Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening systemic illness of abrupt onset and unknown cause. Proteolysis of the blood-clotting protein von Willebrand factor (VWF) observed in normal plasma is decreased in TTP patients. However, the identity of the responsible protease and its role in the pathophysiology of TTP remain unknown. We performed genome-wide linkage analysis in four pedigrees of humans with congenital TTP and mapped the responsible genetic locus to chromosome 9q34. A predicted gene in the identified interval corresponds to a segment of a much larger transcript, identifying a new member of the ADAMTS family of zinc metalloproteinase genes (ADAMTS13). Analysis of patients' genomic DNA identified 12 mutations in the ADAMTS13 gene, accounting for 14 of the 15 disease alleles studied. We show that deficiency of ADAMTS13 is the molecular mechanism responsible for TTP, and suggest that physiologic proteolysis of VWF and/or other ADAMTS13 substrates is required for normal vascular homeostasis.

Histologic study of the effects of occlusal hypofunction following antagonist tooth extraction in the rat.

A histologic study was done to observe the influence of occlusal hypofunction on periodontal tissues and the physiologic drift process, and to elucidate the origin of periodontal ligament narrowing. Twenty-four Wistar rats were used. Hypofunction was induced by extracting the right maxillary molars. Histologic observations were reported on the right lower jaws which were fixed, decalcified, sectioned and stained according to classical histologic methods. Two groups of five animals each were used for a complementary study study using sequential fluorescent labeling in order to evaluate the bone formation rate. After 15 days of hypofunction, the periodontal ligament was obviously narrowed and its structure was disorganized. Woven-bone formation was noted at the top of the interradicular septa, at the bottom of the sockets and along their modeling sides. At 30 days and at intervals up to 3 months, the periodontal ligament remained disorganized and narrowed. The newly-formed bone was engaged in a maturation process. Nevertheless, osteoporosis was also observed at the inferior part of the interradicular septa. Fluorescent labeling confirmed the histologic findings and showed that the induced bone formation is related to periodontal ligament narrowing and the supra-eruption process.