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Sanjeev Kakar Thomas A Einhorn Siddharth Vora Lincoln J Miara Gregory Hon Nathan A Wigner Daniel Toben Kimberly A Jacobsen Maisa O Al-Sebaei Michael Song Philip C Trackman Elise F Morgan Louis C Gerstenfeld George L Barnes 《Journal of bone and mineral research》2007,22(12):1903-1912
Studies have shown that systemic PTH treatment enhanced the rate of bone repair in rodent models. However, the mechanisms through which PTH affects bone repair have not been elucidated. In these studies we show that PTH primarily enhanced the earliest stages of endochondral bone repair by increasing chondrocyte recruitment and rate of differentiation. In coordination with these cellular events, we observed an increased level of canonical Wnt-signaling in PTH-treated bones at multiple time-points across the time-course of fracture repair, supporting the conclusion that PTH responses are at least in part mediated through Wnt signaling. INTRODUCTION: Since FDA approval of PTH [PTH(1-34); Forteo] as a treatment for osteoporosis, there has been interest in its use in other musculoskeletal conditions. Fracture repair is one area in which PTH may have a significant clinical impact. Multiple animal studies have shown that systemic PTH treatment of healing fractures increased both callus volume and return of mechanical competence in models of fracture healing. Whereas the potential for PTH has been established, the mechanism(s) by which PTH produces these effects remain elusive. MATERIALS AND METHODS: Closed femoral fractures were generated in 8-wk-old male C57Bl/6 mice followed by daily systemic injections of either saline (control) or 30 microg/kg PTH(1-34) for 14 days after fracture. Bones were harvested at days 2, 3, 5, 7, 10, 14, 21, and 28 after fracture and analyzed at the tissue level by radiography and histomorphometry and at the molecular and biochemical levels level by RNase protection assay (RPA), real-time PCR, and Western blot analysis. RESULTS: Quantitative muCT analysis showed that PTH treatment induced a larger callus cross-sectional area, length, and total volume compared with controls. Molecular analysis of the expression of extracellular matrix genes associated with chondrogenesis and osteogenesis showed that PTH treated fractures displayed a 3-fold greater increase in chondrogenesis relative to osteogenesis over the course of the repair process. In addition, chondrocyte hypertrophy occurred earlier in the PTH-treated callus tissues. Analysis of the expression of potential mediators of PTH actions showed that PTH treatment significantly induced the expression of Wnts 4, 5a, 5b, and 10b and increased levels of unphosphorylated, nuclear localized beta-catenin protein, a central feature of canonical Wnt signaling. CONCLUSIONS: These results showed that the PTH-mediated enhancement of fracture repair is primarily associated with an amplification of chondrocyte recruitment and maturation in the early fracture callus. Associated with these cellular effects, we observed an increase in canonical Wnt signaling supporting the conclusion that PTH effects on bone repair are mediated at least in part through the activation of Wnt-signaling pathways. 相似文献
23.
Marjan Boerma Gregory R Burton Junru Wang Louis M Fink Robert E McGehee Martin Hauer-Jensen 《Blood coagulation & fibrinolysis》2006,17(3):173-180
Immortalized cell lines offer significant logistical advantages over primary cells when used for in-vitro studies. Immortalized cells may, however, exhibit important differences relative to their primary cell counterparts. In this study, microarrays were used to make a genome-wide comparison between primary human umbilical vein endothelial cells (HUVECs) and EA.hy926, an immortalized HUVEC cell line, in their baseline properties and in their response to inhibition of the mevalonate pathway with an inhibitor of hydroxy methylglutaryl-coenzyme A reductase (statin). HUVECs and EA.hy926 were incubated with control medium, atorvastatin, mevalonate, or a combination of atorvastatin and mevalonate for 24 h. Gene expression profiles were obtained in duplicates using Affymetrix Human Genome U133A 2.0 arrays (Santa Clara, California, USA). Probe-sets were selected according to the following criteria: a twofold or greater increase/decrease in atorvastatin-treated cells compared with untreated cells; a twofold or greater reversal of the effect of atorvastatin by combined treatment with atorvastatin and mevalonate; no significant change in gene expression in cells treated with mevalonate alone compared with untreated cells. Most genes that were expressed by untreated HUVECs, were also expressed by untreated EA.hy926 cells. EA.hy926 cells, however, constitutively expressed a large number of additional genes, many of which were related to cell cycle control and apoptosis. Atorvastatin induced differential expression (> or = twofold) of 103 genes in HUVECs (10 up, 93 down) and 466 genes in EA.hy926 cells (198 up, 268 down). Applying the above selection criteria, thrombomodulin and tissue plasminogen activator were up-regulated in both cell types, whereas, connective tissue growth factor, thrombospondin-1, and cysteine-rich angiogenic inducer 61 were down-regulated. In conclusion, EA.hy926 cells retain most of the characteristics of endothelial cells under baseline conditions as well as after treatment with atorvastatin. It is necessary, however, to carefully select and validate changes in genes that are the focus of studies when using EA.hy926 cells. While this cell line is highly useful in studies on some genes, including genes encoding molecules involved in regulating thrombohemorrhagic homeostasis, they appear to be less suited for studies focused on other genes, particularly those involved in the regulation of cell proliferation and apoptosis. 相似文献
24.
25.
Ganapathy A Prasad Kenneth K Wang Lori S Lutzke Jason T Lewis Schuyler O Sanderson Navtej S Buttar Louis M Wong Kee Song Lynn S Borkenhagen Lawrence J Burgart 《Clinical gastroenterology and hepatology》2006,4(2):173-178
BACKGROUND & AIMS: The aim of this study was to assess the validity of frozen section analysis of endoscopic mucosal resection (EMR) specimens from Barrett's esophagus as compared with permanent sections for the detection of neoplasia. Frozen sections help to give immediate feedback for surgical procedures. It has not been determined whether EMR can be adequately interpreted by using frozen sections to aid endoscopists in completely resecting neoplastic lesions. METHODS: EMR specimens from Barrett's esophagus with high-grade dysplasia (HGD) and/or carcinoma were tested by frozen section. Pathologists evaluated EMR specimens for the depth of invasion as well as the appearance of clear margins of resection. The kappa statistic was calculated to assess the degree of agreement between the frozen section and permanent section diagnoses. RESULTS: Twenty-three consecutive patients underwent 30 EMRs with frozen section diagnosis. Frozen section revealed a carcinoma in 7 specimens (23%) and dysplasia in 20 (66%). Permanent sections found carcinoma in 8 specimens (26%), dysplasia in 19 specimens (63%), and normal or nondysplastic Barrett's esophagus in the remainder. The kappa statistic for the depth of invasion of EMR specimens was 0.93 (near perfect agreement). The kappa statistic for the margins of the EMR specimens was 0.80 (excellent agreement). CONCLUSIONS: This study indicated that frozen section analysis of esophageal EMR specimens is valid as compared with permanent section. This technique might allow rapid evaluation about the degree and depth of involvement of cancers. This allows physicians to make decisions regarding further therapy if margins are involved or decrease the use of EMR for histologically benign-appearing lesions. 相似文献
26.
Resolution of homonymous visual field loss documented with functional magnetic resonance and diffusion tensor imaging. 总被引:5,自引:0,他引:5
Masaki Yoshida Masahiro Ida Thien Huong Nguyen Marie-Therese Iba-Zizen Luc Bellinger Jean Louis Stievenart Takehiko Nagao Shinsuke Kikuchi Takaaki Hara Takuya Shiba Kenji Kitahara Emmanuel Alain Cabanis 《Journal of neuro-ophthalmology》2006,26(1):11-17
A 68-year-old man developed right homonymous hemianopic paracentral scotomas from acute infarction of the left extrastriate area. He was studied over the ensuing 12 months with visual fields, conventional MRI, functional MRI (fMRI), and diffusion tensor imaging (DTI). As the visual field defect became smaller, fMRI demonstrated progressively larger areas of cortical activation. DTI initially showed that the lesioned posterior optic radiations were completely interrupted. This interruption lessened in time and had disappeared by one year after onset. fMRI and DTI are innovative measures to follow functional and structural recovery in the central nervous system. This is the first reported application of these imaging techniques to acute cerebral visual field disorders. 相似文献
27.
Louis Bernard Christophe Sadowski Daniel Monin Richard Stern Blaise Wyssa Peter Rohner Daniel Lew Pierre Hoffmeyer 《Infection control and hospital epidemiology》2004,25(6):512-514
OBJECTIVE: To determine whether bacterial cultures of the wounds of patients undergoing clean orthopedic surgery would help predict infection. METHODS: During 1 year, 1,256 cultures were performed for 1,102 patients who underwent clean orthopedic surgery. Results were analyzed to evaluate their ability to predict postoperative infection. RESULTS: The sensitivity, specificity, positive predictive value, and negative predictive value of the cultures were 38%, 92%, 7%, and 99%, respectively. CONCLUSIONS: Cultures performed during clean orthopedic surgery were not useful for predicting postoperative infection. 相似文献
28.
Angela Alama Federica Barbieri Renato Spaziante Cristina Bruzzo Patrizia Dadati Alessandra Dorcaratto Jean Louis Ravetti 《Journal of clinical neuroscience》2007,14(4):355-358
Forty-four evaluable patients with intracranial meningiomas were assessed for the expression of the cell-cycle regulator cyclin D1 and of proteins involved in proliferation and apoptosis such as PCNA, MIB-1, p53 and bcl-2. Analyses were carried out by western blot and immunohistochemistry after immediate processing of fresh tumor specimens. By western blot, expression of cyclin D1 significantly correlated with p53 (p=0.02) and with proliferative activity, as assessed by PCNA expression (p=0.0009). By immunohistochemistry, a significant relationship between cyclin D1 and the proliferation marker MIB-1 was confirmed (p=0.05), whereas significance with bcl-2 expression was not found (p=0.01). Moreover, although the association with tumor grade appeared of borderline statistical significance (p=0.07), all the grade II/III meningiomas showed increased expression of cyclin D1 and high proliferative activity. In conclusion, data from this preliminary study seem to suggest a potential value of the combined expression of cyclin D1 and proliferation indicators in defining subgroups of meningiomas with a more aggressive biological behavior. 相似文献
29.
Michael C. Kontos Kristin L. Schmidt Michael McCue Louis F. Rossiter Michael Jurgensen Christopher S. Nicholson Robert L. Jesse Joseph P. Ornato James L. Tatum 《Journal of nuclear cardiology》2003,10(3):284-290
BACKGROUND: Our objective was to determine the cost-effectiveness of a comprehensive, risk-based triage system, composed of multiple critical pathways, with the use of early myocardial perfusion imaging (MPI) in low-risk patients. We found previously that a chest pain evaluation system that uses MPI in low-risk patients was safe and effective, but the cost-effectiveness of this approach was not studied. METHODS AND RESULTS: We compared two groups. The Acute Cardiac Team (ACT) group (n = 874) was assigned prospectively to 1 of 4 risk levels by emergency department (ED) physicians. Level 1, 2, and 3 patients were admitted; level 4 patients were evaluated in the ED. Level 3 and 4 patients underwent ED MPI. The control group (n = 713) represented consecutive patients evaluated in the prior year according to standard care and assigned retrospectively to an ACT level based on the presenting electrocardiographic and clinical data. Record and hospital administrative data were assessed for clinical variables, outcomes, lengths of stay, and all expenses incurred within 30 days of the index visit. The baseline characteristics of the two groups were similar, including age, sex, myocardial infarction prevalence, and 30-day revascularization rates within each level or between the two groups. Mean costs per encounter were reduced for the ACT patients for each level, which was significant when all patients were compared ($5,030 +/- $7,081 vs $6,044 +/- $10,432, P =.02). Use of MPI in the low-risk patients was associated with reduced costs (level 3, $4,958 +/- $4,948 vs $5,051 +/- $7,036; level 4, $1,529 +/- $2,664 vs $1,794 +/- $6,854) and was associated with a significantly lower angiography rate and shorter length of stay. CONCLUSIONS: Implementation of a comprehensive strategy for chest pain evaluation and triage reduced overall costs for patients with chest pain on presentation. Acute MPI in the ED setting did not increase net cost. 相似文献
30.
Andreas Nikolis Apostolos Christopoulos Michel Saint-Cyr Carlos Cordoba Louis Guertin Patrick G Harris 《CANADIAN JOURNAL OF PLASTIC SURGERY》2003,11(1):37-40
Complications following free tissue transfer have been well established in the literature. Common and rare causes of free flap failure must be addressed by the treating surgeon when microvascular patency is threatened. With the evolution and prevalence of microsurgery, ‘rare’ causes of free flap failure will become increasingly frequent. A high index of suspicion must be established in patients with multiple failed operative interventions. A case of recurrent free flap failure secondary to heparin-induced thrombocytopenia is presented in a patient with a history of squamous cell carcinoma of the floor of the mouth, and a long-standing history of alcohol and tobacco consumption. 相似文献