu Yu, Yue-Ping Liu, Hai-Liang Liu, Jie Li, Yang Xiang, Yu-Hui Liu, Shu-Sheng Jiao, Lu Liu, Yajiang Wang, Weiling Fu
As a multi-stage disorder, Alzheimer's disease (AD) is quickly becoming one of the most prevalent neurodegenerative diseases worldwide. Thus, a non-invasive, serum-based diagnostic platform is eagerly awaited. The goal of this study was to identify a serum-based biomarker panel using a predictive protein-based algorithm that is able to confidently distinguish AD patients from control subjects. One hundred and fifty-six patients with AD and the same number of gender- and age-matched control participants with standardized clinical assessments and neuroimaging measures were evaluated...
May 31, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28566492/functional-evidence-for-derivation-of-systemic-histiocytic-neoplasms-from-hematopoietic-stem-progenitor-cells
#9
Benjamin H Durham, Damien Roos-Weil, Claude Baillou, Fleur Cohen-Aubart, Akihide Yoshimi, Makoto Miyara, Matthias Papo, Zofia Hélias-Rodzewicz, Nathalie Terrones, Neval Ozkaya, Ahmet Dogan, Raajit Rampal, Fanny Urbain, Lucie Le Fèvre, Eli L Diamond, Christopher Y Park, Thomas Papo, Frédéric Charlotte, Guy Gorochov, Valérie Taly, Olivier A Bernard, Zahir Amoura, Omar Abdel-Wahab, François M Lemoine, Julien Haroche, Jean-François Emile
Langerhans cell histiocytosis (LCH) and the non-LCH neoplasm Erdheim-Chester disease (ECD) are heterogeneous neoplastic disorders marked by infiltration of pathologic macrophage-, dendritic cell-, or monocyte-derived cells in tissues driven by recurrent mutations activating MAPK signaling. Although recent data indicate that at least a proportion of LCH and ECD patients have detectable activating kinase mutations in circulating hematopoietic cells and bone marrow-based hematopoietic progenitors, functional evidence of the cell of origin of histiocytosis from actual patient materials has long been elusive...
July 13, 2017: Blood
https://www.readbyqxmd.com/read/28554148/social-media-in-epilepsy-a-quantitative-and-qualitative-analysis
#10
Ying Meng, Lior Elkaim, Justin Wang, Jessica Liu, Naif M Alotaibi, George M Ibrahim, Aria Fallah, Alexander G Weil, Taufik A Valiante, Andres M Lozano, James T Rutka
BACKGROUND: While the social burden of epilepsy has been extensively studied, an evaluation of social media related to epilepsy may provide novel insight into disease perception, patient needs and access to treatments. The objective of this study is to assess patterns in social media and online communication usage related to epilepsy and its associated topics. METHODS: We searched two major social media platforms (Facebook and Twitter) for public accounts dedicated to epilepsy...
June 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28549684/primary-laparoscopic-gastrojejunostomy-tubes-as-a-feeding-modality-in-the-pediatric-population
#11
Chinwendu Onwubiko, Brent R Weil, Sigrid Bairdain, Amber M Hall, Julia M Perkins, Hariharan Thangarajah, Maireade E McSweeney, C Jason Smithers
PURPOSE: Outcomes associated with primary laparoscopic gastrojejunal (GJ) tube placement in the pediatric population were evaluated. METHODS: A single-institution, retrospective review examined patients undergoing laparoscopic GJ tube placement between June 2011 and December 2014. Outcomes included gastric feeding tolerance, subsequent fundoplication, complications, and mortality. RESULTS: Ninety laparoscopic GJ tubes were placed. Median follow-up was 342days (interquartile range [IQR]=141-561days)...
May 20, 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/28528996/weil-s-disease-and-acute-multifactorial-hepatitis-about-a-case
#12
Cristina Torres Vargas, Ángela Martínez Herreros, Begoña Sacristán Terroba
No abstract text is available yet for this article.
May 18, 2017: Gastroenterología y Hepatología
https://www.readbyqxmd.com/read/28527874/pressor-support-during-a-jarisch-herxheimer-reaction-after-initiation-of-treatment-for-weil-s-disease
#13
Randi Connor-Schuler, Anee Khan, Nikhil Goyal, Erin Zimny
We present a case of Weil's disease complicated by a Jarisch-Herxheimer reaction (JHR) after initiation of antibiotics while in the emergency department requiring invasive monitoring and vasopressor support. The case is followed by a brief review of the JHR which is rarely observed with treatment of leptospirosis. A healthy 28-year-old female who recently returned from the Caribbean presented to the emergency department with flu-like symptoms. The patient appeared jaundiced with conjunctival suffusion and was ultimately treated with the appropriate antibiotics for leptospirosis in the ED...
August 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28489846/-gastrointestinal-bleeding-and-acute-hepatic-failure-by-leptospirosis-an-entity-that-should-not-be-forgotten
#14
Carlos Alventosa Mateu, Lydia Plana Campos, Laura Larrey Ruíz, Raquel Acedo Mayordomo, Laura Sanchís Artero, Laura Peño Muñoz, Paola Concepción Núñez Martínez, Génesis Aurora Castillo López, Mercedes Latorre Sánchez, Juan José Urquijo Ponce, Moisés Diago Madrid, Javier Sempere García-Argüelles
Leptospirosis disease is caused by the spirochete Leptospira. It is a worldwide distribution zoonosis, with predominance in the tropics. In Spain, it is not frequent but some cases have been noticed especially in humid areas surrounded by rivers, lakes or ponds, such as Catalonia, Andalucia or the Valencian Community. It is transmitted by a variety of animals such as cows or rats, that are infected either by direct contact with these animals or their urine, or indirectly by consuming or being in contact with water contaminated by their urine...
January 2017: Revista de Gastroenterología del Perú: órgano Oficial de la Sociedad de Gastroenterología del Perú
https://www.readbyqxmd.com/read/28482955/an-overview-of-tuberculosis-and-migration
#15
P Dhavan, H M Dias, J Creswell, D Weil
With nearly one billion migrants worldwide, migration is both a dynamic and a divisive phenomenon facing the world today. Migrants are a heterogeneous group, and the conditions surrounding migration pathways often pose risks to the physical, mental and social well-being of migrants, with certain subgroups being more vulnerable than others. Several determinants of health and tuberculosis (TB) interplay to increase the vulnerability of migrants to tuberculous infection, TB disease and poor treatment outcomes, making them a key population for TB...
June 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28473450/zika-virus-induces-massive-cytoplasmic-vacuolization-and-paraptosis-like-death-in-infected-cells
#16
Blandine Monel, Alex A Compton, Timothée Bruel, Sonia Amraoui, Julien Burlaud-Gaillard, Nicolas Roy, Florence Guivel-Benhassine, Françoise Porrot, Pierre Génin, Laurent Meertens, Laura Sinigaglia, Nolwenn Jouvenet, Robert Weil, Nicoletta Casartelli, Caroline Demangel, Etienne Simon-Lorière, Arnaud Moris, Philippe Roingeard, Ali Amara, Olivier Schwartz
The cytopathic effects of Zika virus (ZIKV) are poorly characterized. Innate immunity controls ZIKV infection and disease in most infected patients through mechanisms that remain to be understood. Here, we studied the morphological cellular changes induced by ZIKV and addressed the role of interferon-induced transmembrane proteins (IFITM), a family of broad-spectrum antiviral factors, during viral replication. We report that ZIKV induces massive vacuolization followed by "implosive" cell death in human epithelial cells, primary skin fibroblasts and astrocytes, a phenomenon which is exacerbated when IFITM3 levels are low...
June 14, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28472271/annotating-function-to-differentially-expressed-lincrnas-in-myelodysplastic-syndrome-using-a-network-based-method
#17
Keqin Liu, Dominik Beck, Julie A I Thoms, Liang Liu, Weiling Zhao, John E Pimanda, Xiaobo Zhou
Motivation: Long non-coding RNAs (lncRNAs) have been implicated in the regulation of diverse biological functions. The number of newly identified lncRNAs has increased dramatically in recent years but their expression and function have not yet been described from most diseases. To elucidate lncRNA function in human disease, we have developed a novel network based method (NLCFA) integrating correlations between lncRNA, protein coding genes and noncoding miRNAs. We have also integrated target gene associations and protein-protein interactions and designed our model to provide information on the combined influence of mRNAs, lncRNAs and miRNAs on cellular signal transduction networks...
May 4, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28461334/deficiency-in-the-manganese-efflux-transporter-slc30a10-induces-severe-hypothyroidism-in-mice
#18
Steven Hutchens, Chunyi Liu, Thomas Jursa, William Shawlot, Beth K Chaffee, Weiling Yin, Andrea C Gore, Michael Aschner, Donald R Smith, Somshuvra Mukhopadhyay
Manganese is an essential metal that becomes toxic at elevated levels. Loss-of-function mutations in SLC30A10, a cell-surface-localized manganese efflux transporter, cause a heritable manganese metabolism disorder resulting in elevated manganese levels and parkinsonian-like movement deficits. The underlying disease mechanisms are unclear; therefore, treatment is challenging. To understand the consequences of loss of SLC30A10 function at the organism level, we generated Slc30a10 knock-out mice. During early development, knock-outs were indistinguishable from controls...
June 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28444957/epidemiology-of-endometriosis-a-large-population-based-database-study-in-a-2-million-member-health-care-provider
#19
Vered H Eisenberg, Clara Weil, Gabriel Chodick, Varda Shalev
OBJECTIVE: Endometriosis constitutes a significant burden on the quality of life of women, their families, and health systems. The objective of this study is to describe the real-world epidemiology of endometriosis in an unselected low-risk population in Israel. DESIGN: Retrospective population-based study. SETTING AND POPULATION: The computerized databases of Maccabi Healthcare Services (MHS), a 2-million-member healthcare provider representing a quarter of the Israeli population...
April 26, 2017: BJOG: An International Journal of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/28443091/natural-killer-group-2d-ligand-depletion-reconstitutes-natural-killer-cell-immunosurveillance-of-head-and-neck-squamous-cell-carcinoma
#20
Sandra Weil, Stefanie Memmer, Axel Lechner, Volker Huppert, Ariane Giannattasio, Tamara Becker, Andreas Müller-Runte, Karen Lampe, Dirk Beutner, Alexander Quaas, Ralf Schubert, Eva Herrmann, Alexander Steinle, Ulrike Koehl, Lutz Walter, Michael S von Bergwelt-Baildon, Joachim Koch
Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous and aggressive tumor originating from the epithelial lining of the upper aero-digestive tract accounting for 300,000 annual deaths worldwide due to failure of current therapies. The natural killer group 2D (NKG2D) receptors on natural killer (NK) cells and several T cell subsets play an important role for immunosurveillance of HNSCC and are thus targeted by tumor immune evasion strategies in particular by shedding of various NKG2D ligands (NKG2DLs)...
2017: Frontiers in Immunology
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