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Jeffrey Gold

Publications and source records attributed to Jeffrey Gold.

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Invited commentary.

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Heart Valve Prosthesis Implantation↗

Interleukin-10 induces inhibitory C/EBPbeta through STAT-3 and represses HIV-1 transcription in macrophages.

Pulmonary tuberculosis (TB) has been characterized by inflammation with increased pro- or anti-inflammatory cytokines produced by macrophages. We have reported that IFN produces inhibitory C/EBPbeta and represses transcription of the HIV-1 LTR in macrophages. STAT-1 and type I IFN receptor knockout mice have macrophages that are defective in IFN signaling, yet LPS stimulation induces inhibitory C/EBPbeta, demonstrating that other cytokines can induce this repressor. LPS or Mycobacterium tuberculosis-derived lipoarabinomannan induce the anti-inflammatory cytokine interleukin (IL)-10, which represses the HIV-1 LTR in differentiated THP-1 macrophages by inducing inhibitory C/EBPbeta. In contrast, in undifferentiated THP-1 monocytes, IL-10 did not inhibit HIV-1 replication or induce C/EBPbeta. IL-10 signal transduction uses STAT-3, and macrophages from STAT-3-/- mice fail to produce inhibitory C/EBPbeta after LPS or IL-10 stimulation. Transfection of STAT-3 into THP-1 cells enhances C/EBPbeta promoter activity. THP-1 differentiation also increases STAT-3 protein, but not STAT-3 gene transcription, and induces a translational regulator, CUG-binding protein, that was essential for production of C/EBPbeta. Differentiation induced post-transcriptional regulation is required to produce inhibitory C/EBPbeta in response to IL-10. Only macrophages are able to repress HIV-1 LTR promoter activity and inhibit viral replication in response to IL-10 or type I IFN.

Animals↗

Diabetes mellitus increases short-term mortality and morbidity in patients undergoing coronary artery bypass graft surgery.

OBJECTIVES: The aim of this study was to determine the impact of diabetes mellitus (DM) on short-term mortality and morbidity in patients undergoing coronary artery bypass surgery (CABG). BACKGROUND: Diabetes mellitus is present in approximately 20% to 30% of patients undergoing CABG, and the impact of diabetes on short-term outcome is unclear. METHODS: We performed a retrospective cohort study in 434 hospitals from North America. The study population included 146,786 patients undergoing CABG during 1997: 41,663 patients with DM and 105,123 without DM. The primary outcome was 30-day mortality. Secondary outcomes were in-hospital morbidity, infections and composite outcomes of mortality or morbidity and mortality or infection. RESULTS: The 30-day mortality was 3.7% in patients with DM and 2.7% in those without DM; the unadjusted odds ratio was 1.40 (95% confidence interval [CI], 1.31 to 1.49). After adjusting for other baseline risk factors, the overall adjusted odds ratio for diabetics was 1.23 (95% CI, 1.15 to 1.32). Patients treated with oral hypoglycemic medications had adjusted odds ratio 1.13; 95% CI, 1.04 to 1.23, whereas those on insulin had an adjusted odds ratio 1.39; 95% CI, 1.27 to 1.52. Morbidity, infections and the composite outcomes occurred more commonly in diabetic patients and were associated with an adjusted risk about 35% higher in diabetics than nondiabetics, particularly among insulin-treated diabetics (adjusted risk between 1.5 to 1.61). CONCLUSIONS: Diabetes mellitus is an important risk factor for mortality and morbidity among those undergoing CABG. Research is needed to determine if good control of glucose levels during the perioperative time period improves outcome.

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