National Jewish Health

About: National Jewish Health is a healthcare organization based out in Denver, Colorado, United States. It is known for research contribution in the topics: T cell & Asthma. The organization has 883 authors who have published 833 publications receiving 79201 citations. The organization is also known as: National Jewish Medical and Research Center.

Helicity and Vorticity of Pulmonary Arterial Flow in Patients With Pulmonary Hypertension: Quantitative Analysis of Flow Formations.

Abstract: BackgroundQualitative and quantitative flow hemodynamic indexes have been shown to reflect right ventricular (RV) afterload and function in pulmonary hypertension (PH). We aimed to quantify flow he...

Biological potency of German cockroach allergen extracts determined in an inner city population.

Abstract: Summary Background Cockroach allergy is an important cause of inner city asthma. To perform valid studies on the diagnosis and treatment of cockroach allergy, biological potencies of test extracts need to be established, and a surrogate in vitro test for biological potency should be chosen. Methods Sixty-two cockroach-allergic adult subjects were recruited for quantitative skin testing with three commercial German cockroach extracts. The intradermal D50 values were determined using linear interpolation, and the biologic potencies were determined from D50 data. The extracts were also analysed for relative potency, using a competition ELISA, and for specific allergen content, using a two-site ELISA. Results Estimates of each extract's D50 were analysable in 48–55 subjects, with D50s between 10.3 and 11.8. All three extracts were bioequivalent using pre-set criteria. The biological potencies of the extracts were 1738–8570 bioequivalent allergy units (BAU)/mL (geometric mean=3300), and these relative potencies were similar to those estimated by competition ELISA and specific allergen content. IgE against cockroach allergens were detected in sera from 34 subjects with analysable D50s, and 17 subjects had IgE directed against specific cockroach allergens. Although the presence of anti-Bla g 5 correlated with the subjects' skin test responses for 2/3 extracts, no single allergen was immunodominant. Antibody responses among the subjects were heterogeneous. Conclusions Although commercial cockroach extracts are relatively low in potency, immunotherapeutic doses should be achievable. Biological potency may be estimated using D50 testing, a combination of specific allergen determinations, or by an overall potency assay such as the competition ELISA. Capsule Summary The biological potency of three German cockroach allergen extracts, determined in an inner city population, was 1738–8570 BAU/mL. No one allergen was immunodominant, and surrogate in vitro testing methods were examined.

Timing of administration of anti-VLA-4 differentiates airway hyperresponsiveness in the central and peripheral airways in mice.

Abstract: The development of airway hyperresponsiveness (AHR) is correlated with the infiltration into the lungs of activated eosinophils and T lymphocytes. In large part, influx of eosinophils into the lung is dependent on very late activating antigen-4 (VLA-4) expression. However, the kinetics of eosinophil recruitment and the development of AHR are not fully delineated. Airway function was monitored by changes in lung resistance (RL) and dynamic compliance (Cdyn) to methacholine (MCh) inhalation after anti-VLA-4. After ovalbumin (OVA) sensitization and airway challenge of BALB/c mice, AHR increased as did the number of lung inflammatory cells. Administration of anti-VLA-4 to sensitized mice 2 h before the first (of three) OVA airway challenges significantly prevented changes in RL. Moreover, injection of the antibody from 2 h before the first challenge to 42 h after the last challenge significantly prevented the increases in RL, as well as eosinophil and lymphocyte numbers in the bronchoalveolar lavage fluid (BALF); interleukin-5 (IL-5) and leukotriene concentrations in BALF were also significantly inhibited. Interestingly, treatment with anti-VLA-4 only prevented changes in Cdyn and goblet cell hyperplasia when administered 2 h before the first challenge. These studies demonstrate that the timing of anti-VLA-4 administration can selectively affect pathologic processes that contribute to altered airway function in the central and peripheral airways after allergen challenge.

Cloning of a novel signaling molecule, AMSH-2, that potentiates transforming growth factor β signaling

Abstract: Transforming growth factor-βs (TGF-βs), bone morphogenetic proteins (BMPs) and activins are important regulators of developmental cell growth and differentiation Signaling by these factors is mediated chiefly by the Smad family of latent transcription factors There are a large number of uncharacterized cDNA clones that code for novel proteins with homology to known signaling molecules We have identified a novel molecule from the HUGE database that is related to a previously known molecule, AMSH (a ssociated m olecule with the SH 3 domain of STAM), an adapter shown to be involved in BMP signaling Both of these molecules contain a coiled-coil domain located within the amino-terminus region and a JAB (Domain in J un kinase a ctivation domain b inding protein and proteasomal subunits) domain at the carboxy-terminus We show that this novel molecule, which we have designated AMSH-2, is widely expressed and its overexpression potentiates activation of TGF-β-dependent promoters Coimmunoprecipitation studies indicated that Smad7 and Smad2, but not Smad3 or 4, interact with AMSH-2 We show that overexpression of AMSH-2 decreases the inhibitory effect of Smad7 on TGF-β signaling Finally, we demonstrate that knocking down AMSH-2 expression by RNA interference decreases the activation of 3TP-lux reporter in response to TGF-β This report implicates AMSH and AMSH-2 as a novel family of molecules that positively regulate the TGF-β signaling pathway Our results suggest that this effect could be partially explained by AMSH-2 mediated decrease of the action of Smad7 on TGF-β signaling pathway

Recognition of self and altered self by T cells in autoimmunity and allergy.

Abstract: T cell recognition of foreign peptide antigen and tolerance to self peptides is key to the proper function of the immune system. Usually, in the thymus T cells that recognize self MHC + self peptides are deleted and those with the potential to recognize self MHC + foreign peptides are selected to mature. However there are exceptions to these rules. Autoimmunity and allergy are two of the most common immune diseases that can be related to recognition of self. Many genes work together to lead to autoimmunity. Of those, particular MHC alleles are the most strongly associated, reflecting the key importance of MHC presentation of self peptides in autoimmunity. T cells specific for combinations of self MHC and self peptides may escape thymus deletion, and thus be able to drive autoimmunity, for several reasons: the relevant self peptide may be presented at low abundance in the thymus but at high level in particular peripheral tissues; the relevant self peptide may bind to MHC in an unusual register, not present in the thymus but apparent elsewhere; finally the relevant self peptide may be post translationally modified in a tissue specific fashion. In some types of allergy, the peptide + MHC combination may also be fully derived from self. However the combination in question may be modified by the presence of other ligands, such as small drug molecules or metal ions. Thus these types of allergies may act like the post translationally modified peptides involved some types of autoimmunity.