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Institution

National Jewish Health

HealthcareDenver, 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: 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.
Topics: T cell, Asthma, Population, Lung, Antigen


Papers
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Journal Article
TL;DR: Data provide new insight into the nature of one important genetic contribution to murine lupus and suggest that Nba2 may act as an immune response gene that influences Ag-driven B cell responses to self and possibly to exogenous Ags.
Abstract: An NZB locus on distal chromosome 1 has been linked to murine lupus nephritis in backcross analyses of New Zealand mice. This locus, designated Nba2 for New Zealand Black autoimmunity 2, was found to colocalize in both (NZB x SM/J)F1 x NZW and (B6.H2z x NZB)F1 x NZB backcrosses, and was most likely situated between 92 and 97 cM from the centromere. This region of mouse chromosome 1 encodes several candidate genes, including the low affinity Fc gamma receptor genes. Both backcrosses were examined by interval mapping for quantitative trait loci linked with autoantibody and total Ig production. Nba2 was linked with elevated serum levels of multiple autoantibodies, including a variety of antinuclear Abs (anti-dsDNA, anti-chromatin and anti-histone) and autoantibodies to gp70, in both backcrosses. Nba2 was also linked (or showed a trend for linkage) with hypergammaglobulinemia and IgG1, IgG2a, and/or IgG3 levels in each backcross. In the (B6.H2z x NZB)F1 x NZB backcross, MHC was an additional genetic contribution that interacted with Nba2 in the production of autoantibodies and the development of nephritis. Together, these data provide new insight into the nature of one important genetic contribution to murine lupus and suggest that Nba2 may act as an immune response gene that influences Ag-driven B cell responses to self and possibly to exogenous Ags.

131 citations

Journal ArticleDOI
15 Sep 2008
TL;DR: This article summarizes the current data for each cell type and highlights areas that would benefit from further investigation.
Abstract: Our current alveolar paradigm includes three highly specialized cell populations. Alveolar type I cells are flat, elongated cells that presumably enable gas exchange. Alveolar type II cells are small, cuboidal cells with metabolic, secretory, progenitor, and immunologic functions. Alveolar fibroblasts secrete extracellular matrix proteins that support alveolar structure. These cells work together to facilitate respiration. Many years of high-quality research have defined our understanding of alveolar biology. However, there is much to be determined about the factors controlling cellular phenotypes and crosstalk. Moreover, specific questions remain regarding origin, repopulation, and previously unrecognized functions of each cell. This article summarizes the current data for each cell type and highlights areas that would benefit from further investigation.

130 citations

Journal Article
TL;DR: Data suggest that reorganization of filamentous-actin induced by LPS leads to cell stiffening and retention in capillary-sized pores, and may be important in the sequestration of neutrophils in pulmonary capillaries noted in endotoxemia.
Abstract: Intravascular LPS rapidly induces neutrophil sequestration in pulmonary capillaries by mechanisms that, although currently unknown, must take into account the size difference between the neutrophil and capillary diameter. To determine whether LPS alters neutrophil stiffness, and hence the ability of neutrophils to traverse capillaries, neutrophil passage through pulmonary capillaries was modeled by passage through filters with 6.5-microns pores. LPS increased retention in the pores in a concentration-dependent fashion that required the presence of heat-inactivated platelet-poor plasma, and was evident as early as 10 min after stimulation. The effect of LPS on the structural properties of the neutrophil was then studied. LPS induced f-actin reorganization in neutrophils in the presence of plasma. Disruption of actin organization and assembly with cytochalasin D completely inhibited early LPS-induced retention and attenuated retention at later timepoints, indicating that LPS-stimulated retention depends on filament organization. LPS-induced actin assembly and retention were abrogated by an antibody directed against CD14, a putative LPS receptor. CD18-dependent adherence of neutrophils contributed significantly to retention only at later timepoints with no significant contribution to retention at 20 min as determined by inhibition of adherence with the mAb 60.3. Morphometric assessment of neutrophil accumulation in the lungs of rabbits given 1 microgram LPS showed a marked increase in apparent neutrophil number, which was unaltered by antibodies to CD18, suggesting that mechanisms other than adhesion may account for accumulation in vivo. Direct measurements showed that neutrophil stiffness increased with exposure to LPS in a fashion similar to LPS-induced retention and actin organization. Pretreatment of neutrophils with cytochalasin D attenuated the increased stiffness. These data suggest that reorganization of filamentous-actin induced by LPS leads to cell stiffening and retention in capillary-sized pores. Although the organization of f-actin continues to be important in retention at later time points, adherence of cells also contributes significantly to cell retention. The changes in mechanical properties of the neutrophil may be important in the sequestration of neutrophils in pulmonary capillaries noted in endotoxemia.

129 citations

Journal ArticleDOI
TL;DR: The study does not support the use of methotrexate in the treatment of severe asthma, and no significant benefit of metotrexate on asthma control could be shown.
Abstract: Objective To determine the effect of low-dose methotrexate in asthmatic patients on steroid use, asthma symptom scores, pulmonary function, airway reactivity, blood cellular components, and immunoglobulin E levels. Design A randomized, double-blind, parallel, placebo-controlled, 13-week clinical trial with follow-up of patients in an open trial of methotrexate at the conclusion of the double-blind study. Setting An asthma care outpatient clinic. Patients From February 1988 to March 1990, 19 patients with severe, steroid-dependent asthma were enrolled in the study. Two of these patients were excluded from analysis. Interventions Patients were administered methotrexate or placebo intramuscularly, to assure complete absorption, once weekly during the 13-week study. Results Patients on methotrexate and placebo both significantly decreased their steroid dose by 39.6% (95% CI, 25.1% to 54.1%, P = 0.001) and 40.2% (CI, 17.9% to 67.4%, P = 0.003), respectively. Pulmonary function did not differ significantly between the methotrexate and placebo groups. In addition, airway reactivity and symptom scores were unchanged on methotrexate or placebo. No significant toxicities were seen during the course of the 13-week blinded study, but one patient on methotrexate and prednisone in the follow-up period developed Pneumocystis carinii pneumonia and died. Despite continuing methotrexate for up to 1 year, and increasing methotrexate to 30 mg weekly, no significant benefit of methotrexate on asthma control could be shown. Conclusion Our study does not support the use of methotrexate in the treatment of severe asthma.

129 citations

Journal ArticleDOI
07 Oct 1988-Cell
TL;DR: It is concluded that activation of PKC is not essential for the growth-promoting action of interleukin-2, and the abnormality may be at the level of message splicing or stability.

128 citations


Authors

Showing all 901 results

NameH-indexPapersCitations
Thomas V. Colby12650160130
John W. Kappler12246457541
Donald Y.M. Leung12161450873
Philippa Marrack12041654345
Jeffrey M. Drazen11769352493
Peter M. Henson11236954246
David A. Schwartz11095853533
David A. Lynch10871459678
Norman R. Pace10129750252
Kevin K. Brown10038747219
Stanley J. Szefler9955437481
Erwin W. Gelfand9967536059
James D. Crapo9847337510
Yang Xin Fu9739033526
Stephen D. Miller9443330499
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
20233
202214
202113
202017
201917
201841