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.

Modulation of airway responses by prostaglandins in young and fully grown rabbits.

Abstract: Maturational changes have been noted in neurally mediated contractile and relaxant responses in airways from New Zealand White rabbits. In this study, we focused on prostaglandins with bronchoprote...

Central human B cell tolerance manifests with a distinctive cell phenotype and is enforced via CXCR4 signaling in hu-mice

Abstract: Central B cell tolerance, the process restricting the development of many newly generated autoreactive B cells, has been intensely investigated in mouse cells while studies in humans have been hampered by the inability to phenotypically distinguish autoreactive and nonautoreactive immature B cell clones and the difficulty in accessing fresh human bone marrow samples. Using a human immune system mouse model in which all human Igκ+ B cells undergo central tolerance, we discovered that human autoreactive immature B cells exhibit a distinctive phenotype that includes lower activation of ERK and differential expression of CD69, CD81, CXCR4, and other glycoproteins. Human B cells exhibiting these characteristics were observed in fresh human bone marrow tissue biopsy specimens, although differences in marker expression were smaller than in the humanized mouse model. Furthermore, the expression of these markers was slightly altered in autoreactive B cells of humanized mice engrafted with some human immune systems genetically predisposed to autoimmunity. Finally, by treating mice and human immune system mice with a pharmacologic antagonist, we show that signaling by CXCR4 is necessary to prevent both human and mouse autoreactive B cell clones from egressing the bone marrow, indicating that CXCR4 functionally contributes to central B cell tolerance.

A locus on chromosome 9 is associated with differential response of 129S1/SvImJ and FVB/NJ strains of mice to systemic LPS

Abstract: Although polymorphisms in TLR receptors and downstream signaling molecules affect the innate immune response, these variants account for only a portion of the ability of the host to respond to microorganisms. To identify novel genes that regulate the host response to systemic lipopolysaccharide (LPS), we created an F2 intercross between susceptible (FVB/NJ) and resistant (129S1/SvImJ) strains, challenged F2 progeny with LPS via intraperitoneal injection, and phenotyped 605 animals for survival and another 500 mice for serum concentrations of IL-1β and IL-6. Genome-wide scans were performed on pools of susceptible and resistant mice for survival, IL-1β, and IL-6. This approach identified a locus on the telomeric end of the q arm of chromosome 9 (0–40 Mb) that was associated with the differences in morbidity and serum concentrations of IL-1β and IL-6 following systemic LPS in FVB/NJ and 129S1/SvImJ strains of mice. Fine mapping narrowed the locus to 3.7 Mb containing 11 known genes, among which are three inflammatory caspases. We studied expression of genes within the locus by quantitative RT-PCR and showed that Casp1 and Casp12 levels are unaffected by LPS in both strains, whereas Casp4 is highly induced by LPS in FVB/NJ but not in 129S1/SvImJ mice. In conclusion, our mapping results indicate that a 3.7-Mb region on chromosome 9 contains a gene that regulates differential response to LPS in 129S1/SvImJ and FVB/NJ strains of mice. Differences in the induction of Casp4 expression by LPS in the two strains suggest that Casp4 is the most likely candidate gene in this region.

Mechanisms by Which Manganese Porphyrins Affect Signaling in Cancer Cells

Abstract: This chapter explores the role that metalloporphyrins (MnTE-2-PyP, MnTnBuOE-2-PyP, and MnTnHex-2-PyP) play in cancer growth and progression. This review focuses on the effect that metalloporphyrins have on signaling events in cancer cells. The first section reviews published data demonstrating that the redox environment influences cancer growth and progression by regulating cell cycle progression, angiogenesis, invasion, and metastasis. The next section reviews studies performed both in vitro and in vivo demonstrating that the addition of superoxide dismutase (SOD) enzymes reduces cancer growth. Then published data is presented showing that manganese porphyrins, which mimic SOD activity, also inhibit cancer growth. Finally, we review all of the mechanisms that have been published thus far on how manganese porphyrins inhibit cancer growth. Specifically, manganese porphyrins have been shown to alter tumor immunology, metabolism, transcription, and post-translational modifications of target signaling proteins. We hypothesize that by scavenging superoxide and enhancing hydrogen peroxide levels, the manganese porphyrins directly affect redox signaling pathways resulting in reduced tumor growth.

Prognostic Markers and the LAS for Lung Transplantation: Impact of New Revisions for Successful Outcome

Abstract: This chapter reviews the history, development, and institution of the lung allocation score (LAS) in the United States Lung transplantation can be a lifesaving therapy for patients suffering with end-stage lung diseases for which there are no remaining therapeutic options available Unfortunately, there remains an imbalance between the number of patients in need of this therapy and the availability of suitable donor organs for transplantation The LAS was developed in the spirit of the important ethical principles in transplantation of utility and justice More specifically, the objective of the LAS is to decrease waitlist time (and thus risk for waitlist mortality) and to allocate organs based upon medical urgency so as to balance predicted urgency with predicted benefit The institution of the LAS for the allocation of suitable donor lungs to appropriate candidates on May 4, 2005, literally changed the landscape of lung transplantation overnight This chapter also explores the ongoing evolution of the LAS as advancements continue to be made in medical therapies and technologies available for the support and management of end-stage lung diseases