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.

A strategy to determine HLA class II restriction broadly covering the DR, DP, and DQ allelic variants most commonly expressed in the general population

Abstract: Classic ways to determine MHC restriction involve inhibition with locus-specific antibodies and antigen presentation assays with panels of cell lines matched or mismatched at the various loci of interest. However, these determinations are often complicated by T cell epitope degeneracy and promiscuity. We describe a selection of 46 HLA DR, DQ, and DP specificities that provide worldwide population (phenotypic) coverage of almost 90 % at each locus, and account for over 66 % of all genes at each locus. This panel afforded coverage of at least four HLA class II alleles in over 95 % of the individuals in four study populations of diverse ethnicity from the USA and South Africa. Next, a panel of single HLA class II-transfected cell lines, corresponding to these 46 allelic variants was assembled, consisting of lines previously developed and 15 novel lines generated for the present study. The novel lines were validated by assessing their HLA class II expression by FACS analysis, the in vitro peptide binding activity of HLA molecules purified from the cell lines, and their antigen presenting capacity to T cell lines of known restriction. We also show that these HLA class II-transfected cell lines can be used to rapidly and unambiguously determine HLA restriction of epitopes recognized by an individual donor in a single experiment. This panel of lines will enable high throughput determination of HLA restriction, enabling better characterization of HLA class II-restricted T cell responses and facilitating the development of HLA tetrameric staining reagents.

Immunomodulatory Effects of Melatonin in Asthma

Abstract: Patients with nocturnal asthma demonstrate circadian variations in airway inflammation. We hypothesized that melatonin, a circadian rhythm regulator, modulates circadian inflammatory variations in asthma. The effect of melatonin stimulation on peripheral blood mononuclear cell cytokine production was evaluated at 4:00 P.M. and 4:00 A.M. in normal control subjects, patients with nocturnal asthma, and patients with non-nocturnal asthma. Melatonin was proinflammatory, causing significantly increased production of interleukin-1, interleukin-6, and tumor necrosis factor-alpha at 4:00 P.M. and 4:00 A.M. in all subject groups (range, 12.8 +/- 3.3 to 131.72 +/- 16.4%, p 0.05, both cases). At 4:00 P.M., the cytokine response to melatonin of patients with nocturnal asthma was greater than that of control subjects or patients with non-nocturnal asthma and did not change significantly at 4:00 A.M. At 4:00 P.M., the cytokine response of patients with non-nocturnal asthma was less than that of patients with nocturnal asthma and rose significantly at 4:00 A.M. (p = 0.0001, all comparisons). Melatonin is proinflammatory in both patients with asthma and healthy subjects. Patients with nocturnal asthma demonstrate the largest daytime cytokine response and cannot be further stimulated at 4:00 A.M., suggesting chronic overstimulation in vivo. These results suggest differential immunomodulatory effects of melatonin based on asthma clinical phenotype and may indicate an adverse effect of exogenous melatonin in asthma.

The role of the macrophage in apoptosis: hunter, gatherer, and regulator.

Abstract: Clearance of cellular corpses is a critical feature of apoptosis in vivo during development, tissue homeostasis, and resolution of inflammation. As the professional phagocytes of the body, macrophages play a key role in this process. By recognizing emerging signals using several different receptors, macrophages engulf apoptotic cells swiftly and efficiently. In addition, the binding of apoptotic cells profoundly down-regulates the ability of the macrophage to produce inflammatory mediators by inducing the release of antiinflammatory mediators. Finally, macrophages may actually induce cell death in specific cells during embryogenesis.Abnormalities of apoptotic cell clearance may contribute to the pathogenesis of chronic inflammatory diseases, including those of autoimmune etiology. It is also possible that certain malignant tumor cells co-opt the mechanisms for apoptotic cell clearance to avoid immune surveillance by subverting macrophage and dendritic cell responses.

Activation of p38mapk, MKK3, and MKK4 by TNF-alpha in mouse bone marrow-derived macrophages.

Abstract: TNF-alpha regulates the expression of many proinflammatory and profibrogenic gene products in macrophages, and hence plays a vital role in controlling the inflammatory response. We have shown previously that exposure of macrophages to TNF-alpha stimulates the activation of members of the mitogen-activated protein kinase (MAPK) family. In this study, we have investigated the mechanism of activation of the p38mapk by TNF-alpha in mouse bone marrow-derived macrophages. Exposure to TNF-alpha resulted in the activation of p38mapk, as measured by 1) the trans-phosphorylation of recombinant activating transcription factor-2 substrate by immunoprecipitated p38mapk and 2) specific tyrosine phosphorylation of immunoprecipitated p38mapk. In addition, selective ligation of the TNF-alpha receptor CD120a (p55) with human TNF-alpha was sufficient to induce p38mapk activation. Using an in vitro kinase assay with recombinant kinase-inactive p38mapk as substrate in the presence of [gamma-32P]ATP, the upstream kinases MKK3 (mitogen-activated protein kinase kinase 3) and MKK4 were found to be activated in response to TNF-alpha. These findings suggest that TNF-alpha transiently phosphorylates and activates the three members of the MAPK family, namely p42(mapk/erk2), p46 c-Jun amino-terminal kinase/stress-activated protein kinase (JNK/SAPK), and p38mapk following cross-linking of CD120a (p55), and that MKK3 and MKK4 are capable of phosphorylating p38mapk.

Reliability of Histologic Scoring for Lupus Nephritis: A Community-based Evaluation

Abstract: Objective: To determine the reliability of the National Institutes of Health (NIH)-modified semiquantitative histologic scoring system for lupus nephritis. Design: Cross-sectional study, repeated a...