WorldWideScience

Sample records for blood biomarker amplification

  1. Peripheral Blood Biomarkers in Idiopathic Pulmonary Fibrosis

    OpenAIRE

    Vij, Rekha; Noth, Imre

    2012-01-01

    In this article, we review the evidence for peripheral blood biomarkers in idiopathic pulmonary fibrosis (IPF), a life-threatening fibrotic lung disease of unknown etiology. We focus on selected biomarkers present in peripheral blood, as they are easy to obtain, can be measured longitudinally, and have the greatest likelihood of achieving clinical utility. This article concentrates on biomarkers with mechanistic plausibility that may be directly involved in the development of IPF, including K...

  2. Potential blood biomarkers for stroke.

    Science.gov (United States)

    Laborde, Carlos M; Mourino-Alvarez, Laura; Akerstrom, Finn; Padial, Luis R; Vivanco, Fernando; Gil-Dones, Felix; Barderas, Maria G

    2012-08-01

    Stroke is one of the most common causes of death worldwide and a major cause of acquired disability in adults. Despite advances in research during the last decade, prevention and treatment strategies still suffer from significant limitations, and therefore new theoretical and technical approaches are required. Technological advances in the proteomic and metabolomic areas, during recent years, have permitted a more effective search for novel biomarkers and therapeutic targets that may allow for effective risk stratification and early diagnosis with subsequent rapid treatment. This review provides a comprehensive overview of the latest candidate proteins and metabolites proposed as new potential biomarkers in stroke. PMID:22967080

  3. Autologous Blood Transfusion in Sports: Emerging Biomarkers.

    Science.gov (United States)

    Salamin, Olivier; De Angelis, Sara; Tissot, Jean-Daniel; Saugy, Martial; Leuenberger, Nicolas

    2016-07-01

    Despite being prohibited by the World Anti-Doping Agency, blood doping through erythropoietin injection or blood transfusion is frequently used by athletes to increase oxygen delivery to muscles and enhance performance. In contrast with allogeneic blood transfusion and erythropoietic stimulants, there is presently no direct method of detection for autologous blood transfusion (ABT) doping. Blood reinfusion is currently monitored with individual follow-up of hematological variables via the athlete biological passport, which requires further improvement. Microdosage is undetectable, and suspicious profiles in athletes are often attributed to exposure to altitude, heat stress, or illness. Additional indirect biomarkers may increase the sensitivity and specificity of the longitudinal approach. The emergence of "-omics" strategies provides new opportunities to discover biomarkers for the indirect detection of ABT. With the development of direct quantitative methods, transcriptomics based on microRNA or messenger RNA expression is a promising approach. Because blood donation and blood reinfusion alter iron metabolism, quantification of proteins involved in metal metabolism, such as hepcidin, may be applied in an "ironomics" strategy to improve the detection of ABT. As red blood cell (RBC) storage triggers changes in membrane proteins, proteomic methods have the potential to identify the presence of stored RBCs in blood. Alternatively, urine matrix can be used for the quantification of the plasticizer di(2-ethyhexyl)phthalate and its metabolites that originate from blood storage bags, suggesting recent blood transfusion, and have an important degree of sensitivity and specificity. This review proposes that various indirect biomarkers should be applied in combination with mathematical approaches for longitudinal monitoring aimed at improving ABT detection. PMID:27260108

  4. Potential Blood-based Biomarkers for Concussion.

    Science.gov (United States)

    Papa, Linda

    2016-09-01

    Mounting research in the field of sports concussion biomarkers has led to a greater understanding of the effects of brain injury from sports. A recent systematic review of clinical studies examining biomarkers of brain injury following sports-related concussion established that almost all studies have been published either in or after the year 2000. In an effort to prevent chronic traumatic encephalopathy and long-term consequences of concussion, early diagnostic and prognostic tools are becoming increasingly important; particularly in sports and in military personnel, where concussions are common occurrences. Early and tailored management of athletes following a concussion with biomarkers could provide them with the best opportunity to avoid further injury. Should blood-based biomarkers for concussion be validated and become widely available, they could have many roles. For instance, a point-of-care test could be used on the field by trained sport medicine professionals to help detect a concussion. In the clinic or hospital setting, it could be used by clinicians to determine the severity of concussion and be used to screen players for neuroimaging (computed tomography and/or magnetic resonance imaging) and further neuropsychological testing. Furthermore, biomarkers could have a role in monitoring progression of injury and recovery and in managing patients at high risk of repeated injury by being incorporated into guidelines for return to duty, work, or sports activities. There may even be a role for biomarkers as surrogate measures of efficacy in the assessment of new treatments and therapies for concussion. PMID:27482776

  5. Blood biomarker for Parkinson disease: peptoids

    Science.gov (United States)

    Yazdani, Umar; Zaman, Sayed; Hynan, Linda S; Brown, L Steven; Dewey, Richard B; Karp, David; German, Dwight C

    2016-01-01

    Parkinson disease (PD) is the second most common neurodegenerative disease. Because dopaminergic neuronal loss begins years before motor symptoms appear, a biomarker for the early identification of the disease is critical for the study of putative neuroprotective therapies. Brain imaging of the nigrostriatal dopamine system has been used as a biomarker for early disease along with cerebrospinal fluid analysis of α-synuclein, but a less costly and relatively non-invasive biomarker would be optimal. We sought to identify an antibody biomarker in the blood of PD patients using a combinatorial peptoid library approach. We examined serum samples from 75 PD patients, 25 de novo PD patients, and 104 normal control subjects in the NINDS Parkinson’s Disease Biomarker Program. We identified a peptoid, PD2, which binds significantly higher levels of IgG3 antibody in PD versus control subjects (P<0.0001) and is 68% accurate in identifying PD. The PD2 peptoid is 84% accurate in identifying de novo PD. Also, IgG3 levels are significantly higher in PD versus control serum (P<0.001). Finally, PD2 levels are positively correlated with the United Parkinson’s Disease Rating Scale score (r = 0.457, P<0001), a marker of disease severity. The PD2 peptoid may be useful for the early-stage identification of PD, and serve as an indicator of disease severity. Additional studies are needed to validate this PD biomarker. PMID:27812535

  6. BLOOD BIOMARKERS FOR EVALUATION OF PERINATAL ENCEPHALOPATHY

    Directory of Open Access Journals (Sweden)

    Ernest Marshall Graham

    2016-07-01

    Full Text Available Recent research in identification of brain injury after trauma shows many possible blood biomarkers that may help identify the fetus and neonate with encephalopathy. Traumatic brain injury shares many common features with perinatal hypoxic-ischemic encephalopathy. Trauma has a hypoxic component, and one of the 1st physiologic consequences of moderate-severe traumatic brain injury is apnea. Trauma and hypoxia-ischemia initiate an excitotoxic cascade and free radical injury followed by the inflammatory cascade, producing injury in neurons, glial cells and white matter. Increased excitatory amino acids, lipid peroxidation products and alteration in microRNAs and inflammatory markers are common to both traumatic brain injury and perinatal encephalopathy. The blood-brain barrier is disrupted in both leading to egress of substances normally only found in the central nervous system. Brain exosomes may represent ideal biomarker containers, as RNA and protein transported within the vesicles are protected from enzymatic degradation. Evaluation of fetal or neonatal brain derived exosomes that cross the blood-brain barrier and circulate peripherally has been referred to as the liquid brain biopsy. A multiplex of serum biomarkers could improve upon the current imprecise methods of identifying fetal and neonatal brain injury such as fetal heart rate abnormalities, meconium, cord gases at delivery, and Apgar scores. Quantitative biomarker measurements of perinatal brain injury and recovery could lead to operative delivery only in the presence of significant fetal risk, triage to appropriate therapy after birth and measure the effectiveness of treatment.

  7. Blood Biomarkers for Evaluation of Perinatal Encephalopathy

    Science.gov (United States)

    Graham, Ernest M.; Burd, Irina; Everett, Allen D.; Northington, Frances J.

    2016-01-01

    Recent research in identification of brain injury after trauma shows many possible blood biomarkers that may help identify the fetus and neonate with encephalopathy. Traumatic brain injury shares many common features with perinatal hypoxic-ischemic encephalopathy. Trauma has a hypoxic component, and one of the 1st physiologic consequences of moderate-severe traumatic brain injury is apnea. Trauma and hypoxia-ischemia initiate an excitotoxic cascade and free radical injury followed by the inflammatory cascade, producing injury in neurons, glial cells and white matter. Increased excitatory amino acids, lipid peroxidation products, and alteration in microRNAs and inflammatory markers are common to both traumatic brain injury and perinatal encephalopathy. The blood-brain barrier is disrupted in both leading to egress of substances normally only found in the central nervous system. Brain exosomes may represent ideal biomarker containers, as RNA and protein transported within the vesicles are protected from enzymatic degradation. Evaluation of fetal or neonatal brain derived exosomes that cross the blood-brain barrier and circulate peripherally has been referred to as the “liquid brain biopsy.” A multiplex of serum biomarkers could improve upon the current imprecise methods of identifying fetal and neonatal brain injury such as fetal heart rate abnormalities, meconium, cord gases at delivery, and Apgar scores. Quantitative biomarker measurements of perinatal brain injury and recovery could lead to operative delivery only in the presence of significant fetal risk, triage to appropriate therapy after birth and measure the effectiveness of treatment. PMID:27468268

  8. Ultrasensitive Visual Detection of HIV DNA Biomarkers via a Multi-amplification Nanoplatform

    OpenAIRE

    Yuyin Long; Cuisong Zhou; Congmin Wang; Honglian Cai; Cuiyun Yin; Qiufang Yang; Dan Xiao

    2016-01-01

    Methodologies to detect disease biomarkers at ultralow concentrations can potentially improve the standard of living. A facile and label-free multi-amplification strategy is proposed for the ultrasensitive visual detection of HIV DNA biomarkers in real physiological media. This multi-amplification strategy not only exhibits a signficantly low detection limit down to 4.8 pM but also provides a label-free, cost-effective and facile technique for visualizing a few molecules of nucleic acid analy...

  9. Ultrasensitive Detection of Low-Abundance Protein Biomarkers by Mass Spectrometry Signal Amplification Assay.

    Science.gov (United States)

    Du, Ruijun; Zhu, Lina; Gan, Jinrui; Wang, Yuning; Qiao, Liang; Liu, Baohong

    2016-07-01

    A mass spectrometry signal amplification method is developed for the ultrasensitive and selective detection of low-abundance protein biomarkers by utilizing tag molecules on gold nanoparticles (AuNPs). EpCAM and thrombin as model targets are captured by specific aptamers immobilized on the AuNPs. With laser desorption/ionization time-of-flight mass spectrometry (LDI-TOF MS), the mass tag molecules are detected to represent the protein biomarkers. Benefiting from the MS signal amplification, the assay can achieve a limit of detection of 100 aM. The method is further applied to detect thrombin in fetal bovine serum and EpCAM in cell lysates to demonstrate its selectivity and feasibility in complex biological samples. With the high sensitivity and specificity, the protocol shows great promise for providing a new route to single-cell analysis and early disease diagnosis. PMID:27253396

  10. Ultrasensitive Visual Detection of HIV DNA Biomarkers via a Multi-amplification Nanoplatform.

    Science.gov (United States)

    Long, Yuyin; Zhou, Cuisong; Wang, Congmin; Cai, Honglian; Yin, Cuiyun; Yang, Qiufang; Xiao, Dan

    2016-01-01

    Methodologies to detect disease biomarkers at ultralow concentrations can potentially improve the standard of living. A facile and label-free multi-amplification strategy is proposed for the ultrasensitive visual detection of HIV DNA biomarkers in real physiological media. This multi-amplification strategy not only exhibits a signficantly low detection limit down to 4.8 pM but also provides a label-free, cost-effective and facile technique for visualizing a few molecules of nucleic acid analyte with the naked eye. Importantly, the biosensor is capable of discriminating single-based mismatch lower than 5.0 nM in human serum samples. Moreover, the visual sensing platform exhibits excellent specificity, acceptable reusability and a long-term stability. All these advantages could be attributed to the nanofibrous sensing platform that 1) has a high surface-area-to-volume provided by electrospun nanofibrous membrane, and 2) combines glucose oxidase (GOx) biocatalysis, DNAzyme-catalyzed colorimetric reaction and catalytic hairpin assembly (CHA) recycling amplification together. This multi-amplification nanoplatform promises label-free and visual single-based mismatch DNA monitoring with high sensitivity and specificity, suggesting wide applications that range from virus detection to genetic disease diagnosis. PMID:27032385

  11. Discovery of Novel Biomarkers for Alzheimer's Disease from Blood

    Science.gov (United States)

    Long, Jintao; Pan, Genhua; Ifeachor, Emmanuel; Belshaw, Robert; Li, Xinzhong

    2016-01-01

    Blood-based biomarkers for Alzheimer's disease would be very valuable because blood is a more accessible biofluid and is suitable for repeated sampling. However, currently there are no robust and reliable blood-based biomarkers for practical diagnosis. In this study we used a knowledge-based protein feature pool and two novel support vector machine embedded feature selection methods to find panels consisting of two and three biomarkers. We validated these biomarker sets using another serum cohort and an RNA profile cohort from the brain. Our panels included the proteins ECH1, NHLRC2, HOXB7, FN1, ERBB2, and SLC6A13 and demonstrated promising sensitivity (>87%), specificity (>91%), and accuracy (>89%). PMID:27418712

  12. Comparison of Biomarkers in Blood and Saliva in Healthy Adults

    Directory of Open Access Journals (Sweden)

    Sarah Williamson

    2012-01-01

    Full Text Available Researchers measure biomarkers as a reflection of patient health status or intervention outcomes. While blood is generally regarded as the best body fluid for evaluation of systemic processes, substitution of saliva samples for blood would be less invasive and more convenient. The concentration of specific biomarkers may differ between blood and saliva. The objective of this study was to compare multiple biomarkers (27 cytokines in plasma samples, passive drool saliva samples, and filter paper saliva samples in 50 healthy adults. Demographic data and three samples were obtained from each subject: saliva collected on filter paper over 1 minute, saliva collected by passive drool over 30 seconds, and venous blood (3 mL collected by venipuncture. Cytokines were assayed using Bio-Rad multiplex suspension array technology. Descriptive statistics and pairwise correlations were used for data analysis. The sample was 52% male and 74% white. Mean age was 26 (range = 19–63 years, sd = 9.7. The most consistent and highest correlations were between the passive drool and filter paper saliva samples, although relationships were dependent on the specific biomarker. Correlations were not robust enough to support substitution of one collection method for another. There was little correlation between the plasma and passive drool saliva samples. Caution should be used in substituting saliva for blood, and relationships differ by biomarker.

  13. Blood biomarkers in the early stage of cerebral ischemia.

    Science.gov (United States)

    Maestrini, I; Ducroquet, A; Moulin, S; Leys, D; Cordonnier, C; Bordet, R

    2016-03-01

    In ischemic stroke patients, blood-based biomarkers may be applied for the diagnosis of ischemic origin and subtype, prediction of outcomes and targeted treatment in selected patients. Knowledge of the pathophysiology of cerebral ischemia has led to the evaluation of proteins, neurotransmitters, nucleic acids and lipids as potential biomarkers. The present report focuses on the role of blood-based biomarkers in the early stage of ischemic stroke-within 72h of its onset-as gleaned from studies published in English in such patients. Despite growing interest in their potential role in clinical practice, the application of biomarkers for the management of cerebral ischemia is not currently recommended by guidelines. However, there are some promising clinical biomarkers, as well as the N-methyl-d-aspartate (NMDA) peptide and NMDA-receptor (R) autoantibodies that appear to identify the ischemic nature of stroke, and the glial fibrillary acidic protein (GFAP) that might be able to discriminate between acute ischemic and hemorrhagic strokes. Moreover, genomics and proteomics allow the characterization of differences in gene expression, and protein and metabolite production, in ischemic stroke patients compared with controls and, thus, may help to identify novel markers with sufficient sensitivity and specificity. Additional studies to validate promising biomarkers and to identify novel biomarkers are needed. PMID:26988891

  14. ECT2 amplification and overexpression as a new prognostic biomarker for early-stage lung adenocarcinoma.

    Science.gov (United States)

    Murata, Yoshihiko; Minami, Yuko; Iwakawa, Reika; Yokota, Jun; Usui, Shingo; Tsuta, Koji; Shiraishi, Kouya; Sakashita, Shingo; Satomi, Kaishi; Iijima, Tatsuo; Noguchi, Masayuki

    2014-04-01

    Genetic abnormality in early-stage lung adenocarcinoma was examined to search for new prognostic biomarkers. Six in situ lung adenocarcinomas and nine small but invasive adenocarcinomas were examined by array-comparative genomic hybridization, and candidate genes of interest were screened. To examine gene abnormalities, 83 cases of various types of lung carcinoma were examined by quantitative real-time genomic PCR and immunohistochemistry. The results were then verified using another set of early-stage adenocarcinomas. Array-comparative genomic hybridization indicated frequent amplification at chromosome 3q26. Of the seven genes located in this region, we focused on the epithelial cell transforming sequence 2 (ECT2) oncogene, as ECT2 amplification was detected only in invasive adenocarcinoma, and not in in situ carcinoma. Quantitative PCR and immunohistochemistry analyses also detected overexpression of ECT2 in invasive adenocarcinoma, and this was correlated with both the Ki-67 labeling index and mitotic index. In addition, it was associated with disease-free survival and overall survival of patients with lung adenocarcinoma. These results were verified using another set of early-stage adenocarcinomas resected at another hospital. Abnormality of the ECT2 gene occurs at a relatively early stage of lung adenocarcinogenesis and would be applicable as a new biomarker for prognostication of patients with lung adenocarcinoma. PMID:24484057

  15. Automated nucleic acid amplification testing in blood banks: An additional layer of blood safety

    Directory of Open Access Journals (Sweden)

    Pragati Chigurupati

    2015-01-01

    Full Text Available Context: A total of 30 million blood components are transfused each year in India. Blood safety thus becomes a top priority, especially with a population of around 1.23 billion and a high prevalence rate of human immunodeficiency virus (HIV, hepatitis B virus (HBV and hepatitis C virus (HCV in general population. Nucleic acid amplification testing (NAT in blood donor screening has been implemented in many developed countries to reduce the risk of transfusion-transmitted viral infections (TTIs. NAT takes care of the dynamics of window period of viruses and offers the safest blood pack for donation. Aims: The aim of this study is to show the value of NAT in blood screening. Settings and Design: Dhanavantari Blood Bank, Rajahmundry, Andhra Pradesh, India. Subjects and Methods: Over a period of 1 year from January 2012 to December 2012, a total number of 15,000 blood donor samples were subjected to tests for HIV, HBV, and HCV by enzyme-linked immunosorbent assay (ELISA method and 8000 ELISA nonreactive samples were subjected for NAT using multiplex polymerase chain reaction technology. Results: Of the 15,000 donors tested, 525 were seroreactive. In 8000 ELISA negative blood samples subjected to NAT, 4 donor samples were reactive for HBV. The NAT yield was 1 in 2000. Conclusions: NAT could detect HIV, HBV, and HCV cases in blood donor samples those were undetected by serological tests. NAT could interdict 2500 infectious donations among our approximate 5 million annual blood donations.

  16. Quantification of Fewer than Ten Copies of a DNA Biomarker without Amplification or Labeling.

    Science.gov (United States)

    Lee, Yoonhee; Kim, Youngkyu; Lee, Donggyu; Roy, Dhruvajyoti; Park, Joon Won

    2016-06-01

    Polymerase chain reaction (PCR) is a highly sensitive diagnosis technique for detection of nucleic acids and for monitoring residual disease; however, PCR can be unreliable for samples containing very few target molecules. Here, we describe a quantification method, using force-distance (FD) curve based atomic force microscopy (AFM) to detect a target DNA bound to small (1.4-1.9 μm diameter) probe DNA spots, allowing mapping of entire spots to nanometer resolution. Using a synthetic BCR-ABL fusion gene sequence target, we examined samples containing between one and 10 target copies. A high degree of correlation (r(2) = 0.994) between numbers of target copies and detected probe clusters was observed, and the approach could detect the BCR-ABL biomarker when only a single copy was present, although multiple screens were required. Our results clearly demonstrate that FD curve-based imaging is suitable for quantitative analysis of fewer than 10 copies of DNA biomarkers without amplification, modification, or labeling. PMID:27175474

  17. Genome Filtering for New DNA Biomarkers of Loa loa Infection Suitable for Loop-Mediated Isothermal Amplification.

    Directory of Open Access Journals (Sweden)

    Catherine B Poole

    Full Text Available Loa loa infections have emerged as a serious public health problem in patients co-infected with Onchocerca volvulus or Wuchereria bancrofti because of severe adverse neurological reactions after treatment with ivermectin. Accurate diagnostic tests are needed for careful mapping in regions where mass drug administration is underway. Loop-mediated isothermal amplification (LAMP has become a widely adopted screening method because of its operational simplicity, rapidity and versatility of visual detection readout options. Here, we present a multi-step bioinformatic pipeline to generate diagnostic candidates suitable for LAMP and experimentally validate this approach using one of the identified candidates to develop a species-specific LAMP assay for L. loa. The pipeline identified ~140 new L. loa specific DNA repeat families as putative biomarkers of infection. The consensus sequence of one family, repeat family 4 (RF4, was compiled from ~ 350 sequences dispersed throughout the L. loa genome and maps to a L. loa-specific region of the long terminal repeats found at the boundaries of Bel/Pao retrotransposons. PCR and LAMP primer sets targeting RF4 specifically amplified L. loa but not W. bancrofti, O. volvulus, Brugia malayi, human or mosquito DNA. RF4 LAMP detects the DNA equivalent of one microfilaria (100 pg in 25-30 minutes and as little as 0.060 pg of L. loa DNA (~1/1600th of a microfilaria purified from spiked blood samples in approximately 50 minutes. In summary, we have successfully employed a bioinformatic approach to mine the L. loa genome for species-specific repeat families that can serve as new DNA biomarkers for LAMP. The RF4 LAMP assay shows promise as a field tool for the implementation and management of mass drug administration programs and warrants further testing on clinical samples as the next stage in development towards this goal.

  18. Genome Filtering for New DNA Biomarkers of Loa loa Infection Suitable for Loop-Mediated Isothermal Amplification.

    Science.gov (United States)

    Poole, Catherine B; Ettwiller, Laurence; Tanner, Nathan A; Evans, Thomas C; Wanji, Samuel; Carlow, Clotilde K S

    2015-01-01

    Loa loa infections have emerged as a serious public health problem in patients co-infected with Onchocerca volvulus or Wuchereria bancrofti because of severe adverse neurological reactions after treatment with ivermectin. Accurate diagnostic tests are needed for careful mapping in regions where mass drug administration is underway. Loop-mediated isothermal amplification (LAMP) has become a widely adopted screening method because of its operational simplicity, rapidity and versatility of visual detection readout options. Here, we present a multi-step bioinformatic pipeline to generate diagnostic candidates suitable for LAMP and experimentally validate this approach using one of the identified candidates to develop a species-specific LAMP assay for L. loa. The pipeline identified ~140 new L. loa specific DNA repeat families as putative biomarkers of infection. The consensus sequence of one family, repeat family 4 (RF4), was compiled from ~ 350 sequences dispersed throughout the L. loa genome and maps to a L. loa-specific region of the long terminal repeats found at the boundaries of Bel/Pao retrotransposons. PCR and LAMP primer sets targeting RF4 specifically amplified L. loa but not W. bancrofti, O. volvulus, Brugia malayi, human or mosquito DNA. RF4 LAMP detects the DNA equivalent of one microfilaria (100 pg) in 25-30 minutes and as little as 0.060 pg of L. loa DNA (~1/1600th of a microfilaria) purified from spiked blood samples in approximately 50 minutes. In summary, we have successfully employed a bioinformatic approach to mine the L. loa genome for species-specific repeat families that can serve as new DNA biomarkers for LAMP. The RF4 LAMP assay shows promise as a field tool for the implementation and management of mass drug administration programs and warrants further testing on clinical samples as the next stage in development towards this goal.

  19. Genome Filtering for New DNA Biomarkers of Loa loa Infection Suitable for Loop-Mediated Isothermal Amplification.

    Science.gov (United States)

    Poole, Catherine B; Ettwiller, Laurence; Tanner, Nathan A; Evans, Thomas C; Wanji, Samuel; Carlow, Clotilde K S

    2015-01-01

    Loa loa infections have emerged as a serious public health problem in patients co-infected with Onchocerca volvulus or Wuchereria bancrofti because of severe adverse neurological reactions after treatment with ivermectin. Accurate diagnostic tests are needed for careful mapping in regions where mass drug administration is underway. Loop-mediated isothermal amplification (LAMP) has become a widely adopted screening method because of its operational simplicity, rapidity and versatility of visual detection readout options. Here, we present a multi-step bioinformatic pipeline to generate diagnostic candidates suitable for LAMP and experimentally validate this approach using one of the identified candidates to develop a species-specific LAMP assay for L. loa. The pipeline identified ~140 new L. loa specific DNA repeat families as putative biomarkers of infection. The consensus sequence of one family, repeat family 4 (RF4), was compiled from ~ 350 sequences dispersed throughout the L. loa genome and maps to a L. loa-specific region of the long terminal repeats found at the boundaries of Bel/Pao retrotransposons. PCR and LAMP primer sets targeting RF4 specifically amplified L. loa but not W. bancrofti, O. volvulus, Brugia malayi, human or mosquito DNA. RF4 LAMP detects the DNA equivalent of one microfilaria (100 pg) in 25-30 minutes and as little as 0.060 pg of L. loa DNA (~1/1600th of a microfilaria) purified from spiked blood samples in approximately 50 minutes. In summary, we have successfully employed a bioinformatic approach to mine the L. loa genome for species-specific repeat families that can serve as new DNA biomarkers for LAMP. The RF4 LAMP assay shows promise as a field tool for the implementation and management of mass drug administration programs and warrants further testing on clinical samples as the next stage in development towards this goal. PMID:26414073

  20. Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD.

    Science.gov (United States)

    Sun, Wei; Kechris, Katerina; Jacobson, Sean; Drummond, M Bradley; Hawkins, Gregory A; Yang, Jenny; Chen, Ting-Huei; Quibrera, Pedro Miguel; Anderson, Wayne; Barr, R Graham; Basta, Patricia V; Bleecker, Eugene R; Beaty, Terri; Casaburi, Richard; Castaldi, Peter; Cho, Michael H; Comellas, Alejandro; Crapo, James D; Criner, Gerard; Demeo, Dawn; Christenson, Stephanie A; Couper, David J; Curtis, Jeffrey L; Doerschuk, Claire M; Freeman, Christine M; Gouskova, Natalia A; Han, MeiLan K; Hanania, Nicola A; Hansel, Nadia N; Hersh, Craig P; Hoffman, Eric A; Kaner, Robert J; Kanner, Richard E; Kleerup, Eric C; Lutz, Sharon; Martinez, Fernando J; Meyers, Deborah A; Peters, Stephen P; Regan, Elizabeth A; Rennard, Stephen I; Scholand, Mary Beth; Silverman, Edwin K; Woodruff, Prescott G; O'Neal, Wanda K; Bowler, Russell P

    2016-08-01

    Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10-392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the

  1. Epigenetic biomarkers in the blood of patients with urological malignancies.

    Science.gov (United States)

    Ellinger, Jörg; Müller, Stefan C; Dietrich, Dimo

    2015-04-01

    In the era of personalized medicine, there is an urgent need for non-invasive biomarkers to optimize the individual treatment of cancer patients. Epigenetic alterations, including DNA methylation and non-coding RNAs, are a hallmark of malignant tumors. The detection of many of these epigenetic conditions is feasible in bodily fluids, that is, blood plasma and serum, and may therefore be used for liquid biopsy. In this review, we summarize and discuss the current state of research on circulating epigenetic alterations (DNA methylation, miRNA and long non-coding RNA) in serum and plasma of patients with bladder cancer, prostate cancer, renal cell carcinoma and testicular germ cell cancer.

  2. Blood biomarkers in a mouse model of CADASIL.

    Science.gov (United States)

    Primo, Vincent; Graham, Mark; Bigger-Allen, Alexander A; Chick, Joel M; Ospina, Carolina; Quiroz, Yakeel T; Manent, Jan; Gygi, Steven P; Lopera, Francisco; D'Amore, Patricia A; Arboleda-Velasquez, Joseph F

    2016-08-01

    Mutations in NOTCH 3 are the cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a neurological disorder characterized by stroke, and vascular cognitive impairment and dementia. Loss of vascular smooth muscle cells (VSMC) and accumulation of granular osmiophilic material (GOM) deposits are hallmarks of CADASIL. There are no therapies for CADASIL and experimental endpoints to examine the preclinical efficacy of potential drugs are lacking. This study aims to use a mouse carrying the C455R mutation in Notch 3 to identify biomarkers associated with CADASIL. Mass spectrometry and antibody arrays were used to explore the aorta and blood proteomes of CADASIL mice, ELISA assays were utilized for biomarker validation, a ligand-dependent assay was applied to examine the relationship between Notch signaling and biomarker expression, and retinal histology was performed for quantification of VSMC loss in arteries. Two-hundred day-old mice with the C455R CADASIL mutation in Notch 3 mice display robust VSMC loss in retinal arteries and had increased plasma levels of collagen18α1/endostatin (col18α1) and high-temperature requirement A serine peptidase 1 (HTRA1) and reduced levels of Notch 3 extracellular domain (N3ECD), compared to control wild type mice. Measurements of plasma endostatin, HTRA1 and N3ECD, along with VSMC quantification in retinal arteries, may serve as surrogate endpoints for assessing efficacy in preclinical therapeutic studies of CADASIL using mice. PMID:27174004

  3. Blood and sputum biomarkers in COPD and asthma: a review.

    Science.gov (United States)

    Paone, G; Leone, V; Conti, V; De Marchis, L; Ialleni, E; Graziani, C; Salducci, M; Ramaccia, M; Munafò, G

    2016-01-01

    Chronic obstructive pulmonary disease (COPD) and asthma are lung inflammatory diseases that represent major public health problems. The primary, and often unique, method to evaluate lung function is spirometry, which reflects disease severity rather than disease activity. Moreover, its measurements strictly depend on patient's compliance, physician's expertise and data interpretation. The limitations of clinical history and pulmonary function tests have encouraged focusing on new possible tracers of diseases. The increase of the inflammatory response in the lungs represents an early pathological event, so biological markers related to inflammation may play key roles in earlier diagnosis, evaluation of functional impairment and prognosis. Biomarkers are measurable indicators associated with the presence and/or severity of a biological or pathogenic process, which may predict functional impairment, prognosis and response to therapy. The traditional approach based on invasive techniques (bronchoalveolar lavage and biopsies) may be replaced, at least in part, by using less invasive methods to collect specimens (sputum and blood), in which biomarkers could be measured. Proteomics, by the association between different protein profiles and pathogenic processes, is gaining an important role in pulmonary medicine allowing a more precise discrimination between patients with different outcomes and response to therapy. The aim of this review was to evaluate the use of biomarkers of airway inflammation in the context of both research and clinical practice. PMID:26957273

  4. Blood-based biomarkers of aggressive prostate cancer.

    Directory of Open Access Journals (Sweden)

    Men Long Liong

    Full Text Available PURPOSE: Prostate cancer is a bimodal disease with aggressive and indolent forms. Current prostate-specific-antigen testing and digital rectal examination screening provide ambiguous results leading to both under-and over-treatment. Accurate, consistent diagnosis is crucial to risk-stratify patients and facilitate clinical decision making as to treatment versus active surveillance. Diagnosis is currently achieved by needle biopsy, a painful procedure. Thus, there is a clinical need for a minimally-invasive test to determine prostate cancer aggressiveness. A blood sample to predict Gleason score, which is known to reflect aggressiveness of the cancer, could serve as such a test. MATERIALS AND METHODS: Blood mRNA was isolated from North American and Malaysian prostate cancer patients/controls. Microarray analysis was conducted utilizing the Affymetrix U133 plus 2·0 platform. Expression profiles from 255 patients/controls generated 85 candidate biomarkers. Following quantitative real-time PCR (qRT-PCR analysis, ten disease-associated biomarkers remained for paired statistical analysis and normalization. RESULTS: Microarray analysis was conducted to identify 85 genes differentially expressed between aggressive prostate cancer (Gleason score ≥8 and controls. Expression of these genes was qRT-PCR verified. Statistical analysis yielded a final seven-gene panel evaluated as six gene-ratio duplexes. This molecular signature predicted as aggressive (ie, Gleason score ≥8 55% of G6 samples, 49% of G7(3+4, 79% of G7(4+3 and 83% of G8-10, while rejecting 98% of controls. CONCLUSION: In this study, we have developed a novel, blood-based biomarker panel which can be used as the basis of a simple blood test to identify men with aggressive prostate cancer and thereby reduce the overdiagnosis and overtreatment that currently results from diagnosis using PSA alone. We discuss possible clinical uses of the panel to identify men more likely to benefit from

  5. Hepcidin as a new biomarker for detecting autologous blood transfusion.

    Science.gov (United States)

    Leuenberger, Nicolas; Barras, Laura; Nicoli, Raul; Robinson, Neil; Baume, Norbert; Lion, Niels; Barelli, Stefano; Tissot, Jean-Daniel; Saugy, Martial

    2016-05-01

    Autologous blood transfusion (ABT) is an efficient way to increase sport performance. It is also the most challenging doping method to detect. At present, individual follow-up of haematological variables via the athlete biological passport (ABP) is used to detect it. Quantification of a novel hepatic peptide called hepcidin may be a new alternative to detect ABT. In this prospective clinical trial, healthy subjects received a saline injection for the control phase, after which they donated blood that was stored and then transfused 36 days later. The impact of ABT on hepcidin as well as haematological parameters, iron metabolism, and inflammation markers was investigated. Blood transfusion had a particularly marked effect on hepcidin concentrations compared to the other biomarkers, which included haematological variables. Hepcidin concentrations increased significantly: 12 hr and 1 day after blood reinfusion, these concentrations rose by seven- and fourfold, respectively. No significant change was observed in the control phase. Hepcidin quantification is a cost-effective strategy that could be used in an "ironomics" strategy to improve the detection of ABT. Am. J. Hematol. 91:467-472, 2016. © 2016 Wiley Periodicals, Inc. PMID:26822428

  6. Hepcidin as a new biomarker for detecting autologous blood transfusion.

    Science.gov (United States)

    Leuenberger, Nicolas; Barras, Laura; Nicoli, Raul; Robinson, Neil; Baume, Norbert; Lion, Niels; Barelli, Stefano; Tissot, Jean-Daniel; Saugy, Martial

    2016-05-01

    Autologous blood transfusion (ABT) is an efficient way to increase sport performance. It is also the most challenging doping method to detect. At present, individual follow-up of haematological variables via the athlete biological passport (ABP) is used to detect it. Quantification of a novel hepatic peptide called hepcidin may be a new alternative to detect ABT. In this prospective clinical trial, healthy subjects received a saline injection for the control phase, after which they donated blood that was stored and then transfused 36 days later. The impact of ABT on hepcidin as well as haematological parameters, iron metabolism, and inflammation markers was investigated. Blood transfusion had a particularly marked effect on hepcidin concentrations compared to the other biomarkers, which included haematological variables. Hepcidin concentrations increased significantly: 12 hr and 1 day after blood reinfusion, these concentrations rose by seven- and fourfold, respectively. No significant change was observed in the control phase. Hepcidin quantification is a cost-effective strategy that could be used in an "ironomics" strategy to improve the detection of ABT.

  7. Detection of protein biomarker using a blood glucose meter.

    Science.gov (United States)

    Lan, Tian; Xiang, Yu; Lu, Yi

    2015-01-01

    mHeath technologies are recognized to play important roles in the future of personal care and medicine. However, their full potentials have not been reached, as most of current technologies are restricted to monitoring physical and behavioral parameters, such as body temperature, heart rate, blood pressure, and physical movement, while direct monitoring of biomarkers in body fluids can provide much more accurate and useful information for medical diagnostics. A major barrier to realizing the full potential of mHealth is the high costs and long cycles of developing mHealth devices capable of monitoring biomarkers in body fluids. To lower the costs and shorten the developmental cycle, we have demonstrated the leveraging of the most successful portable medical monitoring device on the market, the blood glucose meter (BGM), with FDA-approved smartphone technologies that allow for wireless transmission and remote monitoring of a wide range of non-glucose targets. In this protocol, an aptamer-based assay for quantification of interferon-γ (IFN-γ) using an off-the-shelf BGM is described. In this assay, an aptamer-based target recognition system is employed. When IFN-γ binds to the aptamer, it triggers the release of a reporter enzyme, invertase, which can catalyze the conversion of sucrose (not detected by BGM) to glucose. The glucose being produced is then detected using a BGM. The system mimics a competitive enzyme-linked immunosorbent assay (ELISA), where the traditional immunoassay is replaced by an aptamer binding assay; the reporter protein is replaced by invertase, and finally the optical or fluorescence detector is replaced with widely available BGMs. PMID:25626534

  8. Blood-based biomarkers of microvascular pathology in Alzheimer's disease.

    LENUS (Irish Health Repository)

    Ewers, Michael

    2012-02-01

    Sporadic Alzheimer\\'s disease (AD) is a genetically complex and chronically progressive neurodegenerative disorder with molecular mechanisms and neuropathologies centering around the amyloidogenic pathway, hyperphosphorylation and aggregation of tau protein, and neurofibrillary degeneration. While cerebrovascular changes have not been traditionally considered to be a central part of AD pathology, a growing body of evidence demonstrates that they may, in fact, be a characteristic feature of the AD brain as well. In particular, microvascular abnormalities within the brain have been associated with pathological AD hallmarks and may precede neurodegeneration. In vivo assessment of microvascular pathology provides a promising approach to develop useful biological markers for early detection and pathological characterization of AD. This review focuses on established blood-based biological marker candidates of microvascular pathology in AD. These candidates include plasma concentration of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) that are increased in AD. Measures of endothelial vasodilatory function including endothelin (ET-1), adrenomedullin (ADM), and atrial natriuretic peptide (ANP), as well as sphingolipids are significantly altered in mild AD or during the predementia stage of mild cognitive impairment (MCI), suggesting sensitivity of these biomarkers for early detection and diagnosis. In conclusion, the emerging clinical diagnostic evidence for the value of blood-based microvascular biomarkers in AD is promising, however, still requires validation in phase II and III diagnostic trials. Moreover, it is still unclear whether the described protein dysbalances are early or downstream pathological events and how the detected systemic microvascular alterations relate to cerebrovascular and neuronal pathologies in the AD brain.

  9. Biomarkers for monitoring pre-analytical quality variation of mRNA in blood samples.

    Directory of Open Access Journals (Sweden)

    Hui Zhang

    Full Text Available There is an increasing need for proper quality control tools in the pre-analytical phase of the molecular diagnostic workflow. The aim of the present study was to identify biomarkers for monitoring pre-analytical mRNA quality variations in two different types of blood collection tubes, K2EDTA (EDTA tubes and PAXgene Blood RNA Tubes (PAXgene tubes. These tubes are extensively used both in the diagnostic setting as well as for research biobank samples. Blood specimens collected in the two different blood collection tubes were stored for varying times at different temperatures, and microarray analysis was performed on resultant extracted RNA. A large set of potential mRNA quality biomarkers for monitoring post-phlebotomy gene expression changes and mRNA degradation in blood was identified. qPCR assays for the potential biomarkers and a set of relevant reference genes were generated and used to pre-validate a sub-set of the selected biomarkers. The assay precision of the potential qPCR based biomarkers was determined, and a final validation of the selected quality biomarkers using the developed qPCR assays and blood samples from 60 healthy additional subjects was performed. In total, four mRNA quality biomarkers (USP32, LMNA, FOSB, TNRFSF10C were successfully validated. We suggest here the use of these blood mRNA quality biomarkers for validating an experimental pre-analytical workflow. These biomarkers were further evaluated in the 2nd ring trial of the SPIDIA-RNA Program which demonstrated that these biomarkers can be used as quality control tools for mRNA analyses from blood samples.

  10. 6p22.3 amplification as a biomarker and potential therapeutic target of advanced stage bladder cancer

    Science.gov (United States)

    Zhang, Jianmin; Underwood, Willie; Yang, Nuo; Frangou, Costa; Eng, Kevin; Head, Karen; Bollag, Roni J.; Kavuri, Sravan K.; Rojiani, Amyn M.; Li, Yingwei; Yan, Li; Hill, Annette; Woloszynska-Read, Anna; Wang, Jianmin; Liu, Song; Trump, Donald L.; Candace, Johnson S.

    2013-01-01

    Genetic and epigenetic alterations have been identified as to contribute directly or indirectly to the generation of transitional cell carcinoma of the urinary bladder (TCC-UB). In a comparative fashion much less is known about copy number alterations in TCC-UB, but it appears that amplification of chromosome 6p22 is one of the most frequent changes. Using fluorescence in situ hybridization (FISH) analyses, we evaluated chromosomal 6p22 amplification in a large cohort of bladder cancer patients with complete surgical staging and outcome data. We have also used shRNA knockdown candidate oncogenes in the cell based study. We found that amplification of chromosome 6p22.3 is significantly associated with the muscle-invasive transitional cell carcinoma of the urinary bladder (TCC-UB) (22%) in contrast to superficial TCC-UB (9%) (p=7.2-04). The rate of 6p22.3 amplification in pN>1 patients (32%) is more than twice that in pN0 (16%) patients (p=0.05). Interestingly, we found that 6p22.3 amplification is as twice as high (p=0.0201) in African American (AA) than European American (EA) TCC-UB patients. Moreover, we showed that the expression of some candidate genes (E2F3, CDKAL1 and Sox4) in the 6p22.3 region is highly correlated with the chromosomal amplification. In particular, knockdown of E2F3 inhibits cell proliferation in a 6p22.3-dependent manner, whereas knockdown of CDKAL1 and Sox4 has no effect on cell proliferation. Using gene expression profiling, we further identified some common as well as distinctive subset targets of the E2F3 family members. In summary, our data indicate that E2F3 is a key regulator of cell proliferation in a subset of bladder cancer and the 6p22.3 amplicon is a biomarker of aggressive phenotype in this tumor type. PMID:24231253

  11. Data-driven asthma endotypes defined from blood biomarker and gene expression data

    Science.gov (United States)

    The diagnosis and treatment of childhood asthma is complicated by its mechanistically distinct subtypes (endotypes) driven by genetic susceptibility and modulating environmental factors. Clinical biomarkers and blood gene expression were collected from a stratified, cross-section...

  12. Biomarkers of traumatic injury are transported from brain to blood via the glymphatic system.

    Science.gov (United States)

    Plog, Benjamin A; Dashnaw, Matthew L; Hitomi, Emi; Peng, Weiguo; Liao, Yonghong; Lou, Nanhong; Deane, Rashid; Nedergaard, Maiken

    2015-01-14

    The nonspecific and variable presentation of traumatic brain injury (TBI) has motivated an intense search for blood-based biomarkers that can objectively predict the severity of injury. However, it is not known how cytosolic proteins released from traumatized brain tissue reach the peripheral blood. Here we show in a murine TBI model that CSF movement through the recently characterized glymphatic pathway transports biomarkers to blood via the cervical lymphatics. Clinically relevant manipulation of glymphatic activity, including sleep deprivation and cisternotomy, suppressed or eliminated TBI-induced increases in serum S100β, GFAP, and neuron specific enolase. We conclude that routine TBI patient management may limit the clinical utility of blood-based biomarkers because their brain-to-blood transport depends on glymphatic activity. PMID:25589747

  13. ECT2 amplification and overexpression as a new prognostic biomarker for early-stage lung adenocarcinoma

    OpenAIRE

    Murata, Yoshihiko; Minami, Yuko; Iwakawa, Reika; Yokota, Jun; Usui, Shingo; Tsuta, Koji; Shiraishi, Kouya; Sakashita, Shingo; Satomi, Kaishi; IIJIMA, TATSUO; Noguchi, Masayuki

    2014-01-01

    Genetic abnormality in early-stage lung adenocarcinoma was examined to search for new prognostic biomarkers. Six in situ lung adenocarcinomas and nine small but invasive adenocarcinomas were examined by array-comparative genomic hybridization, and candidate genes of interest were screened. To examine gene abnormalities, 83 cases of various types of lung carcinoma were examined by quantitative real-time genomic PCR and immunohistochemistry. The results were then verified using another set of e...

  14. Glucose encapsulating liposome for signal amplification for quantitative detection of biomarkers with glucometer readout.

    Science.gov (United States)

    Zhao, Yuting; Du, Dan; Lin, Yuehe

    2015-10-15

    A new technology was developed to quantitatively detect a broad range of disease biomarkers and proven to be portable, economical, and conveniently accessible. Measurements were performed based on releasing encapsulated glucose from antibody-tagged liposomes and subsequently detecting the released glucose using a commercial personal glucose meter (GM). The innovative aspect of this approach lies in the quantification of target biomarkers through the detection of glucose, thus expanding the applicability of the GM by broadening the range of target biomarkers instead of detecting only one analyte, glucose. Because of the bilayer membrane of liposomes, which can accommodate tens of thousands of glucose molecules, the sensitivity was greatly enhanced by using glucose encapsulating liposomes as a signal output and an amplifier. Here, the model analyte, protein 53 phosphorylated on Serine 15 (phospho-p53(15)), was captured by primary antibodies bound on magnetic Fe3O4 nanoparticles and then recognized by reporting antibodies conjugated to glucose encapsulating liposomes. Finally, the target phospho-p53(15) was detected by lysing the bound liposomes to release the encapsulated glucose (4 × 10(5) glucose molecules per liposome), which is detected with the GM. This approach was demonstrated to be a universal technology that can be easily produced to quantify a wide variety of biomarkers in medical diagnostics, food safety, public health, and environmental monitoring. In the near future, it is expected that these sensors, in combination with a portable GM, can be used in many fields such as physicians' laboratories, hospitals and the common household. PMID:26005847

  15. Biomarker Analysis of Stored Blood Products: Emphasis on Pre-Analytical Issues

    Directory of Open Access Journals (Sweden)

    Niels Lion

    2010-11-01

    Full Text Available Millions of blood products are transfused every year; many lives are thus directly concerned by transfusion. The three main labile blood products used in transfusion are erythrocyte concentrates, platelet concentrates and fresh frozen plasma. Each of these products has to be stored according to its particular components. However, during storage, modifications or degradation of those components may occur, and are known as storage lesions. Thus, biomarker discovery of in vivo blood aging as well as in vitro labile blood products storage lesions is of high interest for the transfusion medicine community. Pre-analytical issues are of major importance in analyzing the various blood products during storage conditions as well as according to various protocols that are currently used in blood banks for their preparations. This paper will review key elements that have to be taken into account in the context of proteomic-based biomarker discovery applied to blood banking.

  16. Biomarker analysis of stored blood products: emphasis on pre-analytical issues.

    Science.gov (United States)

    Delobel, Julien; Rubin, Olivier; Prudent, Michel; Crettaz, David; Tissot, Jean-Daniel; Lion, Niels

    2010-01-01

    Millions of blood products are transfused every year; many lives are thus directly concerned by transfusion. The three main labile blood products used in transfusion are erythrocyte concentrates, platelet concentrates and fresh frozen plasma. Each of these products has to be stored according to its particular components. However, during storage, modifications or degradation of those components may occur, and are known as storage lesions. Thus, biomarker discovery of in vivo blood aging as well as in vitro labile blood products storage lesions is of high interest for the transfusion medicine community. Pre-analytical issues are of major importance in analyzing the various blood products during storage conditions as well as according to various protocols that are currently used in blood banks for their preparations. This paper will review key elements that have to be taken into account in the context of proteomic-based biomarker discovery applied to blood banking. PMID:21151459

  17. Biomarkers in schizophrenia: A focus on blood based diagnostics and theranostics.

    Science.gov (United States)

    Lai, Chi-Yu; Scarr, Elizabeth; Udawela, Madhara; Everall, Ian; Chen, Wei J; Dean, Brian

    2016-03-22

    Identifying biomarkers that can be used as diagnostics or predictors of treatment response (theranostics) in people with schizophrenia (Sz) will be an important step towards being able to provide personalized treatment. Findings from the studies in brain tissue have not yet been translated into biomarkers that are practical in clinical use because brain biopsies are not acceptable and neuroimaging techniques are expensive and the results are inconclusive. Thus, in recent years, there has been search for blood-based biomarkers for Sz as a valid alternative. Although there are some encouraging preliminary data to support the notion of peripheral biomarkers for Sz, it must be acknowledged that Sz is a complex and heterogeneous disorder which needs to be further dissected into subtype using biological based and clinical markers. The scope of this review is to critically examine published blood-based biomarker of Sz, focusing on possible uses for diagnosis, treatment response, or their relationship with schizophrenia-associated phenotype. We sorted the studies into six categories which include: (1) brain-derived neurotrophic factor; (2) inflammation and immune function; (3) neurochemistry; (4) oxidative stress response and metabolism; (5) epigenetics and microRNA; and (6) transcriptome and proteome studies. This review also summarized the molecules which have been conclusively reported as potential blood-based biomarkers for Sz in different blood cell types. Finally, we further discusses the pitfall of current blood-based studies and suggest that a prediction model-based, Sz specific, blood oriented study design as well as standardize blood collection conditions would be useful for Sz biomarker development. PMID:27014601

  18. Cerebrospinal Fluid and Blood Biomarkers of Neuroaxonal Damage in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Irena Dujmovic

    2011-01-01

    Full Text Available Following emerging evidence that neurodegenerative processes in multiple sclerosis (MS are present from its early stages, an intensive scientific interest has been directed to biomarkers of neuro-axonal damage in body fluids of MS patients. Recent research has introduced new candidate biomarkers but also elucidated pathogenetic and clinical relevance of the well-known ones. This paper reviews the existing data on blood and cerebrospinal fluid biomarkers of neuroaxonal damage in MS and highlights their relation to clinical parameters, as well as their potential predictive value to estimate future disease course, disability, and treatment response. Strategies for future research in this field are suggested.

  19. Different effects of tocolytic medication on blood pressure and blood pressure amplification

    OpenAIRE

    FABRY, ISABELLE; Paepe, Peter; Kips, Jan; Vermeersch, Sebastian; van Bortel, Luc

    2010-01-01

    Abstract Background The importance of tocolysis has been discussed extensively. Beta-2 adrenoceptor agonistic drugs like ritodrine have been the reference tocolytic drugs in most countries. Cardiovascular side-effects are frequent. Atosiban, a newer tocolytic drug, is a competitive antagonist of oxytocin and has fewer cardiovascular side effects. Although large studies exist, there is mainly subjective reporting of adverse reactions with a focus on blood ...

  20. Biomarkers of coagulation, fibrinolysis, endothelial function, and inflammation in arterialized venous blood

    DEFF Research Database (Denmark)

    Gram, Anne Sofie; Skov, Jane; Ploug, Thorkil;

    2014-01-01

    Effects of venous blood arterialization on cardiovascular risk markers are still unknown. We evaluated biomarkers of inflammation, coagulation, fibrinolysis, and endothelial function in arterialized compared with regular venous blood. Cubital venipunctures were obtained from 10 healthy volunteers...... (1929 nmol/l*min vs. 1872 nmol/l*min, P = 0.02). Addition of the FXIIa inhibitor Corn Trypsin Inhibitor (CTI) prior to the thrombin generation test eliminated the ETP difference suggesting that hand heating activates the FXII-dependent coagulation pathway.......Effects of venous blood arterialization on cardiovascular risk markers are still unknown. We evaluated biomarkers of inflammation, coagulation, fibrinolysis, and endothelial function in arterialized compared with regular venous blood. Cubital venipunctures were obtained from 10 healthy volunteers...

  1. Core modular blood and brain biomarkers in social defeat mouse model for post traumatic stress disorder

    OpenAIRE

    Yang, Ruoting; Daigle Jr, Bernie J; Muhie, Seid Y; Hammamieh, Rasha; Jett, Marti; Petzold, Linda; Francis J Doyle

    2013-01-01

    Abstract Background Post-traumatic stress disorder (PTSD) is a severe anxiety disorder that affects a substantial portion of combat veterans and poses serious consequences to long-term health. Consequently, the identification of diagnostic and prognostic blood biomarkers for PTSD is of great interest. Previously, we assessed genome-wide gene expression of seven brain regions and whole blood in a social defeat mouse model subjected to various stress co...

  2. A comparison of consistency of detecting c-MET gene amplification in peripheral blood and tumor tissue of nonsmall cell lung cancer patients

    Directory of Open Access Journals (Sweden)

    Daobao Chen

    2015-01-01

    Conclusion: The consistency of the c-MET gene amplification in peripheral blood and tissue is high. c-MET gene amplification of peripheral blood could be used for clinical diagnosis and treatment in cases when tissue specimen is hard to get.

  3. COPD association and repeatability of blood biomarkers in the ECLIPSE cohort

    Directory of Open Access Journals (Sweden)

    Dickens Jennifer A

    2011-11-01

    Full Text Available Abstract Background There is a need for biomarkers to better characterise individuals with COPD and to aid with the development of therapeutic interventions. A panel of putative blood biomarkers was assessed in a subgroup of the Evaluation of COPD Longitudinally to Identify Surrogate Endpoints (ECLIPSE cohort. Methods Thirty-four blood biomarkers were assessed in 201 subjects with COPD, 37 ex-smoker controls with normal lung function and 37 healthy non-smokers selected from the ECLIPSE cohort. Biomarker repeatability was assessed using baseline and 3-month samples. Intergroup comparisons were made using analysis of variance, repeatability was assessed through Bland-Altman plots, and correlations between biomarkers and clinical characteristics were assessed using Spearman correlation coefficients. Results Fifteen biomarkers were significantly different in individuals with COPD when compared to former or non-smoker controls. Some biomarkers, including tumor necrosis factor-α and interferon-γ, were measurable in only a minority of subjects whilst others such as C-reactive protein showed wide variability over the 3-month replication period. Fibrinogen was the most repeatable biomarker and exhibited a weak correlation with 6-minute walk distance, exacerbation rate, BODE index and MRC dyspnoea score in COPD subjects. 33% (66/201 of the COPD subjects reported at least 1 exacerbation over the 3 month study with 18% (36/201 reporting the exacerbation within 30 days of the 3-month visit. CRP, fibrinogen interleukin-6 and surfactant protein-D were significantly elevated in those COPD subjects with exacerbations within 30 days of the 3-month visit compared with those individuals that did not exacerbate or whose exacerbations had resolved. Conclusions Only a few of the biomarkers assessed may be useful in diagnosis or management of COPD where the diagnosis is based on airflow obstruction (GOLD. Further analysis of more promising biomarkers may reveal

  4. Challenges for red blood cell biomarker discovery through proteomics

    NARCIS (Netherlands)

    Barasa, B.A.; Slijper, M.

    2014-01-01

    Red blood cells are rather unique body cells, since they have lost all organelles when mature, which results in lack of potential to replace proteins that have lost their function. They maintain only a few pathways for obtaining energy and reducing power for the key functions they need to fulfill. T

  5. Nucleic acid amplification technology screening for hepatitis C virus and human immunodeficiency virus for blood donations

    International Nuclear Information System (INIS)

    To investigate the performance of the commercial Roche COBAS AmpliScreen assay, and demonstrate whether the COBAS AmpliScreen human immunodeficiency virus-1 (HIV-1) test, v1.5, and COBAS AmpliScreen hepatitis C virus (HCV) v 2.0 for screening for HIV-1 and HCV RNA in the donated blood units from which plasma mini pools were collected, by nucleic acid amplification technology (NAT), could detect the positive pools and reduce the risk of transmission of infections for those routinely tested by serological assays. The study was performed on 3288 plasma samples collected from blood donors in a period of 13 months, from August 2004 to August 2005, at Al-Hada Armed Forces Hospital, Molecular Pathology Laboratory, Taif, Kingdom of Saudi Arabia. The samples were tested by the reverse transcriptase polymerase chain reaction (RT-PCR) after RNA extraction (this represents the major method in NAT assays), in parallel with the routine serological testing to detect qualitatively for HIV-1 and HCV. The NAT assays that include an automated COBAS AmpliPrep system for RNA extraction and COBAS Amplicor Analyzer using AmpliScreen kits for RT-PCR assays, and the routine serological screening assays for the detection of the HIV-1 and HCV RNA in the plasma samples from the blood donors have shown to be a reliable combination that would meet our requirements. The collected data further confirms the results from the serological assays and enables us to decrease the residual risk of transmission to a minimum with the finding of no seronegative window period donation. The results demonstrate that out of 3288 samples, the percentages of RT-PCR (NAT) negative blood donations that were also confirmed as seronegative were 99% for HCV, and 99.1% for HIV-1. The modified combined systems (automated COBAS AmpliPrep system for RNA extraction and COBAS Amplicor Analyzer using AmpliScreen kits for RT-PCR assays) for NAT screening assays has allowed the release of all blood donations supplied in the

  6. Amplification-Free Detection of Circulating microRNA Biomarkers from Body Fluids Based on Fluorogenic Oligonucleotide-Templated Reaction between Engineered Peptide Nucleic Acid Probes: Application to Prostate Cancer Diagnosis.

    Science.gov (United States)

    Metcalf, Gavin A D; Shibakawa, Akifumi; Patel, Hinesh; Sita-Lumsden, Ailsa; Zivi, Andrea; Rama, Nona; Bevan, Charlotte L; Ladame, Sylvain

    2016-08-16

    Highly abundant in cells, microRNAs (or miRs) play a key role as regulators of gene expression. A proportion of them are also detectable in biofluids making them ideal noninvasive biomarkers for pathologies in which miR levels are aberrantly expressed, such as cancer. Peptide nucleic acids (PNAs) are engineered uncharged oligonucleotide analogues capable of hybridizing to complementary nucleic acids with high affinity and high specificity. Herein, novel PNA-based fluorogenic biosensors have been designed and synthesized that target miR biomarkers for prostate cancer (PCa). The sensing strategy is based on oligonucleotide-templated reactions where the only miR of interest serves as a matrix to catalyze an otherwise highly unfavorable fluorogenic reaction. Validated in vitro using synthetic RNAs, these newly developed biosensors were then shown to detect endogenous concentrations of miR in human blood samples without the need for any amplification step and with minimal sample processing. This low-cost, quantitative, and versatile sensing technology has been technically validated using gold-standard RT-qPCR. Compared to RT-qPCR however, this enzyme-free, isothermal blood test is amenable to incorporation into low-cost portable devices and could therefore be suitable for widespread public screening. PMID:27498854

  7. [Development of microchips for the analysis of biomarkers in blood].

    Science.gov (United States)

    Kataoka, Masatoshi; Abe, Kaori; Hashimoto, Yoshiko; Yamamura, Shohei; Yatsushiro, Shouki

    2012-11-01

    Several types of microchips have been developed for application in clinical diagnosis. A microchip made of cyclic olefin copolymer with straight microchannels (300 microm width and 100 microm depth) was employed for sandwich ELISA for the determination of serum type I C-peptide (PICP), a biomarker of osteoporosis. This assay enabled us to determine PICP with accuracy and high sensitivity, reducing the time for the immunoassay to 1/6, and the consumption of samples and reagents to 1/50 compared with the conventional method. Furthermore, cell microarray chips with 20,944 microchambers (105 microm width and 50 microm depth), made of polystyrene, were employed for malaria diagnosis and the detection of carcinoma cells among the leukocytes. Around 100 erythrocytes or leukocytes were accommodated in each microchamber with the formation of a monolayer. For malaria diagnosis, it offered 10-100 times higher sensitivity in the detection of malaria infected erythrocytes than conventional light microscopy, and easy operation within 15 min. By double staining for epithelial cells on the cell microarray chip, one carcinoma cell could be detected among 1,800,000 leukocytes. These results indicate the potential of microchips for clinic diagnosis.

  8. MicroRNA biomarkers in whole blood for detection of pancreatic cancer

    DEFF Research Database (Denmark)

    Schultz, Nicolai A; Dehlendorff, Christian; Jensen, Benny V;

    2014-01-01

    IMPORTANCE: Biomarkers for the early diagnosis of patients with pancreatic cancer are needed to improve prognosis. OBJECTIVES: To describe differences in microRNA expression in whole blood between patients with pancreatic cancer, chronic pancreatitis, and healthy participants and to identify panels...... of microRNAs for use in diagnosis of pancreatic cancer compared with the cancer antigen 19-9 (CA19-9). DESIGN, SETTING, AND PARTICIPANTS: A case-control study that included 409 patients with pancreatic cancer and 25 with chronic pancreatitis who had been included prospectively in the Danish BIOPAC...... (Biomarkers in Patients with Pancreatic Cancer) study (July 2008-October 2012) plus 312 blood donors as healthy participants. The microRNA expressions in pretreatment whole blood RNA samples were collected and analyzed in 3 randomly determined subcohorts: discovery cohort (143 patients with pancreatic cancer...

  9. A composite peripheral blood gene expression measure as a potential diagnostic biomarker in bipolar disorder

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Peijs, L; Vinberg, M;

    2015-01-01

    -operating characteristic curve of 0.81 (P test. The present findings of altered POLG, OGG1 and NDUFV2 expression point to disturbances within mitochondrial function and DNA repair mechanisms...... as a diagnostic and state biomarker in bipolar disorder. First, messenger RNA levels of 19 candidate genes were assessed in peripheral blood mononuclear cells of 37 rapid cycling bipolar disorder patients in different affective states (depression, mania and euthymia) during a 6-12-month period and in 40 age...... in bipolar disorder. Further, a composite gene expression measure could hold promise as a potential diagnostic biomarker....

  10. Peripheral blood neutrophilia as a biomarker of ozone-induced pulmonary inflammation.

    Directory of Open Access Journals (Sweden)

    Jenny A Bosson

    Full Text Available BACKGROUND: Ozone concentrations are predicted to increase over the next 50 years due to global warming and the increased release of precursor chemicals. It is therefore urgent that good, reliable biomarkers are available to quantify the toxicity of this pollutant gas at the population level. Such a biomarker would need to be easily performed, reproducible, economically viable, and reflective of ongoing pathological processes occurring within the lung. METHODOLOGY: We examined whether blood neutrophilia occurred following a controlled ozone challenge and addressed whether this could serve as a biomarker for ozone-induced airway inflammation. Three separate groups of healthy subjects were exposed to ozone (0.2 ppm, 2h and filtered air (FA on two separate occasions. Peripheral blood samples were collected and bronchoscopy with biopsy sampling and lavages was performed at 1.5h post exposures in group 1 (n=13, at 6h in group 2 (n=15 and at 18h in group 3 (n=15. Total and differential cell counts were assessed in blood, bronchial tissue and airway lavages. RESULTS: In peripheral blood, we observed fewer neutrophils 1.5h after ozone compared with the parallel air exposure (-1.1±1.0x10(9 cells/L, p<0.01, at 6h neutrophil numbers were increased compared to FA (+1.2±1.3x10(9 cells/L, p<0.01, and at 18h this response had fully attenuated. Ozone induced a peak in neutrophil numbers at 6h post exposure in all compartments examined, with a positive correlation between the response in blood and bronchial biopsies. CONCLUSIONS: These data demonstrate a systemic neutrophilia in healthy subjects following an acute ozone exposure, which mirrors the inflammatory response in the lung mucosa and lumen. This relationship suggests that blood neutrophilia could be used as a relatively simple functional biomarker for the effect of ozone on the lung.

  11. Cascade Signal Amplification Based on Copper Nanoparticle-Reported Rolling Circle Amplification for Ultrasensitive Electrochemical Detection of the Prostate Cancer Biomarker.

    Science.gov (United States)

    Zhu, Ye; Wang, Huijuan; Wang, Lin; Zhu, Jing; Jiang, Wei

    2016-02-01

    An ultrasensitive and highly selective electrochemical assay was first attempted by combining the rolling circle amplification (RCA) reaction with poly(thymine)-templated copper nanoparticles (CuNPs) for cascade signal amplification. As proof of concept, prostate specific antigen (PSA) was selected as a model target. Using a gold nanoparticle (AuNP) as a carrier, we synthesized the primer-AuNP-aptamer bioconjugate for signal amplification by increasing the primer/aptamer ratio. The specific construction of primer-AuNP-aptamer/PSA/anti-PSA sandwich structure triggered the effective RCA reaction, in which thousands of tandem poly(thymine) repeats were generated and directly served as the specific templates for the subsequent CuNP formation. The signal readout was easily achieved by dissolving the RCA product-templated CuNPs and detecting the released copper ions with differential pulse stripping voltammetry. Because of the designed cascade signal amplification strategy, the newly developed method achieved a linear range of 0.05-500 fg/mL, with a remarkable detection limit of 0.020 ± 0.001 fg/mL PSA. Finally, the feasibility of the developed method for practical application was investigated by analyzing PSA in the real clinical human serum samples. The ultrasensitivity, specificity, convenience, and capability for analyzing the clinical samples demonstrate that this method has great potential for practical disease diagnosis applications. PMID:26765624

  12. Reference range of blood biomarkers for oxidative stress in Thoroughbred racehorses (2–5 years old)

    Science.gov (United States)

    KUSANO, Kanichi; YAMAZAKI, Masahiko; KIUCHI, Masataka; KANEKO, Kouki; KOYAMA, Katsuhiro

    2016-01-01

    ABSTRACT The oxidant and antioxidant equilibrium is known to play an important role in equine medicine and equine exercise physiology. There are abundant findings in this field; however, not many studies have been conducted for reference ranges of oxidative stress biomarkers in horses. This study was conducted to determine the reference values of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) using blood samples from 372 (191 males, 181 females) Thoroughbred racehorse aged 2 to 5 (3.43 ± 1.10 (mean ± SD)) years old. There were obvious gender differences in oxidative biomarkers, and growth/age-related changes were observed especially in females. Gender and age must be considered when interpreting obtained oxidative stress biomarkers for diagnosis of disease or fitness alterations in Thoroughbred racehorses. PMID:27703408

  13. Data-driven asthma endotypes defined from blood biomarker and gene expression data.

    Directory of Open Access Journals (Sweden)

    Barbara Jane George

    Full Text Available The diagnosis and treatment of childhood asthma is complicated by its mechanistically distinct subtypes (endotypes driven by genetic susceptibility and modulating environmental factors. Clinical biomarkers and blood gene expression were collected from a stratified, cross-sectional study of asthmatic and non-asthmatic children from Detroit, MI. This study describes four distinct asthma endotypes identified via a purely data-driven method. Our method was specifically designed to integrate blood gene expression and clinical biomarkers in a way that provides new mechanistic insights regarding the different asthma endotypes. For example, we describe metabolic syndrome-induced systemic inflammation as an associated factor in three of the four asthma endotypes. Context provided by the clinical biomarker data was essential in interpreting gene expression patterns and identifying putative endotypes, which emphasizes the importance of integrated approaches when studying complex disease etiologies. These synthesized patterns of gene expression and clinical markers from our research may lead to development of novel serum-based biomarker panels.

  14. Huntington's disease biomarker progression profile identified by transcriptome sequencing in peripheral blood.

    Science.gov (United States)

    Mastrokolias, Anastasios; Ariyurek, Yavuz; Goeman, Jelle J; van Duijn, Erik; Roos, Raymund A C; van der Mast, Roos C; van Ommen, GertJan B; den Dunnen, Johan T; 't Hoen, Peter A C; van Roon-Mom, Willeke M C

    2015-10-01

    With several therapeutic approaches in development for Huntington's disease, there is a need for easily accessible biomarkers to monitor disease progression and therapy response. We performed next-generation sequencing-based transcriptome analysis of total RNA from peripheral blood of 91 mutation carriers (27 presymptomatic and, 64 symptomatic) and 33 controls. Transcriptome analysis by DeepSAGE identified 167 genes significantly associated with clinical total motor score in Huntington's disease patients. Relative to previous studies, this yielded novel genes and confirmed previously identified genes, such as H2AFY, an overlap in results that has proven difficult in the past. Pathway analysis showed enrichment of genes of the immune system and target genes of miRNAs, which are downregulated in Huntington's disease models. Using a highly parallelized microfluidics array chip (Fluidigm), we validated 12 of the top 20 significant genes in our discovery cohort and 7 in a second independent cohort. The five genes (PROK2, ZNF238, AQP9, CYSTM1 and ANXA3) that were validated independently in both cohorts present a candidate biomarker panel for stage determination and therapeutic readout in Huntington's disease. Finally we suggest a first empiric formula predicting total motor score from the expression levels of our biomarker panel. Our data support the view that peripheral blood is a useful source to identify biomarkers for Huntington's disease and monitor disease progression in future clinical trials. PMID:25626709

  15. Huntington's disease biomarker progression profile identified by transcriptome sequencing in peripheral blood

    OpenAIRE

    Mastrokolias, Anastasios; Ariyurek, Yavuz; Goeman, Jelle J.; van Duijn, Erik; Roos, Raymund AC; Roos C. van der Mast; van Ommen, GertJan B.; Johan T den Dunnen; 't Hoen, Peter AC; van Roon-Mom, Willeke MC

    2015-01-01

    With several therapeutic approaches in development for Huntington's disease, there is a need for easily accessible biomarkers to monitor disease progression and therapy response. We performed next-generation sequencing-based transcriptome analysis of total RNA from peripheral blood of 91 mutation carriers (27 presymptomatic and, 64 symptomatic) and 33 controls. Transcriptome analysis by DeepSAGE identified 167 genes significantly associated with clinical total motor score in Huntington's dise...

  16. Novel One-Tube-One-Step Real-Time Methodology for Rapid Transcriptomic Biomarker Detection: Signal Amplification by Ternary Initiation Complexes.

    Science.gov (United States)

    Fujita, Hiroto; Kataoka, Yuka; Tobita, Seiji; Kuwahara, Masayasu; Sugimoto, Naoki

    2016-07-19

    We have developed a novel RNA detection method, termed signal amplification by ternary initiation complexes (SATIC), in which an analyte sample is simply mixed with the relevant reagents and allowed to stand for a short time under isothermal conditions (37 °C). The advantage of the technique is that there is no requirement for (i) heat annealing, (ii) thermal cycling during the reaction, (iii) a reverse transcription step, or (iv) enzymatic or mechanical fragmentation of the target RNA. SATIC involves the formation of a ternary initiation complex between the target RNA, a circular DNA template, and a DNA primer, followed by rolling circle amplification (RCA) to generate multiple copies of G-quadruplex (G4) on a long DNA strand like beads on a string. The G4s can be specifically fluorescence-stained with N(3)-hydroxyethyl thioflavin T (ThT-HE), which emits weakly with single- and double-stranded RNA/DNA but strongly with parallel G4s. An improved dual SATIC system, which involves the formation of two different ternary initiation complexes in the RCA process, exhibited a wide quantitative detection range of 1-5000 pM. Furthermore, this enabled visual observation-based RNA detection, which is more rapid and convenient than conventional isothermal methods, such as reverse transcription-loop-mediated isothermal amplification, signal mediated amplification of RNA technology, and RNA-primed rolling circle amplification. Thus, SATIC methodology may serve as an on-site and real-time measurement technique for transcriptomic biomarkers for various diseases.

  17. Whole Blood RNA as a Source of Transcript-Based Nutrition- and Metabolic Health-Related Biomarkers

    Science.gov (United States)

    Petrov, Petar D.; Bonet, M. Luisa; Reynés, Bárbara; Oliver, Paula; Palou, Andreu; Ribot, Joan

    2016-01-01

    Blood cells are receiving an increasing attention as an easily accessible source of transcript-based biomarkers. We studied the feasibility of using mouse whole blood RNA in this context. Several paradigms were studied: (i) metabolism-related transcripts known to be affected in rat tissues and peripheral blood mononuclear cells (PBMC) by fasting and upon the development of high fat diet (HFD)-induced overweight were assessed in whole blood RNA of fasted rats and mice and of HFD-fed mice; (ii) retinoic acid (RA)-responsive genes in tissues were assessed in whole blood RNA of control and RA-treated mice; (iii) lipid metabolism-related transcripts previously identified in PBMC as potential biomarkers of metabolic health in a rat model were assessed in whole blood in an independent model, namely retinoblastoma haploinsufficient (Rb+/-) mice. Blood was collected and stored in RNAlater® at -80°C until analysis of selected transcripts by real-time RT-PCR. Comparable changes with fasting were detected in the expression of lipid metabolism-related genes when RNA from either PBMC or whole blood of rats or mice was used. HFD-induced excess body weight and fat mass associated with expected changes in the expression of metabolism-related genes in whole blood of mice. Changes in gene expression in whole blood of RA-treated mice reproduced known transcriptional actions of RA in hepatocytes and adipocytes. Reduced expression of Fasn, Lrp1, Rxrb and Sorl1 could be validated as early biomarkers of metabolic health in young Rb+/- mice using whole blood RNA. Altogether, these results support the use of whole blood RNA in studies aimed at identifying blood transcript-based biomarkers of nutritional/metabolic status or metabolic health. Results also support reduced expression of Fasn, Lrp1, Rxrb and Sorl1 in blood cells at young age as potential biomarkers of metabolic robustness. PMID:27163124

  18. Identification of biomarkers for cervical cancer in peripheral blood lymphocytes using oligonucleotide microarrays

    Institute of Scientific and Technical Information of China (English)

    SHENG Jie; ZHANG Wei-yuan

    2010-01-01

    Background Oligonucleotide microarrays are increasingly being used to identify gene expression profiles that associated with complex genetic diseases. Peripheral lymphocytes communicate with cells and extracellular matrixes in almost all tissues and organs in human body, suggesting that the gene expression profiles in peripheral lymphocytes may reflect the presence of disease in the body. This study aimed to identify molecular biomarkers for cervical cancer in peripheral blood lymphocytes by using oligonucleotide microarrays.Methods Total RNA was extracted from peripheral blood lymphocytes of 24 early stage cervical cancer patients and 18 healthy controls. We used 22K Human Genome microarrays to profile peripheral blood lymphocytes from 4 early stage cervical cancer patients and compared their gene expression profiles with those from 3 healthy controls. Differentially expressed genes would be identified if they had adjusted P values of less than 0.05 and a groupwise average fold change greater than 1.5 or less than 0.67. Then the selected 5 genes were validated in the remaining 20 early stage cervical cancer patients and the 15 healthy controls by using real-time reverse-transcription polymerase chain reaction (RT-PCR).Results Genes identified by the gene selection program expressed differently between the blood samples of the early stage cervical cancer patients and those of the healthy controls. To validate the gene expression data, 5 genes were analyzed by real-time RT-PCR. In three of the 5 identified genes, tenasin-c (TNC), nuceolin (NCL), and enolase 2 (ENO2) showed a significant up-regulation in the blood samples of the early stage cervical cancer patients versus that of the healthy controls.Conclusions The up-regulation of TNC, NCL, and ENO2 in peripheral blood may be used to identify novel blood biomarkers for detecting cervical cancer in a clinically accessible surrogate tissue, and thus to provide a possibility to develop a noninvasive and predictive

  19. Relative value of diverse brain MRI and blood-based biomarkers for predicting cognitive decline in the elderly

    Science.gov (United States)

    Madsen, Sarah K.; Ver Steeg, Greg; Daianu, Madelaine; Mezher, Adam; Jahanshad, Neda; Nir, Talia M.; Hua, Xue; Gutman, Boris A.; Galstyan, Aram; Thompson, Paul M.

    2016-03-01

    Cognitive decline accompanies many debilitating illnesses, including Alzheimer's disease (AD). In old age, brain tissue loss also occurs along with cognitive decline. Although blood tests are easier to perform than brain MRI, few studies compare brain scans to standard blood tests to see which kinds of information best predict future decline. In 504 older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we first used linear regression to assess the relative value of different types of data to predict cognitive decline, including 196 blood panel biomarkers, 249 MRI biomarkers obtained from the FreeSurfer software, demographics, and the AD-risk gene APOE. A subset of MRI biomarkers was the strongest predictor. There was no specific blood marker that increased predictive accuracy on its own, we found that a novel unsupervised learning method, CorEx, captured weak correlations among blood markers, and the resulting clusters offered unique predictive power.

  20. Loop-mediated isothermal amplification assay for the detection of Ehrlichia canis DNA in blood samples from dogs

    Directory of Open Access Journals (Sweden)

    SA Faggion

    2013-01-01

    Full Text Available The rickettsial bacterium Ehrlichia canis is the etiological agent of canine monocytic ehrlichiosis, one of the most important canine tick-borne diseases in the world. In this study, a loop-mediated isothermal amplification (LAMP assay was developed for detection of E. canis DNA using LAMP primers targeting the groESL operon. Reactions were performed at 60°C for 60 min and the results were visualized by gel electrophoresis. Successful amplification was obtained using plasmid DNA containing a fragment of the groESL operon and DNA extracted from blood samples that tested positive for E. canis by real-time PCR. The specificity of amplification was confirmed by EcoRI restriction of internal sites in the LAMP primers and no cross-reactivity with blood samples positive for Babesia spp., another common tick-borne pathogen, was observed. The high cost of nucleic acid tests (NAT is one of the disadvantages for their large-scale use as routine diagnostic tests. The E. canis LAMP assay developed here is an interesting alternative to PCR since it does not require a thermocycler, thus reducing costs for the veterinary clinical laboratory.

  1. A practical platform for blood biomarker study by using global gene expression profiling of peripheral whole blood.

    Directory of Open Access Journals (Sweden)

    Ze Tian

    Full Text Available BACKGROUND: Although microarray technology has become the most common method for studying global gene expression, a plethora of technical factors across the experiment contribute to the variable of genome gene expression profiling using peripheral whole blood. A practical platform needs to be established in order to obtain reliable and reproducible data to meet clinical requirements for biomarker study. METHODS AND FINDINGS: We applied peripheral whole blood samples with globin reduction and performed genome-wide transcriptome analysis using Illumina BeadChips. Real-time PCR was subsequently used to evaluate the quality of array data and elucidate the mode in which hemoglobin interferes in gene expression profiling. We demonstrated that, when applied in the context of standard microarray processing procedures, globin reduction results in a consistent and significant increase in the quality of beadarray data. When compared to their pre-globin reduction counterparts, post-globin reduction samples show improved detection statistics, lowered variance and increased sensitivity. More importantly, gender gene separation is remarkably clearer in post-globin reduction samples than in pre-globin reduction samples. Our study suggests that the poor data obtained from pre-globin reduction samples is the result of the high concentration of hemoglobin derived from red blood cells either interfering with target mRNA binding or giving the pseudo binding background signal. CONCLUSION: We therefore recommend the combination of performing globin mRNA reduction in peripheral whole blood samples and hybridizing on Illumina BeadChips as the practical approach for biomarker study.

  2. Contaminant concentrations, biochemical and hematological biomarkers in blood of West Indian manatees Trichechus manatus from Brazil.

    Science.gov (United States)

    Anzolin, D G; Sarkis, J E S; Diaz, E; Soares, D G; Serrano, I L; Borges, J C G; Souto, A S; Taniguchi, S; Montone, R C; Bainy, A C D; Carvalho, P S M

    2012-07-01

    The West Indian manatee Trichechus manatus is threatened with extinction in Brazil, and this study focused on nondestructive blood samples analyzed for metals, polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs), as well as biochemical and hematological biomarkers. Studied manatees were kept at Projeto Peixe-Boi headquarters in Pernambuco State, and at two natural areas in estuaries where they are released to the wild. Manatees kept at the natural estuary in Paraiba State have blood concentrations of Al, Pb, Cd, Sn that are 11, 7, 8 and 23 times greater, respectively, than the concentrations found in blood of animals from the same species in Florida, USA. An inhibition of butyrylcholinesterase in manatees kept at the two reintroduction sites in Alagoas and Paraiba States indicated possible exposure of the animals to cholinesterase inhibitor insecticides. PCBs and OCPs were not detected. Results from this study will help delineate conservation efforts in the region. PMID:22626623

  3. Contaminant concentrations, biochemical and hematological biomarkers in blood of West Indian manatees Trichechus manatus from Brazil.

    Science.gov (United States)

    Anzolin, D G; Sarkis, J E S; Diaz, E; Soares, D G; Serrano, I L; Borges, J C G; Souto, A S; Taniguchi, S; Montone, R C; Bainy, A C D; Carvalho, P S M

    2012-07-01

    The West Indian manatee Trichechus manatus is threatened with extinction in Brazil, and this study focused on nondestructive blood samples analyzed for metals, polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs), as well as biochemical and hematological biomarkers. Studied manatees were kept at Projeto Peixe-Boi headquarters in Pernambuco State, and at two natural areas in estuaries where they are released to the wild. Manatees kept at the natural estuary in Paraiba State have blood concentrations of Al, Pb, Cd, Sn that are 11, 7, 8 and 23 times greater, respectively, than the concentrations found in blood of animals from the same species in Florida, USA. An inhibition of butyrylcholinesterase in manatees kept at the two reintroduction sites in Alagoas and Paraiba States indicated possible exposure of the animals to cholinesterase inhibitor insecticides. PCBs and OCPs were not detected. Results from this study will help delineate conservation efforts in the region.

  4. Buccal Cell Cytokeratin 14 Correlates with Multiple Blood Biomarkers of Alzheimer's Disease Risk.

    Science.gov (United States)

    Leifert, Wayne R; Nguyen, Tori; Rembach, Alan; Martins, Ralph; Rainey-Smith, Stephanie; Masters, Colin L; Ames, David; Rowe, Christopher C; Macaulay, S Lance; François, Maxime; Fenech, Michael F

    2015-01-01

    Mild cognitive impairment (MCI) may reflect early stages of neurodegenerative disorders such as Alzheimer's disease (AD). Our hypothesis was that cytokeratin 14 (CK14) expression could be used with blood-based biomarkers such as homocysteine, vitamin B12, and folate to identify individuals with MCI or AD from the Australian Imaging, Biomarkers and Lifestyle (AIBL) flagship study of aging. Buccal cells from 54 individuals were analyzed by a newly developed method that is rapid, automated, and quantitative for buccal cell CK14 expression levels. CK14 was negatively correlated with plasma Mg²⁺ and LDL, while positively correlated with vitamin B12, red cell hematocrit/volume, and basophils in the MCI group and positively correlated with insulin and vitamin B12 in the AD group. The combined biomarker panel (CK14 expression, plasma vitamin B12, and homocysteine) was significantly lower in the MCI (p = 0.003) and AD (p = 0.0001) groups compared with controls. Receiver-operating characteristic curves yielded area under the curve (AUC) values of 0.829 for the MCI (p = 0.002) group and 0.856 for the AD (p = 0.0003) group. These complex associations of multiple related parameters highlight the differences between the MCI and AD cohorts and possibly an underlying metabolic pathology associated with the development of early memory impairment. The changes in buccal cell CK14 expression observed in this pilot study supports previous results suggesting the peripheral biomarkers and metabolic changes are not restricted to brain pathology alone in MCI and AD and could prove useful as a potential biomarker in identifying individuals with an increased risk of developing MCI and eventually AD. PMID:26402008

  5. Circulating microRNAs as biomarkers for detection of autologous blood transfusion.

    Directory of Open Access Journals (Sweden)

    Nicolas Leuenberger

    Full Text Available MicroRNAs (miRNAs are small non-coding RNAs that regulate various biological processes. Cell-free miRNAs measured in blood plasma have emerged as specific and sensitive markers of physiological processes and disease. In this study, we investigated whether circulating miRNAs can serve as biomarkers for the detection of autologous blood transfusion, a major doping technique that is still undetectable. Plasma miRNA levels were analyzed using high-throughput quantitative real-time PCR. Plasma samples were obtained before and at several time points after autologous blood transfusion (blood bag storage time 42 days in 10 healthy subjects and 10 controls without transfusion. Other serum markers of erythropoiesis were determined in the same samples. Our results revealed a distinct change in the pattern of circulating miRNAs. Ten miRNAs were upregulated in transfusion samples compared with control samples. Among these, miR-30b, miR-30c, and miR-26b increased significantly and showed a 3.9-, 4.0-, and 3.0-fold change, respectively. The origin of these miRNAs was related to pulmonary and liver tissues. Erythropoietin (EPO concentration decreased after blood reinfusion. A combination of miRNAs and EPO measurement in a mathematical model enhanced the efficiency of autologous transfusion detection through miRNA analysis. Therefore, our results lay the foundation for the development of miRNAs as novel blood-based biomarkers to detect autologous transfusion.

  6. Exposure to fipronil elevates systolic blood pressure and disturbs related biomarkers in plasma of rats.

    Science.gov (United States)

    Chaguri, Joao Leandro; Godinho, Antonio Francisco; Horta, Daniel França; Gonçalves-Rizzi, Victor Hugo; Possomato-Vieira, Jose Sergio; Nascimento, Regina Aparecida; Dias-Junior, Carlos Alan

    2016-03-01

    Recent reports show that fipronil affects non-target organisms, including environmental species populations and potentially humans. We aimed to examine if fipronil exposure affects the systolic blood pressure and related biomarkers. Thus, fipronil was orally administered to rats (30 mg/kg/day) during 15 days (Fipronil group) or physiological solution (Control group). While fipronil increased significantly the systolic blood pressure (158±13 mmHg), no significant changes were observed in Control group (127±3 mmHg). Significantly, higher levels of fipronil in plasma were observed in Fipronil group (0.46±0.09 μg/mL versus 0.17±0.11 μg/mL in Control group). Fipronil group showed lower weight gain compared with Control group. While fipronil resulted in higher concentrations of endothelin-1, reduced antioxidant capacity and lower levels of circulating matrix metalloproteinase 2 (MMP-2) and nitric oxide (NO) metabolites compared to Control group, no alteration was observed in serum biomarkers of renal and hepatic/biliary functional abilities. Therefore, this study suggests that fipronil causes hypertension and endothelin-1 plays a key role. Also, these findings suggest that reductions of both MMP-2 and NO may contribute with the elevation of systolic blood pressure observed with fipronil.

  7. Rapid detection of cancer related DNA nanoparticulate biomarkers and nanoparticles in whole blood

    Science.gov (United States)

    Heller, Michael J.; Krishnan, Raj; Sonnenberg, Avery

    2010-08-01

    The ability to rapidly detect cell free circulating (cfc) DNA, cfc-RNA, exosomes and other nanoparticulate disease biomarkers as well as drug delivery nanoparticles directly in blood is a major challenge for nanomedicine. We now show that microarray and new high voltage dielectrophoretic (DEP) devices can be used to rapidly isolate and detect cfc-DNA nanoparticulates and nanoparticles directly from whole blood and other high conductance samples (plasma, serum, urine, etc.). At DEP frequencies of 5kHz-10kHz both fluorescent-stained high molecular weight (hmw) DNA, cfc-DNA and fluorescent nanoparticles separate from the blood and become highly concentrated at specific DEP highfield regions over the microelectrodes, while blood cells move to the DEP low field-regions. The blood cells can then be removed by a simple fluidic wash while the DNA and nanoparticles remain highly concentrated. The hmw-DNA could be detected at a level of <260ng/ml and the nanoparticles at <9.5 x 109 particles/ml, detection levels that are well within the range for viable clinical diagnostics and drug nanoparticle monitoring. Disease specific cfc-DNA materials could also be detected directly in blood from patients with Chronic Lymphocytic Leukemia (CLL) and confirmed by PCR genotyping analysis.

  8. Development of loop-mediated isothermal amplification method for detecting Wuchereria bancrofti DNA in human blood and vector mosquitoes.

    Science.gov (United States)

    Takagi, Hidekazu; Itoh, Makoto; Kasai, Shinji; Yahathugoda, Thishan C; Weerasooriya, Mirani V; Kimura, Eisaku

    2011-12-01

    We have developed loop-mediated isothermal amplification (LAMP) method to detect Wuchereria bancrofti DNA. The sensitivity and specificity of LAMP method were equivalent to those of PCR method which detects SspI repeat sequence in W. bancrofti genomic DNA: both methods detected one thousandth of W. bancrofti DNA from one microfilaria (Mf), and did not cross-react with DNAs of Brugia malayi, B. pahangi, Dirofilaria immitis, human and Culex quinquefasciatus. We also examined the sensitivity of LAMP using the mimic samples of patient's blood or blood-fed mosquitoes containing one W. bancrofti Mf per sample. The LAMP method was able to detect W. bancrofti DNA in 1000 μl of blood or in a pool of 60 mosquitoes, indicating its usefulness in detecting/monitoring W. bancrofti infection in humans and vector mosquitoes in endemic areas. PMID:21930238

  9. Eosinophilia in routine blood samples as a biomarker for solid tumor development

    DEFF Research Database (Denmark)

    Andersen, Christen Bertel L; Siersma, V.D.; Hasselbalch, H.C.;

    2014-01-01

    eosinophilia in routine blood samples as a potential biomarker of solid tumor development in a prospective design. MATERIAL AND METHODS: From the Copenhagen Primary Care Differential Count (CopDiff) Database, we identified 356 196 individuals with at least one differential cell count (DIFF) encompassing the...... tumors within the first three years following the DIFF. Using multivariable logistic regression, odds ratios (OR) were calculated and adjusted for previous eosinophilia, sex, age, year, month, C-reactive protein, previous cancer and Charlson's Comorbidity Index. RESULTS: The risk of bladder cancer was...

  10. Biomarkers for early and late stage chronic allograft nephropathy by proteogenomic profiling of peripheral blood.

    Directory of Open Access Journals (Sweden)

    Sunil M Kurian

    Full Text Available BACKGROUND: Despite significant improvements in life expectancy of kidney transplant patients due to advances in surgery and immunosuppression, Chronic Allograft Nephropathy (CAN remains a daunting problem. A complex network of cellular mechanisms in both graft and peripheral immune compartments complicates the non-invasive diagnosis of CAN, which still requires biopsy histology. This is compounded by non-immunological factors contributing to graft injury. There is a pressing need to identify and validate minimally invasive biomarkers for CAN to serve as early predictors of graft loss and as metrics for managing long-term immunosuppression. METHODS: We used DNA microarrays, tandem mass spectroscopy proteomics and bioinformatics to identify genomic and proteomic markers of mild and moderate/severe CAN in peripheral blood of two distinct cohorts (n = 77 total of kidney transplant patients with biopsy-documented histology. FINDINGS: Gene expression profiles reveal over 2400 genes for mild CAN, and over 700 for moderate/severe CAN. A consensus analysis reveals 393 (mild and 63 (moderate/severe final candidates as CAN markers with predictive accuracy of 80% (mild and 92% (moderate/severe. Proteomic profiles show over 500 candidates each, for both stages of CAN including 302 proteins unique to mild and 509 unique to moderate/severe CAN. CONCLUSIONS: This study identifies several unique signatures of transcript and protein biomarkers with high predictive accuracies for mild and moderate/severe CAN, the most common cause of late allograft failure. These biomarkers are the necessary first step to a proteogenomic classification of CAN based on peripheral blood profiling and will be the targets of a prospective clinical validation study.

  11. Inflammation in low back pain may be detected from the peripheral blood: suggestions for biomarker.

    Science.gov (United States)

    Li, Yong; Liu, Jun; Liu, Zong-Zhi; Duan, Da-Peng

    2016-08-01

    Biomarker for prediction of development of low back pain, and disease progression in chronic conditions are virtually non-existent. In the present study, we examined evidence of inflammation in the peripheral blood and demonstrated significant changes in neuroinflammation markers in subjects with chronic low back pain in comparison with control subjects. The present study was performed using peripheral blood from subjects with chronic low back pain and age-matched control subjects. Western blotting, real-time RT-PCR, cell culture and in vitro assays were incorporated to perform the current study. We obtained evidence that the balance between proinflammatory and anti-inflammatory cytokines is misaligned, with decrease in interleukin-10 (IL-10) expression and increase in interleukin-6 (IL-6) expression. Furthermore, we demonstrated increase in CD16 monocyte expression. Cells were cultured under differential conditions to generate M1/M2 macrophages. In the macrophages, opioid secretory capacity was shown to be diminished. Finally, Dragon (repulsive guidance molecule b, RGMb) expression was shown diminished in M1 macrophages, which serves as a key transcriptional inhibitor of IL-6 expression. These biochemical and cellular alterations in chronic low back pain can serve as potential biomarkers for assessing disease initiation, intensity and progression.

  12. Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes

    DEFF Research Database (Denmark)

    Bacos, Karl; Gillberg, Linn; Volkov, Petr;

    2016-01-01

    Aging associates with impaired pancreatic islet function and increased type 2 diabetes (T2D) risk. Here we examine whether age-related epigenetic changes affect human islet function and if blood-based epigenetic biomarkers reflect these changes and associate with future T2D. We analyse DNA...... methylation genome-wide in islets from 87 non-diabetic donors, aged 26-74 years. Aging associates with increased DNA methylation of 241 sites. These sites cover loci previously associated with T2D, for example, KLF14. Blood-based epigenetic biomarkers reflect age-related methylation changes in 83 genes...... demonstrate that blood-based epigenetic biomarkers reflect age-related DNA methylation changes in human islets, and associate with insulin secretion in vivo and T2D....

  13. Optimization of loop-mediated isothermal amplification (LAMP) assays for the detection of Leishmania DNA in human blood samples.

    Science.gov (United States)

    Abbasi, Ibrahim; Kirstein, Oscar D; Hailu, Asrat; Warburg, Alon

    2016-10-01

    Visceral leishmaniasis (VL), one of the most important neglected tropical diseases, is caused by Leishmania donovani eukaryotic protozoan parasite of the genus Leishmania, the disease is prevalent mainly in the Indian sub-continent, East Africa and Brazil. VL can be diagnosed by PCR amplifying ITS1 and/or kDNA genes. The current study involved the optimization of Loop-mediated isothermal amplification (LAMP) for the detection of Leishmania DNA in human blood or tissue samples. Three LAMP systems were developed; in two of those the primers were designed based on shared regions of the ITS1 gene among different Leishmania species, while the primers for the third LAMP system were derived from a newly identified repeated region in the Leishmania genome. The LAMP tests were shown to be sufficiently sensitive to detect 0.1pg of DNA from most Leishmania species. The green nucleic acid stain SYTO16, was used here for the first time to allow real-time monitoring of LAMP amplification. The advantage of real time-LAMP using SYTO 16 over end-point LAMP product detection is discussed. The efficacy of the real time-LAMP tests for detecting Leishmania DNA in dried blood samples from volunteers living in endemic areas, was compared with that of qRT-kDNA PCR. PMID:27288706

  14. Robust and efficient direct multiplex amplification method for large-scale DNA detection of blood samples on FTA cards

    International Nuclear Information System (INIS)

    Deoxyribonucleic acid (DNA) damage arising from radiations widely occurred along with the development of nuclear weapons and clinically wide application of computed tomography (CT) scan and nuclear medicine. All ionizing radiations (X-rays, γ-rays, alpha particles, etc.) and ultraviolet (UV) radiation lead to the DNA damage. Polymerase chain reaction (PCR) is one of the most wildly used techniques for detecting DNA damage as the amplification stops at the site of the damage. Improvements to enhance the efficiency of PCR are always required and remain a great challenge. Here we establish a multiplex PCR assay system (MPAS) that is served as a robust and efficient method for direct detection of target DNA sequences in genomic DNA. The establishment of the system is performed by adding a combination of PCR enhancers to standard PCR buffer, The performance of MPAS was demonstrated by carrying out the direct PCR amplification on l.2 mm human blood punch using commercially available primer sets which include multiple primer pairs. The optimized PCR system resulted in high quality genotyping results without any inhibitory effect indicated and led to a full-profile success rate of 98.13%. Our studies demonstrate that the MPAS provides an efficient and robust method for obtaining sensitive, reliable and reproducible PCR results from human blood samples. (authors)

  15. Blood transcriptomic biomarkers in adult primary care patients with major depressive disorder undergoing cognitive behavioral therapy.

    Science.gov (United States)

    Redei, E E; Andrus, B M; Kwasny, M J; Seok, J; Cai, X; Ho, J; Mohr, D C

    2014-09-16

    An objective, laboratory-based diagnostic tool could increase the diagnostic accuracy of major depressive disorders (MDDs), identify factors that characterize patients and promote individualized therapy. The goal of this study was to assess a blood-based biomarker panel, which showed promise in adolescents with MDD, in adult primary care patients with MDD and age-, gender- and race-matched nondepressed (ND) controls. Patients with MDD received cognitive behavioral therapy (CBT) and clinical assessment using self-reported depression with the Patient Health Questionnaire-9 (PHQ-9). The measures, including blood RNA collection, were obtained before and after 18 weeks of CBT. Blood transcript levels of nine markers of ADCY3, DGKA, FAM46A, IGSF4A/CADM1, KIAA1539, MARCKS, PSME1, RAPH1 and TLR7, differed significantly between participants with MDD (N=32) and ND controls (N=32) at baseline (qdepressed. Thus, blood levels of different transcript panels may identify the depressed from the nondepressed among primary care patients, during a depressive episode or in remission, or follow and predict response to CBT in depressed individuals.

  16. Improved Blood Biomarkers but No Cognitive Effects from 16 Weeks of Multivitamin Supplementation in Healthy Older Adults

    Directory of Open Access Journals (Sweden)

    Elizabeth Harris

    2015-05-01

    Full Text Available Supplementation with vitamins, minerals and phytonutrients may be beneficial for cognition, especially in older adults. The aim of this study was to assess the effects of multivitamin supplementation in older adults on cognitive function and associated blood biomarkers. In a randomised, double blind, placebo-controlled trial, healthy women (n = 68 and men (n = 48 aged 55–65 years were supplemented daily for 16 weeks with women’s and men’s formula multivitamin supplements. Assessments at baseline and post-supplementation included computerised cognitive tasks and blood biomarkers relevant to cognitive aging. No cognitive improvements were observed after supplementation with either formula; however, several significant improvements were observed in blood biomarkers including increased levels of vitamins B6 and B12 in women and men; reduced C-reactive protein in women; reduced homocysteine and marginally reduced oxidative stress in men; as well as improvements to the lipid profile in men. In healthy older people, multivitamin supplementation improved a number of blood biomarkers that are relevant to cognition, but these biomarker changes were not accompanied by improved cognitive function.

  17. Expression profiling reveals novel hypoxic biomarkers in peripheral blood of adult mice exposed to chronic hypoxia.

    Directory of Open Access Journals (Sweden)

    Matias Mosqueira

    Full Text Available Hypoxia induces a myriad of changes including an increase in hematocrit due to erythropoietin (EPO mediated erythropoiesis. While hypoxia is of importance physiologically and clinically, lacunae exist in our knowledge of the systemic and temporal changes in gene expression occurring in blood during the exposure and recovery from hypoxia. To identify these changes expression profiling was conducted on blood obtained from cohorts of C57Bl-10 wild type mice that were maintained at normoxia (NX, exposed for two weeks to normobaric chronic hypoxia (CH or two weeks of CH followed by two weeks of normoxic recovery (REC. Using stringent bioinformatic cut-offs (0% FDR, 2 fold change cut-off, 230 genes were identified and separated into four distinct temporal categories. Class I contained 1 transcript up-regulated in both CH and REC; Class II contained 202 transcripts up-regulated in CH but down-regulated after REC; Class III contained 9 transcripts down-regulated both in CH and REC; Class IV contained 18 transcripts down-regulated after CH exposure but up-regulated after REC. Profiling was independently validated and extended by analyzing expression levels of selected genes as novel biomarkers from our profile (e.g. spectrin alpha-1, ubiquitin domain family-1 and pyrroline-5-carboxylate reductase-1 by performing qPCR at 7 different time points during CH and REC. Our identification and characterization of these genes define transcriptome level changes occurring during chronic hypoxia and normoxic recovery as well as novel blood biomarkers that may be useful in monitoring a variety of physiological and pathological conditions associated with hypoxia.

  18. FREE RADICAL-RELATED DISEASES: THE PREDICTIVE VALUE OF BIOMARKERS IN THE UMBILICAL CORD BLOOD

    Directory of Open Access Journals (Sweden)

    S. Perrone

    2013-12-01

    Full Text Available Despite recent advances in preterm newborns healthcare, the incidence of neonatal pathologies and disabilities still remain unacceptable high. The deficiency of antioxidant systems and the high free radicals (FRs production may cause several neonatal diseases, such as Retinopathy of Prematurity (ROP, Bronchopulmonary Dysplasia (BPD, Necrotizing Enterocolitis (NEC, Patent Ductus Arteriosus (PDA, Periventricular Leukomalacia (PVL and Intraventricular Hemorrhage (IVH, representing facets of the ‘Free Radical-Related Diseases’ (FRD. The aim of this study is to verify the association between FRD and blood levels of reliable oxidative stress (OS biomarkers in preterm newborns. We enrolled 178 preterm newborns born consecutively at the General Hospital “Santa Maria alle Scotte” in Siena, between 23 and 34 weeks (30,36±2.97 of gestational age, with birth-weight from 430 to 2890 grams (1453±593. After birth, we evaluated in the cord blood the markers of potential risk of OS (Non Protein-Bound Iron, NPBI and the markers of FR damage (Total Hydroperoxides, TH; Advanced Oxidation Protein Products, AOPP. For each newborn, we assessed the presence or absence of the following diseases, considering as FRD the presence of one at least: ROP, BPD, NEC, PDA, PVL, IVH. The univariate logistic regression showed a significant association between FRD and OS related markers. Risk assessment of FRD was higher in newborns with higher values of each OS marker: respectively TH (OR=1.013, p=0,000, AOPP (OR=1.017, p=0,036, NPBI (OR=1.077, p=0.039. Perinatal OS exposure is linked to the main diseases of prematurity. The evaluation of OS biomarkers in preterm newborns through the analysis of umbilical cord blood, can be useful and predictive for early identification of infants at risk for FRD in order to devise appropriate and timely prevention and treating strategies.

  19. Arginine Vasopressin Is a Blood-Based Biomarker of Social Functioning in Children with Autism.

    Directory of Open Access Journals (Sweden)

    Dean S Carson

    Full Text Available Brain arginine vasopressin (AVP critically regulates normative social behavior in mammals, and experimental disruption of the AVP signaling pathway produces social impairments in rodent models. We therefore hypothesized that AVP signaling deficits may contribute to social impairments in children with autism spectrum disorder (ASD. Since blood measures (which are far easier to obtain than brain measures of AVP are most meaningful if they are related to brain AVP activity, Study 1 tested the relationship between AVP concentrations in concomitantly collected blood and CSF samples from children and adults (N = 28 undergoing clinical procedures. Study 2 tested whether blood AVP concentrations: 1 differed between children with ASD (N = 57, their ASD discordant siblings (N = 47, and neurotypical controls (N = 55; and 2 predicted social functioning (using the NEPSY-II Theory of Mind and Affect Recognition tasks and the Social Responsiveness Scale in this large, well-characterized child cohort. Blood AVP concentrations significantly and positively predicted CSF AVP concentrations (F1,26 = 7.17, r = 0.46, p = 0.0127 in Study 1. In Study 2, blood AVP concentrations did not differ between groups or by sex, but significantly and positively predicted Theory of Mind performance, specifically in children with ASD, but not in non-ASD children (F1,144 = 5.83, p = 0.017. Blood AVP concentrations can be used: 1 as a surrogate for brain AVP activity in humans; and 2 as a robust biomarker of theory of mind ability in children with ASD. These findings also suggest that AVP biology may be a promising therapeutic target by which to improve social cognition in individuals with ASD.

  20. Altered Blood Biomarker Profiles in Athletes with a History of Repetitive Head Impacts

    Science.gov (United States)

    2016-01-01

    The long-term health effects of concussion and sub-concussive impacts in sport are unknown. Growing evidence suggests both inflammation and neurodegeneration are pivotal to secondary injury processes and the etiology of neurodegenerative diseases. In the present study we characterized circulating brain injury and inflammatory mediators in healthy male and female athletes according to concussion history and collision sport participation. Eighty-seven university level athletes (male, n = 60; female, n = 27) were recruited before the start of the competitive season. Athletes were healthy at the time of the study (no medications, illness, concussion or musculoskeletal injuries). Dependent variables included 29 inflammatory and 10 neurological injury analytes assessed in the peripheral blood by immunoassay. Biomarkers were statistically evaluated using partial least squares multivariate analysis to identify possible relationships to self-reported previous concussion history, number of previous concussions and collision sport participation in male and female athletes. Multiple concussions were associated with increases in peripheral MCP-1 in females, and MCP-4 in males. Collision sport participation was associated with increases in tau levels in males. These results are consistent with previous experimental and clinical findings that suggest ongoing inflammatory and cerebral injury processes after repetitive mild head trauma. However, further validation is needed to correlate systemic biomarkers to repetitive brain impacts, as opposed to the extracranial effects common to an athletic population such as exercise and muscle damage. PMID:27458972

  1. Altered Blood Biomarker Profiles in Athletes with a History of Repetitive Head Impacts.

    Directory of Open Access Journals (Sweden)

    Alex P Di Battista

    Full Text Available The long-term health effects of concussion and sub-concussive impacts in sport are unknown. Growing evidence suggests both inflammation and neurodegeneration are pivotal to secondary injury processes and the etiology of neurodegenerative diseases. In the present study we characterized circulating brain injury and inflammatory mediators in healthy male and female athletes according to concussion history and collision sport participation. Eighty-seven university level athletes (male, n = 60; female, n = 27 were recruited before the start of the competitive season. Athletes were healthy at the time of the study (no medications, illness, concussion or musculoskeletal injuries. Dependent variables included 29 inflammatory and 10 neurological injury analytes assessed in the peripheral blood by immunoassay. Biomarkers were statistically evaluated using partial least squares multivariate analysis to identify possible relationships to self-reported previous concussion history, number of previous concussions and collision sport participation in male and female athletes. Multiple concussions were associated with increases in peripheral MCP-1 in females, and MCP-4 in males. Collision sport participation was associated with increases in tau levels in males. These results are consistent with previous experimental and clinical findings that suggest ongoing inflammatory and cerebral injury processes after repetitive mild head trauma. However, further validation is needed to correlate systemic biomarkers to repetitive brain impacts, as opposed to the extracranial effects common to an athletic population such as exercise and muscle damage.

  2. Blood biomarkers in metal scrap workers accidentally exposed to ionizing radiation: a case study.

    Science.gov (United States)

    Gupta, M L; Srivastava, N N; Dutta, S; Shukla, S K; Dutta, A; Verma, S; Devi, M

    2013-12-01

    The detrimental effect of nuclear accidents due to localized or whole body radiation exposure results in severe cellular damage. The current study was carried out to evaluate radiation-mediated variability in blood components of metal scrap workers exposed accidently to cobalt-60 source. Blood samples collected initially from five hospitalized patients, coded P1-P5, were processed for total leukocyte counts (TLC), platelet (PLT) counts, haemoglobin, estimation of DNA double strand breaks by measuring phosphorylated form of H2AX (γ-H2AX) and chromosomal aberrations (dicentrics). Blood cells count (TLC), in all the patients except P2, was found decreased. Dicentrics increased in all the five patients. γ-H2AX was found significantly elevated in patients P2 and P4. After 3 days, 21 subjects working in close vicinity of accident site were evaluated for the above-mentioned markers to confirm their possibility of radiation exposure; however, all the parameters in these subjects were found within normal limits. Blood from patients P1-P5 was collected again after 11 days. Studies revealed exorbitant increase in γ-H2AX in lymphocytes and monocytes of patients P1, P4 and P5. TLC and PLT count in these patients had fallen further. Dicentrics declined with time in all the five patients. Based on the studied blood biomarkers, we conclude that the five subjects showed signs of radiation exposure. Measurement on radiation dose could not be performed in the current study; however, the generated data particularly on dicentrics provide ample evidence of radiation exposure.

  3. Use of blood based biomarkers in the evaluation of Crohn’s disease and ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Edward; L; Barnes; Choong-Chin; Liew; Samuel; Chao; Robert; Burakoff

    2015-01-01

    Despite significant improvements in our understanding of Crohn’s disease(CD) and ulcerative colitis(UC) in recent years, questions remain regarding the best approaches to assessment and management of these chronic diseases during periods of both relapse and remission. Various serologic biomarkers have been used in the evaluation of patients with both suspected and documented inflammatory bowel disease(IBD), and while each has potential utility in the assessment of patients with IBD, potential limitation remain with each method of assessment. Given these potential shortcomings, there has been increased interest in other means of evaluation of patients with IBD, including an expanding interest in the role of gene expression profiling. Among patients with IBD, gene expression profiles obtained from whole blood have been used to differentiate active from inactive CD, as well as to differentiate between CD, UC, and non-inflammatory diarrheal conditions. There are many opportunities for a non-invasive, blood based test to aid in the assessment of patients with IBD, particularly when considering more invasive means of evaluation including endoscopy with biopsy. Furthermore, as the emphasis on personalized medicine continues to increase, the potential ability of gene expression analysis to predict patient response to individual therapies offers great promise. While whole blood gene expression analysis may not completely replace more traditional means of evaluating patients with suspected or known IBD, it does offer significant potential to expand our knowledge of the underlying genes involved in the development of these diseases.

  4. Identification of specific bovine blood biomarkers with a non-targeted approach using HPLC ESI tandem mass spectrometry.

    Science.gov (United States)

    Lecrenier, M C; Marbaix, H; Dieu, M; Veys, P; Saegerman, C; Raes, M; Baeten, V

    2016-12-15

    Animal by-products are valuable protein sources in animal nutrition. Among them are blood products and blood meal, which are used as high-quality material for their beneficial effects on growth and health. Within the framework of the feed ban relaxation, the development of complementary methods in order to refine the identification of processed animal proteins remains challenging. The aim of this study was to identify specific biomarkers that would allow the detection of bovine blood products and processed animal proteins using tandem mass spectrometry. Seventeen biomarkers were identified: nine peptides for bovine plasma powder; seven peptides for bovine haemoglobin powder, including six peptides for bovine blood meal; and one peptide for porcine blood. They were not detected in several commercial compound feed or feed materials, such as blood by-products of other animal origins, milk-derived products and fish meal. These biomarkers could be used for developing a species-specific and blood-specific detection method. PMID:27451199

  5. Proteomic biomarkers of peripheral blood mononuclear cells obtained from postmenopausal women undergoing an intervention with soy isoflavones

    OpenAIRE

    Fuchs, D; Vafeiadou, K.; Hall, W.L.; Daniel, H; Williams, C.M.; Schroot, J.H.; Wenzel, U.

    2007-01-01

    Background: The incidence of cardiovascular diseases increases after menopause, and soy consumption is suggested to inhibit disease development. Objective: The objective was to identify biomarkers of response to a dietary supplementation with an isoflavone extract in postmenopausal women by proteome analysis of peripheral blood mononuclear cells. Design: The study with healthy postmenopausal woman was performed in a placebo-controlled sequential design. Peripheral mononuclear blood cells were...

  6. Gene expression analysis in pregnant women and their infants identifies unique fetal biomarkers that circulate in maternal blood

    OpenAIRE

    Maron, Jill L.; Johnson, Kirby L.; Slonim, Donna; Lai, Chao-Qiang; Ramoni, Marco; Alterovitz, Gil; Jarrah, Zina; Yang, Zinger; Bianchi, Diana W.

    2007-01-01

    The discovery of fetal mRNA transcripts in the maternal circulation holds great promise for noninvasive prenatal diagnosis. To identify potential fetal biomarkers, we studied whole blood and plasma gene transcripts that were common to 9 term pregnant women and their newborns but absent or reduced in the mothers postpartum. RNA was isolated from peripheral or umbilical blood and hybridized to gene expression arrays. Gene expression, paired Student’s t test, and pathway analyses were performed....

  7. Ratiometric fluorescence transduction by hybridization after isothermal amplification for determination of zeptomole quantities of oligonucleotide biomarkers with a paper-based platform and camera-based detection

    Energy Technology Data Exchange (ETDEWEB)

    Noor, M. Omair; Hrovat, David [Chemical Sensors Group, Department of Chemical and Physical Sciences, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6 (Canada); Moazami-Goudarzi, Maryam [Department of Cell and Systems Biology, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6 (Canada); Espie, George S. [Department of Cell and Systems Biology, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6 (Canada); Department of Biology, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6 (Canada); Krull, Ulrich J., E-mail: ulrich.krull@utoronto.ca [Chemical Sensors Group, Department of Chemical and Physical Sciences, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6 (Canada)

    2015-07-23

    Highlights: • Solid-phase QD-FRET transduction of isothermal tHDA amplicons on paper substrates. • Ratiometric QD-FRET transduction improves assay precision and lowers the detection limit. • Zeptomole detection limit by an iPad camera after isothermal amplification. • Tunable assay sensitivity by immobilizing different amounts of QD–probe bioconjugates. - Abstract: Paper is a promising platform for the development of decentralized diagnostic assays owing to the low cost and ease of use of paper-based analytical devices (PADs). It can be challenging to detect on PADs very low concentrations of nucleic acid biomarkers of lengths as used in clinical assays. Herein we report the use of thermophilic helicase-dependent amplification (tHDA) in combination with a paper-based platform for fluorescence detection of probe-target hybridization. Paper substrates were patterned using wax printing. The cellulosic fibers were chemically derivatized with imidazole groups for the assembly of the transduction interface that consisted of immobilized quantum dot (QD)–probe oligonucleotide conjugates. Green-emitting QDs (gQDs) served as donors with Cy3 as the acceptor dye in a fluorescence resonance energy transfer (FRET)-based transduction method. After probe-target hybridization, a further hybridization event with a reporter sequence brought the Cy3 acceptor dye in close proximity to the surface of immobilized gQDs, triggering a FRET sensitized emission that served as an analytical signal. Ratiometric detection was evaluated using both an epifluorescence microscope and a low-cost iPad camera as detectors. Addition of the tHDA method for target amplification to produce sequences of ∼100 base length allowed for the detection of zmol quantities of nucleic acid targets using the two detection platforms. The ratiometric QD-FRET transduction method not only offered improved assay precision, but also lowered the limit of detection of the assay when compared with the non

  8. A Putative Blood-Based Biomarker for Autism Spectrum Disorder-Associated Ileocolitis

    Science.gov (United States)

    Walker, Stephen J.; Beavers, Daniel P.; Fortunato, John; Krigsman, Arthur

    2016-01-01

    Gastrointestinal symptoms are common in children with autism spectrum disorder (ASD). A significant proportion of children with ASD and gastrointestinal symptoms have histologic evidence of ileocolitis (inflammation of the terminal ileum and/or colon). We previously reported the molecular characterization of gastrointestinal biopsy tissue from ASD children with ileocolitis (ASDIC+) compared to anatomically similar inflamed tissue from typically developing children with inflammatory bowel disease (IBD; i.e. Crohn’s disease or ulcerative colitis) and typically developing children with gastrointestinal symptoms but no evidence of gastrointestinal mucosal inflammation (TDIC−). ASDIC+ children had a gene expression profile that, while primarily overlapping with known IBD, had distinctive differences. The present study confirms these findings and replicates this molecular characterization in a second cohort of cases (ASDIC+) and controls (TDIC−). In these two separate case/control mucosal-based cohorts, we have demonstrated overlap of 59 differentially expressed transcripts (DETs) unique to inflamed ileocolonic tissue from symptomatic ASDIC+ children. We now report that 9 of these 59 transcripts are also differentially expressed in the peripheral blood of the second cohort of ASDIC+ children. This set of transcripts represents a putative blood-based biomarker for ASD-associated ileocolonic inflammation. PMID:27767057

  9. Identification of Blood Let-7e-5p as a Biomarker for Ischemic Stroke

    Science.gov (United States)

    Guo, Yi; Li, Lu; Zhang, Yanwei; Zhou, Li; Yang, Binyao; Wu, Shuang; Zhang, Ying; Xie, Changhui; Li, Shanshan; Cheng, Jinquan

    2016-01-01

    Circulating microRNAs (miRNAs) are emerging as novel disease biomarkers. Using a miRNA microarray, we previously showed that the whole blood level of let-7e-5p was significantly higher in ischemic stroke patients than in control subjects. However, the association between let-7e-5p expression and the occurrence of ischemic stroke remains unknown. In this study, we validated the expression levels of let-7e-5p in two case-control populations using miRNA TaqMan assays and further investigated the potential targets of let-7e-5p. The results suggest that the blood level of let-7e-5p was significantly higher in patients with ischemic stroke than in controls (p<0.05). Higher levels of let-7e-5p were associated with increased occurrence of ischemic stroke (adjusted OR, 1.89; 95% CI, 1.61~2.21, p<0.001) in the combined population. The addition of let-7e-5p to traditional risk factors led to an improvement in the area under the curve, which increased from 0.74 (95% CI, 0.70~0.78) to 0.82 (95% CI, 0.78~0.85), with a net reclassification improvement of 16.76% (p<0.0001) and an integrated discrimination improvement of 0.10 (p<0.0001) for patients with ischemic stroke. Bioinformatics prediction and cell experiments suggested that the expression levels of four genes enriched in the MAPK signaling pathway were down-regulated by let-7e-5p transfection. Specifically, the expression levels of the genes CASP3 and NLK were significantly lower in ischemic stroke patients than in controls and were negatively correlated with let-7e-5p expression. In summary, our study suggests the potential use of blood let-7e-5p as a biomarker for ischemic stroke and indicates its involvement in the related pathomechanism. PMID:27776139

  10. Histone Methylation Marks on Circulating Nucleosomes as Novel Blood-Based Biomarker in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Ugur Gezer

    2015-12-01

    Full Text Available Circulating nucleic acids (CNAs are under investigation as a liquid biopsy in cancer as potential non-invasive biomarkers, as stable structure in circulation nucleosomes could be valuable sources for detection of cancer-specific alterations in histone modifications. Our interest is in histone methylation marks with a focus on colorectal cancer, one of the leading cancers respective the incidence and mortality. Our previous work included the analysis of trimethylations of lysine 9 on histone 3 (H3K9me3 and of lysine 20 on histone 4 (H4K20me3 by chromatin immuno- precipitation-related PCR in circulating nucleosomes. Here we asked whether global immunologic measurement of histone marks in circulation could be a suitable approach to show their potential as biomarkers. In addition to H3K9me3 and H4K20me3 we also measured H3K27me3 in plasma samples from CRC patients (n = 63 and cancer free individuals (n = 40 by ELISA-based methylation assays. Our results show that of three marks, the amounts of H3K27me3 (p = 0.04 and H4K20me3 (p < 0.001 were significantly lower in CRC patients than in healthy controls. For H3K9me3 similar amounts were measured in both groups. Areas under the curve (AUC in receiver operating characteristic (ROC curves indicating the power of CRC detection were 0.620 for H3K27me3, 0.715 for H4K20me3 and 0.769 for the combination of both markers. In conclusion, findings of this preliminary study reveal the potential of blood-based detection of CRC by quantification of histone methylation marks and the additive effect of the marker combination.

  11. Natriuretic Peptides as Cardiovascular Safety Biomarkers in Rats: Comparison With Blood Pressure, Heart Rate, and Heart Weight.

    Science.gov (United States)

    Engle, Steven K; Watson, David E

    2016-02-01

    Cardiovascular (CV) toxicity is an important cause of failure during drug development. Blood-based biomarkers can be used to detect CV toxicity during preclinical development and prioritize compounds at lower risk of causing such toxicities. Evidence of myocardial degeneration can be detected by measuring concentrations of biomarkers such as cardiac troponin I and creatine kinase in blood; however, detection of functional changes in the CV system, such as blood pressure, generally requires studies in animals with surgically implanted pressure transducers. This is a significant limitation because sustained changes in blood pressure are often accompanied by changes in heart rate and together can lead to cardiac hypertrophy and myocardial degeneration in animals, and major adverse cardiovascular events (MACE) in humans. Increased concentrations of NPs in blood correlate with higher risk of cardiac mortality, all-cause mortality, and MACE in humans. Their utility as biomarkers of CV function and toxicity in rodents was investigated by exploring the relationships between plasma concentrations of NTproANP and NTproBNP, blood pressure, heart rate, and heart weight in Sprague Dawley rats administered compounds that caused hypotension or hypertension, including nifedipine, fluprostenol, minoxidil, L-NAME, L-thyroxine, or sunitinib for 1-2 weeks. Changes in NTproANP and/or NTproBNP concentrations were inversely correlated with changes in blood pressure. NTproANP and NTproBNP concentrations were inconsistently correlated with relative heart weights. In addition, increased heart rate was associated with increased heart weights. These studies support the use of natriuretic peptides and heart rate to detect changes in blood pressure and cardiac hypertrophy in short-duration rat studies. PMID:26609138

  12. Alterations of miR-132 are novel diagnostic biomarkers in peripheral blood of schizophrenia patients.

    Science.gov (United States)

    Yu, Hai-chuan; Wu, Jiao; Zhang, Hong-xing; Zhang, Gao-li; Sui, Juan; Tong, Wen-wen; Zhang, Xin-ya; Nie, Li-li; Duan, Ju-hong; Zhang, Li-rong; Lv, Lu-xian

    2015-12-01

    Alterations in microRNAs (miRNAs) have been considered to have diagnostic implications in most diseases, but few studies have reported dysregulated miRNAs in schizophrenia (SCZ). In order to observe an association between miRNAs and SCZ, this study was designed to investigate expression profiling of miRNAs in peripheral blood mononuclear cells (PBMCs). miRNA microarray technology was employed to compare the expression of miRNAs in PBMCs from SCZ patients (n=105) and normal controls (n=130), and real-time quantitative polymerase chain reaction (QPCR) was used to analyze the results. Several important miRNA levels were examined before and after antipsychotic treatment in first-onset SCZ patients. In addition, an SCZ-like rat model was established using dizocilpine (MK-801), and miR-132 expression in PBMCs and whole-brain tissue from SCZ-like rats was studied using QPCR. In humans, dysregulated miRNAs were observed before treatment and QPCR verified that miR-132, miR-134, miR-1271, miR-664(⁎), miR-200c and miR-432 levels were significantly decreased (Panimal assays, miR-132 levels declined in PBMCs and whole-brain tissues (both P<0.05) of the SCZ-like rats compared to controls. For the first time, our results suggest that miR-132 is a potential and superior biomarker in peripheral blood that will allow discrimination of SCZ patients from healthy controls. PMID:25985888

  13. Peripheral blood mRNA expressions of stress biomarkers in manic episode and subsequent remission.

    Science.gov (United States)

    Köse Çinar, Rugül; Sönmez, Mehmet Bülent; Görgülü, Yasemin

    2016-08-01

    Theoretical models of the neuroprogressive nature of bipolar disorder (BD) are based on the hypothesis that it is an accelerated aging disease, with the allostatic load playing a major role. Glucocorticoids, oxidative stress markers, inflammatory cytokines and neurotrophins play important roles in BD. The messenger ribonucleic acid (mRNA) expressions of brain-derived neurotrophic factor (BDNF), tissue plasminogen activator (tPA), glucocorticoid receptor (GR), heat shock protein 70 (HSP70), tumour necrosis factor-alpha (TNF-α) were examined in the peripheral blood of 20 adult male, drug-free BD patients during manic and remission periods and in 20 adult male, healthy controls. mRNA expression was measured using the quantitative real-time polymerase chain reaction (qRT-PCR). Compared to the controls, the expressions of BDNF and tPA mRNA were down-regulated in mania. In remission, BNDF and tPA mRNA levels increased, but they were still lower than those of the controls. Between mania and remission periods, only the change in mRNA levels of BDNF reached statistical significance. The results suggest that BDNF and tPA may be biomarkers of BD and that proteolytic conversion of BDNF may be important in the pathophysiology of BD. The change in BDNF levels between mania and remission could be adaptive and used to follow the progression of BD. PMID:27138695

  14. Seasonal Variations of Complete Blood Count and Inflammatory Biomarkers in the US Population - Analysis of NHANES Data.

    Directory of Open Access Journals (Sweden)

    Bian Liu

    Full Text Available Recent studies reported seasonal differences in gene expression in white blood cells, adipose tissue, and inflammatory biomarkers of the immune system. There is no data on the seasonal variations of these biomarkers in the US general population of both children and adults. Then aim of this study is to explore the seasonal trends in complete blood count (CBC, and C-reactive protein (CRP in a large non-institutionalized US population.Seven cross-sectional data collected in the National Health and Nutrition Examination Survey (NHANES during 1999-2012 were aggregated; participants reporting recent use of prescribed steroids, chemotherapy, immunomodulators and antibiotics were excluded. Linear regression models were used to compare levels of CBC and CRP between winter-spring (November-April and summer-fall (May-October, adjusting for demographics, personal behavioral factors, and chronic disease conditions.A total of 27,478 children and 36,644 adults (≥18 years were included in the study. Levels of neutrophils, white blood cell count (WBC, and CRP were higher in winter-spring than summer-fall (p≤0.05. Red blood cell components were lower in winter-spring than in summer-fall, while the opposite was seen for platelets.This large population-based study found notable seasonal variations in blood cell composition and inflammatory biomarkers, with a more pro-inflammatory immune system seen in winter-spring than summer-fall. The red blood cell patterns could have implications for the observed cardio-vascular seasonality.

  15. Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes

    Science.gov (United States)

    Bacos, Karl; Gillberg, Linn; Volkov, Petr; Olsson, Anders H; Hansen, Torben; Pedersen, Oluf; Gjesing, Anette Prior; Eiberg, Hans; Tuomi, Tiinamaija; Almgren, Peter; Groop, Leif; Eliasson, Lena; Vaag, Allan; Dayeh, Tasnim; Ling, Charlotte

    2016-01-01

    Aging associates with impaired pancreatic islet function and increased type 2 diabetes (T2D) risk. Here we examine whether age-related epigenetic changes affect human islet function and if blood-based epigenetic biomarkers reflect these changes and associate with future T2D. We analyse DNA methylation genome-wide in islets from 87 non-diabetic donors, aged 26–74 years. Aging associates with increased DNA methylation of 241 sites. These sites cover loci previously associated with T2D, for example, KLF14. Blood-based epigenetic biomarkers reflect age-related methylation changes in 83 genes identified in human islets (for example, KLF14, FHL2, ZNF518B and FAM123C) and some associate with insulin secretion and T2D. DNA methylation correlates with islet expression of multiple genes, including FHL2, ZNF518B, GNPNAT1 and HLTF. Silencing these genes in β-cells alter insulin secretion. Together, we demonstrate that blood-based epigenetic biomarkers reflect age-related DNA methylation changes in human islets, and associate with insulin secretion in vivo and T2D. PMID:27029739

  16. Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes.

    Science.gov (United States)

    Bacos, Karl; Gillberg, Linn; Volkov, Petr; Olsson, Anders H; Hansen, Torben; Pedersen, Oluf; Gjesing, Anette Prior; Eiberg, Hans; Tuomi, Tiinamaija; Almgren, Peter; Groop, Leif; Eliasson, Lena; Vaag, Allan; Dayeh, Tasnim; Ling, Charlotte

    2016-01-01

    Aging associates with impaired pancreatic islet function and increased type 2 diabetes (T2D) risk. Here we examine whether age-related epigenetic changes affect human islet function and if blood-based epigenetic biomarkers reflect these changes and associate with future T2D. We analyse DNA methylation genome-wide in islets from 87 non-diabetic donors, aged 26-74 years. Aging associates with increased DNA methylation of 241 sites. These sites cover loci previously associated with T2D, for example, KLF14. Blood-based epigenetic biomarkers reflect age-related methylation changes in 83 genes identified in human islets (for example, KLF14, FHL2, ZNF518B and FAM123C) and some associate with insulin secretion and T2D. DNA methylation correlates with islet expression of multiple genes, including FHL2, ZNF518B, GNPNAT1 and HLTF. Silencing these genes in β-cells alter insulin secretion. Together, we demonstrate that blood-based epigenetic biomarkers reflect age-related DNA methylation changes in human islets, and associate with insulin secretion in vivo and T2D. PMID:27029739

  17. Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes.

    Science.gov (United States)

    Bacos, Karl; Gillberg, Linn; Volkov, Petr; Olsson, Anders H; Hansen, Torben; Pedersen, Oluf; Gjesing, Anette Prior; Eiberg, Hans; Tuomi, Tiinamaija; Almgren, Peter; Groop, Leif; Eliasson, Lena; Vaag, Allan; Dayeh, Tasnim; Ling, Charlotte

    2016-03-31

    Aging associates with impaired pancreatic islet function and increased type 2 diabetes (T2D) risk. Here we examine whether age-related epigenetic changes affect human islet function and if blood-based epigenetic biomarkers reflect these changes and associate with future T2D. We analyse DNA methylation genome-wide in islets from 87 non-diabetic donors, aged 26-74 years. Aging associates with increased DNA methylation of 241 sites. These sites cover loci previously associated with T2D, for example, KLF14. Blood-based epigenetic biomarkers reflect age-related methylation changes in 83 genes identified in human islets (for example, KLF14, FHL2, ZNF518B and FAM123C) and some associate with insulin secretion and T2D. DNA methylation correlates with islet expression of multiple genes, including FHL2, ZNF518B, GNPNAT1 and HLTF. Silencing these genes in β-cells alter insulin secretion. Together, we demonstrate that blood-based epigenetic biomarkers reflect age-related DNA methylation changes in human islets, and associate with insulin secretion in vivo and T2D.

  18. SERS active colloidal nanoparticles for the detection of small blood biomarkers using aptamers

    Science.gov (United States)

    Marks, Haley; Mabbott, Samuel; Jackson, George W.; Graham, Duncan; Cote, Gerard L.

    2015-03-01

    Functionalized colloidal nanoparticles for SERS serve as a promising multifunctional assay component for blood biomarker detection. Proper design of these nanoprobes through conjugation to spectral tags, protective polymers, and sensing ligands can provide experimental control over the sensitivity, range, reproducibility, particle stability, and integration with biorecognition assays. Additionally, the optical properties and degree of electromagnetic SERS signal enhancement can be altered and monitored through tuning the nanoparticle shape, size, material and the colloid's local surface plasmon resonance (LSPR). Aptamers, synthetic affinity ligands derived from nucleic acids, provide a number of advantages for biorecognition of small molecules and toxins with low immunogenicity. DNA aptamers are simpler and more economical to produce at large scale, are capable of greater specificity and affinity than antibodies, are easily tailored to specific functional groups, can be used to tune inter-particle distance and shift the LSPR, and their intrinsic negative charge can be utilized for additional particle stability.1,2 Herein, a "turn-off" competitive binding assay platform involving two different plasmonic nanoparticles for the detection of the toxin bisphenol A (BPA) using SERS is presented. A derivative of the toxin is immobilized onto a silver coated magnetic nanoparticle (Ag@MNP), and a second solid silver nanoparticle (AgNP) is functionalized with the BPA aptamer and a Raman reporter molecule (RRM). The capture (Ag@MNP) and probe (AgNP) particles are mixed and the aptamer binding interaction draws the nanoparticles closer together, forming an assembly that results in an increased SERS signal intensity. This aptamer mediated assembly of the two nanoparticles results in a 100x enhancement of the SERS signal intensity from the RRM. These pre-bound aptamer/nanoparticle conjugates were then exposed to BPA in free solution and the competitive binding event was monitored

  19. Can Genetic Analysis of Putative Blood Alzheimer's Disease Biomarkers Lead to Identification of Susceptibility Loci?

    Science.gov (United States)

    Barber, Robert C; Phillips, Nicole R; Tilson, Jeffrey L; Huebinger, Ryan M; Shewale, Shantanu J; Koenig, Jessica L; Mitchel, Jeffrey S; O'Bryant, Sid E; Waring, Stephen C; Diaz-Arrastia, Ramon; Chasse, Scott; Wilhelmsen, Kirk C

    2015-01-01

    Although 24 Alzheimer's disease (AD) risk loci have been reliably identified, a large portion of the predicted heritability for AD remains unexplained. It is expected that additional loci of small effect will be identified with an increased sample size. However, the cost of a significant increase in Case-Control sample size is prohibitive. The current study tests whether exploring the genetic basis of endophenotypes, in this case based on putative blood biomarkers for AD, can accelerate the identification of susceptibility loci using modest sample sizes. Each endophenotype was used as the outcome variable in an independent GWAS. Endophenotypes were based on circulating concentrations of proteins that contributed significantly to a published blood-based predictive algorithm for AD. Endophenotypes included Monocyte Chemoattractant Protein 1 (MCP1), Vascular Cell Adhesion Molecule 1 (VCAM1), Pancreatic Polypeptide (PP), Beta2 Microglobulin (B2M), Factor VII (F7), Adiponectin (ADN) and Tenascin C (TN-C). Across the seven endophenotypes, 47 SNPs were associated with outcome with a p-value ≤1x10(-7). Each signal was further characterized with respect to known genetic loci associated with AD. Signals for several endophenotypes were observed in the vicinity of CR1, MS4A6A/MS4A4E, PICALM, CLU, and PTK2B. The strongest signal was observed in association with Factor VII levels and was located within the F7 gene. Additional signals were observed in MAP3K13, ZNF320, ATP9B and TREM1. Conditional regression analyses suggested that the SNPs contributed to variation in protein concentration independent of AD status. The identification of two putatively novel AD loci (in the Factor VII and ATP9B genes), which have not been located in previous studies despite massive sample sizes, highlights the benefits of an endophenotypic approach for resolving the genetic basis for complex diseases. The coincidence of several of the endophenotypic signals with known AD loci may point to novel

  20. Can Genetic Analysis of Putative Blood Alzheimer's Disease Biomarkers Lead to Identification of Susceptibility Loci?

    Directory of Open Access Journals (Sweden)

    Robert C Barber

    Full Text Available Although 24 Alzheimer's disease (AD risk loci have been reliably identified, a large portion of the predicted heritability for AD remains unexplained. It is expected that additional loci of small effect will be identified with an increased sample size. However, the cost of a significant increase in Case-Control sample size is prohibitive. The current study tests whether exploring the genetic basis of endophenotypes, in this case based on putative blood biomarkers for AD, can accelerate the identification of susceptibility loci using modest sample sizes. Each endophenotype was used as the outcome variable in an independent GWAS. Endophenotypes were based on circulating concentrations of proteins that contributed significantly to a published blood-based predictive algorithm for AD. Endophenotypes included Monocyte Chemoattractant Protein 1 (MCP1, Vascular Cell Adhesion Molecule 1 (VCAM1, Pancreatic Polypeptide (PP, Beta2 Microglobulin (B2M, Factor VII (F7, Adiponectin (ADN and Tenascin C (TN-C. Across the seven endophenotypes, 47 SNPs were associated with outcome with a p-value ≤1x10(-7. Each signal was further characterized with respect to known genetic loci associated with AD. Signals for several endophenotypes were observed in the vicinity of CR1, MS4A6A/MS4A4E, PICALM, CLU, and PTK2B. The strongest signal was observed in association with Factor VII levels and was located within the F7 gene. Additional signals were observed in MAP3K13, ZNF320, ATP9B and TREM1. Conditional regression analyses suggested that the SNPs contributed to variation in protein concentration independent of AD status. The identification of two putatively novel AD loci (in the Factor VII and ATP9B genes, which have not been located in previous studies despite massive sample sizes, highlights the benefits of an endophenotypic approach for resolving the genetic basis for complex diseases. The coincidence of several of the endophenotypic signals with known AD loci may point

  1. Circulating MicroRNAs in maternal blood as potential biomarkers for fetal hypoxia in-utero.

    Directory of Open Access Journals (Sweden)

    Clare L Whitehead

    Full Text Available Stillbirth affects 1 in 200 pregnancies and commonly arises due to a lack of oxygen supply to the fetus. Current tests to detect fetal hypoxia in-utero lack the sensitivity to identify many babies at risk. Emerging evidence suggests that microRNAs derived from the placenta circulate in the maternal blood during pregnancy and may serve as non-invasive biomarkers for pregnancy complications. In this study, we examined the expression of miRs known to be regulated by hypoxia in two clinical settings of significant fetal hypoxia: 1 labour and 2 fetal growth restriction. Six miRs (miR 210, miR 21, miR 424, miR 199a, miR 20b, and miR 373 were differentially expressed in pregnancies complicated by fetal hypoxia. In healthy term pregnancies there was a 4.2 fold increase in miR 210 (p<0.01, 2.7 fold increase in miR 424 (p<0.05, 2.6 fold increase in miR 199a (p<0.01 and 2.3 fold increase in miR 20b (p<0.05 from prior to labour to delivery of the fetus. Furthermore, the combined expression of miR 21 and miR 20b correlated with the degree of fetal hypoxia at birth determined by umbilical cord lactate delivery (r = 0.79, p = 0.03. In pregnancies complicated by severe preterm fetal growth restriction there was upregulation of the hypoxia-regulated miRs compared to gestation-matched controls: 3.6 fold in miR 210 (p<0.01, 3.6 fold in miR 424 (p<0.05, 5.9 fold in miR 21 (p<0.01, 3.8 fold in miR 199a (p<0.01 and 3.7 fold in miR 20b (p<0.01. Interestingly, the expression of miR 373 in gestation matched controls was very low, but was very highly expressed in FGR (p<0.0001. Furthermore, the expression increased in keeping with the degree of in-utero hypoxia estimated by fetal Doppler velocimetry. We conclude quantifying hypoxia-regulated miRs in the maternal blood may identify pregnancies at risk of fetal hypoxia, enabling early intervention to improve perinatal outcomes.

  2. Milk and blood biomarkers associated to the clinical efficacy of a probiotic for the treatment of infectious mastitis.

    Science.gov (United States)

    Espinosa-Martos, I; Jiménez, E; de Andrés, J; Rodríguez-Alcalá, L M; Tavárez, S; Manzano, S; Fernández, L; Alonso, E; Fontecha, J; Rodríguez, J M

    2016-06-01

    Previous studies have shown the efficacy of oral administration of selected lactobacilli strains to treat mastitis. The objective of this study was to find microbiological, biochemical and/or immunological biomarkers of the probiotic effect. Women with (n=23) and without (n=8) symptoms of mastitis received three daily doses (10(9) cfu) of Lactobacillus salivarius PS2 for 21 days. Samples of milk, blood and urine were collected before and after the probiotic intervention, and screened for a wide spectrum of microbiological, biochemical and immunological parameters. In the mastitis group, L. salivarius PS2 intake led to a reduction in milk bacterial counts, milk and blood leukocyte counts and interleukin (IL)-8 level in milk, an increase in those of immunoglobulin (Ig)E, IgG3, epidermal growth factor and IL-7, a modification of the milk electrolyte profile, and a reduction of some oxidative stress biomarkers. Such biomarkers will be useful in future clinical studies involving a larger cohort. PMID:26925605

  3. Acute induction of anomalous and amyloidogenic blood clotting by molecular amplification of highly substoichiometric levels of bacterial lipopolysaccharide

    Science.gov (United States)

    Mbotwe, Sthembile; Bester, Janette; Robinson, Christopher J.; Kell, Douglas B.

    2016-01-01

    It is well known that a variety of inflammatory diseases are accompanied by hypercoagulability, and a number of more-or-less longer-term signalling pathways have been shown to be involved. In recent work, we have suggested a direct and primary role for bacterial lipopolysaccharide (LPS) in this hypercoagulability, but it seems never to have been tested directly. Here, we show that the addition of tiny concentrations (0.2 ng l−1) of bacterial LPS to both whole blood and platelet-poor plasma of normal, healthy donors leads to marked changes in the nature of the fibrin fibres so formed, as observed by ultrastructural and fluorescence microscopy (the latter implying that the fibrin is actually in an amyloid β-sheet-rich form that on stoichiometric grounds must occur autocatalytically). They resemble those seen in a number of inflammatory (and also amyloid) diseases, consistent with an involvement of LPS in their aetiology. These changes are mirrored by changes in their viscoelastic properties as measured by thromboelastography. As the terminal stages of coagulation involve the polymerization of fibrinogen into fibrin fibres, we tested whether LPS would bind to fibrinogen directly. We demonstrated this using isothermal calorimetry. Finally, we show that these changes in fibre structure are mirrored when the experiment is done simply with purified fibrinogen and thrombin (±0.2 ng l−1 LPS). This ratio of concentrations of LPS : fibrinogen in vivo represents a molecular amplification by the LPS of more than 108-fold, a number that is probably unparalleled in biology. The observation of a direct effect of such highly substoichiometric amounts of LPS on both fibrinogen and coagulation can account for the role of very small numbers of dormant bacteria in disease progression in a great many inflammatory conditions, and opens up this process to further mechanistic analysis and possible treatment. PMID:27605168

  4. Acute induction of anomalous and amyloidogenic blood clotting by molecular amplification of highly substoichiometric levels of bacterial lipopolysaccharide.

    Science.gov (United States)

    Pretorius, Etheresia; Mbotwe, Sthembile; Bester, Janette; Robinson, Christopher J; Kell, Douglas B

    2016-09-01

    It is well known that a variety of inflammatory diseases are accompanied by hypercoagulability, and a number of more-or-less longer-term signalling pathways have been shown to be involved. In recent work, we have suggested a direct and primary role for bacterial lipopolysaccharide (LPS) in this hypercoagulability, but it seems never to have been tested directly. Here, we show that the addition of tiny concentrations (0.2 ng l(-1)) of bacterial LPS to both whole blood and platelet-poor plasma of normal, healthy donors leads to marked changes in the nature of the fibrin fibres so formed, as observed by ultrastructural and fluorescence microscopy (the latter implying that the fibrin is actually in an amyloid β-sheet-rich form that on stoichiometric grounds must occur autocatalytically). They resemble those seen in a number of inflammatory (and also amyloid) diseases, consistent with an involvement of LPS in their aetiology. These changes are mirrored by changes in their viscoelastic properties as measured by thromboelastography. As the terminal stages of coagulation involve the polymerization of fibrinogen into fibrin fibres, we tested whether LPS would bind to fibrinogen directly. We demonstrated this using isothermal calorimetry. Finally, we show that these changes in fibre structure are mirrored when the experiment is done simply with purified fibrinogen and thrombin (±0.2 ng l(-1) LPS). This ratio of concentrations of LPS : fibrinogen in vivo represents a molecular amplification by the LPS of more than 10(8)-fold, a number that is probably unparalleled in biology. The observation of a direct effect of such highly substoichiometric amounts of LPS on both fibrinogen and coagulation can account for the role of very small numbers of dormant bacteria in disease progression in a great many inflammatory conditions, and opens up this process to further mechanistic analysis and possible treatment. PMID:27605168

  5. Paraneoplastic antigen Ma2 autoantibodies as specific blood biomarkers for detection of early recurrence of small intestine neuroendocrine tumors.

    Directory of Open Access Journals (Sweden)

    Tao Cui

    Full Text Available BACKGROUND: Small intestine neuroendocrine tumors (SI-NETs belong to a rare group of cancers. Most patients have developed metastatic disease at the time of diagnosis, for which there is currently no cure. The delay in diagnosis is a major issue in the clinical management of the patients and new markers are urgently needed. We have previously identified paraneoplastic antigen Ma2 (PNMA2 as a novel SI-NET tissue biomarker. Therefore, we evaluated whether Ma2 autoantibodies detection in the blood stream is useful for the clinical diagnosis and recurrence of SI-NETs. METHODOLOGY/PRINCIPAL FINDINGS: A novel indirect ELISA was set up to detect Ma2 autoantibodies in blood samples of patients with SI-NET at different stages of disease. The analysis was extended to include typical and atypical lung carcinoids (TLC and ALC, to evaluate whether Ma2 autoantibodies in the blood stream become a general biomarker for NETs. In total, 124 blood samples of SI-NET patients at different stages of disease were included in the study. The novel Ma2 autoantibody ELISA showed high sensitivity, specificity and accuracy with ROC curve analysis underlying an area between 0.734 and 0.816. Ma2 autoantibodies in the blood from SI-NET patients were verified by western blot and sequential immunoprecipitation. Serum antibodies of patients stain Ma2 in the tumor tissue and neurons. We observed that SI-NET patients expressing Ma2 autoantibody levels below the cutoff had a longer progression and recurrence-free survival compared to those with higher titer. We also detected higher levels of Ma2 autoantibodies in blood samples from TLC and ALC patients than from healthy controls, as previously shown in small cell lung carcinoma samples. CONCLUSION: Here we show that high Ma2 autoantibody titer in the blood of SI-NET patients is a sensitive and specific biomarker, superior to chromogranin A (CgA for the risk of recurrence after radical operation of these tumors.

  6. Amyloidosis, synucleinopathy, and prion encephalopathy in a neuropathic lysosomal storage disease: the CNS-biomarker potential of peripheral blood.

    Directory of Open Access Journals (Sweden)

    Bartholomew J Naughton

    Full Text Available Mucopolysaccharidosis (MPS IIIB is a devastating neuropathic lysosomal storage disease with complex pathology. This study identifies molecular signatures in peripheral blood that may be relevant to MPS IIIB pathogenesis using a mouse model. Genome-wide gene expression microarrays on pooled RNAs showed dysregulation of 2,802 transcripts in blood from MPS IIIB mice, reflecting pathological complexity of MPS IIIB, encompassing virtually all previously reported and as yet unexplored disease aspects. Importantly, many of the dysregulated genes are reported to be tissue-specific. Further analyses of multiple genes linked to major pathways of neurodegeneration demonstrated a strong brain-blood correlation in amyloidosis and synucleinopathy in MPS IIIB. We also detected prion protein (Prnp deposition in the CNS and Prnp dysregulation in the blood in MPS IIIB mice, suggesting the involvement of Prnp aggregation in neuropathology. Systemic delivery of trans-BBB-neurotropic rAAV9-hNAGLU vector mediated not only efficient restoration of functional α-N-acetylglucosaminidase and clearance of lysosomal storage pathology in the central nervous system (CNS and periphery, but also the correction of impaired neurodegenerative molecular pathways in the brain and blood. Our data suggest that molecular changes in blood may reflect pathological status in the CNS and provide a useful tool for identifying potential CNS-specific biomarkers for MPS IIIB and possibly other neurological diseases.

  7. Consensus Guidelines for CSF and Blood Biobanking for CNS Biomarker Studies

    Directory of Open Access Journals (Sweden)

    Charlotte E. Teunissen

    2011-01-01

    Full Text Available There is a long history of research into body fluid biomarkers in neurodegenerative and neuroinflammatory diseases. However, only a few biomarkers in cerebrospinal fluid (CSF are being used in clinical practice. Anti-aquaporin-4 antibodies in serum are currently useful for the diagnosis of neuromyelitis optica (NMO, but we could expect novel CSF biomarkers that help define prognosis and response to treatment for this disease. One of the most critical factors in biomarker research is the inadequate powering of studies performed by single centers. Collaboration between investigators is needed to establish large biobanks of well-defined samples. A key issue in collaboration is to establish standardized protocols for biobanking to ensure that the statistical power gained by increasing the numbers of CSF samples is not compromised by pre-analytical factors. Here, consensus guidelines for CSF collection and biobanking are presented, based on the guidelines that have been published by the BioMS-eu network for CSF biomarker research. We focussed on CSF collection procedures, pre-analytical factors and high quality clinical and paraclinical information. Importantly, the biobanking protocols are applicable for CSF biobanks for research targeting any neurological disease.

  8. Evaluation of biomarkers in plasma, blood, and urine samples from coke oven workers: significance of exposure to polycyclic aromatic hydrocarbons.

    OpenAIRE

    Ovrebø, S; Haugen, A; Farmer, P B; Anderson, D.(California Institute of Technology, Pasadena, USA)

    1995-01-01

    OBJECTIVE--The aim was to assess the significance of two biomarkers; antibody to benzo(a)pyrene DNA adducts and concentration of hydroxyethylvaline haemoglobin adducts in samples from a well studied group of coke oven workers. As a measure of exposure we have used 1-hydroxypyrene in urine. METHODS--Urine and blood samples were collected from coke oven workers and a control group. Samples from coke oven plant workers were collected in January and June. 1-Hydroxypyrene was measured in urine by ...

  9. Analysis of tumor template from multiple compartments in a blood sample provides complementary access to peripheral tumor biomarkers.

    Science.gov (United States)

    Strauss, William M; Carter, Chris; Simmons, Jill; Klem, Erich; Goodman, Nathan; Vahidi, Behrad; Romero, Juan; Masterman-Smith, Michael; O'Regan, Ruth; Gogineni, Keerthi; Schwartzberg, Lee; Austin, Laura K; Dempsey, Paul W; Cristofanilli, Massimo

    2016-05-01

    Targeted cancer therapeutics are promised to have a major impact on cancer treatment and survival. Successful application of these novel treatments requires a molecular definition of a patient's disease typically achieved through the use of tissue biopsies. Alternatively, allowing longitudinal monitoring, biomarkers derived from blood, isolated either from circulating tumor cell derived DNA (ctcDNA) or circulating cell-free tumor DNA (ccfDNA) may be evaluated. In order to use blood derived templates for mutational profiling in clinical decisions, it is essential to understand the different template qualities and how they compare to biopsy derived template DNA as both blood-based templates are rare and distinct from the gold-standard. Using a next generation re-sequencing strategy, concordance of the mutational spectrum was evaluated in 32 patient-matched ctcDNA and ccfDNA templates with comparison to tissue biopsy derived DNA template. Different CTC antibody capture systems for DNA isolation from patient blood samples were also compared. Significant overlap was observed between ctcDNA, ccfDNA and tissue derived templates. Interestingly, if the results of ctcDNA and ccfDNA template sequencing were combined, productive samples showed similar detection frequency (56% vs 58%), were temporally flexible, and were complementary both to each other and the gold standard. These observations justify the use of a multiple template approach to the liquid biopsy, where germline, ctcDNA, and ccfDNA templates are employed for clinical diagnostic purposes and open a path to comprehensive blood derived biomarker access. PMID:27049831

  10. Storage-induced increase in biomarkers of oxidative stress and inflammation in red blood cell components

    DEFF Research Database (Denmark)

    Kucukakin, B.; Kocak, Volkan; Lykkesfeldt, Jens;

    2011-01-01

    buffy-coat reduced red cells in SAG-M additive solution, by assessing biomarkers of oxidative and inflammatory stress during a storage period of 35 days. Study design and methods. Ten units of RBCs were stored for 35 days. Samples were collected from the units at storage days 1, 3, 7, 14, 21, 28 and 35...

  11. Genetic and protein biomarkers in blood for the improved detection of GH abuse.

    Science.gov (United States)

    Ferro, P; Ventura, R; Pérez-Mañá, C; Farré, M; Segura, J

    2016-09-01

    Human Growth Hormone (hGH, somatotropin) is one of the relevant forbidden substances to be detected in sport drug testing. Since the appearance of recombinant hGH (rhGH) in the 80's, its expansion and availability through the black market have increased, so the detection of its abuse continues to be a challenge at present. New techniques or biomarkers that are robust, reliable, sensitive and allowing a large detection time window are welcome. rhGH produces an increase of insulin-like growth factor 1 (IGF-1). FN1 (fibronectin 1) and RAB31 (member of RAS oncogene family) genes have been suggested as two potential biomarkers for IGF-1 abuse. Following this line, in the present study some genetic and proteomic approaches have been performed with fourteen healthy male subjects treated with rhGH (which produces increase of IGF-1 concentrations) to study FN1 gene, FN1 protein, RAB31 gene and RAB31 protein as potential biomarkers for rhGH abuse. The results showed that both, RAB31 and FN1 genes and FN1 protein could be potential biomarkers for rhGH administration. Preliminary assessments of gender, age, acute sport activities and GHRP-2 (pralmorelin, a rhGH releasing peptide) influence suggest they are not relevant confounding factors. Thus, the selected markers present high sensitivity and a larger detection window for rhGH detection than IGF-1 itself. PMID:27243825

  12. Candidate gene networks and blood biomarkers of methamphetamine-associated psychosis: an integrative RNA-sequencing report

    Science.gov (United States)

    Breen, M S; Uhlmann, A; Nday, C M; Glatt, S J; Mitt, M; Metsalpu, A; Stein, D J; Illing, N

    2016-01-01

    The clinical presentation, course and treatment of methamphetamine (METH)-associated psychosis (MAP) are similar to that observed in schizophrenia (SCZ) and subsequently MAP has been hypothesized as a pharmacological and environmental model of SCZ. However, several challenges currently exist in diagnosing MAP accurately at the molecular and neurocognitive level before the MAP model can contribute to the discovery of SCZ biomarkers. We directly assessed subcortical brain structural volumes and clinical parameters of MAP within the framework of an integrative genome-wide RNA-Seq blood transcriptome analysis of subjects diagnosed with MAP (N=10), METH dependency without psychosis (MA; N=10) and healthy controls (N=10). First, we identified discrete groups of co-expressed genes (that is, modules) and tested them for functional annotation and phenotypic relationships to brain structure volumes, life events and psychometric measurements. We discovered one MAP-associated module involved in ubiquitin-mediated proteolysis downregulation, enriched with 61 genes previously found implicated in psychosis and SCZ across independent blood and post-mortem brain studies using convergent functional genomic (CFG) evidence. This module demonstrated significant relationships with brain structure volumes including the anterior corpus callosum (CC) and the nucleus accumbens. Furthermore, a second MAP and psychoticism-associated module involved in circadian clock upregulation was also enriched with 39 CFG genes, further associated with the CC. Subsequently, a machine-learning analysis of differentially expressed genes identified single blood-based biomarkers able to differentiate controls from methamphetamine dependents with 87% accuracy and MAP from MA subjects with 95% accuracy. CFG evidence validated a significant proportion of these putative MAP biomarkers in independent studies including CLN3, FBP1, TBC1D2 and ZNF821 (RNA degradation), ELK3 and SINA3 (circadian clock) and PIGF and

  13. Candidate gene networks and blood biomarkers of methamphetamine-associated psychosis: an integrative RNA-sequencing report.

    Science.gov (United States)

    Breen, M S; Uhlmann, A; Nday, C M; Glatt, S J; Mitt, M; Metsalpu, A; Stein, D J; Illing, N

    2016-01-01

    The clinical presentation, course and treatment of methamphetamine (METH)-associated psychosis (MAP) are similar to that observed in schizophrenia (SCZ) and subsequently MAP has been hypothesized as a pharmacological and environmental model of SCZ. However, several challenges currently exist in diagnosing MAP accurately at the molecular and neurocognitive level before the MAP model can contribute to the discovery of SCZ biomarkers. We directly assessed subcortical brain structural volumes and clinical parameters of MAP within the framework of an integrative genome-wide RNA-Seq blood transcriptome analysis of subjects diagnosed with MAP (N=10), METH dependency without psychosis (MA; N=10) and healthy controls (N=10). First, we identified discrete groups of co-expressed genes (that is, modules) and tested them for functional annotation and phenotypic relationships to brain structure volumes, life events and psychometric measurements. We discovered one MAP-associated module involved in ubiquitin-mediated proteolysis downregulation, enriched with 61 genes previously found implicated in psychosis and SCZ across independent blood and post-mortem brain studies using convergent functional genomic (CFG) evidence. This module demonstrated significant relationships with brain structure volumes including the anterior corpus callosum (CC) and the nucleus accumbens. Furthermore, a second MAP and psychoticism-associated module involved in circadian clock upregulation was also enriched with 39 CFG genes, further associated with the CC. Subsequently, a machine-learning analysis of differentially expressed genes identified single blood-based biomarkers able to differentiate controls from methamphetamine dependents with 87% accuracy and MAP from MA subjects with 95% accuracy. CFG evidence validated a significant proportion of these putative MAP biomarkers in independent studies including CLN3, FBP1, TBC1D2 and ZNF821 (RNA degradation), ELK3 and SINA3 (circadian clock) and PIGF and

  14. Global DNA hypomethylation in peripheral blood leukocytes as a biomarker for cancer risk: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Hae Dong Woo

    Full Text Available BACKGROUND: Good biomarkers for early detection of cancer lead to better prognosis. However, harvesting tumor tissue is invasive and cannot be routinely performed. Global DNA methylation of peripheral blood leukocyte DNA was evaluated as a biomarker for cancer risk. METHODS: We performed a meta-analysis to estimate overall cancer risk according to global DNA hypomethylation levels among studies with various cancer types and analytical methods used to measure DNA methylation. Studies were systemically searched via PubMed with no language limitation up to July 2011. Summary estimates were calculated using a fixed effects model. RESULTS: The subgroup analyses by experimental methods to determine DNA methylation level were performed due to heterogeneity within the selected studies (p<0.001, I(2: 80%. Heterogeneity was not found in the subgroup of %5-mC (p = 0.393, I(2: 0% and LINE-1 used same target sequence (p = 0.097, I(2: 49%, whereas considerable variance remained in LINE-1 (p<0.001, I(2: 80% and bladder cancer studies (p = 0.016, I(2: 76%. These results suggest that experimental methods used to quantify global DNA methylation levels are important factors in the association study between hypomethylation levels and cancer risk. Overall, cancer risks of the group with the lowest DNA methylation levels were significantly higher compared to the group with the highest methylation levels [OR (95% CI: 1.48 (1.28-1.70]. CONCLUSIONS: Global DNA hypomethylation in peripheral blood leukocytes may be a suitable biomarker for cancer risk. However, the association between global DNA methylation and cancer risk may be different based on experimental methods, and region of DNA targeted for measuring global hypomethylation levels as well as the cancer type. Therefore, it is important to select a precise and accurate surrogate marker for global DNA methylation levels in the association studies between global DNA methylation levels in peripheral

  15. Microfluidic bead-based multienzyme-nanoparticle amplification for detection of circulating tumor cells in the blood using quantum dots labels.

    Science.gov (United States)

    Zhang, He; Fu, Xin; Hu, Jiayi; Zhu, Zhenjun

    2013-05-24

    This study reports the development of a microfluidic bead-based nucleic acid sensor for sensitive detection of circulating tumor cells in blood samples using multienzyme-nanoparticle amplification and quantum dot labels. In this method, the microbeads functionalized with the capture probes and modified electron rich proteins were arrayed within a microfluidic channel as sensing elements, and the gold nanoparticles (AuNPs) functionalized with the horseradish peroxidases (HRP) and DNA probes were used as labels. Hence, two signal amplification approaches are integrated for enhancing the detection sensitivity of circulating tumor cells. First, the large surface area of Au nanoparticle carrier allows several binding events of HRP on each nanosphere. Second, enhanced mass transport capability inherent from microfluidics leads to higher capture efficiency of targets because continuous flow within micro-channel delivers fresh analyte solution to the reaction site which maintains a high concentration gradient differential to enhance mass transport. Based on the dual signal amplification strategy, the developed microfluidic bead-based nucleic acid sensor could discriminate as low as 5 fM (signal-to-noise (S/N)3) of synthesized carcinoembryonic antigen (CEA) gene fragments and showed a 1000-fold increase in detection limit compared to the off-chip test. In addition, using spiked colorectal cancer cell lines (HT29) in the blood as a model system, the detection limit of this chip-based approach was found to be as low as 1 HT29 in 1 mL blood sample. This microfluidic bead-based nucleic acid sensor is a promising platform for disease-related nucleic acid molecules at the lowest level at their earliest incidence. PMID:23663673

  16. Genome-Wide Association Analysis of Blood Biomarkers in Chronic Obstructive Pulmonary Disease

    DEFF Research Database (Denmark)

    Kim, Deog Kyeom; Cho, Michael H; Hersh, Craig P;

    2012-01-01

    determinants of COPD. Methods: GWAS was performed for two pneumoproteins, Clara cell secretory protein (CC16) and surfactant protein D (SP-D), and five systemic inflammatory markers (C-reactive protein, fibrinogen, IL-6, IL-8, and tumor necrosis factor-α) in 1,951 subjects with COPD. For genome......-wide significant susceptibility loci affecting biomarker levels were found only for the two pneumoproteins. Two discrete loci affecting CC16, one region near the CC16 coding gene (SCGB1A1) on chromosome 11 and another locus approximately 25 Mb away from SCGB1A1, were identified, whereas multiple SNPs...... nominally associated with COPD in a collaborative GWAS (P = 0.001-0.049), although these COPD associations were not replicated in two additional cohorts. Conclusions: Distant genetic loci and biomarker-coding genes affect circulating levels of COPD-related pneumoproteins. A subset of these protein...

  17. Evaluation of current and new biomarkers in severe preeclampsia: a microarray approach reveals the VSIG4 gene as a potential blood biomarker.

    Directory of Open Access Journals (Sweden)

    Julien Textoris

    Full Text Available Preeclampsia is a placental disease characterized by hypertension and proteinuria in pregnant women, and it is associated with a high maternal and neonatal morbidity. However, circulating biomarkers that are able to predict the prognosis of preeclampsia are lacking. Thirty-eight women were included in the current study. They consisted of 19 patients with preeclampsia (13 with severe preeclampsia and 6 with non-severe preeclampsia and 19 gestational age-matched women with normal pregnancies as controls. We measured circulating factors that are associated with the coagulation pathway (including fibrinogen, fibronectin, factor VIII, antithrombin, protein S and protein C, endothelial activation (such as soluble endoglin and CD146, and the release of total and platelet-derived microparticles. These markers enabled us to discriminate the preeclampsia condition from a normal pregnancy but were not sufficient to distinguish severe from non-severe preeclampsia. We then used a microarray to study the transcriptional signature of blood samples. Preeclampsia patients exhibited a specific transcriptional program distinct from that of the control group of women. Interestingly, we also identified a severity-related transcriptional signature. Functional annotation of the upmodulated signature in severe preeclampsia highlighted two main functions related to "ribosome" and "complement". Finally, we identified 8 genes that were specifically upmodulated in severe preeclampsia compared with non-severe preeclampsia and the normotensive controls. Among these genes, we identified VSIG4 as a potential diagnostic marker of severe preeclampsia. The determination of this gene may improve the prognostic assessment of severe preeclampsia.

  18. Quantifying murine bone marrow and blood radiation dose response following 18F-FDG PET with DNA damage biomarkers

    International Nuclear Information System (INIS)

    Highlights: • Mice received either a range of 18F-FDG activities or whole body X-ray doses. • Blood samples were collected at 24 and 43 h for MN-RET and QPCR analysis. • Regression analysis showed that both types of exposure produced a linear response. • BM doses of 33 mGy (18F-FDG) and 25 mGy X-rays were significantly higher than controls. • No significant difference between internal (18F-FDG) and external (X-ray) was found. - Abstract: The purpose of this study was to quantify the poorly understood radiation doses to murine bone marrow and blood from whole-body fluorine 18 (18F)-fluorodeoxyglucose (FDG) positron emission tomography (PET), by using specific biomarkers and comparing with whole body external low dose exposures. Groups of 3–5 mice were randomly assigned to 10 groups, each receiving either a different activity of 18F-FDG: 0–37 MBq or whole body irradiated with corresponding doses of 0–300 mGy X-rays. Blood samples were collected at 24 h and at 43 h for reticulocyte micronucleus assays and QPCR analysis of gene expression in peripheral blood leukocytes. Blood and bone marrow dose estimates were calculated from injected activities of 18F-FDG and were based on a recommended ICRP model. Doses to the bone marrow corresponding to 33.43 mGy and above for internal 18F-FDG exposure and to 25 mGy and above for external X-ray exposure, showed significant increases in radiation-induced MN-RET formation relative to controls (P < 0.05). Regression analysis showed that both types of exposure produced a linear response with linear regression analysis giving R2 of 0.992 and 0.999 for respectively internal and external exposure. No significant difference between the two data sets was found with a P-value of 0.493. In vivo gene expression dose–responses at 24 h for Bbc3 and Cdkn1 were similar for 18F-FDG and X-ray exposures, with significant modifications occurring for doses over 300 mGy for Bbc3 and at the lower dose of 150 mGy for Cdkn1a. Both

  19. Quantifying murine bone marrow and blood radiation dose response following {sup 18}F-FDG PET with DNA damage biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Manning, Grainne [Biological Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, Oxfordshire OX11 ORQ (United Kingdom); Taylor, Kristina [Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, ON (Canada); Finnon, Paul [Biological Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, Oxfordshire OX11 ORQ (United Kingdom); Lemon, Jennifer A.; Boreham, Douglas R. [Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, ON (Canada); Badie, Christophe, E-mail: christophe.badie@phe.gov.uk [Biological Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, Oxfordshire OX11 ORQ (United Kingdom)

    2014-12-15

    Highlights: • Mice received either a range of {sup 18}F-FDG activities or whole body X-ray doses. • Blood samples were collected at 24 and 43 h for MN-RET and QPCR analysis. • Regression analysis showed that both types of exposure produced a linear response. • BM doses of 33 mGy ({sup 18}F-FDG) and 25 mGy X-rays were significantly higher than controls. • No significant difference between internal ({sup 18}F-FDG) and external (X-ray) was found. - Abstract: The purpose of this study was to quantify the poorly understood radiation doses to murine bone marrow and blood from whole-body fluorine 18 ({sup 18}F)-fluorodeoxyglucose (FDG) positron emission tomography (PET), by using specific biomarkers and comparing with whole body external low dose exposures. Groups of 3–5 mice were randomly assigned to 10 groups, each receiving either a different activity of {sup 18}F-FDG: 0–37 MBq or whole body irradiated with corresponding doses of 0–300 mGy X-rays. Blood samples were collected at 24 h and at 43 h for reticulocyte micronucleus assays and QPCR analysis of gene expression in peripheral blood leukocytes. Blood and bone marrow dose estimates were calculated from injected activities of {sup 18}F-FDG and were based on a recommended ICRP model. Doses to the bone marrow corresponding to 33.43 mGy and above for internal {sup 18}F-FDG exposure and to 25 mGy and above for external X-ray exposure, showed significant increases in radiation-induced MN-RET formation relative to controls (P < 0.05). Regression analysis showed that both types of exposure produced a linear response with linear regression analysis giving R{sup 2} of 0.992 and 0.999 for respectively internal and external exposure. No significant difference between the two data sets was found with a P-value of 0.493. In vivo gene expression dose–responses at 24 h for Bbc3 and Cdkn1 were similar for {sup 18}F-FDG and X-ray exposures, with significant modifications occurring for doses over 300 mGy for Bbc3

  20. Biomarker-based classification of bacterial and fungal whole-blood infections in a genome-wide expression study

    Directory of Open Access Journals (Sweden)

    Andreas eDix

    2015-03-01

    Full Text Available Sepsis is a clinical syndrome that can be caused by bacteria or fungi. Early knowledge on the nature of the causative agent is a prerequisite for targeted anti-microbial therapy. Besides currently used detection methods like blood culture and PCR-based assays, the analysis of the transcriptional response of the host to infecting organisms holds great promise. In this study, we aim to examine the transcriptional footprint of infections caused by the bacterial pathogens Staphylococcus aureus and Escherichia coli and the fungal pathogens Candida albicans and Aspergillus fumigatus in a human whole-blood model. Moreover, we use the expression information to build a random forest classifier to classify if a sample contains a bacterial, fungal, or mock-infection. After normalizing the transcription intensities using stably expressed reference genes, we filtered the gene set for biomarkers of bacterial or fungal blood infections. This selection is based on differential expression and an additional gene relevance measure. In this way, we identified 38 biomarker genes, including IL6, SOCS3, and IRG1 which were already associated to sepsis by other studies. Using these genes, we trained the classifier and assessed its performance. It yielded a 96% accuracy (sensitivities >93%, specificities >97% for a 10-fold stratified cross-validation and a 92% accuracy (sensitivities and specificities >83% for an additional test dataset comprising Cryptococcus neoformans infections. Furthermore, the classifier is robust to Gaussian noise, indicating correct class predictions on datasets of new species. In conclusion, this genome-wide approach demonstrates an effective feature selection process in combination with the construction of a well-performing classification model. Further analyses of genes with pathogen-dependent expression patterns can provide insights into the systemic host responses, which may lead to new anti-microbial therapeutic advances.

  1. Storage-induced increase in biomarkers of oxidative stress and inflammation in red blood cell components

    DEFF Research Database (Denmark)

    Kücükakin, Bülent; Kocak, Volkan; Lykkesfeldt, Jens;

    2011-01-01

    Transfusion of blood components may increase the risk of complications in relation to surgery. During storage, red blood cells (RBCs) undergo structural and functional changes that may reduce function and viability after transfusion. The aim of the study was to evaluate the quality of buffy-coat ...

  2. Detection of cervical cancer biomarker patterns in blood plasma and urine by differential scanning calorimetry and mass spectrometry.

    Directory of Open Access Journals (Sweden)

    Nichola C Garbett

    Full Text Available Improved methods for the accurate identification of both the presence and severity of cervical intraepithelial neoplasia (CIN and extent of spread of invasive carcinomas of the cervix (IC are needed. Differential scanning calorimetry (DSC has recently been shown to detect specific changes in the thermal behavior of blood plasma proteins in several diseases. This methodology is being explored to provide a complementary approach for screening of cervical disease. The present study evaluated the utility of DSC in differentiating between healthy controls, increasing severity of CIN and early and advanced IC. Significant discrimination was apparent relative to the extent of disease with no clear effect of demographic factors such as age, ethnicity, smoking status and parity. Of most clinical relevance, there was strong differentiation of CIN from healthy controls and IC, and amongst patients with IC between FIGO Stage I and advanced cancer. The observed disease-specific changes in DSC profiles (thermograms were hypothesized to reflect differential expression of disease biomarkers that subsequently bound to and affected the thermal behavior of the most abundant plasma proteins. The effect of interacting biomarkers can be inferred from the modulation of thermograms but cannot be directly identified by DSC. To investigate the nature of the proposed interactions, mass spectrometry (MS analyses were employed. Quantitative assessment of the low molecular weight protein fragments of plasma and urine samples revealed a small list of peptides whose abundance was correlated with the extent of cervical disease, with the most striking plasma peptidome data supporting the interactome theory of peptide portioning to abundant plasma proteins. The combined DSC and MS approach in this study was successful in identifying unique biomarker signatures for cervical cancer and demonstrated the utility of DSC plasma profiles as a complementary diagnostic tool to evaluate

  3. Development of a blood-based molecular biomarker test for identification of schizophrenia before disease onset

    Science.gov (United States)

    Chan, M K; Krebs, M-O; Cox, D; Guest, P C; Yolken, R H; Rahmoune, H; Rothermundt, M; Steiner, J; Leweke, F M; van Beveren, N J M; Niebuhr, D W; Weber, N S; Cowan, D N; Suarez-Pinilla, P; Crespo-Facorro, B; Mam-Lam-Fook, C; Bourgin, J; Wenstrup, R J; Kaldate, R R; Cooper, J D; Bahn, S

    2015-01-01

    Recent research efforts have progressively shifted towards preventative psychiatry and prognostic identification of individuals before disease onset. We describe the development of a serum biomarker test for the identification of individuals at risk of developing schizophrenia based on multiplex immunoassay profiling analysis of 957 serum samples. First, we conducted a meta-analysis of five independent cohorts of 127 first-onset drug-naive schizophrenia patients and 204 controls. Using least absolute shrinkage and selection operator regression, we identified an optimal panel of 26 biomarkers that best discriminated patients and controls. Next, we successfully validated this biomarker panel using two independent validation cohorts of 93 patients and 88 controls, which yielded an area under the curve (AUC) of 0.97 (0.95–1.00) for schizophrenia detection. Finally, we tested its predictive performance for identifying patients before onset of psychosis using two cohorts of 445 pre-onset or at-risk individuals. The predictive performance achieved by the panel was excellent for identifying USA military personnel (AUC: 0.90 (0.86–0.95)) and help-seeking prodromal individuals (AUC: 0.82 (0.71–0.93)) who developed schizophrenia up to 2 years after baseline sampling. The performance increased further using the latter cohort following the incorporation of CAARMS (Comprehensive Assessment of At-Risk Mental State) positive subscale symptom scores into the model (AUC: 0.90 (0.82–0.98)). The current findings may represent the first successful step towards a test that could address the clinical need for early intervention in psychiatry. Further developments of a combined molecular/symptom-based test will aid clinicians in the identification of vulnerable patients early in the disease process, allowing more effective therapeutic intervention before overt disease onset. PMID:26171982

  4. Single genome amplification of proviral HIV-1 DNA from dried blood spot specimens collected during early infant screening programs in Lusaka, Zambia.

    Science.gov (United States)

    Seu, Lillian; Mwape, Innocent; Guffey, M Bradford

    2014-07-01

    The ability to evaluate individual HIV-1 virions from the quasispecies of vertically infected infants was evaluated in a field setting at the Centre for Infectious Disease Research in Zambia. Infant heel-prick blood specimens were spotted onto dried blood spot (DBS) filter paper cards at government health clinics. Nucleic acid was extracted and used as a template for HIV-1 proviral DNA detection by a commercial Amplicor HIV-1 PCR test (Roche, version 1.5). On samples that tested positive by commercial diagnostic assay, amplification of DNA was performed using an in-house assay of the 5' and 3' region of the HIV-1 genome. Additionally, fragments covering 1200 nucleotides within pol (full length protease and partial reverse transcriptase) and 1400 nucleotides within env (variable 1-variable 5 region) were further analyzed by single genome amplification (SGA). In summary, we have demonstrated an in-house assay for amplifying the 5' and 3' proviral HIV-1 DNA as well as pol and env proviral DNA fragments from DBS cards collected and analyzed entirely in Zambia. In conclusion, this study shows the feasibility of utilizing DBS cards to amplify the whole proviral HIV-1 genome as well as perform SGA on key HIV-1 genes.

  5. Cellular response of the blood-brain barrier to injury: Potential biomarkers and therapeutic targets for brain regeneration.

    Science.gov (United States)

    Tenreiro, M M; Ferreira, R; Bernardino, L; Brito, M A

    2016-07-01

    Endothelial cells are the main component of the blood-brain barrier (BBB), a vital structure for maintaining brain homeostasis that is seriously disrupted in various neurological pathologies. Therefore, vascular-targeted therapies may bring advantages for the prevention and treatment of brain disorders. In this sense, novel methods to identify and evaluate endothelial damage have been developed and include the detection of circulating endothelial cells, endothelial progenitor cells, endothelial microparticles and exosomes. These cells and cellular structures have been documented in numerous diseases, and increasingly in neurodegenerative disorders, which have led many to assume that they can either be possible biomarkers or tools of repair. Therefore, the purpose of this review is to discuss available data on BBB endothelial damage occurring in two pathologies of the central nervous system, Alzheimer's disease and stroke, which exemplify conditions where chronic and acute vascular damage occur, respectively. The ultimate goal is to identify useful biomarkers and/or therapeutic tools in the healthy and diseased brain that can be used for the treatment of neurodegenerative diseases where BBB permeability and integrity are impaired. PMID:26996728

  6. Ultrasensitive electroanalysis of low-level free microRNAs in blood by maximum signal amplification of catalytic silver deposition using alkaline phosphatase-incorporated gold nanoclusters.

    Science.gov (United States)

    Si, Yanmei; Sun, Zongzhao; Zhang, Ning; Qi, Wei; Li, Shuying; Chen, Lijun; Wang, Hua

    2014-10-21

    An ultrasensitive sandwich-type analysis method has been initially developed for probing low-level free microRNAs (miRNAs) in blood by a maximal signal amplification protocol of catalytic silver deposition. Gold nanoclusters (AuNCs) were first synthesized and in-site incorporated into alkaline phosphatase (ALP) to form the ALP-AuNCs. Unexpectedly, the so incorporated AuNCs could dramatically enhance the catalysis activities of ALP-AuNCs versus native ALP. A sandwiched hybridization protocol was then proposed using ALP-AuNCs as the catalytic labels of the DNA detection probes for targeting miRNAs that were magnetically caught from blood samples by DNA capture probes, followed by the catalytic ligation of two DNA probes complementary to the targets. Herein, the ALP-AuNC labels could act as the bicatalysts separately in the ALP-catalyzed substrate dephosphorylation reaction and the AuNCs-accelerated silver deposition reaction. The signal amplification of ALP-AuNCs-catalyzed silver deposition was thereby maximized to be measured by the electrochemical outputs. The developed electroanalysis strategy could allow for the ultrasensitive detection of free miRNAs in blood with the detection limit as low as 21.5 aM, including the accurate identification of single-base mutant levels in miRNAs. Such a sandwich-type analysis method may circumvent the bottlenecks of the current detection techniques in probing short-chain miRNAs. It would be tailored as an ultrasensitive detection candidate for low-level free miRNAs in blood toward the diagnosis of cancer and the warning or monitoring of cancer metastasis in the clinical laboratory.

  7. Pain in the Blood? Envisioning Mechanism-Based Diagnoses and Biomarkers in Clinical Pain Medicine

    Directory of Open Access Journals (Sweden)

    Emmanuel Bäckryd

    2015-03-01

    Full Text Available Chronic pain is highly prevalent, and pain medicine lacks objective biomarkers to guide diagnosis and choice of treatment. The current U.S. “opioid epidemic” is a reminder of the paucity of effective and safe treatment options. Traditional pain diagnoses according to the International Classification of Diseases are often unspecific, and analgesics are often prescribed on a trial-and-error basis. In contrast to this current state of affairs, the vision of future mechanism-based diagnoses of chronic pain conditions is presented in this non-technical paper, focusing on the need for biomarkers and the theoretical complexity of the task. Pain is and will remain a subjective experience, and as such is not objectively measurable. Therefore, the concept of “noci-marker” is presented as an alternative to “pain biomarker”, the goal being to find objective, measurable correlates of the pathophysiological processes involved in different chronic pain conditions. This vision entails a call for more translational pain research in order to bridge the gap between clinical pain medicine and preclinical science.

  8. Biomarkers measured in buccal and blood leukocyte DNA as proxies for colon tissue global methylation

    OpenAIRE

    Ashbury, Janet E.; Taylor, Sherryl A; Tse, M Yat; Stephen C Pang; Louw, Jacob A; Vanner, Stephen J.; King, Will D

    2014-01-01

    There is increasing interest in clarifying the role of global DNA methylation levels in colorectal cancer (CRC) etiology. Most commonly, in epidemiologic studies, methylation is measured in DNA derived from blood leukocytes as a proxy measure of methylation changes in colon tissue. However, little is known about the correlations between global methylation levels in DNA derived from colon tissue and more accessible tissues such as blood or buccal cells. This cross-sectional study utilized DNA ...

  9. Most Blood Biomarkers Related to Vitamin Status, One-Carbon Metabolism, and the Kynurenine Pathway Show Adequate Preanalytical Stability and Within-Person Reproducibility to Allow Assessment of Exposure or Nutritional Status in Healthy Women and Cardiovascular Patients123

    OpenAIRE

    Midttun, Øivind; Townsend, Mary K.; Nygård, Ottar; Tworoger, Shelley S.; Brennan, Paul; Johansson, Mattias; Ueland, Per Magne

    2014-01-01

    Knowledge of stability during sample transportation and changes in biomarker concentrations within person over time are paramount for proper design and interpretation of epidemiologic studies based on a single measurement of biomarker status. Therefore, we investigated stability and intraindividual vs. interindividual variation in blood concentrations of biomarkers related to vitamin status, one-carbon metabolism, and the kynurenine pathway. Whole blood (EDTA and heparin, n = 12) was stored w...

  10. Combined blood/tissue analysis for cancer biomarker discovery: application to renal cell carcinoma.

    Science.gov (United States)

    Johann, Donald J; Wei, Bih-Rong; Prieto, DaRue A; Chan, King C; Ye, Xiaying; Valera, Vladimir A; Simpson, R Mark; Rudnick, Paul A; Xiao, Zhen; Issaq, Haleem J; Linehan, W Marston; Stein, Stephen E; Veenstra, Timothy D; Blonder, Josip

    2010-03-01

    A method that relies on subtractive tissue-directed shot-gun proteomics to identify tumor proteins in the blood of a patient newly diagnosed with cancer is described. To avoid analytical and statistical biases caused by physiologic variability of protein expression in the human population, this method was applied on clinical specimens obtained from a single patient diagnosed with nonmetastatic renal cell carcinoma (RCC). The proteomes extracted from tumor, normal adjacent tissue and preoperative plasma were analyzed using 2D-liquid chromatography-mass spectrometry (LC-MS). The lists of identified proteins were filtered to discover proteins that (i) were found in the tumor but not normal tissue, (ii) were identified in matching plasma, and (iii) whose spectral count was higher in tumor tissue than plasma. These filtering criteria resulted in identification of eight tumor proteins in the blood. Subsequent Western-blot analysis confirmed the presence of cadherin-5, cadherin-11, DEAD-box protein-23, and pyruvate kinase in the blood of the patient in the study as well as in the blood of four other patients diagnosed with RCC. These results demonstrate the utility of a combined blood/tissue analysis strategy that permits the detection of tumor proteins in the blood of a patient diagnosed with RCC. PMID:20121140

  11. Detection of Bartonella henselae DNA in clinical samples including peripheral blood of immune competent and immune compromised patients by three nested amplifications

    Directory of Open Access Journals (Sweden)

    Karina Hatamoto Kawasato

    2013-02-01

    Full Text Available Bacteria of the genus Bartonella are emerging pathogens detected in lymph node biopsies and aspirates probably caused by increased concentration of bacteria. Twenty-three samples of 18 patients with clinical, laboratory and/or epidemiological data suggesting bartonellosis were subjected to three nested amplifications targeting a fragment of the 60-kDa heat shock protein (HSP, the internal transcribed spacer 16S-23S rRNA (ITS and the cell division (FtsZ of Bartonella henselae, in order to improve detection in clinical samples. In the first amplification 01, 04 and 05 samples, were positive by HSP (4.3%, FtsZ (17.4% and ITS (21.7%, respectively. After the second round six positive samples were identified by nested-HSP (26%, eight by nested-ITS (34.8% and 18 by nested-FtsZ (78.2%, corresponding to 10 peripheral blood samples, five lymph node biopsies, two skin biopsies and one lymph node aspirate. The nested-FtsZ was more sensitive than nested-HSP and nested-ITS (p < 0.0001, enabling the detection of Bartonella henselae DNA in 15 of 18 patients (83.3%. In this study, three nested-PCR that should be specific for Bartonella henselae amplification were developed, but only the nested-FtsZ did not amplify DNA from Bartonella quintana. We conclude that nested amplifications increased detection of B. henselae DNA, and that the nested-FtsZ was the most sensitive and the only specific to B. henselae in different biological samples. As all samples detected by nested-HSP and nested-ITS, were also by nested-FtsZ, we infer that in our series infections were caused by Bartonella henselae. The high number of positive blood samples draws attention to the use of this biological material in the investigation of bartonellosis, regardless of the immune status of patients. This fact is important in the case of critically ill patients and young children to avoid more invasive procedures such as lymph nodes biopsies and aspirates.

  12. [Inflammatory-destructive biomarkers of atherosclerotic plaques instability. Study of arterial wall and blood].

    Science.gov (United States)

    Ragino, Iu I; Cherniavskiĭ, A M; Polonskaia, Ia V; Volkov, A M; Kashtanova, E V; Tsymbal, S Iu; Polovnikova, E M

    2012-01-01

    Concentrations of tumor necrosis factor, interleukin 1- and its receptor antagonist, IL-6, IL-8, IL-18, IL-2, ligand of CD40 receptor (CD40L), high sensitive C-reactive protein (hsCRP), monocyte chemotactic protein -1, endothelial monocyte activating protein II, adhesive molecules (sICAM-1 and sVCAM-1), matrix metalloproteinase (MMP-3, MMP-7, MMP-9), tissue inhibitor of metalloproteinase (TIMP-1) and endothelin-1 were studied in blood and in coronary artery intima/media of men with coronary atherosclerosis without acute coronary syndrome. Blood levels of hsCRP, IL-8, IL-6 and CD40L were higher, while blood levels of sVCAM and TIMP-1 were lower in men with prevalence of unstable atherosclerotic plaques compared to men with prevalence of stable atherosclerotic plaques in coronary arteries. Blood levels of hsCRP, IL-6 and IL-8 correlated with characteristics of coronary artery atherosclerotic plaques instability. Correlation between hsCRP blood level and hsCRP concentration in coronary artery intima/media material was also revealed. PMID:22839584

  13. Microfluidic bead-based multienzyme-nanoparticle amplification for detection of circulating tumor cells in the blood using quantum dots labels

    International Nuclear Information System (INIS)

    Graphical abstract: A microfluidic beads-based nucleic acid sensor for sensitive detection of circulating tumor cells (CTCs) in the blood using multienzyme-nanoparticle amplification and quantum dots labels was developed. The chip-based CTCs analysis could detect reverse transcription-polymerase chain reaction (RT-PCR) products of tumor cell as low as 1 tumor cell (e.g. CEA expressing cell) in 1 mL blood sample. This microfluidic beads-based nucleic acid sensor is a promising platform for disease-related nucleic acid molecules at the lowest level at their earliest incidence. -- Highlights: •Combination of microfluidic bead-based platform and enzyme–probe–AuNPs is proposed. •The developed nucleic acid sensor could respond to 5 fM of tumor associated DNA. •Microfluidic platform and multienzyme-labeled AuNPs greatly enhanced sensitivity. •The developed nucleic acid sensor could respond to RT-PCR products of tumor cell as low as 1 tumor cell in 1 mL blood sample. •We report a sensitive nucleic acid sensor for detection of circulating tumor cells. -- Abstract: This study reports the development of a microfluidic bead-based nucleic acid sensor for sensitive detection of circulating tumor cells in blood samples using multienzyme-nanoparticle amplification and quantum dot labels. In this method, the microbeads functionalized with the capture probes and modified electron rich proteins were arrayed within a microfluidic channel as sensing elements, and the gold nanoparticles (AuNPs) functionalized with the horseradish peroxidases (HRP) and DNA probes were used as labels. Hence, two signal amplification approaches are integrated for enhancing the detection sensitivity of circulating tumor cells. First, the large surface area of Au nanoparticle carrier allows several binding events of HRP on each nanosphere. Second, enhanced mass transport capability inherent from microfluidics leads to higher capture efficiency of targets because continuous flow within micro

  14. Microfluidic bead-based multienzyme-nanoparticle amplification for detection of circulating tumor cells in the blood using quantum dots labels

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, He, E-mail: mzhang_he@126.com; Fu, Xin; Hu, Jiayi; Zhu, Zhenjun

    2013-05-24

    Graphical abstract: A microfluidic beads-based nucleic acid sensor for sensitive detection of circulating tumor cells (CTCs) in the blood using multienzyme-nanoparticle amplification and quantum dots labels was developed. The chip-based CTCs analysis could detect reverse transcription-polymerase chain reaction (RT-PCR) products of tumor cell as low as 1 tumor cell (e.g. CEA expressing cell) in 1 mL blood sample. This microfluidic beads-based nucleic acid sensor is a promising platform for disease-related nucleic acid molecules at the lowest level at their earliest incidence. -- Highlights: •Combination of microfluidic bead-based platform and enzyme–probe–AuNPs is proposed. •The developed nucleic acid sensor could respond to 5 fM of tumor associated DNA. •Microfluidic platform and multienzyme-labeled AuNPs greatly enhanced sensitivity. •The developed nucleic acid sensor could respond to RT-PCR products of tumor cell as low as 1 tumor cell in 1 mL blood sample. •We report a sensitive nucleic acid sensor for detection of circulating tumor cells. -- Abstract: This study reports the development of a microfluidic bead-based nucleic acid sensor for sensitive detection of circulating tumor cells in blood samples using multienzyme-nanoparticle amplification and quantum dot labels. In this method, the microbeads functionalized with the capture probes and modified electron rich proteins were arrayed within a microfluidic channel as sensing elements, and the gold nanoparticles (AuNPs) functionalized with the horseradish peroxidases (HRP) and DNA probes were used as labels. Hence, two signal amplification approaches are integrated for enhancing the detection sensitivity of circulating tumor cells. First, the large surface area of Au nanoparticle carrier allows several binding events of HRP on each nanosphere. Second, enhanced mass transport capability inherent from microfluidics leads to higher capture efficiency of targets because continuous flow within micro

  15. Synthetic pyrethroid effect on blood plasma biomarker enzymes and histological changes in Catla catla.

    Science.gov (United States)

    Muthuviveganandavel, Veerappan; Hwang, Inho; Anita, Vanattayen; Malarani, Pattabiraman S; Selvam, Chandrasekar; Hemalatha, Moorthy; Pandurangan, Muthuraman

    2013-04-01

    Alpha-cypermethrin is an isoform of cypermethrin; it is an active pyrethroid used extensively to control a wide range of pests in agriculture and animal breeding. In this study four groups of six fish were examined. The first group served as a control in fresh water alone, with no pyrethroid. The second, third and fourth groups were exposed to alpha-cypermethrin for 4, 8 and 96 h respectively. At the end of the each exposure period, the fish were sacrificed, and the required muscle tissues were collected for histological examination. The blood was drawn with heparinized needles and processed for serum enzymatic studies. Serum enzymes such as aspartate transaminase (AST), alanine transaminase (ALT), amylase, acid phosphatase (ACP) and gamma-glutamyl transpeptidase (GGT) were measured at 4, 8 and 96 h. AST enzyme activity was significantly increased at 4 h, whereas ALT and amylase enzyme activities were significantly reduced at all the time points. ACP enzyme activity was significantly reduced at 4 and 8 h, whereas GGT enzyme activity was significantly increased at all the time points. Hepatocyte cytoplasmic vacuolisation and degeneration, rupture of blood vessels, and necrosis was found at all time points. Congestion of blood vessels, bulging, distortion of filaments, erosion and disintegration of blood corpuscles and hyperplasia of epithelium were found in treated gills at 4, 8 and 96 h. Breakdown of muscle fibres, vacuolation and accumulation of lipids and melanin in white muscle were observed in treated fish muscle at 4, 8 and 96 h.

  16. Effect of Oral and Vaginal Hormonal Contraceptives on Inflammatory Blood Biomarkers

    Directory of Open Access Journals (Sweden)

    Afshin A. Divani

    2015-01-01

    Full Text Available The use of combined hormonal contraceptives has been reported to increase the level of C-reactive protein (CRP. We assessed the effect of hormonal contraceptive use on inflammatory cytokines including CRP, monocyte chemotactic protein-1, soluble tumor necrosis factor (sTNF, interleukin-6 (IL-6, and soluble CD40 ligand. We used 79 female subjects (19 to 30 years old who were combined oral contraceptives users (n=29, combined vaginal contraceptive users (n=20, and nonusers (n=30 with CRP values of ≤1 (n=46 or ≥3 (n=33. Information on medical history, physical activities, and dietary and sleeping habits were collected. Both oral and vaginal contraceptive users had higher levels of CRP (P<0.0001, compared to nonusers. Only oral contraceptive users exhibited elevated sCD40L (P<0.01. When comparing the groups with CRP ≤ 1 and CRP ≥ 3, levels of IL-6 and sTNF-RI were positively correlated with CRP among oral contraceptive users. We did not observe the same elevation for other inflammatory biomarkers for the CRP ≥ 3 group among vaginal contraceptive users. The clear cause of elevation in CRP level due to the use of different hormonal contraceptive formulations and methods is not well understood. Longitudinal studies with larger sample size are required to better assess the true cause of CRP elevation among hormonal contraceptive users.

  17. Detecting 22q11.2 deletions by use of multiplex ligation-dependent probe amplification on DNA from neonatal dried blood spot samples

    DEFF Research Database (Denmark)

    Sørensen, Karina M; Agergaard, Peter; Olesen, Charlotte;

    2010-01-01

    of 22q11.2 deletions among certain manifestations, eg, congenital heart disease, on selected Danes, a multiplex ligation-dependant probe amplification (MLPA) analysis was designed. The analysis was planned to be performed on DNA extracted from dried blood spot samples (DBSS) obtained from Guthrie cards...... collected during neonatal screening programs. However, the DNA concentration necessary for a standard MLPA analysis (20 ng) could not be attained from DBSS, and a novel MLPA design was developed to permit for analysis on limited amounts of DNA (2 ng). A pilot study is reported here that validates the new...... MLPA design using nine patients diagnosed with the 22q11.2 deletion and 101 controls. All deletions were identified using DNA extracted from DBSS, and no copy number variations were detected in the controls, resulting in a specificity and sensitivity of 100%. It is thereby concluded that the novel MLPA...

  18. Specific, sensitive and rapid detection of human plasmodium knowlesi infection by loop-mediated isothermal amplification (LAMP in blood samples

    Directory of Open Access Journals (Sweden)

    Anthony Claudia N

    2011-07-01

    Full Text Available Abstract Background The emergence of Plasmodium knowlesi in humans, which is in many cases misdiagnosed by microscopy as Plasmodium malariae due to the morphological similarity has contributed to the needs of detection and differentiation of malaria parasites. At present, nested PCR targeted on Plasmodium ssrRNA genes has been described as the most sensitive and specific method for Plasmodium detection. However, this method is costly and requires trained personnel for its implementation. Loop-mediated isothermal amplification (LAMP, a novel nucleic acid amplification method was developed for the clinical detection of P. knowlesi. The sensitivity and specificity of LAMP was evaluated in comparison to the results obtained via microscopic examination and nested PCR. Methods LAMP assay was developed based on P. knowlesi genetic material targeting the apical membrane antigen-1 (AMA-1 gene. The method uses six primers that recognize eight regions of the target DNA and it amplifies DNA within an hour under isothermal conditions (65°C in a water-bath. Results LAMP is highly sensitive with the detection limit as low as ten copies for AMA-1. LAMP detected malaria parasites in all confirm cases (n = 13 of P. knowlesi infection (sensitivity, 100% and none of the negative samples (specificity, 100% within an hour. LAMP demonstrated higher sensitivity compared to nested PCR by successfully detecting a sample with very low parasitaemia ( Conclusion With continuous efforts in the optimization of this assay, LAMP may provide a simple and reliable test for detecting P. knowlesi malaria parasites in areas where malaria is prevalent.

  19. Dual amplified and ultrasensitive electrochemical detection of mutant DNA Biomarkers based on nuclease-assisted target recycling and rolling circle amplifications.

    Science.gov (United States)

    Wang, Qiong; Yang, Cuiyun; Xiang, Yun; Yuan, Ruo; Chai, Yaqin

    2014-05-15

    Based on nicking endonuclease (NEase)-assisted target recycling and rolling circle amplification (RCA) for in situ generation of numerous G-quadruplex/hemin complexes, we developed a new, dual amplified and ultrasensitive electrochemical biosensor for mutant human p53 gene. The target mutant DNA hybridizes with the loop portion of a dithiol-modified hairpin probe (HP) self-assembled on a gold sensing electrode and forms nicking site for the NEase, which cleaves the HP and releases the target DNA. The released target DNA again hybridizes with the intact HP and initiates the DNA recycling process with the assistance of the NEase, leading to the cleavage of a large number of the HPs and the generation of numerous primers for RCA. With rationally designed, G-quadruplex complementary sequence-encoded RCA circular template, subsequent RCA results in the formation of long DNA sequences with massive tandem-repeat G-quadruplex sequences, which further associate with hemin and generate significantly amplified current response for highly sensitive DNA detection down to 0.25 fM. The developed method also exhibits high specificity for the target DNA against single-base mismatched sequence. With the ultrahigh sensitivity feature induced by the dual signal amplification, the proposed method can thus offer new opportunities for the detection of trace amounts of DNA.

  20. DNA repair and cell cycle biomarkers of radiation exposure and inflammation stress in human blood.

    Directory of Open Access Journals (Sweden)

    Helen Budworth

    Full Text Available DNA damage and repair are hallmarks of cellular responses to ionizing radiation. We hypothesized that monitoring the expression of DNA repair-associated genes would enhance the detection of individuals exposed to radiation versus other forms of physiological stress. We employed the human blood ex vivo radiation model to investigate the expression responses of DNA repair genes in repeated blood samples from healthy, non-smoking men and women exposed to 2 Gy of X-rays in the context of inflammation stress mimicked by the bacterial endotoxin lipopolysaccharide (LPS. Radiation exposure significantly modulated the transcript expression of 12 genes of 40 tested (2.2E-06blood ex vivo dataset, and 100% accuracy for discriminating patients who received total body radiation. Three genes of this panel (CDKN1A, FDXR and BBC3 were also highly sensitive to LPS treatment in the absence of radiation exposure, and LPS co-treatment significantly affected their radiation responses. At the protein level, BAX and pCHK2-thr68 were elevated after radiation exposure, but the pCHK2-thr68 response was significantly decreased in the presence of LPS. Our combined panel yields an estimated 4-group accuracy of ∼90% to discriminate between radiation alone, inflammation alone, or combined exposures. Our findings suggest that DNA repair gene expression may be helpful to identify biodosimeters of exposure to radiation, especially within high-complexity exposure scenarios.

  1. Blood glutathione peroxidase-1 mRNA levels can be used as molecular biomarkers to determine dietary selenium requirements in rats.

    Science.gov (United States)

    Sunde, Roger A; Thompson, Kevin M; Evenson, Jacqueline K; Thompson, Britta M

    2009-11-01

    Transcript (mRNA) levels are increasingly being used in medicine as molecular biomarkers for disease and disease risk, including use of whole blood as a target tissue for analysis. Development of blood molecular biomarkers for nutritional status, too, has potential application that parallels opportunities in medicine, including providing solid data for individualized nutrition. We previously reported that blood glutathione peroxidase-1 (Gpx1) mRNA was expressed at levels comparable to major tissues in rats and humans. To determine the efficacy of using blood Gpx1 mRNA to assess selenium (Se) status and requirements, we fed graded levels of Se (0-0.3 microg Se/g as selenite) to weanling male rats. Se status was determined by liver Se concentration and selenoenzyme activity, and selenoprotein mRNA abundance in liver and blood was determined by ribonuclease protection analysis. Liver Se and plasma glutathione peroxidase-3 and liver Gpx1 activities indicated that minimal Se requirements were at 0.08 microg Se/g diet. When total RNA was isolated from whole blood, Gpx1 mRNA in Se-deficient rats decreased to 10% of levels in Se-adequate (0.2 microg Se/g diet) rats. With Se supplementation, blood Gpx1 mRNA levels increased sigmoidally to a plateau with a minimum Se requirement of 0.08 microg Se/g diet, whereas glutathione peroxidase-4 mRNA levels were unaffected. Similarly, Gpx1 mRNA in RNA isolated from fractionated red blood cells decreased in Se-deficient rats to 23% of Se-adequate levels, with a minimum Se requirement of 0.09 microg Se/g diet. Additional studies showed that the preponderance of whole blood Gpx1 mRNA arises from erythroid cells, most likely reticulocytes and young erythrocytes. In summary, whole blood selenoprotein mRNA levels can be used as molecular biomarkers for assessing Se requirements, illustrating that whole blood has potential as a target tissue in development of molecular biomarkers for use in nutrition as well as in medicine.

  2. Blood glutathione peroxidase-1 mRNA levels can be used as molecular biomarkers to determine dietary selenium requirements in rats.

    Science.gov (United States)

    Sunde, Roger A; Thompson, Kevin M; Evenson, Jacqueline K; Thompson, Britta M

    2009-11-01

    Transcript (mRNA) levels are increasingly being used in medicine as molecular biomarkers for disease and disease risk, including use of whole blood as a target tissue for analysis. Development of blood molecular biomarkers for nutritional status, too, has potential application that parallels opportunities in medicine, including providing solid data for individualized nutrition. We previously reported that blood glutathione peroxidase-1 (Gpx1) mRNA was expressed at levels comparable to major tissues in rats and humans. To determine the efficacy of using blood Gpx1 mRNA to assess selenium (Se) status and requirements, we fed graded levels of Se (0-0.3 microg Se/g as selenite) to weanling male rats. Se status was determined by liver Se concentration and selenoenzyme activity, and selenoprotein mRNA abundance in liver and blood was determined by ribonuclease protection analysis. Liver Se and plasma glutathione peroxidase-3 and liver Gpx1 activities indicated that minimal Se requirements were at 0.08 microg Se/g diet. When total RNA was isolated from whole blood, Gpx1 mRNA in Se-deficient rats decreased to 10% of levels in Se-adequate (0.2 microg Se/g diet) rats. With Se supplementation, blood Gpx1 mRNA levels increased sigmoidally to a plateau with a minimum Se requirement of 0.08 microg Se/g diet, whereas glutathione peroxidase-4 mRNA levels were unaffected. Similarly, Gpx1 mRNA in RNA isolated from fractionated red blood cells decreased in Se-deficient rats to 23% of Se-adequate levels, with a minimum Se requirement of 0.09 microg Se/g diet. Additional studies showed that the preponderance of whole blood Gpx1 mRNA arises from erythroid cells, most likely reticulocytes and young erythrocytes. In summary, whole blood selenoprotein mRNA levels can be used as molecular biomarkers for assessing Se requirements, illustrating that whole blood has potential as a target tissue in development of molecular biomarkers for use in nutrition as well as in medicine. PMID:19855070

  3. Multiple Biomarker Panels for Early Detection of Breast Cancer in Peripheral Blood

    Directory of Open Access Journals (Sweden)

    Fan Zhang

    2013-01-01

    Full Text Available Detecting breast cancer at early stages can be challenging. Traditional mammography and tissue microarray that have been studied for early breast cancer detection and prediction have many drawbacks. Therefore, there is a need for more reliable diagnostic tools for early detection of breast cancer due to a number of factors and challenges. In the paper, we presented a five-marker panel approach based on SVM for early detection of breast cancer in peripheral blood and show how to use SVM to model the classification and prediction problem of early detection of breast cancer in peripheral blood. We found that the five-marker panel can improve the prediction performance (area under curve in the testing data set from 0.5826 to 0.7879. Further pathway analysis showed that the top four five-marker panels are associated with signaling, steroid hormones, metabolism, immune system, and hemostasis, which are consistent with previous findings. Our prediction model can serve as a general model for multibiomarker panel discovery in early detection of other cancers.

  4. Programmed death 1 mRNA in peripheral blood as biomarker of acute renal allograft rejection

    Institute of Scientific and Technical Information of China (English)

    WANG Ya-wen; WANG Zhen; SHI Bing-yi

    2011-01-01

    Background Invasive kidney biopsy is a priority diagnostic method for the acute rejection after renal transplantation for the past decades. However, no effective and noninvasive assay for predicting the severity of acute rejection is in wide use at present. This study was designed to investigate the predictive value of programmed death 1 (PD-1) mRNA for acute rejection after renal transplantation with real-time reverse transcriptase polymerase chain reaction (RT-PCR). A noninvasive diagnostic method has been expected to replace the tranditional kidney biopsy for the diagnosis of acute rejection and prediction of the outcome after kidney transplantation.Methods The whole blood samples from 19 subjects with acute rejection, 20 subjects with delayed graft function (DGF)and 21 subjects with stable recipients after kidney transplantation in a single kidney transplantation center between 2006 and 2009 were collected. The messenger RNA (mRNA) of PD-1 was analyzed with real-time RT-PCR. The associations of PD-1 mRNA levels with acute rejection and disease severity were investigated.Results The log-transformed ratio of PD-1 mRNA to GAPDH mRNA was higher in peripheral blood mononuclear cell (PBMC) from the group with acute rejection (4.52±1.1) than that from the group with DGF (1.12±0.6) or the group with normal biopsy results (0.7±0.4) (P <0.01, by the Kruskal-Wallis test). PD-1 mRNA levels were correlated with serum creatinine levels measured at the time of biopsy in the acute rejection group (Spearman's correlation coefficient, r=0.81,P=0.03), but not in the group with DGF or the group with normal biopsy results. PD-1 mRNA levels identified subjects at risk for graft failure within six months after the incident episode of acute rejection.Conclusions Our data suggest that PD-1 status may be a new predictor of acute rejection and the levels of PD-1mRNA in whole blood cells may positively correlate with the severity of acute rejection after renal transplantation

  5. α-synuclein reactive antibodies as diagnostic biomarkers in blood sera of Parkinson's disease patients.

    Directory of Open Access Journals (Sweden)

    Kiran Yanamandra

    Full Text Available BACKGROUND: Auto-antibodies with specificity to self-antigens have been implicated in a wide variety of neurological diseases, including Parkinson's (PD and Alzheimer's diseases, being sensitive indicators of neurodegeneration and focus for disease prevention. Of particular interest are the studies focused on the auto-immune responses to amyloidogenic proteins associated with diseases and their applications in therapeutic treatments such as vaccination with amyloid antigens and antibodies in PD, Alzheimer's disease and potentially other neurodegeneration ailments. METHODOLOGY/PRINCIPAL FINDINGS: Generated auto-antibodies towards the major amyloidogenic protein involved in PD Lewy bodies--α-synuclein and its amyloid oligomers and fibrils were measured in the blood sera of early and late PD patients and controls by using ELISA, Western blot and Biacore surface plasmon resonance. We found significantly higher antibody levels towards monomeric α-synuclein in the blood sera of PD patients compared to controls, though the responses decreased with PD progression (P<0.0001. This indicates potential protective role of autoimmunity in maintaining the body homeostasis and clearing protein species whose disbalance may lead to amyloid assembly. There were no noticeable immune responses towards amyloid oligomers, but substantially increased levels of IgGs towards α-synuclein amyloid fibrils both in PD patients and controls, which subsided with the disease progression (P<0.0001. Pooled IgGs from PD patients and controls interacted also with the amyloid fibrils of Aβ (1-40 and hen lysozyme, however the latter were recognized with lower affinity. This suggests that IgGs bind to the generic amyloid conformational epitope, displaying higher specificity towards human amyloid species associated with neurodegeneration. CONCLUSIONS/SIGNIFICANCE: Our findings may suggest the protective role of autoimmunity in PD and therefore immune reactions towards PD major

  6. A Prototype Biomarker Detector Combining Biomarker Extraction and Fixed Temperature PCR.

    Science.gov (United States)

    Russ, Patricia K; Karhade, Aditya V; Bitting, Anna L; Doyle, Andrew; Solinas, Francesca; Wright, David W; Haselton, Frederick R

    2016-08-01

    PCR is the most sensitive molecular diagnostic available for infectious diseases. The goal for low-resource settings is a simple, inexpensive instrument. Toward this goal, we previously published a self-contained sample preparation instrument that uses magnetics and prearrayed reagents in thin tubing to extract nucleic acids and perform isothermal amplification and detection of extracted biomarkers. To incorporate PCR thermal cycling, after biomarker is magnetically extracted from a patient sample, the section of tubing containing the extracted biomarker and PCR reagents is alternately positioned within two constant temperature blocks. This instrument was evaluated initially by extracting and amplifying a 140 bp fragment of the IS6110 sequence of tuberculosis from TE buffer. The mean cycle threshold for 5 × 10(6) copies of IS6110 was 25.5 ± 1.5 cycles (n = 4), which was significantly different from negative control samples (34.0 ± 2.6 cycles; n = 3). Using a more clinically relevant sample, we extracted and amplified Plasmodium falciparum DNA from malaria-infected human blood cultures. The average cycle threshold for 1% parasitemia samples was 24.7 ± 1.5 cycles (n = 3) and significantly different from negatives (31.5 ± 2.1 cycles; n = 3). This approach integrates biomarker extraction, PCR amplification, and detection in a simple, linear tubing design with potential for use as a low-resource instrument. PMID:26920577

  7. Blood biomarkers are helpful in the prediction of response to chemoradiation in rectal cancer: A prospective, hypothesis driven study on patients with locally advanced rectal cancer

    International Nuclear Information System (INIS)

    Purpose/objective: Chemoradiation (CRT) has been shown to lead to downsizing of an important portion of rectal cancers. In order to tailor treatment at an earlier stage during treatment, predictive models are being developed. Adding blood biomarkers may be attractive for prediction, as they can be collected very easily and determined with excellent reproducibility in clinical practice. The hypothesis of this study was that blood biomarkers related to tumor load, hypoxia and inflammation can help to predict response to CRT in rectal cancer. Material/methods: 295 patients with locally advanced rectal cancer who were planned to undergo CRT were prospectively entered into a biobank protocol ( (NCT01067872)). Blood samples were drawn before start of CRT. Nine biomarkers were selected, based on a previously defined hypothesis, and measured in a standardized way by a certified lab: CEA, CA19-9, LDH, CRP, IL-6, IL-8, CA IX, osteopontin and 25-OH-vitamin D. Outcome was analyzed in two ways: pCR vs. non-pCR and responders (defined as ypT0-2N0) vs. non-responders (all other ypTN stages). Results: 276 patients could be analyzed. 20.7% developed a pCR and 47.1% were classified as responders. In univariate analysis CEA (p = 0.001) and osteopontin (p = 0.012) were significant predictors for pCR. Taking response as outcome CEA (p < 0.001), IL-8 (p < 0.001) and osteopontin (p = 0.004) were significant predictors. In multivariate analysis CEA was the strongest predictor for pCR (OR 0.92, p = 0.019) and CEA and IL-8 predicted for response (OR 0.97, p = 0.029 and OR 0.94, p = 0.036). The model based on biomarkers only had an AUC of 0.65 for pCR and 0.68 for response; the strongest model included clinical data, PET-data and biomarkers and had an AUC of 0.81 for pCR and 0.78 for response. Conclusion: CEA and IL-8 were identified as predictive biomarkers for tumor response and PCR after CRT in rectal cancer. Incorporation of these blood biomarkers leads to an additional accuracy of

  8. Effects of humoral factors on amplification of nonrecognizable erythrocytic and granulocytic precursors. [Rats, radiation effects on blood cell production

    Energy Technology Data Exchange (ETDEWEB)

    Cronkite, E P; Carsten, A L; Cohen, R; Miller, M E; Moccia, G

    1978-01-01

    The purpose of these studies was to evaluate the effects of humoral factors on amplification of nonrecognizable erythrocytic and granulocytic precursors using the in vivo plasma clot diffusion chamber and the in vitro plasma clot culture methods. Plasma erythropoietin levels changes in the reticulocyte concentration and hematocrits of irradiated and non-irradiated Long-Evans rats exposed to hypoxia were also determined. While erythropoietin plasma levels appeared to effect BFU-E and CFU-E growth, results suggest erythropoietin may not be the sole regulator of red cell production and that inhibitors or chalone-like mechanisms may be involved. Measurements made on granulocyte precursors treated with CSF containing L-cell conditioned medium revealed granulocytic colonies and burst-like formations, similar to those seen for erythrocytic growth. There is strong evidence suggesting that CSF is a regulator of granulopoiesis; however, it is not the sole regulator and it appears that inhibitors may play an in vivo role. Growth of colonies with cell numbers not a power of 2 implies either asymmetric nitosis due to loss of genetic information required for continuing division, or differences in concentration of, or ability to recognize inhibitory factors. These possibilities are examined on the basis of results using in vivo and in vitro culture techniques.

  9. Differences in abundances of cell-signalling proteins in blood reveal novel biomarkers for early detection of clinical Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Mateus Rocha de Paula

    Full Text Available BACKGROUND: In November 2007 a study published in Nature Medicine proposed a simple test based on the abundance of 18 proteins in blood to predict the onset of clinical symptoms of Alzheimer's Disease (AD two to six years before these symptoms manifest. Later, another study, published in PLoS ONE, showed that only five proteins (IL-1, IL-3, EGF, TNF- and G-CSF have overall better prediction accuracy. These classifiers are based on the abundance of 120 proteins. Such values were standardised by a Z-score transformation, which means that their values are relative to the average of all others. METHODOLOGY: The original datasets from the Nature Medicine paper are further studied using methods from combinatorial optimisation and Information Theory. We expand the original dataset by also including all pair-wise differences of z-score values of the original dataset ("metafeatures". Using an exact algorithm to solve the resulting Feature Set problem, used to tackle the feature selection problem, we found signatures that contain either only features, metafeatures or both, and evaluated their predictive performance on the independent test set. CONCLUSIONS: It was possible to show that a specific pattern of cell signalling imbalance in blood plasma has valuable information to distinguish between NDC and AD samples. The obtained signatures were able to predict AD in patients that already had a Mild Cognitive Impairment (MCI with up to 84% of sensitivity, while maintaining also a strong prediction accuracy of 90% on a independent dataset with Non Demented Controls (NDC and AD samples. The novel biomarkers uncovered with this method now confirms ANG-2, IL-11, PDGF-BB, CCL15/MIP-1; and supports the joint measurement of other signalling proteins not previously discussed: GM-CSF, NT-3, IGFBP-2 and VEGF-B.

  10. Biomarkers of polycyclic aromatic hydrocarbon-DNA damage and cigarette smoke exposures in paired maternal and newborn blood samples as a measure of differential susceptibility

    Energy Technology Data Exchange (ETDEWEB)

    Whyatt, R.M.; Jedrychowski, W.; Hemminki, K.; Santella, R.M.; Tsai WeiYann; Yang Ke; Perera, F.P. [Columbia University, New York, NY (US). Division of Environmental Health Sciences, Mailman School of Public Health

    2001-07-01

    In this study, we report on three biomarkers measured in paired blood samples collected at birth from 160 mother/newborn pairs from Poland: 70 pairs from Krakow (a city with high air pollution including PAHs) and 90 pairs from Limanowa (an area with lower ambient pollution but greater indoor coal use). Field studies were conducted during January-March 1992. Biomarkers were: WBC aromatic-DNA adducts by {sup 32}P-postlabeling and PAH-DNA adducts by ELISA and plasma cotinine. Correlations were assessed by Spearman's rank test, and differences in biomarker levels were assessed by the Wilcoxon signed-ranks test. A significant correlation between paired newborn/maternal samples was seen for aromatic-DNA adduct levels and plasma cotinine, but not PAH-DNA adduct levels. Among the total cohort, levels of the three biomarkers were higher in newborn samples compared with paired maternal samples. The difference was significant for aromatic-DNA adduct levels (16.6 plus or minus 12.5 versus 14.21 plus or minus 15.4/10{sup 8} nucleotides; P=0.002) and plasma cotinine, but not for PAH-DNA adduct levels. When analyses were restricted to the 80 mother/newborn pairs from whom the blood sample was drawn concurrently, levels of all of the three biomarkers were significantly higher in the newborn compared with paired maternal blood samples (P {lt} 0.05). These results suggest that the fetus has reduced detoxification capabilities and increased susceptibility to DNA damage, especially in light of experimental evidence that transplacental exposures to PAHs are 10-fold lower than paired maternal exposures. Also, these results have implications for risk assessment, which currently does not adequately account for sensitive subsets of the population. 64 refs.

  11. Network-Based Biomarkers for Cold Coagulation Blood Stasis Syndrome and the Therapeutic Effects of Shaofu Zhuyu Decoction in Rats

    Directory of Open Access Journals (Sweden)

    Shulan Su

    2013-01-01

    Full Text Available In this study, the reverse docking methodology was applied to predict the action targets and pathways of Shaofu Zhuyu decoction (SFZYD bioactive ingredients. Furthermore, Traditional Chinese Medicine (TCM cold coagulation blood stasis (CCBS syndrome was induced in female Sprague-Dawley rats with an ice-water bath and epinephrine, and SFZYD was used to treat CCBS syndrome. A metabolomic approach was used to evaluate changes in the metabolic profiles and to analyze the pharmacological mechanism of SFZYD actions. Twenty-three potential protein targets and 15 pathways were discovered, respectively; among these, pathways are associated with inflammation and immunological stress, hormone metabolism, coagulation function, and glycometabolism. There were also changes in the levels of endogenous metabolites of LysoPCs and glucuronides. Twenty endogenous metabolites were identified. Furthermore, the relative quantities of 6 endogenous metabolites in the plasma and 5 in the urine were significantly affected by SFZYD (P<0.05. The pharmacological mechanism of SFZYD was partially associated with glycerophospholipid metabolism and pentose and glucuronate interconversions. In conclusion, our findings demonstrated that TCM CCBS pattern induced by ice water and epinephrine was complex and related to multiple metabolic pathways. SFZYD did regulate the TCM CCBS by multitargets, and biomarkers and SFZYD should be used for the clinical treatment of CCBS syndrome.

  12. OX40 mRNA in peripheral blood as a biomarker of acute renal allograft rejection

    Institute of Scientific and Technical Information of China (English)

    WANG Yu-liang; FU Ying-xin; ZHU Zhi-jun; WANG Hui; SHEN Zhong-yang

    2012-01-01

    Background Acute rejection remains an important cause of renal allograft dysfunction and the need for accurate diagnosis is essential to successfully treat transplant recipients.The purpose of this study was to determine the costimulatory molecules OX40 and OX40L messenger RNA (mRNA) levels in peripheral blood mononuclear cells (PBMCs) to predict acute renal transplant rejection.Methods The whole blood samples from 20 recipients with biopsy-confirmed acute rejection (rejection group),20 recipients with stable graft function and normal biopsy results (stable group) after kidney transplantation,and 20 healthy volunteers (control group) were collected.The mRNA levels of OX40 and OX40L were analyzed with TaqMan real-time reverse transcriptase polymerase chain reaction (RT-PCR).The association of OX40 and OX40L mRNA levels with disease severity was investigated.Results There was no significant difference of OX40,OX40L mRNA levels in PBMCs between the stable group and control group (P>0.05).The levels of OX40 and OX40L mRNA were significantly higher in the rejection group than in the control group (P<0.01 and P<0.05,respectively).Non-significantly higher OX40L mRNA and significantly higher OX40 mRNA in PBMCs were observed in subjects in the rejection group compared with the stable group (P >0.05 and P <0.01,respectively).Receiver operating characteristic (ROC) curve analysis demonstrated that OX40 mRNA levels could discriminate recipients who subsequently suffered acute allograft rejection (area under the curve,0.908).OX40 and OX40L mRNA levels did not significantly correlate with serum creatinine levels in the rejection group (P >0.05).Levels of OX40 mRNA after anti-rejection therapy were lower than those at the time of protocol biopsy in the rejection group (P<0.05).Conclusion Our data suggest that measurement of OX40 mRNA levels after transplant might offer a noninvasive means for recognizing recipients at risk of acute renal allograft rejection.

  13. Multiplex detection of pathogen biomarkers in human blood, serum, and saliva using silicon photonic microring resonators

    Science.gov (United States)

    Estrada, I. A.; Burlingame, R. W.; Wang, A. P.; Chawla, K.; Grove, T.; Wang, J.; Southern, S. O.; Iqbal, M.; Gunn, L. C.; Gleeson, M. A.

    2015-05-01

    Genalyte has developed a multiplex silicon photonic chip diagnostics platform (MaverickTM) for rapid detection of up to 32 biological analytes from a drop of sample in just 10 to 20 minutes. The chips are manufactured with waveguides adjacent to ring resonators, and probed with a continuously variable wavelength laser. A shift in the resonant wavelength as mass binds above the ring resonators is measured and is directly proportional to the amount of bound macromolecules. We present here the ability to multiplex the detection of hemorrhagic fever antigens in whole blood, serum, and saliva in a 16 minute assay. Our proof of concept testing of a multiplex antigencapture chip has the ability to detect Zaire Ebola (ZEBOV) recombinant soluble glycoprotein (rsGP), Marburg virus (MARV) Angola recombinant glycoprotein (rGP) and dengue nonstructural protein I (NS1). In parallel, detection of 2 malaria antigens has proven successful, but has yet to be incorporated into multiplex with the others. Each assay performs with sensitivity ranging from 1.6 ng/ml to 39 ng/ml depending on the antigen detected, and with minimal cross-reactivity.

  14. Blood diagnostic biomarkers for major depressive disorder using multiplex DNA methylation profiles: discovery and validation.

    Science.gov (United States)

    Numata, Shusuke; Ishii, Kazuo; Tajima, Atsushi; Iga, Jun-ichi; Kinoshita, Makoto; Watanabe, Shinya; Umehara, Hidehiro; Fuchikami, Manabu; Okada, Satoshi; Boku, Shuken; Hishimoto, Akitoyo; Shimodera, Shinji; Imoto, Issei; Morinobu, Shigeru; Ohmori, Tetsuro

    2015-01-01

    Aberrant DNA methylation in the blood of patients with major depressive disorder (MDD) has been reported in several previous studies. However, no comprehensive studies using medication-free subjects with MDD have been conducted. Furthermore, the majority of these previous studies has been limited to the analysis of the CpG sites in CpG islands (CGIs) in the gene promoter regions. The main aim of the present study is to identify DNA methylation markers that distinguish patients with MDD from non-psychiatric controls. Genome-wide DNA methylation profiling of peripheral leukocytes was conducted in two set of samples, a discovery set (20 medication-free patients with MDD and 19 controls) and a replication set (12 medication-free patients with MDD and 12 controls), using Infinium HumanMethylation450 BeadChips. Significant diagnostic differences in DNA methylation were observed at 363 CpG sites in the discovery set. All of these loci demonstrated lower DNA methylation in patients with MDD than in the controls, and most of them (85.7%) were located in the CGIs in the gene promoter regions. We were able to distinguish patients with MDD from the control subjects with high accuracy in the discriminant analysis using the top DNA methylation markers. We also validated these selected DNA methylation markers in the replication set. Our results indicate that multiplex DNA methylation markers may be useful for distinguishing patients with MDD from non-psychiatric controls.

  15. Whole blood Nested PCR and Real-time PCR amplification of Talaromyces marneffei specific DNA for diagnosis.

    Science.gov (United States)

    Lu, Sha; Li, Xiqing; Calderone, Richard; Zhang, Jing; Ma, Jianchi; Cai, Wenying; Xi, Liyan

    2016-02-01

    Talaromyces marneffei is a dimorphic pathogenic fungus, which is a life-threatening invasive mycosis in the immunocompromised host. Prompt diagnosis of T. marneffei infection remains difficult although there has been progress in attempts to expedite the diagnosis of this infection. We previously demonstrated the value of nested polymerase chain reaction (PCR) to detect T. marneffei in paraffin embedded tissue samples with high sensitivity and specificity. In this study, this assay was used to detect the DNA of T. marneffei in whole blood samples. Real-time PCR assay was also evaluated to identify T. marneffei in the same samples. Twenty out of 30 whole blood samples (67%) collected from 23 patients were found positive by using the nested PCR assay, while 23/30 (77%) samples were found positive by using the real-time PCR assay. In order to express accurately the fungal loads, we used a normalized linearized plasmid as an internal control for real-time PCR. The assay results were correlated as the initial quantity (copies/μl) with fungal burden. These data indicate that combination of nested PCR and real-time PCR assay provides an attractive alternative for identification of T. marneffei DNA in whole blood samples of HIV-infected patients.

  16. Evaluation of Current and New Biomarkers in Severe Preeclampsia: A Microarray Approach Reveals the VSIG4 Gene as a Potential Blood Biomarker

    OpenAIRE

    Textoris, Julien; Ivorra, Delphine; Ben Amara, Amira; Sabatier, Florence; Ménard, Jean-Pierre; Heckenroth, Hélène; Bretelle, Florence; Mege, Jean-Louis

    2013-01-01

    Preeclampsia is a placental disease characterized by hypertension and proteinuria in pregnant women, and it is associated with a high maternal and neonatal morbidity. However, circulating biomarkers that are able to predict the prognosis of preeclampsia are lacking. Thirty-eight women were included in the current study. They consisted of 19 patients with preeclampsia (13 with severe preeclampsia and 6 with non-severe preeclampsia) and 19 gestational age-matched women with normal pregnancies a...

  17. Mitochondrial DNA as a non-invasive biomarker: accurate quantification using real time quantitative PCR without co-amplification of pseudogenes and dilution bias.

    Science.gov (United States)

    Malik, Afshan N; Shahni, Rojeen; Rodriguez-de-Ledesma, Ana; Laftah, Abas; Cunningham, Phil

    2011-08-19

    Circulating mitochondrial DNA (MtDNA) is a potential non-invasive biomarker of cellular mitochondrial dysfunction, the latter known to be central to a wide range of human diseases. Changes in MtDNA are usually determined by quantification of MtDNA relative to nuclear DNA (Mt/N) using real time quantitative PCR. We propose that the methodology for measuring Mt/N needs to be improved and we have identified that current methods have at least one of the following three problems: (1) As much of the mitochondrial genome is duplicated in the nuclear genome, many commonly used MtDNA primers co-amplify homologous pseudogenes found in the nuclear genome; (2) use of regions from genes such as β-actin and 18S rRNA which are repetitive and/or highly variable for qPCR of the nuclear genome leads to errors; and (3) the size difference of mitochondrial and nuclear genomes cause a "dilution bias" when template DNA is diluted. We describe a PCR-based method using unique regions in the human mitochondrial genome not duplicated in the nuclear genome; unique single copy region in the nuclear genome and template treatment to remove dilution bias, to accurately quantify MtDNA from human samples.

  18. Evidence that the blood biomarker SNTF predicts brain imaging changes and persistent cognitive dysfunction in mild TBI patients

    Directory of Open Access Journals (Sweden)

    Robert eSiman

    2013-11-01

    Full Text Available Although mild traumatic brain injury (mTBI, or concussion, is not typically associated with abnormalities on computed tomography (CT, it nevertheless causes persistent cognitive dysfunction for many patients. Consequently, new prognostic methods for mTBI are needed to identify at-risk cases, especially at an early and potentially treatable stage. Here, we quantified plasma levels of the neurodegeneration biomarker calpain-cleaved alphaII-spectrin N-terminal fragment (SNTF from 38 participants with CT-negative mTBI, orthopedic injury (OI and normal uninjured controls (age range 12-30 years, and compared them with findings from diffusion tensor magnetic resonance imaging (DTI and long-term cognitive assessment. SNTF levels were at least twice the lower limit of detection in 7 of 17 mTBI cases and in 3 of 13 OI cases, but in none of the uninjured controls. An elevation in plasma SNTF corresponded with significant differences in fractional anisotropy and the apparent diffusion coefficient in the corpus callosum and uncinate fasciculus measured by DTI. Furthermore, increased plasma SNTF on the day of injury correlated significantly with cognitive impairment that persisted for at least 3 months, both across all study participants and also among the mTBI cases by themselves. The elevation in plasma SNTF in the subset of OI cases, accompanied by corresponding white matter and cognitive abnormalities, raises the possibility of identifying undiagnosed cases of mTBI. These data suggest that the blood level of SNTF on the day of a CT-negative mTBI may identify a subset of patients at risk of white matter damage and persistent disability. SNTF could have prognostic and diagnostic utilities in the assessment and treatment of mTBI.

  19. Association of EEG, MRI, and regional blood flow biomarkers is predictive of prodromal Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Moretti DV

    2015-10-01

    Full Text Available Davide Vito Moretti IRCCS S Giovanni di Dio Fatebenefratelli, Brescia, Italy Background: Thinning in the temporoparietal cortex, hippocampal atrophy, and a lower regional blood perfusion is connected with prodromal stage of Alzheimer’s disease (AD. Of note, an increase of electroencephalography (EEG upper/low alpha frequency power ratio has also been associated with these major landmarks of prodromal AD.Methods: Clinical and neuropsychological assessment, EEG recording, and high-resolution three-dimensional magnetic resonance imaging were done in 74 grown up subjects with mild cognitive impairment. This information was gathered and has been assessed 3 years postliminary. EEG recording and perfusion single-photon emission computed tomography assessment was done in 27 subjects. Alpha3/alpha2 frequency power ratio, including cortical thickness, was figured for every subject. Contrasts in cortical thickness among the groups were assessed. Pearson’s r relationship coefficient was utilized to evaluate the quality of the relationship between cortical thinning, brain perfusion, and EEG markers.Results: The higher alpha3/alpha2 frequency power ratio group corresponded with more prominent cortical decay and a lower perfusional rate in the temporoparietal cortex. In a subsequent meetup after 3 years, these patients had AD.Conclusion: High EEG upper/low alpha power ratio was connected with cortical diminishing and lower perfusion in the temporoparietal brain area. The increase in EEG upper/low alpha frequency power ratio could be helpful in recognizing people in danger of conversion to AD dementia and this may be quality information in connection with clinical assessment. Keywords: electroencephalography, mild cognitive impairment, hippocampal volume, brain rhythms, biomarkers

  20. Effect of oral acetyl L-carnitine arginate on resting and postprandial blood biomarkers in pre-diabetics

    Directory of Open Access Journals (Sweden)

    Tucker Patrick S

    2009-06-01

    Full Text Available Abstract Background Resting and postprandial oxidative stress is elevated in those with metabolic disorders such as diabetes. Antioxidant supplementation may attenuate the rise in oxidative stress following feeding. Therefore we sought to determine the effects of acetyl L-carnitine arginate (ALCA on resting and postprandial biomarkers of glucose and lipid metabolism, as well as oxidative stress. Methods Twenty-nine pre-diabetic men and women were randomly assigned to either 3 g·day-1 of ALCA (n = 14; 31 ± 3 yrs or placebo (n = 15; 35 ± 3 yrs in a double-blind design, to consume for eight weeks. Fasting blood samples were taken from subjects both pre and post intervention. After each fasting sample was obtained, subjects consumed a high fat, high carbohydrate meal and additional blood samples were taken at 1, 2, 4, and 6 hours post meal. Samples were analyzed for a variety of metabolic variables (e.g., glucose, HbA1c, lipid panel, C-reactive protein, nitrate/nitrite, and several markers of oxidative stress. Area under the curve (AUC was calculated for each variable measured post meal, both pre and post intervention. Results ALCA, but not placebo, resulted in an increase in nitrate/nitrite (25.4 ± 1.9 to 30.1 ± 2.8 μmol·L-1 from pre to post intervention, with post intervention values greater compared to placebo (p = 0.01. No other changes of statistical significance were noted (p > 0.05, although ALCA resulted in slight improvements in glucose (109 ± 5 to 103 ± 5 mg·dL-1, HbA1c (6.6 ± 1.1 to 6.2 ± 1.2%, and HOMA-IR (3.3 ± 1.3 to 2.9 ± 1.2. AUC postprandial data were not statistically different between ALCA and placebo for any variable (p > 0.05. However, nitrate/nitrite demonstrated a moderate effect size (r = 0.35 for increase from pre (139.50 ± 18.35 μmol·L-1·6 hr-1 to post (172.40 ± 21.75 μmol·L-1·6 hr-1 intervention with ALCA, and the magnitude of decrease following feeding was not as pronounced as with placebo

  1. Can Genetic Analysis of Putative Blood Alzheimer’s Disease Biomarkers Lead to Identification of Susceptibility Loci?

    Science.gov (United States)

    Huebinger, Ryan M.; Shewale, Shantanu J.; Koenig, Jessica L.; Mitchel, Jeffrey S.; O’Bryant, Sid E.; Waring, Stephen C.; Diaz-Arrastia, Ramon; Chasse, Scott

    2015-01-01

    Although 24 Alzheimer’s disease (AD) risk loci have been reliably identified, a large portion of the predicted heritability for AD remains unexplained. It is expected that additional loci of small effect will be identified with an increased sample size. However, the cost of a significant increase in Case-Control sample size is prohibitive. The current study tests whether exploring the genetic basis of endophenotypes, in this case based on putative blood biomarkers for AD, can accelerate the identification of susceptibility loci using modest sample sizes. Each endophenotype was used as the outcome variable in an independent GWAS. Endophenotypes were based on circulating concentrations of proteins that contributed significantly to a published blood-based predictive algorithm for AD. Endophenotypes included Monocyte Chemoattractant Protein 1 (MCP1), Vascular Cell Adhesion Molecule 1 (VCAM1), Pancreatic Polypeptide (PP), Beta2 Microglobulin (B2M), Factor VII (F7), Adiponectin (ADN) and Tenascin C (TN-C). Across the seven endophenotypes, 47 SNPs were associated with outcome with a p-value ≤1x10-7. Each signal was further characterized with respect to known genetic loci associated with AD. Signals for several endophenotypes were observed in the vicinity of CR1, MS4A6A/MS4A4E, PICALM, CLU, and PTK2B. The strongest signal was observed in association with Factor VII levels and was located within the F7 gene. Additional signals were observed in MAP3K13, ZNF320, ATP9B and TREM1. Conditional regression analyses suggested that the SNPs contributed to variation in protein concentration independent of AD status. The identification of two putatively novel AD loci (in the Factor VII and ATP9B genes), which have not been located in previous studies despite massive sample sizes, highlights the benefits of an endophenotypic approach for resolving the genetic basis for complex diseases. The coincidence of several of the endophenotypic signals with known AD loci may point to novel

  2. Mitochondrial DNA as a non-invasive biomarker: Accurate quantification using real time quantitative PCR without co-amplification of pseudogenes and dilution bias

    Energy Technology Data Exchange (ETDEWEB)

    Malik, Afshan N., E-mail: afshan.malik@kcl.ac.uk [King' s College London, Diabetes Research Group, Division of Diabetes and Nutritional Sciences, School of Medicine (United Kingdom); Shahni, Rojeen; Rodriguez-de-Ledesma, Ana; Laftah, Abas; Cunningham, Phil [King' s College London, Diabetes Research Group, Division of Diabetes and Nutritional Sciences, School of Medicine (United Kingdom)

    2011-08-19

    Highlights: {yields} Mitochondrial dysfunction is central to many diseases of oxidative stress. {yields} 95% of the mitochondrial genome is duplicated in the nuclear genome. {yields} Dilution of untreated genomic DNA leads to dilution bias. {yields} Unique primers and template pretreatment are needed to accurately measure mitochondrial DNA content. -- Abstract: Circulating mitochondrial DNA (MtDNA) is a potential non-invasive biomarker of cellular mitochondrial dysfunction, the latter known to be central to a wide range of human diseases. Changes in MtDNA are usually determined by quantification of MtDNA relative to nuclear DNA (Mt/N) using real time quantitative PCR. We propose that the methodology for measuring Mt/N needs to be improved and we have identified that current methods have at least one of the following three problems: (1) As much of the mitochondrial genome is duplicated in the nuclear genome, many commonly used MtDNA primers co-amplify homologous pseudogenes found in the nuclear genome; (2) use of regions from genes such as {beta}-actin and 18S rRNA which are repetitive and/or highly variable for qPCR of the nuclear genome leads to errors; and (3) the size difference of mitochondrial and nuclear genomes cause a 'dilution bias' when template DNA is diluted. We describe a PCR-based method using unique regions in the human mitochondrial genome not duplicated in the nuclear genome; unique single copy region in the nuclear genome and template treatment to remove dilution bias, to accurately quantify MtDNA from human samples.

  3. Establishment of loop-mediated isothermal amplification (LAMP) for rapid detection of Brucella spp. and application to milk and blood samples.

    Science.gov (United States)

    Song, Liuyan; Li, Juntao; Hou, Shuiping; Li, Xunde; Chen, Shouyi

    2012-09-01

    Brucella spp. are facultative intracellular bacteria that infect humans and animals. In this study, the loop-mediated isothermal amplification (LAMP) was used to detect the Brucella-specific gene omp25. Reaction conditions were optimized as temperature 65°C, reaction time 60 min, Mg(2+) concentration 8.0 mmol/L, polymerase content Bst DNA, 0.5 μL, deoxyribonucleotide concentration 1.6 mmol/L, and inner/outer primer ratio 1:8. The LAMP method was evaluated with 4 Brucella species and 29 non-Brucella bacteria species. Positive reactions were observed on all the 4 Brucella species but not on any non-Brucella species. The limit of detection of the LAMP method was 3.81 CFU Brucella spp. Using the LAMP method, 7 of 110 raw milk samples and 5 of 59 sheep blood samples were detected positive of Brucella spp. Results indicated that LAMP is a fast, specific, sensitive, inexpensive, and suitable method for diagnosis of Brucella spp. infection.

  4. Blood biomarkers and contaminant levels in feathers and eggs to assess environmental hazards in heron nestlings from impacted sites in Ebro basin (NE Spain)

    Energy Technology Data Exchange (ETDEWEB)

    Barata, C., E-mail: cbmqam@cid.csic.e [Department of Environmental Chemistry, IDAEA-CSIC, Jordi Girona 18, 08034 Barcelona (Spain); Fabregat, M.C. [Department of Environmental Chemistry, IDAEA-CSIC, Jordi Girona 18, 08034 Barcelona (Spain); Cotin, J.; Huertas, D. [Department de Biologia Animal, Universitat de Barcelona, Avgda Diagonal 645, 08028 Barcelona (Spain); Sole, M. [Institut de Ciencies del Mar (ICM-CSIC), Pg. Maritim de la Barceloneta 37-49, 08003 Barcelona (Spain); Quiros, L. [Department of Environmental Chemistry, IDAEA-CSIC, Jordi Girona 18, 08034 Barcelona (Spain); Sanpera, C.; Jover, L.; Ruiz, X. [Department de Biologia Animal, Universitat de Barcelona, Avgda Diagonal 645, 08028 Barcelona (Spain); Grimalt, J.O.; Pina, B. [Department of Environmental Chemistry, IDAEA-CSIC, Jordi Girona 18, 08034 Barcelona (Spain)

    2010-03-15

    Blood biomarkers and levels of major pollutants in eggs and feathers were used to determine pollution effects in nestlings of the Purple Heron Ardea purpurea and the Little Egret Egretta garzetta, sampled on three Ebro River (NE Spain) areas: a reference site, a site affected by the effluents of a chlor-alkali industry and the river Delta. The two impacted heron populations showed mutually different pollutant and response patterns, suggesting different sources of contamination. In the population nesting near the chlor-alkali plant, elevated levels of hexachlorobenzene (HCB) and polychlorobiphenyls (PCBs) in eggs, and mercury in feathers in A. purpurea chicks were related with reduced blood antioxidant defenses and increased levels of micronuclei. In Ebro Delta, high levels of plasmatic lactate dehydrogenase in A. purpurea chicks and high frequency of micronuclei in blood of both species were tentatively associated with intensive agricultural activities taking place in the area. These results provide the first evidence of a biological response in heron chicks to the release of pollutants at a chlor-alkali plant. - High levels of organochlorine and mercury levels in eggs and feathers were related with altered blood biomarkers of heron nesting chicks.

  5. Blood born miRNAs signatures that can serve as disease specific biomarkers are not significantly affected by overall fitness and exercise.

    Directory of Open Access Journals (Sweden)

    Christina Backes

    Full Text Available Blood born micro(miRNA expression pattern have been reported for various human diseases with signatures specific for diseases. To evaluate these biomarkers, it is mandatory to know possible changes of miRNA signatures in healthy individuals under different physiological conditions. We analyzed the miRNA expression in peripheral blood of elite endurance athletes and moderatly active controls. Blood drawing was done before and after exhaustive exercise in each group. After Benjamini-Hochberg adjustment we did not find any miRNA with significant p-values when comparing miRNA expression between the different groups. We found, however, 24 different miRNAs with an expression fold change of minimum 1.5 in at least one of the comparisons (athletes before vs after exercise, athletes before exercise vs controls and athletes after exercise vs controls. The observed changes are not significant in contrast to the expression changes of the blood born miRNA expression reported for many human diseases. These data support the idea of disease associated miRNA patterns useful as biomarkers that are not readily altered by physiological conditions.

  6. Cardiac biomarkers in blood, and pericardial and cerebrospinal fluids of forensic autopsy cases: A reassessment with special regard to postmortem interval.

    Science.gov (United States)

    Chen, Jian-Hua; Inamori-Kawamoto, Osamu; Michiue, Tomomi; Ikeda, Sayuko; Ishikawa, Takaki; Maeda, Hitoshi

    2015-09-01

    Previous studies suggested possible application of postmortem biochemistry of myocardial biomarkers to the investigation of sudden cardiac death; however, differences from clinical findings should be considered in autopsy materials. The present study involved a comprehensive investigation of cardiac troponin T and I (cTnT and cTnI), and creatine kinase MB (CK-MB) in cardiac and peripheral external iliac venous blood, pericardial fluid (PCF) and cerebrospinal fluid (CSF) for reassessment, with special regard to the estimated postmortem interval in relation to the cause of death, reviewing a large number of forensic autopsy cases (n=1923). These cardiac biomarkers showed cause-of-death- and postmortem-time-dependent differences: blood and PCF levels of each marker were higher in hyperthermia (heatstroke), bathwater drowning and chronic congestive heart disease in cases of postmortem interval (PMI) PMI of <48h. CSF cTnI and CK-MB showed similar findings. There was no difference between myocardial infarction and other causes of death to be discriminated, including asphyxiation, drowning and fire fatality. These findings are similar to clinical observations in critical ill patients, suggesting that elevated cardiac biomarkers cannot be a specific finding for death from acute ischemic heart disease, but indicate the severity of myocardial injury in postmortem investigation. PMID:26052007

  7. Proteomic biomarkers of peripheral blood mononuclear cells obtained from postmenopausal women undergoing an intervention with soy isoflavones

    NARCIS (Netherlands)

    Fuchs, D.; Vafeiadou, K.; Hall, W.L.; Daniel, H.; Williams, C.M.; Schroot, J.H.; Wenzel, U.

    2007-01-01

    Background: The incidence of cardiovascular diseases increases after menopause, and soy consumption is suggested to inhibit disease development. Objective: The objective was to identify biomarkers of response to a dietary supplementation with an isoflavone extract in postmenopausal women by proteome

  8. Expression profiling of blood samples from an SU5416 Phase III metastatic colorectal cancer clinical trial: a novel strategy for biomarker identification

    Directory of Open Access Journals (Sweden)

    Smolich Beverly D

    2003-02-01

    Full Text Available Abstract Background Microarray-based gene expression profiling is a powerful approach for the identification of molecular biomarkers of disease, particularly in human cancers. Utility of this approach to measure responses to therapy is less well established, in part due to challenges in obtaining serial biopsies. Identification of suitable surrogate tissues will help minimize limitations imposed by those challenges. This study describes an approach used to identify gene expression changes that might serve as surrogate biomarkers of drug activity. Methods Expression profiling using microarrays was applied to peripheral blood mononuclear cell (PBMC samples obtained from patients with advanced colorectal cancer participating in a Phase III clinical trial. The PBMC samples were harvested pre-treatment and at the end of the first 6-week cycle from patients receiving standard of care chemotherapy or standard of care plus SU5416, a vascular endothelial growth factor (VEGF receptor tyrosine kinase (RTK inhibitor. Results from matched pairs of PBMC samples from 23 patients were queried for expression changes that consistently correlated with SU5416 administration. Results Thirteen transcripts met this selection criterion; six were further tested by quantitative RT-PCR analysis of 62 additional samples from this trial and a second SU5416 Phase III trial of similar design. This method confirmed four of these transcripts (CD24, lactoferrin, lipocalin 2, and MMP-9 as potential biomarkers of drug treatment. Discriminant analysis showed that expression profiles of these 4 transcripts could be used to classify patients by treatment arm in a predictive fashion. Conclusions These results establish a foundation for the further exploration of peripheral blood cells as a surrogate system for biomarker analyses in clinical oncology studies.

  9. Aberrant expression of microRNAs as biomarker for schizophrenia: from acute state to partial remission, and from peripheral blood to cortical tissue.

    Science.gov (United States)

    Lai, C-Y; Lee, S-Y; Scarr, E; Yu, Y-H; Lin, Y-T; Liu, C-M; Hwang, T-J; Hsieh, M H; Liu, C-C; Chien, Y-L; Udawela, M; Gibbons, A S; Everall, I P; Hwu, H-G; Dean, B; Chen, W J

    2016-01-19

    Based on our previous finding of a seven-miRNA (hsa-miR-34a, miR-449a, miR-564, miR-432, miR-548d, miR-572 and miR-652) signature as a potential biomarker for schizophrenia, this study aimed to examine if hospitalization could affect expressions of these miRNAs. We compared their expression levels between acute state and partial remission state in people with schizophrenia (n=48) using quantitative PCR method. Further, to examine whether the blood and brain show similar expression patterns, the expressions of two miRNAs (hsa-miR-34a and hsa-miR-548d) were examined in the postmortem brain tissue of people with schizophrenia (n=25) and controls (n=27). The expression level of the seven miRNAs did not alter after ~2 months of hospitalization with significant improvement in clinical symptoms, suggesting the miRNAs could be traits rather than state-dependent markers. The aberrant expression seen in the blood of hsa-miR-34a and hsa-miR-548d were not present in the brain samples, but this does not discount the possibility that the peripheral miRNAs could be clinically useful biomarkers for schizophrenia. Unexpectedly, we found an age-dependent increase in hsa-miR-34a expressions in human cortical (Brodmann area 46 (BA46)) but not subcortical region (caudate putamen). The correlation between hsa-miR-34a expression level in BA46 and age was much stronger in the controls than in the cases, and the corresponding correlation in the blood was only seen in the cases. The association between the miRNA dysregulations, the disease predisposition and aging warrants further investigation. Taken together, this study provides further insight on the candidate peripheral miRNAs as stable biomarkers for the diagnostics of schizophrenia.

  10. Most blood biomarkers related to vitamin status, one-carbon metabolism, and the kynurenine pathway show adequate preanalytical stability and within-person reproducibility to allow assessment of exposure or nutritional status in healthy women and cardiovascular patients.

    Science.gov (United States)

    Midttun, Oivind; Townsend, Mary K; Nygård, Ottar; Tworoger, Shelley S; Brennan, Paul; Johansson, Mattias; Ueland, Per Magne

    2014-05-01

    Knowledge of stability during sample transportation and changes in biomarker concentrations within person over time are paramount for proper design and interpretation of epidemiologic studies based on a single measurement of biomarker status. Therefore, we investigated stability and intraindividual vs. interindividual variation in blood concentrations of biomarkers related to vitamin status, one-carbon metabolism, and the kynurenine pathway. Whole blood (EDTA and heparin, n = 12) was stored with an icepack for 24 or 48 h, and plasma concentrations of 38 biomarkers were determined. Stability was calculated as change per hour, intraclass correlation coefficient (ICC), and simple Spearman correlation. Within-person reproducibility of biomarkers was expressed as ICC in samples collected 1-2 y apart from 40 postmenopausal women and in samples collected up to 3 y apart from 551 patients with stable angina pectoris. Biomarker stability was similar in EDTA and heparin blood. Most biomarkers were essentially stable, except for choline and total homocysteine (tHcy), which increased markedly. Within-person reproducibility in postmenopausal women was excellent (ICC > 0.75) for cotinine, all-trans retinol, cobalamin, riboflavin, α-tocopherol, Gly, pyridoxal, methylmalonic acid, creatinine, pyridoxal 5'-phosphate, and Ser; was good to fair (ICC of 0.74-0.40) for pyridoxic acid, kynurenine, tHcy, cholecalciferol, flavin mononucleotide, kynurenic acid, xanthurenic acid, 3-hydroxykynurenine, sarcosine, anthranilic acid, cystathionine, homoarginine, 3-hydroxyanthranilic acid, betaine, Arg, folate, total cysteine, dimethylglycine, asymmetric dimethylarginine, neopterin, symmetric dimethylarginine, and Trp; and poor (ICC of 0.39-0.15) for methionine sulfoxide, Met, choline, and trimethyllysine. Similar reproducibilities were observed in patients with coronary heart disease. Thus, most biomarkers investigated were essentially stable in cooled whole blood for up to 48 h and had a

  11. Effect of consumption of fresh and heated virgin coconut oil on the blood pressure and inflammatory biomarkers: An experimental study in Sprague Dawley rats

    OpenAIRE

    Mohammad Afiq Hamsi; Faizah Othman; Srijit Das; Yusof Kamisah; Zar Chi Thent; Haji Mohd Saad Qodriyah; Zaiton Zakaria; Adel Emran; Kogilavani Subermaniam; Kamsiah Jaarin

    2015-01-01

    Background: It is a common practice to heat cooking oil and reuse it in order to cut expenses. The use of repeatedly heated cooking oil predisposes to various cardiovascular diseases. Virgin coconut oil (VCO) is reported to possess antioxidant action. Aim: The study aimed to determine the effect of heating of VCO on the blood pressure (BP) and inflammatory bio-markers. Methods: Thirty male Sprague-Dawley rats were divided into five groups and were fed with the following diet for 24 week...

  12. Feasibility study on blood sample investigations from former Wismut employees with respect to possible biomarkers for arsenic or radiation exposure using proteomics and cDNA microarray technologies. Final report

    International Nuclear Information System (INIS)

    The final report on the feasibility of blood sample investigations from former Wismut employees with respect to possible biomarkers for arsenic or radiation exposure using proteomics and cDNA microarray technologies covers the following topics: blood samples; methodologies: 2D gel electrophoresis; protein identification using MALDI-MS; accomplishment and evaluation of the proteomics and cDNA microarray analysis.

  13. The potential of pathological protein fragmentation in blood-based biomarker development for dementia - with emphasis on Alzheimer's disease

    DEFF Research Database (Denmark)

    Inekci, Dilek; Svendsen Jonesco, Ditte; Kennard, Sophie;

    2015-01-01

    The diagnosis of dementia is challenging and early stages are rarely detected limiting the possibilities for early intervention. Another challenge is the overlap in the clinical features across the different dementia types leading to difficulties in the differential diagnosis. Identifying...... biomarkers that can detect the pre-dementia stage and allow differential diagnosis could provide an opportunity for timely and optimal intervention strategies. Also, such biomarkers could help in selection and inclusion of the right patients in clinical trials of both Alzheimer's disease and other dementia......, as there is a significant crossover between the proteins involved in the different types of dementia. Additionally, CSF sampling makes these biomarkers challenging for presymptomatic identification. We need to focus on disease-specific protein fragmentation to find a fragment pattern unique for each separate dementia type...

  14. 不同PCR扩增试剂盒检验血样DNA的检验结果对比研究%Comparative Study between Test Results of Different PCR Amplification Kits in Testing Blood Sample DNA

    Institute of Scientific and Technical Information of China (English)

    魏万昆

    2014-01-01

    目的:讨论研究Profiler PlusTM、IdentifilerTM以及Powerplex16扩增试剂盒用于检验血样DNA检验结果的差异,并研究其扩张不平衡和基因丢失现象的发生几率。方法:选取150例完全无血缘关系的个体作为研究对象并采集其血样,分别使用两种扩增试剂盒进行检验。对所得不同结果的同一对象再使用3种扩增试剂盒进行检验。将检验所得结果进行比较。结果:3种试剂盒检测的等位基因缺失率比较差异无统计学意义(P>0.05)。Profiler PlusTM检测扩张不平衡率显著高于其余两种试剂盒(P<0.05)。结论:使用PCR扩增试剂盒对血样DNA进行检测时,会出现不同位置的异常基因,可表现为基因缺失及扩增不平衡。但Profiler PlusTM检验扩增不平衡发生率显著高于其余两种试剂盒。在实际生活对血样DNA进行检测时,除需准备主要检测扩增试剂盒外,还需准备其他不同类备用试剂盒用于互相验证及对比,尽量降低基因等位缺失及扩张不平衡发生率。%To discuss and study the difference between testing results of Profiler PlusTM,IdentifilerTM and Powerplex16 amplification kits in testing blood sample DNA,and study the occurrence rate of amplification imbalance and gene deletion phenomenon.Method:150 individuals who had no genetic connection with each other were chosen as research objects,and their blood samples were collected and tested by 2 different amplification kits. Objects with 2 different results were tested again by the third kit. All testing results were compared.Result:There were no significant differences between the 3 kits on allelic gene deletion(P<0.05). Amplification imbalance rate of Profiler PlusTM was obviously higher than the other 2 kits(P<0.05). Conclusion:When testing blood sample DNA with different PCR amplification kits, there might be abnormal genes of different positions which might manifested as gene deletion and

  15. The influence of radiographic phenotype and smoking status on peripheral blood biomarker patterns in chronic obstructive pulmonary disease.

    Directory of Open Access Journals (Sweden)

    Jessica M Bon

    Full Text Available BACKGROUND: Chronic obstructive pulmonary disease (COPD is characterized by both airway remodeling and parenchymal destruction. The identification of unique biomarker patterns associated with airway dominant versus parenchymal dominant patterns would support the existence of unique phenotypes representing independent biologic processes. A cross-sectional study was performed to examine the association of serum biomarkers with radiographic airway and parenchymal phenotypes of COPD. METHODOLOGY/PRINCIPAL FINDINGS: Serum from 234 subjects enrolled in a CT screening cohort was analyzed for 33 cytokines and growth factors using a multiplex protein array. The association of serum markers with forced expiratory volume in one second percent predicted (FEV1% and quantitative CT measurements of airway thickening and emphysema was assessed with and without stratification for current smoking status. Significant associations were found with several serum inflammatory proteins and measurements of FEV1%, airway thickening, and parenchymal emphysema independent of smoking status. The association of select analytes with airway thickening and emphysema was independent of FEV1%. Furthermore, the relationship between other inflammatory markers and measurements of physiologic obstruction or airway thickening was dependent on current smoking status. CONCLUSIONS/SIGNIFICANCE: Airway and parenchymal phenotypes of COPD are associated with unique systemic serum biomarker profiles. Serum biomarker patterns may provide a more precise classification of the COPD syndrome, provide insights into disease pathogenesis and identify targets for novel patient-specific biological therapies.

  16. Mass spectrometry for biomarker development

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Chaochao; Liu, Tao; Baker, Erin Shammel; Rodland, Karin D.; Smith, Richard D.

    2015-06-19

    Biomarkers potentially play a crucial role in early disease diagnosis, prognosis and targeted therapy. In the past decade, mass spectrometry based proteomics has become increasingly important in biomarker development due to large advances in technology and associated methods. This chapter mainly focuses on the application of broad (e.g. shotgun) proteomics in biomarker discovery and the utility of targeted proteomics in biomarker verification and validation. A range of mass spectrometry methodologies are discussed emphasizing their efficacy in the different stages in biomarker development, with a particular emphasis on blood biomarker development.

  17. Cholesterol oxidation products are sensitive and specific blood-based biomarkers for Niemann-Pick C1 disease

    OpenAIRE

    Porter, Forbes D.; Scherrer, David E.; Lanier, Michael H.; Langmade, S. Joshua; Molugu, Vasumathi; Gale, Sarah E.; Olzeski, Dana; Sidhu, Rohini; Dietzen, Dennis J.; Fu, Rao; Wassif, Christopher A.; Yanjanin, Nicole M.; Marso, Steven P.; House, John; Vite, Charles

    2010-01-01

    Niemann-Pick type C1 (NPC1) disease is a rare progressive neurodegenerative disorder characterized by endolysosomal cholesterol accumulation. Previous studies implicating oxidative stress in NPC1 disease pathogenesis raised the possibility that non-enzymatic formation of cholesterol oxidation products could serve as disease biomarkers. We measured these metabolites in the plasma and tissues of the Npc1−/− mouse model and found several cholesterol oxidation products that were elevated in Npc1−...

  18. From human monocytes to genome-wide binding sites--a protocol for small amounts of blood: monocyte isolation/ChIP-protocol/library amplification/genome wide computational data analysis.

    Directory of Open Access Journals (Sweden)

    Sebastian Weiterer

    Full Text Available Chromatin immunoprecipitation in combination with a genome-wide analysis via high-throughput sequencing is the state of the art method to gain genome-wide representation of histone modification or transcription factor binding profiles. However, chromatin immunoprecipitation analysis in the context of human experimental samples is limited, especially in the case of blood cells. The typically extremely low yields of precipitated DNA are usually not compatible with library amplification for next generation sequencing. We developed a highly reproducible protocol to present a guideline from the first step of isolating monocytes from a blood sample to analyse the distribution of histone modifications in a genome-wide manner.The protocol describes the whole work flow from isolating monocytes from human blood samples followed by a high-sensitivity and small-scale chromatin immunoprecipitation assay with guidance for generating libraries compatible with next generation sequencing from small amounts of immunoprecipitated DNA.

  19. Effect of Orange (Citrus sinensis Peel Oil on Lipid Peroxidation, Catalase activity and Hepatic Biomarker levels in Blood Plasma of Normo Rats

    Directory of Open Access Journals (Sweden)

    Ochuko L. Erukainure

    2012-07-01

    Full Text Available Dietary antioxidants are considered beneficial because of their potential protective role against oxidative stress, which is involved in the pathogenesis of multiple diseases such as cancer and coronary heart disease. The effect of feeding orange peel oil on lipid peroxidation, catalase and hepatic biomarkers in blood plasma of normo rats was investigated. Beside mouse chow, four diets were designed to contain 50% of energy as carbohydrate, 35% as fat, and 15% as protein, and one that was lipid-free diet which had distilled water substituted for fat. Groups of five rats were each fed one of these diets, while a fifth group was fed pelletized mouse chow. There was no significant difference in the amount of food consumed, though significant weight lost was observed in all groups except soybean oil. Feeding on orange peel oil led to significant (p<0.05 decrease in lipid peroxidation and catalase activities in comparison to soybean oil. Higher AST and lower ALT activities were observed in orange peel oil fed groups. These results suggest the oil from the orange peels possesses antioxidant potentials which could be protective against oxidative stress, thus useful in its treatment and management. However, the elevated levels of hepatic biomarkers pose a threat of hepatotoxicity thus suggesting that it should be consumed or used as a pharmaceutical ingredient at lower concentrations.

  20. Modulatory effect of pineapple peel extract on lipid peroxidation, catalase activity and hepatic biomarker levels in blood plasma of alcohol-induced oxidative stressed rats

    Institute of Scientific and Technical Information of China (English)

    Okafor OY; Erukainure OL; Ajiboye JA; Adejobi RO; Owolabi FO; Kosoko SB

    2011-01-01

    Objective: To investigate the ability of the methanolic extract of pineapple peel to modulate alcohol-induced lipid peroxidation, changes in catalase activities and hepatic biochemical marker levels in blood plasma. Methods: Oxidative stress was induced by oral administration of ethanol (20% w/v) at a dosage of 5 mL/kg bw in rats. After 28 days of treatment, the rats were fasted overnight and sacrificed by cervical dislocation. Blood was collected with a 2 mL syringe by cardiac puncture and was centrifuged at 3000 rpm for 10 min. The plasma was analyzed to evaluate malondialdehyde (MDA), catalase activity, aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) concentrations. Results: Administration of alcohol caused a drastic increase (87.74%) in MDA level compared with the control. Pineapple peel extract significantly reduced the MDA level by 60.16% at 2.5 mL/kg bw. Rats fed alcohol only had the highest catalase activity, treatment with pineapple peel extract at 2.5 mL/kg bw however, reduced the activity. Increased AST, ALP and ALT activities were observed in rats fed alcohol only respectively, treatment with pineapple peel extract drastically reduced their activities. Conclusions: The positive modulation of lipid peroxidation, catalase activities as well as hepatic biomarker levels of blood plasma by the methanolic extract of pineapple peels under alcohol-induced oxidative stress is an indication of its protective ability in the management of alcohol-induced toxicity.

  1. The use of antioxidative stress enzymes, lipid peroxidation, and red blood cell abnormalities as biomarkers of stress in Periphthalmus papilio of the polluted coastal Lagos lagoon.

    Science.gov (United States)

    Nnamdi, Amaeze H; Olumide, Adebesin A; Adeladun, Adepegba E; Oyenike, Kolapo; Rosemary, Egonmwan I

    2015-03-01

    We assessed the mudskipper, Periphthalmus papilio inhabiting the coast line of the Lagos lagoon, Gulf of Guinea, to determine suitable biomarkers of stress due to its current status as a polluted water body. The gill and liver samples showed evidence of some activities of antioxidative stress enzymes including catalase, superoxide dismutase, glutathione-s-transferase, reduced glutahthione, as well as some detectable levels of lipid peroxidation product. The stress status of the fishes was also elucidated by nuclear abnormalities especially micronucleus formation and the presence of numerous vacuolated red blood cells. Given the current need for more sensitive bioindicators in monitoring pollution in this lagoon, we hereby present these inherent responses in P. papilio as a suitable candidate for incorporation into the current repertoire for ecotoxicological investigations in polluted water bodies of the Gulf of Guinea coastline. PMID:25666650

  2. Integrative analyses of hepatic differentially expressed genes and blood biomarkers during the peripartal period between dairy cows overfed or restricted-fed energy prepartum.

    Directory of Open Access Journals (Sweden)

    Khuram Shahzad

    Full Text Available Using published dairy cattle liver transcriptomics dataset along with novel blood biomarkers of liver function, metabolism, and inflammation we have attempted an integrative systems biology approach applying the classical functional enrichment analysis using DAVID, a newly-developed Dynamic Impact Approach (DIA, and an upstream gene network analysis using Ingenuity Pathway Analysis (IPA. Transcriptome data was generated from experiments evaluating the impact of prepartal plane of energy intake [overfed (OF or restricted (RE] on liver of dairy cows during the peripartal period. Blood biomarkers uncovered that RE vs. OF led to greater prepartal liver distress accompanied by a low-grade inflammation and larger proteolysis (i.e., higher haptoglobin, bilirubin, and creatinine. Post-partum the greater bilirubinaemia and lipid accumulation in OF vs. RE indicated a large degree of liver distress. The re-analysis of microarray data revealed that expression of >4,000 genes was affected by diet × time. The bioinformatics analysis indicated that RE vs. OF cows had a liver with a greater lipid and amino acid catabolic capacity both pre- and post-partum while OF vs. RE cows had a greater activation of pathways/functions related to triglyceride synthesis. Furthermore, RE vs. OF cows had a larger (or higher capacity to cope with ER stress likely associated with greater protein synthesis/processing, and a higher activation of inflammatory-related functions. Liver in OF vs. RE cows had a larger cell proliferation and cell-to-cell communication likely as a response to the greater lipid accumulation. Analysis of upstream regulators indicated a pivotal role of several lipid-related transcription factors (e.g., PPARs, SREBPs, and NFE2L2 in priming the liver of RE cows to better face the early postpartal metabolic and inflammatory challenges. An all-encompassing dynamic model was proposed based on the findings.

  3. Integrative Analyses of Hepatic Differentially Expressed Genes and Blood Biomarkers during the Peripartal Period between Dairy Cows Overfed or Restricted-Fed Energy Prepartum

    Science.gov (United States)

    Shahzad, Khuram; Bionaz, Massimo; Trevisi, Erminio; Bertoni, Giuseppe; Rodriguez-Zas, Sandra L.; Loor, Juan J.

    2014-01-01

    Using published dairy cattle liver transcriptomics dataset along with novel blood biomarkers of liver function, metabolism, and inflammation we have attempted an integrative systems biology approach applying the classical functional enrichment analysis using DAVID, a newly-developed Dynamic Impact Approach (DIA), and an upstream gene network analysis using Ingenuity Pathway Analysis (IPA). Transcriptome data was generated from experiments evaluating the impact of prepartal plane of energy intake [overfed (OF) or restricted (RE)] on liver of dairy cows during the peripartal period. Blood biomarkers uncovered that RE vs. OF led to greater prepartal liver distress accompanied by a low-grade inflammation and larger proteolysis (i.e., higher haptoglobin, bilirubin, and creatinine). Post-partum the greater bilirubinaemia and lipid accumulation in OF vs. RE indicated a large degree of liver distress. The re-analysis of microarray data revealed that expression of >4,000 genes was affected by diet × time. The bioinformatics analysis indicated that RE vs. OF cows had a liver with a greater lipid and amino acid catabolic capacity both pre- and post-partum while OF vs. RE cows had a greater activation of pathways/functions related to triglyceride synthesis. Furthermore, RE vs. OF cows had a larger (or higher capacity to cope with) ER stress likely associated with greater protein synthesis/processing, and a higher activation of inflammatory-related functions. Liver in OF vs. RE cows had a larger cell proliferation and cell-to-cell communication likely as a response to the greater lipid accumulation. Analysis of upstream regulators indicated a pivotal role of several lipid-related transcription factors (e.g., PPARs, SREBPs, and NFE2L2) in priming the liver of RE cows to better face the early postpartal metabolic and inflammatory challenges. An all-encompassing dynamic model was proposed based on the findings. PMID:24914544

  4. Integrative transcriptomic meta-analysis of Parkinson’s disease and depression identifies NAMPT as a potential blood biomarker for de novo Parkinson’s disease

    Science.gov (United States)

    Santiago, Jose A.; Littlefield, Alyssa M.; Potashkin, Judith A.

    2016-01-01

    Emerging research indicates that depression could be one of the earliest prodromal symptoms or risk factors associated with the pathogenesis of Parkinson’s disease (PD), the second most common neurodegenerative disorder worldwide, but the mechanisms underlying the association between both diseases remains unknown. Understanding the molecular networks linking these diseases could facilitate the discovery of novel diagnostic and therapeutics. Transcriptomic meta-analysis and network analysis of blood microarrays from untreated patients with PD and depression identified genes enriched in pathways related to the immune system, metabolism of lipids, glucose, fatty acids, nicotinamide, lysosome, insulin signaling and type 1 diabetes. Nicotinamide phosphoribosyltransferase (NAMPT), an adipokine that plays a role in lipid and glucose metabolism, was identified as the most significant dysregulated gene. Relative abundance of NAMPT was upregulated in blood of 99 early stage and drug-naïve PD patients compared to 101 healthy controls (HC) nested in the cross-sectional Parkinson’s Progression Markers Initiative (PPMI). Thus, here we demonstrate that shared molecular networks between PD and depression provide an additional source of biologically relevant biomarkers. Evaluation of NAMPT in a larger prospective longitudinal study including samples from other neurodegenerative diseases, and patients at risk of PD is warranted. PMID:27680512

  5. 微量全血PCR技术鉴定雏鸡及鸡胚性别%Sex Identification with Direct Whole Blood PCR Amplification in Chicklings and Chicken Embryos

    Institute of Scientific and Technical Information of China (English)

    李治利; 秦清明; 施振旦; 陈海南; 黄群山

    2012-01-01

    为了便于常规PCR技术在鸡性别鉴定上的推广和应用,本研究以成年家鸡全血为模板,应用常规PCR反应缓冲液和Tap DNA聚合酶直接进行PCR扩增,对50μL PCR反应体系中的血样(0.05~4.0 μL)和Tap DNA聚合酶的使用量(0.05~1.5 uL),以及循环次数(30~40)进行了优化,在此基础上对血样的抗凝剂和保存温度进行了探讨,并对62只1日龄雏鸡、80枚12日龄和80枚16日龄鸡胚的血样直接PCR进行了性别鉴定.结果表明,采集血样时可以使用ACD、肝素或EDTA作为抗凝剂,血样可以在4、-20或-80℃至少保存3个月;使用0.1μL全血就能完成雏鸡和鸡胚性别鉴定,全血PCR鉴定性别与性腺性别的符合度为100%.与常规PCR相比,全血PCR节约了检测成本,提高了检测效率,减少了交叉污染可能.%For facilitation of conventional PCR technology to identify chicken sex, this study took the whole blood of adult chicks as a sample by the conventional PCR reaction mix and Tap DNA polymerase for direct PCR amplification, optimization was conducted in adult chicken whole blood (from 0. 05 to 4. 0 μL) , Tap DNA polymerase (from 0. 05 to 1. 5 μL) and cycle number (from 30 to 40) in 50 μL direct PCR amplification system. Anti-coagulant selection and storage temperature of blood sample were evaluated, sex was identified with direct whole blood PCR amplification and compared with gonadal sex in 62 of 1-day-old chicklings, 80 of 12-day-old and 80 of 16-day-old chicken embryos, respectively. The results showed that sex identification with direct PCR amplification with 0. 1 μL whole blood sample was fully consistent with the gonadal sex, therefore it was accuracy in chicklings and chicken embryos. ACD, heparin or DETA could be adopted as anticoagulant and blood samples could be stored at 4, -20 or -80 ℃ for 3 months at least. Compared with conventional PCR, the direct whole blood PCR could be economic, efficient and low possible of cross-contamination.

  6. High-resolution blood-pool-contrast-enhanced MR angiography in glioblastoma: tumor-associated neovascularization as a biomarker for patient survival. A preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Puig, Josep; Blasco, Gerard; Remollo, Sebastian; Hernandez, David; Pedraza, Salvador [Hospital Universitari Dr Josep Trueta, Research Unit of Diagnostic Imaging Institute (IDI), Department of Radiology [Girona Biomedical Research Institute] IDIBGI, Girona (Spain); Daunis-i-Estadella, Josep; Mateu, Gloria [University of Girona, Department of Computer Science, Applied Mathematics and Statistics, Girona (Spain); Alberich-Bayarri, Angel [La Fe Polytechnics and University Hospital, Biomedical Imaging Research Group (GIBI230), La Fe Health Research Institute, Valencia (Spain); Essig, Marco [University of Manitoba, Department of Radiology, Winnipeg (Canada); Jain, Rajan [NYU School of Medicine, Division of Neuroradiology, Department of Radiology, New York, NY (United States); Puigdemont, Montserrat [Hospital Universitari Dr Josep Trueta, Catalan Institute of Oncology (ICO), Hospital Cancer Registry, Girona (Spain); Sanchez-Gonzalez, Javier [Philips Healthcare Iberica, Madrid (Spain); Wintermark, Max [Stanford University, Department of Radiology, Neuroradiology Division, Palo Alto, CA (United States)

    2016-01-15

    The objective of the study was to determine whether tumor-associated neovascularization on high-resolution gadofosveset-enhanced magnetic resonance angiography (MRA) is a useful biomarker for predicting survival in patients with newly diagnosed glioblastomas. Before treatment, 35 patients (25 men; mean age, 64 ± 14 years) with glioblastoma underwent MRI including first-pass dynamic susceptibility contrast (DSC) perfusion and post-contrast T1WI sequences with gadobutrol (0.1 mmol/kg) and, 48 h later, high-resolution MRA with gadofosveset (0.03 mmol/kg). Volumes of interest for contrast-enhancing lesion (CEL), non-CEL, and contralateral normal-appearing white matter were obtained, and DSC perfusion and DWI parameters were evaluated. Prognostic factors were assessed by Kaplan-Meier survival and Cox proportional hazards model. Eighteen (51.42 %) glioblastomas were hypervascular on high-resolution MRA. Hypervascular glioblastomas were associated with higher CEL volume and lower Karnofsky score. Median survival rates for patients with hypovascular and hypervascular glioblastomas treated with surgery, radiotherapy, and chemotherapy were 15 and 9.75 months, respectively (P < 0.001). Tumor-associated neovascularization was the best predictor of survival at 5.25 months (AUC = 0.794, 81.2 % sensitivity, 77.8 % specificity, 76.5 % positive predictive value, 82.4 % negative predictive value) and yielded the highest hazard ratio (P < 0.001). Tumor-associated neovascularization detected on high-resolution blood-pool-contrast-enhanced MRA of newly diagnosed glioblastoma seems to be a useful biomarker that correlates with worse survival. (orig.)

  7. Amylase and blood cell-count hematological radiation-injury biomarkers in a rhesus monkey radiation model-use of multiparameter and integrated biological dosimetry

    International Nuclear Information System (INIS)

    Effective medical management of suspected radiation exposure incidents requires the recording of dynamic medical data (clinical signs and symptoms), biological assessments of radiation exposure, and physical dosimetry in order to provide diagnostic information to the treating physician and dose assessment for personnel radiation protection records. The need to rapidly assess radiation dose in mass-casualty and population-monitoring scenarios prompted an evaluation of suitable biomarkers that can provide early diagnostic information after exposure. We investigated the utility of serum amylase and hematological blood-cell count biomarkers to provide early assessment of severe radiation exposures in a non-human primate model (i.e., rhesus macaques; n=8) exposed to whole-body radiation of 60Co-gamma rays (6.5 Gy, 40cGymin-1). Serum amylase activity was significantly elevated (12.3±3.27- and 2.6±0.058-fold of day zero samples) at 1 and 2-days, respectively, after radiation. Lymphocyte cell counts decreased (≤15% of day zero samples) 1 and 2 days after radiation exposure. Neutrophil cell counts increased at day one by 1.9(±0.38)-fold compared with levels before irradiation. The ratios of neutrophil to lymphocyte cell counts increased by 13(±2.66)- and 4.23(±0.95)-fold at 1 and 2 days, respectively, after irradiation. These results demonstrate that increases in serum amylase activity along with decreases of lymphocyte counts, increases in neutrophil cell counts, and increases in the ratio of neutrophil to lymphocyte counts 1 day after irradiation can provide enhanced early triage discrimination of individuals with severe radiation exposure and injury. Use of the biodosimetry assessment tool (BAT) application is encouraged to permit dynamic recording of medical data in the management of a suspected radiological casualty

  8. High-resolution blood-pool-contrast-enhanced MR angiography in glioblastoma: tumor-associated neovascularization as a biomarker for patient survival. A preliminary study

    International Nuclear Information System (INIS)

    The objective of the study was to determine whether tumor-associated neovascularization on high-resolution gadofosveset-enhanced magnetic resonance angiography (MRA) is a useful biomarker for predicting survival in patients with newly diagnosed glioblastomas. Before treatment, 35 patients (25 men; mean age, 64 ± 14 years) with glioblastoma underwent MRI including first-pass dynamic susceptibility contrast (DSC) perfusion and post-contrast T1WI sequences with gadobutrol (0.1 mmol/kg) and, 48 h later, high-resolution MRA with gadofosveset (0.03 mmol/kg). Volumes of interest for contrast-enhancing lesion (CEL), non-CEL, and contralateral normal-appearing white matter were obtained, and DSC perfusion and DWI parameters were evaluated. Prognostic factors were assessed by Kaplan-Meier survival and Cox proportional hazards model. Eighteen (51.42 %) glioblastomas were hypervascular on high-resolution MRA. Hypervascular glioblastomas were associated with higher CEL volume and lower Karnofsky score. Median survival rates for patients with hypovascular and hypervascular glioblastomas treated with surgery, radiotherapy, and chemotherapy were 15 and 9.75 months, respectively (P < 0.001). Tumor-associated neovascularization was the best predictor of survival at 5.25 months (AUC = 0.794, 81.2 % sensitivity, 77.8 % specificity, 76.5 % positive predictive value, 82.4 % negative predictive value) and yielded the highest hazard ratio (P < 0.001). Tumor-associated neovascularization detected on high-resolution blood-pool-contrast-enhanced MRA of newly diagnosed glioblastoma seems to be a useful biomarker that correlates with worse survival. (orig.)

  9. Hybrid Chirped Pulse Amplification

    Energy Technology Data Exchange (ETDEWEB)

    Jovanovic, I; Barty, C P J

    2002-05-07

    We present a novel chirped pulse amplification method which combines optical parametric amplification and laser amplification. We have demonstrated this hybrid CPA concept with a combination of beta-barium borate and Ti:sapphire. High-efficiency, multi-terawatt compatible amplification is achieved without gain narrowing and without electro-optic modulators using a simple commercial pump laser.

  10. Modulatory effect of pineapple peel extract on lipid peroxidation,catalase activity and hepatic biomarker levels in blood plasma of alcoholinduced oxidative stressed rats

    Institute of Scientific and Technical Information of China (English)

    Okafor; OY; Erukainure; OL; Ajiboye; JA; Adejobi; RO; Owolabi; FO; Kosoko; SB

    2011-01-01

    Objective:To investigate the ability of the methanolic extract of pineapple peel to modulate alcohol-induced lipid peroxidation,changes in catalase activities and hepatic biochemical marker levels in blood plasma.Methods:Oxidative stress was induced by oral administration of ethanol(20%w/v) at a dosage of 5 niL/kg bw in rats.After 28 days of treatment,the rats were fasted overnight and sacrificed by cervical dislocation.Blood was collected with a 2 mL syringe by cardiac puncture and was centrifuged at 3000 rpm for 10 min.The plasma was analyzed to evaluate malondialdehyde(MDA),catalase activity,aspartate aminotransferase(AST),alkaline phosphatase(ALP) and alanine aminotransferase(ALT) concentrations.Results:Administration of alcohol caused a drastic increase(87.74%) in MDA level compared with the control.Pineapple peel extract significantly reduced the MDA level by 60.16%at 2.S mL/kg bw.Rats fed alcohol only had the highest catalase activity,treatment with pineapple peel extract at 2.5 mL/kg bw however, reduced the activity.Increased AST,ALP and ALT activities were observed in rats fed alcohol only respectively,treatment with pineapple peel extract drastically reduced their activities. Conclusions:The positive modulation of lipid peroxidation,catalase activities as well as hepatic biomarker levels of blood plasma by the methanolic extract of pineapple peels under alcoholinduced oxidative stress is an indication of its protective ability in the management of alcoholinduced toxicity.

  11. Effect of exposure to contaminated pond sediments on survival, development, and enzyme and blood biomarkers in veined treefrog (Trachycephalus typhonius) tadpoles.

    Science.gov (United States)

    Peltzer, Paola M; Lajmanovich, Rafael C; Attademo, Andrés M; Junges, Celina M; Cabagna-Zenklusen, Mariana C; Repetti, María R; Sigrist, María E; Beldoménico, Horacio

    2013-12-01

    Sediments are important elements of aquatic ecosystems and in general sediments accumulate diverse toxic substances. Amphibians potentially have a greater risk of exposure to contaminants in sediments, and the test of sediments provides first lines of evidences. Sediment outdoor microcosm experiments were conducted to analyze biological endpoints (survival, development, growth, and morphological and organ malformation), enzyme activity (butyrylcholinesterase, BChE; glutathione-S-transferase, GST; and catalase, CAT) and blood biomarkers in veined treefrog Trachycephalus typhonius tadpoles, a widespread neotropical species. Hatching (stage 23) of T. thyphonius was exposed until they reached metamorphosis (stage 46). Sediment tests were performed and four different treatments were used: three ponds (LTPA, ISP, and SSP) influenced by industrial and agricultural activities and a reference treatment from a forest (RFS). Physical and chemical variables and concentration of nutrients, pesticide residues, and metals were determined. One treatment was metal-rich (LPTA) and two were nutrient-rich (ISP and SSP). Sediment treatments had no significant effect on survival; in contrast they had significant sublethal effects on T. typhonius larval development and growth rates, and affected overall size and shape at stage 38. Principally, in LPTA animals were significantly larger than in RFS, exhibiting swollen bodies, tail muscles and tail fin. In addition, metamorphs from LPTA, ISP, and SSP were smaller and showed signs of emaciation by the end of the experiment. Statistical comparisons showed that the proportions of each type of morphological abnormalities (swollen bodies and diamond shape, gut uncoiling, diverted gut, stiff tails, polydactyly, and visceral and hindlimb hemorrhaging) were significantly greater in metal- and nutrient-rich sediment treatments. Moreover, activities of BChE, GST and CAT, as well as and presence of micronuclei, immature, mitotic, anucleated

  12. Peripheral Blood Mitochondrial DNA as a Biomarker of Cerebral Mitochondrial Dysfunction following Traumatic Brain Injury in a Porcine Model.

    Directory of Open Access Journals (Sweden)

    Todd J Kilbaugh

    Full Text Available Traumatic brain injury (TBI has been shown to activate the peripheral innate immune system and systemic inflammatory response, possibly through the central release of damage associated molecular patterns (DAMPs. Our main purpose was to gain an initial understanding of the peripheral mitochondrial response following TBI, and how this response could be utilized to determine cerebral mitochondrial bioenergetics. We hypothesized that TBI would increase peripheral whole blood relative mtDNA copy number, and that these alterations would be associated with cerebral mitochondrial bioenergetics triggered by TBI.Blood samples were obtained before, 6 h after, and 25 h after focal (controlled cortical impact injury: CCI and diffuse (rapid non-impact rotational injury: RNR TBI. PCR primers, unique to mtDNA, were identified by aligning segments of nuclear DNA (nDNA to mtDNA, normalizing values to nuclear 16S rRNA, for a relative mtDNA copy number. Three unique mtDNA regions were selected, and PCR primers were designed within those regions, limited to 25-30 base pairs to further ensure sequence specificity, and measured utilizing qRT-PCR.Mean relative mtDNA copy numbers increased significantly at 6 and 25 hrs after following both focal and diffuse traumatic brain injury. Specifically, the mean relative mtDNA copy number from three mitochondrial-specific regions pre-injury was 0.84 ± 0.05. At 6 and 25 h after diffuse non-impact TBI, mean mtDNA copy number was significantly higher: 2.07 ± 0.19 (P < 0.0001 and 2.37 ± 0.42 (P < 0.001, respectively. Following focal impact TBI, relative mtDNA copy number was also significantly higher, 1.35 ± 0.12 (P < 0.0001 at 25 hours. Alterations in mitochondrial respiration in the hippocampus and cortex post-TBI correlated with changes in the relative mtDNA copy number measured in peripheral blood.Alterations in peripheral blood relative mtDNA copy numbers may be a novel biosignature of cerebral mitochondrial bioenergetics

  13. Blood plasma clinical-chemical parameters as biomarker endpoints for organohalogen contaminant exposure in Norwegian raptor nestlings

    DEFF Research Database (Denmark)

    Sonne, Christian; Bustnes, Jan O; Herzke, Dorte;

    2012-01-01

    ), golden eagle (n=12) and white-tailed eagle (n=36) nestlings during three consecutive breeding seasons. We found that blood plasma concentrations of calcium, sodium, creatinine, cholesterol, albumin, total protein, urea, inorganic phosphate, protein:creatinine, urea:creatinine and uric acid...... it is uncertain if such changes have any health effects. The OHC concentrations were below concentrations causing reproductive toxicity in adults of other raptor species but similar to those of concern for endocrine disruption of thyroid hormones in e.g., bald eagles....

  14. Use of γ-H2AX Foci Assay on Human Peripheral Blood Lymphocytes as Sensitive Biomarker of Exposure

    International Nuclear Information System (INIS)

    In modern medicine, it is impossible to imagine diagnostics and treatments without equipment that emit radiation (X-ray, CT, PET, etc.). At the same time there is a need to minimize the amount of radiation that the patient will gain during such medical examination. In that manner ALARA (As Low As Reasonably Achievable) principle and dosimetry are the bases of assuring patients safety. The induction of gamma phosphorylated H2AX histone is newly developed tool in biodosimetry, which is more sensitive for the detection of radiation caused DNA damage than currently used micronucleus and comet assay. Gamma phosphorylation of H2AX histone is a consequence of DNA double strand breaks and its role is to trigger the DNA repair mechanisms. In this study, we tested the effect of 2 and 4 Gy X-rays on human peripheral blood lymphocytes from two healthy volunteers using γ-H2AX foci assay. The FITC signal from labelled antibodies was monitored using flow cytometry and clearly demonstrated the difference in control samples and irradiated samples. There was also the difference between the exposed blood samples from the two volunteers. The results of present study reveal new sensitive method that is capable of detecting changes in DNA when exposed to different doses of radiation, and thus potentially optimizing the ALARA principle.(author)

  15. Brain magnetic resonance imaging and manganese concentrations in red blood cells of smelting workers: search for biomarkers of manganese exposure.

    Science.gov (United States)

    Jiang, Yueming; Zheng, Wei; Long, Liling; Zhao, Weijia; Li, Xiangrong; Mo, Xuean; Lu, Jipei; Fu, Xue; Li, Wenmei; Liu, Shouting; Long, Quanyong; Huang, Jinli; Pira, Enrico

    2007-01-01

    The MRI technique has been used in diagnosis of manganism in humans and non-human primates. This cross-sectional study was designed to explore whether the pallidal signal intensity in T1-weighted MRI correlated with Mn levels in the blood compartment among Mn-exposed workers and to understand to what extent the MRI signal could reflect Mn exposure. A group of 18 randomly selected male Mn-exposed workers of which 13 were smelting workers with high exposure (mean of airborne Mn in work place: 1.26 mg/m3; range: 0.31-2.93 mg/m3), and 5 power distribution control workers with low exposure (0.66 mg/m3 and 0.23-0.77 mg/m3) from a ferroalloy factory, and another group of 9 male subjects as controls from a non-smelting factory who were office or cafeteria workers (0.01 mg/m3 and 0-0.03 mg/m3) were recruited for neurological tests, MRI examination, and analysis of Mn in whole blood (MnB), plasma (MnP) or red blood cells (MnRBC). No clinical symptoms and signs of manganism were observed among these workers. MRI data showed average increases of 7.4% (p<0.05) and 16.1% (p<0.01) in pallidal index (PI) among low- and high-exposed workers, respectively, as compared to controls. Fourteen out of 18 Mn-exposed workers (78%) had intensified PI values, while this proportion was even higher (85%) among the high Mn-exposed workers. Among exposed workers, the PI values were significantly associated with MnRBC (r=0.55, p=0.02). Our data suggest that the workers exposed to airborne Mn, but without clinical symptoms, display an exposure-related, intensified MRI signal. The MRI, as well as MnRBC, may be useful in early diagnosis of Mn exposure. PMID:16978697

  16. Blood parameter analysis and morphological alterations as biomarkers on the health of Hoplias malabaricus and Geophagus brasiliensis

    Directory of Open Access Journals (Sweden)

    Silvia Romão

    2006-05-01

    Full Text Available This study aimed to assess the influence of the environment on fish health. Samples of Hoplias malabaricus and Geophagus brasiliensis, were collected from three different environments: area I was urban and areas II and III were rural. Analyses of red blood cell count, microhematocrit, hemoglobin concentration, white blood cell count and differential white cell count in blood smear were carried out. Mean corpuscular volume and mean corpuscular hemoglobin concentration were calculated. To analyze morphological alterations, gills, liver, kidney and gonads were submitted to routine histological processing. Individuals collected from area III had slightly lower blood indices than collected from area I . Severe kidney changes, degeneration of and crystallization within kidney tubules were observed. In area I, crystallization was observed in 92% of the specimens of G. brasiliensis. These results suggested that such alterations were related with poor water circulation in the place.Este trabalho teve como objetivo avaliar a influência do ambiente sobre a higidez dos peixes. Animais, das espécies Hoplias malabaricus e Geophagus brasiliensis foram coletados em três ambientes distintos, sendo ambiente I região urbana e ambientes II e III em região rural. Foram realizadas análises do número total de eritrócitos por microlitro de sangue, microhematócrito, taxa de hemoglobina, porcentagem de leucócito e contagem diferencial de leucócitos em extensão sanguínea. Calcularam-se os índices hematimétricos absolutos: volume corpuscular médio e concentração de hemoglobina corpuscular média. Para análises das alterações morfológicas, brânquias, fígado, gônadas e rim seguiram processamento histológico de rotina. Foram observados índices hematológicos ligeiramente menores em indivíduos coletados no ambiente III em relação aos animais coletados no ambiente I. As análises histológicas de brânquias, fígado e gônadas das espécies G

  17. Effect of supranutritional organic selenium supplementation on postpartum blood micronutrients, antioxidants, metabolites, and inflammation biomarkers in selenium-replete dairy cows.

    Science.gov (United States)

    Hall, Jean A; Bobe, Gerd; Vorachek, William R; Kasper, Katherine; Traber, Maret G; Mosher, Wayne D; Pirelli, Gene J; Gamroth, Mike

    2014-12-01

    Dairy cows have increased nutritional requirements for antioxidants postpartum. Supranutritional organic Se supplementation may be beneficial because selenoproteins are involved in regulating oxidative stress and inflammation. Our objective was to determine whether feeding Se-yeast above requirements to Se-replete dairy cows during late gestation affects blood micronutrients, antioxidants, metabolites, and inflammation biomarkers postpartum. During the last 8-weeks before calving, dairy cows at a commercial farm were fed either 0 (control) or 105 mg Se-yeast once weekly (supranutritional Se-yeast), in addition to Na selenite at 0.3 mg Se/kg dry matter in their rations. Concentrations of whole-blood (WB) Se and serum Se, erythrocyte glutathione (GSH), and serum albumin, cholesterol, α-tocopherol, haptoglobin, serum amyloid A (SAA), calcium, magnesium, phosphorus, non-esterified fatty acids, and β-hydroxybutyrate were measured directly after calving, at 48 h, and 14 days of lactation in 10 cows of each group. Supranutritional Se-yeast supplementation affected indicators of antioxidant status and inflammation. Cows fed a supranutritional Se-yeast supplement during the last 8-weeks of gestation had higher Se concentrations in WB (overall 52 % higher) and serum (overall 36 % higher) at all-time points, had higher SAA concentrations at 48 h (98 % higher), had higher erythrocyte GSH (38 % higher) and serum albumin concentrations (6.6 % higher) at 14 days, and had lower serum cholesterol concentrations and higher α-tocopherol/cholesterol ratios at calving and at 48 h compared with control cows. In conclusion, feeding Se-replete cows during late gestation a supranutritional Se-yeast supplement improves antioxidant status and immune responses after calving without negatively impacting other micronutrients and energy status.

  18. Simultaneous Analysis of SEPT9 Promoter Methylation Status, Micronuclei Frequency, and Folate-Related Gene Polymorphisms: The Potential for a Novel Blood-Based Colorectal Cancer Biomarker

    Directory of Open Access Journals (Sweden)

    Gloria Ravegnini

    2015-12-01

    Full Text Available One challenge in colorectal cancer (CRC is identifying novel biomarkers to be introduced in screening programs. The present study investigated the promoter methylation status of the SEPT9 gene in peripheral blood samples of subjects’ positive fecal occult blood test (FOBT. In order to add new insights, we investigated the association between SEPT9 promoter methylation and micronuclei frequency, and polymorphisms in the folate-related pathway genes. SEPT9 promoter methylation, micronuclei frequency, and genotypes were evaluated on 74 individuals’ FOBT positive. Individuals were subjected to a colonoscopy that provided written informed consent for study participation. SEPT9 promoter methylation status was significantly lower in the CRC group than controls (p = 0.0006. In contrast, the CaCo2 cell-line, analyzed as a tissue specific model of colon adenocarcinoma, showed a significantly higher percentage of SEPT9 promoter methylation compared to the CRC group (p < 0.0001. Linear regression analysis showed an inverse correlation between micronuclei frequency and the decrease in the methylation levels of SEPT9 promoter region among CRC patients (β = −0.926, p = 0.0001. With regard to genotype analysis, we showed the involvement of the DHFR polymorphism (rs70991108 in SEPT9 promoter methylation level in CRC patients only. In particular, the presence of at least one 19 bp del allele significantly correlates with decreased SEPT9 promoter methylation, compared to the 19 bp ins/ins genotype (p = 0.007. While remaining aware of the strengths and limitations of the study, this represents the first evidence of a novel approach for the early detection of CRC, using SEPT9 promoter methylation, micronuclei frequency and genotypes, with the potential to improve CRC risk assessment.

  19. Simultaneous Analysis of SEPT9 Promoter Methylation Status, Micronuclei Frequency, and Folate-Related Gene Polymorphisms: The Potential for a Novel Blood-Based Colorectal Cancer Biomarker.

    Science.gov (United States)

    Ravegnini, Gloria; Zolezzi Moraga, Juan Manuel; Maffei, Francesca; Musti, Muriel; Zenesini, Corrado; Simeon, Vittorio; Sammarini, Giulia; Festi, Davide; Hrelia, Patrizia; Angelini, Sabrina

    2015-12-01

    One challenge in colorectal cancer (CRC) is identifying novel biomarkers to be introduced in screening programs. The present study investigated the promoter methylation status of the SEPT9 gene in peripheral blood samples of subjects' positive fecal occult blood test (FOBT). In order to add new insights, we investigated the association between SEPT9 promoter methylation and micronuclei frequency, and polymorphisms in the folate-related pathway genes. SEPT9 promoter methylation, micronuclei frequency, and genotypes were evaluated on 74 individuals' FOBT positive. Individuals were subjected to a colonoscopy that provided written informed consent for study participation. SEPT9 promoter methylation status was significantly lower in the CRC group than controls (p = 0.0006). In contrast, the CaCo2 cell-line, analyzed as a tissue specific model of colon adenocarcinoma, showed a significantly higher percentage of SEPT9 promoter methylation compared to the CRC group (p < 0.0001). Linear regression analysis showed an inverse correlation between micronuclei frequency and the decrease in the methylation levels of SEPT9 promoter region among CRC patients (β = -0.926, p = 0.0001). With regard to genotype analysis, we showed the involvement of the DHFR polymorphism (rs70991108) in SEPT9 promoter methylation level in CRC patients only. In particular, the presence of at least one 19 bp del allele significantly correlates with decreased SEPT9 promoter methylation, compared to the 19 bp ins/ins genotype (p = 0.007). While remaining aware of the strengths and limitations of the study, this represents the first evidence of a novel approach for the early detection of CRC, using SEPT9 promoter methylation, micronuclei frequency and genotypes, with the potential to improve CRC risk assessment.

  20. Biomarkers of oxidative stress and acetylcholinesterase activity in the blood of grass snake (Natrix natrix L. during prehibernation and posthibernation periods

    Directory of Open Access Journals (Sweden)

    Jelena Gavric

    2015-06-01

    Full Text Available This work examined the enzymatic (superoxide dismutase-CuZn SOD, catalase-CAT, glutathione peroxidase-GSHPx, glutathione reductase-GR, and the biotransformation phase II enzyme glutathione-S-transferase-GST and nonenzymatic (total glutathione-GSH and lipid peroxides-TBARS concentrations biomarkers of oxidative stress and acetylcholinesterase (AChE activity in the blood of the grass snake (Natrix natrix L. during prehibernation and posthibernation. The animals were collected in October (prehibernation and April (posthibernation at the nature reserve Obedska Bara (OB and industrial region Pancevacki Rit (PR in Serbia. In posthibernation, decreased CAT activity and TBARS concentration in specimens from PR, and decreased GR and AChE activities, and TBARS concentration in specimens from OB were observed, whereas GR and GST activities and GSH concentration were significantly elevated in the specimens from PR. In prehibernation, CAT activity and GSH concentration were increased, while GSH-Px, GR, GST and AChE activities and TBARS concentration were decreased in the specimens from PR when compared to animals from OB. During the posthibernation, the activity of CuZn SOD was decreased, while GST and AChE activities were increased in the specimens from PR when compared to the specimens from OB. These differences represented an adaptive mechanism to oxidative stress induced by tissue reoxygenation during arousal from hibernation and could be modulated by environmental pollution.

  1. [Biomarkers in Alzheimer's disease].

    Science.gov (United States)

    García-Ribas, G; López-Sendón Moreno, J L; García-Caldentey, J

    2014-04-01

    The new diagnostic criteria for Alzheimer's disease (AD) include brain imaging and cerebrospinal fluid (CSF) biomarkers, with the aim of increasing the certainty of whether a patient has an ongoing AD neuropathologic process or not. Three CSF biomarkers, Aß42, total tau, and phosphorylated tau, reflect the core pathological features of AD. It is already known that these pathological processes of AD starts decades before the first symptoms, so these biomarkers may provide means of early disease detection. At least three stages of AD could be identified: preclinical AD, mild cognitive impairment due to AD, and dementia due to AD. In this review, we aim to summarize the CSF biomarker data available for each of these stages. We also review the actual research on blood-based biomarkers. Recent studies on healthy elderly subjects and on carriers of dominantly inherited AD mutations have also found biomarker changes that allow separate groups in these preclinical stages. These studies may aid for segregate populations in clinical trials and objectively evaluate if there are changes over the pathological processes of AD. Limits to widespread use of CSF biomarkers, apart from the invasive nature of the process itself, is the higher coefficient of variation for the analyses between centres. It requires strict pre-analytical and analytical procedures that may make feasible multi-centre studies and global cut-off points for the different stages of AD.

  2. High Dietary Iron and Radiation Exposure Increase Biomarkers of Oxidative Stress in Blood and Liver of Rats

    Science.gov (United States)

    Morgan, Jennifer L. L.; Theriot, Corey A.; Wu, Honglu; Smith, Scott M.; Zwart, Sara R.

    2012-01-01

    Radiation exposure and increased iron (Fe) status independently cause oxidative damage that can result in protein, lipid, and DNA oxidation. During space flight astronauts are exposed to both increased radiation and increased Fe stores. Increased body Fe results from a decrease in red blood cell mass and the typically high Fe content of the food system. In this study we investigated the combined effects of radiation exposure (0.375 Gy of Cs-137 every other day for 16 days for a total of 3 Gy) and high dietary Fe (650 mg Fe/kg diet compared to 45 mg Fe/kg for controls) in Sprague-Dawley rats (n=8/group). Liver and serum Fe were significantly increased in the high dietary Fe groups. Likewise, radiation treatment increased serum ferritin and Fe concentrations. These data indicate that total body Fe stores increase with both radiation exposure and excess dietary Fe. Hematocrit decreased in the group exposed to radiation, providing a possible mechanism for the shift in Fe indices after radiation exposure. Markers of oxidative stress were also affected by both radiation and high dietary Fe, evidenced by increased liver glutathione peroxidase (GPX) and serum catalase as well as decreased serum GPX. We thus found preliminary indications of synergistic effects of radiation exposure and increased dietary Fe, warranting further study. This study was funded by the NASA Human Research Project.

  3. Establishment of Elevated Serum Levels of IL-10, IL-8 and TNF-β as Potential Peripheral Blood Biomarkers in Tubercular Lymphadenitis: A Prospective Observational Cohort Study

    Science.gov (United States)

    Abhimanyu; Bose, Mridula; Varma-Basil, Mandira; Jain, Ashima; Sethi, Tavpritesh; Tiwari, Pradeep Kumar; Agrawal, Anurag; Banavaliker, Jayant Nagesh; Bhowmick, Kumar Tapas

    2016-01-01

    Background Tubercular lymphadenitis (TL) is the most common form of extra-pulmonary tuberculosis (TB) consisting about 15–20% of all TB cases. The currently available diagnostic modalities for (TL), are invasive and involve a high index of suspicion, having limited accuracy. We hypothesized that TL would have a distinct cytokine signature that would distinguish it from pulmonary TB (PTB), peripheral tubercular lymphadenopathy (LNTB), healthy controls (HC), other lymphadenopathies (LAP) and cancerous LAP. To assess this twelve cytokines (Tumor Necrosis Factor (TNF)—α, Interferon (IFN) -γ, Interleukin (IL)-2, IL-12, IL-18, IL-1β, IL-10, IL-6, IL-4, IL-1Receptor antagonist (IL-1Ra), IL-8 and TNF-β, which have a role in pathogenesis of tuberculosis, were tested as potential peripheral blood biomarkers to aid the diagnosis of TL when routine investigations prove to be of limited value. Methods and Findings A prospective observational cohort study carried out during 2010–2013. This was a multi-center study with three participating hospitals in Delhi, India where through random sampling cohorts were established. The subjects were above 15 years of age, HIV-negative with no predisposing ailments to TB (n = 338). The discovery cohort (n = 218) had LNTB (n = 50), PTB (n = 84) and HC (n = 84). The independent validation cohort (n = 120) composed of patients with cancerous LAP (n = 35), other LAP (n = 20) as well as with independent PTB (n = 30), LNTB (n = 15) and HC (n = 20). Eight out of twelve cytokines achieved statistical relevance upon evaluation by pairwise and ROC analysis. Further, variable selection using random forest backward elimination revealed six serum biosignatures including IL-12, IL-4, IL-6, IL-10, IL-8 and TNF-β as optimal for classifying the LNTB status of an individual. For the sake of clinical applicability we further selected a three analyte panel (IL-8, IL-10 and TNF-β) which was subjected to multinomial modeling in the independent

  4. Whole blood defensin mRNA expression is a predictive biomarker of docetaxel response in castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Kohli M

    2015-07-01

    Full Text Available Manish Kohli,1 Charles YF Young,2 Donald J Tindall,2 Debashis Nandy,1 Kyle M McKenzie,3 Graham H Bevan,4 Krishna Vanaja Donkena5 1Department of Oncology, 2Department of Urology, 3Department of Geriatric Medicine, Mayo Clinic, Rochester, MN, 4University of Rochester Medical Center, Rochester, NY, 5Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA Abstract: This study tested the potential of circulating RNA-based signals as predictive biomarkers for docetaxel response in patients with metastatic castration-resistant prostate cancer (CRPC. RNA was analyzed in blood from six CRPC patients by whole-transcriptome sequencing (total RNA-sequencing before and after docetaxel treatment using the Illumina’s HiSeq platform. Targeted RNA capture and sequencing was performed in an independent cohort of ten patients with CRPC matching the discovery cohort to confirm differential expression of the genes. Response to docetaxel was defined on the basis of prostate-specific antigen levels and imaging criteria. Two-way analysis of variance was used to compare differential gene expression in patients classified as responders versus nonresponders before and after docetaxel treatment. Thirty-four genes with two-fold differentially expressed transcripts in responders versus nonresponders were selected from total RNA-sequencing for further validation. Targeted RNA capture and sequencing showed that 13/34 genes were differentially expressed in responders. Alpha defensin genes DEFA1, DEFA1B, and DEFA3 exhibited significantly higher expression in responder patients compared with nonresponder patients before administration of chemotherapy (fold change >2.5. In addition, post-docetaxel treatment significantly increased transcript levels of these defensin genes in responders (fold change >2.8. Our results reveal that patients with higher defensin RNA transcripts in blood respond well to docetaxel therapy. We suggest that monitoring DEFA1, DEFA1B, and DEFA3

  5. Effects of Four-Week Supplementation with a Multi-Vitamin/Mineral Preparation on Mood and Blood Biomarkers in Young Adults: A Randomised, Double-Blind, Placebo-Controlled Trial.

    Science.gov (United States)

    White, David J; Cox, Katherine H M; Peters, Riccarda; Pipingas, Andrew; Scholey, Andrew B

    2015-11-01

    This study explored the effects of four-week multi-vitamin and mineral (MVM) supplementation on mood and neurocognitive function in healthy, young adults. Fifty-eight healthy adults, 18-40 years of age (M = 25.82 years, SD = 4.87) participated in this randomised, double-blind, placebo-controlled trial, in which mood and blood biomarkers were assessed at baseline and after four weeks of supplementation. Compared to placebo, MVM supplementation was associated with significantly lowered homocysteine and increased blood B-vitamin levels (p supplementation may have beneficial effects on mood, underpinned by elevated B-vitamins and lowered homocysteine in healthy young adults. PMID:26529011

  6. Effects of Four-Week Supplementation with a Multi-Vitamin/Mineral Preparation on Mood and Blood Biomarkers in Young Adults: A Randomised, Double-Blind, Placebo-Controlled Trial.

    Science.gov (United States)

    White, David J; Cox, Katherine H M; Peters, Riccarda; Pipingas, Andrew; Scholey, Andrew B

    2015-10-30

    This study explored the effects of four-week multi-vitamin and mineral (MVM) supplementation on mood and neurocognitive function in healthy, young adults. Fifty-eight healthy adults, 18-40 years of age (M = 25.82 years, SD = 4.87) participated in this randomised, double-blind, placebo-controlled trial, in which mood and blood biomarkers were assessed at baseline and after four weeks of supplementation. Compared to placebo, MVM supplementation was associated with significantly lowered homocysteine and increased blood B-vitamin levels (p vitamins and lowered homocysteine in healthy young adults.

  7. Effect of consuming a purple-fleshed sweet potato beverage on health-related biomarkers and safety parameters in Caucasian subjects with elevated levels of blood pressure and liver function biomarkers: a 4-week, open-label, non-comparative trial.

    Science.gov (United States)

    Oki, Tomoyuki; Kano, Mitsuyoshi; Watanabe, Osamu; Goto, Kazuhisa; Boelsma, Esther; Ishikawa, Fumiyasu; Suda, Ikuo

    2016-01-01

    An open-label study with one treatment arm was conducted to investigate changes in health-related biomarkers (blood pressure and liver enzyme activity) and the safety of 4 weeks of consuming a purple-fleshed sweet potato beverage in Caucasian subjects. Twenty healthy adults, 18-70 years of age, with a body mass index >25 kg/m(2), elevated blood pressure and elevated levels of liver function biomarkers consumed two cartons of purple-fleshed sweet potato beverage (125 ml, including 117 mg anthocyanin per carton) daily for 4 weeks. Hematology, serum clinical profile, dipstick urinalysis and blood pressure were determined before consumption, at 2 and 4 weeks of consumption and after a 2-week washout period. A trend was found toward lowering systolic blood pressure during the treatment period (p=0.0590). No significant changes were found in diastolic blood pressure throughout the study period. Systolic blood pressure was significantly lower after 4 weeks of consumption compared with before consumption (p=0.0125) and was significantly higher after the 2-week washout period compared with after consumption (p=0.0496). The serum alanine aminotransferase level significantly increased over time, but aspartate aminotransferase and γ-glutamyltransferase levels stayed within the normal range of reference values. Safety parameters of the blood and urine showed no clinically relevant changes. The consumption of a purple-fleshed sweet potato beverage for 4 weeks resulted in no clinically relevant changes in safety parameters of the blood and urine and showed a trend toward lowering systolic blood pressure. PMID:27508114

  8. Detection of disseminated pancreatic cells by amplification of cytokeratin-19 with quantitative RT-PCR in blood, bone marrow and peritoneal lavage of pancreatic carcinoma patients

    Institute of Scientific and Technical Information of China (English)

    Katrin Hoffmann; Christiane Kerner; Wolfgang Wilfert; Marc Mueller; Joachim Thiery; Johann Hauss; Helmut Witzigmann

    2007-01-01

    AIM: To evaluate the diagnostic potential of cytokeratin-19 (CK-19) mRNA for the detection of disseminated tumor cells in blood, bone marrow and peritoneal lavage in patients with ductal adenocarcinoma of the pancreas.METHODS: Sixty-eight patients with pancreatic cancer (n = 37), chronic pancreatitis (n = 16), and non-pancreatic benign surgical diseases (n = 15, control group)were included in the study. Venous blood was taken preoperatively, intraoperatively and at postoperative d 1 and 10. Preoperative bone marrow aspirates and peritoneal lavage taken before mobilization of the tumor were analyzed. All samples were evaluated for disseminated tumor cells by CK-19-specific nested-PCR and quantitative fluorogenic RT-PCR.RESULTS: CK-19 mRNA expression was increased in 24 (64%) blood samples and 11 (30%) of the peritoneal lavage samples in the patients with pancreatic cancer.In 15 (40%) of the patients with pancreatic cancer,disseminated tumor cells were detected in venous blood and bone marrow and/or peritoneal lavage. In the peritoneal lavage, the detection rates were correlated with the tumor size and the tumor differentiation. CK-19 levels were increased in pT3/T4 and moderately/poorly differentiated tumors (G2/G3). Pancreatic cancer patients with at least one CK-19 mRNA-positive sample showed a trend towards shorter survival. Pancreatic cancer patients showed significantly increased detection rates of disseminated tumor cells in blood and peritoneal lavage compared to the controls and the patients with chronic pancreatitis.CONCLUSION: Disseminated tumor cells can be detected in patients with pancreatic ductal adenocarcinoma by CK-19 fluorogenic RT-PCR. In peritoneal lavage, detection rate is correlated with tumor stage and differentiation. In the clinical use, CK-19 is suitable for the distinction between malignant and benign pancreatic disease in combination with other tumor-specific markers.

  9. Study on screening blood donors by nucleic acid amplification technique combined with Enzyme- linked immunosorbent assay%核酸扩增与酶联免疫法联合在血液筛查中的初步应用

    Institute of Scientific and Technical Information of China (English)

    杜勇; 杨亮; 蒋炜; 王佳维; 张哲

    2012-01-01

    Objective;The purpose of this study was to improve security level of clinical blood transfusion and e-valuate the necessity and practicability of the testing methodology based on nucleic acid amplification technique (NAT) in addition to the regular immunoassay test (EIA). Methods; The samples tested as negative by ELISA were screened by NAT with two work flow ( single detection or combined detection). The NAT - positive samples were further tested by Roche COBAS CAP_CTM system and eletro - cheniluminescence(ECL) system to evaluate the virus load and serological properties. Results; 28 NAT-positive samples were detected in the 20,925 ELISA negative donor samples. All samples were HBV DNA positive and 11 among the 28 samples were serology positive. The remaining risk of HBV infection was 0.13% under the routine EIA test. Conclusion; The risk of HBV infection still remain under the current blood donor screening method using repeated ELISA testing. The introduction of NAT test can help to reduce the risk of transfusion - transmitted disease which has a great value to increase the safety of blood.%目的:在酶联免疫法( enzyme immunoassay,EIA)检测的基础上,探讨HBV核酸扩增检测(nucleic acid amplification testing NAT)技术应用于血液筛查的意义.方法:分别使用两种模式(单检或混检)NAT与EIA两遍检测方式同时进行血液筛查,对NAT阳性标本作进一步做鉴别试验和病毒血清标志物.结果:20925份EIA(-)标本共发现28份核酸三项(HBV DNA、HCV RNA、HIV RNA)呈反应性,均为HBV- DNA,即EIA两遍检测合格后的HBV- DNA阳性率0.13%,检测其中11份血清,乙肝标志物均呈阳性.结论:EIA阴性献血者中仍有极少数的HBV感染者,核酸扩增检测和酶联免疫检测互补能够检测出EIA漏检的HBV携带者,对提高HBsAg阴性血液标本中HBV感染检出率具有重要价值.

  10. Highly Sensitive and Selective Immuno-capture/Electrochemical Assay of Acetylcholinesterase Activity in Red Blood Cells: A Biomarker of Exposure to Organophosphorus Pesticides and Nerve Agents

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Aiqiong; Du, Dan; Lin, Yuehe

    2012-02-09

    Acetylcholinesterase (AChE) enzyme activity in red blood cells (RBCs) is a useful biomarker for biomonitoring of exposures to organophosphorus (OP) pesticides and chemical nerve agents. In this paper, we reported a new method for AChE activity assay based on selective immuno-capture of AChE from biological samples followed by enzyme activity assay of captured AChE using a disposable electrochemical sensor. The electrochemical sensor is based on multiwalled carbon nanotubes-gold nanocomposites (MWCNTs-Au) modified screen printed carbon electrode (SPCE). Upon the completion of immunoreaction, the target AChE (including active and inhibited) is captured onto the electrode surface and followed by an electrochemical detection of enzymatic activity in the presence of acetylthiocholine. A linear response is obtained over standard AChE concentration range from 0.1 to 10 nM. To demonstrate the capability of this new biomonitoring method, AChE solutions dosed with different concentration of paraoxon were used to validate the new AChE assay method. AChE inhibition in OP dosed solutions was proportional to its concentration from 0.2 to 50 nM. The new AChE activity assay method for biomonitoring of OP exposure was further validated with in-vitro paraoxon-dosed RBC samples. The established electrochemical sensing platform for AChE activity assay not only avoids the problem of overlapping substrate specificity with esterases by using selective antibody, but also eliminates potential interference from other electroactive species in biological samples. It offers a new approach for sensitive, selective, and rapid AChE activity assay for biomonitoring of exposures to OPs.

  11. Biomarkers for neuromyelitis optica.

    Science.gov (United States)

    Chang, Kuo-Hsuan; Ro, Long-Sun; Lyu, Rong-Kuo; Chen, Chiung-Mei

    2015-02-01

    Neuromyelitis optica (NMO) is an acquired, heterogeneous inflammatory disorder, which is characterized by recurrent optic neuritis and longitudinally extensive spinal cord lesions. The discovery of the serum autoantibody marker, anti-aquaporin 4 (anti-AQP4) antibody, revolutionizes our understanding of pathogenesis of NMO. In addition to anti-AQP4 antibody, other biomarkers for NMO are also reported. These candidate biomarkers are particularly involved in T helper (Th)17 and astrocytic damages, which play a critical role in the development of NMO lesions. Among them, IL-6 in the peripheral blood is associated with anti-AQP4 antibody production. Glial fibrillary acidic protein (GFAP) in CSF demonstrates good correlations with clinical severity of NMO relapses. Detecting these useful biomarkers may be useful in the diagnosis and evaluation of disease activity of NMO. Development of compounds targeting these biomarkers may provide novel therapeutic strategies for NMO. This article will review the related biomarker studies in NMO and discuss the potential therapeutics targeting these biomarkers.

  12. Maternal rumen-protected methionine supplementation and its effect on blood and liver biomarkers of energy metabolism, inflammation, and oxidative stress in neonatal Holstein calves.

    Science.gov (United States)

    Jacometo, C B; Zhou, Z; Luchini, D; Trevisi, E; Corrêa, M N; Loor, J J

    2016-08-01

    In nonruminants, nutrition during pregnancy can program offspring development, metabolism, and health in later life. Rumen-protected Met (RPM) supplementation during the prepartum period improves liver function and immune response in dairy cows. Our aim was to investigate the effects of RPM during late pregnancy on blood biomarkers (23 targets) and the liver transcriptome (24 genes) in neonatal calves from cows fed RPM at 0.08% of diet dry matter/d (MET) for the last 21 d before calving or controls (CON). Blood (n=12 calves per diet) was collected at birth before receiving colostrum (baseline), 24 h after receiving colostrum, 14, 28, and 50 d (post-weaning) of age. Liver was sampled (n=8 calves per diet) via biopsy on d 4, 14, 28, and 50 of age. Growth and health were not affected by maternal diet. The MET calves had greater overall plasma insulin concentration and lower glucose and ratios of glucose-to-insulin and fatty acids-to-insulin, indicating greater systemic insulin sensitivity. Lower concentration of reactive oxygen metabolites at 14 d of age along with a tendency for lower overall concentration of ceruloplasmin in MET calves indicated a lesser degree of stress. Greater expression on d 4 of fructose-bisphosphatase 1 (FBP1), phosphoenolpyruvate carboxykinase 1 (PCK1), and the facilitated bidirectional glucose transporter SLC2A2 in MET calves indicated alterations in gluconeogenesis and glucose uptake and release. The data agree with the greater expression of the glucocorticoid receptor (GR). Greater expression on d 4 of the insulin receptor (INSR) and insulin-responsive serine/threonine-protein kinase (AKT2) in MET calves indicated alterations in insulin signaling. In that context, the similar expression of sterol regulatory element-binding transcription factor 1 (SREBF1) in CON and MET during the preweaning period followed by the marked upregulation regardless of diet after weaning (d 50) support the idea of changes in hepatic insulin sensitivity during

  13. Urinary Biomarkers of Brain Diseases

    Directory of Open Access Journals (Sweden)

    Manxia An

    2015-12-01

    Full Text Available Biomarkers are the measurable changes associated with a physiological or pathophysiological process. Unlike blood, urine is not subject to homeostatic mechanisms. Therefore, greater fluctuations could occur in urine than in blood, better reflecting the changes in human body. The roadmap of urine biomarker era was proposed. Although urine analysis has been attempted for clinical diagnosis, and urine has been monitored during the progression of many diseases, particularly urinary system diseases, whether urine can reflect brain disease status remains uncertain. As some biomarkers of brain diseases can be detected in the body fluids such as cerebrospinal fluid and blood, there is a possibility that urine also contain biomarkers of brain diseases. This review summarizes the clues of brain diseases reflected in the urine proteome and metabolome.

  14. Cocultivation of umbilical cord blood CD34+ cells with retro-transduced hMSCs leads to effective amplification of long-term culture-initiating cells

    Institute of Scientific and Technical Information of China (English)

    Chun-Gang Xie; Jin-Fu Wang; Ying Xiang; Li-Yan Qiu; Bing-Bing Jia; Li-Juan Wang; Guo-Zhong Wang; Guo-Ping Huang

    2006-01-01

    AIM: To establish a novel coculture system for ex vivo expansion of umbilical cord blood(UCB) hematopoietic progenitors using thrombopoietin (TPO)/Flt-3 ligand(FL)-transduced human marrow-derived mesenchymal stem cells (tfhMSCs) as feeder.METHODS: UCB CD34+ cells were isolated and cultured using four culture systems in serum-containing or serumfree medium. Suitable aliquots of cultured cells were used to monitor cell production, clonogenic activity,and long-term culture-initiating culture (LTC-IC) output.Finally, the severe-combined immunodeficient (SCID)mouse-repopulating cell (SRC) assay was performed to confirm ability of the cultured cells to reconstitute longterm hematopoiesis.RESULTS: There were no significant differences in the number of total nucleated cells among different culture systems in serum-containing medium during 21-d culture. However, on d 14, the outputs of CD34+ cells,CFU-C and CFU-GEMM in tfhMSCs coculture system were significantly enhanced. LTC-IC assay demonstrated that the tfhMSCs coculture system had the most powerful activity. The severe-combined immunodeficient (SCID)mouse repopulating cell (SRC) assay confirmed extensive ability of the expanded cells to reconstitute long-term hematopoiesis. Furthermore, PCR analysis demonstrated the presence of human hematopoietic cells in the bone marrow and peripheral blood cells of NOD/SCID mice.CONCLUSION: The TPO/FL-transduced hMSCs, in combination with additive cytokines, can effectively expand hematopoietic progenitors from UCB in vitro and the tfhMSCs coculture system may be a suitable system for ex vivo manipulation of primitive progenitor cells under contact culture conditions.

  15. 核酸检测技术在血液筛查中的应用研究%Application on nucleic acid amplification testin blood screening

    Institute of Scientific and Technical Information of China (English)

    叶贤林; 郑欣; 熊文; 张红; 许晓绚; 曾劲峰

    2011-01-01

    Objective To investigate and analyze the seronegative and NAT-positive donors,and evaluate the feasibility of using NAT in blood screening. Methods Roche PCR, PCR-CHIP, real time fluorescence PCR and TMA were used for the analysis of HBV DNA, HCV RNA and HFV-l RNA, respectively, from seronegative samples. HBV positive donors were also analyzed for the serological markers by quantitative PCR. Results 28 out of 141 288 donations were found HBV DNA positive and the HBV DNA positive rate was 0.020%. 21 cases of donations were found anti-HBc positive and the rate was 0.015%. 17 donors were found HBsAg(-) and 9 follow up samples showed seroconversion; 4 donors showed the characteristic of window period. One case was confirmed HCV RNA positive and the donation was in the window period. Conclusion It is necessary to implement the highly sensitive HBV and HCV NAT test for blood screening.%目的 大样本、多方法调查深圳地区无偿献血人群中乙肝、丙肝和艾滋病病毒血清学阴性者的核酸阳性率,探讨在我国血液筛查中引进核酸扩增技术的必要性,了解和分析献血者血清学阴性核酸阳性感染状况.方法 采用大样本数调查,应用ROCHE PCR-ELISA、PCR-微流芯片、实时荧光PCR方法和CHIRON TMA(转录依赖的扩增技术)多种方法对血清学检测阴性的献血者进行HBV DNA、HCVRNA和HIV-1 RNA检测,对乙肝阳性献血者追踪检测ALT和乙肝两对半标志物,对丙肝核酸阳性献血者追踪检测ALT及抗-HCV及HBV DNA和HCVRNA病毒载量.结果 共对141 288人份血样进行了检测,检出HBsAg(-)、HBV DNA阳性28例,总阳性率为0.020%,其中21例为anti-HBc阳性,占0.015%.HIV-1 RNA未检出阳性,17例HBsAg(-)、HBV DNA阳性样本追踪发现,9例发生了血清转换现象,4例呈窗口期特征,所有追踪的HBV DNA阳性献血者ALT检测结果正常.1例anti-HCV(-)、HCV RNA阳性献血者追踪发现为典型窗口期献血,ALT显著升高.结论 应采用高灵敏

  16. A dual amplification fluorescent strategy for sensitive detection of DNA methyltransferase activity based on strand displacement amplification and DNAzyme amplification.

    Science.gov (United States)

    Cui, Wanling; Wang, Lei; Jiang, Wei

    2016-03-15

    DNA methyltransferase (MTase) plays a critical role in many biological processes and has been regarded as a predictive cancer biomarker and a therapeutic target in cancer treatment. Sensitive detection of DNA MTase activity is essential for early cancer diagnosis and therapeutics. Here, we developed a dual amplification fluorescent strategy for sensitive detection of DNA MTase activity based on strand displacement amplification (SDA) and DNAzyme amplification. A trifunctional double-stranded DNA (dsDNA) probe was designed including a methylation site for DNA MTase recognition, a complementary sequence of 8-17 DNAzyme for synthesizing DNAzyme, and a nicking site for nicking enzyme cleavage. Firstly, the trifunctional dsDNA probe was methylated by DNA MTase to form the methylated dsDNA. Subsequently, HpaII restriction endonuclease specifically cleaved the residue of unmethylated dsDNA. Next, under the action of polymerase and nicking enzyme, the methylared dsDNA initiated SDA, releasing numbers of 8-17 DNAzymes. Finally, the released 8-17 DNAzymes triggered DNAzyme amplification reaction to induce a significant fluorescence enhancement. This strategy could detect DNA MTase activity as low as 0.0082U/mL. Additionally, the strategy was successfully applied for evaluating the inhibitions of DNA MTase using two anticancer drugs, 5-azacytidine and 5-aza-2'-deoxycytidine. The results indicate the proposed strategy has a potential application in early cancer diagnosis and therapeutics.

  17. Effect of consumption of fresh and heated virgin coconut oil on the blood pressure and inflammatory biomarkers: An experimental study in Sprague Dawley rats

    Directory of Open Access Journals (Sweden)

    Mohammad Afiq Hamsi

    2015-03-01

    Conclusion: Repeatedly heated VCO caused an elevation in the BP. The BP elevation was associated with a significant increase in the inflammatory bio-markers (VCAM-1, ICAM-1 and CRP, TXB2 and a significant reduction in the plasma PGI2 level.

  18. Effect of parsley (Petroselinum crispum) intake on urinary apigenin excretion, blood antioxidant enzymes and biomarkers for oxidative stress in human subjects

    DEFF Research Database (Denmark)

    Nielsen, S. E.; Young, J.F.; Daneshvar, B.;

    1999-01-01

    with parsley (P catalase (EC 1.11.1.6) and glutathione peroxidase (EC 1.11.1.9) activities did not change. No significant changes were observed in plasma protein 2-adipic semialdehyde residues, a biomarker of plasma protein oxidation...

  19. Effects of Four-Week Supplementation with a Multi-Vitamin/Mineral Preparation on Mood and Blood Biomarkers in Young Adults: A Randomised, Double-Blind, Placebo-Controlled Trial

    Science.gov (United States)

    White, David J.; Cox, Katherine H. M.; Peters, Riccarda; Pipingas, Andrew; Scholey, Andrew B.

    2015-01-01

    This study explored the effects of four-week multi-vitamin and mineral (MVM) supplementation on mood and neurocognitive function in healthy, young adults. Fifty-eight healthy adults, 18–40 years of age (M = 25.82 years, SD = 4.87) participated in this randomised, double-blind, placebo-controlled trial, in which mood and blood biomarkers were assessed at baseline and after four weeks of supplementation. Compared to placebo, MVM supplementation was associated with significantly lowered homocysteine and increased blood B-vitamin levels (p < 0.01). MVM treatment was also associated with significantly improved mood, as measured by reduced scores on the “depression-dejection” subscale of the Profile of Mood States (p = 0.018). These findings suggest that the four weeks of MVM supplementation may have beneficial effects on mood, underpinned by elevated B-vitamins and lowered homocysteine in healthy young adults. PMID:26529011

  20. Impact of age, BMI and HbA1c levels on the genome-wide DNA methylation and mRNA expression patterns in human adipose tissue and identification of epigenetic biomarkers in blood

    DEFF Research Database (Denmark)

    Rönn, Tina; Volkov, Petr; Gillberg, Linn;

    2015-01-01

    of candidate genes for obesity, type 2 diabetes and cancer in human adipose tissue. Importantly, we demonstrate that epigenetic biomarkers in blood can mirror age-related epigenetic signatures in target tissues for metabolic diseases such as adipose tissue.......Increased age, BMI and HbA1c levels are risk factors for several non-communicable diseases. However, the impact of these factors on the genome-wide DNA methylation pattern in human adipose tissue remains unknown. We analyzed the DNA methylation of ∼480 000 sites in human adipose tissue from 96...... males and 94 females and related methylation to age, BMI and HbA1c. We also compared epigenetic signatures in adipose tissue and blood. Age was significantly associated with both altered DNA methylation and expression of 1050 genes (e.g. FHL2, NOX4 and PLG). Interestingly, many reported epigenetic...

  1. Effects of Four-Week Supplementation with a Multi-Vitamin/Mineral Preparation on Mood and Blood Biomarkers in Young Adults: A Randomised, Double-Blind, Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    David J. White

    2015-10-01

    Full Text Available This study explored the effects of four-week multi-vitamin and mineral (MVM supplementation on mood and neurocognitive function in healthy, young adults. Fifty-eight healthy adults, 18–40 years of age (M = 25.82 years, SD = 4.87 participated in this randomised, double-blind, placebo-controlled trial, in which mood and blood biomarkers were assessed at baseline and after four weeks of supplementation. Compared to placebo, MVM supplementation was associated with significantly lowered homocysteine and increased blood B-vitamin levels (p < 0.01. MVM treatment was also associated with significantly improved mood, as measured by reduced scores on the “depression-dejection” subscale of the Profile of Mood States (p = 0.018. These findings suggest that the four weeks of MVM supplementation may have beneficial effects on mood, underpinned by elevated B-vitamins and lowered homocysteine in healthy young adults.

  2. The Seneca Amplification Construction

    Directory of Open Access Journals (Sweden)

    Wallace Chafe

    2012-01-01

    Full Text Available The polysynthetic morphology of the Northern Iroquoian languages presents a challenge to studies of clause combining. The discussion here focuses on a Seneca construction that may appear within a single clause but may also straddle clause boundaries. It amplifies the information provided by a referent, here called the trigger, that is introduced by the pronominal prefix within a verb or occasionally in some other way. The particle neh signals that further information about that referent will follow. This construction is found at four levels of syntactic complexity. At the first level the trigger and its amplification occur within the same prosodic phrase and the amplification is a noun. At the second level the amplification occurs in a separate prosodic phrase but remains a noun. At the third level the amplification exhibits verb morphology but has been lexicalized with a nominal function. At the fourth level the amplification functions as a full clause and neh serves as a marker of clause combining. Several varieties of amplification are discussed, as are cases in which the speaker judges that no amplification is needed. It is suggested that the typologically similar Caddo language illustrates a situation in which this construction could never arise, simply because Caddo verbs lack the pronominal element that triggers the construction in Seneca.

  3. Polydopamine/dialdehyde starch/chitosan composite coating for in-tube solid-phase microextraction and in-situ derivation to analysis of two liver cancer biomarkers in human blood.

    Science.gov (United States)

    Wu, Shiju; Cai, Cuicui; Cheng, Jing; Cheng, Min; Zhou, Hongbin; Deng, Jiali

    2016-09-01

    In order to highly enrich two liver cancer biomarkers (hexanal and 2-butanone) in human blood, in this study, natural nontoxic polydopamine/dialdehyde starch/chitosan (PD/DAS/CHI) coating material was synthesized and immobilized on the inner wall of polytetrafluoro-ethlyene (PTFE) tube. It was used to develop the method based on in-tube solid-phase microextraction (IT-SPME) with in-situ derivatization (ISD) coupled to high performance liquid chromatography for the determination of the above mentioned two liver cancer biomarkers in human blood. The simple, rapid and sensitive IT-SPME-ISD method can be finished within 11 min. Under optimum conditions, the limits of detection (LODs) were 1.4 and 1.6 nmol L(-1) for hexanal and 2-butanone, respectively. The relative recoveries from real human blood samples were in the range from 70% to 91% with the intra- and inter-day precisions less than 7.2%. Furthermore, this method was successfully applied for the analysis of hexanal and 2-butanone in blood samples from healthy people with 0.42 ± 0.05 and 0.34 ± 0.04 μmol L(-1), while liver cancer patients with 1.90 ± 0.07  μmol L(-1) and 0.91 ± 0.07 μmol L(-1), respectively. The t-test's results showed there is a statistically significant difference between the data from healthy persons and liver cancer patients. Hence, the developed method might be applied in the screening of suspected liver cancer patients.

  4. Complementarity of ELISA and nucleic acid amplification test in blood screening%血筛用酶联免疫吸附试验与核酸检测互补性探讨和研究

    Institute of Scientific and Technical Information of China (English)

    曾劲峰; 叶贤林; 马兰; 张红; 庄乃保; 李活

    2008-01-01

    目的 为了提高临床输血的安全性,探讨核酸检测(NAT)与酶联免疫吸附试验(ELISA)技术在血液筛查工作中的互补特性.方法 对2007年6月至2008年3月采集的无偿献血者标本共计45 022例用ELISA血清学检测方法对血液传染性指标HBsAg、抗-HCV、抗-HIV、梅毒螺旋体、丙氨酸氨基转移酶(ALT)进行检测,各项指标均正常的标本用NAT技术检测,以研究2种检测方法的互补性.结果 45 022例标本中血清学检测及ALT不合格人数共计803例,不合格率为1.98%.对各项检测指标合格的36 806例标本进行核酸检测,结果HBV-DNA呈阳性3例.HBV-RNA、HIV-RNA均未检出.结论 NAT与ELISA的血液筛查检测互补作用主要体现在3个方面:1)病理生理过程互补,检测窗口期的长短主要由检测对象的生理属性来决定,而非检测方法缺陷.2)检测方法学互补,由于检测方法学的不同使得NAT技术的检测灵敏度明显高于ELISA血清学检测方法.3)影响各自实验的错误发生各不相同.%Objective To investigate the complementarity of ELISA and nucleic acid amplification test(NAT)in blood screening,and to improve the security of clinieal blood transfusion.Methods A total of 45 022 blood samples from the blood donors without payment from June 2007to March 2008 were enrolled in the study.ELISA was applied to determining HBsAg,anti-HCV,anti-HIV,anti-treponema pallidum(anti-TP)and ALT,and then the normal samples for the above parameters(serologically negative for HBsAg.anti-HCV, anti-HIV,anti-TP and ALT)were detected with NAT.The complementarity of ELISA and NAT was analyzed.Results Totally 803 cases(1.98%)were unqualified(serologically positive)out of the 45 022 blood samples.The qualified 36 806samples were further detected with NAT.The results showed 3 cases were HBV-DNA positive,but none was positive for HBV-RNA and HIV-RNA.Conclusion The complementary action of ELISA and NAT is due to different window phase for detected

  5. Lipopolysaccharide-Induced CXCL10 mRNA Level and Six Stimulant-mRNA Combinations in Whole Blood: Novel Biomarkers for Bortezomib Responses Obtained from a Prospective Multicenter Trial for Patients with Multiple Myeloma.

    Directory of Open Access Journals (Sweden)

    Takashi Watanabe

    Full Text Available To identify predictive biomarkers for clinical responses to bortezomib treatment, 0.06 mL of each whole blood without any cell separation procedures was stimulated ex vivo using five agents, and eight mRNAs were quantified. In six centers, heparinized peripheral blood was prospectively obtained from 80 previously treated or untreated, symptomatic multiple myeloma (MM patients with measurable levels of M-proteins. The blood sample was procured prior to treatment as well as 2-3 days and 1-3 weeks after the first dose of bortezomib, which was intravenously administered biweekly or weekly, during the first cycle. Six stimulant-mRNA combinations; that is, lipopolysaccharide (LPS-granulocyte-macrophage colony-stimulating factor (GM-CSF, LPS-CXCL chemokine 10 (CXCL10, LPS-CCL chemokine 4 (CCL4, phytohemagglutinin-CCL4, zymosan A (ZA-GMCSF and ZA-CCL4 showed significantly higher induction in the complete and very good partial response group than in the stable and progressive disease group, as determined by both parametric (t-test and non-parametric (unpaired Mann-Whitney test tests. Moreover, LPS-induced CXCL10 mRNA expression was significantly suppressed 2-3 days after the first dose of bortezomib in all patients, as determined by both parametric (t-test and non-parametric (paired Wilcoxon test tests, whereas the complete and very good partial response group showed sustained suppression 1-3 weeks after the first dose. Thus, pretreatment LPS-CXCL10 mRNA and/or the six combinations may serve as potential biomarkers for the response to bortezomib treatment in MM patients.

  6. Impact of age, BMI and HbA1c levels on the genome-wide DNA methylation and mRNA expression patterns in human adipose tissue and identification of epigenetic biomarkers in blood.

    Science.gov (United States)

    Rönn, Tina; Volkov, Petr; Gillberg, Linn; Kokosar, Milana; Perfilyev, Alexander; Jacobsen, Anna Louisa; Jørgensen, Sine W; Brøns, Charlotte; Jansson, Per-Anders; Eriksson, Karl-Fredrik; Pedersen, Oluf; Hansen, Torben; Groop, Leif; Stener-Victorin, Elisabet; Vaag, Allan; Nilsson, Emma; Ling, Charlotte

    2015-07-01

    Increased age, BMI and HbA1c levels are risk factors for several non-communicable diseases. However, the impact of these factors on the genome-wide DNA methylation pattern in human adipose tissue remains unknown. We analyzed the DNA methylation of ∼480 000 sites in human adipose tissue from 96 males and 94 females and related methylation to age, BMI and HbA1c. We also compared epigenetic signatures in adipose tissue and blood. Age was significantly associated with both altered DNA methylation and expression of 1050 genes (e.g. FHL2, NOX4 and PLG). Interestingly, many reported epigenetic biomarkers of aging in blood, including ELOVL2, FHL2, KLF14 and GLRA1, also showed significant correlations between adipose tissue DNA methylation and age in our study. The most significant association between age and adipose tissue DNA methylation was found upstream of ELOVL2. We identified 2825 genes (e.g. FTO, ITIH5, CCL18, MTCH2, IRS1 and SPP1) where both DNA methylation and expression correlated with BMI. Methylation at previously reported HIF3A sites correlated significantly with BMI in females only. HbA1c (range 28-46 mmol/mol) correlated significantly with the methylation of 711 sites, annotated to, for example, RAB37, TICAM1 and HLA-DPB1. Pathway analyses demonstrated that methylation levels associated with age and BMI are overrepresented among genes involved in cancer, type 2 diabetes and cardiovascular disease. Our results highlight the impact of age, BMI and HbA1c on epigenetic variation of candidate genes for obesity, type 2 diabetes and cancer in human adipose tissue. Importantly, we demonstrate that epigenetic biomarkers in blood can mirror age-related epigenetic signatures in target tissues for metabolic diseases such as adipose tissue. PMID:25861810

  7. Early amplification options.

    Science.gov (United States)

    Gabbard, Sandra Abbott; Schryer, Jennifer

    2003-01-01

    Children with permanent hearing loss have been remediated with hearing amplification devices for decades. The influx of young infants identified with hearing loss through successful newborn hearing screening programs has established a need for amplification resources for infants within the first six months of life. For the approximately two of every 1000 infants born who are identified with bilateral hearing loss [Mehl and Thomson, 1998, Pediatrics 101, p. e4], the use of amplification is commonly the first step in treating the sequella of their loss. The use of hearing aids, combined with early intervention, has been shown to significantly improve the speech and language skills of young children with hearing loss [Yoshinaga-Itano, 2000, Seminars in Hearing 21, p. 309]. Speech and language delays have contributed to compromised academic performance of school aged children with hearing loss [Johnson et al., 1997, Educational Audiology Handbook, Singular Publishing, San Diego]. Most hard-of-hearing and deaf children use hearing aids and other assistive listening devices every day throughout their lifetime and the life expectancy of a hearing aid is only five to eight years. The current challenge for pediatric audiologists is selecting and evaluating the available amplification to provide the best options for children and their families. Amplification technology has seen an explosion in growth the past few years and the options continue to expand rapidly. This article examines currently available amplification technology and reviews the selection criteria that may be used for infants and young children. Issues such as style, type, amplification features, signal processing strategies, and verification and validation tools are also discussed. PMID:14648816

  8. Impact of chronic exposure to gasoline automotive exhaust gases on some bio-markers affecting the hormonal sexual function, the kidney function and blood parameters, in the rat

    International Nuclear Information System (INIS)

    The automotive exhaust gases constitute an important source of urban pollution. The objective of this study is to explore, in the rat, the effects of repetitive exposure to gasoline automotive exhaust gases on the level variations of serum testosterone, blood lead, bone lead, blood carbon monoxide, on the kidney function and blood parameters. 200 rats inhaling a mixture of air and automotive exhaust gas (10/1, v/v), are distributed in 4 groups treated during 15, 30, 45 and 60 days. They are compared to non treated controls. Our results show a decrease of serum testosterone level. This result is the origin of a masculine sterility already demonstrated in our laboratory. This sterility seems to be reversible because polluted rats regain their sexual activity, 2 months after stopping of the pollutant treatment. An increase of the blood carbon monoxide level with a lead accumulation in blood and in the tail is noticed. Biochemical analyses show that glycaemia, urea, and creatininaemia increase in treated animals. The urinary rate of creatinine decreases. These results indicate kidney deficiency. Our results show also in treated animals an increase of the number of red blood corpuscles, of hematocrit, of the blood level of haemoglobin and of the VGM, and a decrease of the CGMH. The carbon monoxide and the lead detected in blood of the treated animals are the origin of these perturbations. In conclusion, our results show that gasoline automotive exhaust gas induces, in the rat, a decrease of serum testosterone level. The carbon monoxide and the lead present in the exhaust gas, and detected in blood and in the tail of the treated animals, are the origin of sexual, kidney and blood parameters perturbations. (author)

  9. 核酸扩增技术在广州市献血员血液筛查中的应用价值%Evaluation of Nucleic Acid Amplification Screening for Blood Donors in Guangzhou

    Institute of Scientific and Technical Information of China (English)

    明凯华; 雷秀霞; 徐邦牢; 罗丽香; 胡洁洁

    2015-01-01

    【目的】评价核酸扩增技术(NAT)在广州市献血员血液筛查的应用价值。【方法】收集22139名无偿献血员血样,采用酶联免疫吸附试验(ELISA)检测乙型肝炎病毒(HBV)、丙型肝炎病毒(HCV)、梅毒螺旋体(TP)和人免疫缺陷病毒(HIV),并检测谷丙转氨酶(ALT)水平。对四项ELISA检测阴性和ALT≤40U/L者血样,用COBASs201系统进行HBVDNA、HCVRNA、HIVRNA检测。NAT反应性样本、HBV、HCV和HIVELISA检测阳性血样以COBASAmpliScreen试剂盒鉴定。【结果】22139名献血员中,21776例双试剂血清免疫学检测阴性,其中19例为NAT反应阳性,检出率0.087%(19/21776),后经NAT鉴定检测,HBV、HCV和HIV反应阳性检出率分别为0.051%(11/21776)、0.028%(6/21776)和0.009%(2/21776)。126例HBsAg阳性样本中,25例NAT阴性,其中15例HBsAg中和试验阳性,为低水平慢性感染携带者。50例anti‐HCV阳性血样,4例为NAT阴性,补充ELISA检测为anti‐HCV阴性。16例anti‐HIV阳性样本中,7例为NAT阴性,其单样品核酸检测(ID‐NAT)和补充ELISA检测均为anti‐HIV阴性。【结论】NAT血液筛查对HBV、HCV和HIV经ELISA检测阴性样本的检出率较高,在该地开展NAT血液筛查,对于降低输血残余危险有重大意义。少量HBsAg阳性的低水平感染慢性携带者,汇集核酸检测(MP‐NAT)阴性,HBsAg筛查依然是必不可少的筛查手段。%[Objective] To evaluate the application value of nucleic acid amplification technology (NAT) in screening of blood donors in Guangzhou .[Methods] Blood samples from 22 ,139 blood donors in Guangzhou were collected .Enzyme‐linked immunosorbent assay (ELISA) was used to detect the levels of hepatitis B sur‐face antigen (HBsAg ) ,anti‐hepatitis C virus (anti‐HCV ) ,anti‐human immunodeficiency virus (anti‐HIV ) and anti‐Treponemia pallid (anti‐TP) .And the

  10. Quantum Feedback Amplification

    Science.gov (United States)

    Yamamoto, Naoki

    2016-04-01

    Quantum amplification is essential for various quantum technologies such as communication and weak-signal detection. However, its practical use is still limited due to inevitable device fragility that brings about distortion in the output signal or state. This paper presents a general theory that solves this critical issue. The key idea is simple and easy to implement: just a passive feedback of the amplifier's auxiliary mode, which is usually thrown away. In fact, this scheme makes the controlled amplifier significantly robust, and furthermore it realizes the minimum-noise amplification even under realistic imperfections. Hence, the presented theory enables the quantum amplification to be implemented at a practical level. Also, a nondegenerate parametric amplifier subjected to a special detuning is proposed to show that, additionally, it has a broadband nature.

  11. Air pollution source apportionment before, during, and after the 2008 Beijing Olympics and association of sources to aldehydes and biomarkers of blood coagulation, pulmonary and systemic inflammation, and oxidative stress in healthy young adults

    Science.gov (United States)

    Altemose, Brent A.

    Based on principal component analysis (PCA) of air pollution data collected during the Summer Olympic Games held in Beijing, China during 2008, the five source types of air pollution identified -- natural soil/road dust, vehicle and industrial combustion, vegetative burning, oil combustion, and secondary formation, were all distinctly lower during the Olympics. This was particularly true for vehicle and industrial combustion and oil combustion, and during the main games period between the opening and closing ceremonies. The reduction in secondary formation was reflective of a reduction in nitrogen oxides, but this also contributed to increased ozone concentrations during the Olympic period. Among three toxic aldehydes measured in Beijing during the same time period, only acetaldehyde had a reduction in mean concentration during the Olympic air pollution control period compared to the pre-Olympic period. Accordingly, acetaldehyde was significantly correlated with primary emission sources including vegetative burning and oil combustion, and with several pollutants emitted mainly from primary sources. In contrast, formaldehyde and acrolein increased during the Olympic air pollution control period; accordingly both were significantly correlated with ozone and with the secondary formation source type. These findings indicate primary sources may dominate for acetaldehyde while secondary sources may dominate for formaldehyde and acrolein. Biomarkers for pulmonary inflammation (exhaled breath condensate (EBC) pH, exhaled nitric oxide, and EBC nitrite) and hemostasis and blood coagulation (vWF and sCD62p) were most consistently associated with vehicle and industrial combustion, oil combustion, and vegetative burning. The systemic inflammation biomarker 8-OHdG was most consistently associated with vehicle and industrial combustion. In contrast, the associations between the biomarkers and the aldehydes were generally not significant or in the hypothesized direction, although

  12. Advances in Biomarker Research in Parkinson's Disease.

    Science.gov (United States)

    Mehta, Shyamal H; Adler, Charles H

    2016-01-01

    Parkinson's disease (PD) is the second most common neurodegenerative disease, and the numbers are projected to double in the next two decades with the increase in the aging population. An important focus of current research is to develop interventions to slow the progression of the disease. However, prerequisites to it include the development of reliable biomarkers for early diagnosis which would identify at-risk groups and disease progression. In this review, we present updated evidence of already known clinical biomarkers (such as hyposmia and rapid eye movement (REM) sleep behavior disorder (RBD)) and neuroimaging biomarkers, as well as newer possible markers in the blood, CSF, and other tissues. While several promising candidates and methods to assess these biomarkers are on the horizon, it is becoming increasingly clear that no one candidate will clearly fulfill all the roles as a single biomarker. A multimodal and combinatorial approach to develop a battery of biomarkers will likely be necessary in the future. PMID:26711276

  13. Exploring Biomarkers for Alzheimer's Disease.

    Science.gov (United States)

    Sharma, Neeti; Singh, Anshika Nikita

    2016-07-01

    Alzheimer's Disease (AD) is one of the most common form of dementia occurring in elderly population worldwide. Currently Aβ42, tau and p-tau in the cerebrospinal fluid is estimated for confirmation of AD. CSF which is being used as the potent source for biomarker screening is obtained by invasive lumbar punctures. Thus, there is an urgent need of minimal invasive methods for identification of diagnostic markers for early detection of AD. Blood serum and plasma serves as an appropriate source, due to minimal discomfort to the patients, promoting frequent testing, better follow-up and better consent to clinical trials. Hence, the need of the hour demands discovery of diagnostic and prognostic patient specific signature biomarkers by using emerging technologies of mass spectrometry, microarrays and peptidomics. In this review we summarize the present scenario of AD biomarkers such as circulatory biomarkers, blood based amyloid markers, inflammatory markers and oxidative stress markers being investigated and also some of the potent biomarkers which might be able to predict early onset of Alzheimer's and delay cognitive impairment. PMID:27630867

  14. C - reactive protein and chitinase 3-like protein 1 as biomarkers of spatial redistribution of retinal blood vessels on digital retinal photography in patients with diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Sonja Predrag Cekic

    2014-08-01

    Full Text Available The aim of the study was to investegate the correlation between the levels of CRP and YKL-40 in blood samples with morphometric parameters of retinal blood vessels in patients with diabetic retinopathy.Blood laboratory examination of 90 patients included the measurement of glycemia, HbA1C, total cholesterol, LDL-C, HDL-C, triglycerides and CRP. Levels of YKL-40 were detected and measured in serum by ELISA (Micro VueYKL-40 EIA Kit, Quidel Corporation, San Diego, USA.Morphmetric analysis was performed with ImageJ software (http://rsbweb.nih.gov/ij/ for digital retinal photography. We measured the number, diameter of retinal blood vessels in five different parts concentric to the optic disc. Differences between the morphometric parameters and the blood test analysis results were evaluated using the Student’s t – test. One Way ANOVA was used to establish the significance of differences.CRP and YKL-40 levels were moderately higher in the group of patients with severe diabetic retinopathy. Levels of YKL-40 correlated positively with diameter and negatively with number of retinal blood vessels. The average number of the blood vessels per retinal zone was significantly higher in the group of patients with mild non-proliferative diabetic retinopathy than in the group with severe form in the optic disc and all five retinal zones. The average outer diameter of the evaluated retinal zones and optic disc vessels was significantly higher in the group with severe compared to the group with mild diabetic retinopathy.Morphological analysis of the retinal vessels on digital fundus photography and correlation with YKL-40 may be valuable for the follow-up of diabetic retinopathy.

  15. C-reactive protein and chitinase 3-like protein 1 as biomarkers of spatial redistribution of retinal blood vessels on digital retinal photography in patients with diabetic retinopathy.

    Science.gov (United States)

    Cekić, Sonja; Cvetković, Tatjana; Jovanović, Ivan; Jovanović, Predrag; Pesić, Milica; Stanković Babić, Gordana; Milenković, Svetislav; Risimić, Dijana

    2014-08-20

    The aim of the study was to investigate the correlation between the levels of C-reactive protein (CRP) and chitinase 3-like protein 1 (YKL-40) in blood samples with morpohometric parameters of retinal blood vessels in patients with diabetic retinopathy. Blood laboratory examination of 90 patients included the measurement of glycemia, HbA1C, total cholesterol, LDL-C, HDL-C, triglycerides and CRP. Levels of YKL-40 were detected and measured in serum by ELISA (Micro VueYKL-40 EIA Kit, Quidel Corporation, San Diego, USA). YKL-40 correlated positively with diameter and negatively with number of retinal blood vessels. The average number of the blood vessels per retinal zone was significantly higher in the group of patients with mild non-proliferative diabetic retinopathy than in the group with severe form in the optic disc and all five retinal zones. The average outer diameter of the evaluated retinal zones and optic disc vessels was significantly higher in the group with severe compared to the group with mild diabetic retinopathy. Morphological analysis of the retinal vessels on digital fundus photography and correlation with YKL-40 may be valuable for the follow-up of diabetic retinopathy.

  16. Correlation of SHOX2 Gene Amplification and DNA Methylation in Lung Cancer Tumors

    Directory of Open Access Journals (Sweden)

    Liebenberg Volker

    2011-03-01

    Full Text Available Abstract Background DNA methylation in the SHOX2 locus was previously used to reliably detect lung cancer in a group of critical controls, including 'cytologically negative' samples with no visible tumor cell content, at a high specificity based on the analysis of bronchial lavage samples. This study aimed to investigate, if the methylation correlates with SHOX2 gene expression and/or copy number alterations. An amplification of the SHOX2 gene locus together with the observed tumor-specific hypermethylation might explain the good performance of this marker in bronchial lavage samples. Methods SHOX2 expression, gene copy number and DNA methylation were determined in lung tumor tissues and matched morphologically normal adjacent tissues (NAT from 55 lung cancer patients. Quantitative HeavyMethyl (HM real-time PCR was used to detect SHOX2 DNA methylation levels. SHOX2 expression was assayed with quantitative real-time PCR, and copy numbers alterations were measured with conventional real-time PCR and array CGH. Results A hypermethylation of the SHOX2 locus in tumor tissue as compared to the matched NAT from the same patient was detected in 96% of tumors from a group of 55 lung cancer patients. This correlated highly significantly with the frequent occurrence of copy number amplification (p SHOX2 gene showed no difference. Conclusions Frequent gene amplification correlated with hypermethylation of the SHOX2 gene locus. This concerted effect qualifies SHOX2 DNA methylation as a biomarker for lung cancer diagnosis, especially when sensitive detection is needed, i.e. in bronchial lavage or blood samples.

  17. Biomarkers of manganese intoxication.

    Science.gov (United States)

    Zheng, Wei; Fu, Sherleen X; Dydak, Ulrike; Cowan, Dallas M

    2011-01-01

    Manganese (Mn), upon absorption, is primarily sequestered in tissue and intracellular compartments. For this reason, blood Mn concentration does not always accurately reflect Mn concentration in the targeted tissue, particularly in the brain. The discrepancy between Mn concentrations in tissue or intracellular components means that blood Mn is a poor biomarker of Mn exposure or toxicity under many conditions and that other biomarkers must be established. For group comparisons of active workers, blood Mn has some utility for distinguishing exposed from unexposed subjects, although the large variability in mean values renders it insensitive for discriminating one individual from the rest of the study population. Mn exposure is known to alter iron (Fe) homeostasis. The Mn/Fe ratio (MIR) in plasma or erythrocytes reflects not only steady-state concentrations of Mn or Fe in tested individuals, but also a biological response (altered Fe homeostasis) to Mn exposure. Recent human studies support the potential value for using MIR to distinguish individuals with Mn exposure. Additionally, magnetic resonance imaging (MRI), in combination with noninvasive assessment of γ-aminobutyric acid (GABA) by magnetic resonance spectroscopy (MRS), provides convincing evidence of Mn exposure, even without clinical symptoms of Mn intoxication. For subjects with long-term, low-dose Mn exposure or for those exposed in the past but not the present, neither blood Mn nor MRI provides a confident distinction for Mn exposure or intoxication. While plasma or erythrocyte MIR is more likely a sensitive measure, the cut-off values for MIR among the general population need to be further tested and established. Considering the large accumulation of Mn in bone, developing an X-ray fluorescence spectroscopy or neutron-based spectroscopy method may create yet another novel non-invasive tool for assessing Mn exposure and toxicity. PMID:20946915

  18. Systematic large-scale meta-analysis identifies a panel of two mRNAs as blood biomarkers for colorectal cancer detection.

    Science.gov (United States)

    Rodia, Maria Teresa; Ugolini, Giampaolo; Mattei, Gabriella; Montroni, Isacco; Zattoni, Davide; Ghignone, Federico; Veronese, Giacomo; Marisi, Giorgia; Lauriola, Mattia; Strippoli, Pierluigi; Solmi, Rossella

    2016-05-24

    Colorectal cancer (CRC) is the third most common cancer in the world. A significant survival rate is achieved if it is detected at an early stage. A whole blood screening test, without any attempt to isolate blood fractions, could be an important tool to improve early detection of colorectal cancer. We searched for candidate markers with a novel approach based on the Transcriptome Mapper (TRAM), aimed at identifying specific RNAs with the highest differential expression ratio between colorectal cancer tissue and normal blood samples. This tool permits a large-scale systematic meta-analysis of all available data obtained by microarray experiments. The targeting of RNA took into consideration that tumour phenotypic variation is associated with changes in the mRNA levels of genes regulating or affecting this variation.A real time quantitative reverse transcription polymerase chain reaction (qRT- PCR) was applied to the validation of candidate markers in the blood of 67 patients and 67 healthy controls. The expression of genes: TSPAN8, LGALS4, COL1A2 and CEACAM6 resulted as being statistically different.In particular ROC curves attested for TSPAN8 an AUC of 0.751 with a sensitivity of 83.6% and a specificity of 58.2% at a cut off of 10.85, while the panel of the two best genes showed an AUC of 0.861 and a sensitivity of 92.5% with a specificity of 67.2%.Our preliminary study on a total of 134 subjects showed promising results for a blood screening test to be validated in a larger cohort with the staging stratification and in patients with other gastrointestinal diseases. PMID:26993598

  19. Testes sanguíneos de biomarcadores para diagnóstico e tratamento de desordens mentais: foco em esquizofrenia Biomarker blood tests for diagnosis and management of mental disorders: focus on schizophrenia

    Directory of Open Access Journals (Sweden)

    Sabine Bahn

    2012-01-01

    can supplement or replace the long standing interview-based methods for diagnosis. Despite this, the regulatory agencies now agree that improvements over the current methods are essential. Furthermore, these agencies stipulate that biomarkers are important for future drug development and have initiated efforts to modernize methods and techniques to support these efforts. Here, we review the challenges faced by this endeavour from the point of view of psychiatrists, general practitioners, the regulatory agencies and biomarker scientists. We also describe the development of a novel molecular blood-test for schizophrenia as a first promising step towards achieving this goal.

  20. Peripheral blood minimal residual disease may replace bone marrow minimal residual disease as an immunophenotypic biomarker for impending relapse in acute myeloid leukemia.

    Science.gov (United States)

    Zeijlemaker, W; Kelder, A; Oussoren-Brockhoff, Y J M; Scholten, W J; Snel, A N; Veldhuizen, D; Cloos, J; Ossenkoppele, G J; Schuurhuis, G J

    2016-03-01

    As relapses are common in acute myeloid leukemia (AML), early relapse prediction is of high importance. Although conventional minimal residual disease (MRD) measurement is carried out in bone marrow (BM), peripheral blood (PB) would be an advantageous alternative source. This study aims to investigate the specificity of leukemia-associated immunophenotypes used for MRD detection in blood samples. Consistency of PB MRD as compared with BM MRD was determined in flow cytometric data of 205 paired BM and PB samples of 114 AML patients. A significant correlation was found between PB and BM MRD (r=0.67, Pconsolidation therapy. As PB MRD appeared to be an independent predictor for response duration, the highly specific PB MRD assay may have a prominent role in future MRD assessment in AML. PMID:26373238

  1. Flux amplification in SSPX

    Science.gov (United States)

    Lodestro, Lynda; Hooper, E. B.; Jayakumar, R. J.; Pearlstein, L. D.; Wood, R. D.; McLean, H. S.

    2007-11-01

    Flux amplification---the ratio of poloidal flux enclosed between the magnetic and geometric axes to that between the separatrix and the geometric axis---is a key measure of efficiency for edge-current-driven spheromaks. With the new, modular capacitor bank, permitting flexible programming of the gun current, studies of flux amplification under various drive scenarios can be performed. Analysis of recent results of pulsed operation with the new bank finds an efficiency ˜ 0.2, in selected shots, of the conversion of gun energy to confined magnetic energy during the pulses, and suggests a route toward sustained efficiency at 0.2. Results of experiments, a model calculation of field build-up, and NIMROD simulations exploring this newly suggested scenario will be presented.

  2. Phthalate Diesters and Their Metabolites in Human Breast Milk, Blood or Serum, and Urine as Biomarkers of Exposure in Vulnerable Populations

    OpenAIRE

    Högberg, Johan; Hanberg, Annika; Berglund, Marika; Skerfving, Staffan; Remberger, Mikael; Calafat, Antonia M.; Filipsson, Agneta Falk; Jansson, Bo; Johansson, Niklas; Appelgren, Malin; Håkansson, Helen

    2007-01-01

    Background Phthalates may pose a risk for perinatal developmental effects. An important question relates to the choice of suitable biological matrices for assessing exposure during this period. Objectives This study was designed to measure the concentrations of phthalate diesters or their metabolites in breast milk, blood or serum, and urine and to evaluate their suitability for assessing perinatal exposure to phthalates. Methods In 2001, 2–3 weeks after delivery, 42 Swedish primipara provide...

  3. Identification biomarkers for cervical cancer in peripheral blood lymphocytes by oligonucleotide microarrays%应用寡核苷酸芯片筛选宫颈癌患者外周血生物标志物的研究

    Institute of Scientific and Technical Information of China (English)

    盛洁; 张为远

    2010-01-01

    Objective To identify the molecular biomarkers for cervical cancer in peripheral blood lymphocytes by oligonucleatide microarrays. Methods Human genome oligonucleotide microarray analysis included 4 early-stage cervical cancer patients and 3 controls. The selected genes from the microarray analysis were validated in additional 20 early-stage cervical cancer patients and 15 controls by real-time reverse-transcription polymerase chain reaction (RT-PCR). Results Genes identified by gene selection program were expressed differently in the blood samples of early-stage cervical cancer from those of healthy controls. To validate the gene expression data, 5 genes were analyzed by real-time RT-PCR. In three of 5 identified genes, tenasin-c, nucleolin, and enolase 2 (ENO2) showed a significant up-regulation in blood samples of early-stage cervical cancer patients versus that of the controls. Conclusion The up-regulation of tenasin-c, nucleolin and ENO2 in peripheral blood may be used to identify novel blood biomarkers for detecting cervical cancer in a clinically accessible surrogate tissue. Thus it may offer a possibility of developing a non-invasive and predictive diagnostic tool for the disease.%目的 应用人类全基因组寡核苷酸芯片技术在宫颈癌患者外周血中确定生物分子标志物.方法 从24例早期宫颈癌患者和18例正常对照者的外周血淋巴细胞中提取总RNA.应用微阵列技术,采用人类全基因组寡核苷酸芯片检测4例宫颈癌患者和3例正常对照者的差异表达基因,再对20例宫颈癌患者和15例正常对照者将初步筛选出的5个候选基因用实时定量逆转录多聚酶链反应(RT-PCR)的方法进行验证.结果 筛选得到57个差异表达基因,其中38个基因表达上调,19个基因表达下调;对初步筛选出的5个候选基因经实时定量逆转录多聚酶链反应的方法进行验证后发现黏合素-C、核仁素和磷酸丙酮酸水合酶2(enolase 2,ENO2)基因在宫

  4. Mini-P-gp and P-gp Co-Expression in Brown Trout Erythrocytes: A Prospective Blood Biomarker of Aquatic Pollution

    OpenAIRE

    Emeline Valton; Christian Amblard; François Desmolles; Bruno Combourieu; Frédérique Penault-Llorca; Mahchid Bamdad

    2015-01-01

    In aquatic organisms, such as fish, blood is continually exposed to aquatic contaminants. Multidrug Resistance (MDR) proteins are ubiquitous detoxification membrane pumps, which recognize various xenobiotics. Moreover, their expression is induced by a large class of drugs and pollutants. We have highlighted the co-expression of a mini P-gp of 75 kDa and a P-gp of 140 kDa in the primary culture of brown trout erythrocytes and in the erythrocytes of wild brown trout collected from three rivers ...

  5. Estimating lifetime risk from spot biomarker data and intra‐class correlation coefficients (ICC)

    Science.gov (United States)

    Human biomarker measurements in tissues including blood, breath, and urine can serve as efficient surrogates for environmental monitoring because a single biological sample integrates personal exposure across all environmental media and uptake pathways. However, biomarkers repres...

  6. Current status of biomarker research in neurology

    OpenAIRE

    Polivka, Jiri; Krakorova, Kristyna; Peterka, Marek; Topolcan, Ondrej

    2016-01-01

    Neurology is one of the typical disciplines where personalized medicine has been recently becoming an important part of clinical practice. In this article, the brief overview and a number of examples of the use of biomarkers and personalized medicine in neurology are described. The various issues in neurology are described in relation to the personalized medicine and diagnostic, prognostic as well as predictive blood and cerebrospinal fluid biomarkers. Such neurological domains discussed in t...

  7. Gamma-H2AX as a biomarker of DNA damage induced by ionizing radiation in targeted and bystander human artificial skin models and peripheral blood lymphocytes

    Science.gov (United States)

    Redon, Christophe; Dickey, Jennifer; Bonner, William; Sedelnikova, Olga

    Ionizing radiation (IR) exposure is inevitable. In addition to exposure from cosmic rays, the sun and radioactive substances, modern society has created new sources of radiation exposure such as space and high altitude journeys, X-ray diagnostics, radiological treatments and the increasing threat of radiobiological terrorism. For these reasons, a reliable, reproducible and sensitive assessment of dose and time exposure to IR is essential. We developed a minimally invasive diagnostic test for IR exposure based on detection of a phosphorylated variant of histone H2AX (gamma-H2AX), which occurs specifically at sites of DNA double-strand breaks (DSBs). The phosphorylation of thousands of H2AX molecules forms a gamma-H2AX focus in the chromatin flanking the DSB site that can be detected in situ. We analyzed gamma- H2AX focus formation in both directly irradiated cells as well as in un-irradiated "bystanders" in close contact with irradiated cells. In order to insure minimal invasiveness, we examined commercially available artificial skin models as a surrogate for human skin biopsies as well as peripheral blood lymphocytes. In human skin models, cells in a thin plane were microbeamirradiated and gamma-H2AX formation was measured both in irradiated and in distal bystander cells over time. In irradiated cells DSB formation reached a maximum at 15-30 minutes post- IR and then declined within several hours; all cells were affected. In marked contrast, the incidence of DSBs in bystander cells reached a maximum by 12-48 hours post-irradiation, gradually decreasing over the 7 day time course. At the maxima, 40-60% of bystander cells were affected. Similarly, we analyzed blood samples exposed to IR ex vivo at doses ranging from 0.02 to 3 Gy. The amount of DNA damage was linear in respect to radiation dose and independent of the age or sex of the blood donor. The method is highly reproducible and highly sensitive. In directly irradiated cells, the number of gamma-H2AX foci peaked

  8. Coherent white light amplification

    Science.gov (United States)

    Jovanovic, Igor; Barty, Christopher P.

    2004-05-25

    A system for coherent simultaneous amplification of a broad spectral range of light that includes an optical parametric amplifier and a source of a seed pulse is described. A first angular dispersive element is operatively connected to the source of a seed pulse. A first imaging telescope is operatively connected to the first angular dispersive element and operatively connected to the optical parametric amplifier. A source of a pump pulse is operatively connected to the optical parametric amplifier. A second imaging telescope is operatively connected to the optical parametric amplifier and a second angular dispersive element is operatively connected to the second imaging telescope.

  9. Nano and Microparticle-Enhanced Immunosensor Approaches for the Detection of Cancer Biomarker Proteins

    Science.gov (United States)

    Mani, Vigneshwaran

    Accurate, sensitive, point-of-care multiplexed protein measurements are critical for early disease detection and monitoring, impacting biomarker and drug discovery, and personalized medicine. Significant application involves monitoring panels of proteins in the blood that are biomarkers for diagnosing cancer. However, measurements of biomarker panels in blood or other bodily fluids have been slow to integrate into current practice of cancer diagnostics partly due to the lack of technically simple, low-cost, sensitive, point-of-care multiplexed measurement devices, as well as the lack of rigorously validated protein panels. The present thesis in part addresses these limitations by the development of electrochemical and surface plasmon resonance (SPR) immunosensors utilizing 1mum superparamagnetic labels for accurate detection of prostate cancer biomarker proteins in patient serum samples. Electrochemical discrete immunosensors featuring nanostructured surface with densely packed 5 nm glutathione-coated gold nanoparticles coupled with multi-enzyme magnetic particle (MP) labels enabled measurement of prostate specific antigen (PSA) with a detection limit (DL) of 0.5 pg mL-1 in undiluted serum. Such low DLs are attributed to high surface area, conductivity of nanostructured surface, and multi-enzyme signal amplification. DLs are further improved by utilizing MP bioconjugated with more than 100,000 antibody labels to offline capture proteins from the serum sample matrix, minimizing nonspecific binding of interfering proteins on sensor surface before detection. This approach provided an unprecedented 10 fg DL mL-1 for PSA in undiluted serum using a flow SPR biosensor. Finally electrochemical microfluidic immunoarrays featuring nanostructured surface and offline protein capture by multi-label MPs enabled multiplexed detection of prostate cancer biomarkers PSA and interleukin-6 (IL-6). These approaches provided up to 1000-fold lower DLs compared to commercial bead based

  10. Cerebral blood flow measured by arterial-spin labeling MRI: A useful biomarker for characterization of minimal hepatic encephalopathy in patients with cirrhosis

    International Nuclear Information System (INIS)

    Purpose: To investigate the role of arterial-spin labeling (ASL) MRI to non-invasively characterize the patterns of cerebral blood flow (CBF) changes in cirrhotic patients and to assess the potential of ASL MRI to characterize minimal hepatic encephalopathy (MHE). Materials and methods: This study was approved by the local ethics committee, and written informed consent was obtained from all participants. Thirty six cirrhosis patients without overt hepatic encephalopathy (16 MHE patients and 20 non hepatic encephalopathy (non-HE) patients) and 25 controls underwent ASL MRI, and CBF was measured for each subject. One-way ANOCOVA test with age and gender as covariences was used to compare CBF difference among three groups, and post hoc analysis was performed between each two groups. Region-based correlation analysis was applied between Child–Pugh score, venous blood ammonia level, neuropsychological tests and CBF values in cirrhosis patients. Receiver operator characteristic (ROC) analysis was used for assessing CBF measurements in ASL MRI to differentiate MHE from non-HE patients. Results: The gray matter CBF of MHE patients (71.09 ± 11.88 mL min−1 100 g−1) was significantly higher than that of non-HE patients (55.28 ± 12.30 mL min−1 100 g−1, P < 0.01) and controls (52.09 ± 9.27 mL min−1 100 g−1, P < 0.001). Voxel-wise ANOCOVA results showed that CBFs were significantly different among three groups in multiple gray matter areas (P < 0.05, Bonferroni corrected). Post hoc comparisons showed that CBF of these brain regions was increased in MHE patients compared with controls and non-HE patients (P < 0.05, Bonferroni corrected). CBF of the right putamen was of the highest sensitivity (93.8%) and moderate specificity (75.0%) for characterization of MHE when using the cutoff value of 50.57 mL min−1 100 g−1. CBFs in the bilateral median cingulate gyri, left supramarginal gyrus, right angular gyrus, right heschl gyrus and right superior temporal gyrus

  11. Cerebral blood flow measured by arterial-spin labeling MRI: A useful biomarker for characterization of minimal hepatic encephalopathy in patients with cirrhosis

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Gang [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu, 210002 (China); College of Civil Aviation, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, 210016 (China); Zhang, Long Jiang, E-mail: kevinzhlj@163.com [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu, 210002 (China); Zhong, Jianhui [Department of Imaging Sciences, University of Rochester School of Medicine and Dentistry, Box648, 601 Elmwood Avenue, Rochester, NY 14642-8648 (United States); Wang, Ze [Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, 3900 Chestnut St., Philadelphia, PA 19104 (United States); Qi, Rongfeng; Shi, Donghong [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu, 210002 (China); Lu, Guang Ming, E-mail: cjr.luguangming@vip.163.com [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu, 210002 (China)

    2013-11-01

    Purpose: To investigate the role of arterial-spin labeling (ASL) MRI to non-invasively characterize the patterns of cerebral blood flow (CBF) changes in cirrhotic patients and to assess the potential of ASL MRI to characterize minimal hepatic encephalopathy (MHE). Materials and methods: This study was approved by the local ethics committee, and written informed consent was obtained from all participants. Thirty six cirrhosis patients without overt hepatic encephalopathy (16 MHE patients and 20 non hepatic encephalopathy (non-HE) patients) and 25 controls underwent ASL MRI, and CBF was measured for each subject. One-way ANOCOVA test with age and gender as covariences was used to compare CBF difference among three groups, and post hoc analysis was performed between each two groups. Region-based correlation analysis was applied between Child–Pugh score, venous blood ammonia level, neuropsychological tests and CBF values in cirrhosis patients. Receiver operator characteristic (ROC) analysis was used for assessing CBF measurements in ASL MRI to differentiate MHE from non-HE patients. Results: The gray matter CBF of MHE patients (71.09 ± 11.88 mL min{sup −1} 100 g{sup −1}) was significantly higher than that of non-HE patients (55.28 ± 12.30 mL min{sup −1} 100 g{sup −1}, P < 0.01) and controls (52.09 ± 9.27 mL min{sup −1} 100 g{sup −1}, P < 0.001). Voxel-wise ANOCOVA results showed that CBFs were significantly different among three groups in multiple gray matter areas (P < 0.05, Bonferroni corrected). Post hoc comparisons showed that CBF of these brain regions was increased in MHE patients compared with controls and non-HE patients (P < 0.05, Bonferroni corrected). CBF of the right putamen was of the highest sensitivity (93.8%) and moderate specificity (75.0%) for characterization of MHE when using the cutoff value of 50.57 mL min{sup −1} 100 g{sup −1}. CBFs in the bilateral median cingulate gyri, left supramarginal gyrus, right angular gyrus, right

  12. Current and emerging biomarkers of hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Yang X

    2012-08-01

    Full Text Available Xi Yang, William F Salminen, Laura K SchnackenbergDivision of Systems Biology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USAAbstract: Drug-induced liver injury (DILI is of great concern to human health. Generally, liver function and injury is evaluated based upon clinical signs, a select group of serum clinical biomarkers, and occasionally liver biopsies. While alanine aminotransferase, the most commonly used biomarker of hepatocellular injury, is a sensitive marker of liver injury, it is not necessarily specific for liver injury. Furthermore, alanine aminotransferase levels may not always correlate with the extent of injury. Therefore, new hepatotoxicity biomarkers are needed that are more predictive and specific indicators of liver injury and altered function. In addition, no current biomarker provides prognostic information about ultimate outcome once injury occurs, and any new biomarker filling this need is desperately needed. The omics technologies, including genomics, proteomics, and metabolomics, are being used in preclinical animal studies as well as clinical studies to evaluate markers of hepatotoxicity in easily obtained biofluids, such as urine and serum. Recently, the evaluation of circulating microRNAs in urine and blood has also shown promise for the identification of novel, sensitive markers of liver injury. This review evaluates the current status of proposed biomarkers of hepatotoxicity from the omics platforms, as well as from analysis of microRNAs. A brief description of the qualification of proposed biomarkers is also given.Keywords: biomarkers, hepatotoxicity, metabolomics, microRNA, proteomics, transcriptomics

  13. DNA Methylation Biomarkers: Cancer and Beyond

    Directory of Open Access Journals (Sweden)

    Thomas Mikeska

    2014-09-01

    Full Text Available Biomarkers are naturally-occurring characteristics by which a particular pathological process or disease can be identified or monitored. They can reflect past environmental exposures, predict disease onset or course, or determine a patient’s response to therapy. Epigenetic changes are such characteristics, with most epigenetic biomarkers discovered to date based on the epigenetic mark of DNA methylation. Many tissue types are suitable for the discovery of DNA methylation biomarkers including cell-based samples such as blood and tumor material and cell-free DNA samples such as plasma. DNA methylation biomarkers with diagnostic, prognostic and predictive power are already in clinical trials or in a clinical setting for cancer. Outside cancer, strong evidence that complex disease originates in early life is opening up exciting new avenues for the detection of DNA methylation biomarkers for adverse early life environment and for estimation of future disease risk. However, there are a number of limitations to overcome before such biomarkers reach the clinic. Nevertheless, DNA methylation biomarkers have great potential to contribute to personalized medicine throughout life. We review the current state of play for DNA methylation biomarkers, discuss the barriers that must be crossed on the way to implementation in a clinical setting, and predict their future use for human disease.

  14. Integrated mRNA and miRNA expression profiling in blood reveals candidate biomarkers associated with endurance exercise in the horse

    Science.gov (United States)

    Mach, Núria; Plancade, Sandra; Pacholewska, Alicja; Lecardonnel, Jérôme; Rivière, Julie; Moroldo, Marco; Vaiman, Anne; Morgenthaler, Caroline; Beinat, Marine; Nevot, Alizée; Robert, Céline; Barrey, Eric

    2016-01-01

    The adaptive response to extreme endurance exercise might involve transcriptional and translational regulation by microRNAs (miRNAs). Therefore, the objective of the present study was to perform an integrated analysis of the blood transcriptome and miRNome (using microarrays) in the horse before and after a 160 km endurance competition. A total of 2,453 differentially expressed genes and 167 differentially expressed microRNAs were identified when comparing pre- and post-ride samples. We used a hypergeometric test and its generalization to gain a better understanding of the biological functions regulated by the differentially expressed microRNA. In particular, 44 differentially expressed microRNAs putatively regulated a total of 351 depleted differentially expressed genes involved variously in glucose metabolism, fatty acid oxidation, mitochondrion biogenesis, and immune response pathways. In an independent validation set of animals, graphical Gaussian models confirmed that miR-21-5p, miR-181b-5p and miR-505-5p are candidate regulatory molecules for the adaptation to endurance exercise in the horse. To the best of our knowledge, the present study is the first to provide a comprehensive, integrated overview of the microRNA-mRNA co-regulation networks that may have a key role in controlling post-transcriptomic regulation during endurance exercise. PMID:26960911

  15. Efficient Audio Power Amplification - Challenges

    DEFF Research Database (Denmark)

    Andersen, Michael Andreas E.

    2005-01-01

    For more than a decade efficient audio power amplification has evolved and today switch-mode audio power amplification in various forms are the state-of-the-art. The technical steps that lead to this evolution are described and in addition many of the challenges still to be faced and where extens...

  16. Efficient audio power amplification - challenges

    Energy Technology Data Exchange (ETDEWEB)

    Andersen, Michael A.E.

    2005-07-01

    For more than a decade efficient audio power amplification has evolved and today switch-mode audio power amplification in various forms are the state-of-the-art. The technical steps that lead to this evolution are described and in addition many of the challenges still to be faced and where extensive research and development are needed is covered. (au)

  17. Biomarkers in Computational Toxicology

    Science.gov (United States)

    Biomarkers are a means to evaluate chemical exposure and/or the subsequent impacts on toxicity pathways that lead to adverse health outcomes. Computational toxicology can integrate biomarker data with knowledge of exposure, chemistry, biology, pharmacokinetics, toxicology, and e...

  18. Loss of KLF14 triggers centrosome amplification and tumorigenesis.

    Science.gov (United States)

    Fan, Guangjian; Sun, Lianhui; Shan, Peipei; Zhang, Xianying; Huan, Jinliang; Zhang, Xiaohong; Li, Dali; Wang, Tingting; Wei, Tingting; Zhang, Xiaohong; Gu, Xiaoyang; Yao, Liangfang; Xuan, Yang; Hou, Zhaoyuan; Cui, Yongping; Cao, Liu; Li, Xiaotao; Zhang, Shengping; Wang, Chuangui

    2015-01-01

    Centrosome amplification is frequent in cancer, but the underlying mechanisms remain unclear. Here we report that disruption of the Kruppel-like factor 14 (KLF14) gene in mice causes centrosome amplification, aneuploidy and spontaneous tumorigenesis. Molecularly, KLF14 functions as a transcriptional repressor of Plk4, a polo-like kinase whose overexpression induces centrosome overduplication. Transient knockdown of KLF14 is sufficient to induce Plk4-directed centrosome amplification. Clinically, KLF14 transcription is significantly downregulated, whereas Plk4 transcription is upregulated in multiple types of cancers, and there exists an inverse correlation between KLF14 and Plk4 protein expression in human breast and colon cancers. Moreover, KLF14 depletion promotes AOM/DSS-induced colon tumorigenesis. Our findings reveal that KLF14 reduction serves as a mechanism leading to centrosome amplification and tumorigenesis. On the other hand, forced expression of KLF14 leads to mitotic catastrophe. Collectively, our findings identify KLF14 as a tumour suppressor and highlight its potential as biomarker and therapeutic target for cancer. PMID:26439168

  19. Combination of biomarkers

    DEFF Research Database (Denmark)

    Thurfjell, Lennart; Lötjönen, Jyrki; Lundqvist, Roger;

    2012-01-01

    The New National Institute on Aging-Alzheimer's Association diagnostic guidelines for Alzheimer's disease (AD) incorporate biomarkers in the diagnostic criteria and suggest division of biomarkers into two categories: Aβ accumulation and neuronal degeneration or injury.......The New National Institute on Aging-Alzheimer's Association diagnostic guidelines for Alzheimer's disease (AD) incorporate biomarkers in the diagnostic criteria and suggest division of biomarkers into two categories: Aβ accumulation and neuronal degeneration or injury....

  20. Is blood pressure reduction a valid surrogate endpoint for stroke prevention? an analysis incorporating a systematic review of randomised controlled trials, a by-trial weighted errors-in-variables regression, the surrogate threshold effect (STE and the biomarker-surrogacy (BioSurrogate evaluation schema (BSES

    Directory of Open Access Journals (Sweden)

    Lassere Marissa N

    2012-03-01

    Full Text Available Abstract Background Blood pressure is considered to be a leading example of a valid surrogate endpoint. The aims of this study were to (i formally evaluate systolic and diastolic blood pressure reduction as a surrogate endpoint for stroke prevention and (ii determine what blood pressure reduction would predict a stroke benefit. Methods We identified randomised trials of at least six months duration comparing any pharmacologic anti-hypertensive treatment to placebo or no treatment, and reporting baseline blood pressure, on-trial blood pressure, and fatal and non-fatal stroke. Trials with fewer than five strokes in at least one arm were excluded. Errors-in-variables weighted least squares regression modelled the reduction in stroke as a function of systolic blood pressure reduction and diastolic blood pressure reduction respectively. The lower 95% prediction band was used to determine the minimum systolic blood pressure and diastolic blood pressure difference, the surrogate threshold effect (STE, below which there would be no predicted stroke benefit. The STE was used to generate the surrogate threshold effect proportion (STEP, a surrogacy metric, which with the R-squared trial-level association was used to evaluate blood pressure as a surrogate endpoint for stroke using the Biomarker-Surrogacy Evaluation Schema (BSES3. Results In 18 qualifying trials representing all pharmacologic drug classes of antihypertensives, assuming a reliability coefficient of 0.9, the surrogate threshold effect for a stroke benefit was 7.1 mmHg for systolic blood pressure and 2.4 mmHg for diastolic blood pressure. The trial-level association was 0.41 and 0.64 and the STEP was 66% and 78% for systolic and diastolic blood pressure respectively. The STE and STEP were more robust to measurement error in the independent variable than R-squared trial-level associations. Using the BSES3, assuming a reliability coefficient of 0.9, systolic blood pressure was a B + grade and

  1. New sepsis biomarkers

    Institute of Scientific and Technical Information of China (English)

    Dolores Limongi; Cartesio DAgostini; Marco Ciotti

    2016-01-01

    Sepsis remains a leading cause of death in the intensive care units and in all age groups worldwide. Early recognition and diagnosis are key to achieving improved outcomes. Therefore, novel biomarkers that might better inform clinicians treating such patients are surely needed. The main attributes of successful biomarkers would be high sensitivity, specificity, possibility of bedside monitoring and financial accessibility. A panel of sepsis biomarkers along with currently used laboratory tests will facilitate earlier diagnosis, timely treatment and improved outcome may be more effective than single biomarkers. In this review, we summarize the most recent advances on sepsis biomarkers evaluated in clinical and experimental studies.

  2. Biomarkers in Parkinson's disease (recent update).

    Science.gov (United States)

    Sharma, Sushil; Moon, Carolyn Seungyoun; Khogali, Azza; Haidous, Ali; Chabenne, Anthony; Ojo, Comfort; Jelebinkov, Miriana; Kurdi, Yousef; Ebadi, Manuchair

    2013-09-01

    Parkinson's disease (PD) is the second most common neurodegenerative disorder mostly affecting the aging population over sixty. Cardinal symptoms including, tremors, muscle rigidity, drooping posture, drooling, walking difficulty, and autonomic symptoms appear when a significant number of nigrostriatal dopaminergic neurons are already destroyed. Hence we need early, sensitive, specific, and economical peripheral and/or central biomarker(s) for the differential diagnosis, prognosis, and treatment of PD. These can be classified as clinical, biochemical, genetic, proteomic, and neuroimaging biomarkers. Novel discoveries of genetic as well as nongenetic biomarkers may be utilized for the personalized treatment of PD during preclinical (premotor) and clinical (motor) stages. Premotor biomarkers including hyper-echogenicity of substantia nigra, olfactory and autonomic dysfunction, depression, hyposmia, deafness, REM sleep disorder, and impulsive behavior may be noticed during preclinical stage. Neuroimaging biomarkers (PET, SPECT, MRI), and neuropsychological deficits can facilitate differential diagnosis. Single-cell profiling of dopaminergic neurons has identified pyridoxal kinase and lysosomal ATPase as biomarker genes for PD prognosis. Promising biomarkers include: fluid biomarkers, neuromelanin antibodies, pathological forms of α-Syn, DJ-1, amyloid β and tau in the CSF, patterns of gene expression, metabolomics, urate, as well as protein profiling in the blood and CSF samples. Reduced brain regional N-acetyl-aspartate is a biomarker for the in vivo assessment of neuronal loss using magnetic resonance spectroscopy and T2 relaxation time with MRI. To confirm PD diagnosis, the PET biomarkers include [(18)F]-DOPA for estimating dopaminergic neurotransmission, [(18)F]dG for mitochondrial bioenergetics, [(18)F]BMS for mitochondrial complex-1, [(11)C](R)-PK11195 for microglial activation, SPECT imaging with (123)Iflupane and βCIT for dopamine transporter, and urinary

  3. Next generation Chirped Pulse Amplification

    Energy Technology Data Exchange (ETDEWEB)

    Nees, J.; Biswal, S.; Mourou, G. [Univ. Michigan, Center for Ultrafast Optical Science, Ann Arbor, MI (United States); Nishimura, Akihiko; Takuma, Hiroshi

    1998-03-01

    The limiting factors of Chirped Pulse Amplification (CPA) are discussed and experimental results of CPA in Yb:glass regenerative amplifier are given. Scaling of Yb:glass to the petawatt level is briefly discussed. (author)

  4. Detection of maternal DNA in umbilical cord plasma by fluorescent PCR amplification of short tandem repeat sequences.

    Science.gov (United States)

    Bauer, M; Orescovic, I; Schoell, W M; Bianchi, D W; Pertl, B

    2001-09-01

    Recently, maternal DNA was detected in umbilical cord blood using PCR amplification of minisatellite sequences. The presence of maternal DNA was demonstrated in 1% to 100% of umbilical cord blood samples. The objective of this study was to determine the frequency of cord blood contamination by maternal genetic material. We used fluorescent PCR amplification of highly polymorphic short tandem repeat (STR) markers to detect maternal DNA in umbilical cord plasma. PMID:11708473

  5. Biomarkers of Alzheimer’s disease in body fluids

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Various innovative diagnostic methods for Alzheimer’s disease (AD) have been developed in view of the increasing preva-lence and consequences of later-life dementia. Biomarkers in cerebrospinal fluid (CSF) and blood for AD are primarily based on the detection of components derived from amyloid plaques and neurofibrillary tangles (NFTs). Published reports on CSF and blood biomarkers in AD indicate that although biomarkers in body fluids may be utilized in the clinical diagnosis of AD, there are no specific markers that permit accurate and reliable diagnosis of early-stage AD or the monitoring of disease pro-gression.

  6. Exploring Biomarkers for Alzheimer’s Disease

    Science.gov (United States)

    Singh, Anshika Nikita

    2016-01-01

    Alzheimer’s Disease (AD) is one of the most common form of dementia occurring in elderly population worldwide. Currently Aβ42, tau and p-tau in the cerebrospinal fluid is estimated for confirmation of AD. CSF which is being used as the potent source for biomarker screening is obtained by invasive lumbar punctures. Thus, there is an urgent need of minimal invasive methods for identification of diagnostic markers for early detection of AD. Blood serum and plasma serves as an appropriate source, due to minimal discomfort to the patients, promoting frequent testing, better follow-up and better consent to clinical trials. Hence, the need of the hour demands discovery of diagnostic and prognostic patient specific signature biomarkers by using emerging technologies of mass spectrometry, microarrays and peptidomics. In this review we summarize the present scenario of AD biomarkers such as circulatory biomarkers, blood based amyloid markers, inflammatory markers and oxidative stress markers being investigated and also some of the potent biomarkers which might be able to predict early onset of Alzheimer’s and delay cognitive impairment. PMID:27630867

  7. Umbilical Cord Mercury Concentration as Biomarker of Prenatal Exposure to Methylmercury

    DEFF Research Database (Denmark)

    Grandjean, Philippe; Budtz-Jørgensen, Esben; Jørgensen, Poul J.;

    2005-01-01

    biomarker, exposure assessment, food contamination, hair analysis, mercury/analysis, methylmercury compounds/analysis, organomercury compounds/blood, pregnancy, prenatal exposure delayed effects, preschool child, seafood, umbilical cord.......biomarker, exposure assessment, food contamination, hair analysis, mercury/analysis, methylmercury compounds/analysis, organomercury compounds/blood, pregnancy, prenatal exposure delayed effects, preschool child, seafood, umbilical cord....

  8. Translation of neurological biomarkers to clinically relevant platforms.

    Science.gov (United States)

    Hayes, Ronald L; Robinson, Gillian; Muller, Uwe; Wang, Kevin K W

    2009-01-01

    Like proteomics more generally, neuroproteomics has recently been linked to the discovery of biochemical markers of central nervous system (CNS) injury and disease. Although neuroproteomics has enjoyed considerable success in discovery of candidate biomarkers, there are a number of challenges facing investigators interested in developing clinically useful platforms to assess biomarkers for damage to the CNS. These challenges include intrinsic physiological complications such as the blood-brain barrier. Effective translation of biomarkers to clinical practice also requires development of entirely novel pathways and product development strategies. Drawing from lessons learned from applications of biomarkers to traumatic brain injury, this study outlines major elements of such a pathway. As with other indications, biomarkers can have three major areas of application: (1) drug development; (2) diagnosis and prognosis; (3) patient management. Translation of CNS biomarkers to practical clinical platforms raises a number of integrated elements. Biomarker discovery and initial selection needs to be integrated at the earliest stages with components that will allow systematic prioritization and triage of biomarker candidates. A number of important criteria need to be considered in selecting clinical biomarker candidates. Development of proof of concept assays and their optimization and validation represent an often overlooked feature of biomarker translational research. Initial assay optimization should confirm that assays can detect biomarkers in relevant clinical samples. Since access to human clinical samples is critical to identification of biomarkers relevant to injury and disease as well as for assay development, design of human clinical validation studies is an important component of translational biomarker research platforms. Although these clinical studies share much in common with clinical trials for assessment of drug therapeutic efficacy, there are a number of

  9. Exploration of new HCC biomarkers

    Directory of Open Access Journals (Sweden)

    Regina M. Santella

    2007-02-01

    Full Text Available

    Analysis of plasma/serum for levels of viral antigens or antibodies to viral proteins has been used extensively as an early biomarker of potential risk of HCC. In addition, detection of elevated levels of alpha-fetoprotein is commonly used for early identification of HCC. Unfortunately, both of these approaches are not highly sensitive or specific. As a result, there is continuing investigation to identify additional biomarkers that may help in the early identification of cases. The use of DNA isolated from plasma or serum for detection of gene specific methylation has been discussed previously. In addition, tumor DNA isolated from blood has been analyzed for the presence of p53 mutations and found in a subset of cases to be present years prior to diagnosis as for methylated DNA. The general level of DNA present in blood has also been suggested as a potential biomarker of cancer.

    Among the newer methods being tested are the detection of specific mutations in HBV. In many cases of HCC in China and Africa a double mutation, an A to T transversion at nucleotide 1762 and a G to A transition at nucleotide 1764 (1762T/1764A have been found. These mutations have been associated with increased severity of HBV infection and cirrhosis suggesting that they might be a useful biomarker for high risk subjects.

    The field of proteomics also holds promise for the development of new biomarkers. A number of groups are developing mass spectrometry methods for the identification of serum/plasma proteomic patterns that will distinguish bloods of HCC cases from those of controls. While some interesting preliminary data have been developed for several cancers, much additional work needs to be done in this area

  10. Respiratory Toxicity Biomarkers

    Science.gov (United States)

    The advancement in high throughput genomic, proteomic and metabolomic techniques have accelerated pace of lung biomarker discovery. A recent growth in the discovery of new lung toxicity/disease biomarkers have led to significant advances in our understanding of pathological proce...

  11. Biomarkers in Autism

    Directory of Open Access Journals (Sweden)

    Robert eHendren

    2014-08-01

    Full Text Available Autism spectrum disorders (ASD are complex, heterogeneous disorders caused by an interaction between genetic vulnerability and environmental factors. In an effort to better target the underlying roots of ASD for diagnosis and treatment, efforts to identify reliable biomarkers in genetics, neuroimaging, gene expression and measures of the body’s metabolism are growing. For this article, we review the published studies of potential biomarkers in autism and conclude that while there is increasing promise of finding biomarkers that can help us target treatment, there are none with enough evidence to support routine clinical use unless medical illness is suspected. Promising biomarkers include those for mitochondrial function, oxidative stress, and immune function. Genetic clusters are also suggesting the potential for useful biomarkers.

  12. Optical chirped beam amplification and propagation

    Science.gov (United States)

    Barty, Christopher P.

    2004-10-12

    A short pulse laser system uses dispersive optics in a chirped-beam amplification architecture to produce high peak power pulses and high peak intensities without the potential for intensity dependent damage to downstream optical components after amplification.

  13. Double regenerative amplification of picosecond pulses

    Science.gov (United States)

    Bai, Zhen-ao; Chen, Li-yuan; Bai, Zhen-xu; Chen, Meng; Li, Gang

    2012-04-01

    An double Nd:YAG regenerative amplification picosecond pulse laser is demonstrated under the semiconductor saturable absorption mirror(SESAM) mode-locking technology and regenerative amplification technology, using BBO crystal as PC electro-optic crystal. The laser obtained is 20.71ps pulse width at 10 KHz repetition rate, and the energy power is up to 4W which is much larger than the system without pre-amplification. This result will lay a foundation for the following amplification.

  14. Use of Obesity Biomarkers in Cardiovascular Epidemiology

    Directory of Open Access Journals (Sweden)

    Tobias Pischon

    2009-01-01

    Full Text Available Obesity is an established risk factor for cardiovascular disease (CVD, yet, the underlying mechanisms are only poorly understood. The adipose tissue produces a variety of hormones and cytokines and thereby actively participates in a network of biomarkers that may be relevant for the development of CVD. Such obesity biomarkers have a great potential to better characterize the obesity phenotype that may be relevant for the risk of CVD beyond anthropometric parameters. They may be used to support mechanistic studies, to help identify individuals at risk for CVD, and to evaluate the effect of preventive measures. The present article discusses the role of some of the most promising obesity biomarkers in cardiovascular epidemiology, including inflammatory markers, adiponectin, resistin, and fetuin-A. Importantly, some of these markers have been related to cardiovascular risk even after accounting for anthropometric parameters. Further, the potential ability to manipulate blood levels of some of these biomarkers through medication, diet and lifestyle make them attractive markers for cardiovascular risk. However, many open questions remain – especially with regard to the causal role of the factors as well as with regard to the extent of improvement in CVD prediction by these markers – before measurement of these biomarkers may be recommended on a public health level.

  15. Biomarkers in the Management of Difficult Asthma.

    Science.gov (United States)

    Schleich, Florence; Sophie, Demarche; Renaud, Louis

    2016-01-01

    Difficult asthma is a heterogeneous disease of the airways including various types of bronchial inflammation and various degrees of airway remodeling. Therapeutic response of severe asthmatics can be predicted by the use of biomarkers of Type2-high or Type2-low inflammation. Based on sputum cell analysis, four inflammatory phenotypes have been described. As induced sputum is timeconsuming and expensive technique, surrogate biomarkers are useful in clinical practice. Eosinophilic phenotype is likely to reflect ongoing adaptive immunity in response to allergen. Several biomarkers of eosinophilic asthma are easily available in clinical practice (blood eosinophils, serum IgE, exhaled nitric oxyde, serum periostin). Neutrophilic asthma is thought to reflect innate immune system activation in response to pollutants or infectious agents while paucigranulocytic asthma is thought to be not inflammatory and characterized by smooth muscle dysfunction. We currently lack of user-friendly biomarkers of neutrophilic asthma and airway remodeling. In this review, we summarize the biomarkers available for the management of difficult asthma. PMID:26467509

  16. Comprehensive human genome amplification using multiple displacement amplification

    OpenAIRE

    Dean, Frank B.; Hosono, Seiyu; Fang, Linhua; Wu, Xiaohong; Faruqi, A. Fawad; Bray-Ward, Patricia; Zhenyu SUN; Zong, Qiuling; Du, Yuefen; Du, Jing; Driscoll, Mark; Song, Wanmin; Kingsmore, Stephen F.; Egholm, Michael; Lasken, Roger S.

    2002-01-01

    Fundamental to most genetic analysis is availability of genomic DNA of adequate quality and quantity. Because DNA yield from human samples is frequently limiting, much effort has been invested in developing methods for whole genome amplification (WGA) by random or degenerate oligonucleotide-primed PCR. However, existing WGA methods like degenerate oligonucleotide-primed PCR suffer from incomplete coverage and inadequate average DNA size. We describe a method, termed multi...

  17. Whole genome amplification and its impact on CGH array profiles

    Directory of Open Access Journals (Sweden)

    Meldrum Cliff

    2008-07-01

    Full Text Available Abstract Background Some array comparative genomic hybridisation (array CGH platforms require a minimum of micrograms of DNA for the generation of reliable and reproducible data. For studies where there are limited amounts of genetic material, whole genome amplification (WGA is an attractive method for generating sufficient quantities of genomic material from miniscule amounts of starting material. A range of WGA methods are available and the multiple displacement amplification (MDA approach has been shown to be highly accurate, although amplification bias has been reported. In the current study, WGA was used to amplify DNA extracted from whole blood. In total, six array CGH experiments were performed to investigate whether the use of whole genome amplified DNA (wgaDNA produces reliable and reproducible results. Four experiments were conducted on amplified DNA compared to unamplified DNA and two experiments on unamplified DNA compared to unamplified DNA. Findings All the experiments involving wgaDNA resulted in a high proportion of losses and gains of genomic material. Previously, amplification bias has been overcome by using amplified DNA in both the test and reference DNA. Our data suggests that this approach may not be effective, as the gains and losses introduced by WGA appears to be random and are not reproducible between different experiments using the same DNA. Conclusion In light of these findings, the use of both amplified test and reference DNA on CGH arrays may not provide an accurate representation of copy number variation in the DNA.

  18. cNEUPRO: Novel Biomarkers for Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Philipp Spitzer

    2010-01-01

    Full Text Available “clinical NEUroPROteomics of neurodegenerative diseases” (cNEUPRO is a Specific Targeted Research Project (STREP within the sixth framework program of the European Commission dedicated to the search for novel biomarker candidates for Alzheimer's disease and other neurodegenerative diseases. The ultimate goal of cNEUPRO is to identify one or more valid biomarker(s in blood and CSF applicable to support the early and differential diagnosis of dementia disorders. The consortium covers all steps required for the discovery of novel biomarker candidates such as acquisition of high quality CSF and blood samples from relevant patient groups and controls, analysis of body fluids by various methods, and finally assay development and assay validation. Here we report the standardized procedures for diagnosis and preanalytical sample-handling within the project, as well as the status of the ongoing research activities and some first results.

  19. Neurotoxicity and Biomarkers of Lead Exposure:a Review

    Institute of Scientific and Technical Information of China (English)

    Kang-sheng Liu; Jia-hu Hao; Yu Zeng; Fan-chun Dai; Ping-qing Gu

    2013-01-01

    Appropriate selection and measurement of lead biomarkers of exposure are critically important for health care management purposes, public health decision making, and primary prevention synthesis. Lead is one of the neurotoxicants that seems to be involved in the etiology of psychologies. Biomarkers are generally classified into three groups:biomarkers of exposure, effect, and susceptibility.The main body compartments that store lead are the blood, soft tissues, and bone;the half-life of lead in these tissues is measured in weeks for blood, months for soft tissues, and years for bone. Within the brain, lead-induced damage in the prefrontal cerebral cortex, hippocampus, and cerebellum can lead to a variety of neurological disorders, such as brain damage, mental retardation, behavioral problems, nerve damage, and possibly Alzheimer’s disease, Parkinson’s disease, and schizophrenia. This paper presents an overview of biomarkers of lead exposure and discusses the neurotoxic effects of lead with regard to children and adults.

  20. Metabolic products as biomarkers

    Science.gov (United States)

    Melancon, M.J.; Alscher, R.; Benson, W.; Kruzynski, G.; Lee, R.F.; Sikka, H.C.; Spies, R.B.; Huggett, Robert J.; Kimerle, Richard A.; Mehrle, Paul M.=; Bergman, Harold L.

    1992-01-01

    Ideally, endogenous biomarkers would indicate both exposure and environmental effects of toxic chemicals; however, such comprehensive biochemical and physiological indices are currently being developed and, at the present time, are unavailable for use in environmental monitoring programs. Continued work is required to validate the use of biochemical and physiological stress indices as useful components of monitoring programs. Of the compounds discussed only phytochelatins and porphyrins are currently in biomarkers in a useful state; however, glutathione,metallothioneins, stress ethylene, and polyamines are promising as biomarkers in environmental monitoring.

  1. Biomarkers in Severe Asthma.

    Science.gov (United States)

    Wan, Xiao Chloe; Woodruff, Prescott G

    2016-08-01

    Biomarkers have been critical for studies of disease pathogenesis and the development of new therapies in severe asthma. In particular, biomarkers of type 2 inflammation have proven valuable for endotyping and targeting new biological agents. Because of these successes in understanding and marking type 2 inflammation, lack of knowledge regarding non-type 2 inflammatory mechanisms in asthma will soon be the major obstacle to the development of new treatments and management strategies in severe asthma. Biomarkers can play a role in these investigations as well by providing insight into the underlying biology in human studies of patients with severe asthma. PMID:27401625

  2. Epikardiales Fett als Biomarker? // Epicardial Adipose Tissue as a Biomarker?

    Directory of Open Access Journals (Sweden)

    Tscharre M

    2016-01-01

    Full Text Available Epicardial adipose tissue as the “visceral” adipose tissue of the heart is arousing more and more scientific interest, as it has numerous local and systemic effects. There is no fascia separating the epicardial adipose tissue and the myocardium and they both share its blood supply via the coronary arteries, thus allowing a possible interaction. Under normal physiological conditions, epicardial adipose tissue has mainly anti-atherogenic, thermogenic and mechanical characteristics. Under pathological conditions it becomes harmful to the myocardium and the coronary arteries. Important features in the clinical setting are correlations with coronary artery disease, heart failure, atrial fibrillation and visceral adipose tissue, thus acting as a possible biomarker of cardiovascular risk. p bKurzfassung:/b Das epikardiale Fettgewebe erweckt als „viszerales“ Fettdepot des Herzens mit zahlreichen lokalen und systemischen Effekten immer mehr wissenschaftliches Interesse. Das Fehlen einer trennenden Faszie zwischen epikardialem Fettgewebe und Myokard und die gemeinsame Blutversorgung durch die Koronararterien erlauben eine potenzielle Interaktion. Unter normalen physiologischen Verhältnissen hat das epikardiale Fettgewebe hauptsächlich anti-atherogene, thermogenetische und mechanische Funktionen. Unter pathologischen Verhältnissen schädigt es das Myokard und die Koronararterien. Einen klinischen Stellenwert hat es aufgrund von Korrelationen mit koronarer Herzerkrankung, Herzinsuffizienz, Vorhofflimmern und viszeralem Fettgewebe. Dadurch könnte es als neuer Biomarker für das kardiovaskuläre Risiko dienen.

  3. Explorative investigation of biomarkers of brain damage and coagulation system activation in clinical stroke differentiation

    DEFF Research Database (Denmark)

    Undén, Johan; Strandberg, Karin; Malm, Jan;

    2009-01-01

    INTRODUCTION: A simple and accurate method of differentiating ischemic stroke and intracerebral hemorrhage (ICH) is potentially useful to facilitate acute therapeutic management. Blood measurements of biomarkers of brain damage and activation of the coagulation system may potentially serve as nov......: This exploratory study indicated that blood levels of biomarkers GFAP and APC-PCI, prior to neuroimaging, may rule out ICH in a mixed stroke population.......INTRODUCTION: A simple and accurate method of differentiating ischemic stroke and intracerebral hemorrhage (ICH) is potentially useful to facilitate acute therapeutic management. Blood measurements of biomarkers of brain damage and activation of the coagulation system may potentially serve as novel...... diagnostic tools for stroke subtypes. METHODS: Ninety-seven stroke patients were prospectively investigated in a multicenter design with blood levels of brain biomarkers S100B, neuron specific enolase (NSE), glial fibrillary acidic protein (GFAP) as well as a coagulation biomarker, activated protein C...

  4. Plasma Biomarkers Can Predict Treatment Response in Tuberculosis Patients

    OpenAIRE

    Lee, Meng-Rui; Tsai, Chia-Jung; Wang, Wei-Jie; Chuang, Tzu-Yi; Yang, Chih-Mann; Chang, Lih-Yu; Lin, Ching-Kai; Wang, Jann-Yuan; Shu, Chin-Chong; Lee, Li-Na; Yu, Chong-Jen

    2015-01-01

    Abstract Despite numerous studies, there has been little progress in the use of biomarkers for predicting treatment response in patients with tuberculosis (TB). Patients with culture-confirmed pulmonary TB between 2010 and 2014 were prospectively recruited. Blood samples were taken upon diagnosis and 2 months after the start of standard anti-TB treatment. A pilot study utilizing measurement of TB-antigen-stimulated cytokines was conducted to select potential biomarkers for further testing. Ou...

  5. Systematic Evaluation of the Prognostic Impact and Intratumour Heterogeneity of Clear Cell Renal Cell Carcinoma Biomarkers

    DEFF Research Database (Denmark)

    Gulati, Sakshi; Martinez, Pierre; Joshi, Tejal;

    2014-01-01

    and statistical analysisBiomarker association with CSS was analysed by univariate and multivariate analyses. Results and limitationsA total of 17 of 28 biomarkers (TP53 mutations; amplifications of chromosomes 8q, 12, 20q11.21q13.32, and 20 and deletions of 4p, 9p, 9p21.3p24.1, and 22q; low EDNRB and TSPAN7...... that were significant in univariate analysis were enriched, and chromosomal instability indices were increased in samples expressing the ccB signature. The study may be underpowered to validate low-prevalence biomarkers. ConclusionsThe ccB signature was the only independent prognostic biomarker. Enrichment...... of multiple poor prognosis genetic alterations in ccB samples indicated that several events may be required to establish this aggressive phenotype, catalysed in some tumours by chromosomal instability. Multiregion assessment may improve the precision of this biomarker. Patient summaryWe evaluated the ability...

  6. Hybrid chirped pulse amplification system

    Science.gov (United States)

    Barty, Christopher P.; Jovanovic, Igor

    2005-03-29

    A hybrid chirped pulse amplification system wherein a short-pulse oscillator generates an oscillator pulse. The oscillator pulse is stretched to produce a stretched oscillator seed pulse. A pump laser generates a pump laser pulse. The stretched oscillator seed pulse and the pump laser pulse are directed into an optical parametric amplifier producing an optical parametric amplifier output amplified signal pulse and an optical parametric amplifier output unconverted pump pulse. The optical parametric amplifier output amplified signal pulse and the optical parametric amplifier output laser pulse are directed into a laser amplifier producing a laser amplifier output pulse. The laser amplifier output pulse is compressed to produce a recompressed hybrid chirped pulse amplification pulse.

  7. Validation of New Cancer Biomarkers

    DEFF Research Database (Denmark)

    Duffy, Michael J; Sturgeon, Catherine M; Söletormos, Georg;

    2015-01-01

    in advancing a newly discovered cancer candidate biomarker from pilot studies to clinical application. Four main steps are necessary for a biomarker to reach the clinic: analytical validation of the biomarker assay, clinical validation of the biomarker test, demonstration of clinical value from performance...... of the biomarker test, and regulatory approval. In addition to these 4 steps, all biomarker studies should be reported in a detailed and transparent manner, using previously published checklists and guidelines. Finally, all biomarker studies relating to demonstration of clinical value should be registered before...

  8. Significant biomarkers for the management of hepatocellular carcinoma.

    Science.gov (United States)

    Kondo, Yasuteru; Kimura, Osamu; Shimosegawa, Tooru

    2015-06-01

    Surveillance of hepatocellular carcinoma (HCC) is important for early detection. Imaging tests including computed tomography, magnetic resonance imaging and ultrasonography with or without various kinds of contrast medium are important options for detecting HCC. In addition to the imaging tests, various kinds of biomarkers including alpha-fetoprotein (AFP), lectin-bound AFP (AFP-L3) and protein induced by vitamin K absence or antagonist II (PIVKA-II) have been widely used to detect HCC and analyze treatment response. Recently, various kinds of novel biomarkers (proteins and miRNA) have been found to predict the malignancy potential of HCC and treatment response to specific therapies. Moreover, various combinations of well-established biomarkers and novel biomarkers have been tested to improve sensitivity and specificity. In practical terms, biomarkers that can be analyzed using peripheral blood samples might be more useful than immunohistochemical techniques. It has been reported that quantification of cytokines in peripheral blood and the analysis of peripheral immune subsets could be good biomarkers for managing HCC. Here, we describe the usefulness of and update well-established and novel biomarkers for the management of HCC. PMID:25855582

  9. Significant biomarkers for the management of hepatocellular carcinoma.

    Science.gov (United States)

    Kondo, Yasuteru; Kimura, Osamu; Shimosegawa, Tooru

    2015-06-01

    Surveillance of hepatocellular carcinoma (HCC) is important for early detection. Imaging tests including computed tomography, magnetic resonance imaging and ultrasonography with or without various kinds of contrast medium are important options for detecting HCC. In addition to the imaging tests, various kinds of biomarkers including alpha-fetoprotein (AFP), lectin-bound AFP (AFP-L3) and protein induced by vitamin K absence or antagonist II (PIVKA-II) have been widely used to detect HCC and analyze treatment response. Recently, various kinds of novel biomarkers (proteins and miRNA) have been found to predict the malignancy potential of HCC and treatment response to specific therapies. Moreover, various combinations of well-established biomarkers and novel biomarkers have been tested to improve sensitivity and specificity. In practical terms, biomarkers that can be analyzed using peripheral blood samples might be more useful than immunohistochemical techniques. It has been reported that quantification of cytokines in peripheral blood and the analysis of peripheral immune subsets could be good biomarkers for managing HCC. Here, we describe the usefulness of and update well-established and novel biomarkers for the management of HCC.

  10. Biomarker time out.

    Science.gov (United States)

    Petzold, Axel; Bowser, Robert; Calabresi, Paolo; Zetterberg, Henrik; Uitdehaag, Bernard M J

    2014-10-01

    The advancement of knowledge relies on scientific investigations. The timing between asking a question and data collection defines if a study is prospective or retrospective. Prospective studies look forward from a point in time, are less prone to bias and are considered superior to retrospective studies. This conceptual framework conflicts with the nature of biomarker research. New candidate biomarkers are discovered in a retrospective manner. There are neither resources nor time for prospective testing in all cases. Relevant sources for bias are not covered. Ethical questions arise through the time penalty of an overly dogmatic concept. The timing of sample collection can be separated from testing biomarkers. Therefore the moment of formulating a hypothesis may be after sample collection was completed. A conceptual framework permissive to asking research questions without the obligation to bow to the human concept of calendar time would simplify biomarker research, but will require new safeguards against bias.

  11. Biomarkers in Airway Diseases

    Directory of Open Access Journals (Sweden)

    Janice M Leung

    2013-01-01

    Full Text Available The inherent limitations of spirometry and clinical history have prompted clinicians and scientists to search for surrogate markers of airway diseases. Although few biomarkers have been widely accepted into the clinical armamentarium, the authors explore three sources of biomarkers that have shown promise as indicators of disease severity and treatment response. In asthma, exhaled nitric oxide measurements can predict steroid responsiveness and sputum eosinophil counts have been used to titrate anti-inflammatory therapies. In chronic obstructive pulmonary disease, inflammatory plasma biomarkers, such as fibrinogen, club cell secretory protein-16 and surfactant protein D, can denote greater severity and predict the risk of exacerbations. While the multitude of disease phenotypes in respiratory medicine make biomarker development especially challenging, these three may soon play key roles in the diagnosis and management of airway diseases.

  12. Biomarkers of chronic alcohol misuse

    Directory of Open Access Journals (Sweden)

    Gonzalo P

    2014-01-01

    Full Text Available Philippe Gonzalo,1 Sylvie Radenne,2 Sylvie Gonzalo31Laboratoire de Biochimie, Centre Hospitalier Universitaire de Saint-Etienne, Saint-Etienne, France; 2Service d'Hépatologie-Gastroentérologie, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France; 3Laboratoire Biomnis, Lyon, FranceAbstract: Biological markers of chronic alcoholism can be divided into two groups: direct and indirect markers. Direct markers (mainly blood or serum and urine ethanol, ethylglucuronide, ethyl sulfate, and phosphatidylethanol directly track the intake of alcohol and vary in their sensitivity and kinetics of appearance and clearance. Indirect markers (mean corpuscular volume,γ-glutamyl transferase, alanine aminotransferase and aspartate aminotransferase, and carbohydrate-deficient transferrin are biological parameters that are influenced by a steady and significant alcohol intake. We discuss the values of these tests and the relevance of their prescriptions for the clinical evaluation of heavy drinking. We indicate, when known, the pathophysiological mechanism of their elevations. We also discuss the amount and time of alcohol consumption required to give a positive result and the duration of abstinence required for the return to normal values. The forensic use of these biomarkers will not be considered in this review.Keywords: alcoholism, biomarker, CDT, relapse, alcohol-induced liver disease

  13. Spheromak Impedance and Current Amplification

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, T K; Hua, D D; Stallard, B W

    2002-01-31

    It is shown that high current amplification can be achieved only by injecting helicity on the timescale for reconnection, {tau}{sub REC}, which determines the effective impedance of the spheromak. An approximate equation for current amplification is: dI{sub TOR}{sup 2}/dt {approx} I{sup 2}/{tau}{sub REC} - I{sub TOR}{sup 2}/{tau}{sub closed} where I is the gun current, I{sub TOR} is the spheromak toroidal current and {tau}{sub CLOSED} is the ohmic decay time of the spheromak. Achieving high current amplification, I{sub TOR} >> I, requires {tau}{sub REC} <<{tau}{sub CLOSED}. For resistive reconnection, this requires reconnection in a cold zone feeding helicity into a hot zone. Here we propose an impedance model based on these ideas in a form that can be implemented in the Corsica-based helicity transport code. The most important feature of the model is the possibility that {tau}{sub REC} actually increases as the spheromak temperature increases, perhaps accounting for the ''voltage sag'' observed in some experiments, and a tendency toward a constant ratio of field to current, B {proportional_to} I, or I{sub TOR} {approx} I. Program implications are discussed.

  14. Biomarkers for immune thrombocytopenia

    OpenAIRE

    Yu, Lingjia; Zhang, Chunmei; Zhang, Liping; Shi, Yongyu; Ji, Xuebin

    2015-01-01

    Immune thrombocytopenia is an autoimmune disease with abnormal biomarkers. Immune thrombocytopenia pathogenesis is a complicated process in which the patient’s immune system is activated by platelet autoantigens resulting in immune mediated platelet destruction or suppression of platelet production. The autoantibodies produced by autoreactive B cells against self antigens are considered to play a crucial role. In addition, biomarkers such as transforming growth factor-beta1,Toll-like receptor...

  15. Hypermethylated DNA, a Biomarker for colorectal cancer

    DEFF Research Database (Denmark)

    Rasmussen, Simon Ladefoged; Krarup, Henrik Bygum; Sunesen, Kåre Gotschalck;

    2016-01-01

    AIM: In colorectal cancer (CRC), improved methods for early detection are essential for increasing survival. Hypermethylated DNA in blood or stool has been proposed as a biomarker for CRC. In recent years, biochemical methods have improved, and several hypermethylated genes that are sensitive....... In blood samples, hypermethylated P16, HLTF, TMEFF1, ALX4, VIM, and FBN2 were associated with poor prognosis, hypermethylated APC, TAC1, SEPT9, NEUROG1, RASSF1A, SDC2, and THBD were detected in early-stage CRC, and hypermethylated P16 and TFPI2 could detect CRC recurrence. In stool samples, hypermethylated...

  16. Direct Y-STR amplification of body fluids deposited on commonly found crime scene substrates.

    Science.gov (United States)

    Dargay, Amanda; Roy, Reena

    2016-04-01

    Body fluids detected on commonly found crime scene substrates require extraction, purification and quantitation of DNA prior to amplification and generation of short tandem repeat (STR) DNA profiles. In this research Y-STR profiles were generated via direct amplification of blood and saliva deposited on 12 different substrates. These included cigarette butts, straws, grass, leaves, woodchips and seven different types of fabric. After depositing either 0.1 μL of blood or 0.5 μL of saliva, each substrate containing the dry body fluid stain was punched using a Harris 1.2 mm micro-punch. Each of these punched substrates, a total of 720 samples, containing minute amount of blood or saliva was either amplified directly without any pre-treatment, or was treated with one of the four washing reagents or buffer. In each of these five experimental groups the substrates containing the body fluid remained in the amplification reagent during the thermal cycling process. Each sample was amplified with the three direct Y-STR amplification kits; AmpFℓSTR(®) Yfiler(®) Direct, Yfiler(®) Plus Amplification Kits and the PowerPlex(®) Y23 System. Complete and concordant Y-STR profiles were successfully obtained from most of these 12 challenging crime scene objects when the stains were analyzed by at least one of the five experimental groups. The reagents and buffer were interchangeable among the three amplification kits, however, pre-treatment with these solutions did not appear to enhance the quality or the number of the full profiles generated with direct amplification. This study demonstrates that blood and saliva deposited on these simulated crime scene objects can be amplified directly.

  17. Blood Clots

    Science.gov (United States)

    ... Index A-Z Blood Clots Blood clots are semi-solid masses of blood that can be stationary (thrombosis) ... treated? What are blood clots? Blood clots are semi-solid masses of blood. Normally, blood flows freely through ...

  18. Circulating Biomarker Panels in Alzheimer's Disease.

    Science.gov (United States)

    Zafari, Sachli; Backes, Christina; Meese, Eckart; Keller, Andreas

    2015-01-01

    The early diagnosis of diseases frequently represents an important unmet clinical need supporting in-time treatment of pathologies. This also applies to neurodegenerative diseases such as Alzheimer's disease (AD), the most common form of dementia, estimated to affect millions of individuals worldwide. The respective diagnostic and prognostic markers, especially for the preclinical stages of AD, are expected to improve patients' outcome significantly. In the last decades, many approaches to detecting AD have been developed, including markers to discover changes in amyloid-β levels [from cerebrospinal fluid (CSF) or using positron emission tomography] or other brain imaging technologies such as structural magnetic resonance imaging (MRI), functional-connectivity MRI or task-related functional MRI. A major challenge is the detection of AD using minimally or even noninvasive biomarkers from body fluids such as plasma or serum. Circulating biomarker candidates based on mRNAs or proteins measured from blood cells, plasma or serum have been proposed for various pathologies including AD. As for other diseases, there is a tendency to use marker signatures obtained by high-throughput approaches, which allow the generation of profiles of hundreds to thousands of biomarkers simultaneously [microarrays, mass spectrometry or next-generation sequencing (NGS)]. Beyond mRNAs and proteins, recent approaches have measured small noncoding RNA (so-called microRNA) profiles in AD patients' blood samples using NGS or array-based technologies. Generally, the development of marker panels is in its early stages and requires further, substantial clinical validation. In this review, we provide an overview of different circulating AD biomarkers, starting with a brief summary of CSF markers and focusing on novel biomarker signatures such as small noncoding RNA profiles.

  19. Heralded amplification of photonic qubits.

    Science.gov (United States)

    Bruno, Natalia; Pini, Vittorio; Martin, Anthony; Verma, Varun B; Nam, Sae Woo; Mirin, Richard; Lita, Adriana; Marsili, Francesco; Korzh, Boris; Bussières, Félix; Sangouard, Nicolas; Zbinden, Hugo; Gisin, Nicolas; Thew, Rob

    2016-01-11

    We demonstrate postselection free heralded qubit amplification for Time-Bin qubits and single photon states in an all-fibre, telecom-wavelength, scheme that highlights the simplicity, stability and potential for fully integrated photonic solutions. Exploiting high-efficiency superconducting detectors, the gain, fidelity and the performance of the amplifier are studied as a function of loss. We also demonstrate the first heralded single photon amplifier with independent sources. This provides a significant advance towards demonstrating device-independent quantum key distribution as well as fundamental tests of quantum mechanics over extended distances. PMID:26832244

  20. Resonant primordial gravitational waves amplification

    Directory of Open Access Journals (Sweden)

    Chunshan Lin

    2016-01-01

    Full Text Available We propose a mechanism to evade the Lyth bound in models of inflation. We minimally extend the conventional single-field inflation model in general relativity (GR to a theory with non-vanishing graviton mass in the very early universe. The modification primarily affects the tensor perturbation, while the scalar and vector perturbations are the same as the ones in GR with a single scalar field at least at the level of linear perturbation theory. During the reheating stage, the graviton mass oscillates coherently and leads to resonant amplification of the primordial tensor perturbation. After reheating the graviton mass vanishes and we recover GR.

  1. Idiopathic recurrent calcium urolithiasis (IRCU: pathophysiology evaluated in light of oxidative metabolism, without and with variation of several biomarkers in fasting urine and plasma - a comparison of stone-free and -bearing male patients, emphasizing mineral, acid-base, blood pressure and protein status*

    Directory of Open Access Journals (Sweden)

    Schwilie PO

    2011-08-01

    Full Text Available Abstract Background IRCU is traditionally considered as lifestyle disease (associations with, among others, overweight, obesity, hypertension, type-2 diabetes, arising from excess, in 24 h urine, of calcium (Ca salts (calcium oxalate (CaOx, calcium phosphate (CaPi, supersaturation of, and crystallization in, tubular fluid and urine, causing crystal-induced epithelial cell damage, proteinuria, crystal aggregation and uroliths. Methods Another picture emerges from the present uncontrolled study of 154 male adult IRCU patients (75 stone-bearing (SB and 79 age-matched stone-free (SF, in whom stone-forming and other parameters in fasting urine and plasma were contrasted with five biomarkers (see footnote of oxidative metabolism (OM, without and with variation of markers. Results 1 In SB vs. SF unstratified OM biomarkers were statistically unchanged, but the majority of patients was overweight; despite, in SB vs. SF urine pH, total and non-albumin protein concentration were elevated, fractional urinary uric acid excretion and blood bicarbonate decreased, whereas urine volume, sodium, supersaturation with CaOx and CaPi (as hydroxyapatite were unchanged; 2 upon variation of OM markers (strata below and above median numerous stone parameters differed significant!', among others urine volume, total protein, Ca/Pi ratio, pH, sodium, potassium, plasma Ca/Pi ratio and parathyroid hormone, blood pressure, renal excretion of non-albumin protein and other substances; 3 a significant shift from SF to SB patients occurred with increase of urine pH, decrease of blood bicarbonate, and increase of diastolic blood pressure, whereas increase of plasma uric acid impacted only marginally; 4 in both SF and SB patients a strong curvilinear relationship links a rise of urine Ca/Pi to urine Ca/Pi divided by plasma Ca/Pi, but in SB urine Ca/Pi failed to correlate significantly with urine hydroxyapatite supersaturation; 5 also in SB, plasma Ca/Pi and urinary nitrate were

  2. Dynamics and Control of DNA Sequence Amplification

    CERN Document Server

    Marimuthu, Karthikeyan

    2014-01-01

    DNA amplification is the process of replication of a specified DNA sequence \\emph{in vitro} through time-dependent manipulation of its external environment. A theoretical framework for determination of the optimal dynamic operating conditions of DNA amplification reactions, for any specified amplification objective, is presented based on first-principles biophysical modeling and control theory. Amplification of DNA is formulated as a problem in control theory with optimal solutions that can differ considerably from strategies typically used in practice. Using the Polymerase Chain Reaction (PCR) as an example, sequence-dependent biophysical models for DNA amplification are cast as control systems, wherein the dynamics of the reaction are controlled by a manipulated input variable. Using these control systems, we demonstrate that there exists an optimal temperature cycling strategy for geometric amplification of any DNA sequence and formulate optimal control problems that can be used to derive the optimal tempe...

  3. Functional MRI and CT biomarkers in oncology

    Energy Technology Data Exchange (ETDEWEB)

    Winfield, J.M. [Institute of Cancer Research and Royal Marsden NHS Foundation Trust, CRUK Imaging Centre at the Institute of Cancer Research, Sutton (United Kingdom); Institute of Cancer Research and Royal Marsden Hospital, MRI Unit, Sutton (United Kingdom); Payne, G.S.; DeSouza, N.M. [Institute of Cancer Research and Royal Marsden NHS Foundation Trust, CRUK Imaging Centre at the Institute of Cancer Research, Sutton (United Kingdom)

    2015-04-01

    Imaging biomarkers derived from MRI or CT describe functional properties of tumours and normal tissues. They are finding increasing numbers of applications in diagnosis, monitoring of response to treatment and assessment of progression or recurrence. Imaging biomarkers also provide scope for assessment of heterogeneity within and between lesions. A wide variety of functional parameters have been investigated for use as biomarkers in oncology. Some imaging techniques are used routinely in clinical applications while others are currently restricted to clinical trials or preclinical studies. Apparent diffusion coefficient, magnetization transfer ratio and native T{sub 1} relaxation time provide information about structure and organization of tissues. Vascular properties may be described using parameters derived from dynamic contrast-enhanced MRI, dynamic contrast-enhanced CT, transverse relaxation rate (R{sub 2}*), vessel size index and relative blood volume, while magnetic resonance spectroscopy may be used to probe the metabolic profile of tumours. This review describes the mechanisms of contrast underpinning each technique and the technical requirements for robust and reproducible imaging. The current status of each biomarker is described in terms of its validation, qualification and clinical applications, followed by a discussion of the current limitations and future perspectives. (orig.)

  4. Biomarkers: A potential prognostic tool for silicosis

    Directory of Open Access Journals (Sweden)

    Jai Krishna Pandey

    2012-01-01

    Full Text Available Long-term exposure to respirable dust containing silica leads to pneumoconiosis/silicosis. The disease is irreversible and incurable, and only preventive steps such as job rotation, use of personal protective equipment, etc., remain solutions to the problem. Under such a situation, early diagnosis or prediction may become very useful to control the disease. Biomarkers are biological parameters in blood serum that change their values with deposition of dust in the lung and onset of lung fibrosis. Since these biomarkers can help us to diagnose and in the prognosis of the disease before it is actually diagnosed by the conventional X-ray technique and lung function test used for diagnosis of silicosis. The present paper describes the various types of available biomarkers, their application and usefulness. The paper also suggests that further study of the behavior/level of these biomarkers on a specific subject with time may provide more useful information of a confirmatory nature for prevention of dust-linked diseases.

  5. [Key laboratory diagnostic biomarkers of coronary atherosclerosis].

    Science.gov (United States)

    Ragino, Iu I; Cherniavskiĭ, A M; Eremenko, N V; Shakhtshneĭder, E V; Polonskaia, Ia V; Tsymbal, S Iu; Ivanova, M V; Voevoda, M I

    2011-01-01

    Laboratory lipid and lipoprotein biomarkers (total cholesterol - CH, triglycerides - TG, low-density and high-density lipoprotein cholesterol- LDL-CH, HDL-CH, apolipoproteins B and A1 - apoB, apoA1), carbohydrate biomarkers (plasma glucose, basal insulin), high sensitive C-reactive protein (hsCRP) and oxidative biomarkers (basal level of lipid peroxidation [LPO] products in LDL, LDL resistance to oxidation in vitro, oxidative modification of apoLDL and level of LDL lipophilic antioxidants) were studied in 388 men aged 42-70 years: 96 citizens of Western Siberia with angiographically documented coronary atherosclerosis and coronary heart disease (CHD); 292 men of population sample of citizens of Novosibirsk, including 44 men with CHD confirmed by standardized criteria and methods. Significant associations were found of coronary atherosclerosis and CHD with laboratory diagnostic biomarkers like blood levels of HDL-CH, TG, apoB, apoA1, basal insulin, hsCRP and basal level of LPO products in LDL and LDL resistance to oxidation. PMID:21627612

  6. Novel biomarkers for pulmonary arterial hypertension.

    Science.gov (United States)

    Anwar, Anjum; Ruffenach, Gregoire; Mahajan, Aman; Eghbali, Mansoureh; Umar, Soban

    2016-01-01

    Pulmonary arterial hypertension is a deadly disease characterized by elevated pulmonary arterial pressures leading to right ventricular hypertrophy and failure. The confirmatory gold standard test is the invasive right heart catheterization. The disease course is monitored by pulmonary artery systolic pressure measurement via transthoracic echocardiography. A simple non-invasive test to frequently monitor the patients is much needed. Search for a novel biomarker that can be detected by a simple test is ongoing and many different options are being studied. Here we review some of the new and unique pre-clinical options for potential pulmonary hypertension biomarkers. These biomarkers can be broadly categorized based on their association with endothelial cell dysfunction, inflammation, epigenetics, cardiac function, oxidative stress, metabolism,extracellular matrix, and volatile compounds in exhaled breath condensate. A biomarker that can be detected in blood, urine or breath condensate and correlates with disease severity, progression and response to therapy may result in significant cost reduction and improved patient outcomes. PMID:27439993

  7. Concurrent AURKA and MYCN Gene Amplifications Are Harbingers of Lethal TreatmentRelated Neuroendocrine Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Juan Miguel Mosquera

    2013-01-01

    Full Text Available Neuroendocrine prostate cancer (NEPC, also referred to as anaplastic prostate cancer, is a lethal tumor that most commonly arises in late stages of prostate adenocarcinoma (PCA with predilection to metastasize to visceral organs. In the current study, we explore for evidence that Aurora kinase A (AURKA and N-myc (MYCN gene abnormalities are harbingers of treatment-related NEPC (t-NEPC. We studied primary prostate tissue from 15 hormone naïve PCAs, 51 castration-resistant prostate cancers, and 15 metastatic tumors from 72 patients at different stages of disease progression to t-NEPC, some with multiple specimens. Histologic evaluation, immunohistochemistry, and fluorescence in situ hybridization were performed and correlated with clinical variables. AURKA amplification was identified in overall 65% of PCAs (hormone naïve and treated from patients that developed t-NEPC and in 86% of metastases. Concurrent amplification of MYCN was present in 70% of primary PCAs, 69% of treated PCAs, and 83% of metastases. In contrast, in an unselected PCA cohort, AURKA and MYCN amplifications were identified in only 5% of 169 cases. When metastatic t-NEPC was compared to primary PCA from the same patients, there was 100% concordance of ERG rearrangement, 100% concordance of AURKA amplification, and 60% concordance of MYCN amplification. In tumors with mixed features, there was also 100% concordance of ERG rearrangement and 94% concordance of AURKA and MYCN co-amplification between areas of NEPC and adenocarcinoma. AURKA and MYCN amplifications may be prognostic and predictive biomarkers, as they are harbingers of tumors at risk of progressing to t-NEPC after hormonal therapy.

  8. Circulating microRNAs as Prognostic and Predictive Biomarkers in Patients with Colorectal Cancer

    OpenAIRE

    Jakob Vasehus Schou; Julia Sidenius Johansen; Dorte Nielsen; Simona Rossi

    2016-01-01

    MiRNAs are suggested as promising cancer biomarkers. They are stable and extractable from a variety of clinical tissue specimens (fresh frozen or formalin fixed paraffin embedded tissue) and a variety of body fluids (e.g., blood, urine, saliva). However, there are several challenges that need to be solved, considering their potential as biomarkers in cancer, such as lack of consistency between biomarker panels in independent studies due to lack of standardized sample handling and processing, ...

  9. Microarray-Based Analysis of Methylation Status of CpGs in Placental DNA and Maternal Blood DNA – Potential New Epigenetic Biomarkers for Cell Free Fetal DNA-Based Diagnosis

    OpenAIRE

    Hatt, Lotte; Aagaard, Mads M.; Graakjaer, Jesper; Bach, Cathrine; Sommer, Steffen; Inge E Agerholm; Kølvraa, Steen; Bojesen, Anders

    2015-01-01

    Epigenetic markers for cell free fetal DNA in the maternal blood circulation are highly interesting in the field of non-invasive prenatal testing since such markers will offer a possibility to quantify the amount of fetal DNA derived from different chromosomes in a maternal blood sample. The aim of the present study was to define new fetal specific epigenetic markers present in placental DNA that can be utilized in non-invasive prenatal diagnosis. We have conducted a high-resolution methylati...

  10. Biomarkers of the Dementia

    Directory of Open Access Journals (Sweden)

    Mikio Shoji

    2011-01-01

    Full Text Available Recent advances in biomarker studies on dementia are summarized here. CSF Aβ40, Aβ42, total tau, and phosphorylated tau are the most sensitive biomarkers for diagnosis of Alzheimer's disease (AD and prediction of onset of AD from mild cognitive impairment (MCI. Based on this progress, new diagnostic criteria for AD, MCI, and preclinical AD were proposed by National Institute of Aging (NIA and Alzheimer's Association in August 2010. In these new criteria, progress in biomarker identification and amyloid imaging studies in the past 10 years have added critical information. Huge contributions of basic and clinical studies have established clinical evidence supporting these markers. Based on this progress, essential therapy for cure of AD is urgently expected.

  11. A PCR amplification method without DNA extraction.

    Science.gov (United States)

    Li, Hongwei; Xu, Haiyue; Zhao, Chunjiang; Sulaiman, Yiming; Wu, Changxin

    2011-02-01

    To develop a simple and inexpensive method for direct PCR amplification of animal DNA from tissues, we optimized different components and their concentration in lysis buffer systems. Finally, we acquired the optimized buffer system composed of 10 mmol tris(hydroxymethyl)aminomethane (Tris)-Cl (pH 8.0), 2 mmol ethylene diamine tetraacetic (EDTA) (pH 8.0), 0.2 mol NaCl and 200 μg/mL Proteinase K. Interestingly, the optimized buffer is also very effective when working with common human sample types, including blood, buccal cells and hair. The direct PCR method requires fewer reagents (Tris-Cl, EDTA, Protease K and NaCl) and less incubation time (only 35 min). The cost of treating every sample is less than $0.02, and all steps can be completed on a thermal cycler in a 96-well format. So, the proposed method will significantly improve high-throughput PCR-based molecular assays in animal systems and in common human sample types.

  12. Dynamics and control of DNA sequence amplification

    International Nuclear Information System (INIS)

    DNA amplification is the process of replication of a specified DNA sequence in vitro through time-dependent manipulation of its external environment. A theoretical framework for determination of the optimal dynamic operating conditions of DNA amplification reactions, for any specified amplification objective, is presented based on first-principles biophysical modeling and control theory. Amplification of DNA is formulated as a problem in control theory with optimal solutions that can differ considerably from strategies typically used in practice. Using the Polymerase Chain Reaction as an example, sequence-dependent biophysical models for DNA amplification are cast as control systems, wherein the dynamics of the reaction are controlled by a manipulated input variable. Using these control systems, we demonstrate that there exists an optimal temperature cycling strategy for geometric amplification of any DNA sequence and formulate optimal control problems that can be used to derive the optimal temperature profile. Strategies for the optimal synthesis of the DNA amplification control trajectory are proposed. Analogous methods can be used to formulate control problems for more advanced amplification objectives corresponding to the design of new types of DNA amplification reactions

  13. Dynamics and control of DNA sequence amplification

    Energy Technology Data Exchange (ETDEWEB)

    Marimuthu, Karthikeyan [Department of Chemical Engineering and Center for Advanced Process Decision-Making, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213 (United States); Chakrabarti, Raj, E-mail: raj@pmc-group.com, E-mail: rajc@andrew.cmu.edu [Department of Chemical Engineering and Center for Advanced Process Decision-Making, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213 (United States); Division of Fundamental Research, PMC Advanced Technology, Mount Laurel, New Jersey 08054 (United States)

    2014-10-28

    DNA amplification is the process of replication of a specified DNA sequence in vitro through time-dependent manipulation of its external environment. A theoretical framework for determination of the optimal dynamic operating conditions of DNA amplification reactions, for any specified amplification objective, is presented based on first-principles biophysical modeling and control theory. Amplification of DNA is formulated as a problem in control theory with optimal solutions that can differ considerably from strategies typically used in practice. Using the Polymerase Chain Reaction as an example, sequence-dependent biophysical models for DNA amplification are cast as control systems, wherein the dynamics of the reaction are controlled by a manipulated input variable. Using these control systems, we demonstrate that there exists an optimal temperature cycling strategy for geometric amplification of any DNA sequence and formulate optimal control problems that can be used to derive the optimal temperature profile. Strategies for the optimal synthesis of the DNA amplification control trajectory are proposed. Analogous methods can be used to formulate control problems for more advanced amplification objectives corresponding to the design of new types of DNA amplification reactions.

  14. Risk Perception and Social Amplification

    International Nuclear Information System (INIS)

    This paper seeks to consider social amplification as it applies to risk perception. Perceptions of the magnitude of a risk are conditioned by issues such as the degree of uncertainty in probability and consequences, the nature of the consequences and the relative weightings placed on probability and consequences. Risk perceptions are also influenced by factors such as confidence in the operator of an industrial process, trust in the regulator and the perceived fairness of regulatory decision-making. Different people may hold different views about these issues and there may also be difficulties in communication. The paper identifies and discusses self-reinforcing mechanisms, which will be labelled 'lock-in' here. They appear to apply in many situations where social amplification is observed. Historically, the term 'lock-in' has been applied mainly in the technological context but, in this paper, four types of lock-in are identified, namely scientific/technological, economic, social and institutional lock-in. One type of lock-in tends to lead to the next and all are buttressed by people's general acceptance of the familiar, fear of the unknown and resistance to change. The regulator seeks to make decisions which achieve the common good rather than supporting or perpetuating any set of vested interests. In this regard the locked-in positions of stakeholders, whether organisations, interest groups, or individual members of the public, are obstacles and challenges. Existing methods of consultation are unsatisfactory in terms of achieving a proper and productive level of dialogue with stakeholders

  15. Renal biomarkers in domestic species.

    Science.gov (United States)

    Hokamp, Jessica A; Nabity, Mary B

    2016-03-01

    Current conventional tests of kidney damage and function in blood (serum creatinine and urea nitrogen) and urine (urine protein creatinine ratio and urine specific gravity) are widely used for diagnosis and monitoring of kidney disease. However, they all have important limitations, and additional markers of glomerular filtration rate and glomerular and tubular damage are desirable, particularly for earlier detection of renal disease when therapy is most effective. Additionally, urinary markers of kidney damage and function may help localize damage to the affected portion of the kidney. In general, the presence of high- and intermediate-molecular weight proteins in the urine are indicative of glomerular damage, while low-molecular weight proteins and enzymes in the urine suggest tubular damage due to decreased reabsorption of proteins, direct tubular damage, or both. This review aims to discuss many of these new blood and urinary biomarkers in domestic veterinary species, focusing primarily on dogs and cats, how they may be used for diagnosis of renal disease, and their limitations. Additionally, a brief discussion of serum creatinine is presented, highlighting its limitations and important considerations for its improved interpretation in domestic species based on past literature and recent studies. PMID:26918420

  16. Biomarkers for systemic lupus erythematosus.

    Science.gov (United States)

    Ahearn, Joseph M; Liu, Chau-Ching; Kao, Amy H; Manzi, Susan

    2012-04-01

    The urgent need for lupus biomarkers was demonstrated in September 2011 during a Workshop sponsored by the Food and Drug Administration: Potential Biomarkers Predictive of Disease Flare. After 2 days of discussion and more than 2 dozen presentations from thought leaders in both industry and academia, it became apparent that highly sought biomarkers to predict lupus flare have not yet been identified. Even short of the elusive biomarker of flare, few biomarkers for systemic lupus erythematosus (SLE) diagnosis, monitoring, and stratification have been validated and employed for making clinical decisions. This lack of reliable, specific biomarkers for SLE hampers proper clinical management of patients with SLE and impedes development of new lupus therapeutics. As such, the intensity of investigation to identify lupus biomarkers is climbing a steep trajectory, lending cautious optimism that a validated panel of biomarkers for lupus diagnosis, monitoring, stratification, and prediction of flare may soon be in hand.

  17. Early detection of recurrence after curative resection for colorectal cancer - obstacles when using soluble biomarkers?

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Jess, Per; Aldulaymi, Bahir Hadi Mohammed;

    2013-01-01

    Abstract Objective. Results from monitoring studies using biomarkers in blood samples aiming at early detection of recurrent colorectal cancer (CRC) are presently evaluated. However, some serological biomarker levels are influenced by the surgical trauma, which may complicate translation of the l...

  18. Biomarkers in Barrett's esophagus.

    Science.gov (United States)

    Reid, Brian J; Blount, Patricia L; Rabinovitch, Peter S

    2003-04-01

    This article provides a framework for clinicians who are attempting the difficult task of interpreting the Barrett's biomarker literature with the goal of improving care for their patients. Although many articles. including more that 60 proposed biomarkers, have been published on this subject, only a few describe phase 3 and 4 studies that are of interest to the clinical gastroenterologist (Table 1). For year, dysplasia grade has been the sole means of risk stratification for patients with BE, and it likely will continue to be used in the foreseeable future. The current authors believe that dysplasia classification can be valuable using the team management approach and quality controls described previously. Significant problems, however, have emerged in phase 2 through 4 studies of dysplasia that make it imperative for the Barrett's field to incorporate additional biomarkers as they are validated. These problems include poor reproducibility of dysplasia interpretations, poor predictive value for negative, indefinite, and low-grade dysplasia, and inconsistent results for HGD in different centers, all of which makes it virtually impossible to develop national guidelines for surveillance. Some studies have even suggested that endoscopic biopsy surveillance using dysplasia may not be worthwhile. Currently, flow cytometric tetraploidy and aneuploidy have progressed furthest in biomarker validation (see Table 1). With proper handling, endoscopic biopsy specimens can be shipped to reference laboratories that have the instruments, computer analytic methods, and expertise to reproducibly detect tetraploidy and aneuploidy. The results of phase 4 studies indicate that flow cytometry appears to be useful in detecting a subset of patients who do not have HGD and yet have an increased risk of progression to cancer that cannot be identified by dysplasia grade. For many reasons, the authors anticipate that the number of validated biomarkers will increase substantially in the

  19. Diagnosis of brugian filariasis by loop-mediated isothermal amplification.

    Directory of Open Access Journals (Sweden)

    Catherine B Poole

    Full Text Available In this study we developed and evaluated a Brugia Hha I repeat loop-mediated isothermal amplification (LAMP assay for the rapid detection of Brugia genomic DNA. Amplification was detected using turbidity or fluorescence as readouts. Reactions generated a turbidity threshold value or a clear visual positive within 30 minutes using purified genomic DNA equivalent to one microfilaria. Similar results were obtained using DNA isolated from blood samples containing B. malayi microfilariae. Amplification was specific to B. malayi and B. timori, as no turbidity was observed using DNA from the related filarial parasites Wuchereria bancrofti, Onchocerca volvulus or Dirofilaria immitis, or from human or mosquito. Furthermore, the assay was most robust using a new strand-displacing DNA polymerase termed Bst 2.0 compared to wild-type Bst DNA polymerase, large fragment. The results indicate that the Brugia Hha I repeat LAMP assay is rapid, sensitive and Brugia-specific with the potential to be developed further as a field tool for diagnosis and mapping of brugian filariasis.

  20. Diagnosis of brugian filariasis by loop-mediated isothermal amplification.

    Science.gov (United States)

    Poole, Catherine B; Tanner, Nathan A; Zhang, Yinhua; Evans, Thomas C; Carlow, Clotilde K S

    2012-01-01

    In this study we developed and evaluated a Brugia Hha I repeat loop-mediated isothermal amplification (LAMP) assay for the rapid detection of Brugia genomic DNA. Amplification was detected using turbidity or fluorescence as readouts. Reactions generated a turbidity threshold value or a clear visual positive within 30 minutes using purified genomic DNA equivalent to one microfilaria. Similar results were obtained using DNA isolated from blood samples containing B. malayi microfilariae. Amplification was specific to B. malayi and B. timori, as no turbidity was observed using DNA from the related filarial parasites Wuchereria bancrofti, Onchocerca volvulus or Dirofilaria immitis, or from human or mosquito. Furthermore, the assay was most robust using a new strand-displacing DNA polymerase termed Bst 2.0 compared to wild-type Bst DNA polymerase, large fragment. The results indicate that the Brugia Hha I repeat LAMP assay is rapid, sensitive and Brugia-specific with the potential to be developed further as a field tool for diagnosis and mapping of brugian filariasis.

  1. Diagnosis of brugian filariasis by loop-mediated isothermal amplification.

    Science.gov (United States)

    Poole, Catherine B; Tanner, Nathan A; Zhang, Yinhua; Evans, Thomas C; Carlow, Clotilde K S

    2012-01-01

    In this study we developed and evaluated a Brugia Hha I repeat loop-mediated isothermal amplification (LAMP) assay for the rapid detection of Brugia genomic DNA. Amplification was detected using turbidity or fluorescence as readouts. Reactions generated a turbidity threshold value or a clear visual positive within 30 minutes using purified genomic DNA equivalent to one microfilaria. Similar results were obtained using DNA isolated from blood samples containing B. malayi microfilariae. Amplification was specific to B. malayi and B. timori, as no turbidity was observed using DNA from the related filarial parasites Wuchereria bancrofti, Onchocerca volvulus or Dirofilaria immitis, or from human or mosquito. Furthermore, the assay was most robust using a new strand-displacing DNA polymerase termed Bst 2.0 compared to wild-type Bst DNA polymerase, large fragment. The results indicate that the Brugia Hha I repeat LAMP assay is rapid, sensitive and Brugia-specific with the potential to be developed further as a field tool for diagnosis and mapping of brugian filariasis. PMID:23272258

  2. Tsunami Amplification due to Focusing

    Science.gov (United States)

    Moore, C. W.; Kanoglu, U.; Titov, V. V.; Aydin, B.; Spillane, M. C.; Synolakis, C. E.

    2012-12-01

    Tsunami runup measurements over the periphery of the Pacific Ocean after the devastating Great Japan tsunami of 11 March 2011 showed considerable variation in far-field and near-field impact. This variation of tsunami impact have been attributed to either directivity of the source or by local topographic effects. Directivity arguments alone, however, cannot explain the complexity of the radiated patterns in oceans with trenches and seamounts. Berry (2007, Proc. R. Soc. Lond. A 463, 3055-3071) discovered how such underwater features may concentrate tsunamis into cusped caustics and thus cause large local amplifications at specific focal points. Here, we examine focusing and local amplification, not by considering the effects of underwater diffractive lenses, but by considering the details of the dipole nature of the initial profile, and propose that certain regions of coastline are more at-risk, not simply because of directivity but because typical tsunami deformations create focal regions where abnormal tsunami wave height can be registered (Marchuk and Titov, 1989, Proc. IUGG/IOC International Tsunami Symposium, Novosibirsk, USSR). In this work, we present a new general analytical solution of the linear shallow-water wave equation for the propagation of a finite-crest-length source over a constant depth without any restriction on the initial profile. Unlike the analytical solution of Carrier and Yeh (2005, Comp. Mod. Eng. & Sci. 10(2), 113-121) which was restricted to initial conditions with Gaussian profiles and involved approximation, our solution is not only exact, but also general and allows the use of realistic initial waveform such as N-waves as defined by Tadepalli and Synolakis (1994, Proc. R. Soc. Lond. A 445, 99-112). We then verify our analytical solution for several typical wave profiles, both with the NOAA tsunami forecast model MOST (Titov and Synolakis, 1998, J. Waterw. Port Coast. Ocean Eng. 124(4), 157-171) which is validated and verified through

  3. Proteomic Biomarkers of Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Natacha Diaz-Prieto

    2008-01-01

    Full Text Available Biomarkers provide a powerful approach to understanding the spectrum of cardiovascular diseases. They have application in screening, diagnostic, prognostication, prediction of recurrences and monitoring of therapy. The “omics” tool are becoming very useful in the development of new biomarkers in cardiovascular diseases. Among them, proteomics is especially fitted to look for new proteins in health and disease and is playing a significant role in the development of new diagnostic tools in cardiovascular diagnosis and prognosis. This review provides an overview of progress in applying proteomics to atherosclerosis. First, we describe novel proteins identified analysing atherosclerotic plaques directly. Careful analysis of proteins within the atherosclerotic vascular tissue can provide a repertoire of proteins involved in vascular remodelling and atherogenesis. Second, we discuss recent data concerning proteins secreted by atherosclerotic plaques. The definition of the atheroma plaque secretome resides in that proteins secreted by arteries can be very good candidates of novel biomarkers. Finally we describe proteins that have been differentially expressed (versus controls by individual cells which constitute atheroma plaques (endothelial cells, vascular smooth muscle cells, macrophages and foam cells as well as by circulating cells (monocytes, platelets or novel biomarkers present in plasma.

  4. Proteomic Biomarkers of Atherosclerosis.

    Science.gov (United States)

    Vivanco, F; Padial, L R; Darde, V M; de la Cuesta, F; Alvarez-Llamas, G; Diaz-Prieto, Natacha; Barderas, M G

    2008-01-01

    SUMMARY: Biomarkers provide a powerful approach to understanding the spectrum of cardiovascular diseases. They have application in screening, diagnostic, prognostication, prediction of recurrences and monitoring of therapy. The "omics" tool are becoming very useful in the development of new biomarkers in cardiovascular diseases. Among them, proteomics is especially fitted to look for new proteins in health and disease and is playing a significant role in the development of new diagnostic tools in cardiovascular diagnosis and prognosis. This review provides an overview of progress in applying proteomics to atherosclerosis. First, we describe novel proteins identified analysing atherosclerotic plaques directly. Careful analysis of proteins within the atherosclerotic vascular tissue can provide a repertoire of proteins involved in vascular remodelling and atherogenesis. Second, we discuss recent data concerning proteins secreted by atherosclerotic plaques. The definition of the atheroma plaque secretome resides in that proteins secreted by arteries can be very good candidates of novel biomarkers. Finally we describe proteins that have been differentially expressed (versus controls) by individual cells which constitute atheroma plaques (endothelial cells, vascular smooth muscle cells, macrophages and foam cells) as well as by circulating cells (monocytes, platelets) or novel biomarkers present in plasma. PMID:19578499

  5. Emerging Biomarkers in Glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    McNamara, Mairéad G.; Sahebjam, Solmaz; Mason, Warren P., E-mail: warren.mason@uhn.ca [Pencer Brain Tumor Centre, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, Ontario M5G 2M9 (Canada)

    2013-08-22

    Glioblastoma, the most common primary brain tumor, has few available therapies providing significant improvement in survival. Molecular signatures associated with tumor aggressiveness as well as with disease progression and their relation to differences in signaling pathways implicated in gliomagenesis have recently been described. A number of biomarkers which have potential in diagnosis, prognosis and prediction of response to therapy have been identified and along with imaging modalities could contribute to the clinical management of GBM. Molecular biomarkers including O(6)-methlyguanine-DNA-methyltransferase (MGMT) promoter and deoxyribonucleic acid (DNA) methylation, loss of heterozygosity (LOH) of chromosomes 1p and 19q, loss of heterozygosity 10q, isocitrate dehydrogenase (IDH) mutations, epidermal growth factor receptor (EGFR), epidermal growth factor, latrophilin, and 7 transmembrane domain-containing protein 1 on chromosome 1 (ELTD1), vascular endothelial growth factor (VEGF), tumor suppressor protein p53, phosphatase and tensin homolog (PTEN), p16INK4a gene, cytochrome c oxidase (CcO), phospholipid metabolites, telomerase messenger expression (hTERT messenger ribonucleic acid [mRNA]), microRNAs (miRNAs), cancer stem cell markers and imaging modalities as potential biomarkers are discussed. Inclusion of emerging biomarkers in prospective clinical trials is warranted in an effort for more effective personalized therapy in the future.

  6. Nucleic acid sequence-based amplification with oligochromatography for detection of Trypanosoma brucei in clinical samples

    NARCIS (Netherlands)

    C.M. Mugasa; T. Laurent; G.J. Schoone; P.A. Kager; G.W. Lubega; H.D.F.H. Schallig

    2009-01-01

    Molecular tools, such as real-time nucleic acid sequence-based amplification (NASBA) and PCR, have been developed to detect Trypanosoma brucei parasites in blood for the diagnosis of human African trypanosomiasis (HAT). Despite good sensitivity, these techniques are not implemented in HAT control pr

  7. Multiscale image contrast amplification (MUSICA)

    Science.gov (United States)

    Vuylsteke, Pieter; Schoeters, Emile P.

    1994-05-01

    This article presents a novel approach to the problem of detail contrast enhancement, based on multiresolution representation of the original image. The image is decomposed into a weighted sum of smooth, localized, 2D basis functions at multiple scales. Each transform coefficient represents the amount of local detail at some specific scale and at a specific position in the image. Detail contrast is enhanced by non-linear amplification of the transform coefficients. An inverse transform is then applied to the modified coefficients. This yields a uniformly contrast- enhanced image without artefacts. The MUSICA-algorithm is being applied routinely to computed radiography images of chest, skull, spine, shoulder, pelvis, extremities, and abdomen examinations, with excellent acceptance. It is useful for a wide range of applications in the medical, graphical, and industrial area.

  8. Mechanisms of Metal-Induced Centrosome Amplification

    OpenAIRE

    Holmes, Amie L.; Wise, John Pierce

    2010-01-01

    Exposure to toxic and carcinogenic metals is widespread; however, their mechanisms of action remain largely unknown. One potential mechanism for metal-induced carcinogenicity and toxicity is centrosome amplification. Here, we review the mechanisms for metal-induced centrosome amplification, including arsenic, chromium, mercury and nano-titanium dioxide.

  9. Neuroimaging Biomarkers for Psychosis

    Science.gov (United States)

    Hager, Brandon M.

    2015-01-01

    Background Biomarkers provide clinicians with a predictable model for the diagnosis, treatment and follow-up of medical ailments. Psychiatry has lagged behind other areas of medicine in the identification of biomarkers for clinical diagnosis and treatment. In this review, we investigated the current state of neuroimaging as it pertains to biomarkers for psychosis. Methods We reviewed systematic reviews and meta-analyses of the structural (sMRI), functional (fMRI), diffusion-tensor (DTI), Positron emission tomography (PET) and spectroscopy (MRS) studies of subjects at-risk or those with an established schizophrenic illness. Only articles reporting effect-sizes and confidence intervals were included in an assessment of robustness. Results Out of the identified meta-analyses and systematic reviews, 21 studies met the inclusion criteria for assessment. There were 13 sMRI, 4 PET, 3 MRS, and 1 DTI studies. The search terms included in the current review encompassed familial high risk (FHR), clinical high risk (CHR), First episode (FES), Chronic (CSZ), schizophrenia spectrum disorders (SSD), and healthy controls (HC). Conclusions Currently, few neuroimaging biomarkers can be considered ready for diagnostic use in patients with psychosis. At least in part, this may be related to the challenges inherent in the current symptom-based approach to classifying these disorders. While available studies suggest a possible value of imaging biomarkers for monitoring disease progression, more systematic research is needed. To date, the best value of imaging data in psychoses has been to shed light on questions of disease pathophysiology, especially through the characterization of endophenotypes. PMID:25883891

  10. Risk Perception and Social Amplification

    Energy Technology Data Exchange (ETDEWEB)

    Smith, R.E. [Environment Agency (United Kingdom)

    2001-07-01

    This paper seeks to consider social amplification as it applies to risk perception. Perceptions of the magnitude of a risk are conditioned by issues such as the degree of uncertainty in probability and consequences, the nature of the consequences and the relative weightings placed on probability and consequences. Risk perceptions are also influenced by factors such as confidence in the operator of an industrial process, trust in the regulator and the perceived fairness of regulatory decision-making. Different people may hold different views about these issues and there may also be difficulties in communication. The paper identifies and discusses self-reinforcing mechanisms, which will be labelled 'lock-in' here. They appear to apply in many situations where social amplification is observed. Historically, the term 'lock-in' has been applied mainly in the technological context but, in this paper, four types of lock-in are identified, namely scientific/technological, economic, social and institutional lock-in. One type of lock-in tends to lead to the next and all are buttressed by people's general acceptance of the familiar, fear of the unknown and resistance to change. The regulator seeks to make decisions which achieve the common good rather than supporting or perpetuating any set of vested interests. In this regard the locked-in positions of stakeholders, whether organisations, interest groups, or individual members of the public, are obstacles and challenges. Existing methods of consultation are unsatisfactory in terms of achieving a proper and productive level of dialogue with stakeholders.

  11. Microarray-Based Analysis of Methylation Status of CpGs in Placental DNA and Maternal Blood DNA--Potential New Epigenetic Biomarkers for Cell Free Fetal DNA-Based Diagnosis.

    Directory of Open Access Journals (Sweden)

    Lotte Hatt

    Full Text Available Epigenetic markers for cell free fetal DNA in the maternal blood circulation are highly interesting in the field of non-invasive prenatal testing since such markers will offer a possibility to quantify the amount of fetal DNA derived from different chromosomes in a maternal blood sample. The aim of the present study was to define new fetal specific epigenetic markers present in placental DNA that can be utilized in non-invasive prenatal diagnosis. We have conducted a high-resolution methylation specific beadchip microarray study assessing more than 450.000 CpG sites. We have analyzed the DNA methylation profiles of 10 maternal blood samples and compared them to 12 1st trimesters chorionic samples from normal placentas, identifying a number of CpG sites that are differentially methylated in maternal blood cells compared to chorionic tissue. To strengthen the utility of these differentially methylated CpG sites to be used with methyl-sensitive restriction enzymes (MSRE in PCR-based NIPD, we furthermore refined the list of selected sites, containing a restriction sites for one of 16 different methylation-sensitive restriction enzymes. We present a list of markers on chromosomes 13, 18 and 21 with a potential for aneuploidy testing as well as a list of markers for regions harboring sub-microscopic deletion- or duplication syndromes.

  12. Circulating microRNAs as biomarkers of adult Crohn's disease

    DEFF Research Database (Denmark)

    Jensen, Michael D; Andersen, Rikke F; Christensen, Henry;

    2015-01-01

    OBJECTIVE: Previous studies have found a differential expression of microRNAs (miRNAs) in the blood of patients with Crohn's disease (CD) compared with healthy controls. The aim of this study was to identify circulating miRNAs expressed in CD and assess their performance as biomarkers in patients...

  13. Comparison of Peripheral and Central Schizophrenia Biomarker Profiles

    NARCIS (Netherlands)

    L.W. Harris (Laura); S. Pietsch (Sandra); T.M.K. Cheng (Tammy); E. Schwarz (Emanuel); P.C. Guest (Paul); S. Bahn (Sabine)

    2012-01-01

    textabstractWe have recently shown that a molecular biomarker signature comprised of inflammatory, hormonal and growth factors occurs in the blood serum from first onset schizophrenia patients. Here, we use the same platform to investigate post mortem brain tissue (Brodmann area 10) from schizophren

  14. Cardiac Biomarkers and Cycling Race

    Directory of Open Access Journals (Sweden)

    Caroline Le Goff, Jean-François Kaux, Sébastien Goffaux, Etienne Cavalier

    2015-06-01

    Full Text Available In cycling as in other types of strenuous exercise, there exists a risk of sudden death. It is important both to understand its causes and to see if the behavior of certain biomarkers might highlight athletes at risk. Many reports describe changes in biomarkers after strenuous exercise (Nie et al., 2011, but interpreting these changes, and notably distinguishing normal physiological responses from pathological changes, is not easy. Here we have focused on the kinetics of different cardiac biomarkers: creatin kinase (CK, creating kinase midbrain (CK-MB, myoglobin (MYO, highly sensitive troponin T (hs-TnT and N-terminal brain natriuretic peptide (NT-proBNP. The population studied was a group of young trained cyclists participating in a 177-km cycling race. The group of individuals was selected for maximal homogeneity. Their annual training volume was between 10,000 and 16,000 kilometers. The rhythm of races is comparable and averages 35 km/h, depending on the race’s difficulty. The cardiac frequency was recorded via a heart rate monitor. Three blood tests were taken. The first blood test, T0, was taken approximately 2 hours before the start of the race and was intended to gather values which would act as references for the following tests. The second blood test, T1, was realized within 5 minutes of their arrival. The third and final blood test, T3, was taken 3 hours following their arrival. The CK, CK-MB, MYO, hs-TnT and NT-proBNP were measured on the Roche Diagnostic modular E (Manhein, Germany. For the statistical analysis, an ANOVA and post hoc test of Scheffé were calculated with the Statistica Software version 9.1. We noticed an important significant variation in the cardiac frequency between T0 and T1 (p < 0.0001, T0 and T3 (p < 0.0001, and T1 and T3 (p < 0.01. Table 1 shows the results obtained for the different biomarkers. CK and CK-MB showed significant variation between T0-T1 and T0-T3 (p < 0.0001. Myoglobin increased significantly

  15. Blood transfusions

    Science.gov (United States)

    ... called homologous blood donation. Many communities have a blood bank at which any healthy person can donate blood. ... need to arrange with your hospital or local blood bank before your surgery to have directed donor blood. ...

  16. The COPD Biomarker Qualification Consortium (CBQC)

    DEFF Research Database (Denmark)

    Casaburi, Richard; Celli, Bartolome; Crapo, James;

    2013-01-01

    industry and academia conducted a workshop to survey the available information that could contribute to new tools. Based on this, a collaborative project, the COPD Biomarkers Qualification Consortium, was initiated. The Consortium in now actively preparing integrated data sets from existing resources......, and no interested party has been in a position to undertake such a process. In order to facilitate the development of novel tools to assess new treatments, the Food and Drug Administration, in collaboration with the COPD Foundation, the National Heart Lung and Blood Institute and scientists from the pharmaceutical...

  17. Linking Arctic amplification and local feedbacks

    Science.gov (United States)

    Balcerak, Ernie

    2011-11-01

    Climate simulations show that as the Earth warms, the Arctic warms more than the average global warming. However, models differ on how much more the Arctic warms, and although scientists have proposed a variety of mechanisms to explain the Arctic warming amplification, there is no consensus on the main reasons for it. To shed light on this issue, Hwang et al. investigated the relationship between Arctic amplification and poleward energy transport and local Arctic feedbacks, such as changes in cloud cover or ice loss, across a group of models. The researchers noted that differences in atmospheric energy transport did not explain the ranges of polar amplification; rather, models with more amplification showed less energy transport into high latitudes. The authors found that decreasing energy transport is due to a coupled relationship between Arctic amplification and energy transport: Arctic amplification reduces the equator-to-pole temperature gradient, which strongly decreases energy transport. They suggest that this coupled relationship should be taken into account in studies of Arctic amplification. (Geophysical Research Letters, doi:10.1029/2011GL048546, 2011)

  18. Biomarkers of Guillain-Barré Syndrome: Some Recent Progress, More Still to Be Explored

    Directory of Open Access Journals (Sweden)

    Ying Wang

    2015-01-01

    Full Text Available Guillain-Barré syndrome (GBS, the axonal subtype of which is mainly triggered by C. jejuni with ganglioside-mimicking lipooligosaccharides (LOS, is an immune-mediated disorder in the peripheral nervous system (PNS accompanied by the disruption of the blood-nerve barrier (BNB and the blood-cerebrospinal fluid barrier (B-CSF-B. Biomarkers of GBS have been extensively explored and some of them are proved to assist in the clinical diagnosis and in monitoring disease progression as well as in assessing the efficacy of immunotherapy. Herein, we systemically review the literature on biomarkers of GBS, including infection-/immune-/BNB, B-CSF-B, and PNS damage-associated biomarkers, aiming at providing an overview of GBS biomarkers and guiding further investigations. Furthermore, we point out further directions for studies on GBS biomarkers.

  19. Procalcitonin as an adjunctive biomarker in sepsis

    Directory of Open Access Journals (Sweden)

    Mahua Sinha

    2011-01-01

    Full Text Available Sepsis can sometimes be difficult to substantiate, and its distinction from non-infectious conditions in critically ill patients is often a challenge. Serum procalcitonin (PCT assay is one of the biomarkers of sepsis. The present study was aimed to assess the usefulness of PCT assay in critically ill patients with suspected sepsis. The study included 40 patients from the intensive care unit with suspected sepsis. Sepsis was confirmed clinically and/or by positive blood culture. Serum PCT was assayed semi-quantitatively by rapid immunochromatographic technique (within 2 hours of sample receipt. Among 40 critically ill patients, 21 had clinically confirmed sepsis. There were 12 patients with serum PCT ≥10 ng/ml (8, blood culture positive; 1, rickettsia; 2, post-antibiotic blood culture sterile; and 1, non-sepsis; 7 patients with PCT 2-10 ng/ml (4, blood culture positive; 1, falciparum malaria; 2, post-antibiotic blood culture sterile; 3 patients with PCT of 0.5 to 2 ng/ml (sepsis in 1 patient; and 18 patients with PCT < 0.5 ng/ml (sepsis in 2 patients. Patients with PCT ≥ 2 ng/ml had statistically significant correlation with the presence of sepsis (P<0.0001. The PCT assay revealed moderate sensitivity (86% and high specificity (95% at a cut-off ≥ 2 ng/ml. The PCT assay was found to be a useful biomarker of sepsis in this study. The assay could be performed and reported rapidly and provided valuable information before availability of culture results. This might assist in avoiding unwarranted antibiotic usage.

  20. Biomarkers for pancreatic carcinogenesis

    OpenAIRE

    Hustinx, S.R.

    2007-01-01

    Pancreatic cancer is a devastating disease. Most pancreatic cancers (approximately 85%) are diagnosed at a late, incurable stage. The poor prognosis and late presentation of pancreatic cancer patients underscore the importance of early detection, which is the sine qua non for the fight against pancreatic cancer. It is hoped for the future that the understanding of genetic alterations will lead to the rapid discovery of an effective biomarker of pancreatic carcinogenesis. In this thesis we vis...

  1. Biomarkers of Ovarian Reserve

    Directory of Open Access Journals (Sweden)

    William E. Roudebush

    2008-01-01

    Full Text Available The primary function of the female ovary is the production of a mature and viable oocyte capable of fertilization and subsequent embryo development and implantation. At birth, the ovary contains a finite number of oocytes available for folliculogenesis. This finite number of available oocytes is termed “the ovarian reserve”. The determination of ovarian reserve is important in the assessment and treatment of infertility. As the ovary ages, the ovarian reserve will decline. Infertility affects approximately 15-20% of reproductive aged couples. The most commonly used biomarker assay to assess ovarian reserve is the measurement of follicle stimulating hormone (FSH on day 3 of the menstrual cycle. However, antimüllerian hormone and inhibin-B are other biomarkers of ovarian reserve that are gaining in popularity since they provide direct determination of ovarian status, whereas day 3 FSH is an indirect measurement. This review examines the physical tools and the hormone biomarkers used to evaluate ovarian reserve.

  2. The effect of whole genome amplification on samples originating from more than one donor

    DEFF Research Database (Denmark)

    Thacker, C.R.; Balogh, M.K.; Børsting, Claus;

    2006-01-01

    In this study, the GenomiPhi(TM) DNA Amplification Kit (Amersham Biosciences) was used to investigate the potential of whole genome amplification (WGA) when considering samples originating from more than one donor. DNA was extracted from blood samples, quantified and normalised before being mixed...... found to match the expected peak ratios regardless of the starting concentration of DNA. With samples mixed in the ratio of 1:7 and 1:15, and when the concentration of starting material was at the manufacturer's lower limit, too few minor component peaks were found to allow for statistical analysis...

  3. Quantum Amplitude Amplification and Estimation

    CERN Document Server

    Brassard, G; Mosca, M; Tapp, A; Brassard, Gilles; Hoyer, Peter; Mosca, Michele; Tapp, Alain

    2000-01-01

    Consider a Boolean function $\\chi: X \\to \\{0,1\\}$ that partitions set $X$ between its good and bad elements, where $x$ is good if $\\chi(x)=1$ and bad otherwise. Consider also a quantum algorithm $\\mathcal A$ such that $A \\ket{0} = \\sum_{x\\in X} \\alpha_x \\ket{x}$ is a quantum superposition of the elements of $X$, and let $a$ denote the probability that a good element is produced if $A \\ket{0}$ is measured. If we repeat the process of running $A$, measuring the output, and using $\\chi$ to check the validity of the result, we shall expect to repeat $1/a$ times on the average before a solution is found. *Amplitude amplification* is a process that allows to find a good $x$ after an expected number of applications of $A$ and its inverse which is proportional to $1/\\sqrt{a}$, assuming algorithm $A$ makes no measurements. This is a generalization of Grover's searching algorithm in which $A$ was restricted to producing an equal superposition of all members of $X$ and we had a promise that a single $x$ existed such tha...

  4. Biological features and biomarkers in hepatocellularcarcinoma

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Similar to other cancers, a multistep process of carcinogenesisis observed in hepatocellular carcinoma (HCC).Although the mechanisms underlying the developmentof HCC have been investigated in terms of oncology,virology, and stem cell biology, the whole picture ofhepatocarcinogenesis remains to be elucidated. Recentprogress in molecular biology has provided clues tothe underlying cause of various diseases. In particular,sequencing technologies, such as whole genome andexome sequencing analyses, have made an impacton genomic research on a variety of cancers includingHCC. Comprehensive genomic analyses have detectednumerous abnormal genetic alterations, such asmutations and copy number alterations. Based on thesefindings, signaling pathways and cancer-related genesinvolved in hepatocarcinogenesis could be analyzed indetail. Simultaneously, a number of novel biomarkers,both from tissue and blood samples, have been recentlyreported. These biomarkers have been successfullyapplied to early diagnosis and prognostic prediction ofpatients with HCC. In this review, we focus on the recentdevelopments in molecular cancer research on HCC andexplain the biological features and novel biomarkers.

  5. Prognostic factors and biomarkers of congenital obstructive nephropathy.

    Science.gov (United States)

    Chevalier, Robert L

    2016-09-01

    Congenital obstructive nephropathy (CON) is the leading cause of chronic kidney disease (CKD) in children. Anomalies of the urinary tract are often associated with abnormal nephrogenesis, which is compounded by obstructive injury and by maternal risk factors associated with low birth weight. Currently available fetal and postnatal imaging and analytes of amniotic fluid, urine, or blood lack predictive value. For ureteropelvic junction obstruction, biomarkers are needed for optimal timing of pyeloplasty; for posterior urethral valves, biomarkers of long-term prognosis and CKD are needed. The initial nephron number may be a major determinant of progression of CKD, and most patients with CON who progress to renal failure reach this point in adulthood, presumably compounded by episodes of acute kidney injury. Biomarkers of tubular injury may be of particular value in predicting the need for surgical intervention or in tracking progression of CKD, and must be adjusted for patient age. Discovery of new biomarkers may depend on "unbiased" proteomics, whereby patterns of urinary peptide fragments from patients with CON are analyzed in comparison to controls. Most promising are the analysis of urinary exosomes (restricting biomarkers to relevant tubular cells) and quantitative magnetic resonance imaging techniques allowing precise determination of nephron number and tubular mass. The greatest need is for large prospective multicenter studies with centralized biomarker sample repositories to follow patients with CON from fetal life through adulthood. PMID:26667236

  6. Isothermal DNA amplification in vitro: the helicase-dependent amplification system.

    Science.gov (United States)

    Jeong, Yong-Joo; Park, Kkothanahreum; Kim, Dong-Eun

    2009-10-01

    Since the development of polymerase chain reaction, amplification of nucleic acids has emerged as an elemental tool for molecular biology, genomics, and biotechnology. Amplification methods often use temperature cycling to exponentially amplify nucleic acids; however, isothermal amplification methods have also been developed, which do not require heating the double-stranded nucleic acid to dissociate the synthesized products from templates. Among the several methods used for isothermal DNA amplification, the helicase-dependent amplification (HDA) is discussed in this review with an emphasis on the reconstituted DNA replication system. Since DNA helicase can unwind the double-stranded DNA without the need for heating, the HDA system provides a very useful tool to amplify DNA in vitro under isothermal conditions with a simplified reaction scheme. This review describes components and detailed aspects of current HDA systems using Escherichia coli UvrD helicase and T7 bacteriophage gp4 helicase with consideration of the processivity and efficiency of DNA amplification. PMID:19629390

  7. Raman amplification in optical communication systems

    DEFF Research Database (Denmark)

    Kjær, Rasmus

    2008-01-01

    Fiber Raman amplifiers are investigated with the purpose of identifying new applications and limitations for their use in optical communication systems. Three main topics are investigated, namely: New applications of dispersion compensating Raman amplifiers, the use Raman amplification to increase...

  8. Can Anomalous Amplification be Attained without Postselection?

    Science.gov (United States)

    Martínez-Rincón, Julián; Liu, Wei-Tao; Viza, Gerardo I.; Howell, John C.

    2016-03-01

    We present a parameter estimation technique based on performing joint measurements of a weak interaction away from the weak-value-amplification approximation. Two detectors are used to collect full statistics of the correlations between two weakly entangled degrees of freedom. Without discarding of data, the protocol resembles the anomalous amplification of an imaginary-weak-value-like response. The amplification is induced in the difference signal of both detectors allowing robustness to different sources of technical noise, and offering in addition the advantages of balanced signals for precision metrology. All of the Fisher information about the parameter of interest is collected. A tunable phase controls the strength of the amplification response. We experimentally demonstrate the proposed technique by measuring polarization rotations in a linearly polarized laser pulse. We show that in the presence of technical noise the effective sensitivity and precision of a split detector is increased when compared to a conventional continuous-wave balanced detection technique.

  9. Can Anomalous Amplification be Attained Without Postselection?

    CERN Document Server

    Martínez-Rincón, Julián; Viza, Gerardo I; Howell, John C

    2015-01-01

    We present a parameter estimation technique based on performing joint measurements of a weak interaction away from the weak-value-amplification approximation. Two detectors are used to collect full statistics of the correlations between two weakly entangled degrees of freedom. Without the need of postselection, the protocol resembles the anomalous amplification of an imaginary-weak-value-like response. The amplification is induced in the difference signal of both detectors allowing robustness to different sources of technical noise, and offering in addition the advantages of balanced signals for precision metrology. All of the Fisher information about the parameter of interest is collected, and a phase controls the amplification response. We experimentally demonstrate the proposed technique by measuring polarization rotations in a linearly polarized laser pulse. The effective sensitivity and precision of a split detector is increased when compared to a conventional continuous-wave balanced detection technique...

  10. Stochastic sensors designed for assessment of biomarkers specific to obesity.

    Science.gov (United States)

    Cioates Negut, Catalina; Stefan-van Staden, Raluca-Ioana; Ungureanu, Eleonora-Mihaela; Udeanu, Denisa Ioana

    2016-09-01

    Two stochastic sensors based on the following oleamides: 1-adamantyloleamide and N,N-dimethyl-N-(2-oleylamidoethyl)amine physically immobilized on graphite paste were designed. The sensors were able to determine simultaneously from the whole blood of Wistar rats three biomarkers specific to obesity: leptin, interleukin-6 (IL-6) and plasminogen activator inhibitor 1 (PAI-1). The whole blood samples were obtained from Wistar rats treated with oleoylethanolamide (OEA), (Z)-N-[(1S)-2-hidroxy-1-(phenylmethyl) ethyl]-9octadecenamide (OLA), and with the aqueous solution of 1% Tween 80 used as solvent for oleamides formulations (control samples). The proposed sensors were very sensitive and reliable for the assay of obesity biomarkers in whole blood of rats.

  11. Stochastic sensors designed for assessment of biomarkers specific to obesity.

    Science.gov (United States)

    Cioates Negut, Catalina; Stefan-van Staden, Raluca-Ioana; Ungureanu, Eleonora-Mihaela; Udeanu, Denisa Ioana

    2016-09-01

    Two stochastic sensors based on the following oleamides: 1-adamantyloleamide and N,N-dimethyl-N-(2-oleylamidoethyl)amine physically immobilized on graphite paste were designed. The sensors were able to determine simultaneously from the whole blood of Wistar rats three biomarkers specific to obesity: leptin, interleukin-6 (IL-6) and plasminogen activator inhibitor 1 (PAI-1). The whole blood samples were obtained from Wistar rats treated with oleoylethanolamide (OEA), (Z)-N-[(1S)-2-hidroxy-1-(phenylmethyl) ethyl]-9octadecenamide (OLA), and with the aqueous solution of 1% Tween 80 used as solvent for oleamides formulations (control samples). The proposed sensors were very sensitive and reliable for the assay of obesity biomarkers in whole blood of rats. PMID:27288757

  12. Fibrosis biomarkers in workers exposed to MWCNTs.

    Science.gov (United States)

    Fatkhutdinova, Liliya M; Khaliullin, Timur O; Vasil'yeva, Olga L; Zalyalov, Ramil R; Mustafin, Ilshat G; Kisin, Elena R; Birch, M Eileen; Yanamala, Naveena; Shvedova, Anna A

    2016-05-15

    Multi-walled carbon nanotubes (MWCNT) with their unique physico-chemical properties offer numerous technological advantages and are projected to drive the next generation of manufacturing growth. As MWCNT have already found utility in different industries including construction, engineering, energy production, space exploration and biomedicine, large quantities of MWCNT may reach the environment and inadvertently lead to human exposure. This necessitates the urgent assessment of their potential health effects in humans. The current study was carried out at NanotechCenter Ltd. Enterprise (Tambov, Russia) where large-scale manufacturing of MWCNT along with relatively high occupational exposure levels was reported. The goal of this small cross-sectional study was to evaluate potential biomarkers during occupational exposure to MWCNT. All air samples were collected at the workplaces from both specific areas and personal breathing zones using filter-based devices to quantitate elemental carbon and perform particle analysis by TEM. Biological fluids of nasal lavage, induced sputum and blood serum were obtained from MWCNT-exposed and non-exposed workers for assessment of inflammatory and fibrotic markers. It was found that exposure to MWCNTs caused significant increase in IL-1β, IL6, TNF-α, inflammatory cytokines and KL-6, a serological biomarker for interstitial lung disease in collected sputum samples. Moreover, the level of TGF-β1 was increased in serum obtained from young exposed workers. Overall, the results from this study revealed accumulation of inflammatory and fibrotic biomarkers in biofluids of workers manufacturing MWCNTs. Therefore, the biomarkers analyzed should be considered for the assessment of health effects of occupational exposure to MWCNT in cross-sectional epidemiological studies. PMID:26902652

  13. Rolling circle amplification of metazoan mitochondrialgenomes

    Energy Technology Data Exchange (ETDEWEB)

    Simison, W. Brian; Lindberg, D.R.; Boore, J.L.

    2005-07-31

    Here we report the successful use of rolling circle amplification (RCA) for the amplification of complete metazoan mt genomes to make a product that is amenable to high-throughput genome sequencing techniques. The benefits of RCA over PCR are many and with further development and refinement of RCA, the sequencing of organellar genomics will require far less time and effort than current long PCR approaches.

  14. Multiple biomarkers responses in Prochilodus lineatus allowed assessing changes in the water quality of Salado River basin (Santa Fe, Argentina)

    Energy Technology Data Exchange (ETDEWEB)

    Cazenave, Jimena, E-mail: jcazenave@inali.unl.edu.a [Laboratorio de Ictiologia, Instituto Nacional de Limnologia (INALI-CONICET-UNL), Paraje El Pozo, Ciudad Universitaria UNL, 3000 Santa Fe (Argentina); Bacchetta, Carla; Parma, Maria J.; Scarabotti, Pablo A. [Laboratorio de Ictiologia, Instituto Nacional de Limnologia (INALI-CONICET-UNL), Paraje El Pozo, Ciudad Universitaria UNL, 3000 Santa Fe (Argentina); Wunderlin, Daniel A. [Dto. Bioquimica Clinica-CIBICI-CONICET, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Haya de la Torre esq Medina Allende, Ciudad Universitaria, 5000 Cordoba (Argentina)

    2009-11-15

    This field study assessed water quality of Salado River basin by using a set of biomarkers in the fish Prochilodus lineatus. Multiple biomarkers were measured, including morphological indexes (condition factor, liver somatic index), hematological (red and white blood cells) and biochemical (glucose, total protein and cholinesterase activity) parameters. Besides, detoxication and oxidative stress markers (antioxidant enzymes, lipid peroxidation) were measured in liver, gills and kidney. Despite water quality assessment did not show marked differences among sites, biomarkers responses indicate that fish are living under stressful environmental conditions. According to multivariate analysis glucose, glutathione S-transferase activity, lipid peroxidation levels and the count of white blood cells are key biomarkers to contribute to discrimination of sites. So, we suggest use those biomarkers in future monitoring of freshwater aquatic systems. - A battery of biomarkers was successfully applied to assess the health of the fish Prochilodus lineatus from Salado River basin.

  15. Inflammatory Biomarkers as Differential Predictors of Antidepressant Response

    Directory of Open Access Journals (Sweden)

    Kenji Hashimoto

    2015-04-01

    Full Text Available Although antidepressants are generally effective in the treatment of major depressive disorder (MDD, it can still take weeks before patients feel the full antidepressant effects. Despite the efficacy of standard treatments, approximately two-thirds of patients with MDD fail to respond to pharmacotherapy. Therefore, the identification of blood biomarkers that can predict the treatment response to antidepressants would be highly useful in order to improve this situation. This article discusses inflammatory molecules as predictive biomarkers for antidepressant responses to several classes of antidepressants, including the N-methyl-d-aspartate (NMDA receptor antagonist ketamine.

  16. Biomarker Identification Using Text Mining

    Directory of Open Access Journals (Sweden)

    Hui Li

    2012-01-01

    Full Text Available Identifying molecular biomarkers has become one of the important tasks for scientists to assess the different phenotypic states of cells or organisms correlated to the genotypes of diseases from large-scale biological data. In this paper, we proposed a text-mining-based method to discover biomarkers from PubMed. First, we construct a database based on a dictionary, and then we used a finite state machine to identify the biomarkers. Our method of text mining provides a highly reliable approach to discover the biomarkers in the PubMed database.

  17. Biomarkers in Prostate Cancer Epidemiology

    Directory of Open Access Journals (Sweden)

    Mudit Verma

    2011-09-01

    Full Text Available Understanding the etiology of a disease such as prostate cancer may help in identifying populations at high risk, timely intervention of the disease, and proper treatment. Biomarkers, along with exposure history and clinical data, are useful tools to achieve these goals. Individual risk and population incidence of prostate cancer result from the intervention of genetic susceptibility and exposure. Biochemical, epigenetic, genetic, and imaging biomarkers are used to identify people at high risk for developing prostate cancer. In cancer epidemiology, epigenetic biomarkers offer advantages over other types of biomarkers because they are expressed against a person’s genetic background and environmental exposure, and because abnormal events occur early in cancer development, which includes several epigenetic alterations in cancer cells. This article describes different biomarkers that have potential use in studying the epidemiology of prostate cancer. We also discuss the characteristics of an ideal biomarker for prostate cancer, and technologies utilized for biomarker assays. Among epigenetic biomarkers, most reports indicate GSTP1 hypermethylation as the diagnostic marker for prostate cancer; however, NKX2-5, CLSTN1, SPOCK2, SLC16A12, DPYS, and NSE1 also have been reported to be regulated by methylation mechanisms in prostate cancer. Current challenges in utilization of biomarkers in prostate cancer diagnosis and epidemiologic studies and potential solutions also are discussed.

  18. Onshore seismic amplifications due to bathymetric features

    Science.gov (United States)

    Rodríguez-Castellanos, A.; Carbajal-Romero, M.; Flores-Guzmán, N.; Olivera-Villaseñor, E.; Kryvko, A.

    2016-08-01

    We perform numerical calculations for onshore seismic amplifications, taking into consideration the effect of bathymetric features on the propagation of seismic movements. To this end, the boundary element method is applied. Boundary elements are employed to irradiate waves and, consequently, force densities can be obtained for each boundary element. From this assumption, Huygens’ principle is applied, and since the diffracted waves are built at the boundary from which they are radiated, this idea is equivalent to Somigliana’s representation theorem. The application of boundary conditions leads to a linear system being obtained (Fredholm integral equations). Several numerical models are analyzed, with the first one being used to verify the proposed formulation, and the others being used to estimate onshore seismic amplifications due to the presence of bathymetric features. The results obtained show that compressional waves (P-waves) generate onshore seismic amplifications that can vary from 1.2 to 5.2 times the amplitude of the incident wave. On the other hand, the shear waves (S-waves) can cause seismic amplifications of up to 4.0 times the incident wave. Furthermore, an important result is that in most cases the highest seismic amplifications from an offshore earthquake are located on the shoreline and not offshore, despite the seafloor configuration. Moreover, the influence of the incident angle of seismic waves on the seismic amplifications is highlighted.

  19. Biomarkers for nutrient intake with focus on alternative sampling techniques.

    Science.gov (United States)

    Holen, T; Norheim, F; Gundersen, T E; Mitry, P; Linseisen, J; Iversen, P O; Drevon, C A

    2016-01-01

    Biomarkers of nutrient intake or nutrient status are important objective measures of foods/nutrients as one of the most important environmental factors people are exposed to. It is very difficult to obtain accurate data on individual food intake, and there is a large variation of nutrient composition of foods consumed in a population. Thus, it is difficult to obtain precise measures of exposure to different nutrients and thereby be able to understand the relationship between diet, health, and disease. This is the background for investing considerable resources in studying biomarkers of nutrients believed to be important in our foods. Modern technology with high sensitivity and specificity concerning many nutrient biomarkers has allowed an interesting development with analyses of very small amounts of blood or tissue material. In combination with non-professional collection of blood by finger-pricking and collection on filters or sticks, this may make collection of samples and analyses of biomarkers much more available for scientists as well as health professionals and even lay people in particular in relation to the marked trend of self-monitoring of body functions linked to mobile phone technology. Assuming standard operating procedures are used for collection, drying, transport, extraction, and analysis of samples, it turns out that many analytes of nutritional interest can be measured like metabolites, drugs, lipids, vitamins, minerals, and many types of peptides and proteins. The advantage of this alternative sampling technology is that non-professionals can collect, dry, and mail the samples; the samples can often be stored under room temperature in a dry atmosphere, requiring small amounts of blood. Another promising area is the potential relation between the microbiome and biomarkers that may be measured in feces as well as in blood. PMID:27551313

  20. Blood culture

    Science.gov (United States)

    Culture - blood ... A blood sample is needed . The site where blood will be drawn is first cleaned with an antiseptic such ... organism from the skin getting into (contaminating) the blood sample and causing a false-positive result (see ...

  1. Blood Thinners

    Science.gov (United States)

    If you have some kinds of heart or blood vessel disease, or if you have poor blood flow to your brain, your doctor may recommend that you take a blood thinner. Blood thinners reduce the risk of heart ...

  2. Blood Basics

    Science.gov (United States)

    ... Patient Group Links Advocacy Toolkit Home For Patients Blood Basics Blood is a specialized body fluid. It ... about 9 pints. Jump To: The Components of Blood and Their Importance Many people have undergone blood ...

  3. Blood pressure

    Science.gov (United States)

    ... the walls of the arteries is called blood pressure. Blood pressure is measured both as the heart contracts, which ... as it relaxes, which is called diastole. Normal blood pressure is considered to be a systolic blood pressure ...

  4. Heat induces gene amplification in cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Bin, E-mail: yanbin@mercyhealth.com [Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS 39213 (United States); Mercy Cancer Center, Mercy Medical Center-North Iowa, Mason City, IA 50401 (United States); Ouyang, Ruoyun [Department of Respiratory Medicine, The Second Xiangya Hospital, Xinagya School of Medicine, Central South University, Changsha 410011 (China); Huang, Chenghui [Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS 39213 (United States); Department of Oncology, The Third Xiangya Hospital, Xinagya School of Medicine, Central South University, Changsha 410013 (China); Liu, Franklin [Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710 (United States); Neill, Daniel [Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS 39213 (United States); Li, Chuanyuan [Dermatology, Duke University Medical Center, Durham, NC 27710 (United States); Dewhirst, Mark [Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710 (United States)

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer This study discovered that heat exposure (hyperthermia) results in gene amplification in cancer cells. Black-Right-Pointing-Pointer Hyperthermia induces DNA double strand breaks. Black-Right-Pointing-Pointer DNA double strand breaks are considered to be required for the initiation of gene amplification. Black-Right-Pointing-Pointer The underlying mechanism of heat-induced gene amplification is generation of DNA double strand breaks. -- Abstract: Background: Hyperthermia plays an important role in cancer therapy. However, as with radiation, it can cause DNA damage and therefore genetic instability. We studied whether hyperthermia can induce gene amplification in cancer cells and explored potential underlying molecular mechanisms. Materials and methods: (1) Hyperthermia: HCT116 colon cancer cells received water-submerged heating treatment at 42 or 44 Degree-Sign C for 30 min; (2) gene amplification assay using N-(phosphoacetyl)-L-aspartate (PALA) selection of cabamyl-P-synthetase, aspartate transcarbarmylase, dihydro-orotase (cad) gene amplified cells; (3) southern blotting for confirmation of increased cad gene copies in PALA-resistant cells; (4) {gamma}H2AX immunostaining to detect {gamma}H2AX foci as an indication for DNA double strand breaks. Results: (1) Heat exposure at 42 or 44 Degree-Sign C for 30 min induces gene amplification. The frequency of cad gene amplification increased by 2.8 and 6.5 folds respectively; (2) heat exposure at both 42 and 44 Degree-Sign C for 30 min induces DNA double strand breaks in HCT116 cells as shown by {gamma}H2AX immunostaining. Conclusion: This study shows that heat exposure can induce gene amplification in cancer cells, likely through the generation of DNA double strand breaks, which are believed to be required for the initiation of gene amplification. This process may be promoted by heat when cellular proteins that are responsible for checkpoints, DNA replication, DNA repair and

  5. Heat induces gene amplification in cancer cells

    International Nuclear Information System (INIS)

    Highlights: ► This study discovered that heat exposure (hyperthermia) results in gene amplification in cancer cells. ► Hyperthermia induces DNA double strand breaks. ► DNA double strand breaks are considered to be required for the initiation of gene amplification. ► The underlying mechanism of heat-induced gene amplification is generation of DNA double strand breaks. -- Abstract: Background: Hyperthermia plays an important role in cancer therapy. However, as with radiation, it can cause DNA damage and therefore genetic instability. We studied whether hyperthermia can induce gene amplification in cancer cells and explored potential underlying molecular mechanisms. Materials and methods: (1) Hyperthermia: HCT116 colon cancer cells received water-submerged heating treatment at 42 or 44 °C for 30 min; (2) gene amplification assay using N-(phosphoacetyl)-L-aspartate (PALA) selection of cabamyl-P-synthetase, aspartate transcarbarmylase, dihydro-orotase (cad) gene amplified cells; (3) southern blotting for confirmation of increased cad gene copies in PALA-resistant cells; (4) γH2AX immunostaining to detect γH2AX foci as an indication for DNA double strand breaks. Results: (1) Heat exposure at 42 or 44 °C for 30 min induces gene amplification. The frequency of cad gene amplification increased by 2.8 and 6.5 folds respectively; (2) heat exposure at both 42 and 44 °C for 30 min induces DNA double strand breaks in HCT116 cells as shown by γH2AX immunostaining. Conclusion: This study shows that heat exposure can induce gene amplification in cancer cells, likely through the generation of DNA double strand breaks, which are believed to be required for the initiation of gene amplification. This process may be promoted by heat when cellular proteins that are responsible for checkpoints, DNA replication, DNA repair and telomere functions are denatured. To our knowledge, this is the first study to provide direct evidence of hyperthermia induced gene amplification.

  6. Obtaining Human Ischemic Stroke Gene Expression Biomarkers from Animal Models: A Cross-species Validation Study.

    Science.gov (United States)

    Wang, Yingying; Cai, Yunpeng

    2016-01-01

    Recent studies have revealed the systematic altering of gene expression in human peripheral blood during the early stages of ischemic stroke, which suggests a new potential approach for the rapid diagnosis or prediction of stroke onset. Nevertheless, due to the difficulties of collecting human samples during proper disease stages, related studies are rather restricted. Many studies have instead been performed on manipulated animal models for investigating the regulation patterns of biomarkers during different stroke stages. An important inquiry is how well the findings of animal models can be replicated in human cases. Here, a method is proposed based on PageRank scores of miRNA-mRNA interaction network to select ischemic stroke biomarkers derived from rat brain samples, and biomarkers are validated with two human peripheral blood gene expression datasets. Hierarchical clustering results revealed that the achieved biomarkers clearly separate the blood gene expression of stroke patients and healthy people. Literature searches and functional analyses further validated the biological significance of these biomarkers. Compared to the traditional methods, such as differential expression, the proposed approach is more stable and accurate in detecting cross-species biomarkers with biological relevance, thereby suggesting an efficient approach of re-using gene biomarkers obtained from animal-model studies for human diseases. PMID:27407070

  7. Genetic Heterogeneity of HER2 Amplification and Telomere Shortening in Papillary Thyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    Paola Caria

    2016-10-01

    Full Text Available Extensive research is dedicated to understanding if sporadic and familial papillary thyroid carcinoma are distinct biological entities. We have previously demonstrated that familial papillary thyroid cancer (fPTC cells exhibit short relative telomere length (RTL in both blood and tissues and that these features may be associated with chromosome instability. Here, we investigated the frequency of HER2 (Human Epidermal Growth Factor Receptor 2 amplification, and other recently reported genetic alterations in sporadic PTC (sPTC and fPTC, and assessed correlations with RTL and BRAF mutational status. We analyzed HER2 gene amplification and the integrity of ALK, ETV6, RET, and BRAF genes by fluorescence in situ hybridization in isolated nuclei and paraffin-embedded formalin-fixed sections of 13 fPTC and 18 sPTC patients. We analyzed BRAFV600E mutation and RTL by qRT-PCR. Significant HER2 amplification (p = 0.0076, which was restricted to scattered groups of cells, was found in fPTC samples. HER2 amplification in fPTCs was invariably associated with BRAFV600E mutation. RTL was shorter in fPTCs than sPTCs (p < 0.001. No rearrangements of other tested genes were observed. These findings suggest that the association of HER2 amplification with BRAFV600E mutation and telomere shortening may represent a marker of tumor aggressiveness, and, in refractory thyroid cancer, may warrant exploration as a site for targeted therapy.

  8. Current advances in biomarkers for targeted therapy in triple-negative breast cancer

    Directory of Open Access Journals (Sweden)

    Fleisher B

    2016-10-01

    Full Text Available Brett Fleisher,1 Charlotte Clarke,2 Sihem Ait-Oudhia1 1Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, FL, 2Department of Translational Research, UT MD Anderson Cancer Center, Houston, TX, USA Abstract: Triple-negative breast cancer (TNBC is a complex heterogeneous disease characterized by the absence of three hallmark receptors: human epidermal growth factor receptor 2, estrogen receptor, and progesterone receptor. Compared to other breast cancer subtypes, TNBC is more aggressive, has a higher prevalence in African-Americans, and more frequently affects younger patients. Currently, TNBC lacks clinically accepted targets for tailored therapy, warranting the need for candidate biomarkers. BiomarkerBase, an online platform used to find biomarkers reported in clinical trials, was utilized to screen all potential biomarkers for TNBC and select only the ones registered in completed TNBC trials through clinicaltrials.gov. The selected candidate biomarkers were classified as surrogate, prognostic, predictive, or pharmacodynamic (PD and organized by location in the blood, on the cell surface, in the cytoplasm, or in the nucleus. Blood biomarkers include vascular endothelial growth factor/vascular endothelial growth factor receptor and interleukin-8 (IL-­8; cell surface biomarkers include EGFR, insulin-like growth factor binding protein, c-Kit, c-Met, and PD-L1; cytoplasm biomarkers include PIK3CA, pAKT/S6/p4E-BP1, PTEN, ALDH1, and the PIK3CA/AKT/mTOR-related metabolites; and nucleus biomarkers include BRCA1, the glucocorticoid receptor, TP53, and Ki67. Candidate biomarkers were further organized into a “cellular protein network” that demonstrates potential connectivity. This review provides an inventory and reference point for promising biomarkers for breakthrough targeted therapies in TNBC. Keywords: anti-cancer directed pharmacotherapy, difficult

  9. One New Method of Nucleic Acid Amplification-Loop-mediated Isothermal Amplification of DNA

    Institute of Scientific and Technical Information of China (English)

    Xue-en FANG; Jian LI; Qin CHEN

    2008-01-01

    Loop-mediated isothermal amplification (LAMP) is a novel nucleic acid amplification method, which amplifies DNA with high specificity, sensitivity, rapidity and efficiency under isothermal conditions using a set of four specially designed primers and a Bst DNA polymerase with strand displacement activity. The basic principle, characteristics, development of LAMP and its applications are summarized in this article.

  10. Emerging biomarkers in psoriatic arthritis.

    Science.gov (United States)

    Paek, So Yeon; Han, Ling; Weiland, Matthew; Lu, Chuan-Jian; McKinnon, Kathleen; Zhou, Li; Lim, Henry W; Elder, James T; Mi, Qing-Sheng

    2015-12-01

    Psoriasis is an immune-mediated skin disease which affects 2-4% of the worldwide population. Approximately 20-30% of patients with psoriasis develop psoriatic arthritis (PsA), a frequently destructive and disabling condition. As skin manifestations precede joint symptoms in nearly all patients with PsA, identification of biomarkers for early prediction of joint damage is an important clinical need. Because not all patients with PsA respond to treatment in the same fashion, identification of biomarkers capable of predicting therapeutic response is also imperative. Here, we review existing literature and discuss current investigations to identify potential biomarkers for PsA disease activity, with particular emphasis on microRNAs as novel markers of interest. Serum (soluble) biomarkers, peripheral osteoclast precursor as cellular biomarkers, and genetic loci associated with skin and joint disease are also reviewed. PMID:26602058

  11. Epigenetic biomarkers in liver cancer.

    Science.gov (United States)

    Banaudha, Krishna K; Verma, Mukesh

    2015-01-01

    Liver cancer (hepatocellular carcinoma or HCC) is a major cancer worldwide. Research in this field is needed to identify biomarkers that can be used for early detection of the disease as well as new approaches to its treatment. Epigenetic biomarkers provide an opportunity to understand liver cancer etiology and evaluate novel epigenetic inhibitors for treatment. Traditionally, liver cirrhosis, proteomic biomarkers, and the presence of hepatitis viruses have been used for the detection and diagnosis of liver cancer. Promising results from microRNA (miRNA) profiling and hypermethylation of selected genes have raised hopes of identifying new biomarkers. Some of these epigenetic biomarkers may be useful in risk assessment and for screening populations to identify who is likely to develop cancer. Challenges and opportunities in the field are discussed in this chapter.

  12. HCC Biomarkers in China and Taiwan

    Directory of Open Access Journals (Sweden)

    Regina M. Santella

    2007-02-01

    those who went on to develop HCC. Biologic response markers include measurement of specific mutations in the p53 gene. These studies have demonstrated dramatic differences in mutational spectra of HCC depending on the geographic location. Other early response markers measure tumor DNA released into the blood stream. This DNA has been shown to carry the same genetic and epigenetic changes as does the tumor. In particular, detection of mutations in p53 and methylation of a number of tumor suppressor genes including p16, RASSF1A, MGMT, etc have been analyzed. While not yet applied to HCC cases, the area of proteomic and metabolomics may also lead to useful biomarkers of HCC. In terms of genetic susceptibility, a number of investigators are determining whether single nucleotide polymorphisms are related to HCC risk. The genes investigated to date have included those in the carcinogen metabolism, oxidative stress and DNA repair pathways. While definitive studies are still lacking, the data suggest that, in combination with environmental exposures, genetic factors may also be important in HCC risk.

    The ultimate goal of these biomarker studies is the early identification of high risk individuals so that they can be targeted for enhanced screening or chemopreventive strategies.

  13. Biomarker Investigations Related to Pathophysiological Pathways in Schizophrenia and Psychosis

    Directory of Open Access Journals (Sweden)

    Gursharan eChana

    2013-06-01

    Full Text Available Post-mortem brain investigations of schizophrenia have generated swathes of data in the last few decades implicating candidate genes and proteins, the relation of these findings to peripheral biomarker indicators and symptomatology remain to be elucidated. While biomarkers for disease do not have to be involved with underlying pathophysiology and may be largely indicative of diagnosis or prognosis, the ideal may be a biomarker that is involved in underlying disease processes and which is therefore more likely to change with progression of the illness as well as potentially being more responsive to treatment. One of the main difficulties in conducting biomarker investigations for major psychiatric disorders is the relative inconsistency in clinical diagnoses between disorders such as bipolar and schizophrenia. This has led some researchers to investigate biomarkers associated with core symptoms of these disorders, such as psychosis. The aim of this review is to evaluate the contribution of post-mortem brain investigations to elucidating the pathophysiology pathways involved in schizophrenia and psychosis, with an emphasis on major neurotransmitter systems that have been implicated. This data will then be compared to functional neuroimaging findings as well as findings from blood based gene expression investigations in schizophrenia in order to highlight the relative overlap in pathological processes between these different modalities used to elucidate pathogenesis of schizophrenia. In addition we will cover some recent and exciting findings demonstrating microRNA dysregulation in both the blood and the brain in patients with schizophrenia. These changes are pertinent to the topic due to their known role in post-transcriptional modification of gene expression with the potential to contribute or underlie gene expression changes observed in schizophrenia. Finally, we will discuss how post-mortem studies may aid future biomarker investigations.

  14. Biomarkers for lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Zangar, Richard C.; Varnum, Susan M.

    2014-09-02

    A biomarker, method, test kit, and diagnostic system for detecting the presence of lymphoma in a person are disclosed. The lymphoma may be Hodgkin's lymphoma or non-Hodgkin's lymphoma. The person may be a high-risk subject. In one embodiment, a plasma sample from a person is obtained. The level of at least one protein listed in Table S3 in the plasma sample is measured. The level of at least one protein in the plasma sample is compared with the level in a normal or healthy subject. The lymphoma is diagnosed based upon the level of the at least one protein in the plasma sample in comparison to the normal or healthy level.

  15. Biomarkers in differentiating clinical dengue cases: A prospective cohort study

    Directory of Open Access Journals (Sweden)

    Gary Kim Kuan Low

    2015-12-01

    Full Text Available Objective: To evaluate five biomarkers (neopterin, vascular endothelial growth factor-A, thrombomodulin, soluble vascular cell adhesion molecule 1 and pentraxin 3 in differentiating clinical dengue cases. Methods: A prospective cohort study was conducted whereby the blood samples were obtained at day of presentation and the final diagnosis were obtained at the end of patients’ follow-up. All patients included in the study were 15 years old or older, not pregnant, not infected by dengue previously and did not have cancer, autoimmune or haematological disorder. Median test was performed to compare the biomarker levels. A subgroup Mann-Whitney U test was analysed between severe dengue and non-severe dengue cases. Monte Carlo method was used to estimate the 2-tailed probability (P value for independent variables with unequal number of patients. Results: All biomarkers except thrombomodulin has P value < 0.001 in differentiating among the healthy subjects, non-dengue fever, dengue without warning signs and dengue with warning signs/severe dengue. Subgroup analysis for all the biomarkers between severe dengue and non-severe dengue cases was not statistically significant except vascular endothelial growth factor-A (P < 0.05. Conclusions: Certain biomarkers were able to differentiate the clinical dengue cases. This could be potentially useful in classifying and determining the severity of dengue infected patients in the hospital.

  16. Biomarkers of cardiovascular stress in obstructive sleep apnea.

    Science.gov (United States)

    Maeder, Micha T; Mueller, Christian; Schoch, Otto D; Ammann, Peter; Rickli, Hans

    2016-09-01

    Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder associated with "cardiovascular stress", i.e. cardiovascular risk factors, cardiovascular diseases, and an increased risk of heart failure, stroke, and death. Experimental and clinical studies have characterized potential underlying mechanisms including biventricular dysfunction, atherosclerosis, and arrhythmia. Assessment of these cardiovascular features of OSA requires a spectrum of clinical tools including ECG, echocardiography, exercise testing, and angiography. In contrast to many cardiovascular diseases, the role of blood biomarkers to characterize cardiovascular function and cardiovascular risk in OSA is poorly defined. In the present review we summarize the available data on biomarkers potentially providing information on cardiovascular features in OSA patients without overt cardiovascular disease. The vast majority of studies on biomarkers of cardiovascular stress in OSA evaluated B-type natriuretic peptide (BNP)/N-terminal-B-type natriuretic peptide (NT-proBNP), and cardiac troponins (cTn). Although some studies found significant associations between these cardiac biomarkers and the presence and severity of OSA, data remain conflicting. Also, the detailed pathophysiological mechanisms underlying the link between OSA and hemodynamic cardiac stress (BNP/NT-proBNP) and cardiomyocyte damage (cTn) are poorly understood. Major research efforts are required to establish the clinical role of cardiovascular biomarkers in patients with OSA. PMID:27380998

  17. Time varying arctic climate change amplification

    Energy Technology Data Exchange (ETDEWEB)

    Chylek, Petr [Los Alamos National Laboratory; Dubey, Manvendra K [Los Alamos National Laboratory; Lesins, Glen [DALLHOUSIE U; Wang, Muyin [NOAA/JISAO

    2009-01-01

    During the past 130 years the global mean surface air temperature has risen by about 0.75 K. Due to feedbacks -- including the snow/ice albedo feedback -- the warming in the Arctic is expected to proceed at a faster rate than the global average. Climate model simulations suggest that this Arctic amplification produces warming that is two to three times larger than the global mean. Understanding the Arctic amplification is essential for projections of future Arctic climate including sea ice extent and melting of the Greenland ice sheet. We use the temperature records from the Arctic stations to show that (a) the Arctic amplification is larger at latitudes above 700 N compared to those within 64-70oN belt, and that, surprisingly; (b) the ratio of the Arctic to global rate of temperature change is not constant but varies on the decadal timescale. This time dependence will affect future projections of climate changes in the Arctic.

  18. ESTIMATION OF AMPLIFICATION FACTOR IN EARTHQUAKE ENGINEERING

    Directory of Open Access Journals (Sweden)

    Nazarov Yuriy Pavlovich

    2015-03-01

    Full Text Available The authors are the developers of Odyssey Software (Eurosoft Co. for the analysis of seismological data and computing of seismic loads and their parameters. While communicating with the users of the software, the authors have revealed some uncertainty about both understanding of the term "amplification factor (AF" and calculation of the amplification factor using various methods. In this article, a simple example shows that the determination of the amplification factor as the ratio of the acceleration’s spectrum to the maximal acceleration is derived from the classical definition of AF in the form of the ratio of maximal dynamic displacement to the displacement by the action of static load. Deterministic and probabilistic ap-proaches for the calculating of the AF were discussed. There was an example of AFs calculation and their envelopes for translational and rotational components of seismic impact by using Odyssey Software.

  19. Amplification, Redundancy, and Quantum Chernoff Information

    Science.gov (United States)

    Zwolak, Michael; Riedel, C. Jess; Zurek, Wojciech H.

    2014-04-01

    Amplification was regarded, since the early days of quantum theory, as a mysterious ingredient that endows quantum microstates with macroscopic consequences, key to the "collapse of the wave packet," and a way to avoid embarrassing problems exemplified by Schrödinger's cat. Such a bridge between the quantum microworld and the classical world of our experience was postulated ad hoc in the Copenhagen interpretation. Quantum Darwinism views amplification as replication, in many copies, of the information about quantum states. We show that such amplification is a natural consequence of a broad class of models of decoherence, including the photon environment we use to obtain most of our information. This leads to objective reality via the presence of robust and widely accessible records of selected quantum states. The resulting redundancy (the number of copies deposited in the environment) follows from the quantum Chernoff information that quantifies the information transmitted by a typical elementary subsystem of the environment.

  20. On Arbitrary Phases in Quantum Amplitude Amplification

    CERN Document Server

    Hoyer, P

    2000-01-01

    We consider the use of arbitrary phases in quantum amplitude amplification which is a generalization of quantum searching. We prove that the phase condition in amplitude amplification is given by $\\tan(\\phi/2)=\\tan(\\phi/2)(1-2a)$, where $\\phi$ and $\\phi$ are the phases used and where $a$ is the success probability of the given algorithm. Thus the choice of phases depends nontrivially and nonlinearly on the success probability. Utilizing this condition, we give methods for constructing quantum algorithms that succeed with certainty and for implementing arbitrary rotations. We also conclude that phase errors of order up to $\\frac{1}{\\sqrt{a}}$ can be tolerated in amplitude amplification.

  1. FLUORESCENCE IN SITU HYBRIDIZATION COMBINED WITH IMMUNOFLUORESCENT STAINING FOR RAPID DETECTION OF Nmyc AMPLIFICATION IN NEUROBLASTOMA

    Institute of Scientific and Technical Information of China (English)

    WANG Wei王伟; Marianne Ifversen; ZHAO Chun-ting赵春亭; WANG Hong-yi汪洪毅; ZHAO Hong-guo赵洪国

    2004-01-01

    Objective: To establish a method to improve the detection of disseminated tumor cells in bone marrow and peripheral blood samples of neuroblastoma patients and analysis of cytogenetic aberration. Methods: Immunofluorescent staining was performed using a cocktail of primary monoclonal neuroblastoma antibodies (14.G2a, 5.1H11). Fluorescence in situ hybridization was applied with fluorescent probes specific for Nmyc genes afterwards. A novel computer assisted scanning system for automatic search, image analysis and repositioning of these positive cells was developed. Fifty-six bone marrow and peripheral blood samples from 7 patients were evaluated by this method. Results: Fluorescence in situ hybridization can be combined with immunofluorescent staining in detecting Nmyc amplification in neuroblastoma patients. Fluorescence in situ hybridization results correlated well with data obtained by conventional cytogenetic procedures. Conclusion: The technique described allows search of tumor cells in the bone marrow as well as detection of Nmyc amplification in interphase nuclei.

  2. Are circulating microRNAs peripheral biomarkers for Alzheimer's disease?

    Science.gov (United States)

    Kumar, Subodh; Reddy, P Hemachandra

    2016-09-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory loss, multiple cognitive abnormalities and intellectual impairments. Currently, there are no drugs or agents that can delay and/or prevent the progression of disease in elderly individuals, and there are no peripheral biomarkers that can detect AD early in its pathogenesis. Research has focused on identifying biomarkers for AD so that treatment can be begun as soon as possible in order to restrict or prevent intellectual impairments, memory loss, and other cognitive abnormalities that are associated with the disease. One such potential biomarker is microRNAs that are found in circulatory biofluids, such as blood and blood components, serum and plasma. Blood and blood components are primary sources where miRNAs are released in either cell-free form and then bind to protein components, or are in an encapsulated form with microvesicle particles. Exosomal miRNAs are known to be stable in biofluids and can be detected by high throughput techniques, like microarray and RNA sequencing. In AD brain, enriched miRNAs encapsulated with exosomes crosses the blood brain barrier and secreted in the CSF and blood circulations. This review summarizes recent studies that have identified miRNAs in the blood, serum, plasma, exosomes, cerebral spinal fluids, and extracellular fluids as potential biomarkers of AD. Recent research has revealed only six miRNAs - miR-9, miR-125b, miR-146a, miR-181c, let-7g-5p, and miR-191-5p - that were reported by multiple investigators. Some studies analyzed the diagnostic potential of these six miRNAs through receiver operating curve analysis which indicates the significant area-under-curve values in different biofluid samples. miR-191-5p was found to have the maximum area-under-curve value (0.95) only in plasma and serum samples while smaller area-under-curve values were found for miR-125, miR-181c, miR-191-5p, miR-146a, and miR-9. This article shortlisted the

  3. Integrated Microfluidic Nucleic Acid Isolation, Isothermal Amplification, and Amplicon Quantification

    Directory of Open Access Journals (Sweden)

    Michael G. Mauk

    2015-10-01

    Full Text Available Microfluidic components and systems for rapid (<60 min, low-cost, convenient, field-deployable sequence-specific nucleic acid-based amplification tests (NAATs are described. A microfluidic point-of-care (POC diagnostics test to quantify HIV viral load from blood samples serves as a representative and instructive example to discuss the technical issues and capabilities of “lab on a chip” NAAT devices. A portable, miniaturized POC NAAT with performance comparable to conventional PCR (polymerase-chain reaction-based tests in clinical laboratories can be realized with a disposable, palm-sized, plastic microfluidic chip in which: (1 nucleic acids (NAs are extracted from relatively large (~mL volume sample lysates using an embedded porous silica glass fiber or cellulose binding phase (“membrane” to capture sample NAs in a flow-through, filtration mode; (2 NAs captured on the membrane are isothermally (~65 °C amplified; (3 amplicon production is monitored by real-time fluorescence detection, such as with a smartphone CCD camera serving as a low-cost detector; and (4 paraffin-encapsulated, lyophilized reagents for temperature-activated release are pre-stored in the chip. Limits of Detection (LOD better than 103 virons/sample can be achieved. A modified chip with conduits hosting a diffusion-mode amplification process provides a simple visual indicator to readily quantify sample NA template. In addition, a companion microfluidic device for extracting plasma from whole blood without a centrifuge, generating cell-free plasma for chip-based molecular diagnostics, is described. Extensions to a myriad of related applications including, for example, food testing, cancer screening, and insect genotyping are briefly surveyed.

  4. [Novel biomarkers for diabetic nephropathy].

    Science.gov (United States)

    Araki, Shin-ichi

    2014-02-01

    Diabetic nephropathy is a leading cause of end-stage renal disease worldwide. An early clinical sign of this complication is an increase of urinary albumin excretion, called microalbuminuria, which is not only a predictor of the progression of nephropathy, but also an independent risk factor for cardiovascular disease. Although microalbuminuria is clinically important to assess the prognosis of diabetic patients, it may be insufficient as an early and specific biomarker of diabetic nephropathy because of a large day-to-day variation and lack of a good correlation of microalbuminuria with renal dysfunction and pathohistological changes. Thus, more sensitive and specific biomarkers are needed to improve the diagnostic capability of identifying patients at high risk. The factors involved in renal tubulo-interstitial damage, the production and degradation of extracellular matrix, microinflammation, etc., are investigated as candidate molecules. Despite numerous efforts so far, the assessment of these biomarkers is still a subject of ongoing investigations. Recently, a variety of omics and quantitative techniques in systems biology are rapidly emerging in the field of biomarker discovery, including proteomics, transcriptomics, and metabolomics, and they have been applied to search for novel putative biomarkers of diabetic nephropathy. Novel biomarkers or their combination with microalbuminuria provide a better diagnostic accuracy than microalbuminuria alone, and may be useful for establishing personal medicine. Furthermore, the identification of novel biomarkers may provide insight into the mechanisms underlying diabetic nephropathy.

  5. Continuous phase amplification with a Sagnac interferometer

    CERN Document Server

    Starling, David J; Williams, Nathan S; Jordan, Andrew N; Howell, John C

    2009-01-01

    We describe a weak value inspired phase amplification technique in a Sagnac interferometer. We monitor the relative phase between two paths of a slightly misaligned interferometer by measuring the average position of a split-Gaussian mode in the dark port. Although we monitor only the dark port, we show that the signal varies linearly with phase and that we can obtain similar sensitivity to balanced homodyne detection. We derive the source of the amplification both with classical wave optics and as an inverse weak value.

  6. Parametric Amplification For Detecting Weak Optical Signals

    Science.gov (United States)

    Hemmati, Hamid; Chen, Chien; Chakravarthi, Prakash

    1996-01-01

    Optical-communication receivers of proposed type implement high-sensitivity scheme of optical parametric amplification followed by direct detection for reception of extremely weak signals. Incorporates both optical parametric amplification and direct detection into optimized design enhancing effective signal-to-noise ratios during reception in photon-starved (photon-counting) regime. Eliminates need for complexity of heterodyne detection scheme and partly overcomes limitations imposed on older direct-detection schemes by noise generated in receivers and by limits on quantum efficiencies of photodetectors.

  7. Advances in Gas Chromatographic Methods for the Identification of Biomarkers in Cancer

    Directory of Open Access Journals (Sweden)

    Konstantinos A. Kouremenos, Mikael Johansson, Philip J. Marriott

    2012-01-01

    Full Text Available Screening complex biological specimens such as exhaled air, tissue, blood and urine to identify biomarkers in different forms of cancer has become increasingly popular over the last decade, mainly due to new instruments and improved bioinformatics. However, despite some progress, the identification of biomarkers has shown to be a difficult task with few new biomarkers (excluding recent genetic markers being considered for introduction to clinical analysis. This review describes recent advances in gas chromatographic methods for the identification of biomarkers in the detection, diagnosis and treatment of cancer. It presents a general overview of cancer metabolism, the current biomarkers used for cancer diagnosis and treatment, a background to metabolic changes in tumors, an overview of current GC methods, and collectively presents the scope and outlook of GC methods in oncology.

  8. Circulating microRNAs as Prognostic and Predictive Biomarkers in Patients with Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Jakob Vasehus Schou

    2016-06-01

    Full Text Available MiRNAs are suggested as promising cancer biomarkers. They are stable and extractable from a variety of clinical tissue specimens (fresh frozen or formalin fixed paraffin embedded tissue and a variety of body fluids (e.g., blood, urine, saliva. However, there are several challenges that need to be solved, considering their potential as biomarkers in cancer, such as lack of consistency between biomarker panels in independent studies due to lack of standardized sample handling and processing, use of inconsistent normalization approaches, and differences in patients populations. Focusing on colorectal cancer (CRC, divergent results regarding circulating miRNAs as prognostic or predictive biomarkers are reported in the literature. In the present review, we summarize the current data on circulating miRNAs as prognostic/predictive biomarkers in patients with localized and metastatic CRC (mCRC.

  9. Detection of HER2 amplification in circulating free DNA in patients with breast cancer

    OpenAIRE

    Page, K; Hava, N.; Ward, B; Brown, J.; Guttery, D S; Ruangpratheep, C; Blighe, K; Sharma, A.; Walker, R. A.; Coombes, R. C.; Shaw, J. A.

    2011-01-01

    Background: Human epidermal growth factor receptor 2 (HER2) is amplified and overexpressed in 20–25% of breast cancers. This study investigated circulating free DNA (cfDNA) for detection of HER2 gene amplification in patients with breast cancer. Methods: Circulating free DNA was extracted from plasma of unselected patients with primary breast cancer (22 before surgery and 68 following treatment), 30 metastatic patients and 98 female controls using the QIAamp Blood DNA Mini Kit (Qiagen). The r...

  10. Identification of biomarkers for Mycobacterium tuberculosis infection and disease in BCG-vaccinated young children in Southern India

    DEFF Research Database (Denmark)

    Dhanasekaran, S; Jenum, S; Stavrum, R;

    2013-01-01

    in discriminating between TB disease and controls (AUC 91.7%). A combination of 11 biomarkers predicted latent TB with moderate discriminatory power (AUC 72.2%). In conclusion, RAB33A is a potential biomarker for TB disease, whereas CD4, TGFβ-1 and IL-2, IL-13 may identify latent TB in children.......Pediatric tuberculosis (TB) often goes undiagnosed because of the lack of reliable diagnostic methods. With the aim of assessing biomarker(s) that can aid in the diagnosis of TB infection and disease, we investigated 746 Indian children with suspected TB. Whole-blood mRNA from 210 children...

  11. Blood Types

    Science.gov (United States)

    ... How Can I Help a Friend Who Cuts? Blood Types KidsHealth > For Teens > Blood Types Print A A ... or straight hair instead of curly. ...Make Eight Blood Types The different markers that can be found in ...

  12. Serum Glycoprotein Biomarker Discovery and Qualification Pipeline Reveals Novel Diagnostic Biomarker Candidates for Esophageal Adenocarcinoma.

    Science.gov (United States)

    Shah, Alok K; Cao, Kim-Anh Lê; Choi, Eunju; Chen, David; Gautier, Benoît; Nancarrow, Derek; Whiteman, David C; Saunders, Nicholas A; Barbour, Andrew P; Joshi, Virendra; Hill, Michelle M

    2015-11-01

    were independently verified by lectin magnetic bead array-immunoblotting, confirming the validity of the relative quantitation approach. Thus, we have identified candidate biomarkers, which, following large-scale clinical evaluation, can be developed into diagnostic blood tests. A key feature of the pipeline is the potential for rapid translation of the candidate biomarkers to lectin-immunoassays.

  13. Asynchronicity of facial blood perfusion in migraine.

    Directory of Open Access Journals (Sweden)

    Nina Zaproudina

    Full Text Available Asymmetrical changes in blood perfusion and asynchronous blood supply to head tissues likely contribute to migraine pathophysiology. Imaging was widely used in order to understand hemodynamic variations in migraine. However, mapping of blood pulsations in the face of migraineurs has not been performed so far. We used the Blood Pulsation Imaging (BPI technique, which was recently developed in our group, to establish whether 2D-imaging of blood pulsations parameters can reveal new biomarkers of migraine. BPI characteristics were measured in migraineurs during the attack-free interval and compared to healthy subjects with and without a family history of migraine. We found a novel phenomenon of transverse waves of facial blood perfusion in migraineurs in contrast to healthy subjects who showed synchronous blood delivery to both sides of the face. Moreover, the amplitude of blood pulsations was symmetrically distributed over the face of healthy subjects, but asymmetrically in migraineurs and subjects with a family history of migraine. In the migraine patients we found a remarkable correlation between the side of unilateral headache and the direction of the blood perfusion wave. Our data suggest that migraine is associated with lateralization of blood perfusion and asynchronous blood pulsations in the facial area, which could be due to essential dysfunction of the autonomic vascular control in the face. These findings may further enhance our understanding of migraine pathophysiology and suggest new easily available biomarkers of this pathology.

  14. Analysis of diabetic retinopathy biomarker VEGF gene by computational approaches

    OpenAIRE

    Jayashree Sadasivam; Ramesh, N; Vijayalakshmi, K.; Vinni Viridi; Shiva prasad

    2012-01-01

    Diabetic retinopathy, the most common diabetic eye disease, is caused by changes in the blood vessels of the retina which remains the major cause. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. One of the biomarker for Diabetic retinopathy has been identified as Vascular Endothelial Growth Factor ( VEGF )gene by computational analysis. VEGF is a sub-family of growth factors, the platelet-derived growth factor family of cystine-knot growth factors...

  15. Comparison of Peripheral and Central Schizophrenia Biomarker Profiles

    OpenAIRE

    Harris, Laura W; Sandra Pietsch; Tammy M K Cheng; Emanuel Schwarz; Guest, Paul C.; Sabine Bahn

    2012-01-01

    textabstractWe have recently shown that a molecular biomarker signature comprised of inflammatory, hormonal and growth factors occurs in the blood serum from first onset schizophrenia patients. Here, we use the same platform to investigate post mortem brain tissue (Brodmann area 10) from schizophrenia patients who were mainly chronically ill and drug treated. Twenty-one analytes are differentially expressed in post-mortem brain tissue. Comparison with our previous mRNA profiling studies of th...

  16. Peripheral Biomarkers in Animal Models of Major Depressive Disorder

    OpenAIRE

    Lucia Carboni

    2013-01-01

    Investigations of preclinical biomarkers for major depressive disorder (MDD) encompass the quantification of proteins, peptides, mRNAs, or small molecules in blood or urine of animal models. Most studies aim at characterising the animal model by including the assessment of analytes or hormones affected in depressive patients. The ultimate objective is to validate the model to better understand the neurobiological basis of MDD. Stress hormones or inflammation-related analytes associated with M...

  17. Immunoelectrophoresis - blood

    Science.gov (United States)

    IEP - serum; Immunoglobulin electrophoresis - blood; Gamma globulin electrophoresis; Serum immunoglobulin electrophoresis ... A blood sample is needed. For information on how this is done, see: Venipuncture

  18. Biomarkers of mercury exposure in two eastern Ukraine cities

    Science.gov (United States)

    Gibb, H.; Haver, C.; Kozlov, K.; Centeno, J.A.; Jurgenson, V.; Kolker, A.; Conko, K.M.; Landa, E.R.; Xu, H.

    2011-01-01

    This study evaluates biomarkers of mercury exposure among residents of Horlivka, a city in eastern Ukraine located in an area with geologic and industrial sources of environmental mercury, and residents of Artemivsk, a nearby comparison city outside the mercury-enriched area. Samples of urine, blood, hair, and nails were collected from study participants, and a questionnaire was administered to obtain data on age, gender, occupational history, smoking, alcohol consumption, fish consumption, tattoos, dental amalgams, home heating system, education, source of drinking water, and family employment in mines. Median biomarker mercury concentrations in Artemivsk were 0.26 ??g/g-Cr (urine), 0.92 ??g/L (blood), 0.42 ??g/g (hair), 0.11 ??g/g (toenails), and 0.09 ??g/g (fingernails); median concentrations in Horlivka were 0.15 ??g/g-Cr (urine), 1.01 ??g/L (blood), 0.14 ??g/g (hair), 0.31 ??g/g (toenails), and 0.31 ??g/g (fingernails). Biomarkers of mercury exposure for study participants from Horlivka and Artemivsk are low in comparison with occupationally exposed workers at a mercury recycling facility in Horlivka and in comparison with exposures known to be associated with clinical effects. Blood and urinary mercury did not suggest a higher mercury exposure among Horlivka residents as compared with Artemivsk; however, three individuals living in the immediate vicinity of the mercury mines had elevated blood and urinary mercury, relative to overall results for either city. For a limited number of residents from Horlivka (N = 7) and Artemivsk (N = 4), environmental samples (vacuum cleaner dust, dust wipes, soil) were collected from their residences. Mercury concentrations in vacuum cleaner dust and soil were good predictors of blood and urinary mercury. Copyright ?? 2011 JOEH, LLC.

  19. Biomarker in archaeological soils

    Science.gov (United States)

    Wiedner, Katja; Glaser, Bruno; Schneeweiß, Jens

    2015-04-01

    The use of biomarkers in an archaeological context allow deeper insights into the understanding of anthropogenic (dark) earth formation and from an archaeological point of view, a completely new perspective on cultivation practices in the historic past. During an archaeological excavation of a Slavic settlement (10th/11th C. A.D.) in Brünkendorf (Wendland region in Northern Germany), a thick black soil (Nordic Dark Earth) was discovered that resembled the famous terra preta phenomenon. For the humid tropics, terra preta could act as model for sustainable agricultural practices and as example for long-term CO2-sequestration into terrestrial ecosystems. The question was whether this Nordic Dark Earth had similar properties and genesis as the famous Amazonian Dark Earth in order to find a model for sustainable agricultural practices and long term CO2-sequestration in temperate zones. For this purpose, a multi-analytical approach was used to characterize the sandy-textured Nordic Dark Earth in comparison to less anthropogenically influenced soils in the adjacent area in respect of ecological conditions (e.g. amino sugar), input materials (faeces) and the presence of stable soil organic matter (black carbon). Amino sugar analyses showed that Nordic Dark Earth contained higher amounts of microbial residues being dominated by soil fungi. Faecal biomarkers such as stanols and bile acids indicated animal manure from omnivores and herbivores but also human excrements. Black carbon content of about 30 Mg ha-1 in the Nordic Dark Earth was about four times higher compared to the adjacent soil and in the same order of magnitude compared to terra preta. Our data strongly suggest parallels to anthropogenic soil formation in Amazonia and in Europe by input of organic wastes, faecal material and charred organic matter. An obvious difference was that in terra preta input of human-derived faecal material dominated while in NDE human-derived faecal material played only a minor role

  20. Biomarkers of latent TB infection

    DEFF Research Database (Denmark)

    Ruhwald, Morten; Ravn, Pernille

    2009-01-01

    For the last 100 years, the tuberculin skin test (TST) has been the only diagnostic tool available for latent TB infection (LTBI) and no biomarker per se is available to diagnose the presence of LTBI. With the introduction of M. tuberculosis-specific IFN-gamma release assays (IGRAs), a new area of...... in vitro immunodiagnostic tests for LTBI based on biomarker readout has become a reality. In this review, we discuss existing evidence on the clinical usefulness of IGRAs and the indefinite number of potential new biomarkers that can be used to improve diagnosis of latent TB infection. We also...... present early data suggesting that the monocyte-derived chemokine inducible protein-10 may be useful as a novel biomarker for the immunodiagnosis of latent TB infection....

  1. Desert Amplification in a Warming Climate

    Science.gov (United States)

    Zhou, Liming

    2016-08-01

    Here I analyze the observed and projected surface temperature anomalies over land between 50°S-50°N for the period 1950–2099 by large-scale ecoregion and find strongest warming consistently and persistently seen over driest ecoregions such as the Sahara desert and the Arabian Peninsula during various 30-year periods, pointing to desert amplification in a warming climate. This amplification enhances linearly with the global mean greenhouse gases(GHGs) radiative forcing and is attributable primarily to a stronger GHGs-enhanced downward longwave radiation forcing reaching the surface over drier ecoregions as a consequence of a warmer and thus moister atmosphere in response to increasing GHGs. These results indicate that desert amplification may represent a fundamental pattern of global warming associated with water vapor feedbacks over land in low- and mid- latitudes where surface warming rates depend inversely on ecosystem dryness. It is likely that desert amplification might involve two types of water vapor feedbacks that maximize respectively in the tropical upper troposphere and near the surface over deserts, with both being very dry and thus extremely sensitive to changes of water vapor.

  2. Optical Pattern Recognition With Self-Amplification

    Science.gov (United States)

    Liu, Hua-Kuang

    1994-01-01

    In optical pattern recognition system with self-amplification, no reference beam used in addressing mode. Polarization of laser beam and orientation of photorefractive crystal chosen to maximize photorefractive effect. Intensity of recognition signal is orders of magnitude greater than other optical correlators. Apparatus regarded as real-time or quasi-real-time optical pattern recognizer with memory and reprogrammability.

  3. Social amplification of risk: a conceptual framework

    International Nuclear Information System (INIS)

    One of the most perplexing problems in risk analysis is why some relatively minor risks or risk events, as assessed by technical experts, often elicit strong public concerns and result in substantial impacts upon society and economy. This article sets forth a conceptual framework that seeks to link systematically the technical assessment of risk with psychological, sociological, and cultural perspectives of risk perception and risk-related behavior. The main thesis is that hazards interact with psychological, social, institutional, and cultural processes in ways that may amplify or attenuate public responses to the risk or risk event. A structural description of the social amplification of risk is now possible. Amplification occurs at two stages: in the transfer of information about the risk, and in the response mechanisms of society. Signals about risk are processed by individual and social amplification stations, including the scientist who communicates the risk assessment, the news media, cultural groups, interpersonal networks, and others. Key steps of amplifications can be identified at each stage. The amplified risk leads to behavioral responses, which, in turn, result in secondary impacts. Models are presented that portray the elements and linkages in the proposed conceptual framework

  4. Desert Amplification in a Warming Climate

    Science.gov (United States)

    Zhou, Liming

    2016-01-01

    Here I analyze the observed and projected surface temperature anomalies over land between 50°S-50°N for the period 1950–2099 by large-scale ecoregion and find strongest warming consistently and persistently seen over driest ecoregions such as the Sahara desert and the Arabian Peninsula during various 30-year periods, pointing to desert amplification in a warming climate. This amplification enhances linearly with the global mean greenhouse gases(GHGs) radiative forcing and is attributable primarily to a stronger GHGs-enhanced downward longwave radiation forcing reaching the surface over drier ecoregions as a consequence of a warmer and thus moister atmosphere in response to increasing GHGs. These results indicate that desert amplification may represent a fundamental pattern of global warming associated with water vapor feedbacks over land in low- and mid- latitudes where surface warming rates depend inversely on ecosystem dryness. It is likely that desert amplification might involve two types of water vapor feedbacks that maximize respectively in the tropical upper troposphere and near the surface over deserts, with both being very dry and thus extremely sensitive to changes of water vapor. PMID:27538725

  5. Desert Amplification in a Warming Climate.

    Science.gov (United States)

    Zhou, Liming

    2016-01-01

    Here I analyze the observed and projected surface temperature anomalies over land between 50°S-50°N for the period 1950-2099 by large-scale ecoregion and find strongest warming consistently and persistently seen over driest ecoregions such as the Sahara desert and the Arabian Peninsula during various 30-year periods, pointing to desert amplification in a warming climate. This amplification enhances linearly with the global mean greenhouse gases(GHGs) radiative forcing and is attributable primarily to a stronger GHGs-enhanced downward longwave radiation forcing reaching the surface over drier ecoregions as a consequence of a warmer and thus moister atmosphere in response to increasing GHGs. These results indicate that desert amplification may represent a fundamental pattern of global warming associated with water vapor feedbacks over land in low- and mid- latitudes where surface warming rates depend inversely on ecosystem dryness. It is likely that desert amplification might involve two types of water vapor feedbacks that maximize respectively in the tropical upper troposphere and near the surface over deserts, with both being very dry and thus extremely sensitive to changes of water vapor. PMID:27538725

  6. Cardiac Biomarkers and Cycling Race

    OpenAIRE

    Caroline Le Goff, Jean-François Kaux, Sébastien Goffaux, Etienne Cavalier

    2015-01-01

    In cycling as in other types of strenuous exercise, there exists a risk of sudden death. It is important both to understand its causes and to see if the behavior of certain biomarkers might highlight athletes at risk. Many reports describe changes in biomarkers after strenuous exercise (Nie et al., 2011), but interpreting these changes, and notably distinguishing normal physiological responses from pathological changes, is not easy. Here we have focused on the kinetics of different cardiac bi...

  7. Biomarkers in Acute Lung Injury

    OpenAIRE

    Bhargava, Maneesh; Wendt, Chris

    2012-01-01

    Acute Respiratory Distress Syndrome (ARDS) and Acute Lung Injury (ALI) result in high permeability pulmonary edema causing hypoxic respiratory failure with high morbidity and mortality. As the population ages, the incidence of ALI is expected to rise. Over the last decade, several studies have identified biomarkers in plasma and bronchoalveolar lavage fluid providing important insights into the mechanisms involved in the pathophysiology of ALI. Several biomarkers have been validated in subjec...

  8. Biomarkers in Prostate Cancer Epidemiology

    OpenAIRE

    Mudit Verma; Mukesh Verma; Payal Patel

    2011-01-01

    Understanding the etiology of a disease such as prostate cancer may help in identifying populations at high risk, timely intervention of the disease, and proper treatment. Biomarkers, along with exposure history and clinical data, are useful tools to achieve these goals. Individual risk and population incidence of prostate cancer result from the intervention of genetic susceptibility and exposure. Biochemical, epigenetic, genetic, and imaging biomarkers are used to identify people at high ris...

  9. Analysis of biomarker data a practical guide

    CERN Document Server

    Looney, Stephen W

    2015-01-01

    A "how to" guide for applying statistical methods to biomarker data analysis Presenting a solid foundation for the statistical methods that are used to analyze biomarker data, Analysis of Biomarker Data: A Practical Guide features preferred techniques for biomarker validation. The authors provide descriptions of select elementary statistical methods that are traditionally used to analyze biomarker data with a focus on the proper application of each method, including necessary assumptions, software recommendations, and proper interpretation of computer output. In addition, the book discusses

  10. Deep biomarkers of human aging: Application of deep neural networks to biomarker development.

    Science.gov (United States)

    Putin, Evgeny; Mamoshina, Polina; Aliper, Alexander; Korzinkin, Mikhail; Moskalev, Alexey; Kolosov, Alexey; Ostrovskiy, Alexander; Cantor, Charles; Vijg, Jan; Zhavoronkov, Alex

    2016-05-01

    One of the major impediments in human aging research is the absence of a comprehensive and actionable set of biomarkers that may be targeted and measured to track the effectiveness of therapeutic interventions. In this study, we designed a modular ensemble of 21 deep neural networks (DNNs) of varying depth, structure and optimization to predict human chronological age using a basic blood test. To train the DNNs, we used over 60,000 samples from common blood biochemistry and cell count tests from routine health exams performed by a single laboratory and linked to chronological age and sex. The best performing DNN in the ensemble demonstrated 81.5 % epsilon-accuracy r = 0.90 with R(2) = 0.80 and MAE = 6.07 years in predicting chronological age within a 10 year frame, while the entire ensemble achieved 83.5% epsilon-accuracy r = 0.91 with R(2) = 0.82 and MAE = 5.55 years. The ensemble also identified the 5 most important markers for predicting human chronological age: albumin, glucose, alkaline phosphatase, urea and erythrocytes. To allow for public testing and evaluate real-life performance of the predictor, we developed an online system available at http://www.aging.ai. The ensemble approach may facilitate integration of multi-modal data linked to chronological age and sex that may lead to simple, minimally invasive, and affordable methods of tracking integrated biomarkers of aging in humans and performing cross-species feature importance analysis. PMID:27191382

  11. Deep biomarkers of human aging: Application of deep neural networks to biomarker development

    Science.gov (United States)

    Putin, Evgeny; Mamoshina, Polina; Aliper, Alexander; Korzinkin, Mikhail; Moskalev, Alexey; Kolosov, Alexey; Ostrovskiy, Alexander; Cantor, Charles; Vijg, Jan; Zhavoronkov, Alex

    2016-01-01

    One of the major impediments in human aging research is the absence of a comprehensive and actionable set of biomarkers that may be targeted and measured to track the effectiveness of therapeutic interventions. In this study, we designed a modular ensemble of 21 deep neural networks (DNNs) of varying depth, structure and optimization to predict human chronological age using a basic blood test. To train the DNNs, we used over 60,000 samples from common blood biochemistry and cell count tests from routine health exams performed by a single laboratory and linked to chronological age and sex. The best performing DNN in the ensemble demonstrated 81.5 % epsilon-accuracy r = 0.90 with R2 = 0.80 and MAE = 6.07 years in predicting chronological age within a 10 year frame, while the entire ensemble achieved 83.5% epsilon-accuracy r = 0.91 with R2 = 0.82 and MAE = 5.55 years. The ensemble also identified the 5 most important markers for predicting human chronological age: albumin, glucose, alkaline phosphatase, urea and erythrocytes. To allow for public testing and evaluate real-life performance of the predictor, we developed an online system available at http://www.aging.ai. The ensemble approach may facilitate integration of multi-modal data linked to chronological age and sex that may lead to simple, minimally invasive, and affordable methods of tracking integrated biomarkers of aging in humans and performing cross-species feature importance analysis. PMID:27191382

  12. Neuroimmune biomarkers in schizophrenia.

    Science.gov (United States)

    Tomasik, Jakub; Rahmoune, Hassan; Guest, Paul C; Bahn, Sabine

    2016-09-01

    Schizophrenia is a heterogeneous psychiatric disorder with a broad spectrum of clinical and biological manifestations. Due to the lack of objective tests, the accurate diagnosis and selection of effective treatments for schizophrenia remains challenging. Numerous technologies have been employed in search of schizophrenia biomarkers. These studies have suggested that neuroinflammatory processes may play a role in schizophrenia pathogenesis, at least in a subgroup of patients. The evidence indicates alterations in both pro- and anti-inflammatory molecules in the central nervous system, which have also been found in peripheral tissues and may correlate with schizophrenia symptoms. In line with these findings, certain immunomodulatory interventions have shown beneficial effects on psychotic symptoms in schizophrenia patients, in particular those with distinct immune signatures. In this review, we evaluate these findings and their potential for more targeted drug interventions and the development of companion diagnostics. Although currently no validated markers exist for schizophrenia patient stratification or the prediction of treatment efficacy, we propose that utilisation of inflammatory markers for diagnostic and theranostic purposes may lead to novel therapeutic approaches and deliver more effective care for schizophrenia patients. PMID:25124519

  13. Electromagnetic waves amplification in a coaxial triode with virtual cathode

    Energy Technology Data Exchange (ETDEWEB)

    Grigoryev, V.P.; Antoshkin, M.Y.; Koval, T.V.; Kuryakov, A.M. [Tomsk Politechnical Univ. (Russian Federation)

    1995-11-01

    The present paper presents the results of analytical and numerical investigations on the amplification of microwaves in the vircator triode of coaxial making. The range of a parameters of the greatest amplification was define for TH and TE-modes.

  14. Biomarkers for personalized oncology: recent advances and future challenges.

    Science.gov (United States)

    Kalia, Madhu

    2015-03-01

    Cancer is a group of diseases characterized by the uncontrolled growth and spread of abnormal cells and oncology is a branch of medicine that deals with tumors. The last decade has seen significant advances in the development of biomarkers in oncology that play a critical role in understanding molecular and cellular mechanisms which drive tumor initiation, maintenance and progression. Clinical molecular diagnostics and biomarker discoveries in oncology are advancing rapidly as we begin to understand the complex mechanisms that transform a normal cell into an abnormal one. These discoveries have fueled the development of novel drug targets and new treatment strategies. The standard of care for patients with advanced-stage cancers has shifted away from an empirical treatment strategy based on the clinical-pathological profile to one where a biomarker driven treatment algorithm based on the molecular profile of the tumor is used. Recent advances in multiplex genotyping technologies and high-throughput genomic profiling by next-generation sequencing make possible the rapid and comprehensive analysis of the cancer genome of individual patients even from very little tumor biopsy material. Predictive (diagnostic) biomarkers are helpful in matching targeted therapies with patients and in preventing toxicity of standard (systemic) therapies. Prognostic biomarkers identify somatic germ line mutations, changes in DNA methylation, elevated levels of microRNA (miRNA) and circulating tumor cells (CTC) in blood. Predictive biomarkers using molecular diagnostics are currently in use in clinical practice of personalized oncotherapy for the treatment of five diseases: chronic myeloid leukemia, colon, breast, lung cancer and melanoma and these biomarkers are being used successfully to evaluate benefits that can be achieved through targeted therapy. Examples of these molecularly targeted biomarker therapies are: tyrosine kinase inhibitors in chronic myeloid leukemia and

  15. Dual-signal amplification strategy for ultrasensitive photoelectrochemical immunosensing of α-fetoprotein.

    Science.gov (United States)

    Li, Yong-Jie; Ma, Meng-Jie; Zhu, Jun-Jie

    2012-12-01

    An ultrasensitive photoelectrochemical immunoassay of cancer biomarker α-fetoprotein (AFP) is proposed that uses titanium dioxide (TiO(2)) coupled with AFP-CdTe-GOx bioconjugate, which featured AFP antigen and glucose oxidase (GOx) labels linked to CdTe quantum dots (QDs) for signal amplification. The synthesized CdTe QDs yielded a homogeneous and narrow size distribution, which allowed the binding of AFP and GOx on CdTe QDs. Greatly enhanced sensitivity for AFP came from a dual signal amplification strategy. First, an effective matching of energy levels between the conduction bands of CdTe QDs and TiO(2) allowed for fast electron injection from excited CdTe QDs to TiO(2) upon irradiation, which reduced the recombination process of electron-hole pairs and prompted photoelectrochemical performance. Second, GOx enzyme could catalyze glucose to produce H(2)O(2), which acted as a sacrificial electron donor to scavenge the photogenerated holes in the valence band of CdTe QDs, further causing an enhanced photocurrent. Thus, on the basis of the dual signal amplification strategy, the competitive immunosensor based on the specific binding of anti-AFP antibodies to AFP and AFP-CdTe-GOx bioconjugates was achieved. This proposed biosensor for AFP possessed largely increased linear detection range from 0.5 pg/mL to 10 μg/mL with a detection limit of 0.13 pg/mL. The proposed amplification strategy shows high sensitivity, stability, and reproducibility and can become a promising platform for other protein detection. PMID:23140135

  16. A new evolutionary theory deduced mathematically from entropy amplification

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A new evolutionary theory which is able to unite the present evolutionary debates is deduced mathematically from the principle of entropy amplification.It suggests that the extensive evolution is driven by the amplification of entropy,or microscopic diversity,and the biological evolution is driven by the amplification of biodiversity.Forming high hierarchies is the most important way for the amplification and brings out spontaneously three kinds of selection.This theory has some positive cultural meanings.

  17. Parametric Amplification of Vacuum Fluctuations in a Spinor Condensate

    DEFF Research Database (Denmark)

    Klempt, C.; Topic, O.; Gebreyesus, G.;

    2010-01-01

    Parametric amplification of vacuum fluctuations is crucial in modern quantum optics, enabling the creation of squeezing and entanglement. We demonstrate the parametric amplification of vacuum fluctuations for matter waves using a spinor F=2 87Rb condensate. Interatomic interactions lead to correl......Parametric amplification of vacuum fluctuations is crucial in modern quantum optics, enabling the creation of squeezing and entanglement. We demonstrate the parametric amplification of vacuum fluctuations for matter waves using a spinor F=2 87Rb condensate. Interatomic interactions lead...

  18. DNA Methylation as a Biomarker for Preeclampsia

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Cindy M.; Ralph, Jody L.; Wright, Michelle L.; Linggi, Bryan E.; Ohm, Joyce E.

    2014-10-01

    Background: Preeclampsia contributes significantly to pregnancy-associated morbidity and mortality as well as future risk of cardiovascular disease in mother and offspring, and preeclampsia in offspring. The lack of reliable methods for early detection limits the opportunities for prevention, diagnosis, and timely treatment. Purpose: The purpose of this study was to explore distinct DNA methylation patterns associated with preeclampsia in both maternal cells and fetal-derived tissue that represent potential biomarkers to predict future preeclampsia and inheritance in children. Method: A convenience sample of nulliparous women (N = 55) in the first trimester of pregnancy was recruited for this prospective study. Genome-wide DNA methylation was quantified in first-trimester maternal peripheral white blood cells and placental chorionic tissue from normotensive women and those with preeclampsia (n = 6/group). Results: Late-onset preeclampsia developed in 12.7% of women. Significant differences in DNA methylation were identified in 207 individual linked cytosine and guanine (CpG) sites in maternal white blood cells collected in the first trimester (132 sites with gain and 75 sites with loss of methylation), which were common to approximately 75% of the differentially methylated CpG sites identified in chorionic tissue of fetal origin. Conclusion: This study is the first to identify maternal epigenetic targets and common targets in fetal-derived tissue that represent putative biomarkers for early detection and heritable risk of preeclampsia. Findings may pave the way for diagnosis of preeclampsia prior to its clinical presentation and acute damaging effects, and the potential for prevention of the detrimental long-term sequelae.

  19. Quantitation of viral load using real-time amplification techniques

    NARCIS (Netherlands)

    Niesters, H G

    2001-01-01

    Real-time PCR amplification techniques are currently used to determine the viral load in clinical samples for an increasing number of targets. Real-time PCR reduces the time necessary to generate results after amplification. In-house developed PCR and nucleic acid sequence-based amplification (NASBA

  20. Plasmonic Terahertz Amplification in Graphene-Based Asymmetric Hyperbolic Metamaterial

    Directory of Open Access Journals (Sweden)

    Igor Nefedov

    2015-05-01

    Full Text Available We propose and theoretically explore terahertz amplification, based on stimulated generation of plasmons in graphene asymmetric hyperbolic metamaterials (AHMM, strongly coupled to terahertz radiation. In contrast to the terahertz amplification in resonant nanocavities, AHMM provides a wide-band THz amplification without any reflection in optically thin graphene multilayers.

  1. Mechanism-based bioanalysis and biomarkers for hepatic chemical stress.

    Science.gov (United States)

    Antoine, D J; Mercer, A E; Williams, D P; Park, B K

    2009-08-01

    Adverse drug reactions, in particular drug-induced hepatotoxicity, represent a major challenge for clinicians and an impediment to safe drug development. Novel blood or urinary biomarkers of chemically-induced hepatic stress also hold great potential to provide information about pathways leading to cell death within tissues. The earlier pre-clinical identification of potential hepatotoxins and non-invasive diagnosis of susceptible patients, prior to overt liver disease is an important goal. Moreover, the identification, validation and qualification of biomarkers that have in vitro, in vivo and clinical transferability can assist bridging studies and accelerate the pace of drug development. Drug-induced chemical stress is a multi-factorial process, the kinetics of the interaction between the hepatotoxin and the cellular macromolecules are crucially important as different biomarkers will appear over time. The sensitivity of the bioanalytical techniques used to detect biological and chemical biomarkers underpins the usefulness of the marker in question. An integrated analysis of the biochemical, molecular and cellular events provides an understanding of biological (host) factors which ultimately determine the balance between xenobiotic detoxification, adaptation and liver injury. The aim of this review is to summarise the potential of novel mechanism-based biomarkers of hepatic stress which provide information to connect the intracellular events (drug metabolism, organelle, cell and whole organ) ultimately leading to tissue damage (apoptosis, necrosis and inflammation). These biomarkers can provide both the means to inform the pharmacologist and chemist with respect to safe drug design, and provide clinicians with valuable tools for patient monitoring. PMID:19621999

  2. New perspectives in the search for reliable biomarkers in Alzheimer disease

    Directory of Open Access Journals (Sweden)

    Laura Moreno

    2015-03-01

    Full Text Available Background and Objectives: The search for accurate biomarkers in Alzheimer Disease (AD, on of the most devastating neurodegenerative diseases, remains essential to enable an early prognosis and diagnosis of the disease and to provide more efficient therapeutic strategies. A wide variety of potential biomarkers are has been identified by neuroimaging techniques and by the analysis of fluid samples, such as cerebrospinal fluid (CSF or blood. Recently, a growing number of studies are focused on the discovery of reliable blood-based biomarkers in blood, especially in the prodromal stage of AD, which can predict the conversion of asymptomatic cases to AD demented cases. In this review, the latest challenges in the search for accurate biomarkers of AD is revised, in particular, an update in blood-based biomarkers is described in depth. Conclusions: Finally, the close link among AD and other neurodegenerative diseases is discussed, mainly based on the last discovered mutation, the chromosome 9 open reading frame 72, C9ORF72.

  3. DNA Labeling Generates a Unique Amplification Probe for Sensitive Photoelectrochemical Immunoassay of HIV-1 p24 Antigen.

    Science.gov (United States)

    Zhao, Wei-Wei; Han, Ying-Mei; Zhu, Yuan-Cheng; Zhang, Nan; Xu, Jing-Juan; Chen, Hong-Yuan

    2015-06-01

    Photoelectrochemical (PEC) immunoassay is an attractive methodology as it allows for an elegant and sensitive protein assay. However, advanced PEC immunoassay remains challenging and the established amplifications rely almost exclusively on the labeling of various enzymes, which usually suffer the inferior stabilities. Here we report the development and validation of the DNA labeling that leads to a unique amplification probe for the sensitive PEC immunoassay of HIV-1 capsid protein, p24 antigen, an important biomarker of human immune deficiency virus (HIV). Following the sandwich immunobinding, the DNA tags could be released and the subsequent dipurinization of the oligonucleotide strands enables the easy oxidation of free nucleobases at a CdTe quantum dots (QDs) modified ITO transducer. Such DNA tags induced PEC amplification and readout permits the exquisite assay of HIV-1 p24 antigen with high sensitivity. As compared to the existing method of enzymatic labeling, the easy preparation and stability of these labels make them very suitable for PEC amplification. Another merit of this method is that it separates the immunobinding from the PEC transducer, which eliminates the commonly existing affection during the biorecognition processes. This work paves a new route for the PEC immunoassay of HIV-1 p24 antigen and provides a general format for the PEC biomolecular detection by means of the DNA labeling.

  4. RNA amplification for successful gene profiling analysis

    Directory of Open Access Journals (Sweden)

    Wang Ena

    2005-07-01

    Full Text Available Abstract The study of clinical samples is often limited by the amount of material available to study. While proteins cannot be multiplied in their natural form, DNA and RNA can be amplified from small specimens and used for high-throughput analyses. Therefore, genetic studies offer the best opportunity to screen for novel insights of human pathology when little material is available. Precise estimates of DNA copy numbers in a given specimen are necessary. However, most studies investigate static variables such as the genetic background of patients or mutations within pathological specimens without a need to assess proportionality of expression among different genes throughout the genome. Comparative genomic hybridization of DNA samples represents a crude exception to this rule since genomic amplification or deletion is compared among different specimens directly. For gene expression analysis, however, it is critical to accurately estimate the proportional expression of distinct RNA transcripts since such proportions directly govern cell function by modulating protein expression. Furthermore, comparative estimates of relative RNA expression at different time points portray the response of cells to environmental stimuli, indirectly informing about broader biological events affecting a particular tissue in physiological or pathological conditions. This cognitive reaction of cells is similar to the detection of electroencephalographic patterns which inform about the status of the brain in response to external stimuli. As our need to understand human pathophysiology at the global level increases, the development and refinement of technologies for high fidelity messenger RNA amplification have become the focus of increasing interest during the past decade. The need to increase the abundance of RNA has been met not only for gene specific amplification, but, most importantly for global transcriptome wide, unbiased amplification. Now gene

  5. Femtomolar detection of a cancer biomarker protein in serum with ultralow background current by anodic stripping voltammetry.

    Science.gov (United States)

    Shiddiky, Muhammad J A; Kithva, Prakash H; Rauf, Sakandar; Trau, Matt

    2012-05-22

    An electrochemical immunosensor for the detection of a cancer biomarker protein in serum at femtomolar concentrations with ultralow background response has been developed, which consists of (i) a hydrophilic polyacrylic acid brush-modified indium tin oxide substrate as an antifouling substrate and (ii) a graphene-quantum dots-antibody 'bionanoconjugate' as a signal amplification label in voltammetric detection of targets in a glassy carbon electrode. PMID:22618633

  6. Circadian Forensics : Estimating blood trace deposition time using rhythmic biomarkers

    NARCIS (Netherlands)

    K. Lech (Karolina)

    2016-01-01

    markdownabstractThe main objectives of criminal investigation are to determine the who, the how and the when of the crime. Who was the perpetrator that committed the criminal offense; how did the crime happen; and when or at what time did the crime happen. Currently, there are methods which allow th

  7. Artificial blood

    Directory of Open Access Journals (Sweden)

    Sarkar Suman

    2008-01-01

    Full Text Available Artificial blood is a product made to act as a substitute for red blood cells. While true blood serves many different functions, artificial blood is designed for the sole purpose of transporting oxygen and carbon dioxide throughout the body. Depending on the type of artificial blood, it can be produced in different ways using synthetic production, chemical isolation, or recombinant biochemical technology. Development of the first blood substitutes dates back to the early 1600s, and the search for the ideal blood substitute continues. Various manufacturers have products in clinical trials; however, no truly safe and effective artificial blood product is currently marketed. It is anticipated that when an artificial blood product is available, it will have annual sales of over $7.6 billion in the United States alone.

  8. Amplification of postwildfire peak flow by debris

    Science.gov (United States)

    Kean, J. W.; McGuire, L. A.; Rengers, F. K.; Smith, J. B.; Staley, D. M.

    2016-08-01

    In burned steeplands, the peak depth and discharge of postwildfire runoff can substantially increase from the addition of debris. Yet methods to estimate the increase over water flow are lacking. We quantified the potential amplification of peak stage and discharge using video observations of postwildfire runoff, compiled data on postwildfire peak flow (Qp), and a physically based model. Comparison of flood and debris flow data with similar distributions in drainage area (A) and rainfall intensity (I) showed that the median runoff coefficient (C = Qp/AI) of debris flows is 50 times greater than that of floods. The striking increase in Qp can be explained using a fully predictive model that describes the additional flow resistance caused by the emergence of coarse-grained surge fronts. The model provides estimates of the amplification of peak depth, discharge, and shear stress needed for assessing postwildfire hazards and constraining models of bedrock incision.

  9. Gravito-magnetic amplification in cosmology

    CERN Document Server

    Tsagas, Christos G

    2009-01-01

    Magnetic fields interact with gravitational waves in various ways. We consider the coupling between the Weyl and the Maxwell fields in cosmology and study the effects of the former on the latter. The approach is fully analytical and the results are gauge-invariant. We show that the nature and the outcome of the gravito-magnetic interaction depends on the electric properties of the cosmic medium. When the conductivity is high, gravitational waves reduce the standard (adiabatic) decay rate of the B-field, leading to its superadiabatic amplification. In poorly conductive environments, on the other hand, Weyl-curvature distortions can result into the resonant amplification of large-scale cosmological magnetic fields. Driven by the gravitational waves, these B-fields oscillate with an amplitude that is found to diverge when the wavelengths of the two sources coincide. We present technical and physical aspects of the gravito-magnetic interaction and discuss its potential implications.

  10. Diffusive shock acceleration and magnetic field amplification

    CERN Document Server

    Schure, K M; Drury, L O'C; Bykov, A M

    2012-01-01

    Diffusive shock acceleration is the theory of particle acceleration through multiple shock crossings. In order for this process to proceed at a rate that can be reconciled with observations of high-energy electrons in the vicinity of the shock, and for cosmic rays protons to be accelerated to energies up to observed galactic values, significant magnetic field amplification is required. In this review we will discuss various theories on how magnetic field amplification can proceed in the presence of a cosmic ray population. On both short and long scales, cosmic ray streaming can induce instabilities that act to amplify the magnetic field. Developments in this area that have occurred over the past decade are the main focus of this paper.

  11. Parametric nanomechanical amplification at very high frequency.

    Science.gov (United States)

    Karabalin, R B; Feng, X L; Roukes, M L

    2009-09-01

    Parametric resonance and amplification are important in both fundamental physics and technological applications. Here we report very high frequency (VHF) parametric resonators and mechanical-domain amplifiers based on nanoelectromechanical systems (NEMS). Compound mechanical nanostructures patterned by multilayer, top-down nanofabrication are read out by a novel scheme that parametrically modulates longitudinal stress in doubly clamped beam NEMS resonators. Parametric pumping and signal amplification are demonstrated for VHF resonators up to approximately 130 MHz and provide useful enhancement of both resonance signal amplitude and quality factor. We find that Joule heating and reduced thermal conductance in these nanostructures ultimately impose an upper limit to device performance. We develop a theoretical model to account for both the parametric response and nonequilibrium thermal transport in these composite nanostructures. The results closely conform to our experimental observations, elucidate the frequency and threshold-voltage scaling in parametric VHF NEMS resonators and sensors, and establish the ultimate sensitivity limits of this approach.

  12. Biomarkers of therapeutic responses in chronic Chagas disease: state of the art and future perspectives

    Directory of Open Access Journals (Sweden)

    Maria-Jesus Pinazo

    2015-05-01

    Full Text Available The definition of a biomarker provided by the World Health Organization is any substance, structure, or process that can be measured in the body, or its products and influence, or predict the incidence or outcome of disease. Currently, the lack of prognosis and progression markers for chronic Chagas disease has posed limitations for testing new drugs to treat this neglected disease. Several molecules and techniques to detect biomarkers in Trypanosoma cruzi-infected patients have been proposed to assess whether specific treatment with benznidazole or nifurtimox is effective. Isolated proteins or protein groups from different T. cruzi stages and parasite-derived glycoproteins and synthetic neoglycoconjugates have been demonstrated to be useful for this purpose, as have nucleic acid amplification techniques. The amplification of T. cruzi DNA using the real-time polymerase chain reaction method is the leading test for assessing responses to treatment in a short period of time. Biochemical biomarkers have been tested early after specific treatment. Cytokines and surface markers represent promising molecules for the characterisation of host cellular responses, but need to be further assessed.

  13. Introduction to Quantum Noise, Measurement and Amplification

    OpenAIRE

    Clerk, A. A.; Devoret, M. H.; Girvin, S. M.; Marquardt, F.; Schoelkopf, R. J.

    2008-01-01

    The topic of quantum noise has become extremely timely due to the rise of quantum information physics and the resulting interchange of ideas between the condensed matter and AMO/quantum optics communities. This review gives a pedagogical introduction to the physics of quantum noise and its connections to quantum measurement and quantum amplification. After introducing quantum noise spectra and methods for their detection, we describe the basics of weak continuous measurements. Particular atte...

  14. Circulating Biomarkers of Interstitial Lung Disease in Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Harpreet K. Lota

    2012-01-01

    Full Text Available Interstitial lung disease (ILD is a major cause of morbidity and mortality in patients with systemic sclerosis (SSc. Although a large proportion of SSc patients have only limited interstitial involvement with an indolent course, in a significant minority ILD is progressive, requiring prompt treatment and careful monitoring. One of the main challenges for the clinician treating this highly variable disease is the early identification of patients at risk of progressive ILD, while avoiding potentially toxic treatments in those whose disease is inherently stable. Easily available and repeatable biomarkers that allow estimation of the risk of ILD progression and early response to treatment are highly desirable. In this paper, we review the evidence for circulating biomarkers with potential roles in diagnosis, monitoring of disease activity, or determining prognosis. Peripheral blood biomarkers offer the advantages of being readily obtained, non-invasive, and serially monitored. Several possible candidates have emerged from studies performed so far, including SP-D, KL-6, and CCL18. Presently however, there are few prospective studies evaluating the predictive ability of prospective biomarkers after adjustment for disease severity. Future carefully designed, prospective studies of well characterised patients with ILD, with optimal definition of disease severity and outcome measures are needed.

  15. MicroRNAs in Diabetic Nephropathy: From Biomarkers to Therapy.

    Science.gov (United States)

    Simpson, Kate; Wonnacott, Alexa; Fraser, Donald J; Bowen, Timothy

    2016-03-01

    Recent estimates suggest that 1 in 12 of the global population suffers from diabetes mellitus. Approximately 40 % of those affected will go on to develop diabetes-related chronic kidney disease or diabetic nephropathy (DN). DN is a major cause of disability and premature death. Existing tests for prognostic purposes are limited and can be invasive, and interventions to delay progression are challenging. MicroRNAs (miRNAs) are a recently described class of molecular regulators found ubiquitously in human tissues and bodily fluids, where they are highly stable. Alterations in miRNA expression profiles have been observed in numerous diseases. Blood and tissue miRNAs are already established cancer biomarkers, and cardiovascular, metabolic and immune disease miRNA biomarkers are under development. Urinary miRNAs represent a potential novel source of non-invasive biomarkers for kidney diseases, including DN. In addition, recent data suggest that miRNAs may have therapeutic applications. Here, we review the utility of miRNAs as biomarkers for the early detection and progression of DN, assess emerging data on miRNAs implicated in DN pathology and discuss how the data from both fields may contribute to the development of novel therapeutic agents. PMID:26973290

  16. Non-instrumented nucleic acid amplification assay

    Science.gov (United States)

    Weigl, Bernhard H.; Domingo, Gonzalo; Gerlach, Jay; Tang, Dennis; Harvey, Darrel; Talwar, Nick; Fichtenholz, Alex; van Lew, Bill; LaBarre, Paul

    2008-02-01

    We have developed components of a diagnostic disposable platform that has the dual purpose of providing molecular diagnostics at the point of care (POC) as well as stabilizing specimens for further analysis via a centralized surveillance system. This diagnostic is targeted for use in low-resource settings by minimally trained health workers. The disposable device does not require any additional instrumentation and will be almost as rapid and simple to use as a lateral flow strip test - yet will offer the sensitivity and specificity of nucleic acid amplification tests (NAATs). The low-cost integrated device is composed of three functional components: (1) a sample-processing subunit that generates clean and stabilized DNA from raw samples containing nucleic acids, (2) a NA amplification subunit, and (3) visual amplicon detection sub-unit. The device integrates chemical exothermic heating, temperature stabilization using phase-change materials, and isothermal nucleic acid amplification. The aim of developing this system is to provide pathogen detection with NAAT-level sensitivity in low-resource settings where there is no access to instrumentation. If a disease occurs, patients would be tested with the disposable in the field. A nucleic acid sample would be preserved within the spent disposable which could be sent to a central laboratory facility for further analysis if needed.

  17. Methodology and Applications of Disease Biomarker Identification in Human Serum

    Directory of Open Access Journals (Sweden)

    Ziad J. Sahab

    2007-01-01

    Full Text Available Biomarkers are biomolecules that serve as indicators of biological and pathological processes, or physiological and pharmacological responses to a drug treatment. Because of the high abundance of albumin and heterogeneity of plasma lipoproteins and glycoproteins, biomarkers are difficult to identify in human serum. Due to the clinical significance the identification of disease biomarkers in serum holds great promise for personalized medicine, especially for disease diagnosis and prognosis. This review summarizes some common and emerging proteomics techniques utilized in the separation of serum samples and identification of disease signatures. The practical application of each protein separation or identification technique is analyzed using specific examples. Biomarkers of cancers of prostate, breast, ovary, and lung in human serum have been reviewed, as well as those of heart disease, arthritis, asthma, and cystic fibrosis. Despite the advancement of technology few biomarkers have been approved by the Food and Drug Administration for disease diagnosis and prognosis due to the complexity of structure and function of protein biomarkers and lack of high sensitivity, specificity, and reproducibility for those putative biomarkers. The combination of different types of technologies and statistical analysis may provide more effective methods to identify and validate new disease biomarkers in blood.Abbreviations: 2-DE, two-dimensional gel electrophoresis; 2DLC-MS, two-dimensional liquid chromatography mass spectrometry; CA 15.3, cancer antigen 15.3; CA 19–9, cancer antigen 19–9, a tumor-associated antigen; CA125, cancer antigen 125, a mucin-like protein; CEA, carcinoembryonic antigen; CF, Cystic Fibrosis; CRP, C-reactive protein; ELISA, enzyme-linked immunosorbent assay; ESI-MS/MS, electrospray ionization tandem mass spectrometry; FDA, Food and Drug Administration; IPG, immobilized pH gradient; MALDI-TOF-MS, matrix-assisted laser desorption

  18. Biomarkers of silicosis: Potential candidates

    Directory of Open Access Journals (Sweden)

    Tiwari R

    2005-01-01

    Full Text Available Silica dust is widely prevalent in the atmosphere and more common than the other types of dust, thus making silicosis the most frequently occurring pneumoconiosis. In India also, studies carried out by National Institute of Occupational Health have shown high prevalence of silicosis in small factories and even in nonoccupational exposed subjects. The postero-anterior chest radiographs remain the key tool in diagnosing and assessing the extent and severity of interstitial lung disease. Although Computed Tomography detects finer anatomical structure than radiography it could not get popularity because of its cost. On the basis of histological features of silicosis many potential biomarkers such as Cytokines, Tumor Necrosis Factor, Interleukin 1, Angiotensin Converting Enzyme, Serum Copper, Fas ligand (FasL, etc. have been tried. However, further studies are needed to establish these potential biomarkers as true biomarker of silicosis.

  19. Biomarkers in fibromyalgia: a review

    Directory of Open Access Journals (Sweden)

    Giacomelli C

    2014-02-01

    Full Text Available Camillo Giacomelli,* Francesca Sernissi,* Alessandra Rossi, Stefano Bombardieri, Laura BazzichiRheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy *These authors contributed equally to the manuscript Abstract: Fibromyalgia is a common syndrome diagnosed by clinical criteria. The main symptom of fibromyalgia is pain, but patients frequently also complain about other nonspecific symptoms, such as headache, sleep disturbance, mood disorder, and cognitive impairment. In the light of the multifactorial origin of the disease and of the lack of objective diagnostic findings, several attempts have been made to find a reliable biomarker. For this reason, over the years, a number of patients and various biological samples have been studied, using many different approaches and techniques. Despite this, none of these studies has been able to find the proper biomarker. The aim of this review is to provide a critical overview of the current environment characterizing the search for fibromyalgia biomarkers. Keywords: genetics, proteomics, oxidative stress, fibromyalgia

  20. Bias in Peripheral Depression Biomarkers

    DEFF Research Database (Denmark)

    Carvalho, André F; Köhler, Cristiano A; Brunoni, André R;

    2016-01-01

    BACKGROUND: To aid in the differentiation of individuals with major depressive disorder (MDD) from healthy controls, numerous peripheral biomarkers have been proposed. To date, no comprehensive evaluation of the existence of bias favoring the publication of significant results or inflating effect...... sizes has been conducted. METHODS: Here, we performed a comprehensive review of meta-analyses of peripheral nongenetic biomarkers that could discriminate individuals with MDD from nondepressed controls. PubMed/MEDLINE, EMBASE, and PsycINFO databases were searched through April 10, 2015. RESULTS: From 15......-analyses, while 11 meta-analyses had evidence of small-study effects. CONCLUSIONS: Our findings suggest that there is an excess of studies with statistically significant results in the literature of peripheral biomarkers for MDD. The selective publication of 'positive studies' and the selective reporting...

  1. Biomarkers in inflammatory bowel diseases

    DEFF Research Database (Denmark)

    Bennike, Tue; Birkelund, Svend; Stensballe, Allan;

    2014-01-01

    Unambiguous diagnosis of the two main forms of inflammatory bowel diseases (IBD): Ulcerative colitis (UC) and Crohn's disease (CD), represents a challenge in the early stages of the diseases. The diagnosis may be established several years after the debut of symptoms. Hence, protein biomarkers...... for early and accurate diagnostic could help clinicians improve treatment of the individual patients. Moreover, the biomarkers could aid physicians to predict disease courses and in this way, identify patients in need of intensive treatment. Patients with low risk of disease flares may avoid treatment...... with medications with the concomitant risk of adverse events. In addition, identification of disease and course specific biomarker profiles can be used to identify biological pathways involved in the disease development and treatment. Knowledge of disease mechanisms in general can lead to improved future...

  2. Blood smear

    Science.gov (United States)

    ... osmotic fragility ) Deficiency of an enzyme called lecithin cholesterol acyl transferase Abnormalities of hemoglobin , the protein in ... sickle and Pappenheimer Red blood cells, target cells Formed elements of blood References Bain BJ. The peripheral ...

  3. Colorectal Cancer Biomarkers: Where Are We Now?

    Directory of Open Access Journals (Sweden)

    Maria Gonzalez-Pons

    2015-01-01

    Full Text Available Colorectal cancer is one of the major causes of cancer-related death in the Western world. Patient survival is highly dependent on the tumor stage at the time of diagnosis. Reduced sensitivity to chemotherapy is still a major obstacle in effective treatment of advanced disease. Due to the fact that colorectal cancer is mostly asymptomatic until it progresses to advanced stages, the implementation of screening programs aimed at early detection is essential to reduce incidence and mortality rates. Current screening and diagnostic methods range from semi-invasive procedures such as colonoscopy to noninvasive stool-based tests. The combination of the absence of symptoms, the semi-invasive nature of currently used methods, and the suboptimal accuracy of fecal blood tests results in colorectal cancer diagnosis at advanced stages in a significant number of individuals. Alterations in gene expression leading to colorectal carcinogenesis are reflected in dysregulated levels of nucleic acids and proteins, which can be used for the development of novel, minimally invasive molecular biomarkers. The purpose of this review is to discuss the commercially available colorectal cancer molecular diagnostic methods as well as to highlight some of the new candidate predictive and prognostic molecular markers for tumor, stool, and blood samples.

  4. Biomarker Detection using PS2-Thioaptamers Project

    Data.gov (United States)

    National Aeronautics and Space Administration — AM Biotechnologies (AM) will develop a system to detect and quantify bone demineralization biomarkers as outlined in SBIR Topic "Technologies to Detect Biomarkers"....

  5. Proteomics in Discovery of Hepatocellular Carcinoma Biomarkers

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To discover new proteomic biomarkers of hepatocellular carcinoma. Methods: Surface enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry was used to discover biomarkers for differentiating hepatocellular carcinoma and chronic liver disease. A population of 50 patients with hepatocellular carcinoma and 33 patients with chronic liver disease was studied. Results: Twelve proteomic biomarkers of hepatocellular carcinoma were detected in this study. Three proteomic biomarkers were highly expressed in hepatocellular carcinoma and nine proteomic biomarkers were highly expressed in chronic liver disease. The most valuable proteomic biomarker with m/z=11498 had no similar diagnostic value as α-fetoprotein. Conclusion:Some of the twelve proteomic biomarkers may become new biomarkers of hepatocellular carcinoma.

  6. Loop mediated isothermal amplification: An innovative gene amplification technique for animal diseases.

    Science.gov (United States)

    Sahoo, Pravas Ranjan; Sethy, Kamadev; Mohapatra, Swagat; Panda, Debasis

    2016-05-01

    India being a developing country mainly depends on livestock sector for its economy. However, nowadays, there is emergence and reemergence of more transboundary animal diseases. The existing diagnostic techniques are not so quick and with less specificity. To reduce the economy loss, there should be a development of rapid, reliable, robust diagnostic technique, which can work with high degree of sensitivity and specificity. Loop mediated isothermal amplification assay is a rapid gene amplification technique that amplifies nucleic acid under an isothermal condition with a set of designed primers spanning eight distinct sequences of the target. This assay can be used as an emerging powerful, innovative gene amplification diagnostic tool against various pathogens of livestock diseases. This review is to highlight the basic concept and methodology of this assay in livestock disease. PMID:27284221

  7. Ultrasensitive detection of microRNA through rolling circle amplification on a DNA tetrahedron decorated electrode.

    Science.gov (United States)

    Miao, Peng; Wang, Bidou; Meng, Fanyu; Yin, Jian; Tang, Yuguo

    2015-03-18

    MicroRNAs are a class of evolutionally conserved, small noncoding RNAs involved in the regulation of gene expression and affect a variety of biological processes including cellular differentiation, immunological response, tumor development, and so on. Recently, microRNAs have been identified as promising disease biomarkers. In this work, we have fabricated a novel electrochemical method for ultrasensitive detection of microRNA. Generally, a DNA tetrahedron decorated gold electrode is employed as the recognition interface. Then, hybridizations between DNA tetrahedron, microRNA, and primer probe initiate rolling circle amplification (RCA) on the electrode surface. Silver nanoparticles attached to the RCA products provide significant electrochemical signals and a limit of detection as low as 50 aM is achieved. Moreover, homology microRNA family members with only one or two mismatches can be successfully distinguished. Therefore, this proposed method reveals great advancements toward improved disease diagnosis and prognosis.

  8. Personalized medicine using DNA biomarkers: a review

    OpenAIRE

    Ziegler, Andreas; Koch, Armin; Krockenberger, Katja; Großhennig, Anika

    2012-01-01

    Biomarkers are of increasing importance for personalized medicine, with applications including diagnosis, prognosis, and selection of targeted therapies. Their use is extremely diverse, ranging from pharmacodynamics to treatment monitoring. Following a concise review of terminology, we provide examples and current applications of three broad categories of biomarkers—DNA biomarkers, DNA tumor biomarkers, and other general biomarkers. We outline clinical trial phases for identifying and validat...

  9. Stability and Reliability of Plasma Level of Lipid Biomarkers and Their Correlation with Dietary Fat Intake

    Directory of Open Access Journals (Sweden)

    Sang-Ah Lee

    2008-01-01

    Full Text Available The reliability and stability of plasma lipid biomarkers and their association with dietary fat intake were evaluated among 48 subjects who were randomly chosen from the participants of a validation study of the population-based cohort, the Shanghai Men's Health Study (SMHS. Four spot blood samples, one taken each season, were measured for total cholesterol, triglyceride, HDL-cholesterol, and LDL-cholesterol levels. The reliability and stability of these measurements were assessed by intraclass correlation coefficients (ICC and by the correlations between a randomly chosen measurement with the mean of measurements across seasons using a bootstrap approach. The median levels for total cholesterol, triglycerides, HDL-cholesterol, and LDL-cholesterol were 177.5, 164.5, 41.0, and 102.5 (mg/dl, respectively. The ICCs of the biomarkers ranged from 0.58 (LDL-cholesterol to 0.83 (HDL-cholesterol. The correlation between randomly chosen spot measurements and the mean measurement were 0.91, 0.86, 0.93, and 0.83 for total cholesterol, triglycerides, HDL-cholesterol, and LDL-cholesterol, respectively. The correlations of lipid biomarkers with dietary fat intake and other lifestyle factors were comparable to other previous reports. In conclusion, this study suggests that measurements of lipid biomarkers from a single spot blood sample are a good representation of the average blood levels of these biomarkers in the study population and could be a useful tool for epidemiological studies.

  10. Comprehensive Phenotyping in Multiple Sclerosis: Discovery Based Proteomics and the Current Understanding of Putative Biomarkers

    Directory of Open Access Journals (Sweden)

    Kevin C. O’Connor

    2006-01-01

    Full Text Available Currently, there is no single test for multiple sclerosis (MS. Diagnosis is confirmed through clinical evaluation, abnormalities revealed by magnetic resonance imaging (MRI, and analysis of cerebrospinal fluid (CSF chemistry. The early and accurate diagnosis of the disease, monitoring of progression, and gauging of therapeutic intervention are important but elusive elements of patient care. Moreover, a deeper understanding of the disease pathology is needed, including discovery of accurate biomarkers for MS. Herein we review putative biomarkers of MS relating to neurodegeneration and contributions to neuropathology, with particular focus on autoimmunity. In addition, novel assessments of biomarkers not driven by hypotheses are discussed, featuring our application of advanced proteomics and metabolomics for comprehensive phenotyping of CSF and blood. This strategy allows comparison of component expression levels in CSF and serum between MS and control groups. Examination of these preliminary data suggests that several CSF proteins in MS are differentially expressed, and thus, represent putative biomarkers deserving of further evaluation.

  11. [Iron deficiency in elderly patients: use of biomarkers].

    Science.gov (United States)

    Le Petitcorps, Hélène; Monti, Alexandra; Pautas, Éric

    2015-01-01

    Iron deficiency, due to blood loss or malabsorption, is commonly observed in geriatric practice. In elderly people, association of inflammatory diseases to iron loss makes diagnosis of absolute iron deficiency sometimes difficult. In case of inflammation, the interpretation of usual biomarkers of iron deficiency (serum ferritin, transferrin saturation, serum iron) may be difficult. The recent discovery of the role of hepcidine in the iron homeostasis, in physiological and pathological situation, contributes to better understanding of the iron regulation. The aim of this short paper is to underline some specificities of elderly iron physiology, to explain hepcidine's role in physiological and pathological situations and to propose a diagnostic approach for a better interpretation of usual biomarkers, in order to differentiate absolute iron deficiency and functional iron deficiency.

  12. Role of proteomics in the discovery of autism biomarkers

    International Nuclear Information System (INIS)

    The epidemiology of autism is continuously increasing all over the world with social, behavioural and economical burdens. Autism is considered as a multi-factorial disorder, influenced by genetic, neurological, environmental and immunological aspects. Autism is still believed to be incurable disorder with little information about the role of proteins patterns in the diagnosis of the disease. Knowing the applications of proteomic tools, it is possible to identify quantitative and qualitative protein patterns in a wide variety of tissues and body fluids such as blood, urine, saliva and cerebrospinal fluid in order to establish specific diagnostic and prognostic biomarkers. The aim of this review is to provide an overview of the various protocols available for proteomics by using mass spectrometry analysis, discuss reports in which these techniques have been previously applied in biomarker discovery for the diagnosis of autism, and consider the future development of this area of research. (author)

  13. Biomarkers in sarcoidosis: a review

    Directory of Open Access Journals (Sweden)

    Ahmadzai H

    2014-08-01

    Full Text Available Hasib Ahmadzai,1,2 Wei Sheng Joshua Loke,1 Shuying Huang,1 Cristan Herbert,1 Denis Wakefield,3 Paul S Thomas2 1Inflammation and Infection Research Centre (IIRC, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia; 2Department of Respiratory Medicine, Prince of Wales Hospital, Randwick, Sydney, NSW, Australia; 3Immunology of the Eye Clinic, St Vincent's Clinic, Darlinghurst, Sydney, NSW, Australia Abstract: Sarcoidosis is a systemic granulomatous disease of undetermined etiology invariably affecting the lungs and thoracic lymph nodes. It has been termed an “immune paradox”, as there is peripheral anergy despite exaggerated inflammation at disease sites. The disease is usually self-limiting, although some individuals experience unremitting inflammation that may progress into pulmonary fibrosis and death. The inflammatory process is largely a T helper-1-driven immune response. Given its heterogeneous clinical manifestations, diagnosis is usually a clinical conundrum. Clinical and radiological findings alone are often inadequate to confirm the diagnosis. At present, sarcoidosis is usually a diagnosis of exclusion, confirmed by histological evidence of noncaseating granulomas in the absence of known granulomagenic agents. This has compelled researchers to look for disease-specific biomarkers that can help diagnose sarcoidosis and delineate its disease course, severity, and prognosis. In this review we highlight various investigations used to diagnose sarcoidosis, outline proposed biomarkers, and discuss novel methods of sampling biomarkers. Keywords: sarcoidosis, biomarkers, inflammatory markers, exhaled breath condensate, proteomics, granuloma

  14. Biomarkers of satiation and satiety

    NARCIS (Netherlands)

    Graaf, C. de; Blom, W.A.M.; Smeets, P.A.M.; Stafleu, A.; Hendriks, H.F.J.

    2004-01-01

    This review's objective is to give a critical summary of studies that focused on physiologic measures relating to subjectively rated appetite, actual food intake, or both. Biomarkers of satiation and satiety may be used as a tool for assessing the satiating efficiency of foods and for understanding

  15. Biomarkers of replicative senescence revisited

    DEFF Research Database (Denmark)

    Nehlin, Jan

    2016-01-01

    of telomere length and associated damage, and the accompanying changes that take place elicit signals that have an impact on a number of molecules and downstream events. Precise measurements of replicative senescence biomarkers in biological samples from individuals could be clinically associated...

  16. Human telomerase RNA component (hTERC gene amplification detected by FISH in precancerous lesions and carcinoma of the larynx

    Directory of Open Access Journals (Sweden)

    Liu Yu

    2012-03-01

    Full Text Available Abstract Background Gain of 3q26 is frequently observed in squamous cell carcinomas of mucosal origin, including those originating in the head and neck region. The human telomerase RNA component (hTERC gene, which is located on chromosome 3q26, encodes for an RNA subunit of telomerase that maintains the length of telomeres through cellular divisions, and is activated in malignant diseases. The present study was designed to detect hTERC amplification in laryngeal lesions and evaluate whether this might serve as a supportive biomarker in histopathological analysis for in the diagnosis of laryngeal lesions. Methods Fluorescent in situ hybridization (FISH was applied on formalin-fixed paraffin-embedded blocks of 93 laryngeal specimens, including 14 normal epithelium (NE, 15 mild dysplasia (Md, 18 moderate dysplasia (MD, 16 severe dysplasia (SD, 9 carcinoma in situ (CIS, and 21 invasive carcinoma (IC. Results By histopathologic examination, hTERC amplification rates in NE, Md, MD, SD, CIS and IC cases were 0% (0/14, 13.33% (2/15, 72.22% (13/18, 81.25% (13/16, 100% (9/9 and 100% (21/21, respectively. Amplification of hTERC was significantly associated with histopathologic diagnosis (P Conclusions The hTERC amplification is important in the development of laryngeal squamous cell carcinoma (LSCC. FISH detection of hTERC amplification may provide an effective approach in conjunction with histopathologic evaluation for differential diagnosis of laryngeal lesions. Virtual Slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2226606266791985

  17. Cord Blood

    Directory of Open Access Journals (Sweden)

    Saeed Abroun

    2014-05-01

    Full Text Available   Stem cells are naïve or master cells. This means they can transform into special 200 cell types as needed by body, and each of these cells has just one function. Stem cells are found in many parts of the human body, although some sources have richer concentrations than others. Some excellent sources of stem cells, such as bone marrow, peripheral blood, cord blood, other tissue stem cells and human embryos, which last one are controversial and their use can be illegal in some countries. Cord blood is a sample of blood taken from a newborn baby's umbilical cord. It is a rich source of stem cells, umbilical cord blood and tissue are collected from material that normally has no use following a child’s birth. Umbilical cord blood and tissue cells are rich sources of stem cells, which have been used in the treatment of over 80 diseases including leukemia, lymphoma and anemia as bone marrow stem cell potency.  The most common disease category has been leukemia. The next largest group is inherited diseases. Patients with lymphoma, myelodysplasia and severe aplastic anemia have also been successfully transplanted with cord blood. Cord blood is obtained by syringing out the placenta through the umbilical cord at the time of childbirth, after the cord has been detached from the newborn. Collecting stem cells from umbilical blood and tissue is ethical, pain-free, safe and simple. When they are needed to treat your child later in life, there will be no rejection or incompatibility issues, as the procedure will be using their own cells. In contrast, stem cells from donors do have these potential problems. By consider about cord blood potency, cord blood banks (familial or public were established. In IRAN, four cord blood banks has activity, Shariati BMT center cord blood bank, Royan familial cord blood banks, Royan public cord blood banks and Iranian Blood Transfusion Organ cord blood banks. Despite 50,000 sample which storage in these banks, but the

  18. Biomarkers and childhood asthma: improving control today and tomorrow.

    Science.gov (United States)

    Liu, Andrew H

    2005-01-01

    Although we aim to normalize the lives of children with asthma by controlling their day and night symptoms and preventing exacerbations and morbidity, optimal childhood asthma management may result when the assessment and monitoring of asthma includes measured biomarkers--meaning objective, biological measures of lung dysfunction and inflammation. Precedence for such an approach to optimizing disease control and outcomes can be appreciated in comparing asthma with insulin-dependent diabetes mellitus (IDDM) management in children. Optimal management of these chronic conditions shares the fundamental goals to eliminate day and night symptoms and prevent exacerbations and morbidity. However, IDDM management focuses primarily on peripheral blood biomarkers of tight control (i.e., daily serum glucose levels) and predictors of long-term morbidity (i.e., hemoglobin A1C, or hemoglobin "remodeling" due to chronically poor control of glucose) for optimal assessment and monitoring and to best achieve these clinical objectives (Alemzadeh R, et al. Diabetes mellitus in children. In Nelson Textbook of Pediatrics, 17th ed. Behrman RE, Kliegman RM, and Jenson HB (Eds). Philadelphia: W.B. Saunders Co., 1947-1972, 2004). The improved outcomes in IDDM have resulted primarily from the progress to a biomarker-based assessment to achieve tight, optimal control and not, presently, as a dramatic change in therapy. The progress in IDDM management provides a compelling paradigm to consider for improving childhood asthma management. Indeed, the time is good to not only consider some newly available biomarkers, but also to reconsider some biomarkers of lung dysfunction, inflammation, and atopy that could be broadly used today. This article reconsiders the use of current and emerging measures of lung dysfunction, inflammation, and atopy in assessing tight control and long-term risk. Concluding emphasis will be placed on what can be implemented today.

  19. Perspectives for multimodal neurochemical and imaging biomarkers in Alzheimer's disease.

    Science.gov (United States)

    Teipel, Stefan J; Sabri, Osama; Grothe, Michel; Barthel, Henryk; Prvulovic, David; Buerger, Katharina; Bokde, Arun L W; Ewers, Michael; Hoffmann, Wolfgang; Hampel, Harald

    2013-01-01

    The diagnosis of Alzheimer's disease (AD) is presently going through a paradigm shift from disease categories to dimensions and toward the implementation of biomarkers to support identification of predementia and even preclinical asymptomatic stages of the disease. We outline the methodological basis of presently available biomarkers and technological methodologies in AD, including exploratory and hypothesis-based plasma and blood candidates, cerebrospinal fluid markers of amyloid load and axonal destruction, and imaging markers of amyloid deposition, synaptic dysfunction, cortical functional and structural disconnection, and regional atrophy. We integrate biomarker findings into a comprehensive model of AD pathogenesis from healthy aging to cognitive decline, the resilience to cerebral amyloid load (RECAL) matrix. The RECAL framework integrates factors of risk and resilience to cerebral amyloid load for individual risk prediction. We show the clinical consequences when the RECAL matrix is operationalized into a diagnostic algorithm both for individual counseling of subjects and for the identification of at risk samples for primary and secondary preventive trials. We discuss the implication of biomarkers for the identification of prodromal AD for the primary care system that seems presently not even prepared to cope with the increasing number of subjects afflicted with late stage AD dementia, let alone future cohorts of subjects searching counseling or treatment of predementia and asymptomatic stages of AD. The paradigm shift in AD diagnosis and its operationalization into a diagnostic framework will have major implications for our understanding of disease pathogenesis. Now, for the first time, we have access to in vivo markers of key events in AD pathogenesis integrated into a heuristic framework that makes strong predictions on pattern of multimodal biomarkers in different stages of AD. Critical testing of these predictions will help us to modify or even falsify

  20. Clinical utility of asthma biomarkers: from bench to bedside

    Directory of Open Access Journals (Sweden)

    Vijverberg SJH

    2013-08-01

    Full Text Available Susanne JH Vijverberg,1,2,* Bart Hilvering,2,* Jan AM Raaijmakers,1 Jan-Willem J Lammers,2 Anke-Hilse Maitland-van der Zee,1,* Leo Koenderman2,* 1Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands; 2Department of Respiratory Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands *These authors contributed equally to this work Abstract: Asthma is a chronic disease characterized by airway inflammation, bronchial hyperresponsiveness, and recurrent episodes of reversible airway obstruction. The disease is very heterogeneous in onset, course, and response to treatment, and seems to encompass a broad collection of heterogeneous disease subtypes with different underlying pathophysiological mechanisms. There is a strong need for easily interpreted clinical biomarkers to assess the nature and severity of the disease. Currently available biomarkers for clinical practice – for example markers in bronchial lavage, bronchial biopsies, sputum, or fraction of exhaled nitric oxide (FeNO – are limited due to invasiveness or lack of specificity. The assessment of markers in peripheral blood might be a good alternative to study airway inflammation more specifically, compared to FeNO, and in a less invasive manner, compared to bronchoalveolar lavage, biopsies, or sputum induction. In addition, promising novel biomarkers are discovered in the field of breath metabolomics (eg, volatile organic compounds and (pharmacogenomics. Biomarker research in asthma is increasingly shifting from the assessment of the value of single biomarkers to multidimensional approaches in which the clinical value of a combination of various markers is studied. This could eventually lead to the development of a clinically applicable algorithm composed of various markers and clinical features to phenotype asthma and improve diagnosis and asthma management

  1. Hair Manganese as an Exposure Biomarker among Welders.

    Science.gov (United States)

    Reiss, Boris; Simpson, Christopher D; Baker, Marissa G; Stover, Bert; Sheppard, Lianne; Seixas, Noah S

    2016-03-01

    Quantifying exposure and dose to manganese (Mn) containing airborne particles in welding fume presents many challenges. Common biological markers such as Mn in blood or Mn in urine have not proven to be practical biomarkers even in studies where positive associations were observed. However, hair Mn (MnH) as a biomarker has the advantage over blood and urine that it is less influenced by short-term variability of Mn exposure levels because of its slow growth rate. The objective of this study was to determine whether hair can be used as a biomarker for welders exposed to manganese. Hair samples (1cm) were collected from 47 welding school students and individual air Mn (MnA) exposures were measured for each subject. MnA levels for all days were estimated with a linear mixed model using welding type as a predictor. A 30-day time-weighted average MnA (MnA30d) exposure level was calculated for each hair sample. The association between MnH and MnA30d levels was then assessed. A linear relationship was observed between log-transformed MnA30d and log-transformed MnH. Doubling MnA30d exposure levels yields a 20% (95% confidence interval: 11-29%) increase in MnH. The association was similar for hair washed following two different wash procedures designed to remove external contamination. Hair shows promise as a biomarker for inhaled Mn exposure given the presence of a significant linear association between MnH and MnA30d levels.

  2. Arterial pulse pressure amplification described by means of a nonlinear wave model: characterization of human aging

    Science.gov (United States)

    Alfonso, M.; Cymberknop, L.; Armentano, R.; Pessana, F.; Wray, S.; Legnani, W.

    2016-04-01

    The representation of blood pressure pulse as a combination of solitons captures many of the phenomena observed during its propagation along the systemic circulation. The aim of this work is to analyze the applicability of a compartmental model for propagation regarding the pressure pulse amplification associated with arterial aging. The model was applied to blood pressure waveforms that were synthesized using solitons, and then validated by waveforms obtained from individuals from differentiated age groups. Morphological changes were verified in the blood pressure waveform as a consequence of the aging process (i.e. due to the increase in arterial stiffness). These changes are the result of both a nonlinear interaction and the phenomena present in the propagation of nonlinear mechanic waves.

  3. Core-shell hydrogel particles harvest, concentrate and preserve labile low abundance biomarkers.

    Directory of Open Access Journals (Sweden)

    Caterina Longo

    Full Text Available BACKGROUND: The blood proteome is thought to represent a rich source of biomarkers for early stage disease detection. Nevertheless, three major challenges have hindered biomarker discovery: a candidate biomarkers exist at extremely low concentrations in blood; b high abundance resident proteins such as albumin mask the rare biomarkers; c biomarkers are rapidly degraded by endogenous and exogenous proteinases. METHODOLOGY AND PRINCIPAL FINDINGS: Hydrogel nanoparticles created with a N-isopropylacrylamide based core (365 nm-shell (167 nm and functionalized with a charged based bait (acrylic acid were studied as a technology for addressing all these biomarker discovery problems, in one step, in solution. These harvesting core-shell nanoparticles are designed to simultaneously conduct size exclusion and affinity chromatography in solution. Platelet derived growth factor (PDGF, a clinically relevant, highly labile, and very low abundance biomarker, was chosen as a model. PDGF, spiked in human serum, was completely sequestered from its carrier protein albumin, concentrated, and fully preserved, within minutes by the particles. Particle sequestered PDGF was fully protected from exogenously added tryptic degradation. When the nanoparticles were added to a 1 mL dilute solution of PDGF at non detectable levels (less than 20 picograms per mL the concentration of the PDGF released from the polymeric matrix of the particles increased within the detection range of ELISA and mass spectrometry. Beyond PDGF, the sequestration and protection from degradation for a series of additional very low abundance and very labile cytokines were verified. CONCLUSIONS AND SIGNIFICANCE: We envision the application of harvesting core-shell nanoparticles to whole blood for concentration and immediate preservation of low abundance and labile analytes at the time of venipuncture.

  4. The sensitivity of real-time PCR amplification targeting invasive Salmonella serovars in biological specimens

    Directory of Open Access Journals (Sweden)

    Chau Tran

    2010-05-01

    Full Text Available Abstract Background PCR amplification for the detection of pathogens in biological material is generally considered a rapid and informative diagnostic technique. Invasive Salmonella serovars, which cause enteric fever, can be commonly cultured from the blood of infected patients. Yet, the isolation of invasive Salmonella serovars from blood is protracted and potentially insensitive. Methods We developed and optimised a novel multiplex three colour real-time PCR assay to detect specific target sequences in the genomes of Salmonella serovars Typhi and Paratyphi A. We performed the assay on DNA extracted from blood and bone marrow samples from culture positive and negative enteric fever patients. Results The assay was validated and demonstrated a high level of specificity and reproducibility under experimental conditions. All bone marrow samples tested positive for Salmonella, however, the sensitivity on blood samples was limited. The assay demonstrated an overall specificity of 100% (75/75 and sensitivity of 53.9% (69/128 on all biological samples. We then tested the PCR detection limit by performing bacterial counts after inoculation into blood culture bottles. Conclusions Our findings corroborate previous clinical findings, whereby the bacterial load of S. Typhi in peripheral blood is low, often below detection by culture and, consequently, below detection by PCR. Whilst the assay may be utilised for environmental sampling or on differing biological samples, our data suggest that PCR performed directly on blood samples may be an unsuitable methodology and a potentially unachievable target for the routine diagnosis of enteric fever.

  5. Annexin A9 (ANXA9) biomarker and therapeutic target in epithelial cancer

    Science.gov (United States)

    Hu, Zhi; Kuo, Wen-Lin; Neve, Richard M.; Gray, Joe W.

    2012-06-12

    Amplification of the ANXA9 gene in human chromosomal region 1q21 in epithelial cancers indicates a likelihood of both in vivo drug resistance and metastasis, and serves as a biomarker indicating these aspects of the disease. ANXA9 can also serve as a therapeutic target. Interfering RNAs (iRNAs) (such as siRNA and miRNA) and shRNA adapted to inhibit ANXA9 expression, when formulated in a therapeutic composition, and delivered to cells of the tumor, function to treat the epithelial cancer.

  6. Multicollinearity may lead to artificial interaction: an example from a cross sectional study of biomarkers.

    Science.gov (United States)

    Sithisarankul, P; Weaver, V M; Diener-West, M; Strickland, P T

    1997-06-01

    Collinearity is the situation which arises in multiple regression when some or all of the explanatory variables are so highly correlated with one another that it becomes very difficult, if not impossible, to disentangle their influences and obtain a reasonably precise estimate of their effects. Suppressor variable is one of the extreme situations of collinearity that one variable can substantially increase the multiple correlation when combined with a variable that is only modestly correlated with the response variable. In this study, we describe the process by which we disentangled and discovered multicollinearity and its consequences, namely artificial interaction, using the data from cross-sectional quantification of several biomarkers. We showed how the collinearity between one biomarker (blood lead level) and another (urinary trans, trans-muconic acid) and their interaction (blood lead level* urinary trans, trans-muconic acid) can lead to the observed artificial interaction on the third biomarker (urinary 5-aminolevulinic acid).

  7. Parametric Amplification of Gravitational Fluctuations during Reheating

    International Nuclear Information System (INIS)

    Cosmological perturbations can undergo amplification by parametric resonance during preheating even on scales larger than the Hubble radius, without violating causality. A unified description of gravitational and matter fluctuations is crucial to determine the strength of the instability. To extract specific signatures of the oscillating inflaton field during reheating, it is essential to focus on a variable describing metric fluctuations which is constant in the standard analyses of inflation. For a massive inflaton without self-coupling, we find no additional growth of superhorizon modes during reheating beyond the usual predictions. For a massless self-coupled inflaton, there is a sub-Hubble scale resonance. copyright 1999 The American Physical Society

  8. Amplification Effects and Unconventional Monetary Policies

    Directory of Open Access Journals (Sweden)

    Cécile BASTIDON GILLES

    2012-02-01

    Full Text Available Global financial crises trigger off amplification effects, which allow relatively small shocks to propagate through the whole financial system. For this reason, the range of Central banks policies is now widening beyond conventional monetary policies and lending of last resort. The aim of this paper is to establish a rule for this practice. The model is based on the formalization of funding conditions in various types of markets. We conduct a comprehensive analysis of the “unconventional monetary policies”, and especially quantify government bonds purchases by the Central bank.

  9. Optimization of laser capture microdissection and RNA amplification for gene expression profiling of prostate cancer

    Directory of Open Access Journals (Sweden)

    Vasmatzis George

    2007-03-01

    Full Text Available Abstract Background To discover prostate cancer biomarkers, we profiled gene expression in benign and malignant cells laser capture microdissected (LCM from prostate tissues and metastatic prostatic adenocarcinomas. Here we present methods developed, optimized, and validated to obtain high quality gene expression data. Results RNase inhibitor was included in solutions used to stain frozen tissue sections for LCM, which improved RNA quality significantly. Quantitative PCR assays, requiring minimal amounts of LCM RNA, were developed to determine RNA quality and concentration. SuperScript II™ reverse transcriptase was replaced with SuperScript III™, and SpeedVac concentration was eliminated to optimize linear amplification. The GeneChip® IVT labeling kit was used rather than the Enzo BioArray™ HighYield™ RNA transcript labeling kit since side-by-side comparisons indicated high-end signal saturation with the latter. We obtained 72 μg of labeled complementary RNA on average after linear amplification of about 2 ng of total RNA. Conclusion Unsupervised clustering placed 5/5 normal and 2/2 benign prostatic hyperplasia cases in one group, 5/7 Gleason pattern 3 cases in another group, and the remaining 2/7 pattern 3 cases in a third group with 8/8 Gleason pattern 5 cases and 3/3 metastatic prostatic adenocarcinomas. Differential expression of alpha-methylacyl coenzyme A racemase (AMACR and hepsin was confirmed using quantitative PCR.

  10. A simple isothermal DNA amplification method to screen black flies for Onchocerca volvulus infection.

    Science.gov (United States)

    Alhassan, Andy; Makepeace, Benjamin L; LaCourse, Elwyn James; Osei-Atweneboana, Mike Y; Carlow, Clotilde K S

    2014-01-01

    Onchocerciasis is a debilitating neglected tropical disease caused by infection with the filarial parasite Onchocerca volvulus. Adult worms live in subcutaneous tissues and produce large numbers of microfilariae that migrate to the skin and eyes. The disease is spread by black flies of the genus Simulium following ingestion of microfilariae that develop into infective stage larvae in the insect. Currently, transmission is monitored by capture and dissection of black flies and microscopic examination of parasites, or using the polymerase chain reaction to determine the presence of parasite DNA in pools of black flies. In this study we identified a new DNA biomarker, encoding O. volvulus glutathione S-transferase 1a (OvGST1a), to detect O. volvulus infection in vector black flies. We developed an OvGST1a-based loop-mediated isothermal amplification (LAMP) assay where amplification of specific target DNA is detectable using turbidity or by a hydroxy naphthol blue color change. The results indicated that the assay is sensitive and rapid, capable of detecting DNA equivalent to less than one microfilaria within 60 minutes. The test is highly specific for the human parasite, as no cross-reaction was detected using DNA from the closely related and sympatric cattle parasite Onchocerca ochengi. The test has the potential to be developed further as a field tool for use in the surveillance of transmission before and after implementation of mass drug administration programs for onchocerciasis.

  11. A simple isothermal DNA amplification method to screen black flies for Onchocerca volvulus infection.

    Directory of Open Access Journals (Sweden)

    Andy Alhassan

    Full Text Available Onchocerciasis is a debilitating neglected tropical disease caused by infection with the filarial parasite Onchocerca volvulus. Adult worms live in subcutaneous tissues and produce large numbers of microfilariae that migrate to the skin and eyes. The disease is spread by black flies of the genus Simulium following ingestion of microfilariae that develop into infective stage larvae in the insect. Currently, transmission is monitored by capture and dissection of black flies and microscopic examination of parasites, or using the polymerase chain reaction to determine the presence of parasite DNA in pools of black flies. In this study we identified a new DNA biomarker, encoding O. volvulus glutathione S-transferase 1a (OvGST1a, to detect O. volvulus infection in vector black flies. We developed an OvGST1a-based loop-mediated isothermal amplification (LAMP assay where amplification of specific target DNA is detectable using turbidity or by a hydroxy naphthol blue color change. The results indicated that the assay is sensitive and rapid, capable of detecting DNA equivalent to less than one microfilaria within 60 minutes. The test is highly specific for the human parasite, as no cross-reaction was detected using DNA from the closely related and sympatric cattle parasite Onchocerca ochengi. The test has the potential to be developed further as a field tool for use in the surveillance of transmission before and after implementation of mass drug administration programs for onchocerciasis.

  12. A simple isothermal DNA amplification method to screen black flies for Onchocerca volvulus infection.

    Science.gov (United States)

    Alhassan, Andy; Makepeace, Benjamin L; LaCourse, Elwyn James; Osei-Atweneboana, Mike Y; Carlow, Clotilde K S

    2014-01-01

    Onchocerciasis is a debilitating neglected tropical disease caused by infection with the filarial parasite Onchocerca volvulus. Adult worms live in subcutaneous tissues and produce large numbers of microfilariae that migrate to the skin and eyes. The disease is spread by black flies of the genus Simulium following ingestion of microfilariae that develop into infective stage larvae in the insect. Currently, transmission is monitored by capture and dissection of black flies and microscopic examination of parasites, or using the polymerase chain reaction to determine the presence of parasite DNA in pools of black flies. In this study we identified a new DNA biomarker, encoding O. volvulus glutathione S-transferase 1a (OvGST1a), to detect O. volvulus infection in vector black flies. We developed an OvGST1a-based loop-mediated isothermal amplification (LAMP) assay where amplification of specific target DNA is detectable using turbidity or by a hydroxy naphthol blue color change. The results indicated that the assay is sensitive and rapid, capable of detecting DNA equivalent to less than one microfilaria within 60 minutes. The test is highly specific for the human parasite, as no cross-reaction was detected using DNA from the closely related and sympatric cattle parasite Onchocerca ochengi. The test has the potential to be developed further as a field tool for use in the surveillance of transmission before and after implementation of mass drug administration programs for onchocerciasis. PMID:25299656

  13. Gold nanoparticle-based lateral flow biosensor for rapid visual detection of Leishmania-specific DNA amplification products.

    Science.gov (United States)

    Toubanaki, Dimitra K; Athanasiou, Evita; Karagouni, Evdokia

    2016-08-01

    Leishmaniasis is a disease, caused by Leishmania parasites, which infect humans and animals, posing a major social and economic burden worldwide. The need for accurate and sensitive disease diagnosis led to the widespread adoption of PCR amplification. Detection of the amplification products (i.e. gel electrophoresis) require time-consuming protocols performed by trained personnel, with high cost. Aim of the present study was the simplification of PCR product detection, using a nucleic acid lateral flow, combined with functionalized gold nanoparticles. Amplification reactions targeting kinetoplastid DNA of Leishmania spp were performed on canine blood samples and a positive signal was formed as a red test zone. The visual detection was completed in 20min. Extensive optimization enabled the detection of 100fmol of target DNA. Clinical samples of infected dog blood were analyzed with high specificity. Overall, the proposed lateral flow biosensor can be considered an appealing alternative platform for Leishmania-specific amplification products detection with low cost and attractive simplicity. PMID:27255490

  14. Quantitative Perfusion and Permeability Biomarkers in Brain Cancer from Tomographic CT and MR Images

    OpenAIRE

    Eilaghi, Armin; Yeung, Timothy; d’Esterre, Christopher; Bauman, Glenn; Yartsev, Slav; Easaw, Jay; Fainardi, Enrico; Lee, Ting-Yim; Frayne, Richard

    2016-01-01

    Dynamic contrast-enhanced perfusion and permeability imaging, using computed tomography and magnetic resonance systems, are important techniques for assessing the vascular supply and hemodynamics of healthy brain parenchyma and tumors. These techniques can measure blood flow, blood volume, and blood–brain barrier permeability surface area product and, thus, may provide information complementary to clinical and pathological assessments. These have been used as biomarkers to enhance the treatme...

  15. Amplification of fluorescence using collinear picosecond optical parametric amplification at degeneracy

    Institute of Scientific and Technical Information of China (English)

    Zhang Jing; Zhang Qiu-Lin; Jiang Man; Zhang Dong-Xiang; Feng Bao-Hua; Zhang Jing-Yuan

    2012-01-01

    We demonstrate the output characteristic of broadband parametric amplification of incoherent light pulses in a 355-nm pumped degenerate picosecond optical parametric amplification with either saturated or unsaturated amplification.The optical parametric amplifier is seeded by the fluorescence generated in a solution of pyridine-1 dye in ethanol.With the saturated amplification,we can obtain high energy incoherent light pulses,whose full widtth at half maximum bandwidth varies from 16 nm to 53 nm for the different phase matching angles near degeneracy.Moreover,the unsaturated bandwidth of the amplified pulses fits well to the calculated result at degeneracy.Selecting s-polarized fluorescence with a Glan-Taylor prism,the maximum bandwidth of the amplified fluorescence is found to be 59 nm for a purely s-polarized seed.The maximum output energy is 0.67 mJ for the optical parametric amplifier.By using an optical filter and compressor,the generated high energy incoherent light has great potential as the incoherent pump,signal or idler wave of a parametric down-conversion process,so that a wave with a high degree of coherence can be generated from an incoherent pump light.

  16. Amplification and thrifty single-molecule sequencing of recurrent somatic structural variations.

    Science.gov (United States)

    Patel, Anand; Schwab, Richard; Liu, Yu-Tsueng; Bafna, Vineet

    2014-02-01

    Deletion of tumor-suppressor genes as well as other genomic rearrangements pervade cancer genomes across numerous types of solid tumor and hematologic malignancies. However, even for a specific rearrangement, the breakpoints may vary between individuals, such as the recurrent CDKN2A deletion. Characterizing the exact breakpoints for structural variants (SVs) is useful for designating patient-specific tumor biomarkers. We propose AmBre (Amplification of Breakpoints), a method to target SV breakpoints occurring in samples composed of heterogeneous tumor and germline DNA. Additionally, AmBre validates SVs called by whole-exome/genome sequencing and hybridization arrays. AmBre involves a PCR-based approach to amplify the DNA segment containing an SV's breakpoint and then confirms breakpoints using sequencing by Pacific Biosciences RS. To amplify breakpoints with PCR, primers tiling specified target regions are carefully selected with a simulated annealing algorithm to minimize off-target amplification and maximize efficiency at capturing all possible breakpoints within the target regions. To confirm correct amplification and obtain breakpoints, PCR amplicons are combined without barcoding and simultaneously long-read sequenced using a single SMRT cell. Our algorithm efficiently separates reads based on breakpoints. Each read group supporting the same breakpoint corresponds with an amplicon and a consensus amplicon sequence is called. AmBre was used to discover CDKN2A deletion breakpoints in cancer cell lines: A549, CEM, Detroit562, MOLT4, MCF7, and T98G. Also, we successfully assayed RUNX1-RUNX1T1 reciprocal translocations by finding both breakpoints in the Kasumi-1 cell line. AmBre successfully targets SVs where DNA harboring the breakpoints are present in 1:1000 mixtures.

  17. Multiplex allele-specific target amplification based on PCR suppression

    OpenAIRE

    Broude, Natalia E.; Zhang, Lingang; Woodward, Karen; Englert, David; Cantor, Charles R.

    2001-01-01

    We have developed a strategy for multiplex PCR based on PCR suppression. PCR suppression allows DNA target amplification with only one sequence-specific primer per target and a second primer that is common for all targets. Therefore, an n-plex PCR would require only n + 1 primers. We have demonstrated uniform, efficient amplification of targeted sequences in 14-plex PCR. The high specificity of suppression PCR also provides multiplexed amplification with allele specifi...

  18. Loss of KLF14 triggers centrosome amplification and tumorigenesis

    OpenAIRE

    Fan, Guangjian; Sun, Lianhui; Shan, Peipei; Zhang, Xianying; Huan, Jinliang; Li, Dali; Wang, Tingting; Wei, Tingting; Zhang, Xiaohong; Gu, Xiaoyang; Yao, Liangfang; Xuan, Yang; Hou, Zhaoyuan; Cui, Yongping; Cao, Liu

    2015-01-01

    Centrosome amplification is frequent in cancer, but the underlying mechanisms remain unclear. Here we report that disruption of the Kruppel-like factor 14 (KLF14) gene in mice causes centrosome amplification, aneuploidy and spontaneous tumorigenesis. Molecularly, KLF14 functions as a transcriptional repressor of Plk4, a polo-like kinase whose overexpression induces centrosome overduplication. Transient knockdown of KLF14 is sufficient to induce Plk4-directed centrosome amplification. Clinical...

  19. Sensitivity of MRI tumor biomarkers to VEGFR inhibitor therapy in an orthotopic mouse glioma model.

    Directory of Open Access Journals (Sweden)

    Christian T Farrar

    Full Text Available MRI biomarkers of tumor edema, vascular permeability, blood volume, and average vessel caliber are increasingly being employed to assess the efficacy of tumor therapies. However, the dependence of these biomarkers on a number of physiological factors can compromise their sensitivity and complicate the assessment of therapeutic efficacy. Here we examine the response of these MRI tumor biomarkers to cediranib, a potent vascular endothelial growth factor receptor (VEGFR inhibitor, in an orthotopic mouse glioma model. A significant increase in the tumor volume and relative vessel caliber index (rVCI and a slight decrease in the water apparent diffusion coefficient (ADC were observed for both control and cediranib treated animals. This contrasts with a clinical study that observed a significant decrease in tumor rVCI, ADC and volume with cediranib therapy. While the lack of a difference between control and cediranib treated animals in these biomarker responses might suggest that cediranib has no therapeutic benefit, cediranib treated mice had a significantly increased survival. The increased survival benefit of cediranib treated animals is consistent with the significant decrease observed for cediranib treated animals in the relative cerebral blood volume (rCBV, relative microvascular blood volume (rMBV, transverse relaxation time (T2, blood vessel permeability (K(trans, and extravascular-extracellular space (ν(e. The differential response of pre-clinical and clinical tumors to cediranib therapy, along with the lack of a positive response for some biomarkers, indicates the importance of evaluating the whole spectrum of different tumor biomarkers to properly assess the therapeutic response and identify and interpret the therapy-induced changes in the tumor physiology.

  20. Tissue inhibitor of metalloproteinase 1 (TIMP-1) as a biomarker in gastric cancer

    DEFF Research Database (Denmark)

    Grunnet, Mie; Mau-Sørensen, Morten; Brünner, Nils

    2013-01-01

    The value of Tissue Inhibitor of MetalloProteinase-1 (TIMP-1) as a biomarker in patients with gastric cancer (GC) is widely debated. The aim of this review is to evaluate available literature describing the association between levels of TIMP-1 in tumor tissue and/or blood and the prognosis...

  1. Using shark biomarkers as tools for biomonitoring the health of atlantic waters

    Directory of Open Access Journals (Sweden)

    Luís Miguel Fonseca Alves

    2014-06-01

    Fluorimetric and spectrophotometric techniques were used to quantify all biomarkers using a microplate reader. Chemical analysis were also performed, targeting contaminants on blood, liver and muscle tissues. Results and discussion Sampling and homogenization/processing protocols were optimized and can now be readily and consistently fo

  2. Identification of Circulating Biomarker Candidates for Hepatocellular Carcinoma (HCC: An Integrated Prioritization Approach.

    Directory of Open Access Journals (Sweden)

    Faryal Mehwish Awan

    Full Text Available Hepatocellular carcinoma (HCC is the world's third most widespread cancer. Currently available circulating biomarkers for this silently progressing malignancy are not sufficiently specific and sensitive to meet all clinical needs. There is an imminent and pressing need for the identification of novel circulating biomarkers to increase disease-free survival rate. In order to facilitate the selection of the most promising circulating protein biomarkers, we attempted to define an objective method likely to have a significant impact on the analysis of vast data generated from cutting-edge technologies. Current study exploits data available in seven publicly accessible gene and protein databases, unveiling 731 liver-specific proteins through initial enrichment analysis. Verification of expression profiles followed by integration of proteomic datasets, enriched for the cancer secretome, filtered out 20 proteins including 6 previously characterized circulating HCC biomarkers. Finally, interactome analysis of these proteins with midkine (MDK, dickkopf-1 (DKK-1, current standard HCC biomarker alpha-fetoprotein (AFP, its interacting partners in conjunction with HCC-specific circulating and liver deregulated miRNAs target filtration highlighted seven novel statistically significant putative biomarkers including complement component 8, alpha (C8A, mannose binding lectin (MBL2, antithrombin III (SERPINC1, 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1, alcohol dehydrogenase 6 (ADH6, beta-ureidopropionase (UPB1 and cytochrome P450, family 2, subfamily A, polypeptide 6 (CYP2A6. Our proposed methodology provides a swift assortment process for biomarker prioritization that eventually reduces the economic burden of experimental evaluation. Further dedicated validation studies of potential putative biomarkers on HCC patient blood samples are warranted. We hope that the use of such integrative secretome, interactome and miRNAs target filtration approach will

  3. Comparison of peripheral and central schizophrenia biomarker profiles.

    Directory of Open Access Journals (Sweden)

    Laura W Harris

    Full Text Available We have recently shown that a molecular biomarker signature comprised of inflammatory, hormonal and growth factors occurs in the blood serum from first onset schizophrenia patients. Here, we use the same platform to investigate post mortem brain tissue (Brodmann area 10 from schizophrenia patients who were mainly chronically ill and drug treated. Twenty-one analytes are differentially expressed in post-mortem brain tissue. Comparison with our previous mRNA profiling studies of the same patient samples in another frontal cortical area showed that 9 of these molecules were also altered at the transcriptional level. Furthermore, 9 of the molecules were also altered in serum from living first onset schizophrenia patients compared to controls. We propose a model in which the brain and periphery are coordinated through hormones and other regulatory molecules released into the blood via the diffuse neuroendocrine system. These findings provide further evidence for the systemic nature of schizophrenia and give added validity to the concept that schizophrenia can be investigated through studies of blood-based biomarkers.

  4. Meeting Report--NASA Radiation Biomarker Workshop

    Energy Technology Data Exchange (ETDEWEB)

    Straume, Tore; Amundson, Sally A,; Blakely, William F.; Burns, Frederic J.; Chen, Allen; Dainiak, Nicholas; Franklin, Stephen; Leary, Julie A.; Loftus, David J.; Morgan, William F.; Pellmar, Terry C.; Stolc, Viktor; Turteltaub, Kenneth W.; Vaughan, Andrew T.; Vijayakumar, Srinivasan; Wyrobek, Andrew J.

    2008-05-01

    A summary is provided of presentations and discussions from the NASA Radiation Biomarker Workshop held September 27-28, 2007, at NASA Ames Research Center in Mountain View, California. Invited speakers were distinguished scientists representing key sectors of the radiation research community. Speakers addressed recent developments in the biomarker and biotechnology fields that may provide new opportunities for health-related assessment of radiation-exposed individuals, including for long-duration space travel. Topics discussed include the space radiation environment, biomarkers of radiation sensitivity and individual susceptibility, molecular signatures of low-dose responses, multivariate analysis of gene expression, biomarkers in biodefense, biomarkers in radiation oncology, biomarkers and triage following large-scale radiological incidents, integrated and multiple biomarker approaches, advances in whole-genome tiling arrays, advances in mass-spectrometry proteomics, radiation biodosimetry for estimation of cancer risk in a rat skin model, and confounding factors. Summary conclusions are provided at the end of the report.

  5. Oral Fluids that Detect Cardiovascular Disease Biomarkers

    Science.gov (United States)

    Foley, Joseph D.; Sneed, J. Darrell; Steinhubl, Steven R; Kolasa, Justin; Ebersole, Jeffrey L.; Lin, Yushun; Kryscio, Richard J.; McDevitt, John T.; Campbell, Charles L.; Miller, Craig S.

    2013-01-01

    Objective To determine the utility of oral fluids for assessment of coronary and cardiovascular (CVD) health. Study Design Twenty-nine patients with pre-existing CVD disease underwent an invasive cardiac procedure (alcohol septal ablation or percutaneous coronary intervention) and provided unstimulated whole saliva (UWS), sublingual swabs (LS), gingival swabs (GS) and serum at 0, 8, 16, 24, 48 hr. Concentrations of 13 relevant biomarkers were determined and correlated with levels in serum and the oral fluids. Results Concentrations of the majority of biomarkers were higher in UWS than LS and GS. Coronary and CVD disease biomarkers in UWS correlated better with serum than LS and GS based on group status and measures of time effect. Seven biomarkers demonstrated time effect changes consistent with serum biomarkers, including C-reactive protein and troponin I. Conclusions Changes in serum biomarker profiles are reflected in oral fluids suggesting that oral fluid biomarkers could aid in the assessment of cardiac ischemia/necrosis. PMID:22769406

  6. Blood-Based Gene Expression Signatures of Infants and Toddlers with Autism

    Science.gov (United States)

    Glatt, Stephen J.; Tsuang, Ming T.; Winn, Mary; Chandler, Sharon D.; Collins, Melanie; Lopez, Linda; Weinfeld, Melanie; Carter, Cindy; Schork, Nicholas; Pierce, Karen; Courchesne, Eric

    2012-01-01

    Objective: Autism spectrum disorders (ASDs) are highly heritable neurodevelopmental disorders that onset clinically during the first years of life. ASD risk biomarkers expressed early in life could significantly impact diagnosis and treatment, but no transcriptome-wide biomarker classifiers derived from fresh blood samples from children with…

  7. Blood / Money

    OpenAIRE

    Strong, Thomas

    1997-01-01

    Marilyn Strathern has argued that "nature" in Euro-American culture has appeared as constraint; it has figured the givens of existence on which human artifice is seen to construct "society" or "culture."(5) Among those givens is the notion that human beings are naturally individuals. And blood, too, images individuality: "The very thought of blood, individual blood, touches the deepest feelings in man about life and death" ([RIchard Titmuss] 16.) Transfusion medicine, then, draws on a series ...

  8. Experimental noiseless linear amplification using weak measurements

    Science.gov (United States)

    Ho, Joseph; Boston, Allen; Palsson, Matthew; Pryde, Geoff

    2016-09-01

    The viability of quantum communication schemes rely on sending quantum states of light over long distances. However, transmission loss can degrade the signal strength, adding noise. Heralded noiseless amplification of a quantum signal can provide a solution by enabling longer direct transmission distances and by enabling entanglement distillation. The central idea of heralded noiseless amplification—a conditional modification of the probability distribution over photon number of an optical quantum state—is suggestive of a parallel with weak measurement: in a weak measurement, learning partial information about an observable leads to a conditional back-action of a commensurate size. Here we experimentally investigate the application of weak, or variable-strength, measurements to the task of heralded amplification, by using a quantum logic gate to weakly couple a small single-optical-mode quantum state (the signal) to an ancilla photon (the meter). The weak measurement is carried out by choosing the measurement basis of the meter photon and, by conditioning on the meter outcomes, the signal is amplified. We characterise the gain of the amplifier as a function of the measurement strength, and use interferometric methods to show that the operation preserves the coherence of the signal.

  9. Space Optical Communications Using Laser Beam Amplification

    Science.gov (United States)

    Agrawal, Govind

    2015-01-01

    The Space Optical Communications Using Laser Beam Amplification (SOCLBA) project will provide a capability to amplify a laser beam that is received in a modulating retro-reflector (MRR) located in a satellite in low Earth orbit. It will also improve the pointing procedure between Earth and spacecraft terminals. The technology uses laser arrays to strengthen the reflected laser beam from the spacecraft. The results of first year's work (2014) show amplification factors of 60 times the power of the signal beam. MMRs are mirrors that reflect light beams back to the source. In space optical communications, a high-powered laser interrogator beam is directed from the ground to a satellite. Within the satellite, the beam is redirected back to ground using the MMR. In the MMR, the beam passes through modulators, which encode a data signal onto the returning beam. MMRs can be used in small spacecraft for optical communications. The SOCLBA project is significant to NASA and small spacecraft due to its application to CubeSats for optical data transmission to ground stations, as well as possible application to spacecraft for optical data transmission.

  10. Optimization of noncollinear optical parametric amplification

    Science.gov (United States)

    Schimpf, D. N.; Rothardt, J.; Limpert, J.; Tünnermann, A.

    2007-02-01

    Noncollinearly phase-matched optical parametric amplifiers (NOPAs) - pumped with the green light of a frequency doubled Yb-doped fiber-amplifier system 1, 2 - permit convenient generation of ultrashort pulses in the visible (VIS) and near infrared (NIR) 3. The broad bandwidth of the parametric gain via the noncollinear pump configuration allows amplification of few-cycle optical pulses when seeded with a spectrally flat, re-compressible signal. The short pulses tunable over a wide region in the visible permit transcend of frontiers in physics and lifescience. For instance, the resulting high temporal resolution is of significance for many spectroscopic techniques. Furthermore, the high magnitudes of the peak-powers of the produced pulses allow research in high-field physics. To understand the demands of noncollinear optical parametric amplification using a fiber pump source, it is important to investigate this configuration in detail 4. An analysis provides not only insight into the parametric process but also determines an optimal choice of experimental parameters for the objective. Here, the intention is to design a configuration which yields the shortest possible temporal pulse. As a consequence of this analysis, the experimental setup could be optimized. A number of aspects of optical parametric amplifier performance have been treated analytically and computationally 5, but these do not fully cover the situation under consideration here.

  11. Magnetic Field Amplification in Young Galaxies

    CERN Document Server

    Schober, Jennifer; Klessen, Ralf S

    2013-01-01

    The Universe at present is highly magnetized, with fields of the order of a few 10^-5 G and coherence lengths larger than 10 kpc in typical galaxies like the Milky Way. We propose that the magnetic field was amplified to this values already during the formation and the early evolution of the galaxies. Turbulence in young galaxies is driven by accretion as well as by supernova (SN) explosions of the first generation of stars. The small-scale dynamo can convert the turbulent kinetic energy into magnetic energy and amplify very weak primordial magnetic seed fields on short timescales. The amplification takes place in two phases: in the kinematic phase the magnetic field grows exponentially, with the largest growth on the smallest non-resistive scale. In the following non-linear phase the magnetic energy is shifted towards larger scales until the dynamo saturates on the turbulent forcing scale. To describe the amplification of the magnetic field quantitatively we model the microphysics in the interstellar medium ...

  12. Seismic Wave Amplification in 3D Alluvial Basins: 3D/1D Amplification Ratios from Fast Multipole BEM Simulations

    CERN Document Server

    Fajardo, Kristel C Meza; Chaillat, Stéphanie; Lenti, Luca

    2016-01-01

    In this work, we study seismic wave amplification in alluvial basins having 3D standard geometries through the Fast Multipole Boundary Element Method in the frequency domain. We investigate how much 3D amplification differs from the 1D (horizontal layering) case. Considering incident fields of plane harmonic waves, we examine the relationships between the amplification level and the most relevant physical parameters of the problem (impedance contrast, 3D aspect ratio, vertical and oblique incidence of plane waves). The FMBEM results show that the most important parameters for wave amplification are the impedance contrast and the so-called equivalent shape ratio. Using these two parameters, we derive simple rules to compute the fundamental frequency for various 3D basin shapes and the corresponding 3D/1D amplification factor for 5% damping. Effects on amplification due to 3D basin asymmetry are also studied and incorporated in the derived rules.

  13. Utility of sepsis biomarkers and the infection probability score to discriminate sepsis and systemic inflammatory response syndrome in standard care patients.

    Directory of Open Access Journals (Sweden)

    Franz Ratzinger

    might be used as a rule for when to take blood cultures or using nucleic acid amplification tests for microbiological diagnostics.

  14. Early prediction of acute kidney injury biomarkers after endovascular stent graft repair of aortic aneurysm: a prospective observational study

    OpenAIRE

    Ueta, Kazuyoshi; Watanabe, Michiko; Iguchi, Naoya; Uchiyama, Akinori; Shirakawa, Yukitoshi; Kuratani, Toru; Sawa, Yoshiki; Fujino, Yuji

    2014-01-01

    Background Acute kidney injury (AKI) is a common and serious condition usually detected some time after onset by changes in serum creatinine (sCr). Although stent grafting to repair aortic aneurysms is associated with AKI caused by surgical procedures or the use of contrast agents, early biomarkers for AKI have not been adequately examined in stent graft recipients. We studied biomarkers including urinary neutrophil gelatinase-associated lipocalin (NGAL), blood NGAL, N-acetyl-β-d-glucosaminid...

  15. Determination of thiocyanate (biomarkers of ETS) and other inorganic ions in human nasal discharge samples using ion chromatography.

    Science.gov (United States)

    Narkowicz, Sylwia; Polkowska, Żaneta; Marć, Mariusz; Simeonov, Vasil; Namieśnik, Jacek

    2013-10-01

    Environmental tobacco smoke (ETS) is a mixture of air and tobacco smoke containing more than 4000 chemical substances. In view of the health risks of many of these substances, studies are needed to determine biomarkers of exposure to ETS constituents in people who actively or passively are exposed to the toxic compounds. The methodologies for determining most biomarkers from saliva, urine and blood samples are known, but methods for analyzing these compounds in nasal discharges are not available. The objective of this work was to develop an analytical procedure for the determination of thiocyanate and other biomarker compounds in samples of nasal discharge using ion chromatography.

  16. Understanding Blood Counts

    Science.gov (United States)

    ... Lab and Imaging Tests Understanding Blood Counts Understanding Blood Counts Understanding Blood Counts SHARE: Print Glossary Blood cell counts give ... your blood that's occupied by red cells. Normal Blood Counts Normal blood counts fall within a range ...

  17. Impact of plasma transaminase levels on the peripheral blood glutamate levels and memory functions in healthy subjects ☆

    OpenAIRE

    Kamada, Yoshihiro; Hashimoto, Ryota; Yamamori, Hidenaga; Yasuda, Yuka; Takehara, Tetsuo; Fujita, Yuko; Hashimoto, Kenji; Miyoshi, Eiji

    2016-01-01

    Background & aims Blood aspartate aminotransferase (AST) and alanine transaminase (ALT) levels are the most frequently reliable biomarkers of liver injury. Although AST and ALT play central roles in glutamate production as transaminases, peripheral blood levels of AST and ALT have been regarded only as liver injury biomarkers. Glutamate is a principal excitatory neurotransmitter, which affects memory functions in the brain. In this study, we investigated the impact of blood transaminase level...

  18. Biomarkers of the Metabolic Syndrome and Breast Cancer Prognosis

    Directory of Open Access Journals (Sweden)

    Meng-Hua Tao

    2010-04-01

    Full Text Available In spite of its public health importance, our understanding of the mechanisms of breast carcinogenesis and progress is still evolving. The metabolic syndrome (MS is a constellation of biochemical abnormalities including visceral adiposity, hyperglycemia, hyperinsulinemia, dyslipidemia and high blood pressure. The components of the MS have all been related to late-stage disease and even to a poor prognosis of breast cancer through multiple interacting mechanisms. In this review, we aim to present a summary of recent advances in the understanding of the contribution of the MS to breast cancer with the emphasis on the role of biomarkers of the MS in the prognosis of breast cancer.

  19. Biomarkers of the Metabolic Syndrome and Breast Cancer Prognosis

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Qiu-Li; Xu, Wang-Hong, E-mail: mtao@buffalo.edu [Department of Epidemiology, School of Public Health, Fudan University, Shanghai 200032 (China); Tao, Meng-Hua, E-mail: mtao@buffalo.edu [Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY 14214 (United States)

    2010-04-28

    In spite of its public health importance, our understanding of the mechanisms of breast carcinogenesis and progress is still evolving. The metabolic syndrome (MS) is a constellation of biochemical abnormalities including visceral adiposity, hyperglycemia, hyperinsulinemia, dyslipidemia and high blood pressure. The components of the MS have all been related to late-stage disease and even to a poor prognosis of breast cancer through multiple interacting mechanisms. In this review, we aim to present a summary of recent advances in the understanding of the contribution of the MS to breast cancer with the emphasis on the role of biomarkers of the MS in the prognosis of breast cancer.

  20. Biomarkers used in Environmental Health with focus on Endocrine Disrupters

    DEFF Research Database (Denmark)

    Krüger, Tanja; Ghisari, Mandana; Long, Manhai;

    2012-01-01

    Endocrine-disrupting chemicals (EDCs) are compounds that either mimic or block endogenous hormones and can disrupt the normal function of the body. Bio-monitoring is the assessment of internal doses of EDCs and has been used for decades to provide information about exposures to chemicals giving...... in human blood is important and ex vivo cell systems have been introduced to enable the assessment of the integrated level of xenobiotic transactivity in humans. Biomonitoring studies for exposure biomarkers have shown that there are geographical differences in the bioaccumulated POP levels...