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Céline Chipoy Martine Berreur Séverine Couillaud Gilbert Pradal Fran?ois Vallette Caroline Colombeix Fran?oise Rédini Dominique Heymann Frédéric Blanchard 《Journal of bone and mineral research》2004,19(11):1850-1861
The effects of OSM on proliferation and differentiation of osteosarcoma and nontransformed osteoblasts were analyzed. OSM downregulates osteoblast markers but induces the glial fibrillary acidic protein by the combined activation of PKCdelta and STAT3, offering new lines of therapeutic investigations. INTRODUCTION: Oncostatin M (OSM) is a multifunctional cytokine of the interleukin-6 family implicated in embryonic development, differentiation, inflammation, and regeneration of various tissues, mainly the liver, bone, and the central nervous and hematopoietic systems. One particularity of OSM relies on its growth inhibitory and pro-differentiating effects on a variety of tumor cell lines such as melanoma, providing arguments for a therapeutic application of OSM. The objective of this study was to analyze the effects of OSM on osteosarcoma cell lines proliferation and differentiation. MATERIALS AND METHODS: Proliferation was analyzed by 3H thymidine incorporation. Differentiation was analyzed by semiquantitative RT-PCR and immunocytochemistry for various markers. Alizarin red S staining was used to evaluate bone nodule formation. Morphological changes were studied by confocal and electron microscopy. Western blotting, kinases inhibitors, and dominant negative STAT3 were used to identified the signaling pathways implicated. RESULTS: OSM inhibits the growth of rat osteosarcoma cell lines as well as normal osteoblasts, in correlation with induction of the cyclin-dependent kinases inhibitor p21WAF1. However, OSM reduces osteoblast markers such as alkaline phosphatase, osteocalcin, and bone sialoprotein, leading to strong inhibition of mineralized nodule formation. This inhibitory effect is restricted to mature osteoblasts and differentiated osteosarcoma because OSM effectively stimulates osteoblast markers and bone nodule formation in early, but not late, bone marrow mesenchymal stem cell (BMSC) cultures. In osteosarcoma cells or BMSC, OSM induces expression of the glial fibrillary acidic protein (GFAP) as well as morphological and ultrastructural changes, for example, elongated shape and bundles of microfilaments in cell processes. Rottlerin (PKCdelta inhibitor), and to a lesser degree UO126 (MEK/ERK inhibitor), prevents the loss of osteoblastic markers by OSM, whereas dominant negative STAT3 prevents GFAP induction. CONCLUSIONS: These results highlight the particular gene expression profile of OSM-treated osteosarcoma cells and BMSCs, suggesting either a osteocytic or a glial-like phenotype. Together with the implication of PKCdelta, ERK1/2, and STAT3, these results offer new lines of investigations for neural cell transplantation and osteosarcoma therapy. 相似文献
34.
U. Bolm-Audorff S. Brandenburg T. Brüning H. Dupuis R. Ellegast G. Elsner K. Franz H. Grasshoff V. Grosser L. Hanisch B. Hartmann E. Hartung† K. G. Hering G. Heuchert M. Jäger J. Krämer Dr. A. Kranig E. Ludolph A. Luttmann A. Nienhaus W. Pieper K. D. Pöhl T. Remé D. Riede G. Rompe K. Schäfer S. Schilling E. Schmitt F. Schröter A. Seidler M. Spallek M. Weber 《Trauma und Berufskrankheit》2005,7(4):320-332
The first part of this serial paper dealt with the medical criteria used in evaluation of the clinical picture caused by physical stress and the evaluation of other candidate causes and was published in issue no. 3/2005 (pp. 711–752) of Trauma and Berufskrankheit. This follow-up paper (II) presents criteria to be used in the evaluation of whether it is necessary to give up the occupations putting the spine at risk and in estimation of the degree of disability. 相似文献
35.
G R Seabrook D Karp D D Schmitt D F Bandyk J B Towne 《American journal of surgery》1990,160(5):501-505
Lifetime anticoagulation has become a therapeutic option for surgical patients with hypercoagulable states or prosthetic arterial bypass grafts. However, physicians may not achieve optimal anticoagulation or may attempt to limit the length of the therapy period because of the perceived morbidity from hemorrhagic complications of Coumadin therapy. A protocol for anticoagulant therapy monitored and regulated by a vascular nurse-clinician was reviewed. Coumadin was prescribed for 1,891 patient-months to 93 patients to maintain their prothrombin time 1.5 to 2 times control (range: 18 to 24 seconds). The mean (+/- SD) prothrombin time for the study population was 19.8 +/- 1.8 seconds. During follow-up, 472 (14%) of 3,479 prothrombin times measured were below the therapeutic range (n = 232) or prolonged (n = 240), prompting an adjustment in the Coumadin dose in 82 (88%) patients. Four patients developed recurrent vascular graft thrombosis while receiving anticoagulation. There were 6 major and 11 minor hemorrhagic complications. Patients with a chronic risk for arterial or venous thrombosis can have out-patient anticoagulant therapy administered at optimal intensity and regulated safely with a low incidence of hemorrhagic and thrombotic events. 相似文献
36.
Zusammenfassung Halbstrukturierte Inteviews mit 248 (ehemaligen) jüdischen Emigranten und Lagerh?ftlingen in Deutschland und drei Ziell?ndern
der jüdischen Emigration zeigen, da? Erinnerungen an traumatische Erlebnisse im Nationalsozialismus in zahlreichen allt?glichen
Kontexten auftreten und von zentraler Bedeutung für die Wahrnehmung der pers?nlichen Lebenssituation im Alter sind. Auf der
Grundlage der Ergebnisse einer Pilotstudie zur Frage nach der subjektiven Gliederung des Lebenslaufs bei (ehemaligen) jüdischen
Emigranten und Lagerh?ftlingen werden unterschiedliche Abschnitte der pers?nlichen Entwicklung nach dem Holocaust unterschieden.
Selbsteinsch?tzungen der Untersuchungsteilnehmer zur Intensit?t von Erinnerungen an traumatische Erlebnisse in diesen Entwicklungsabschnitten
unterstützen die Annahme, da? belastende Erinnerungen im Alter deutlich zugenommen haben. Die Untersuchungsteilnehmer unterscheiden
sich erheblich in den Formen der Auseinandersetzung mit solchen Erinnerungen. Einige Untersuchungsteilnehmer reagierten mit
Depressionen, Angstzust?nden, Gefühlen von überlebensschuld und Rückzug aus sozialen Beziehungen. Andere engagierten sich
hingegen in hohem Ma?e in sozialen Beziehungen, vor allem zu Angeh?rigen der jüngeren Generation, um dadurch zur Vermeidung
von Diskriminierung, Rassismus und Fremdenfeindlichkeit beizutragen.
Eingegangen: 14. August 1997, Akzeptiert: 26. Januar 1998 相似文献
37.
Dr. Caroline S. Zeind Pharm.D. Dr. Kerry O. Cleveland M.D. Dr. Madhavi Menon M.D. Dr. James R. Brown Pharm.D. Dr. David K. Solomon Pharm.D. 《Pharmacotherapy》1996,16(4):547-561
The optimum therapy for cryptococcal meningitis in patients with the acquired immunodeficiency syndrome (AIDS) remains unresolved. Traditional therapy consists of amphotericin B with or without flucytosine. Obstacles exist in administering these agents to patients with AIDS. Mortality rates during initial therapy are relatively high. Given the lack of proved benefit, we do not recommend adding flucytosine to amphotericin B routinely. The search for more efficacious and less toxic agents continues. The oral triazoles, especially fluconazole, have increased the options for treatment of this disease. New strategies and novel approaches in managing cryptococcal meningitis in patients with AIDS continue to be developed. 相似文献
38.
Oral administration of myelin basic protein (MBP) inhibits clinical and histopathological manifestations of experimental autoimmune encephalomyelitis (EAE), but only partially reduces serum anti-MBP antibody titers. We report here that orally administered MBP alters the isotypic distribution of anti-MBP antibody-forming cells (AFC) among various lymphoid tissues, with the most profound differences seen in mucosal tissues. We observed an isotype-selective reduction in anti-MBP IgA but not IgM AFC frequencies in Peyer's patches. The anti-MBP IgA AFC frequencies could be reconstituted by addition of interleukin 4 (IL-4) and interleukin 5 (IL-5). The cytokines did not appear to generate de novo responses since no increases in anti-MBP IgA AFC frequencies were observed in control cultures. These results indicate that decreased antibody production, as a result of oral antigen administration, can be reversed by exposure to the appropriate cytokines. 相似文献
39.
Paul G. Egland Dale A. Pelletier Marilyn Dispensa Jane Gibson Caroline S. Harwood 《Proceedings of the National Academy of Sciences of the United States of America》1997,94(12):6484-6489
A reductive benzoate pathway is the central conduit for the anaerobic biodegradation of aromatic pollutants and lignin monomers. Benzene ring reduction requires a large input of energy and this metabolic capability has, so far, been reported only in bacteria. To determine the molecular basis for this environmentally important process, we cloned and analyzed genes required for the anaerobic degradation of benzoate and related compounds from the phototrophic bacterium, Rhodopseudomonas palustris. A cluster of 24 genes was identified that includes twelve genes likely to be involved in anaerobic benzoate degradation and additional genes that convert the related compounds 4-hydroxybenzoate and cyclohexanecarboxylate to benzoyl-CoA. Genes encoding benzoyl-CoA reductase, a novel enzyme able to overcome the resonance stability of the aromatic ring, were identified by directed mutagenesis. The gene encoding the ring-cleavage enzyme, 2-ketocyclohexanecarboxyl-CoA hydrolase, was identified by assaying the enzymatic activity of the protein expressed in Escherichia coli. Physiological data and DNA sequence analyses indicate that the benzoate pathway consists of unusual enzymes for ring reduction and cleavage interposed among enzymes homologous to those catalyzing fatty acid degradation. The cloned genes should be useful as probes to identify benzoate degradation genes from other metabolically distinct groups of anaerobic bacteria, such as denitrifying bacteria and sulfate-reducing bacteria. 相似文献
40.
Objective: Referred obese adolescents often display psychological problems. The present study aimed at investigating whether Young's schema theory constitutes a comprehensive framework to understand psychopathology in youth in general and in referred obese adolescents in particular. Methods: 91 youngsters referred for obesity treatment and 91 normal weight controls (all between 12 and 18 years of age) filled out the Young Schema Questionnaire and the Youth Self‐Report. Parents were asked to complete the Child Behavior Checklist. Results: The obese youngsters displayed an overall greater severity of dysfunctional schemas than normal weight controls. The obese group scored significantly higher for the schemas Emotional Deprivation, Social Isolation/Alienation, Defectiveness/Shame, Failure to Achieve, Dependence/Incompetence and Subjugation. Social Isolation/Alienation and Vulnerability to Harm/Illness were highly predictive for internalizing symptoms in youth. The schemas Entitlement and Dependence/Incompetence were predictive for externalizing symptoms in youth. Conclusion: Referred obese individuals display high levels of maladaptive schemas and these are generally related to internalizing and externalizing symptoms. Copyright © 2007 John Wiley & Sons, Ltd. 相似文献