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1.
Based on its proven anabolic effects on bone in osteoporosis patients, recombinant parathyroid hormone (PTH1-34) has been evaluated as a potential therapy for skeletal repair. In animals, the effect of PTH1-34 has been investigated in various skeletal repair models such as fractures, allografting, spinal arthrodesis and distraction
osteogenesis. These studies have demonstrated that intermittent PTH1-34 treatment enhances and accelerates the skeletal repair process via a number of mechanisms, which include effects on mesenchymal
stem cells, angiogenesis, chondrogenesis, bone formation and resorption. Furthermore, PTH1-34 has been shown to enhance bone repair in challenged animal models of aging, inflammatory arthritis and glucocorticoid-induced
bone loss. This pre-clinical success has led to off-label clinical use and a number of case reports documenting PTH1-34 treatment of delayed-unions and non-unions have been published. Although a recently completed phase 2 clinical trial of PTH1-34 treatment of patients with radius fracture has failed to achieve its primary outcome, largely because of effective healing
in the placebo group, several secondary outcomes are statistically significant, highlighting important issues concerning the
appropriate patient population for PTH1-34 therapy in skeletal repair. Here, we review our current knowledge of the effects of PTH1-34 therapy for bone healing, enumerate several critical unresolved issues (e.g., appropriate dosing regimen and indications)
and discuss the long-term potential of this drug as an adjuvant for endogenous tissue engineering. 相似文献
2.
Proteins in the molecular weight range of 10 000–170 000 were separated by high performance gel permeation chromatography. Silica particles with 30 nm or 50 nm pores were derivatized with glycidoxy-propyltrimethoxysilane and used as support. The proteins were eluted with 50% formic acid. A protein fraction which induces endodermal and mesodermal tissues in amphibian gastrula ectoderm was purified by this method. 相似文献
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Growing cultures of an autolysis-defective pneumococcal mutant were exposed to [3H]benzylpenicillin at various multiples of the minimal inhibitory concentration and incubated until the growth of the cultures was halted. During the process of growth inhibition, we determined the rates and degree of acylation of the five penicillin-binding proteins (PBPs) and the rates of peptidoglycan incorporation, protein synthesis, and turbidity increase. The time required for the onset of the inhibitory effects of benzylpenicillin was inversely related to the concentration of the antibiotic, and inhibition of peptidoglycan incorporation always preceded inhibition of protein synthesis and growth. When cultures first started to show the onset of growth inhibition, the same characteristic fraction of each PBP was in the acylated form in all cases, irrespective of the antibiotic concentration. Apparently, saturation of one or more PBPs with the antibiotic beyond these threshold levels is needed to bring about interference with normal peptidoglycan production and cellular growth. Although it was not possible to correlate the inhibition of cell wall synthesis or cell growth with the degree of acylation (percentage saturation) of any single PBP, there was a correlation between the amount of peptidoglycan synthesized and the actual amount of PBP 2b that was not acylated. In cultures exposed to benzylpenicillin concentrations greater than eight times the minimal inhibitory concentration, the rates of peptidoglycan incorporation underwent a rapid decline when bacterial growth stopped. However, in cultures exposed to lower concentrations of benzylpenicillin (one to six times the minimal inhibitory concentration) peptidoglycan synthesis continued at constant rate for prolonged periods, after the turbidity had ceased to increase. We conclude that inhibition of bacterial growth does not require a complete inhibition or even a major decline in the rate of peptidoglycan incorporation. Rather, inhibition of growth must be caused by an as yet undefined process that stops cell division when the rate of incorporation of peptidoglycan (or synthesis of protein) falls below a critical value. 相似文献
7.
Molecular mechanisms of ceramide-mediated CD95 clustering. 总被引:2,自引:0,他引:2
H Grassmé H Schwarz E Gulbins 《Biochemical and biophysical research communications》2001,284(4):1016-1030
Receptor clustering has been suggested as a crucial mechanism to initiate receptor signaling. Here we show that ceramide in sphingolipid-rich membrane rafts mediates clustering of CD95. Neutralization of surface ceramide or inhibition of its endogenous generation prevented CD95 clustering. Furthermore, application of ceramide at the cell surface triggered clustering of active but not inactive CD95. Apoptosis was inhibited by neutralization of surface ceramide or inhibition of ceramide release in vitro and in vivo. Thus, we conclude that surface ceramide mediates CD95 clustering, which is required for initiation of apoptosis, at least in some cell types. 相似文献
8.
Antoine Wystrach Sebastian Schwarz Patrick Schultheiss Guy Beugnon Ken Cheng 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2011,197(2):167-179
The Australian desert ant Melophorus bagoti often follows stereotypical routes through a cluttered landscape containing both distant panoramic views and obstacles (plants)
to navigate around. We created an artificial obstacle course for the ants between a feeder and their nest. Landmarks comprised
natural objects in the landscape such as logs, branches, and tussocks. Many ants travelled stereotypical routes home through
the obstacle course in training, threading repeatedly the same gaps in the landmarks. Manipulations altering the relations
between the landmarks and the surrounding panorama, however, affected the routes in two major ways. Both interchanging the
positions of landmarks (transpositions) and displacing the entire landmark set along with the starting position of the ants
(translations) (1) reduced the stereotypicality of the route, and (2) increased turns and meanders during travel. The ants
might have used the entire panorama in view-based travel, or the distal panorama might prime the identification and use of
landmarks en route. Despite the large data set, both options (not mutually exclusive) remain viable. 相似文献
9.
W. O. van der Knaap Jacqueline F. N. van Leeuwen Tomasz Goslar Robert Krisai Willy Tinner 《Vegetation History and Archaeobotany》2012,21(1):37-60
Three mires and a small lake in the Swiss and Austrian Alps were studied palynologically at high resolution, covering the
last 1,000, 400, 50 and 1,200 years, respectively. Methodological lessons include: (1) Sub-decadal resolution in upper, little-decomposed
peat layers reveals recurrent marked fluctuations in both percentages and influx of regional tree-pollen types, reflecting
variations in pollen production rather than in plant-population sizes. (2) Intermittent, single-spectrum pollen maxima in
samples of sub-decadal resolution indicate pollen transport in clumps. This type of pollen transport may remain unrecognized
in sections with lower sampling resolution, which may then lead to inappropriate interpretation in terms of plant-population
sizes. (3) The detection of short-lived phases of human impact in decomposed peat requires sampling intervals as close as
0.2 cm. (4) PAR (pollen influx) may reflect vegetation dynamics more faithfully than percentages. Reliable PAR, however, is
difficult to achieve in Alpine mires due to past human impact on peat growth, even when complex depth–age modelling techniques
are used. Critical comparison of PAR with percentages is therefore essential. (5) Careful consideration of spatial scales
in pollen signals (local–regional and subdivisions) is essential for a realistic palaeo-ecological interpretation. Results
in terms of past human impact on vegetation are summarized as follows: (1) Trends in pollen types reflecting regional human
action are in general agreement with earlier findings for the western Swiss Alps, allowing for regional differences. (2) All
mires in the Alps investigated here and in an earlier study experienced human impact during the last millennium. The studied
small lake, lying in sub-alpine pasture, records forest dynamics at a lower elevation since a.d. 800. 相似文献
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