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JOURNAL ARTICLE
Zoltan Rumbus, Kata Fekete, Leonardo Kelava, Bibor Gardos, Krisztian Klonfar, Patrik Keringer, Erika Pinter, Eszter Pakai, Andras Garami
AIMS: Systemic administration of ammonium chloride (NH4 Cl), an acidifying agent used in human patients and experimental conditions, causes hypothermia in mice, however, the mechanisms of the thermoregulatory response to NH4 Cl and whether it develops in other species remained unknown. MAIN METHODS: We studied body temperature (Tb ) changes in rats and mice induced by intraperitoneal administration of NH4 Cl after blockade of transient receptor potential vanilloid-1 (TRPV1) or ankyrin-1 (TRPA1) channels...
April 12, 2024: Life Sciences
#2
JOURNAL ARTICLE
Virginia Mumford, Magdalena Z Raban, Ling Li, Erin Fitzpatrick, Amanda Woods, Alison Merchant, Tim Badgery-Parker, Peter Gates, Melissa Baysari, Ric O Day, Geoffrey Ambler, Luciano Dalla-Pozza, Madlen Gazarian, Alan Gardo, Peter Barclay, Les White, Johanna I Westbrook
AIMS: The potential harm associated with medication errors is widely reported, but data on actual harm are limited. When actual harm has been measured, assessment processes are often poorly described, limiting their ability to be reproduced by other studies. Our aim was to design and implement a new process to assess actual harm resulting from medication errors in paediatric inpatient care. METHODS: Prescribing errors were identified through retrospective medical record reviews (n = 26 369 orders) and medication administration errors through direct observation (n = 5137 administrations) in a tertiary paediatric hospital...
March 26, 2024: British Journal of Clinical Pharmacology
#3
JOURNAL ARTICLE
Polina Petkova-Kirova, Nicoletta Murciano, Giulia Iacono, Julia Jansen, Greta Simionato, Min Qiao, Carmen Van der Zwaan, Maria Giustina Rotordam, Thomas John, Laura Hertz, Arjan J Hoogendijk, Nadine Becker, Christian Wagner, Marieke Von Lindern, Stephane Egee, Emile Van den Akker, Lars Kaestner
The Gárdos channel (KCNN4) and Piezo1 are the best-known ion channels in the red blood cell (RBC) membrane. Nevertheless, the quantitative electrophysiological behavior of RBCs and its heterogeneity are still not completely understood. Here, we use state-of-the-art biochemical methods to probe for the abundance of the channels in RBCs. Furthermore, we utilize automated patch clamp, based on planar chips, to compare the activity of the two channels in reticulocytes and mature RBCs. In addition to this characterization, we performed membrane potential measurements to demonstrate the effect of channel activity and interplay on the RBC properties...
January 24, 2024: International Journal of Molecular Sciences
#4
JOURNAL ARTICLE
Ino de Bruijn, Ritika Kundra, Brooke Mastrogiacomo, Thinh Ngoc Tran, Luke Sikina, Tali Mazor, Xiang Li, Angelica Ochoa, Gaofei Zhao, Bryan Lai, Adam Abeshouse, Diana Baiceanu, Ersin Ciftci, Ugur Dogrusoz, Andrew Dufilie, Ziya Erkoc, Elena Garcia Lara, Zhaoyuan Fu, Benjamin E Gross, Charles D Haynes, Allison Heath, David M Higgins, Prasanna Jagannathan, Karthik Kalletla, Priti Kumari, James R Lindsay, Aaron Lisman, Bas Leenknegt, Pieter Lukasse, Divya Madala, Ramyasree Madupuri, Pim van Nierop, Oleguer Plantalech, Joyce Quach, Adam Resnick, Sander Y A Rodenburg, Baby A Satravada, Fedde Schaeffer, Robert Sheridan, Jessica Singh, Rajat Sirohi, Selcuk Onur Sumer, Sjoerd van Hagen, Avery Wang, Manda Wilson, Hongxin Zhang, Kelsey Zhu, Nicole Rusk, Samantha Brown, Jessica A Lavery, Katherine S Panageas, Julia E Rudolph, Michele L LeNoue-Newton, Jeremy L Warner, Xindi Guo, Haley Hunter-Zinck, Thomas V Yu, Shirin Pillai, Chelsea Nichols, Stuart M Gardos, John Philip, Genie Bpc Core Team, Aacr Project Genie Consortium, Kenneth L Kehl, Gregory J Riely, Deb Schrag, Jocelyn Lee, Michael V Fiandalo, Shawn M Sweeney, Trevor J Pugh, Chris Sander, Ethan Cerami, Jianjiong Gao, Nikolaus Schultz
International cancer registries make real-world genomic and clinical data available, but their joint analysis remains a challenge. AACR Project GENIE, an international cancer registry collecting data from 19 cancer centers, makes data from >130,000 patients publicly available through the cBioPortal for Cancer Genomics (https://genie.cbioportal.org). For 25,000 patients, additional real-world longitudinal clinical data, including treatment and outcome data, are being collected by the AACR Project GENIE Biopharma Collaborative using the PRISSMM data curation model...
September 5, 2023: Cancer Research
#5
REVIEW
Kelly Lambert, Robert Gardos, Helen Coolican, Lauren Pickel, Hoon-Ki Sung, Angela Yee-Moon Wang, Albert Cm Ong
Polycystic kidney disease (PKD) is a chronic, progressive hereditary condition characterized by abnormal development and growth of cysts in the kidneys and other organs. There is increasing interest in exploring whether dietary modifications may prevent or slow the disease course in people with PKD. Although vasopressin-receptor agonists have emerged as a novel drug treatment in advancing care for people with PKD, several recent landmark trials and clinical discoveries also have provided new insights into potential dietary-related therapeutic strategies...
March 2023: Seminars in Nephrology
#6
JOURNAL ARTICLE
Alicia Rivera, Christopher Vega, Arelys Ramos-Rivera, Enrique R Maldonado, Gregory N Prado, Hope E Karnes, Yuri A Fesko, L Michael Snyder, Seth L Alper, Jose R Romero
Increased endothelin-1 (ET-1) levels in patients with sickle cell disease (SCD) and transgenic mouse models of SCD contribute to disordered hematological, vascular, and inflammatory responses. Mineralocorticoid receptor (MR) activation by aldosterone, a critical component of the Renin-Angiotensin-Aldosterone-System, modulates inflammation and vascular reactivity, partly through increased ET-1 expression. However, the role of MR in SCD remains unclear. We hypothesized that MR blockade in transgenic SCD mice would reduce ET-1 levels, improve hematological parameters, and reduce inflammation...
August 2023: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
#7
JOURNAL ARTICLE
Jérémy Esnault, Sarah Scussel, Benjamin Gaudillat, Quentin Lejarre, Matéo Toussaint, Marianne Duployer, Miklós Gárdos, Péter Bán, Patrick Mavingui, Pablo Tortosa, Julien Cattel
The production of mosquitoes for control programs or basic research is facilitated by the standardization of rearing conditions allowing the daily manipulation of thousands of individuals. It is crucial to develop mechanical or electronic systems for controlling the density of mosquitoes at each development stage with the aim of reducing costs, time, and human errors. We present herein an automatic mosquito counter using a recirculating water system allowing rapid and reliable counting of pupae without detectable increased mortality...
May 3, 2023: Journal of Medical Entomology
#8
JOURNAL ARTICLE
John S Gibson, David C Rees
INTRODUCTION: In sickle cell disease (SCD), a single amino acid substitution at β6 of the haemoglobin (Hb) chain replaces glutamate with valine, forming HbS instead of the normal adult HbA. Loss of a negative charge, and the conformational change in deoxygenated HbS molecules, enables formation of HbS polymers. These not only distort red cell morphology but also have other profound effects so that this simple aetiology belies a complex pathogenesis with multiple complications. Although SCD represents a common severe inherited disorder with life-long consequences, approved treatments remain inadequate...
February 20, 2023: Expert Opinion on Therapeutic Targets
#9
JOURNAL ARTICLE
George Vaisey, Priyam Banerjee, Alison J North, Christoph A Haselwandter, Roderick MacKinnon
Piezo1 is the stretch activated Ca2+ channel in red blood cells that mediates homeostatic volume control. Here, we study the organization of Piezo1 in red blood cells using a combination of super-resolution microscopy techniques and electron microscopy. Piezo1 adopts a non-uniform distribution on the red blood cell surface, with a bias toward the biconcave 'dimple'. Trajectories of diffusing Piezo1 molecules, which exhibit confined Brownian diffusion on short timescales and hopping on long timescales, also reflect a bias toward the dimple...
December 14, 2022: ELife
#10
JOURNAL ARTICLE
Johanna I Westbrook, Ling Li, Magdalena Z Raban, Virginia Mumford, Tim Badgery-Parker, Peter Gates, Erin Fitzpatrick, Alison Merchant, Amanda Woods, Melissa Baysari, Cheryl McCullagh, Ric Day, Madlen Gazarian, Michael Dickinson, Karla Seaman, Lucciano Dalla-Pozza, Geoffrey Ambler, Peter Barclay, Alan Gardo, Tracey O'Brien, Draga Barbaric, Les White
Electronic medication management (eMM) systems are designed to improve safety, but there is little evidence of their effectiveness in paediatrics. This study assesses the short-term (first 70 days of eMM use) and long-term (one-year) effectiveness of an eMM system to reduce prescribing errors, and their potential and actual harm. We use a stepped-wedge cluster randomised controlled trial (SWCRCT) at a paediatric referral hospital, with eight clusters randomised for eMM implementation. We assess long-term effects from an additional random sample of medication orders one-year post-eMM...
December 13, 2022: NPJ Digital Medicine
#11
JOURNAL ARTICLE
Leïla Ghesh, Thomas Besnard, Madeleine Joubert, Véronique Picard, Claudine Le Vaillant, Claire Beneteau
Dehydrated hereditary stomatocytosis (DHS) (MIM#194380) is a rare autosomal dominant disorder of red blood cell permeability, characterized by a partially or fully compensated nonimmune hemolytic anemia. PIEZO1 is the major gene involved with hundreds of families described, some of which present transient perinatal edema of varying severity. A smaller subset of individuals harbors pathogenic variants in KCNN4, sometimes referred as "Gardos channelopathy." Up to now, only six pathogenic variants in KCNN4 have been reported in 13 unrelated families...
August 28, 2022: Clinical Genetics
#12
JOURNAL ARTICLE
B Allegrini, S Jedele, L David Nguyen, M Mignotet, R Rapetti-Mauss, C Etchebest, O Fenneteau, A Loubat, A Boutet, C Thomas, J Durin, A Petit, C Badens, L Garçon, L Da Costa, H Guizouarn
The K+ channel activated by the Ca2+ , KCNN4, has been shown to contribute to red blood cell dehydration in the rare hereditary hemolytic anemia, the dehydrated hereditary stomatocytosis. We report two de novo mutations on KCNN4 , We reported two de novo mutations on KCNN4 , V222L and H340N, characterized at the molecular, cellular and clinical levels. Whereas both mutations were shown to increase the calcium sensitivity of the K+ channel, leading to channel opening for lower calcium concentrations compared to WT KCNN4 channel, there was no obvious red blood cell dehydration in patients carrying one or the other mutation...
2022: Frontiers in Physiology
#13
JOURNAL ARTICLE
Alicia Rivera, Joshua A Nasburg, Heesung Shim, Boris E Shmukler, Jason Kitten, Jay G Wohlgemuth, Jeffrey S Dlott, L Michael Snyder, Carlo Brugnara, Heike Wulff, Seth L Alper
Red cell volume is a major determinant of HbS concentration in sickle cell disease. Cellular deoxy-HbS concentration determines the delay time, the interval between HbS deoxygenation and deoxy-HbS polymerization. Major membrane transporter protein determinants of sickle red cell volume include the SLC12/KCC K-Cl cotransporters KCC3/SLC12A6 and KCC1/SLC12A4, and the KCNN4/KCa3.1 Ca2+ -activated K+ channel (Gardos channel). Among standard inhibitors of KCC-mediated K-Cl cotransport, only [(dihydroindenyl)oxy]acetic acid (DIOA) has been reported to lack inhibitory activity against the related bumetanide-sensitive erythroid Na-K-2Cl cotransporter NKCC1/SLC12A2...
September 1, 2022: American Journal of Physiology. Cell Physiology
#14
JOURNAL ARTICLE
Sasha Waldstein, Sarah Arnold-Croop, Laura Carrel, M Elaine Eyster
No abstract text is available yet for this article.
August 2021: EJHaem
#15
JOURNAL ARTICLE
Kathrin Brömmel, Christian Paul Konken, Frederik Börgel, Henry Obeng-Darko, Sonja Schelhaas, Etmar Bulk, Thomas Budde, Albrecht Schwab, Michael Schäfers, Bernhard Wünsch
Expression of the Ca2+ activated potassium channel 3.1 (KCa 3.1) channel (also known as the Gàrdos channel) is dysregulated in many tumor entities and has predictive power with respect to patient survival. Therefore, a positron emission tomography (PET) tracer targeting this ion channel could serve as a potential diagnostic tool by imaging the KCa 3.1 channel in vivo . It was envisaged to synthesize [18 F]senicapoc ([18 F]1) since senicapoc (1) shows high affinity and excellent selectivity towards the KCa 3...
September 6, 2021: RSC Advances
#16
JOURNAL ARTICLE
Raphael Gonen, Max Platkov, Ziv Gardos, Sheli Shayir, Inna Levitsky, Marcelo Weinstein, Esther Manor
Many chromosome assays rely on the quantification of chromosome abnormalities in cells, and one important abnormality is the existence of more than one centromere for each chromosome. The quantification of such abnormalities has been studied before. However, this process is labor-intensive and time consuming. Thus, this assay is challenging for ex-laboratory applications, where speed is required. We present a visualization method that uses a cheap stain-DAPI, long (e.g., high-resolution) chromosomes and our modified C-banding method for labeling chromosomes...
February 8, 2022: Cell Biochemistry and Biophysics
#17
JOURNAL ARTICLE
Ralfs Buks, Tracy Dagher, Maria Giustina Rotordam, David Monedero Alonso, Sylvie Cochet, Emilie-Fleur Gautier, Philippe Chafey, Bruno Cassinat, Jean-Jacques Kiladjian, Nadine Becker, Isabelle Plo, Stéphane Egée, Wassim El Nemer
Over 95% of Polycythemia Vera (PV) patients carry the V617F mutation in the tyrosine kinase Janus kinase 2 (JAK2), resulting in uncontrolled erythroid proliferation and a high risk of thrombosis. Using mass spectrometry, we analyzed the RBC membrane proteome and showed elevated levels of multiple Ca2+ binding proteins as well as endoplasmic-reticulum-residing proteins in PV RBC membranes compared with RBC membranes from healthy individuals. In this study, we investigated the impact of JAK2V617F on (1) calcium homeostasis and RBC ion channel activity and (2) protein expression and sorting during terminal erythroid differentiation...
December 24, 2021: Cells
#18
JOURNAL ARTICLE
David Monedero Alonso, Laurent Pérès, Aline Hatem, Guillaume Bouyer, Stéphane Egée
Handbooks of physiology state that the strategy adopted by red blood cells (RBCs) to preserve cell volume is to maintain membrane permeability for cations at its minimum. However, enhanced cation permeability can be measured and observed in specific physiological and pathophysiological situations such as in vivo senescence, storage at low temperature, sickle cell anemia and many other genetic defects affecting transporters, membrane or cytoskeletal proteins. Among cation pathways, cation channels are able to dissipate rapidly the gradients that are built and maintained by the sodium and calcium pumps...
2021: Frontiers in Physiology
#19
JOURNAL ARTICLE
Julia Jansen, Min Qiao, Laura Hertz, Xijia Wang, Elisa Fermo, Anna Zaninoni, Raffaella Colombatti, Ingolf Bernhardt, Paola Bianchi, Lars Kaestner
In patients with Gárdos channelopathy (p.R352H), an increased concentration of intracellular Ca2+ was previously reported. This is a surprising finding because the Gárdos channel (KCa3.1) is a K+ channel. Here, we confirm the increased intracellular Ca2+ for patients with the KCa3.1 mutation p.S314P. Furthermore, we provide the concept of KCa3.1 activity resulting in a flickering of red blood cell (RBC) membranepotential, which activates the CaV2.1 channel allowing Ca2+ to enter the RBC. Activity of the nonselective cation channel Piezo1 modulates the aforementioned interplay in away that a closed Piezo1 is in favor of the KCa3...
September 14, 2021: Blood Advances
#20
JOURNAL ARTICLE
Philippe Chadebech, Gwellaouen Bodivit, Gaétana Di Liberto, Alicia Jouard, Corinne Vasseur, France Pirenne, Pablo Bartolucci
BACKGROUND: Blood transfusion remains a key treatment for managing occlusive episodes and painful crises in sickle-cell disease (SCD). In that clinical context, red blood cells (RBCs) from donors and transfused to patients, may be affected by plasma components in the recipients' blood. Senescence lesion markers appear on the red cells after transfusion, shortening the RBC lifespan in circulation. In the specific context of SCD, senescence signals can also trigger the occlusive painful events, typical of the disease...
June 30, 2021: Biomolecules
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