No abstract

BackgroundAn arg120gly (R120G) missense mutation in HSPB5 (α-β-crystallin ), which belongs to the small heat shock protein (HSP) family, causes desmin-related cardiomyopathy (DRM), a muscle disease that is characterized by the formation of inclusion bodies, which can contain pre-amyloid oligomer intermediates (amyloid oligomer). While we have shown that small HSPs can directly interrupt amyloid oligomer formation, the in vivo protective effects of the small HSPs on the development of DRM is still uncertain.Methodology/Principal FindingsIn order to extend the previous in vitro findings to in vivo, we used geranylgeranylacetone (GGA), a potent HSP inducer. Oral administration of GGA resulted not only in up-regulation of the expression level of HSPB8 and HSPB1 in the heart of HSPB5 R120G transgenic (R120G TG) mice, but also reduced amyloid oligomer levels and aggregates. Furthermore, R120G TG mice treated with GGA exhibited decreased heart size and less interstitial fibrosis, as well as improved cardiac function and survival compared to untreated R120G TG mice. To address possible mechanism(s) for these beneficial effects, cardiac-specific transgenic mice expressing HSPB8 were generated. Overexpression of HSPB8 led to a reduction in amyloid oligomer and aggregate formation, resulting in improved cardiac function and survival. Treatment with GGA as well as the overexpression of HSPB8 also inhibited cytochrome c release from mitochondria, activation of caspase-3 and TUNEL-positive cardiomyocyte death in the R120G TG mice.Conclusions/SignificanceExpression of small HSPs such as HSPB8 and HSPB1 by GGA may be a new therapeutic strategy for patients with DRM.

Objective: The purpose of this study was to explore the association of hypodontia patterns and variations in craniofacial morphology in Japanese orthodontic patients. Materials and Methods: A total of 50 girls with hypodontia (the total group) were selected and categorized into anterior, posterior, and anterior-posterior groups according to the location of the congenitally missing teeth. By using the lateral cephalograms of each subject, 28 angular and 37 linear measurements were made. The cephalometric data were statistically analyzed and compared among the groups and with the Japanese cephalometric standards from 36 age-matched female subjects without hypodontia or malocclusion (the control group). Results: Every hypodontia group showed shorter anterior and overall cranial base lengths, shorter maxillary length, greater retroclination and elongation of mandibular incisors, and a larger interincisal angle than the control group. The total and anterior-posterior groups especially exhibited a significantly more prognathic mandible, larger retroclination of maxillary incisors, and a more counterclockwise-rotated occlusal plane. Furthermore, these skeletal and dental deviations were more remarkable in the anterior-posterior group than in either the anterior or the posterior group. Anterior hypodontia exerted as much influence on craniofacial morphology as posterior hypodontia. Conclusions: When orthodontic treatment is performed on patients with hypodontia, not only the number but also the distribution of missing teeth should be taken into consideration, though there was no significant difference in craniofacial morphology between anterior hypodontia and posterior hypodontia.

The purpose of this study was to examine the effects of advanced hypodontia on craniofacial morphology in Japanese patients. We defined advanced hypodontia as a congenital absence of four or more permanent teeth, excluding the third molars. Lateral cephalometric radiographs of 20 female orthodontic patients (age range, 8.5 to 19 years; mean age, 13.9 years) were examined. Twentyeight angular and 37 linear measurements were taken from each cephalogram, and these cephalometric data were statistically analyzed and compared with the Japanese cephalometric standards. The most frequently missing teeth were the mandibular and maxillary second premolars, followed by the maxillary first premolars and the maxillary first molars, in that order. Compared with the Japanese standards, a smaller cranial base length and angle, a shorter maxillary length, a slightly prognathic and upward-rotated mandible, and retroclination of the upper and lower incisors were found in the patients studied.These craniofacial anomalies should be taken into consideration in treatment planning and mechanotherapy.

Bolton's values can be used with confidence for the typical Japanese orthodontic population. The use of the actual millimeters of correction for the tooth size ratios could help orthodontists avoid underestimating the prevalence of clinically significant tooth size discrepancies.