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.

Coordinate production by a T cell hybridoma of gamma interferon and three other lymphokine activities: multiple activities of a single lymphokine?

Abstract: The T cell hybridoma FS7-20, produced by the fusion of normal B10.BR T cells to the AKR thymoma BW5147, was found when stimulated with concanavalin A (Con A) to produce the lymphokines: interleukin 2 (IL 2), interferon-gamma (IFN gamma), macrophage-activating factor (MAF), Ia induction factor IaIF), and the B cell helper factor interleukin X (IL X). The clones and subclones of FS7-20 varied dramatically in their ability to produce these lymphokines, presumably because of karyotypic variations. The ability to produce IL 2 segregated independently from the ability to produce the four other lymphokine activities; however, production of the latter activities showed a strong correlation. This coordinate production of IFN gamma, MAF, IaIF, and IL X was also observed with a cloned normal cytotoxic T cell line, cr15. These results suggest either that IFN gamma, MAF, IaIF, and IL X are all manifestations of a single molecular species or that, although these activities are different structurally, their production is controlled by a common genetic mechanism. In support of the first possibility, the IFN gamma, MAF, IaIF, and IL X activity produced by FS7-20 were all found to be equally sensitive to inactivation at pH 2. These results illustrate the usefulness of using T cell hybridomas for the study of lymphokines.

Lack of toxicity of a STAT3 decoy oligonucleotide.

Abstract: Background STAT3 overexpression has been detected in several cancers including head and neck squamous cell carcinoma (HNSCC). Previous studies using intratumoral administration of a STAT3 decoy oligonucleotide that abrogates STAT3-mediated gene transcription in preclinical cancer models have demonstrated antitumor efficacy. This study was conducted to observe the toxicity and biologic effects of the STAT3 decoy in a non-human primate model, in anticipation of initiating a clinical trial in HNSCC patients.

Regulation of synthesis and activity of the PLSTIRE protein (cyclin-dependent kinase 6 (cdk6)), a major cyclin D-associated cdk4 homologue in normal human T lymphocytes.

Abstract: The PLSTIRE protein (cyclin-dependent kinase 6 (cdk6)), which shares extensive sequence homology (approximately 70%) with cdk4, was identified as the earliest inducible member of the cdk family of proteins in human T lymphocytes induced to proliferate in vitro by stimulation either with phorbol 12,13-dibutyrate and ionomycin (PDB/I) or PHA. The p40cdk6 protein was present in resting cells and increased amounts were detected 6 h after stimulation. It increased in amount throughout the first cell cycle but was present in reduced amounts at later times. Activity of the kinase, determined by in vitro phosphorylation of recombinant truncated retinoblastoma tumor suppressor gene (Rb) protein (p60Rb), paralleled p40cdk6 protein amounts. Cyclins D2 and D3 were the major cyclins associated with p40cdk6, with D2 predominating in early G1 phase. Both PDB and ionomycin were required for maximal accumulation of p40cdk6, but either agent alone stimulated some increase in amount and activity of the protein. p40cdk6 also increased in amount in cells activated in the presence of cyclosporin A or FK506, drugs that inhibit production of IL-2 and cell proliferation, suggesting that initial induction occurred independently of IL-2-mediated cell cycle progression. Furthermore, increased accumulation of p40cdk6 protein and activity occurred in cells rendered "competent" (responsive to IL-2) by a brief treatment with PDB/I. Thus, increased accumulation of the protein and its activity begin before IL-2/IL-2 receptor interaction, suggesting that the cdk6-cyclin D2 complex might be involved in acquisition of the competent state in human T lymphocytes.

B-cell-receptor-dependent positive and negative selection in immature B cells.

Abstract: This review touches on only a small part of the complex biology of B cells, but serves to illustrate the point that the antigen receptor is the most important of many cell-surface receptors affecting cell-fate decisions. Receptor expression is necessary, but not sufficient, for cell survival. It is also essential that a B cell's antigen-receptor specificity be appropriate for its environment. The need to balance reactivity with self tolerance has resulted in an intricate feedback control (affected by both the recombinase and cell survival) that regulates independent selection events at the level of the receptor and the cell.

Oral desensitization to rifampin and ethambutol in mycobacterial disease.

Abstract: The incidence of disease caused by Mycobacterium tuberculosis (including drug-resistant strains) and M. avium complex (MAC) is increasing. Hypersensitivity reactions to antimycobacterial agents are relatively uncommon, but when they occur they may result in cessation of therapeutic medications. We report our experience with rapid oral desensitization to ethambutol and rifampin in a group of 10 patients with mycobacterial disease who had experienced cutaneous hypersensitivity reactions to these drugs. An adaptation of the rapid oral desensitization protocol for penicillin was used, with the dosing intervals increased to account for the different kinetics of these drugs. Adverse reactions were few and easily treated without necessitating cessation of therapy. We conclude that oral desensitization to rifampin and ethambutol by our protocol is safe and effective, allowing these patients to proceed with an optimal antimycobacterial regimen.