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1.
Takeshi Sakata Yongmei Wang Bernard P Halloran Hashem Z Elalieh Jay Cao Daniel D Bikle 《Journal of bone and mineral research》2004,19(3):436-446
We showed that unloading markedly diminished the effects of IGF-I to activate its signaling pathways, and the disintegrin echistatin showed a similar block in osteoprogenitor cells. Furthermore, unloading decreased alphaVbeta3 integrin expression. These results show that skeletal unloading induces resistance to IGF-I by inhibiting activation of the IGF-I signaling pathways at least in part through downregulation of integrin signaling. INTRODUCTION: We have previously reported that skeletal unloading induces resistance to insulin-like growth factor-I (IGF-I) with respect to bone formation. However, the underlying mechanism remains unclear. The aim of this study was to clarify how skeletal unloading induces resistance to the effects of IGF-I administration in vivo and in vitro with respect to bone formation. MATERIALS AND METHODS: We first determined the response of bone to IGF-I administration in vivo during skeletal unloading. We then evaluated the response of osteoprogenitor cells isolated from unloaded bones to IGF-I treatment in vitro with respect to activation of the IGF-I signaling pathways. Finally we examined the potential role of integrins in mediating the responsiveness of osteoprogenitor cells to IGF-I. RESULTS: IGF-I administration in vivo significantly increased proliferation of osteoblasts. Unloading markedly decreased proliferation and blocked the ability of IGF-I to increase proliferation. On a cellular level, IGF-I treatment in vitro stimulated the activation of its receptor, Ras, ERK1/2 (p44/42 MAPK), and Akt in cultured osteoprogenitor cells from normally loaded bones, but these effects were markedly diminished in cells from unloaded bones. These results were not caused by altered phosphatase activity or changes in receptor binding to IGF-I. Inhibition of the Ras/MAPK pathway was more impacted by unloading than that of Akt. The disintegrin echistatin (an antagonist of the alphaVbeta3 integrin) blocked the ability of IGF-I to stimulate its receptor phosphorylation and osteoblast proliferation, similar to that seen in cells from unloaded bone. Furthermore, unloading significantly decreased the mRNA levels both of alphaV and beta3 integrin subunits in osteoprogenitor cells. CONCLUSION: These results indicate that skeletal unloading induces resistance to IGF-I by inhibiting the activation of IGF-I signaling pathways, at least in part, through downregulation of integrin signaling, resulting in decreased proliferation of osteoblasts and their precursors. 相似文献
2.
E MOLKE JENSEN K. A. THIESSEN AA. CHRISTENSEN 《Acta anaesthesiologica Scandinavica》1986,30(2):109-110
The effect of 4 mg oral naloxone on preoperative gastric volume and pH of gastric aspirate was studied in a double-blind, randomized study. Twenty patients received 10 ml of naloxone (4 mg) mixed with 10 ml of orange juice, and 20 patients received 10 ml of isotonic saline mixed with 10 ml of orange juice, 2 h before surgery. Gastric content was obtained immediately after intubation of the trachea. No significant difference in gastric volume and pH of gastric aspirate was found between the two groups. It is concluded that naloxone does not affect gastric emptying and gastric acid secretion to a degree great enough to protect against aspiration of gastric contents into the lungs. 相似文献
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Smoking and female infertility: a systematic review and meta-analysis 总被引:11,自引:10,他引:11
The high prevalence of smoking among women in their reproductive years
continues to be a matter of concern. The negative effects of smoking on
general health are well known, but smoking may also affect fertility. The
objective of the present study was to perform a systematic review of the
literature to determine whether there is an association between smoking and
risk of infertility in women of reproductive age, and to assess the size of
this effect. In the 12 studies used for this meta- analysis, the overall
value of the odds ratio (OR) for risk of infertility in women smokers
versus non-smokers was 1.60 [95% confidence interval (CI) 1.34-1.91].
Studies of subfertile women undergoing in-vitro fertilization (IVF)
treatment also show a reduction in fecundity among women smokers. A
meta-analysis of nine studies found an OR of 0.66 (95% CI 0.49-0.88) for
pregnancies per number of IVF- treated cycles in smokers versus
non-smokers. Despite the potential limitations of meta-analyses of
observational studies, the evidence presented in this review is compelling
because of the consistency of effect across different study designs, sample
size and types of outcome. However, continued reassurance is needed that
the calculated overall effect is not in fact due to confounding variables.
相似文献
8.
Positional cloning of the gene for X-linked retinitis pigmentosa 3: homology with the guanine-nucleotide-exchange factor RCC1 总被引:6,自引:7,他引:6
Roepman R; van Duijnhoven G; Rosenberg T; Pinckers AJ; Bleeker-Wagemakers LM; Bergen AA; Post J; Beck A; Reinhardt R; Ropers HH; Cremers FP; Berger W 《Human molecular genetics》1996,5(7):1035-1041
The gene for retinitis pigmentosa 3 (RP3), the most frequent form of X-
linked RP (XLRP), has been mapped previously to a chromosome interval of
less than 1000 kbp between the DXS1110 marker and the OTC locus at
Xp21.1-p11.4. Employing a novel technique, YAC Representation Hybridization
(YRH)', we have recently identified a small XLRP associated microdeletion
in this interval, as well as several putative exons including the 3' end of
a gene that was truncated by the deletion. cDNA library screening and
sequencing of a cosmid centromeric to the deletion has now enabled us to
identify numerous additional exons and to detect several point mutations in
patients with XLRP. The predicted gene product shows homology to RCC1, the
guanine-nucleotide- exchange factor (GEF) of the Ras-like GTPase Ran. Our
findings suggest that we have cloned the long-sought RP3 gene, and that it
may encode the GEF of a retina-specific GTP-binding protein.
相似文献
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Lundberg S; Rasmussen C; Berg AA; Lindblom B 《Human reproduction (Oxford, England)》1998,13(6):1490-1492
Falloposcopy is a transvaginal microendoscopic technique to explore the
human Fallopian tube from the uterotubal ostium to the fimbrial end.
Falloposcopy provides a unique possibility to visualize endotubal disease
and may be used therapeutically for removal of debris and for cutting down
filmy intraluminal adhesions. To assess the clinical performance of
falloposcopy as part of an infertility investigation, a total of 43 women
scheduled for laparoscopy as part of an investigation of infertility had a
falloposcopy performed in conjunction with the laparoscopy. All women were
investigated at Danderyd Hospital, Stockholm and Akademiska Hospital,
Uppsala, during 1995 and 1996. Images from the endosalpinx were obtained in
26 of 43 women (60.5%). In 10 women (23.3%), it was possible to obtain
images from both tubes. No images were of sufficient quality to describe
the entire tubal mucosa in detail. Falloposcopy represents a unique tool
for visualization of endotubal disease and may provide a valuable
instrument for in-vivo exploration of tubal physiology. However, certain
technical problems limit the usefulness of this method in routine clinical
practice. These technical problems have to be solved before falloposcopy
can achieve a central position in investigation and treatment of tubal
disease.
相似文献