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.

Distal lung dysfunction at night in nocturnal asthma.

Abstract: We have previously shown that patients with nocturnal worsening of asthma (nocturnal asthma) exhibit increased parenchymal inflammation at night. To evaluate the functional significance of this parenchymal inflammation, 10 subjects with nocturnal asthma (NA), four subjects with non-nocturnal asthma (NNA), and four normal control subjects underwent bronchoscopy with measurement of peripheral airways resistance (Rp) at 4:00 p.m. and at 4:00 a.m. Employing a wedged bronchoscope technique, Rp was measured. Flow was stopped, and the pressure reached after 10 s of decay was termed the plateau pressure. The time constant of this decay ( τ ) was measured, and the peripheral compliance (Cp) was calculated as τ /Rp. The NA group exhibited the highest Rp values at 4:00 p.m. and at 4:00 a.m. as compared with the NNA and control groups, but all groups were significantly different from each other at 4:00 p.m.: NA, 0.113 ± 0.02 cm H2O/ml/min; NNA, 0.033 ± 0.005 cm H2O/ml/min; Control subjects, 0.010 ± 0.001 cm H2O/ ml/m...

Selective suppression of neutrophil accumulation in ongoing pulmonary inflammation by systemic inhibition of p38 mitogen-activated protein kinase.

Abstract: The p38 mitogen-activated protein kinase (MAPK) signaling pathway regulates a wide range of inflammatory responses in many different cells. Inhibition of p38 MAPK before exposing a cell to stress stimuli has profound anti-inflammatory effects, but little is known about the effects of p38 MAPK inhibition on ongoing inflammatory responses. LPS-induced activation of p38 MAPK in human neutrophils was inhibited by poststimulation exposure to a p38 MAPK inhibitor (M39). Release of TNF-alpha, macrophage-inflammatory protein (MIP)-2 (MIP-1beta), and IL-8 by LPS-stimulated neutrophils was also reduced by poststimulation p38 MAPK inhibition. In contrast, release of monocyte chemoattractant protein-1 was found to be p38 MAPK independent. Ongoing chemotaxis toward IL-8 was eliminated by p38 MAPK inhibition, although the rate of nondirectional movement was not reduced. A murine model of acute LPS-induced lung inflammation was used to study the effect of p38 MAPK inhibition in ongoing pulmonary inflammation. Initial pulmonary cell responses occur within 4 h of stimulation in this model, so M39 was administered 4 h or 12 h after exposure of the animals to aerosolized LPS to avoid inhibition of cytokine release. Quantities of TNF-alpha, MIP-2, KC, or monocyte chemoattractant protein-1 recovered from bronchial alveolar lavage or serum were not changed. Recruitment of neutrophils, but not other leukocytes, to the airspaces was significantly reduced. Together, these data demonstrate the selective reduction of LPS-induced neutrophil recruitment to the airspaces, independent of suppression of other inflammatory responses. These findings support the feasibility of p38 MAPK inhibition as a selective intervention to reduce neutrophilic inflammation.

Longitudinal Change in the BODE Index Predicts Mortality in Severe Emphysema

Abstract: Rationale: The predictive value of longitudinal change in BODE (Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity) index has received limited attention. We hypothesized that decrease in a modified BODE (mBODE) would predict survival in National Emphysema Treatment Trial (NETT) patients. Objectives: To determine how the mBODE score changes in patients with lung volume reduction surgery versus medical therapy and correlations with survival. Methods: Clinical data were recorded using standardized instruments. The mBODE was calculated and patient-specific mBODE trajectories during 6, 12, and 24 months of follow-up were estimated using separate regressions for each patient. Patients were classified as having decreasing, stable, increasing, or missing mBODE based on their absolute change from baseline. The predictive ability of mBODE change on survival was assessed using multivariate Cox regression models. The index of concordance was used to directly compare the predictive ability of mBODE and its separate components. Measurements and Main Results: The entire cohort (610 treated medically and 608 treated surgically) was characterized by severe airflow obstruction, moderate breathlessness, and increased mBODE at baseline. A wide distribution of change in mBODE was seen at follow-up. An increase in mBODE of more than 1 point was associated with increased mortality in surgically and medically treated patients. Surgically treated patients were less likely to experience death or an increase greater than 1 in mBODE. Indices of concordance showed that mBODE change predicted survival better than its separate components. Conclusions: The mBODE demonstrates short- and intermediate-term responsiveness to intervention in severe chronic obstructive pulmonary disease. Increase in mBODE of more than 1 point from baseline to 6, 12, and 24 months of follow-up was predictive of subsequent mortality. Change in mBODE may prove a good surrogate measure of survival in therapeutic trials in severe chronic obstructive pulmonary disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00000606).

Recognition of trophoblasts by gamma delta T cells.

Abstract: The juxtaposition of maternal and fetal tissues in the hemochorial placenta has led to speculation that maternal recognition of fetal Ags present on trophoblasts might play an important role in reproductive biology We report here for the first time such recognition of trophoblasts by T lymphocyte hybridomas representative of certain cells present in the maternal decidua Trophoblast recognition is TCR dependent and is mediated by members of the V gamma 1+ subset of gamma delta T lymphocytes, a population that we previously have shown to be associated with heat shock protein-60 reactivity Recognition occurred in experiments in which trophoblast clones or freshly prepared trophoblasts were used and requires cell-cell interaction Although the maternal-fetal immune relationship typically has been cast in terms of an allograft, the T cell recognition of trophoblasts as described herein is not MHC-restricted, inasmuch as freshly prepared trophoblasts from beta 2-microglobulin-deficient mice were found to be stimulatory Furthermore, the trophoblast ligand that mediates this recognition is probably a conserved mammalian molecule, because a human trophoblast cell line is also stimulatory Our findings suggest a novel form of T cell recognition, and may provide an enhanced understanding of the maternal-fetal immune relationship