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61.
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Chukwuka C Okafor Hana Haleem-Smith Patrice Laqueriere Paul A Manner Rocky S Tuan 《Journal of orthopaedic research》2006,24(3):461-473
Continual loading and articulation cycles undergone by metallic (e.g., titanium) alloy arthroplasty prostheses lead to liberation of a large number of metallic debris particulates, which have long been implicated as a primary cause of periprosthetic osteolysis and postarthroplasty aseptic implant loosening. Long-term stability of total joint replacement prostheses relies on proper integration between implant biomaterial and osseous tissue, and factors that interfere with this integration are likely to cause osteolysis. Because multipotent mesenchymal stem cells (MSCs) located adjacent to the implant have an osteoprogenitor function and are critical contributors to osseous tissue integrity, when their functions or activities are compromised, osteolysis will most likely occur. To date, it is not certain or sufficiently confirmed whether MSCs endocytose titanium particles, and if so, whether particulate endocytosis has any effect on cellular responses to wear debris. This study seeks to clarify the phenomenon of titanium endocytosis by human MSCs (hMSCs), and investigates the influence of endocytosis on their activities. hMSCs incubated with commercially pure titanium particles exhibited internalized particles, as observed by scanning electron microscopy and confocal laser scanning microscopy, with time-dependent reduction in the number of extracellular particles. Particulate endocytosis was associated with reduced rates of cellular proliferation and cell-substrate adhesion, suppressed osteogenic differentiation, and increased rate of apoptosis. These cellular effects of exposure to titanium particles were reduced when endocytosis was inhibited by treatment with cytochalasin D, and no significant effect was seen when hMSCs were treated only with conditioned medium obtained from particulate-treated cells. These findings strongly suggest that the biological responses of hMSCs to wear debris are triggered primarily by the direct endocytosis of titanium particulates, and not mediated by secreted soluble factors. In this manner, therapeutical approaches that suppress particle endocytosis could reduce the bioreactivity of hMSCs to particulates, and enhance long-term orthopedic implant prognosis by minimizing wear-debris periprosthethic osteolysis. 相似文献
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Lucia Nogovà MD Volker Diehl MD Andreas Engert MD 《Current hematologic malignancy reports》2006,1(1):60-65
Lymphocyte-predominant Hodgkin’s lymphoma (LPHL) differs in histologic and clinical presentation from classical Hodgkin’s
lymphoma (cHL). Treatment of LPHL patients using standard Hodgkin’s lymphoma protocols leads to complete remission in more
than 95% of patients. Survival and freedom from treatment failure are substantially worse in advanced-stage patients than
for early-stage patients. Thus, patients in advanced stages and those in early stages with unfavorable risk factors should
be treated similar to those with cHL. In contrast, patients with early-stage LPHL without risk factors might be sufficiently
treated with reduced-intensity programs having less severe adverse effects. As a result, treatment of early LPHL is rather
heterogeneous, including radiotherapy using extended-fleld technique, involved-fleld radiotherapy (IF-RT), combined-modality
treatment, and, more recently, monoclonal antibodies. Watch-and-wait strategy plays an important role in pediatric oncology,
to avoid adverse effects associated with therapy. IF-RT seems to be emerging as a treatment of choice for patients with stage
IA LPHL; most larger study groups, such as the German Hodgkin Study Group and the European Organisation for Research and Treatment
of Cancer, have adopted IF-RT as the treatment of choice for these patients. 相似文献
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BCR-ABL activity and its response to drugs can be determined in CD34+ CML stem cells by CrkL phosphorylation status using flow cytometry. 总被引:2,自引:0,他引:2
A Hamilton L Elrick S Myssina M Copland H J?rgensen J V Melo T Holyoake 《Leukemia》2006,20(6):1035-1039
In chronic myeloid leukaemia, CD34(+) stem/progenitor cells appear resistant to imatinib mesylate (IM) in vitro and in vivo. To investigate the underlying mechanism(s) of IM resistance, it is essential to quantify Bcr-Abl kinase status at the stem cell level. We developed a flow cytometry method to measure CrkL phosphorylation (P-CrkL) in samples with <10(4) cells. The method was first validated in wild-type (K562) and mutant (BAF3) BCR-ABL(+) as well as BCR-ABL(-) (HL60) cell lines. In response to increasing IM concentration, there was a linear reduction in P-CrkL, which was Bcr-Abl specific and correlated with known resistance. The results were comparable to those from Western blotting. The method also proved to be reproducible with small samples of normal and Ph(+) CD34(+) cells and was able to discriminate between Ph(-), sensitive and resistant Ph(+) cells. This assay should now enable investigators to unravel the mechanism(s) of IM resistance in stem cells. 相似文献
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D Yinon L Lowenstein S Suraya R Beloosesky O Zmora A Malhotra G Pillar 《The European respiratory journal》2006,27(2):328-333
Pre-eclamptic toxaemia (PET) may be associated with both endothelial dysfunction (ED) and sleep-disordered breathing (SDB). It was hypothesised that females with PET would demonstrate both SDB and ED, and that a correlation between these two would suggest a potential causative association. A total of 17 females with PET and 25 matched females with uncomplicated pregnancy were studied. They underwent a nocturnal ambulatory sleep study (using Watch_PAT100) and noninvasive evaluation of endothelial function utilising the reactive hyperaemia test (using Endo_PAT 2000). A higher ratio of post- to pre-occlusion pulse-wave amplitude (endothelial function index (EFI)) indicated better endothelial function. Females with PET had a significantly higher respiratory disturbance index (RDI) and lower EFI than controls (18.4+/-8.4 versus 8.3+/-1.3.h(-1), and 1.5+/-0.1 versus 1.8+/-0.1, respectively). Blood pressure significantly correlated with RDI and with EFI. EFI tended to correlate with RDI. In conclusion, these results suggest that both sleep-disordered breathing and endothelial dysfunction are more likely to occur in females with pre-eclamptic toxaemia than in females with uncomplicated pregnancies. The current authors speculate that respiratory disturbances contribute to the functional abnormality of the blood vessels seen in females with pre-eclamptic toxaemia, although causality cannot be determined based on this study. 相似文献