Project description:In this study, we describe a potential novel gene expression biomarker for early post-irradiation biodosimetry purposes in BARD1 and we portray the practicability of the established gene expression biomarkers AEN, FDXR and DDB2 after exposure to low dose radiation. Future in-vivo experiments and the inclusion of novel examination procedures present promising approaches to gain further insights into transcriptomic changes after low-level exposure in medical imaging.
Project description:In this study, we display traceable impact of energetically-varying CT irradiation on gene regulation with common upregulation of five radiation-responsive genes after single-energy (80 kV or 150kV) and dual-energy CT (80kV + 150kV) exposure. Furthermore, no evdidence for an elevated radiobiological effectiveness in respect to transcriptional impact of low energy photons emitted during dual-energy CT was found.
Project description:The secretome of y-irradiated peripheral blood mononuclear cells (PBMC) is well known for its pleiotropic effects on tissue protection and regeneration. Irradiation of PBMC lead to necroptosis of a certain amount of PBMC in a cell-sorter analysis. The aim of this study was to investiage the trancriptomic changes of PBMC and PBMC subsets (CD4, CD8, CD19, CD56, CD14) in response to y-irradiation
Project description:Acute rejection (AR) of corneal transplants (CT) has a profound effect on subsequent graft survival but detailed immunological studies in human CT recipients are lacking. In this multi-site, cross-sectional study, clinical details and blood samples were collected from adults with clinically-diagnosed AR of full thickness (FT)-CT (n=35) and posterior lamellar (PL)-CT (n=21) along with Stable CT recipients (n=177) and adults with non-transplanted corneal disease (n=40). For those with AR, additional samples were collected 3 months later. Immune cell analysis was performed by whole-genome microarrays (whole blood) and high dimensional multi-color flow cytometry (peripheral blood mononuclear cells). For both, no activation signature was identified within the B cell and T cell repertoire at the time of AR diagnosis. Nonetheless, in FT- but not PL-CT recipients, AR was associated with differences in B cell maturity and regulatory CD4+ T-cell frequency compared to stable allografts. Our results suggest that, in contrast to solid organ transplants, genetic or cellular assays of peripheral blood are unlikely to be clinically exploitable for prediction or diagnosis of AR. However, further investigation of circulating B cell and T cell subpopulations may provide insights into the regulation of anti-donor immune response in human CT recipients with differing AR risk.
Project description:In the current study, we investigated the gene expression response of blood cells of non-human primates that were whole thorax irradiated with a 10.1 Gy total dose. Partial irradiation of the NHP in the upper half of the body allows study of late radiation lung injury while avoiding acute respiratory syndromes related to hematopoietic and gastrointestinal injury. In this study, we report gene expression changes in the peripheral blood, an easily biopsied tissue, up to a month after radiation injury to the lungs. We isolated total RNA from peripheral blood at 3 days before irradiation, and then from the same animals on days 2, 5 and 30 after irradiation. Using Agilent Human Whole Genome microarrays, we identified 1187 genes that were significantly differentially expressed across the 30-day time course of this study. We identified common biological functions affected that persisted across the 30-day study, such as immune response. Response to oxygen-containing compounds and bacterial molecules were implicated by the gene expression changes at both the earliest day 2 and last, day 30 time-point and suggest that although cells are being recycled through the body in a 30-day time course after exposure to irradiation, the damage to blood cells and immunity, specifically the response to infections might persist throughout the study .
Project description:Ionizing Radition is known to cause cell damage. Human peripheral blood mononuclear cells have long been used to study radiation induced gene expression profiling. Within this study we evaluated gene and microRNA expression alterations of human PBMC irradiated with 60 Gy g-ray. Cells were cultured for 2, 4 and 20h after irradiation before RNA was isolated and Agilent whole human GenomeOligo Microarray was performed.
Project description:Background: Non-human primates, such as Rhesus macaques, are a powerful model for studies of the cellular and physiological effects of radiation, development of radiation biodosimetry, and for understanding the impact of radiation on human health. Here, we study the effects of 4 Gy total body irradiation (TBI) at the molecular level out to 28 days and at the cytogenetic level out to 56 days after exposure. We combine the global transcriptomic and proteomic responses in peripheral whole blood to assess the impact of acute TBI exposure at extended times post irradiation. Results: The overall mRNA response in the first week reflects a strong inflammatory reaction, infection response with neutrophil and platelet activation. At 1 week, cell cycle arrest and re-entry processes were enriched among mRNA changes, oncogene-induced senescence and MAPK signaling among the proteome changes. Influenza life cycle and infection pathways initiate earlier in mRNA and are reflected among the proteomic changes during the first week. Transcription factor proteins SRC, TGF and NFATC2 were immediately induced at 1 day after irradiation with increased transcriptional activity as predicted by mRNA changes persisting up to 1 week. Cell counts revealed a mild / moderate hematopoietic acute radiation syndrome (H-ARS) reaction to irradiation with expected lymphopenia, neutropenia and thrombocytopenia that resolved within 30 days. Measurements of micronuclei per binucleated cell levels in cytokinesis-blocked T-lymphocytes remained high in the range 0.27-0.33 up to 28 days and declined to 0.1 by day 56. Conclusions: Overall, we show that the TBI 4 Gy dose in NHPs induces many cellular changes that persist up to 1 month after exposure, consistent with damage, death, and repopulation of blood cells.
Project description:This pilot clinical trial studies low-dose total body irradiation and donor peripheral blood stem cell transplant followed by donor lymphocyte infusion in treatment patients with non-Hodgkin lymphoma, chronic lymphocytic leukemia, or multiple myeloma. Giving total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When healthy stem cells from a donor are infused into the patient they may help the patient’s bone marrow make stem cells, red blood cells, white blood cells, and platelets. Once the donated stem cells begin working, the patient’s immune system may see the remaining cancer cells as not belonging in the patient’s body and destroy them. Giving an infusion of the donor’s white blood cells (donor lymphocyte infusion) may boost this effect.