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.

The small airways in asthma

Abstract: Airway inflammation is the basis for airway hyper-reactivity that results in the signs and symptoms of asthma. Great strides have been made in the past several decades to target airway inflammation using topical inhaled corticosteroids. In some cases, despite reported improvement in large airways indices on treatment, clinical control of asthma is not attained. Inflammation of the distal airways is now realized as playing a greater role in asthma control, and newer techniques are available to assess the smaller airways. Changes in formulations of inhaled corticosteroids and smaller particle size of medication allows for more effective targeting of the smaller airways.

Cigarette Smoke Exposure Impairs β-Cell Function Through Activation of Oxidative Stress and Ceramide Accumulation

Abstract: ObjectivesEpidemiological studies indicate that first- and second-hand cigarette smoke (CS) exposure are important risk factors for the development of type 2 diabetes (T2D). Additionally, elevated diabetes risk has been reported to occur within a short period of time after smoking cessation, and health risks associated with smoking are increased when combined with obesity. At present, the mechanisms underlying these associations remain incompletely understood. The objective of this study was to test the impact of CS exposure on pancreatic {beta}-cell function using rodent and in vitro models.nnMethodsBeginning at 8 weeks of age, C57BL/6J mice were concurrently fed high fat-diet (HFD) and exposed to CS for 11 weeks, followed by an additional 11 weeks of smoking cessation with continued HFD exposure. Glucose tolerance testing was performed during CS exposure and during the cessation period. Cultured {beta}-cells (INS-1) and primary islets were exposed ex vivo to CS extract (CSE), and {beta}-cell function and viability were tested. Since CS increases ceramide in lungs cells and these bioactive sphingolipids have been implicated in pancreatic {beta}-cell dysfunction in diabetes, islet and {beta}-cell sphingolipid levels were measured in islets from CS-exposed mice and in CSE-treated islets and INS-1 cells using liquid chromatography-tandem mass spectrometry.nnResultsCompared to HFD-fed ambient air-exposed mice, HFD-fed and CS- exposed mice had reduced weight gain and better glucose tolerance during the active smoking period. Following smoking cessation, CS-mice exhibited rapid weight gain and a significantly greater increase in glucose intolerance compared to non-smoking control mice. CS-exposed mice had higher serum proinsulin/insulin ratios, indicative of {beta}-cell dysfunction, significantly lower {beta}-cell mass (p=0.02), and reduced {beta}-cell proliferation (p=0.006), and increased islet ceramide accumulation. Ex vivo exposure of isolated islets to CSE was sufficient to increase islet ceramide accumulation, reduce insulin gene expression and glucose-stimulated insulin secretion, and increase {beta}-cell oxidative and ER stress. Treatment with the antioxidant N-acetylcysteine, markedly attenuated the effects of CSE on ceramide levels, restored {beta}-cell function and survival, and increased cyclin D2 expression, while also reducing activation of {beta}-cell ER and oxidative stress.nnConclusionsOur results indicate that CS exposure inhibits insulin production, processing, and secretion and reduced {beta}-cell viability and proliferation. These effects were linked to increased {beta}-cell oxidative and ER stress and ceramide accumulation. Mice fed HFD continued to experience detrimental effects of CS exposure even during smoking cessation. Elucidation of mechanisms by which CS exposure impairs {beta}-cell function in synergy with obesity will help design therapeutic and preventive interventions for both active and former smokers.

Isolation of a cDNA clone complementary to sequences for a 34-kilodalton protein which is a pp60v-src substrate.

Abstract: We have isolated a partial cDNA clone containing sequences complementary to a mRNA encoding a 34- to 36-kilodalton normal chicken cell protein which is a substrate for pp60v-src kinase activity. Using this 34-kilodalton cDNA clone as a probe, we determined that the size of the 34-kilodalton mRNA was 1,100 nucleotides and the level of the 34-kilodalton RNA was the same in various tissues of mature chickens but was significantly higher in chicken embryo fibroblast cells.

Hin-2 nucleic acid molecules, proteins, antibodies, homologues, receptors, and uses thereof

Abstract: Disclosed are HIN-2 proteins and homologues, nucleic acid molecules encoding HIN-2 proteins and homologues, antibodies that selectively bind to HIN-2 proteins and homologues; compositions comprising HIN-2 proteins and homologues, nucleic acid molecules, or antibodies; and methods of making and using HIN-2 proteins and homologues, nucleic acid molecules, and antibodies. Also disclosed are receptors and ligands that selectively bind to HIN-2, as well as fragments and homologues of such receptors, agonists and antagonists of such receptors, and methods of using such receptors to regulate the biological activity mediated by HIN-2.