This 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
View SamplesThis is a phase I randomized, double-blind, placebo-controlled crossover study which sought to evaluate a single dose of AMG 811, an anti-IFN antibody, in patients with DLE.
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 SamplesThis study is designed to determine effects on parameters routinely measured in toxicology studies
No associated publication
Sex, Specimen part, Treatment, Subject, Time
View SamplesGene expression profiling has been used as a tool to gain mechanistic understanding of adverse effects in response to compound exposure. However, little is known about how the common handling procedures of experimental animals during a preclinical study alter their baseline gene expression. We report on gene expression changes in the livers of female Sprague-Dawley rats following common handling procedures. Insight on baseline gene expression changes obtained in this study will allow us to evaluate how these changes may affect interpretation of gene expression profiles following compound exposure. Rats were divided into three groups (n = 10 per group): one group was not subjected to handling procedures, euthanized on day 2, and served as controls for both handled groups. Animals in the other two groups were weighed, subjected to restraint in Broome restrainers, and administered water via oral gavage daily for 1 or 4 days with tail vein blood collections at 1, 2, 4, and 8 hours postdose on days 1 and 4 followed by euthanasia on day 2 or 5. Significantly altered genes were identified in livers of animals following 1 or 4 days of handling when compared to the unhandled animals. Gene changes in animals handled for 4 days were similar to those handled for 1 day, suggesting a lack of habituation. The altered genes were primarily immune function related genes. These findings, along with a correlating increase in corticosterone levels suggest that common handling procedures may cause a minor immune system perturbance.
No associated publication
Sex, Age, Specimen part, Treatment, Time
View SamplesTo 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
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