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1.
Resuscitation ; 69(2): 253-61, 2006 May.
Article in English | MEDLINE | ID: mdl-16563601

ABSTRACT

OBJECTIVE: Despite widespread training with CPR guidelines, CPR is often poorly performed. We explore relationships between knowledge of CPR guidelines and performance (compression rate, compression depth, compression to ventilation ratio, and ventilation volume). METHODS: Sixty professional EMTs were sampled at 26 randomly ordered EMS response stations from an urban system of 31 stations. A recording manikin and video model were used to assess performance in a standardized scenario, and a survey was used to assess guideline knowledge. Survey and performance outcomes were categorized prospectively as correct or incorrect based on the International CPR Guidelines from 2000. Relationships were modeled with logistic regression. Covariates included years of work experience, frequency of CPR performance, and ALS versus BLS EMT level. RESULTS: Compression rate was between 80 and 120 min(-1) in 56% (33/59) of trials. Compression depth was 1.5-2 in. in 39% (23/59), compression to ventilation ratio approximated to 15:2 in 42% (25/59), and ventilation volume was 800-1,200 cm(3) in 13% (8/60). Accurate knowledge of the CPR guidelines was associated with better performance of chest compression rate and compression to ventilation ratio. Adjusted OR (95% CI) were 4.6 (1.2-18.1) for compression rate, 1.7 (0.4-6.5) for compression depth, 4.5 (1.1-18.5) for compression to ventilation ratio, and 9.0 (0.2-351) for ventilation volume. CONCLUSIONS: Although accurate knowledge of guidelines is associated with increased odds of correct performance of some aspects of CPR, overall performance remains poor.


Subject(s)
Cardiopulmonary Resuscitation/standards , Clinical Competence , Emergency Medical Technicians/standards , Guideline Adherence , Practice Guidelines as Topic , Adult , Cardiopulmonary Resuscitation/methods , Cross-Sectional Studies , Female , Humans , Logistic Models , Male , Surveys and Questionnaires
2.
J Leukoc Biol ; 78(2): 515-23, 2005 Aug.
Article in English | MEDLINE | ID: mdl-15894584

ABSTRACT

Interferon-gamma (IFN-gamma) is a pleiotropic cytokine involved in aspects of immune regulation, cell proliferation, and host defense mechanisms directed toward various cancers. Some of the biological functions of IFN-gamma are achieved through inhibition of gene expression, although the mechanisms by which IFN-gamma suppresses gene transcription are poorly understood. Herein, we demonstrate the molecular basis by which IFN-gamma mediates suppression of the matrix metalloproteinase-9 (MMP-9) gene. IFN-gamma-activated signal transducer and activator of transcription-1alpha (STAT-1alpha) suppresses MMP-9 gene transcription, which is dependent on phosphorylation of tyrosine 701 but not phosphorylation of serine 727. The coactivator cyclic AMP response element-binding protein-binding protein (CBP) is an important component of induction of MMP-9 gene transcription. IFN-gamma induces the in vivo association of STAT-1alpha and CBP and decreases the association of CBP to the MMP-9 promoter. IFN-gamma does not influence the stability of CBP nor does IFN-gamma affect chromatin-remodeling events on the MMP-9 promoter. IFN-gamma inhibits the assembly of the MMP-9 transcription complex by suppressing H3/H4 acetylation and inhibiting recruitment of Pol II to the MMP-9 promoter. These findings indicate that IFN-gamma/STAT-1alpha exert their inhibitory effects by affecting multiple aspects of MMP-9 gene transcription.


Subject(s)
Antineoplastic Agents/pharmacology , Down-Regulation/drug effects , Interferon-gamma/pharmacology , Matrix Metalloproteinase 9/biosynthesis , Nuclear Proteins/metabolism , Trans-Activators/metabolism , Transcription Factors/metabolism , Acetylation/drug effects , Antineoplastic Agents/metabolism , CREB-Binding Protein , Chromatin Assembly and Disassembly/drug effects , Chromatin Assembly and Disassembly/physiology , Cyclic AMP/metabolism , DNA Polymerase II/metabolism , Down-Regulation/physiology , HeLa Cells , Histones/metabolism , Humans , Interferon-Stimulated Gene Factor 3 , Interferon-gamma/metabolism , Phosphorylation/drug effects , Protein Processing, Post-Translational/drug effects , Protein Processing, Post-Translational/physiology , Protein Transport/drug effects , Protein Transport/physiology , Response Elements/physiology , Second Messenger Systems/drug effects , Second Messenger Systems/physiology
3.
Mol Cell Biol ; 24(12): 5496-509, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15169910

ABSTRACT

Transcriptional activation of eukaryotic genes depends on the precise and ordered recruitment of activators, chromatin modifiers/remodelers, coactivators, and general transcription factors to the promoters of target genes. Using the human matrix metalloproteinase 9 (MMP-9) gene as a model system, we investigated the sequential assembly and dynamic formation of transcription complexes on a human promoter under the influence of mitogen signaling. We find that, coincident with activation of the MMP-9 gene, activators, chromatin remodeling complexes, and coactivators are recruited to the preassembled MMP-9 promoter in a stepwise and coordinated order, which is dependent on activation of MEK-1/extracellular signal-regulated kinase and NF-kappa B signaling pathways. Conversely, corepressor complexes are released from the MMP-9 promoter after transcriptional activation. Histone modifications shift from repressive to permissive modifications concurrent with activation of the MMP-9 gene. Chromatin remodeling induced by Brg-1 is required for MMP-9 gene transcription, which is concomitant with initiation of transcription. Therefore, coordination of cell signaling, chromatin remodeling, histone modifications, and stepwise recruitment of transcription regulators is critical to precisely regulate MMP-9 gene transcription in a temporally and spatially dependent manner. Given the important role of MMP-9 in both normal development and pathological conditions, understanding MMP-9 gene regulation is of great relevance.


Subject(s)
Chromatin/genetics , Chromatin/metabolism , Histones/metabolism , Matrix Metalloproteinase 9/genetics , Podophyllin/analogs & derivatives , Binding Sites , Gene Expression Regulation, Enzymologic , HeLa Cells , Humans , MAP Kinase Signaling System , Models, Biological , NF-kappa B/metabolism , Podophyllin/metabolism , Podophyllotoxin/analogs & derivatives , Promoter Regions, Genetic , RNA, Messenger/genetics , RNA, Messenger/metabolism , Signal Transduction , Tetradecanoylphorbol Acetate/pharmacology , Transcription Factor AP-1/metabolism , Transcription, Genetic/drug effects
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