ABSTRACT
The lipaemic index can be used to assess whether or not blood samples are suitable for laboratory analysis. However, little is known about which patients have a raised lipaemic index. In this article we study patient demographics and serum lipid concentrations in samples showing a raised lipaemic index. Of the 4271 patient samples measured in the month of July 2014, a total of 310 had a lipaemic index 0.4. Blood samples showing a raised lipaemic index were studied in a retrospective patient case review of laboratory results. Overall, 7.3% of all samples measured had a raised lipaemic index 0.4. This study found that males were more likely to have a high lipaemic index (56%) and neonates were the group most frequently producing lipaemic samples (30.6%). The correlation between the lipaemic index and the triglyceride concentration showed an r2 value of only 0.37 (r = 0.61), and the correlation between cholesterol and lipaemic index showed an r2 value of 0.16 (r = -0.41). Male and neonatal samples were most likely to show a raised lipaemic index. There was a positive correlation between sample triglyceride and lipaemic index and an inverse correlation with cholesterol concentration and the lipaemic index, although this did not account for all the variance. Thus, other factors may also be important in the expression of the lipaemic index.
Subject(s)
Hyperlipidemias/blood , Lipids/blood , Adolescent , Adult , Aged , Blood Chemical Analysis , Child , Child, Preschool , England/epidemiology , Female , Humans , Hyperlipidemias/epidemiology , Infant , Infant, Newborn , Linear Models , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Young AdultSubject(s)
Biomarkers/blood , Creatine Kinase/blood , Inpatients/statistics & numerical data , Intensive Care Units/statistics & numerical data , Adolescent , Adult , Age Factors , Aged , Female , Humans , Length of Stay , Male , Middle Aged , Pneumonia/blood , Pneumonia/diagnosis , Pneumonia/enzymology , Prognosis , Reference Values , Renal Insufficiency/blood , Renal Insufficiency/diagnosis , Renal Insufficiency/enzymology , Respiratory Insufficiency/blood , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/enzymology , Sepsis/blood , Sepsis/diagnosis , Sepsis/enzymology , Sex Factors , Young AdultABSTRACT
Post-transcriptional control of gene expression is mediated by the interaction of RNA-binding proteins with their cognate mRNAs that specifically regulate their stability, localization and translation. mRNA-binding proteins are multifunctional and it has been proposed therefore that a combinatorial RNA-binding protein code exists that allows specific protein sub-complexes to control cytoplasmic gene expression under a range of pathophysiological conditions. We show that polypyrimidine tract-binding protein (PTB) is central to one such complex that forms in apoptotic cells. Thus, during apoptosis initiated by TNF-related apoptosis inducing ligand there is a change in the repertoire of RNA-binding proteins with which PTB interacts. We show that altering the cellular levels of PTB and its binding partners, either singly or in combination, is sufficient to directly change the rates of apoptosis with increased expression of PTB, YBX1, PSF and NONO/p54(nrb) accelerating this process. Mechanistically, we show that these proteins post-transcriptionally regulate gene expression, and therefore apoptotic rates, by interacting with and stimulating the activity of RNA elements (internal ribosome entry segments) found in mRNAs that are translated during apoptosis. Taken together, our data show that PTB function is controlled by a set of co-recruited proteins and importantly provide further evidence that it is possible to dictate cell fate by modulating cytoplasmic gene expression pathways alone.
Subject(s)
Apoptosis/drug effects , Polypyrimidine Tract-Binding Protein/metabolism , TNF-Related Apoptosis-Inducing Ligand/pharmacology , Cell Nucleus/metabolism , Cyclin T/genetics , Cyclin T/metabolism , DNA-Binding Proteins , HeLa Cells , Histone-Lysine N-Methyltransferase/genetics , Histone-Lysine N-Methyltransferase/metabolism , Humans , MCF-7 Cells , Nuclear Matrix-Associated Proteins/antagonists & inhibitors , Nuclear Matrix-Associated Proteins/genetics , Nuclear Matrix-Associated Proteins/metabolism , Octamer Transcription Factors/antagonists & inhibitors , Octamer Transcription Factors/genetics , Octamer Transcription Factors/metabolism , PTB-Associated Splicing Factor , Polypyrimidine Tract-Binding Protein/antagonists & inhibitors , Polypyrimidine Tract-Binding Protein/genetics , RNA Interference , RNA, Messenger/metabolism , RNA, Small Interfering/metabolism , RNA-Binding Proteins/antagonists & inhibitors , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Y-Box-Binding Protein 1/metabolismABSTRACT
The 5' untranslated region of the proto-oncogene c-myc contains an internal ribosome entry segment (IRES) and c-myc translation can therefore be initiated by internal ribosome entry as well as by cap-dependent mechanisms. It has been shown previously that in patients with multiple myeloma (MM) and in MM-derived cell lines there is a C to T mutation in the c-myc IRES that increases IRES activity and the corresponding synthesis of c-myc protein although it is not fully understood how this occurs. Our data show that two recently identified c-myc IRES trans-acting factors, Y-box binding protein 1 (YB-1) and polypyrimidine tract-binding protein 1 (PTB-1), bind more strongly (approximately 3.5- and 2-fold respectively) to the mutated version of the c-myc IRES and in vitro these proteins exert their effect synergistically to stimulate IRES activity of the mutant IRES 4.5-fold more than the wild-type version. Importantly, we show that there is a strong correlation between the expression of PTB-1, YB-1 and c-myc in MM-derived cell lines, suggesting that by reducing either PTB-1 or YB-1 protein levels it is possible to decrease c-myc expression and inhibit cell proliferation of MM-derived cell lines.
