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https://www.readbyqxmd.com/read/29032017/editorial-next-generation-sequencing-technology-a-new-tool-for-killer-cell-immunoglobulin-like-receptor-allele-typing-in-hematopoietic-stem-cell-transplantation
#1
B Maniangou, C Retière, K Gagne
Killer cell Immunoglobulin-like Receptor (KIR) genes are a family of genes located together within the leukocyte receptor cluster on human chromosome 19q13.4. To date, 17 KIR genes have been identified including nine inhibitory genes (2DL1/L2/L3/L4/L5A/L5B, 3DL1/L2/L3), six activating genes (2DS1/S2/S3/S4/S5, 3DS1) and two pseudogenes (2DP1, 3DP1) classified into group A (KIR A) and group B (KIR B) haplotypes. The number and the nature of KIR genes vary between the individuals. In addition, these KIR genes are known to be polymorphic at allelic level (907 alleles described in July 2017)...
October 11, 2017: Transfusion Clinique et Biologique: Journal de la Société Française de Transfusion Sanguine
https://www.readbyqxmd.com/read/29016852/potassium-channel-dysfunction-underlies-purkinje-neuron-spiking-abnormalities-in-spinocerebellar-ataxia-type-2
#2
James M Dell'Orco, Stefan M Pulst, Vikram G Shakkottai
Alterations in Purkinje neuron firing often accompany ataxia, but the molecular basis for these changes is poorly understood. In a mouse model of spinocerebellar ataxia type 2 (SCA2), a progressive reduction in Purkinje neuron firing frequency accompanies cell atrophy. We investigated the basis for altered Purkinje neuron firing in SCA2. A reduction in the expression of large-conductance calcium-activated potassium (BK) channels and Kv3.3 voltage-gated potassium channels accompanies the inability of Purkinje neurons early in disease to maintain repetitive spiking...
October 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28935562/n-2-methoxyphenyl-benzenesulfonamide-a-novel-regulator-of-neuronal-g-protein-gated-inward-rectifier-k-channels
#3
Kenneth B Walsh, Elaine A Gay, Bruce E Blough, David W Geurkink
G protein-gated inward rectifier K(+) (GIRK) channels are members of the super-family of proteins known as inward rectifier K(+) (Kir) channels and are expressed throughout the peripheral and central nervous systems. Neuronal GIRK channels are the downstream targets of a number of neuromodulators including opioids, somatostatin, dopamine and cannabinoids. Previous studies have demonstrated that the ATP-sensitive K(+) channel, another member of the Kir channel family, is regulated by sulfonamide drugs. Therefore, to determine if sulfonamides also modulate GIRK channels, we screened a library of arylsulfonamide compounds using a GIRK channel fluorescent assay that utilized pituitary AtT20 cells expressing GIRK channels along with the somatostatin type-2 and -5 receptors...
September 18, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28804970/arrhythmogenic-gene-remodelling-in-elderly-patients-with-type-2-diabetes-with-aortic-stenosis-and-normal-left-ventricular-ejection-fraction
#4
R Ashrafi, P Modi, A Y Oo, D M Pullan, K Jian, H Zhang, J Yanni Gerges, G Hart, M R Boyett, G K Davis, J P H Wilding
What is the central question of this study? Type 2 diabetes is associated with a higher rate of ventricular arrhythmias compared with the non-diabetic population, but the associated myocardial gene expression changes are unknown; furthermore, it is also unknown whether any changes are attributable to chronic hyperglycaemia or are a consequence of structural changes. What is the main finding and its importance? We found downregulation of left ventricular ERG gene expression and increased NCX1 gene expression in humans with type 2 diabetes compared with control patients with comparable left ventricular hypertrophy and possible myocardial fibrosis...
August 14, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28801811/association-of-variably-expressed-kir3dl1-alleles-with-psoriatic-disease
#5
Jeffrey Berinstein, Remy Pollock, Fawnda Pellett, Arane Thavaneswaran, Vinod Chandran, Dafna D Gladman
The purpose of this study is to examine the genetic interaction of variably expressed killer cell immunoglobulin-like receptor (KIR) 3DL1 alleles with their cognate ligand, human leukocyte antigen (HLA)-Bw4, in susceptibility to psoriatic disease (PsD). A novel allelic typing system was developed to differentiate KIR3DL1 alleles (*High, *Low, *Null expression, and 3DS1), in PsD patients, including those with psoriatic arthritis (PsA) and cutaneous psoriasis without arthritis (PsC) and healthy controls. Frequencies of each KIR3DL1 allele, Bw4-80I and Bw4-80T, as well as the genetic interaction between the KIR3DL1 alleles and the Bw4 epitope were analyzed...
August 11, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28751893/patients-lacking-a-kir-ligand-of-hla-group-c1-or-c2-have-a-better-outcome-after-umbilical-cord-blood-transplantation
#6
Carmen Martínez-Losada, Carmen Martín, Rafael Gonzalez, Bárbara Manzanares, Estefania García-Torres, Concha Herrera
Donor natural killer (NK) cells can destroy residual leukemic cells after allogeneic hematopoietic stem cell transplantation. This effect is based on the interaction of killer-cell immunoglobulin-like receptors (KIR) of donor NK cells with ligands of the major histocompatibility complex found on the surface of the target cells. HLA-C1 subtypes provide the ligand for KIR2DL2 and KIR2DL3 and the HLA-C2 subtypes for KIR2DL1. We have studied the probability of relapse (PR) after single-unit unrelated cord blood transplantation (UCBT) in relation to the potential graft-vs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28747464/lethal-digenic-mutations-in-the-k-channels-kir4-1-kcnj10-and-slack-kcnt1-associated-with-severe-disabling-seizures-and-neurodevelopmental-delay
#7
Sonia Majed Hasan, Ameera Balobaid, Alessandro Grottesi, Omar Dabbagh, Marta Cenciarini, Rifaat Rawashdeh, Afaf Al-Sagheir, Cecilia Bove, Lara Macchioni, Mauro Pessia, Mohammed Al-Owain, Maria Cristina D'Adamo
A 2-year-old boy presented profound developmental delay, failure to thrive, ataxia, hypotonia and tonic-clonic seizures that caused the death of the patient. Targeted and whole-exome sequencing revealed two heterozygous missense variants: a novel mutation in KCNJ10 gene that encodes for the inwardly-rectifying K(+) channel Kir4.1 and another previously characterized mutation in KCNT1 that encodes for the Na(+)-activated K(+) channel known as Slo2.2 or SLACK. The objectives of this study were to perform the clinical and genetic characterization of the proband and his family and to examine the functional consequence of the Kir4...
July 26, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28695288/introduction-mhc-kir-and-governance-of-specificity
#8
REVIEW
Adrian Kelly, John Trowsdale
The MHC controls specificity, to ensure that appropriate immune responses are mounted to invading pathogens whilst maintaining tolerance to the host. It encodes molecules that act as sentinels, providing a snapshot of the health of the interior and exterior of the cell for immune surveillance. To maintain the ability to respond appropriately to any disease requires a delicate balance of expression and function, and many subtleties of the system have been described at the gene, individual and population level...
August 2017: Immunogenetics
https://www.readbyqxmd.com/read/28688202/influence-of-human-leukocyte-antigen-hla-alleles-and-killer-cell-immunoglobulin-like-receptors-kir-types-on-heparin-induced-thrombocytopenia-hit
#9
Jason H Karnes, Christian M Shaffer, Robert Cronin, Lisa Bastarache, Silvana Gaudieri, Ian James, Rebecca Pavlos, Heidi E Steiner, Jonathan D Mosley, Simon Mallal, Joshua C Denny, Elizabeth J Phillips, Dan M Roden
Heparin-induced thrombocytopenia (HIT) is an unpredictable, life-threatening, immune-mediated reaction to heparin. Variation in human leukocyte antigen (HLA) genes is now used to prevent immune-mediated adverse drug reactions. Combinations of HLA alleles and killer cell immunoglobulin-like receptors (KIR) are associated with multiple autoimmune diseases and infections. The objective of this study is to evaluate the association of HLA alleles and KIR types, alone or in the presence of different HLA ligands, with HIT...
September 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28659916/hla-bw4-i-80-isoform-differentially-influences-clinical-outcome-as-compared-to-hla-bw4-t-80-and-hla-a-bw4-isoforms-in-rituximab-or-dinutuximab-based-cancer-immunotherapy
#10
Amy K Erbe, Wei Wang, Patrick K Reville, Lakeesha Carmichael, KyungMann Kim, Eneida A Mendonca, Yiqiang Song, Jacquelyn A Hank, Wendy B London, Arlene Naranjo, Fangxin Hong, Michael D Hogarty, John M Maris, Julie R Park, M F Ozkaynak, Jeffrey S Miller, Andrew L Gilman, Brad Kahl, Alice L Yu, Paul M Sondel
Killer-cell immunoglobulin-like receptors (KIRs) are a family of glycoproteins expressed primarily on natural killer cells that can regulate their function. Inhibitory KIRs recognize MHC class I molecules (KIR-ligands) as ligands. We have reported associations of KIRs and KIR-ligands for patients in two monoclonal antibody (mAb)-based trials: (1) A Children's Oncology Group (COG) trial for children with high-risk neuroblastoma randomized to immunotherapy treatment with dinutuximab (anti-GD2 mAb) + GM-CSF + IL-2 + isotretinion or to treatment with isotretinoin alone and (2) An Eastern Cooperative Oncology Group (ECOG) trial for adults with low-tumor burden follicular lymphoma responding to an induction course of rituximab (anti-CD20 mAb) and randomized to treatment with maintenance rituximab or no-maintenance rituximab...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28619748/pore-polarity-and-charge-determine-differential-block-of-kir1-1-and-kir7-1-potassium-channels-by-small-molecule-inhibitor-vu590
#11
Sujay V Kharade, Jonathan H Sheehan, Eric E Figueroa, Jens Meiler, Jerod S Denton
VU590 was the first publicly disclosed, submicromolar-affinity (IC50 = 0.2 μM), small-molecule inhibitor of the inward rectifier potassium (Kir) channel and diuretic target, Kir1.1. VU590 also inhibits Kir7.1 (IC50 ∼ 8 μM), and has been used to reveal new roles for Kir7.1 in regulation of myometrial contractility and melanocortin signaling. Here, we employed molecular modeling, mutagenesis, and patch clamp electrophysiology to elucidate the molecular mechanisms underlying VU590 inhibition of Kir1.1 and Kir7...
September 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28613412/myoendothelial-coupling-through-cx40-contributes-to-edh-induced-vasodilation-in-murine-renal-arteries-evidence-from-experiments-and-modelling
#12
Jens Christian Brasen, Cor de Wit, Charlotte Mehlin Sorensen
Regulation of renal vascular resistance plays a major role in controlling arterial blood pressure. The endothelium participates in this regulation as endothelial derived hyperpolarization plays a significant role in smaller renal arteries and arterioles but the exact mechanisms are still unknown AIM: to investigate the role of vascular gap junctions and potassium channels in the renal endothelial derived hyperpolarization. METHODS: in interlobar arteries from wild-type and connexin40 knock-out mice we assessed the role of calcium activated small (SK) and intermediate (IK) conductance potassium channels...
June 14, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28600190/understanding-the-checkpoint-blockade-in-lung-cancer-immunotherapy
#13
REVIEW
Maria Giovanna Dal Bello, Angela Alama, Simona Coco, Irene Vanni, Francesco Grossi
Immunotherapies have changed the treatment strategy of some types of tumor including melanoma and, more recently, non-small-cell lung cancer (NSCLC). Immune checkpoints are crucial for the maintenance of self-tolerance and it is known that some tumors use checkpoint systems to evade antitumor immune response. The treatment of advanced NSCLC by immune-checkpoint blockade targeting the programmed cell death protein-1 (PD1/PDL1) and cytotoxic T-lymphocyte antigen 4 (CTLA4) pathways has led to significant clinical benefit either as monotherapy or in combination therapy...
August 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28582449/hiv-1-adaptation-to-nk-cell-mediated-immune-pressure
#14
Marjet Elemans, Lies Boelen, Michael Rasmussen, Søren Buus, Becca Asquith
The observation, by Alter et al., of the enrichment of NK cell "escape" variants in individuals carrying certain Killer-cell Immunoglobulin-like Receptor (KIR) genes is compelling evidence that natural killer (NK) cells exert selection pressure on HIV-1. Alter et al hypothesise that variant peptide, in complex with HLA class I molecules binds KIR receptors and either increases NK cell inhibition or decreases NK cell activation compared to wild type peptide thus leading to virus escape from the NK cell response...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28579987/killer-immunoglobulin-like-receptor-allele-determination-using-next-generation-sequencing-technology
#15
Bercelin Maniangou, Nolwenn Legrand, Mehdi Alizadeh, Ulysse Guyet, Catherine Willem, Gaëlle David, Eric Charpentier, Alexandre Walencik, Christelle Retière, Katia Gagne
The impact of natural killer (NK) cell alloreactivity on hematopoietic stem cell transplantation (HSCT) outcome is still debated due to the complexity of graft parameters, HLA class I environment, the nature of killer cell immunoglobulin-like receptor (KIR)/KIR ligand genetic combinations studied, and KIR(+) NK cell repertoire size. KIR genes are known to be polymorphic in terms of gene content, copy number variation, and number of alleles. These allelic polymorphisms may impact both the phenotype and function of KIR(+) NK cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28536356/hla-c-kir-ligands-determine-the-impact-of-anti-thymocyte-globulin-atg-on-graft-versus-host-and-graft-versus-leukemia-effects-following-hematopoietic-stem-cell-transplantation
#16
Johannes Clausen, Alexandra Böhm, Irene Straßl, Olga Stiefel, Veronika Buxhofer-Ausch, Sigrid Machherndl-Spandl, Josef König, Stefan Schmidt, Hansjörg Steitzer, Martin Danzer, Hedwig Kasparu, Ansgar Weltermann, David Nachbaur
Rabbit anti-thymocyte globulins (ATGs) are widely used for the prevention of acute and chronic graft versus host disease (aGVHD, cGVHD) following allogeneic hematopoietic stem cell transplantation (HSCT). However, most prospective and retrospective studies did not reveal an overall survival (OS) benefit associated with ATG. Homozygosity for human leukocyte antigen (HLA)-C group 1 killer-cell immunoglobulin-like receptor ligands (KIR-L), i.e. C1/1 KIR-L status, was recently shown to be a risk factor for severe aGVHD...
March 28, 2017: Biomedicines
https://www.readbyqxmd.com/read/28528709/association-between-the-killer-cell-immunoglobulin-like-receptor-a-haplotype-and-childhood-acute-lymphoblastic-leukemia
#17
Awad E Osman, Abdullah AlJuryyan, Hanan Alharthi, May Almoshary
Killer immunoglobulin-like receptors (KIRs) have the ability to regulate natural killer (NK) cell function through inhibition/activation mechanisms. Healthy human cells express HLA class I ligands on their surface, which are recognized by NK cells to avoid spontaneous cell destruction. The associations of KIRs and/or HLA class 1 ligands in leukemic patients have been studied in some populations, with some of these studies demonstrating an association of specific types with leukemia. KIRs and their corresponding HLA class 1 ligands were investigated in Saudi patients with ALL and AML and compared to healthy controls...
May 18, 2017: Human Immunology
https://www.readbyqxmd.com/read/28466469/recipient-donor-kir-ligand-matching-prevents-cmv-reactivation-post-haploidentical-t-cell-replete-transplantation
#18
Xiang-Yu Zhao, Xue-Yi Luo, Xing-Xing Yu, Xiao-Su Zhao, Ting-Ting Han, Ying-Jun Chang, Ming-Rui Huo, Lan-Ping Xu, Xiao-Hui Zhang, Kai-Yan Liu, Dan Li, Zheng-Fan Jiang, Xiao-Jun Huang
Licensed natural killer (NK) cells have been demonstrated to have anti-cytomegalovirus (CMV) activity. We prospectively analysed the human leucocyte antigen typing of donor-recipient pairs and the killer cell immunoglobulin-like receptor (KIR) typing of donors for 180 leukaemia patients to assess the predictive roles of licensed NK cells on CMV reactivation post-T-cell-replete haploidentical stem cell transplantation. Multivariate analysis showed that donor-recipient KIR ligand graft-versus-host or host-versus-graft direction mismatch was associated with increased refractory CMV infection (Hazard ratio = 2·556, 95% confidence interval, 1·377-4·744, P = 0·003) post-transplantation...
June 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28446610/conformational-changes-at-cytoplasmic-intersubunit-interactions-control-kir-channel-gating
#19
COMPARATIVE STUDY
Shizhen Wang, William F Borschel, Sarah Heyman, Phillip Hsu, Colin G Nichols
The defining structural feature of inward-rectifier potassium (Kir) channels is the unique Kir cytoplasmic domain. Recently we showed that salt bridges located at the cytoplasmic domain subunit interfaces (CD-Is) of eukaryotic Kir channels control channel gating via stability of a novel inactivated closed state. The cytoplasmic domains of prokaryotic and eukaryotic Kir channels show similar conformational rearrangements to the common gating ligand, phosphatidylinositol bisphosphate (PIP2), although these exhibit opposite coupling to opening and closing transitions...
June 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28425222/class-iii-antiarrhythmic-drugs-amiodarone-and-dronedarone-impair-kir-2-1-backward-trafficking
#20
Yuan Ji, Hiroki Takanari, Muge Qile, Lukas Nalos, Marien J C Houtman, Fee L Romunde, Raimond Heukers, Paul M P van Bergen En Henegouwen, Marc A Vos, Marcel A G van der Heyden
Drug-induced ion channel trafficking disturbance can cause cardiac arrhythmias. The subcellular level at which drugs interfere in trafficking pathways is largely unknown. KIR 2.1 inward rectifier channels, largely responsible for the cardiac inward rectifier current (IK1 ), are degraded in lysosomes. Amiodarone and dronedarone are class III antiarrhythmics. Chronic use of amiodarone, and to a lesser extent dronedarone, causes serious adverse effects to several organs and tissue types, including the heart. Both drugs have been described to interfere in the late-endosome/lysosome system...
October 2017: Journal of Cellular and Molecular Medicine
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