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- Brown, Kelly, 1973, et al.
(författare)
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Robust TLR4-induced gene expression patterns are not an accurate indicator of human immunity.
- 2010
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Ingår i: Journal of translational medicine. - : Springer Science and Business Media LLC. - 1479-5876. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: Activation of Toll-like receptors (TLRs) is widely accepted as an essential event for defence against infection. Many TLRs utilize a common signalling pathway that relies on activation of the kinase IRAK4 and the transcription factor NF-kappaB for the rapid expression of immunity genes. METHODS: 21K DNA microarray technology was used to evaluate LPS-induced (TLR4) gene responses in blood monocytes from a child with an IRAK4-deficiency. In vitro responsiveness to LPS was confirmed by real-time PCR and ELISA and compared to the clinical predisposition of the child and IRAK4-deficient mice to Gram negative infection. RESULTS: We demonstrated that the vast majority of LPS-responsive genes in IRAK4-deficient monocytes were greatly suppressed, an observation that is consistent with the described role for IRAK4 as an essential component of TLR4 signalling. The severely impaired response to LPS, however, is inconsistent with a remarkably low incidence of Gram negative infections observed in this child and other children with IRAK4-deficiency. This unpredicted clinical phenotype was validated by demonstrating that IRAK4-deficient mice had a similar resistance to infection with Gram negative S. typhimurium as wildtype mice. A number of immunity genes, such as chemokines, were expressed at normal levels in human IRAK4-deficient monocytes, indicating that particular IRAK4-independent elements within the repertoire of TLR4-induced responses are expressed. CONCLUSIONS: Sufficient defence to Gram negative immunity does not require IRAK4 or a robust 'classic' inflammatory and immune response.
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| 2. |
- Rautaharju, PM, et al.
(författare)
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Comparability of 12-lead ECGs derived from EASI leads with standard 12-lead ECGs in the classification of acute myocardial ischemia and old myocardial infarction
- 2002
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Ingår i: Journal of Electrocardiology. - : Elsevier BV. - 1532-8430 .- 0022-0736. ; 35:4, part 2, s. 35-39
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Tidskriftsartikel (refereegranskat)abstract
- We compared 12-lead electrocardiograms (ECGs) derived with an improved transformation matrix from EASI leads and standard 12-lead ECGs in the detection of acute myocardial ischemia and old infarction (MI). For the ischemia test, we used ECGs of 40 patients recorded prior to and at peak inflation during percutaneous transluminal coronary angioplasty, and for old MI we used test ECGs of 382 non-MI subjects and of 472 patients with prior MI documented by enzyme findings. Two experienced ECG readers served as separate, independent standards for lead-set comparisons, and the Philips ECG analysis program also classified the ECGs. The results showed no significant differences between the two lead sets in the detection of acute inflation-induced ischemia or of old MI according to coding by the electrocardiographers or the computer program. No significant differences were found between the electrocardiographers and the lead sets for acute ischemia. Classification differences between the electrocardiographers were larger than those between the lead sets for acute and old MI and were significant for the latter (P <.001). A more detailed comparison of the lead sets suggested a possible need for modified old-MI criteria and optimization of ST classification thresholds for acute ischemic injury, specific for the EASI 12-lead ECG. We conclude that the EASI-derived 12-lead ECG deserves serious consideration as an alternative to the standard 12-lead ECG in emergency situations and for monitoring in acute-care setting.
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