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排序方式: 共有235条查询结果,搜索用时 15 毫秒
101.
102.
Eliot T. McKinley Gregory D. Ayers R. Adam Smith Samir A. Saleh Ping Zhao Mary Kay Washington Robert J. Coffey H. Charles Manning 《PloS one》2013,8(3)
Background
Non-invasive imaging biomarkers of cellular proliferation hold great promise for quantifying response to personalized medicine in oncology. An emerging approach to assess tumor proliferation utilizes the positron emission tomography (PET) tracer 3’-deoxy-3’[18F]-fluorothymidine, [18F]-FLT. Though several studies have associated serial changes in [18F]-FLT-PET with elements of therapeutic response, the degree to which [18F]-FLT-PET quantitatively reflects proliferative index has been continuously debated for more that a decade. The goal of this study was to elucidate quantitative relationships between [18F]-FLT-PET and cellular metrics of proliferation in treatment naïve human cell line xenografts commonly employed in cancer research.Methods and Findings
[18F]-FLT-PET was conducted in human cancer xenograft-bearing mice. Quantitative relationships between PET, thymidine kinase 1 (TK1) protein levels and immunostaining for proliferation markers (Ki67, TK1, PCNA) were evaluated using imaging-matched tumor specimens. Overall, we determined that [18F]-FLT-PET reflects TK1 protein levels, yet the cell cycle specificity of TK1 expression and the extent to which tumors utilize thymidine salvage for DNA synthesis decouple [18F]-FLT-PET data from standard estimates of proliferative index.Conclusions
Our findings illustrate that [18F]-FLT-PET reflects tumor proliferation as a function of thymidine salvage pathway utilization. Unlike more general proliferation markers, such as Ki67, [18F]-FLT PET reflects proliferative indices to variable and potentially unreliable extents. [18F]-FLT-PET cannot discriminate moderately proliferative, thymidine salvage-driven tumors from those of high proliferative index that rely primarily upon de novo thymidine synthesis. Accordingly, the magnitude of [18F]-FLT uptake should not be considered a surrogate of proliferative index. These data rationalize the diversity of [18F]-FLT-PET correlative results previously reported and suggest future best-practices when [18F]-FLT-PET is employed in oncology. 相似文献103.
Blue light from light-emitting diodes elicits a dose-dependent suppression of melatonin in humans 总被引:1,自引:0,他引:1
West KE Jablonski MR Warfield B Cecil KS James M Ayers MA Maida J Bowen C Sliney DH Rollag MD Hanifin JP Brainard GC 《Journal of applied physiology (Bethesda, Md. : 1985)》2011,110(3):619-626
Light suppresses melatonin in humans, with the strongest response occurring in the short-wavelength portion of the spectrum between 446 and 477 nm that appears blue. Blue monochromatic light has also been shown to be more effective than longer-wavelength light for enhancing alertness. Disturbed circadian rhythms and sleep loss have been described as risk factors for astronauts and NASA ground control workers, as well as civilians. Such disturbances can result in impaired alertness and diminished performance. Prior to exposing subjects to short-wavelength light from light-emitting diodes (LEDs) (peak λ = 469 nm; 1/2 peak bandwidth = 26 nm), the ocular safety exposure to the blue LED light was confirmed by an independent hazard analysis using the American Conference of Governmental Industrial Hygienists exposure limits. Subsequently, a fluence-response curve was developed for plasma melatonin suppression in healthy subjects (n = 8; mean age of 23.9 ± 0.5 years) exposed to a range of irradiances of blue LED light. Subjects with freely reactive pupils were exposed to light between 2:00 and 3:30 AM. Blood samples were collected before and after light exposures and quantified for melatonin. The results demonstrate that increasing irradiances of narrowband blue-appearing light can elicit increasing plasma melatonin suppression in healthy subjects (P < 0.0001). The data were fit to a sigmoidal fluence-response curve (R(2) = 0.99; ED(50) = 14.19 μW/cm(2)). A comparison of mean melatonin suppression with 40 μW/cm(2) from 4,000 K broadband white fluorescent light, currently used in most general lighting fixtures, suggests that narrow bandwidth blue LED light may be stronger than 4,000 K white fluorescent light for suppressing melatonin. 相似文献
104.
Prion strains are characterized by differences in the outcome of disease, most notably incubation period and neuropathological features. While it is established that the disease specific isoform of the prion protein, PrP(Sc), is an essential component of the infectious agent, the strain-specific relationship between PrP(Sc) properties and the biological features of the resulting disease is not clear. To investigate this relationship, we examined the amplification efficiency and conformational stability of PrP(Sc) from eight hamster-adapted prion strains and compared it to the resulting incubation period of disease and processing of PrP(Sc) in neurons and glia. We found that short incubation period strains were characterized by more efficient PrP(Sc) amplification and higher PrP(Sc) conformational stabilities compared to long incubation period strains. In the CNS, the short incubation period strains were characterized by the accumulation of N-terminally truncated PrP(Sc) in the soma of neurons, astrocytes and microglia in contrast to long incubation period strains where PrP(Sc) did not accumulate to detectable levels in the soma of neurons but was detected in glia similar to short incubation period strains. These results are inconsistent with the hypothesis that a decrease in conformational stability results in a corresponding increase in replication efficiency and suggest that glia mediated neurodegeneration results in longer survival times compared to direct replication of PrP(Sc) in neurons. 相似文献
105.
Mehan MR Ayers D Thirstrup D Xiong W Ostroff RM Brody EN Walker JJ Gold L Jarvis TC Janjic N Baird GS Wilcox SK 《PloS one》2012,7(4):e35157
Lung cancer remains the most common cause of cancer-related mortality. We applied a highly multiplexed proteomic technology (SOMAscan) to compare protein expression signatures of non small-cell lung cancer (NSCLC) tissues with healthy adjacent and distant tissues from surgical resections. In this first report of SOMAscan applied to tissues, we highlight 36 proteins that exhibit the largest expression differences between matched tumor and non-tumor tissues. The concentrations of twenty proteins increased and sixteen decreased in tumor tissue, thirteen of which are novel for NSCLC. NSCLC tissue biomarkers identified here overlap with a core set identified in a large serum-based NSCLC study with SOMAscan. We show that large-scale comparative analysis of protein expression can be used to develop novel histochemical probes. As expected, relative differences in protein expression are greater in tissues than in serum. The combined results from tissue and serum present the most extensive view to date of the complex changes in NSCLC protein expression and provide important implications for diagnosis and treatment. 相似文献
106.
107.
108.
Matulevicius S Rohatgi A Khera A Das SR Owens A Ayers CR Timaran CH Rosero EB Drazner MH Peshock RM de Lemos JA 《Apoptosis : an international journal on programmed cell death》2008,13(10):1281-1289
Background Caspase-3, an apoptosis protease, is expressed in atherosclerotic plaques. We examined the relationship between plasma caspase-3
levels, aortic compliance, and atherosclerosis.
Methods Caspase-3 was measured in 3,221 subjects from the Dallas Heart Study. Electron beam computed tomography measures of coronary
calcium (CAC) (n = 2,404) and magnetic resonance imaging (MRI) measures of abdominal aortic wall thickness (AWT) (n = 2,208) and aortic compliance (AC) (n = 2,328) were obtained. Multivariate analyses were performed, adjusting for age, sex, ethnicity, body mass index (BMI), traditional
cardiovascular risk factors, and cardiac medications.
Results In univariable analysis, caspase-3 associated with CAC (P < 0.0001), AWT (P = 0.002), and AC (P < 0.0001). After multivariable adjustment, 4th quartile caspase-3 (compared to 1st quartile) was significantly associated
with CAC (P = 0.004), AWT (P = 0.02), and AC (P < 0.0001) with similar findings for caspase-3 as a continuous variable.
Conclusions Caspase-3 independently associates with CAC, AWT, and AC, suggesting a link between apoptosis and atherosclerosis. 相似文献
109.
110.
MacInnes CD Smith SM Tinline RR Ayers NR Bachmann P Ball DG Calder LA Crosgrey SJ Fielding C Hauschildt P Honig JM Johnston DH Lawson KF Nunan CP Pedde MA Pond B Stewart RB Voigt DR 《Journal of wildlife diseases》2001,37(1):119-132
The province of Ontario (Canada) reported more laboratory confirmed rabid animals than any other state or province in Canada or the USA from 1958-91, with the exception of 1960-62. More than 95% of those cases occurred in the southern 10% of Ontario (approximately 100,000 km2), the region with the highest human population density and greatest agricultural activity. Rabies posed an expensive threat to human health and significant costs to the agricultural economy. The rabies variant originated in arctic foxes: the main vector in southern Ontario was the red fox (Vulpes vulpes), with lesser involvement of the striped skunk (Mephitis mephitis). The Ontario Ministry of Natural Resources began a 5 yr experiment in 1989 to eliminate terrestrial rabies from a approximately 30,000 km2 study area in the eastern end of southern Ontario. Baits containing oral rabies vaccine were dropped annually in the study area at a density of 20 baits/km2 from 1989-95. That continued 2 yr beyond the original 5 yr plan. The experiment was successful in eliminating the arctic fox variant of rabies from the whole area. In the 1980's, an average of 235 rabid foxes per year were reported in the study area. None have been reported since 1993. Cases of fox rabies in other species also disappeared. In 1995, the last bovine and companion animal cases were reported and in 1996 the last rabid skunk occurred. Only bat variants of rabies were present until 1999, when the raccoon variant entered from New York (USA). The success of this experiment led to an expansion of the program to all of southern Ontario in 1994. Persistence of terrestrial rabies, and ease of elimination, appeared to vary geographically, and probably over time. Ecological factors which enhance or reduce the long term survival of rabies in wild foxes are poorly understood. 相似文献