WorldWideScience

Sample records for b1 biomarker blood

  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. Effects of Aflatoxin B1 and Fumonisin B1 on Blood Biochemical Parameters in Broilers

    OpenAIRE

    Tessari; Kobashigawa; Cardoso; Ledoux; Rottinghaus; Oliveira

    2010-01-01

    The individual and combined effects of dietary aflatoxin B1 (AFB1) and fumonisin B1 (FB1) on liver pathology, serum levels of aspartate amino-transferase (AST) and plasma total protein (TP) of broilers were evaluated from 8 to 41 days of age. Dietary treatments included a 3 × 3 factorial arrangement with three levels of AFB1 (0, 50 and 200 μg AFB1/kg), and three levels of FB1 (0, 50 and 200 mg FB1/kg). At 33 days post feeding, with the exception of birds fed 50 mg FB1 only, concentrations of ...

  3. Effects of Aflatoxin B1 and Fumonisin B1 on Blood Biochemical Parameters in Broilers

    Science.gov (United States)

    Tessari, Eliana N. C.; Kobashigawa, Estela; Cardoso, Ana Lúcia S. P.; Ledoux, David R.; Rottinghaus, George E.; Oliveira, Carlos A. F.

    2010-01-01

    The individual and combined effects of dietary aflatoxin B1 (AFB1) and fumonisin B1 (FB1) on liver pathology, serum levels of aspartate amino-transferase (AST) and plasma total protein (TP) of broilers were evaluated from 8 to 41 days of age. Dietary treatments included a 3 × 3 factorial arrangement with three levels of AFB1 (0, 50 and 200 μg AFB1/kg), and three levels of FB1 (0, 50 and 200 mg FB1/kg). At 33 days post feeding, with the exception of birds fed 50 mg FB1 only, concentrations of AST were higher (p Broilers receiving the highest levels of AFB1 and FB1 had bile duct proliferation and trabecular disorder in liver samples. AFB1 singly or in combination with FB at the levels studied, caused liver damage and an increase in serum levels of AST. PMID:22069595

  4. 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

  5. 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

  6. 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

  7. CYP1A1 and CYP1B1 in human lymphocytes as biomarker of exposure: effect of dioxin exposure and polymorphisms

    Energy Technology Data Exchange (ETDEWEB)

    Duursen, M. van; Sanderson, T.; Berg, M. van den [Inst. for Risk Assessment Sciences, Utrecht (Netherlands)

    2004-09-15

    There are several known genetic polymorphisms of the CYP1A1 and CYP1B1 genes. A polymorphism in the 3'-untranslated region of the CYP1A1 gene (CYP1A1 MspI or CYP1A1 m1) is often studied in relation with breast or lung cancer, but little is known about the functional effect of this polymorphism. An amino acid substitution in codon 432 (Val to Leu) of the CYP1B1 gene is associated with a lower catalytic activity of the enzyme. However, the involvement of these polymorphisms on the inducibility of CYP1A1 and CYP1B1 gene expression is unclear. CYP1A1 and CYP1B1 mRNA expression levels can be determined in peripheral blood lymphocytes. This makes them potential candidates for use as biomarker of exposure to environmental compounds. Interindividual variations in mRNA expression patterns, catalytic activity and polymorphisms are very important factors when CYP1A1 and CYP1B1 expression patterns are used as biomarker of exposure, but little is known about it. Spencer et al. showed a concentration-dependent increase of CYP1B1 mRNA in lymphocytes upon exposure in vitro to 2,3,7,8-tetrachloro-p-dibenzodioxin (TCDD), the most potent dioxin. Yet, only a few studies describe the in vivo correlation between polymorphisms, mRNA expression level and exposure to environmental factors. In this study, we wanted to obtain a better insight in the CYP1A1 and CYP1B1 mRNA expression and enzyme activity in human lymphocytes. We determined the constitutive CYP1A1 and CYP1B1 mRNA expression in lymphocytes of ten healthy volunteers and the variability in sensitivity toward enzyme induction by TCDD. Further, the CYP1A1 m1 and CYP1B1 Val432Leu polymorphisms were determined.

  8. Calcium montmorillonite clay reduces urinary biomarkers of fumonisin B1 exposure in rats and humans

    Science.gov (United States)

    Background: Fumonisin B1 (FB1) is often a co-contaminant with aflatoxin (AF) in grains and may enhance AF’s carcinogenicity by acting as a cancer promoter. An oral dose of calcium montmorillonite clay (i.e. NovaSil, NS) was able to reduce aflatoxin exposure in a Ghanaian population at risk. In vitro...

  9. 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

  10. 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

  11. 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

  12. Effects of Ginkgo biloba extract on expression of biomarkers during aflatoxin B1-induced hepatocarcinogenesis in Wistar rats

    Institute of Scientific and Technical Information of China (English)

    Yanrong Hao; Jianjia Su; Chao Ou; Ji Cao; Fang Yang; Xiaoxian Duan; Chun Yang; Yuan Li

    2012-01-01

    Objective: The aim of this study was to study the effect of Ginkgo biloba extract (EGb761) on metabolism of aflatoxin B1 (AFB1) in Wistar rats. Methods: Seventy one Wistar rats were assigned at random to groups A, B and C. Rats in groups A, B were injected with AFB1 (intraperitoneal, 100–200 μg/kg body weight, 1–3 times/week). Group C was normal control. Rats in group B were fed in food with EGb761, while rats in groups A, C were given normal food. Blood samples were collected and liver biopsies were performed on the 14th, 28th and 42nd week. All the rats were sacrificed on the 64th week. The incidence of hepatocarcinoma was investigated. The hepatic phase I drug-metabolizing enzyme Cytochrome-P450 (CYP450) and phase II metabolizing enzyme glutathione S-transferase (GST) were analyzed with spectrometry. Serum AFB1-lysine adduct levels were assessed with high performance liquid chromatography (HPLC). The expression of 8-hydroxydeoxy-guanosine (8-OHdG) was measured with immunohistochemistry. Results: The incidence of hepatocellular carcinoma (HCC) in group B was significantly lower than that in group A (26.92% vs 76.00%, P < 0.001). No HCC developed in group C. EGb761 showed no effects on the activities of CYP450 and GST in rat liver tissues. The level of AFB1-lysine adduct reached the peak (4356.01 pg/mg albumin) at the 14th week in group A. EGb761 significantly inhibited the formation of AFB1-lysine adduct in serum by 13.07% at the 14th week (P = 0.033), and 73.63% at the 42nd week (P = 0.002). The expression of 8-OHdG protein in rat liver tissues in group B was significantly lower than that in group A at the 28th, 42nd, and 64th week (P < 0.05). Conclu-sion: The main mechanism underlying the effect of EGb761 in blocking hepatocarcinogenesis induced by AFB1 may not be fully attributable to its influence on the activity of liver phase I and phase II metabolizing enzymes. EGb761 inhibits the produc-tion of AFB1-lysine adducts, decreases the expression of 8-OHd

  13. Blood manganese as an exposure biomarker: State of the evidence

    OpenAIRE

    Baker, Marissa G.; Simpson, Christopher D.; Stover, Bert; Sheppard, Lianne; Checkoway, Harvey; Racette, Brad A.; Seixas, Noah. S.

    2014-01-01

    Despite evidence of adverse health effects resulting from exposure to manganese (Mn), biomarkers of exposure are poorly understood. To enhance understanding, mean blood Mn (MnB) and mean air Mn (MnA) were extracted from 63 exposure groups in 24 published papers, and the relationship was modeled using segmented regression. On a log/log scale, a positive association between MnA and MnB was observed among studies reporting MnA concentrations above about 10 μg/m3, although interpretation is limit...

  14. 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

  15. Blood manganese as an exposure biomarker: State of the evidence

    Science.gov (United States)

    Baker, Marissa G.; Simpson, Christopher D.; Stover, Bert; Sheppard, Lianne; Checkoway, Harvey; Racette, Brad A.; Seixas, Noah S.

    2014-01-01

    Despite evidence of adverse health effects resulting from exposure to manganese (Mn), biomarkers of exposure are poorly understood. To enhance understanding, mean blood Mn (MnB) and mean air Mn (MnA) were extracted from 63 exposure groups in 24 published papers, and the relationship was modeled using segmented regression. On a log/log scale, a positive association between MnA and MnB was observed among studies reporting MnA concentrations above about 10 μg/m3, although interpretation is limited by largely cross-sectional data, study design variability, and differences in exposure monitoring methods. Based on the results of the segmented regression, we hypothesize that below the concentration of about 10 μg/m3, Mn in the body is dominated by dietary Mn, and additional inhaled Mn only causes negligible changes in Mn levels unless the inhaled amount is substantial. However, stronger study designs are required to account for temporal characteristics of the MnA to MnB relationships which reflect the underlying physiology and toxicokinetics of Mn uptake and distribution. Thus, we present an inception cohort study design we have conducted among apprentice welders, and the analytical strengths this study design offers. To determine if blood could be a useful biomarker for Mn to be utilized by industrial hygienists in general industry requires additional time-specific analyses, which our inception cohort study design will allow. PMID:24579750

  16. 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

  17. 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.

  18. 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

  19. 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...

  20. 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

  1. 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.

  2. 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

  3. 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

  4. Effects of 5-HT1B/1D receptor agonist rizatriptan on cerebral blood flow and blood volume in normal circulation.

    Science.gov (United States)

    Okazawa, Hidehiko; Tsuchida, Tatsuro; Pagani, Marco; Mori, Tetsuya; Kobayashi, Masato; Tanaka, Fumiko; Yonekura, Yoshiharu

    2006-01-01

    To investigate the vasoconstrictor effect of 5-hydroxytryptamine (5-HT1B/1D) receptor agonists for migraine treatment, changes in cerebral blood flow (CBF) and blood volume induced by rizatriptan were assessed by positron emission tomography (PET). Eleven healthy volunteers underwent PET studies before and after rizatriptan administration. Dynamic PET data were acquired after bolus injection of H2(15)O to analyze CBF and arterial-to-capillary blood volume (V0) images using the three-weighted integral method. After a baseline scan, three further acquisitions were performed at 40 to 50, 60 and 70 to 80 mins after drug administration. Global and regional differences in CBF and V0 between conditions were compared using absolute values in the whole brain and cortical regions, as well as statistical parametric mapping (SPM) analysis. The global and regional values for CBF and V0 decreased significantly after rizatriptan administration compared with the baseline condition. However, both values recovered to baseline within 80 mins after treatment. The maximal reduction in global CBF and V0 was approximately 13% of baseline value. The greatest decrease in CBF was observed approximately 60 mins after drug administration, whereas the maximal reduction in V0 was observed approximately 5 mins earlier. Statistical parametric mapping did not highlight any regional differences between conditions. Thus, in brain circulation, rizatriptan caused significant CBF and V0 decreases, which are consistent with the vasoconstrictor effect of triptans on the large cerebral arteries. The gradual recovery in the late phase from the maximal CBF and V0 decrease suggests that rizatriptan does not affect the cerebral autoregulatory response in small arteries induced by CBF reduction. PMID:15944648

  5. 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...

  6. DNA Methylation in Peripheral Blood: A Potential Biomarker for Cancer Molecular Epidemiology

    OpenAIRE

    Li, Lian; Choi, Ji-Yeob; Lee, Kyoung-Mu; Sung, Hyuna; Park, Sue K; Oze, Isao; Pan, Kai-Feng; You, Wei-cheng; Chen, Ying-Xuan; Fang, Jing-Yuan; Matsuo, Keitaro; Kim, Woo Ho; Yuasa, Yasuhito; Kang, Daehee

    2012-01-01

    Aberrant DNA methylation is associated with cancer development and progression. There are several types of specimens from which DNA methylation pattern can be measured and evaluated as an indicator of disease status (from normal biological process to pathologic condition) and even of pharmacologic response to therapy. Blood-based specimens such as cell-free circulating nucleic acid and DNA extracted from leukocytes in peripheral blood may be a potential source of noninvasive cancer biomarkers...

  7. Global DNA hypomethylation in peripheral blood mononuclear cells as a biomarker of cancer risk

    Science.gov (United States)

    Global DNA hypomethylation is an early molecular event in carcinogenesis. Whether methylation measured in peripheral blood mononuclear cells (PBMCs) DNA is a clinically reliable biomarker for early detection or cancer risk assessment is to be established. From an original sample-set of 753 male and...

  8. 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

  9. 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...

  10. Biomarkers for Monitoring Pre-Analytical Quality Variation of mRNA in Blood Samples

    OpenAIRE

    Zhang, Hui; Korenková, Vlasta; Sjöback, Robert; Švec, David; Björkman, Jens; Kruhøffer, Mogens; Verderio, Paolo; Pizzamiglio, Sara; Ciniselli, Chiara Maura; Wyrich, Ralf; Oelmueller, Uwe; Kubista, Mikael; Lindahl, Torbjørn; Lönneborg, Anders; Rian, Edith

    2014-01-01

    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 dif...

  11. 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.

  12. Cell-free microRNAs in blood and other body fluids, as cancer biomarkers.

    Science.gov (United States)

    Ortiz-Quintero, Blanca

    2016-06-01

    The discovery of cell-free microRNAs (miRNAs) in serum, plasma and other body fluids has yielded an invaluable potential source of non-invasive biomarkers for cancer and other non-malignant diseases. miRNAs in the blood and other body fluids are highly stable in biological samples and are resistant to environmental conditions, such as freezing, thawing or enzymatic degradation, which makes them convenient as potential biomarkers. In addition, they are more easily sampled than tissue miRNAs. Altered levels of cell-free miRNAs have been found in every type of cancer analysed, and increasing evidence indicates that they may participate in carcinogenesis by acting as cell-to-cell signalling molecules. This review summarizes the biological characteristics and mechanisms of release of cell-free miRNAs that make them promising candidates as non-invasive biomarkers of cancer. PMID:27218664

  13. 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

  14. 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.

  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. Identification of potential gene expression biomarkers for the surveillance of anabolic agents in bovine blood cells.

    Science.gov (United States)

    Riedmaier, Irmgard; Tichopad, Ales; Reiter, Martina; Pfaffl, Michael W; Meyer, Heinrich H D

    2009-04-01

    In the EU, the use of anabolic steroids in food producing animals has been forbidden since 1988. The routine methods used in practice are based on the detection of hormonal residues. To overcome these routine methods, growth-promoting agents are sometimes administered at concentrations below the detection limit and new anabolic substances are designed. Therefore, new monitoring systems are needed to overcome the misuse of anabolic agents in meat production. In this study, a new monitoring system was applied: the quantification of mRNA gene expression changes by quantitative real time reverse transcription polymerase chain reaction (qRT-PCR). Blood was selected as ideal tissue for biomarker screening. From the literature, it is known that steroid hormones affect mRNA gene expression of the different blood cells, which can easily be taken from the living animal. In an animal trial, 18 Nguni heifers were separated to two groups of nine animals. One group served as untreated control and the other group was treated with a combination of trenbolone acetate plus estradiol for 39 days in order to allow the detection of the effect on mRNA expression in blood at three time points. Candidate genes used for developing a biomarker pattern were chosen by screening the actual literature for anabolic effects on blood cells. It could be demonstrated that the combination of trenbolone acetate plus estradiol significantly influences mRNA expression of the steroid receptors (ER-alpha and GR-alpha), the apoptosis regulator Fas, the proinflammatory interleukins IL-1alpha, IL-1beta and IL-6 and of MHCII, CK, MTPN, RBM5 and Actin-beta. Advanced statistical analysis by Principal Components Analysis (PCA) indicated that these genes represent potential biomarkers for this hormone combination in whole blood. PMID:19298887

  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. 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.

  1. 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

  2. [Advances in Biomarkers of Mild Traumatic Brain Injury in Cerebrospinal Fluid and Blood].

    Science.gov (United States)

    Huang, Wen; Li, Shang-xun; Li, Xue-jian; Xu, Hong-yun

    2015-12-01

    Mild traumatic brain injury (MTBI) is defined as a mild brain trauma resulting in a short loss of consciousness and alteration of mental status. It may also occasionally develop persistent and progressive symptoms. It has been confirmed that MTBI causes changes of anatomic structures in central nervous system and biomarkers in the body fluid. However, there is no sufficient research on relevance among threshold for the brain injury, individual vulnerability and duration of disturbance of consciousness. Furthermore, there are no reliable diagnostic methods to establish whether a blow to the head is sufficient to cause the brain injury. This review provides references for biomarkers in cerebrospinal fluid and blood associated with TBI. It also provides application status and potential prospects for further assessment and diagnosis of MTBI. PMID:27141807

  3. 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

  4. DJ-1 isoforms in whole blood as potential biomarkers of Parkinson disease

    Science.gov (United States)

    Lin, Xiangmin; Cook, Travis J.; Zabetian, Cyrus P.; Leverenz, James B.; Peskind, Elaine R.; Hu, Shu-Ching; Cain, Kevin C.; Pan, Catherine; Edgar, John Scott; Goodlett, David R.; Racette, Brad A.; Checkoway, Harvey; Montine, Thomas J.; Shi, Min; Zhang, Jing

    2012-01-01

    DJ-1 is a multifunctional protein that plays an important role in oxidative stress, cell death, and synucleinopathies, including Parkinson disease. Previous studies have demonstrated that total DJ-1 levels decrease in the cerebrospinal fluid, but do not change significantly in human plasma from patients with Parkinson disease when compared with controls. In this study, we measured total DJ-1 and its isoforms in whole blood of patients with Parkinson disease at various stages, Alzheimer disease, and healthy controls to identify potential peripheral biomarkers of PD. In an initial discovery study of 119 subjects, 7 DJ-1 isoforms were reliably detected, and blood levels of those with 4-hydroxy-2-nonenal modifications were discovered to be altered in late-stage Parkinson disease. This result was further confirmed in a validation study of another 114 participants, suggesting that, unlike total DJ-1 levels, post-translationally modified isoforms of DJ-1 from whole blood are candidate biomarkers of late-stage Parkinson disease. PMID:23233873

  5. 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.

  6. 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...

  7. Are Blood-Based Protein Biomarkers for Alzheimer's Disease also Involved in Other Brain Disorders?:A Systematic Review

    OpenAIRE

    Chiam, Justin Tao Wen; Dobson, Richard James Butler; Kiddle, Steven John; Sattlecker, Martina

    2015-01-01

    Background: Alzheimer's disease (AD) biomarkers are urgently needed for both early and accurate diagnosis and prediction of disease progression. Past research has studied blood-based proteins as potential AD biomarkers, revealing many candidate proteins. To date only limited effort has been made to investigate the disease specificity of AD candidate proteins and whether these proteins are also involved in other neurodegenerative or psychiatric conditions.Objective: This review seeks to determ...

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. Effects of Aerobic Fitness and Adiposity on Coagulation Biomarkers in Men vs. Women with Elevated Blood Pressure

    OpenAIRE

    Wilson, Kathleen L.; Lianne Tomfohr; Kate Edwards; Cindy Knott; Suzi Hong; Laura Redwine; Karen Calfas; Rock, Cheryl L.; Roland von Känel; Mills, Paul J.

    2012-01-01

    ABSTRACTA hypercoagulable state is a potential mechanism linking elevated blood pressure (BP), adiposity and a sedentary lifestyle to development of coronary heart disease (CHD). We examined relationships among aerobic fitness and adiposity in 76 sedentary subjects with elevated BP. Blood levels of plasminogen activator inhibitor-1 (PAI-1), D-dimer, von Willebrand factor (vWF) and thrombomodulin were assessed as biomarkers of coagulation. In individuals with elevated BP, percent body fat and ...

  16. 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...

  17. 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....

  18. Simultaneous Determination of Underivatized Vitamin B1 and B6 in Whole Blood by Reversed Phase Ultra High Performance Liquid Chromatography Tandem Mass Spectrometry.

    Directory of Open Access Journals (Sweden)

    Johan Puts

    Full Text Available Vitamin B1 (thiamine-diphosphate and B6 (pyridoxal-5'phosphate are micronutrients. Analysis of these micronutrients is important to diagnose potential deficiency which often occurs in elderly people due to malnutrition, in severe alcoholism and in gastrointestinal compromise due to bypass surgery or disease. Existing High Performance Liquid Chromatography (HPLC based methods include the need for derivatization and long analysis time. We developed an Ultra High Performance Liquid Chromatography Tandem Mass spectrometry (UHPLC-MS/MS assay with internal standards for simultaneous measurement of underivatized thiamine-diphosphate and pyridoxal-5'phosphate without use of ion pairing reagent.Whole blood, deproteinized with perchloric acid, containing deuterium labelled internal standards thiamine-diphosphate(thiazole-methyl-D3 and pyridoxal-5'phosphate(methyl-D3, was analyzed by UHPLC-MS/MS. The method was validated for imprecision, linearity, recovery and limit of quantification. Alternate (quantitative method comparisons of the new versus currently used routine HPLC methods were established with Deming regression.Thiamine-diphosphate and pyridoxal-5'phosphate were measured within 2.5 minutes instrumental run time. Limits of detection were 2.8 nmol/L and 7.8 nmol/L for thiamine-diphosphate and pyridoxal-5'phosphate respectively. Limit of quantification was 9.4 nmol/L for thiamine-diphosphate and 25.9 nmol/L for pyridoxal-5'phosphate. The total imprecision ranged from 3.5-7.7% for thiamine-diphosphate (44-157 nmol/L and 6.0-10.4% for pyridoxal-5'phosphate (30-130 nmol/L. Extraction recoveries were 101-102% ± 2.5% (thiamine-diphosphate and 98-100% ± 5% (pyridoxal-5'phosphate. Deming regression yielded slopes of 0.926 and 0.990 in patient samples (n = 282 and national proficiency testing samples (n = 12 respectively, intercepts of +3.5 and +3 for thiamine-diphosphate (n = 282 and n = 12 and slopes of 1.04 and 0.84, intercepts of -2.9 and +20 for

  19. Effect of p53 Arg72Pro polymorphism on the induction of micronucleus by aflatoxin B1 in in vitro in human blood lymphocytes.

    Science.gov (United States)

    Bayram, Süleyman; Rencüzoğulları, Eyyüp; Almas, Abdullah Muttalip; Genç, Ahmet

    2016-07-01

    Aflatoxin B1 (AFB1) is a class 1 carcinogen produced by Aspergillus flavus and Aspergillus parasiticus that can contaminate a variety of food substances, the liver being its target organ. A common p53 Arg72Pro polymorphism resulting in the substitution of an arginine amino acid by proline amino acid in the transactivating domain has been demonstrated to affect p53 function. The aim of this study is to investigate association between p53 Arg72Pro polymorphism and the frequencies of spontaneous and AFB1-induced DNA damage in peripheral blood lymphocytes from 100 healthy individuals in Turkish population. In vitro cytokinesis-blocked micronucleus (CBMN) assay was used to detect the spontaneous and AFB1-induced DNA damage whereas, genotyping of p53 Arg72Pro polymorphism was carried out by using a polymerase chain reaction restriction fragment length polymorphism assay. During 68 h incubation time, lymphocytes treated with AFB1 (1.56 μg/mL) and S9 mix for a total of 3 h (48-51 h). Treatment of the lymphocytes with AFB1significantly increased the overall frequencies of micronucleus (MN) when compared to untreated cultures (1.23 ± 0.05 versus 0.55 ± 0.02; p < 0.001). Moreover, genotype analysis revealed a statistically significant association between Pro/Pro genotype of p53 Arg72Pro polymorphism and increased frequencies of MN both spontaneous and AFB1-induced cultures when compared Arg/Arg genotype (0.69 ± 0.19 versus 0.46 ± 0.13, p < 0.001; 1.59 ± 0.65 versus 1.01 ± 0.41 p < 0.001; respectively). Our data indicate that p53 Arg72Pro polymorphism plays a significant role in human sensitivity to the genotoxic effects of AFB1. Further investigations in larger sample size and with different ethnic origins as well as including more functional single nucleotide polymorphisms might lead to the identification of novel genetic factors responsible for susceptibility to human carcinogens such as AFB1. PMID:26738694

  20. Fractal discrimination of random fractal aggregates and its application in biomarker analysis for blood coagulation

    International Nuclear Information System (INIS)

    Highlights: ► Establishment of a potential bio-marker able to characterise bio-gels post their Gel-Point is presented. ► Spectral dimension is sensitive to fibrin internal network structure. ► Fractal simulation elucidates why spectral dimension displays this distinctive capacity. - Abstract: A recent rheological study has established that the fractal dimension, df, of an incipient clot, formed at the Gel Point (sol–gel transition) of coagulating blood is a significant new biomarker of haemostasis. In whole healthy blood, incipient clots show a clearly defined value of df = 1.7 within a narrow range, which represents a new ‘healthy index’ for normal clotting. The addition of unfractionated heparin significantly prolongs the onset of clot formation with a corresponding reduction of df as a function of heparin dose. However, as clots mature they exhibit (i) an expected increase in df and (ii) a significant increase to spread of these values, i.e. df’s in the range 2.0–2.5, limiting the use of df as a discriminant of clot microstructure. The present study, details how and why the spectral dimension, ds, can be used to accommodate this shortcoming and allow discrimination of mature forms of clot microstructure in indistinguishable in terms of their fractal dimension. To elucidate why ds permits discrimination a numerical experiment was conducted on computationally generated random fractal aggregates (RFAs) with a priori set value of df. Starting from RFAs with a df of 1.7, mature RFAs are evolved from these incipient templates by two differing growth processes achieving a final df of 2.1. Fractal and statistical analysis of the mature RFAs reveals, for the first time, that their differing internal structure is manifest in the magnitude of ds. The potential clinical significance of these findings is discussed in terms of the possibility of exploiting the incipient clot’s ability to template the internal arrangement of the mature clot to better predict

  1. 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

  2. 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

  3. Vitamin B1

    Science.gov (United States)

    ... Prize Alfred Nobel's Life and Work Teachers' Questionnaire Vitamin B1 - About The Chicken Farm educational game and ... the game window. Reading: "Christian Eijkman, Beriberi and Vitamin B1" - Who was Eijkman and why did he ...

  4. Similar Source of Differential Blood mRNAs in Lung Cancer and Pulmonary Inflammatory Diseases: Calls for Improved Strategy for Identifying Cancer-Specific Biomarkers

    OpenAIRE

    Hong, Guini; Chen, Beibei; Li, Hongdong; Zhang, Wenjing; Zheng, Tingting; Li, Shan; Shi, Tongwei; Ao, Lu; Guo, Zheng

    2014-01-01

    Background Many studies try to identify cancer diagnostic biomarkers by comparing peripheral whole blood (PWB) of cancer samples and healthy controls, explicitly or implicitly assuming that such biomarkers are potential candidate biomarkers for distinguishing cancer from nonmalignant inflammation-associated diseases. Methods Multiple PWB gene expression profiles for lung cancer/inflammation-associated pulmonary diseases were used for differential mRNAs identification and comparison and for pr...

  5. Metabolomics as a Tool for Discovery of Biomarkers of Autism Spectrum Disorder in the Blood Plasma of Children

    OpenAIRE

    West, Paul R.; Amaral, David G.; Bais, Preeti; Smith, Alan M.; Egnash, Laura A.; Ross, Mark E.; Palmer, Jessica A.; Fontaine, Burr R.; Conard, Kevin R.; Corbett, Blythe A.; Cezar, Gabriela G.; Donley, Elizabeth L. R.; Burrier, Robert E.

    2014-01-01

    Background The diagnosis of autism spectrum disorder (ASD) at the earliest age possible is important for initiating optimally effective intervention. In the United States the average age of diagnosis is 4 years. Identifying metabolic biomarker signatures of ASD from blood samples offers an opportunity for development of diagnostic tests for detection of ASD at an early age. Objectives To discover metabolic features present in plasma samples that can discriminate children with ASD from typical...

  6. Metabolomics as a tool for discovery of biomarkers of autism spectrum disorder in the blood plasma of children.

    Directory of Open Access Journals (Sweden)

    Paul R West

    Full Text Available The diagnosis of autism spectrum disorder (ASD at the earliest age possible is important for initiating optimally effective intervention. In the United States the average age of diagnosis is 4 years. Identifying metabolic biomarker signatures of ASD from blood samples offers an opportunity for development of diagnostic tests for detection of ASD at an early age.To discover metabolic features present in plasma samples that can discriminate children with ASD from typically developing (TD children. The ultimate goal is to identify and develop blood-based ASD biomarkers that can be validated in larger clinical trials and deployed to guide individualized therapy and treatment.Blood plasma was obtained from children aged 4 to 6, 52 with ASD and 30 age-matched TD children. Samples were analyzed using 5 mass spectrometry-based methods designed to orthogonally measure a broad range of metabolites. Univariate, multivariate and machine learning methods were used to develop models to rank the importance of features that could distinguish ASD from TD.A set of 179 statistically significant features resulting from univariate analysis were used for multivariate modeling. Subsets of these features properly classified the ASD and TD samples in the 61-sample training set with average accuracies of 84% and 86%, and with a maximum accuracy of 81% in an independent 21-sample validation set.This analysis of blood plasma metabolites resulted in the discovery of biomarkers that may be valuable in the diagnosis of young children with ASD. The results will form the basis for additional discovery and validation research for 1 determining biomarkers to develop diagnostic tests to detect ASD earlier and improve patient outcomes, 2 gaining new insight into the biochemical mechanisms of various subtypes of ASD 3 identifying biomolecular targets for new modes of therapy, and 4 providing the basis for individualized treatment recommendations.

  7. 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

  8. Simultaneous Determination of Underivatized Vitamin B1 and B6 in Whole Blood by Reversed Phase Ultra High Performance Liquid Chromatography Tandem Mass Spectrometry

    OpenAIRE

    Puts, Johan; de Groot, Monique; Haex, Martin; Jakobs, Bernadette

    2015-01-01

    Background Vitamin B1 (thiamine-diphosphate) and B6 (pyridoxal-5’phosphate) are micronutrients. Analysis of these micronutrients is important to diagnose potential deficiency which often occurs in elderly people due to malnutrition, in severe alcoholism and in gastrointestinal compromise due to bypass surgery or disease. Existing High Performance Liquid Chromatography (HPLC) based methods include the need for derivatization and long analysis time. We developed an Ultra High Performance Liquid...

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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 ...

  15. 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

    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...

  16. 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

  17. 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

  18. 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

    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...

  19. 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...

  20. 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

  1. No Evidence to Suggest that the Use of Acetylcholinesterase Inhibitors Confounds the Results of Two Blood-Based Biomarker Studies in Alzheimer's Disease

    OpenAIRE

    Chiam, Justin Tao Wen; Lunnon, Katie; Voyle, Nicola; Proitsi, Petroula; Coppola, Giovanni; Geschwind, Daniel,; Nelson, Sally; Johnston, Caroline; Soininen, Hilkka; Kłoszewska, Iwona; Mecocci, Patrizia; Tsolakik, Magda; Vellas, Bruno; Hodges, Angela; Lovestone, Simon

    2015-01-01

    Background: There is an urgent need to discover Alzheimer's disease (AD) biomarkers that are both easily measured and reliable. Research into blood-based biomarkers for AD using transcriptomics and proteomics has been an attractive and promising area of research. However, to date researchers have not looked into the possibility of AD medication being a confounding factor in these studies. Objective: This study explored whether acetylcholinesterase inhibitors (AChEIs), the main class of AD med...

  2. 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

  3. CYP7B1

    DEFF Research Database (Denmark)

    Roos, P; Svenstrup, K; Danielsen, E R;

    2014-01-01

    UNLABELLED: The SPG5A subtype of Hereditary Spastic Paraplegia (HSP) is a rare autosomal recessive neurodegenerative disorder caused by mutations in the CYP7B1 gene, which encodes a steroid cytochrome P450 7α-hydroxylase. This enzyme provides the primary metabolic route for neurosteroids. Clinica......UNLABELLED: The SPG5A subtype of Hereditary Spastic Paraplegia (HSP) is a rare autosomal recessive neurodegenerative disorder caused by mutations in the CYP7B1 gene, which encodes a steroid cytochrome P450 7α-hydroxylase. This enzyme provides the primary metabolic route for neurosteroids...

  4. 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

  5. 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

  6. 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.

  7. 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 ...

  8. 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

  9. Bovine blood biomarkers as a way of processed animal proteins detection in feedingstuffs

    OpenAIRE

    Lecrenier, Marie-Caroline; Marbaix, Hélène; Veys, Pascal; Dieu, Marc; Raes, Martine; Berben, Gilbert; Saegerman, Claude; Baeten, Vincent

    2015-01-01

    The prohibition of using animal by-products in feedingstuffs depends on two factors: their nature defined by the tissue/cell type and the species of origin, and on their destination (pets, fur animals or other farmed animals). Proteomics is particularly well-suited to the purpose of PAPs detection as it is a tissue and species-specific method. The aim of this study was the identification and the selection of specific peptide biomarkers using tandem mass spectrometry for the detection of b...

  10. 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

  11. 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...

  12. 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 ...

  13. The Red Blood Cell as a Gender-Associated Biomarker in Metabolic Syndrome: A Pilot Study

    OpenAIRE

    Elisabetta Straface; Lucrezia Gambardella; Antonella Mattatelli; Emanuele Canali; Francesca Boccalini; Luciano Agati; Walter Malorni

    2011-01-01

    In the present pilot study (56 patients), some red blood cell parameters in samples from patients with metabolic syndrome and subclinical atherosclerosis, but without any sign of coronary artery disease, have been analyzed. The main goal of this work was to determine, in this preclinical state, new peripheral gender-associated bioindicators of possible diagnostic or prognostic value. In particular, three different “indicators” of red blood cell injury and aging have been evaluated: glycophori...

  14. 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

  15. A case-controlled validation study of a blood-based seven-gene biomarker panel for colorectal cancer in Malaysia

    Directory of Open Access Journals (Sweden)

    Yip Kok-Thye

    2010-09-01

    Full Text Available Abstract Background Colorectal cancer (CRC screening is key to CRC prevention and mortality reduction, but patient compliance with CRC screening is low. We previously reported a blood-based test for CRC that utilizes a seven-gene panel of biomarkers. The test is currently utilized clinically in North America for CRC risk stratification in the average-risk North American population in order to improve screening compliance and to enhance clinical decision making. Methods In this study, conducted in Malaysia, we evaluated the seven-gene biomarker panel validated in a North American population using blood samples collected from local patients. The panel employs quantitative RT-PCR (qRT-PCR to analyze gene expression of the seven biomarkers (ANXA3, CLEC4D, TNFAIP6, LMNB1, PRRG4, VNN1 and IL2RB that are differentially expressed in CRC patients as compared with controls. Blood samples from 210 patients (99 CRC and 111 controls were collected, and total blood RNA was isolated and subjected to quantitative RT-PCR and data analysis. Results The logistic regression analysis of seven-gene panel has an area under the curve (AUC of 0.76 (95% confidence interval: 0.70 to 0.82, 77% specificity, 61% sensitivity and 70% accuracy, comparable to the data obtained from the North American investigation of the same biomarker panel. Conclusions Our results independently confirm the results of the study conducted in North America and demonstrate the ability of the seven biomarker panel to discriminate CRC from controls in blood samples drawn from a Malaysian population.

  16. CYTOKINES IN LACRIMAL FLUID AND BLOOD SERUM: EARLY BIOMARKERS OF AGE-RELATED MACULAR DEGENERATION

    Directory of Open Access Journals (Sweden)

    O. S. Slepova

    2015-06-01

    Full Text Available The article presents results of multiplex cytokine assays in blood serum and lacrimal fluid at the initial and intermediate stages of age-related macular degeneration (AMD. Some features of local and systemic disturbances in the cytokine profile were detected in these patients. It was revealed that the initial stage of AMD was associated with elevated IL-17 levels in lacrimal fluid, along with imbalance between the local increase and systemic decrease of TGF-β1 amounts. Intermediate-stage AMD was associated with increased levels of the most cytokines assayed (except of TGF-β1 in blood serum and lacrimal fluid, thus suggesting stimulation of both pro-inflammatory and angiogenic responses, like as activation of anti-inflammatory and anti-infective factors. 

  17. 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.

  18. Global Screening of Human Cord Blood Proteomes for Biomarkers of Toxic Exposure and Effect

    OpenAIRE

    Colquhoun, David R.; Goldman, Lynn R.; Cole, Robert N.; Gucek, Marjan; Mansharamani, Malini; Witter, Frank R.; Apelberg, Benjamin J.; Halden, Rolf U.

    2008-01-01

    Background Exposures of pregnant women to natural and manmade chemicals can lead to negative health effects in the baby, ranging from low birth weight to developmental defects. In some cases, diseases were postulated to have their basis in toxic exposure in utero or in early childhood. Therefore, an understanding of fetal responses to environmental exposures is essential. To that end, cord blood is a readily accessible biofluid whose proteomic makeup remains mostly unexplored when compared wi...

  19. DJ-1 isoforms in whole blood as potential biomarkers of Parkinson disease

    OpenAIRE

    Lin, Xiangmin; Cook, Travis J.; Zabetian, Cyrus P.; Leverenz, James B.; Peskind, Elaine R.; Hu, Shu-Ching; Cain, Kevin C.; Pan, Catherine; Edgar, John Scott; Goodlett, David R.; Racette, Brad A.; Checkoway, Harvey; Montine, Thomas J.; Shi, Min; Zhang, Jing

    2012-01-01

    DJ-1 is a multifunctional protein that plays an important role in oxidative stress, cell death, and synucleinopathies, including Parkinson disease. Previous studies have demonstrated that total DJ-1 levels decrease in the cerebrospinal fluid, but do not change significantly in human plasma from patients with Parkinson disease when compared with controls. In this study, we measured total DJ-1 and its isoforms in whole blood of patients with Parkinson disease at various stages, Alzheimer diseas...

  20. Biomarkers for Monitoring Pre-Analytical Quality Variation of mRNA in Blood Samples

    Czech Academy of Sciences Publication Activity Database

    Zhang, H.; Korenková, Vlasta; Sjoback, R.; Švec, David; Bjorkman, J.; Kruhoffer, M.; Verderio, P.; Pizzamiglio, S.; Ciniselli, Ch.M.; Wyrich, R.; Oelmueller, U.; Kubista, Mikael; Lindahl, T.; Lonneborg, A.; Rian, E.

    2014-01-01

    Roč. 9, č. 11/e111644 (2014). E-ISSN 1932-6203 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109 Institutional research plan: CEZ:AV0Z50520701 Institutional support: RVO:86652036 Keywords : GENE-EXPRESSION PROFILES * HUMAN WHOLE-BLOOD * TIME RT-PCR Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.234, year: 2014

  1. Effects of metals on blood oxidative stress biomarkers and acetylcholinesterase activity in dice snakes (Natrix tessellata from Serbia

    Directory of Open Access Journals (Sweden)

    Gavrić Jelena P.

    2015-01-01

    Full Text Available The effects of waterborne metals in water on the activities of blood copper-zinc superoxide dismutase (CuZnSOD, catalase (CAT, glutathione peroxidase (GSH-Px, glutathione reductase (GR, glutathione-S-transferase (GST, and acetylcholinesterase (AChE, and on the concentrations of total glutathione (GSH and lipid peroxides (TBARS in the blood of dice snakes (Natrix tessellata caught in Obedska Bara, Sebia (control area, with snakes caught in Pančevački Rit, a contaminated area in Serbia were examined. The activities of CAT, GSH-Px, GR and AChE, and the concentration of TBARS were significantly decreased, while GST activity and GSH concentration were significantly increased in snakes from the contaminated area compared to specimens from the control area. Significantly increased concentrations of Al, As, B, Ba, Ca, Cu, Fe, K, Li, Mn, Na, Ni and Zn in the water at the contaminated area as compared to control area were detected. The metals Ag, Bi, Cd, Co, Hg, In and Tl were not observed in any of the localities. Cr, Mo and Pb were not detected at the control area but were observed at the contaminated area. The concentrations of Sr were similar at both sites. The concentration of Mg was 2-fold higher at the control site than at the contaminated area. The obtained results show that most of the investigated blood biomarkers correlate with concentrations of metals present in the environment. These findings suggest that dice snakes are sensitive bioindicator species for monitoring the effects of increased metal concentrations in the environment. [Projekat Ministarstva nauke Republike Srbije, br. 173041 i br. 173043

  2. Identification of multiple novel protein biomarkers shed by human serous ovarian tumors into the blood of immunocompromised mice and verified in patient sera.

    Directory of Open Access Journals (Sweden)

    Lynn A Beer

    Full Text Available The most cancer-specific biomarkers in blood are likely to be proteins shed directly by the tumor rather than less specific inflammatory or other host responses. The use of xenograft mouse models together with in-depth proteome analysis for identification of human proteins in the mouse blood is an under-utilized strategy that can clearly identify proteins shed by the tumor. In the current study, 268 human proteins shed into mouse blood from human OVCAR-3 serous tumors were identified based upon human vs. mouse species differences using a four-dimensional plasma proteome fractionation strategy. A multi-step prioritization and verification strategy was subsequently developed to efficiently select some of the most promising biomarkers from this large number of candidates. A key step was parallel analysis of human proteins detected in the tumor supernatant, because substantially greater sequence coverage for many of the human proteins initially detected in the xenograft mouse plasma confirmed assignments as tumor-derived human proteins. Verification of candidate biomarkers in patient sera was facilitated by in-depth, label-free quantitative comparisons of serum pools from patients with ovarian cancer and benign ovarian tumors. The only proteins that advanced to multiple reaction monitoring (MRM assay development were those that exhibited increases in ovarian cancer patients compared with benign tumor controls. MRM assays were facilely developed for all 11 novel biomarker candidates selected by this process and analysis of larger pools of patient sera suggested that all 11 proteins are promising candidate biomarkers that should be further evaluated on individual patient blood samples.

  3. 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.

  4. 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

  5. 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.

  6. Using condition factor and blood variable biomarkers in fish to assess water quality.

    Science.gov (United States)

    Sadauskas-Henrique, Helen; Sakuragui, Marise M; Paulino, Marcelo G; Fernandes, Marisa N

    2011-10-01

    The condition factor and blood variables, including erythrocyte lipid peroxidation (LPO) and the activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), in two ecologically distinct fish species (Astyanax fasciatus and Pimelodus maculatus) were evaluated at five sites in the Furnas Hydroelectric Power Station reservoir (Brazil) to assess water quality. Aldrin/dieldrin, endosulfan, heptachlor epoxide, and metolachlor were detected at different concentrations in four of the sites. Condition factor was not directly affected by such contaminants. A negative correlation between hematocrit and heptachlor was detected in P. maculatus. Positive correlations between red blood cells and heptachlor as well as an interactive effect of metolachlor and aldrin/dieldrin were detected in A. fasciatus. The erythrocytes of both species collected from the contaminated sites showed high levels of LPO, an increase in SOD and GPx activities and a decrease in CAT activity. Although the leukocyte number and the differential percentage of leukocytes varied among the sites, the hematological variables, the LPO levels, and the antioxidant enzyme activities could be used to assess water quality, regardless of the differences in the responses of the fish species. PMID:21152972

  7. Low molecular weight blood plasma proteome – a source of differential diagnostic biomarkers of ovarian cancer

    Directory of Open Access Journals (Sweden)

    V. Ye. Shevchenko

    2014-11-01

    Full Text Available At present, there is no screening test for the early detecting of ovarian cancer, one of the most lethal form of gynaecological malignancy in the worldwide. In this study the new methodology for the search of tumor markers of ovarian cancer, involving profiling the low-molecular blood plasma proteomes, is developed, unified and approved. The given approach included three basic components: pre-preparation of samples, matrix-assisted laser desorption / ionization time-of-flight mass spectrometry and bioinformatics software for mass spectral data processing. Opportunities and prospects of the developed approach for the detection of potential ovarian cancer markers were shown. For search of potential tumor markers, screening of 56 blood plasma samples from ovarian cancer patients and 36 benign ovarian neoplasia samples were carried out.As a result of the present research, peptides / polypeptides which can be used in future for detecting this pathology were found out.

  8. aflatoxina b1

    Directory of Open Access Journals (Sweden)

    A. Valdivia

    2004-01-01

    Full Text Available Con el objetivo de probar que la suplementación dietética de ácido elágico (AE o N-Acetilcisteína (NAC en pollos de engorda, atenúa los efectos de una intoxicación aguda por la aflatoxina B1 (AFB1, se intoxicaron con AFB1 pura, tres grupos de diez pollos cada uno (3.0 mb/kg pc, IP. Otros tres grupos recibieron solamente el vehículo (aceite de maíz 2.0 ml/kg pc, IP. Cuatro días antes se administró un alimento testigo, o bien, la misma dieta adicionada con AE (2.5 g/kg o NAC (200 mg/kg pc/6 h. A las 24 horas de la administración de AFB1, se cuantificaron las concentraciones hepáticas de glutatión (GSH, de actividad enzimática específica de la transferasa de glutatión (GST, alanina aminotransferasa, aspartato aminotransferasa y de proteínas hepáticas totales. Los resultados mostraron que NAC atenúa el impacto negativo de la AFB1 sobre el crecimiento corporal y al igual que AE, incrementa la GST y revierte parcialmente los efectos de AFB1 sobre GSH, lo cual sugiere que ambas sustancias pudieran conferir un efecto protector de las aves

  9. B1 Aerogels

    DEFF Research Database (Denmark)

    Duer, Karsten; Svendsen, Sv Aa Højgaard

    1996-01-01

    , engineering and architectural basis which will support the appropriate use of aerogels in windows, solar collectors and passive solar applications, with the aim of saving or producing thermal energy for use in buildings".This objective is in very good agreement with the general scope of task 18 but where Task...... properties of aerogel as a material for window applications3. Construction of an aerogel DGU and measurement of key performance parameters. The goal for the aerogel DGU was to reach a Total Solar Energy Transmittance above 0.75 and a U-value below 0.5 W/m²K. These are values that can not be simultaneously......The report summarizes the work that has been carried out within the project "B1 AEROGELS" as a part of the IEA SH&CP Task 18 "Advanced Glazing and Associated Materials For Solar And Building Applications".By providing at the same time thermal insulation and transparency the silica aerogel is a very...

  10. 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

  11. 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.

  12. Cold homes are associated with poor biomarkers and less blood pressure check-up: English Longitudinal Study of Ageing, 2012-2013.

    Science.gov (United States)

    Shiue, Ivy

    2016-04-01

    It has been known that outdoor temperature influences seasonal fluctuation of blood pressure and cholesterol levels, but the role of indoor temperature has been less studied. Therefore, the aim of the present study was to examine the associations between indoor temperature and biomarkers in a countrywide and population-based setting. Data was retrieved from the English Longitudinal Study of Ageing, 2012-2013. Information on demographics, room temperature and a series of biomarkers measured in the blood and lung was obtained at household interviews. t test, chi-square test and a generalized linear model were performed cross-sectionally. Of 7997 older adults with the valid indoor temperature measurements, there were 1301 (16.3 %) people who resided in cold homes (up. Those who resided in cold homes had higher blood pressure readings, worse handgrip, lower vitamin D levels, higher cholesterol levels, higher insulin-like growth factor levels, higher haemoglobin levels, lower level of white blood cell count and worse lung conditions. One in six older adults aged 50 and above in England resided in cold homes and had poor biomarker values. For the future research direction, studies with a longitudinal approach to systematically monitor indoor temperature, biomarkers and health and wellbeing would be suggested. From the practice and policy perspectives, increasing health knowledge on the adverse effect of low indoor temperature on risks of cardiac and respiratory conditions, affording to the heating and re-designing of residential buildings to keep warm by using efficient energy, should be kept as priority. PMID:26873825

  13. Blood Biomarkers of Late Pregnancy Exposure to Trihalomethanes in Drinking Water and Fetal Growth Measures and Gestational Age in a Chinese Cohort

    OpenAIRE

    Cao, Wen-Cheng; Zeng, Qiang; Luo, Yan; Chen, Hai-Xia; Miao, Dong-Yue; Li, Li; Cheng, Ying-Hui; Li, Min; Wang, Fan; You, Ling; Wang, Yi-Xin; Yang, Pan; Lu, Wen-Qing

    2015-01-01

    Background: Previous studies have suggested that elevated exposure to disinfection by-products (DBPs) in drinking water during gestation may result in adverse birth outcomes. However, the findings of these studies remain inconclusive. Objective: The purpose of our study was to examine the association between blood biomarkers of late pregnancy exposure to trihalomethanes (THMs) in drinking water and fetal growth and gestational age. Methods: We recruited 1,184 pregnant women between 2011 and 2...

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

    OpenAIRE

    Erukainure, Ochuko L.

    2012-01-01

    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 lip...

  15. Relationship of concentrations of cortisol in hair with health, biomarkers in blood, and reproductive status in dairy cows.

    Science.gov (United States)

    Burnett, Tracy A; Madureira, Augusto M L; Silper, Bruna F; Tahmasbi, Abdolmansour; Nadalin, Audrey; Veira, Douglas M; Cerri, Ronaldo L A

    2015-07-01

    Hair cortisol has been used to measure chronic stress in dairy cows as it offers the advantage of being noninvasive, fast, and able to indicate levels of cortisol over long periods. The aim of this study was to determine the associations between hair cortisol with clinical disorders, reproductive status, and the development of subclinical endometritis in dairy cows. Furthermore, we aimed to determine the association between hair cortisol concentrations and blood markers associated with metabolic status and acute inflammation. In experiment 1, cows (n=64) were hair sampled every 3wk from the tail switch beginning at calving (d 0) until d 126 for cortisol analysis; blood samples were collected every 3wk from d 0 until 42 for β-hydroxybutyrate and glucose analysis. In experiment 2, cows (n=54) were chosen retrospectively by diagnosis of subclinical endometritis (END), subclinical endometritis and at least 1 clinical disease (END+CLIN), or as healthy (control) using a cytobrush and ultrasonography at 30±3d in milk. At the same time, animals were hair sampled for cortisol analysis and blood sampled for haptoglobin and ceruloplasmin analysis. Health records were recorded throughout both experimental periods. Animals with clinical disease presented higher cortisol concentrations than clinically healthy animals in experiment 1 [geometric mean (95% confidence interval); 8.8 (7.8, 9.9) vs. 10.7 (9.6, 12.0) pg/mg]; however, animals diagnosed with subclinical endometritis in experiment 2 did not differ in hair cortisol concentrations [11.7 (9.8, 14.0), 12.2 (9.3, 15.9), 10.5 (8.1, 13.6) pg/mg for control, END, and END+CLIN, respectively]. In experiment 1, an effect of sample day was noted, where d 21 had higher cortisol concentrations than d 42, 84, and 126, but not from d 0 for both parities. Within both experiments, a parity effect was present where multiparous animals consistently had higher cortisol concentrations than primiparous animals. Multiparous cows that became

  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. 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.

  18. 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

  19. 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.

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

    International Nuclear Information System (INIS)

    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.

  1. 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

  2. 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

  3. 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.

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

    International Nuclear Information System (INIS)

    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. 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. 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. These results establish a foundation for the further exploration of peripheral blood cells as a surrogate system for biomarker analyses in clinical oncology studies

  5. 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

  6. 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.

  7. Acid-labile protein-adducted heterocyclic aromatic amines in human blood are not viable biomarkers of dietary exposure: A systematic study.

    Science.gov (United States)

    Cooper, Kevin M; Brennan, Sarah F; Woodside, Jayne V; Cantwell, Marie; Guo, Xiaoxiao; Mooney, Mark; Elliott, Christopher T; Cuskelly, Geraldine J

    2016-05-01

    Heterocyclic aromatic amines (HCA) are carcinogenic mutagens formed during cooking of protein-rich foods. HCA residues adducted to blood proteins have been postulated as biomarkers of HCA exposure. However, the viability of quantifying HCAs following hydrolytic release from adducts in vivo and correlation with dietary intake are unproven. To definitively assess the potential of labile HCA-protein adducts as biomarkers, a highly sensitive UPLC-MS/MS method was validated for four major HCAs: 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) and 2-amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline (7,8-DiMeIQx). Limits of detection were 1-5 pg/ml plasma and recoveries 91-115%. Efficacy of hydrolysis was demonstrated by HCA-protein adducts synthesised in vitro. Plasma and 7-day food diaries were collected from 122 fasting adults consuming their habitual diets. Estimated HCA intakes ranged from 0 to 2.5 mg/day. An extensive range of hydrolysis conditions was examined for release of adducted HCAs in plasma. HCA was detected in only one sample (PhIP, 9.7 pg/ml), demonstrating conclusively for the first time that acid-labile HCA adducts do not reflect dietary HCA intake and are present at such low concentrations that they are not feasible biomarkers of exposure. Identification of biomarkers remains important. The search should concentrate on stabilised HCA-peptide markers and use of untargeted proteomic and metabolomic approaches. PMID:26993956

  8. 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.

  9. 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.

  10. 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−...

  11. Susceptibility Contrast Magnetic Resonance Imaging Determination of Fractional Tumor Blood Volume: A Noninvasive Imaging Biomarker of Response to the Vascular Disrupting Agent ZD6126

    International Nuclear Information System (INIS)

    Purpose: To assess tumor fractional blood volume (ξ), determined in vivo by susceptibility contrast magnetic resonance imaging (MRI) as a noninvasive imaging biomarker of tumor response to the vascular disrupting agent ZD6126. Methods and Materials: The transverse MRI relaxation rate R2* of rat GH3 prolactinomas was quantified prior to and following injection of 2.5 mgFe/kg feruglose, an ultrasmall superparamagnetic iron oxide intravascular contrast agent, and ξ (%) was determined from the change in R2*. The rats were then treated with either saline or 50 mg/kg ZD6126, and ξ measured again 24 hours later. Following posttreatment MRI, Hoechst 33342 (15 mg/kg) was administered to the rats and histological correlates from composite images of tumor perfusion and necrosis sought. Results: Irrespective of treatment, tumor volume significantly increased over 24 hours. Saline-treated tumors showed no statistically significant change in ξ, whereas a significant (p = 0.002) 70% reduction in ξ of the ZD6126-treated cohort was determined. Hoechst 33342 uptake was associated with viable tumor tissue and was significantly (p = 0.004) reduced and restricted to the rim of the ZD6126-treated tumors. A significant positive correlation between posttreatment ξ and Hoechst 33342 uptake was obtained (r = 0.83, p = 0.002), providing validation of the MRI-derived measurements of fractional tumor blood volume. Conclusions: These data clearly highlight the potential of susceptibility contrast MRI with ultrasmall superparamagnetic iron oxide contrast agents to provide quantitative imaging biomarkers of fractional tumor blood volume at high spatial resolution to assess tumor vascular status and response to vascular disrupting agents

  12. Whole Grain Rye Intake, Reflected by a Biomarker, Is Associated with Favorable Blood Lipid Outcomes in Subjects with the Metabolic Syndrome – A Randomized Study

    Science.gov (United States)

    Magnusdottir, Ola Kally; Landberg, Rikard; Gunnarsdottir, Ingibjorg; Cloetens, Lieselotte; Åkesson, Björn; Rosqvist, Fredrik; Schwab, Ursula; Herzig, Karl-Heinz; Hukkanen, Janne; Savolainen, Markku J.; Brader, Lea; Hermansen, Kjeld; Kolehmainen, Marjukka; Poutanen, Kaisa; Uusitupa, Matti; Risérus, Ulf; Thorsdottir, Inga

    2014-01-01

    Background and Aim Few studies have explored the possible plasma cholesterol lowering effects of rye consumption. The aim of this secondary analysis in the SYSDIET study was to investigate the association between plasma alkylresorcinols (AR), a biomarker for whole grain wheat and rye intake, and blood lipid concentrations in a population with metabolic syndrome. Furthermore, we analyzed the associations between the AR C17∶0/C21∶0 ratio, a suggested marker of the relative intake of whole grain/bran rye, and blood lipid concentrations. Methods Participants were 30–65 years of age, with body mass index (BMI) 27–40 kg/m2 and had metabolic syndrome. Individuals were recruited through six centers in the Nordic countries and randomized either to a healthy Nordic diet (ND, n = 93), rich in whole grain rye and wheat, as well as berries, fruits and vegetables, rapeseed oil, three fish meals per week and low-fat dairy products, or a control diet (n = 65) for 18/24 weeks. Associations between total plasma AR concentration and C17∶0/C21∶0 homologue ratio and blood lipids were investigated in pooled (ND + control group) regression analyses at 18/24 weeks adjusted for baseline value for the dependent variable, age, BMI and statin use. Results When adjusted for confounders, total plasma AR at 18/24 weeks was not significantly associated with blood lipids but the AR ratio C17∶0/C21∶0 was inversely associated with LDL cholesterol concentrations (B (95% CI): −0.41 (−0.80 to −0.02)), log LDL/HDL cholesterol ratio (−0.20 (−0.37 to −0.03)), log non-HDL cholesterol (−0.20 (−0.37 to −0.03)), log apolipoprotein B (−0.12 (−0.24 to 0.00)) and log triglyceride concentrations (−0.35 (−0.59 to −0.12)). Discussion Increased proportion of whole grain rye, reflected by a biomarker, in the diet is associated with favorable blood lipid outcomes, a relationship that should be further investigated. Trial Registration ClinicalTrials.gov NCT00992641

  13. 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.

  14. Amyloid-β-Secondary Structure Distribution in Cerebrospinal Fluid and Blood Measured by an Immuno-Infrared-Sensor: A Biomarker Candidate for Alzheimer's Disease.

    Science.gov (United States)

    Nabers, Andreas; Ollesch, Julian; Schartner, Jonas; Kötting, Carsten; Genius, Just; Hafermann, Henning; Klafki, Hans; Gerwert, Klaus; Wiltfang, Jens

    2016-03-01

    The misfolding of the Amyloid-beta (Aβ) peptide into β-sheet enriched conformations was proposed as an early event in Alzheimer's Disease (AD). Here, the Aβ peptide secondary structure distribution in cerebrospinal fluid (CSF) and blood plasma of 141 patients was measured with an immuno-infrared-sensor. The sensor detected the amide I band, which reflects the overall secondary structure distribution of all Aβ peptides extracted from the body fluid. We observed a significant downshift of the amide I band frequency of Aβ peptides in Dementia Alzheimer type (DAT) patients, which indicated an overall shift to β-sheet. The secondary structure distribution of all Aβ peptides provides a better marker for DAT detection than a single Aβ misfold or the concentration of a specific oligomer. The discrimination between DAT and disease control patients according to the amide I frequency was in excellent agreement with the clinical diagnosis (accuracy 90% for CSF and 84% for blood). The amide I band maximum above or below the decisive marker frequency appears as a novel spectral biomarker candidate of AD. Additionally, a preliminary proof-of-concept study indicated an amide I band shift below the marker band already in patients with mild cognitive impairment due to AD. The presented immuno-IR-sensor method represents a promising, simple, robust, and label-free diagnostic tool for CSF and blood analysis. PMID:26828829

  15. 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.

  16. 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

  17. 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

    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...

  18. Changes in cytokine and biomarker blood levels in patients with colorectal cancer during dendritic cell-based vaccination

    DEFF Research Database (Denmark)

    Burgdorf, Stefan; Claesson, Mogens; Nielsen, Hans; Rosenberg, Jacob

    Introduction. Immunotherapy based on dendritic cell vaccination has exciting perspectives for treatment of cancer. In order to clarify immunological mechanisms during vaccination it is essential with intensive monitoring of the responses. This may lead to optimization of treatment and prediction of......-inflammatory cytokines in serum of patients who achieved stable disease following vaccination suggest the occurrence of vaccine-induced Th1 responses. Since Th1 responses seem to be essential in cancer immunotherapy this may indicate a therapeutic potential of the vaccine....... responding patients. The aim of this study was to evaluate cytokine and biomarker responses in patients with colorectal cancer treated with a cancer vaccine based on dendritic cells pulsed with an allogeneic melanoma cell lysate. Material and methods. Plasma and serum samples were collected prior to...

  19. Changes in cytokine and biomarker blood levels in patients with colorectal cancer during dendritic cell-based vaccination

    DEFF Research Database (Denmark)

    Burgdorf, Stefan K; Claesson, Mogens Helweg; Nielsen, Hans J; Rosenberg, Jacob

    2009-01-01

    Introduction. Immunotherapy based on dendritic cell vaccination has exciting perspectives for treatment of cancer. In order to clarify immunological mechanisms during vaccination it is essential with intensive monitoring of the responses. This may lead to optimization of treatment and prediction of......-inflammatory cytokines in serum of patients who achieved stable disease following vaccination suggest the occurrence of vaccine-induced Th1 responses. Since Th1 responses seem to be essential in cancer immunotherapy this may indicate a therapeutic potential of the vaccine....... responding patients. The aim of this study was to evaluate cytokine and biomarker responses in patients with colorectal cancer treated with a cancer vaccine based on dendritic cells pulsed with an allogeneic melanoma cell lysate. Material and methods. Plasma and serum samples were collected prior to...

  20. Development and Validation of a Prognostic Model Using Blood Biomarker Information for Prediction of Survival of Non-Small-Cell Lung Cancer Patients Treated With Combined Chemotherapy and Radiation or Radiotherapy Alone (NCT00181519, NCT00573040, and NCT00572325)

    International Nuclear Information System (INIS)

    Purpose: Currently, prediction of survival for non-small-cell lung cancer patients treated with (chemo)radiotherapy is mainly based on clinical factors. The hypothesis of this prospective study was that blood biomarkers related to hypoxia, inflammation, and tumor load would have an added prognostic value for predicting survival. Methods and Materials: Clinical data and blood samples were collected prospectively (NCT00181519, NCT00573040, and NCT00572325) from 106 inoperable non-small-cell lung cancer patients (Stages I-IIIB), treated with curative intent with radiotherapy alone or combined with chemotherapy. Blood biomarkers, including lactate dehydrogenase, C-reactive protein, osteopontin, carbonic anhydrase IX, interleukin (IL) 6, IL-8, carcinoembryonic antigen (CEA), and cytokeratin fragment 21-1, were measured. A multivariate model, built on a large patient population (N = 322) and externally validated, was used as a baseline model. An extended model was created by selecting additional biomarkers. The model's performance was expressed as the area under the curve (AUC) of the receiver operating characteristic and assessed by use of leave-one-out cross validation as well as a validation cohort (n = 52). Results: The baseline model consisted of gender, World Health Organization performance status, forced expiratory volume, number of positive lymph node stations, and gross tumor volume and yielded an AUC of 0.72. The extended model included two additional blood biomarkers (CEA and IL-6) and resulted in a leave-one-out AUC of 0.81. The performance of the extended model was significantly better than the clinical model (p = 0.004). The AUC on the validation cohort was 0.66 and 0.76, respectively. Conclusions: The performance of the prognostic model for survival improved markedly by adding two blood biomarkers: CEA and IL-6.

  1. 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

    Raptors are exposed to biomagnifying and toxic organohalogenated compounds (OHCs) such as organochlorines, brominated flame retardants and perfluorinated compounds. To investigate how OHC exposure may affect biochemical pathways we collected blood plasma from Norwegian northern goshawk (n=56......), 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...... were also negatively correlated to PCBs and PFCs, respectively. The most significant relationships were found for the highly contaminated northern goshawks and white-tailed eagles. The statistical relationships between OHCs and BCCPs indicate that biochemical pathways could be influenced while it is...

  2. Using a Systems Pharmacology Model of the Blood Coagulation Network to Predict the Effects of Various Therapies on Biomarkers

    OpenAIRE

    S. Nayak; Lee, D.; Patel-Hett, S; Pittman, DD; Martin, SW; Heatherington, AC; Vicini, P.; F. Hua

    2015-01-01

    A number of therapeutics have been developed or are under development aiming to modulate the coagulation network to treat various diseases. We used a systems model to better understand the effect of modulating various components on blood coagulation. A computational model of the coagulation network was built to match in-house in vitro thrombin generation and activated Partial Thromboplastin Time (aPTT) data with various concentrations of recombinant factor VIIa (FVIIa) or factor Xa added to n...

  3. 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.

  4. 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

  5. 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.)

  6. 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.)

  7. 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

  8. 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

  9. 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)

  10. 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

  11. 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

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

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    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.

  13. 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.

  14. Detection of Alpha-Methylacyl-CoA Racemase (AMACR, a Biomarker of Prostate Cancer, in Patient Blood Samples Using a Nanoparticle Electrochemical Biosensor

    Directory of Open Access Journals (Sweden)

    Chung Chiun Liu

    2012-09-01

    Full Text Available Although still commonly used in clinical practice to screen and diagnose prostate cancer, there are numerous weaknesses of prostate-specific antigen (PSA testing, including lack of specificity and the inability to distinguish between aggressive and indolent cancers. A promising prostate cancer biomarker, alpha-methylacyl-CoA racemase (AMACR, has been previously demonstrated to distinguish cancer from healthy and benign prostate cells with high sensitivity and specificity. However, no accurate clinically useful assay has been developed. This study reports the development of a single use, disposable biosensor for AMACR detection. Human blood samples were used to verify its validity, reproducibility and reliability. Plasma samples from 9 healthy males, 10 patients with high grade prostatic intraepithelial neoplasia (HGPIN, and 5 prostate cancer patients were measured for AMACR levels. The average AMACR levels in the prostate cancer patients was 10 fold higher (mean(SD = 0.077 (0.10 than either the controls (mean(SD = 0.005 (0.001 or HGPIN patients (mean(SD = 0.004 (0.0005. At a cutoff of between 0.08 and 0.9, we are able to achieve 100% accuracy in separating prostate cancer patients from controls. Our results provide strong evidence demonstrating that this biosensor can perform as a reliable assay for prostate cancer detection and diagnosis.

  15. 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.

  16. Expression of Two Basic mRNA Biomarkers in Peripheral Blood of Patients with Non-Small Cell Lung Cancer Detected by Real-Time RT-PCR, Individually and Simultaneously

    OpenAIRE

    Karimi, Shirin; Mohamadnia, Abdolreza; Nadji, Seyed Alireza; Yadegarazari, Reza; Khosravi, Adnan; Bahrami, Naghmeh; Saidijam, Massoud

    2015-01-01

    Introduction: Although extensive research has been conducted on lung cancer markers, a singular clinically applicable marker has not been found yet. The objective of this study was to evaluate the sensitivity and the specificity of carcinoembryonic antigen (CEA) mRNA and lung-specific X protein (LUNX) mRNA biomarkers in peripheral blood to detect lung cancer individually and simultaneously. Methods: Thirty patients affected by lung cancer and 30 healthy individuals were studied in this resear...

  17. 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

  18. 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

  19. 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

  20. 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.

  1. The body vitamin B1 levels of rats fed a diet containing the minimum requirement of vitamin B1 is reduced by exercise.

    Science.gov (United States)

    Shibata, Katsumi; Fukuwatari, Tsutomu

    2013-01-01

    It is thought that increasing energy expenditure increases consumption of vitamin B1, leading to an increase in the requirement of vitamin B1. However, evidence supporting this hypothesis is lacking. To examine the hypothesis, initially, we determined the minimum requirement of vitamin B1 for weaning rats. We found that the minimum requirement of vitamin B1 for optimum growth of weaning rats was around 0.786 mg thiamin/kg diet. Next, rats fed a diet containing the minimum requirement of vitamin B1 were forced to swim until exhaustion. Concentrations of vitamin B1 in the blood and liver as well as urinary excretion of swimming rats decreased significantly compared with those of non-swimming rats (prats fed the diet containing a sufficient amount of vitamin B1 (4.720 mg thiamin/kg diet), vitamin B1 amounts in the blood, liver and urine were not affected by swimming. We clearly and firstly showed the reduction of body vitamin B1 following increases in energy expenditure. PMID:23727637

  2. 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

  3. 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.

  4. Cytogenetic damage in Turkish coke oven workers exposed to polycyclic aromatic hydrocarbons: Association with CYP1A1, CYP1B1, EPHX1, GSTM1, GSTT1, and GSTP1 gene polymorphisms.

    Science.gov (United States)

    Ada, Ahmet Oguz; Demiroglu, Canan; Yilmazer, Meltem; Suzen, Halit Sinan; Demirbag, Ali Eba; Efe, Sibel; Alemdar, Yilmaz; Iscan, Mumtaz; Burgaz, Sema

    2013-09-01

    The aim of this study was to determine the frequencies of chromosomal aberrations (CA) and cytochalasin-blocked micronuclei (CBMN) in peripheral blood lymphocytes from Turkish coke oven workers and the influence of CYP1A1, CYP1B1, EPHX1, GSTM1, GSTT1, and GSTP1 gene polymorphisms on these biomarkers. Cytogenetic analysis showed that occupational exposure significantly increased the CA and CBMN frequencies. Gene polymorphisms, on the other hand, did not affect CA or CBMN in either exposed or control subjects. However, due to the limited sample size, our findings need to be verified in future studies with a larger sample. PMID:24084344

  5. Aflatoxin B1: Mechanism of mutagenesis

    Directory of Open Access Journals (Sweden)

    Regina M. Santella

    2007-02-01

    Full Text Available

    Aflatoxins are a group of toxic and carcinogenic fungal metabolites that frequently contaminate corn, peanuts and other products. Aflatoxin B1 (AFB1, the most potent of these, is metabolized by the cytochrome P450 system into a number of hydroxylated metabolites and glutathione conjugates in the process of conversion to more hydrophilic forms for urinary excretion. Unfortunately, one of these metabolites is the aflatoxin-8,9-epoxide that is produced in two forms, endo and exo. Glutathione S-transferases (GST are able to conjugate and detoxify this reactive intermediate. Species differences in susceptibility to the effects of AFB1 are partially related to differences in expression of specific GSTs that are able to conjugate the epoxide to glutathione. The exo epoxide is able to intercalate into DNA and this is followed by reaction of the C8 position of the epoxide with the N7 position of guanine.

    NMR studies of oligonucleotide duplexes containing the adduct have demonstrated that the adduct exists with the aromatic portion intercalated on the 5' face of the guanine residue with Watson-Crick base pairing maintained.

    However, this covalent adduct is chemically unstable due to the charge on the ribose ring. As a result, the guanine can be released from the DNA leaving an apurinic site. This released guanine adduct can be detected in the urine and serves as a biomarker of exposure to AFB1. Alternatively, the ribose ring opens forming a stable formamidopyrimidine (FAPY adduct. This adduct somewhat stabilizes the DNA duplex. Time course studies in animals have demonstrated that the N7 adduct is rapidly removed, probably because it causes more distortion in the helix, while the FAPY adduct is more

  6. Biomarkers of environmental benzene exposure.

    OpenAIRE

    Weisel, C; Yu, R; Roy, A; Georgopoulos, P.

    1996-01-01

    Environmental exposures to benzene result in increases in body burden that are reflected in various biomarkers of exposure, including benzene in exhaled breath, benzene in blood and urinary trans-trans-muconic acid and S-phenylmercapturic acid. A review of the literature indicates that these biomarkers can be used to distinguish populations with different levels of exposure (such as smokers from nonsmokers and occupationally exposed from environmentally exposed populations) and to determine d...

  7. Aflatoxin B1content in patients with hepatic diseases Aflatoxina B1 en pacientes con enfermedades hepáticas

    Directory of Open Access Journals (Sweden)

    Clara López

    2002-08-01

    Full Text Available Aflatoxins are toxic metabolites of some Aspergillus flavus, A. parasiticus and A. nomius strains that occur in many foods and feeds. There are four major natural occurring aflatoxins: B1, B2, G1 and G2. These toxins can cause illness in human beings and animals. Aflatoxin B1 is the most abundant and toxic member of the family, and it is also the most potent hepatocarcinogen known. In order to estimate the potential human health risk of AFB1, it is useful to measure blood concentration. The presence of aflatoxin B1 in patients was evaluated by high-performance liquid chromatography, in serum samples, obtained from 20 patient volunteers with hepatic disease. Out of the 20 patients, the presence of AFB1 was detected in only one of them, in a concentration of 0.47 ng/cm³. Nevertheless, this result should draw the attention of control organizations in Argentina to the need for a thorough food and feed inspection.Las aflatoxinas son metabolitos tóxicos producidos por cepas de Aspergillus flavus, A. parasiticus y A. nomius, presentes en alimentos y piensos. Las cuatro aflatoxinas principales son: aflatoxina B1, B2, G1 y G2. Dichas toxinas pueden causar enfermedades tanto en seres humanos como en animales. La aflatoxina B1 es la más abundante y la más tóxica del grupo y es también el más potente hepatocarcinógeno conocido. El objetivo de este trabajo fue detectar la presencia de aflatoxina B1 en sangre humana para estimar el riesgo potencial de la salud. La determinación de aflatoxina B1 fue realizada por cromatografía líquida de alto rendimiento, en suero de 20 pacientes voluntarios con enfermedades hepáticas. En sólo uno de estos pacientes se detectó la presencia de aflatoxina B1, en una concentración de 0.47ng/cm³. Estos resultados deberían ser tenidos en cuenta por los responsables de la vigilancia y control de los alimentos en la Argentina.

  8. 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.

  9. Plexin-B1 silencing inhibits ovarian cancer cell migration and invasion

    International Nuclear Information System (INIS)

    . Plexin-B1 expression correlates with malignant phenotypes of serous ovarian tumors, probably via phosphorylation of AKT at Ser473, suggesting that Plexin-B1 might be a useful biomarker and/or a novel therapeutic target

  10. 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.

  11. Fungal degradation of aflatoxin B1.

    Science.gov (United States)

    Shantha, T

    1999-01-01

    A number of fungal cultures were screened to select an organism suitable to be used in the detoxification of aflatoxin B1. They were co-cultured in Czapek-Dox-Casamino acid medium with aflatoxin B1 producing Aspergillus flavus. Several fungal cultures were found to prevent synthesis of aflatoxin B1 in liquid culture medium. Among these Phoma sp., Mucor sp., Trichoderma harzianum, Trichoderma sp. 639, Rhizopus sp. 663, Rhizopus sp. 710, Rhizopus sp. 668, Alternaria sp. and some strains belonging to the Sporotrichum group (ADA IV B14(a), ADA SF VI BF (9), strain 720) could inhibit aflatoxin synthesis by > or =90%. A few fungi, namely ADA IV B1, ADA F1, ADA F8, also belonging to the Sporotrichum group, were less efficient than the Phoma sp. The Cladosporium sp. and A. terreus sp. were by far the least efficient, registering aflatoxin biosynthesis are also capable of degrading the preformed toxin. Among these, Phoma sp. was the most efficient destroying about 99% of aflatoxin B1. The cell free extract of Phoma sp. destroyed nearly 50 microg aflatoxin B1 100 ml(-1) culture medium (90% of the added toxin), and this was more effective than its own culture filtrate over 5 days incubation at 28+/-2 degrees C. The degradation was gradual: 35% at 24 h, 58% at 48 h, 65% at 72 h, 85% at 96 h and 90% at 120 h. The possibility of a heat stable enzymatic activity in the cell free extract of Phoma is proposed. PMID:10945479

  12. Observation of B-meson decays to b_1 pi and b_1 K

    CERN Document Server

    Aubert, B; Boutigny, D; Karyotakis, Yu; Lees, J P; Poireau, V; Prudent, X; Tisserand, V; Zghiche, A; Garra Tico, J; Graugès-Pous, E; López, L; Palano, A; Pappagallo, M; Eigen, G; Stugu, B; Sun, L; Abrams, G S; Battaglia, M; Brown, D N; Button-Shafer, J; Cahn, R N; Groysman, Y; Jacobsen, R G; Kadyk, J A; Kerth, L T; Kolomensky, Yu G; Kukartsev, G; Lopes-Pegna, D; Lynch, G; Mir, L M; Orimoto, T J; Osipenkov, I L; Ronan, M T; Tackmann, K; Tanabé, T; Wenzel, W A; Del Amo-Sánchez, P; Hawkes, C M; Watson, A T; Held, T; Koch, H; Pelizaeus, M; Schröder, T; Steinke, M; Walker, D; Asgeirsson, D J; Çuhadar-Dönszelmann, T; Fulsom, B G; Hearty, C; Mattison, T S; McKenna, J A; Khan, A; Saleem, M; Teodorescu, L; Blinov, V E; Bukin, A D; Druzhinin, V P; Golubev, V B; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Todyshev, K Yu; Bondioli, M; Curry, S; Eschrich, I; Kirkby, D; Lankford, A J; Lund, P; Mandelkern, M; Martin, E C; Stoker, D P; Abachi, S; Buchanan, C; Foulkes, S D; Gary, J W; Liu, F; Long, O; Shen, B C; Zhang, L; Paar, H P; Rahatlou, S; Sharma, V; Berryhill, J W; Campagnari, C; Cunha, A; Dahmes, B; Hong, T M; Kovalskyi, D; Richman, J D; Beck, T W; Eisner, A M; Flacco, C J; Heusch, C A; Kroseberg, J; Lockman, W S; Schalk, T; Schumm, B A; Seiden, A; Wilson, M G; Winstrom, L O; Chen, E; Cheng, C H; Fang, F; Hitlin, D G; Narsky, I; Piatenko, T; Porter, F C; Andreassen, R; Mancinelli, G; Meadows, B T; Mishra, K; Sokoloff, M D; Blanc, F; Bloom, P C; Chen, S; Ford, W T; Hirschauer, J F; Kreisel, A; Nagel, M; Nauenberg, U; Olivas, A; Smith, J G; Ulmer, K A; Wagner, S R; Zhang, J; Gabareen, A M; Soffer, A; Toki, W H; Wilson, R J; Winklmeier, F; Altenburg, D D; Feltresi, E; Hauke, A; Jasper, H; Merkel, J; Petzold, A; Spaan, B; Wacker, K; Klose, V; Kobel, M J; Lacker, H M; Mader, W F; Nogowski, R; Schubert, J; Schubert, K R; Schwierz, R; Sundermann, J E; Volk, A; Bernard, D; Bonneaud, G R; Latour, E; Lombardo, V; Thiebaux, C; Verderi, M; Clark, P J; Gradl, W; Muheim, F; Playfer, S; Robertson, A I; Watson, J E; Xie, Y; Andreotti, M; Bettoni, D; Bozzi, C; Calabrese, R; Cecchi, A; Cibinetto, G; Franchini, P; Luppi, E; Negrini, M; Petrella, A; Piemontese, L; Prencipe, E; Santoro, V; Anulli, F; Baldini-Ferroli, R; Calcaterra, A; De Sangro, R; Finocchiaro, G; Pacetti, S; Patteri, P; Peruzzi, I M; Piccolo, M; Rama, M; Zallo, A; Buzzo, A; Contri, R; Lo Vetere, M; Macri, M M; Monge, M R; Passaggio, S; Patrignani, C; Robutti, E; Santroni, A; Tosi, S; Chaisanguanthum, K S; Morii, M; Wu, J; Dubitzky, R S; Marks, J; Schenk, S; Uwer, U; Bard, D J; Dauncey, P D; Flack, R L; Nash, J A; Panduro-Vazquez, W; Tibbetts, M; Behera, P K; Chai, X; Charles, M J; Mallik, U; Ziegler, V; Cochran, J; Crawley, H B; Dong, L; Eyges, V; Meyer, W T; Prell, S; Rosenberg, E I; Rubin, A E; Gao, Y Y; Gritsan, A V; Guo, Z J; Lae, C K; Denig, A G; Fritsch, M; Schott, G; Arnaud, N; Bequilleux, J; D'Orazio, A; Davier, M; Grosdidier, G; Höcker, A; Lepeltier, V; Le Diberder, F; Lutz, A M; Pruvot, S; Rodier, S; Roudeau, P; Schune, M H; Serrano, J; Sordini, V; Stocchi, A; Wang, W F; Wormser, G; Lange, D J; Wright, D M; Bingham, I; Burke, J P; Chavez, C A; Forster, I J; Fry, J R; Gabathuler, E; Gamet, R; Hutchcroft, D E; Payne, D J; Schofield, K C; Touramanis, C; Bevan, A J; George, K A; Di Lodovico, F; Menges, W; Sacco, R; Cowan, G; Flächer, H U; Hopkins, D A; Paramesvaran, S; Salvatore, F; Wren, A C; Brown, D N; Davis, C L; Allison, J; Barlow, N R; Barlow, R J; Chia, Y M; Edgar, C L; Lafferty, G D; West, T J; Yi, J I; Anderson, J; Chen, C; Jawahery, A; Roberts, D A; Simi, G; Tuggle, J M; Blaylock, G; Dallapiccola, C; Hertzbach, S S; Li, X; Moore, T B; Salvati, E; Saremi, S; Cowan, R; Dujmic, D; Fisher, P H; Koeneke, K; Sciolla, G; Sekula, S J; Spitznagel, M; Taylor, F; Yamamoto, R K; Zhao, M; Zheng, Y; Mclachlin, S E; Patel, P M; Robertson, S H; Lazzaro, A; Palombo, F; Bauer, J M; Cremaldi, L; Eschenburg, V; Godang, R; Kroeger, R; Sanders, D A; Summers, D J; Zhao, H W; Brunet, S; Côté, D; Simard, M; Taras, P; Viaud, F B; Nicholson, H; De Nardo, Gallieno; Fabozzi, F; Lista, L; Monorchio, D; Sciacca, C; Baak, M A; Raven, G; Snoek, H L; Jessop, C P; Knoepfel, K J; LoSecco, J M; Benelli, G; Corwin, L A; Honscheid, K; Kagan, H; Kass, R; Morris, J P; Rahimi, A M; Regensburger, J J; Wong, Q K; Blount, N L; Brau, J E; Frey, R; Igonkina, O; Kolb, J A; Lu, M; Rahmat, R; Sinev, N B; Strom, D; Strube, J; Torrence, E; Gagliardi, N; Gaz, A; Margoni, M; Morandin, M; Pompili, A; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Voci, C; Ben-Haim, E; Briand, H; Calderini, G; Chauveau, J; David, P; Del Buono, L; De La Vaissière, C; Hamon, O; Leruste, P; Malcles, J; Ocariz, J; Pérez, A; Prendki, J; Gladney, L; Biasini, M; Covarelli, R; Manoni, E; Angelini, C; Batignani, G; Bettarini, S; Carpinelli, M; Cenci, R; Cervelli, A; Forti, F; Giorgi, M A; Lusiani, A; Marchiori, G; Mazur, M A; Morganti, M; Neri, N; Paoloni, E; Rizzo, G; Walsh, J J; Haire, M; Biesiada, J; Elmer, P; Lau, Y P; Lü, C; Olsen, J; Smith, A J S; Telnov, A V; Baracchini, E; Bellini, F; Cavoto, G; Del Re, D; Di Marco, E; Faccini, R; Ferrarotto, F; Ferroni, F; Gaspero, M; Jackson, P D; Li Gioi, L; Mazzoni, M A; Morganti, S; Piredda, G; Polci, F; Renga, F; Voena, C; Ebert, M; Hartmann, T; Schröder, H; Waldi, R; Adye, T; Castelli, G; Franek, B; Olaiya, E O; Ricciardi, S; Röthel, W; Wilson, F F; Emery, S; Escalier, M; Gaidot, A; Ganzhur, S F; Hamel de Monchenault, G; Kozanecki, W; Vasseur, G; Yéche, C; Zito, M; Chen, X R; Liu, H; Park, W; Purohit, M V; Wilson, J R; Allen, M T; Aston, D; Bartoldus, R; Bechtle, P; Berger, N; Claus, R; Coleman, J P; Convery, M R; Dingfelder, J C; Dorfan, J; Dubois-Felsmann, G P; Dunwoodie, W; Field, R C; Glanzman, T; Gowdy, S J; Graham, M T; Grenier, P; Hast, C; Hrynóva, T; Innes, W R; Kaminski, J; Kelsey, M H; Kim, H; Kim, P; Kocian, M L; Leith, D W G S; Li, S; Luitz, S; Lüth, V; Lynch, H L; MacFarlane, D B; Marsiske, H; Messner, R; Müller, D R; O'Grady, C P; Ofte, I; Perazzo, A; Perl, M; Pulliam, T; Ratcliff, B N; Roodman, A; Salnikov, A A; Schindler, R H; Schwiening, J; Snyder, A; Stelzer, J; Su, D; Sullivan, M K; Suzuki, K; Swain, S K; Thompson, J M; Vavra, J; Van Bakel, N; Wagner, A P; Weaver, M; Wisniewski, W J; Wittgen, M; Wright, D H; Yarritu, A K; Yi, K; Young, C C; Burchat, P R; Edwards, A J; Majewski, S A; Petersen, B A; Wilden, L; Ahmed, S; Alam, M S; Bula, R; Ernst, J A; Jain, V; Pan, B; Saeed, M A; Wappler, F R; Zain, S B; Krishnamurthy, M; Spanier, S M; Eckmann, R; Ritchie, J L; Ruland, A M; Schilling, C J; Schwitters, R F; Izen, J M; Lou, X C; Ye, S; Bianchi, F; Gallo, F; Gamba, D; Pelliccioni, M; Bomben, M; Bosisio, L; Cartaro, C; Cossutti, F; Della Ricca, G; Lanceri, L; Vitale, L; Azzolini, V; Lopez-March, N; Martínez-Vidal, F; Milanes, D A; Oyanguren, A; Albert, J; Banerjee, Sw; Bhuyan, B; Hamano, K; Kowalewski, R; Nugent, I M; Roney, J M; Sobie, R J; Harrison, P F; Ilic, J; Latham, T E; Mohanty, G B; Band, H R; Chen, X; Dasu, S; Flood, K T; Hollar, J J; Kutter, P E; Pan, Y; Pierini, M; Prepost, R; Wu, S L; Neal, H

    2007-01-01

    We present the results of searches for decays of B mesons to final states with a b_1 meson and a charged pion or kaon. The data, collected with the BaBar detector at the Stanford Linear Accelerator Center, represent 382 million B-Bbar pairs produced in e+e- annihilation. The results for the branching fractions are, in units of 10^{-6}, B(B+ -> b1^0 pi+) = 6.7 +/- 1.7 +/- 1.0 (4.0 sigma), B(B+ -> b1^0 K+ = 9.1+/- 1.7+/- 1.0 (5.3 sigma), B(B0 -> b1^-/+ pi^+/-) = 10.9 +/- 1.2 +/- 0.9 (8.9 sigma), and B(B0 -> b1^-K+) = 7.4 +/- 1.0 +/- 1.0 (6.1 sigma), with the assumption that B(b_1 -> omega pi)=1. We also measure charge and flavor asymmetries Ach(B+ -> b1^0 pi+) = 0.05 +/- 0.16 +/- 0.02, Ach(B+ -> b1^0 K+ = -0.46 +/- 0.20 +/- 0.02, Ach(B0 -> b1^-/+ pi^+/-) = -0.05 +/- 0.10 +/- 0.02, C(B0 -> b1^-/+ pi^+/-) = -0.22 +/- 0.23 +/- 0.05, deltaC(B0 -> b1^-/+ pi^+/-) = -1.04 +/- 0.23 +/- 0.08, and Ach(B0 -> b1^-K+) = -0.07 +/- 0.12 +/- 0.02, The first error quoted is statistical, the second systematic, and for the branch...

  13. A Blood Spot Method for Detecting Fumonisin-Induced Changes in Putative Sphingolipid Biomarkers in LM/Bc Mice and Humans

    Science.gov (United States)

    Fumonisin B1 (FB1) is a toxic chemical produced by molds. The molds that produce fumonisin are common in corn. Consumption of contaminated corn by farm animals has been shown to be the cause of disease. Fumonisin has been hypothesized to be an environmental risk factor for diseases in humans in c...

  14. 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.; Lauridsen, S. T.; Knuthsen, Pia; Sandström, B.; Dragsted, Lars Ove

    1999-01-01

    Seven men and seven women participated in a randomized crossover trial to study the effect of intake of parsley (Petroselinum crispum), containing high levels of the flavone apigenin, on the urinary excretion of flavones and on biomarkers for oxidative stress. The subjects received a strictly...... intervention with parsley (P <0.005) as compared with the levels on the basic diet, whereas erythrocyte 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. In this short-term investigation, an overall decreasing trend in the activity of antioxidant enzymes was observed during the 2-week study. The decreased activity of SOD was strongly correlated at the individual level with an increased oxidative damage to plasma proteins. However, the intervention...

  15. 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

  16. 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.

  17. Biomarkers for Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Rikako Ishigamori

    2010-09-01

    Full Text Available Colorectal cancer (CRC is the third most common epithelial malignancy in the world. Since CRC develops slowly from removable precancerous lesions, detection of the lesion at an early stage by regular health examinations can reduce the incidence and mortality of this malignancy. Colonoscopy significantly improves the detection rate of CRC, but the examination is expensive and inconvenient. Therefore, we need novel biomarkers that are non-invasive to enable us to detect CRC quite early. A number of validation studies have been conducted to evaluate genetic, epigenetic or protein markers for identification in the stool and/or serum. Currently, the fecal occult blood test is the most widely used method of screening for CRC. However, advances in genomics and proteomics will lead to the discovery of novel non-invasive biomarkers.

  18. 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)

  19. 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

    Seven men and seven women participated in a randomized crossover trial to study the effect of intake of parsley (Petroselinum crispum), containing high levels of the flavone apigenin, on the urinary excretion of flavones and on biomarkers for oxidative stress. The subjects received a strictly....... In this short-term investigation, an overall decreasing trend in the activity of antioxidant enzymes was observed during the 2-week study. The decreased activity of SOD was strongly correlated at the individual level with an increased oxidative damage to plasma proteins. However, the intervention with parsley...

  20. Imaging Biomarkers or Biomarker Imaging?

    Directory of Open Access Journals (Sweden)

    Markus Mitterhauser

    2014-06-01

    Full Text Available Since biomarker imaging is traditionally understood as imaging of molecular probes, we highly recommend to avoid any confusion with the previously defined term “imaging biomarkers” and, therefore, only use “molecular probe imaging (MPI” in that context. Molecular probes (MPs comprise all kinds of molecules administered to an organism which inherently carry a signalling moiety. This review highlights the basic concepts and differences of molecular probe imaging using specific biomarkers. In particular, PET radiopharmaceuticals are discussed in more detail. Specific radiochemical and radiopharmacological aspects as well as some legal issues are presented.

  1. 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

  2. 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.

  3. 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

  4. 118-B-1 excavation treatability test procedures

    International Nuclear Information System (INIS)

    This treatability study has two purposes: to support development of the approach to be used for burial ground remediation, and to provide specific engineering information for the design of burial grounds receiving waste generated from the 100 Area removal actions. Data generated from this test will also provide performance and cost information necessary for detailed analysis of alternatives for burial ground remediation. Further details on the test requirements, milestones and data quality objectives are described in detail in the 118-B-1 Excavation Treatability Test Plan (DOE/RL-94-43). These working procedures are intended for use by field personnel to implement the requirements of the milestone. A copy of the detailed Test Plan will be kept on file at the on-site field support trailer, and will be available for review by field personnel

  5. 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.

  6. 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

  7. 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...

  8. 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

  9. 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 ...

  10. Up-regulation and subcellular localization of hnRNP A2/B1 in the development of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Hepatocellular carcinoma (HCC) is one of the world's leading causes of death among cancer patients. It is important to find a new biomarker that diagnoses HCC and monitors its treatment. In our previous work, we screened a single-chain antibody (scFv) N14, which could specifically recognize human HepG2 HCC cells but not human non-cancerous liver LO2 cells. However, the antigen it recognized in the cells remained unknown. Recombinant scFv N14 antibody was expressed as an active antibody. Using this antibody with a combination of immunological and proteomic approaches, we identified the antigen of scFv N14 antibody as the heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1). The expression of hnRNP A2/B1 in HCC cells was then investigated by semi-quantitative RT-PCR and immunohistochemistry. We found that the up-regulation of hnRNP A2/B1 was measured at both transcriptional and translational levels in rat HCC cells but not in rat hepatic cells. We also found that in various human hepatic tissues, hnRNP A2/B1 was highly expressed in both human hepatitis virus positive liver tissues and human HCC tissues but not in normal liver tissues. Interestingly, we observed that the localization of hnRNP A2/B1 in HCC cells was altered during the development of HCC. In human hepatitis virus infected tissues hnRNP A2/B1 resides exclusively in the nuclei of hepatocytes. However, when the HCC progressed from a well differentiated to a poorly differentiated stage, hnRNP A2/B1 was increasingly localized in the cytoplasm. In contrast, the HCC tissues with hnRNP A2/B1 highly expressed in the nucleus decreased. This work is the first to show that hnRNP A2/B1 is the antigen specifically recognized by the scFv N14 antibody in HCC cells. The over-expression of hnRNP A2/B1 was confirmed in cultured human and rat HCC cell lines, human virus related hepatitis liver tissues and human HCC tissues. The increased localization of hnRNP A2/B1 in the cytoplasm of HCC cells was revealed

  11. Vitamin B1 (thiamine) and dementia.

    Science.gov (United States)

    Gibson, Gary E; Hirsch, Joseph A; Fonzetti, Pasquale; Jordan, Barry D; Cirio, Rosanna T; Elder, Jessica

    2016-03-01

    The earliest and perhaps best example of an interaction between nutrition and dementia is related to thiamine (vitamin B1). Throughout the last century, research showed that thiamine deficiency is associated with neurological problems, including cognitive deficits and encephalopathy. Multiple similarities exist between classical thiamine deficiency and Alzheimer's disease (AD) in that both are associated with cognitive deficits and reductions in brain glucose metabolism. Thiamine-dependent enzymes are critical components of glucose metabolism that are reduced in the brains of AD patients and by thiamine decline, and a decrease in their levels could account for the reduction in glucose metabolism. In preclinical models, reduced thiamine can drive AD-like abnormalities, including memory deficits, neuritic plaques, and hyperphosphorylation of tau. Furthermore, excess thiamine diminishes AD-like pathologies. In addition to dietary deficits, drugs or other manipulations that interfere with thiamine absorption can cause thiamine deficiency. Elucidating the reasons why the brains of AD patients are functionally thiamine deficient and determining the effects of thiamine restoration may provide critical information to help treat patients with AD. PMID:26971083

  12. Increased selective 10B-uptake by malignant melanoma using systemic administration of 10B1-BPA·fructose complex

    International Nuclear Information System (INIS)

    10B1-para-Boronophenylalanine (10B1-BPA) has selective affinity for malignant melanoma. In the authors' first human case, they succeeded in obtaining complete regression of a metastatic subcutaneous melanoma lesion by neutron capture therapy (NCT) using distant perilesional injections of 10B1-BPA hydrochloride. Furthermore, they have cured primary cutaneous melanoma lesions of various types in 5 additional patients by single or one repeated NCT using a combination of oral administration, subcutaneous and distant perilesional injections of 10B1-BPA·fructose complex at around pH 7.4. They have been pursuing NCT using increased systemic administration of 10B1-BPA, which can lead to cure of multiple (widely-distributed) melanoma lesions. In this study, they analyzed boron dynamics in melanoma, skin and blood in tumor-bearing hamsters and a human patient after intravenous (i.v.) or subcutaneous (s.c.) injection of 10B1-BPA·fructose complex

  13. Assessment of Multi-Mycotoxin Exposure in Southern Italy by Urinary Multi-Biomarker Determination

    OpenAIRE

    Solfrizzo, Michele; Gambacorta, Lucia; Visconti, Angelo

    2014-01-01

    Human exposure assessment to deoxynivalenol (DON), aflatoxin B1 (AFB1), fumonisin B1 (FB1), zearalenone (ZEA) and ochratoxin A (OTA) can be performed by measuring their urinary biomarkers. Suitable biomarkers of exposure for these mycotoxins are DON + de-epoxydeoxynivalenol (DOM-1), aflatoxin M1 (AFM1), FB1, ZEA + α-zearalenol (α-ZOL) + β-zearalenol (β-ZOL) and OTA, respectively. An UPLC-MS/MS multi-biomarker method was used to detect and measure incidence and levels of these biomarkers in ur...

  14. Calcium Homeostasis and Muscle Energy Metabolism Are Modified in HspB1-Null Mice

    OpenAIRE

    Brigitte Picard; Malek Kammoun; Mohammed Gagaoua; Christiane Barboiron; Bruno Meunier; Christophe Chambon; Isabelle Cassar-Malek

    2016-01-01

    Hsp27—encoded by HspB1—is a member of the small heat shock proteins (sHsp, 12–43 kDa (kilodalton)) family. This protein is constitutively present in a wide variety of tissues and in many cell lines. The abundance of Hsp27 is highest in skeletal muscle, indicating a crucial role for muscle physiology. The protein identified as a beef tenderness biomarker was found at a crucial hub in a functional network involved in beef tenderness. The aim of this study was to analyze the proteins impacted by...

  15. 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

  16. 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...

  17. Biomarkers of Peripheral Arterial Disease

    OpenAIRE

    Cooke, John P.; Wilson, Andrew M.

    2010-01-01

    Atherosclerotic arterial occlusive disease affecting the lower extremities is also known as peripheral arterial disease (PAD). This disorder affects 8 to 12 million individuals in the United States, and is also increasingly prevalent in Europe and Asia (1–4). Unfortunately, most patients are not diagnosed and are not optimally treated. A blood test for PAD, if sufficiently sensitive and specific, would be expected to improve recognition and treatment of these individuals. Even a biomarker pan...

  18. Compound list: aflatoxin B1 [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available aflatoxin B1 AFB1 00165 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/aflat...oxin_B1.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/aflatoxin_B1.Rat.in_vivo.Liver.Single.zip ...

  19. 76 FR 60457 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-09-29

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of... Proposed Issuance of Letter of Offer Pursuant to Section 36(b)(1)of the Arms Export Control Act...

  20. 77 FR 46417 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2012-08-03

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section... Section 36(b)(1) Of the Arms Export Control Act, as amended (i) Prospective Purchaser: Thailand (ii)...

  1. 77 FR 42707 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2012-07-20

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of... Letter of Offer Pursuant to Section 36(b)(1) of the Arms Export Control Act, as amended (i)...

  2. 76 FR 60467 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-09-29

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of... Letter of Offer Pursuant to Section 36(b)(1) of the Arms Export Control Act (i) Prospective...

  3. 78 FR 62588 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-10-22

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of... Letter of Offer Pursuant to Section 36(b)(1) of the Arms Export Control Act, as amended (i)...

  4. 76 FR 60471 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-09-29

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section... Proposed Issuance of Letter of Offer Pursuant to Section 36(b)(1) of the Arms Export Control Act,...

  5. 78 FR 62600 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-10-22

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of... Proposed Issuance of Letter of Offer Pursuant to Section 36(b)(1) of the Arms Export Control Act,...

  6. 78 FR 15004 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-03-08

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of... Proposed Issuance of Letter of Offer Pursuant to Section 36(b)(1) of the Arms Export Control Act,...

  7. 78 FR 46579 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-08-01

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section... Letter of Offer Pursuant to Section 36(b)(1) of the Arms Export Control Act, as Amended (i)...

  8. 77 FR 37879 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2012-06-25

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section... Proposed Issuance of Letter of Offer Pursuant to Section 36(b)(1) of the Arms Export Control Act,...

  9. 78 FR 50047 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-08-16

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of... Letter of Offer Pursuant to Section 36(b) (1) Of the Arms Export Control Act, as amended (i)...

  10. 77 FR 51780 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2012-08-27

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section... Letter of Offer Pursuant to Section 36(b)(1) of the Arms Export Control Act, as amended (i)...

  11. 77 FR 42711 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2012-07-20

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section... Letter of Offer Pursuant to Section 36(b)(1) of the Arms Export Control Act, as Amended (i)...

  12. 76 FR 76954 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-12-09

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section... Proposed Issuance of Letter of Offer Pursuant to Section 36(b)(1) of the Arms Export Control Act,...

  13. 78 FR 72066 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-12-02

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section... Proposed Issuance of Letter of Offer Pursuant to Section 36(b)(1) of the Arms Export Control Act,...

  14. 78 FR 26324 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-05-06

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of... No. 13-20 Notice of Proposed Issuance of Letter of Offer Pursuant to Section 36(b)(1) of the...

  15. 77 FR 75617 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2012-12-21

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of... Proposed Issuance of Letter of Offer Pursuant to Section 36(b)(1) of the Arms Export Control Act,...

  16. 76 FR 56181 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-09-12

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section... Section 36(b)(1) of the Arms Export Control Act, as amended (i) Prospective Purchaser: Peru (ii)...

  17. 76 FR 77809 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-12-14

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of... Letter of Offer Pursuant to Section 36(b)(1) of the Arms Export Control Act, as Amended (i)...

  18. 78 FR 701 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-01-04

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of... Letter of Offer Pursuant to Section 36(b)(1) of the Arms Export Control Act, as amended (i)...

  19. 76 FR 60455 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-09-29

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section... Proposed Issuance of Letter of Offer Pursuant to Section 36(b)(1) of the Arms Export Control Act,...

  20. 77 FR 37881 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2012-06-25

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of... Proposed Issuance of Letter of Offer Pursuant to Section 36(b)(1) of the Arms Export Control Act,...

  1. 78 FR 78939 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-12-27

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section... Transmittal No. 13-68 Notice of Proposed Issuance of Letter of Offer Pursuant to Section 36(b)(1) of the...

  2. 26 CFR 301.7701(b)-1 - Resident alien.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Resident alien. 301.7701(b)-1 Section 301.7701... ADMINISTRATION PROCEDURE AND ADMINISTRATION Definitions § 301.7701(b)-1 Resident alien. (a) Scope. Section 301.7701(b)-1(b) provides rules for determining whether an alien individual is a lawful permanent...

  3. 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

  4. 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

  5. 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

  6. 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.

  7. Cytochrome 450 1B1 (CYP1B1 polymorphisms associated with response to docetaxel in Castration-Resistant Prostate Cancer (CRPC patients

    Directory of Open Access Journals (Sweden)

    Price Douglas K

    2010-09-01

    Full Text Available Abstract Background The selection of patients according to key genetic characteristics may help to tailor chemotherapy and optimize the treatment in Castration-Resistant Prostate Cancer (CRPC patients. Functional polymorphisms within the cytochrome P450 1B1 (CYP1B1 gene have been associated with alterations in enzymatic expression and activity and may change sensitivity to the widely used docetaxel regimen. Methods CYP1B1 genotyping was performed on blood samples of 60 CRPC patients treated with docetaxel, using TaqMan probes-based assays. Association between CYP1B1-142C>G (leading to the 48ArgGly transition, 4326C>G (432LeuVal, and 4390A>G (453AsnSer polymorphisms and treatment response, progression-free-survival (PFS and overall-survival (OS was estimated using Pearson χ2 test, Kaplan-Meier curves and Log-rank test. Results Patients carrying the CYP1B1-432ValVal genotype experienced a significantly lower response-rate (P = 0.014, shorter progression-free-survival (P = 0.032 and overall-survival (P Conclusions CYP1B1-4326C>G (432LeuVal polymorphism emerged as possible predictive marker of response and clinical outcome to docetaxel in CRPC patients and may represent a potential new tool for treatment optimization. Larger prospective trials are warranted to validate these findings, which might be applied to the future practice of CRPC treatment.

  8. Biomarkers in dementia: clinical utility and new directions

    OpenAIRE

    Ahmed, R. M.; Paterson, R. W.; Warren, J D; Zetterberg, H.; O'Brien, J. T.; Fox, N C; Halliday, G. M.; Schott, J M

    2014-01-01

    Imaging, cerebrospinal fluid (CSF) and blood-based biomarkers have the potential to improve the accuracy by which specific causes of dementia can be diagnosed in vivo, provide insights into the underlying pathophysiology, and may be used as inclusion criteria and outcome measures for clinical trials. While a number of imaging and CSF biomarkers are currently used for each of these purposes, this is an evolving field, with numerous potential biomarkers in varying stages of research and develop...

  9. Effects of chlorophyll and chlorophyllin on low-dose aflatoxin B1 pharmacokinetics in human volunteers: A pilot study

    International Nuclear Information System (INIS)

    Chlorophyll (Chla) and chlorophyllin (CHL) were shown previously to reduce carcinogen bioavailability, biomarker damage, and tumorigenicity in trout and rats. These findings were partially extended to humans (Proc Natl Acad Sci USA 98, 14601-14606 (2001)), where CHL reduced excretion of aflatoxin B1 (AFB1)-DNA repair products in Chinese unavoidably exposed to dietary AFB1. However, neither AFB1 pharmacokinetics nor Chla effects were examined. We conducted a small unblinded crossover study to establish AFB1 pharmacokinetic parameters in human volunteers, and to explore possible effects of CHL or Chla co-treatment on those parameters. For protocol 1, fasted subjects received an IRB-approved dose of 14C-AFB1 (30 ng, 5 nCi) by capsule with 100 ml water, followed by normal eating and drinking after hr 2. Blood and cumulative urine samples were collected over 72 hr, and 14C-AFB1 equivalents were determined by Accelerator Mass Spectrometry. Protocols 2 and 3 were similar except capsules also contained 150 mg of purified Chla, or CHL, respectively. All protocols were repeated 3 times for each of three volunteers. The study revealed rapid human AFB1 uptake (plasma ka 5.05 ± 1.10 hr-1, Tmax 1.0 hr) and urinary elimination (95% complete by 24 hr) kinetics. Chla and CHL treatment each significantly impeded AFB1 absorption and reduced Cmax and AUC's (plasma and urine) in one or more subjects. These initial results provide AFB1 pharmacokinetic parameters previously unavailable for humans, and suggest that Chla or CHL co-consumption may limit the bioavailability of ingested aflatoxin in humans, as they do in animal models.

  10. 26 CFR 301.6223(b)-1 - Notice group.

    Science.gov (United States)

    2010-04-01

    ... October 4, 2001. For years beginning prior to October 4, 2001, see § 301.6223(b)-1T contained in 26 CFR... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Notice group. 301.6223(b)-1 Section 301.6223(b... ADMINISTRATION PROCEDURE AND ADMINISTRATION Assessment In General § 301.6223(b)-1 Notice group. (a) In...

  11. 26 CFR 301.6226(b)-1 - 5-percent group.

    Science.gov (United States)

    2010-04-01

    ... beginning prior to October 4, 2001, see § 301.6226(b)-1T contained in 26 CFR part 1, revised April 1, 2001. ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false 5-percent group. 301.6226(b)-1 Section 301.6226... ADMINISTRATION PROCEDURE AND ADMINISTRATION Assessment In General § 301.6226(b)-1 5-percent group. (a) In...

  12. Surface Binding of Aflatoxin B1 by Lactic Acid Bacteria

    OpenAIRE

    Haskard, Carolyn A.; El-Nezami, Hani S.; Kankaanpää, Pasi E.; Salminen, Seppo; Ahokas, Jorma T.

    2001-01-01

    Specific lactic acid bacterial strains remove toxins from liquid media by physical binding. The stability of the aflatoxin B1 complexes formed with 12 bacterial strains in both viable and nonviable (heat- or acid-treated) forms was assessed by repetitive aqueous extraction. By the fifth extraction, up to 71% of the total aflatoxin B1 remained bound. Nonviable bacteria retained the highest amount of aflatoxin B1. Lactobacillus rhamnosus strain GG (ATCC 53103) and L. rhamnosus strain LC-705 (DS...

  13. 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

  14. 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....

  15. 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...

  16. Calcium Homeostasis and Muscle Energy Metabolism Are Modified in HspB1-Null Mice

    Directory of Open Access Journals (Sweden)

    Brigitte Picard

    2016-05-01

    Full Text Available Hsp27—encoded by HspB1—is a member of the small heat shock proteins (sHsp, 12–43 kDa (kilodalton family. This protein is constitutively present in a wide variety of tissues and in many cell lines. The abundance of Hsp27 is highest in skeletal muscle, indicating a crucial role for muscle physiology. The protein identified as a beef tenderness biomarker was found at a crucial hub in a functional network involved in beef tenderness. The aim of this study was to analyze the proteins impacted by the targeted invalidation of HspB1 in the Tibialis anterior muscle of the mouse. Comparative proteomics using two-dimensional gel electrophoresis revealed 22 spots that were differentially abundant between HspB1-null mice and their controls that could be identified by mass spectrometry. Eighteen spots were more abundant in the muscle of the mutant mice, and four were less abundant. The proteins impacted by the absence of Hsp27 belonged mainly to calcium homeostasis (Srl and Calsq1, contraction (TnnT3, energy metabolism (Tpi1, Mdh1, PdhB, Ckm, Pygm, ApoA1 and the Hsp proteins family (HspA9. These data suggest a crucial role for these proteins in meat tenderization. The information gained by this study could also be helpful to predict the side effects of Hsp27 depletion in muscle development and pathologies linked to small Hsps.

  17. Could a B-1 cell derived phagocyte "be one" of the peritoneal macrophages during LPS-driven inflammation?

    Directory of Open Access Journals (Sweden)

    Ana Flavia Popi

    Full Text Available The inflammatory response is driven by signals that recruit and elicit immune cells to areas of tissue damage or infection. The concept of a mononuclear phagocyte system postulates that monocytes circulating in the bloodstream are recruited to inflamed tissues where they give rise to macrophages. A recent publication demonstrated that the large increase in the macrophages observed during infection was the result of the multiplication of these cells rather than the recruitment of blood monocytes. We demonstrated previously that B-1 cells undergo differentiation to acquire a mononuclear phagocyte phenotype in vitro (B-1CDP, and we propose that B-1 cells could be an alternative origin for peritoneal macrophages. A number of recent studies that describe the phagocytic and microbicidal activity of B-1 cells in vitro and in vivo support this hypothesis. Based on these findings, we further investigated the differentiation of B-1 cells into phagocytes in vivo in response to LPS-induced inflammation. Therefore, we investigated the role of B-1 cells in the composition of the peritoneal macrophage population after LPS stimulation using osteopetrotic mice, BALB/Xid mice and the depletion of monocytes/macrophages by clodronate treatment. We show that peritoneal macrophages appear in op/op((-/- mice after LPS stimulation and exhibit the same Ig gene rearrangement (VH11 that is often found in B-1 cells. These results strongly suggest that op/op((-/- peritoneal "macrophages" are B-1CDP. Similarly, the LPS-induced increase in the macrophage population was observed even following monocyte/macrophage depletion by clodronate. After monocyte/macrophage depletion by clodronate, LPS-elicited macrophages were observed in BALB/Xid mice only following the transfer of B-1 cells. Based on these data, we confirmed that B-1 cell differentiation into phagocytes also occurs in vivo. In conclusion, the results strongly suggest that B-1 cell derived phagocytes are a component of

  18. OECD 28-days oral toxicity study on fumonisin B1

    NARCIS (Netherlands)

    Nijs M de; Egmond HP van; Jong WH de; Loveren H van; LPI; ARO; MGB

    1999-01-01

    Het beschreven experiment werd uitgevoerd om inzicht te verkrijgen over effecten van lage doseringen fumonisine B1 op target organen en het immuunsysteem. Mannelijke ratten van drie weken oud werden oraal via maagsonde behandeld met 0, 0,19, 0,75 of 3 mg/kg lichaamsgewicht fumonisine B1, dagelij

  19. 26 CFR 1.7702B-1 - Consumer protection provisions.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Consumer protection provisions. 1.7702B-1 Section 1.7702B-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME... policies, unintentional lapse, disclosure, prohibitions against post-claims underwriting, minimum...

  20. 29 CFR 2520.104b-1 - Disclosure.

    Science.gov (United States)

    2010-07-01

    ... of this chapter, and section 414(b) of the Internal Revenue Code of 1954 and 26 CFR 1.414(f) (40 FR... 29 Labor 9 2010-07-01 2010-07-01 false Disclosure. 2520.104b-1 Section 2520.104b-1 Labor... REPORTING AND DISCLOSURE UNDER THE EMPLOYEE RETIREMENT INCOME SECURITY ACT OF 1974 RULES AND REGULATIONS...

  1. 78 FR 26326 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-05-06

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section...)(1) of the Arms Export Control Act, as amended (i) Prospective Purchaser: United Kingdom (ii)...

  2. 75 FR 60424 - 36(b)(1) Arms Sales Notifications

    Science.gov (United States)

    2010-09-30

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notifications AGENCY: Defense Security Cooperation Agency, DoD...(b)(1) arms sales notifications to fulfill the requirements of section 155 of Public Law...

  3. 76 FR 26707 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-05-09

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements...

  4. 76 FR 28956 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-05-19

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of...

  5. 75 FR 62792 - 36(b)(1) Arms Sales Notifications

    Science.gov (United States)

    2010-10-13

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notifications AGENCY: Defense Security Cooperation Agency, DoD... 36(b)(1) arms sales notifications to fulfill the requirements of section 155 of Public Law...

  6. 75 FR 74014 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2010-11-30

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of...

  7. 75 FR 81993 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2010-12-29

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of...

  8. 76 FR 37075 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-06-24

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of...

  9. 76 FR 37078 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-06-24

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of...

  10. 75 FR 20571 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2010-04-20

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD...(b)(1) arms sales notifications to fulfill the requirements of section 155 of Public Law...

  11. 75 FR 62767 - 36(b)(1) Arms Sales Notifications

    Science.gov (United States)

    2010-10-13

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notifications AGENCY: Defense Security Cooperation Agency, DoD... 36(b)(1) arms sales notifications to fulfill the requirements of section 155 of Public Law...

  12. 76 FR 29212 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-05-20

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements...

  13. 75 FR 48646 - 36(b)(1) Arms Sales Notifications

    Science.gov (United States)

    2010-08-11

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notifications AGENCY: Defense Security Cooperation Agency, DoD... 36(b)(1) arms sales notifications to fulfill the requirements of section 155 of Public Law...

  14. 76 FR 37071 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-06-24

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of...

  15. 75 FR 74011 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2010-11-30

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of...

  16. 76 FR 38371 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-06-30

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of...

  17. 17 CFR 260.10b-1 - Calculation of percentages.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Calculation of percentages. 260.10b-1 Section 260.10b-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... Calculation of percentages. The percentages of voting securities and other securities specified in section...

  18. SerpinB1 Promotes Pancreatic β Cell Proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Quaamari, Abdelfattah; Dirice, Ercument; Gedeon, Nicholas; Hu, Jiang; Zhou, Jian-Ying; Shirakawa, Jun; Hou, Lifei; Goodman, Jessica; Karampelias, Christos; Qiang, Guifeng; Boucher, Jeremie; Martinez, Rachael; Gritsenko, Marina A.; De Jesus, Dario F.; Kahraman, Sevim; Bhatt, Shweta; Smith, Richard D.; Beer, Hans-Dietmar; Jungtrakoon, Prapaporn; Gong, Yanping; Goldfine, Allison B.; Liew, Chong Wee; Doria, Alessandro; Andersson, Olov; Qian, Weijun; Remold-O' Donnell, Eileen; Kulkami, Rohit N.

    2016-01-12

    Compensatory β-cell growth in response to insulin resistance is a common feature in diabetes. We recently reported that liver-derived factors participate in this compensatory response in the liver insulin receptor knockout (LIRKO) mouse, a model of significant islet hyperplasia. Here we show that serpinB1 is a liver-derived secretory protein that controls β-cell proliferation. SerpinB1 is abundant in the hepatocyte secretome and sera derived from LIRKO mice. SerpinB1 and small molecule compounds that partially mimic serpinB1 activity enhanced proliferation of zebrafish, mouse and human β-cells. We report that serpinB1-induced β-cell replication requires protease inhibition activity and mice lacking serpinB1 exhibit attenuated β-cell replication in response to insulin resistance. Finally, SerpinB1-treatment of islets modulated signaling proteins in growth and survival pathways such as MAPK, PKA and GSK3. Together, these data implicate SerpinB1 as a protein that can potentially be harnessed to enhance functional β-cell mass in patients with diabetes.

  19. 26 CFR 1.280B-1 - Demolition of structures.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 3 2010-04-01 2010-04-01 false Demolition of structures. 1.280B-1 Section 1... (CONTINUED) INCOME TAXES Items Not Deductible § 1.280B-1 Demolition of structures. (a) In general. Section 280B provides that, in the case of the demolition of any structure, no deduction otherwise...

  20. 26 CFR 31.3401(b)-1 - Payroll period.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Payroll period. 31.3401(b)-1 Section 31.3401(b... Collection of Income Tax at Source § 31.3401(b)-1 Payroll period. (a) The term payroll period means the... elapsed and receives the remainder at the end of the week, the payroll period is still the calendar...

  1. 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 and...

  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. Fast 3D B1 mapping. President award proceedings

    International Nuclear Information System (INIS)

    We propose a fast 3-dimensional (3D) B1 mapping method using 3D FLASH (fast low angle shot) with preparation pulses. We optimized scan parameters using a simulation of spin relaxation to achieve the shortest acquisition time while maintaining the accuracy of the B1 map and then applied the method to phantom imaging using a 3-tesla scanner and compared the results with those using DAM (double angle method) to evaluate accuracy. Although there was a slight offset in the B1 value, the distribution of the B1 map was similar between the proposed method and DAM. Acquisition time was 18.3 s for the proposed method and 160 s for DAM. We demonstrated that the proposed method provides fast 3D B1 mapping with equivalent accuracy to that of DAM. (author)

  4. Wind tunnel tests of Risø-B1-18 and Risø-B1-24

    DEFF Research Database (Denmark)

    Fuglsang, P.; Bak, Christian; Gaunaa, Mac;

    2003-01-01

    This report contains 2D measurements of the Risø-B1-18 and Risø-B1-24 airfoils. The aerodynamic properties were derived from pressure measurements on the airfoil surface and in the wake. The measurements were conducted in the VELUX open jet wind tunnel,which has a background turbulence intensity of...

  5. SF3B1 Association with Chromatin Determines Splicing Outcomes

    Directory of Open Access Journals (Sweden)

    Nir Kfir

    2015-04-01

    Full Text Available Much remains unknown concerning the mechanism by which the splicing machinery pinpoints short exons within intronic sequences and how splicing factors are directed to their pre-mRNA targets. One probable explanation lies in differences in chromatin organization between exons and introns. Proteomic, co-immunoprecipitation, and sedimentation analyses described here indicate that SF3B1, an essential splicing component of the U2 snRNP complex, is strongly associated with nucleosomes. ChIP-seq and RNA-seq analyses reveal that SF3B1 specifically binds nucleosomes located at exonic positions. SF3B1 binding is enriched at nucleosomes positioned over short exons flanked by long introns that are also characterized by differential GC content between exons and introns. Disruption of SF3B1 binding to such nucleosomes affects splicing of these exons similarly to SF3B1 knockdown. Our findings suggest that the association of SF3B1 with nucleosomes is functionally important for splice-site recognition and that SF3B1 conveys splicing-relevant information embedded in chromatin structure.

  6. 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 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...... exploratory study indicated that blood levels of biomarkers GFAP and APC-PCI, prior to neuroimaging, may rule out ICH in a mixed stroke population....

  7. The b1 structure function and nuclear pions

    International Nuclear Information System (INIS)

    The b1 structure function is measurable in deep inelastic scattering from polarized nuclei with unpolarized beams. The contributions of nuclear pions are evaluated and found to be small, about 2%. 8 refs

  8. 77 FR 70151 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2012-11-23

    ... Section 36(b)(1) of the Arms Export Control Act, as amended (i) Prospective Purchaser: Indonesia. (ii.... Programs are contained in the system in the form of microprocessors with Read Only Memory (ROM) maps,...

  9. Supercritical Fluid Extraction of Aflatoxin B 1 from Soil

    Science.gov (United States)

    This research describes the development of a Supercritical Fluid Extraction (SFE) method to recover aflatoxin B1 from fortified soil. The effects of temperature, pressure, modifier (identity and percentage), and extraction type were assessed. Using the optimized SFE conditions, ...

  10. 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....

  11. A Clinical Research on the Level of Blood Lipid,Folic Acid,Vitamin B1 2 and Thyroid Hormone of Patients with Mild Cognitive Impairment%老年轻度认知障碍患者血脂、叶酸、维生素B12和甲状腺激素水平的临床研究

    Institute of Scientific and Technical Information of China (English)

    杨青云; 麦惠玲; 陈玉成; 吴满辉

    2015-01-01

    目的:研究老年轻度认知障碍患者血脂、叶酸、维生素 B12、甲状腺激素水平之间的关系。方法:选择2012年7月~2014年9月住院的患者360例,分为MCI组、AD组、对照组,各110、120、70例,比较上述物质的水平。结果:MCI、AD组LDL-C、TC水平比对照组高,维生素B12、叶酸、FT3、T3水平比对照组低,AD组 TSH 比对照组低,MCI 组 TSH 比 AD组高,差异有统计学意义(P<0.05)。结论:TSH 对MCI转 AD 检测具有参考价值,补充叶酸、维生素 B12、降低血脂、保持甲状腺功能正常可能能够防治MCI、AD。%Objective:To study the relationship among the level of blood lipid folic acid,vitamin B12 and thyroid hormone of the elderly patients with mild cognitive impairment.Methods:Select 360 patients hospital-ized during the period from July 2012 to September 2014,,divided them into MCI group AD group and con-trol group,the case in each group were 110,120,70 respectively,compare the level of the components a-bove.Results:In MCI group and AD group ,the level of LDL-Cand TC were higher than that of the control group,the level of vitamin B12,folic acid,FT3 and T3 were lower than that of the control group,the level of TSH of AD group was lower than that of control group,while that of the MCI group was higher than that of the AD group,the difference was statistically significant (P<0.05).Conclusion:TSH can be taken as an reference to detect the transformation from CI to AD detection ,it helps to complement folic acid and vitamin B12,lower the level of blood lipid,maintain normal thyroid function ,prevent and cure MCI and AD.

  12. ESTIMATION OF AFLATOXIN B1 IN FEED INGREDIENTS AND COMPOUND POULTRY FEEDS

    Directory of Open Access Journals (Sweden)

    Bashir Mahmood Bhatti, Tanzeela Talat and Rozina Sardar

    2001-02-01

    Full Text Available A total of 3230 samples of feed ingredients of vegetable and animal origin and commercially available compound poultry feed received over a period of 5 years at Feed Testing Laboratory of the Institute were tested for Aflatoxin B1 contents (ppb . In all feed ingredients and compound feed stuffs, minimum level of aflatoxin B1 was 13 ppb and maximum level was found to be 78 ppb. No correlation of aflatoxin levels with month of collection of the year which are subject to variation in temperature and humidity could be detected. Mean values of aflatoxin concentration in feed stuffs such as rice, rice polish, wheat bran, wheat bread, maize, fish meal, blood meal, bone meal, guar meal, corn gluten 30%, corn gluten 60%, sun flower meal, soyabean meal and cotton seed meal were found to be higher than safe level of 20 ppb recommended by FDA.

  13. 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

  14. Occurrence of aflatoxin B1 in natural products.

    Science.gov (United States)

    Prado, Guilherme; Altoé, Aline F; Gomes, Tatiana C B; Leal, Alexandre S; Morais, Vanessa A D; Oliveira, Marize S; Ferreira, Marli B; Gomes, Mateus B; Paschoal, Fabiano N; von S Souza, Rafael; Silva, Daniela A; Cruz Madeira, Jovita E G

    2012-10-01

    The media claims for the consumption of natural resource-based food have gradually increased in both developing and developed countries. The interest in the safety of these products is partially due to the possible presence of toxigenic fungi acting as mycotoxin producers, such as aflatoxins produced during the secondary metabolism of Aspergillus flavus, A. parasiticus and A. nomius. Aflatoxins, mainly aflatoxin B1, are directly associated with liver cancer in human beings. This paper is aimed at evaluating the presence of aflatoxin B1 in a few vegetable drugs, dried plant extracts and industrialized products traded in 2010 in the city of Belo Horizonte, State of Minas Gerais, Brazil. The method used for the quantification of aflatoxin B1 was based on extraction through acetone:water (85:15), immunoaffinity column purification followed by separation and detection in high efficiency liquid chromatography. Under the conditions of analysis, the Limits of Detection and Quantification were 0.6 µg kg(-1) and 1.0 µg kg(-1) respectively. The complete sets of analyses were carried out in duplicate. Aflatoxin B1 was noticed in a single sample (aflatoxin B1 contamination in the products under analysis. However, it is required to establish a broad monitoring program in order to obtain additional data and check up on the actual extension of contamination. PMID:24031973

  15. Occurrence of aflatoxin B1 in natural products

    Directory of Open Access Journals (Sweden)

    Guilherme Prado

    2012-12-01

    Full Text Available The media claims for the consumption of natural resource-based food have gradually increased in both developing and developed countries. The interest in the safety of these products is partially due to the possible presence of toxigenic fungi acting as mycotoxin producers, such as aflatoxins produced during the secondary metabolism of Aspergillus flavus, A. parasiticus and A. nomius. Aflatoxins, mainly aflatoxin B1, are directly associated with liver cancer in human beings. This paper is aimed at evaluating the presence of aflatoxin B1 in a few vegetable drugs, dried plant extracts and industrialized products traded in 2010 in the city of Belo Horizonte, State of Minas Gerais, Brazil. The method used for the quantification of aflatoxin B1 was based on extraction through acetone:water (85:15, immunoaffinity column purification followed by separation and detection in high efficiency liquid chromatography. Under the conditions of analysis, the Limits of Detection and Quantification were 0.6 µg kg-1 and 1.0 µg kg-1respectively. The complete sets of analyses were carried out in duplicate. Aflatoxin B1 was noticed in a single sample (< 1.0 µg kg-1. The results revealed low aflatoxin B1contamination in the products under analysis. However, it is required to establish a broad monitoring program in order to obtain additional data and check up on the actual extension of contamination.

  16. Mutational properties of the primary aflatoxin B1-DNA adduct.

    OpenAIRE

    Bailey, E A; Iyer, R S; Stone, M. P.; Harris, T M; Essigmann, J M

    1996-01-01

    The mutagenic activity of the major DNA adduct formed by the liver carcinogen aflatoxin B1 (AFB1) was investigated in vivo. An oligonucleotide containing a single 8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B1 (AFB1-N7-Gua) adduct was inserted into the single-stranded genome of bacteriophage M13. Replication in SOS-induced Escherichia coli yielded a mutation frequency for AFB1-N7-Gua of 4%. The predominant mutation was G --> T, identical to the principal mutation in human liver tumors believ...

  17. Variability in equatorial B0 and B1

    International Nuclear Information System (INIS)

    Variability of ionospheric profile parameters B0 and B1, below the F2 peak is investigated for an equatorial station at two levels of solar activities. The whole 24 hours of the day and the four seasons of the year are covered. Absolute and relative variability indices were utilized in the study. Some evidences of correlations of variability index and profiles parameters were observed. Daytime values of relative variability in B1 at solar minimum were found to be greater than those of solar maximum. (author)

  18. Seasonal behaviour of B0 and B1

    International Nuclear Information System (INIS)

    A preliminary analysis of the thickness parameter B0 and the shape parameter B1 is presented. Noon electron density profiles recorded at five ionospheric stations during different seasonal and solar activity conditions are used in the study. The results show that both parameters present a seasonal trend with minimum value for B0 during the local winter and maximum during the local summer. This behaviour is inverted for B1. Discrepancies with IRI-90 model are found. (author). 8 refs, 4 figs, 2 tabs

  19. Base substitution mutations induced by metabolically activated aflatoxin B1.

    Science.gov (United States)

    Foster, P L; Eisenstadt, E; Miller, J H

    1983-05-01

    We have determined the base substitutions generated by metabolically activated aflatoxin B1 in the lacI gene of a uvrB- strain of Escherichia coli. By monitoring over 70 different nonsense mutation sites, we show that activated aflatoxin B1 specifically induced GxC leads to TxA transversions. One possible pathway leading to this base change involves depurination at guanine residues. We consider this mechanism of mutagenesis in the light of our other findings that the carcinogens benzo[a]pyrene diol epoxide and N-acetoxyacetylaminofluorene also specifically induce GxC leads to TxA transversions. PMID:6405385

  20. Base substitution mutations induced by metabolically activated aflatoxin B1.

    OpenAIRE

    Foster, P. L.; Eisenstadt, E; Miller, J H

    1983-01-01

    We have determined the base substitutions generated by metabolically activated aflatoxin B1 in the lacI gene of a uvrB- strain of Escherichia coli. By monitoring over 70 different nonsense mutation sites, we show that activated aflatoxin B1 specifically induced GxC leads to TxA transversions. One possible pathway leading to this base change involves depurination at guanine residues. We consider this mechanism of mutagenesis in the light of our other findings that the carcinogens benzo[a]pyren...

  1. 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

  2. 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.

  3. Hematological Parameters and the State of Liver Cells of Rats After Oral Administration of Aflatoxin B1 Alone and Together with Nanodiamonds

    Science.gov (United States)

    Mogilnaya, O. A.; Puzyr, A. P.; Baron, A. V.; Bondar, V. S.

    2010-05-01

    Hematological parameters and the state of liver cells of rats were examined in vivo after the animals received aflatoxin B1 (AfB1) alone and together with modified nanodiamonds (MND) synthesized by detonation. The rats that had received the MND hydrosol had elevated leukocyte levels, mainly due to higher granulocyte counts and somewhat increased monocyte counts compared to control rats. Hematological parameters of the rats that had received AfB1 alone differed from those of the control rats in another way: total white blood cell counts were significantly lower due to the decreased lymphocyte counts. In rats that had consumed AfB1 with the MND hydrosol, changes in hematological parameters were less pronounced than in rats that had consumed either AfB1 or MND. Electron microscopy showed that hepatocytes of the rats that had received the MND hydrosol or AfB1 with the MND hydrosol contained elevated levels of lipid inclusions and lysosomes. Hyperplasia of the smooth endoplasmic reticulum (EPR) was revealed in liver specimens of the rats that had received AfB1. Results of the study suggest the conclusion about mutual mitigation of the effects of nanoparticles and the mycotoxin on rats blood and liver cells after AfB1 has adsorbed on MND.

  4. Hematological Parameters and the State of Liver Cells of Rats After Oral Administration of Aflatoxin B1 Alone and Together with Nanodiamonds

    Directory of Open Access Journals (Sweden)

    Baron AV

    2010-01-01

    Full Text Available Abstract Hematological parameters and the state of liver cells of rats were examined in vivo after the animals received aflatoxin B1 (AfB1 alone and together with modified nanodiamonds (MND synthesized by detonation. The rats that had received the MND hydrosol had elevated leukocyte levels, mainly due to higher granulocyte counts and somewhat increased monocyte counts compared to control rats. Hematological parameters of the rats that had received AfB1 alone differed from those of the control rats in another way: total white blood cell counts were significantly lower due to the decreased lymphocyte counts. In rats that had consumed AfB1 with the MND hydrosol, changes in hematological parameters were less pronounced than in rats that had consumed either AfB1 or MND. Electron microscopy showed that hepatocytes of the rats that had received the MND hydrosol or AfB1 with the MND hydrosol contained elevated levels of lipid inclusions and lysosomes. Hyperplasia of the smooth endoplasmic reticulum (EPR was revealed in liver specimens of the rats that had received AfB1. Results of the study suggest the conclusion about mutual mitigation of the effects of nanoparticles and the mycotoxin on rats blood and liver cells after AfB1 has adsorbed on MND.

  5. Biomarkers of acute lung injury: worth their salt?

    Directory of Open Access Journals (Sweden)

    Proudfoot Alastair G

    2011-12-01

    Full Text Available Abstract The validation of biomarkers has become a key goal of translational biomedical research. The purpose of this article is to discuss the role of biomarkers in the management of acute lung injury (ALI and related research. Biomarkers should be sensitive and specific indicators of clinically important processes and should change in a relevant timeframe to affect recruitment to trials or clinical management. We do not believe that they necessarily need to reflect pathogenic processes. We critically examined current strategies used to identify biomarkers and which, owing to expedience, have been dominated by reanalysis of blood derived markers from large multicenter Phase 3 studies. Combining new and existing validated biomarkers with physiological and other data may add predictive power and facilitate the development of important aids to research and therapy.

  6. 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.

  7. 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.

  8. 26 CFR 53.4942(b)-1 - Operating foundations.

    Science.gov (United States)

    2010-04-01

    ... described in section 501(c) (3), maintains a large library of manuscripts and other historical reference....4942(b)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... its library. Sometimes S obtains the right to publish the scholar's work, although this is not...

  9. Aflatoxin B1 changes protein phosphorylation in ratlivers

    International Nuclear Information System (INIS)

    A study was conducted on the effect of aflatoxin B1 on protein phosphorylation in rat livers by incubation of soluble and insoluble cell fractions with [γ32P] ATP. SDS polyacrylamide gel electrophoresis indicated that a total of eight rat liver phosphoproteins were affected during a feeding period of 36 weeks on a carcinogenic aflatoxin B1 containing diet compared to the non-carcinogenic diet. Five of the affected phospho-proteins were found in the soluble fraction, while the remaining three were found in the insoluble fraction. The rats were fed on a synthetic diet contaminated with 1-2mg aflatoxin B1 per kg food. The appearance of only two of these phosphoproteins were c-AMP dependend. DEAE-cellulose chromatography employed to separate the different histone kinase activities in soluble rat cell fractions showed that the specific activity of histone kinase I activity decreased while the histone kinase II activity stayed unchanged for rats submitted to the aflatoxin B1 containing diet compared to those on the normal non-carcinogenic diet

  10. 76 FR 18731 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-04-05

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD...)(1) arms sales notification. This is published to fulfill the requirements of section 155 of...

  11. 75 FR 9182 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2010-03-01

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD...)(1) arms sales notification to fulfill the requirements of section 155 of Public Law 104-164 dated...

  12. 75 FR 11865 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2010-03-12

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD...)(1) arms sales notification to fulfill the requirements of section 155 of Public Law 104-164 dated...

  13. 76 FR 18726 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-04-05

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD...)(1) arms sales notification. This is published to fulfill the requirements of section 155 of...

  14. 76 FR 8716 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-02-15

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD...)(1) arms sales notification. This is published to fulfill the requirements of section 155 of...

  15. 78 FR 62592 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-10-22

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... Republic of Singapore to contribute to regional security. Its contributions to counter-piracy...

  16. 78 FR 22848 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-04-17

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... regional security. Its contributions to counter-piracy and counterterrorism efforts continue to stabilize...

  17. Aspergillus flavus and aflatoxin B1 in flour production.

    Science.gov (United States)

    Halt, M

    1994-10-01

    This paper discusses the results of investigations of contamination with aflatoxin-producing fungi and aflatoxin B1 affecting 545 samples of wheat grains, 475 samples of intermediate products of wheat grain being milled to flour (like middlings) and 238 samples of flour. A significant contamination with moulds was detected in analyzed samples. Although Aspergillus (34.87%) and Penicillium (32.37%) dominated, other types were also present, e.g., Cladosporium, Fusarium, Mucor, Alternaria, Rhizopus, Absidia and Trichoderma (listed in order of frequency). The presence of Aspergillus flavus, the known aflatoxin producer, was detected in 9.94% of analyzed samples. Isolates of A. Flavus were capable of producing aflatoxin B1 under favourable conditions. Aflatoxin B1 was found in 76.8% of samples contaminated with A. flavus. The highest contamination with aflatoxin B1 was detected in wheat grain samples (mean value of 16.3 micrograms/kg) and in intermediate products of wheat grain being milled to flour (mean value of 11.13 micrograms/kg). Contamination was lower in flour samples (mean value of 4.13 micrograms/kg). With regard to proposed standards given by the FAO and WHO, under which the content of aflatoxin should not exceed 30 micrograms/kg in food products, only two of 96 samples did not meet these criteria. PMID:7859854

  18. 76 FR 72180 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-11-22

    ... Section 36(b)(1) of the Arms Export Control Act, as amended (i) Prospective Purchaser: Malaysia. (ii... Arms Export Control Act. Policy Justification Malaysia--AIM-9X-2 SIDEWINDER Missiles The Government of Malaysia has requested a possible sale of 20 AIM- 9X-2 SIDEWINDER Block II All-Up-Round Missiles, 8...

  19. 76 FR 69707 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-11-09

    ... defeat perimeter security threats and readily employ counter- and anti-terrorism measures. The RSLF... Section 36(b)(1) of the Arms Export Control Act, as Amended (i) Prospective Purchaser: Kingdom of Saudi... million. Other 2 million. Total 33 million. *As defined in Section 47(6) of the Arms Export Control...

  20. 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 ...

  1. 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.

  2. 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...

  3. Proximity Ligation Assays for Disease Biomarkers Analysis

    OpenAIRE

    Nong, Rachel Yuan

    2011-01-01

    One of the pressing needs in the field of disease biomarker discovery is new technologies that could allow high performance protein analysis in different types of clinical material, such as blood and solid tissues. This thesis includes four approaches that address important limitations of current technologies, thus enabling highly sensitive, specific and parallel protein measurements. Paper I describes a method for sensitive singleplex protein detection in complex biological samples, namely s...

  4. Kadar Asam Urat Serum sebagai Biomarker Preeklamsi

    OpenAIRE

    Neli Sumanti; Noormartany; Muhammad Alamsyah; Tiene Rostini

    2013-01-01

    Preeclampsia remains a health problem that becomes one of the causes of maternal deaths besides bleeding and infection. The etiology and pathogenesis of preeclampsia are unclear. Increased serum uric acid levels is seen simultaneously with the increase of blood pressure and occurred before the onset of proteinuria. Therefore, the uric acid can be used as a biomarker. The aim of this study was to analyze the serum uric acid levels between normal and preeclampsia pregnancies. The study was cond...

  5. Mitochondrial DNA as a Cancer Biomarker

    OpenAIRE

    Jakupciak, John P.; Wang, Wendy; Markowitz, Maura E; Ally, Delphine; Coble, Michael; Srivastava, Sudhir; Maitra, Anirban; Barker, Peter E.; Sidransky, David; O’Connell, Catherine D.

    2005-01-01

    As part of a national effort to identify biomarkers for the early detection of cancer, we developed a rapid and high-throughput sequencing protocol for the detection of sequence variants in mitochondrial DNA. Here, we describe the development and implementation of this protocol for clinical samples. Heteroplasmic and homoplasmic sequence variants occur in the mitochondrial genome in patient tumors. We identified these changes by sequencing mitochondrial DNA obtained from tumors and blood from...

  6. 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

  7. 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

  8. Common Variants in the ATP2B1 Gene Are Associated With Susceptibility to Hypertension

    Science.gov (United States)

    Tabara, Yasuharu; Kohara, Katsuhiko; Kita, Yoshikuni; Hirawa, Nobuhito; Katsuya, Tomohiro; Ohkubo, Takayoshi; Hiura, Yumiko; Tajima, Atsushi; Morisaki, Takayuki; Miyata, Toshiyuki; Nakayama, Tomohiro; Takashima, Naoyuki; Nakura, Jun; Kawamoto, Ryuichi; Takahashi, Norio; Hata, Akira; Soma, Masayoshi; Imai, Yutaka; Kokubo, Yoshihiro; Okamura, Tomonori; Tomoike, Hitonobu; Iwai, Naoharu; Ogihara, Toshio; Inoue, Itsuro; Tokunaga, Katsushi; Johnson, Toby; Caulfield, Mark; Munroe, Patricia; Umemura, Satoshi; Ueshima, Hirotsugu; Miki, Tetsuro

    2016-01-01

    Hypertension is one of the most common complex genetic disorders. We have described previously 38 single nucleotide polymorphisms (SNPs) with suggestive association with hypertension in Japanese individuals. In this study we extend our previous findings by analyzing a large sample of Japanese individuals (n=14 105) for the most associated SNPs. We also conducted replication analyses in Japanese of susceptibility loci for hypertension identified recently from genome-wide association studies of European ancestries. Association analysis revealed significant association of the ATP2B1 rs2070759 polymorphism with hypertension (P=5.3×10−5; allelic odds ratio: 1.17 [95% CI: 1.09 to 1.26]). Additional SNPs in ATP2B1 were subsequently genotyped, and the most significant association was with rs11105378 (odds ratio: 1.31 [95% CI: 1.21 to 1.42]; P=4.1×10−11). Association of rs11105378 with hypertension was cross-validated by replication analysis with the Global Blood Pressure Genetics consortium data set (odds ratio: 1.13 [95% CI: 1.05 to 1.21]; P=5.9×10−4). Mean adjusted systolic blood pressure was highly significantly associated with the same SNP in a meta-analysis with individuals of European descent (P=1.4×10−18). ATP2B1 mRNA expression levels in umbilical artery smooth muscle cells were found to be significantly different among rs11105378 genotypes. Seven SNPs discovered in published genome-wide association studies were also genotyped in the Japanese population. In the combined analysis with replicated 3 genes, FGF5 rs1458038, CYP17A1, rs1004467, and CSK rs1378942, odds ratio of the highest risk group was 2.27 (95% CI: 1.65 to 3.12; P=4.6×10−7) compared with the lower risk group. In summary, this study confirmed common genetic variation in ATP2B1, as well as FGF5, CYP17A1, and CSK, to be associated with blood pressure levels and risk of hypertension. PMID:20921432

  9. Validation of New Cancer Biomarkers

    DEFF Research Database (Denmark)

    Duffy, Michael J; Sturgeon, Catherine M; Söletormos, Georg; Barak, Vivian; Molina, Rafael; Hayes, Daniel F; Diamandis, Eleftherios P; Bossuyt, Patrick

    2015-01-01

    BACKGROUND: Biomarkers are playing increasingly important roles in the detection and management of patients with cancer. Despite an enormous number of publications on cancer biomarkers, few of these biomarkers are in widespread clinical use. CONTENT: In this review, we discuss the key steps 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...

  10. 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.

  11. 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...

  12. Total imprecision of exposure biomarkers: implications for calculating exposure limits

    DEFF Research Database (Denmark)

    Grandjean, Philippe; Budtz-Jørgensen, Esben

    2007-01-01

    of exposure limits. METHODS: In a birth cohort study, mercury concentrations in cord blood, cord tissue, and maternal hair were used as biomarkers of prenatal methylmercury exposure. We determined their mutual correlations and their associations with the child's neurobehavioral outcome variables at...... age 7 years. With at least three exposure parameters available, factor analysis and structural equation modeling could be applied to determine the total imprecision of each biomarker. The estimated imprecision was then applied to adjust benchmark dose calculations and the derived exposure limits....... RESULTS: The exposure biomarkers correlated well with one another, but the cord blood mercury concentration showed the best associations with neurobehavioral deficits. Factor analysis and structural equation models showed a total imprecision of the cord-blood parameter of 25-30%, and almost twice as much...

  13. Occupational exposure to aflatoxin B1: new (old) occupational risk!

    OpenAIRE

    Viegas, Susana; Veiga, Luísa; Almeida, Ana; Carolino, Elisabete; Paula FIGUEIREDO; Viegas, Carla

    2015-01-01

    Contrary to fungi, exposure to mycotoxins is not usually identified as a risk factor present in occupational settings. This is probably due to the inexistence of limits regarding concentration of airborne mycotoxins, and also due to the fact that these compounds are rarely monitored in occupational environments. Aflatoxin B1 (AFB1) is the most prevalent aflatoxin and is associated with carcinogenicity, teratogenicity, genotoxicity and immunotoxicity but only a few studies examined exposure in...

  14. CobB1 deacetylase activity in Streptomyces coelicolor

    Czech Academy of Sciences Publication Activity Database

    Mikulík, Karel; Felsberg, Jürgen; Kudrnáčová, E.; Bezoušková, Silvia; Šetinová, Dita; Stodůlková, Eva; Zídková, J.; Zídek, Václav

    2012-01-01

    Roč. 90, č. 2 (2012), s. 179-187. ISSN 0829-8211 R&D Projects: GA AV ČR(CZ) IAA500110805; GA ČR GA303/09/0475 Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z50200510 Keywords : sirtuin * NAD(+)dependent deacetylation activity CobB1 * Streptomyces coeliocolor Subject RIV: EE - Microbiology, Virology Impact factor: 2.915, year: 2012

  15. Biochemical characterization of the GM2 gangliosidosis B1 variant

    Directory of Open Access Journals (Sweden)

    J.C. Tutor

    2004-06-01

    Full Text Available The deficiency of the A isoenzyme of ß-hexosaminidase (Hex produced by different mutations of the gene that codes for the alpha subunit (Tay-Sachs disease has two variants with enzymological differences: the B variant consists of the absence of Hex A isoenzyme and the B1 variant produces an inactive Hex A isoenzyme for the hydrolysis of the GM2 ganglioside and synthetic substrates with negative charge. In contrast to the early childhood form of the B variant, the B1 variant appears at a later clinical stage (3 to 7 years of age with neurodegenerative symptoms leading to the death of the patient in the second decade of life. The most frequent mutation responsible for the GM2 gangliosidosis B1 variant is R178H, which has a widespread geographic and ethnic distribution. The highest incidence has been described in Portugal, which has been suggested as the point of origin of this mutation. Biochemical characterization of this lysosomal disease is carried out using negatively charged synthetic alpha subunit-specific sulfated substrates, since Hex A isoenzyme heat-inactivation assays are not applicable. However, the determination of the apparent activation energy of Hex using the neutral substrate 3,3'-dichlorophenolsulfonphthaleinyl N-acetyl-ß-D-glucosaminide, may offer a valid alternative. The presence of an alpha subunit in the alphaß heterodimer Hex A means that its activation energy (41.8 kJ/mol is significantly lower than that of the ßß homodimer Hex B (75.1 kJ/mol; however, as mutation inactivates the alpha subunit, the Hex A of the B1 variant presents an activation energy that is similar to that of the Hex B isoenzyme.

  16. Rapid Immunoenzyme Assay of Aflatoxin B1 Using Magnetic Nanoparticles

    OpenAIRE

    Urusov, Alexandr E.; Alina V. Petrakova; Vozniak, Maxim V.; Zherdev, Anatoly V.; Boris B. Dzantiev

    2014-01-01

    The main limitations of microplate-based enzyme immunoassays are the prolonged incubations necessary to facilitate heterogeneous interactions, the complex matrix and poorly soluble antigens, and the significant sample dilutions often required because of the presence of organic extractants. This study presents the use of antibody immobilization on the surface of magnetic particles to overcome these limitations in the detection of the mycotoxin, aflatoxin B1. Features of the proposed system are...

  17. Occurrence of aflatoxin B1 in natural products

    OpenAIRE

    Guilherme Prado; Altoé, Aline F.; Tatiana C. B. Gomes; Leal, Alexandre S.; Morais, Vanessa A. D.; Marize S. Oliveira; Marli B. Ferreira; Gomes, Mateus B.; Fabiano N. Paschoal; Rafael von S. Souza; Daniela A. Silva; Cruz Madeira, Jovita E. G.

    2012-01-01

    The media claims for the consumption of natural resource-based food have gradually increased in both developing and developed countries. The interest in the safety of these products is partially due to the possible presence of toxigenic fungi acting as mycotoxin producers, such as aflatoxins produced during the secondary metabolism of Aspergillus flavus, A. parasiticus and A. nomius. Aflatoxins, mainly aflatoxin B1, are directly associated with liver cancer in human beings. This paper is aime...

  18. Biomarkers for Alzheimer's disease therapeutic trials.

    Science.gov (United States)

    Hampel, Harald; Wilcock, Gordon; Andrieu, Sandrine; Aisen, Paul; Blennow, Kaj; Broich, K; Carrillo, Maria; Fox, Nick C; Frisoni, Giovanni B; Isaac, Maria; Lovestone, Simon; Nordberg, Agneta; Prvulovic, David; Sampaio, Christina; Scheltens, Philip; Weiner, Michael; Winblad, Bengt; Coley, Nicola; Vellas, Bruno

    2011-12-01

    The development of disease-modifying treatments for Alzheimer's disease requires innovative trials with large numbers of subjects and long observation periods. The use of blood, cerebrospinal fluid or neuroimaging biomarkers is critical for the demonstration of disease-modifying therapy effects on the brain. Suitable biomarkers are those which reflect the progression of AD related molecular mechanisms and neuropathology, including amyloidogenic processing and aggregation, hyperphosphorylation, accumulation of tau and neurofibrillary tangles, progressive functional, metabolic and structural decline, leading to neurodegeneration, loss of brain tissue and cognitive symptoms. Biomarkers should be used throughout clinical trial phases I-III of AD drug development. They can be used to enhance inclusion and exclusion criteria, or as baseline predictors to increase the statistical power of trials. Validated and qualified biomarkers may be used as outcome measures to detect treatment effects in pivotal clinical trials. Finally, biomarkers can be used to identify adverse effects. Questions regarding which biomarkers should be used in clinical trials, and how, are currently far from resolved. The Oxford Task Force continues and expands the work of our previous international expert task forces on disease-modifying trials and on endpoints for Alzheimer's disease clinical trials. The aim of this initiative was to bring together a selected number of key international opinion leaders and experts from academia, regulatory agencies and industry to condense the current knowledge and state of the art regarding the best use of biological markers in Alzheimer's disease therapy trials and to propose practical recommendations for the planning of future AD trials. PMID:21130138

  19. Improving MRI surface coil decoupling to reduce B1 distortion

    Science.gov (United States)

    Larson, Christian

    As clinical MRI systems continue to advance, larger focus is being given to image uniformity. Good image uniformity begins with generating uniform magnetic fields, which are easily distorted by induced currents on receive-only surface coils. It has become an industry standard to combat these induced currents by placing RF blocking networks on surface coils. This paper explores the effect of blocking network impedance of phased array surface coils on B1 distortion. It has been found and verified, that traditional approaches for blocking network design in complex phased arrays can leave undesirable B1 distortions at 3 Tesla. The traditional approach of LC tank blocking is explored, but shifts from the idea that higher impedance equals better B1 distortion at 3T. The result is a new design principle for a tank with a finite inductive reactance at the Larmor Frequency. The solution is demonstrated via simulation using a simple, single, large tuning loop. The same loop, along with a smaller loop, is used to derive the new design principle, which is then applied to a complex phased array structure.

  20. Wind tunel tests of Risoe-B1-18 and Risoe-B1-24

    Energy Technology Data Exchange (ETDEWEB)

    Fuglsang, P.; Bak, C.; Gaunaa, M.; Antoniou, I.

    2003-01-01

    This report contains 2D measurements of the Risoe-B1-18 and Risoe-B1-24 airfoils. The aerodynamic properties were derived from pressure measurements on the airfoil surface and in the wake. The measurements were conducted in the VELUX open jet wind tunnel, which has a background turbulence intensity of 1%, and an inlet flow velocity of 42 m/s. The airfoil sections had a chord of 0.600 m giving a Reynolds number of 1.6Oe106. The span was 1.9 m and end plates were used to minimize 3D flow effects. The measurements comprised both static and dynamic inflow. Static inflow covered angles of attack from 5o to 30 deg. Dynamic inflow was obtained by pitching the airfoil in a harmonic motion around various mean angles of attack. The test matrix involved smooth flow, various kinds of leading edge roughness, stall strips, vortex generators and Gurney flaps in different combinations. The quality of the measurements was good and the agreement between measurements and numerical CFD predictions with EllipSys2D was good. For both airfoils predictions with turbulent flow captured very well the shapes of lift and drag curves as well as the magnitude of maximum lift. Measurements of Risoe-B1-18 showed that the maximum lift coefficient was 1.64 at an angle of attack of approximately 13 deg. The airfoil was not very sensitive to leading edge roughness despite its high maximum lift. Measurements with stall strips showed that stall strips could control the level of maximum lift. The Risoe-B1-24 measurements showed that the maximum lift coefficient was 1.62 at an angle of attack of approximately 14 deg. The airfoil was only little sensitive to leading edge roughness despite its high relative thickness and high maximum lift. Measurements with delta wing shaped vortex generators increased the maximum lift coefficient to 2.02 and measurements with Gurney flaps increased the maximum lift coefficient to 1.85. Measurements with combination of vortex generators and Gurney flaps showed a maximum

  1. Laminin A, B1, B2, S and M subunits in the postnatal rat liver development and after partial hepatectomy

    DEFF Research Database (Denmark)

    Wewer, U M; Engvall, E; Paulsson, M; Yamada, Y; Albrechtsen, R

    1992-01-01

    The expression of laminin subunits (A, B1, B2, S and M) in the perisinusoidal space of the rat liver was studied in early postnatal life, in the adult, and after partial hepatectomy. In the perisinusoidal space of the normal adult rat, laminin was detected with polyclonal antibodies only in small...... liver (biliary ducts and blood vessels) irrespective of the age of animals exhibited B1, B2 and S immunoreactivity. Laminin A was restricted to the larger blood vessels and could not be detected in the biliary ducts. In the adult rat, immunoreactivity for the A-like M subunit was absent except for some...... neonatal rats as compared to adult rats. S-laminin mRNA could readily be demonstrated in neonatal rat livers by Northern blot analysis, whereas A and M could not. Expression of S and M-laminin transcripts were demonstrated by polymerase chain reaction, but we were unable to obtain a laminin A product...

  2. 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

  3. Biomarkers associated with obstructive sleep apnea: A scoping review.

    Science.gov (United States)

    Canto, Graziela De Luca; Pachêco-Pereira, Camila; Aydinoz, Secil; Major, Paul W; Flores-Mir, Carlos; Gozal, David

    2015-10-01

    The overall validity of biomarkers in the diagnosis of obstructive sleep apnea (OSA) remains unclear. We conducted a scoping review to provide assessments of biomarkers characteristics in the context of obstructive sleep apnea (OSA) and to identify gaps in the literature. A scoping review of studies in humans without age restriction that evaluated the potential diagnostic value of biological markers (blood, exhaled breath condensate, salivary, and urinary) in the OSA diagnosis was undertaken. Retained articles were those focused on the identification of biomarkers in subjects with OSA, the latter being confirmed with a full overnight or home-based polysomnography (PSG). Search strategies for six different databases were developed. The methodology of selected studies was classified using an adaptation of the evidence quality criteria from the American Academy of Pediatrics. Additionally the biomarkers were classified according to their potential clinical application. We identified 572 relevant studies, of which 117 met the inclusion criteria. Eighty-two studies were conducted in adults, 34 studies involved children, and one study had a sample composed of both adults and children. Most of the studies evaluated blood biomarkers. Potential diagnostic biomarkers were found in nine pediatric studies and in 58 adults studies. Only nine studies reported sensitivity and specificity, which varied substantially from 43% to 100%, and from 45% to 100%, respectively. Studies in adults have focused on the investigation of IL-6, TNF-α and hsCRP. There was no specific biomarker that was tested by a majority of authors in pediatric studies, and combinatorial urine biomarker approaches have shown preliminary promising results. In adults IL-6 and IL-10 seem to have a favorable potential to become a good biomarker to identify OSA. PMID:25645128

  4. 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, ...

  5. Biomarkers in Alzheimer’s Disease Analysis by Mass Spectrometry-Based Proteomics

    OpenAIRE

    Yahui Liu; Hong Qing; Yulin Deng

    2014-01-01

    Alzheimer’s disease (AD) is a common chronic and destructive disease. The early diagnosis of AD is difficult, thus the need for clinically applicable biomarkers development is growing rapidly. There are many methods to biomarker discovery and identification. In this review, we aim to summarize Mass spectrometry (MS)-based proteomics studies on AD and discuss thoroughly the methods to identify candidate biomarkers in cerebrospinal fluid (CSF) and blood. This review will also discuss the potent...

  6. 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...

  7. Biomarkers: A potential prognostic tool for silicosis.

    Science.gov (United States)

    Pandey, Jai Krishna; Agarwal, Deepa

    2012-09-01

    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. PMID:23776317

  8. 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.)

  9. 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

  10. 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.

  11. Occupational Exposure to Aflatoxin B1 in a Portuguese Poultry Slaughterhouse.

    Science.gov (United States)

    Viegas, Susana; Veiga, Luísa; Almeida, Ana; dos Santos, Mateus; Carolino, Elisabete; Viegas, Carla

    2016-03-01

    Aflatoxin B1 (AFB1) is a secondary metabolite produced by the fungi Aspergillus flavus and is the most potent hepatocarcinogen known in mammals and has been classified by the International Agency of Research on Cancer as Group 1 carcinogen. Although dietary exposure to AFB1 has been extensively documented, there are still few studies dedicated to the problem of occupational exposure. Considering recent findings regarding AFB1 occupational exposure in poultry production, it was considered relevant to clarify if there is also exposure in poultry slaughterhouses. Occupational exposure assessment to AFB1 was done with a biomarker of internal dose that measures AFB1 in the serum by enzyme-linked immunosorbent assay. Thirty workers from a slaughterhouse were enrolled in this study. A control group (n = 30) was also considered in order to know AFB1 background levels for Portuguese population. Fourteen workers (47.0%) showed detectable levels of AFB1 with values from 1.06 to 4.03ng ml(-1), with a mean value of 1.73ng ml(-1). No AFB1 was detected in serum of individuals used as controls. Despite uncertainties regarding the exposure route that is contributing more to exposure (inhalation or dermal) is possible to state that exposure to AFB1 is occurring in the slaughterhouse studied. It seems that reducing AFB1 contamination in poultry production can have a positive result in this occupational setting. PMID:26568583

  12. 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.

  13. 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...

  14. 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

  15. Serum Biomarkers of (AntiOxidant Status for Epidemiological Studies

    Directory of Open Access Journals (Sweden)

    Eugène Jansen

    2015-11-01

    Full Text Available In this review, we disclose a selection of serum/plasma biomarkers of (antioxidant status related to nutrition, which can be used for measurements in large-scale epidemiological studies. From personal experience, we have come to the following proposal of a set of biomarkers for nutritional intake, (antioxidant status, and redox status. We have selected the individual antioxidant vitamins E and A, and the carotenoids which can be measured in large series by HPLC. In addition, vitamin C was selected, which can be measured by an auto-analyzer or HPLC. As a biomarker for oxidative stress, the ROM assay (reactive oxygen metabolites was selected; for the redox status, the total thiol assay; and for the total antioxidant status the BAP assay (biological antioxidant potential. All of these biomarkers can be measured in large quantities by an auto-analyzer. Critical points in biomarker validation with respect to blood sampling, storage conditions, and measurements are discussed. With the selected biomarkers, a good set is presented for use in the risk assessment between nutrition and (chronic diseases in large-scale epidemiological studies. Examples of the successful application of these biomarkers in large international studies are presented.

  16. The CHESS survey of the L1157-B1 shock

    Science.gov (United States)

    Busquet, G.; Lefloch, B.; Benedettini, M.; Codella, C.; Cabrit, S.; Ceccarelli, C.; Vasta, M.; Viti, S.; Giannini, T.; Nisini, B.; Cernicharo, J.; Lorenzani, A.

    2012-03-01

    Outflows generated by protostars heavily affect the kinematics and chemistry of the hosting molecular cloud due to strong shocks. These shocks heats and compress the ambient dense gas switching on a complex chemistry that leads to an enhancement of the abundance of several species, as reported in ``chemically active'' outflows, whose archetype is the outflow of the low-mass Class 0 protostar L1157. We present the results of the spectral survey of the shock region L1157-B1 carried out with PACS, SPIRE and HIFI instruments in the framework of the Herschel key program CHESS. The high spectral resolution data from HIFI show that different excitation conditions coexist in the B1 shock while the high PACS spatial resolution data shows a different spatial distribution of the the detected specie. We will discuss the properties of the different gas components and present the physical conditions derived from different species. We will present a first comparison with shock models highlighting the complex structure of this shocked region.

  17. Screening and Initial Binding Assessment of Fumonisin B1 Aptamers

    Directory of Open Access Journals (Sweden)

    Maria C. DeRosa

    2010-11-01

    Full Text Available Fumonisins are mycotoxins produced by Fusarium verticillioides and F. proliferatum, fungi that are ubiquitous in corn (maize. Insect damage and some other environmental conditions result in the accumulation of fumonisins in corn-based products worldwide. Current methods of fumonisin detection rely on the use of immunoaffinity columns and high-performance liquid chromatography (HPLC. The use of aptamers offers a good alternative to the use of antibodies in fumonisin cleanup and detection due to lower costs and improved stability. Aptamers are single-stranded oligonucleotides that are selected using Systematic Evolution of Ligands by EXponential enrichment (SELEX for their ability to bind to targets with high affinity and specificity. Sequences obtained after 18 rounds of SELEX were screened for their ability to bind to fumonisin B1. Six unique sequences were obtained, each showing improved binding to fumonisin B1 compared to controls. Sequence FB1 39 binds to fumonisin with a dissociation constant of 100 ± 30 nM and shows potential for use in fumonisin biosensors and solid phase extraction columns.

  18. Rapid Immunoenzyme Assay of Aflatoxin B1 Using Magnetic Nanoparticles

    Directory of Open Access Journals (Sweden)

    Alexandr E. Urusov

    2014-11-01

    Full Text Available The main limitations of microplate-based enzyme immunoassays are the prolonged incubations necessary to facilitate heterogeneous interactions, the complex matrix and poorly soluble antigens, and the significant sample dilutions often required because of the presence of organic extractants. This study presents the use of antibody immobilization on the surface of magnetic particles to overcome these limitations in the detection of the mycotoxin, aflatoxin B1. Features of the proposed system are a high degree of nanoparticle dispersion and methodologically simple immobilization of the antibodies by adsorption. Reactions between the immobilized antibodies with native and labeled antigens are conducted in solution, thereby reducing the interaction period to 5 min without impairing the analytical outcome. Adsorption of immunoglobulins on the surface of magnetic nanoparticles increases their stability in aqueous-organic media, thus minimizing the degree of sample dilution required. Testing barley and maize extracts demonstrated a limit of aflatoxin B1 detection equal to 20 pg/mL and total assay duration of 20 min. Using this method, only the 3-fold dilution of the initial methanol/water (60/40 extraction mixture in the microplate wells is necessary. The proposed pseudo-homogeneous approach could be applied toward immunodetection of a wide range of compounds.

  19. Rapid immunoenzyme assay of aflatoxin B1 using magnetic nanoparticles.

    Science.gov (United States)

    Urusov, Alexandr E; Petrakova, Alina V; Vozniak, Maxim V; Zherdev, Anatoly V; Dzantiev, Boris B

    2014-01-01

    The main limitations of microplate-based enzyme immunoassays are the prolonged incubations necessary to facilitate heterogeneous interactions, the complex matrix and poorly soluble antigens, and the significant sample dilutions often required because of the presence of organic extractants. This study presents the use of antibody immobilization on the surface of magnetic particles to overcome these limitations in the detection of the mycotoxin, aflatoxin B1. Features of the proposed system are a high degree of nanoparticle dispersion and methodologically simple immobilization of the antibodies by adsorption. Reactions between the immobilized antibodies with native and labeled antigens are conducted in solution, thereby reducing the interaction period to 5 min without impairing the analytical outcome. Adsorption of immunoglobulins on the surface of magnetic nanoparticles increases their stability in aqueous-organic media, thus minimizing the degree of sample dilution required. Testing barley and maize extracts demonstrated a limit of aflatoxin B1 detection equal to 20 pg/mL and total assay duration of 20 min. Using this method, only the 3-fold dilution of the initial methanol/water (60/40) extraction mixture in the microplate wells is necessary. The proposed pseudo-homogeneous approach could be applied toward immunodetection of a wide range of compounds. PMID:25412219

  20. Commercialisation of Biomarker Tests for Mental Illnesses: Advances and Obstacles.

    Science.gov (United States)

    Chan, Man K; Cooper, Jason D; Bahn, Sabine

    2015-12-01

    Substantial strides have been made in the field of biomarker research for mental illnesses over the past few decades. However, no US FDA-cleared blood-based biomarker tests have been translated into routine clinical practice. Here, we review the challenges associated with commercialisation of research findings and discuss how these challenges can impede scientific impact and progress. Overall evidence indicates that a lack of research funding and poor reproducibility of findings were the most important obstacles to commercialization of biomarker tests. Fraud, pre-analytical and analytical limitations, and inappropriate statistical analysis are major contributors to poor reproducibility. Increasingly, these issues are acknowledged and actions are being taken to improve data validity, raising the hope that robust biomarker tests will become available in the foreseeable future. PMID:26549771

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. Parâmetros hematológicos de frangos de corte alimentados com ração contendo aflatoxina B1 e fumonisina B1 Hematological parameters of broiler chicks fed rations containing aflatoxin B1 and fumonisin B1

    Directory of Open Access Journals (Sweden)

    Eliana Neire Castiglioni Tessari

    2006-06-01

    Full Text Available O objetivo deste trabalho foi avaliar os efeitos da aflatoxina B1 (AFB1 e da fumonisina B1 (FB1 sobre o hemograma e o leucograma de frangos alimentados com ração contendo as toxinas isoladamente e em associação, nos níveis de 0, 50 e 200mig de AFB1/kg, e/ou 0, 50 e 200mg de FB1/kg. O delineamento experimental foi inteiramente casualizado, em esquema fatorial 3x3, com 9 tratamentos e 12 repetições, totalizando 108 aves. Os frangos foram alimentados com as rações contaminadas do 8° até o 41° dia de vida. As aves de todos os grupos alimentados com micotoxinas apresentaram redução (PThe aim of the present study was to evaluate the effects of dietary aflatoxin B1 (AFB1 and fumonisin B1 (FB1 on the hemogram and leucogram of broilers. The mycotoxins were added to rations, singly and in combination, at levels of 0, 50 and 200mug AFB1/kg, and/or 0, 50 and 200mg FB1/kg. A completely randomized 3 x 3 factorial design was used, with 9 treatments and 12 replications per treatment (total: 108 birds. Broilers were fed the contaminated rations from day-old 8 to 41. All the mycotoxin-treated groups had decreased (P<0.05 values of hematocrit, hemoglobin concentration and erythrocyte counts, which are common characteristics of anemia. The most affected birds were from groups receiving the highest levels of the combined mycotoxins. Lower (P<0.05 white blood cells counts were also noted in all groups fed mycotoxin-contaminated feeds, however, this reduction was more severe in broilers fed 200mug AFB1/kg, alone or in association with FB1. The conclusion is that both AFB1 and FB1, singly or in combination at the levels studied, can negatively affect the hematological parameters of broiler chicks.

  7. 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

  8. 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...

  9. Biomarkers in Alzheimer’s Disease Analysis by Mass Spectrometry-Based Proteomics

    Directory of Open Access Journals (Sweden)

    Yahui Liu

    2014-05-01

    Full Text Available Alzheimer’s disease (AD is a common chronic and destructive disease. The early diagnosis of AD is difficult, thus the need for clinically applicable biomarkers development is growing rapidly. There are many methods to biomarker discovery and identification. In this review, we aim to summarize Mass spectrometry (MS-based proteomics studies on AD and discuss thoroughly the methods to identify candidate biomarkers in cerebrospinal fluid (CSF and blood. This review will also discuss the potential research areas on biomarkers.

  10. Altered pattern of Naïve and memory B cells and B1 cells in patients with chronic granulomatous disease.

    OpenAIRE

    2014-01-01

    Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder characterized by a greatly increased susceptibility to severe fungal and bacterial infections caused by defects in NADPH oxidase of phagocytic cells. We aimed to investigate immunophenotype alterations of naïve and memory B cells and B1a cells in peripheral whole blood from Iranian patients with CGD. Flow cytometric analysis was performed on peripheral blood samples from 31 CGD patients and 23 healthy controls (HC...

  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

    DEFF Research Database (Denmark)

    Hatt, Lotte; Aagaard, Mads M; Graakjaer, Jesper;

    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 methylation specific beadchip microarray study assessing more than 450.000 CpG sites. We have analyzed the DNA...... with a potential for aneuploidy testing as well as a list of markers for regions harboring sub-microscopic deletion- or duplication syndromes....

  12. 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

  13. 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.

  14. Fumonisin B1 and the kidney: modes of action for renal tumor formation by fumonisin B1 in rodents.

    Science.gov (United States)

    Müller, Stephanie; Dekant, Wolfgang; Mally, Angela

    2012-10-01

    The mycotoxin fumonisin B1 (FB1) is an important contaminant of maize and maize-based products. In rodent toxicity studies, FB1 was shown to be hepato- and nephrotoxic, and to induce renal tumors in rats when administered via the diet. Of particular note are the aggressive growth characteristics of FB1-induced tumors with a high potential to metastasize. While genotoxicity does not appear to contribute to FB1 carcinogenicity, it is well established that FB1-mediated disruption of sphingolipid metabolism plays a key role in FB1 toxicity. This review provides an overview on human dietary exposure to FB1, FB1 toxicity and carcinogenicity, and potential mechanisms involved in FB1-mediated tumor formation, with a particular focus on cellular functions of sphingolipids and biological consequences of FB1-mediated perturbation of sphingolipid metabolism. PMID:22771819

  15. Exosomes: the future of biomarkers in medicine.

    Science.gov (United States)

    Properzi, Francesca; Logozzi, Mariantonia; Fais, Stefano

    2013-10-01

    Exosomes are nanovesicles secreted into the extracellular environment upon internal vesicle fusion with the plasma membrane. The molecular content of exosomes is a fingerprint of the releasing cell type and of its status. For this reason, and because they are released in easily accessible body fluids such as blood and urine, they represent a precious biomedical tool. A growing body of evidence suggests that exosomes may be used as biomarkers for the diagnosis and prognosis of malignant tumors. This article focuses on the exploitation of exosomes as diagnostic tools for human tumors and discusses possible applications of the same strategies to other pathologies, such as neurodegenerative diseases. PMID:24044569

  16. Effects of aflatoxin B1 and fumonisin B1 on body weight, antibody titres and histology of broiler chicks.

    Science.gov (United States)

    Tessari, E N C; Oliveira, C A F; Cardoso, A L S P; Ledoux, D R; Rottinghaus, G E

    2006-06-01

    1. Our objective was to evaluate the toxic effects of aflatoxin B1 (AFB1) and fumonisin B1 (FB1), administered singly or in combination to broilers. 2. Feeds were prepared with concentrations equal to 0, 50 and 200 microg AFB1/kg, and/or 0, 50 and 200 mg FB1/kg, and offered to broiler chicks from 8 to 41 d of age. The experimental design was totally randomised, in a 3 x 3 factorial arrangement with 9 treatments and 12 birds per treatment. Animals were vaccinated against Newcastle disease on d 14 of life and killed at 41 d. 3. Compared with controls, all mycotoxin-treated groups at 41 d had lower body weight and weight gain, and higher relative heart weight. The relative weight of the liver increased only in birds fed diets containing 200 mg FB1, singly or in combination with AFB1. 4. At 35 d, all groups receiving mycotoxin-treated rations had reduced geometrical mean antibody titres, with birds from groups fed combinations of AFB1 and FB1/kg having even lower values, when compared to the other groups. 5. Histological changes were observed only in liver from birds fed mycotoxin-contaminated rations, and in kidneys of birds fed the diet containing 200 microg AFB1 and 200 mg FB1/kg. Main alterations included vacuolar degeneration and cell proliferation of bile ducts in the liver, and hydropic degeneration in renal tubules in the kidneys. 6. We concluded that AFB1 and FB1 in combination have primarily additive effects on body weight, liver structure and immunological response of broilers at the concentrations used. PMID:16787861

  17. 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.

  18. The ceramide inhibitor fumonisin B1 mitigates the pulmonary effects of low-dose diesel exhaust inhalation in mice.

    Science.gov (United States)

    Shaheen, Hazem M; Onoda, Atsuto; Shinkai, Yusuke; Nakamura, Masayuki; El-Ghoneimy, Ashraf A; El-Sayed, Yasser S; Takeda, Ken; Umezawa, Masakazu

    2016-10-01

    Recent studies have suggested that inhalation of diesel exhaust (DE), a major source of air pollution, results in pulmonary alterations; however, the effects of DE at low concentrations are poorly understood. Therefore, this study was conducted to elucidate the pulmonary effects of low-level exposure to DE and the potential role of a ceramide de novo biosynthesis inhibitor, fumonisin B1 (FB1) to ameliorate the DE-toxicity. Male C57BL/6J mice underwent 1- or 7-day experiments (4 equal groups/experiment) and were assigned to the control, DE (0.1mg/m(3)), FB1 (6.75mg/kg body weight SC at days 0, 3 and 6) or DE+FB1 groups. DE and/or FB1 treatment had no effect on the expression of Nos2, a biomarker of oxidative stress. Ceramide production in the bronchial epithelial cells and Sphk1 mRNA expression were induced in the lung after the 7-day DE exposure and were partially suppressed by the FB1 treatment. Additionally, the effects of DE on SP-A and SP-D mRNA expression were also suppressed by the FB1 treatment. These results suggest that ceramide and Sphk1 may be sensitive biomarkers for low-level DE-induced pulmonary effects. Collectively, ceramide likely contributes to the DE-induced early stage of airway inflammation, which is considered a potential pulmonary target during low-level DE exposure. PMID:27376354

  19. Imaging biomarkers in tauopathies.

    Science.gov (United States)

    Dani, Melanie; Edison, Paul; Brooks, David J

    2016-01-01

    Abnormally aggregated tau protein is central to the pathophysiology of Alzheimer's disease, frontotemporal dementia variants, progressive supranuclear palsy, corticobasal degeneration and chronic traumatic encephalopathy. The post-mortem cortical density of hyperphosphorylated tau tangles correlates with pre-morbid cognitive dysfunction and neuron loss. Selective PET ligands including [18F]THK5117, [18F]THK5351, [18F]AV1451 (T807) and [11C]PBB3 now provide in vivo imaging information about the timing and distribution of tau in the early phases of neurodegenerative diseases. They are potential imaging biomarkers for both supporting diagnosis and tracking disease progression. Here, we discuss the challenges posed in developing selective tau ligands as biomarkers, their state of development and the new clinical information that has been revealed. PMID:26299160

  20. Towards Improved Biomarker Research

    DEFF Research Database (Denmark)

    Kjeldahl, Karin

    actually identify strong biomarkers when strict validation is applied; the latter phenomenon is to some extentmasked by a publication bias, but has been widely observed among researchers working with omics data. In this thesis, the background of this apparent small effect size of the biomarkers is...... is used both for regression and classification purposes. This method has proven its strong worth in the multivariate data analysis throughout an enormous range of applications; a very classic data type is near infrared (NIR) data, but many similar data types have also be very successful. On that...... application types are different and introduce a larger complexity, weaker signals andmany potential sources of experimental and analytical bias and errors. The risk of the latter is further increased by the complexity of the entire omics experimental setup which often involves various project partners with...

  1. Biomarkers for hepatocellular carcinoma.

    Science.gov (United States)

    Behne, Tara; Copur, M Sitki

    2012-01-01

    The hepatocellular carcinoma (HCC) is one of the most common malignant tumors and carries a poor survival rate. The management of patients at risk for developing HCC remains challenging. Increased understanding of cancer biology and technological advances have enabled identification of a multitude of pathological, genetic, and molecular events that drive hepatocarcinogenesis leading to discovery of numerous potential biomarkers in this disease. They are currently being aggressively evaluated to establish their value in early diagnosis, optimization of therapy, reducing the emergence of new tumors, and preventing the recurrence after surgical resection or liver transplantation. These markers not only help in prediction of prognosis or recurrence but may also assist in deciding appropriate modality of therapy and may represent novel potential targets for therapeutic interventions. In this paper, a summary of most relevant available data from published papers reporting various tissue and serum biomarkers involved in hepatocellular carcinoma was presented. PMID:22655201

  2. 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

  3. 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...

  4. Dietary modulation of the biotransformation and genotoxicity of aflatoxin B1

    International Nuclear Information System (INIS)

    Diet and its various components are consistently identified as among the most important ‘risk factors’ for cancer worldwide, yet great uncertainty remains regarding the relative contribution of nutritive (e.g., vitamins, calories) vs. non-nutritive (e.g., phytochemicals, fiber, contaminants) factors in both cancer induction and cancer prevention. Among the most potent known human dietary carcinogens is the mycotoxin, aflatoxin B1 (AFB). AFB and related aflatoxins are produced as secondary metabolites by the molds Aspergillus flavus and Aspergillus parasiticus that commonly infect poorly stored foods including peanuts, pistachios, corn, and rice. AFB is a potent hepatocarcinogenic agent in numerous animal species, and has been implicated in the etiology of human hepatocellular carcinoma. Recent research has shown that many diet-derived factors have great potential to influence AFB biotransformation, and some efficiently protect from AFB-induced genotoxicity. One key mode of action for reducing AFB-induced carcinogenesis in experimental animals was shown to be the induction of detoxification enzymes such as certain glutathione-S-transferases that are regulated through the Keap1–Nrf2–ARE signaling pathway. Although initial studies utilized the dithiolthione drug, oltipraz, as a prototypical inducer of antioxidant response, dietary components such as suforaphane (SFN) are also effective inducers of this pathway in rodent models. However, human GSTs in general do not appear to be extensively induced by SFN, and GSTM1 – the only human GST with measurable catalytic activity toward aflatoxin B1-8,9-epoxide (AFBO; the genotoxic metabolite of AFB), does not appear to be induced by SFN, at least in human hepatocytes, even though its expression in human liver cells does appear to offer considerable protection against AFB–DNA damage. Although induction of detoxification pathways has served as the primary mechanistic focus of chemoprevention studies, protective

  5. 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.

  6. Molecular ions in the protostellar shock L1157-B1

    CERN Document Server

    Podio, L; Ceccarelli, C; Codella, C; Bachiller, R

    2014-01-01

    We perform a complete census of molecular ions with an abundance larger than 1e-10 in the protostellar shock L1157-B1 by means of an unbiased high-sensitivity survey obtained with the IRAM-30m and Herschel/HIFI. By means of an LVG radiative transfer code the gas physical conditions and fractional abundances of molecular ions are derived. The latter are compared with estimates of steady-state abundances in the cloud and their evolution in the shock calculated with the chemical model Astrochem. We detect emission from HCO+, H13CO+, N2H+, HCS+, and, for the first time in a shock, from HOCO+, and SO+. The bulk of the emission peaks at blueshifted velocity, ~ 0.5-3 km/s with respect to systemic, has a width of ~ 4-8 km/s, and is associated with the outflow cavities (T_kin ~ 20-70 K, n(H2) ~ 1e5 cm-3). Observed HCO+ and N2H+ abundances are in agreement with steady-state abundances in the cloud and with their evolution in the compressed and heated gas in the shock for cosmic rays ionization rate Z = 3e-16 s-1. HOCO+...

  7. Phosphorous chemistry in the shocked region L1157 B1

    CERN Document Server

    Aota, Takuhiro

    2012-01-01

    We study the evolution of phosphorous-bearing species in one-dimensional C-shock models. We find that the abundances of P-bearing species depend sensitively on the elemental abundance of P in the gas phase and on the abundance of N atoms in the pre-shock gas. The observed abundance of PN and the non-detection of PO towards L1157 B1 are reproduced in C-shock models with shock velocity v=20km s-1 and pre-shock density n(H2) =10^4 - 10^5, if the elemental abundance of P in the gas phase is 10^-9 and the N-atom abundance is n(N)/nH - 10^-5 in the pre-shock gas. We also find that P-chemistry is sensitive to O- and N-chemistry, because N atoms are destroyed mainly by OH and NO. We identify the reactions of O-bearing and N-bearing species that significantly affect P chemistry.

  8. 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 ...

  9. Blood transfusions

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000431.htm Blood transfusions To use the sharing features on this ... several sources of blood which are described below. Blood From the Public (Volunteer Blood Donation) The most ...

  10. 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 ...

  11. 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 ...

  12. 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 ...

  13. 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

  14. Association between tortilla consumption and human urinary fumonisin B1 levels in a Mexican population.

    Science.gov (United States)

    Gong, Yun Yun; Torres-Sanchez, Luisa; Lopez-Carrillo, Lizbeth; Peng, Jian He; Sutcliffe, Anne E; White, Kay L; Humpf, Hans-Ulrich; Turner, Paul C; Wild, Christopher P

    2008-03-01

    Fumonisins are mycotoxins produced by Fusarium spp. and commonly contaminate maize and maize products worldwide. Fumonisins are rodent carcinogens and have been associated with human esophageal cancer. However, the lack of a valid exposure biomarker has hindered both the assessment of human exposure and the evaluation of disease risk. A sensitive liquid chromatography-mass spectrometry method to measure urinary fumonisin B1 (FB1) following extraction on Oasis MAX cartridges was established and applied to urine samples from women in a cohort recruited in Morelos County, Mexico. Urinary FB1 was compared with dietary information on tortilla consumption. FB1 recovery in spiked samples averaged 94% as judged by deuterium-labeled FB1 internal standard. Urinary FB1 was determined in 75 samples from women selected based on low, medium, or high consumption of maize-based tortillas. The geometric mean (95% confidence interval) of urinary FB1 was 35.0 (18.8-65.2), 63.1 (36.8-108.2), and 147.4 (87.6-248.0) pg/mL and the frequency of samples above the detection limit (set at 20 pg FB1/mL urine) was 45%, 80%, and 96% for the low, medium, and high groups, respectively. Women with high intake had a 3-fold higher average FB1 levels compared with the "low intake" group (F = 7.3; P = 0.0015). Urinary FB1 was correlated with maize intake (P(trend) = 0.001); the correlation remained significant after adjusting for age, education, and place of residence. This study suggests that measurement of urinary FB1 is sufficiently sensitive for fumonisin exposure assessment in human populations and could be a valuable tool in investigating the associated health effects of exposure. PMID:18349288

  15. PENGARUH KETEBALAN SUBSTRAT PADA FERMENTASI TEMPE TERHADAP KADAR VITAMIN B1 (THE INFLUENCE OF SUBSTRATE THICKNESS DURING TEMPE FERMENTATION ON VITAMINS B1 LEVEL

    Directory of Open Access Journals (Sweden)

    Fifi Retiaty

    2012-12-01

    Full Text Available ABSTRACT The level of vitamin B1 in tempe could be increased by modifying the surface of substrate during soybean fermentation. This research aimed to know the influence of substrate thickness during soybean fermentation into tempe to the levels of vitamin B1. The design of this research was completed randomized design with two replication. Vitamin B1 content was analyzed on raw soybeans, boiled soybeans, and tempe using spectrophotometer methods. The substrate thicknesses examined were 0.25 cm, 0.50 cm and 1.00cm. Vitamin B1 level on raw soybean was 0.7436 mg percent and on boiled soybean was 0.4898 mg percent, while in tempe with substrate thickness  0.25 cm, 0.50 cm and 1.00 cm, the vitamin B1 contents were 1.1413, 0.9044, and 0.7130 mg percent respectively. The thickness of tempe substrate affected on vitamin B1 content. A thinner substrate resulted on higher vitamin B1 level. Keywords: fermentation, tempe, vitamin B1   ABSTRAK Kadar vitamin B1 pada tempe dapat ditingkatkan dengan memodifikasi permukaan dari substrat dalam fermentasi kedelai. Tujuan penelitian ini adalah untuk mengetahui pengaruh ketebalan substrat pada fermentasi kedelai menjadi tempe terhadap kadar vitamin B1. Disain penelitian ini adalah Rancangan Acak Lengkap dengan dua kali ulangan. Kadar vitamin B1 dianalisis pada kedelai mentah, kedelai rebus, dan tempe dengan menggunakan metode spektrofotometri. Ketebalan substrat yang diteliti adalah 0.25 cm, 0,50 cm, 1,00 cm. Kadar vitamin B1 pada  kedelai mentah adalah 0,7436 mg persen dan pada kedelai rebus adalah 0.4898 mg persen. Sedangkan kadar vitamin B1 pada tempe dengan ketebalan 0,25, 0,5 dan 1 cm secara berturut-turut adalah 1,1413 mg persen , 0,9044 mg persen dan 0,7130 mg persen. Ketebalan substar tempe berpengaruh pada kandungan vitamin B1. Semakin tipis substrat, akan menghasilkan vitamin B1 yang semakin tinggi. [Penel Gizi Makan 2012, 35(2: 182-188]   Kata Kunci: fermentasi, tempe, vitamin B1

  16. 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

  17. 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.

  18. Multiple biomarkers responses in Prochilodus lineatus allowed assessing changes in the water quality of Salado River basin (Santa Fe, Argentina)

    International Nuclear Information System (INIS)

    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.

  19. 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

  20. Fumonisin B1 facilitates seizures induced by pentylenetetrazol in mice.

    Science.gov (United States)

    Poersch, Alice Bertotto; Trombetta, Francielle; Souto, Naiéli Schiefelbein; de Oliveira Lima, Camilla; Braga, Ana Cláudia Monteiro; Dobrachinski, Fernando; Ribeiro, Leandro Rodrigo; Soares, Félix Alexandre Antunes; Fighera, Michele Rechia; Royes, Luiz Fernando Freire; Oliveira, Mauro Schneider; Furian, Ana Flávia

    2015-01-01

    Fumonisin B1 (FB1) is a Fusarium spp. mycotoxin which constitutes a major public health issue because of its worldwide distribution and diversity of toxic effects.While the liver and kidney are considered the major target organs of FB1 toxicity in several species, evidence indicates that FB1 may be toxic to the brain. To further investigate the effects of FB1 on the central nervous system the present study aimed to test the hypothesis that acute FB1 exposure causes brain hyperexcitability and the potential underlying mechanisms. For these purposes, adult male C57BL/6 mice were injected with FB1 (8 mg/kg, i.p.) or its vehicle and 30 min thereafter received with a low dose of the classical convulsant pentylenetetrazol (PTZ, 30 mg/kg, i.p.) or its vehicle. After behavioral evaluation the cerebral cortex and the hippocampus were collected for analysis of Na(+),K(+)-ATPase activity, mitochondrial membrane potential (ΔΨm) and mitochondrial complex I and II activities. We found that FB1 reduced the latency for PTZ-induced myoclonic jerks and increased the number of these events. After exposure to FB1 total and α1 Na(+),K(+)-ATPase activities increased in cerebral cortex, whereas the same enzyme activities decreased in the hippocampus. Although no changes in mitochondrial complex I and II activities were found, acute exposure to FB1 increased ΔΨm in the cerebral cortex. Altogether, present results indicate that FB1 causes brain hyperexcitability in vivo, and that mitochondrial dysfunction may represent a potential underlying mechanism. PMID:26342287

  1. Aflatoxin B1 Degradation by a Pseudomonas Strain

    Directory of Open Access Journals (Sweden)

    Lancine Sangare

    2014-10-01

    Full Text Available Aflatoxin B1 (AFB1, one of the most potent naturally occurring mutagens and carcinogens, causes significant threats to the food industry and animal production. In this study, 25 bacteria isolates were collected from grain kernels and soils displaying AFB1 reduction activity. Based on its degradation effectiveness, isolate N17-1 was selected for further characterization and identified as Pseudomonas aeruginosa. P. aeruginosa N17-1 could degrade AFB1, AFB2 and AFM1 by 82.8%, 46.8% and 31.9% after incubation in Nutrient Broth (NB medium at 37 °C for 72 h, respectively. The culture supernatant of isolate N17-1 degraded AFB1 effectively, whereas the viable cells and intra cell extracts were far less effective. Factors influencing AFB1 degradation by the culture supernatant were investigated. Maximum degradation was observed at 55 °C. Ions Mn2+ and Cu2+ were activators for AFB1 degradation, however, ions Mg2+, Li+, Zn2+, Se2+, Fe3+ were strong inhibitors. Treatments with proteinase K and proteinase K plus SDS significantly reduced the degradation activity of the culture supernatant. No degradation products were observed based on preliminary LC-QTOF/MS analysis, indicating AFB1 was metabolized to degradation products with chemical properties different from that of AFB1. The results indicated that the degradation of AFB1 by P. aeruginosa N17-1 was enzymatic and could have a great potential in industrial applications. This is the first report indicating that the isolate of P. aeruginosa possesses the ability to degrade aflatoxin.

  2. Biomarkers in inflammatory bowel diseases

    DEFF Research Database (Denmark)

    Bennike, Tue; Birkelund, Svend; Stensballe, Allan;

    2014-01-01

    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...... before. In this review, we report the current status of the proteomics IBD biomarkers and discuss various emerging proteomic strategies for identifying and characterizing novel biomarkers, as well as suggesting future targets for analysis....

  3. 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

  4. Novel Compound Heterozygous Mutations in the CYP27B1 Gene Lead to Pseudovitamin D-Deficient Rickets.

    Science.gov (United States)

    Koek, W Nadia H; Zillikens, M Carola; van der Eerden, Bram C J; van Leeuwen, Johannes P T M

    2016-09-01

    Pseudovitamin D deficiency is the consequence of a genetic defect in the CYP27B1 gene resulting in diminished or absent conversion of 25-hydroxyvitamin D3 (25-(OH)D3) into 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and leads to growth retardation and rickets, usually in the first 2 years of life. DNA obtained from human leucocytes from a patient suspected of pseudovitamin D deficiency and her healthy parents was sequenced for a genetic defect in the CYP27B1 gene. In silico analyses on the mutations were performed using online available software. The 1α-hydroxylase activity of the patient, her parents, and a sample derived from a mixed buffy coat of healthy blood donors was measured by culturing peripheral blood mononuclear cells with 25-(OH)D3 and measuring 1,25-(OH)2D3 production. DNA sequencing of the patient suspected of pseudovitamin D deficiency revealed compound heterozygosity in the CYP27B1 gene for a (c413G>T) mutation in exon 3 (R138L) and a (c1232G>A) mutation in exon 8 (C411Y). In silico analyses confirmed that mutations at these positions are probably damaging for the protein since the amino acids are situated in a highly conserved region. In vitro analyses showed a nearly absent 1α-hydroxylase activity in the patient compared to the healthy blood donors. Her healthy parents each of whom carried one of the mutations also had compromised conversion of 25-(OH)D3 into 1,25-(OH)2D3 in peripheral blood mononuclear cells, being only marginally higher than in the patient. We discovered novel compound heterozygous mutations in the CYP27B1 gene in a young girl presenting with pseudovitamin D-deficient rickets, leading to severely decreased 1,25-(OH)2D3 production. Furthermore, both heterozygous parents showed a diminished 1α-hydroxylase activity. PMID:27364341

  5. 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.

  6. 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.

  7. 17 CFR 270.57b-1 - Exemption for downstream affiliates of business development companies.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Exemption for downstream affiliates of business development companies. 270.57b-1 Section 270.57b-1 Commodity and Securities Exchanges....57b-1 Exemption for downstream affiliates of business development companies....

  8. 26 CFR 1.263(b)-1 - Expenditures for advertising or promotion of good will.

    Science.gov (United States)

    2010-04-01

    ... good will. 1.263(b)-1 Section 1.263(b)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Items Not Deductible § 1.263(b)-1 Expenditures for... section 733 or section 451 of the Internal Revenue Code of 1939, in computing its excess profits...

  9. 26 CFR 53.4941(b)-1 - Imposition of additional taxes.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 17 2010-04-01 2010-04-01 false Imposition of additional taxes. 53.4941(b)-1...) MISCELLANEOUS EXCISE TAXES (CONTINUED) FOUNDATION AND SIMILAR EXCISE TAXES Taxes on Self-Dealing § 53.4941(b)-1 Imposition of additional taxes. (a) Tax on self-dealer. Section 4941(b)(1) of the Code imposes an excise...

  10. 22 CFR 9b.1 - Press access to the Department of State.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Press access to the Department of State. 9b.1 Section 9b.1 Foreign Relations DEPARTMENT OF STATE GENERAL REGULATIONS GOVERNING DEPARTMENT OF STATE PRESS BUILDING PASSES § 9b.1 Press access to the Department of State. (a) Media correspondents without valid Department of State press building...

  11. Chiral Biomarkers in Meteorites

    Science.gov (United States)

    Hoover, Richard B.

    2010-01-01

    The chirality of organic molecules with the asymmetric location of group radicals was discovered in 1848 by Louis Pasteur during his investigations of the rotation of the plane of polarization of light by crystals of sodium ammonium paratartrate. It is well established that the amino acids in proteins are exclusively Levorotary (L-aminos) and the sugars in DNA and RNA are Dextrorotary (D-sugars). This phenomenon of homochirality of biological polymers is a fundamental property of all life known on Earth. Furthermore, abiotic production mechanisms typically yield recemic mixtures (i.e. equal amounts of the two enantiomers). When amino acids were first detected in carbonaceous meteorites, it was concluded that they were racemates. This conclusion was taken as evidence that they were extraterrestrial and produced by abiologically. Subsequent studies by numerous researchers have revealed that many of the amino acids in carbonaceous meteorites exhibit a significant L-excess. The observed chirality is much greater than that produced by any currently known abiotic processes (e.g. Linearly polarized light from neutron stars; Circularly polarized ultraviolet light from faint stars; optically active quartz powders; inclusion polymerization in clay minerals; Vester-Ulbricht hypothesis of parity violations, etc.). This paper compares the measured chirality detected in the amino acids of carbonaceous meteorites with the effect of these diverse abiotic processes. IT is concluded that the levels observed are inconsistent with post-arrival biological contamination or with any of the currently known abiotic production mechanisms. However, they are consistent with ancient biological processes on the meteorite parent body. This paper will consider these chiral biomarkers in view of the detection of possible microfossils found in the Orgueil and Murchison carbonaceous meteorites. Energy dispersive x-ray spectroscopy (EDS) data obtained on these morphological biomarkers will be

  12. 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

  13. A preliminary study on the physiological effects of aflatoxin B-1 lactating water buffaloes

    International Nuclear Information System (INIS)

    Aflatoxin B-1 is one of the biologically active mycotoxins, produced as contaminants in human and animal food by a variety of spoilage molds. The effects of administering aflatoxin B-1 on plasma proteins, total thyroxine, cholesterol, zinc and iron were studied in eight lactating buffaloes (3rd and 8th season of lactation). The toxin was first tested in one animal which received single doses of 400, 1000 and 1500 ug each, mixed with 1 Kg ration, given one week apart. Blood, milk and urine samples were collected over the next 120 hrs. The toxin was not detected in either milk or urine. One week later, the latter dose was offered daily, but the animal lost its appetite and did not consume any of the ration offered on the second day. On the third day through the sixth, the toxin (1500 ug in 5 ml chloroform) was injected into the rumen through the flank region using a long needle and a syringe. However, the toxin could not be detected in either milk or urine. After another week, the dose was increased to 5000 ug intraruminally given for 2 days. The toxin appeared in milk and urine. The other seven animals were then included in the experiment and blood samples were collected 10 and 34 hours after dosing. The results obtained (from the pilot test) showed a transient decrease in serum albumin which lasted for 10-24 hours after oral administration of 400, 1000 and 1500 ug in food. This phenomenon was also confirmed in all animals at 34 hrs. after the intraruminal administration of 5000 ug (p>0.01). On the other hand, serum cholesterol was increased (P>0.01). Serum zinc was also increased though insignificantly. However, no appreciable changes were noted in either serum iron or total thyroxine. This experiment has shown that physiological responses may occur before the detection of the toxin in body fluids. It is suggested that measurement of plasma proteins and cholesterol can be used as a test for the toxic effect of aflatoxin, especially at low doses; a case similar to

  14. 偏头痛治疗曙光初现5-HT1B/1D受体激动剂的临床应用%Clinical application of 5-HT1B/1D receptor agonist(triptan) to the treatment of migraine--a ray of sunlight

    Institute of Scientific and Technical Information of China (English)

    张石革; 马国辉

    2004-01-01

    OBJECTIVE:Migraine is a common and frequently-occurring disease in neuromedicine.with understading of mechanism of migraine,new anti-migraine drugs have been found constantly to summarize the aspect of clinical application and progress on 5-HT1B/1D receptor agonist(Triptan).METHODS: To collecte medical literatures in recent years at home and abroad.CONCLUSION:Advance in 5-HT1B/1D receptor agonist has been swiftly in recent years, it has higher selectivity to 5-HT1B/1D receptor, contraction of cerebral vessel and arteriae temporalis, efficacy being related to dosage, promoting distribution of blood flow,so 5-HT1B/1D receptor agonist(triptan) plays an important roles in treatment of migraine.

  15. CYP1B1 expression, a potential risk factor for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Goth-Goldstein, Regine; Erdmann, Christine A.; Russell, Marion

    2001-05-31

    CYP1B1 expression in non-tumor breast tissue from breast cancer patients and cancer-free individuals was determined to test the hypothesis that high CYP1B1 expression is a risk factor for breast cancer. Large interindividual variations in CYP1B1 expression were found with CYP1B1 levels notably higher in breast cancer patients than cancer-free individuals. The results indicate that CYP1B1 might play a role in breast cancer either through increased PAH activation or through metabolism of endogenous estrogen to a carcinogenic derivative.

  16. Neuronal SH2B1 is essential for controlling energy and glucose homeostasis

    OpenAIRE

    Ren, Decheng; Zhou, Yingjiang; Morris, David; Li, Minghua; Li, Zhiqin; Rui, Liangyou

    2007-01-01

    SH2B1 (previously named SH2-B), a cytoplasmic adaptor protein, binds via its Src homology 2 (SH2) domain to a variety of protein tyrosine kinases, including JAK2 and the insulin receptor. SH2B1-deficient mice are obese and diabetic. Here we demonstrated that multiple isoforms of SH2B1 (α, β, γ, and/or δ) were expressed in numerous tissues, including the brain, hypothalamus, liver, muscle, adipose tissue, heart, and pancreas. Rat SH2B1β was specifically expressed in neural tissue in SH2B1-tran...

  17. Important roles of multiple Sp1 binding sites and epigenetic modifications in the regulation of the methionine sulfoxide reductase B1 (MsrB1 promoter

    Directory of Open Access Journals (Sweden)

    Favaloro Bartolo

    2007-05-01

    Full Text Available Abstract Background Methionine sulfoxide reductases (Msrs are enzymes that catalyze the reduction of oxidized methionine residues. Most organisms that were genetically modified to lack the MsrA gene have shown shortening of their life span. Methionine sulfoxide reductases B (MsrB proteins codified by three separate genes, named MsrB1, MsrB2, and MsrB3, are included in the Msrs system. To date, the mechanisms responsible for the transcriptional regulation of MsrB genes have not been reported. The aim of this study was to investigate the regulation of MsrB1 selenoprotein levels through transcriptional regulation of the MsrB1 gene in MDA-MB231 and MCF-7 breast carcinoma cell lines. Results A MsrB1 gene promoter is located 169 base pairs upstream from the transcription start site. It contains three Sp1 binding sites which are sufficient for maximal promoter activity in transient transfection experiments. High levels of MsrB1 transcript, protein and promoter activity were detected in low metastatic MCF7 human breast cancer cells. On the contrary, very low levels of both MsrB1 transcript and promoter activity were detected in the highly metastatic counterpart MDA-MB231 cells. A pivotal role for Sp1 in the constitutive expression of the MsrB1 gene was demonstrated through transient expression of mutant MsrB1 promoter-reporter gene constructs and chromatin immunoprecipitation experiments. Since Sp1 is ubiquitously expressed, these sites, while necessary, are not sufficient to explain the patterns of gene expression of MsrB1 in various human breast cancer cells. MDA-MB231 cells can be induced to express MsrB1 by treatment with 5-Aza-2'-deoxycytidine, a demethylating agent. Therefore, the MsrB1 promoter is controlled by epigenetic modifications. Conclusion The results of this study provide the first insights into the transcriptional regulation of the human MsrB1 gene, including the discovery that the Sp1 transcription factor may play a central role in its

  18. DNA methylation based biomarkers: Practical considerations and applications

    DEFF Research Database (Denmark)

    Nielsen, Helene Myrtue; How Kit, Alexandre; Tost, Jorg

    2012-01-01

    biochemical molecules such as proteins, DNA, RNA or lipids, whereby protein biomarkers have been the most extensively studied and used, notably in blood-based protein quantification tests or immunohistochemistry. The rise of interest in epigenetic mechanisms has allowed the identification of a new type of...... specific and sensitive than commonly used protein biomarkers, which could clearly justify their use in clinics. However, very few of them are at the moment used in clinics and even less commercial tests are currently available. The objective of this review is to discuss the advantages of DNA methylation as...... biomarker, DNA methylation, which is of great potential for many applications. This stable and heritable covalent modification mostly affects cytosines in the context of a CpG dinucleotide in humans. It can be detected and quantified by a number of technologies including genome-wide screening methods as...

  19. Selective boron accumulation in human ocular melanoma by 10B1-para-boronophenylalanine administration for neutron capture therapy

    International Nuclear Information System (INIS)

    Malignant melanoma occurs not only in the skin but also in ocular tissues. Ocular melanoma located superficially as in conjunctiva can be treated successfully by BNCT. In the present study, we investigated 10B dynamics in ocular melanoma and the surrounding normal tissues, to evaluate the possibility of applying BNCT to ocular melanoma. In three ocular melanoma patients, 10B concentration in melanoma after administration of 10B-BPA by oral or drip infusion ranged from 10.4 to 21.5 ppm. The boron concentrations in lens and vitreous body were lower than blood level, whereas higher than blood in sclera and palpebral skin. These results suggest that we can treat such a superficial melanoma lesions as conjunctival melanoma by BNCT using 10B1-BPA. (author)

  20. Effect of vitamin B1 and mixtures of B1 with other vitamins on cytostatic efficiency of sanazole under irradiation. A study in vitro

    International Nuclear Information System (INIS)

    Experiments in vitro, using bacteria Escherichia coli (AB 1157) as a biological model, showed that the cytostatic efficiency of sanazole (AK-2123, a nitrotriazole-type radiosensitizer) in radiation treatment can be strongly influenced by the presence of various vitamins. In airfree media the sanazole action is increased by a factor of 2.5 in the presence of vitamin (vit.) B1, vit. C E-acetate and β-carotene, whereas vit. B1 used individually possesses a 2.7-times higher cytostatic activity than sanazole itself. In media containing air the highest increase of sanazole action is observed in the presence of vit. B1 and C, whereas the individual use of vit. B1 shows a radiation protection effect. In media saturated with N2O the addition of the vit. B1 and C causes a 1.8-times larger sanazole activity, but the application of vit. B1 alone brings about a very high radiation protection. >From studies of vit. B1-radiolysis it can be concluded that OH radicals are the major primary transients leading to substrate degradation. The results are of interest for the radiation therapy of cancer

  1. 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.

  2. 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.

  3. 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 ...

  4. Blood Types

    Science.gov (United States)

    ... confidence to respond in emergency situations with the skills that can help to save a life. Learn more » Red Cross Information Donating Blood Learn About Blood Hosting a Blood Drive For Hospitals Engage with Us About Us Media ...

  5. Montelukast Disposition: No Indication of Transporter-Mediated Uptake in OATP2B1 and OATP1B1 Expressing HEK293 Cells

    OpenAIRE

    Marie Brännström; Pär Nordell; Britta Bonn; Davis, Andrew M.; Anna-Pia Palmgren; Constanze Hilgendorf; Katarina Rubin; Ken Grime

    2015-01-01

    Clinical studies with montelukast show variability in effect and polymorphic OATP2B1-dependent absorption has previously been implicated as a possible cause. This claim has been challenged with conflicting data and here we used OATP2B1-transfected HEK293 cells to clarify the mechanisms involved. For montelukast, no significant difference in cell uptake between HEK-OATP2B1 and empty vector cell lines was observed at pH 6.5 or pH 7.4, and no concentration-dependent uptake was detected. Monteluk...

  6. 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

  7. 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.

  8. 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

  9. 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

  10. Heat shock protein B1-deficient mice display impaired wound healing.

    Directory of Open Access Journals (Sweden)

    Jonathan Crowe

    Full Text Available There is large literature describing in vitro experiments on heat shock protein (hspB1 but understanding of its function in vivo is limited to studies in mice overexpressing human hspB1 protein. Experiments in cells have shown that hspB1 has chaperone activity, a cytoprotective role, regulates inflammatory gene expression, and drives cell proliferation. To investigate the function of the protein in vivo we generated hspB1-deficient mice. HspB1-deficient fibroblasts display increased expression of the pro-inflammatory cytokine, interleukin-6, compared to wild-type cells, but reduced proliferation. HspB1-deficient fibroblasts exhibit reduced entry into S phase and increased expression of cyclin-dependent kinase inhibitors p27(kip1 and p21(waf1. The expression of hspB1 protein and mRNA is also controlled by the cell cycle. To investigate the physiological function of hspB1 in regulating inflammation and cell proliferation we used an excisional cutaneous wound healing model. There was a significant impairment in the rate of healing of wounds in hspB1-deficient mice, characterised by reduced re-epithelialisation and collagen deposition but also increased inflammation. HspB1 deficiency augments neutrophil infiltration in wounds, driven by increased chemokine (C-X-C motif ligand 1 expression. This appears to be a general mechanism as similar results were obtained in the air-pouch and peritonitis models of acute inflammation.

  11. Optimisation of Liquid Phase Separation on an Aflatoxin B1 Radioimmunoassay Kit

    International Nuclear Information System (INIS)

    Aflatoxins are secondary metabolites of Aspergillus flavus and A. parasiticus, which grow on a wide variety of food, feeds and their products. Aflatoxin, particularly aflatoxin B1 (AfB1) has wide biological activities including toxic, teratogenic, mutagenic and carcinogenic. Therefore the AfB1 content in foods should be met the requirement of food safety standard. Radioimmunoassay (RIA) technique is one of immunochemical methods or immunoassays which has been considered to be sensitive, specific, accurate and practical for detection of aflatoxin. This technique is based on immunological reaction using radioactive tracer. AfB1 was indirectly radiolabelled and then purified by using a solvent extraction. The tracer was then undergone a immunological testing by using a polyclonal antibody of AfB1. In order to produce AfB1 RIA kit which meets the standard quality’s requirement there are two parameters that have to be optimised. First is optimisation of kit components which consist : standard AfB1, AfB1 tracer (125I-AfB1) and AfB1 antibody. (author)

  12. Imaging Biomarkers in Immunotherapy

    Science.gov (United States)

    Juergens, Rosalyn A.; Zukotynski, Katherine A.; Singnurkar, Amit; Snider, Denis P.; Valliant, John F.; Gulenchyn, Karen Y.

    2016-01-01

    Immune-based therapies have been in use for decades but recent work with immune checkpoint inhibitors has now changed the landscape of cancer treatment as a whole. While these advances are encouraging, clinicians still do not have a consistent biomarker they can rely on that can accurately select patients or monitor response. Molecular imaging technology provides a noninvasive mechanism to evaluate tumors and may be an ideal candidate for these purposes. This review provides an overview of the mechanism of action of varied immunotherapies and the current strategies for monitoring patients with imaging. We then describe some of the key researches in the preclinical and clinical literature on the current uses of molecular imaging of the immune system and cancer. PMID:26949344

  13. 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.

  14. 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.

  15. Cell stress promotes the association of phosphorylated HspB1 with F-actin.

    Directory of Open Access Journals (Sweden)

    Joseph P Clarke

    Full Text Available Previous studies have suggested that the small heat shock protein, HspB1, has a direct influence on the dynamics of cytoskeletal elements, in particular, filamentous actin (F-actin polymerization. In this study we have assessed the influence of HspB1 phosphorylation on its interaction(s with F-actin. We first determined the distribution of endogenous non-phosphorylated HspB1, phosphorylated HspB1 and F-actin in neuroendocrine PC12 cells by immunocytochemistry and confocal microscopy. We then investigated a potential direct interaction between HspB1 with F-actin by precipitating F-actin directly with biotinylated phalloidin followed by Western analyses; the reverse immunoprecipitation of HspB1 was also carried out. The phosphorylation influence of HspB1 in this interaction was investigated by using pharmacologic inhibition of p38 MAPK. In control cells, HspB1 interacts with F-actin as a predominantly non-phosphorylated protein, but subsequent to stress there is a redistribution of HspB1 to the cytoskeletal fraction and a significantly increased association of pHspB1 with F-actin. Our data demonstrate HspB1 is found in a complex with F-actin both in phosphorylated and non-phosphorylated forms, with an increased association of pHspB1 with F-actin after heat stress. Overall, our study combines both cellular and biochemical approaches to show cellular localization and direct demonstration of an interaction between endogenous HspB1 and F-actin using methodolgy that specifically isolates F-actin.

  16. Radiative transition probabilities for the B 1PI - X 1SIGMA+ and B 1PI - A 1SIGMA+ of 7LiH

    International Nuclear Information System (INIS)

    The recently reported (J. Chem. Phys. 66, 5412 (1977)) hybrid potential curves for the X 1Σ+ and A 1Σ+ states of LiH and the herein reported hybrid potential curve for the B 1Pi state of LiH are combined with the ab initio transition moments of Docken and Hinze (J. Chem. Phys. 57, 4936 (1972)) to calculate radiative transition probabilities between all B 1Pi (v' less than or equal to 2) and all X 1Σ+ (v'' less than or equal to 23) and A 1Σ+ (v'' less than or equal to 26) vibrational levels of 7LiH. The strongest single emission band found is the B 1Pi (v' = 2) → X 1Σ+ (v'' = 23) band between the highest ''long-range'' levels in each potential. For all B 1Pi levels, the emission is dominated by B → X rather than B → A emission

  17. NOAA Climate Data Record (CDR) of Gridded Satellite Data from ISCCP B1 (GridSat-B1) Infrared Channel Brightness Temperature, Version 2

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Gridded Satellite (GridSat-B1) data provides a uniform set of quality controlled geostationary satellite observations for the visible, infrared window and...

  18. Metabolism of aflatoxin B1 and identification of the major aflatoxin B1-DNA adducts formed in cultured human bronchus and colon

    DEFF Research Database (Denmark)

    1979-01-01

    Aflatoxin B1 and benzo(a)pyrene were activated by both cultured human bronchus and human colon as measured by binding to cellular DNA and protein. The binding of aflatoxin B1 to DNA was dose dependent, and the level of binding was higher in cultured human bronchus than it was in the colon. When...... found in these two peaks, and the ratio of radioactivity between the peaks was nearly 1. In colonic DNA, the ratio between Structures 1 and 11 was approximately 2. These observations add aflatoxin B1 to the list of chemical procarcinogens metabolized by cultured human tissues and in which the carcinogen-DNA...... adducts are similar to the adducts formed in animal tissue susceptible to the carcinogenic action of aflatoxin B1....

  19. New biomarkers for sepsis

    Directory of Open Access Journals (Sweden)

    Li-xin XIE

    2013-01-01

    Full Text Available There is a higher sepsis rate in the intensive care unit (ICU patients, which is one of the most important causes for patient death, but the sepsis lacks specific clinical manifestations. Exploring sensitive and specific molecular markers for infection that accurately reflect infection severity and prognosis is very clinically important. In this article, based on our previous study, we introduce some new biomarkers with high sensitivity and specificity for the diagnosis and predicting the prognosis and severity of sepsis. Increase of serum soluble(s triggering receptor expressed on myeloid cells-1 (sTREM-1 suggests a poor prognosis of septic patients, and changes of locus rs2234237 of sTREM-1 may be the one of important mechanisms. Additionally, urine sTREM-1 can provide an early warning of possible secondary acute kidney injury (AKI in sepsis patients. Serum sCD163 level was found to be a more important factor than procalcitonin (PCT and C-reactive protein (CRP in prognosis of sepsis, especially severe sepsis. Moreover, urine sCD163 also shows excellent performance in the diagnosis of sepsis and sepsis-associated AKI. Circulating microRNAs, such as miR-150, miR-297, miR-574-5p, miR -146a , miR-223, miR -15a and miR-16, also play important roles in the evaluation of status of septic patients. In the foreseeable future, newly-emerging technologies, including proteomics, metabonomics and trans-omics, may exert profound effects on the discovery of valuable biomarkers for sepsis.

  20. Quantification of differential ErbB1 and ErbB2 cell surface expression and spatial nanoclustering through plasmon coupling.

    Science.gov (United States)

    Wang, Jing; Yu, Xinwei; Boriskina, Svetlana V; Reinhard, Björn M

    2012-06-13

    Cell surface receptors play ubiquitous roles in cell signaling and communication and their expression levels are important biomarkers for many diseases. Expression levels are, however, only one factor that determines the physiological activity of a receptor. For some surface receptors, their distribution on the cell surface, especially their clustering, provides additional mechanisms for regulation. To access this spatial information robust assays are required that provide detailed insight into the organization of cell surface receptors on nanometer length scales. In this manuscript, we demonstrate through combination of scattering spectroscopy, electron microscopy, and generalized multiple particle Mie theory (GMT) simulations that the density- and morphology-dependent spectral response of Au nanoparticle (NP) immunolabels bound to the epidermal growth factor receptors ErbB1 and ErbB2 encodes quantitative information of both the cell surface expression and spatial clustering of the two receptors in different unliganded in vitro cancer cell lines (SKBR3, MCF7, A431). A systematic characterization of the collective spectral responses of NPs targeted at ErbB1 and ErbB2 at various NP concentrations indicates differences in the large-scale organization of ErbB1 and ErbB2 in cell lines that overexpress these receptors. Validation experiments in the scanning electron microscope (SEM) confirm that NPs targeted at ErbB1 on A431 are more strongly clustered than NPs bound to ErbB2 on SKBR3 or MCF7 at overall comparable NP surface densities. This finding is consistent with the existence of larger receptor clusters for ErbB1 than for ErbB2 in the plasma membranes of the respective cells. PMID:22587495

  1. The zebrafish sf3b1b460 mutant reveals differential requirements for the sf3b1 pre-mRNA processing gene during neural crest development.

    Science.gov (United States)

    An, Min; Henion, Paul D

    2012-01-01

    The functions of gene regulatory networks that control embryonic cell diversification occur on a background of constitutively active molecular machinery necessary for the elaboration of genetic interactions. The essential roles of subsets of such "housekeeping" genes in the regulation of specific aspects of development have become increasingly clear. Pre-mRNA processing is essential for production of functional transcripts by, for example, excision of introns. We have cloned the zebrafish toast(b460) locus and found that it encodes splicing factor 3b, subunit 1 (sf3b1). The sf3b1(b460) mutation causes aberrant splicing of sf3b1 resulting in functional and predicted non-functional transcripts and a 90% reduction in full-length Sf3b1 protein. The sf3b1(b460) mutation was isolated in a mutagenesis screen based on the absence of neural crest-derived melanophores. Further analysis revealed specific earlier defects in neural crest development, whereas the early development of other ectodermal populations appears unaffected. The expression of essential transcriptional regulators of neural crest development are severely disrupted in sf3b1(b460) mutants, due in part to defects in pre-mRNA processing of a subset of these factors, leading to defects in neural crest sublineage specification, survival and migration. Misexpression of a subset of these factors rescues aspects of neural crest development in mutant embryos. Our results indicate that although sf3b1 is a ubiquitously essential gene, the degree to which it is required exhibits tissue-type specificity during early embryogenesis. Further, the developmental defects caused by the sf3b1(b460) mutation provide insights into genetic interactions among members of the gene regulatory network controlling neural crest development. PMID:22562198

  2. Evidence for the eta_b(2S) and observation of h_b(1P) -> eta_b(1S) gamma and h_b(2P) -> eta_b(1S) gamma

    CERN Document Server

    Mizuk, R; Bondar, A; Pedlar, T K; Adachi, I; Aihara, H; Arinstein, K; Aulchenko, V; Aushev, T; Aziz, T; Bakich, A M; Bay, A; Belous, K; Bhardwaj, V; Bhuyan, B; Bischofberger, M; Bonvicini, G; Bozek, A; Bračko, M; Browder, T E; Chekelian, V; Chen, A; Chen, P; Cheon, B G; Chilikin, K; Chistov, R; Cho, I -S; Cho, K; Choi, S -K; Choi, Y; Dalseno, J; Danilov, M; Doležal, Z; Drásal, Z; Drutskoy, A; Eidelman, S; Epifanov, D; Fast, J E; Gaur, V; Gabyshev, N; Garmash, A; Golob, B; Haba, J; Hara, T; Hayasaka, K; Hayashii, H; Horii, Y; Hoshi, Y; Hou, W -S; Hsiung, Y B; Hyun, H J; Iijima, T; Ishikawa, A; Itoh, R; Iwabuchi, M; Iwasaki, Y; Iwashita, T; Jaegle, I; Julius, T; Kang, J H; Kapusta, P; Kawasaki, T; Kim, H J; Kim, H O; Kim, J H; Kim, K T; Kim, M J; Kim, Y J; Kinoshita, K; Ko, B R; Koblitz, S; Kodyš, P; Korpar, S; Kouzes, R T; Križan, P; Krokovny, P; Kuhr, T; Kumita, T; Kuzmin, A; Kwon, Y -J; Lange, J S; Lee, S -H; Li, J; Libby, J; Liu, C; Liu, Y; Liu, Z Q; Liventsev, D; Louvot, R; Matvienko, D; McOnie, S; Miyabayashi, K; Miyata, H; Mohanty, G B; Mohapatra, D; Moll, A; Muramatsu, N; Mussa, R; Nakao, M; Natkaniec, Z; Ng, C; Nishida, S; Nishimura, K; Nitoh, O; Nozaki, T; Ohshima, T; Okuno, S; Olsen, S L; Onuki, Y; Pakhlov, P; Pakhlova, G; Park, C W; Park, H; Pestotnik, R; Petrič, M; Piilonen, L E; Poluektov, A; Röhrken, M; Sakai, Y; Sandilya, S; Santel, D; Sanuki, T; Sato, Y; Schneider, O; Schwanda, C; Senyo, K; Seon, O; Sevior, M E; Shapkin, M; Shen, C P; Shibata, T -A; Shiu, J -G; Shwartz, B; Sibidanov, A; Simon, F; Smerkol, P; Sohn, Y -S; Sokolov, A; Solovieva, E; Stanič, S; Starič, M; Sumihama, M; Sumiyoshi, T; Tanida, K; Tatishvili, G; Teramoto, Y; Tikhomirov, I; Trabelsi, K; Tsuboyama, T; Uchida, M; Uehara, S; Uglov, T; Unno, Y; Uno, S; Vanhoefer, P; Varner, G; Varvell, K E; Vinokurova, A; Vorobyev, V; Wang, C H; Wang, M -Z; Wang, P; Wang, X L; Watanabe, M; Watanabe, Y; Williams, K M; Won, E; Yabsley, B D; Yamaoka, J; Yamashita, Y; Yuan, C Z; Zhang, Z P; Zhilich, V

    2012-01-01

    We report the first evidence for the eta_b(2S) using the h_b(2P)->eta_b(2S)gamma transition and the first observation of the h_b(1P)->eta_b(1S)gamma and h_b(2P)->eta_b(1S)gamma transitions. The mass and width of the eta_b(1S) and eta_b(2S) are measured to be m_etab(1S)=(9402.4+-1.5+-1.8)MeV/c^2, m_etab(2S)=(9999.0+-3.5 +2.8-1.9)MeV/c^2 and Gamma_etab(1S)=(10.8 +4.0-3.7 +4.5-2.0)MeV. We also update the h_b(1P) and h_b(2P) mass measurements. We use a 133.4/fb data sample collected at energies near the Upsilon(5S) resonance with the Belle detector at the KEKB asymmetric-energy e+e- collider.

  3. Montelukast Disposition: No Indication of Transporter-Mediated Uptake in OATP2B1 and OATP1B1 Expressing HEK293 Cells.

    Science.gov (United States)

    Brännström, Marie; Nordell, Pär; Bonn, Britta; Davis, Andrew M; Palmgren, Anna-Pia; Hilgendorf, Constanze; Rubin, Katarina; Grime, Ken

    2015-01-01

    Clinical studies with montelukast show variability in effect and polymorphic OATP2B1-dependent absorption has previously been implicated as a possible cause. This claim has been challenged with conflicting data and here we used OATP2B1-transfected HEK293 cells to clarify the mechanisms involved. For montelukast, no significant difference in cell uptake between HEK-OATP2B1 and empty vector cell lines was observed at pH 6.5 or pH 7.4, and no concentration-dependent uptake was detected. Montelukast is a carboxylic acid, a relatively potent inhibitor of OATP1B1, OATP1B3, and OATP2B1, and has previously been postulated to be actively transported into human hepatocytes. Using OATP1B1-transfected HEK293 cells and primary human hepatocytes in the presence of OATP inhibitors we demonstrate for the first time that active OATP-dependent transport is unlikely to play a significant role in the human disposition of montelukast. PMID:26694455

  4. Montelukast Disposition: No Indication of Transporter-Mediated Uptake in OATP2B1 and OATP1B1 Expressing HEK293 Cells

    Directory of Open Access Journals (Sweden)

    Marie Brännström

    2015-12-01

    Full Text Available Clinical studies with montelukast show variability in effect and polymorphic OATP2B1-dependent absorption has previously been implicated as a possible cause. This claim has been challenged with conflicting data and here we used OATP2B1-transfected HEK293 cells to clarify the mechanisms involved. For montelukast, no significant difference in cell uptake between HEK-OATP2B1 and empty vector cell lines was observed at pH 6.5 or pH 7.4, and no concentration-dependent uptake was detected. Montelukast is a carboxylic acid, a relatively potent inhibitor of OATP1B1, OATP1B3, and OATP2B1, and has previously been postulated to be actively transported into human hepatocytes. Using OATP1B1-transfected HEK293 cells and primary human hepatocytes in the presence of OATP inhibitors we demonstrate for the first time that active OATP-dependent transport is unlikely to play a significant role in the human disposition of montelukast.

  5. Flavonoids exhibit diverse effects on CYP11B1 expression and cortisol synthesis

    International Nuclear Information System (INIS)

    CYP11B1 catalyzes the final step of cortisol biosynthesis. The effects of flavonoids on transcriptional expression and enzyme activity of CYP11B1 were investigated using the human adrenocortical H295R cell model. All tested nonhydroxylated flavones including 3′,4′-dimethoxyflavone, α-naphthoflavone, and β-naphthoflavone upregulated CYP11B1 expression and cortisol production, whereas apigenin and quercetin exhibited potent cytotoxicity and CYP11B1 repression at high concentrations. Nonhydroxylated flavones stimulated CYP11B1-catalyzed cortisol formation at transcriptional level. Resveratrol increased endogenous and substrate-supported cortisol production like nonhydroxylated flavones tested, but it had no effect on CYP11B1 gene expression and enzyme activity. Resveratrol appeared to alter cortisol biosynthesis at an earlier step. The Ad5 element situated in the − 121/− 106 region was required for basal and flavone-induced CYP11B1 expression. Overexpression of COUP-TFI did not improve the responsiveness of Ad5 to nonhydroxylated flavones. Although COUP-TFI overexpression increased CYP11B1 and CYP11B2 promoter activation, its effect was not mediated through the common Ad5 element. Treating cells with PD98059 (a flavone-type MEK1 inhibitor) increased CYP11B1 promoter activity, but not involving ERK signaling because phosphorylation of ERK1/2 remained unvarying throughout the course of treatment. Likewise, AhR was not responsible for the CYP11B1-modulating effects of flavonoids because inconsistency with their effects on AhR activation. 3′,4′-dimethoxyflavone and 8-Br-cAMP additively activated CYP11B1 promoter activity. H-89 reduced 3′,4′-dimethoxyflavone-induced CYP11B1 promoter activation but to a lesser extent as compared to its inhibition on cAMP-induced transactivation. Our data suggest that constant exposure to nonhydroxylated flavones raises a potential risk of high basal and cAMP-induced cortisol synthesis in consequence of increased CYP11B1

  6. Flavonoids exhibit diverse effects on CYP11B1 expression and cortisol synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Li-Chuan; Li, Lih-Ann, E-mail: lihann@nhri.org.tw

    2012-02-01

    CYP11B1 catalyzes the final step of cortisol biosynthesis. The effects of flavonoids on transcriptional expression and enzyme activity of CYP11B1 were investigated using the human adrenocortical H295R cell model. All tested nonhydroxylated flavones including 3′,4′-dimethoxyflavone, α-naphthoflavone, and β-naphthoflavone upregulated CYP11B1 expression and cortisol production, whereas apigenin and quercetin exhibited potent cytotoxicity and CYP11B1 repression at high concentrations. Nonhydroxylated flavones stimulated CYP11B1-catalyzed cortisol formation at transcriptional level. Resveratrol increased endogenous and substrate-supported cortisol production like nonhydroxylated flavones tested, but it had no effect on CYP11B1 gene expression and enzyme activity. Resveratrol appeared to alter cortisol biosynthesis at an earlier step. The Ad5 element situated in the − 121/− 106 region was required for basal and flavone-induced CYP11B1 expression. Overexpression of COUP-TFI did not improve the responsiveness of Ad5 to nonhydroxylated flavones. Although COUP-TFI overexpression increased CYP11B1 and CYP11B2 promoter activation, its effect was not mediated through the common Ad5 element. Treating cells with PD98059 (a flavone-type MEK1 inhibitor) increased CYP11B1 promoter activity, but not involving ERK signaling because phosphorylation of ERK1/2 remained unvarying throughout the course of treatment. Likewise, AhR was not responsible for the CYP11B1-modulating effects of flavonoids because inconsistency with their effects on AhR activation. 3′,4′-dimethoxyflavone and 8-Br-cAMP additively activated CYP11B1 promoter activity. H-89 reduced 3′,4′-dimethoxyflavone-induced CYP11B1 promoter activation but to a lesser extent as compared to its inhibition on cAMP-induced transactivation. Our data suggest that constant exposure to nonhydroxylated flavones raises a potential risk of high basal and cAMP-induced cortisol synthesis in consequence of increased CYP11B1

  7. Correlated Biomarker Measurement Error: An Important Threat to Inference in Environmental Epidemiology

    OpenAIRE

    Pollack, A. Z.; Perkins, N.J.; Mumford, S. L.; A. Ye; Schisterman, E.F.

    2012-01-01

    Utilizing multiple biomarkers is increasingly common in epidemiology. However, the combined impact of correlated exposure measurement error, unmeasured confounding, interaction, and limits of detection (LODs) on inference for multiple biomarkers is unknown. We conducted data-driven simulations evaluating bias from correlated measurement error with varying reliability coefficients (R), odds ratios (ORs), levels of correlation between exposures and error, LODs, and interactions. Blood cadmium a...

  8. 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...

  9. 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...

  10. Altered pattern of Naïve and memory B cells and B1 cells in patients with chronic granulomatous disease.

    Science.gov (United States)

    Mohsenzadegan, Monireh; Fattahi, Fahimeh; Fattahi, Fatemeh; Mirshafiey, Abbas; Fazlollahi, Mohammad Reza; Naderi Beni, Fariba; Movahedi, Masoud; Pourpak, Zahra

    2014-06-01

    Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder characterized by a greatly increased susceptibility to severe fungal and bacterial infections caused by defects in NADPH oxidase of phagocytic cells. We aimed to investigate immunophenotype alterations of naïve and memory B cells and B1a cells in peripheral whole blood from Iranian patients with CGD. Flow cytometric analysis was performed on peripheral blood samples from 31 CGD patients and 23 healthy controls (HC) to study naïve (IgD+/CD27-), memory (CD27+) B and B1a (CD5+) cells. Soluble CD27 (sCD27) and immunoglobulins were also measured by ELISA and the nephelometric method, respectively. We found significantly higher levels of naïve B cells and B1a cells but lower levels of memory B cells in CGD patients compared to HC.. There was no significant difference in soluble CD27 (sCD27) alteration between CGD patients and HC. Our findings suggested a role for NADPH oxidase in process of B cell differentiation and impairing conversion of naïve B cells to memory B cells and altered B1a cells in CGD patients. Increased susceptibility of CGD patients to opportunistic infections and autoimmune disorders could be partly explained by the altered phenotype of B lymphocytes in these patients. PMID:24659119

  11. Altered pattern of Naïve and memory B cells and B1 cells in patients with chronic granulomatous disease.

    Directory of Open Access Journals (Sweden)

    Monireh Mohsenzadegan

    2014-06-01

    Full Text Available Chronic granulomatous disease (CGD is a rare primary immunodeficiency disorder characterized by a greatly increased susceptibility to severe fungal and bacterial infections caused by defects in NADPH oxidase of phagocytic cells. We aimed to investigate immunophenotype alterations of naïve and memory B cells and B1a cells in peripheral whole blood from Iranian patients with CGD. Flow cytometric analysis was performed on peripheral blood samples from 31 CGD patients and 23 healthy controls (HC to study naïve (IgD+/CD27-, memory (CD27+ B and B1a (CD5+ cells. Soluble CD27 (sCD27 and immunoglobulins were also measured by ELISA and the nephelometric method, respectively. We found significantly higher levels of naïve B cells and B1a cells but lower levels of memory B cells in CGD patients compared to HC.. There was no significant difference in soluble CD27 (sCD27 alteration between CGD patients and HC. Our findings suggested a role for NADPH oxidase in process of B cell differentiation and impairing conversion of naïve B cells to memory B cells and altered B1a cells in CGD patients. Increased susceptibility of CGD patients to opportunistic infections and autoimmune disorders could be partly explained by the altered phenotype of B lymphocytes in these patients.

  12. AhR- and ER-mediated activities in human blood samples collected from PCB-contaminated and background region in Slovakia

    Energy Technology Data Exchange (ETDEWEB)

    Pliskova, M. [Veterinary Researcch Institute, Brno (Czech Republic); Canton, R.F.; Duursen, M.B.M. van [Utrecht Univ. (NL). Institute for Risk Assessment Sciences (IRAS)] (and others)

    2004-09-15

    Endocrine disruption mediated through activation of aryl hydrocarbon receptor (AhR) and estrogen receptor (ER) by polychlorinated biphenyls (PCBs) and other persistent organic pollutants (POPs) has been studied extensively both in vivo and in vitro. Non-ortho- and mono-ortho-substituted polychlorinated biphenyls (PCBs) are potent AhR agonists therefore, increased dioxin-like activity of complex blood samples might reflect an increased exposure to PCBs. The induction of expression of CYP1A1 and CYP1B1 in different tissues, including lymphocytes, also depends on activation of AhR and it could be useful as a potential biomarker of exposure to dioxin-like compounds. Using various in vivo and in vitro models, the exposure to PCBs or hydroxy-PCBs has been reported to lead to either induction of ER-mediated activity or to an antiestrogenic effect associated with a suppression of estradiol-induced ER-dependent gene expression. Nevertheless, relative (anti)estrogenic potencies of a large set of prevalent environmental PCBs have not been yet compared in a single bioassay. A cross-talk between AhR and ER has been suggested to lead to a suppression of ER-mediated gene expression. Therefore, presence of dioxin-like compounds in blood could potentially suppress the ER-mediated activity. Additionally, AhR-dependent induction of CYP1A1 and especially CYP1B1, two enzymes involved in oxidative metabolism of estradiol and other estrogens, might enhance the metabolism of estradiol and it has been suggested to cause a potential depression of estrogen levels in the body. The aim of the present study was to determine dioxin-like, estrogenic and antiestrogenic activities in human blood samples collected in two Eastern Slovakia regions differently polluted with PCBs using established in vitro bioassays. We also studied mRNA expression of CYP1A1 and 1B1 in lymphocytes and the genotypes of CYP1B1 as possible biomarkers of exposure for PCBs and related compounds. The biological data obtained

  13. 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.

  14. Stark-modulation spectroscopy of the B(1)[3Π] state of PbO

    International Nuclear Information System (INIS)

    We report detailed spectroscopic measurements of the X(0)[1Σ+](v=0)→B(1)[3Π](v=5) transition in PbO. Using a Stark-modulated laser absorption technique, we have measured the hyperfine constant of 207PbO in the B(1) state, as well as the B(1)(v=5) rotational constant, X-B isotope shifts, etc. The hyperfine constant of the B(1) state is of interest as a benchmark for calculations of PbO electronic structure related to experiments to search for the electric dipole moment of the electron

  15. Ascorbate-Glutathione Cycle Alteration in Cadmium Sensitive Rice Mutant cadB-1

    Institute of Scientific and Technical Information of China (English)

    SHEN Guo-ming; ZHU Cheng; DU Qi-zhen; SHANGGUAN Li-na

    2012-01-01

    A rice cadmium (Cd) sensitive mutant cadB-1 was obtained using Agrobacterium tumefaciens mediated system.After exposure of cadB-1 and wild type (WT) rice seedlings to a range of Cd concentrations for 10 d,Cd accumulated to higher levels in roots,stems and leaves of both cadB-1 and WT with increasing external Cd concentrations,and the inhibition of seedling growth in cadB-1 was more serious than in WT.Hydrogen peroxide accumulation was higher in leaves and roots of cadB-1.The ratios of reduced glutathione (GSH)/oxidized glutathione (GSSG),ascorbate (ASC)/dehydroascorbate (DHA) and reduced nicotinamide adenine dinucleotide phosphate (NADPH)/oxidized nicotinamide adenine dinucleotide phosphate (NADP+) were lower in cadB-1 than in WT both in leaves and roots under high Cd levels.The activities of ascorbate peroxidase (APX),glutathione peroxidase (GR),dehydroascorbate reductase (DHAR) and monodehydroascorbate reductase (MDHAR) were also lower in cadB-1 than in WT both in leaves and roots under the treatment of high levels of Cd.Our results suggest that under Cd stress,the ASC-GSH cycle was more seriously inhibited in cadB-1 than in WT,indicating that the mutant cadB-1 is less able to scavenge reactive oxygen species and sensitive to Cd.

  16. Lamin B1 Is a Novel Therapeutic Target of Betulinic Acid in Pancreatic Cancer

    Science.gov (United States)

    Li, Lei; Du, Yiqi; Kong, Xiangyu; Li, Zhaoshen; Jia, Zhiliang; Cui, Jiujie; Gao, Jun; Wang, Guokun; Xie, Keping

    2013-01-01

    Purpose Betulinic acid (BA), a naturally occurring pentacyclic triterpenoid, exhibits potent anti-tumor activities, whereas the underlying mechanisms remain unclear. In current study, we sought to determine the role and regulation of lamin B1 expression in human pancreatic cancer pathogenesis and BA-based therapy. Experimental Design We used cDNA microarray to identify BA target genes and used tissue microarray to determine the expression levels of lamin B1 in pancreatic cancer tissues and to define their relationship with the clinicopathologic characteristics of pancreatic cancer. We also used in vitro and in vivo models to determine the biological impacts of altered lamin B1 expression on and mechanisms underlying lamin B1 overexpression in human pancreatic cancer. Results We found that lamin B1 was significantly downregulated by BA treatment in pancreatic cancer in both in vitro culture and xenograft models. Overexpression of lamin B1 was pronounced in human pancreatic cancer and increased lamin B1 expression was directly associated with low grade differentiation, increased incidence of distant metastasis and poor prognosis of pancreatic cancer patients. Furthermore, knockdown of lamin B1 significantly attenuated the proliferation, invasion and tumorigenicity of pancreatic cancer cells. Conclusions Lamin B1 plays an important role in pancreatic cancer pathogenesis and is a novel therapeutic target of BA treatment. PMID:23857605

  17. Network biomarkers, interaction networks and dynamical network biomarkers in respiratory diseases

    OpenAIRE

    Wu, Xiaodan; Chen, Luonan; Wang, Xiangdong

    2014-01-01

    Identification and validation of interaction networks and network biomarkers have become more critical and important in the development of disease-specific biomarkers, which are functionally changed during disease development, progression or treatment. The present review headlined the definition, significance, research and potential application for network biomarkers, interaction networks and dynamical network biomarkers (DNB). Disease-specific interaction networks, network biomarkers, or DNB...

  18. Kadar Asam Urat Serum sebagai Biomarker Preeklamsi

    Directory of Open Access Journals (Sweden)

    Neli Sumanti

    2013-06-01

    Full Text Available Preeclampsia remains a health problem that becomes one of the causes of maternal deaths besides bleeding and infection. The etiology and pathogenesis of preeclampsia are unclear. Increased serum uric acid levels is seen simultaneously with the increase of blood pressure and occurred before the onset of proteinuria. Therefore, the uric acid can be used as a biomarker. The aim of this study was to analyze the serum uric acid levels between normal and preeclampsia pregnancies. The study was conducted in Dr.Hasan Sadikin Hospital Bandung between March and May 2011, using cross sectional study design. Subjects were 45 inpartu normal pregnant women as control and 44 in partu pregnant women with preeclampsia accordance with inclusion and exclusion criteria. Levels of uric acid in normal pregnancy are 3,43 ±0.14 mg/dL. In this study uric acid levels resulting in cut-off levels of 4,8 mg/dL with a sensitivity value of 93%, and specificity 80%. Conclusions: uric acid levels in at term preeclampsia are higher compared with normal pregnancies. Increased levels of uric acid can be considered as one of biomarkers of preeclampsia, hence the serum uric acid levels used as serial examinations in pregnant women during antenatal care.

  19. Impact of HSD11B1 polymorphisms on BMI and components of the metabolic syndrome in patients receiving psychotropic treatments

    KAUST Repository

    Quteineh, Lina

    2015-01-01

    Background Metabolic syndrome (MetS) associated with psychiatric disorders and psychotropic treatments represents a major health issue. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is an enzyme that catalyzes tissue regeneration of active cortisol from cortisone. Elevated enzymatic activity of 11β-HSD1 may lead to the development of MetS. Methods We investigated the association between seven HSD11B1 gene (encoding 11β-HSD1) polymorphisms and BMI and MetS components in a psychiatric sample treated with potential weight gain-inducing psychotropic drugs (n=478). The polymorphisms that survived Bonferroni correction were analyzed in two independent psychiatric samples (n R1 =168, n R2 =188) and in several large population-based samples (n 1 =5338; n 2 =123 865; n 3 >100 000). Results HSD11B1 rs846910-A, rs375319-A, and rs4844488-G allele carriers were found to be associated with lower BMI, waist circumference, and diastolic blood pressure compared with the reference genotype (P corrected <0.05). These associations were exclusively detected in women (n=257) with more than 3.1 kg/m 2, 7.5 cm, and 4.2 mmHg lower BMI, waist circumference, and diastolic blood pressure, respectively, in rs846910-A, rs375319-A, and rs4844488-G allele carriers compared with noncarriers (P corrected <0.05). Conversely, carriers of the rs846906-T allele had significantly higher waist circumference and triglycerides and lower high-density lipoprotein-cholesterol exclusively in men (P corrected =0.028). The rs846906-T allele was also associated with a higher risk of MetS at 3 months of follow-up (odds ratio: 3.31, 95% confidence interval: 1.53-7.17, P corrected =0.014). No association was observed between HSD11B1 polymorphisms and BMI and MetS components in the population-based samples. Conclusions Our results indicate that HSD11B1 polymorphisms may contribute toward the development of MetS in psychiatric patients treated with potential weight gain-inducing psychotropic drugs, but do not

  20. Biomarcadores para avaliação da exposição humana às micotoxinas Biomarkers for assessment of human exposure to mycotoxins

    Directory of Open Access Journals (Sweden)

    Érika Bando

    2007-06-01

    of biomarkers, which elucidates the cause/effect and dose/effect relation in the evaluation of health risks for clinical and laboratory diagnostic purposes. The MEDLINE review about the use of biomarkers for assessment of aflatoxins, fumonisins, deoxynivalenol and ochratoxin A was carried out from 1981 to 2005. The biomarkers for assessment of human exposure to aflatoxins were the urinary metabolites of aflatoxin B1: aflatoxin M1, aflatoxin P1, aflatoxin Q1, the free aflatoxin in serum or plasma, the AFB-N7-guanine adducts and the albumin adducts or mutation in the tumour suppressor gene p53 present in human biological fluids. As far as fumonisins are concerned, levels of free fumonisin B1 and fumonisin B2, or levels of sphinganine and sphingosin, were quantified in blood and urine. As exposure biomarkers, deoxynivalenol has its own metabolism products and adducts (protein/DNA present in human fluids. As to ochratoxin A exposure, we measure it in biological fluids, once it enables us to prevent or minimize the incidence of deaths or illnesses provoked by chemical exposure.

  1. 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....

  2. 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

  3. 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

  4. 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

  5. Biomarkers for Allergen Immunotherapy: A "Panoromic" View.

    Science.gov (United States)

    Moingeon, Philippe

    2016-02-01

    Biomarkers (BMKs) are biological parameters that can be measured to predict or monitor disease severity or treatment efficacy. The induction of regulatory dendritic cells (DCs) concomitantly with a downregulation of proallergic DC2s (ie, DCs supporting the differentiation of T-helper lymphocyte type 2 cells) in the blood of patients allergic to grass pollen has been correlated with the early onset of allergen immunotherapy efficacy. The combined use of omics technologies to compare biological samples from clinical responders and nonresponders is being implemented in the context of nonhypothesis-driven approaches. Such comprehensive "panoromic" strategies help identify completely novel candidate BMKs, to be subsequently validated as companion diagnostics in large-scale clinical trials. PMID:26617233

  6. The COPD Biomarker Qualification Consortium (CBQC)

    DEFF Research Database (Denmark)

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

    2013-01-01

    Abstract Knowledge about the pathogenesis and pathophysiology of chronic obstructive pulmonary disease (COPD) has advanced dramatically over the last 30 years. Unfortunately, this has had little impact in terms of new treatments. Over the same time frame, only one new class of medication for COPD...... 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...... 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 that...

  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. 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...

  9. 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...... with their chronological age and present health status, help define their current rate of aging and contribute to establish personalized therapy plans to reduce, counteract or even avoid the appearance of aging biomarkers....

  10. 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

  11. Activation of kinin B1 receptor evokes hyperthermia through a vagal sensory mechanism in the rat

    Directory of Open Access Journals (Sweden)

    Talbot Sébastien

    2012-09-01

    Full Text Available Abstract Background Kinins are mediators of pain and inflammation. Their role in thermoregulation is, however, unknown despite the fact the B1 receptor (B1R was found implicated in lipopolysaccharide (LPS-induced fever. The aim of this study was to investigate the mechanism by which peripheral B1R affects body core temperature in a rat model known to show up-regulated levels of B1R. Methods Male Sprague–Dawley rats received streptozotocin (STZ, 65 mg/kg; i.p. to enhance B1R expression. Control rats received the vehicle only. One week later, rectal temperature was measured in awake rats after i.p. injection of increasing doses (0.01 to 5 mg/kg of des-Arg9-Bradykinin (BK and Sar-[D-Phe8]des-Arg9-BK (B1R agonists or BK (B2R agonist. The mechanism of B1R-induced hyperthermia was addressed using specific inhibitors and in rats subjected to subdiaphragmatic vagal nerve ligation. B1R mRNA level was measured by quantitative Real Time-polymerase chain reaction (qRT-PCR and B1R was localized by confocal microscopy. Results B1R agonists (0.1 to 5 mg/kg showed transient (5- to 30-minute and dose-dependent increases of rectal temperature (+1.5°C in STZ-treated rats, but not in control rats. BK caused no effect in STZ and control rats. In STZ-treated rats, B1R agonist-induced hyperthermia was blocked by antagonists/inhibitors of B1R (SSR240612, cyclooxygenase-2 (COX-2 (niflumic acid and nitric oxide synthase (NOS (L-NAME, and after vagal nerve ligation. In contrast, COX-1 inhibition (indomethacin had no effect on B1R agonist-induced hyperthermia. In STZ-treated rats, B1R mRNA was significantly increased in the hypothalamus and the vagus nerve where it was co-localized with calcitonin-gene-related peptide in sensory C-fibers. Conclusion B1R, which is induced in inflammatory diseases, could contribute to hyperthermia through a vagal sensory mechanism involving prostaglandins (via COX-2 and nitric oxide.

  12. 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.

  13. Radiation-resistant B-1 cells: A possible initiating cells of neoplastic transformation.

    Science.gov (United States)

    Guimarães-Cunha, Caroline Ferreira; Alvares-Saraiva, Anuska Marcelino; de Souza Apostolico, Juliana; Popi, Ana Flavia

    2016-07-01

    The role of B-1 cells in the hyperproliferative hematologic disease has been described. Several reports bring evidences that B-1 cells are the main cell population in the chronic lymphatic leukemia. It is also described that these cells have an important involvement in the lupus erythematous systemic. The murine model used to investigate both disease models is NZB/NZW. Data from literature point that mutation in micro-RNA 15a and 16 are the responsible for the B-1 hyperplasia in these mice. Interestingly, it was demonstrated that NZB/NZW B-1 cells are radioresistant, contrariwise to observe in other mouse lineage derived B-1 cells and B-2 cells. However, some reports bring evidences that a small percentage of B-1 cells in healthy mice are also able to survive to irradiation. Herein, we aim to investigate the malignant potential of ionizing-radiation resistant B-1 cells in vitro. Our main goal is to establish a model that mimics the neoplastic transformation originate to a damage exposure of DNA, and not only related to intrinsic mutations. Data shown here demonstrated that radiation-resistant B-1 cells were able to survive long periods in culture. Further, these cells show proliferation index increase in relation to non-irradiated B-1 cells. In addition, radiation resistant B-1 cells showed hyperploid, morphologic alterations, increased induction of apoptosis after anti-IgM stimulation. Based on these results, we could suggest that radiation resistant B-1 cells showed some modifications in that could be related to induction of malignant potential. PMID:26898918

  14. 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

  15. 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.

  16. Evidence for the h_b(1P) meson in the decay Upsilon(3S) --> pi0 h_b(1P)

    Energy Technology Data Exchange (ETDEWEB)

    Lees, J.P.

    2011-08-12

    Using a sample of 122 million {Upsilon}(3S) events recorded with the BABAR detector at the PEP-II asymmetric-energy e{sup +}e{sup -} collider at SLAC, we search for the h{sub b}(1P) spin-singlet partner of the P-wave {chi}{sub b}(1P) states in the sequential decay {Upsilon}(3S) {yields} {pi}{sup 0}h{sub b}(1P), h{sub b}(1P) {yields} {gamma}{eta}{sub b}(1S). We observe an excess of events above background in the distribution of the recoil mass against the {pi}{sup 0} at mass 9902 {+-} 4(stat.) {+-} 1(syst.) MeV/c{sup 2}. The width of the observed signal is consistent with experimental resolution, and its significance is 3.0 {sigma}, including systematic uncertainties. We obtain the value (3.7 {+-} 1.1 (stat.) {+-} 0.7 (syst.)) x 10{sup -4} for the product branching fraction {Beta}({Upsilon}(3S) {yields} {pi}{sup 0}h{sub b}) x {Beta}(h{sub b} {yields} {gamma}{eta}{sub b}).

  17. 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.

  18. 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

  19. 26 CFR 1.6050B-1 - Information returns by person making unemployment compensation payments.

    Science.gov (United States)

    2010-04-01

    ... unemployment compensation payments. 1.6050B-1 Section 1.6050B-1 Internal Revenue INTERNAL REVENUE SERVICE... Information returns by person making unemployment compensation payments. For taxable years beginning after December 31, 1978, every person who makes payments of unemployment compensation (as defined in section...

  20. 26 CFR 1.410(b)-1 - Minimum coverage requirements (before 1994).

    Science.gov (United States)

    2010-04-01

    ....410(b)-1(b)(2). (6) Integration with Social Security Act. See section 401(a)(5) and the regulations thereunder for rules relating to integration of plans with the Social Security Act. (7) Different age and... service. The plan can be shown not to satisfy the requirements of IRC section 410(b)(1)(A) as follows:...

  1. 26 CFR 31.3302(b)-1 - Additional credit against tax.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Additional credit against tax. 31.3302(b)-1...) EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE Federal Unemployment Tax Act (Chapter 23, Internal Revenue Code of 1954) § 31.3302(b)-1...

  2. The use of MR B+1 imaging for validation of FDTD electromagnetic simulations of human anatomies

    International Nuclear Information System (INIS)

    In this study, MR B+1 imaging is employed to experimentally verify the validity of FDTD simulations of electromagnetic field patterns in human anatomies. Measurements and FDTD simulations of the B+1 field induced by a 3 T MR body coil in a human corpse were performed. It was found that MR B+1 imaging is a sensitive method to measure the radiofrequency (RF) magnetic field inside a human anatomy with a precision of approximately 3.5%. A good correlation was found between the B+1 measurements and FDTD simulations. The measured B+1 pattern for a human pelvis consisted of a global, diagonal modulation pattern plus local B+1 heterogeneties. It is believed that these local B+1 field variations are the result of peaks in the induced electric currents, which could not be resolved by the FDTD simulations on a 5 mm3 simulation grid. The findings from this study demonstrate that B+1 imaging is a valuable experimental technique to gain more knowledge about the dielectric interaction of RF fields with the human anatomy

  3. UNC93B1 mediates host resistance to infection with Toxoplasma gondii.

    Directory of Open Access Journals (Sweden)

    Mariane B Melo

    Full Text Available UNC93B1 associates with Toll-Like Receptor (TLR 3, TLR7 and TLR9, mediating their translocation from the endoplasmic reticulum to the endolysosome, hence allowing proper activation by nucleic acid ligands. We found that the triple deficient '3d' mice, which lack functional UNC93B1, are hyper-susceptible to infection with Toxoplasma gondii. We established that while mounting a normal systemic pro-inflammatory response, i.e. producing abundant MCP-1, IL-6, TNFα and IFNγ, the 3d mice were unable to control parasite replication. Nevertheless, infection of reciprocal bone marrow chimeras between wild-type and 3d mice with T. gondii demonstrated a primary role of hemopoietic cell lineages in the enhanced susceptibility of UNC93B1 mutant mice. The protective role mediated by UNC93B1 to T. gondii infection was associated with impaired IL-12 responses and delayed IFNγ by spleen cells. Notably, in macrophages infected with T. gondii, UNC93B1 accumulates on the parasitophorous vacuole. Furthermore, upon in vitro infection the rate of tachyzoite replication was enhanced in non-activated macrophages carrying mutant UNC93B1 as compared to wild type gene. Strikingly, the role of UNC93B1 on intracellular parasite growth appears to be independent of TLR function. Altogether, our results reveal a critical role for UNC93B1 on induction of IL-12/IFNγ production as well as autonomous control of Toxoplasma replication by macrophages.

  4. 26 CFR 48.4161(b)-1 - Imposition and rates of tax; bows and arrows.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Imposition and rates of tax; bows and arrows. 48.4161(b)-1 Section 48.4161(b)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES MANUFACTURERS AND RETAILERS EXCISE TAXES Sporting Goods §...

  5. Construction and Virulence of Filamentous Hemagglutinin Protein B1 Mutant of Pasteurella multocida in Chickens

    Institute of Scientific and Technical Information of China (English)

    GUO Dong-chun; QU Lian-dong; SUN Yan; ZHANG Ai-qin; LIU Jia-sen; LU Yan; LIU Pei-xin; YUAN Dong-wei; JIANG Qian; SI Chang-de

    2014-01-01

    Pasteurella multocida, a Gram-negative nonmotile coccobacillus, is the causative agent of fowl cholera, bovine hemorrhagic septicemia, enzoonotic pneumonia and swine atropic rhinitis. Two iflamentous hemagglutinin genes, fhaB1 and fhaB2, are the potential virulence factors. In this study, an inactivation fhaB1 mutant of P. multocida in avian strain C48-102 was constructed by a kanamycin-resistance cassette. The virulence of the fhaB1 mutant and the wild type strain was assessed in chickens by intranasal and intramuscular challenge. The inactivation of fhaB1 resulted in a high degree of attenuation when the chickens were challenged intranasally and a lesser degree when challenged intramuscularly. The fhaB1 mutant and the wild type strain were investigated their sensitivity to the antibody-dependent classical complement-mediated killing pathway in 90%convalescent chicken serum. The fhaB1 mutant was serum sensitive as the viability has reduced between untreated serum and heat inactivated chicken serum (P<0.007). These results conifrmed that FhaB1 played the critical roles in the bacterial pathogenesis and further studies were needed to investigate the mechanism which caused reduced virulence of the fhaB1 mutant.

  6. Sulfolobus Replication Factor C stimulates the activity of DNA Polymerase B1

    DEFF Research Database (Denmark)

    Xing, Xuanxuan; Zhang, Likui; Guo, Li;

    2014-01-01

    Replication factor C (RFC) is known to function in loading proliferating cell nuclear antigen (PCNA) onto primed DNA, allowing PCNA to tether DNA polymerase for highly processive DNA synthesis in eukaryotic and archaeal replication. In this report, we show that an RFC complex from the...... with the ability of RFC to facilitate DNA binding by PolB1 through protein-protein interaction. These results suggest that Sulfolobus RFC may play a role in recruiting DNA polymerase for efficient primer extension, in addition to clamp loading, during DNA replication....... hyperthermophilic archaea of the genus Sulfolobus physically interacts with DNA polymerase B1 (PolB1) and enhances both the polymerase and 3'-5' exonuclease activities of PolB1 in an ATP-independent manner. Stimulation of the PolB1 activity by RFC is independent of the ability of RFC to bind DNA but is consistent...

  7. 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 ...

  8. Cyp26b1 within the growth plate regulates bone growth in juvenile mice

    International Nuclear Information System (INIS)

    Highlights: • Retinoic acid and Cyp26b1 were oppositely localized in growth plate cartilage. • Cyp26b1 deletion in chondrocytes decreased bone growth in juvenile mice. • Cyp26b1 deletion reduced chondrocyte proliferation and growth plate height. • Vitamin A-depletion partially reversed growth plate abnormalities caused by Cyp26b1 deficiency. • Cyp26b1 regulates bone growth by controlling chondrocyte proliferation. - Abstract: Retinoic acid (RA) is an active metabolite of vitamin A and plays important roles in embryonic development. CYP26 enzymes degrade RA and have specific expression patterns that produce a RA gradient, which regulates the patterning of various structures in the embryo. However, it has not been addressed whether a RA gradient also exists and functions in organs after birth. We found localized RA activities in the diaphyseal portion of the growth plate cartilage were associated with the specific expression of Cyp26b1 in the epiphyseal portion in juvenile mice. To disturb the distribution of RA, we generated mice lacking Cyp26b1 specifically in chondrocytes (Cyp26b1Δchon cKO). These mice showed reduced skeletal growth in the juvenile stage. Additionally, their growth plate cartilage showed decreased proliferation rates of proliferative chondrocytes, which was associated with a reduced height in the zone of proliferative chondrocytes, and closed focally by four weeks of age, while wild-type mouse growth plates never closed. Feeding the Cyp26b1 cKO mice a vitamin A-deficient diet partially reversed these abnormalities of the growth plate cartilage. These results collectively suggest that Cyp26b1 in the growth plate regulates the proliferation rates of chondrocytes and is responsible for the normal function of the growth plate and growing bones in juvenile mice, probably by limiting the RA distribution in the growth plate proliferating zone

  9. Key role for spinal dorsal horn microglial kinin B1 receptor in early diabetic pain neuropathy

    Directory of Open Access Journals (Sweden)

    Couture Réjean

    2010-06-01

    Full Text Available Abstract Background The pro-nociceptive kinin B1 receptor (B1R is upregulated on sensory C-fibres, astrocytes and microglia in the spinal cord of streptozotocin (STZ-diabetic rat. This study aims at defining the role of microglial kinin B1R in diabetic pain neuropathy. Methods Sprague-Dawley rats were made diabetic with STZ (65 mg/kg, i.p., and 4 days later, two specific inhibitors of microglial cells (fluorocitrate, 1 nmol, i.t.; minocycline, 10 mg/kg, i.p. were administered to assess the impact on thermal hyperalgesia, allodynia and mRNA expression (qRT-PCR of B1R and pro-inflammatory markers. Spinal B1R binding sites ((125I-HPP-desArg10-Hoe 140 were also measured by quantitative autoradiography. Inhibition of microglia was confirmed by confocal microscopy with the specific marker Iba-1. Effects of intrathecal and/or systemic administration of B1R agonist (des-Arg9-BK and antagonists (SSR240612 and R-715 were measured on neuropathic pain manifestations. Results STZ-diabetic rats displayed significant tactile and cold allodynia compared with control rats. Intrathecal or peripheral blockade of B1R or inhibition of microglia reversed time-dependently tactile and cold allodynia in diabetic rats without affecting basal values in control rats. Microglia inhibition also abolished thermal hyperalgesia and the enhanced allodynia induced by intrathecal des-Arg9-BK without affecting hyperglycemia in STZ rats. The enhanced mRNA expression (B1R, IL-1β, TNF-α, TRPV1 and Iba-1 immunoreactivity in the STZ spinal cord were normalized by fluorocitrate or minocycline, yet B1R binding sites were reduced by 38%. Conclusion The upregulation of kinin B1R in spinal dorsal horn microglia by pro-inflammatory cytokines is proposed as a crucial mechanism in early pain neuropathy in STZ-diabetic rats.

  10. Cyp26b1 within the growth plate regulates bone growth in juvenile mice

    Energy Technology Data Exchange (ETDEWEB)

    Minegishi, Yoshiki [Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Department of Plastic and Reconstructive Surgery, University of Fukui Hospital, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193 (Japan); Department of Plastic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Sakai, Yasuo [Department of Plastic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Department of Plastic Surgery, Bellland General Hospital, 500-3 Higashiyama Naka-ku, Sakai, Osaka 599-8247 (Japan); Yahara, Yasuhito [Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Akiyama, Haruhiko [Department of Orthopaedic Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagito, Gifu 501-1194 (Japan); Yoshikawa, Hideki [Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Hosokawa, Ko [Department of Plastic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Tsumaki, Noriyuki, E-mail: ntsumaki@cira.kyoto-u.ac.jp [Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Japan Science and Technology Agency, CREST, Tokyo 102-0075 (Japan)

    2014-11-07

    Highlights: • Retinoic acid and Cyp26b1 were oppositely localized in growth plate cartilage. • Cyp26b1 deletion in chondrocytes decreased bone growth in juvenile mice. • Cyp26b1 deletion reduced chondrocyte proliferation and growth plate height. • Vitamin A-depletion partially reversed growth plate abnormalities caused by Cyp26b1 deficiency. • Cyp26b1 regulates bone growth by controlling chondrocyte proliferation. - Abstract: Retinoic acid (RA) is an active metabolite of vitamin A and plays important roles in embryonic development. CYP26 enzymes degrade RA and have specific expression patterns that produce a RA gradient, which regulates the patterning of various structures in the embryo. However, it has not been addressed whether a RA gradient also exists and functions in organs after birth. We found localized RA activities in the diaphyseal portion of the growth plate cartilage were associated with the specific expression of Cyp26b1 in the epiphyseal portion in juvenile mice. To disturb the distribution of RA, we generated mice lacking Cyp26b1 specifically in chondrocytes (Cyp26b1{sup Δchon} cKO). These mice showed reduced skeletal growth in the juvenile stage. Additionally, their growth plate cartilage showed decreased proliferation rates of proliferative chondrocytes, which was associated with a reduced height in the zone of proliferative chondrocytes, and closed focally by four weeks of age, while wild-type mouse growth plates never closed. Feeding the Cyp26b1 cKO mice a vitamin A-deficient diet partially reversed these abnormalities of the growth plate cartilage. These results collectively suggest that Cyp26b1 in the growth plate regulates the proliferation rates of chondrocytes and is responsible for the normal function of the growth plate and growing bones in juvenile mice, probably by limiting the RA distribution in the growth plate proliferating zone.

  11. Identification of a cyclin B1-derived CTL epitope eliciting spontaneous responses in both cancer patients and healthy donors

    DEFF Research Database (Denmark)

    Andersen, Rikke Sick; Sørensen, Rikke Bæk; Ritter, Cathrin;

    2011-01-01

    With the aim to identify cyclin B1-derived peptides with high affinity for HLA-A2, we used three in silico prediction algorithms to screen the protein sequence for possible HLA-A2 binders. One peptide scored highest in all three algorithms, and the high HLA-A2-binding affinity of this peptide was...... verified in an HLA stabilization assay. By stimulation with peptide-loaded dendritic cells a CTL clone was established, which was able to kill two breast cancer cell lines in an HLA-A2-dependent and peptide-specific manner, demonstrating presentation of the peptide on the surface of cancer cells....... Furthermore, blood from cancer patients and healthy donors was screened for spontaneous T-cell reactivity against the peptide in IFN-¿ ELISPOT assays. Patients with breast cancer, malignant melanoma, or renal cell carcinoma hosted powerful and high-frequency T-cell responses against the peptide. In addition...

  12. Identification of a cyclin B1-derived CTL epitope eliciting spontaneous responses in both cancer patients and healthy donors

    DEFF Research Database (Denmark)

    Andersen, Rikke Sick; Sørensen, Rikke Bæk; Ritter, Cathrin;

    2011-01-01

    With the aim to identify cyclin B1-derived peptides with high affinity for HLA-A2, we used three in silico prediction algorithms to screen the protein sequence for possible HLA-A2 binders. One peptide scored highest in all three algorithms, and the high HLA-A2-binding affinity of this peptide was...... verified in an HLA stabilization assay. By stimulation with peptide-loaded dendritic cells a CTL clone was established, which was able to kill two breast cancer cell lines in an HLA-A2-dependent and peptide-specific manner, demonstrating presentation of the peptide on the surface of cancer cells....... Furthermore, blood from cancer patients and healthy donors was screened for spontaneous T-cell reactivity against the peptide in IFN-γ ELISPOT assays. Patients with breast cancer, malignant melanoma, or renal cell carcinoma hosted powerful and high-frequency T-cell responses against the peptide. In addition...

  13. 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.

  14. 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

  15. Collagen fragment biomarkers as serological biomarkers of lean body mass

    DEFF Research Database (Denmark)

    Nedergaard, A.; Dalgas, U.; Primdahl, H.;

    2015-01-01

    Background Loss of muscle mass and function is an important complication to ageing and a range of pathologies, including, but not restricted to, cancer, organ failures, and sepsis. A number of interventions have been proposed ranging from exercise to anabolic pharmacological therapy, with varying...... success. Easily applicable serological biomarkers of lean and/or muscle mass and change therein would benefit monitoring of muscle mass during muscle atrophy as well as during recovery. We set out to validate if novel peptide biomarkers derived from Collagen III and VI were markers of lean body mass (LBM...

  16. Interaction of vitamin B1 with bovine serum albumin investigation using vitamin B1-selective electrode: potentiometric and molecular modeling study.

    Science.gov (United States)

    Hosseinzadeh, Reza; Khorsandi, Khatereh

    2016-09-01

    Vitamin B1 or thiamin is one of the B vitamins. All B vitamins help the body to convert food (carbohydrates) into fuel (glucose), which produces energy. The B vitamins are necessary for healthy skin, eyes, hair, and liver. It also could help the nervous system function properly, and is necessary for brain functions. Drug interactions with protein can affect the distribution of the drug and eliminate the drug in living systems. In this study, the binding of thiamine hydrochloride (vitamin B1) to bovine serum albumin (BSA) was evaluated using a new proposed vitamin B1 (thiamine)-selective membrane electrode under various experimental conditions, such as pH, ionic strength, and protein concentration; in addition molecular modeling was applied as well. The binding isotherms plotted based on potentiometric data and analyzed using the Wyman binding potential concept. The apparent binding constant was determined and used for the calculation of intrinsic Gibbs free energy of binding. According to the electrochemical and molecular docking results, it can be concluded that the hydrophobic interactions and hydrogen binding are major interactions between BSA and vitamin B1. PMID:26372107

  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. Differential Effects of Glycyrrhiza Species on Genotoxic Estrogen Metabolism: Licochalcone A Downregulates P450 1B1, whereas Isoliquiritigenin Stimulates It.

    Science.gov (United States)

    Dunlap, Tareisha L; Wang, Shuai; Simmler, Charlotte; Chen, Shao-Nong; Pauli, Guido F; Dietz, Birgit M; Bolton, Judy L

    2015-08-17

    Estrogen chemical carcinogenesis involves 4-hydroxylation of estrone/estradiol (E1/E2) by P450 1B1, generating catechol and quinone genotoxic metabolites that cause DNA mutations and initiate/promote breast cancer. Inflammation enhances this effect by upregulating P450 1B1. The present study tested the three authenticated medicinal species of licorice [Glycyrrhiza glabra (GG), G. uralensis (GU), and G. inflata (GI)] used by women as dietary supplements for their anti-inflammatory activities and their ability to modulate estrogen metabolism. The pure compounds, liquiritigenin (LigF), its chalcone isomer isoliquiritigenin (LigC), and the GI-specific licochalcone A (LicA) were also tested. The licorice extracts and compounds were evaluated for anti-inflammatory activity by measuring inhibition of iNOS activity in macrophage cells: GI ≫ GG > GU and LigC ≅ LicA ≫ LigF. The Michael acceptor chalcone, LicA, is likely responsible for the anti-inflammatory activity of GI. A sensitive LC-MS/MS assay was employed to quantify estrogen metabolism by measuring 2-MeOE1 as nontoxic and 4-MeOE1 as genotoxic biomarkers in the nontumorigenic human mammary epithelial cell line, MCF-10A. GG, GU, and LigC increased 4-MeOE1, whereas GI and LicA inhibited 2- and 4-MeOE1 levels. GG, GU (5 μg/mL), and LigC (1 μM) also enhanced P450 1B1 expression and activities, which was further increased by inflammatory cytokines (TNF-α and IFN-γ). LicA (1, 10 μM) decreased cytokine- and TCDD-induced P450 1B1 gene expression and TCDD-induced xenobiotic response element luciferase reporter (IC50 = 12.3 μM), suggesting an antagonistic effect on the aryl hydrocarbon receptor, which regulates P450 1B1. Similarly, GI (5 μg/mL) reduced cytokine- and TCDD-induced P450 1B1 gene expression. Collectively, these data suggest that, of the three licorice species that are used in botanical supplements, GI represents the most promising chemopreventive licorice extract for women's health. Additionally, the

  19. A subset of AID-dependent B-1a cells initiates hypersensitivity and pneumococcal pneumonia resistance.

    Science.gov (United States)

    Askenase, Phillip W; Bryniarski, Krzysztof; Paliwal, Vipin; Redegeld, Frank; Groot Kormelink, Thomas; Kerfoot, Steven; Hutchinson, Andrew T; van Loveren, Henk; Campos, Regis; Itakura, Atsuko; Majewska-Szczepanik, Monika; Yamamoto, Natsuo; Nazimek, Katarzyn; Szczepanik, Marian; Ptak, Wold

    2015-12-01

    We propose that there is a special B-1a B cell subset ("sB-1a" cells) that mediates linked processes very early after immunization to initiate cutaneous contact sensitivity (CS), delayed-type hypersensitivity (DTH), and immune resistance to pneumococcal pneumonia. Our published data indicate that in CS and DTH, these initiating processes are required for elicitation of the delayed onset and late-occurring classical T cell-mediated responses. sB-1a cells resemble memory B2 cells, as they are stimulated within 1 h of immunization and depend on T helper cytokines-uniquely IL-4 from hepatic iNKT cells--for activation and rapid migration from the peritoneal cavity to the spleen to secrete IgM antibody (Ab) and Ab-derived free light chains (FLCs) by only 1 day after immunization. Unlike conventional B-1a (cB-1a) cell-produced IgM natural Ab, IgM Ab produced by sB-1a cells has high Ag affinity owing to immunoglobulin V-region mutations induced by activation-induced cytidine deaminase (AID). The dominant cB-1a cells are increased in immunized AID-deficient mice but do not mediate initiation, CS, or pneumonia resistance because natural Ab has relatively low Ag affinity because of unmutated germ-line V regions. In CS and DTH, sB-1a IgM Ag affinity is sufficiently high to mediate complement activation for generation of C5a that, together with vasoactive mediators such as TNF-α released by FLC-sensitized mast cells, activate local endothelium for extravascular recruitment of effector T cells. We conclude by discussing the possibility of functional sB-1 cells in humans. PMID:26662721

  20. SH2B1 regulation of energy balance, body weight, and glucose metabolism

    Institute of Scientific and Technical Information of China (English)

    Liangyou; Rui

    2014-01-01

    The Src homology 2B(SH2B)family members(SH2B1,SH2B2 and SH2B3)are adaptor signaling proteins containing characteristic SH2 and PH domains.SH2B1(also called SH2-B and PSM)and SH2B2(also called APS)are able to form homo-or hetero-dimers via their N-terminal dimerization domains.Their C-terminal SH2 domains bind to tyrosyl phosphorylated proteins,including Janus kinase 2(JAK2),TrkA,insulin receptors,insulin-like growth factor-1 receptors,insulin receptor substrate-1(IRS1),and IRS2.SH2B1 enhances leptin signaling by both stimulating JAK2 activity and assembling a JAK2/IRS1/2 signaling complex.SH2B1 promotes insulin signaling by both enhancing insulin receptor catalytic activity and protecting against dephosphorylation of IRS proteins.Accordingly,genetic deletion of SH2B1 results in severe leptin resistance,insulin resistance,hyperphagia,obesity,and type 2 diabetes in mice.Neuronspecific overexpression of SH2B1βtransgenes protects against diet-induced obesity and insulin resistance.SH2B1 in pancreaticβcells promotesβcell expansion and insulin secretion to counteract insulin resistance in obesity.Moreover,numerous SH2B1 mutations are genetically linked to leptin resistance,insulin resistance,obesity,and type 2 diabetes in humans.Unlike SH2B1,SH2B2 and SH2B3 are not required for the maintenance of normal energy and glucose homeostasis.The metabolic function of the SH2B family is conserved from insects to humans.

  1. Propeptide of cathepsin B1 from human blood fluke: structure-function mapping and small mimetics design

    Czech Academy of Sciences Publication Activity Database

    Horn, Martin; Jílková, Adéla; Vondrášek, Jiří; Caffrey, C. R.; Mareš, Michael

    Portorož : -, 2010. s. 72-72. [Symposium on Proteases , Inhibitors and Biological Control /12./. 25.9.-29.9.2010, Portorož] R&D Projects: GA ČR GA203/09/1585 Institutional research plan: CEZ:AV0Z40550506 Keywords : protease * schistosoma * propeptide Subject RIV: CE - Biochemistry

  2. 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

  3. Effects of CYP7B1-mediated catalysis on estrogen receptor activation.

    Science.gov (United States)

    Pettersson, Hanna; Lundqvist, Johan; Norlin, Maria

    2010-09-01

    Most of the many biological effects of estrogens are mediated via the estrogen receptors ERalpha and beta. The current study examines the role of CYP7B1-mediated catalysis for activation of ER. Several reports suggest that CYP7B1 may be important for hormonal action but previously published studies are contradictory concerning the manner in which CYP7B1 affects ERbeta-mediated response. In the current study, we examined effects of several CYP7B1-related steroids on ER activation, using an estrogen response element (ERE) reporter system. Our studies showed significant stimulation of ER by 5-androstene-3beta,17beta-diol (Aene-diol) and 5alpha-androstane-3beta,17beta-diol (3beta-Adiol). In contrast, the CYP7B1-formed metabolites from these steroids did not activate the receptor, indicating that CYP7B1-mediated metabolism abolishes the ER-stimulating effect of these compounds. The mRNA level of HEM45, a gene known to be stimulated by estrogens, was strongly up-regulated by Aene-diol but not by its CYP7B1-formed metabolite, further supporting this concept. We did not observe stimulation by dehydroepiandrosterone (DHEA) or 7alpha-hydroxy-DHEA, previously suggested to affect ERbeta-mediated response. As part of these studies we examined metabolism of Aene-diol in pig liver which is high in CYP7B1 content. These experiments indicate that CYP7B1-mediated metabolism of Aene-diol is of a similar rate as the metabolism of the well-known CYP7B1 substrates DHEA and 3beta-Adiol. CYP7B1-mediated metabolism of 3beta-Adiol has been proposed to influence ERbeta-mediated growth suppression. Our results indicate that Aene-diol also might be important for ER-related pathways. Our data indicate that low concentrations of Aene-diol can trigger ER-mediated response equally well for both ERalpha and beta and that CYP7B1-mediated conversion of Aene-diol into a 7alpha-hydroxymetabolite will result in loss of action. PMID:20553962

  4. DISTRIBUTION Of AFLATOXIN B1 FROM POULTRY FEED TO DIFFERENT BODY TISSUES OF BROILERS

    Directory of Open Access Journals (Sweden)

    Farida Begum, A. Rehman1, G. Maliha and J. Nuzhat

    2001-07-01

    Full Text Available This study was carried out to know the distribution of aflatoxin B1 In various edible tissues of broilers from poultry feed at the stage of marketing. For this purpose liver, kidney, dressed meat and poultry feed of the representative flocks were collected and oven dried. The aflatoxin B1 contents of the samples were .e; determined through thin layer chromatography, The data thus collected were statistically analyzed and the results showed that the aflatoxin B1 level was higher (P<0.01 in liver as compared to kidneys and meat.

  5. Use of gamma irradiation to prevent aflatoxin B1 production in smoked dried fish

    International Nuclear Information System (INIS)

    Smoked dried fish bought from the Nigerian market was inoculated with spores of Aspergillus flavus (U.I. 81) and irradiated with doses of 0.625, 1.25, 2.50 and 5.00 kGy gamma irradiation. The effect on aflatoxin B1 production on subsequent incubation for 8 days as stationary cultures was measured. The amount of aflatoxin B1 produced was found to decrease with increased gamma irradiation dose levels. The non-irradiated control produced significantly (at 1% level) greater amounts of aflatoxin B1 as compared to the treated cultures. (author)

  6. Lipid Polymorphism Induced by Surfactant Peptide SP-B1-25

    OpenAIRE

    Farver, R. Suzanne; Mills, Frank D.; Antharam, Vijay C.; Chebukati, Janetricks N.; Fanucci, Gail E.; Long, Joanna R.

    2010-01-01

    Pulmonary surfactant protein B (SP-B) is an essential protein for lowering surface tension in the alveoli. SP-B1-25, a peptide comprised of the N-terminal 25 amino-acid residues of SP-B, is known to retain much of the biological activity of SP-B. Circular dichroism has shown that when SP-B1-25 interacts with negatively charged lipid vesicles, it contains significant helical structure for the lipid compositions and peptide/lipid ratios studied here. The effect of SP-B1-25 on lipid organization...

  7. 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

  8. 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.

  9. 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.

  10. Association between cell-bound blood amyloid-β(1–40) levels and hippocampus volume

    OpenAIRE

    Sotolongo-Grau, Oscar; Pesini, Pedro; Valero, Sergi; Lafuente, Asunción; Buendía, Mar; Pérez-Grijalba, Virginia; José, Itziar San; Ibarria, Marta; Tejero, Miguel A; Giménez, Joan; Hernández, Isabel; Tárraga, Lluís; Ruiz, Agustín; Boada, Mercé; Sarasa, Manuel

    2014-01-01

    Introduction The identification of early, preferably presymptomatic, biomarkers and true etiologic factors for Alzheimer’s disease (AD) is the first step toward establishing effective primary and secondary prevention programs. Consequently, the search for a relatively inexpensive and harmless biomarker for AD continues. Despite intensive research worldwide, to date there is no definitive plasma or blood biomarker indicating high or low risk of conversion to AD. Methods Magnetic resonance imag...

  11. Gene-gene-environment interactions between drugs, transporters, receptors, and metabolizing enzymes: Statins, SLCO1B1, and CYP3A4 as an example.

    Science.gov (United States)

    Sadee, Wolfgang

    2013-09-01

    Pharmacogenetic biomarker tests include mostly specific single gene-drug pairs, capable of accounting for a portion of interindividual variability in drug response and toxicity. However, multiple genes are likely to contribute, either acting independently or epistatically, with the CYP2C9-VKORC1-warfarin test panel, an example of a clinically used gene-gene-dug interaction. I discuss here further instances of gene-gene-drug interactions, including a proposed dynamic effect on statin therapy by genetic variants in both a transporter (SLCO1B1) and a metabolizing enzyme (CYP3A4) in liver cells, the main target site where statins block cholesterol synthesis. These examples set a conceptual framework for developing diagnostic panels involving multiple gene-drug combinations. PMID:23436703

  12. Brief report: biomarkers of aortic vascular prosthetic graft infection in a porcine model with Staphylococcus aureus

    DEFF Research Database (Denmark)

    Langerhuus, S. N.; Tønnesen, E. K.; Jensen, K. H.;

    2010-01-01

    -renal aorta exposed by laparotomy; “CLEAN” pigs had an aortic graft inserted; “LOW” and “HIGH” pigs had an aortic graft inserted and, subsequently, S. aureus were inoculated on the graft material (5 × 104 colony-forming units [CFU] and 1 × 106 CFU, respectively). Biomarkers were evaluated prior to surgery...... and on day 2, 5, 7, and 14 post-operatively in blood samples. Of all biomarkers evaluated, CRP was superior for diagnosing S. aureus AVPGI in pigs, with a sensitivity of 0.86 and a specificity of 0.75.......Aortic vascular prosthetic graft infection (AVPGI) with Staphylococcus aureus is a feared post-operative complication. This study was conducted to evaluate the clinical signs and potential biomarkers of infection in a porcine AVPGI model. The biomarkers evaluated were: C-reactive protein (CRP...

  13. 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"....

  14. 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.

  15. Inclusive prompt χ _{c,b}(1^{++}) production at the LHC

    Science.gov (United States)

    Shuvaev, A. G.; Khoze, V. A.; Martin, A. D.; Ryskin, M. G.

    2015-12-01

    We study the prompt production of the χ _c(1^+) and χ _b(1^+) mesons at high energies. Unlike χ (0^+,2^+) production, χ (1^+) mesons cannot be created at LO via the fusion of two on-mass-shell gluons, that is, gg→ χ _{c,b}(1^+) are not allowed. However, the available experimental data show that the cross sections for χ _c(1^+) and χ _c(2^+) are comparable. We therefore investigate four other χ (1^+) production mechanisms: namely, (i) the standard NLO process gg→ χ _{c,b}(1^+)+g, (ii) via gluon virtuality, (iii) via gluon reggeisation and, finally, (iv) the possibility to form χ _{c,b}(1^+) by the fusion of three gluons, where one extra gluon comes from another parton cascade, as in the Double Parton Scattering processes.

  16. Observation and Properties of L=1 B_1 and B_2* Mesons

    CERN Document Server

    Abazov, V M; Abolins, M; Acharya, B S; Adams, M; Adams, T; Aguiló, E; Ahn, S H; Ahsan, M; Alexeev, G D; Alkhazov, G; Alton, A; Alverson, G; Alves, G A; Anastasoaie, M; Ancu, L S; Andeen, T; Anderson, S; Andrieu, B; Anzelc, M S; Arnoud, Y; Arov, M; Arthaud, M; Askew, A; Åsman, B; Assis-Jesus, A C S; Atramentov, O; Autermann, C; Avila, C; Ay, C; Badaud, F; Baden, A; Bagby, L; Baldin, B; Bandurin, D V; Banerjee, S; Banerjee, P; Barberis, E; Barfuss, A F; Bargassa, P; Baringer, P; Barreto, J; Bartlett, J F; Bassler, U; Bauer, D; Beale, S; Bean, A; Begalli, M; Begel, M; Belanger-Champagne, C; Bellantoni, L; Bellavance, A; Benítez, J A; Beri, S B; Bernardi, G; Bernhard, R; Berntzon, L; Bertram, I; Besançon, M; Beuselinck, R; Bezzubov, V A; Bhat, P C; Bhatnagar, V; Biscarat, C; Blazey, G; Blekman, F; Blessing, S; Bloch, D; Bloom, K; Böhnlein, A; Boline, D; Bolton, T A; Borissov, G; Bos, K; Bose, T; Brandt, A; Brock, R; Brooijmans, G; Bross, A; Brown, D; Buchanan, N J; Buchholz, D; Bühler, M; Büscher, V; Burdin, S; Burke, S; Burnett, T H; Buszello, C P; Butler, J M; Calfayan, P; Calvet, S; Cammin, J; Caron, S; Carvalho, W; Casey, B C K; Cason, N M; Castilla-Valdez, H; Chakrabarti, S; Chakraborty, D; Chan, K M; Chan, K; Chandra, A; Charles, F; Cheu, E; Chevallier, F; Cho, D K; Choi, S; Choudhary, B; Christofek, L; Christoudias, T; Cihangir, S; Claes, D; Clément, C; Clement, B; Coadou, Y; Cooke, M; Cooper, W E; Corcoran, M; Couderc, F; Cousinou, M C; Crepe-Renaudin, S; Cutts, D; Cwiok, M; Da Motta, H; Das, A; Davies, G; De, K; De Jong, S J; de Jong, P; De La Cruz-Burelo, E; De Oliveira Martins, C; Degenhardt, J D; Déliot, F; Demarteau, M; Demina, R; Denisov, D; Denisov, S P; Desai, S; Diehl, H T; Diesburg, M; Dominguez, A; Dong, H; Dudko, L V; Duflot, L; Dugad, S R; Duggan, D; Duperrin, A; Dyer, J; Dyshkant, A; Eads, M; Edmunds, D; Ellison, J; Elvira, V D; Enari, Y; Eno, S; Ermolov, P; Evans, H; Evdokimov, A; Evdokimov, V N; Ferapontov, A V; Ferbel, T; Fiedler, F; Filthaut, F; Fisher, W; Fisk, H E; Ford, M; Fortner, M; Fox, H; Fu, S; Fuess, S; Gadfort, T; Galea, C F; Gallas, E; Galyaev, E; García, C; García-Bellido, A; Gavrilov, V; Gay, P; Geist, W; Gelé, D; Gerber, C E; Gershtein, Yu; Gillberg, D; Ginther, G; Gollub, N; Gómez, B; Goussiou, A; Grannis, P D; Greenlee, H; Greenwood, Z D; Gregores, E M; Grenier, G; Gris, P; Grivaz, J F; Grohsjean, A; Grünendahl, S; Grünewald, M W; Guo, J; Guo, F; Gutíerrez, P; Gutíerrez, G; Haas, A; Hadley, N J; Haefner, P; Hagopian, S; Haley, J; Hall, I; Hall, R E; Han, L; Hanagaki, K; Hansson, P; Harder, K; Harel, A; Harrington, R; Hauptman, J M; Hauser, R; Hays, J; Hebbeker, T; Hedin, D; Hegeman, J G; Heinmiller, J M; Heinson, A P; Heintz, U; Hensel, C; Herner, K; Hesketh, G; Hildreth, M D; Hirosky, R; Hobbs, J D; Hoeneisen, B; Hoeth, H; Hohlfeld, M; Hong, S J; Hooper, R; Hossain, S; Houben, P; Hu, Y; Hubacek, Z; Hynek, V; Iashvili, I; Illingworth, R; Ito, A S; Jabeen, S; Jaffré, M; Jain, S; Jakobs, K; Jarvis, C; Jesik, R; Johns, K; Johnson, C; Johnson, M; Jonckheere, A; Jonsson, P; Juste, A; Käfer, D; Kahn, S; Kajfasz, E; Kalinin, A M; Kalk, J R; Kalk, J M; Kappler, S; Karmanov, D; Kasper, J; Kasper, P; Katsanos, I; Kau, D; Kaur, R; Kaushik, V; Kehoe, R; Kermiche, S; Khalatyan, N; Khanov, A; Kharchilava, A I; Kharzheev, Yu M; Khatidze, D; Kim, H; Kim, T J; Kirby, M H; Kirsch, M; Klima, B; Kohli, J M; Konrath, J P; Kopal, M; Korablev, V M; Kothari, B; Kozelov, A V; Krop, D; Kryemadhi, A; Kühl, T; Kumar, A; Kunori, S; Kupco, A; Kurca, T; Kvita, J; Lacroix, F; Lam, D; Lammers, S; Landsberg, G L; Lazoflores, J; Lebrun, P; Lee, W M; Leflat, A; Lehner, F; Lellouch, J; Lesne, V; Lévêque, J; Lewis, P; Li, J; Li, Q Z; Li, L; Lietti, S M; Lima, J G R; Lincoln, D; Linnemann, J; Lipaev, V V; Lipton, R; Liu, Y; Liu, Z; Lobo, L; Lobodenko, A; Lokajícek, M; Lounis, A; Love, P; Lubatti, H J; Lyon, A L; Maciel, A K A; Mackin, D; Madaras, R J; Mättig, P; Magass, C; Magerkurth, A; Makovec, N; Mal, P K; Malbouisson, H B; Malik, S; Malyshev, V L; Mao, H S; Maravin, Y; Martin, B; McCarthy, R; Melnitchouk, A; Mendes, A; Mendoza, L; Mercadante, P G; Merkin, M; Merritt, K W; Meyer, J; Meyer, A; Michaut, M; Millet, T; Mitrevski, J; Molina, J; Mommsen, R K; Mondal, N K; Moore, R W; Moulik, T; Muanza, G S; Mulders, M; Mulhearn, M; Mundal, O; Mundim, L; Nagy, E; Naimuddin, M; Narain, M; Naumann, N A; Neal, H A; Negret, J P; Neustroev, P; Nilsen, H; Nomerotski, A; Novaes, S F; Nunnemann, T; O'Dell, V; O'Neil, D C; Obrant, G; Ochando, C; Onoprienko, D; Oshima, N; Osta, J; Otec, R; Oteroy-Garzon, G J; Owen, M; Padley, P; Pangilinan, M; Parashar, N; Park, S J; Park, S K; Parsons, J; Partridge, R; Parua, N; Patwa, A; Pawloski, G; Penning, B; Perea, P M; Peters, K; Peters, Y; Petroff, P; Petteni, M; Piegaia, R; Piper, J; Pleier, M A; Podesta-Lerma, P L M; Podstavkov, V M; Pogorelov, Y; Pol, M E; Polozov, P; Pompo, A; Pope, B G; Popov, A V; Potter, C; Prado da Silva, W L; Prosper, H B; Protopopescu, S D; Qian, J; Quadt, A; Quinn, B; Rakitine, A; Rangel, M S; Rani, K J; Ranjan, K; Ratoff, P N; Renkel, P; Reucroft, S; Rich, P; Rijssenbeek, M; Ripp-Baudot, I; Rizatdinova, F K; Robinson, S; Rodrigues, R F; Royon, C; Rubinov, P; Ruchti, R; Safronov, G; Sajot, G; Sánchez-Hernández, A; Sanders, M P; Santoro, A F S; Savage, G; Sawyer, L; Scanlon, T; Schaile, A D; Schamberger, R D; Scheglov, Y; Schellman, H; Schieferdecker, P; Schliephake, T; Schmitt, C; Schwanenberger, C; Schwartzman, A; Schwienhorst, R; Sekaric, J; Sen-Gupta, S; Severini, H; Shabalina, E; Shamim, M; Shary, V; Shchukin, A A; Shivpuri, R K; Shpakov, D; Siccardi, V; Simák, V; Sirotenko, V I; Skubic, P L; Slattery, P F; Smirnov, D; Smith, R P; Snow, J; Snow, G R; Snyder, S; Söldner-Rembold, S; Sonnenschein, L; Sopczak, A; Sosebee, M; Soustruznik, K; Souza, M; Spurlock, B; Stark, J; Steele, J; Stolin, V; Stone, A; Stoyanova, D A; Strandberg, J; Strandberg, S; Strang, M A; Strauss, M; Strauss, E; Ströhmer, R; Strom, D; Strovink, M; Stutte, L; Sumowidagdo, S; Svoisky, P; Sznajder, A; Talby, M; Tamburello, P; Tanasijczuk, A; Taylor, W; Telford, P; Temple, J; Tiller, B; Tissandier, F; Titov, M; Tokmenin, V V; Tomoto, M; Toole, T; Torchiani, I; Trefzger, T; Tsybychev, D; Tuchming, B; Tully, C; Tuts, P M; Unalan, R; Uvarov, S; Uvarov, L; Uzunyan, S; Vachon, B; Van den Berg, P J; van Eijk, B; Van Kooten, R; Van Leeuwen, W M; Varelas, N; Varnes, E W; Vartapetian, A H; Vasilyev, I A; Vaupel, M; Verdier, P; Vertogradov, L S; Verzocchi, M; Villeneuve-Séguier, F; Vint, P; Vokac, P; Von Törne, E; Voutilainen, M; Vreeswijk, M; Wagner, R; Wahl, H D; Wang, L; Wang, M H L; Warchol, J; Watts, G; Wayne, M; Weber, M; Weber, G; Weerts, H; Wenger, A; Wermes, N; Wetstein, M; White, A; Wicke, D; Wilson, G W; Williams, M R J; Wimpenny, S J; Wobisch, M; Wood, D R; Wyatt, T R; Xie, Y; Yacoob, S; Yamada, R; Yan, M; Yasuda, T; Yatsunenko, Y A; Yip, K; Yoo, H D; Youn, S W; Yu, J; Yu, C; Yurkewicz, A; Zatserklyaniy, A; Zeitnitz, C; Zhang, D; Zhao, T; Zhou, B; Zhu, J; Zielinski, M; Zieminska, D; Zieminski, A; Zivkovic, L; Zutshi, V; Zverev, E G

    2007-01-01

    Excited B mesons B_1 and B_2* are observed directly for the first time as two separate states in fully reconstructed decays to B+(*) pi-. The mass of B_1 is measured to be (5720.6 +- 2.4 +- 1.4) MeV/c^2 and the mass difference DeltaM between B_2* and B_1 is (26.2 +- 3.1 +- 0.9) MeV/c^2, giving the mass of the B_2* as (5746.8 +- 2.4 +- 1.7) MeV/c^2. The production rate for B_1 and B_2* mesons is determined to be a fraction (13.9 +- 1.9 +- 3.2)% of the production rate of the B+ meson.

  17. Inclusive prompt χc,b(1++) production at the LHC

    International Nuclear Information System (INIS)

    We study the prompt production of the χc(1+) and χb(1+) mesons at high energies. Unlike χ(0+,2+) production, χ(1+) mesons cannot be created at LO via the fusion of two on-mass-shell gluons, that is, gg → χc,b(1+) are not allowed. However, the available experimental data show that the cross sections for χc(1+) and χc(2+) are comparable. We therefore investigate four other χ(1+) production mechanisms: namely, (i) the standard NLO process gg → χc,b(1+) + g, (ii) via gluon virtuality, (iii) via gluon reggeisation and, finally, (iv) the possibility to form χc,b(1+) by the fusion of three gluons, where one extra gluon comes from another parton cascade, as in the Double Parton Scattering processes. (orig.)

  18. Inclusive prompt χc,b(1++) production at the LHC

    International Nuclear Information System (INIS)

    We study the prompt production of the χc(1+) and χb(1+) mesons at high energies. Unlike χ(0+,2+) production, χ(1+) mesons cannot be created at LO via the fusion of two on-mass-shell gluons, that is, gg→χc,b(1+) are not allowed. However, the available experimental data show that the cross sections for χc(1+) and χc(2+) are comparable. We therefore investigate four other χ(1+) production mechanisms: namely, (i) the standard NLO process gg→χc,b(1+)+g, (ii) via gluon virtuality, (iii) via gluon reggeisation and, finally, (iv) the possibility to form χc,b(1+) by the fusion of three gluons, where one extra gluon comes from another parton cascade, as in the Double Parton Scattering processes

  19. Aflatoxin B1 induced upregulation of protein arginine methyltransferase 5 in human cell lines.

    Science.gov (United States)

    Ghufran, Md Sajid; Ghosh, Krishna; Kanade, Santosh R

    2016-09-01

    The exposure of naturally occurring mycotoxins affects human health and play a vital role in cancer initiation and progression. Aflatoxin B1 is a difuranocoumarin mycotoxin, classified as a group I carcinogen. The present study was conducted to assess the effect of aflatoxin B1 on epigenetic regulatory proteins. The protein arginine methyltransferase 5 expression was induced upon aflatoxin B1 treatment in a dose and time dependent manner. Further global arginine methylation was also increased in the same manner. This is the first report showing the induction of epigenetic regulatory protein, protein arginine methyltransferase 5 upon aflatoxin B1 treatment. Further study is required to establish the detailed pathway of PRMT5 induction. PMID:27242039

  20. MISR Level 1B1 Local Mode Radiance Data V002

    Data.gov (United States)

    National Aeronautics and Space Administration — This is the Local Mode Level 1B1 Product containing the DNs radiometrically scaled to radiances with no geometric resampling (Suggested Usage: The MISR Instrument...