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Mast cell activation syndrome

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https://www.readbyqxmd.com/read/29137981/umbilical-cord-derived-mesenchymal-stem-cells-alleviated-inflammation-and-inhibited-apoptosis-in-interstitial-cystitis-via-akt-mtor-signaling-pathway
#1
Juncong Xie, Bolong Liu, Jialiang Chen, Yuancheng Xu, Hailun Zhan, Fei Yang, Wenbiao Li, Xiangfu Zhou
Interstitial cystitis (IC) is a bladder syndrome characterized by pelvic pain and urinary frequency without infection or other identifiable pathology. There are no effective treatments to cure IC. This study investigated the effects of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) injection on IC rat model. Furthermore, we used a coculture system to find the possible molecular mechanism on the human uroepithelial cells (SV-HUC-1), which was the cell model of IC. A rat model of IC was established via systemic injection with cyclophosphamide (CYP) and a cell model of IC was induced by being exposed to tumor necrosis factor (TNF)-α (10 ng/ml)...
November 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29118019/acyloxyacyl-hydrolase-modulates-pelvic-pain-severity
#2
Wenbin Yang, Ryan E Yaggie, Mingchen C Jiang, Charles N Rudick, Joseph D Done, Charles J Heckman, John M Rosen, Anthony J Schaeffer, David J Klumpp
Chronic pelvic pain causes significant patient morbidity and is a bane to clinicians. Using a murine neurogenic cystitis model that recapitulates key aspects of interstitial cystitis/bladder pain syndrome (IC), we recently showed that pseudorabies virus (PRV) induces severe pelvic allodynia in BALB/c mice, relative to C57BL/6 mice. Here, we report that a quantitative trait locus (QTL) analysis of PRV-induced allodynia in F2CxB progeny identified a polymorphism on chromosome 13, rs6314295, significantly associated with allodynia (LOD=3...
November 8, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29083538/functional-dyspepsia-and-duodenal-eosinophilia-a-new-disease-model
#3
REVIEW
Kening Fan, Nicholas J Talley
Functional dyspepsia (FD) is a highly prevalent disorder that affects more than 10% of the population. In the past decade, the conceptual underpinning of FD has begun to change, and new data are unraveling the underlying pathophysiological mechanisms of this disorder with a focus on the duodenum. The Rome IV criteria were published in 2016, and notably suggests that gastroesophageal reflux disease and irritable bowel syndrome may all be part of the same disease spectrum as FD. Helicobacter pylori explains a minority of FD cases and in Rome IV is considered a separate entity...
October 30, 2017: Journal of Digestive Diseases
https://www.readbyqxmd.com/read/29048112/how-we-diagnose-and-treat-systemic-mastocytosis-in-adults
#4
REVIEW
Robyn M Scherber, Uma Borate
Rapid advances in the understanding of the molecular biology, data from translational and clinical trials, and retrospective analyses has influenced the diagnosis and treatment of systemic mastocytosis (SM). Many options have existed for the symptomatic management of SM patients, but recent evolution in regards to the molecular underpinnings of this disease and our ability to distinguish clonal mastocytosis from mast cell activation syndrome has changed our treatment paradigm and opened new opportunities for understanding genetic risk, transformation to mast cell leukaemia, and treatment choices...
October 19, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/29026603/downregulation-of-mucosal-mast-cell-activation-and-immune-response-in-diarrhoea-irritable-bowel-syndrome-by-oral-disodium-cromoglycate-a-pilot-study
#5
Beatriz Lobo, Laura Ramos, Cristina Martínez, Mar Guilarte, Ana M González-Castro, Carmen Alonso-Cotoner, Marc Pigrau, Inés de Torres, Bruno K Rodiño-Janeiro, Eloisa Salvo-Romero, Marina Fortea, Cristina Pardo-Camacho, Danila Guagnozzi, Fernando Azpiroz, Javier Santos, María Vicario
BACKGROUND AND GOAL: Diarrhoea-predominant irritable bowel syndrome (IBS-D) exhibits intestinal innate immune and mucosal mast cell (MC) activation. MC stabilisers have been shown to improve IBS symptoms but the mechanism is unclear. Our primary aim was to investigate the effect of oral disodium cromoglycate (DSCG) on jejunal MC activation and specific innate immune signalling pathways in IBS-D, and secondarily, its potential clinical benefit. STUDY: Mucosal MC activation (by ultrastructural changes, tryptase release and gene expression) and innate immune signalling (by protein and gene expression) were quantified in jejunal biopsies from healthy (HS; n = 16) and IBS-D subjects after six months of either treatment with DSCG (600 mg/day, IBS-D-DSCG group; n = 18) or without treatment (IBS-D-NT group; n = 25)...
October 2017: United European Gastroenterology Journal
https://www.readbyqxmd.com/read/28988349/mastocytosis-in-children
#6
REVIEW
Nicholas Klaiber, Santhosh Kumar, Anne-Marie Irani
PURPOSE OF REVIEW: In this review, we examine the current understanding of the pathogenesis, clinical presentations, diagnostic tools, and treatment options of pediatric mastocytosis as well as the natural history of the disease. RECENT FINDINGS: We discuss the emerging concept of mast cell activation syndrome. Mastocytosis in children presents most commonly as isolated cutaneous lesions and is a relatively rare occurrence with excellent prognosis and spontaneous regression often occurring by adolescence...
October 7, 2017: Current Allergy and Asthma Reports
https://www.readbyqxmd.com/read/28947947/discovery-of-cdz173-leniolisib-representing-a-structurally-novel-class-of-pi3k-delta-selective-inhibitors
#7
Klemens Hoegenauer, Nicolas Soldermann, Frédéric Zécri, Ross S Strang, Nadege Graveleau, Romain M Wolf, Nigel G Cooke, Alexander B Smith, Gregory J Hollingworth, Joachim Blanz, Sascha Gutmann, Gabriele Rummel, Amanda Littlewood-Evans, Christoph Burkhart
The predominant expression of phosphoinositide 3-kinase δ (PI3Kδ) in leukocytes and its critical role in B and T cell functions led to the hypothesis that selective inhibitors of this isoform would have potential as therapeutics for the treatment of allergic and inflammatory disease. Targeting specifically PI3Kδ should avoid potential side effects associated with the ubiquitously expressed PI3Kα and β isoforms. We disclose how morphing the heterocyclic core of previously discovered 4,6-diaryl quinazolines to a significantly less lipophilic 5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine, followed by replacement of one of the phenyl groups with a pyrrolidine-3-amine, led to a compound series with an optimal on-target profile and good ADME properties...
September 14, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28945834/midostaurin-a-magic-bullet-that-blocks-mast-cell-expansion-and-activation
#8
P Valent, C Akin, K Hartmann, T I George, K Sotlar, B Peter, K V Gleixner, K Blatt, W R Sperr, P W Manley, O Hermine, H C Kluin-Nelemans, M Arock, H-P Horny, A Reiter, J Gotlib
Clinically relevant features in patients with systemic mastocytosis (SM) include the cosmetic burden of lesional skin, mediator-related symptoms, and organ damage resulting from mast cell (MC) infiltration in advanced forms of SM. Regardless of the SM variant, expansion of neoplastic MC in the skin and other organs is triggered by mutant forms of KIT, the most prevalent being D816V. Activation of MC with subsequent release of chemical mediators is often caused by IgE-dependent mechanisms in these patients. Midostaurin, also known as PKC412, blocks the kinase activity of wild-type KIT and KIT D816V, counteracts KIT-dependent growth of neoplastic MC, and inhibits IgE-dependent mediator secretion...
October 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28934791/a-practical-guide-for-treatment-of-pain-in-patients-with-systemic-mast-cell-activation-disease
#9
Stefan Wirz, Gerhard J Molderings
Systemic mast cell activation disease (MCAD, a subclass of mastocytosis), which has a prevalence of around 17% (at least in the German population), is characterized by accumulation of genetically altered dysfunctional mast cells with abnormal release of these cells' mediators. Since mast cells affect functions in potentially every organ system, often without causing abnormalities in routine laboratory or radiologic testing, this disease has to be considered routinely in the differential diagnosis of patients with chronic multisystem polymorbidity of a generally inflammatory and allergic theme...
September 2017: Pain Physician
https://www.readbyqxmd.com/read/28887433/the-neurobeachin-like-2-protein-regulates-mast-cell-homeostasis
#10
Sebastian Drube, Randy Grimlowski, Carsten Deppermann, Julia Fröbel, Florian Kraft, Nico Andreas, David Stegner, Jan Dudeck, Franziska Weber, Mandy Rödiger, Christiane Göpfert, Julia Drube, Daniela Reich, Bernhard Nieswandt, Anne Dudeck, Thomas Kamradt
The neurobeachin-like 2 protein (Nbeal2) belongs to the family of beige and Chediak-Higashi (BEACH) domain proteins. Loss-of-function mutations in the human NBEAL2 gene or Nbeal2 deficiency in mice cause gray platelet syndrome, a bleeding disorder characterized by macrothrombocytopenia, splenomegaly, and paucity of α-granules in megakaryocytes and platelets. We found that in mast cells, Nbeal2 regulates the activation of the Shp1-STAT5 signaling axis and the composition of the c-Kit/STAT signalosome. Furthermore, Nbeal2 mediates granule formation and restricts the expression of the transcription factors, IRF8, GATA2, and MITF as well as of the cell-cycle inhibitor p27, which are essential for mast cell differentiation, proliferation, and cytokine production...
October 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28860846/ambroxol-for-the-treatment-of-fibromyalgia-science-or-fiction
#11
Kai-Uwe Kern, Myriam Schwickert
Fibromyalgia appears to present in subgroups with regard to biological pain induction, with primarily inflammatory, neuropathic/neurodegenerative, sympathetic, oxidative, nitrosative, or muscular factors and/or central sensitization. Recent research has also discussed glial activation or interrupted dopaminergic neurotransmission, as well as increased skin mast cells and mitochondrial dysfunction. Therapy is difficult, and the treatment options used so far mostly just have the potential to address only one of these aspects...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28828984/the-efficacy-and-potential-mechanisms-of-chinese-herbal-medicine-on-irritable-bowel-syndrome
#12
Zijuan Bi, Yu Zheng, Jianye Yuan, Zhaoxiang Bian
Irritable bowel syndrome (IBS) is one of the most common functional bowel disorders (FBD), which is characterized by recurrent abdominal pain, abdominal bloating/distention associated with defecation or changed bowel habits. Currently, there is no evidence of obvious anatomic or physiologic abnormalities on the routine diagnostic examinations. There are multiple pathological factors involved in IBS responsible for its heterogeneous nature, although the exact etiology and pathology of IBS are not well known and it is disappointed to develop biomarkers for this disorder...
August 21, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28800865/anaphylaxis
#13
REVIEW
Daniel LoVerde, Onyinye I Iweala, Ariana Eginli, Guha Krishnaswamy
Anaphylaxis is a systemic, life-threatening disorder triggered by mediators released by mast cells and basophils activated via allergic (IgE-mediated) or nonallergic (non-IgE-mediated) mechanisms. It is a rapidly evolving, multisystem process involving the integumentary, pulmonary, gastrointestinal, and cardiovascular systems. Anaphylaxis and angioedema are serious disorders that can lead to fatal airway obstruction and culminate in cardiorespiratory arrest, resulting in hypoxemia and/or shock. Often, these disorders can be appropriately managed in an outpatient setting; however, these conditions can be severe enough to warrant evaluation of the patient in the ED and in some cases, hospitalization, and management in an ICU...
August 8, 2017: Chest
https://www.readbyqxmd.com/read/28780942/mast-cell-activation-syndromes
#14
REVIEW
Cem Akin
Mast cell activation is common and possibly necessary for maintenance of survival. Disordered mast cell activation occurs when mast cells are pathologically overproduced or if their activation is out of proportion to the perceived threat to homeostasis. Mast cell activation syndrome refers to a group of disorders with diverse causes presenting with episodic multisystem symptoms as the result of mast cell mediator release. Despite introduction of diagnostic criteria and some advances in treatment in the last decade, many areas of mast cell activation syndrome are in need of research...
August 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28757265/pathophysiology-of-eosinophilic-esophagitis
#15
Kelly M O'Shea, Seema S Aceves, Evan S Dellon, Sandeep K Gupta, Jonathan M Spergel, Glenn T Furuta, Marc E Rothenberg
Eosinophilic esophagitis (EoE) is an emerging disease that is distinguished from gastroesophageal reflux disease (GERD) by the expression of a unique esophageal transcriptome and the interplay of early life environmental factors with distinct genetic susceptibility elements at 5q22 (TSLP) and 2p23 (CAPN14). Rare genetic syndromes have uncovered the contribution of barrier disruption, mediated in part by defective desmosomes and dysregulated transforming factor beta (TGF-β) production and signaling, to EoE pathophysiology...
July 27, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28740494/insights-in-anaphylaxis-and-clonal-mast-cell-disorders
#16
REVIEW
David González-de-Olano, Iván Álvarez-Twose
The prevalence of anaphylaxis among patients with clonal mast cell disorders (MCD) is clearly higher comparing to the general population. Due to a lower frequency of symptoms outside of acute episodes, clonal MCD in the absence of skin lesions might sometimes be difficult to identify which may lead to underdiagnosis, and anaphylaxis is commonly the presenting symptom in these patients. Although the release of mast cell (MC) mediators upon MC activation might present with a wide variety of symptoms, particular clinical features typically characterize MC mediator release episodes in patients with clonal MCD without skin involvement...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28721077/food-protein-induced-enterocolitis-syndrome-a-review-of-the-literature-with-focus-on-clinical-management
#17
REVIEW
Marine Michelet, Dominique Schluckebier, Laetitia-Marie Petit, Jean-Christoph Caubet
Food protein-induced enterocolitis syndrome (FPIES) is a potentially severe presentation of non-IgE-mediated gastrointestinal food allergy (non-IgE-GI-FA) with heterogeneous clinical manifestations. Acute FPIES is typically characterized by profuse vomiting and lethargy, occurring classically 1-4 hours after ingestion of the offending food. When continuously exposed to the incriminated food, a chronic form has been described with persistent vomiting, diarrhea, and/or failure to thrive. Although affecting mainly infants, FPIES has also been described in adults...
2017: Journal of Asthma and Allergy
https://www.readbyqxmd.com/read/28684647/hypersensitivity-to-antipyretics-pathogenesis-diagnosis-and-management
#18
REVIEW
Q U Lee
Antipyretics are commonly prescribed drugs and hypersensitivity occurs at rates of 0.01% to 0.3%. Hypersensitivity can be due to immune mechanisms that include type I to IV hypersensitivity. Type I hypersensitivity results from specific immunoglobulin E production following sensitisation on first exposure. Subsequent exposures elicit degranulation of mast cells, culminating an immediate reaction. Non-type I hypersensitivity is a delayed reaction that involves various effector cells, resulting in maculopapular rash, fixed drug eruptions, drug reaction with eosinophilia and systemic symptoms, and Stevens-Johnson syndrome/toxic epidermal necrolysis...
July 7, 2017: Hong Kong Medical Journal, Xianggang Yi Xue za Zhi
https://www.readbyqxmd.com/read/28684600/frontline-science-corticotropin-releasing-factor-receptor-subtype-1-is-a-critical-modulator-of-mast-cell-degranulation-and-stress-induced-pathophysiology
#19
Saravanan Ayyadurai, Amelia J Gibson, Susan D'Costa, Elizabeth L Overman, Laura J Sommerville, Ashwini C Poopal, Emily Mackey, Yihang Li, Adam J Moeser
Life stress is a major risk factor in the onset and exacerbation of mast cell-associated diseases, including allergy/anaphylaxis, asthma, and irritable bowel syndrome. Although it is known that mast cells are highly activated upon stressful events, the mechanisms by which stress modulates mast cell function and disease pathophysiology remains poorly understood. Here, we investigated the role of corticotropin-releasing factor receptor subtype 1 (CRF1) in mast cell degranulation and associated disease pathophysiology...
July 6, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28629749/a-distinct-biomolecular-profile-identifies-monoclonal-mast-cell-disorders-in-patients-with-idiopathic-anaphylaxis
#20
Melody C Carter, Avanti Desai, Hirsh D Komarow, Yun Bai, Sarah T Clayton, Alicia S Clark, Karina N Ruiz-Esteves, Lauren M Long, Daly Cantave, Todd M Wilson, Linda M Scott, Olga Simakova, Mi-Yeon Jung, Jamie Hahn, Irina Maric, Dean D Metcalfe
BACKGROUND: Clonal mast cell disorders are known to occur in a subset of patients with systemic reactions to Hymenoptera stings. This observation has prompted the question of whether clonal mast cell disorders also occur in patients with idiopathic anaphylaxis (IA). OBJECTIVE: We sought to determine the prevalence of clonal mast cell disorders among patients with IA, criteria to identify those patients who require a bone marrow biopsy, and whether the pathogenesis of IA involves a hyperresponsive mast cell compartment...
June 16, 2017: Journal of Allergy and Clinical Immunology
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