54 research outputs found

    The behavior of osteoblast-like cells on various substrates with functional blocking of integrin-β1 and integrin-β3

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    This study was designed to examine the influence of integrin subunit-β1 and subunit-β3 on the behavior of primary osteoblast-like cells, cultured on calcium phosphate (CaP)-coated and non coated titanium (Ti). Osteoblast-like cells were incubated with specific monoclonal antibodies against integrin-β1 and integrin-β3 to block the integrin function. Subsequently, cells were seeded on Ti discs, either non coated or provided with a 2 μm carbonated hydroxyapatite coating using Electrostatic Spray Deposition. Results showed that on CaP coatings, cellular attachment was decreased after a pre-treatment with either anti-integrin-β1 or anti-integrin-β3 antibodies. On Ti, cell adhesion was only slightly affected after a pre-treatment with anti-integrin-β3 antibodies. Scanning electron microscopy showed that on both types of substrate, cellular morphology was not changed after a pre-treatment with either antibody. With quantitative PCR, it was shown for both substrates that mRNA expression of integrin-β1 was increased after a pre-treatment with either anti-integrin-β1 or anti-integrin-β3 antibodies. Furthermore, after a pre-treatment with either antibody, mRNA expression of integrin-β3 and ALP was decreased, on both types of substrate. In conclusion, osteoblast-like cells have the ability to compensate to great extent for the blocking strategy as applied here. Still, integrin-β1 and β3 seem to play different roles in attachment, proliferation, and differentiation of osteoblast-like cells, and responses on CaP-coated substrates differ to non coated Ti. Furthermore, the influence on ALP expression suggests involvement of both integrin subunits in signal transduction for cellular differentiation

    Modelling ageing and age-related disease

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    An increased lifespan comes with an associated increase in disease incidence, and is the major risk factor for age-related diseases. To face this societal challenge search for new treatments has intensified requiring good preclinical models, whose complexity and accuracy is increasing. However, the influence of ageing is often overlooked. Furthermore, phenotypic assessment of ageing models is in need of standardisation to enable the accurate evaluation of pre-clinical intervention studies in line with clinical translation

    Interrogating open issues in cancer precision medicine with patient-derived xenografts

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    External validation of a clinical scoring system for the risk of gestational diabetes mellitus

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    Aim: A prediction rule for gestational diabetes mellitus (GDM) could be helpful in early detection and increased efficiency of screening. A prediction rule by means of a clinical scoring system is available, but has never been validated externally. The aim of this study was to validate the scoring system. Methods: We used data from a prospective cohort study. Women were assigned a score based on age, BMI and ethnicity. Performance of the scoring system was evaluated in terms of discrimination and calibration (agreement between clinical score and observed probability of GDM). We compared the efficiency of a screening strategy derived from the scoring system with conventional screening. Results: We studied 1266 women. Forty-seven women had GDM (3.7%). The scoring system discriminated moderately (area under the curve = 0.64 (95% Cl 0.56-0.72)). Calibration was limited (chi(2) = 8.89, p = 0.06). The screening strategy derived from the scoring system reduced the number of women needed to be screened with 25% for a comparable detection rate to universal screening. Conclusion: Despite moderate discriminative capacity and calibration of the scoring system, the screening strategy based on the scoring system appears clinically useful. There is need for better prediction models for GDM. (C) 2009 Elsevier Ireland Ltd. All rights reserved
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