A distal conserved sequence element controls Ifng gene expression by T cells and NK cells.

Chromatin dynamics that regulate Ifng gene expression are incompletely understood. By using cross-species comparative sequence analyses, we have identified conserved noncoding sequences (CNSs) upstream of the Ifng gene, one of which, located -22 kb from the transcriptional start site, contains clustered consensus binding sequences of transcription factors that function in T cell differentiation. CNS-22 was uniquely associated with histone modifications typical of accessible chromatin in both T helper 1 (Th1) and Th2 cells and demonstrated significant and selective T-bet (T-box transcription factor expressed in T cells, Tbx21)-dependent binding and enhancer activity in Th1 cells.

Toll-like receptor signaling inhibits structural development of the distal fetal mouse lung.

We tested the hypothesis that innate immune signaling in utero could disrupt the structural development of the fetal lung, contributing to the pathogenesis of bronchopulmonary dysplasia. Injection of Escherichia coli lipopolysaccharide (LPS) into the amniotic fluid of E15 BALB/cJ mice increased the luminal volume density of fetal mouse lungs at embryonic day (E) 17 and E18. LPS also increased luminal volume and decreased distal lung branching in fetal mouse lung explants.

Oral administration of an Apo A-I mimetic Peptide synthesized from D-amino acids dramatically reduces atherosclerosis in mice independent of plasma cholesterol.

When apolipoprotein A-I mimetic peptides synthesized from either D- or L-amino acids were given orally to LDL receptor-null mice, only the peptide synthesized from D-amino acids was stable in the circulation and enhanced the ability of HDL to protect LDL against oxidation. The peptide synthesized from L-amino acids was rapidly degraded and excreted in the urine. When a peptide synthesized from D-amino acids (D-4F) was administered orally to LDL receptor-null mice on a Western diet, lesions decreased by 79%.

Identification of a human glioma-associated growth factor gene, granulin, using differential immuno-absorption.

Identification of the genes that are differentially expressed in brain tumor cells but not in normal brain cells is important for understanding the molecular basis of these neurological cancers and for defining possible targets for therapeutic intervention. In an effort to discover potentially antigenic proteins that may be involved in the malignant transformation and progression of human glioblastomas, a novel antibody-based approach was developed to identify and isolate gene products that are expressed in brain tumors versus normal brain tissue. Using this method, whereby tumor-specific antibodies were isolated and used to screen a glioblastoma cDNA expression library, 28 gene products were identified.

A humoral response to oligodendrocyte-specific protein in MS: a potential molecular mimic.

Objective: To determine the antibody response to oligodendrocyte-specific protein (OSP) in patients with MS.

Background: OSP is a recently identified CNS-specific myelin protein that is abundant and therefore a candidate autoantigen in MS.

Methods: The presence of anti-OSP antibodies was determined using Western blot analysis, peptide blots, and ELISA in patients with MS and in other neurologic and normal control subjects.