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.

Antiretroviral treatment interruptions and risk of non-opportunistic diseases

Abstract: Structured treatment interruptions have been studied as a strategy to reduce antiretroviral toxicities and expenditures in the treatment of HIV-infected individuals. Paradoxically, in addition to the increased incidence of death and opportunistic infections, these interruptions in therapy have resulted in the development of a number of non-opportunistic diseases, including cardiovascular events, renal insufficiency, hepatic failure, and non-AIDS-defining malignancies. Hypotheses regarding these findings suggest that the augmented stimulation of the host response to unabated viral replication may contribute to these comorbidities. Increased expression of chemokine receptor 5 and proinflammatory cytokines, disruption of immune cell function, and reduction in key inflammatory cells have been studied as potential mechanisms. Additionally, the increased inflammatory response has been shown to increase intracellular levels of nucleoside and nucleotide reverse transcriptase inhibitors, resulting in increased toxic manifestations. Structured treatment interruptions should be avoided in the management of HIV-infected individuals.

Live Imaging of IL-4-Expressing T Follicular Helper Cells in Explanted Lymph Nodes.

Abstract: The generation of class-switched, high-affinity, antibody-producing B cells plays a critical role in the establishment of type 2 immunity to intestinal helminths as well as in the pathogenesis of allergy and asthma. The generation of these high-affinity, antibody-producing B cells occurs in germinal centers (GC) and relies on interactions with follicular dendritic cells (FDCs) and T follicular helper (Tfh) cells. One critical mediator produced by Tfh cells in GCs is interleukin-4 (IL-4). Tfh-derived IL-4 drives class switching to type 2 antibody isotypes IgE and IgG1 and is required for high-affinity IgG1 production. In vivo detection of IL-4-expressing Tfh cells is required to better understand the role of these cells during the GC response. Detection of IL-4-expressing cells has been greatly improved by the generation of the IL-44get reporter mice, which read out IL-4 expression as green fluorescent protein (GFP). Much has been learned from these mice with regard to type 2 immunity using flow cytometry and immunohistochemistry. However, these methods do not allow the study of cellular behavior and interactions in real time. In contrast, multi-photon microscopy allows for deep tissue imaging and tracking of multiple cell types in intact tissues over time. Here, we describe a protocol for in vivo detection of IL-4-expressing Tfh cells in an explanted popliteal lymph node by multi-photon microscopy. The dynamics of Tfh cell motility and their interactions with FDC networks in the GCs were analyzed.

Hypoxia-Inducible Factors and Adenosine Signaling in Vascular Growth

Abstract: Low oxygen environment or hypoxia is conducive towards vascular growth and endothelial proliferation. Therefore it is an essential element in both disease and development. Hypoxia stabilizes the hypoxia-inducible transcription factors -1α and -2α and also increases adenosine levels thereby activating the adenosine receptor signaling pathways. While these pathways have been described independently to a greater extent, increasing evidence suggests that there is significant crosstalk. Here we will summarize the contributions and interdependence of hypoxia-inducible transcription factors and the adenosine receptor pathways in vascular growth.

Methods and compositions for beryllium-induced Disease

Abstract: The present invention provides for methods for detection, diagnosis and prognosis of beryllium-induced disease. In one embodiment, the methods include exposing immune cells from subjects suspected of having beryllium-induced disease to beryllium and assessing the Th-1 cytokines produced. Other embodiments include the use of exposing immune cells from subjects suspected of having beryllium-induced disease to beryllium and assessing Th-1 cytokines produced and using these assessments to indicate the stage of progression of the disease. Therapeutic methods involve assessing the onset or progression of beryllium-induced disease before during and after exposure to a treatment for the disease.

Response to Zee, P., Melantonin for the Treatment of Advanced Sleep Phase Disorder. SLEEP 2008;31:923.

Abstract: WE APPRECIATE THE COMPLIMENT, CAREFUL REVIEW AND CONSTRUCTIVE CRITICISM OF DR. ZEE.1 DR. ZEE POINTS OUT THAT BOTH THE REVIEW AND the practice parameter emphasize that there are no outcome studies directly evaluating the effect of timed melatonin in the treatment of advanced sleep phase disorder (APSD). After careful consideration, we agree with Dr. Zee's criticism, and we will make appropriate correction to this practice parameter. In the task force review paper, a theoretical basis for the use of timed melatonin in APSD is presented. In our practice parameter paper, use of timed melatonin is listed as one among various indicated therapies for APSD, but the recommendation is given as an “Option” strength recommendation. An “Option” level recommendation is a “patient care strategy that reflects uncertain clinical use. The term option implies either inconclusive or conflicting evidence or conflicting expert opinion.” The inclusion of timed melatonin as an option for APSD was based upon committee consensus, but there was limited effort to evaluate consensus about the magnitude of risks involved in the use of timed melatonin for this specific recommendation. Although caution is advised by many regarding melatonin therapy, there has been little in the way of methodical study, and since adverse event reporting is not systematic it does not always provide reliable evidence on which to base a recommendation.2 This points out a potential weakness with the methods currently employed to develop recommendations for practice. The Standards of Practice Committee of the AASM has used an evaluation system based on the Oxford System.3,4 In this system, the strength of the supporting evidence for efficacy is the major focus. There are fewer explicit guidelines to use when weighing the strength of perceived costs or risks. The SPC strives to provide sensible, graded, evidence-based, peer-reviewed recommendations while not restricting sleep specialists from employing therapies that seem reasonable (by consensus) and have few demonstrated risks, but may not yet have been sufficiently studied. Newer methods of assessing evidence, such as the GRADE method, strive to make risk/benefit analyses in the development of recommendations more explicit and transparent.5,6 The SPC is committed to learning and incorporating such new developments in evidence-based medicine techniques. We agree with Dr. Zee's criticism, and in retrospect feel that we should not have included timed melatonin as an “indicated therapy.” It would have been better to state that there was insufficient information to make a recommendation regarding timed melatonin for this application. We will place a correction of this particular recommendation on the AASM website, which will remove the recommendation for use of timed melatonin in APSD.