Neutralizing IgG antibodies are a biomarker of sustained efficacy after peanut oral immunotherapy.

Background: Clinical efficacy of oral immunotherapy (OIT) has been associated with the induction of blocking antibodies, particularly those capable of disrupting IgE-allergen interactions. Previously, we identified mAbs to Ara h 2 and structurally characterized their epitopes.

Objective: We investigated longitudinal changes during OIT in antibody binding to conformational epitopes and correlated the results with isotype and clinical efficacy.

An engineered immunomodulatory IgG1 Fc suppresses autoimmune inflammation through pathways shared with i.v. immunoglobulin.

Immunoglobulin G (IgG) antibodies in the form of high-dose intravenous immunoglobulin (IVIG) exert immunomodulatory activity and are used in this capacity to treat inflammatory and autoimmune diseases. Reductionist approaches have revealed that terminal sialylation of the single asparagine-linked (N-linked) glycan at position 297 of the IgG1 Fc bestows antiinflammatory activity, which can be recapitulated by introduction of an F241A point mutation in the IgG1 Fc (FcF241A). Here, we examined the antiinflammatory activity of CHO-K1 cell-produced FcF241A in vivo in models of autoimmune inflammation and found it to be independent of sialylation.

Improved low molecular weight Myc-Max inhibitors.

Compounds that selectively prevent or disrupt the association between the c-Myc oncoprotein and its obligate heterodimeric partner Max (Myc-Max compounds) have been identified previously by high-throughput screening of chemical libraries. Although these agents specifically inhibit the growth of c-Myc-expressing cells, their clinical applicability is limited by their low potency. We describe here several chemical modifications of one of these original compounds, 10058-F4, which result in significant improvements in efficacy.

Elucidation of stannin function using microarray analysis: implications for cell cycle control.

Stannin (Snn) is a highly conserved, vertebrate protein whose cellular function is unclear. We have recently demonstrated in human umbilical vein endothelial cells (HUVECs) that Snn gene expression is significantly induced by tumor necrosis factor-alpha (TNF-alpha) in a protein kinase C-epsilon (PKC-epsilon)-dependent manner. In HUVEC, TNF-alpha stimulation of HUVECs results in altered gene expression, and a slowing or halting of cell growth.

The protein stannin binds 14-3-3zeta and modulates mitogen-activated protein kinase signaling.

The molecular mechanisms underlying the selective toxicity of trimethyltin (TMT) remain unclear. Stannin (Snn), a protein preferentially expressed in TMT-sensitive cells, provides a direct link to the molecular basis for TMT toxicity. Recent evidence demonstrated that Snn peptides bind and de-alkylate TMT to dimethyltin (DMT); Snn may mediate both TMT and DMT toxicity.

Protein kinase C epsilon regulates tumor necrosis factor-alpha-induced stannin gene expression.

Stannin (Snn) is a highly conserved vertebrate protein that has been closely linked to trimethyltin (TMT) toxicity. We have previously demonstrated that Snn is required for TMT-induced cell death. Others have shown that TMT exposure results in tumor necrosis factor-alpha (TNFalpha) production and that TNFalpha treatment induces Snn gene expression in human umbilical vein endothelial cells (HUVECs).

Stannin, a protein that localizes to the mitochondria and sensitizes NIH-3T3 cells to trimethyltin and dimethyltin toxicity.

Stannin (Snn) is a highly conserved, 88-amino acid protein that may mediate the selective toxicity of organotins. Snn is localized in tissues with known sensitivity to trimethyltin (TMT), including the central nervous system, immune system, spleen, kidney and lung. Cells in culture that do not express Snn show considerable resistance to TMT toxicity.

The methyl-CpG binding protein MBD1 interacts with the p150 subunit of chromatin assembly factor 1.

DNA promoter hypermethylation has been shown to be a functional mechanism of transcriptional repression. This epigenetic gene silencing is thought to involve the recruitment of chromatin-remodeling factors, such as histone deacetylases, to methylated DNA via a family of proteins called methyl-CpG binding proteins (MBD1 to -4). MBD1, a member of this family, exhibits transcription-repressive activity, but to this point no interacting protein partners have been identified.