ABSTRACT
OBJECTIVES: To compare the accuracy of point-of-care capillary and venous/arterial samples to laboratory testing of venous/arterial samples in critically sick shocked and non-shocked patients. This is a prospective case-control study including capillary, venous, and arterial blood samples from 268 critically ill patients. The King Fahd Military Medical Complex in Dhahran, Saudi Arabia, was the site of this investigation. RESULTS: We were able to obtain data on 268 patients for this investigation. POCT and lab findings of venous and central blood did not differ significantly (P = 0.389 and 0.208), while POCT indicated somewhat higher results with venous glucose concentrations of 10.18 and 10.05 (POCT and lab tests respectively) and 9.18 and 9.54 (POCT and lab tests respectively). In addition, the mean differences between POC and laboratory analyses of venous, arterial, and central glucose were 0.13, - 1.75, and - 0.36 mmol/L for venous, arterial, and central glucose, respectively. Except for arterial blood glucose, we did not observe a significant difference between POCT and routine laboratory analysis of glucose concentrations in critically ill patients. Compared to laboratory blood analysis, the use of POCT is marginally accurate, with no difference between shocked and non-shocked patients.
Subject(s)
Point-of-Care Systems , Shock , Humans , Blood Glucose/analysis , Critical Illness , Case-Control Studies , Veins/chemistryABSTRACT
Activation of cytokine signaling via the leukemia inhibitory factor receptor (LIFR) plays an integral role in hematopoiesis, osteogenesis, and placental development, along with mediating neurotrophic mechanisms. However, the regulatory control of the LIFR gene has remained largely unexplored. Here, we characterize the LIFR gene as a novel target of the RUNX1 transcription factor. The RUNX1 transcription factor is an essential regulator of hematopoiesis and is a frequent target of point mutations and chromosomal alterations in leukemia. RUNX1 regulates hematopoiesis through its control of genes important for hematopoietic cell growth, proliferation, and differentiation, including a number of cytokines and cytokine receptors. LIFR is regulated by two alternate promoters: a placental-specific and a ubiquitously active general promoter. We show that both of these promoters are regulated by RUNX1. However, in myeloid cells LIFR expression is driven solely by the general LIFR promoter with our data indicating that the placental promoter is epigenetically silenced in these cells. While RUNX1 activates the LIFR general promoter, the oncogenic RUNX1-ETO fusion protein generated by the t(8;21) translocation commonly associated with acute myeloid leukemia represses promoter activity. The data presented here establish LIFR as a transcriptional target of RUNX1 and suggest that disruption of RUNX1 activity in myeloid cells may result in altered LIFR signaling in these cells.
Subject(s)
Core Binding Factor Alpha 2 Subunit/metabolism , Receptors, OSM-LIF/metabolism , Blotting, Western , Cell Differentiation/genetics , Cell Differentiation/physiology , Cell Line, Tumor , Cell Proliferation/genetics , Cell Proliferation/physiology , Chromatin Immunoprecipitation , Chromosome Aberrations , Core Binding Factor Alpha 2 Subunit/genetics , Humans , Myeloid Cells/metabolism , Point Mutation/genetics , Promoter Regions, Genetic/genetics , Protein Binding/genetics , Protein Binding/physiology , Receptors, Cytokine/genetics , Receptors, Cytokine/metabolism , Receptors, OSM-LIF/geneticsABSTRACT
The RUNX1 gene, which is essential for normal hematopoiesis, is frequently rearranged by the t(8;21) chromosomal translocation in acute myeloid leukemia. The resulting RUNX1-ETO fusion protein contributes to leukemic progression by directing aberrant association of transcriptional cofactors and epigenetic modifiers to RUNX1 target genes. For example, the GM-CSF gene is activated by RUNX1, but is repressed by RUNX1-ETO. Here we show that RUNX1 normally cooperates with the histone acetyltransferase, CBP, to regulate GM-CSF expression at two levels. Firstly, it directs the establishment of a competent chromatin environment at the GM-CSF promoter prior to gene activation. It then participates in the transcriptional activation of the promoter in response to immune stimuli. In contrast, RUNX1-ETO, which cannot associate with CBP, is unable to transactivate the GM-CSF promoter and is associated with the generation of a repressive chromatin environment at the promoter.
Subject(s)
Core Binding Factor Alpha 2 Subunit/physiology , Epigenesis, Genetic , Granulocyte-Macrophage Colony-Stimulating Factor/genetics , Promoter Regions, Genetic , Transcription, Genetic , Base Sequence , Cell Line , Chromatin Immunoprecipitation , DNA Primers , Humans , RNA, Small InterferingABSTRACT
Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections were assessed among 81 Bahraini and 34 Saudi hemodialysis patients and 7714 Bahraini and 2330 Saudi blood donors. Higher prevalence of HCV (9.24% vs 0.30%), hepatitis B surface antigen (5.88% vs 0.62%) were seen in patients versus control patients, and in Saudi patients compared with Bahraini patients. HCV genotypes were HCV 1a/1b plus HCV 4 among Bahraini patients and HCV 2/2a plus HCV 4 among Saudi patients. This is the first report on viral hepatitis in Bahrain and the first to compare HBV/HCV among dialysis patients in the Eastern Arabian Peninsula.
