Subject(s)
Attitude of Health Personnel , Euthanasia, Animal , Terminal Care/psychology , Veterinarians/psychology , Adult , Aged , Animals , Clinical Competence , Communication , Education, Veterinary , Female , Humans , Male , Middle Aged , Physician-Patient Relations , Surveys and Questionnaires , United Kingdom , Veterinarians/statistics & numerical data , Young AdultABSTRACT
Virus infection of host cells activates a set of cellular genes, including cytokines, IFNs, and chemokines, involved in antiviral defense and immune activation. Previous studies demonstrated that virus-induced transcriptional activation of a member of the human CC-chemokine RANTES required activation of the latent transcription factors IFN-regulatory factor (IRF)-3 and NF-kappa B via posttranslational phosphorylation. In the present study, we further characterized the regulatory control of RANTES transcription during virus infection using in vivo genomic footprinting analyses. IRF-3, the related IRF-7, and NF-kappa B are identified as important in vivo binding factors required for the cooperative induction of RANTES transcription after virus infection. Using fibroblastic or myeloid cells, we demonstrate that the kinetics and strength of RANTES virus-induced transcription are highly dependent on the preexistence of IRFs and NF-kappa B. Use of dominant negative mutants of either I kappa B-alpha or IRF-3 demonstrate that disruption of either pathway dramatically abolishes the ability of the other to bind and activate RANTES expression. Furthermore, coexpression of IRF-3, IRF-7, and p65/p50 leads to synergistic activation of RANTES promoter transcription. These studies reveal a model of virus-mediated RANTES promoter activation that involves cooperative synergism between IRF-3/IRF-7 and NF-kappa B factors.
Subject(s)
Chemokine CCL5/biosynthesis , Chemokine CCL5/genetics , DNA-Binding Proteins/physiology , Gene Expression Regulation, Viral/immunology , NF-kappa B/physiology , Transcription Factors/physiology , Base Sequence , Binding Sites/genetics , Binding Sites/immunology , Cell Line , DNA-Binding Proteins/metabolism , Drug Synergism , Humans , Interferon Regulatory Factor-3 , Interferon Regulatory Factor-7 , Interferon Type I/physiology , Molecular Sequence Data , Promoter Regions, Genetic/immunology , Protein Binding/genetics , Protein Binding/immunology , Respirovirus/genetics , Respirovirus/immunology , Response Elements/immunology , Transcription Factors/metabolism , Transfection , U937 CellsABSTRACT
An aggressive IV admixture program in a 600 bed tertiary care teaching institution was implemented. Four intensive care units primarily caring for cardiology patients are the responsibility of a satellite pharmacy, which in January of 1986 began preparation of intravenous infusion medications (IVIMs), commonly referred to as "drip medications." By adopting this service, the pharmacy helped reduce workloads of nursing at a time of increasing demand owing to a rising acuity level of the patient population. The predominance of labor was shifted to less expensive and more available pharmacy technicians. Increased quality control and flexibility in constituents were also achieved. The satellite pharmacists became recognized as "expert" in the compatibility and administration of the IVIMs they prepared expanding their role in the ICU. The service demonstrates the ability of the pharmacy to prepare IV products even under the most critical circumstances.
