Synthetic glucocorticoids are used therapeutically for a variety of conditions. Both the efficacy and toxicity of corticosteroids arise from their pharmacologically exaggerated effects on target and non-target tissues. For example, beneficial effects deriving from inhibition of the immune system are accompanied by toxic side effects that include hyperglycemia, dyslipidaemia, muscle wasting, fatty liver, and an increased risk of atherosclerosis. Our previous time series analyzing the gene expression responses following a single bolus dose of methylprednisolone (MPL) provided interesting insight into the genomic responses of liver, skeletal muscle and kidney to corticosteroids. One objective with such extensive gene array time series data is to cluster genes into groups with common mechanisms of regulation. These clusters can be used to construct biologically rational models of the cascade of events that result in broad systemic phenomena such as diabetes, with the ultimate aim of therapeutic intervention at specific steps within the cascade
Microarray analysis of the temporal response of skeletal muscle to methylprednisolone: comparative analysis of two dosing regimens.
Time
View SamplesExposure to Polychlorobiphenyls (PCBs) is known to cause serious health effects in human but the gene expression profiles leading to development of differnet diseases and disorders are not fully understood. The knowledge of global gene expression will help us to devlop early disease or disorder biomarkers for PCB induced health effects.
Global gene expression and Ingenuity biological functions analysis on PCBs 153 and 138 induced human PBMC in vitro reveals differential mode(s) of action in developing toxicities.
Sex, Age, Specimen part, Treatment
View SamplesExposure to Polychlorobiphenyls (PCBs) is known to cause serious health effects in human but the gene expression profiles leading to development of differnet diseases and disorders are not fully understood. The knowledge of global gene expression will help us to devlop early disease or disorder biomarkers for PCB induced health effects.
Global gene expression and Ingenuity biological functions analysis on PCBs 153 and 138 induced human PBMC in vitro reveals differential mode(s) of action in developing toxicities.
Sex, Age, Specimen part, Treatment
View SamplesIn intact animals, time of drug administration may be an important factor influencing drug response. Our general goal seeks to incorporate circadian time into the study of corticosteroid regulated gene expression. This study is designed to examine fluctuations in gene expression in skeletal muscle within the 24 hour circadian cycle in normal animals. Circadian time is relevant to designing optimal corticosteroid dosing regimens. Since levels of endogenous steroid exhibit circadian fluctuations, it is our hypothesis that the expression of genes controlled by corticosteroids either directly or indirectly will also exhibit a circadian pattern in normal animals.
Relationships between circadian rhythms and modulation of gene expression by glucocorticoids in skeletal muscle.
No sample metadata fields
View SamplesEsophageal carcinoma is the third most common gastrointestinal malignancy worldwide and is generally unresponsive to therapy. African Americans have an increased risk for esophageal squamous cell cancer (ESCC), the subtype that shows marked variation in geographic frequency. To identify key genes involved in ESC carcinogenesis in African Americans we conducted microarray expression profiling and found a significant dysregulation of genes encoding stress response and drug-metabolizing enzymes, mainly in NRF2 pathway. The involvement of NRF2 mediated oxidative damage represent a key step in the evolution of African American ESCC. Loss of activity of these enzymes would confer increased sensitivity of esophageal cells to xenobiotics, such as alcohol and tobacco smoke, and may account for the high incidence of ESCC in this ethnic group. The differential expression profile also indicates an inflammatory component and tissue regeneration in ESCC tumorigenesis. Together, these findings suggest a remarkable interplay of genetic and environmental factors in the pathogenesis of African American ESCC.
African-American esophageal squamous cell carcinoma expression profile reveals dysregulation of stress response and detox networks.
Race
View SamplesExposure to Polychlorobiphenyls (PCBs) is known to cause serious health effects in human but the gene expression profiles leading to development of differnet diseases and disorders are not fully understood. The knowledge of global gene expression will help us to devlop early disease or disorder biomarkers for PCB induced health effects.
Transcriptional profiling and biological pathway analysis of human equivalence PCB exposure in vitro: indicator of disease and disorder development in humans.
Sex, Age, Specimen part, Treatment
View SamplesExposure to polychlorobiphenyls (PCBs) is known to cause serious health effects in human but the gene expression profiles leading to development of different diseases and disorders are not fully understood. The knowledge of global gene expression will help us to develop early disease or disorder biomarkers for PCB-induced health effects.
Differential gene expression and a functional analysis of PCB-exposed children: understanding disease and disorder development.
Sex, Age, Specimen part, Race
View SamplesExposure to Persistant Organic Pollutants (POPs) is known to cause serious health effects in human but the gene expression profiles leading to development of differnet diseases and disorders are not fully understood. The knowledge of global gene expression will help us to devlop early disease or disorder biomarkers for POP induced health effects.
Analysis of the toxicogenomic effects of exposure to persistent organic pollutants (POPs) in Slovakian girls: correlations between gene expression and disease risk.
Sex, Age, Specimen part, Race
View SamplesWith advances in supportive therapy in the last two decades, mortality rates from ALI/ARDS have improved somewhat, but remain around 30 to 40% with significant morbidity in survivors. Several promising treatments are in various stages of evaluation, but many have failed to prove beneficial in large randomized clinical trials (RCT). The first definitive step forward in ALI therapeutics occurred recently as a result of a large RCT demonstrating a mortality decrease from 40 to 31% with the use of low-volume ventilation strategies. From this, it is clear that the opportunity for successful intervention in ALI exists. However, therapeutic advances remain frustrated by the lack of complete understanding of ALI pathophysiology. This stresses the importance of integrating basic and clinical research of the molecular pathogenesis of this disease. The conclusions of a recent National Heart, Lung, and Blood Institute (NHLBI) Working Group on ALI support this type of research as a priority for future investigations of ALI. One of the areas of research given priority by this ALI Working Group is the issue of ALI severity progression and the role of cells of innate immunity in this process. Currently, the processes that determine which ALI patients progress to ARDS and which do not are unclear. As with many phenotype differences, there is most likely a genetic component involved. The basis for this has been demonstrated. For example, a surfactant protein B (SP-B) polymorphism appears to increase a patients risk of developing ALI from pneumonia. Additionally, a polymorphism in the promoter region of the gene for interleukin-6 (IL-6) has been associated with a poor prognosis in patients with ARDS. Understanding the intracellular processes of these genes and the cells expressing them in ALI progression could lead to the identification of molecular markers of ALI severity and eventually to the development of targeted therapies. An examination of genetically uniform animals will provide a clearer insight into the interaction between immune cells in ALI progression as well as guide future human experiments.
Sepsis alters the megakaryocyte-platelet transcriptional axis resulting in granzyme B-mediated lymphotoxicity.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Multi-omic integrated networks connect DNA methylation and miRNA with skeletal muscle plasticity to chronic exercise in Type 2 diabetic obesity.
Sex, Specimen part, Treatment
View Samples