Institution
National Jewish Health
Healthcare•Denver, Colorado, United States•
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.
Topics: Asthma, T cell, Population, Antigen, Lung
Papers published on a yearly basis
Papers
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TL;DR: It is suggested that IL-5 and eosinophils are essential for development of the LPR, but not EPR, in this model.
Abstract: Early-phase reactions (EPRs) and late-phase reactions (LPRs) are characteristic features of bronchial asthma, although the pathogenetic mechanisms responsible for each of the responses are not fully defined. A murine model of EPRs and LPRs was developed to investigate the role of IL-5 and eosinophils in development of both responses. After initial intraperitoneal sensitization and airway challenge to ovalbumin (OVA), mice were provoked by additional exposure to OVA. An EPR, characterized by a transient increase in airway responsiveness, was observed 5‐30 minutes after antigen provocation. This response was followed by an LPR that reached its maximum at 6 hours after challenge and was characterized by increased airway responsiveness and significant lung eosinophilia. The EPR was blocked by cromoglycate and albuterol, whereas the LPR was abolished by cromoglycate and hydrocortisone. Before provocation with allergen, administration of anti‐IL-5 antibody prevented the influx of eosinophils into the lung tissue and abolished the LPR but not EPR. These results suggest that IL-5 and eosinophils are essential for development of the LPR, but not EPR, in this model. J. Clin. Invest. 104:301‐308 (1999).
214 citations
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TL;DR: Heterogeneity in the regulation of HR expression on antigen-specific T cells may play a role in determining sites of involvement in tissue-directed allergic responses, as compared with nonatopics or allergic patients without skin involvement.
Abstract: The extravasation of T cells at sites of inflammation is critically dependent on the activity of homing receptors (HR) involved in endothelial cell recognition and binding Two such HR (the cutaneous lymphocyte antigen [CLA] and L-selectin) have been shown to be selectively involved in T cell migration to skin and peripheral lymph nodes, respectively This study was designed to assess the relationship between the organ specificity of an allergic reaction to food and the expression of HR on T cells activated in vitro by the relevant food allergen Peripheral blood mononuclear cells were isolated from seven milk allergic children with a history of eczema when exposed to milk All patients had a positive prick skin test and double-blind placebo-controlled food challenge to milk 10 children with either allergic eosinophilic gastroenteritis or milk-induced enterocolitis and 8 nonatopic adults served as controls Five-parameter flow cytometry using monoclonal antibodies was used for detection of the specific HR on freshly isolated T cells versus T cell blasts induced by a 6-d incubation with casein, as compared with Candida albicans After in vitro stimulation with casein, but not C albicans, patients with milk allergy and atopic dermatitis had a significantly greater percentage of CLA+ T cells (P < 001) than controls with milk-induced enterocolitis, allergic eosinophilic gastroenteritis, or nonatopic healthy controls In contrast, the percentage of L-selectin-expressing T cells did not differ significantly between these groups These data suggest that after casein stimulation allergic patients with milk-induced skin disease have an expanded population of CLA+ T cells, as compared with nonatopics or allergic patients without skin involvement We postulate that heterogeneity in the regulation of HR expression on antigen-specific T cells may play a role in determining sites of involvement in tissue-directed allergic responses
212 citations
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TL;DR: Overall, the results emphasize a frequent alteration in the human CD8 TCR repertoire, most likely related to an environmental exposure, in both healthy individuals and patients with rheumatoid arthritis.
Abstract: In the course of studying the circulating TCR repertoire in humans, we noted several individuals with an increase in the percentage of CD8+ T cells expressing a particular V region. In some cases, these CD8 expansions were dramatic, occupying over 40% of the total CD8 repertoire. Using a panel of mAbs to different TCR V regions, we found that over 30% of healthy adults (> 35 years of age) harbor an expansion that alters the peripheral blood CD8 TCR repertoire. A wide range of V regions were expressed by these expansions. Considering that the mAbs used cover only a portion of the V beta repertoire, the data suggest that over 70% of adults are likely to harbor such expansions. Junctional region sequencing showed that the CD8 subset expansions were clonal, and serial studies as long as 4 years showed that they persisted indefinitely. Expansions were not identified in the CD4 population. Discordant expression of one large V beta 6.7+ clone was found in one identical twin set, suggesting the possibility that an environmental exposure is involved in their generation and/or expansion. In one large family, we found five family members with a large CD8 subset expansion. Remarkably similar usage of J beta regions was noted, and two individuals demonstrated V beta 3-expressing clones with homologous CDR3 regions, differing by only one major substitution. The repertoire data from this family suggest that the T cell clones have arisen in response to a common Ag. Studies of patients with rheumatoid arthritis found a significantly increased frequency of circulating CD8 subset expansions that expressed a different V region repertoire compared with the healthy individuals studied. Overall, our results emphasize a frequent alteration in the human CD8 TCR repertoire, most likely related to an environmental exposure, in both healthy individuals and patients with rheumatoid arthritis. The presence of these expansions will be important to consider in any study of human TCR repertoire, and their implication for health and disease will be important to understand.
210 citations
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TL;DR: It is reported that psr-1, the Caenorhabditis elegans homolog of PSR, is important for cell corpse engulfment and suggests that PSR-1 is likely an upstream receptor for the signaling pathway containing CED-2, C ED-5,CED-10, and CED -12 proteins and plays an important role in recognizing phosphatidylserine during phagocytosis.
Abstract: During apoptosis, phosphatidylserine, which is normally restricted to the inner leaflet of the plasma membrane, is exposed on the surface of apoptotic cells and has been suggested to act as an “eat-me” signal to trigger phagocytosis. It is unclear how phagocytes recognize phosphatidylserine. Recently, a putative phosphatidylserine receptor (PSR) was identified and proposed to mediate recognition of phosphatidylserine and phagocytosis. We report that psr-1, the Caenorhabditis elegans homolog of PSR, is important for cell corpse engulfment. In vitro PSR-1 binds preferentially phosphatidylserine or cells with exposed phosphatidylserine. In C. elegans, PSR-1 acts in the same cell corpse engulfment pathway mediated by intracellular signaling molecules CED-2 (homologous to the human CrkII protein), CED-5 (DOCK180), CED-10 (Rac GTPase), and CED-12 (ELMO), possibly through direct interaction with CED-5 and CED-12. Our findings suggest that PSR-1 is likely an upstream receptor for the signaling pathway containing CED-2, CED-5, CED-10, and CED-12 proteins and plays an important role in recognizing phosphatidylserine during phagocytosis.
209 citations
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Harvard University1, Pennsylvania State University2, Wake Forest University3, University of California, San Francisco4, University of Texas Medical Branch5, Washington University in St. Louis6, University of Wisconsin-Madison7, Duke University8, National Jewish Health9, University of California, San Diego10
TL;DR: In asthma patients with B16 Arg/Arg and B16 Gly/Gly genotypes, combination treatment with salmeterol and inhaled corticosteroids improved airway function when compared with inhaled Corticosteroid therapy alone.
205 citations
Authors
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Name | H-index | Papers | Citations |
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Thomas V. Colby | 126 | 501 | 60130 |
John W. Kappler | 122 | 464 | 57541 |
Donald Y.M. Leung | 121 | 614 | 50873 |
Philippa Marrack | 120 | 416 | 54345 |
Jeffrey M. Drazen | 117 | 693 | 52493 |
Peter M. Henson | 112 | 369 | 54246 |
David A. Schwartz | 110 | 958 | 53533 |
David A. Lynch | 108 | 714 | 59678 |
Norman R. Pace | 101 | 297 | 50252 |
Kevin K. Brown | 100 | 387 | 47219 |
Stanley J. Szefler | 99 | 554 | 37481 |
Erwin W. Gelfand | 99 | 675 | 36059 |
James D. Crapo | 98 | 473 | 37510 |
Yang Xin Fu | 97 | 390 | 33526 |
Stephen D. Miller | 94 | 433 | 30499 |