Read by QxMD icon Read


Halima W M Al Balushi, Yasser Wali, Maha Al Awadi, Taimoora Al-Subhi, David C Rees, John N Brewin, Anke Hannemann, John S Gibson
Studying different sickle cell genotypes may throw light on the pathogenesis of sickle cell disease (SCD). Here, the clinical profile, red cell sickling and K(+) permeability in 29 SCD patients (15 patients with severe disease and 14 with a milder form) of HbA/S-Oman genotype were analysed. The super sickling nature of this Hb variant was confirmed. The red cell membrane permeability to K(+) was markedly abnormal with elevated activities of Psickle , Gardos channel and KCl cotransporter (KCC). Results were consistent with Ca(2+) entry and Mg(2+) loss via Psickle stimulating Gardos channel and KCC activities...
July 12, 2017: British Journal of Haematology
Raphaël Rapetti-Mauss, Véronique Picard, Corinne Guitton, Khaldoun Ghazal, Valérie Proulle, Catherine Badens, Olivier Soriani, Loïc Garçon, Hélène Guizouarn
No abstract text is available yet for this article.
June 15, 2017: Haematologica
Elisa Fermo, Anna Bogdanova, Polina Petkova-Kirova, Anna Zaninoni, Anna Paola Marcello, Asya Makhro, Pascal Hänggi, Laura Hertz, Jens Danielczok, Cristina Vercellati, Nadia Mirra, Alberto Zanella, Agostino Cortelezzi, Wilma Barcellini, Lars Kaestner, Paola Bianchi
The Gardos channel is a Ca(2+) sensitive, K(+) selective channel present in several tissues including RBCs, where it is involved in cell volume regulation. Recently, mutations at two different aminoacid residues in KCNN4 have been reported in patients with hereditary xerocytosis. We identified by whole exome sequencing a new family with two members affected by chronic hemolytic anemia carrying mutation R352H in the KCNN4 gene. No additional mutations in genes encoding for RBCs cytoskeletal, membrane or channel proteins were detected...
May 11, 2017: Scientific Reports
Ahmet Zehir, Ryma Benayed, Ronak H Shah, Aijazuddin Syed, Sumit Middha, Hyunjae R Kim, Preethi Srinivasan, Jianjiong Gao, Debyani Chakravarty, Sean M Devlin, Matthew D Hellmann, David A Barron, Alison M Schram, Meera Hameed, Snjezana Dogan, Dara S Ross, Jaclyn F Hechtman, Deborah F DeLair, JinJuan Yao, Diana L Mandelker, Donavan T Cheng, Raghu Chandramohan, Abhinita S Mohanty, Ryan N Ptashkin, Gowtham Jayakumaran, Meera Prasad, Mustafa H Syed, Anoop Balakrishnan Rema, Zhen Y Liu, Khedoudja Nafa, Laetitia Borsu, Justyna Sadowska, Jacklyn Casanova, Ruben Bacares, Iwona J Kiecka, Anna Razumova, Julie B Son, Lisa Stewart, Tessara Baldi, Kerry A Mullaney, Hikmat Al-Ahmadie, Efsevia Vakiani, Adam A Abeshouse, Alexander V Penson, Philip Jonsson, Niedzica Camacho, Matthew T Chang, Helen H Won, Benjamin E Gross, Ritika Kundra, Zachary J Heins, Hsiao-Wei Chen, Sarah Phillips, Hongxin Zhang, Jiaojiao Wang, Angelica Ochoa, Jonathan Wills, Michael Eubank, Stacy B Thomas, Stuart M Gardos, Dalicia N Reales, Jesse Galle, Robert Durany, Roy Cambria, Wassim Abida, Andrea Cercek, Darren R Feldman, Mrinal M Gounder, A Ari Hakimi, James J Harding, Gopa Iyer, Yelena Y Janjigian, Emmet J Jordan, Ciara M Kelly, Maeve A Lowery, Luc G T Morris, Antonio M Omuro, Nitya Raj, Pedram Razavi, Alexander N Shoushtari, Neerav Shukla, Tara E Soumerai, Anna M Varghese, Rona Yaeger, Jonathan Coleman, Bernard Bochner, Gregory J Riely, Leonard B Saltz, Howard I Scher, Paul J Sabbatini, Mark E Robson, David S Klimstra, Barry S Taylor, Jose Baselga, Nikolaus Schultz, David M Hyman, Maria E Arcila, David B Solit, Marc Ladanyi, Michael F Berger
Tumor molecular profiling is a fundamental component of precision oncology, enabling the identification of genomic alterations in genes and pathways that can be targeted therapeutically. The existence of recurrent targetable alterations across distinct histologically defined tumor types, coupled with an expanding portfolio of molecularly targeted therapies, demands flexible and comprehensive approaches to profile clinically relevant genes across the full spectrum of cancers. We established a large-scale, prospective clinical sequencing initiative using a comprehensive assay, MSK-IMPACT, through which we have compiled tumor and matched normal sequence data from a unique cohort of more than 10,000 patients with advanced cancer and available pathological and clinical annotations...
June 2017: Nature Medicine
J I Westbrook, L Li, M Z Raban, M T Baysari, V Mumford, M Prgomet, A Georgiou, T Kim, R Lake, C McCullagh, L Dalla-Pozza, J Karnon, T A O'Brien, G Ambler, R Day, C T Cowell, M Gazarian, R Worthington, C U Lehmann, L White, D Barbaric, A Gardo, M Kelly, P Kennedy
INTRODUCTION: Medication errors are the most frequent cause of preventable harm in hospitals. Medication management in paediatric patients is particularly complex and consequently potential for harms are greater than in adults. Electronic medication management (eMM) systems are heralded as a highly effective intervention to reduce adverse drug events (ADEs), yet internationally evidence of their effectiveness in paediatric populations is limited. This study will assess the effectiveness of an eMM system to reduce medication errors, ADEs and length of stay (LOS)...
October 21, 2016: BMJ Open
Mauro C Wesseling, Lisa Wagner-Britz, Duc Bach Nguyen, Salome Asanidze, Judy Mutua, Nagla Mohamed, Benjamin Hanf, Mehrdad Ghashghaeinia, Lars Kaestner, Ingolf Bernhardt
BACKGROUND/AIMS: In previous publications we were able to demonstrate the exposure of phosphatidylserine (PS) in the outer membrane leaflet after activation of red blood cells (RBCs) by lysophosphatidic acid (LPA), phorbol-12 myristate-13acetate (PMA), or 4-bromo-A23187 (A23187). It has been concluded that three different mechanisms are responsible for the PS exposure in human RBCs: (i) Ca2+-stimulated scramblase activation (and flippase inhibition) by A23187, LPA, and PMA; (ii) PKCα activation by LPA and PMA; and (iii) enhanced lipid flip flop caused by LPA...
2016: Cellular Physiology and Biochemistry
Immacolata Andolfo, Roberta Russo, Antonella Gambale, Achille Iolascon
After the first proposed model of the red blood cell membrane skeleton 36 years ago, several additional proteins have been discovered during the intervening years, and their relationship with the pathogenesis of the related disorders have been somewhat defined. The knowledge of erythrocyte membrane structure is important because it represents the model for spectrin-based membrane skeletons in all cells and because defects in its structure underlie multiple hemolytic anemias. This review summarizes the main features of erythrocyte membrane disorders, dividing them into structural and altered permeability defects, focusing particularly on the most recent advances...
November 2016: Haematologica
Raphael Rapetti-Mauss, Olivier Soriani, Henri Vinti, Catherine Badens, Hélène Guizouarn
No abstract text is available yet for this article.
November 2016: Haematologica
P Wong
A fraction of erythrocytes appear as target cells in stained blood smears in sickle cell disease, due to a inheritance of the hemoglobin variant Hb S, polymerizing upon deoxygenation. These cells appear in a three dimension as thin cups. A process of their formation in this disease is proposed based on a band 3-based mechanism of the erythrocyte shape control, able to explain the erythrocyte echinocytosis by glucose depletion. It indicates that their formation is due to a stomatocytogenic slow outward transport of the dibasic form of endogenous Pi with an H(+) by band 3, promoted by the decrease of the Donnan ratio, which decreases cell pH and volume, attributed by a decrease of cell KCl concentration by the higher efflux of K(+)Cl(-) cotransport and Ca(2+) activation of the Gardos channel...
August 2016: Medical Hypotheses
Catherine Badens, Hélène Guizouarn
Genetic defects of erythrocyte transport proteins cause disorders of red blood cell volume that are characterized by abnormal permeability to the cations Na(+) and K(+) and, consequently, by changes in red cell hydration. Clinically, these disorders are associated with chronic haemolytic anaemia of variable severity and significant co-morbidities, such as iron overload. This review provides an overview of recent insights into the molecular basis of this group of rare anaemias involving cation channels and transporters dysfunction...
September 2016: British Journal of Haematology
Michael H Eubank, David M Hyman, Amritha D Kanakamedala, Stuart M Gardos, Jonathan M Wills, Peter D Stetson
The Information Systems Department at Memorial Sloan Kettering Cancer Center developed the DARWIN Cohort Management System (DCMS). The DCMS identifies and tracks cohorts of patients based on genotypic and clinical data. It assists researchers and treating physicians in enrolling patients to genotype-matched IRB-approved clinical trials. The DCMS sends automated, actionable, and secure email notifications to users with information about eligible or enrolled patients before their upcoming appointments. The system also captures investigators input via annotations on patient eligibility and preferences on future status updates...
July 2016: Journal of the American Medical Informatics Association: JAMIA
Srikanth Nagalla, Samir K Ballas
BACKGROUND: Sickle cell disease is an inherited disorder of hemoglobin, resulting in abnormal red blood cells. These are rigid and may block blood vessels leading to acute painful crises and other complications. Recent research has focused on therapies to rehydrate the sickled cells by reducing the loss of water and ions from them. Little is known about the effectiveness and safety of such drugs. This is an updated version of a previously published review. OBJECTIVES: To assess the relative risks and benefits of drugs to rehydrate sickled red blood cells...
March 4, 2016: Cochrane Database of Systematic Reviews
A Hannemann, D C Rees, S Tewari, J S Gibson
Sickle cell disease (SCD) in patients of HbSC genotype is considered similar, albeit milder, to that in homozygous HbSS individuals--but with little justification. In SCD, elevated red cell cation permeability is critical as increased solute loss causes dehydration and encourages sickling. Recently, we showed that the KCl cotransporter (KCC) activity in red cells from HbSC patients correlated significantly with disease severity, but that in HbSS patients did not. Two transporters involved in red cell dehydration, the conductive channels Psickle and the Gardos channel, behaved similarly in red cells from the two genotypes, but were significantly less active in HbSC patients...
November 2015: EBioMedicine
Venée N Tubman, Pedro Mejia, Boris E Shmukler, Amy K Bei, Seth L Alper, James R Mitchell, Carlo Brugnara, Manoj T Duraisingh
Senicapoc, a Gardos channel inhibitor, prevented erythrocyte dehydration in clinical trials of patients with sickle cell disease. We tested the hypothesis that senicapoc-induced blockade of the Gardos channel inhibits Plasmodium growth. Senicapoc inhibited in vitro growth of human and primate plasmodia during the clinical blood stage. Senicapoc treatment suppressed P. yoelii parasitemia in vivo in C57BL/6 mice. The reassuring safety and biochemical profile of senicapoc encourage its use in antimalarial development...
October 12, 2015: Antimicrobial Agents and Chemotherapy
Edyta Glogowska, Kimberly Lezon-Geyda, Yelena Maksimova, Vincent P Schulz, Patrick G Gallagher
Hereditary xerocytosis (HX; MIM 194380) is an autosomal-dominant hemolytic anemia characterized by primary erythrocyte dehydration. In many patients, heterozygous mutations associated with delayed channel inactivation have been identified in PIEZO1. This report describes patients from 2 well-phenotyped HX kindreds, including from one of the first HX kindreds described, who lack predicted heterozygous PIEZO1-linked variants. Whole-exome sequencing identified novel, heterozygous mutations affecting the Gardos channel, encoded by the KCNN4 gene, in both kindreds...
September 10, 2015: Blood
Immacolata Andolfo, Roberta Russo, Francesco Manna, Boris E Shmukler, Antonella Gambale, Giuseppina Vitiello, Gianluca De Rosa, Carlo Brugnara, Seth L Alper, L Michael Snyder, Achille Iolascon
Dehydrated hereditary stomatocytosis (DHSt) is an autosomal dominant congenital hemolytic anemia with moderate splenomegaly and often compensated hemolysis. Affected red cells are characterized by a nonspecific cation leak of the red cell membrane, reflected in elevated sodium content, decreased potassium content, elevated MCHC and MCV, and decreased osmotic fragility. The majority of symptomatic DHSt cases reported to date have been associated with gain-of-function mutations in the mechanosensitive cation channel gene, PIEZO1...
October 2015: American Journal of Hematology
Raphael Rapetti-Mauss, Caroline Lacoste, Véronique Picard, Corinne Guitton, Elise Lombard, Marie Loosveld, Vanessa Nivaggioni, Nathalie Dasilva, David Salgado, Jean-Pierre Desvignes, Christophe Béroud, Patrick Viout, Monique Bernard, Olivier Soriani, Henri Vinti, Valérie Lacroze, Madeleine Feneant-Thibault, Isabelle Thuret, Hélène Guizouarn, Catherine Badens
The Gardos channel is a Ca(2+)-sensitive, intermediate conductance, potassium selective channel expressed in several tissues including erythrocytes and pancreas. In normal erythrocytes, it is involved in cell volume modification. Here, we report the identification of a dominantly inherited mutation in the Gardos channel in 2 unrelated families and its association with chronic hemolysis and dehydrated cells, also referred to as hereditary xerocytosis (HX). The affected individuals present chronic anemia that varies in severity...
September 10, 2015: Blood
Stuart M Cahalan, Viktor Lukacs, Sanjeev S Ranade, Shu Chien, Michael Bandell, Ardem Patapoutian
Red blood cells (RBCs) experience significant mechanical forces while recirculating, but the consequences of these forces are not fully understood. Recent work has shown that gain-of-function mutations in mechanically activated Piezo1 cation channels are associated with the dehydrating RBC disease xerocytosis, implicating a role of mechanotransduction in RBC volume regulation. However, the mechanisms by which these mutations result in RBC dehydration are unknown. In this study, we show that RBCs exhibit robust calcium entry in response to mechanical stretch and that this entry is dependent on Piezo1 expression...
2015: ELife
Andrea M Belanger, Christian Keggi, Tamir Kanias, Mark T Gladwin, Daniel B Kim-Shapiro
BACKGROUND: Sickle cell disease (SCD) is characterized by hemoglobin polymerization upon deoxygenation. Polymerization causes the sickle cells to become rigid and misshapen (sickling). Red blood cell (RBC) dehydration greatly increases polymerization. Cycles of sickling and unsickling cause an influx of calcium that leads to loss of potassium via the calcium-activated Gardos channel, which dehydrates the cells leading to increased polymerization. In this study the effects of nitric oxide (NO) and its congeners on RBC deformability were examined, focusing on sickle RBCs (sRBCs)...
October 2015: Transfusion
Elena B Kostova, Boukje M Beuger, Thomas R L Klei, Pasi Halonen, Cor Lieftink, Roderick Beijersbergen, Timo K van den Berg, Robin van Bruggen
Even though red blood cell (RBC) vesiculation is a well-documented phenomenon, notably in the context of RBC aging and blood transfusion, the exact signalling pathways and kinases involved in this process remain largely unknown. We have established a screening method for RBC vesicle shedding using the Ca(2+) ionophore ionomycin which is a rapid and efficient method to promote vesiculation. In order to identify novel pathways stimulating vesiculation in RBC, we screened two libraries: the Library of Pharmacologically Active Compounds (LOPAC) and the Selleckchem Kinase Inhibitor Library for their effects on RBC from healthy donors...
2015: Bioscience Reports
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"