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Graefe's disease

Els Daeseleire, Evelyne De Graef, Geertrui Rasschaert, Thijs De Mulder, Tina Van den Meersche, Els Van Coillie, Jeroen Dewulf, Marc Heyndrickx
The widespread use of antibiotics in animals is causing concerns about the growing risk for development and the spread of antibiotic-resistant bacteria. Antibiotic consumption is higher in animals than in humans as reported in a joint publication of EFSA (European Food Safety Agency), ECDC (European Centre for Disease Prevention and Control), and EMA (European Medicines Agency) using data from 2011 and 2012. Both in humans and animals, positive associations between the consumption of antibiotics and resistant bacteria are observed...
May 2016: Drug Testing and Analysis
Jennifer M Allen, Danielle M Graef, Jennifer H Ehrentraut, Brooklee L Tynes, Valerie M Crabtree
BACKGROUND: Sleep disruption is a common comorbidity of pediatric pain. Consequences of pain and disrupted sleep, evidence for the pain-sleep relation, and how aspects of illness, treatment, and pharmacological pain management may contribute to or exacerbate these issues are presented. AIMS: This conceptual review explored the relation between pain and sleep in children diagnosed with chronic medical or developmental conditions. The goal of this review is to expand upon the literature by examining common themes in sleep disturbances associated with painful conditions across multiple pediatric illnesses...
July 15, 2016: CNS Neuroscience & Therapeutics
Ariadna P Velázquez, Martin Graef
Macroautophagy (hereafter autophagy) is a highly conserved homeostasis and quality control process critically linked to neurodegeneration, metabolic diseases, cancer, and aging. A key feature of autophagy is the de novo formation of autophagosomes, double-membrane vesicular structures encapsulating cytoplasmic cargo for vacuolar turnover and recycling. The membrane rearrangements underlying nucleation, expansion, closure, and vacuolar fusion of autophagosomes are driven by multicomponent core autophagy machinery in cooperation with numerous factors involved in a variety of cellular processes...
August 2, 2016: Autophagy
David S Siegel, Meletios Dimopoulos, Sundar Jagannath, Hartmut Goldschmidt, Simon Durrant, Jonathan L Kaufman, Xavier Leleu, Arnon Nagler, Fritz Offner, Thorsten Graef, Joseph E Eid, Jennifer Houp, Christine Gause, Scott Vuocolo, Kenneth C Anderson
BACKGROUND: The present global, open-label, single-arm, multicenter, phase IIb study was designed to determine the efficacy and tolerability of oral vorinostat combined with standard doses of bortezomib in patients with multiple myeloma considered refractory to novel myeloma agents. PATIENTS AND METHODS: Eligible patients were age ≥ 18 years, had received ≥ 2 previous regimens, had disease refractory to ≥ 1 previous bortezomib-containing regimen, and had received ≥ 1 dose of an immunomodulatory drug (thalidomide or lenalidomide)-based regimen...
June 2016: Clinical Lymphoma, Myeloma & Leukemia
Ariadna P Velázquez, Takashi Tatsuta, Ruben Ghillebert, Ingmar Drescher, Martin Graef
Lipid droplets (LDs) are conserved organelles for intracellular neutral lipid storage. Recent studies suggest that LDs function as direct lipid sources for autophagy, a central catabolic process in homeostasis and stress response. Here, we demonstrate that LDs are dispensable as a membrane source for autophagy, but fulfill critical functions for endoplasmic reticulum (ER) homeostasis linked to autophagy regulation. In the absence of LDs, yeast cells display alterations in their phospholipid composition and fail to buffer de novo fatty acid (FA) synthesis causing chronic stress and morphologic changes in the ER...
March 14, 2016: Journal of Cell Biology
Florian Graef, Sarah Gordon, Claus-Michael Lehr
Infectious diseases are becoming a major menace to the state of health worldwide, with difficulties in effective treatment especially of nosocomial infections caused by Gram-negative bacteria being increasingly reported. Inadequate permeation of anti-infectives into or across the Gram-negative bacterial cell envelope, due to its intrinsic barrier function as well as barrier enhancement mediated by resistance mechanisms, can be identified as one of the major reasons for insufficient therapeutic effects. Several in vitro, in silico, and in cellulo models are currently employed to increase the knowledge of anti-infective transport processes into or across the bacterial cell envelope; however, all such models exhibit drawbacks or have limitations with respect to the information they are able to provide...
March 5, 2016: Current Topics in Microbiology and Immunology
Juan G Arbelaez, Matthew T Feng, Tomas J Pena, Marianne O Price, Francis W Price
PURPOSE: The goal of this study was to provide an update of significant corneal literature published in 2013. DESIGN: This study is a systematic literature review. METHODS: We conducted a systematic review of the English-language literature published from January 1, 2013, to December 31, 2013, using the following PubMed search and Medical Subject Headings terms: cornea transplantation, keratoplasty, Descemet membrane endothelial keratoplasty, Descemet stripping endothelial keratoplasty, cross linking, pre-Descemet's layer, Rho-associated kinase, keratoprosthesis, infectious keratitis, corneal dystrophy, corneal astigmatism, and keratoconus...
January 2015: Asia-Pacific Journal of Ophthalmology
Osama Sabri, Georg-Alexander Becker, Philipp M Meyer, Swen Hesse, Stephan Wilke, Susanne Graef, Marianne Patt, Julia Luthardt, Gudrun Wagenknecht, Alexander Hoepping, René Smits, Annegret Franke, Bernhard Sattler, Bernd Habermann, Petra Neuhaus, Steffen Fischer, Solveig Tiepolt, Winnie Deuther-Conrad, Henryk Barthel, Peter Schönknecht, Peter Brust
α4β2* nicotinic receptors (α4β2* nAChRs) could provide a biomarker in neuropsychiatric disorders (e.g., Alzheimer's and Parkinson's diseases, depressive disorders, and nicotine addiction). However, there is a lack of α4β2* nAChR specific PET radioligands with kinetics fast enough to enable quantification of nAChR within a reasonable time frame. Following on from promising preclinical results, the aim of the present study was to evaluate for the first time in humans the novel PET radioligand (-)-[(18)F]Flubatine, formerly known as (-)-[(18)F]NCFHEB, as a tool for α4β2* nAChR imaging and in vivo quantification...
September 2015: NeuroImage
Roopa Ramamoorthi, Katy M Graef, Jennifer Dent
Schistosomiasis, one of 17 diseases deemed to be neglected by the World Health Organization, has received little attention from the biopharmaceutical industry. Due to this, only a handful of drugs have been developed to treat schistosomiasis, with only one, praziquantel, used in most endemic regions. Growing concern over resistance coupled with praziquantel's incomplete efficacy across all stages of the Schistosoma platyhelminth life cycle highlights the urgent need for new drugs. The WIPO Re:Search consortium is a platform whereupon biopharmaceutical company compounds are being repurposed to efficiently and cost-effectively develop new drugs for neglected diseases such as schistosomiasis...
2015: Future Medicinal Chemistry
Steven P Treon, Christina K Tripsas, Kirsten Meid, Diane Warren, Gaurav Varma, Rebecca Green, Kimon V Argyropoulos, Guang Yang, Yang Cao, Lian Xu, Christopher J Patterson, Scott Rodig, James L Zehnder, Jon C Aster, Nancy Lee Harris, Sandra Kanan, Irene Ghobrial, Jorge J Castillo, Jacob P Laubach, Zachary R Hunter, Zeena Salman, Jianling Li, Mei Cheng, Fong Clow, Thorsten Graef, M Lia Palomba, Ranjana H Advani
BACKGROUND: MYD88(L265P) and CXCR4(WHIM) mutations are highly prevalent in Waldenström's macroglobulinemia. MYD88(L265P) triggers tumor-cell growth through Bruton's tyrosine kinase, a target of ibrutinib. CXCR4(WHIM) mutations confer in vitro resistance to ibrutinib. METHODS: We performed a prospective study of ibrutinib in 63 symptomatic patients with Waldenström's macroglobulinemia who had received at least one previous treatment, and we investigated the effect of MYD88 and CXCR4 mutations on outcomes...
April 9, 2015: New England Journal of Medicine
Jennifer R Brown, Jacqueline C Barrientos, Paul M Barr, Ian W Flinn, Jan A Burger, Anh Tran, Fong Clow, Danelle F James, Thorsten Graef, Jonathan W Friedberg, Kanti Rai, Susan O'Brien
The safety and efficacy of ibrutinib, an oral inhibitor of Bruton tyrosine kinase, were evaluated with chemoimmunotherapy (CIT) in a multicenter phase 1b study. Patients with relapsed/refractory chronic lymphocytic leukemia received bendamustine and rituximab (BR) or fludarabine, cyclophosphamide, and rituximab (FCR) for up to 6 cycles with daily ibrutinib (420 mg) until progressive disease or unacceptable toxicity. Enrollment to FCR-ibrutinib closed early due to a lack of fludarabine-naïve previously treated patients...
May 7, 2015: Blood
Wendy N Gray, Shana L Boyle, Danielle M Graef, David M Janicke, Christopher D Jolley, Lee A Denson, Robert N Baldassano, Kevin A Hommel
OBJECTIVES: Health-related quality of life (HRQOL) is an important, but understudied construct in pediatric inflammatory bowel disease. Family level predictors of HRQOL have been understudied as are the mechanisms through which disease activity affects HRQOL. The present study examines the relation between a family level factor (parenting stress) and HRQOL in youth with Crohn disease. Parenting stress is examined as a mechanism through which disease activity affects HRQOL. METHODS: A total of 99 adolescents with Crohn disease and their parents were recruited across 3 sites...
June 2015: Journal of Pediatric Gastroenterology and Nutrition
Roopa Ramamoorthi, Katy M Graef, Jennifer Dent
Neglected tropical diseases (NTDs), malaria, and tuberculosis have a devastating effect on an estimated 1.6 billion people worldwide. The World Intellectual Property Organization (WIPO) Re:Search consortium accelerates the development of new drugs, vaccines, and diagnostics for these diseases by connecting the assets and resources of pharmaceutical companies, such as compound libraries and expertise, to academic or nonprofit researchers with novel product discovery or development ideas. As the WIPO Re:Search Partnership Hub Administrator, BIO Ventures for Global Health (BVGH) fields requests from researchers, identifies Member organizations able to fulfill these requests, and helps forge mutually beneficial collaborations...
December 2014: International Journal for Parasitology, Drugs and Drug Resistance
Roopa Ramamoorthi, Katy M Graef, Anatole Krattiger, Jennifer C Dent
No abstract text is available yet for this article.
November 26, 2014: Chemical Reviews
A Khammanivong, B H Gorden, A M Frantz, A J Graef, E B Dickerson
Canine hemangiosarcoma is a rapidly progressive disease that is poorly responsive to conventional chemotherapy. Despite numerous attempts to advance treatment options and improve outcomes, drug resistance remains a hurdle to successful therapy. To address this problem, we used recently characterized progenitor cell populations derived from canine hemangiosarcoma cell lines and grown as non-adherent spheres to identify potential drug resistance mechanisms as well as drug-resistant cell populations. Cells from sphere-forming cultures displayed enhanced resistance to chemotherapy drugs, expansion of dye-excluding side populations and altered ATP-binding cassette (ABC) transporter expression...
September 2016: Veterinary and Comparative Oncology
Abhishek Ghosh, Susanta K Padhy, Gourav Gupta, Manoj K Goyal
Convergence spasm (CS) means intermittent episodes of convergence, miosis and accommodation with disconjugate gaze mimicking abducens palsy. The organic causes range from metabolic to host of neurological and ophthalmic diseases that we describe. It was first described as a presentation of psychogenic disorders by von Graefe as early as in 1856. Nonetheless, patients exhibiting this sign are often subjected to plethora of unnecessary, sophisticated and invasive diagnostic procedures. Such functional cases were treated with either cycloplegic/placebo eye drop or amytal abreaction...
July 2014: Indian Journal of Psychological Medicine
Heike Zimdahl, Carina Ittrich, Ulrike Graefe-Mody, Bernhard O Boehm, Michael Mark, Hans-Juergen Woerle, Klaus A Dugi
AIMS/HYPOTHESIS: Individuals carrying variants of the transcription factor 7-like 2 gene (TCF7L2) are at increased risk for type 2 diabetes. These metabolic genetic risk factors have been linked to diminished pancreatic islet-cell responsiveness to incretins, thus pharmacological interventions aimed at amplifying endogenous incretin biology may be affected. However, clinical evidence from randomised controlled trials so far is lacking. We investigated the influence of TCF7L2 risk alleles on the response to treatment with the dipeptidylpeptidase-4 (DPP-4) inhibitor linagliptin from four 24 week, phase III, placebo-controlled trials...
September 2014: Diabetologia
Christian Stemberger, Patricia Graef, Marcus Odendahl, Julia Albrecht, Georg Dössinger, Florian Anderl, Veit R Buchholz, Georg Gasteiger, Matthias Schiemann, Götz U Grigoleit, Friedhelm R Schuster, Arndt Borkhardt, Birgitta Versluys, Torsten Tonn, Erhard Seifried, Hermann Einsele, Lothar Germeroth, Dirk H Busch, Michael Neuenhahn
Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) are threatened by potentially lethal viral manifestations like cytomegalovirus (CMV) reactivation. Because the success of today's virostatic treatment is limited by side effects and resistance development, adoptive transfer of virus-specific memory T cells derived from the stem cell donor has been proposed as an alternative therapeutic strategy. In this context, dose minimization of adoptively transferred T cells might be warranted for the avoidance of graft-versus-host disease (GVHD), in particular in prophylactic settings after T-cell-depleting allo-HSCT protocols...
July 24, 2014: Blood
Francesc Pérez-Brangulí, Himanshu K Mishra, Iryna Prots, Steven Havlicek, Zacharias Kohl, Domenica Saul, Christine Rummel, Jonatan Dorca-Arevalo, Martin Regensburger, Daniela Graef, Elisabeth Sock, Juan Blasi, Teja W Groemer, Ursula Schlötzer-Schrehardt, Jürgen Winkler, Beate Winner
Hereditary spastic paraplegias are a group of inherited motor neuron diseases characterized by progressive paraparesis and spasticity. Mutations in the spastic paraplegia gene SPG11, encoding spatacsin, cause an autosomal-recessive disease trait; however, the precise knowledge about the role of spatacsin in neurons is very limited. We for the first time analyzed the expression and function of spatacsin in human forebrain neurons derived from human pluripotent stem cells including lines from two SPG11 patients and two controls...
September 15, 2014: Human Molecular Genetics
Marianne Patt, Georg A Becker, Udo Grossmann, Bernd Habermann, Andreas Schildan, Stephan Wilke, Winnie Deuther-Conrad, Susanne Graef, Steffen Fischer, René Smits, Alexander Hoepping, Gudrun Wagenknecht, Jörg Steinbach, Hermann-Josef Gertz, Swen Hesse, Peter Schönknecht, Peter Brust, Osama Sabri
INTRODUCTION: (-)-[(18)F]Flubatine is a PET tracer with high affinity and selectivity for the nicotinic acetylcholine α4β2 receptor subtype. A clinical trial assessing the availability of this subtype of nAChRs was performed. From a total participant number of 21 Alzheimer's disease (AD) patients and 20 healthy controls (HCs), the following parameters were determined: plasma protein binding, metabolism and activity distribution between plasma and whole blood. METHODS: Plasma protein binding and fraction of unchanged parent compound were assessed by ultracentrifugation and HPLC, respectively...
July 2014: Nuclear Medicine and Biology
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