Three-dimensional condylar changes from Herbst appliance and multibracket treatment: A comparison with matched Class II elastics.

INTRODUCTION: The purpose of this study was to quantify and qualify the 3-dimensional (3D) condylar changes using mandibular 3D regional superimposition techniques in adolescent patients with Class II Division 1 malocclusions treated with either a 2-phase or single-phase approach. METHODS: Twenty patients with Herbst appliances who met the inclusion criteria and had cone-beam computed tomography (CBCT) images taken before, 8 weeks after Herbst removal, and after the completion of multibracket appliance treatment constituted the Herbst group. They were compared with 11 subjects with Class II malocclusion who were treated with elastics and multibracket appliances and who had CBCT images taken before and after treatment. Three-dimensional models generated from the CBCT images were registered on the mandible using 3D voxel-based superimposition techniques and analyzed using semitransparent overlays and point-to-point measurements. RESULTS: The magnitude of lateral condylar growth during the orthodontic phase (T2-T3) was greater than that during the orthopedic phase (T1-T2) for all condylar fiducials with the exception of the superior condyle (P <0.05). Conversely, posterior condylar growth was greater during the orthopedic phase than the subsequent orthodontic phase for all condylar fiducials (P <0.05). The magnitude of vertical condylar development was similar during both the orthopedic (T1-T2) and orthodontic phases (T2-T3) across all condylar fiducials (P <0.05). Posterior condylar growth during the orthodontic phase (T2-T3) of the 2-phase approach decreased for all condylar fiducials with the exception of the posterior condylar fiducial (P <0.05) when compared with the single-phase approach. CONCLUSIONS: Two-phase treatment using a Herbst appliance accelerates condylar growth when compared with a single-phase regime with Class II elastics. Whereas the posterior condylar growth manifested primarily during the orthopedic phase, the vertical condylar gains occurred in equal magnitude throughout both phases of the 2-phase treatment regime.

Spinal learning in the adult mouse using the Horridge paradigm.

The spinal cord is endogenously capable of several forms of adaptive plasticity and learning, including functional re-training, instrumental, and Pavlovian learning. Understanding the mechanisms of spinal plasticity could lead to improved therapies for spinal cord injury and other neuromotor disorders. We describe and demonstrate techniques for eliciting spinal learning in the adult mouse using the Horridge paradigm. In the Horridge paradigm, instrumental learning occurs when a nociceptive leg stimulus is made to be contingent on leg position and the spinal cord learns to maintain the ankle in a flexed position. Using fine-wire intramuscular stimulating electrodes, an inexpensive real-time video tracking system, and DC current stimulation, we were able to elicit instrumental spinal learning from mouse lumbrosacral spinal cords that were functionally isolated from the brain. This technique makes it more feasible to use the powerful genetic manipulations available in mice to better understand the processes of spinal learning, memory, and plasticity.

Human sterile alpha motif domain 9, a novel gene identified as down-regulated in aggressive fibromatosis, is absent in the mouse.

BACKGROUND: Neoplasia can be driven by mutations resulting in dysregulation of transcription. In the mesenchymal neoplasm, aggressive fibromatosis, subtractive hybridization identified sterile alpha motif domain 9 (SAMD9) as a substantially down regulated gene in neoplasia. SAMD9 was recently found to be mutated in normophosphatemic familial tumoral calcinosis. In this study, we studied the gene structure and function of SAMD9, and its paralogous gene, SAMD9L, and examined these in a variety of species. RESULTS: SAMD9 is located on human chromosome 7q21.2 with a paralogous gene sterile alpha motif domain 9 like (SAMD9L) in the head-to-tail orientation. Although both genes are present in a variety of species, the orthologue for SAMD9 is lost in the mouse lineage due to a unique genomic rearrangement. Both SAMD9 and SAMD9L are ubiquitously expressed in human tissues. SAMD9 is expressed at a lower level in a variety of neoplasms associated with beta-catenin stabilization, such as aggressive fibromatosis, breast, and colon cancers. SAMD9 and SAMD9L contain an amino-terminal SAM domain, but the remainder of the predicted protein structure does not exhibit substantial homology to other known protein motifs. The putative protein product of SAMD9 localizes to the cytoplasm. In vitro data shows that SAMD9 negatively regulates cell proliferation. Over expression of SAMD9 in the colon cancer cell line, SW480, reduces the volume of tumors formed when transplanted into immune-deficient mice. CONCLUSION: SAMD9 and SAMD9L are a novel family of genes, which play a role regulating cell proliferation and suppressing the neoplastic phenotype. This is the first report as far as we know about a human gene that exists in rat, but is lost in mouse, due to a mouse specific rearrangement, resulting in the loss of the SAMD9 gene.

An association between the 4G polymorphism in the PAI-1 promoter and the development of aggressive fibromatosis (desmoid tumor) in familial adenomatous polyposis patients.

Aggressive fibromatosis is a mesenchymal neoplasm associated with mutations resulting in beta-catenin mediated transcriptional activation. Plasminogen activator inhibitor-1 (PAI-1) is expressed at a high level in aggressive fibromatosis, and using transgenic mice, we found that PAI-1 plays an important role in aggressive fibromatosis tumor formation. Familial adenomatous polyposis is associated with Adenomatous Polyposis Coli gene mutations resulting in beta-catenin mediated transcriptional activation, yet only some patients develop aggressive fibromatosis. Since PAI-1 expression is influenced by a promoter 4G/5G polymorphism, we investigated the incidence of this polymorphism in familial adenomatous polyposis patients who did and who did not develop aggressive fibromatosis, as well as sporadic aggressive fibromatosis patients. There was a trend towards association of the 4G allele (associated with high PAI-1 expression) with the development of aggressive fibromatosis in familial adenomatous polyposis patients (50% vs. 19%, P = 0.1). In familial adenomatous polyposis patients who did not develop aggressive fibromatosis, there was a significantly lower proportion of patients with a 4G allele compared to the healthy control (19% vs. 51%, P = 0.0286). The lower incidence of 4G polymorphism in the PAI-1 promoter may be preventive against the development of aggressive fibromatosis. This data provides additional evidence supporting an important role for PAI-1 in the pathogenesis of aggressive fibromatosis.