Alpha-1-Antitrypsin Enhances Primary Human Macrophage Immunity Against Non-tuberculous Mycobacteria.

The association between non-tuberculous mycobacterial lung disease and alpha-1-antitrypsin (AAT) deficiency is likely due, in part, to underlying emphysema or bronchiectasis. But there is increasing evidence that AAT itself enhances host immunity against microbial pathogens and thus deficiency could compromise host protection. The goal of this project is to determine if AAT could augment macrophage activity against non-tuberculous mycobacteria.

A comparison of specific IgE and skin prick test results to common environmental allergens using the HYTEC™ 288.

Although skin-prick testing (SPT) is commonly used by allergists in the evaluation of allergy, in-vitro testing for specific IgE (sIgE) is an attractive alternate because it can be performed remotely and is of utility when SPT is contraindicated, as in patients on anti-histamines, or with dermatitis or severe eczema. It is, however, necessary to determine the extent of correlation between the in-vitro and in-vivo methods. In this study, we examined the qualitative concordance between SPT and sIgE as measured on the HYTEC™288 platform for 10 commonly encountered inhalant allergens in 232 subjects, and analysed the performance characteristics for the HYTEC™288.

Pioglitazone restores phagocyte mitochondrial oxidants and bactericidal capacity in chronic granulomatous disease.

Background: Deficient production of reactive oxygen species (ROS) by the phagocyte nicotinamide adenine dinucleotide (NADPH) oxidase in patients with chronic granulomatous disease (CGD) results in susceptibility to certain pathogens secondary to impaired oxidative killing and mobilization of other phagocyte defenses. Peroxisome proliferator-activated receptor (PPAR) γ agonists, including pioglitazone, approved for type 2 diabetes therapy alter cellular metabolism and can heighten ROS production. It was hypothesized that pioglitazone treatment of gp91(phox-/-) mice, a murine model of human CGD, would enhance phagocyte oxidant production and killing of Staphylococcus aureus, a significant pathogen in patients with this disorder.

IgG antibodies produced during subcutaneous allergen immunotherapy mediate inhibition of basophil activation via a mechanism involving both FcgammaRIIA and FcgammaRIIB.

The majority of human subjects who receive subcutaneous allergen immunotherapy (IT) develop decreased sensitivity to their allergens. Multiple factors may explain the efficacy of IT, some evidence support a role for allergen specific IgG antibodies. There is controversy whether such antibodies act by blocking allergen binding to IgE or initiation of active inhibitory signaling through low affinity IgG receptors (FcgammaRIIB) on mast cells and basophils.

Leukotriene-E4 in human urine: Comparison of on-line purification and liquid chromatography-tandem mass spectrometry to affinity purification followed by enzyme immunoassay.

A new analytical method suitable for high throughput measurements of LTE(4) in human urine is described. The methodology utilizes on-line enrichment and liquid chromatography/tandem mass spectrometry (LC/MS/MS). The novel LC/MS/MS method is rapid, linear from 5 to 500pg/ml in spiked urine samples of both healthy and asthmatic subjects and more accurate and precise than enzyme immunoassay (EIA) and previous LC/MS/MS methods.

Novel method for quantitative ANA measurement using near-infrared imaging.

Antinuclear antibodies (ANA) have been detected in patients with systemic rheumatic diseases and are used in the screening and/or diagnosis of autoimmunity in patients as well as mouse models of systemic autoimmunity. Indirect immunofluorescence (IIF) on HEp-2 cells is the gold standard for ANA screening. However, its usefulness is limited in diagnosis, prognosis and monitoring of disease activity due to the lack of standardization in performing the technique, subjectivity in interpreting the results and the fact that it is only semi-quantitative.

Response to sublingual immunotherapy with grass pollen extract: monotherapy versus combination in a multiallergen extract.

Background: To date, there have been no randomized, double-blind studies showing the effectiveness of sublingual immunotherapy with multiple allergens.

Objective: The purpose of this study was to examine whether the efficacy of sublingual immunotherapy (SLIT) with standardized timothy extract was reduced by combination with other allergen extracts.

Methods: A single-center, randomized, double-blind, placebo-controlled trial with SLIT was conducted.

Toll-like receptor 2 down-regulation in established mouse allergic lungs contributes to decreased mycoplasma clearance.

Rationale: Respiratory Mycoplasma pneumoniae (Mp) infection is involved in asthma pathobiology, but whether the established allergic airway inflammation compromises lung innate immunity and subsequently predisposes patients with asthma to Mp infection remains unknown.

Objectives: To test whether the established allergic airway inflammation compromises host innate immunity (e.g.

Interaction between cigarette smoke and mycoplasma infection: a murine model.

Cigarette smoke has a major impact on health issues worldwide. Although genetics certainly is a factor in the sensitivity to cigarette smoke, other lung environmental factors, such as infection, potentially could interact with cigarette smoke to induce inflammatory changes associated with various diseases. Four groups of BALB/c mice (smoking only; smoking + M.

Immunologic response to administration of standardized dog allergen extract at differing doses.

Background: The immunologic response to immunotherapy with dog extract is not well characterized.

Objective: The purpose of this study was to examine the immunologic response to 3 doses of dog extract expressed as their Can f 1 content.

Methods: Cluster immunotherapy was administered to 28 patients with dog allergy who were randomly assigned to 1 of 4 treatment arms: placebo or acetone-precipitated extract containing 0.

Chronic urticaria sera increase basophil CD203c expression.

Background: Approximately 40% of patients with chronic idiopathic urticaria have antibodies to the alpha subunit of the high-affinity IgE receptor. CD203c is a basophil activation marker known to be upregulated by cross-linking of the FcepsilonRIalpha receptor and may serve as a useful marker to identify these patients.

Objective: The primary objective was to assess the affect of sera from patients with chronic idiopathic urticaria on basophil CD203c expression.

Repeated respiratory Mycoplasma pneumoniae infections in mice: effect of host genetic background.

Respiratory Mycoplasma pneumoniae (Mp) infection is involved in several acute and chronic lung diseases including community-acquired pneumonia, asthma and chronic obstructive pulmonary disease. In the chronic disease process, recurrent respiratory bacterial infections could occur, which may result in varying degrees of symptoms and lung inflammation among patients. However, the lung immunologic differences of host responses to repeated bacterial (i.

Aerosolized sodium hypochlorite inhibits viability and allergenicity of mold on building materials.

Background: Commercial and residential buildings can become contaminated with molds, which may trigger allergic disorders. Mold remediation efforts may require costly replacement of mold-contaminated building materials. Disinfectants that contain dilute sodium hypochlorite can kill mold and are practical to use.

TLR2 signaling is critical for Mycoplasma pneumoniae-induced airway mucin expression.

Excessive airway mucin production contributes to airway obstruction in lung diseases such as asthma and chronic obstructive pulmonary disease. Respiratory infections, such as atypical bacterium Mycoplasma pneumoniae (Mp), have been proposed to worsen asthma and chronic obstructive pulmonary disease in part through increasing mucin. However, the molecular mechanisms involved in infection-induced airway mucin overexpression remain to be determined.

Mycoplasma pneumoniae infection increases airway collagen deposition in a murine model of allergic airway inflammation.

Mycoplasma pneumoniae (Mp) has been linked to chronic asthma. Airway remodeling (e.g.

Surfactant protein A binds Mycoplasma pneumoniae with high affinity and attenuates its growth by recognition of disaturated phosphatidylglycerols.

Surfactant Protein A (SP-A) is an abundant, multifunctional lectin that resides within the bronchoalveolar compartment of the lung and plays an important role in the innate immunity of the organ. Mycoplasma pneumoniae is a human pathogen that resides in the same compartment as SP-A, and we examined the interaction between the two. Preparations of human and rat SP-A recognized the mycoplasma with high affinity in the presence of Ca(2+), exhibiting apparent K(')(d) values in the nanomolar range.

Inhaled fluticasone propionate reduces concentration of Mycoplasma pneumoniae, inflammation, and bronchial hyperresponsiveness in lungs of mice.

Background: Mycoplasma pneumoniae has been shown to induce airway inflammation and bronchial hyperresponsiveness (BHR) in mice. Inhaled corticosteroids are the mainstay of asthma treatment, but their effects on M. pneumoniae and associated airway inflammation and BHR are poorly understood.

Lysophosphatidylcholines prime the NADPH oxidase and stimulate multiple neutrophil functions through changes in cytosolic calcium.

A mixture of lysophosphatidylcholines (lyso-PCs) are generated during blood storage and are etiologic in models of acute lung injury. We hypothesize that lyso-PCs stimulate polymorphonuclear neutrophils (PMNs) through Ca(2)(+)-dependent signaling. The lyso-PC mix (0.