To evaluate and characterize gene expression changes and toxicity following oral gavage administration of AMG A & AMG B in male Sprague Dawley rats.
Application of genomics for identification of systemic toxicity triggers associated with VEGF-R inhibitors.
No sample metadata fields
View SamplesTo evaluate gene expression changes in mixed tissue samples used as process controls in male Sprague Dawley rats over time.
Assessment of repeated microarray experiments using mixed tissue RNA reference samples.
No sample metadata fields
View SamplesCD30L and CD30 are cell-surface glycoproteins in the TNF and TNFR superfamilies, respectively. Their expression is limited to immune cells and is tightly regulated. Cell surface expression of CD30 is restricted to subpopulations of activated T and B cells. CD30L is expressed primarily on activated T cells and subpopulations of B cells. The significance of CD30/CD30L interactions in immune regulation is not fully understood. Reported activities of CD30/CD30L in immune responses imply roles in regulation of secondary memory and antibody responses. Depending on the experimental system, both positive and negative regulation of immunoglobulin class switching and antibody production have been reported. Additionally, the biological activity of CD30/CD30L in animals has been difficult to assess due to the restricted and tightly regulated expression of this receptor-ligand pair. We generated transgenic mice with constitutive T cell specific overexpression of CD30L as a tool to help unravel the consequences of CD30/CD30L interactions in vivo. CD30L transgenic mice displayed a phenotype and responses to antigen challenge supporting a role for CD30/CD30L in promoting immunoglobulin class switching and antibody production. CD30L transgenic mice had increased numbers of germinal centers, elevated class-switched immunoglobulin isotypes, increased germinal center B cells and plasma cells, upregulation of genes indicative of B-cell activity, and exaggerated antibody responses to immune challenge. Interestingly, despite the heightened B-cell activity in CD30L transgenic mice, CD30L overexpression on T cells did not result in overt autoimmunity. Our results demonstrate that overexpression of CD30L on T cells promotes T cell-dependent B cell responses characterized by secondary antibody responses.
No associated publication
Sex
View SamplesThe purpose was to determine AcP- and AcPb-dependent gene responses to IL-1 by virally-reconstituting AcP-deficient mouse embryonic cortical neurons with CD25 (control), full length AcP, AcPb or the combination of both. A control population was transduced with a CD25-expressing virus. Half the samples were stimulated with IL-1-beta for four hours, RNA was analyzed by microarray.
A central nervous system-restricted isoform of the interleukin-1 receptor accessory protein modulates neuronal responses to interleukin-1.
Specimen part
View SamplesThe objective of the present study is to examine the potential role of the pregnane x receptor (PXR) in mice treated with an small molecule inhibitor for beta-secretase (CMP013)
No associated publication
Specimen part, Treatment
View SamplesMale, adolescent A/J mice (4-5 week old) were either infected (IP) with coxsackievirus B3 (CVB3; 105 pfu) or PBS. CVB3 is a cardiotropic virus which leads to cardiac inflammation and fibrosis within 9 days after IP injection. We wanted to know how the virus would impact long term cardiac function, and whether changes in cardiac function could be associated with cardiac transcriptional regulation. At days 3, 9 and 30 days post-infection, hearts were imaged with 2D echocardiography (Sonos 5500, Philips). Briefly, mice were anesthesized subcutaneously with ketamine (0.45mg/kg) and xylazine (0.03mg/kg). Mice were placed in a dorsal recumbency position and the following systolic and diastolic measurements were taken (N=5 heart beats) using an S-12 (12MHz; Sonos 5000, Philips) probe: parasternal long axis, and short axis at the level of the mitral valve and papillary muscles. Measurements were utilized for calculation of wall thickness and functional parameters. Then, heart tissues were flash frozen (N=4 mice/group except CVB3 infected 30 day samples N=2) for hybridization to Affymetrix MG U74Av2 arrays.
No associated publication
No sample metadata fields
View SamplesThis study is designed to compare and contrast the temporal and spatial changes in bone formation rates and transcriptional profiles in cortical and cancellous bone cell populations enriched by laser capture microdissection (LCM) in ovariectomized rats administered Scl-Ab by subcutaneous injection for up to 26 consecutive weeks, followed by a recovery period of up to 18 weeks.
Time-dependent cellular and transcriptional changes in the osteoblast lineage associated with sclerostin antibody treatment in ovariectomized rats.
Sex, Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Brief Report: Pharmacodynamics, Safety, and Clinical Efficacy of AMG 811, a Human Anti-Interferon-γ Antibody, in Patients With Discoid Lupus Erythematosus.
Specimen part, Disease
View SamplesChondro/osteoblastic and cardiovascular-disease associated genes are modulated in human coronary artery smooth muscle cells that calcify in the presence of phosphate and vitamin D sterols.
Chondro/osteoblastic and cardiovascular gene modulation in human artery smooth muscle cells that calcify in the presence of phosphate and calcitriol or paricalcitol.
No sample metadata fields
View SamplesSeven novel and potent Raf small molecule kinase inhibitors were evaluated in 7-day oral repeat-dose rat toxicity studies. All compounds tested induced hyperplasia in multiple tissues. Microarrays were used to investigate transciptional changes associated by treatment with a single compound to gain insight into the cellular changes that may contribute to the tissue hyperplasia.
Raf inhibition causes extensive multiple tissue hyperplasia and urinary bladder neoplasia in the rat.
Sex, Specimen part, Treatment
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