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.

B cell receptor expression level determines the fate of developing B lymphocytes: receptor editing versus selection.

Abstract: During B lymphocyte development, antibody genes are assembled by DNA recombination. Successful cell surface expression of IgM promotes developmental progression. However, when antigen receptors bind autoantigen, development is blocked and ongoing antibody gene recombination occurs, which often alters antibody specificity in a process called receptor editing. We demonstrate here a significant role of developmental block and receptor editing in B cell receptor quality control. During development a functional, non-self-reactive receptor undergoes receptor editing if its expression is below a certain threshold. Doubling the receptor gene dose promotes development in the absence of autoantigen, but allows editing when autoantigen is present. Thus, both underexpressed and harmful B cell receptors can undergo correction by receptor editing.

Sleep Problems in Primary Care: A North Carolina Family Practice Research Network (NC-FP-RN) Study

Abstract: Background: The prevalence and nature of sleep disorders in primary care has not been widely studied. As part of a survey conducted in 5 family practice offices in North Carolina, we screened adult patients for sleep syndromes and sought to ascertain which demographic status and health status were associated with these disorders. Methods: We approached 2963 consecutive adults who presented for office visits to the 5 study practices. The 4-page study questionnaire, which was available in English and Spanish, included items on insomnia, excessive daytime sleepiness, obstructive sleep apnea syndrome, and restless legs syndrome. Analyses evaluated the relationship between sleep syndromes and demographic factors, health status, and disability. Results: We enrolled 1935 patients (65.3% response rate). More than half reported excessive daytime sleepiness, one third had insomnia, more than 25% had symptoms of restless legs syndrome, and 13% to 33% reported obstructive sleep apnea syndrome symptoms. Participants who rated their health as poor reported significantly higher rates of all sleep disturbance items. Patients with hypertension, pain syndromes, and depression had a significantly increased risk for all sleep complaints. Patients who reported limited activity had a significant risk of restless legs syndrome. Conclusion: Sleep complaints are highly prevalent in primary care populations. Patients with the highest risk for sleep disturbance are those with pain, mental illness, limited activity, and overall “poor physical and mental health.” Because sleep disorders are associated with a significant health impact, positive responses to questions regarding sleep symptoms should prompt further diagnostic inquiry.

MK2 controls the level of negative feedback in the NF-κB pathway and is essential for vascular permeability and airway inflammation

Abstract: We demonstrate that mitogen-activated protein kinase–activated kinase-2 (MK2) is essential for localized Th2-type inflammation and development of experimental asthma. MK2 deficiency does not affect systemic Th2 immunity, but reduces endothelial permeability, as well as adhesion molecule and chemokine expression. NF-κB regulates transcription of adhesion molecules and chemokines. We show that MK2 and its substrate HSP27 are essential for sustained NF-κB activation. MK2 and HSP27 prevent nuclear retention of p38 by sequestering it in the cytosol. As a result, MK2 precludes excessive phosphorylation of MSK1. By reducing MSK1 activity, MK2 prevents p65 NF-κB hyperphosphorylation and excessive IκBα transcription. IκBα mediates nuclear export of p65. By reducing IκBα level, MK2 prevents premature export of NF-κB from the nucleus. Thus, the MK2–HSP27 pathway regulates the NF-κB transcriptional output by switching the activation pattern from high level, but short lasting, to moderate-level, but long lasting. This pattern of activation is essential for many NF-κB–regulated genes and development of inflammation. Thus, the MK2–HSP27 pathway is an excellent target for therapeutic control of localized inflammatory diseases.

Genome-wide search for sarcoidosis susceptibility genes in African Americans.

Abstract: Sarcoidosis, a systemic granulomatous disease of unknown etiology, likely results from an environmental insult in a genetically susceptible host. In the US, African Americans are more commonly affected with sarcoidosis and suffer greater morbidity than Caucasians. We searched for sarcoidosis susceptibility loci by conducting a genome-wide, sib pair multipoint linkage analysis in 229 African-American families ascertained through two or more sibs with a history of sarcoidosis. Using the Haseman–Elston regression technique, linkage peaks with P-values less than 0.05 were identified on chromosomes 1p22, 2p25, 5p15-13, 5q11, 5q35, 9q34, 11p15 and 20q13 with the most prominent peak at D5S2500 on chromosome 5q11 (P=0.0005). We found agreement for linkage with the previously reported genome scan of a German population at chromosomes 1p and 9q. Based on the multiple suggestive regions for linkage found in our study population, it is likely that more than one gene influences sarcoidosis susceptibility in African Americans. Fine mapping of the linked regions, particularly on chromosome 5q, should help to refine linkage signals and guide further sarcoidosis candidate gene investigation.

Clinical and radiologic manifestations of hypersensitivity pneumonitis.

Abstract: Hypersensitivity pneumonitis (HP) is an inflammatory interstitial lung disease caused by recurring exposure to a variety of occupational and environmental antigens. It features widely variable clinical, radiologic, and histopathologic findings. Because the clinical findings of HP mimic multiple other diseases, a high degree of clinical suspicion and a thorough occupational and environmental history are essential for accurate diagnosis. There is no single pathognomonic feature for HP; rather, diagnosis relies on a constellation of clinical, radiologic, and pathologic findings. The radiologic manifestations, particularly the high-resolution computed tomography (HRCT) pattern, provide important clues and frequently point clinicians towards the correct diagnosis. The HRCT findings in HP may include ground-glass opacification, centrilobular nodules, air trapping (mosaic pattern), fibrosis, emphysema, or more frequently a combination of these. The combination of a mosaic pattern with ground-glass opacification and centrilobular nodules is particularly suggestive of the diagnosis. The best long-term prognosis is achieved with early diagnosis and removal from exposure.