Impact of Human FcγR Gene Polymorphisms on IgG-Triggered Cytokine Release: Critical Importance of Cell Assay Format.

Monoclonal antibody (mAb) immunotherapy has transformed the treatment of allergy, autoimmunity, and cancer. The interaction of mAb with Fc gamma receptors (FcγR) is often critical for efficacy. The genes encoding the low-affinity FcγR have single nucleotide polymorphisms (SNPs) and copy number variation that can impact IgG Fc:FcγR interactions.

Engineered hexavalent Fc proteins with enhanced Fc-gamma receptor avidity provide insights into immune-complex interactions.

Autoantibody-mediated diseases are currently treated with intravenous immunoglobulin, which is thought to act in part via blockade of Fc gamma receptors, thereby inhibiting autoantibody effector functions and subsequent pathology. We aimed to develop recombinant molecules with enhanced Fc receptor avidity and thus increased potency over intravenous immunoglobulin. Here we describe the molecular engineering of human Fc hexamers and explore their therapeutic and safety profiles.

An assessment of the statistical methods used to analyse toxicology studies.

The Statisticians in the Pharmaceutical Industry Toxicology Special Interest Group has collated and compared statistical analysis methods for a number of toxicology study types including general toxicology, genetic toxicology, safety pharmacology and carcinogenicity. In this paper, we present the study design, experimental units and analysis methods.

Effect of acarbose on milk yield and composition in early-lactation dairy cattle fed a ration to induce subacute ruminal acidosis.

Subacute ruminal acidosis reduces lactation performance in dairy cattle and most often occurs in animals fed a high concentrate:forage ration with large amounts of readily fermentable starch, which results in increased production of volatile fatty acids and lactic acid and a reduction in ruminal pH. Acarbose is commercially available (Glucobay, Bayer, Wuppertal, Germany) and indicated for the control of blood glucose in diabetic patients. In cattle, acarbose acts as an alpha-amylase and glucosidase inhibitor that slows the rate of degradation of starch to glucose, thereby reducing the rate of volatile fatty acid production and maintaining rumen pH at higher levels.