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951.
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PTH has diverse effects on bone metabolism: anabolic when given intermittently, catabolic when given continuously. The cellular
mechanisms underlying the varying target cell response are not clear yet. PTH induces RGS-2, a member of the Regulator of
G-protein Signaling protein family, via cAMP/PKA, and inactivates PKC-mediated signaling. To investigate intracellular signaling
pathways with different PTH concentration-time patterns, we treated UMR 106-01 osteoblast-like cells in a perfusion system.
PTH was administered intermittently (4 min/h, 10−7 M) or continuously at an equivalent cumulative dose (6.6 × 10−9 M). cAMP was measured using radioimmunoassay, mRNA levels using real-time rtPCR and ribonuclease protection assay, and protein
levels using Western immunoblotting. A single PTH pulse transiently increased cAMP levels by 2000% ± 1200%. In contrast to
continuous PTH exposure, cAMP induction remained unchanged with intermittent PTH, ruling out desensitization of the PTH receptor.
In continuously perfused cells, RGS-2 abundance was three to five times higher than in cells intermittently exposed to PTH
for up to 12 h. MKP-1 and -3 were significantly less induced with pulsatile PTH; exposure-mode-dependent differences in MMP-13
and IGFBP-5 were small. Pulsatile but not continuous PTH administration prevents PTHrP receptor desensitization and accumulation
of RGS-2 in osteoblasts, which should preserve PKC-dependent signaling. 相似文献
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H. Pette 《Journal of neurology》1941,152(3-4):109-111
Ohne ZusammenfassungBei der Feier, die im festlich geschmückten großen Hörsaal des Universitätskrankenhauses Eppendorf stattfand, wurde Prof. Nonne in Anerkennung seiner Verdienste um die Neurologie die Goethe-Medaille für Kunst und Wissenschaft verliehen. 相似文献
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The Institute of Medicine distinguishes between programs based on who is targeted: the entire population (universal), those
at risk (selective), or persons exhibiting the early stages of use or related problem behavior (indicated). Evaluations suggest
that although universal programs can be effective in reducing and preventing substance use, selective and indicated programs
are both more effective and have greater cost-benefit ratios. This paper tests these assumptions by comparing the impact of
these program types in reducing and preventing substance use at the individual level (i.e., those exposed to intervention
services) and in the population (i.e., those exposed and not exposed to intervention services). A meta-analysis was performed
on 43 studies of 25 programs to examine program comparability across IOM categories. When examining unadjusted effect sizes
at the individual level, universal programs were modestly more successful in reducing tobacco use, but selective and indicated
programs were modestly more successful in reducing alcohol and marijuana use. When adjusted to the population level, the average
effect sizes for selective and indicated programs were reduced by approximately half. At the population level, universal programs
were more successful in reducing tobacco and marijuana use and selective and indicated programs were more successful in reducing
alcohol use. Editors’ Strategic Implications: The authors’ focus on the public health value of a prevention strategy is compelling and provides a model for analyses of
other strategies and content areas. 相似文献