Bone histomorphometric measures of physical activity in children from Medieval England

Objectives: Histomorphometric studies show consistent links between physical activity patterns and the microstructure underlying the size and shape of bone. Here we adopt a combined bone approach to explore variation in microstructure of ribs and humeri related to physical activity and historical records of manual labor in skeletal samples of children (n=175) from medieval England. The humerus reflects greater biomechanically induced microstructural variation than the rib which is used here as a control. Variation in microstructure is sought between regions in England (Canterbury, York, Newcastle), and between high- and low-status children from Canterbury. Materials and Methods: Thin-sections were prepared from the humerus or rib and features of bone remodeling were recorded using high-resolution microscopy and image analysis software. Results: The density and size of secondary osteons in the humerus differed significantly in children from Canterbury when compared to those from York and Newcastle. Amongst the older children, secondary osteon circularity and diameter differed significantly between higher and lower status children. Discussion: By applying bone remodeling principles to the histomorphometric data we infer that medieval children in Canterbury engaged in less physically demanding activities than children from York or Newcastle. Within Canterbury, high-status and low-status children experienced similar biomechanical loading until around seven years of age. After this age low-status children performed activities that resulted in more habitual loading on their arm bones than the high-status children. This inferred change in physical activity is consistent with historical textual evidence that describes children entering the work force at this age

Cortical histomorphometry of the human humerus during ontogeny

Modeling and remodeling are two key determinants of human skeletal growth though little is known about the histomorphometry of cortical bone during ontogeny. In this study we examined the density and geometric properties of primary and secondary osteons (osteon area and diameter, vascular canal area and diameter) in sub-periosteal cortical bone from the human humerus (n=84) between birth and age 18 years. Sections were removed from the anterior midshaft aspect of humeri from skeletons. Age-at-death was reconstructed using standard osteological techniques. Analyses revealed significant correlation between the histomorphometric variables and age. Higher densities of primary osteons occurred between infancy and seven years of age but were almost completely replaced by secondary osteons after 14 years of age. The geometry of primary osteons was less clearly related to age. Secondary osteons were visible after two years of age, and reached their greatest densities in the oldest individuals. Osteon size was positively but weakly influenced by age. Our data implies that modeling and remodeling are age dependent processes that vary markedly from birth to adulthood in the human humerus

Expression of cyclooxygenase-2 (COX-2) in tumour and stroma compartments in cervical cancer: clinical implications

This study aims at investigating the relationship between cyclooxygenase-2 expression in tumour vs stroma inflammatory compartment and its possible clinical role. The study included 99 stage IB-IV cervical cancer patients: immunostaining of tumour tissue sections was performed with rabbit antiserum against cyclooxygenase-2. CD3, CD4, CD8, CD25, Mast Cell Tryptase monoclonal antibodies were used to characterise stroma inflammatory cells in nine cervical tumours. An inverse relation was found between cyclooxygenase-2 levels (cyclooxygenase-2 IDV) of tumour vs stroma compartment (r=−0.44, P<0.0001). The percentage of cases showing high tumour/stromal cyclooxygenase-2 IDV ratio was significantly higher in patients who did not respond to treatment (93.3%) with respect to patients with partial (60.5%), and complete (43.7%) response (P= 0.009). Cases with a high tumour/stroma cyclooxygenase-2 IDV ratio had a shorter overall survival rate than cases with a low tumour/stroma cyclooxygenase-2 IDV (P<0.0001). In the multivariate analysis advanced stage and the status of tumour/stroma cyclooxygenase-2 IDV ratio retained an independent negative prognostic role. The proportion of CD3+, CD4+, and CD25+ cells was significantly lower in tumours with high tumour/stroma cyclooxygenase-2 IDV ratio, while a higher percentage of mast cells was detected in tumours showing high tumour/stroma cyclooxygenase-2 IDV ratio. Our study showed the usefulness of assessing cyclooxygenase-2 status both in tumour and stroma compartment in order to identify cervical cancer patients endowed with a very poor chance of response to neoadjuvant therapy and unfavourable prognosis

Treatment with interleukin-2 in malignant pleural mesothelioma: immunological and angiogenetic assessment and prognostic impact

BACKGROUND: Administration of interleukin-2 (IL-2) has shown some effects on malignant pleural mesothelioma (MPM) tumour regression. The purpose of this study was to investigate the ability of IL-2 to modify immunological effector cells and angiogenesis in MPM patients and their prognostic value. METHODS: Tumour-infiltrating lymphocytes (CD4, CD8, Foxp3), mast cells (MCs) (tryptase and chymase), microvessel count (MVC) and VEGF were determined by immunohistochemistry in two series of MPM patients: 60 patients treated with intra-pleural preoperative IL-2 and 33 patients untreated. RESULTS: Tryptase MCs, and CD8 and Foxp3 lymphocytes were significantly increased in the IL-2-treated group, whereas MVC was significantly lower in the same group. Moreover, in the IL-2-treated group, greater tryptase + MCs and greater Foxp3 lymphocytes were associated with improved and poorer clinical outcomes, respectively. Notably, when these two immunological parameters were combined, they predicted outcomes more effectively. CONCLUSIONS: This study showed that IL-2 treatment leads to a significant increase of immunological parameters, concomitantly with a reduction in vasculature, providing new insight into the cancer mechanisms mediated by IL-2. Moreover, these results suggest that tryptase-positive MCs and Foxp3 + lymphocytes predict clinical outcomes in IL-2-treated patients, highlighting the critical role of the inflammatory response in mesothelioma cancer progression. British Journal of Cancer (2009) 101, 1869-1875. doi:10.1038/sj.bjc.6605438 www.bjcancer.com (C) 2009 Cancer Research U

Three-dimensional reconstruction of Haversian systems in human cortical bone using synchrotron radiation-based micro-CT: morphology and quantification of branching and transverse connections across age

This study uses synchrotron radiation-based micro-computed tomography (CT) scans to reconstruct three-dimensional networks of Haversian systems in human cortical bone in order to observe and analyse interconnectivity of Haversian systems and the development of total Haversian networks across different ages. A better knowledge of how Haversian systems interact with each other is essential to improve understanding of remodeling mechanisms and bone maintenance; however, previous methodological approaches (e.g. serial sections) did not reveal enough detail to follow the specific morphology of Haversian branching, for example. Accordingly, the aim of the present study was to identify the morphological diversity of branching patterns and transverse connections, and to understand how they change with age. Two types of branching morphologies were identified: lateral branching, resulting in small osteon branches bifurcating off of larger Haversian canals; and dichotomous branching, the formation of two new osteonal branches from one. The reconstructions in this study also suggest that Haversian systems frequently target previously existing systems as a path for their course, resulting in a cross-sectional morphology frequently referred to as \u27type II osteons\u27. Transverse connections were diverse in their course from linear to oblique to curvy. Quantitative assessment of age-related trends indicates that while in younger human individuals transverse connections were most common, in older individuals more evidence of connections resulting from Haversian systems growing inside previously existing systems was found. Despite these changes in morphological characteristics, a relatively constant degree of overall interconnectivity is maintained throughout life. Altogether, the present study reveals important details about Haversian systems and their relation to each other that can be used towards a better understanding of cortical bone remodeling as well as a more accurate interpretation of morphological variants of osteons in cross-sectional microscopy. Permitting visibility of reversal lines, synchrotron radiation-based micro-CT is a valuable tool for the reconstruction of Haversian systems, and future analyses have the potential to further improve understanding of various important aspects of bone growth, maintenance and health

Expression of T cell receptor-alpha and -beta subunits in human thymocytes. An immunocytologic study.

The expression of the T cell receptor (Ti)-alpha and -beta subunits in human thymocytes was studied with the use of two rabbit antisera directed at constant regions of human Ti-alpha- and Ti-beta-chains (H36 and H38, respectively). Immunoperoxidase techniques were employed to count by light and electron microscopy the cells, in the various thymocyte subsets, bearing Ti-alpha and Ti-beta subunits. Of the unfractionated thymocytes, 88% +/- 5 SD and 56% +/- 8 SD were labeled by H38 and H36, respectively. More than 90% of cells in cluster of differentiation (CD)-1+ (mainly cortical) and CD1-CD3+ (mainly medullary) subsets were stained with H38. When tested by H36, 51% +/- 6 SD of CD1+ and 81% +/- 8 SD of CD1-CD3+ thymocytes were positive. In the immature CD3-CD1- subpopulation, less than 3% of cells reacted with H36, whereas 15% +/- 3 SD were stained by H38. Flow cytometry revealed that CD1+ (mainly cortical) thymocytes expressed CD3 surface antigen in a percentage similar to that of CD1+ cells positive for Ti-alpha subunits. Indirect double labeling procedures with immunogold- and peroxidase-conjugated second antibodies demonstrated that almost all CD1+/Ti-alpha + cells expressed the surface CD3 antigen, whereas a large proportion of CD1+/Ti-beta + cells did not. These results indicate a sequential expression of Ti-beta and Ti-alpha subunits during intrathymic T cell differentiation. They also suggest that assembly and surface expression of the CD3-Ti complex are linked to the production of Ti-alpha-chains in addition to Ti-beta subunits. Last, the expression of Ti-alpha and Ti-beta subunits was studied in peanut agglutinin (PNA)+, CD1+ blasts representing the main, spontaneously proliferating intrathymic pool. The lack of Ti-alpha and Ti-beta subunits and the absence of surface CD3 antigen on most of these blasts suggest that immature T cells are compelled to proliferate in the thymus in a CD3-Ti complex independent manner

Tamoxifen retinopathy

A 63-year-old female on long-term, high-dose tamoxifen treatment for metastatic breast cancer developed bilateral intraretinal refractile opacities, lesions at the level of the retinal pigment epithelium, and cystoid macular oedema