Sedimentation velocity analytical ultracentrifugation (SV-AUC) measurements confirmed that the aggregates were present in solution,

and revealed that the IgG1 aggregate was composed of a predominant species, whereas the IgG2 aggregate was heterogeneous. Tertiary structural changes accompanied antibody aggregation as evidenced by greater ANS (8-Anilino-1-naphthalene selleck kinase inhibitor sulfonic acid) binding to the aggregates over monomer, and differences in disulfide character and tryptophan environments between monomer, oligomer and aggregate species, as observed by near-UV circular dichroism (CD). Differences between subclasses were observed in the secondary structural changes that accompanied aggregation, particularly in the intermolecular beta-sheet and turn structures between the monomer and aggregate species. Free thiol determination showed similar to 2.4-fold lower quantity of free cysteines in the IgG1 subclass, consistent with the 2.4-fold reduction in aggregation of the IgG1 form when compared with IgG2 under these conditions. These observations suggested an important

role for disulfide bond formation, as well as secondary and tertiary structural transitions, during antibody aggregation. Such degradations may be minimized using appropriate formulation conditions.”
“Collagen type Ill glomerulopathy (Col3GP) is a rare renal disease characterized by massive glomerular accumulations of collagen type Ill. The Selleck AG-120 disease occurs in both humans and animals, and has been presumed to be heritable with an autosomal recessive inheritance pattern. The pathogenesis is unknown. We describe herein a condition of canine autosomal recessive Col3GP. This spontaneously occurring canine disease was incidentally diagnosed in six mongrel dogs. We then established and studied a pedigree segregating the disease to confirm the genetic nature and inheritance of canine

Col3GP. Twenty-nine percent of offspring (14/48) were affected, strongly supporting a simple autosomal recessive inheritance pattern. Kidney specimens were studied by light microscopy, electron AS1842856 datasheet microscopy (EM), immunohistochemistry and in situ hybridization. Characteristic findings of Col3GP previously reported in both humans and animals were demonstrated, including massive glomerular collagen type Ill deposition, and evidence of local mesangial collagen type Ill synthesis was found. We propose that canine Col3GP may serve as an animal model of human Col3GP. Our initial studies, using simple segregation analysis, showed that the Col3A1 gene was not involved in the disease.