Population-based, three-dimensional analysis of age- and sex-related femur shaft geometry differences.

This study deals with differences of femoral geometric focus on the bowing and width. Analysis using three-dimensional skeletonization showed increase of femoral bowing and femur width over life (more in women), and widening of the medullary canal only in women after 50 years old, not in men. INTRODUCTION: The changes in femur geometry that occur with aging and lead to fragility or insufficiency fracture remain unclear. The role of the lower limb geometry, including the femur and femoral bowing, has become a point of discussion, especially in atypical femur fracture. This study aimed to analyze femur shaft geometry using three-dimensional skeletonization. METHODS: We acquired computed tomography images of both femurs obtained. A total of 1400 age- and sex-stratified participants were enrolled and were divided into subgroups according to age (by decade) and sex. The computed tomography images were used to produce 3-dimensional samplings of anatomical elements of the human femur using reconstruction and parametrization from these datasets. The process of skeletonization was conducted to obtain compact representation of the femur. With the skeletonization, we were able to compare all parameters according to age and sex. RESULTS: The femur length was 424.4 ± 28.6 mm and was longer in men (P < 0.001). The minimum diameter of the medullary canal was 8.9 ± 2.0 mm. The radius of curvature (ROC) was 906.9 ± 193.3 mm. Men had a larger femur length, femur outer diameter, and the narrowest medullary diameter (P < 0.001, respectively). Women had significantly smaller ROC (P < 0.001). ROC decreased by 19.4% in men and 23.6% in women between the ages of 20 to 89 years. Femur width increased over life by 11.4% in men and 24.5% in women. Between the ages of 50 and 89 years, the medullary canal appears to have increased by 32.7% in women. CONCLUSION: This geometry analysis demonstrated that femoral bowing and femoral width increased related to aging, and that the medullary canal widened after the age of 50 years in women. This cross-sectional study revealed important age- and sex-related differences in femur shaft geometry that occur with aging.

Overexpression of secretory leukocyte peptidase inhibitor (SLPI) does not modulate experimental osteoarthritis but may be a biomarker for the disease.

OBJECTIVE: Osteoarthritic cartilage destruction can be regulated by the balance between proteases and anti-proteases. Here, we sought to identify novel cellular protease inhibitors associated with osteoarthritis (OA) pathogenesis. METHODS: Candidate molecules were screened from microarray data of chondrocytes treated with OA-associated catabolic factors. The functions of candidate molecules in OA pathogenesis were examined in primary-culture mouse articular chondrocytes and mouse models of OA, such as those stimulated by destabilization of the medial meniscus (DMM) or intra-articular (IA) injection of adenovirus expressing the candidate gene. The value of the selected candidate molecule as a biomarker of OA was examined by measuring its circulating levels in human and mouse blood. RESULTS: Bioinformatic analysis identified secretory leukocyte peptidase inhibitor (SLPI) as a highly upregulated cellular protease inhibitor in chondrocytes treated with pathogenic catabolic factors, including interleukin (IL)-1ß, hypoxia-inducible factor (HIF)-2α, and zinc importer ZIP8. The adenovirus-mediated overexpression of SLPI in joint tissues did not cause any OA-like change or modulate DMM- or HIF-2α-induced experimental OA in mice. SLPI also did not markedly modulate the expression of OA-associated catabolic or anabolic factors in chondrocytes. However, SLPI was specifically upregulated in OA cartilage, and the serum SLPI levels were significantly elevated in human OA patients and experimental OA mice, suggesting that SLPI may be a biomarker of OA. CONCLUSION: Although SLPI is upregulated in OA chondrocytes, it does not appear to per se modulate OA development in mice. However, it may be a potential biomarker of OA in humans and animal models.

Comparative genomic hybridization analysis of rice dwarf mutants induced by gamma irradiation.

Comparative genomic hybridization (CGH) is a powerful tool used to analyze changes in copy number, polymorphisms, and structural variations in the genome. Gene copy number variation (CNV) is a common form of natural diversity in the genome, which can create new genes and alter gene structure. Thus, CNVs may influence phenotypic variation and gene expression. In this study, to detect CNVs, we irradiated rice seeds with gamma rays (300 Gy) and selected two dwarf mutagenized plants, GA-III-189 and -1052, in the M3 generation. These plants were subjected to CGH analysis using Agilent's RICE CGH array. Most of the CNVs identified were less than 10 kb in length. We detected 90 amplified and 18 deleted regions in GA-III-189, and 99 amplified and 11 deleted regions in GA-III-1052. Of note, CNVs were located on chromosome 12 in both GA-III-189 and -1052, which contained 39 commonly amplified regions in 29 genes. The commonly amplified genes included six genes encoding F-box domain-containing proteins. Alterations in these F-box domain-containing genes were confirmed by quantitative RT-PCR. Integration of CGH and gene expression data identified copy number aberrations and novel genes potentially involved in the dwarf phenotype. These CGH and gene expression data may be useful for uncovering the mechanisms underlying the dwarf phenotype.

Clinical spectrum of CNS aquaporin-4 autoimmunity.

OBJECTIVES: Traditionally, neuromyelitis optica (NMO) was known to involve only the optic nerves and spinal cord. However, the discovery of highly specific anti-aquaporin-4 (AQP4) antibody for NMO enabled us to identify more diverse clinical manifestations. Here, we describe the demographic and clinical characteristics of patients who were anti-AQP4-antibody positive, represented by CNS AQP4 autoimmunity. METHODS: In total, 388 consecutive patients with inflammatory demyelinating CNS diseases were tested for the anti-AQP4 antibody and 106 seropositive patients who were positive by ELISA or cell-based assay were included. RESULTS: Ninety-seven patients were women, and 9 men. The median age at onset was 32 years. The median annualized relapse rate was 1.14 during the median follow-up of 7.0 years. When the 2006 revised diagnostic criteria for NMO were applied, 72% of patients met the criteria, and 28% had a limited form of NMO. Brain symptoms were observed in 51% of patients, and 24% of patients presented with brain symptoms as their first manifestation. Severe residual visual impairment or ambulatory disability was observed in 42% of patients. The median intervals to Expanded Disability Status Scale (EDSS) 6 and severe visual impairment in at least one eye were 12 and 11 years, respectively. A multivariate analysis revealed a delay of more than 4 years before appropriate immunotherapy was independently associated with reaching severe disability of more than EDSS 6. CONCLUSION: The spectrum of neurologic manifestations and the disease course associated with CNS AQP4 autoimmunity is broader than previously recognized.