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Search Results: 1 - 10 of 401677 matches for " Gail M Gauvreau "
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IL-4 and IL-13 Differentially Regulate TLR-Induced Eosinophil-Basophil Differentiation of Cord Blood CD34+ Progenitor Cells
Pia Reece, Gail M. Gauvreau, Roma Sehmi, Judah A. Denburg
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0100734
Abstract: Intrauterine environmental exposures have been shown to influence neonatal immunity and subsequent allergic disease development. We have previously shown that fewer lipopolysaccharide (LPS)-stimulated eosinophil-basophil (Eo/B) colonies grow from cord blood (CB) of high-atopic risk infants, compared to low-atopic risk infants. In the present study, we investigated whether a surrogate ex vivo TH2 milieu (i.e., either IL-4 or IL-13) could represent an underlying mechanism to explain our previous findings. CB CD34+ cells from healthy donors were cultured with IL-4 or IL-13 (in combination with LPS) and assessed for Eo/B differentiation using methylcellulose cultures and flow cytometry for related intracellular signalling pathways. Pharmacological inhibitors were added to the methylcellulose cultures to determine the effect of blocking intracellular signalling in CB CD34+ cells in relation to Eo/B colony forming unit (CFU) formation. Stimulation of CD34+ cells with IL-4, but not IL-13, reduced Eo/B CFU formation in the presence of LPS; this was found to be dependent on IL-4Rα and not IL-13Rα1. Additionally, IL-4 reduced the expression of ERK 1/2 after LPS stimulation, which was recovered by inhibition of IL-4Rα. While IL-13 did not have an inhibitory effect on ERK 1/2 expression, inhibition of ERK 1/2 significantly reduced Eo/B CFU formation. Thus, the responsiveness of CB CD34+ progenitor cells to LPS is differentially regulated by the TH2 cytokines, IL-4 and IL-13. This may have implications for in utero interactions between placental-derived pro-allergic cytokines and neonatal progenitor cells influencing Eo/B-mediated inflammatory responses in early life.
Functional genomics of the peripheral blood response to allergen inhalation challenge
Kam Sarah HY,Ruan Jian,Gauvreau Gail M,O'Byrne Paul M
Allergy, Asthma & Clinical Immunology , 2010, DOI: 10.1186/1710-1492-6-s3-p3
Bone marrow contribution to eosinophilic inflammation
Denburg, Judah A;Wood, Lorna;Gauvreau, Gail;Sehmi, Roma;Inman, Mark D;O'Byrne, Paul M;
Memórias do Instituto Oswaldo Cruz , 1997, DOI: 10.1590/S0074-02761997000800006
Abstract: allergen-induced bone marrow responses are observable in human allergic asthmatics, involving specific increases in eosinophil-basophil progenitors (eo/b-cfu), measured either by hemopoietic assays or by flow cytometric analyses of cd34-positive, il-3ra-positive, and/or il-5-responsive cell populations. the results are consistent with the upregulation of an il-5-sensitive population of progenitors in allergen-induced late phase asthmatic responses. studies in vitro on the phenotype of developing eosinophils and basophils suggest that the early acquisition of il-5ra, as well as the capacity to produce cytokines such as gm-csf and il-5, are features of the differentiation process. these observations are consistent with findings in animal models, indicating that allergen-induced increases in bone marrow progenitor formation depend on hemopoietic factor(s) released post-allergen. the possibility that there is constitutive marrow upregulation of eosinophilopoiesis in allergic airways disease is also an area for future investigation.
The Effect of PPAR Agonists on the Migration of Mature and Immature Eosinophils
Steven G. Smith,Haruki Imaoka,Neha Punia,Anam Irshad,Luke L. Janssen,Roma Sehmi,Gail M. Gauvreau
PPAR Research , 2012, DOI: 10.1155/2012/235231
Abstract: PPARγ agonists can either enhance or inhibit eosinophil migration, which is a sum of directional migration (chemotaxis) and random cell movement (chemokinesis). To date, the effects of PPAR agonists on chemokinesis have not been examined. This study investigates the effects of PPARα, δ, and γ agonists on eosinophil migration and chemokinesis. Eosinophils purified from blood of atopic donors were preincubated with rosiglitazone (PPARγ agonist), GW9578 (PPARα agonist), GW501516 (PPARδ agonist), or diluent. The effects of PPAR agonists were examined on eosinophil chemokinesis, eotaxin-induced migration of eosinophils, and migration of IL-5Rα+ CD34+ cells. Expressions of CCR3, phospho-p38, phospho-ERK, and calcium release were also measured in eosinophils after rosiglitazone treatment. Low concentrations of rosiglitazone, but not GW9578 or GW501516, increased chemokinesis of eosinophils ( ), and SDF-1α-induced migration of immature eosinophils ( ). Rosiglitazone had an effect on eosinophil calcium flux but had no effect on expression of CCR3 or phosphorylation of p38 or ERK. In contrast, high concentrations of rosiglitazone inhibited eosinophil migration ( ). The effect of rosiglitazone on eosinophil migration and chemokinesis appears to be through modification of calcium signaling, which alludes to a novel PPAR-mediated mechanism to modulate eosinophil function. 1. Introduction Eosinophils are effector cells which contribute to the pathology of allergic diseases [1]. They are recruited from the blood into inflamed tissue by local release of chemokines [2, 3]. Eotaxin-1, which is one of the most potent eosinophil chemokines, signals through chemokine receptor 3 (CCR3). Novel approaches toward inhibiting migration of effector cells such as eosinophils are being investigated for treatment of allergic asthma. The peroxisome proliferator-activated receptors (PPARs) are metabolite-activated transcription factors that have been shown to regulate metabolic and inflammatory responses [4]. There are three identified subtypes of PPARs: PPARα [5], PPARγ [6], and PPARδ [7], which have attracted interest as therapeutic targets in lung disease due to their preferential expression on human airway smooth muscle [8] and inflammatory cells [9] and increased expression during inflammatory events [10, 11]. In murine models of allergic asthma, PPARα and PPARγ agonists (rosiglitazone and GW9578, resp.) inhibit eosinophil influx to the lung following airway antigen challenge [12, 13]. The PPARγ agonist was more effective than the PPARα agonist, while the PPARδ agonist had no
Roflumilast attenuates allergen-induced inflammation in mild asthmatic subjects
Gail M Gauvreau, Louis-Philippe Boulet, Christine Schmid-Wirlitsch, Johanne C?té, MyLinh Duong, Kieran J Killian, Joanne Milot, Francine Deschesnes, Tara Strinich, Richard M Watson, Dirk Bredenbr?ker, Paul M O'Byrne
Respiratory Research , 2011, DOI: 10.1186/1465-9921-12-140
Abstract: 25 subjects with mild allergic asthma were randomized to oral roflumilast 500 mcg or placebo, once daily for 14 days in a double-blind, placebo-controlled, crossover study. Allergen challenge was performed on Day 14, and FEV1 was measured until 7 h post challenge. Methacholine challenge was performed on Days 1 (pre-dose), 13 (24 h pre-allergen), and 15 (24 h post-allergen), and sputum induction was performed on Days 1, 13, 14 (7 h post-allergen), and 15.Roflumilast inhibited the allergen-induced late phase response compared to placebo; maximum % fall in FEV1 (p = 0.02) and the area under the curve (p = 0.01). Roflumilast had a more impressive effect inhibiting allergen-induced sputum eosinophils, neutrophils, and eosinophil cationic protein (ECP) at 7 h post-allergen (all p = 0.02), and sputum neutrophils (p = 0.04), ECP (p = 0.02), neutrophil elastase (p = 0.0001) and AHR (p = 0.004) at 24 h post-allergen.This study demonstrates a protective effect of roflumilast on allergen-induced airway inflammation. The observed attenuation of sputum eosinophils and neutrophils demonstrates the anti-inflammatory properties of PDE4 inhibition and supports the roles of both cell types in the development of late phase bronchoconstriction and AHR.ClinicalTrials.gov: NCT01365533Asthma is characterized by the presence of cough, wheeze, dyspnea, reversible airway obstruction and airway hyperresponsiveness. Eosinophils are cells recognized to be a key feature of allergic asthma [1], however patients with severe asthma have increases in both eosinophils and neutrophils in their sputum [2]. Furthermore, severe asthma exacerbations are associated with bronchial mucosal eosinophilia and neutrophilia, as well as upregulation of CXC chemoattractants and their receptors [3]. Although current asthma therapies such as corticosteroids are effective in inhibiting eosinophilic inflammation through Th2 suppression, they may enhance neutrophil accumulation into the airways and until now therapies th
Gene-Metabolite Expression in Blood Can Discriminate Allergen-Induced Isolated Early from Dual Asthmatic Responses
Amrit Singh, Masatsugu Yamamoto, Sarah H. Y. Kam, Jian Ruan, Gail M. Gauvreau, Paul M. O'Byrne, J. Mark FitzGerald, Robert Schellenberg, Louis-Philippe Boulet, Gabriella Wojewodka, Cynthia Kanagaratham, Juan B. De Sanctis, Danuta Radzioch, Scott J. Tebbutt
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0067907
Abstract: Some asthmatic individuals undergoing allergen inhalation challenge develop an isolated early response whereas others develop a dual response (early plus late response). In the present study we have used transcriptomics (microarrays) and metabolomics (mass spectrometry) of peripheral blood to identify molecular patterns that can discriminate allergen-induced isolated early from dual asthmatic responses. Peripheral blood was obtained prior to (pre-) and 2 hours post allergen inhalation challenge from 33 study participants. In an initial cohort of 14 participants, complete blood counts indicated significant differences in neutrophil and lymphocyte counts at pre-challenge between early and dual responders. At post-challenge, significant genes (ALOX15, FADS2 and LPCAT2) and metabolites (lysolipids) were enriched in lipid metabolism pathways. Enzymes encoding for these genes are involved in membrane biogenesis and metabolism of fatty acids into pro-inflammatory and anti-inflammatory mediators. Correlation analysis indicated a strong negative correlation between ALOX15, FADS2, and IL5RA expression with 2-arachidonoylglycerophosphocholine levels in dual responders. However, measuring arachidonic acid and docosahexaenoic acid levels in a validation cohort of 19 participants indicated that the free form of DHA (nmoles/μg of protein) was significantly (p = 0.03) different between early and dual responders after allergen challenge. Collectively these results may suggest an imbalance in lipid metabolism which dictates pro- (anti-) inflammatory and pro-resolving mechanisms. Future studies with larger sample sizes may reveal novel mechanisms and therapeutic targets of the late phase asthmatic response.
Bone marrow contribution to eosinophilic inflammation
Denburg Judah A,Wood Lorna,Gauvreau Gail,Sehmi Roma
Memórias do Instituto Oswaldo Cruz , 1997,
Abstract: Allergen-induced bone marrow responses are observable in human allergic asthmatics, involving specific increases in eosinophil-basophil progenitors (Eo/B-CFU), measured either by hemopoietic assays or by flow cytometric analyses of CD34-positive, IL-3Ralpha-positive, and/or IL-5-responsive cell populations. The results are consistent with the upregulation of an IL-5-sensitive population of progenitors in allergen-induced late phase asthmatic responses. Studies in vitro on the phenotype of developing eosinophils and basophils suggest that the early acquisition of IL-5Ralpha, as well as the capacity to produce cytokines such as GM-CSF and IL-5, are features of the differentiation process. These observations are consistent with findings in animal models, indicating that allergen-induced increases in bone marrow progenitor formation depend on hemopoietic factor(s) released post-allergen. The possibility that there is constitutive marrow upregulation of eosinophilopoiesis in allergic airways disease is also an area for future investigation.
Differences in Mean Number of Consonant-Vowel-Consonant Words Decoded between Letter-Sound Readers and Non Letter-Sound Readers  [PDF]
Gail M. Wolf
Open Journal of Nursing (OJN) , 2014, DOI: 10.4236/ojn.2014.46047

Children’s failure to develop simple word decoding skills in early years is linked to future poor reading, school dropout, and poor health [1] [2]. Letter-sound knowledge is needed for word decoding development; however questions remain on what types of letter-sound knowledge help children decode simple words [3]. This study investigated the differences in mean number of consonant-vowel-consonant (CVC) words decoded between two groups of children, a letter-sound reading group and non letter-sound reading group. Children aged 4 to 6 in both groups, attempted to decode a variety of simple words such as tan, sit, hen, pig, dot, and fun. Analysis determined word decoding differences existed between the two groups. The alternate hypothesis was accepted; the letter-sound reading group had a significantly higher mean in number of consonant-vowel-consonant words decoded compared to the non letter-sound reading group. The study informs the teaching approaches needed to

Developing Reading Automaticity and Fluency: Revisiting What Reading Teachers Know, Putting Confirmed Research into Current Practice  [PDF]
Gail M. Wolf
Creative Education (CE) , 2018, DOI: 10.4236/ce.2018.96062
Abstract: This article revisits research on reading automaticity and fluency with the goal of helping beginning reading teachers put confirmed research findings into current classroom practice. The article examines the concepts of automaticity and fluency, how both impact the development of skillful reading. The article reviews research on: a) reading strategies children use, and b) repeat reading teaching strategies to develop fluency. Case scenarios illustrate key findings. Based on the research and case scenarios, four conclusions are drawn: 1) The terms automaticity and fluency are often interchanged; the concepts are not the same; 2) Understanding the differences between automaticity and fluency can impact repeat reading teaching strategies; 3) There is an assumption that rapid word recognition is the same cognitive process as automatic word decoding; and 4) There are two pathways to fluent reading, rapid word recognition, and automatic decoding ability. The article presents a theoretical model which aligns with childhood learning theories, offering teachers a variation in repeat reading teaching strategies. Rather than repeating reading the same text, opportunities to read slightly different, decodable text improves decoding, builds fluency, and thus strengthens children’s reading comprehension of complex text.
Asian Indian Celebrations of Ethnicity: Perspectives from the Mid-western United States
M. Gail Hickey
International Journal of Intangible Heritage , 2012,
Abstract: Asian Indians are among the fastest growing immigrant groups in the United States today. Eighty-two percent of Asian Indian immigrants now living in the U.S. arrived between 1980 and 2000, and their population more than doubled in the 1990s. Currently, the U.S. Asian Indian population totals more than 3.2 million (U.S. Census 2010, March 2011 Update). The majority of Asian Indians residing in the United States are English language proficient, have a high socio-economic status, are better educated than the general populace, and are well represented among professional career groups (Chandras, 1997; Mogelonsky, 1995; Helweg and Helweg, 1990; Takaki, 1989). In spite of their strong presence in U.S. institutions and economy, little research has focused on the everyday experiences of Asian Indian families in the United States (Mehra, 1997; Bhola, 1996). Voices of Asian Indian women in particular, have been absent from the literature. This paper explores U.S. Asian Indian women's efforts to retain ethnic culture during their transition into American society, with particular emphasis on public and private celebrations.
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