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91.
Glasow A Barrett A Petrie K Gupta R Boix-Chornet M Zhou DC Grimwade D Gallagher R von Lindern M Waxman S Enver T Hildebrandt G Zelent A 《Blood》2008,111(4):2374-2377
The retinoic acid receptor (RAR) alpha gene (RARA) encodes 2 major isoforms and mediates positive effects of all-trans retinoic acid (ATRA) on myelomonocytic differentiation. Expression of the ATRA-inducible (RARalpha2) isoform increases with myelomonocytic differentiation and appears to be down-regulated in many acute myeloid leukemia (AML) cell lines. Here, we demonstrate that relative to normal myeloid stem/progenitor cells, RARalpha2 expression is dramatically reduced in primary AML blasts. Expression of the RARalpha1 isoform is also significantly reduced in primary AML cells, but not in AML cell lines. Although the promoters directing expression of RARalpha1 and RARalpha2 are respectively unmethylated and methylated in AML cell lines, these regulatory regions are unmethylated in all the AML patient cell samples analyzed. Moreover, in primary AML cells, histones associated with the RARalpha2 promoter possessed diminished levels of H3 acetylation and lysine 4 methylation. These results underscore the complexities of the mechanisms responsible for deregulation of gene expression in AML and support the notion that diminished RARA expression contributes to leukemogenesis. 相似文献
92.
93.
Kazlauskaite R Evans AT Villabona CV Abdu TA Ambrosi B Atkinson AB Choi CH Clayton RN Courtney CH Gonc EN Maghnie M Rose SR Soule SG Tordjman K;Consortium for Evaluation of Corticotropin Test in Hypothalamic-Pituitary Adrenal Insufficiency 《The Journal of clinical endocrinology and metabolism》2008,93(11):4245-4253
94.
Catherine M Lowndes Ellie Sherrard-Smith Ciara Dangerfield Yoon H Choi Nathan Green Mark Jit Rob D Marshall Catherine Mercer Emma Harding-Esch Anthony Nardone Rebecca Howell-Jones John Bason Owen A Johnson Christopher P Price Charlotte A Gaydos S Tariq Sadiq Peter J White 《Lancet》2014
BackgroundChlamydia trachomatis is the most commonly diagnosed bacterial sexually transmitted infection in Britain. Present standards specify treatment within 14 days of testing positive; point-of-care testing (POCT) can eliminate this delay and potentially reduce loss to follow-up; its greater convenience might increase testing. 90-min nucleic acid amplification tests are the best available POCTs for chlamydia, with alternatives under development. However, cost-effectiveness depends on cost-per-test, sensitivity and specificity, and the effect of POCT on transmission.MethodsWe developed a user-friendly web-based method, based on a transmission-dynamic model for chlamydia, to assess the epidemiological impact and cost-effectiveness of introducing POCT in different local settings. The model uses behavioural and prevalence data from the National Survey of Sexual Attitudes and Lifestyles, and Public Health England surveillance data; these data inform on local-level variation, which is represented by sampling parameter values from within their ranges of uncertainty and selecting parameter sets that reproduce local coverage and diagnosis rates. The user can select different local settings, and vary sensitivity and specificity for the tests, specify costs (fixed and unit costs, including staff time), and then assess the effect of introducing POCT in different clinical services by comparison with a situation with no POCT. In the model, presumptive treatment is represented, which we expect to be reduced with the introduction of POCT because test results would be rapidly available to guide treatment.FindingsChanges in numbers of infections and diagnoses occurring under different scenarios (including conventional testing) were estimated, with uncertainty ranges, allowing calculation of total costs, and cost per infection (and serious sequelae) averted, while accommodating the considerable variation in chlamydia testing coverage, positivity, and diagnosis rates. Potential changes in sexual behaviour between test and treatment could determine the relative contribution of increased treatment rates and reduced treatment delay to the reduction in prevalence as a consequence of POCT.InterpretationThe effect of POCT was dependent on both the test performance characteristics and the assumptions about the implementation of the test across local services. Exploration of many uncertainties surrounding chlamydia epidemiology and screening implementation is possible with this model. This method can complement local and national knowledge, and contribute to local-level management of chlamydia infection.FundingInnovate UK (Technology Strategy Board), UK Medical Research Council, and the National Institute for Health Research. The Electronic Self-Testing Instruments for Sexually Transmitted Infection (eSTI2) Consortium eSTI2 is Funded under the UKCRC Translational Infection Research (TIR) Initiative supported by the Medical Research Council (Grant Number G0901608) with contributions to the Grant from the Biotechnology and Biological Sciences Research Council, the National Institute for Health Research on behalf of the Department of Health, the Chief Scientist Office of the Scottish Government Health Directorates, and the Wellcome Trust 相似文献
95.
M. Tariq Bhatti 《Current neurology and neuroscience reports》1996,6(5):403-413
Retinitis pigmentosa (RP) refers to a group of inherited retinal diseases with phenotypic and genetic heterogeneity. The pathophysiologic
basis of the progressive visual loss in patients with RP is not completely understood but is felt to be due to a primary retinal
photoreceptor cell degenerative process mainly affecting the rods of the peripheral retina. In most cases RP is seen in isolation
(nonsyndromic), but in some other cases it may be a part of a genetic, metabolic, or neurologic syndrome or disorder. Nyctalopia,
or night blindness, is the most common symptom of RP. The classic fundus appearance of RP includes retinal pigment epithelial
cell changes resulting in retinal hypo- or hyperpigmentation ("salt-and-pepper"), retinal granularity, and bone spicule formation.
The retinal vessels are often narrowed or attenuated and there is a waxy pallor appearance of the optic nerve head. Electroretinography
will demonstrate rod and cone photoreceptor cell dysfunction and is a helpful test in the diagnosis and monitoring of patients
with RP. A detailed history with pedigree analysis, a complete ocular examination, and the appropriate paraclinical testing
should be performed in patients complaining of visual difficulties at night or in dim light. This review discusses the clinical
manifestations of RP as well as describing the various systemic diseases, with a special emphasis on neurologic diseases,
associated with a pigmentary retinopathy. 相似文献
96.
97.
Ligation-mediated single nucleotide polymorphism detection coupled with an efficient method of signal enhancement, such as rolling-circle amplification, hyperbranched rolling-circle amplification or PCR, has provided the foundation for the development of variable single nucleotide polymorphism genotyping and analyzing methods for different applications. Several methods based on the above approaches have been developed, enabling rapid genotyping of a large number of single nucleotide polymorphisms directly from a small amount of genomic DNA and large-scale multiplex single nucleotide polymorphism (>1000 single nucleotide polymorphisms per assay) analysis on microarrays. This review categorizes different approaches and describes the principles of each approach for single nucleotide polymorphism detection. Possible future research directions including the development of optimized methods for analysis of cytologic samples and other applications are also discussed. 相似文献
98.
99.
Tariq A. Hameed Shawn D. Teague Mani Vembar Ekta Dharaiya Jonas Rydberg 《The international journal of cardiovascular imaging》2009,25(2):267-278
Computed tomography angiography (CTA) of the thorax other than cardiac CTA, is utilized for a multitude of conditions and ranges in application from a diagnostic test, to presurgical planning and postsurgical follow-up. Helical CTA without electrocardiogram (ECG) gating has been routinely utilized for the evaluation of thoracic vasculature. However, its applicability can be limited in the evaluation of the thoracic aorta and pulmonary vasculature because of the artifacts resulting from cardiac motion. Traditional retrospective ECG-gated helical scans address this issue but at the price of a high radiation dose to the patient. In this paper we review CTA dose reduction strategies for non-coronary indications, examine field of view requirements, and discuss breath hold challenges for ECG-gated acquisitions. In addition, we present clinical examples performed using low-dose prospective gating technique for evaluation of the aorta acquired on a 256-slice multidetector computed tomography system. 相似文献
100.
Chromium (Cr) and nickel (Ni) are widely used industrial chemicals. Welders in India are inclined to possible occupational Cr and Ni exposure. The carcinogenic potential of metals is a major issue in defining human health risk from exposure. Hence, in the present investigation, 102 welders and an equal number of control subjects were monitored for DNA damage in blood leucocytes utilizing the Comet assay. The two groups had similar mean ages and smoking prevalences. A few subjects were randomly selected for estimation of Cr and Ni content in whole blood by inductively coupled plasma mass spectrometry. The Comet assay was carried out to quantify basal DNA damage. The mean comet tail length was used to measure DNA damage. Welders had higher Cr and Ni content when compared with controls (Cr, 151.65 versus 17.86 micro g/l; Ni 132.39 versus 16.91 micro g/l; P < 0.001). The results indicated that the welders had a larger mean comet tail length than that of the controls (mean +/- SD, 23.05 +/- 3.86 versus 8.94 +/- 3.16; P < 0.001). In addition, the micronucleus test on buccal epithelial cells was carried out in a few randomly selected subjects. Welders showed a significant increase in micronucleated cells compared with controls (1.30 versus 0.32; P < 0.001). Analysis of variance revealed that occupational exposure (P < 0.05) had a significant effect on DNA mean tail length, whereas smoking and age had no significant effect on DNA damage. The current study suggested that chronic occupational exposure to Cr and Ni during welding could lead to increased levels of DNA damage. 相似文献