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: Asthma & T cell. 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.

The TAO of MEKK.

Abstract: Cloning and characterization of MEKK1 in 1993 revealed that in addition to Raf there were other pathways activated by extracellular stimuli that were responsible for ERK activation. Since then, three additional MEKK family members have been cloned adding even further diversity to the regulation of MAPK pathways. The MEKK family members are regulated by a diverse array of extracellular stimuli ranging from growth factors to DNA damaging stimuli and so are important for the cell to sense exposure to various environmental stimuli. One important aspect of MEKK biology is that they can potentially serve in more than one pathway. Regulation of MEKK family members often involves LMWG proteins, phosphorylation and subcellular localization. With regard to at least MEKK1, serine/threonine kinases such as NIK, GLK and HPK1 appear also to be important for regulation. Of the MEKK family members, the biological role of MEKK1 is best characterized and studies have shown that MEKK1 is important in mediating survival vs. apoptosis, possibly via its ability to regulate transcription factors, the expression of death receptors and their ligands. The biological roles of MEKK2, 3 and 4 are under investigation and undoubtedly homologous deletion of these MEKK family members will be invaluable at determining the biological functions of these MEKKs. At present, the MEKK family members are characterized as localized sensors that control cell responses at the level of gene expression, metabolism and the cytoskeleton

Differential susceptibilities to chronic beryllium disease contributed by different Glu69 HLA-DPB1 and -DPA1 alleles

Abstract: Chronic beryllium disease (CBD) is associated with the allelic substitution of a Glu69 in the HLA-DPB1 gene. Although up to 97% of CBD patients may have the Glu69 marker, about 30-45% of beryllium-exposed, unaffected individuals carry the same marker. Because CBD occurs in only 1-6% of exposed workers, the presence of Glu69 does not appear to be the sole genetic factor underlying the disease development. Using two rounds of direct automated DNA sequencing to precisely assign HLA-DPB1 haplotypes, we have discovered highly significant Glu69-containing allele frequency differences between the CBD patients and a beryllium-exposed, nondiseased control group. Individuals with DPB1 Glu69 in both alleles were almost exclusively found in the CBD group (6/20) vs the control group (1/75). Whereas most Glu69 carriers from the control group had a DPB1 allele *0201 (68%), most Glu69 carriers from the CBD group had a non-*0201 DPB1 Glu69-carrying allele (84%). The DPB1 allele *0201 was almost exclusively (29/30) associated with DPA1 *01 alleles, while the non-*0201 Glu69-containing DPB1 alleles were closely associated with DPA1 *02 alleles (26/29). Relatively rare Glu69-containing alleles *1701, *0901, and *1001 had extremely high frequencies in the CBD group (50%), as compared with the control group (6.7%). Therefore, the most common Glu69-containing DPB1 allele, *0201, does not seem to be a major disease allele. The results suggest that it is not the mere presence of Glu69, per se, but specific Glu69-containing alleles and their copy number (homozygous or heterozygous) that confer the greatest susceptibility to CBD in exposed individuals.

Relationship of infant feeding to recurrent wheezing at age 6 years.

Abstract: Objectives: To investigate the relationship of infant feeding to recurrent wheezing at age 6 years and to assess whether this relationship is altered by a history of wheezing lower respiratory tract illnesses. Design: Prospective, longitudinal study of healthy infants followed up from birth to 6 years of age. Setting: Nonselected health maintenance organization population in Tucson, Arizona. Participants: There were 1246 healthy infants enrolled at birth, 988 of whom had data on both infant feeding and wheezing at age 6 years. Interventions: None. Main Outcome Measures: Recurrent wheeze (four or more episodes in the past year) was assessed by a questionnaire that was completed by parents when the children were 6 years old. Children were classified by atopic status on the basis of skin prick tests. Results: Breast-feeding information was collected prospectively, and lower respiratory tract illnesses in the first 3 years of life were diagnosed by the pediatrician. Being breast-fed was associated with lower rates of recurrent wheeze at age 6 years (3.1% vs 9.7%, P Conclusions: Recurrent wheeze at age 6 years is less common among nonatopic children who were breast-fed as infants. This effect is independent of whether the child wheezed with a lower respiratory tract illness in the first 6 months of life. (Arch Pediatr Adolesc Med. 1995;149:758-763)

Exhaled nitric oxide identifies the persistent eosinophilic phenotype in severe refractory asthma

Abstract: Background The fractional concentration of exhaled nitric oxide (FE NO ) is increased in asthma, correlates with eosinophilic inflammation, and decreases after steroid therapy. Objective We sought to examine whether persistent eosinophilia would be accompanied by an increased FE NO level despite steroid therapy in patients with severe refractory asthma (SRA) as manifestations of steroid resistance. Methods Subjects with SRA, subjects with mild-moderate asthma, and healthy control subjects had FE NO measured, followed by endobronchial biopsy and bronchoalveolar lavage. Tissue and bronchoalveolar lavage inflammatory cells were assessed for all subjects, and eosinophil status (EOS + /EOS − ) was determined for subjects with SRA. Results Twenty-four subjects with SRA, 15 subjects with moderate-mild asthma, and 17 healthy control subjects were studied. Subjects with EOS + SRA had significantly higher median FE NO levels compared with levels in subjects with EOS − SRA ( P = .0084) and all other groups. In subjects with SRA, FE NO levels correlated with tissue eosinophils ( r s = 0.54, P = .007), lymphocytes ( r s = 0.40, P = .003), and mast cells ( r s = 0.44, P = .05). FE NO levels of greater than 72.9 ppb were associated with a sensitivity of 0.56 and a specificity of 1.0 for EOS + status in subjects with SRA. Conclusion FE NO measurement identified the subgroup of subjects with SRA with persistent eosinophilia despite steroid therapy. Further studies are needed on the use of FE NO to monitor response to therapy over time in subjects with SRA.

Connective Tissue Disease-associated Interstitial Lung Diseases (CTD-ILD) — Report from OMERACT CTD-ILD Working Group

Abstract: Objective Interstitial lung disease (ILD) is common in connective tissue disease (CTD) and is the leading cause of mortality. Investigators have used certain outcome measures in randomized controlled trials (RCT) in CTD-ILD, but the lack of a systematically developed, CTD-specific index that captures all measures relevant and meaningful to patients with CTD-ILD has left a large and conspicuous gap in CTD-ILD research. Methods The CTD-ILD working group, under the aegis of the Outcome Measures in Rheumatology (OMERACT) initiative, has completed a consensus group exercise to reach harmony on core domains and items for inclusion in RCT in CTD-ILD. During the OMERACT 12 meeting, consensus was sought on domains and core items for inclusion in RCT. In addition, consensus was pursued on a definition of response in RCT. Consensus was defined as ≥ 75% agreement among the participants. Results OMERACT 12 participants endorsed the domains with minimal modifications. Clinically meaningful progression for CTD-ILD was proposed as ≥ 10% relative decline in forced vital capacity (FVC) or ≥ 5% to Conclusion There is consensus on domains for inclusion in RCT in CTD-ILD and on a definition of clinically meaningful progression. Data-driven approaches to validate these results in different cohorts and RCT are needed.