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11.
Severe freezing injury was produced in the hind foot of 26 mongrel dogs. All dogs were given daily whirlpool treatment and protective bandaging for 14 days following injury. In addition, certain dogs received a vasodilator, fasciotomy, or both vasodilator and fasciotomy following injury. Deep foot temperatures, foot volumes, tissue pressures, and 14 day tissue loss-salvage scores were compared. Significant differences between fasciotomy and nonfasciotomy dogs were seen in foot temperature, volume, and tissue pressure immediately following fasciotomy. Though there was no significant difference in 14 day tissue loss, there was clinically apparent prolongation of integrity of the local vascular system for 2 to 5 days following fasciotomy, and total foot salvage in several dogs receiving fasciotomy. 相似文献
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Smith GD Zhou L Rowe LR Jarboe EA Collins BT Bentz JS Wittwer CT Chadwick BE 《Acta cytologica》2011,55(6):576-583
Objective: To detect BRAF V600E mutation in thyroid fine-needle aspiration (FNA) slides and needle rinses (NR). Study Design: Tumor-enriched DNA was extracted from FNA smears, formalin-fixed paraffin-embedded (FFPE) sections, or NR specimens from 37 patients with confirmed papillary thyroid carcinoma or benign findings. An allele-specific primer selectively amplified the 1799 T>A BRAF mutation while simultaneously blocking amplification of wild-type (WT) BRAF with an unlabeled probe during PCR. Mutation detection was accomplished by melting analysis of the probe. Results: Allele-specific/blocking probe PCR confirmed the BRAF mutation status for 20 of 24 paired FNA/FFPE samples previously tested by fluorescent probe real-time PCR. For the other 4 cases, the sensitive PCR method detected the BRAF mutation in all paired FNA/FFPE samples. Previously, the mutation had been detected in only the FFPE samples. The BRAF mutation was also detected in some NR specimens. Conclusion: Treatment of patients with thyroid nodules is guided by FNA biopsy, which can be scantly cellular, necessitating a sensitive test that can detect low levels of BRAF V600E mutation in a WT background. We report increased detection of BRAF V600E in FNA specimens using allele-specific/blocking probe PCR, which has an analytical sensitivity of 0.01%. 相似文献
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GMF-Knockout Mice are Unable to Induce Brain-Derived Neurotrophic Factor after Exercise 总被引:2,自引:0,他引:2
We earlier reported that overexpression of glia maturation factor (GMF) in cultured astrocytes enhances the production of brain-derived neurotrophic factor (BDNF). The current study was conducted to find out whether BDNF production is impaired in animals devoid of GMF. To this end GMF-knockout (KO) mice were subjected to exercise and the neurotrophin mRNAs were determined by real-time RT-PCR. Compared to wild-type (WT) mice, there is a decrease in exercise-induced BDNF in the KO mice. The observation was correlated with the finding that, in WT mice, exercise increases GMF expression. The results are consistent with the hypothesis that GMF is necessary for exercise-induction of BDNF, and that GMF may promote neuroprotection through BDNF production. 相似文献
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Sarah E. Diamond Joel G. Kingsolver 《Proceedings. Biological sciences / The Royal Society》2011,278(1703):289-297
Immune defences are an important component of fitness. Yet susceptibility to pathogens is common, suggesting the presence of ecological and evolutionary limitations on immune defences. Here, we use structural equation modelling to quantify the direct effects of resource quality and selection history, and their indirect effects mediated via body condition prior to an immune challenge on encapsulation and melanization immune defences in the tobacco hornworm, Manduca sexta. We also investigate allocation trade-offs among immune defences and growth rate following an immune challenge. We found considerable variation in the magnitude and direction of the direct effects of resource quality and selection history on immune defences and their indirect effects mediated via body condition and allocation trade-offs. Greater resource quality and evolutionary exposure to pathogens had positive direct effects on encapsulation and melanization. The indirect effect of resource quality on encapsulation mediated via body condition was substantial, whereas indirect effects on melanization were negligible. Individuals in better condition prior to the immune challenge had greater encapsulation; however, following the immune challenge, greater encapsulation traded off with slower growth rate. Our study demonstrates the importance of experimentally and analytically disentangling the relative contributions of direct and indirect effects to understand variation in immune defences. 相似文献
15.
Khare SD Kipnis Y Greisen P Takeuchi R Ashani Y Goldsmith M Song Y Gallaher JL Silman I Leader H Sussman JL Stoddard BL Tawfik DS Baker D 《Nature chemical biology》2012,8(3):294-300
The ability to redesign enzymes to catalyze noncognate chemical transformations would have wide-ranging applications. We developed a computational method for repurposing the reactivity of metalloenzyme active site functional groups to catalyze new reactions. Using this method, we engineered a zinc-containing mouse adenosine deaminase to catalyze the hydrolysis of a model organophosphate with a catalytic efficiency (k(cat)/K(m)) of ~10(4) M(-1) s(-1) after directed evolution. In the high-resolution crystal structure of the enzyme, all but one of the designed residues adopt the designed conformation. The designed enzyme efficiently catalyzes the hydrolysis of the R(P) isomer of a coumarinyl analog of the nerve agent cyclosarin, and it shows marked substrate selectivity for coumarinyl leaving groups. Computational redesign of native enzyme active sites complements directed evolution methods and offers a general approach for exploring their untapped catalytic potential for new reactivities. 相似文献
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Matthew A.J. Duncton Eugene L. Piatnitski Chekler Reeti Katoch-Rouse Dan Sherman Wai C. Wong Leon M. Smith Joel K. Kawakami Alexander S. Kiselyov Daniel L. Milligan Chris Balagtas Yaron R. Hadari Ying Wang Sheetal N. Patel Robin L. Rolster James R. Tonra David Surguladze Stan Mitelman Paul Kussie Peter Bohlen Jacqueline F. Doody 《Bioorganic & medicinal chemistry》2009,17(2):731-740
A series of arylphthalazine derivatives were synthesized and evaluated as antagonists of VEGF receptor II (VEGFR-2). IM-094482 57, which was prepared in two steps from commercially available starting materials, was found to be a potent inhibitor of VEGFR-2 in enzymatic, cellular and mitogenic assays (comparable activity to ZD-6474). Additionally, 57 inhibited the related receptor, VEGF receptor I (VEGFR-1), and showed excellent exposure when dosed orally to female CD-1 mice. 相似文献
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Grace PM Hurley D Barratt DT Tsykin A Watkins LR Rolan PE Hutchinson MR 《Journal of neurochemistry》2012,122(5):976-994
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