Idiopathic hypereosinophilic syndrome with skull base involvement.

Idiopathic hypereosinophilic syndrome (HES) is a heterogeneous disorder characterized by prolonged eosinophilia without an identifiable cause, ultimately resulting in organ dysfunction. Three major types of neurologic involvement have been well defined in HES; however, to our knowledge, inflammatory pseudotumor (IPT) in association with HES has not been reported. We present a case of IPT of the skull base in a patient with HES that suggests that HES may result in an exaggerated immunologic or inflammatory response leading to the formation of IPT.

Amino acid sequence environment modulates the disruption by osteogenesis imperfecta glycine substitutions in collagen-like peptides.

Ostoegenesis imperfecta (OI) or "brittle bone" disease is associated with mutations in the genes for type I collagen chains and produces variable phenotypes, ranging from lethal cases at birth to mild cases with increased bone fractures. The most common OI mutations are single base substitutions leading to replacement of Gly by another residue, breaking the typical (Gly-X-Y)n repeating sequence pattern of the collagen triple-helix. Triple-helical peptides were designed to focus on residues 892-921 of the alpha1 chain of type I collagen, where two OI Gly-->Ser mutations are found in close proximity, a mild mutation at site 901 and a lethal mutation at site 913. Peptides were designed to include amino acid sequences around these mutation sites, and were synthesized with the normal sequence or with the Gly-->Ser mutated sequence. The peptide including the normal sequence residues 892-909 with four Gly-Pro-Hyp triplets at the C-terminus formed a stable triple-helix, and introduction of a Ser residue for Gly at the 901 mutation site led to a 50% loss of triple-helix content and a decrease in thermal stability, with little effect on folding. A peptide including residues 904-921 again formed a stable triple-helix, but the introduction of the Gly-->Ser substitution at site 913 led to a much greater decrease in thermal stability. These studies demonstrate the impact of local sequences flanking the Gly substitution on structural consequences and support the concept of variability and regional effects along the collagen molecule.