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mast cell activation disorder

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https://www.readbyqxmd.com/read/28074060/s100a8-a9-and-s100a9-reduce-acute-lung-injury
#1
Yuka Hiroshima, Kenneth Hsu, Nicodemus Tedla, Sze Wing Wong, Sharron Chow, Naomi Kawaguchi, Carolyn L Geczy
S100A8 and S100A9 are myeloid cell-derived proteins that are elevated in several types of inflammatory lung disorders. Pro- and anti-inflammatory properties are reported and these proteins are proposed to activate TLR4. S100A8 and S100A9 can function separately, likely through distinct receptors but a systematic comparison of their effects in vivo are limited. Here we assess inflammation in murine lung following S100A9 and S100A8/A9 inhalation. Unlike S100A8, S100A9 promoted mild neutrophil and lymphocyte influx, possibly mediated in part, by increased mast cell degranulation and selective upregulation of some chemokine genes, particularly CXCL-10...
January 11, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28057422/structure-activity-relationship-study-and-discovery-of-indazole-3-carboxamides-as-calcium-release-activated-calcium-channel-blockers
#2
Sha Bai, Masazumi Nagai, Steffi K Koerner, Aristidis Veves, Lijun Sun
Aberrant activation of mast cells contributes to the development of numerous diseases including cancer, autoimmune disorders, as well as diabetes and its complications. The influx of extracellular calcium via the highly calcium selective calcium-release activated calcium (CRAC) channel controls mast cell functions. Intracellular calcium homeostasis in mast cells can be maintained via the modulation of the CRAC channel, representing a critical point for therapeutic interventions. We describe the structure-activity relationship study (SAR) of indazole-3-carboxamides as potent CRAC channel blockers and their ability to stabilize mast cells...
December 27, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28038453/histone-deacetylase-inhibitor-saha-mediates-mast-cell-death-and-epigenetic-silencing-of-constitutively-active-d816v-kit-in-systemic-mastocytosis
#3
Katarina Lyberg, Hani Abdulkadir Ali, Jennine Grootens, Matilda Kjellander, Malin Tirfing, Michel Arock, Hans Hägglund, Gunnar Nilsson, Johanna Ungerstedt
Systemic mastocytosis (SM) is a clonal bone marrow disorder, where therapeutical options are limited. Over 90% of the patients carry the D816V point mutation in the KIT receptor that renders this receptor constitutively active. We assessed the sensitivity of primary mast cells (MC) and mast cell lines HMC1.2 (D816V mutated), ROSA (KIT WT) and ROSA (KIT D816V) cells to histone deacetylase inhibitor (HDACi) treatment. We found that of four HDACi, suberoyl anilide hydroxamic acid (SAHA) was the most effective in killing mutated MC...
December 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/28027594/neuroimmune-factors-in-functional-gastrointestinal-disorders-a-focus-on-irritable-bowel-syndrome
#4
REVIEW
G E Boeckxstaens, M M Wouters
BACKGROUND: Abnormal abdominal pain perception is the most bothersome and difficult to treat symptom of functional gastrointestinal disorders (FGIDs). Visceral pain stimuli are perceived and transmitted by afferent neurons residing in the dorsal root ganglia that have sensory nerve endings in the gut wall and mesentery. Accumulating evidence indicates that peripheral activation and sensitization of these sensory nerve endings by bioactive mediators released by activated immune cells, in particular mast cells, can lead to aberrant neuroimmune interactions and the development and maintenance of visceral hypersensitivity...
December 27, 2016: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/27998003/vitamin-d-contributes-to-mast-cell-stabilization
#5
Zhi-Qiang Liu, Xiao-Xi Li, Shu-Qi Qiu, Yong Yu, Mao-Gang Li, Li-Tao Yang, Lin-Jing Li, Shuai Wang, Peng-Yuan Zheng, Zhi-Gang Liu, Ping-Chang Yang
BACKGROUND AND AIMS: Mast cells are the major effector cells in allergic disorders and many other informatory disorders. The mechanism of mast cell stabilization is not fully understood. Cumulative reports indicate that vitamin D (VitD) contributes to the homeostasis in the body. This study tests a hypothesis that VitD is required in the maintenance of the stability of mast cells. METHODS: The stability of mast cell lines, HMC1 cells, RBL-2H3 cells, p815 cells and mouse bone marrow-derived mast cells (BMMC) was tested in the presence or absence of VitD3...
December 20, 2016: Allergy
https://www.readbyqxmd.com/read/27942432/mast-cell-clonal-disorders-classification-diagnosis-and-management
#6
REVIEW
Merel C Onnes, Luciana K Tanno, Joanne N G Oude Elberink
Mast cell clonal disorders are characterized by the clonal proliferation of pathological mast cells as a result of somatic mutations in the KIT gene, most commonly the D816V mutation. Accumulation and degranulation of these cells causes a wide variety of symptoms. Mast cell clonal disorders can be divided into mastocytosis and monoclonal mast cell activation syndrome, depending of the level of clonality. The severity of mastocytosis varies from an indolent variant with a good prognosis, to an aggressive condition with short life expectancy...
2016: Current Treatment Options in Allergy
https://www.readbyqxmd.com/read/27927825/an-update-on-mast-cell-disorders
#7
Hannah Cookson, Clive Grattan
Disorders of mast cell activation can be classified as primary (mastocytosis), secondary (reactive) or idiopathic. This article discusses how to recognise and approach the diagnosis of patients suspected to have symptoms of abnormal mast cell activation. Given the highly varied and often complex symptomatology of such patients, we advocate applying a logical step-wise approach to investigating these patients to ensure the correct diagnosis is made. Treatments of mast cell activation disorders are discussed, dividing them into those that ameliorate the effects of mast cell mediators and those that act to stabilise the mast cell...
December 2016: Clinical Medicine: Journal of the Royal College of Physicians of London
https://www.readbyqxmd.com/read/27920467/possible-therapeutic-role-of-ige-blockade-in-irritable-bowel-syndrome
#8
EDITORIAL
Eli Magen, Tinatin Chikovani
Omalizumab is a humanized monoclonal antibody that binds to the high-affinity type-I IgE Fc receptors on mast cells (MCs) and basophils, inhibiting the IgE immune pathway. Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder, and dysregulation of the immune system likely contributes to its etiology and/or symptomatology. Colonic biopsies from patients with IBS demonstrate considerable increase in the number of degranulating MCs releasing histamine in proximity to nerves, and this event may underlie the common IBS symptom of abdominal pain...
November 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27908847/homeostasis-of-the-gut-barrier-and-potential-biomarkers
#9
Jerry M Wells, Robert J Brummer, Muriel Derrien, Thomas T MacDonald, Freddy Troost, Patrice D Cani, Vassilia Theodorou, Jan Dekker, Agnes Méheust, Willem M de Vos, Annick Mercenier, Arjen Nauta, Clara L Garcia-Rodenas
The gut barrier plays a crucial role by spatially compartmentalizing bacteria to the lumen through the production of secreted mucus and is fortified by the production of sIgA and antimicrobial peptides and proteins. With exception of sIgA the expression of these protective barrier factors is largely controlled by innate immune recognition of microbial molecular ligands. Several specialized adaptations and checkpoints are operating in the mucosa to scale the immune response according to the threat and prevent overreaction to the trillions of symbionts inhabiting the human intestine...
December 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27896225/the-urokinase-urokinase-receptor-system-in-mast-cells-effects-of-its-functional-interaction-with-fmlf-receptors
#10
Francesca Wanda Rossi, Nella Prevete, Felice Rivellese, Filomena Napolitano, Nunzia Montuori, Loredana Postiglione, Carmine Selleri, Amato de Paulis
Mast cell and basophils express the high affinity receptor for IgE (FcɛRI) and are primary effector cells of allergic disorders. The urokinase (uPA)-mediated plasminogen activation system is involved in physiological and pathological events based on cell migration and tissue remodelling, such as inflammation, wound healing, angiogenesis and metastasis. uPA is a serine protease that binds uPAR, a high affinity glycosyl-phosphatidyl-inositol (GPI)-anchored receptor. uPAR focuses uPA activity at the cell surface and activates intracellular signaling through lateral interactions with integrins, receptor tyrosine kinases and the G-protein-coupled family of fMLF chemotaxis receptors (FPRs)...
November 2016: Translational Medicine @ UniSa
https://www.readbyqxmd.com/read/27889928/elucidating-the-role-of-cyclooxygenase-2-in-the-pathogenesis-of-oral-lichen-planus-an-immunohistochemical-study-with-supportive-histochemical-analysis
#11
Pratyush Singh, Jasleen Grover, Aditi Amit Byatnal, Vasudeva Guddattu, Raghu Radhakrishnan, Monica Charlotte Solomon
OBJECTIVE: Oral lichen planus (OLP) is a chronic, inflammatory disorder that affects the oral mucous membrane. During an inflammatory response, several chemokines and cytokines are released by the cells of the immune system. Activation of MMPs, along with mast cell-derived chymase and tryptase, degrades the basement membrane structural proteins, resulting in basement membrane breaks. AIM: To investigate the association between the COX-2 expressions, presence of intact or degranulating mast cells within the connective tissue and the extent of basement membrane discontinuity in OLP cases...
November 7, 2016: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/27834692/factor-xii-as-a-therapeutic-target-in-thromboembolic-and-inflammatory-diseases
#12
Katrin F Nickel, Andy T Long, Tobias A Fuchs, Lynn M Butler, Thomas Renné
Coagulation factor XII (FXII, Hageman factor) is a plasma protease that in its active form (FXIIa) initiates the procoagulant and proinflammatory contact system. This name arises from FXII's unique mechanism of activation that is induced by binding (contact) to negatively charged surfaces. Various substances have the capacity to trigger FXII contact-activation in vivo including mast cell-derived heparin, misfolded protein aggregates, collagen, nucleic acids, and polyphosphate. FXII deficiency is not associated with bleeding, and for decades, the factor was considered to be dispensable for coagulation in vivo...
January 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27822310/anaphylactic-shock-during-cement-implantation-of-a-total-hip-arthroplasty-in-a-patient-with-underlying-mastocytosis-case-report-of-a-rare-intraoperative-complication
#13
Anita Ten Hagen, Pieter Doldersum, Tom van Raaij
BACKGROUND: Cemented total hip arthroplasty (THA) is a safe and common procedure. In rare cases life threatening bone cement implantation syndrome (BCIS) may occur, which is commonly caused by pulmonary embolism (PE). CASE PRESENTATION: We describe the rare case of a 70-year old patient who underwent an elective total hip replacement. Before surgery he was diagnosed with underlying systemic indolent mastocytosis, a rare pathological disorder that may result in anaphylaxis after massive systemic mast cell activation...
2016: Patient Safety in Surgery
https://www.readbyqxmd.com/read/27786273/the-nedd4-2-ndfip1-axis-is-a-negative-regulator-of-ige-mediated-mast-cell-activation
#14
Kwok Ho Yip, Natasha Kolesnikoff, Nicholas Hauschild, Lisa Biggs, Angel F Lopez, Stephen J Galli, Sharad Kumar, Michele A Grimbaldeston
Cross-linkage of the high-affinity immunoglobulin E (IgE) receptor (FcɛRI) on mast cells by antigen ligation has a critical role in the pathology of IgE-dependent allergic disorders, such as anaphylaxis and asthma. Restraint of intracellular signal transduction pathways that promote release of mast cell-derived pro-inflammatory mediators is necessary to dampen activation and restore homoeostasis. Here we show that the ligase Nedd4-2 and the adaptor Ndfip1 (Nedd4 family interacting protein 1) limit the intensity and duration of IgE-FcɛRI-induced positive signal transduction by ubiquitinating phosphorylated Syk, a tyrosine kinase that is indispensable for downstream FcɛRI signalosome activity...
October 27, 2016: Nature Communications
https://www.readbyqxmd.com/read/27779084/mast-cell-disorders-in-drug-hypersensitivity
#15
Patrizia Bonadonna, Massimiliano Bonifacio, Roberta Zanotti
Mastocytosis is a clonal disease characterized by proliferation and accumulation of mast cells (MC) in different tissues, preferentially skin and bone marrow, leading to a wide variety of clinical manifestations, mainly caused by the inappropriate release of MC mediators. As a consequence, patients with mastocytosis may experience symptoms due to massive MC activation and release of mediators. Anaphylaxis is the most frequent manifestation of this phenomenon.Drugs are possible triggers of anaphylaxis in patients with mastocytosis, even though the association between mastocytosis and drug anaphylaxis does not appear to be as strong as anaphylaxis after hymenoptera sting; nevertheless, MC disorders might be ruled out in cases of severe systemic reactions to drugs...
September 28, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27758758/effects-of-rupatadine-on-platelet-activating-factor-paf-induced-human-mast-cell-degranulation-compared-with-desloratadine-and-levocetirizine-the-maspaf-study
#16
R Muñoz-Cano, E Ainsua-Enrich, I Torres-Atencio, M Martin, J Sánchez-Lopez, J Bartra, C Picado, J Mullol, A Valero
RATIONALE: Platelet activating factor (PAF) is a lipid mediator involved in the pathophysiology of several allergic diseases, such as the amplification of mast cell (MC) activation in anaphylaxis. Rupatadine is an antihistamine with demonstrated anti-PAF effect but its capacity to inhibit PAF-induced MC degranulation has not been fully evaluated. OBJECTIVE: To investigate the ability of rupatadine to inhibit PAF-induced MC degranulation compared with desloratadine and levocetirizine, to confirm dual rupatadine anti-H1 and anti-PAF activities...
October 19, 2016: Journal of Investigational Allergology & Clinical Immunology
https://www.readbyqxmd.com/read/27738395/current-approach-to-cutaneous-mastocytosis-in-childhood
#17
REVIEW
Zeynep Tamay, Deniz Özçeker
Mastocytosis is a heterogeneous disorder characterized by clonal proliferation and accumulation of mast cells in one of more organs which may lead to different clinical pictures. Pathological increase and activation of mast cells in various tissues can cause different clinical pictures. Cutaneous mastocytosis limited to the skin is the most typical clinical picture observed in children and systemic mastocytosis is very rare in the pediatric age group. The diagnosis of cutaneous mastocytosis is based on clinical findings, but is often delayed due to lack of clinical awareness of the disease and lack of its consideration in the differential diagnosis...
September 2016: Türk Pediatri Arşivi
https://www.readbyqxmd.com/read/27708358/increased-duodenal-eosinophil-degranulation-in-patients-with-functional-dyspepsia-a-prospective-study
#18
Lijun Du, Jinhua Shen, John J Kim, Yunxian Yu, Liqin Ma, Ning Dai
Functional dyspepsia (FD) is a functional gastrointestinal disorder diagnosed by symptom-based criteria. It has been said that duodenal immune activation plays a role in the pathogenesis of FD. The primary aims of the study were to compare the total number of duodenal eosinophil and evaluate the eosinophil degranulation rate, number of duodenal degranulated eosinophil and mast cell between patients with FD and healthy subjects. We enrolled 96 patients with FD and 24 healthy controls at Sir Run Run Shaw Hospital...
October 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27701827/beneficial-effects-of-co-ultramicronized-palmitoylethanolamide-luteolin-in-a-mouse-model-of-autism-and-in-a-case-report-of-autism
#19
Bartolomeo Bertolino, Rosalia Crupi, Daniela Impellizzeri, Giuseppe Bruschetta, Marika Cordaro, Rosalba Siracusa, Emanuela Esposito, Salvatore Cuzzocrea
AIMS: Autism spectrum disorder (ASD) is a condition defined by social communication deficits and repetitive restrictive behaviors. Association of the fatty acid amide palmitoylethanolamide (PEA) with the flavonoid luteolin displays neuroprotective and antiinflammatory actions in different models of central nervous system pathologies. We hypothesized that association of PEA with luteolin might have therapeutic utility in ASD, and we employed a well-recognized autism animal model, namely sodium valproate administration, to evaluate cognitive and motor deficits...
January 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/27694038/targeting-mast-cells-uncovering-prolific-therapeutic-role-in-myriad-diseases
#20
REVIEW
Jatinder Singh, Ramanpreet Shah, Dhandeep Singh
The mast cells are integral part of immune system and they have pleiotropic physiological functions in our body. Any type of abnormal stimuli causes the mast cells receptors to spur the otherwise innocuous mast cells to degranulate and release inflammatory mediators like histamine, cytokines, chemokines and prostaglandins. These mediators are involved in various diseases like allergy, asthma, mastocytosis, cardiovascular disorders, etc. Herein, we describe the receptors involved in degranulation of mast cells and are broadly divided into four categories: G-protein coupled receptors, ligand gated ion channels, immunoreceptors and pattern recognition receptors...
November 2016: International Immunopharmacology
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