Trauma-induced lung injury is associated with infiltration of activated TLR expressing myeloid cells.

INTRODUCTION: Traumatic injury with hemorrhage (TH) induces an inflammatory response in the lung resulting in lung injury involving activation of immune cells including myeloid cells (i.e., monocytes, granulocytes and macrophages), in part through TLRs. TLRs, via the recognition of damage associated molecular patterns (DAMPs), are a key link between tissue injury and inflammation. Nonetheless, the role of TLRs in myeloid cell activation and TH-induced lung injury remains ill defined. METHODS: C57BL/6 male mice were subjected to TH or sham treatment (n = 4-6 /group). Lung tissues were collected two hrs. after injury. Single cells were isolated from the lungs by enzymatic digestion and myeloid cell TLR expression and activation (i.e., cytokine production) were assessed using flow cytometry techniques. RESULTS: The injury was associated with a profound change in the lung myeloid cell population. TH markedly increased lung CD11b+ monocyte numbers and Gr1+ granulocyte numbers as compared to sham mice. The number of cells expressing TLR2, TLR4, and TLR9 were increased 4-7 fold in the TH mice. Activation for elevated cytokine (TNFα, IL-10) production was observed in the lung monocyte population of the TH mice. CONCLUSIONS: Trauma-induced lung injury is associated with infiltration of the lungs with TLR expressing myeloid cells that are activated for elevated cytokine responses. This elevation in TLR expression may contribute to DAMP-mediated pulmonary complications of an inflammatory nature and warrants further investigation.

Memory for previously viewed radiographs and the effect of prior knowledge of memory task.

RATIONALE AND OBJECTIVES: To investigate the effect of being forewarned that they would be asked to identify repeated images on radiologists' recognition of previously interpreted versus new chest radiographs. MATERIALS AND METHODS: Thirteen radiologists viewed 60 posterior-anterior chest radiographs, 31 with and 29 without nodules, in two sets of 40 images each. Eight radiologists were forewarned and five radiologists were not forewarned of the memory task. Twenty images in each of the two sets were unique to each set and 20 images occurred in both sets. The readers indicated the presence or absence of any nodules during both readings, and in the second reading session they also indicated whether they thought each image had also occurred in the first reading. RESULTS: There was no significant difference in recognition memory performance between forewarned and not-forewarned readers. Overall accuracy in distinguishing previously-viewed from new images was 60.7%. CONCLUSIONS: Being forewarned of the memory task did not improve recognition memory.

Detection of ß cell death in diabetes using differentially methylated circulating DNA.

In diabetes mellitus, ß cell destruction is largely silent and can be detected only after significant loss of insulin secretion capacity. We have developed a method for detecting ß cell death in vivo by amplifying and measuring the proportion of insulin 1 DNA from ß cells in the serum. By using primers that are specific for DNA methylation patterns in ß cells, we have detected circulating copies of ß cell-derived demethylated DNA in serum of mice by quantitative PCR. Accordingly, we have identified a relative increase of ß cell-derived DNA after induction of diabetes with streptozotocin and during development of diabetes in nonobese diabetic mice. We have extended the use of this assay to measure ß cell-derived insulin DNA in human tissues and serum. We found increased levels of demethylated insulin DNA in subjects with new-onset type 1 diabetes compared with age-matched control subjects. Our method provides a noninvasive approach for detecting ß cell death in vivo that may be used to track the progression of diabetes and guide its treatment.