53 research outputs found

    Precision CW laser automatic tracking system investigated

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    Precision laser tracker capable of tracking a low acceleration target to an accuracy of about 20 microradians rms is being constructed and tested. This laser tracking has the advantage of discriminating against other optical sources and the capability of simultaneously measuring range

    Effects of G/A polymorphism, rs266882, in the androgen response element 1 of the PSA gene on prostate cancer risk, survival and circulating PSA levels

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    Prostate-specific antigen (PSA) is a protease produced in the prostate that cleaves insulin-like growth factor binding protein-3 and other proteins. Production is mediated by the androgen receptor (AR) binding to the androgen response elements (ARE) in the promoter region of the PSA gene. Studies of a single nucleotide polymorphism (PSA −158 G/A, rs266882) in ARE1 of the PSA gene have been conflicting for risk of prostate cancer and effect on plasma PSA levels. In this nested case–control analysis of 500 white cases and 676 age- and smoking-matched white controls in the Physicians' Health Study we evaluated the association of rs266882 with risk and survival of prostate cancer and prediagnostic total and free PSA plasma levels, alone or in combination with AR CAG repeats. We used conditional logistic regression, linear regression and Cox regression, and found no significant associations between rs266882 (GG allele vs AA allele) and overall prostate cancer risk (RR=1.21, 95% confidence intervals (CI): 0.88–1.67) or prostate cancer-specific survival (RR=0.94, 95%CI: 0.56–1.58). Similarly, no associations were found among high grade or advanced stage tumours, or by calendar year of diagnosis. There was no significant association between rs266882 and baseline total or free PSA levels or the AR CAG repeats, nor any interaction associated with prostate cancer risk. Meta-analysis of 12 studies of rs266882 and overall prostate cancer risk was null

    Serum estrogen levels and prostate cancer risk in the prostate cancer prevention trial: a nested case–control study

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    OBJECTIVE: Finasteride reduces prostate cancer risk by blocking the conversion of testosterone to dihydrotestosterone. However, whether finasteride affects estrogens levels or change in estrogens affects prostate cancer risk is unknown. METHODS: These questions were investigated in a case-control study nested within the prostate cancer prevention trial (PCPT) with 1,798 biopsy-proven prostate cancer cases and 1,798 matched controls. RESULTS: Among men on placebo, no relationship of serum estrogens with risk of prostate cancer was found. Among those on finasteride, those in the highest quartile of baseline estrogen levels had a moderately increased risk of Gleason score < 7 prostate cancer (for estrone, odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.06-2.15; for estradiol, OR = 1.50, 95% CI = 1.03-2.18). Finasteride treatment increased serum estrogen concentrations; however, these changes were not associated with prostate cancer risk. CONCLUSION: Our findings confirm those from previous studies that there are no associations of serum estrogen with prostate cancer risk in untreated men. In addition, finasteride results in a modest increase in serum estrogen levels, which are not related to prostate cancer risk. Whether finasteride is less effective in men with high serum estrogens, or finasteride interacts with estrogen to increase cancer risk, is uncertain and warrants further investigation

    Intestinal strongyloidiasis and hyperinfection syndrome

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    In spite of recent advances with experiments on animal models, strongyloidiasis, an infection caused by the nematode parasite Strongyloides stercoralis, has still been an elusive disease. Though endemic in some developing countries, strongyloidiasis still poses a threat to the developed world. Due to the peculiar but characteristic features of autoinfection, hyperinfection syndrome involving only pulmonary and gastrointestinal systems, and disseminated infection with involvement of other organs, strongyloidiasis needs special attention by the physician, especially one serving patients in areas endemic for strongyloidiasis. Strongyloidiasis can occur without any symptoms, or as a potentially fatal hyperinfection or disseminated infection. Th(2 )cell-mediated immunity, humoral immunity and mucosal immunity have been shown to have protective effects against this parasitic infection especially in animal models. Any factors that suppress these mechanisms (such as intercurrent immune suppression or glucocorticoid therapy) could potentially trigger hyperinfection or disseminated infection which could be fatal. Even with the recent advances in laboratory tests, strongyloidiasis is still difficult to diagnose. But once diagnosed, the disease can be treated effectively with antihelminthic drugs like Ivermectin. This review article summarizes a case of strongyloidiasis and various aspects of strongyloidiasis, with emphasis on epidemiology, life cycle of Strongyloides stercoralis, clinical manifestations of the disease, corticosteroids and strongyloidiasis, diagnostic aspects of the disease, various host defense pathways against strongyloidiasis, and available treatment options

    Retinoid and carotenoid status in serum and liver among patients at high-risk for liver cancer

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    BACKGROUND: Approximately 2.7 million Americans are chronically infected with hepatitis C virus (HCV). HCV patients with cirrhosis form the largest group of persons at high risk for hepatocellular carcinoma (HCC). Increased oxidative stress is regarded as a major mechanism of HCV-related liver disease progression. Deficiencies in retinoid and carotenoid antioxidants may represent a major modifiable risk factor for disease progression. This study aims to identify key predictors of serum antioxidant levels in patients with HCV, to examine the relationship between retinoid/carotenoid concentrations in serum and hepatic tissue, to quantify the association between systemic measures of oxidative stress and antioxidant status, and to examine the relationship between retinoids and stellate cell activation. METHODS: Patients undergoing liver biopsy (n = 69) provided fasting blood, fresh tissue, urine and completed a diet history questionnaire. Serum and questionnaire data from healthy volunteers (n = 11), normal liver tissue from public repositories and patients without liver disease (n = 11) were also collected. Urinary isoprostanes, serum and tissue retinoid concentrations were obtained by UHPLC-MS-MS. Immunohistochemistry for αSMA was performed on FFPE sections and subsequently quantified via digital image analysis. Associations between urinary isoprostanes, αSMA levels, and retinoids were assessed using Spearman correlation coefficients and non-parametric tests were utilized to test differences among disease severity groups. RESULTS: There was a significant inverse association between serum retinol, lycopene, and RBP4 concentrations with fibrosis stage. Serum β-carotene and lycopene were strongly associated with their respective tissue concentrations. There was a weak downward trend of tissue retinyl palmitate with increasing fibrosis stage. Tissue retinyl palmitate was inversely and significantly correlated with hepatic αSMA expression, a marker for hepatic stellate cell activation (r = −0.31, P < 0.02). Urinary isoprostanes levels were inversely correlated with serum retinol, β-carotene, and RBP4. CONCLUSIONS: A decrease in serum retinol, β-carotene, and RBP4 is associated with early stage HCV. Retinoid and carotenoid levels decline as disease progresses, and our data suggest that this decline occurs early in the disease process, even before fibrosis is apparent. Measures of oxidative stress are associated with fibrosis stage and concurrent antioxidant depletion. Vitamin A loss is accompanied by stellate cell activation in hepatic tissue. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12876-016-0432-5) contains supplementary material, which is available to authorized users

    Detection of Bacterial <em>16S</em> rRNA and Identification of Four Clinically Important Bacteria by Real-Time PCR

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    <div><p>Within the paradigm of clinical infectious disease research, <em>Acinetobacter baumannii</em>, <em>Escherichia coli</em>, <em>Klebsiella pneumoniae</em>, and <em>Pseudomonas aeruginosa</em> represent the four most clinically relevant, and hence most extensively studied bacteria. Current culture-based methods for identifying these organisms are slow and cumbersome, and there is increasing need for more rapid and accurate molecular detection methods. Using bioinformatic tools, 962,279 bacterial <em>16S</em> rRNA gene sequences were aligned, and regions of homology were selected to generate a set of real-time PCR primers that target 93.6% of all bacterial 16S rRNA sequences published to date. A set of four species-specific real-time PCR primer pairs were also designed, capable of detecting less than 100 genome copies of <em>A. baumannii</em>, <em>E. coli</em>, <em>K. pneumoniae</em>, and <em>P. aeruginosa</em>. All primers were tested for specificity <em>in vitro</em> against 50 species of Gram-positive and –negative bacteria. Additionally, the species-specific primers were tested against a panel of 200 clinical isolates of each species, randomly selected from a large repository of clinical isolates from diverse areas and sources. A comparison of culture and real-time PCR demonstrated 100% concordance. The primers were incorporated into a rapid assay capable of positive identification from plate or broth cultures in less than 90 minutes. Furthermore, our data demonstrate that current targets, such as the <em>uidA</em> gene in <em>E.coli</em>, are not suitable as species-specific genes due to sequence variation. The assay described herein is rapid, cost-effective and accurate, and can be easily incorporated into any research laboratory capable of real-time PCR.</p> </div

    Primer characteristics.

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    1<p>Probe sequences were generated for the <i>secE</i> and <i>yccT</i> real-time PCR primers, but no <i>in vitro</i> testing was performed. The probe sequences are provided here for the benefit of researchers wishing to perform multiplex real-time PCR reactions using these primers. All primers have an optimal annealing temperature of 56°C.</p>2<p>Primer efficiency was calculated from the slope and intercept of the trendline produced following amplification of serial dilutions of genomic DNA from the ATCC strains of each species, as described previously <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0048558#pone.0048558-McGann1" target="_blank">[14]</a>.</p>3<p>Amplicon size in base pairs.</p

    Amplification and melting curves for selected isolates.

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    <p>(<b>A</b>) Amplification curves of three of the eight <i>E. coli</i> isolates that were <i>uidA</i>-negative, but <i>yccT</i>-positive; MRSN 1628 (Red line), MRSN 1681 (Blue Line), and MRSN 7544 (Green Line). MRSN 7851 (Yellow Line) was both <i>uidA</i> and <i>yccT</i>-positive. <i>E.coli</i> ATCC 35218 (Black line) was used as a positive control and <i>K. pneumoniae</i> ATCC 1706 (Grey Line) was used a negative control. Each amplification curve is one representative sample from quintuplicate experiments. (<b>B</b>) Melting curve analysis of the amplicons produced by the <i>yccT</i> primer pair from 30 clinical isolates of <i>E. coli</i> demonstrating a highly conserved sequence in all strains. Melting curve of the <i>yccT</i> amplicon from <i>E. coli</i> ATCC 35218 is shown in red. All 30 isolates represented diverse pulse-types as determined by PFGE. RFU - Relative Fluorescent Units; -d(RFU)dt – Relative change in RFU over time (in seconds).</p

    Accelerator Neutrino Neutron Interaction Experiment (ANNIE): Preliminary Results and Physics Phase Proposal

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    Submitted to the Fermi National Accelerator Laboratory Physics Advisory CommitteeSubmitted to the Fermi National Accelerator Laboratory Physics Advisory CommitteeThe R&D mission of the Accelerator Neutrino Neutron Interaction Experiment (ANNIE) is described in detail. ANNIE is: (1) an important measurement of neutrino-nucleus interactions focusing specifically on neutron production, and (2) an R&D effort focused on using new photodetector technology and chemical additives to make advanced water-base neutrino detectors. The ANNIE experiment consists of a small Water Cherenkov detector, instrumented with both conventional photomultiplier tubes (PMTs) and Large Area Picosecond Photodetectors (LAPPDs) deployed on the Booster Neutrino Beam (BNB) at Fermilab. The experiment is designed to proceed in two stages: a partially-instrumented test-beam run using only PMTs (Phase I) for the purpose of measuring critical neutron backgrounds to the experiment; and a physics run with a fully-instrumented detector (Phase II). This paper gives preliminary results of the first phase and described the detector design upgrades necessary for the next phase
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