Analysis Of Long Bones Research Articles

Effect of Herceptin on the development and progression of skeletal metastases in a xenograft model of human breast cancer

We examined the effects of Herceptin, a bioengineered monoclonal antibody directed against Her-2/neu oncogene on skeletal metastasis using a xenograft model of breast cancer. Treatment of Her-2 overexpressing human breast cancer cells BT-474 with Herceptin caused a dose-dependent decrease in cell proliferation. In in vivo studies, BT-474 cells (1 x 10(5)) were injected into the left ventricle of female BALB/c nu/nu mice. Intraperitoneal (i.p.) infusion of Herceptin (1 mg/kg twice a week for 5 weeks) from the day of tumor cell inoculation or at the time of radiologically detectable skeletal metastasis either slowed the development or prevented the progression of skeletal metastasis as compared to control groups of animals receiving nonspecific IgG. Bone histological analysis of long bones showed the ability of Herceptin to reduce the ratio of tumor volume to bone volume as well as mitotic index, effects that were more pronounced when Herceptin treatment was initiated from the day of tumor cell inoculation. While immunohistochemical analysis of long bones showed no difference in the production of Her-2, phosphorylated (P) Her-2 and MAPK, a significantly lower level of P-MAPK was seen in bones of Herceptin treated animals. These studies demonstrate the ability of Herceptin to inhibit the development and abrogate the progression of skeletal metastases associated with breast cancer by blocking the HER-2-mediated signaling pathways.

Targeted expression of SHH affects chondrocyte differentiation, growth plate organization, and Sox9 expression.

The role of Hedgehogs (Hh) in murine skeletal development was studied by overexpressing human Sonic Hedgehog (SHH) in chondrocytes of transgenic mice using the collagen II promoter/enhancer. Overexpression caused a lethal craniorachischisis with major alterations in long bones because of defects in chondrocyte differentiation. Hedgehogs (Hhs) are a family of secreted polypeptides that play important roles in vertebrate development, controlling many critical steps of cell differentiation and patterning. Skeletal development is affected in many different ways by Hhs. Genetic defects and anomalies of Hhs signaling pathways cause severe abnormalities in the appendicular, axial, and cranial skeleton in man and other vertebrates. Genetic manipulation of mouse embryos was used to study in vivo the function of SHH in skeletal development. By DNA microinjection into pronuclei of fertilized oocytes, we have generated transgenic mice that express SHH specifically in chondrocytes using the cartilage-specific collagen II promoter/enhancer. Transgenic skeletal development was studied at different embryonic stages by histology. The expression pattern of specific chondrocyte molecules was studied by immunohistochemistry and in situ hybridization. Transgenic mice died at birth with severe craniorachischisis and other skeletal defects in ribs, sternum, and long bones. Detailed analysis of long bones showed that chondrocyte differentiation was blocked at prehypertrophic stages, hindering endochondral ossification and trabecular bone formation, with specific defects in different limb segments. The growth plate was highly disorganized in the tibia and was completely absent in the femur and humerus, leading to skeletal elements entirely made of cartilage surrounded by a thin layer of bone. In this cartilage, chondrocytes maintained a columnar organization that was perpendicular to the bone longitudinal axis and directed toward its outer surface. The expression of SHH receptor, Patched-1 (Ptc1), was greatly increased in all cartilage, as well as the expression of parathyroid hormone-related protein (PTHrP) at the articular surface; while the expression of Indian Hedgehog (Ihh), another member of Hh family that controls the rate of chondrocyte maturation, was greatly reduced and restricted to the displaced chondrocyte columns. Transgenic mice also revealed the ability of SHH to upregulate the expression of Sox9, a major transcription factor implicated in chondrocyte-specific gene expression, in vivo and in vitro, acting through the proximal 6.8-kb-long Sox9 promoter. Transgenic mice show that continuous expression of SHH in chondrocytes interferes with cell differentiation and growth plate organization and induces high levels and diffuse expression of Sox9 in cartilaginous bones.

Bone strength and related traits in HcB/Dem recombinant congenic mice.

Fracture susceptibility depends jointly on bone mineral content (BMC), gross bone anatomy, and bone microarchitecture and quality. Overall, it has been estimated that 50-70% of bone strength is determined genetically. Because of the difficulty of performing studies of the genetics of bone strength in humans, we have used the HcB/Dem series of recombinant congenic (RC) mice to investigate this phenotype. We performed a comprehensive phenotypic analysis of the HcB/Dem strains including morphological analysis of long bones, measurement of ash percentage, and biomechanical testing. Body mass, ash percentage, and moment of inertia each correlated moderately but imperfectly with biomechanical performance. Several chromosome regions, on chromosomes 1, 2, 8, 10, 11, and 12, show sufficient evidence of linkage to warrant closer examination in further crosses. These studies support the view that mineral content, diaphyseal diameter, and additional nonmineral material properties contributing to overall bone strength are controlled by distinct sets of genes. Moreover, the mapping data are consistent with the existence of pleiotropic loci for bone strength-related phenotypes. These findings show the importance of factors other than mineral content in determining skeletal performance and that these factors can be dissected genetically.

Biomechanical beam analysis of long bones from a late 18th century slave cemetery in Cape Town, South Africa.

This study aims to quantify the physical demands of a sample of late 18th century skeletons from an unmarked burial site on Cobern Street, Cape Town, South Africa. Historical studies suggest that these individuals were either slaves or "free black" people of low socioeconomic standing. Cortical cross-sectional areas of paired humeri and tibiae from the Cobern Street collection (N = 29), a modern cadaver collection (N = 31), and a hunter-gatherer collection (N = 30) were compared by means of biomechanical beam analysis on computerized tomography scans. Results showed that the Cobern Street sample, both males and females, were closer to the modern group in total tibial cortical area and in the second moments and polar moments of cortical area, than to the hunter-gatherer group. It is assumed that these results can be explained by differences in lower limb activity. Tibial strength properties showed the hunter-gatherer peoples to be highly mobile and active walkers in comparison to the Cobern Street and modern samples. The males from the Cobern Street sample showed significantly higher values for humeral strength properties than either the hunter-gatherer or modern individuals, attesting to their status as manual laborers. The humeral cross-sectional strength properties for females were very similar between the Cobern Street and modern groups but again significantly different from the hunter-gatherer sample. The domestic chores performed by females of the recent cadaver sample may be very similar to those performed by the Cobern Street sample.

Biomechanical beam analysis of long bones from a late 18th century slave cemetery in Cape Town, South Africa

This study aims to quantify the physical demands of a sample of late 18th century skeletons from an unmarked burial site on Cobern Street, Cape Town, South Africa. Historical studies suggest that these individuals were either slaves or “free black” people of low socioeconomic standing. Cortical cross-sectional areas of paired humeri and tibiae from the Cobern Street collection (N = 29), a modern cadaver collection (N = 31), and a hunter-gatherer collection (N = 30) were compared by means of biomechanical beam analysis on computerized tomography scans. Results showed that the Cobern Street sample, both males and females, were closer to the modern group in total tibial cortical area and in the second moments and polar moments of cortical area, than to the hunter-gatherer group. It is assumed that these results can be explained by differences in lower limb activity. Tibial strength properties showed the hunter-gatherer peoples to be highly mobile and active walkers in comparison to the Cobern Street and modern samples. The males from the Cobern Street sample showed significantly higher values for humeral strength properties than either the hunter-gatherer or modern individuals, attesting to their status as manual laborers. The humeral cross-sectional strength properties for females were very similar between the Cobern Street and modern groups but again significantly different from the hunter-gatherer sample. The domestic chores performed by females of the recent cadaver sample may be very similar to those performed by the Cobern Street sample. Am J Phys Anthropol 112:207–216, 2000. © 2000 Wiley-Liss, Inc.

Finite element modelling of the vibrational behaviour of the human femur using CT-based individualized geometrical and material properties

Frequency analysis of long bones has been investigated as a tool to assess bone quality or integrity. The objective of the present paper was to develop a three-dimensional finite element model of a fresh human femur with geometrical and mechanical properties derived from quantitative computer tomography images. This model was then exercised and the results were compared to those obtained from a vibration analysis technique. The percent relative error between the numerically and experimentally derived results was found about 4%. Finally, the influence of mechanical properties on the resonant spectre was studied. The results exhibit the limitations of the vibrational technique to detect slight material changes

Trace and heavy metals in infants, analysis of long bones from Ficana, Italy, 8–6th century bc

Abstract Long bones (mostly femurs) of 19 infants (0–14-months-old) from 8–6th century bc burials at Ficana, Italy, have been analysed for 10 major and minor elements, using particle induced X-ray and gamma-ray emission (PIXE and PIGE). Fe, Mn, Cu and Pb values were considered as being primarily the result of post-mortem conditions. Ca and Zn values may also be influenced by post-mortem conditions, but the methodological difficulties present in analysing infants might play some part in the results. Sr values most probably represented the pre-mortem conditions of the infants. Multivariate statistical techniques were used in the analysis of the results. The observed variations in strontium values may be due to social variations in the diets of infants and their mothers.

Elemental analysis of long bones of infants from ficana excavations

External beam PIXE and PIGE methods were applied to the analysis of elemental concentrations of bones from nineteen child burials from the Ficana excavations. Concentrations of ten minor and major elements (Na, P, Ca, Mn, Fe, Cu, Zn, Br, Sr and Pb) were determined. The Fe, Mn, Cu and Pb values were concluded to be primarily the result of post-mortem conditions while the elements Sr and Zn most probably present the pre-mortem conditions.

Computer aided stress analysis of long bones utilizing computed tomography

A computer aided analysis method has been developed which utilizes computed tomography (CT) and a finite element (FE) computer program to determine the stress-displacement pattern in a long bone section. The CT data file provides the geometry, the apparent density and the elastic properties for the three-dimensional FE model. A developed pre-processor generates the FE model of a human diaphyseal tibia section which is then analyzed by the SAP IV finite element program. The results obtained are sorted and displayed by a developed post-processor and compared with stresses and deformations from the literature. The model generation method was verified by applying it to a model of simple geometry and boundary conditions, then comparing the results with the analytical solution of the same problem. The convergence behavior of nodal displacements was tested as a function of mesh refinement. This method provides an automatic, versatile, non-invasive and accurate tool of long bone modeling for finite element stress analysis.

Changes in Activities with the Shift to Agriculture in the Southeastern United States

Changes in Activities with the Shift to Agriculture in the Southeastern United States

An extended structural analysis of long bones—Application to the human tibia

A computer model is used to investigate the importance of several assumptions associated with whole bone modeling. The importance of shearing deformations relative to bending deformations, and the coupling between transverse loading and torsion are shown to be negligible. A more rigorous solution for torsion in hollow, irregular solids, the three dimensional twisted geometry of the tibia and the values chosen for Young's modulus and Poisson's ratio are all shown to be significant factors. The material properties are assumed to be linear, elastic and isotropic. The analysis is concerned primarily with modeling the response of the whole bone to loads transmitted through the epiphyses, and with detailed stress distributions in the diaphysis. An outline of the computer model and the experimental data are presented.