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Gelfand, erwin

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https://www.readbyqxmd.com/read/29042028/importance-of-the-leukotriene-b4-blt1-and-ltb4-blt2-pathways-in-asthma
#1
REVIEW
Erwin W Gelfand
For several decades, the leukotriene pathways have been implicated as playing a central role in the pathophysiology of asthma. The presence and elevation of numerous metabolites in the blood, sputum, and bronchoalveolar lavage fluid from asthmatics or experimental animals adds support to this notion. However, targeting of the leukotriene pathways has had, in general, limited success. The single exception in asthma therapy has been targeting of the cysteinyl leukotriene receptor 1, which clinically has proven effective but only in certain clinical situations...
October 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28679735/hematopoietic-stem-cell-transplantation-in-29-patients-hemizygous-for-hypomorphic-ikbkg-nemo-mutations
#2
Charline Miot, Kohsuke Imai, Chihaya Imai, Anthony J Mancini, Zeynep Yesim Kucuk, Tokomki Kawai, Ryuta Nishikomori, Etsuro Ito, Isabelle Pellier, Sophie Dupuis Girod, Jeremie Rosain, Shinya Sasaki, Shanmuganathan Chandrakasan, Jana Pachlopnik Schmid, Tsubasa Okano, Estelle Colin, Alberto Olaya-Vargas, Marco Yamazaki-Nakashimada, Waseem Qasim, Sara Espinosa Padilla, Andrea Jones, Alfons Krol, Nyree Cole, Stephen Jolles, Jack Bleesing, Thomas Vraetz, Andrew R Gennery, Mario Abinun, Tayfun Güngör, Beatriz Costa-Carvalho, Antonio Condino-Neto, Paul Veys, Steven M Holland, Gulbu Uzel, Despina Moshous, Benedicte Neven, Stéphane Blanche, Stephan Ehl, Rainer Döffinger, Smita Y Patel, Anne Puel, Jacinta Bustamante, Erwin W Gelfand, Jean-Laurent Casanova, Jordan S Orange, Capucine Picard
X-linked recessive ectodermal dysplasia with immunodeficiency is a rare primary immunodeficiency caused by hypomorphic mutations of the IKBKG gene encoding the nuclear factor κB essential modulator (NEMO) protein. This condition displays enormous allelic, immunological, and clinical heterogeneity, and therapeutic decisions are difficult because NEMO operates in both hematopoietic and nonhematopoietic cells. Hematopoietic stem cell transplantation (HSCT) is potentially life-saving, but the small number of case reports available suggests it has been reserved for only the most severe cases...
September 21, 2017: Blood
https://www.readbyqxmd.com/read/28658551/spectrum-of-t-lymphocyte-activities-regulating-allergic-lung-inflammation
#3
REVIEW
Erwin W Gelfand, Anthony Joetham, Meiqin Wang, Katsuyuki Takeda, Michaela Schedel
Despite advances in the treatment of asthma, optimization of symptom control remains an unmet need in many patients. These patients, labeled severe asthma, are responsible for a substantial fraction of the disease burden. In these patients, research is needed to define the cellular and molecular pathways contributing to disease which in large part are refractory to corticosteroid treatment. The causes of steroid-resistant asthma are multifactorial and result from complex interactions of genetics, environmental factors, and innate and adaptive immunity...
July 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28629746/severe-disease-and-greater-impairment-of-nf-%C3%AE%C2%BAb-activation-in-i%C3%AE%C2%BAba-point-mutants-versus-truncation-mutants-in-autosomal-dominant-anhidrotic-ectodermal-dysplasia-with-immune-deficiency
#4
Daniel Petersheim, Michel J Massaad, Saetbyul Lee, Alessia Scarselli, Caterina Cancrini, Kunihiko Moriya, Yoji Sasahara, Arjan C Lankester, Morna Dorsey, Daniela Di Giovanni, Liliana Bezrodnik, Hidenori Ohnishi, Ryuta Nishikomori, Kay Tanita, Hirokazu Kanegane, Tomohiro Morio, Erwin W Gelfand, Ashish Jain, Elizabeth Secord, Capucine Picard, Jean-Laurent Casanova, Michael H Albert, Troy R Torgerson, Raif S Geha
BACKGROUND: Autosomal dominant anhidrotic ectodermal dysplasia with immune deficiency (AD EDA-ID) is caused by heterozygous point mutations at or close to S32 and S36 or N-terminal truncations in IκBα that impair its phosphorylation and degradation, and thus activation of the canonical NF-κB pathway. The outcome of hematopoietic stem cell transplantation is poor in AD EDA-ID despite achievement of chimerism. Mice heterozygous for the S32I mutation in IκBα have impaired non-canonical NF-κB activity and defective lymphorganogenesis...
June 16, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28628108/germline-hypomorphic-card11-mutations-in-severe-atopic-disease
#5
Chi A Ma, Jeffrey R Stinson, Yuan Zhang, Jordan K Abbott, Michael A Weinreich, Pia J Hauk, Paul R Reynolds, Jonathan J Lyons, Celeste G Nelson, Elisa Ruffo, Batsukh Dorjbal, Salomé Glauzy, Natsuko Yamakawa, Swadhinya Arjunaraja, Kelsey Voss, Jennifer Stoddard, Julie Niemela, Yu Zhang, Sergio D Rosenzweig, Joshua J McElwee, Thomas DiMaggio, Helen F Matthews, Nina Jones, Kelly D Stone, Alejandro Palma, Matías Oleastro, Emma Prieto, Andrea R Bernasconi, Geronimo Dubra, Silvia Danielian, Jonathan Zaiat, Marcelo A Marti, Brian Kim, Megan A Cooper, Neil Romberg, Eric Meffre, Erwin W Gelfand, Andrew L Snow, Joshua D Milner
Few monogenic causes for severe manifestations of common allergic diseases have been identified. Through next-generation sequencing on a cohort of patients with severe atopic dermatitis with and without comorbid infections, we found eight individuals, from four families, with novel heterozygous mutations in CARD11, which encodes a scaffolding protein involved in lymphocyte receptor signaling. Disease improved over time in most patients. Transfection of mutant CARD11 expression constructs into T cell lines demonstrated both loss-of-function and dominant-interfering activity upon antigen receptor-induced activation of nuclear factor-κB and mammalian target of rapamycin complex 1 (mTORC1)...
August 2017: Nature Genetics
https://www.readbyqxmd.com/read/28606988/recurrent-rhinovirus-infections-in-a-child-with-inherited-mda5-deficiency
#6
Ian T Lamborn, Huie Jing, Yu Zhang, Scott B Drutman, Jordan K Abbott, Shirin Munir, Sangeeta Bade, Heardley M Murdock, Celia P Santos, Linda G Brock, Evan Masutani, Emmanuel Y Fordjour, Joshua J McElwee, Jason D Hughes, Dave P Nichols, Aziz Belkadi, Andrew J Oler, Corinne S Happel, Helen F Matthews, Laurent Abel, Peter L Collins, Kanta Subbarao, Erwin W Gelfand, Michael J Ciancanelli, Jean-Laurent Casanova, Helen C Su
MDA5 is a cytosolic sensor of double-stranded RNA (ds)RNA including viral byproducts and intermediates. We studied a child with life-threatening, recurrent respiratory tract infections, caused by viruses including human rhinovirus (HRV), influenza virus, and respiratory syncytial virus (RSV). We identified in her a homozygous missense mutation in IFIH1 that encodes MDA5. Mutant MDA5 was expressed but did not recognize the synthetic MDA5 agonist/(ds)RNA mimic polyinosinic-polycytidylic acid. When overexpressed, mutant MDA5 failed to drive luciferase activity from the IFNB1 promoter or promoters containing ISRE or NF-κB sequence motifs...
July 3, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28479331/forkhead-box-protein-3-demethylation-is-associated-with-tolerance-induction-in-peanut-induced-intestinal-allergy
#7
Meiqin Wang, Ivana V Yang, Elizabeth J Davidson, Anthony Joetham, Katsuyuki Takeda, Brian P O'Connor, Erwin W Gelfand
BACKGROUND: Regulatory T (Treg) cells play an essential role in the maintenance of immune homeostasis in allergic diseases. OBJECTIVES: We sought to define the mechanisms underlying induction of tolerance to peanut protein and prevention of the development of peanut allergy. METHODS: High or low doses of peanut extract were administered to pups every day for 2 weeks before peanut sensitization and challenge. After challenge, symptoms, Treg cell numbers, and forkhead box protein 3 (Foxp3), TH2 and TH17 cytokine, and Tgfβ expression in mesenteric lymph node (MLN) CD4(+) T cells and jejunum were monitored...
May 4, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28223227/mitogen-activated-protein-kinases-as-therapeutic-targets-for-asthma
#8
REVIEW
MirHojjat Khorasanizadeh, Mahsa Eskian, Erwin W Gelfand, Nima Rezaei
Corticosteroid-resistant asthmatics, although comprising only a portion of the asthma population, account for most of the morbidity, mortality and economic burden associated with asthma. Moreover, corticosteroids are not effective inhibitors of airway remodeling changes, and their long-term use is associated with debilitating systemic side effects. Therefore, potent and safe novel therapeutic alternatives, targeting basic pathophysiological mechanisms responsible for the severe asthmatic phenotype are urgently needed...
February 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28213886/dysregulation-of-metabolic-pathways-in-a-mouse-model-of-allergic-asthma
#9
K D Quinn, M Schedel, Y Nkrumah-Elie, A Joetham, M Armstrong, C Cruickshank-Quinn, R Reisdorph, E W Gelfand, N Reisdorph
BACKGROUND: Asthma is a complex lung disease resulting from the interplay of genetic and environmental factors. To understand the molecular changes that occur during the development of allergic asthma without genetic and environmental confounders, an experimental model of allergic asthma in mice was used. Our goals were to (1) identify changes at the small molecule level due to allergen exposure, (2) determine perturbed pathways due to disease, and (3) determine whether small molecule changes correlate with lung function...
September 2017: Allergy
https://www.readbyqxmd.com/read/27542981/inducible-and-naturally-occurring-regulatory-t%C3%A2-cells-enhance-lung-allergic-responses-through-divergent-transcriptional-pathways
#10
Anthony Joetham, Michaela Schedel, Brian P O'Connor, Soohyun Kim, Katsuyuki Takeda, Jordan Abbott, Erwin W Gelfand
BACKGROUND: Regulatory T cells attenuate development of asthma in wild-type (WT) mice, with both naturally occurring regulatory T (nTreg) cells and inducible regulatory T (iTreg) cells exhibiting suppressive activity. When transferred into CD8-deficient (CD8(-/-)) recipients, both cell types enhanced development of allergen-induced airway hyperresponsiveness. OBJECTIVE: We sought to determine whether the pathways leading to enhancement of lung allergic responses by transferred nTreg and iTreg cells differed...
April 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27464698/in-vivo-assessment-of-airway-function-in-the-mouse-model
#11
Azzeddine Dakhama, Erwin W Gelfand
This chapter describes two procedures commonly used to examine airway function in mice. Airway function can be assessed in vivo using noninvasive or invasive methods. Noninvasive methods can be used to monitor respiratory function in mice without the involvement of restraint, anesthesia, or surgery. The methods allow for multiple animals to be monitored simultaneously and can be used in longitudinal studies requiring repeated measurements on the same animals. Invasive methods are used to assess airway function under anesthesia, in mechanically ventilated mice...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27351934/il-23-is-essential-for-the-development-of-elastase-induced-pulmonary-inflammation-and-emphysema
#12
Utako Fujii, Nobuaki Miyahara, Akihiko Taniguchi, Koichi Waseda, Daisuke Morichika, Etsuko Kurimoto, Hikari Koga, Mikio Kataoka, Erwin W Gelfand, Daniel J Cua, Akihiko Yoshimura, Mitsune Tanimoto, Arihiko Kanehiro
We recently reported that IL-17A plays a critical role in the development of porcine pancreatic elastase (PPE)-induced emphysema. The proliferation of T-helper type 17 (Th17) cells was induced by IL-23. To determine the contribution of IL-23 to the development of pulmonary emphysema, a mouse model of PPE-induced emphysema was used in which responses of IL-23p19-deficient (IL-23(-/-)) and wild-type (WT) mice were compared. Intratracheal instillation of PPE induced emphysematous changes in the lungs and was associated with increased levels of IL-23 in lung homogenates...
November 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27340385/immunomodulatory-effects-of-ambroxol-on-airway-hyperresponsiveness-and-inflammation
#13
Katsuyuki Takeda, Nobuaki Miyahara, Shigeki Matsubara, Christian Taube, Kenichi Kitamura, Astushi Hirano, Mitsune Tanimoto, Erwin W Gelfand
Ambroxol is used in COPD and asthma to increase mucociliary clearance and regulate surfactant levels, perhaps through anti-oxidant and anti-inflammatory activities. To determine the role and effect of ambroxol in an experimental model of asthma, BALB/c mice were sensitized to ovalbumin (OVA) followed by 3 days of challenge. Airway hyperresponsiveness (AHR), lung cell composition and histology, and cytokine and protein carbonyl levels in bronchoalveolar lavage (BAL) fluid were determined. Ambroxol was administered either before the first OVA challenge or was begun after the last allergen challenge...
June 2016: Immune Network
https://www.readbyqxmd.com/read/27059534/combined-blockade-of-the-histamine-h1-and-h4-receptor-suppresses-peanut-induced-intestinal-anaphylaxis-by-regulating-dendritic-cell-function
#14
M Wang, J Han, J Domenico, Y S Shin, Y Jia, E W Gelfand
BACKGROUND: Signaling through histamine receptors on dendritic cells (DCs) may be involved in the effector phase of peanut-induced intestinal anaphylaxis. OBJECTIVES: The objective of this study was to determine the role of histamine H1 (H1R) and H4 receptors (H4R) in intestinal allergic responses in a model of peanut allergy. METHODS: Balb/c mice were sensitized and challenged with peanut. During the challenge phase, mice were treated orally with the H1R antagonist, loratadine, and/or the H4R antagonist, JNJ7777120...
November 2016: Allergy
https://www.readbyqxmd.com/read/26981933/loss-of-b-cells-in-patients-with-heterozygous-mutations-in-ikaros
#15
H S Kuehn, B Boisson, C Cunningham-Rundles, J Reichenbach, A Stray-Pedersen, E W Gelfand, P Maffucci, K R Pierce, J K Abbott, K V Voelkerding, S T South, N H Augustine, J S Bush, W K Dolen, B B Wray, Y Itan, A Cobat, H S Sorte, S Ganesan, S Prader, T B Martins, M G Lawrence, J S Orange, K R Calvo, J E Niemela, J-L Casanova, T A Fleisher, H R Hill, A Kumánovics, M E Conley, S D Rosenzweig
BACKGROUND: Common variable immunodeficiency (CVID) is characterized by late-onset hypogammaglobulinemia in the absence of predisposing factors. The genetic cause is unknown in the majority of cases, and less than 10% of patients have a family history of the disease. Most patients have normal numbers of B cells but lack plasma cells. METHODS: We used whole-exome sequencing and array-based comparative genomic hybridization to evaluate a subset of patients with CVID and low B-cell numbers...
March 17, 2016: New England Journal of Medicine
https://www.readbyqxmd.com/read/26472810/contrasting-roles-for-the-receptor-for-advanced-glycation-end-products-on-structural-cells-in-allergic-airway-inflammation-vs-airway-hyperresponsiveness
#16
Akihiko Taniguchi, Nobuaki Miyahara, Koichi Waseda, Etsuko Kurimoto, Utako Fujii, Yasushi Tanimoto, Mikio Kataoka, Yasuhiko Yamamoto, Erwin W Gelfand, Hiroshi Yamamoto, Mitsune Tanimoto, Arihiko Kanehiro
The receptor for advanced glycation end-products (RAGE) is a multiligand receptor that belongs to the immunoglobulin superfamily. RAGE is reported to be involved in various inflammatory disorders; however, studies that address the role of RAGE in allergic airway disease are inconclusive. RAGE-sufficient (RAGE+/+) and RAGE-deficient (RAGE-/-) mice were sensitized to ovalbumin, and airway responses were monitored after ovalbumin challenge. RAGE-/- mice showed reduced eosinophilic inflammation and goblet cell metaplasia, lower T helper type 2 (Th2) cytokine production from spleen and peribronchial lymph node mononuclear cells, and lower numbers of group 2 innate lymphoid cells in the lung compared with RAGE+/+ mice following sensitization and challenge...
October 15, 2015: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/26407265/a-toddler-with-rash-encephalopathy-and-hemolytic-anemia
#17
Christiana Smith, Cullen Dutmer, D Scott Schmid, Megan K Dishop, William J Bellini, Erwin W Gelfand, Edwin J Asturias
No abstract text is available yet for this article.
December 2015: Journal of the Pediatric Infectious Diseases Society
https://www.readbyqxmd.com/read/25872769/experimentally-manipulated-sleep-duration-in-adolescents-with-asthma-feasibility-and-preliminary-findings
#18
RANDOMIZED CONTROLLED TRIAL
Lisa J Meltzer, Anna Faino, Stanley J Szefler, Matthew Strand, Erwin W Gelfand, Dean W Beebe
OBJECTIVE: To examine the impact of sleep duration on lung function and asthma symptoms in adolescents. METHODS: Ten adolescents with asthma (60% female, 60% Caucasian, mean age = 13.7 years, range 12-17) completed a 3-week randomized, cross-over sleep manipulation protocol. Following a week of self-selected sleep duration, adolescents were randomized to a five-night deficient sleep opportunity (6.5 hr in bed) or a healthy sleep opportunity (10 hr in bed) obtained by systematically changing bedtimes...
December 2015: Pediatric Pulmonology
https://www.readbyqxmd.com/read/25772592/the-other-side-of-asthma-steroid-refractory-disease-in-the-absence-of-th2-mediated-inflammation
#19
EDITORIAL
Erwin W Gelfand, Rafeul Alam
No abstract text is available yet for this article.
May 2015: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/25312762/eosinophils-contribute-to-the-resolution-of-lung-allergic-responses-following-repeated-allergen-challenge
#20
Katsuyuki Takeda, Yoshiki Shiraishi, Shigeru Ashino, Junyan Han, Yi Jia, Meiqin Wang, Nancy A Lee, James J Lee, Erwin W Gelfand
BACKGROUND: Eosinophils accumulate at the site of allergic inflammation and are critical effector cells in allergic diseases. Recent studies have also suggested a role for eosinophils in the resolution of inflammation. OBJECTIVE: To determine the role of eosinophils in the resolution phase of the response to repeated allergen challenge. METHODS: Eosinophil-deficient (PHIL) and wild-type (WT) littermates were sensitized and challenged to ovalbumin (OVA) 7 or 11 times...
February 2015: Journal of Allergy and Clinical Immunology
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