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  • 1
    ISSN: 1433-2965
    Keywords: Dual-energy X-ray absorptiometry ; Osteoporosis ; Radiogrammetry ; Radiographic absorptiometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The best method for the diagnosis of osteoporosis and assessment of fracture risk is currently considered to be bone densitometry. The most commonly used dual-energy X-ray absorptiometry (DXA) methods may sometimes not predict bone mass accurately in every skeletal site, are expensive and not widely available. The recent development of computed analysis of a plain radiograph of the hand might provide a practical, inexpensive and rapid method for evaluation of bone mineral status. In this study we evaluated 20 healthy premenopausal and 660 postmenopausal women. In 36 of these subjects a second evaluation was carried out after 2 years of therapy with calcium supplements. The internal and external diameters of the second metacarpal and the metacarpal and ultradistal radial bone density were evaluated using a technical device developed in our laboratory and marketed by NIM, Verona, Italy (Osteoradiometer). The radio-graphic images, captured by a video camera, were digitized and studied by computed analysis. In 150 subjects bone density at the level of the lumbar spine, femur, and ultradistal and proximal radius was also measured by DXA techniques. Both external (D) and internal (d) diameters increase significantly with age and years since menopause (YSM), whereas metacarpal index (D−d/D) and metacarpal and ultradistal radial bone density decrease significantly with age and YSM. The ratio between metacarpal bone mineral content and the cortical area (volumetric metacarpal bone density) did not change with age. Significant correlations were found between radiometric findings and DXA measurements. The best correlation coefficients were between bone density measured at the level of the ultradistal radius by DXA and radiographic absorptiometry. In the 2-year follow-up study, a 4.9% and 6.2% decline in radial metacarpal bone density respectively were observed, but the difference was statistically significant only for the latter. In conclusion, computed radiogrammetry is closely correlated with all DXA measurements and may be useful in screening of large populations, providing a simple, inexpensive and sufficiently precise method for evaluation of bone mineral status. Further studies are warranted for assessing the accuracy of radiogrammetry for longitudinal investigations and its capacity to predict fracture risk.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-675X
    Keywords: Apoptosis ; caspases ; leukaemic cells ; minor groove binders
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Treatment of HL60 and Jurkat leukaemic cell lines, both not expressing p53, with the new non-covalent DNA minor groove binder α-bromoacryloyl-distamycin (PNU 151807), induces apoptosis as shown either morphologically or by DNA laddering formation. We evaluated the p53-independent mechanisms of activation of apoptosis in these cell systems, by determining the levels of different caspases at different times after treatment with PNU 151807. Through Western blotting analysis we could measure the cleavage of the 110 Kd form of PARP in both HL60 and Jurkat cells and correspondingly the activation of CPP32-caspase 3. The levels of caspase-1 did not change at any time after drug treatment. By using the tetrapeptidic sequence recognized by caspase-3 (DEVD-AMC) or by caspase-1 (YVAD-AMC) linked to fluorogenic substrate, we also demonstrated that only the DEVD sequence was recognized and cleaved after drug treatment, while no significant changes were found for YVAD peptides. PNU 151807-induced DNA fragmentation and DEVD-cleavage were both inhibited by concomitant treatment with the specific inhibitor DEVD-CHO, but not by YVAD-CHO, clearly demonstrating the direct activation of caspase-3-like caspases in the induction of programmed cell death in these cell lines after minor groove binder exposure.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-675X
    Keywords: Apoptosis ; bcr-abl ; cisplatin ; chronic myeloid ; leukaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Chronic myeloid leukaemia (CML) cell lines expressing the bcr-abl fusion gene are resistant to drug-induced apoptosis. Using a human CML cell line (EM2), we investigated the effects of cisplatinum (DDP), Doxorubicin and Tallimustine on the level of p210, the product of the hybrid bcr-abl gene, and on the induction of apoptosis. DDP exposure of this cell line resulted in a decrease of p210 levels with a concomitant activation of apoptosis. At all the concentrations tested, neither Doxorubicin nor Tallimustine were able to induce DNA fragmentation nor to reduce the levels of the fusion protein p210. The reduction in the p210 levels induced by DDP were also observed at mRNA level as observed with RT-PCR, suggesting that, at least in part, the decrease in p210 levels was the result of a reduction in the transcription of the bcr-abl fusion gene. The DDP-induced DNA fragmentation and decrease in p210 levels, were observed in EM2 cells but not in another human CML cell line (K562) which overexpresses the fusion gene. In K562 cells the levels of bcr-abl, although decreased, remained well detectable after DDP treatment. Data indicate that it may be possible to investigate compounds able to contrast the resistance to DNA-damage induced apoptosis of CML cell lines.
    Type of Medium: Electronic Resource
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