JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
A microRNA upregulated in asthma airway T cells promotes TH2 cytokine production.
Nat. Immunol.
PUBLISHED: 07-31-2014
Show Abstract
Hide Abstract
MicroRNAs (miRNAs) exert powerful effects on immunological function by tuning networks of target genes that orchestrate cell activity. We sought to identify miRNAs and miRNA-regulated pathways that control the type 2 helper T cell (TH2 cell) responses that drive pathogenic inflammation in asthma. Profiling miRNA expression in human airway-infiltrating T cells revealed elevated expression of the miRNA miR-19a in asthma. Modulating miR-19 activity altered TH2 cytokine production in both human and mouse T cells, and TH2 cell responses were markedly impaired in cells lacking the entire miR-17?92 cluster. miR-19 promoted TH2 cytokine production and amplified inflammatory signaling by direct targeting of the inositol phosphatase PTEN, the signaling inhibitor SOCS1 and the deubiquitinase A20. Thus, upregulation of miR-19a in asthma may be an indicator and a cause of increased TH2 cytokine production in the airways.
Related JoVE Video
Asthma: NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases.
Ann Am Thorac Soc
PUBLISHED: 04-24-2014
Show Abstract
Hide Abstract
Asthma is a common disease with enormous public health costs, and its primary prevention is an ambitious and important goal. Understanding of how host and environmental factors interact to cause asthma is incomplete, but persistent questions about mechanisms should not stop clinical research efforts aimed at reducing the prevalence of childhood asthma. Achieving the goal of primary prevention of asthma will involve integrated and parallel sets of research activities in which mechanism-oriented studies of asthma inception proceed alongside clinical intervention studies to test biologically plausible prevention ideas. For example, continued research is needed, particularly in young children, to uncover biomarkers that identify asthma risk and provide potential targets of intervention, and to improve understanding of the role of microbial factors in asthma risk and disease initiation. In terms of clinical trials that could be initiated now or in the near future, we recommend three interventions for testing: (1) preventing asthma through prophylaxis against respiratory syncytial virus and human rhinovirus infections of the airway; (2) immune modulation, using prebiotics, probiotics, and bacterial lysates; and (3) prevention of allergen sensitization and allergic inflammation, using anti-IgE. These interventions should be tested while other, more universal prevention measures that may promote lung health are also investigated. These potential universal lung health measures include prevention of preterm delivery; reduced exposure of the fetus and young infant to environmental pollutants, including tobacco smoke; prevention of maternal and child obesity; and management of psychosocial stress.
Related JoVE Video
Accumulation of BDCA1? dendritic cells in interstitial fibrotic lung diseases and Th2-high asthma.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Dendritic cells (DCs) significantly contribute to the pathology of several mouse lung disease models. However, little is known of the contribution of DCs to human lung diseases. In this study, we examined infiltration with BDCA1? DCs of human lungs in patients with interstitial lung diseases or asthma. Using flow cytometry, we found that these DCs increased by 5?6 fold in the lungs of patients with idiopathic pulmonary fibrosis or hypersensitivity pneumonitis, which are both characterized by extensive fibrosis in parenchyma. The same DC subset also significantly increased in the lung parenchyma of patients with chronic obstructive pulmonary disease, although the degree of increase was relatively modest. By employing immunofluorescence microscopy using Fc?RI and MHCII as the specific markers for BDCA1? DCs, we found that the numbers of BDCA1? DCs also significantly increased in the airway epithelium of Th2 inflammation-associated asthma. These findings suggest a potential contribution of BDCA1? DCs in human lung diseases associated with interstitial fibrosis or Th2 airway inflammation.
Related JoVE Video
A qPCR-based metric of Th2 airway inflammation in asthma.
Clin Transl Allergy
PUBLISHED: 06-07-2013
Show Abstract
Hide Abstract
Using microarray profiling of airway epithelial cells, we previously identified a Th2-high molecular phenotype of asthma based on expression of periostin, CLCA1 and serpinB2 and characterized by specific inflammatory, remodeling, and treatment response features. The goal of the current study was to develop a qPCR-based assay of Th2 inflammation to overcome the limitations of microarray-based methods.
Related JoVE Video
Measures of gene expression in sputum cells can identify TH2-high and TH2-low subtypes of asthma.
J. Allergy Clin. Immunol.
PUBLISHED: 02-07-2013
Show Abstract
Hide Abstract
The 3-gene signature of periostin, chloride channel accessory 1 (CLCA1), and Serpin ?2 (SERPINB2) in airway epithelial brushings is used to classify asthma into TH2-high and TH2-low endotypes. Little is known about the utility of gene profiling in sputum as a molecular phenotyping method.
Related JoVE Video
A Soluble Fucose-Specific Lectin from Aspergillus fumigatus Conidia - Structure, Specificity and Possible Role in Fungal Pathogenicity.
PLoS ONE
PUBLISHED: 01-01-2013
Show Abstract
Hide Abstract
Aspergillus fumigatus is an important allergen and opportunistic pathogen. Similarly to many other pathogens, it is able to produce lectins that may be involved in the host-pathogen interaction. We focused on the lectin AFL, which was prepared in recombinant form and characterized. Its binding properties were studied using hemagglutination and glycan array analysis. We determined the specificity of the lectin towards l-fucose and fucosylated oligosaccharides, including ?1-6 linked core-fucose, which is an important marker for cancerogenesis. Other biologically relevant saccharides such as sialic acid, d-mannose or d-galactose were not bound. Blood group epitopes of the ABH and Lewis systems were recognized, Le(Y) being the preferred ligand among others. To provide a correlation between the observed functional characteristics and structural basis, AFL was crystallized in a complex with methyl-?,l-selenofucoside and its structure was solved using the SAD method. Six binding sites, each with different compositions, were identified per monomer and significant differences from the homologous AAL lectin were found. Structure-derived peptides were utilized to prepare anti-AFL polyclonal antibodies, which suggested the presence of AFL on the Aspergillus conidia, confirming its expression in vivo. Stimulation of human bronchial cells by AFL led to IL-8 production in a dose-dependent manner. AFL thus probably contributes to the inflammatory response observed upon the exposure of a patient to A. fumigatus. The combination of affinity to human epithelial epitopes, production by conidia and pro-inflammatory activity is remarkable and shows that AFL might be an important virulence factor involved in an early stage of A. fumigatus infection.
Related JoVE Video
The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-?-1,3-galactose.
J. Allergy Clin. Immunol.
PUBLISHED: 01-21-2011
Show Abstract
Hide Abstract
In 2009, we reported a novel form of delayed anaphylaxis to red meat that is related to serum IgE antibodies to the oligosaccharide galactose-?-1,3-galactose (alpha-gal). Most of these patients had tolerated meat for many years previously. The implication is that some exposure in adult life had stimulated the production of these IgE antibodies.
Related JoVE Video
Hexaphenylbenzene as a rigid template for the straightforward syntheses of "star-shaped" glycodendrimers.
J. Org. Chem.
PUBLISHED: 12-29-2010
Show Abstract
Hide Abstract
Original glycodendrimers emanating from propargylated hexaphenylbenzene cores and containing up to 54 peripheral sugar ligands have been synthesized by Cu(I)-catalyzed [1,3]-dipolar cycloadditions using both convergent and divergent approaches.
Related JoVE Video
Gene expression patterns of Th2 inflammation and intercellular communication in asthmatic airways.
J. Immunol.
PUBLISHED: 12-27-2010
Show Abstract
Hide Abstract
Asthma is canonically thought of as a disorder of excessive Th2-driven inflammation in the airway, although recent studies have described heterogeneity with respect to asthma pathophysiology. We have previously described distinct phenotypes of asthma based on the presence or absence of a three-gene "Th2 signature" in bronchial epithelium, which differ in terms of eosinophilic inflammation, mucin composition, subepithelial fibrosis, and corticosteroid responsiveness. In the present analysis, we sought to describe Th2 inflammation in human asthmatic airways quantitatively with respect to known mediators of inflammation and intercellular communication. Using whole-genome microarray and quantitative real-time PCR analysis of endobronchial biopsies from 27 mild-to-moderate asthmatics and 13 healthy controls with associated clinical and demographic data, we found that asthmatic Th2 inflammation is expressed over a variable continuum, correlating significantly with local and systemic measures of allergy and eosinophilia. We evaluated a composite metric describing 79 coexpressed genes associated with Th2 inflammation against the biological space comprising cytokines, chemokines, and growth factors, identifying distinctive patterns of inflammatory mediators as well as Wnt, TGF-?, and platelet-derived growth factor family members. This integrated description of the factors regulating inflammation, cell migration, and tissue remodeling in asthmatic airways has important consequences for the pathophysiological and clinical impacts of emerging asthma therapeutics targeting Th2 inflammation.
Related JoVE Video
The H antigen at epithelial surfaces is associated with susceptibility to asthma exacerbation.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 08-23-2010
Show Abstract
Hide Abstract
Acute asthma exacerbations, precipitated by viral infections, are a significant cause of morbidity, but not all patients with asthma are equally susceptible.
Related JoVE Video
Roles of epithelial cell-derived periostin in TGF-beta activation, collagen production, and collagen gel elasticity in asthma.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 07-26-2010
Show Abstract
Hide Abstract
Periostin is considered to be a matricellular protein with expression typically confined to cells of mesenchymal origin. Here, by using in situ hybridization, we show that periostin is specifically up-regulated in bronchial epithelial cells of asthmatic subjects, and in vitro, we show that periostin protein is basally secreted by airway epithelial cells in response to IL-13 to influence epithelial cell function, epithelial-mesenchymal interactions, and extracellular matrix organization. In primary human bronchial epithelial cells stimulated with periostin and epithelial cells overexpressing periostin, we reveal a function for periostin in stimulating the TGF-beta signaling pathway in a mechanism involving matrix metalloproteinases 2 and 9. Furthermore, conditioned medium from the epithelial cells overexpressing periostin caused TGF-beta-dependent secretion of type 1 collagen by airway fibroblasts. In addition, mixing recombinant periostin with type 1 collagen in solution caused a dramatic increase in the elastic modulus of the collagen gel, indicating that periostin alters collagen fibrillogenesis or cross-linking and leads to stiffening of the matrix. Epithelial cell-derived periostin in asthma has roles in TGF-beta activation and collagen gel elasticity in asthma.
Related JoVE Video
Accumulation of intraepithelial mast cells with a unique protease phenotype in T(H)2-high asthma.
J. Allergy Clin. Immunol.
PUBLISHED: 03-01-2010
Show Abstract
Hide Abstract
Previously, we found that mast cell tryptases and carboxypeptidase A3 (CPA3) are differentially expressed in the airway epithelium in asthmatic subjects. We also found that asthmatic subjects can be divided into 2 subgroups ("T(H)2 high" and "T(H)2 low" asthma) based on epithelial cell gene signatures for the activity of T(H)2 cytokines.
Related JoVE Video
Safety and efficacy of an inhaled epidermal growth factor receptor inhibitor (BIBW 2948 BS) in chronic obstructive pulmonary disease.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 12-10-2009
Show Abstract
Hide Abstract
Epidermal growth factor receptor (EGFR) activation is implicated in mucin hypersecretion in chronic obstructive pulmonary disease (COPD).
Related JoVE Video
Effect of beta2-adrenergic receptor polymorphism on response to longacting beta2 agonist in asthma (LARGE trial): a genotype-stratified, randomised, placebo-controlled, crossover trial.
Lancet
PUBLISHED: 11-26-2009
Show Abstract
Hide Abstract
Some studies suggest that patients with asthma who are homozygous for arginine at the 16th amino acid position of the beta2-adrenergic receptor (B16 Arg/Arg) benefit less from treatment with longacting beta2 agonists and inhaled corticosteroids than do those homozygous for glycine (B16 Gly/Gly). We investigated whether there is a genotype-specific response to treatment with a longacting beta2 agonist in combination with inhaled corticosteroid.
Related JoVE Video
Distinct roles of FOXA2 and FOXA3 in allergic airway disease and asthma.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 07-23-2009
Show Abstract
Hide Abstract
Increased production of mucus is a prominent feature of asthma. IL-13-driven mucous cell metaplasia is associated with decreased expression of the transcription factor FOXA2 and increased expression of the related transcription factor FOXA3 in animal and cell culture models.
Related JoVE Video
T-helper type 2-driven inflammation defines major subphenotypes of asthma.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 05-29-2009
Show Abstract
Hide Abstract
T-helper type 2 (Th2) inflammation, mediated by IL-4, IL-5, and IL-13, is considered the central molecular mechanism underlying asthma, and Th2 cytokines are emerging therapeutic targets. However, clinical studies increasingly suggest that asthma is heterogeneous.
Related JoVE Video
Differential enzymatic activity of common haplotypic versions of the human acidic Mammalian chitinase protein.
J. Biol. Chem.
PUBLISHED: 05-12-2009
Show Abstract
Hide Abstract
Mouse models have shown the importance of acidic mammalian chitinase activity in settings of chitin exposure and allergic inflammation. However, little is known regarding genetic regulation of AMCase enzymatic activity in human allergic diseases. Resequencing the AMCase gene exons we identified 8 non-synonymous single nucleotide polymorphisms including three novel variants (A290G, G296A, G339T) near the gene area coding for the enzyme active site, all in linkage disequilibrium. AMCase protein isoforms, encoded by two gene-wide haplotypes, and differentiated by these three single nucleotide polymorphisms, were recombinantly expressed and purified. Biochemical analysis revealed the isoform encoded by the variant haplotype displayed a distinct pH profile exhibiting greater retention of chitinase activity at acidic and basic pH values. Determination of absolute kinetic activity found the variant isoform encoded by the variant haplotype was 4-, 2.5-, and 10-fold more active than the wild type AMCase isoform at pH 2.2, 4.6, and 7.0, respectively. Modeling of the AMCase isoforms revealed positional changes in amino acids critical for both pH specificity and substrate binding. Genetic association analyses of AMCase haplotypes for asthma revealed significant protective associations between the variant haplotype in several asthma cohorts. The structural, kinetic, and genetic data regarding the AMCase isoforms are consistent with the Th2-priming effects of environmental chitin and a role for AMCase in negatively regulating this stimulus.
Related JoVE Video
Ex vivo sputum analysis reveals impairment of protease-dependent mucus degradation by plasma proteins in acute asthma.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 05-07-2009
Show Abstract
Hide Abstract
Airway mucus plugs, composed of mucin glycoproteins mixed with plasma proteins, are an important cause of airway obstruction in acute severe asthma, and they are poorly treated with current therapies.
Related JoVE Video
Eosinophilic and neutrophilic inflammation in asthma: insights from clinical studies.
Proc Am Thorac Soc
PUBLISHED: 04-24-2009
Show Abstract
Hide Abstract
Cellular inflammation of the airways with eosinophils and neutrophils is a characteristic feature of asthma and is considered relevant to the pathogenesis of the disease. Studies of large numbers of subjects with well-characterized asthma in recent years has resulted in new insights about the clinical and pathologic correlates of eosinophilic and neutrophilic inflammation in asthma. For example, eosinophilic asthma is a distinct phenotype of asthma that is associated pathologically by thickening of the basement membrane zone and pharmacologically by corticosteroid responsiveness. In contrast, noneosinophilic asthma, a sizeable subgroup of asthma that includes patients with severe disease, is not characterized by thickening of the basement membrane zone, and it appears to be relatively corticosteroid resistant. Eosinophilic and neutrophilic asthma are not mutually exclusive subtypes of asthma. Rather, neutrophils accumulate in the airways in patients with asthma with more severe airflow obstruction, where eosinophils may also be present in excess. In addition, neutrophils are prominent in airway secretions during acute severe asthma exacerbations, where it is possible that they have roles in both the initiation and resolution of attacks. These insights about the relationships between cellular inflammation and disease phenotypes of asthma support the concept that different subgroups of patients with asthma, despite clinically similar features, can be defined by specific cellular and molecular markers. The promise now is that these markers will ultimately guide personalized treatment programs.
Related JoVE Video
An integrated nano-scale approach to profile miRNAs in limited clinical samples.
Am J Clin Exp Immunol
Show Abstract
Hide Abstract
Profiling miRNA expression in cells that directly contribute to human disease pathogenesis is likely to aid the discovery of novel drug targets and biomarkers. However, tissue heterogeneity and the limited amount of human diseased tissue available for research purposes present fundamental difficulties that often constrain the scope and potential of such studies. We established a flow cytometry-based method for isolating pure populations of pathogenic T cells from bronchial biopsy samples of asthma patients, and optimized a high-throughput nano-scale qRT-PCR method capable of accurately measuring 96 miRNAs in as little as 100 cells. Comparison of circulating and airway T cells from healthy and asthmatic subjects revealed asthma-associated and tissue-specific miRNA expression patterns. These results establish the feasibility and utility of investigating miRNA expression in small populations of cells involved in asthma pathogenesis, and set a precedent for application of our nano-scale approach in other human diseases. The microarray data from this study (Figure 7) has been submitted to the NCBI Gene Expression Omnibus (GEO; http://ncbi.nlm.nih.gov/geo) under accession no. GSE31030.
Related JoVE Video
Calcium-activated chloride channel TMEM16A modulates mucin secretion and airway smooth muscle contraction.
Proc. Natl. Acad. Sci. U.S.A.
Show Abstract
Hide Abstract
Mucous cell hyperplasia and airway smooth muscle (ASM) hyperresponsiveness are hallmark features of inflammatory airway diseases, including asthma. Here, we show that the recently identified calcium-activated chloride channel (CaCC) TMEM16A is expressed in the adult airway surface epithelium and ASM. The epithelial expression is increased in asthmatics, particularly in secretory cells. Based on this and the proposed functions of CaCC, we hypothesized that TMEM16A inhibitors would negatively regulate both epithelial mucin secretion and ASM contraction. We used a high-throughput screen to identify small-molecule blockers of TMEM16A-CaCC channels. We show that inhibition of TMEM16A-CaCC significantly impairs mucus secretion in primary human airway surface epithelial cells. Furthermore, inhibition of TMEM16A-CaCC significantly reduces mouse and human ASM contraction in response to cholinergic agonists. TMEM16A-CaCC blockers, including those identified here, may positively impact multiple causes of asthma symptoms.
Related JoVE Video
Periostin is a systemic biomarker of eosinophilic airway inflammation in asthmatic patients.
J. Allergy Clin. Immunol.
Show Abstract
Hide Abstract
Eosinophilic airway inflammation is heterogeneous in asthmatic patients. We recently described a distinct subtype of asthma defined by the expression of genes inducible by T(H)2 cytokines in bronchial epithelium. This gene signature, which includes periostin, is present in approximately half of asthmatic patients and correlates with eosinophilic airway inflammation. However, identification of this subtype depends on invasive airway sampling, and hence noninvasive biomarkers of this phenotype are desirable.
Related JoVE Video
Network analysis identifies a putative role for the PPAR and type 1 interferon pathways in glucocorticoid actions in asthmatics.
BMC Med Genomics
Show Abstract
Hide Abstract
Asthma is a chronic inflammatory airway disease influenced by genetic and environmental factors that affects ~300 million people worldwide, leading to ~250,000 deaths annually. Glucocorticoids (GCs) are well-known therapeutics that are used extensively to suppress airway inflammation in asthmatics. The airway epithelium plays an important role in the initiation and modulation of the inflammatory response. While the role of GCs in disease management is well understood, few studies have examined the holistic effects on the airway epithelium.
Related JoVE Video
Cluster analysis of obesity and asthma phenotypes.
PLoS ONE
Show Abstract
Hide Abstract
Asthma is a heterogeneous disease with variability among patients in characteristics such as lung function, symptoms and control, body weight, markers of inflammation, and responsiveness to glucocorticoids (GC). Cluster analysis of well-characterized cohorts can advance understanding of disease subgroups in asthma and point to unsuspected disease mechanisms. We utilized an hypothesis-free cluster analytical approach to define the contribution of obesity and related variables to asthma phenotype.
Related JoVE Video
Asthma outcomes: biomarkers.
J. Allergy Clin. Immunol.
Show Abstract
Hide Abstract
Measurement of biomarkers has been incorporated within clinical research studies of asthma to characterize the population and associate the disease with environmental and therapeutic effects.
Related JoVE Video
A large subgroup of mild-to-moderate asthma is persistently noneosinophilic.
Am. J. Respir. Crit. Care Med.
Show Abstract
Hide Abstract
Airway eosinophilia is typical of asthma, and many controller treatments target eosinophilic disease. Asthma is clinically heterogeneous, however, and a subgroup of people with asthma do not have airway eosinophilia. The size of this subgroup is uncertain because prior studies have not examined repeated measures of sputum cytology to determine when people with asthma have intermittent versus persistent sputum eosinophila and when they are persistently noneosinophilic.
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.