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Sample records for potential endogenous marker

  1. Endogenous biotin as a marker of adrenocortical cells with steroidogenic potential.

    PubMed

    Paul, Alex; Laufer, Ed

    2011-04-10

    Interpretation of adrenal cortex phenotypes is greatly facilitated by simultaneous examination of multiple markers at single cell resolution. However, the availability of multiple appropriate antibodies can be rate limiting, while their cognate antigens are often subject to variable accessibility. Specific markers not subject to these constraints thus have obvious utility. Here we report that endogenous biotin, when detected in fixed, frozen tissue sections using fluorescent streptavidin, is a specific marker of apparently all cells with steroidogenic potential in the murine adrenal cortex. While streptavidin stains presteroidogenic and mature cortical cells, it does not label the adrenal capsule, medulla or vascular endothelium. Developmental profiles reveal adrenal endogenous biotin labeling from E13.5 through adulthood. Comparisons with zonal markers, hypothalamic-pituitary-adrenal (HPA) axis-remodeled tissue, transgenic Shh-nLacZ or Gli1-nLacZ animals, and Shh mutant embryos further demonstrate the utility of this approach. Fluorescent streptavidin applied using a simple one-step staining protocol thus provides a potent counterstain for use in adrenal analyses. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  2. Endogenous biotin as a marker of adrenocortical cells with steroidogenic potential

    PubMed Central

    Paul, Alex; Laufer, Ed

    2011-01-01

    Interpretation of adrenal cortex phenotypes is greatly facilitated by simultaneous examination of multiple markers at single cell resolution. However the availability of multiple appropriate antibodies can be rate limiting, while their cognate antigens are often subject to variable accessibility. Specific markers not subject to these constraints thus have obvious utility. Here we report that endogenous biotin, when detected in fixed, frozen tissue sections using fluorescent streptavidin, is a specific marker of apparently all cells with steroidogenic potential in the murine adrenal cortex. While streptavidin stains presteroidogenic and mature cortical cells, it does not label the adrenal capsule, medulla or vascular endothelium. Developmental profiles reveal adrenal endogenous biotin labeling from E13.5 through adulthood. Comparisons with zonal markers, hypothalamic-pituitary-adrenal (HPA) axis-remodeled tissue, transgenic Shhn-LacZ or Gli1-nLacZ animals, and Shh mutant embryos further demonstrate the utility of this approach. Fluorescent streptavidin applied using a simple one-step staining protocol thus provides a potent counterstain for use in adrenal analyses. PMID:21256921

  3. Endogenous versus exogenous markers of adult neurogenesis in canaries and other birds: advantages and disadvantages.

    PubMed

    Balthazart, Jacques; Ball, Gregory F

    2014-12-15

    Although the existence of newborn neurons had originally been suggested, but not broadly accepted, based on studies in adult rodent brains, the presence of an active neurogenesis process in adult homoeothermic vertebrates was first firmly established in songbirds. Adult neurogenesis was initially studied with the tritiated thymidine technique, later replaced by the injection and detection of the marker of DNA replication 5-bromo-2'-deoxyuridine (BrdU). More recently, various endogenous markers were used to identify young neurons or cycling neuronal progenitors. We review here the respective advantages and pitfalls of these different approaches in birds, with specific reference to the microtubule-associated protein, doublecortin (DCX), that has been extensively used to identify young newly born neurons in adult brains. All these techniques of course have limitations. Exogenous markers label cells replicating their DNA only during a brief period and it is difficult to select injection doses that would exhaustively label all these cells without inducing DNA damage that will also result in some form of labeling during repair. On the other hand, specificity of endogenous markers is difficult to establish due to problems related to the specificity of antibodies (these problems can be, but are not always, addressed) and more importantly because it is difficult, if not impossible, to prove that a given marker exhaustively and specifically labels a given cell population. Despite these potential limitations, these endogenous markers and DCX staining in particular clearly represent a useful approach to the detailed study of neurogenesis especially when combined with other techniques such as BrdU. © 2014 Wiley Periodicals, Inc.

  4. Bacopa monnieri modulates endogenous cytoplasmic and mitochondrial oxidative markers in prepubertal mice brain.

    PubMed

    Shinomol, George K; Muralidhara

    2011-02-15

    Bacopa monnieri (BM) an herb, found throughout the Indian subcontinent in wet, damp and marshy areas is used in Ayurvedic system of medicine for improving intellect/memory, treatment of anxiety and neuropharmacological disorders. Although extensively given to children as a memory enhancer, no data exists on its ability to modulate neuronal oxidative stress in prepubertal animal models. Hence in this study, we examined if dietary intake of BM leaf powder has the propensity to modulate endogenous markers of oxidative stress, redox status (reduced GSH, thiol status), response of antioxidant defenses (enzymic), protein oxidation and cholinergic function in various brain regions of prepubertal (PP) mice. PP mice maintained on a BM-enriched diet (0.5 and 1%) for 4 weeks showed a significant diminution of basal oxidative markers (malondialdehyde levels, reactive species generation, hydroperoxide levels and protein carbonyls) in both cytoplasm and mitochondria of all brain regions. This was accompanied with enhanced reduced glutathione, thiol levels and elevated activities of antioxidant enzymes (catalase, glutathione peroxidase, superoxide dismutase). Significant reduction in the activity of acetyl cholinesterase enzyme in all brain regions suggested the potential of BM leaf powder to modulate cholinergic function. Further evidence that dietary intake of BM leaf powder confers the prepubertal brain with additional capacity to cope up with neurotoxic prooxidants was obtained by exposing cortical/cerebellar synaptosomes of normal and BM fed mice to 3-nitropropionic acid (3-NPA). While synaptosomes from control mice exhibited a concentration related lipid peroxidation and ROS generation, synaptosomes obtained from BM fed mice showed only a marginal induction at the highest concentration clearly suggesting their increased resistance to 3-NPA-induced oxidative stress. Collectively these data clearly indicate the potential of Bacopa monnieri to modulate endogenous markers of

  5. Potential Markers in Cardiac Hypertrophy?

    PubMed

    Malinowski, Bartosz; Fulgheri, Gabriele; Wicinski, Michal; Grzesk, Elzbieta; Odrowaz-Sypniewska, Grazyna; Grześk, Grzegorz; Darwish, Nasser

    2012-07-01

    Cardiomyopathies are diagnosed based on medical history of patient (symptoms and family history), physical examination, results of echocardiogram and in some situations additionally ECG or chest-X-ray results. Currently used non-invasive diagnostic methods, could be complemented by biochemical tests. In this review some emerging potential biomarkers such as: osteopontin, ST-2 receptor, osteoprotegerin, neopterin, urocortins, growth differentiation factor 15 and urotensin II are described. In current article human and non human investigations have been reviewed, since rat is most commonly used model in experimental cardiology and gives important foundations to clinical knowledge.

  6. Concurrent use of REM latency, dexamethasone suppression, clonidine, and apomorphine tests as biological markers of endogenous depression: a pilot study.

    PubMed

    Ansseau, M; Scheyvaerts, M; Doumont, A; Poirrier, R; Legros, J J; Franck, G

    1984-07-01

    In a sample of 12 major depressive inpatients, endogenous subtype (8 primary and 4 secondary) defined by Research Diagnostic Criteria, we compared the sensitivity of four potential biological markers: latency of rapid eye movement (REM) sleep (recorded during at least 4 consecutive nights), dexamethasone suppression, and the clonidine and apomorphine tests. Shortened REM latency (less than 50 minutes during at least 1 night) identified 67% of depressives (87% of primary and 25% of secondary); nonsuppression after dexamethasone identified 50% of depressives (62% of primary and 25% of secondary); blunted growth hormone (GH) response after clonidine identified 75% of depressives (100% of primary and 25% of secondary); and blunted GH response after apomorphine identified 42% of depressives (62% of primary and 0% of secondary). Ninety-two percent of patients were correctly identified by at least one biological marker (100% of primary and 75% of secondary depressives). Of 67% of patients positive on at least two biological markers, all were primary depressives (100%). These four biological markers do not necessarily identify the same population, suggesting that their concurrent use may yield the highest level of diagnostic sensitivity.

  7. Potential markers of preeclampsia – a review

    PubMed Central

    Grill, Simon; Rusterholz, Corinne; Zanetti-Dällenbach, Rosanna; Tercanli, Sevgi; Holzgreve, Wolfgang; Hahn, Sinuhe; Lapaire, Olav

    2009-01-01

    Preeclampsia is a leading cause of maternal and fetal/neonatal mortality and morbidity worldwide. The early identification of patients with an increased risk for preeclampsia is therefore one of the most important goals in obstetrics. The availability of highly sensitive and specific physiologic and biochemical markers would allow not only the detection of patients at risk but also permit a close surveillance, an exact diagnosis, timely intervention (e.g. lung maturation), as well as simplified recruitment for future studies looking at therapeutic medications and additional prospective markers. Today, several markers may offer the potential to be used, most likely in a combinatory analysis, as predictors or diagnostic tools. We present here the current knowledge on the biology of preeclampsia and review several biochemical markers which may be used to monitor preeclampsia in a future, that, we hope, is not to distant from today. PMID:19602262

  8. Competitive endogenous RNA network: potential implication for systemic lupus erythematosus.

    PubMed

    Li, Lian-Ju; Zhao, Wei; Tao, Sha-Sha; Leng, Rui-Xue; Fan, Yin-Guang; Pan, Hai-Feng; Ye, Dong-Qing

    2017-06-01

    Competitive endogenous RNA (ceRNA) hypothesis proposes that RNA transcripts, both coding and non-coding, crosstalk with and coregulate each other using microRNA response elements (MREs). CeRNA analysis tremendously expands functional information of coding and non-coding RNAs. Mounting evidence have shown that various types of RNAs, including pseudogenes, long non-coding RNAs, circular RNAs, and messenger RNAs, can function as ceRNAs in distinct physiological and pathophysiological states. Many validated ceRNA pairs participate in the initiation and progression of cancers, and systemic ceRNA network analyses revealing potential of ceRNAs in diagnosis, therapy, and prognosis of cancers have also been performed. Areas covered: This review concisely introduces ceRNA hypothesis and characteristics of ceRNA regulations. The major sections focus on representative examples of both protein coding and non-coding RNA transcripts acting as ceRNAs. CeRNA prediction programs and databases and implications of ceRNA network in cancers are then discussed. In the end, we surmise potential implications of ceRNA network for SLE. Expert opinion: The role of ceRNA network in systemic lupus erythematosus (SLE) remains undefined. We speculate that dissecting ceRNA network in SLE may help expand our comprehension of roles of transcriptome, particularly non-coding transcripts, and richen our knowledge of pathogenesis, diagnosis, and therapy of SLE.

  9. Biological redundancy of endogenous GPCR ligands in the gut and the potential for endogenous functional selectivity

    PubMed Central

    Thompson, Georgina L.; Canals, Meritxell; Poole, Daniel P.

    2014-01-01

    This review focuses on the existence and function of multiple endogenous agonists of the somatostatin and opioid receptors with an emphasis on their expression in the gastrointestinal tract. These agonists generally arise from the proteolytic cleavage of prepropeptides during peptide maturation or from degradation of peptides by extracellular or intracellular endopeptidases. In other examples, endogenous peptide agonists for the same G protein-coupled receptors can be products of distinct genes but contain high sequence homology. This apparent biological redundancy has recently been challenged by the realization that different ligands may engender distinct receptor conformations linked to different intracellular signaling profiles and, as such the existence of distinct ligands may underlie mechanisms to finely tune physiological responses. We propose that further characterization of signaling pathways activated by these endogenous ligands will provide invaluable insight into the mechanisms governing biased agonism. Moreover, these ligands may prove useful in the design of novel therapeutic tools to target distinct signaling pathways, thereby favoring desirable effects and limiting detrimental on-target effects. Finally we will discuss the limitations of this area of research and we will highlight the difficulties that need to be addressed when examining endogenous bias in tissues and in animals. PMID:25506328

  10. Regional variation in use of exogenous and endogenous glomerular filtration rate (GFR) markers in Sweden

    PubMed Central

    Vilhelmsdotter Allander, Susanne; Marké, Lars-Åke; Wihlen, Björn; Svensson, Maria; Elinder, Carl-Gustaf

    2012-01-01

    Background Markers of renal function (glomerular filtration rate (GFR)) are frequently used in the Swedish health care. GFR is usually estimated based on plasma creatinine concentration, but plasma cystatin C concentration, creatinine clearance, iohexol clearance, and 51Cr-EDTA clearance are also used. These markers are all part of the daily patient care, but there is little specific information on the clinical use of these markers. The aim of this study was to compare the use of these various GFR markers in different parts of Sweden and potential changes over time. Methods Retrospective study using questionnaires to collect information for the years 2006–2009 divided per county on the specific use of GFR markers with type of test reports. Results Plasma/serum creatinine concentration (96%) is by far the dominating GFR marker in Sweden, while cystatin C concentration (3.5%), creatinine clearance (0.1%), iohexol clearance (0.1%), and 51Cr-EDTA clearance (0.1%) are less frequently used. The use of GFR markers, including creatinine, continues to increase on a national level with the exception of creatinine clearance and 51Cr-EDTA clearance. There were considerable variations between different counties in the use of GFR markers and the type of test reports that the laboratories provided. Conclusions The inter-county variations of GFR markers used in Sweden are large and indicate that savings associated with optimized test utilization in this regard could be substantial. Regional habits and traditions are likely to influence the variations in GFR marker use. PMID:22401136

  11. Expression of endogenous retroviruses is negatively regulated by the pluripotency marker Rex1/Zfp42

    PubMed Central

    Guallar, D.; Pérez-Palacios, R.; Climent, M.; Martínez-Abadía, I.; Larraga, A.; Fernández-Juan, M.; Vallejo, C.; Muniesa, P.; Schoorlemmer, J.

    2012-01-01

    Rex1/Zfp42 is a Yy1-related zinc-finger protein whose expression is frequently used to identify pluripotent stem cells. We show that depletion of Rex1 levels notably affected self-renewal of mouse embryonic stem (ES) cells in clonal assays, in the absence of evident differences in expression of marker genes for pluripotency or differentiation. By contrast, marked differences in expression of several endogenous retroviral elements (ERVs) were evident upon Rex1 depletion. We demonstrate association of REX1 to specific elements in chromatin-immunoprecipitation assays, most strongly to muERV-L and to a lower extent to IAP and musD elements. Rex1 regulates muERV-L expression in vivo, as we show altered levels upon transient gain-and-loss of Rex1 function in pre-implantation embryos. We also find REX1 can associate with the lysine-demethylase LSD1/KDM1A, suggesting they act in concert. Similar to REX1 binding to retrotransposable elements (REs) in ES cells, we also detected binding of the REX1 related proteins YY1 and YY2 to REs, although the binding preferences of the two proteins were slightly different. Altogether, we show that Rex1 regulates ERV expression in mouse ES cells and during pre-implantation development and suggest that Rex1 and its relatives have evolved as regulators of endogenous retroviral transcription. PMID:22844087

  12. A new metabolomics-based strategy for identification of endogenous markers of urine adulteration attempts exemplified for potassium nitrite.

    PubMed

    Steuer, Andrea E; Arnold, Kim; Schneider, Tom D; Poetzsch, Michael; Kraemer, Thomas

    2017-08-16

    Urine adulteration to circumvent positive drug testing represents a problem for toxicological laboratories. While creatinine is a suitable marker for dilution, detection of chemicals is often performed by dipstick tests associated with high rates of false positives. Several methods would be necessary to check for all possible adulterants. Untargeted mass spectrometry (MS) methods used in metabolomics should theoretically allow detecting concentration changes of any endogenous urinary metabolite or presence of new biomarkers produced by chemical adulteration. As a proof of concept study, urine samples from 10 volunteers were treated with KNO2 and analyzed by high-resolution MS. For statistical data evaluation, XCMS(plus) and MetaboAnalyst were used. Compound identification was performed by database searches using an in-house database, Chemspider, METLIN, HMDB, and NIST. Principle component analysis revealed clear separation between treated and untreated urine samples. In detail, 307 features showed significant concentration changes with fold changes greater than 2 (79 decreased; 228 increased). Mainly amino acids (e.g., histidine, methylhistidine, di- and trimethyllysine) and purines (uric acid) were detected in lower amounts. 5-HO-isourate was found to be formed as a new compound from uric acid and, e.g., imidazole lactate concentrations increased due to the breakdown of histidine. This metabolomics-based strategy allowed for a broad identification range of markers of urinary adulteration. More studies will be needed to investigate routine applicability of identified potential markers exploring urinary conditions of their formation and stability. Selected markers might then be integrated into routine MS screening procedures allowing for detection of adulteration within routine MS analysis. Graphical Abstract ᅟ.

  13. Hepatic endogenous defense potential of propolis after mercury intoxication.

    PubMed

    Bhadauria, Monika; Shukla, Sangeeta; Mathur, Ramesh; Agrawal, Om P; Shrivastava, Sadhana; Johri, Sonia; Joshi, Deepmala; Singh, Varsha; Mittal, Deepak; Nirala, Satendra Kumar

    2008-12-01

    Exposure to mercuric chloride (HgCl(2) ; 5 mg kg(-1) body weight; i.p.) induced oxidative stress in mice and substantially increased lipid peroxidation (LPO) and oxidized glutathione (GSSG) levels, decreased the level of reduced glutathione (GSH) and various antioxidant enzymes in liver and also increased the activities of liver marker enzymes in serum. Therapy with propolis extract, a resinous wax-like beehive product (200 mg kg(-1) orally, after mercury administration), for 3 days inhibited LPO and the formation of GSSG and increased the level of GSH in the liver. Release of serum transaminases, alkaline phosphatase, lactate dehydrogenase and γ-glutamyl transpeptidase were significantly restored after propolis treatment. The activities of antioxidant enzymes, that is, superoxide dismutase, catalase, glutathione-S-transferase and glucose-6-phosphate dehydrogenase, were also concomitantly restored towards normal levels after propolis administration. These observations clearly demonstrate that propolis treatment augments antioxidant defense against mercury-induced toxicity and provide evidence that propolis has therapeutic potential as a hepatoprotective agent. © 2008 ISZS, Blackwell Publishing and IOZ/CAS.

  14. Potential markers of oxidative stress in stroke.

    PubMed

    Cherubini, Antonio; Ruggiero, Carmelinda; Polidori, M Cristina; Mecocci, Patrizia

    2005-10-01

    Free radical production is increased in ischemic and hemorrhagic stroke, leading to oxidative stress that contributes to brain damage. The measurement of oxidative stress in stroke would be extremely important for a better understanding of its pathophysiology and for identifying subgroups of patients that might receive targeted therapeutic intervention. Since direct measurement of free radicals and oxidized molecules in the brain is difficult in humans, several biological substances have been investigated as potential peripheral markers. Among lipid peroxidation products, malondialdehyde, despite its relevant methodological limitations, is correlated with the size of ischemic stroke and clinical outcome, while F2-isoprostanes appear to be promising, but they have not been adequately evaluated. 8-Hydroxy-2-deoxyguanosine has been extensively investigated as markers of oxidative DNA damage but no study has been done in stroke patients. Also enzymatic and nonenzymatic antioxidants have been proposed as indirect markers. Among them ascorbic acid, alpha-tocopherol, uric acid, and superoxide dismutase are related to brain damage and clinical outcome. After a critical evaluation of the literature, we conclude that, while an ideal biomarker is not yet available, the balance between antioxidants and by-products of oxidative stress in the organism might be the best approach for the evaluation of oxidative stress in stroke patients.

  15. Pharmacological Potential of the Endogenous Dipeptide Kyotorphin and Selected Derivatives

    PubMed Central

    Perazzo, Juliana; Castanho, Miguel A. R. B.; Sá Santos, Sónia

    2017-01-01

    The endogenous peptide kyotorphin (KTP) has been extensively studied since it was discovered in 1979. The dipeptide is distributed unevenly over the brain but the majority is concentrated in the cerebral cortex. The putative KTP receptor has not been identified yet. As many other neuropeptides, KTP clearance is mediated by extracellular peptidases and peptide transporters. From the wide spectrum of biological activity of KTP, analgesia was by far the most studied. The mechanism of action is still unclear, but researchers agree that KTP induces Met-enkephalins release. More recently, KTP was proposed as biomarker of Alzheimer disease. Despite all that, KTP limited pharmacological value prompted researchers to develop derivatives more lipophilic and therefore more prone to cross the blood–brain barrier (BBB), and also more resistant to enzymatic degradation. Conjugation of KTP with functional molecules, such as ibuprofen, generated a new class of compounds with additional biological properties. Moreover, the safety profile of these derivatives compared to opioids and their efficacy as neuroprotective agents greatly increases their pharmacological value. PMID:28127286

  16. Surgical site markers: potential source of infection.

    PubMed

    Driessche, Ann Marie

    2012-01-01

    Observing licensed independent practitioners mark surgical sites with all types of marking pens is a concern related to the potential spread of infections from patient to patient. The practice of using the same marking pen to mark a surgical site has been questioned as a source of cross contamination. A literature review was done on recent studies and best practice recommendations to determine whether marking pens can act as fomites for nosocomial infections. The review indicated that surgical site markers, ink pens, and aging permanent marking pens can be a source for cross-infection with methicillin-resistant Staphylococcus aureus, other bacteria, fungus, or virus. The type of marking pens used and the act of using the same marking pen from patient to patient could contribute to nosocomial infections. The literature reviewed recommends a single time use of a surgical marking pen. Interventions to prevent cross contamination and postoperative surgical site infections are a major concern in the care of the orthopaedic patient.

  17. Endogenous thrombin potential in Behçet's disease: relationship with thrombosis and anticoagulant therapy.

    PubMed

    Mejía, Juan-Carlos; Espinosa, Gerard; Tàssies, Dolors; Reverter, Joan-Carles; Cervera, Ricard

    2014-01-01

    To analyse the relationship between an automated thrombin generation test, the endogenous thrombin potential (ETP), and other hypercoagulability markers, with vascular involvement in patients with Behçet's disease (BD). Patients and methods. We analysed 56 BD patients (30 men; mean age, 34.4 ± 14.3 years) without any known thrombophilic factor, of which 17 had previously suffered from thrombosis (deep venous thrombosis in 14 and ischaemic stroke in 3), and 56 controls matched for age and sex. Additionally, we also evaluated 20 plasma samples with an international normalised ratio (INR) between 1.5 and 5.0 obtained from patients with atrial fibrillation but without a history of embolic events that were under treatment with acenocumarol. Thrombin generation was measured as ETP with a chromogenic assay in an automated analyser. Factor VIII, von Willebrand factor antigen, prothrombin fragment 1.2, D-dimer and plasmin-antiplasmin complexes were also measured. BD patients showed higher ETP values than controls (471.3± 49.3 vs. 427.5± 31.3 mA; p<0.001). Additionally, BD patients with a history of thrombosis had higher ETP values than patients without thrombosis (496.6± 36.5 vs. 460.7± 50.5 mA; p<0.01). Factor VIII and von Willebrand factor antigen were also elevated in BD patients, but only von Willebrand factor antigen showed statistically significant differences between BD patients with and without thrombosis. Acenocumarol treatment reduced thrombin generation in BD patients in parallel to INR levels, reaching values similar to those of patients with atrial fibrillation and similar INR. BD is associated with thrombosis, and increased thrombin generation (measured as ETP) is a promising marker of hypercoagulability.

  18. Fatty acids are potential endogenous regulators of aldosterone secretion.

    PubMed

    Goodfriend, T L; Ball, D L; Elliott, M E; Morrison, A R; Evenson, M A

    1991-05-01

    Adrenal glomerulosa cells washed with delipidated albumin produced increased amounts of aldosterone in response to angiotensin-II (AII) or (Bu)2cAMP. Albumin treatment also increased binding of 125I-labeled AII to high affinity binding sites on adrenal cells. Lipid extracts of albumin solutions that were used to wash cells inhibited AII binding and aldosterone responses by washed glomerulosa cells. Chromatographic fractionation and mass spectroscopic analysis indicated that the inhibitors removed from cells by albumin were long chain fatty acids. Exogenous fatty acids not only inhibited AII binding, but they inhibited basal aldosterone production and increments in aldosterone caused by AII or dbcAMP, suggesting an effect on postreceptor steps in aldosteronogenesis. The most potent and most abundant fatty acids removed from adrenal cells were oleic, linoleic, and arachidonic. These fatty acids inhibited at micromolar concentrations in the absence of albumin and at somewhat higher concentrations in its presence. Cells that had been washed, then inhibited by exogenous oleic acid in vitro, were restored to their enhanced responsiveness by a second albumin wash, making it unlikely that cell damage is the mechanism of inhibition by fatty acids. Responses of fasciculata cells were not potentiated by albumin washes, and cortisol production was less sensitive than aldosterone production to exogenous fatty acids. Binding of ANP to glomerulosa cells was not affected by albumin or fatty acids. These results combined with clinical correlations make it plausible that unesterified fatty acids are naturally occurring regulators of the adrenal glomerulosa. Insulin's ability to lower plasma levels of fatty acids may be one way that it causes sodium retention.

  19. Irradiation-Dependent Effects on Tumor Perfusion and Endogenous and Exogenous Hypoxia Markers in an A549 Xenograft Model

    SciTech Connect

    Fokas, Emmanouil; Haenze, Joerg; Kamlah, Florentine; Eul, Bastian G.; Lang, Nico; Keil, Boris; Heverhagen, Johannes T.; Engenhart-Cabillic, Rita; An Hanxiang; Rose, Frank

    2010-08-01

    Purpose: Hypoxia is a major determinant of tumor radiosensitivity, and microenvironmental changes in response to ionizing radiation (IR) are often heterogenous. We analyzed IR-dependent changes in hypoxia and perfusion in A549 human lung adenocarcinoma xenografts. Materials and Methods: Immunohistological analysis of two exogenously added chemical hypoxic markers, pimonidazole and CCI-103F, and of the endogenous marker Glut-1 was performed time dependently after IR. Tumor vessels and apoptosis were analyzed using CD31 and caspase-3 antibodies. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and fluorescent beads (Hoechst 33342) were used to monitor vascular perfusion. Results: CCI-103F signals measuring the fraction of hypoxic areas after IR were significantly decreased by approximately 50% when compared with pimonidazole signals, representing the fraction of hypoxic areas from the same tumors before IR. Interestingly, Glut-1 signals were significantly decreased at early time point (6.5 h) after IR returning to the initial levels at 30.5 h. Vascular density showed no difference between irradiated and control groups, whereas apoptosis was significantly induced at 10.5 h post-IR. DCE-MRI indicated increased perfusion 1 h post-IR. Conclusions: The discrepancy between the hypoxic fractions of CCI-103F and Glut-1 forces us to consider the possibility that both markers reflect different metabolic alterations of tumor microenvironment. The reliability of endogenous markers such as Glut-1 to measure reoxygenation in irradiated tumors needs further consideration. Monitoring tumor microvascular response to IR by DCE-MRI and measuring tumor volume alterations should be encouraged.

  20. Endogenous Voltage Potentials and the Microenvironment: Bioelectric Signals that Reveal, Induce and Normalize Cancer

    PubMed Central

    Chernet, Brook; Levin, Michael

    2014-01-01

    Cancer may be a disease of geometry: a misregulation of the field of information that orchestrates individual cells’ activities towards normal anatomy. Recent work identified molecular mechanisms underlying a novel system of developmental control: bioelectric gradients. Endogenous spatio-temporal differences in resting potential of non-neural cells provide instructive cues for cell regulation and complex patterning during embryogenesis and regeneration. It is now appreciated that these cues are an important layer of the dysregulation of cell: cell interactions that leads to cancer. Abnormal depolarization of resting potential (Vmem) is a convenient marker for neoplasia and activates a metastatic phenotype in genetically-normal cells in vivo. Moreover, oncogene expression depolarizes cells that form tumor-like structures, but is unable to form tumors if this depolarization is artificially prevented by misexpression of hyperpolarizing ion channels. Vmem triggers metastatic behaviors at considerable distance, mediated by transcriptional and epigenetic effects of electrically-modulated flows of serotonin and butyrate. While in vivo data on voltages in carcinogenesis comes mainly from the amphibian model, unbiased genetic screens and network profiling in rodents and human tissues reveal several ion channel proteins as bona fide oncogene and promising targets for cancer drug development. However, we propose that a focus on specific channel genes is just the tip of the iceberg. Bioelectric state is determined by post-translational gating of ion channels, not only from genetically-specified complements of ion translocators. A better model is a statistical dynamics view of spatial Vmem gradients. Cancer may not originate at the single cell level, since gap junctional coupling results in multi-cellular physiological networks with multiple stable attractors in bioelectrical state space. New medical applications await a detailed understanding of the mechanisms by which organ

  1. The impact of angiotensin II receptor blockade and the DASH diet on markers of endogenous fibrinolysis.

    PubMed

    Erlinger, T P; Conlin, P R; Macko, R F; Bohannon, A D; Miller, E R; Moore, T J; Svetkey, L P; Appel, L J

    2002-06-01

    Hypertension is associated with impaired fibrinolysis. Both angiotensin receptor blockers (ARB) and the DASH (Dietary Approaches to Stop Hypertension) diet effectively lower blood pressure in hypertensive patients. Some evidence suggests that treatment with ARBs could increase fibrinolysis, however, data is conflicting. The impact of the DASH diet on fibrinolytic parameters is not known. Fifty-five hypertensive participants (35 African-American, 20 white) were randomly assigned to receive 8 weeks of either a control diet or the DASH diet. The diets did not differ in sodium content (approximately 3 g/day). Within each diet, individuals were randomly assigned to receive losartan or placebo for 4 weeks in double-blind, cross-over fashion. Tissue plasminogen activator (t-PA) antigen, t-PA activity, plasminogen activator inhibitor-1 (PAI-1) activity and plasma renin activity (PRA) were measured at the end of a 2-week run-in period on the control diet and after each treatment period. The DASH diet did not affect markers of fibrinolysis. Losartan significantly lowered t-PA antigen levels (-1.8 ng/mL, P = 0.045), but had no effect on t-PA or PAI-1 activities. This effect was more pronounced in whites (-4.1 ng/mL (P = 0.003)) compared with African-Americans (-0.3 ng/mL (P = 0.7), P-interaction = 0.03). Results were not materially affected by adjustment for basline values or changes in blood pressure. This study demonstrates that losartan reduces t-PA antigen levels in white, but not African-American hypertensive individuals. In contrast, the DASH diet had no significant effect on markers of fibrinolysis in whites or African-Americans.

  2. Evaluation of cystatin C as an endogenous marker of glomerular filtration rate in dogs.

    PubMed

    Almy, Frederic S; Christopher, Mary M; King, Don P; Brown, Scott A

    2002-01-01

    Cystatin C is a cysteine protease inhibitor produced by all nucleated cells. It is freely filtered by the glomerulus and is unaffected by nonrenal factors such as inflammation and gender. Because of greater sensitivity and specificity, cystatin C has been proposed to replace creatinine as a marker of glomerular filtration rate (GFR) in humans. The aims of this study were to validate an automated assay in canine plasma and to evaluate the usefulness of cystatin C as a marker of GFR in dogs. Western blotting was used to demonstrate cross-reactivity of an anti-human cystatin C antibody. An immunoturbidimetric assay was used to detect cystatin C in 25 clinically healthy dogs and 25 dogs with renal failure. Mean cystatin C concentration in the healthy dogs and the dogs with renal failure was 1.08 +/- 0.16 mg/L and 4.37 +/- 1.79 mg/L respectively. Intra- and interassay variability was <5%. The assay was linear (r = .974) between 0.14 and 7.53 mg/L. Both cystatin C and creatinine concentrations were measured in banked, frozen serum from 20 remnant kidney model dogs and 10 volume-depleted dogs for which GFR measurements by exogenous creatinine clearance had been determined previously. In the remnant kidney model, cystatin C was better correlated with GFR than creatinine (r = .79 versus .54) but was less well correlated with GFR in volume-depleted dogs (r = .54 versus .95). GFR measurements were repeated in the remnant kidney model dogs 60 days after initial GFR measurements. At this time, cystatin C and creatinine concentrations correlated equally well with GFR (r = .891 versus .894, respectively). Cystatin C concentration is a reasonable alternative to creatinine for screening dogs with decreased GFR due to chronic renal failure.

  3. Plasmid selection in Escherichia coli using an endogenous essential gene marker

    PubMed Central

    Goh, Shan; Good, Liam

    2008-01-01

    Background Antibiotic resistance genes are widely used for selection of recombinant bacteria, but their use risks contributing to the spread of antibiotic resistance. In particular, the practice is inappropriate for some intrinsically resistant bacteria and in vaccine production, and costly for industrial scale production. Non-antibiotic systems are available, but require mutant host strains, defined media or expensive reagents. An unexplored concept is over-expression of a host essential gene to enable selection in the presence of a chemical inhibitor of the gene product. To test this idea in E. coli, we used the growth essential target gene fabI as the plasmid-borne marker and the biocide triclosan as the selective agent. Results The new cloning vector, pFab, enabled selection by triclosan at 1 μM. Interestingly, pFab out-performed the parent pUC19-ampicillin system in cell growth, plasmid stability and plasmid yield. Also, pFab was toxic to host cells in a way that was reversed by triclosan. Therefore, pFab and triclosan are toxic when used alone but in combination they enhance growth and plasmid production through a gene-inhibitor interaction. Conclusion The fabI-triclosan model system provides an alternative plasmid selection method based on essential gene over-expression, without the use of antibiotic-resistance genes and conventional antibiotics. PMID:18694482

  4. Serum cystatin C-A useful endogenous marker of renal function in intensive care unit patients at risk for or with acute renal failure?

    PubMed

    Royakkers, Annick A N M; van Suijlen, Jeroen D E; Hofstra, Lieuwe S; Kuiper, Michael A; Bouman, Catherine S C; Spronk, Peter E; Schultz, Marcus J

    2007-01-01

    Critically ill patients are at high risk for developing acute renal failure (ARF). The prevention of ARF is of outmost importance in order to improve the increased morbidity and mortality associated with ARF. Unfortunately, there is lack of adequate endogenous markers that can identify renal dysfunction early - this hampers timely application of measures to prevent further renal damage. The use of exogenous markers of renal function is not only time-consuming but also expensive, and therefore can not be used on a regular basis in the intensive care unit. Both the presently used endogenous and exogenous markers are not reliable during continuous renal replacement therapy (CRRT) because these markers are removed by the therapy itself impeding early detection of recovering of renal function. Cystatin C has been proposed as an alternative endogenous marker of renal function for more than 15 years. In this manuscript we review the literature on the role of cystatin C as marker for renal function, focusing on the critically ill patient. Serum cystatin C concentrations have been found to relate to renal impairment and suggest that cystatin C is more sensitive to detect mild decreases in GFR. Cystatin C could be an important tool both to recognize early renal dysfunction and to identify renal recovery while on CRRT in the critically ill patient, however, we are in need of more studies.

  5. Challenges in testing genetically modified crops for potential increases in endogenous allergen expression for safety.

    PubMed

    Panda, R; Ariyarathna, H; Amnuaycheewa, P; Tetteh, A; Pramod, S N; Taylor, S L; Ballmer-Weber, B K; Goodman, R E

    2013-02-01

    Premarket, genetically modified (GM) plants are assessed for potential risks of food allergy. The major risk would be transfer of a gene encoding an allergen or protein nearly identical to an allergen into a different food source, which can be assessed by specific serum testing. The potential that a newly expressed protein might become an allergen is evaluated based on resistance to digestion in pepsin and abundance in food fractions. If the modified plant is a common allergenic source (e.g. soybean), regulatory guidelines suggest testing for increases in the expression of endogenous allergens. Some regulators request evaluating endogenous allergens for rarely allergenic plants (e.g. maize and rice). Since allergic individuals must avoid foods containing their allergen (e.g. peanut, soybean, maize, or rice), the relevance of the tests is unclear. Furthermore, no acceptance criteria are established and little is known about the natural variation in allergen concentrations in these crops. Our results demonstrate a 15-fold difference in the major maize allergen, lipid transfer protein between nine varieties, and complex variation in IgE binding to various soybean varieties. We question the value of evaluating endogenous allergens in GM plants unless the intent of the modification was production of a hypoallergenic crop.

  6. Differential effects of endogenous lithium on neurobehavioural functioning: a study on auditory evoked potentials.

    PubMed

    Norra, Christine; Feilhauer, Johanna; Wiesmüller, Gerhard Andreas; Kunert, Hanns Jürgen

    2010-06-30

    Lithium occurs naturally in food and water. Low environmental concentrations in drinking water are associated with mental illnesses and behavioural offences, and at therapeutic dosages it is used to treat psychiatric (especially affective) disorders, partly by facilitating serotonergic (5-HT) neurotransmission. As little is known about the psychophysiological role of nutritional lithium in the general population, endogenous lithium concentrations were hypothesised to be associated with measurable effects on emotional liability and the loudness dependence (LD) that is proposed as one of the most valid indicators of 5-HT neurotransmission. Auditory evoked potentials of healthy volunteers [N=36] with high (>2.5 microg/l) or low (<1.5 microg/l) lithium serum concentrations were recorded. Emotional liability was assessed using the Brief Symptom Inventory (BSI). Low-lithium levels correlated with Somatisation while correlations between lithium and LD were not significant. Still, LD correlated positively with Paranoid Ideation, negatively with Anxiety and, in the high-lithium group, inversely with further aspects of emotional liability (Depression, Psychological Distress). In conclusion, the effects of low levels of endogenous lithium are associated with emotional liability, and high levels with some protective effects, although findings remain inconclusive regarding LD. Potential benefits of endogenous lithium on neurobehavioural functioning, especially in high-risk individuals, would have public health implications.

  7. HOX Genes as Potential Markers of Circulating Tumour Cells.

    PubMed

    Morgan, R; El-Tanani, M

    2016-01-01

    Circulating tumour cells (CTCs) have significant diagnostic potential as they can reflect both the presence and recurrence of a wide range of cancers. However, this potential continues to be limited by the lack of robust and accessible isolation technologies. An alternative to isolation might be their direct detection amongst other peripheral blood cells, although this would require markers that allow them to be distinguished from an exceptionally high background signal. This review assesses the potential role of HOX genes, a family of homeodomain containing transcription factors with key roles in both embryonic development and oncogenesis, as unique and possibly disease specific markers of CTCs.

  8. Characterization of carbonic anhydrase IX (CA IX) as an endogenous marker of chronic hypoxia in live human tumor cells

    SciTech Connect

    Vordermark, Dirk . E-mail: vordermark_d@klinik.uni-wuerzburg.de; Kaffer, Anja; Riedl, Susanne; Katzer, Astrid; Flentje, Michael

    2005-03-15

    Purpose: Published clinical studies provide conflicting data regarding the prognostic significance of carbonic anhydrase IX (CA IX) overexpression as an endogenous marker of tumor hypoxia and its comparability with other methods of hypoxia detection. We performed a systematic analysis of CA IX protein levels under various in vitro conditions of tumor hypoxia in HT 1080 human fibrosarcoma and FaDu human pharyngeal carcinoma cells. Because sorting of live CA IX positive cells from tumors provides a tool to study the radiosensitivity of chronically hypoxic cells, we modified and tested a CA IX flow cytometry protocol on mixed hypoxic/aerobic suspensions of HT 1080 and FaDu cells. Methods and materials: HT 1080 and FaDu cells were treated with up to 24 h of in vitro hypoxia and up to 96 h of reoxygenation. To test the effect of nonhypoxic stimuli, glucose and serum availability, pH and cell density were modified. CA IX protein was quantified in Western blots of whole-cell lysates. Mixed suspensions with known percentages of hypoxic cells were prepared for CA IX flow cytometry. The same mixtures were assayed for clonogenic survival after 10 Gy. Results: Hypoxia-induced CA IX protein expression was seen after >6 h at {<=}5% O{sub 2}, and protein was stable over 96 h of reoxygenation in both cell lines. Glucose deprivation abolished the hypoxic CA IX response, and high cell density caused CA IX induction under aerobic conditions. Measured percentages of CA IX-positive cells in mixtures closely reflected known percentages of hypoxic cells in HT 1080 and were associated with radioresistance of mixtures after 10 Gy. Conclusion: CA IX is a stable marker of current or previous chronic hypoxia but influenced by nonhypoxic stimuli. Except the time course of accumulation, all properties of this marker resembled our previous findings for hypoxia-inducible factor-1{alpha}. A modified flow cytometry protocol provided good separability of CA IX-negative and -positive cells in vitro

  9. Topographic differences in adult neurogenesis in the mouse hippocampus: a stereology-based study using endogenous markers.

    PubMed

    Jinno, Shozo

    2011-05-01

    The hippocampus plays a critical role in various cognitive and affective functions. Increasing evidence shows that these functions are topographically distributed along the dorsoventral (septotemporal) and transverse axes of the hippocampus. For instance, dorsal hippocampus is involved in spatial memory and learning whereas ventral hippocampus is related to emotion. Here, we examined the topographic differences (dorsal vs. ventral; suprapyramidal vs. infrapyramidal) in adult neurogenesis in the mouse hippocampus using endogenous markers. The optical disector was applied to estimate the numerical densities (NDs) of labeled cells in the granule cell layer. The NDs of radial glia-like progenitors labeled by brain lipid binding protein were significantly lower in the infrapyramidal blade of the ventral DG than in other subdivisions. The NDs of doublecortin-expressing cells presumed neural progenitors and immature granule cells were significantly higher in the suprapyramidal blade of the dorsal DG than in the other subdivisions. The NDs of calretinin-expressing cells presumed young granule cells at the postmitotic stage were significantly higher in the suprapyramidal blade than in the infrapyramidal blade in the dorsal DG. No significant regional differences were detected in the NDs of dividing cells identified by proliferating cell nuclear antigen. Taken together, these findings suggest that a larger pool of immature granule cells in dorsal hippocampus might be responsible for spatial learning and memory, whereas a smaller pool of radial glia-like progenitors in ventral hippocampus might be associated with the susceptibility to affective disorders. Cell number estimation using a 300-μm-thick hypothetical slice indicates that regional differences in immature cells might contribute to the formation of topographic gradients in mature granule cells in the adult hippocampus. Our data also emphasizes the importance of considering such differences when evaluating changes in

  10. The role of endogenous molecules in modulating pain through transient receptor potential vanilloid 1 (TRPV1).

    PubMed

    Morales-Lázaro, Sara L; Simon, Sidney A; Rosenbaum, Tamara

    2013-07-01

    Pain is a physiological response to a noxious stimulus that decreases the quality of life of those sufferring from it. Research aimed at finding new therapeutic targets for the treatment of several maladies, including pain, has led to the discovery of numerous molecular regulators of ion channels in primary afferent nociceptive neurons. Among these receptors is TRPV1 (transient receptor potential vanilloid 1), a member of the TRP family of ion channels. TRPV1 is a calcium-permeable channel, which is activated or modulated by diverse exogenous noxious stimuli such as high temperatures, changes in pH, and irritant and pungent compounds, and by selected molecules released during tissue damage and inflammatory processes. During the last decade the number of endogenous regulators of TRPV1's activity has increased to include lipids that can negatively regulate TRPV1, as is the case for cholesterol and PIP2 (phosphatidylinositol 4,5-biphosphate) while, in contrast, other lipids produced in response to tissue injury and ischaemic processes are known to positively regulate TRPV1. Among the latter, lysophosphatidic acid activates TRPV1 while amines such as N-acyl-ethanolamines and N-acyl-dopamines can sensitize or directly activate TRPV1. It has also been found that nucleotides such as ATP act as mediators of chemically induced nociception and pain and gases, such as hydrogen sulphide and nitric oxide, lead to TRPV1 activation. Finally, the products of lipoxygenases and omega-3 fatty acids among other molecules, such as divalent cations, have also been shown to endogenously regulate TRPV1 activity. Here we provide a comprehensive review of endogenous small molecules that regulate the function of TRPV1. Acting through mechanisms that lead to sensitization and desensitization of TRPV1, these molecules regulate pathways involved in pain and nociception. Understanding how these compounds modify TRPV1 activity will allow us to comprehend how some pathologies are associated with

  11. The role of endogenous molecules in modulating pain through transient receptor potential vanilloid 1 (TRPV1)

    PubMed Central

    Morales-Lázaro, Sara L; Simon, Sidney A; Rosenbaum, Tamara

    2013-01-01

    Pain is a physiological response to a noxious stimulus that decreases the quality of life of those sufferring from it. Research aimed at finding new therapeutic targets for the treatment of several maladies, including pain, has led to the discovery of numerous molecular regulators of ion channels in primary afferent nociceptive neurons. Among these receptors is TRPV1 (transient receptor potential vanilloid 1), a member of the TRP family of ion channels. TRPV1 is a calcium-permeable channel, which is activated or modulated by diverse exogenous noxious stimuli such as high temperatures, changes in pH, and irritant and pungent compounds, and by selected molecules released during tissue damage and inflammatory processes. During the last decade the number of endogenous regulators of TRPV1's activity has increased to include lipids that can negatively regulate TRPV1, as is the case for cholesterol and PIP2 (phosphatidylinositol 4,5-biphosphate) while, in contrast, other lipids produced in response to tissue injury and ischaemic processes are known to positively regulate TRPV1. Among the latter, lysophosphatidic acid activates TRPV1 while amines such as N-acyl-ethanolamines and N-acyl-dopamines can sensitize or directly activate TRPV1. It has also been found that nucleotides such as ATP act as mediators of chemically induced nociception and pain and gases, such as hydrogen sulphide and nitric oxide, lead to TRPV1 activation. Finally, the products of lipoxygenases and omega-3 fatty acids among other molecules, such as divalent cations, have also been shown to endogenously regulate TRPV1 activity. Here we provide a comprehensive review of endogenous small molecules that regulate the function of TRPV1. Acting through mechanisms that lead to sensitization and desensitization of TRPV1, these molecules regulate pathways involved in pain and nociception. Understanding how these compounds modify TRPV1 activity will allow us to comprehend how some pathologies are associated with

  12. Endogenous serotonin facilitates hippocampal long-term potentiation at CA3/CA1 synapses.

    PubMed

    Mlinar, Boris; Stocca, Gabriella; Corradetti, Renato

    2015-02-01

    Encoding of episodic memory requires long-term potentiation (LTP) of neurotransmission at excitatory synapses of the hippocampal circuitry. Previous data obtained with the application of exogenous 5-hydroxytryptamine (5-HT) in hippocampal slices indicate that 5-HT blocks LTP, which contrasts with the facilitatory effect of selective serotonin reuptake inhibitors (SSRIs) on learning and memory observed in vivo. Here, we investigated the effects of endogenous 5-HT, released from terminals by the monoamine releaser 3,4-methylenedioxymethamphetamine (MDMA), on LTP of field EPSPs induced by theta-burst stimulation and recorded at CA3/CA1 synapses of rat hippocampal slices. LTP was greater in the presence of MDMA (10 µM; 45.76 ± 15.75%; n = 28) than in controls (31.26 ± 11.03; n = 21; p < 0.01). This facilitatory effect on LTP persisted when the entry of MDMA in noradrenergic terminals was prevented by the selective noradrenaline reuptake inhibitor nisoxetine (44.90 ± 14.07%; n = 27 vs. 34.49 ± 12.94%; n = 20 in controls; p < 0.05). In both conditions, the facilitation of LTP was abolished by the SSRI citalopram that prevented the entry of MDMA in 5-HT terminals and the subsequent 5-HT release. These data show that, unlike exogenous 5-HT application, release of endogenous 5-HT does not impair cellular mechanisms responsible for induction of LTP, indicating that 5-HT is not detrimental to learning and memory. Moreover, facilitation of LTP by endogenous 5-HT may underlie the in vivo positive effects of augmented 5-HT tone on cognitive performance.

  13. [Endogenous potentials evoked by acoustic stimulus in children with idiopathic headache--preliminary report].

    PubMed

    Steczkowska-Klucznik, Małgorzata; Kroczka, Sławomir; Domaradzka, Ewa; Kaciński, Marek

    2004-01-01

    Endogenous evoked potentials (P300) are elicited by several stimuli, and are electrophysiological consequence of cognitive processing. Abnormalities have often been reported in dementive syndromes, demyelinating diseases, metabolic disorders, CNS tumors, phacomatoses, neuroinfections, attention deficit hyperactivity disorder and epilepsy. The role of this element of neurophysiological characteristics is debated in migraine, pato-genetically undefined, and other primary headaches. The aim of this research was to determine whether the parameters of endogenous responses to the transient auditory stimulation in children with migraine differ from parameters obtained from children with tension-type headache, and whether the results are different in children with primary headaches compared with headache-free controls. 56 patients, 27 girls and 29 boys aged from 10 to 18 years, recruited from the Department of Pediatric Neurology and Headache Outpatient Clinic of University Children's Hospital of Cracow were studied between 1.04.2004 and 31.08.2004. 21 children affected with migraine, 17 with aura, 4 without aura, and 15 children with frequent episodic tension-type headache (ETTH) were diagnosed according to IHS criteria, and compared with 20 sex- and age-matched headache-free controls. Endogenous evoked potentials P300 were performed in all children using auditory oddball paradigm, averaging 60 responses to stimuli different from the background activity. Responses were recorded using superficial electrodes placed on the frontal (Fz), middle (Cz) and parietal (Pz) region, while reference electrodes on the ear lobes. The procedure of average out of target and non target stimuli was repeated three times in each patient. The parameters of latency and amplitude of P300 were not significantly different between children with migraine, without aura and ETTH, and healthy controls. On the contrary, the amplitude of responses was lower in children with ETTH than in controls. However

  14. Therapeutic potential and biological role of endogenous antioxidant enzymes in multiple sclerosis pathology.

    PubMed

    Schreibelt, Gerty; van Horssen, Jack; van Rossum, Saskia; Dijkstra, Christine D; Drukarch, Benjamin; de Vries, Helga E

    2007-12-01

    Reactive oxygen species contribute to the formation and persistence of multiple sclerosis (MS) lesions by acting on distinct pathological processes. To counteract the detrimental effects of ROS the central nervous system is endowed with a protective mechanism consisting of enzymatic and non-enzymatic antioxidants. Expression of most antioxidant enzymes is regulated through the transcription factor nuclear factor-E2-related factor (Nrf2) and antioxidant response elements (ARE) in the genes encoding enzymatic antioxidants and is induced by oxidative stress. In brain tissue of MS patients, enhanced expression of Nrf2/ARE-regulated antioxidants is suggestive of the occurrence of oxidative stress in these lesions. Antioxidant therapy may therefore represent an attractive treatment of MS. Several studies have shown that antioxidant therapy is beneficial in vitro and in vivo in animal models for MS. However, the use of exogenous antioxidants for MS treatment has drawbacks, as large amounts of antioxidants are required to achieve functional antioxidant levels in the central nervous system. Therefore, the induction of endogenous antioxidant enzymes by activators of the Nrf2/ARE pathway may be an interesting approach to obtain sufficient levels of antioxidants to interfere with pathological processes underlying MS lesion formation. In this review we summarize and discuss the biological role, regulation and potential therapeutic effects of endogenous antioxidant enzymes in MS. We propose that antioxidants may inhibit the development and progression of MS lesions and may therefore represent an attractive therapeutic target for the treatment of MS and other oxidative stress-related neurological diseases.

  15. Event-related potentials in performance monitoring are influenced by the endogenous opioid system.

    PubMed

    Pfabigan, Daniela M; Pripfl, Jürgen; Kroll, Sara L; Sailer, Uta; Lamm, Claus

    2015-10-01

    Recent research suggests that not only the dopamine neurotransmitter system but also the endogenous opioid system is involved in performance monitoring and the generation of prediction error signals. Heightened performance monitoring is also associated with psychopathology such as internalizing disorders. Therefore, the current study investigated the potential link between the functional opioid peptide prodynorphin (PDYN) 68 bp VNTR genetic polymorphism and neuronal correlates of performance monitoring. To this end, 47 healthy participants genotyped for this polymorphism, related to high-, intermediate-, and low-expression levels of PDYN, performed a choice-reaction task while their electroencephalogram (EEG) was recorded. On the behavioural level, no differences between the three PDYN groups could be observed. EEG data, however, showed significant differences. High PDYN expression individuals showed heightened neural error processing indicated by higher ERN amplitudes, compared to intermediate and low expression individuals. Later stages of error processing, indexed by late Pe amplitudes, and stimulus-driven conflict processing, indexed by N2 amplitudes, were not affected by PDYN genotype. The current results corroborate the notion of an indirect effect of endogenous opioids on performance monitoring, probably mediated by the mesencephalic dopamine system. Overall, enhanced ERN amplitudes suggest a hyper-active performance monitoring system in high PDYN expression individuals, and this might also be an indicator of a higher risk for internalizing disorders.

  16. Volatile compounds as potential defective coffee beans' markers.

    PubMed

    Toci, Aline T; Farah, Adriana

    2008-06-01

    Although Brazil is the largest raw coffee producer and exporter in the world, a large amount of its Arabica coffee production is considered inappropriate for exportation. This by-product of coffee industry is called PVA due to the presence of black (P), green (V) and sour (A) defective beans, which are known to contribute considerably for cup quality decrease. Data on the volatile composition of Brazilian defective coffee beans are scarce. In this study, we evaluated the volatile composition of defective coffee beans (two lots) compared to good quality beans from the respective lots. Potential defective beans' markers were identified. In the raw samples, 2-methylpyrazine and 2-furylmethanol acetate were identified only in black-immature beans and butyrolactone only in sour beans, while benzaldehyde and 2,3,5,6-tetramethylpyrazine showed to be potential markers of defective beans in general. In the roasted PVA beans, pyrazine, 2,3-butanediol meso, 2-methyl-5-(1-propenyl)pyrazine, hexanoic acid, 4-ethyl-guayacol and isopropyl p-cresol sulfide also showed to be potential defective coffee beans' markers. Copyright © 2007 Elsevier Ltd. All rights reserved.

  17. Metabolic Perturbation and Potential Markers in Patients with Esophageal Cancer

    PubMed Central

    Wang, Kun; Liu, Gaoshuang; Wang, Yuqing; Xu, Jin; Liu, Linsheng; Li, Mengjie; Shi, Jian

    2017-01-01

    Clinical diagnosis of esophageal cancer (EC) at early stage is rather difficult. This study aimed to profile the molecules in serum and tissue and identify potential biomarkers in patients with EC. A total of 64 volunteers were recruited, and 83 samples (24 EC serum samples, 21 serum controls, 19 paired EC tissues, and corresponding tumor-adjacent tissues) were analyzed. The gas chromatography time-of-flight mass spectrometry (GC/TOF-MS) was employed, and principal component analysis was used to reveal the discriminatory metabolites and identify the candidate markers of EC. A total of 41 in serum and 36 identified compounds in tissues were relevant to the malignant prognosis. A marked metabolic reprogramming of EC was observed, including enhanced anaerobic glycolysis and glutaminolysis, inhibited tricarboxylic acid (TCA) cycle, and altered lipid metabolism and amino acid turnover. Based on the potential markers of glucose, glutamic acid, lactic acid, and cholesterol, the receiver operating characteristic (ROC) curves indicated good diagnosis and prognosis of EC. EC patients showed distinct reprogrammed metabolism involved in glycolysis, TCA cycle, glutaminolysis, and fatty acid metabolism. The pivotal molecules in the metabolic pathways were suggested as the potential markers to facilitate the early diagnosis of human EC. PMID:28512469

  18. Endogenous Gradients of Resting Potential Instructively Pattern Embryonic Neural Tissue via Notch Signaling and Regulation of Proliferation

    PubMed Central

    Pai, Vaibhav P.; Lemire, Joan M.; Paré, Jean-François; Lin, Gufa; Chen, Ying

    2015-01-01

    Biophysical forces play important roles throughout embryogenesis, but the roles of spatial differences in cellular resting potentials during large-scale brain morphogenesis remain unknown. Here, we implicate endogenous bioelectricity as an instructive factor during brain patterning in Xenopus laevis. Early frog embryos exhibit a characteristic hyperpolarization of cells lining the neural tube; disruption of this spatial gradient of the transmembrane potential (Vmem) diminishes or eliminates the expression of early brain markers, and causes anatomical mispatterning of the brain, including absent or malformed regions. This effect is mediated by voltage-gated calcium signaling and gap-junctional communication. In addition to cell-autonomous effects, we show that hyperpolarization of transmembrane potential (Vmem) in ventral cells outside the brain induces upregulation of neural cell proliferation at long range. Misexpression of the constitutively active form of Notch, a suppressor of neural induction, impairs the normal hyperpolarization pattern and neural patterning; forced hyperpolarization by misexpression of specific ion channels rescues brain defects induced by activated Notch signaling. Strikingly, hyperpolarizing posterior or ventral cells induces the production of ectopic neural tissue considerably outside the neural field. The hyperpolarization signal also synergizes with canonical reprogramming factors (POU and HB4), directing undifferentiated cells toward neural fate in vivo. These data identify a new functional role for bioelectric signaling in brain patterning, reveal interactions between Vmem and key biochemical pathways (Notch and Ca2+ signaling) as the molecular mechanism by which spatial differences of Vmem regulate organogenesis of the vertebrate brain, and suggest voltage modulation as a tractable strategy for intervention in certain classes of birth defects. PMID:25762681

  19. Identification of potential protein markers of noble rot infected grapes.

    PubMed

    Lorenzini, Marilinda; Millioni, Renato; Franchin, Cinzia; Zapparoli, Giacomo; Arrigoni, Giorgio; Simonato, Barbara

    2015-07-15

    The evaluation of Botrytis cinerea as noble rot on withered grapes is of great importance to predict the wine sensory/organoleptic properties and to manage the winemaking process of Amarone, a passito dry red wine. This report describes the first proteomic analysis of grapes infected by noble rot under withering conditions to identify possible markers of fungal infection. 2-D gel electrophoresis revealed that protein profiles of infected and not infected grape samples are significantly different in terms of number of spots and relative abundance. Protein identification by MS analysis allowed to identify only in infected berries proteins of B. cinerea that represent potential markers of the presence of the fungus in the withered grapes.

  20. [Endogenous and exogenous evoked potentials in the most common neurologic syndromes during development].

    PubMed

    Zgorzalewicz, M

    2001-01-01

    This paper presents the application of endo- and egzogenic evoked potentials (EP) in the most frequent neurological syndromes in children and adolescents on the basis of the author's own experiences. The advantages of the method are: objectiveness, noninvasive and the possibility of numerous repetitions. The principles of EPs application and interpretation are established by the recommendations of the International Federation of Clinical Neurophysiology. The analysis of the results contains morphology of recording, latencies and amplitudes of potentials. EPs constitute the important research method in child neurology. They are useful in diagnostics of demyelinating, degenerative and metabolic diseases, tumours of the nervous system, phacomatoses, infections and cerebrovascular disorders, CNS traumas and in cases of psychomotor retardation. The importance of this method consists in 1. diagnosis of symptomatic and asymptomatic pathological processes, 2. localization of the lesion, 3. confirmation of clinical diagnosis, 4. aid in differentiation, 5. monitoring of the treatment, 6. observation of the disease dynamics, 7. evaluation of the prognosis. Endogenic potentials enable neurophysiological evaluation of cognitive processes. Especially P 300 is analyzed in the range of its latency, amplitude and topography. P 300 is evaluated in relation to syndromes and diseases of developmental age, mostly in epilepsy, headaches, tumours, CVS traumas and minimal brain dysfunction.

  1. Endogenous Small-Noncoding RNAs and Potential Functions in Desiccation Tolerance in Physcomitrella Patens

    PubMed Central

    Xia, Jing; Wang, Xiaoqin; Perroud, Pierre-François; He, Yikun; Quatrano, Ralph; Zhang, Weixiong

    2016-01-01

    Early land plants like moss Physcomitrella patens have developed remarkable drought tolerance. Phytohormone abscisic acid (ABA) protects seeds during water stress by activating genes through transcription factors such as ABSCISIC ACID INSENSITIVE (ABI3). Small noncoding RNA (sncRNA), including microRNAs (miRNAs) and endogenous small-interfering RNAs (endo-siRNAs), are key gene regulators in eukaryotes, playing critical roles in stress tolerance in plants. Combining next-generation sequencing and computational analysis, we profiled and characterized sncRNA species from two ABI3 deletion mutants and the wild type P. patens that were subject to ABA treatment in dehydration and rehydration stages. Small RNA profiling using deep sequencing helped identify 22 novel miRNAs and 6 genomic loci producing trans-acting siRNAs (ta-siRNAs) including TAS3a to TAS3e and TAS6. Data from degradome profiling showed that ABI3 genes (ABI3a/b/c) are potentially regulated by the plant-specific miR536 and that other ABA-relevant genes are regulated by miRNAs and ta-siRNAs. We also observed broad variations of miRNAs and ta-siRNAs expression across different stages, suggesting that they could potentially influence desiccation tolerance. This study provided evidence on the potential roles of sncRNA in mediating desiccation-responsive pathways in early land plants. PMID:27443635

  2. Delta9-tetrahydrocannabinol and endogenous cannabinoid anandamide directly potentiate the function of glycine receptors.

    PubMed

    Hejazi, Nadia; Zhou, Chunyi; Oz, Murat; Sun, Hui; Ye, Jiang Hong; Zhang, Li

    2006-03-01

    Anandamide (AEA) and delta9-tetrahydrocannabinol (THC) are endogenous and exogenous ligands, respectively, for cannabinoid receptors. Whereas most of the pharmacological actions of cannabinoids are mediated by CB1 receptors, there is also evidence that these compounds can produce effects that are not mediated by the activation of identified cannabinoid receptors. Here, we report that THC and AEA, in a CB1 receptor-independent manner, cause a significant potentiation of the amplitudes of glycine-activated currents (I(Gly)) in acutely isolated neurons from rat ventral tegmental area (VTA) and in Xenopus laevis oocytes expressing human homomeric (alpha1) and heteromeric (alpha1beta1) subunits of glycine receptors (GlyRs). The potentiation of I(Gly) by THC and AEA is concentration-dependent, with respective EC50 values of 86 +/- 9 and 319 +/- 31 nM for alpha1 homomeric receptors, 73 +/- 8 and 318 +/- 24 nM for alpha1beta1 heteromeric receptors, and 115 +/- 13 and 230 +/- 29 nM for native GlyRs in VTA neurons. The effects of THC and AEA are selective for I(Gly), because GABA-activated current in VTA neurons or in X. laevis oocytes expressing alpha2beta3gamma2 GABA(A) receptor subunits were unaffected by these compounds. The maximal potentiation by THC and AEA was observed at the lowest concentration of glycine; with increasing concentrations of glycine, the potentiation significantly decreased. The site for THC and AEA seems to be distinct from that of the alcohol and volatile anesthetics. The results indicate that THC and AEA, in pharmacologically relevant concentrations, directly potentiate the function of GlyRs through an allosteric mechanism.

  3. Current insights on the regenerative potential of the periosteum: molecular, cellular, and endogenous engineering approaches.

    PubMed

    Colnot, Céline; Zhang, Xinping; Knothe Tate, Melissa L

    2012-12-01

    While century old clinical reports document the periosteum's remarkable regenerative capacity, only in the past decade have scientists undertaken mechanistic investigations of its regenerative potential. At a Workshop at the 2012 Annual Meeting of Orthopaedic Research Society, we reviewed the molecular, cellular, and tissue scale approaches to elucidate the mechanisms underlying the periosteum's regenerative potential as well as translational therapies engineering solutions inspired by its remarkable regenerative capacity. The entire population of osteoblasts within periosteum, and at endosteal and trabecular bone surfaces within the bone marrow, derives from the embryonic perichondrium. Periosteal cells contribute more to cartilage and bone formation within the callus during fracture healing than do cells of the bone marrow or endosteum, which do not migrate out of the marrow compartment. Furthermore, a current healing paradigm regards the activation, expansion, and differentiation of periosteal stem/progenitor cells as an essential step in building a template for subsequent neovascularization, bone formation, and remodeling. The periosteum comprises a complex, composite structure, providing a niche for pluripotent cells and a repository for molecular factors that modulate cell behavior. The periosteum's advanced, "smart" material properties change depending on the mechanical, chemical, and biological state of the tissue. Understanding periosteum development, progenitor cell-driven initiation of periosteum's endogenous tissue building capacity, and the complex structure-function relationships of periosteum as an advanced material are important for harnessing and engineering ersatz materials to mimic the periosteum's remarkable regenerative capacity. Copyright © 2012 Orthopaedic Research Society.

  4. Corneal Sensitivity as a Potential Marker of Diabetic Neuropathy.

    PubMed

    Sitompul, Ratna

    2017-04-01

    Diabetes mellitus (DM) is a complex and chronic metabolic disorder leading to many complications. One of the most common complications of DM is diabetic neuropathy. There are many studies exploring corneal sensitivity as a potential marker of diabetic neuropathy. This review aims to explore association between corneal sensitivity and diabetic neuropathy. In diabetic neuropathy, corneal sensitivity is impaired due to low level of corneal nerve trophic factors, impaired sensory nerve fibers, and lost communication of dendtritic cell. In diabetic patients, this condition can be assessed by several techniques, such as Cochet Bonnet aesthesiometry, non-contact corneal aesthesiometry, and confocal microscopy. Few promising therapeutic targets for impaired corneal sensitivity include stem cell and growth factor therapy that can be used to prevent complication in patient with diabetic neurotrophic keratopathy. Impaired corneal sensitivity serve as a potential marker of diabetic neuropathy. Doctors, opthalmologists and internists, should anticipate the possibility of observing the following changes in diabetic patients with neuropathy by using corneal sensitivity assessment test.

  5. Molecular bioelectricity: how endogenous voltage potentials control cell behavior and instruct pattern regulation in vivo

    PubMed Central

    Levin, Michael

    2014-01-01

    In addition to biochemical gradients and transcriptional networks, cell behavior is regulated by endogenous bioelectrical cues originating in the activity of ion channels and pumps, operating in a wide variety of cell types. Instructive signals mediated by changes in resting potential control proliferation, differentiation, cell shape, and apoptosis of stem, progenitor, and somatic cells. Of importance, however, cells are regulated not only by their own Vmem but also by the Vmem of their neighbors, forming networks via electrical synapses known as gap junctions. Spatiotemporal changes in Vmem distribution among nonneural somatic tissues regulate pattern formation and serve as signals that trigger limb regeneration, induce eye formation, set polarity of whole-body anatomical axes, and orchestrate craniofacial patterning. New tools for tracking and functionally altering Vmem gradients in vivo have identified novel roles for bioelectrical signaling and revealed the molecular pathways by which Vmem changes are transduced into cascades of downstream gene expression. Because channels and gap junctions are gated posttranslationally, bioelectrical networks have their own characteristic dynamics that do not reduce to molecular profiling of channel expression (although they couple functionally to transcriptional networks). The recent data provide an exciting opportunity to crack the bioelectric code, and learn to program cellular activity at the level of organs, not only cell types. The understanding of how patterning information is encoded in bioelectrical networks, which may require concepts from computational neuroscience, will have transformative implications for embryogenesis, regeneration, cancer, and synthetic bioengineering. PMID:25425556

  6. Cannabis sativa and the endogenous cannabinoid system: therapeutic potential for appetite regulation.

    PubMed

    Farrimond, Jonathan A; Mercier, Marion S; Whalley, Benjamin J; Williams, Claire M

    2011-02-01

    The herb Cannabis sativa (C. sativa) has been used in China and on the Indian subcontinent for thousands of years as a medicine. However, since it was brought to the UK and then the rest of the western world in the late 19th century, its use has been a source of controversy. Indeed, its psychotropic side effects are well reported but only relatively recently has scientific endeavour begun to find valuable uses for either the whole plant or its individual components. Here, we discuss evidence describing the endocannabinoid system, its endogenous and exogenous ligands and their varied effects on feeding cycles and meal patterns. Furthermore we also critically consider the mounting evidence which suggests non-Δ(9) tetrahydrocannabinol phytocannabinoids play a vital role in C. sativa-induced feeding pattern changes. Indeed, given the wide range of phytocannabinoids present in C. sativa and their equally wide range of intra-, inter- and extra-cellular mechanisms of action, we demonstrate that non-Δ(9) tetrahydrocannabinol phytocannabinoids retain an important and, as yet, untapped clinical potential.

  7. l-Serine potentiates fluoroquinolone activity against Escherichia coli by enhancing endogenous reactive oxygen species production.

    PubMed

    Duan, Xiangke; Huang, Xue; Wang, Xiaoyu; Yan, Shuangquan; Guo, Siyao; Abdalla, Abualgasim Elgaili; Huang, Changwu; Xie, Jianping

    2016-08-01

    The increase in multiple antimicrobial-resistant bacteria seriously threatens global public health. Novel effective strategies are urgently needed. l-Serine was reported as the most effective amino acid inhibitor against bacterial growth and can sensitize Escherichia coli cells to gentamicin. It is currently unknown whether l-serine affects other type of antibiotics such as β-lactams and fluoroquinolones. Using E. coli, we studied the combination of l-serine with diverse antibiotics against laboratory and clinical E. coli cultures and persisters. The intracellular NAD(+)/NADH level and ROS were determined using kits. Total cellular iron was determined by using a colorimetric ferrozine-based assay. Exogenous l-serine sensitized E. coli ATCC 25922 and clinically isolated fluoroquinolone-resistant E. coli to fluoroquinolones. This potentiation is independent of growth phase. Addition of serine increases the production of NADH. The underlying mechanism of this strategy is that the combination of serine with ofloxacin or moxifloxacin increases the NAD(+)/NADH ratio, disrupts the Fe-S clusters and increases the production of endogenous reactive oxygen species. Furthermore, we used a serine and ofloxacin or moxifloxacin combination in vitro to combat bacterial persister cells, compared with antibiotic treatment alone; combinational treatments of persister cells with antibiotics and l-serine resulted in a significantly greater decrease in cell viability. To our knowledge, this is the first report that l-serine can potentiate the action of ofloxacin or moxifloxacin against Gram-negative bacteria and could constitute a new strategy for the eradication of bacterial infections. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Dynamic regulation of human endogenous retroviruses mediates factor-induced reprogramming and differentiation potential

    PubMed Central

    Ohnuki, Mari; Tanabe, Koji; Sutou, Kenta; Teramoto, Ito; Sawamura, Yuka; Narita, Megumi; Nakamura, Michiko; Tokunaga, Yumie; Nakamura, Masahiro; Watanabe, Akira; Yamanaka, Shinya; Takahashi, Kazutoshi

    2014-01-01

    Pluripotency can be induced in somatic cells by overexpressing transcription factors, including POU class 5 homeobox 1 (OCT3/4), sex determining region Y-box 2 (SOX2), Krüppel-like factor 4 (KLF4), and myelocytomatosis oncogene (c-MYC). However, some induced pluripotent stem cells (iPSCs) exhibit defective differentiation and inappropriate maintenance of pluripotency features. Here we show that dynamic regulation of human endogenous retroviruses (HERVs) is important in the reprogramming process toward iPSCs, and in re-establishment of differentiation potential. During reprogramming, OCT3/4, SOX2, and KLF4 transiently hyperactivated LTR7s—the long-terminal repeats of HERV type-H (HERV-H)—to levels much higher than in embryonic stem cells by direct occupation of LTR7 sites genome-wide. Knocking down LTR7s or long intergenic non-protein coding RNA, regulator of reprogramming (lincRNA-RoR), a HERV-H–driven long noncoding RNA, early in reprogramming markedly reduced the efficiency of iPSC generation. KLF4 and LTR7 expression decreased to levels comparable with embryonic stem cells once reprogramming was complete, but failure to resuppress KLF4 and LTR7s resulted in defective differentiation. We also observed defective differentiation and LTR7 activation when iPSCs had forced expression of KLF4. However, when aberrantly expressed KLF4 or LTR7s were suppressed in defective iPSCs, normal differentiation was restored. Thus, a major mechanism by which OCT3/4, SOX2, and KLF4 promote human iPSC generation and reestablish potential for differentiation is by dynamically regulating HERV-H LTR7s. PMID:25097266

  9. [Prediction by means of endogenous and exogenous evoked potentials of the favorable evolution of a prolonged coma].

    PubMed

    Michel, C; Denison, S; Minne, C; Guérit, J M

    1998-09-01

    A neurophysiological follow-up (EEG, exogenous and endogenous evoked potentials--EP) was performed over a 4-month period in a patient who presented a long-lasting coma following a cardiac arrest and an amniotic embolism. A pure anoxic aetiology was ruled out starting from the second day on the basis of a dissociation between mildly altered flash visual EP and markedly altered somatosensory EP, indicating focal brain-stem pathology. Endogenous EP reappeared after 12 days. This patient recovered consciousness after 51 days. Despite the absence of MRI abnormalities, we put forward the hypothesis that a brain-stem embolism had, in fact, worsened the clinical picture of an actually moderate anoxia. This case exemplifies the interest of an integrated neurophysiological approach (EEG, exogenous three-modality EP and endogenous EP) in the early evaluation of coma. It also illustrates the complement between structural imaging and functional assessment of the nervous system.

  10. Potential usefulness of biological markers in risk assessment

    SciTech Connect

    Perera, F.

    1987-12-01

    Substantial data have been generated during the last 5 years in experimental systems and human populations which shed light on the potential usefulness of biological markers in human cancer risk assessment. Following a brief review of overall progress to date in the biomonitoring of human populations, this paper turns to the growing body of data regarding carcinogen-DNA and protein adducts as illustrative markers of biologically effective dose of carcinogens. The data base illustrates considerable human interindividual variation in binding and the presence of significant background levels of adducts-both of which support the absence of human population thresholds for exposure to carcinogens. The contribution of adduct data to our understanding of the shape of low-dose-response curve and the reliability of interspecies extrapolation, as well as the relevance of adducts to cancer risk, are also discussed. Even though adducts can now be useful in hazard identification or qualitative risk assessment,more research is needed before they can serve as quantitative predictors of human cancer risk.

  11. Asymmetric Meckel Cave Enlargement: A Potential Marker of PHACES Syndrome.

    PubMed

    Wright, J N; Wycoco, V

    2017-06-01

    PHACES syndrome is a complex of morphologic abnormalities of unknown cause and includes posterior fossa abnormalities; head and neck infantile hemangiomas; arterial, cardiac, and eye anomalies; and sternal or abdominal wall defects. Accurate identification of the syndrome is important for optimal treatment. The purpose of this study was to investigate the incidence of asymmetric Meckel cave enlargement, a potential novel imaging marker, in a population of patients referred for evaluation of possible PHACES syndrome. Eighty-five patients referred for neuroimaging evaluation of possible PHACES syndrome were identified and stratified on the basis of their ultimate clinical PHACES diagnosis categorization into PHACES, possible PHACES, or not PHACES. MR imaging studies were subsequently reviewed for the presence or absence of unilateral Meckel cave enlargement, with the reviewer blinded to the ultimate PHACES syndrome categorization. Twenty-five of 85 patients (29%) were ultimately categorized as having PHACES or possible PHACES according to consensus guidelines. Asymmetric Meckel cave enlargement was present in 76% (19/25) of these patients and in 82% (19/23) of only those patients with definite PHACES. This finding was present in none of the 60 patients determined not to have PHACES syndrome. In 7/19 patients (37%) with this finding, subtle MR imaging abnormalities consistent with PHACES were missed on the initial MR imaging interpretation. Asymmetric Meckel cave enlargement was a common feature of patients with PHACES in our cohort and may serve as a novel imaging marker. Increased awareness of this imaging feature has the potential to increase the diagnostic accuracy of PHACES. © 2017 by American Journal of Neuroradiology.

  12. Gastrointestinal Endogenous Protein-Derived Bioactive Peptides: An in Vitro Study of Their Gut Modulatory Potential.

    PubMed

    Dave, Lakshmi A; Hayes, Maria; Mora, Leticia; Montoya, Carlos A; Moughan, Paul J; Rutherfurd, Shane M

    2016-04-01

    A recently proposed paradigm suggests that, like their dietary counterparts, digestion of gastrointestinal endogenous proteins (GEP) may also produce bioactive peptides. With an aim to test this hypothesis, in vitro digests of four GEP namely; trypsin (TRYP), lysozyme (LYS), mucin (MUC), serum albumin (SA) and a dietary protein chicken albumin (CA) were screened for their angiotensin-I converting (ACE-I), renin, platelet-activating factor-acetylhydrolase (PAF-AH) and dipeptidyl peptidase-IV inhibitory (DPP-IV) and antioxidant potential following simulated in vitro gastrointestinal digestion. Further, the resultant small intestinal digests were enriched to obtain peptides between 3-10 kDa in size. All in vitro digests of the four GEP were found to inhibit ACE-I compared to the positive control captopril when assayed at a concentration of 1 mg/mL, while the LYS < 3-kDa permeate fraction inhibited renin by 40% (±1.79%). The LYS < 10-kDa fraction inhibited PAF-AH by 39% (±4.34%), and the SA < 3-kDa fraction inhibited DPP-IV by 45% (±1.24%). The MUC < 3-kDa fraction had an ABTS-inhibition antioxidant activity of 150 (±24.79) µM trolox equivalent and the LYS < 10-kDa fraction inhibited 2,2-Diphenyl-1-picrylhydrazyl (DPPH) by 54% (±1.62%). Moreover, over 190 peptide-sequences were identified from the bioactive GEP fractions. The findings of the present study indicate that GEP are a significant source of bioactive peptides which may influence gut function.

  13. Gastrointestinal Endogenous Protein-Derived Bioactive Peptides: An in Vitro Study of Their Gut Modulatory Potential

    PubMed Central

    Dave, Lakshmi A.; Hayes, Maria; Mora, Leticia; Montoya, Carlos A.; Moughan, Paul J.; Rutherfurd, Shane M.

    2016-01-01

    A recently proposed paradigm suggests that, like their dietary counterparts, digestion of gastrointestinal endogenous proteins (GEP) may also produce bioactive peptides. With an aim to test this hypothesis, in vitro digests of four GEP namely; trypsin (TRYP), lysozyme (LYS), mucin (MUC), serum albumin (SA) and a dietary protein chicken albumin (CA) were screened for their angiotensin-I converting (ACE-I), renin, platelet-activating factor-acetylhydrolase (PAF-AH) and dipeptidyl peptidase-IV inhibitory (DPP-IV) and antioxidant potential following simulated in vitro gastrointestinal digestion. Further, the resultant small intestinal digests were enriched to obtain peptides between 3–10 kDa in size. All in vitro digests of the four GEP were found to inhibit ACE-I compared to the positive control captopril when assayed at a concentration of 1 mg/mL, while the LYS < 3-kDa permeate fraction inhibited renin by 40% (±1.79%). The LYS < 10-kDa fraction inhibited PAF-AH by 39% (±4.34%), and the SA < 3-kDa fraction inhibited DPP-IV by 45% (±1.24%). The MUC < 3-kDa fraction had an ABTS-inhibition antioxidant activity of 150 (±24.79) µM trolox equivalent and the LYS < 10-kDa fraction inhibited 2,2-Diphenyl-1-picrylhydrazyl (DPPH) by 54% (±1.62%). Moreover, over 190 peptide-sequences were identified from the bioactive GEP fractions. The findings of the present study indicate that GEP are a significant source of bioactive peptides which may influence gut function. PMID:27043546

  14. Cell-Derived Nanoparticles are Endogenous Modulators of Sepsis With Therapeutic Potential.

    PubMed

    Kunz, Natalia; Xia, Brent T; Kalies, Kai-Uwe; Klinger, Matthias; Gemoll, Timo; Habermann, Jens K; Whitacre, Brynne E; Seitz, Aaron P; Kalies, Kathrin; Caldwell, Charles C

    2017-09-01

    Cell-derived nanoparticles (CDNPs) containing cytosolic proteins and RNAs/DNAs can be isolated from stressed eukaryotic cells. Previously, CDNPs isolated from cultured cells exerted immunomodulatory activities in different infections. Here, we sought to elucidate the role of CDNPs using a murine model of cecal ligation and puncture (CLP). We hypothesized that CDNPs influence the immune response at the site of infection, where severe cellular stress occurs. We observed early CDNP accumulation in the peritoneum after 4 h and continued CDNP presence 24 h after CLP. To determine whether CDNPs influence the host response to sepsis, we isolated CDNPs from a murine fibroblast cell line stressed by nutrient-deprivation, and injected them into septic mice. CDNP-treated mice demonstrated decreased peritoneal interleukin 6 levels and an approximately 2-log lower bacterial load compared with control mice 24 h after CLP. Additionally, a 20% CFU reduction was observed when incubating CDNPs with Pseudomona aeroginosa, indicating that CDNPs are bactericidal. To identify CDNP-responsive cells, CFSE-labeled CDNPs were injected into mice at the time of CLP. We observed that CDNPs were preferentially ingested by F4/80 macrophages, and to a lesser degree, associated with inflammatory monocytes and neutrophils. Strikingly, CDNP-ingesting cells demonstrated elevated CD11b and MHCII expression compared with control cells. Altogether, our data indicate that CDNPs enhance the immune response at the site of infection and promote bacterial clearance, by direct bacterial killing and increasing phagocyte activation. Thus, CDNPs represent a novel, unexplored endogenous sepsis modulator with therapeutic potential.

  15. Ubiquitin: a potential cerebrospinal fluid progression marker in Huntington's disease.

    PubMed

    Vinther-Jensen, T; Simonsen, A H; Budtz-Jørgensen, E; Hjermind, L E; Nielsen, J E

    2015-10-01

    Finding early and dynamic biomarkers in Huntington's disease is a key to understanding the early pathology of Huntington's disease and potentially to tracking disease progression. This would benefit the future evaluation of potential neuroprotective and disease-modifying therapies, as well as aid in identifying an optimal time point for initiating a potential therapeutic intervention. This explorative proteomics study evaluated cerebrospinal fluid from 94 Huntington's disease gene-expansion carriers (39 premanifest and 55 manifest) and 27 Huntington's disease gene-expansion negative individuals using surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry. Differences in peak intensity from SELDI-TOF spectra were evaluated. Levels of 10 peaks were statistically significantly different between manifest gene-expansion carriers and controls. One of them identified as ubiquitin was shown to be dependent on the Unified Huntington Disease Rating Scale Total Functional Capacity, a pseudo-measure of disease severity (P = 0.001), and the Symbol Digit Modalities Test (0.04) in manifest and CAG-age product score (P = 0.019) in all gene-expansion carriers. Multiple studies have shown that the ubiquitin-proteasome system is involved in Huntington's disease pathogenesis and understanding of this involvement may have therapeutic potential in humans. This is the first study on cerebrospinal fluid to confirm the involvement of the ubiquitin-proteasome system in Huntington's disease. Furthermore it is shown that ubiquitin increases with disease progression and CAG-age product score and therefore may have the potential as a Huntington's disease progression marker, also prior to motor onset. © 2015 EAN.

  16. Endogenous digitalis

    PubMed Central

    Bagrov, Alexei Y; Shapiro, Joseph I

    2008-01-01

    SUMMARY Endogenous digitalis-like factors, also called cardiotonic steroids, have been thought for nearly half a century to have important roles in health and disease. The endogenous cardiotonic steroids ouabain and marinobufagenin have been identified in humans, and an effector mechanism has been delineated by which these hormones signal through the sodium/potassium-transporting ATPase. These findings have increased interest in this field substantially. Although cardiotonic steroids were first considered important in the regulation of renal sodium transport and arterial pressure, subsequent work has implicated these hormones in the control of cell growth, apoptosis and fibrosis, among other processes. This Review focuses on the role of endogenous cardiotonic steroids in the pathophysiology of essential hypertension, congestive heart failure, end-stage renal disease and pre-eclampsia. We also discuss potential therapeutic strategies that have emerged as a result of the increased understanding of the regulation and actions of cardiotonic steroids. PMID:18542120

  17. Network analysis reveals potential markers for pediatric adrenocortical carcinoma

    PubMed Central

    Kulshrestha, Anurag; Suman, Shikha; Ranjan, Rakesh

    2016-01-01

    Pediatric adrenocortical carcinoma (ACC) is a rare malignancy with a poor outcome. Molecular mechanisms of pediatric ACC oncogenesis and advancement are not well understood. Accurate and timely diagnosis of the disease requires identification of new markers for pediatric ACC. Differentially expressed genes (DEGs) were identified from the gene expression profile of pediatric ACC and obtained from Gene Expression Omnibus. Gene Ontology functional and pathway enrichment analysis was implemented to recognize the functions of DEGs. A protein–protein interaction (PPI) and gene–gene functional interaction (GGI) network of DEGs was constructed. Hub gene detection and enrichment analysis of functional modules were performed. Furthermore, a gene regulatory network incorporating DEGs–microRNAs–transcription factors was constructed and analyzed. A total of 431 DEGs including 228 upregulated and 203 downregulated DEGs were screened. These genes were largely involved in cell cycle, steroid biosynthesis, and p53 signaling pathways. Upregulated genes, CDK1, CCNB1, CDC20, and BUB1B, were identified as the common hubs of PPI and GGI networks. All the four common hub genes were also part of modules of the PPI network. Moreover, all the four genes were also present in the largest module of GGI network. A gene regulatory network consisting of 82 microRNAs and 100 transcription factors was also constructed. CDK1, CCNB1, CDC20, and BUB1B may serve as potential biomarker of pediatric ACC and as potential targets for therapeutic approach, although experimental studies are required to authenticate our findings. PMID:27555782

  18. Molecular markers: a potential resource for ginger genetic diversity studies.

    PubMed

    Ismail, Nor Asiah; Rafii, M Y; Mahmud, T M M; Hanafi, M M; Miah, Gous

    2016-12-01

    Ginger is an economically important and valuable plant around the world. Ginger is used as a food, spice, condiment, medicine and ornament. There is available information on biochemical aspects of ginger, but few studies have been reported on its molecular aspects. The main objective of this review is to accumulate the available molecular marker information and its application in diverse ginger studies. This review article was prepared by combing material from published articles and our own research. Molecular markers allow the identification and characterization of plant genotypes through direct access to hereditary material. In crop species, molecular markers are applied in different aspects and are useful in breeding programs. In ginger, molecular markers are commonly used to identify genetic variation and classify the relatedness among varieties, accessions, and species. Consequently, it provides important input in determining resourceful management strategies for ginger improvement programs. Alternatively, a molecular marker could function as a harmonizing tool for documenting species. This review highlights the application of molecular markers (isozyme, RAPD, AFLP, SSR, ISSR and others such as RFLP, SCAR, NBS and SNP) in genetic diversity studies of ginger species. Some insights on the advantages of the markers are discussed. The detection of genetic variation among promising cultivars of ginger has significance for ginger improvement programs. This update of recent literature will help researchers and students select the appropriate molecular markers for ginger-related research.

  19. Oxidative Stress in COPD: Sources, Markers, and Potential Mechanisms

    PubMed Central

    McGuinness, Adam John Anthony; Sapey, Elizabeth

    2017-01-01

    Markers of oxidative stress are increased in chronic obstructive pulmonary disease (COPD) and reactive oxygen species (ROS) are able to alter biological molecules, signaling pathways and antioxidant molecule function, many of which have been implicated in the pathogenesis of COPD. However, the involvement of ROS in the development and progression of COPD is not proven. Here, we discuss the sources of ROS, and the defences that have evolved to protect against their harmful effects. We address the role that ROS may have in the development and progression of COPD, as well as current therapeutic attempts at limiting the damage they cause. Evidence has indicated that the function of several key cells appears altered in COPD patients, and expression levels of important oxidant and antioxidant molecules may be abnormal. Therapeutic trials attempting to restore equilibrium to these molecules have not impacted upon all facets of disease and whilst the theory behind ROS influence in COPD appears sound, current models testing relevant pathways to tissue damage are limited. The heterogeneity seen in COPD patients presents a challenge to our understanding, and further research is essential to identify potential targets and stratified COPD patient populations where ROS therapies may be maximally efficacious. PMID:28212273

  20. Marker formation vs. marker offset - on the resolution potential of tectono-geomorphic records

    NASA Astrophysics Data System (ADS)

    Zielke, Olaf

    2017-04-01

    Understanding the recurrence and actual size of large and damaging earthquakes is an important step towards mitigating the hazard of future seismic events. Coseismically displaced geomorphic and stratigraphic markers are commonly utilized to constrain the recurrence history of surface-rupturing events. An underlying assumption of this approach is that the formation of new geomorphic markers is (distinctly) more frequent than the occurrence of surface-rupturing earthquakes that will disrupt and offset them (the markers). If this assumption is valid, then the offsets that are caused by individual earthquakes can be distinguished, providing valuable information on the causative earthquake size and its variability. Many of the currently existing earthquake recurrence models, such as the characteristic, the uniform-slip, and the variable-slip earthquake model were formulated following this general approach and the underlying assumption. However, whether this assumption is valid or not is essentially never tested or questioned. How sensitive are those recurrence models with regards to the validity of the afore-mentioned assumption that marker formation is more frequent than marker offset? Could it be that the observed recurrence characteristics represent the properties of climatic forcing rather than tectonic activity? To address this question, I utilize a statistical model in which I create markers and then displace them by sampling from a number of different probability distributions for marker formation and offset. In doing so, I create a library of recurrence patterns in which the corresponding patterns depend on timing and relative strength of marker formation and marker offset events. In my presentation I compare these model results with reported earthquake recurrence data (i.e., slip accumulation patterns). This comparison indicates that the surface displacement of ground-rupturing earthquakes is required to exhibit some form of "characteristic" behavior (with

  1. Quantification and Potential Functions of Endogenous Agonists of Transient Receptor Potential Channels in Patients With Irritable Bowel Syndrome.

    PubMed

    Cenac, Nicolas; Bautzova, Tereza; Le Faouder, Pauline; Veldhuis, Nicholas A; Poole, Daniel P; Rolland, Corinne; Bertrand, Jessica; Liedtke, Wolfgang; Dubourdeau, Marc; Bertrand-Michel, Justine; Zecchi, Lisa; Stanghellini, Vincenzo; Bunnett, Nigel W; Barbara, Giovanni; Vergnolle, Nathalie

    2015-08-01

    In mice, activation of the transient receptor potential cation channels (TRP) TRPV1, TRPV4, and TRPA1 causes visceral hypersensitivity. These receptors and their agonists might be involved in development of irritable bowel syndrome (IBS). We investigated whether polyunsaturated fatty acid (PUFA) metabolites, which activate TRPs, are present in colon tissues from patients with IBS and act as endogenous agonists to induce hypersensitivity. We analyzed colon biopsy samples from 40 patients with IBS (IBS biopsies) and 11 healthy individuals undergoing colorectal cancer screening (controls), collected during colonoscopy at the University of Bologna, Italy. Levels of the PUFA metabolites that activate TRPV1 (12-hydroperoxyeicosatetraenoic acid, 15-hydroxyeicosatetraenoic acid, 5-hydroxyeicosatetraenoic acid, and leukotriene B4), TRPV4 (5,6-epoxyeicosatrienoic acid [EET] and 8,9-EET), and TRPA1 (PGA1, 8-iso-prostaglandin A2, and 15-deoxy-Δ-prostaglandin J2) were measured in biopsies and their supernatants using liquid chromatography and tandem mass spectrometry; we also measured levels of the PUFA metabolites prostaglandin E2 (PGE2) and resolvins. C57Bl6 mice were given intrathecal injections of small interfering RNAs to reduce levels of TRPV4, or control small interfering RNAs, along with colonic injections of biopsy supernatants; visceral hypersensitivity was measured based on response to colorectal distension. Mouse sensory neurons were cultured and incubated with biopsy supernatants and lipids extracted from biopsies or colons of mice. Immunohistochemistry was used to detect TRPV4 in human dorsal root ganglia samples (from the National Disease Research Interchange). Levels of the TRPV4 agonist 5,6-EET, but not levels of TRPV1 or TRPA1 agonists, were increased in IBS biopsies compared with controls; increases correlated with pain and bloating scores. Supernatants from IBS biopsies, but not from controls, induced visceral hypersensitivity in mice. Small interfering RNA

  2. Metabolic fate of endogenous molecular damage: Urinary glutathione conjugates of DNA-derived base propenals as markers of inflammation

    PubMed Central

    Jumpathong, Watthanachai; Chan, Wan; Taghizadeh, Koli; Babu, I. Ramesh; Dedon, Peter C.

    2015-01-01

    Although mechanistically linked to disease, cellular molecules damaged by endogenous processes have not emerged as significant biomarkers of inflammation and disease risk, due in part to poor understanding of their pharmacokinetic fate from tissue to excretion. Here, we use systematic metabolite profiling to define the fate of a common DNA oxidation product, base propenals, to discover such a biomarker. Based on known chemical reactivity and metabolism in liver cell extracts, 15 candidate metabolites were identified for liquid chromatography-coupled tandem mass spectrometry (LC-MS/MS) quantification in urine and bile of rats treated with thymine propenal (Tp). Analysis of urine revealed three metabolites (6% of Tp dose): thymine propenoate and two mercapturate derivatives of glutathione conjugates. Bile contained an additional four metabolites (22% of Tp dose): cysteinylglycine and cysteine derivatives of glutathione adducts. A bis-mercapturate was observed in urine of untreated rats and increased approximately three- to fourfold following CCl4-induced oxidative stress or treatment with the DNA-cleaving antitumor agent, bleomycin. Systematic metabolite profiling thus provides evidence for a metabolized DNA damage product as a candidate biomarker of inflammation and oxidative stress in humans. PMID:26283391

  3. Reducing endogenous estrogen during prepuberal life does not affect boar libido or sperm fertilizing potential.

    PubMed

    Berger, Trish; Conley, Alan J

    2014-09-01

    Increasing sperm production per breeding male has economic significance with increasing use of artificial insemination. Manipulations to increase sperm production in livestock will only be useful if libido and sperm fertilizing capacity are not adversely affected. Reducing endogenous estrogens in the postnatal interval increases the number of Sertoli cells and hence testicular sperm production capacity. These experiments were designed to evaluate the effects of reducing endogenous estrogens on libido and sperm fertilizing capacity. Boars were treated with an aromatase inhibitor, letrozole, to reduce testicular estrogen production between 1 and 6 weeks of age or between 11 and 16 weeks of age, and the littermates to these boars were treated with the canola oil vehicle. Letrozole treatment did not affect time to first mount at 22 weeks of age, regardless of whether the treatment occurred from 1 to 6 weeks of age (118 seconds vs. 233 seconds, SEM = 161 for letrozole-treated and vehicle-treated boars, respectively) or from 11 to 16 weeks of age (107 seconds vs. 67 seconds, SEM = 63 for letrozole-treated and vehicle-treated boars, respectively). Similarly, sperm fertilizing ability and in vivo fertility were equivalent in letrozole-treated boars and their vehicle-treated littermates. Surprisingly, the increase in Sertoli cell numbers observed in the letrozole-treated boars at 20 weeks of age (5.8 vs. 4.3 billion, SEM = 0.5; P < 0.05) was not maintained to 40 weeks of age in their letrozole-treated littermates. Reducing endogenous estrogen production neonatally or prepuberally had no detectable adverse effect on libido or sperm fertilizing capacity.

  4. Endogenous miRNA and Target Concentrations Determine Susceptibility to Potential ceRNA Competition

    PubMed Central

    Bosson, Andrew D.; Zamudio, Jesse R.; Sharp, Phillip A.

    2016-01-01

    SUMMARY Target competition (ceRNA crosstalk) within miRNA-regulated gene networks has been proposed to influence biological systems. To assess target competition, we characterize and quantitate miRNA networks in two cell types. Argonaute iCLIP reveals that hierarchical binding of high- to low-affinity miRNA targets is a key characteristic of in vivo activity. Quantification of cellular miRNA and mRNA/ncRNA target pool levels indicates that miRNA:target pool ratios and an affinity partitioned target pool accurately predict in vivo Ago binding profiles and miRNA susceptibility to target competition. Using single-cell reporters, we directly test predictions and estimate that ~3,000 additional high-affinity target sites can affect active miRNA families with low endogenous miRNA:target ratios, such as miR-92/25. In contrast, the highly expressed miR-294 and let-7 families are not susceptible to increases of nearly 10,000 sites. These results show differential susceptibility based on endogenous miRNA:target pool ratios and provide a physiological context for ceRNA competition in vivo. PMID:25449132

  5. Endogenous neurotrophins are required for the induction of GABAergic long-term potentiation in the neonatal rat hippocampus.

    PubMed

    Gubellini, Paolo; Ben-Ari, Yehezkel; Gaïarsa, Jean-Luc

    2005-06-15

    In the developing rat hippocampus, GABAergic synapses undergo a Ca2+-dependent long-term potentiation (LTP(GABA-A)); this form of synaptic plasticity is induced in CA3 pyramidal neurons by delivering repetitive depolarizing pulses (DPs) to the recorded neuron, and it is expressed as a long-lasting increase in the frequency and amplitude of spontaneous GABA(A) receptor-mediated postsynaptic currents. In the present study, we examined the role of endogenous tropomyosin-related kinase receptor B (TrkB) receptor ligands and associated protein tyrosine kinases (PTKs) in the induction of LTP(GABA-A). The application of Lavendustin A, a broad spectrum PTK inhibitor, blocked the induction of LTP(GABA-A), whereas Lavendustin B, its inactive form, had no effect. Moreover, k-252a and k-252b, two alkaloids that inhibit the kinase activity of the Trk receptor family, also prevented the induction of LTP(GABA-A). On hippocampal slices incubated with the soluble form of TrkB receptor IgG (TrkB-IgG), which prevents the activation of TrkB receptors by endogenous ligands, DPs failed to induce LTP(GABA-A), whereas the incubation with TrkA-IgG or TrkC-IgG had no such effect. Altogether, these data indicate that endogenous TrkB ligands and associated PTK activity are necessary for the induction of GABAergic LTP in the developing rat hippocampus.

  6. Markers

    ERIC Educational Resources Information Center

    Healthy Schools Network, Inc., 2011

    2011-01-01

    Dry erase whiteboards come with toxic dry erase markers and toxic cleaning products. Dry erase markers labeled "nontoxic" are not free of toxic chemicals and can cause health problems. Children are especially vulnerable to environmental health hazards; moreover, schools commonly have problems with indoor air pollution, as they are more densely…

  7. CD14 mediated endogenous TNF-alpha release in HL60 AML cells: a potential model for CD14 mediated endogenous cytokine release in the treatment of AML.

    PubMed

    Treon, S P; Anand, B; Ulevitch, R; Broitman, S A

    1994-01-01

    In previous studies, HL60 AML cells treated with tumor necrosis factor-alpha (TNF), interferon-gamma (IFN), and lipopolysaccharides (LPS) displayed decreased growth and viability, enhanced monocytic pathway differentiation and endogenous TNF release. Endogenous TNF release by LPS/TNF/IFN treated HL60 cells was postulated to play a role with the above findings. In these studies, HL60 cells expressed CD14 when treated with TNF, IFN, and LPS. CD14 mediates TNF release in monocytes/macrophages in response to binding of LPS with LPS binding protein (LBP). CD14 was not expressed in either untreated or LPS only treated HL60 cells. CD14 expression was present and greater with HL60 cells cultured with LPS/TNF/IFN vs TNF/IFN (47.47% vs 9.07% positive, respectively) suggesting synergism for LPS in CD14 induction. CD14 expression was associated with endogenous TNF release, and with significantly higher levels by HL60 cells treated with LPS/TNF/IFN vs TNF/IFN (p < 0.001). Addition of anti-CD14 antibody significantly reduced release of TNF in TNF/IFN (p < 0.001) and LPS/TNF/IFN (p = 0.0013) treated cells. KG1 and U937 AML cells treated with LPS, TNF, and IFN did not express CD14, nor release TNF. A model for inducing release of endogenous growth inhibitory cytokines by CD14 bearing AML cells is proposed as an approach to AML therapy.

  8. A potential role for endogenous proteins as sacrificial sunscreens and antioxidants in human tissues.

    PubMed

    Hibbert, Sarah A; Watson, Rachel E B; Gibbs, Neil K; Costello, Patrick; Baldock, Clair; Weiss, Anthony S; Griffiths, Christopher E M; Sherratt, Michael J

    2015-08-01

    Excessive ultraviolet radiation (UVR) exposure of the skin is associated with adverse clinical outcomes. Although both exogenous sunscreens and endogenous tissue components (including melanins and tryptophan-derived compounds) reduce UVR penetration, the role of endogenous proteins in absorbing environmental UV wavelengths is poorly defined. Having previously demonstrated that proteins which are rich in UVR-absorbing amino acid residues are readily degraded by broadband UVB-radiation (containing UVA, UVB and UVC wavelengths) here we hypothesised that UV chromophore (Cys, Trp and Tyr) content can predict the susceptibility of structural proteins in skin and the eye to damage by physiologically relevant doses (up to 15.4 J/cm(2)) of solar UVR (95% UVA, 5% UVB). We show that: i) purified suspensions of UV-chromophore-rich fibronectin dimers, fibrillin microfibrils and β- and γ-lens crystallins undergo solar simulated radiation (SSR)-induced aggregation and/or decomposition and ii) exposure to identical doses of SSR has minimal effect on the size or ultrastructure of UV chromophore-poor tropoelastin, collagen I, collagen VI microfibrils and α-crystallin. If UV chromophore content is a factor in determining protein stability in vivo, we would expect that the tissue distribution of Cys, Trp and Tyr-rich proteins would correlate with regional UVR exposure. From bioinformatic analysis of 244 key structural proteins we identified several biochemically distinct, yet UV chromophore-rich, protein families. The majority of these putative UV-absorbing proteins (including the late cornified envelope proteins, keratin associated proteins, elastic fibre-associated components and β- and γ-crystallins) are localised and/or particularly abundant in tissues that are exposed to the highest doses of environmental UVR, specifically the stratum corneum, hair, papillary dermis and lens. We therefore propose that UV chromophore-rich proteins are localised in regions of high UVR exposure

  9. EST-SSR markers derived from an elite barley cultivar (Hordeum vulgare L. 'Morex'): polymorphism and genetic marker potential.

    PubMed

    Emebiri, Livinus C

    2009-08-01

    Microsatellites or simple sequence repeats have become the markers of choice for marker-assisted selection because of their low template DNA requirement, high reproducibility, and high level of polymorphism. This study investigated a new set of barley (Hordeum vulgare L.) EST-derived SSR markers designed to target gene sequences expressed during grain development, as they are more likely to be important in determining grain quality. The EST sequences (HVSMEh and HVSMEi) were derived from cDNA libraries of the elite six-rowed cultivar Morex, made from spikes harvested at 5 to 45 days after pollination. Approximately half of the 110 SSR markers derived from the ESTs were polymorphic in a panel of 8 diverse barley genotypes, with PIC values between 0.19 and 0.79. Twenty of the new markers were mapped to chromosomal locations using 2 doubled haploid populations. To demonstrate marker potential, quantitative trait locus (QTL) analyses were carried out with phenotypic data on wort beta-glucan content and beta-glucanase activity, two traits with a long history of genetic studies. Most of the EST-SSR markers mapped to within 10 cM of the cellulose synthase (HvCesA) and cellulose synthase-like (HvCslF) genes, which provides highly informative functional markers for tracking these genes in breeding programs. It was also observed that on any given chromosome, the QTL for beta-glucan content and beta-glucanase activity were rarely coincident but tended to occur in adjacent intervals along chromosomal regions, which agreed with their independent genetic basis; the adjacent localization may be important for coordination of cell wall degradation during germination and malting.

  10. Noninvasive molecular imaging of hypoxia in human xenografts: comparing hypoxia-induced gene expression with endogenous and exogenous hypoxia markers.

    PubMed

    He, Fuqiu; Deng, Xuelong; Wen, Bixiu; Liu, Yueping; Sun, Xiaorong; Xing, Ligang; Minami, Akiko; Huang, Yunhong; Chen, Qing; Zanzonico, Pat B; Ling, C Clifton; Li, Gloria C

    2008-10-15

    Tumor hypoxia is important in the development and treatment of human cancers. We have developed a novel xenograft model for studying and imaging of hypoxia-induced gene expression. A hypoxia-inducible dual reporter herpes simplex virus type 1 thymidine kinase and enhanced green fluorescence protein (HSV1-TKeGFP), under the control of hypoxia response element (9HRE), was stably transfected into human colorectal HT29 cancer cells. Selected clones were further enriched by repeated live cell sorting gated for hypoxia-induced eGFP expression. Fluorescent microscopy, fluorescence-activated cell sorting, and radioactive substrate trapping assays showed strong hypoxia-induced expression of eGFP and HSV1-tk enzyme in the HT29-9HRE cells in vitro. Sequential micropositron emission tomography (PET) imaging of tumor-bearing animals, using the hypoxic cell tracer (18)F-FMISO and the reporter substrate (124)I-FIAU, yielded similar tumor hypoxia images for the HT29-9HRE xenograft but not in the parental HT29 tumor. Using autoradiography and IHC, detailed spatial distributions in tumor sections were obtained and compared for the following hypoxia-associated biomarkers in the HT29-9HRE xenograft: (124)I-FIAU, (18)F-FMISO, Hoechst (perfusion), lectin-TRITC (functional blood vessels), eGFP, pimonidazole, EF5, and CA9. Intratumoral distributions of (124)I-FIAU and (18)F-FMISO were similar, and eGFP, pimonidazole, EF5, and CA9 colocalized in the same areas but not in well-perfused regions that were positive for Hoechst and lectin-TRITC. In enabling the detection of hypoxia-induced molecular events and mapping their distribution in vivo with serial noninvasive positron emission tomography imaging, and multiple variable analysis with immunohistochemistry and fluorescence microscopy, this human xenograft model provides a valuable tool for studying tumor hypoxia and in validating existing and future exogenous markers for tumor hypoxia.

  11. Stem Cell Derived Retinal Pigment Epithelium: The Role of Pigmentation as Maturation Marker and Gene Expression Profile Comparison with Human Endogenous Retinal Pigment Epithelium.

    PubMed

    Bennis, A; Jacobs, J G; Catsburg, L A E; Ten Brink, J B; Koster, C; Schlingemann, R O; van Meurs, J; Gorgels, T G M F; Moerland, P D; Heine, V M; Bergen, A A

    2017-07-21

    In age-related macular degeneration (AMD) the retinal pigment epithelium (RPE) deteriorates, leading to photoreceptor decay and severe vision loss. New therapeutic strategies aim at RPE replacement by transplantation of pluripotent stem cell (PSC)-derived RPE. Several protocols to generate RPE have been developed where appearance of pigmentation is commonly used as indicator of RPE differentiation and maturation. It is, however, unclear how different pigmentation stages reflect developmental stages and functionality of PSC-derived RPE cells. We generated human embryonic stem cell-derived RPE (hESC-RPE) cells and investigated their gene expression profiles at early pigmentation (EP) and late pigmentation (LP) stages. In addition, we compared the hESC-RPE samples with human endogenous RPE. We used a common reference design microarray (44 K). Our analysis showed that maturing hESC-RPE, upon acquiring pigmentation, expresses markers specific for human RPE. Interestingly, our analysis revealed that EP and LP hESC-RPE do not differ much in gene expression. Our data further showed that pigmented hESC-RPE has a significant lower expression than human endogenous RPE in the visual cycle and oxidative stress pathways. In contrast, we observed a significantly higher expression of pathways related to the process adhesion-to-polarity model that is typical of developing epithelial cells. We conclude that, in vitro, the first appearance of pigmentation hallmarks differentiated RPE. However, further increase in pigmentation does not result in much significant gene expression changes and does not add important RPE functionalities. Consequently, our results suggest that the time span for obtaining differentiated hESC-RPE cells, that are suitable for transplantation, may be greatly reduced.

  12. The Late Positive Potential: A Neurophysiological Marker for Emotion Regulation in Children

    ERIC Educational Resources Information Center

    Dennis, Tracy A.; Hajcak, Greg

    2009-01-01

    Background: The ability to modulate emotional responses, or emotion regulation, is a key mechanism in the development of mood disruptions. Detection of a neural marker for emotion regulation thus has the potential to inform early detection and intervention for mood problems. One such neural marker may be the late positive potential (LPP), which is…

  13. The Late Positive Potential: A Neurophysiological Marker for Emotion Regulation in Children

    ERIC Educational Resources Information Center

    Dennis, Tracy A.; Hajcak, Greg

    2009-01-01

    Background: The ability to modulate emotional responses, or emotion regulation, is a key mechanism in the development of mood disruptions. Detection of a neural marker for emotion regulation thus has the potential to inform early detection and intervention for mood problems. One such neural marker may be the late positive potential (LPP), which is…

  14. Microvesicles: potential markers and mediators of endothelial dysfunction.

    PubMed

    Liu, Ming-Lin; Williams, Kevin Jon

    2012-04-01

    Microvesicles (also known as microparticles) are small membranous structures that are released from platelets and cells upon activation or during apoptosis. Microvesicles have been found in blood, urine, synovial fluid, extracellular spaces of solid organs, atherosclerotic plaques, tumors, and elsewhere. Here, we focus on new clinical and basic work that implicates microvesicles as markers and mediators of endothelial dysfunction and hence novel contributors to cardiovascular and other diseases. Advances in the detection of microvesicles and the use of cell type-specific markers to determine their origin have allowed studies that associated plasma concentrations of specific microvesicles with major types of endothelial dysfunction - namely, inappropriate or maladaptive vascular tone, leukocyte recruitment, and thrombosis. Recent investigations have highlighted microvesicular transport of key biologically active molecules besides tissue factor, such as ligands for pattern-recognition receptors, elements of the inflammasome, and morphogens. Microvesicles generated from human cells under different pathologic circumstances, for example, during cholesterol loading or exposure to endotoxin, carry different subsets of these molecules and thereby alter endothelial function through several distinct, well characterized molecular pathways. Clinical and basic studies indicate that microvesicles may be novel markers and mediators of endothelial dysfunction. This work has advanced our understanding of the development of cardiovascular and other diseases. Opportunities and obstacles to clinical applications are discussed.

  15. A potential role for endogenous proteins as sacrificial sunscreens and antioxidants in human tissues

    PubMed Central

    Hibbert, Sarah A.; Watson, Rachel E.B.; Gibbs, Neil K.; Costello, Patrick; Baldock, Clair; Weiss, Anthony S.; Griffiths, Christopher E.M.; Sherratt, Michael J.

    2015-01-01

    Excessive ultraviolet radiation (UVR) exposure of the skin is associated with adverse clinical outcomes. Although both exogenous sunscreens and endogenous tissue components (including melanins and tryptophan-derived compounds) reduce UVR penetration, the role of endogenous proteins in absorbing environmental UV wavelengths is poorly defined. Having previously demonstrated that proteins which are rich in UVR-absorbing amino acid residues are readily degraded by broadband UVB-radiation (containing UVA, UVB and UVC wavelengths) here we hypothesised that UV chromophore (Cys, Trp and Tyr) content can predict the susceptibility of structural proteins in skin and the eye to damage by physiologically relevant doses (up to 15.4 J/cm2) of solar UVR (95% UVA, 5% UVB). We show that: i) purified suspensions of UV-chromophore-rich fibronectin dimers, fibrillin microfibrils and β- and γ-lens crystallins undergo solar simulated radiation (SSR)-induced aggregation and/or decomposition and ii) exposure to identical doses of SSR has minimal effect on the size or ultrastructure of UV chromophore-poor tropoelastin, collagen I, collagen VI microfibrils and α-crystallin. If UV chromophore content is a factor in determining protein stability in vivo, we would expect that the tissue distribution of Cys, Trp and Tyr-rich proteins would correlate with regional UVR exposure. From bioinformatic analysis of 244 key structural proteins we identified several biochemically distinct, yet UV chromophore-rich, protein families. The majority of these putative UV-absorbing proteins (including the late cornified envelope proteins, keratin associated proteins, elastic fibre-associated components and β- and γ-crystallins) are localised and/or particularly abundant in tissues that are exposed to the highest doses of environmental UVR, specifically the stratum corneum, hair, papillary dermis and lens. We therefore propose that UV chromophore-rich proteins are localised in regions of high UVR exposure

  16. The biotechnological potential of fibrinolytic enzymes in the dissolution of endogenous blood thrombi.

    PubMed

    Kotb, Essam

    2014-01-01

    Formation of endogenous thrombi in blood vessels is one of the leading causes of death in our modern life. According to data provided by the World Health Organization (WHO) in 2000, heart diseases are responsible for 29% of the total mortality rate in the world. For this, a tremendous amount of research has been done in the area of prevention and treatment of these diseases. The classical therapy of these thrombi relies upon the use of antiplatelets, anticoagulants, or even surgeries. Relatively recently, the fibrinolytic enzymes produced by microorganisms, snakes, earthworms, insects, plants, and other organisms are being successfully used in the treatment of blood clots, especially with regard to the direct dissolving action on fibrin in tandem with less cost and side effects in comparison with the first-generation thrombolytic agents, streptokinase and urokinase. Furthermore, recombinant DNA technology has succeeded in improving and decreasing the undesirable effects of the first generation of enzymes. Recombinant PAs or rt-PAs like alteplase, retelase, saruplase, tenecteplase, lanoteplase, and desmoteplase became available in the drug markets with advantages of less binding loci with PAI-1 to avoid degradation while providing faster and more complete reperfusion in a greater number of patients with less risk of bleeding and intracranial hemorrhage. This review is the first to cover all the natural and recombinant thrombolytic agents used in enzyme therapy.

  17. THE POTENTIAL ROLE OF ENDOGENOUS STEM CELLS IN REGENERATION OF THE INNER EAR

    PubMed Central

    Martinez-Monedero, Rodrigo; Oshima, Kazuo; Heller, Stefan; Edge, Albert S.B.

    2007-01-01

    Stem cells in various mammalian tissues retain the capacity to renew themselves and may be able to restore damaged tissue. Their existence has been proven by genetic tracer studies that demonstrate their differentiation into multiple tissue types and by their ability to self-renew through proliferation. Stem cells from the adult nervous system proliferate to form clonal floating colonies called spheres in vitro, and recent studies have demonstrated sphere formation by cells in the cochlea in addition to the vestibular system and the auditory ganglia, indicating that these tissues contain cells with stem cell properties. The presence of stem cells in the inner ear raises the hope of regeneration of mammalian inner ear cells but is difficult to correlate with the lack spontaneous regeneration seen in the inner ear after tissue damage. Loss of stem cells postnatally in the cochlea may correlate with the loss of regenerative capacity and may limit our ability to stimulate regeneration. Retention of sphere forming capacity in adult vestibular tissues suggests that the limited capacity for repair may be attributed to the continued presence of progenitor cells. Future strategies for regeneration must consider the distribution of endogenous stem cells in the inner ear and whether cells with the capacity for regeneration are retained. PMID:17321086

  18. Thioredoxin Interacting Protein Is a Potential Regulator of Glucose and Energy Homeostasis in Endogenous Cushing's Syndrome

    PubMed Central

    Lekva, Tove; Bollerslev, Jens; Sahraoui, Afaf; Scholz, Hanne; Bøyum, Hege; Evang, Johan Arild; Godang, Kristin; Aukrust, Pål; Ueland, Thor

    2013-01-01

    Recent studies have described bone as an endocrine organ regulating glucose metabolism, with insulin signaling regulating osteocalcin secretion and osteocalcin regulating β cell function. We have previously demonstrated increased bone expression of TXNIP in patients with endogenous Cushing's syndrome (CS), and we hypothesized that TXNIP could contribute to the dysregulated glucose metabolism in CS. We studied 33 CS patients and 29 matched controls, with bone biopsies from nine patients, before and after surgical treatment. In vitro, the effect of silencing TXNIP (siTXNIP) in osteoblasts, including its effect on human islet cells, was examined. Our major findings were: (i) The high mRNA levels of TXNIP in bone from CS patients were significantly associated with high levels of glucose and insulin, increased insulin resistance, and decreased insulin sensitivity in these patients. (ii) Silencing TXNIP in osteoblasts enhanced their OC response to insulin and glucose and down-regulated interleukin (IL)-8 levels in these cells. (iii) Conditional media from siTXNIP-treated osteoblasts promoted insulin content and anti-inflammatory responses in human islet cells. We recently demonstrated that the thioredoxin/TXNIP axis may mediate some detrimental effects of glucocorticoid excess on bone tissue in CS. Here we show that alterations in this axis also may affect glucose metabolism in these patients. PMID:23691179

  19. Endogenous viral sequences and their potential contribution to heritable virus resistance in plants

    PubMed Central

    Mette, M.F.; Kanno, T.; Aufsatz, W.; Jakowitsch, J.; van der Winden, J.; Matzke, M.A.; Matzke, A.J.M.

    2002-01-01

    Tobacco endogenous pararetroviruses (TEPRVs) represent the first virus-derived repetitive sequence family found in plants. The sequence conservation of TEPRVs and the lack of an exogenous form of the virus suggest that TEPRVs serve a beneficial function, perhaps by furnishing virus resistance via homologous sequence interactions. This hypothesis is supported by the observation that TEPRVs are methylated and negligibly transcribed. Moreover, transgenes driven by the TEPRV enhancer are silenced and methylated when introduced into tobacco, but remain active and unmethylated in non-host species devoid of sequences homologous to TEPRVs. In transgenic Arabidopsis, the TEPRV enhancer is active primarily in shoot meristems. This suggests that the virus giving rise to TEPRVs could infect germ cell precursors, a prerequisite for meiotically heritable insertions into host chromosomes. The copy number, organization and methylation of TEPRVs in tetraploid tobacco and one of its diploid ancestors, Nicotiana sylvestris, the presumed original host for the virus, have remained constant since polyploid formation. The remarkable conservation of these features in two independently evolving species further supports a role for TEPRVs in viral immunity. PMID:11823438

  20. Potential immunological markers for diagnosis and therapeutic assessment of toxocariasis.

    PubMed

    Rubinsky-Elefant, Guita; Hoshino-Shimizu, Sumie; Jacob, Cristina Miuki Abe; Sanchez, Maria Carmen Arroyo; Ferreira, Antonio Walter

    2011-01-01

    In human toxocariasis, there are few approaches using immunological markers for diagnosis and therapeutic assessment. An immunoblot (IB) assay using excretory-secretory Toxocara canis antigen was standardized for monitoring IgG, IgE and IgA antibodies in 27 children with toxocariasis (23 visceral, three mixed visceral and ocular, and one ocular form) for 22-116 months after chemotherapy. IB sensitivity was 100% for IgG antibodies to bands of molecular weight 29-38, 48-54, 95-116, 121-162, >205 kDa, 80.8% for IgE to 29-38, 48-54, 95-121, > 205 kDa, and 65.4% for IgA to 29-38, 48-54, 81-93 kDa. Candidates for diagnostic markers should be IgG antibodies to bands of low molecular weight (29-38 and 48-54 kDa). One group of patients presented the same antibody reactivity to all bands throughout the follow-up study; in the other group, antibodies decayed partially or completely to some or all bands, but these changes were not correlated with time after chemotherapy. Candidates for monitoring patients after chemotherapy may be IgG antibodies to > 205 kDa fractions, IgA to 29-38, 48-54, 81-93 kDa and IgE to 95-121 kDa. Further identification of antigen epitopes related to these markers will allow the development of sensitive and specific immunoassays for the diagnosis and therapeutic assessment of toxocariasis.

  1. Biomarker and competing endogenous RNA potential of tumor-specific long noncoding RNA in chromophobe renal cell carcinoma

    PubMed Central

    He, Hai-Tao; Xu, Mu; Kuang, Ye; Han, Xiao-Yun; Wang, Ming-Qi; Yang, Qing

    2016-01-01

    Background Accumulating evidence suggests long noncoding RNAs (lncRNAs) play important roles in the initiation and progression of cancers. However, their functions in chromophobe renal cell carcinoma (chRCC) are not fully understood. Methods We analyzed the expression profiles of lncRNA, microRNA, and protein-coding RNA, along with the clinical information of 59 primary chRCC patients collected from The Cancer Genome Atlas database to identify lncRNA biomarkers for prognosis. We also constructed an lncRNA–microRNA–mRNA coexpression network (competitive endogenous RNAs network) by bioinformational approach. Results One hundred and forty-two lncRNAs were found to be differentially expressed between the cancer and normal tissues (fold change ≥1.5, P<0.001). Among them, 12 lncRNAs were also differentially expressed with the corresponding clinical characteristics (fold change ≥1.5, P<0.01). Besides, 7 lncRNAs (COL18A1-AS, BRE-AS1, SNHG7, TMEM51-AS1, C21orf62-AS1, LINC00336, and LINC00882) were identified to be significantly correlated with overall survival (log-rank P<0.05). A competitive endogenous RNA network in chRCC containing 16 lncRNAs, 18 miRNAs, and 168 protein-coding RNAs was constructed. Conclusion Our results identified specific lncRNAs associated with chRCC progression and prognosis, and presented competing endogenous RNA potential of lncRNAs in the tumor. PMID:27799788

  2. Mobilization of Endogenous Bone Marrow Derived Endothelial Progenitor Cells and Therapeutic Potential of Parathyroid Hormone after Ischemic Stroke in Mice

    PubMed Central

    Wang, Li-Li; Chen, Dongdong; Lee, Jinhwan; Gu, Xiaohuan; Alaaeddine, Ghina; Li, Jimei; Wei, Ling; Yu, Shan Ping

    2014-01-01

    Stroke is a major neurovascular disorder threatening human life and health. Very limited clinical treatments are currently available for stroke patients. Stem cell transplantation has shown promising potential as a regenerative treatment after ischemic stroke. The present investigation explores a new concept of mobilizing endogenous stem cells/progenitor cells from the bone marrow using a parathyroid hormone (PTH) therapy after ischemic stroke in adult mice. PTH 1-34 (80 µg/kg, i.p.) was administered 1 hour after focal ischemia and then daily for 6 consecutive days. After 6 days of PTH treatment, there was a significant increase in bone marrow derived CD-34/Fetal liver kinase-1 (Flk-1) positive endothelial progenitor cells (EPCs) in the peripheral blood. PTH treatment significantly increased the expression of trophic/regenerative factors including VEGF, SDF-1, BDNF and Tie-1 in the brain peri-infarct region. Angiogenesis, assessed by co-labeled Glut-1 and BrdU vessels, was significantly increased in PTH-treated ischemic brain compared to vehicle controls. PTH treatment also promoted neuroblast migration from the subventricular zone (SVZ) and increased the number of newly formed neurons in the peri-infarct cortex. PTH-treated mice showed significantly better sensorimotor functional recovery compared to stroke controls. Our data suggests that PTH therapy improves endogenous repair mechanisms after ischemic stroke with functional benefits. Mobilizing endogenous bone marrow-derived stem cells/progenitor cells using PTH and other mobilizers appears an effective and feasible regenerative treatment after ischemic stroke. PMID:24503654

  3. Low dietary potassium intakes and high dietary estimates of net endogenous acid production are associated with low bone mineral density in premenopausal women and increased markers of bone resorption in postmenopausal women.

    PubMed

    Macdonald, Helen M; New, Susan A; Fraser, William D; Campbell, Marion K; Reid, David M

    2005-04-01

    The Western diet may be a risk factor for osteoporosis. Excess acid generated from high protein intakes increases calcium excretion and bone resorption. Fruit and vegetable intake could balance this excess acidity by providing alkaline salts of potassium. Algorithms based on dietary intakes of key nutrients can be used to approximate net endogenous acid production (NEAP) and to explore the association between dietary acidity and bone health. We investigated the relation between dietary potassium and protein, NEAP (with an algorithm including the ratio of protein to potassium intake), and potential renal acid load (with an algorithm including dietary protein, phosphorous, potassium, magnesium, and calcium) and markers of bone health. Measurements of bone mineral density (BMD) (n = 3226) and urinary bone resorption markers (n = 2929) at the lumbar spine and femoral neck were performed in perimenopausal and early postmenopausal women aged 54.9 +/- 2.2 y (x +/- SD) in 1997-1999. BMD (g/cm(2)), free pyridinoline (fPYD), and free deoxypyridinoline (fDPD) were expressed relative to creatinine. Dietary intake was assessed with a food-frequency questionnaire. Comparison of the highest with the lowest quartile of potassium intake or the lowest with the highest NEAP showed a 6-8% increase in fPYD/creatinine and fDPD/creatinine. A difference of 8% in BMD was observed between the highest and lowest quartiles of potassium intake in the premenopausal group (n = 337). Dietary potassium, an indicator of NEAP and fruit and vegetable intake, may exert a modest influence on markers of bone health, which over a lifetime may contribute to a decreased risk of osteoporosis.

  4. Insulin resistance: potential role of the endogenous nitric oxide synthase inhibitor ADMA.

    PubMed

    Sydow, Karsten; Mondon, Carl E; Cooke, John P

    2005-07-01

    The insulin resistance syndrome (IRS) is considered to be a new target of risk-reduction therapy. The IRS is a cluster of closely associated and interdependent abnormalities and clinical outcomes that occur more commonly in insulin-resistant/hyperinsulinemic individuals. This syndrome predisposes individuals to type 2 diabetes, cardiovascular diseases, essential hypertension, certain forms of cancer, polycystic ovary syndrome, nonalcoholic fatty liver disease, and sleep apnea. In patients at high risk for cardiovascular diseases, endothelial dysfunction is observed in morphologically intact vessels even before the onset of clinically manifest vascular disease. Indeed, there are several lines of evidence that indicate that endothelial function is compromised in situations where there is reduced sensitivity to endogenous insulin. It is well established that a decreased bioavailability of nitric oxide (NO) contributes to endothelial dysfunction. Furthermore, NO may modulate insulin sensitivity. Activation of NO synthase (NOS) augments blood flow to insulin-sensitive tissues (i.e. skeletal muscle, liver, adipose tissue), and its activity is impaired in insulin resistance. Inhibition of NOS reduces the microvascular delivery of nutrients and blunts insulin-stimulated glucose uptake in skeletal muscle. Furthermore, induction of hypertension by administration of the NOS inhibitor NG-monomethyl-L-arginine is also associated with insulin resistance in rats. Increased levels of asymmetric dimethylarginine (ADMA) are associated with endothelial vasodilator dysfunction and increased risk of cardiovascular diseases. An intriguing relationship exists between insulin resistance and ADMA. Plasma levels of ADMA are positively correlated with insulin resistance in nondiabetic, normotensive people. New basic research insights that provide possible mechanisms underlying the development of insulin resistance in the setting of impaired NO bioavailability will be discussed.

  5. Advances in Carcinogenic Metal Toxicity and Potential Molecular Markers

    PubMed Central

    Koedrith, Preeyaporn; Seo, Young Rok

    2011-01-01

    Metal compounds such as arsenic, cadmium, chromium, cobalt, lead, mercury, and nickel are classified as carcinogens affecting human health through occupational and environmental exposure. However, the underlying mechanisms involved in tumor formation are not well clarified. Interference of metal homeostasis may result in oxidative stress which represents an imbalance between production of free radicals and the system’s ability to readily detoxify reactive intermediates. This event consequently causes DNA damage, lipid peroxidation, protein modification, and possibly symptomatic effects for various diseases including cancer. This review discusses predominant modes of action and numerous molecular markers. Attention is paid to metal-induced generation of free radicals, the phenomenon of oxidative stress, damage to DNA, lipid, and proteins, responsive signal transduction pathways with major roles in cell growth and development, and roles of antioxidant enzymatic and DNA repair systems. Interaction of non-enzymatic antioxidants (carotenoids, flavonoids, glutathione, selenium, vitamin C, vitamin E, and others) with cellular oxidative stress markers (catalase, glutathione peroxidase, and superoxide dismutase) as well as certain regulatory factors, including AP-1, NF-κB, Ref-1, and p53 is also reviewed. Dysregulation of protective pathways, including cellular antioxidant network against free radicals as well as DNA repair deficiency is related to oncogenic stimulation. These observations provide evidence that emerging oxidative stress-responsive regulatory factors and DNA repair proteins are putative predictive factors for tumor initiation and progression. PMID:22272150

  6. Potential diagnostic markers for disseminated intravascular coagulation of sepsis.

    PubMed

    Iba, Toshiaki; Ito, Takashi; Maruyama, Ikuro; Jilma, Bernd; Brenner, Thorsten; Müller, Marcella C A; Juffermans, Nicole P; Thachil, Jecko

    2016-03-01

    Disseminated intravascular coagulation (DIC) is an acquired thrombo-haemorrhagic disorder which arises in clinical scenarios like sepsis, trauma and malignancies. The clinic-laboratory diagnosis of DIC is made in a patient who develops the combination of laboratory abnormalities in the appropriate clinical scenario. The most common laboratory parameters in this setting have been the clotting profile, platelet count, serum fibrinogen and fibrin degradation markers. These tests had the advantage that they could be performed easily and in most laboratories. However, with the better understanding of the pathophysiology of DIC, in recent years, more specific tests have been suggested to be useful in this setting. The newer tests can also prove to be useful in prognostication in DIC. In addition, they may provide assistance in the selection and monitoring of patients diagnosed with DIC. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Action-potential broadening and endogenously sustained bursting are substrates of command ability in a feeding neuron of Pleurobranchaea.

    PubMed

    Gillette, R; Gillette, M U; Davis, W J

    1980-03-01

    1. The ventral white cells (VWC's) of the buccal ganglion of Pleurobranchaea, so named for their position and color, are a bilateral pair of neuron somata. Each sends a single axon out its contralateral stomatogastric nerve and has a dendritic field originating close to the soma. 2. The vwcs exhibit spontaneous episodes of prolonged depolarization (duration 1--4 min) accompanied by repetitive action-potential activity and separated by regular intervals of 3--30 min. Such prolonged burst episodes can be triggered by short pulses of depolarizing current. During the repetitive activity of the spontaneous bursts or that driven by imposed depolarization, the action potentials progressively broaden to 5--16 times their initial duration. 3. During spontaneous bursting or activity driven by imposed depolarization, the cyclic motor output of the feeding network is initiated or accelerated with a latency corresponding with the development of appreciable VWC spike broadening. When broadening of antidromic VWC spikes is suppressed by imposed hyperpolarization of the soma, the frequency of feeding cycles is significantly lower than when broadened spikes are allowed to develop. When trains of spikes are driven by depolarizing current, the motor output of the feeding network is not initiated until the VWC spikes have broadened to a repeatable "threshold" duration, regardless of the intensity of the depolarizing current. 4. The endogenous production of prolonged burst episodes, triggered by depolarizing current pulses, and progressive spike broadening can be demonstrated in the surgically isolated VWC soma. 5. The paired VWCs are strongly electrically coupled and display highly synchronous activity. They receive synaptic inputs from many previously identified interneurons of the feeding network and are thus reciprocally coupled within the network. 6. These results demonstrate that the capacity of this neuron to generate broadened action potentials during repetitive activity

  8. Stock-still behavior: a potential developmental marker.

    PubMed

    Sherkow, Susan P; Weinstein, Lissa; Kamens, Sarah R; Megyes, Matthew; Tishman, Lynn P; Williams, Cheryl

    2008-01-01

    During the course of a pilot study of toddlers' behavior and play, the experimenters observed a previously undocumented behavior. This behavior now labeled "stock-still" behavior, was noted at the age of 17.5 months and consisted of the toddlers' standing motionless at or near the doorway of a nursery when previously they had marched, seemingly intrepid, into the room on their own. A prospective study of eight children was undertaken to test the hypothesis that this behavior reliably occurs at a set time during the child's development. Analysis of videotape footage determined that the behavior did not occur as an isolated event but instead was part of a series of one to six individual events within a window spanning two to eight weeks, during a discrete period of time from ages 15.5 months to 18.5 months. It was hypothesized that this behavior may be a developmental marker of the moment when a toddler cognitively and affectively registers the differences between "inside" and "outside," self and other and inner space and outer space. This developmental step is manifested behaviorally as the child's ability to inhibit her responses to previously compelling external stimuli. This hypothesis, as well as its limitations, is herein discussed, and additional clarifying observations are suggested.

  9. Identification of potential genetic markers for improved growth rate in channel catfish

    USDA-ARS?s Scientific Manuscript database

    Identification of genetic polymorphism associated with muscle growth would improve selection efficiency of channel catfish broodstock. Because faster growth is typically associated with increased food intake, factors involved in food intake regulation may serve as potential gene markers for selecti...

  10. [Contribution of endogenous potentials to the study of cognitive development in children: review of the literature].

    PubMed

    Robaey, P

    1987-09-01

    A review of the studies concerning age-related changes of the cognitive event-related potentials is presented. Graded changes (with little or no difference in waveform morphology but shifts in component latency or amplitude) draw to continuous developmental models, but morphological waveform differences are assumed to reflect fundamental differences in modes of cognitive processing. The authors equally present an experimental paradigm indicating that a multifactorial model of amplitude variations is able to reflect the passing from one cognitive stage to the next one, according to Piaget's theory.

  11. Endogenous opioids are involved in morphine and dipyrone analgesic potentiation in the tail flick test in rats.

    PubMed

    Hernández-Delgadillo, Gloria P; Cruz, Silvia L

    2006-09-28

    The combined administration of low doses of opiates with non-steroidal anti-inflammatory drugs can produce additive or supra-additive analgesic effects while reducing unwanted side effects. We have recently reported that co-administration of morphine with dipyrone (metamizol) produces analgesic potentiation both in naïve and in morphine-tolerant rats. The purpose of this work was to determine the role of opioids on the acute potentiation observed between morphine and dipyrone i.v. in the rat tail flick test. To do this, two experiments were done. In the first one, naloxone was administered 10 min before morphine (3.1 mg/kg), dipyrone (600 mg/kg) or their combination at the same doses. Control animals received saline instead of naloxone. In the second experiment, naloxone (or saline) was given 2 min after reaching the maximal peak effect with each individual analgesic treatment. When naloxone was i.v. administered prior to analgesics, it completely blocked morphine effects, partially prevented morphine/dipyrone antinociception and delayed dipyrone-induced nociception. At 3.1 mg/kg, naloxone produced an increased nociception. When naloxone was given after analgesics, it dose-dependently blocked the effects of morphine alone and in combination with dipyrone but with different potency in each case. As to dipyrone, naloxone delayed the time to antinociceptive peak effect. Taken together, these results support the notion that endogenous opioids are involved in the analgesic potentiation observed with the combination of morphine plus dipyrone.

  12. Endogenous histamine facilitates long-term potentiation in the hippocampus during walking.

    PubMed

    Luo, Tao; Leung, L Stan

    2010-06-09

    Long-term potentiation (LTP) in hippocampal CA1 depends on the behavioral state of LTP induction. We hypothesize that histaminergic activity in the septohippocampal system, which is active during walking compared with other behavioral states, is responsible for the behavioral dependence of LTP. Field basal-dendritic EPSPs of CA1 pyramidal cells were recorded in freely behaving rats, and LTP was induced by a single 200 Hz stimulation train (0.5 s duration). Basal-dendritic LTP was facilitated when induced during walking compared with awake immobility (IMM) or rapid-eye-movement sleep. The facilitation of basal-dendritic LTP during walking was abolished by lesion of tuberomammillary nucleus (TMN) neurons with orexin-saporin or by intramedial-septal infusion of the H(1) histaminergic blocker triprolidine but not the H(2) histaminergic blocker cimetidine. Conversely, histamine infusion in the medial septum enhanced the basal-dendritic LTP induced during IMM to a magnitude similar to that induced during walking. Basal-dendritic LTP induced during walking was not further enhanced by intraseptal histamine infusion. Combined with the previous result that behavior-dependent LTP is mediated by cholinergic septohippocampal neurons, we conclude that the facilitation of basal-dendritic LTP in CA1 during walking was mediated by TMN histaminergic afferents acting on H(1) receptors in the medial septum, which may then enhance cholinergic and noncholinergic inputs to the hippocampus.

  13. 3-Iodothyronamine, a Novel Endogenous Modulator of Transient Receptor Potential Melastatin 8?

    PubMed

    Khajavi, Noushafarin; Mergler, Stefan; Biebermann, Heike

    2017-01-01

    The decarboxylated and deiodinated thyroid hormone (TH) derivative, 3-iodothyronamine (3-T1AM), is suggested to be involved in energy metabolism and thermoregulation. G protein-coupled receptors (GPCRs) are known as the main targets for 3-T1AM; however, transient receptor potential channels (TRPs) were also recently identified as new targets of 3-T1AM. This article reviews the current knowledge of a putative novel role of 3-T1AM in the modulation of TRPs. Specifically, the TRP melastatin 8 (TRPM8) was identified as a target of 3-T1AM in different cell types including neoplastic cells, whereby 3-T1AM significantly increased cytosolic Ca(2+) through TRPM8 activation. Similarly, the β-adrenergic receptor is involved in 3-T1AM-induced Ca(2+) influx. Therefore, it has been suggested that 3-T1AM-induced Ca(2+) mobilization might be due to β-adrenergic receptor/TRPM8 channel interaction, which adds to the complexity of GPCR regulation by TRPs. It has been revealed that TRPM8 activation leads to a decline in TRPV1 activity, which may be of therapeutic benefit in clinical circumstances such as treatment of TRPV1-mediated inflammatory hyperalgesia, colitis, and dry eye syndrome. This review also summarizes the inverse association between changes in TRPM8 and TRPV1 activity after 3-T1AM stimulation. This finding prompted further detailed investigations of the interplay between 3-T1AM and the GPCR/TRPM8 axis and indicated the probability of additional GPCR/TRP constellations that are modulated by this TH derivative.

  14. Acne - a potential skin marker of internal disease.

    PubMed

    Pace, Joseph L

    2015-01-01

    Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder in adult women. Hyperandrogenism is the crux of the pathogenesis of both acne and hirsutism, the most frequent clinical presentations of the syndrome. The chronic anovulation that may occur, often but not always associated with enlarged cystic ovaries, has long been recognized as an important feature of PCOS. In recent years major changes have occurred with regard to PCOS: Although management of the common cutaneous manifestations, mainly acne, hirsutism, alopecia, and acanthosis nigricans, remains strictly within the realm of daily dermatologic practice, the pendulum is shifting toward greater awareness of the longer-term systemic implications of PCOS, with emphasis on the unique opportunity and privileged position of the dermatologist to diagnose this potentially serious problem at an early stage, when effective long-term treatment can be instituted. Patients need to be advised that PCOS cannot be cured but can be controlled. Management should involve a multidisciplinary team with emphasis on lifestyle change, insulin sensitizing agents, androgen blockers, and attention to specific cutaneous manifestations.

  15. Maitotoxin Is a Potential Selective Activator of the Endogenous Transient Receptor Potential Canonical Type 1 Channel in Xenopus laevis Oocytes.

    PubMed

    Flores, Pedro L; Rodríguez, Emma; Zapata, Estrella; Carbó, Roxana; Farías, José María; Martínez, Martín

    2017-06-25

    Maitotoxin (MTX) is the most potent marine toxin known to date. It is responsible for a particular human intoxication syndrome called ciguatera fish poisoning (CFP). Several reports indicate that MTX is an activator of non-selective cation channels (NSCC) in different cell types. The molecular identity of these channels is still an unresolved topic, and it has been proposed that the transient receptor potential (TRP) channels are involved in this effect. In Xenopus laevis oocytes, MTX at picomolar (pM) concentrations induces the activation of NSCC with functional and pharmacological properties that resemble the activity of TRP channels. The purpose of this study was to characterize the molecular identity of the TRP channel involved in the MTX response, using the small interference RNA (siRNA) approach and the two-electrode voltage-clamp technique (TEVC). The injection of a specifically designed siRNA to silence the transient receptor potential canonical type 1 (TRPC1) protein expression abolished the MTX response. MTX had no effect on oocytes, even at doses 20-fold higher compared to cells without injection. Total mRNA and protein levels of TRPC1 were notably diminished. The TRPC4 siRNA did not change the MTX effect, even though it was important to note that the protein level was reduced by the silencing of TRPC4. Our results suggest that MTX could be a selective activator of TRPC1 channels in X. laevis oocytes and a useful pharmacological tool for further studies on these TRP channels.

  16. IDENTIFYING POTENTIAL MARKERS OF THE SUN'S GIANT CONVECTIVE SCALE

    SciTech Connect

    McIntosh, Scott W.; Wang, Xin; Leamon, Robert J.; Scherrer, Philip H.

    2014-04-01

    Line-of-sight magnetograms from the Helioseismic and Magnetic Imager (HMI) of the Solar Dynamics Observatory (SDO) are analyzed using a diagnostic known as the magnetic range of influence (MRoI). The MRoI is a measure of the length over which a photospheric magnetogram is balanced and so its application gives the user a sense of the connective length scales in the outer solar atmosphere. The MRoI maps and histograms inferred from the SDO/HMI magnetograms primarily exhibit four scales: a scale of a few megameters that can be associated with granulation, a scale of a few tens of megameters that can be associated with super-granulation, a scale of many hundreds to thousands of megameters that can be associated with coronal holes and active regions, and a hitherto unnoticed scale that ranges from 100 to 250 Mm. We infer that this final scale is an imprint of the (rotationally driven) giant convective scale on photospheric magnetism. This scale appears in MRoI maps as well-defined, spatially distributed concentrations that we have dubbed ''g-nodes''. Furthermore, using coronal observations from the Atmospheric Imaging Assembly on SDO, we see that the vicinity of these g-nodes appears to be a preferred location for the formation of extreme-ultraviolet (and likely X-Ray) brightpoints. These observations and straightforward diagnostics offer the potential of a near real-time mapping of the Sun's largest convective scale, a scale that possibly reaches to the very bottom of the convective zone.

  17. Maitotoxin Is a Potential Selective Activator of the Endogenous Transient Receptor Potential Canonical Type 1 Channel in Xenopus laevis Oocytes

    PubMed Central

    Flores, Pedro L.; Rodríguez, Emma; Zapata, Estrella; Carbó, Roxana; Farías, José María; Martínez, Martín

    2017-01-01

    Maitotoxin (MTX) is the most potent marine toxin known to date. It is responsible for a particular human intoxication syndrome called ciguatera fish poisoning (CFP). Several reports indicate that MTX is an activator of non-selective cation channels (NSCC) in different cell types. The molecular identity of these channels is still an unresolved topic, and it has been proposed that the transient receptor potential (TRP) channels are involved in this effect. In Xenopus laevis oocytes, MTX at picomolar (pM) concentrations induces the activation of NSCC with functional and pharmacological properties that resemble the activity of TRP channels. The purpose of this study was to characterize the molecular identity of the TRP channel involved in the MTX response, using the small interference RNA (siRNA) approach and the two-electrode voltage-clamp technique (TEVC). The injection of a specifically designed siRNA to silence the transient receptor potential canonical type 1 (TRPC1) protein expression abolished the MTX response. MTX had no effect on oocytes, even at doses 20-fold higher compared to cells without injection. Total mRNA and protein levels of TRPC1 were notably diminished. The TRPC4 siRNA did not change the MTX effect, even though it was important to note that the protein level was reduced by the silencing of TRPC4. Our results suggest that MTX could be a selective activator of TRPC1 channels in X. laevis oocytes and a useful pharmacological tool for further studies on these TRP channels. PMID:28672825

  18. Segmental distribution of some common molecular markers for colorectal cancer (CRC): influencing factors and potential implications.

    PubMed

    Papagiorgis, Petros Christakis

    2016-05-01

    Proximal and distal colorectal cancers (CRCs) are regarded as distinct disease entities, evolving through different genetic pathways and showing multiple clinicopathological and molecular differences. Segmental distribution of some common markers (e.g., KRAS, EGFR, Ki-67, Bcl-2, COX-2) is clinically important, potentially affecting their prognostic or predictive value. However, this distribution is influenced by a variety of factors such as the anatomical overlap of tumorigenic molecular events, associations of some markers with other clinicopathological features (stage and/or grade), and wide methodological variability in markers' assessment. All these factors represent principal influences followed by intratumoral heterogeneity and geographic variation in the frequency of detection of particular markers, whereas the role of other potential influences (e.g., pre-adjuvant treatment, interaction between markers) remains rather unclear. Better understanding and elucidation of the various influences may provide a more accurate picture of the segmental distribution of molecular markers in CRC, potentially allowing the application of a novel patient stratification for treatment, based on particular molecular profiles in combination with tumor location.

  19. The pro-angiogenic cytokine pleiotrophin potentiates cardiomyocyte apoptosis through inhibition of endogenous AKT/PKB activity.

    PubMed

    Li, Jinliang; Wei, Hong; Chesley, Alan; Moon, Chanil; Krawczyk, Melissa; Volkova, Maria; Ziman, Bruce; Margulies, Kenneth B; Talan, Mark; Crow, Michael T; Boheler, Kenneth R

    2007-11-30

    Pleiotrophin is a development-regulated cytokine and growth factor that can promote angiogenesis, cell proliferation, or differentiation, and it has been reported to have neovasculogenic effects in damaged heart. Developmentally, it is prominently expressed in fetal and neonatal hearts, but it is minimally expressed in normal adult heart. Conversely, we show in a rat model of myocardial infarction and in human dilated cardiomyopathy that pleiotrophin is markedly up-regulated. To elucidate the effects of pleiotrophin on cardiac contractile cells, we employed primary cultures of rat neonatal and adult cardiomyocytes. We show that pleiotrophin is released from cardiomyocytes in vitro in response to hypoxia and that the addition of recombinant pleiotrophin promotes caspase-mediated genomic DNA fragmentation in a dose- and time-dependent manner. Functionally, it potentiates the apoptotic response of neonatal cardiomyocytes to hypoxic stress and to ultraviolet irradiation and of adult cardiomyocytes to hypoxia-reoxygenation. Moreover, UV-induced apoptosis in neonatal cardiomyocytes can be partially inhibited by small interfering RNA-mediated knockdown of endogenous pleiotrophin. Mechanistically, pleiotrophin antagonizes IGF-1 associated Ser-473 phosphorylation of AKT/PKB, and it concomitantly decreases both BAD and GSK3beta phosphorylation. Adenoviral expression of constitutively active AKT and lithium chloride-mediated inhibition of GSK3beta reduce the potentiated programmed cell death elicited by pleiotrophin. These latter data indicate that pleiotrophin potentiates cardiomyocyte cell death, at least partially, through inhibition of AKT signaling. In conclusion, we have uncovered a novel function for pleiotrophin on heart cells following injury. It fosters cardiomyocyte programmed cell death in response to pro-apoptotic stress, which may be critical to myocardial injury repair.

  20. The routine determination of the endogenous thrombin potential, first results in different forms of hyper- and hypocoagulability.

    PubMed

    Wielders, S; Mukherjee, M; Michiels, J; Rijkers, D T; Cambus, J P; Knebel, R W; Kakkar, V; Hemker, H C; Béguin, S

    1997-04-01

    The area under the thrombin generation curve (the endogenous thrombin potential; ETP) has been proposed as a parameter for plasma-based hypercoagulability and to monitor anticoagulant treatment. We present an ETP assay for the routine laboratory using a centrifugal analyser. Throughput is 30 samples/h, within and between run imprecision is 4-5.6%. Suitable substrates were developed for the ranges of 10-500% and 2-100% of normal. Independent of tissue factor concentration (if > 4 pM), the normal value of the extrinsic ETP is 384.8 +/- 51.7 nM.min. The intrinsic ETP, triggered by ellagic acid, is 414 +/- 41 nM.min. The ETP is decreased to 15 and 35% of normal by oral anticoagulation (INR 2.5-4.0) and by heparin administration (APTT 1.5-2.5 x control). The ETP is increased in untreated subjects with congenital antithrombin deficiency and in women using oral contraceptives. In deep vein thrombosis (phlebographically confirmed), it is increased by 29.4% (extrinsic) and 53% (intrinsic). In (angiographically assessed) coronary artery disease the increase is by 10% and 17% respectively.

  1. An investigation of the potential of DIP-STR markers for DNA mixture analyses.

    PubMed

    Cereda, G; Biedermann, A; Hall, D; Taroni, F

    2014-07-01

    The genetic characterization of unbalanced mixed stains remains an important area where improvement is imperative. In fact, using the standard tools of forensic DNA profiling (i.e., STR markers), the profile of the minor contributor in mixed DNA stains cannot be successfully detected if its quantitative share of DNA is less than 10% of the mixed trace. This is due to the fact that the major contributor's profile "masks" that of the minor contributor. Besides known remedies to this problem, such as Y-STR analysis, a new compound genetic marker that consists of a Deletion/Insertion Polymorphism (DIP) linked to a Short Tandem Repeat (STR) polymorphism, has recently been developed and proposed. These novel markers are called DIP-STR markers. This paper compares, from a statistical and forensic perspective, the potential usefulness of these novel DIP-STR markers (i) with traditional STR markers in cases of moderately unbalanced mixtures, and (ii) with Y-STR markers in cases of female-male mixtures. This is done through a comparison of the distribution of 100,000 likelihood ratio values obtained using each method on simulated mixtures. This procedure is performed assuming, in turn, the prosecution's and the defence's point of view.

  2. [Endogenous hypertriglyceridemia].

    PubMed

    Tsukamoto, Kazuhisa

    2013-09-01

    Endogenous hypertriglyceridemia, which includes familial hypertriglyceridemia and idiopathic hypertriglyceridemia, is characterized by the increased level of VLDL-triglycerides in the blood. Increased production of VLDL from the liver and the decreased catabolism of VLDL-TG in the vessel, which are also the main metabolic features of insulin resistance, have been proposed to be the causes of endogenous hypertriglyceridemia. Genetic factors responsible for endogenous hypertriglyceridemia have been elucidated in several studies, however, these factors have so far not been clearly identified yet; thus the causes of endogenous hypertriglyceridemia would be polygenic. Recent advances in the genetic analytical methods like genome-wide association study would hopefully unveil the whole pictures of endogenous hypertriglyceridemia.

  3. Exogenous Oct4 in combination with valproic acid increased neural progenitor markers: an approach for enhancing the repair potential of the brain.

    PubMed

    Dehghan, Samaneh; Asadi, Sareh; Hajikaram, Maryam; Soleimani, Masoud; Mowla, Seyed Javad; Fathollahi, Yaghoub; Ahmadiani, Abolhassan; Javan, Mohammad

    2015-02-01

    Attempts are aimed to introduce new approaches toward enhancing the brain's potential for repair in neurodegenerative diseases and traumatic injuries. Here we report an increased expression of pluripotency and progenitor markers within the brain following pretreatment with valproic acid (VPA) and in vivo transfection of inducible Oct4-expressing viral particles. Systemic administration of VPA was performed for one week prior to an intracerebroventricular injection of the Oct4-expressing vector into the right side of the brain. Oct4 expression was induced by doxycycline from day 1 post-transfection for an additional week. Real time-PCR and immunohistofluorescence were used for evaluation of marker expression. Real time-PCR analyses of samples collected from the area of transfection within the injected-lateral ventricle revealed increased expression of some stem cell and progenitor markers, which included endogenous Oct4, Nanog, Klf4, c-Myc, Pax6 and Sox1. Expressions of Oct4, SSEA1 and Nanog were further confirmed by immunohistofluorescence. The increased neural progenitor and pluripotency markers due to Oct4 overexpression did not lead to teratoma formation during a 100day follow-up. Our findings suggest that the application of Oct4 as a reprogramming factor in conjunction with VPA, an epigenetic modifier, might be a potential strategy for increasing the brain's capability to repair itself. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Endogenous thrombin potential following hemostatic therapy with 4-factor prothrombin complex concentrate: a 7-day observational study of trauma patients

    PubMed Central

    2014-01-01

    Introduction Purified prothrombin complex concentrate (PCC) is increasingly used as hemostatic therapy for trauma-induced coagulopathy (TIC). However, the impact of PCC administration on coagulation status among patients with TIC has not been adequately investigated. Methods In this observational, descriptive study, data relating to thrombin generation were obtained from plasma samples gathered prospectively from trauma patients upon emergency room (ER) admission and over the following 7 days. Standard coagulation tests, including measurement of antithrombin (AT) and fibrinogen, were performed. Three groups were investigated: patients receiving no coagulation therapy (NCT group), patients receiving fibrinogen concentrate only (FC group), and patients treated with PCC and fibrinogen concentrate (FC-PCC group). Results The study population (77 patients) was predominantly male (84.4%); mean age was 40 ± 15 years and mean injury severity score was 25.6 ± 12.7. There were no significant differences between the three study groups in thrombin-related parameters upon ER admission. Endogenous thrombin potential (ETP) was significantly higher in the FC-PCC group compared with the NCT group on days 1 to 4 and the FC group on days 1 to 3. AT levels were significantly lower in the FC-PCC group from admission until day 3 (versus FC group) or day 4 (versus NCT group). Fibrinogen increased over time, with no significant between-group differences after ER admission. Despite ETP being higher, prothrombin time and activated partial thromboplastin time were significantly prolonged in the FC-PCC group from admission until day 3 to 4. Conclusions Treatment with PCC increased ETP for several days, and patients receiving PCC therapy had low AT concentrations. These findings imply a potential pro-thrombotic state not reflected by standard coagulation tests. This is probably important given the postoperative acute phase increase in fibrinogen levels, although studies with

  5. Evaluation of endogenous allergens for the safety evaluation of genetically engineered food crops: review of potential risks, test methods, examples and relevance.

    PubMed

    Goodman, Richard E; Panda, Rakhi; Ariyarathna, Harsha

    2013-09-04

    The safety of food produced from genetically engineered (GE) crops is assessed for potential risks of food allergy on the basis of an international consensus guideline outlined by the Codex Alimentarius Commission (2003). The assessment focuses on evaluation of the potential allergenicity of the newly expressed protein(s) as the primary potential risk using a process that markedly limits risks to allergic consumers. However, Codex also recommended evaluating a second concern, potential increases in endogenous allergens of commonly allergenic food crops that might occur due to insertion of the gene. Unfortunately, potential risks and natural variation of endogenous allergens in non-GE varieties are not understood, and risks from increases have not been demonstrated. Because regulatory approvals in some countries are delayed due to increasing demands for measuring endogenous allergens, we present a review of the potential risks of food allergy, risk management for food allergy, and test methods that may be used in these evaluations. We also present new data from our laboratory studies on the variation of the allergenic lipid transfer protein in non-GE maize hybrids as well as data from two studies of endogenous allergen comparisons for three GE soybean lines, their nearest genetic soy lines, and other commercial lines. We conclude that scientifically based limits of acceptable variation cannot been established without an understanding of natural variation in non-GE crops. Furthermore, the risks from increased allergen expression are minimal as the risk management strategy for food allergy is for allergic individuals to avoid consuming any food containing their allergenic source, regardless of the crop variety.

  6. Potential coeliac disease markers and autoimmunity in olmesartan induced enteropathy: A population-based study.

    PubMed

    Esteve, Maria; Temiño, Rocío; Carrasco, Anna; Batista, Lissette; Del Val, Adolfo; Blé, Michel; Santaolaria, Santos; Molina-Infante, Javier; Soriano, Germán; Agudo, Sandra; Zabana, Yamile; Andújar, Xavier; Aceituno, Montserrat; Ribes, Josepa; Madridejos, Rosa; Fernández-Bañares, Fernando

    2016-02-01

    (1) Assess the population-based incidence of severe olmesartan-associated enteropathy. (2) To describe patients of the Spanish registry. (3) Evaluate markers of potential coeliac disease and associated autoimmunity. Crude incidence rates in the area of Terrassa (Catalonia) were calculated. Clinical characteristics of patients in the Spanish registry were collected. Duodenal lymphocyte subpopulations and anti-TG2 IgA deposits were assessed in a subset of patients. Annual incidence rates (2011-2014) ranged from 0 to 22 cases per 10(4) treated patients. Twenty patients were included in the Spanish registry. Nineteen (95%) exhibited villous atrophy and 16 (80%) had severe enteropathy. Lupus-like disease occurred during olmesartan treatment in 3 patients. HLA-DQ2/DQ8 was positive in 64%. Markers of potential coeliac disease were present in 4 out of 8 patients (positive anti-TG2 deposits and/or increased CD3+gammadelta+ intraepithelial lymphocytes and reduced CD3-). Histopathological changes and clinical manifestations including autoimmune disorders improved after olmesartan discontinuation but not after gluten-free diet, irrespective of the presence or absence of coeliac markers. Incidence of severe olmesartan-associated enteropathy was low. Autoimmune phenomena were present in a subset of cases and reversed after olmesartan removal. A genetic coeliac disease background and the presence of potential coeliac markers might uncover predisposing factors. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  7. The modulatory effect of Moringa oleifera leaf extract on endogenous antioxidant systems and inflammatory markers in an acetaminophen-induced nephrotoxic mice model.

    PubMed

    Karthivashan, Govindarajan; Kura, Aminu Umar; Arulselvan, Palanisamy; Md Isa, Norhaszalina; Fakurazi, Sharida

    2016-01-01

    N-Acetyl-p-Aminophenol (APAP), also known as acetaminophen, is the most commonly used over-the counter analgesic and antipyretic medication. However, its overdose leads to both liver and kidney damage. APAP-induced toxicity is considered as one of the primary causes of acute liver failure; numerous scientific reports have focused majorly on APAP hepatotoxicity. Alternatively, not many works approach APAP nephrotoxicity focusing on both its mechanisms of action and therapeutic exploration. Moringa oleifera (MO) is pervasive in nature, is reported to possess a surplus amount of nutrients, and is enriched with several bioactive candidates including trace elements that act as curatives for various clinical conditions. In this study, we evaluated the nephro-protective potential of MO leaf extract against APAP nephrotoxicity in male Balb/c mice. A single-dose acute oral toxicity design was implemented in this study. Group 2, 3, 4 and 5 received a toxic dose of APAP (400 mg/kg of bw, i.p) and after an hour, these groups were administered with saline (10 mL/kg), silymarin-positive control (100 mg/kg of bw, i.p), MO leaf extract (100 mg/kg of bw, i.p), and MO leaf extract (200 mg/kg bw, i.p) respectively. Group 1 was administered saline (10 mL/kg) during both the sessions. APAP-treated mice exhibited a significant elevation of serum creatinine, blood urea nitrogen, sodium, potassium and chloride levels. A remarkable depletion of antioxidant enzymes such as SOD, CAT and GSH-Px with elevated MDA levels has been observed in APAP treated kidney tissues. They also exhibited a significant rise in pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and decreased anti-inflammatory (IL-10) cytokine level in the kidney tissues. Disorganized glomerulus and dilated tubules with inflammatory cell infiltration were clearly observed in the histology of APAP treated mice kidneys. All these pathological changes were reversed in a dose-dependent manner after MO leaf extract treatment

  8. The modulatory effect of Moringa oleifera leaf extract on endogenous antioxidant systems and inflammatory markers in an acetaminophen-induced nephrotoxic mice model

    PubMed Central

    Karthivashan, Govindarajan; Kura, Aminu Umar; Arulselvan, Palanisamy; Md. Isa, Norhaszalina

    2016-01-01

    N-Acetyl-p-Aminophenol (APAP), also known as acetaminophen, is the most commonly used over-the counter analgesic and antipyretic medication. However, its overdose leads to both liver and kidney damage. APAP-induced toxicity is considered as one of the primary causes of acute liver failure; numerous scientific reports have focused majorly on APAP hepatotoxicity. Alternatively, not many works approach APAP nephrotoxicity focusing on both its mechanisms of action and therapeutic exploration. Moringa oleifera (MO) is pervasive in nature, is reported to possess a surplus amount of nutrients, and is enriched with several bioactive candidates including trace elements that act as curatives for various clinical conditions. In this study, we evaluated the nephro-protective potential of MO leaf extract against APAP nephrotoxicity in male Balb/c mice. A single-dose acute oral toxicity design was implemented in this study. Group 2, 3, 4 and 5 received a toxic dose of APAP (400 mg/kg of bw, i.p) and after an hour, these groups were administered with saline (10 mL/kg), silymarin—positive control (100 mg/kg of bw, i.p), MO leaf extract (100 mg/kg of bw, i.p), and MO leaf extract (200 mg/kg bw, i.p) respectively. Group 1 was administered saline (10 mL/kg) during both the sessions. APAP-treated mice exhibited a significant elevation of serum creatinine, blood urea nitrogen, sodium, potassium and chloride levels. A remarkable depletion of antioxidant enzymes such as SOD, CAT and GSH-Px with elevated MDA levels has been observed in APAP treated kidney tissues. They also exhibited a significant rise in pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and decreased anti-inflammatory (IL-10) cytokine level in the kidney tissues. Disorganized glomerulus and dilated tubules with inflammatory cell infiltration were clearly observed in the histology of APAP treated mice kidneys. All these pathological changes were reversed in a dose-dependent manner after MO leaf extract treatment

  9. Characterization of phenotype markers and neuronotoxic potential of polarised primary microglia in vitro

    PubMed Central

    Chhor, Vibol; Le Charpentier, Tifenn; Lebon, Sophie; Oré, Marie-Virgine; Celador, Idoia Lara; Josserand, Julien; Degos, Vincent; Jacotot, Etienne; Hagberg, Henrik; Sävman, Karin; Mallard, Carina; Gressens, Pierre; Fleiss, Bobbi

    2013-01-01

    Microglia mediate multiple facets of neuroinflammation, including cytotoxicity, repair, regeneration, and immunosuppression due to their ability to acquire diverse activation states, or phenotypes. Modulation of microglial phenotype is an appealing neurotherapeutic strategy but a comprehensive study of classical and more novel microglial phenotypic markers in vitro is lacking. The aim of this study was to outline the temporal expression of a battery of phenotype markers from polarised microglia to generate an in vitro tool for screening the immunomodulatory potential of novel compounds. We characterised expression of thirty-one macrophage/microglial phenotype markers in primary microglia over time (4, 12, 36, and 72 h), using RT-qPCR or multiplex protein assay. Firstly, we selected Interleukin-4 (IL-4) and lipopolysaccharide (LPS) as the strongest M1–M2 polarising stimuli, from six stimuli tested. At each time point, markers useful to identify that microglia were M1 included iNOS, Cox-2 and IL-6 and a loss of M2a markers. Markers useful for quantifying M2b-immunomodulatory microglia included, increased IL-1RA and SOCS3 and for M2a-repair and regeneration, included increased arginase-1, and a loss of the M1 and M2b markers were discriminatory. Additional markers were regulated at fewer time points, but are still likely important to monitor when assessing the immunomodulatory potential of novel therapies. Further, to facilitate identification of how novel immunomodulatory treatments alter the functional affects of microglia, we characterised how the soluble products from polarised microglia affected the type and rate of neuronal death; M1/2b induced increasing and M2a-induced decreasing neuronal loss. We also assessed any effects of prior activation state, to provide a way to identify how a novel compound may alter phenotype depending on the stage of injury/insult progression. We identified generally that a prior M1/2b reduced the ability of microglia to switch to

  10. Human gut endogenous proteins as a potential source of angiotensin-I-converting enzyme (ACE-I)-, renin inhibitory and antioxidant peptides.

    PubMed

    Dave, Lakshmi A; Hayes, Maria; Montoya, Carlos A; Rutherfurd, Shane M; Moughan, Paul J

    2016-02-01

    It is well known that endogenous bioactive proteins and peptides play a substantial role in the body's first line of immunological defence, immune-regulation and normal body functioning. Further, the peptides derived from the luminal digestion of proteins are also important for body function. For example, within the peptide database BIOPEP (http://www.uwm.edu.pl/biochemia/index.php/en/biopep) 12 endogenous antimicrobial and 64 angiotensin-I-converting enzyme (ACE-I) inhibitory peptides derived from human milk and plasma proteins are listed. The antimicrobial peptide database (http://aps.unmc.edu/AP/main.php) lists over 111 human host-defence peptides. Several endogenous proteins are secreted in the gut and are subject to the same gastrointestinal digestion processes as food proteins derived from the diet. The human gut endogenous proteins (GEP) include mucins, serum albumin, digestive enzymes, hormones, and proteins from sloughed off epithelial cells and gut microbiota, and numerous other secreted proteins. To date, much work has been carried out regarding the health altering effects of food-derived bioactive peptides but little attention has been paid to the possibility that GEP may also be a source of bioactive peptides. In this review, we discuss the potential of GEP to constitute a gut cryptome from which bioactive peptides such as ACE-I inhibitory, renin inhibitory and antioxidant peptides may be derived. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. An efficient method to find potentially universal population genetic markers, applied to metazoans

    PubMed Central

    2010-01-01

    Background Despite the impressive growth of sequence databases, the limited availability of nuclear markers that are sufficiently polymorphic for population genetics and phylogeography and applicable across various phyla restricts many potential studies, particularly in non-model organisms. Numerous introns have invariant positions among kingdoms, providing a potential source for such markers. Unfortunately, most of the few known EPIC (Exon Primed Intron Crossing) loci are restricted to vertebrates or belong to multigenic families. Results In order to develop markers with broad applicability, we designed a bioinformatic approach aimed at avoiding multigenic families while identifying intron positions conserved across metazoan phyla. We developed a program facilitating the identification of EPIC loci which allowed slight variation in intron position. From the Homolens databases we selected 29 gene families which contained 52 promising introns for which we designed 93 primer pairs. PCR tests were performed on several ascidians, echinoderms, bivalves and cnidarians. On average, 24 different introns per genus were amplified in bilaterians. Remarkably, five of the introns successfully amplified in all of the metazoan genera tested (a dozen genera, including cnidarians). The influence of several factors on amplification success was investigated. Success rate was not related to the phylogenetic relatedness of a taxon to the groups that most influenced primer design, showing that these EPIC markers are extremely conserved in animals. Conclusions Our new method now makes it possible to (i) rapidly isolate a set of EPIC markers for any phylum, even outside the animal kingdom, and thus, (ii) compare genetic diversity at potentially homologous polymorphic loci between divergent taxa. PMID:20836842

  12. Ramipril and Losartan Exert a Similar Long-Term Effect upon Markers of Heart Failure, Endogenous Fibrinolysis, and Platelet Aggregation in Survivors of ST-Elevation Myocardial Infarction: A Single Centre Randomized Trial.

    PubMed

    Marinšek, Martin; Sinkovič, Andreja

    2016-01-01

    Blocking the renin-angiotensin-aldosterone system in ST-elevation myocardial infarction (STEMI) patients prevents heart failure and recurrent thrombosis. Our aim was to compare the effects of ramipril and losartan upon the markers of heart failure, endogenous fibrinolysis, and platelet aggregation in STEMI patients over the long term. After primary percutaneous coronary intervention (PPCI), 28 STEMI patients were randomly assigned ramipril and 27 losartan, receiving therapy for six months with dual antiplatelet therapy (DAPT). We measured N-terminal proBNP (NT-proBNP), ejection fraction (EF), plasminogen-activator-inhibitor type 1 (PAI-1), and platelet aggregation by closure times (CT) at the baseline and after six months. Baseline NT-proBNP ≥ 200 pmol/mL was observed in 48.1% of the patients, EF < 55% in 49.1%, and PAI-1 ≥ 3.5 U/mL in 32.7%. Six-month treatment with ramipril or losartan resulted in a similar effect upon PAI-1, NT-proBNP, EF, and CT levels in survivors of STEMI, but in comparison to control group, receiving DAPT alone, ramipril or losartan treatment with DAPT significantly increased mean CT (226.7 ± 80.3 sec versus 158.1 ± 80.3 sec, p < 0.05). Ramipril and losartan exert a similar effect upon markers of heart failure and endogenous fibrinolysis, and, with DAPT, a more efficient antiplatelet effect in long term than DAPT alone.

  13. Evaluation of colon cancer-specific antigen 2 as a potential serum marker for colorectal cancer.

    PubMed

    Leman, Eddy S; Schoen, Robert E; Magheli, Ahmed; Sokoll, Lori J; Chan, Daniel W; Getzenberg, Robert H

    2008-03-01

    A blood test to detect colon cancer at a preventable stage would represent a major advancement. We have previously identified colon cancer-specific markers using focused proteomics analysis of nuclear structural proteins. Two of these markers, colon cancer-specific antigen (CCSA)-3 and CCSA-4, have been developed into blood-based markers that are able to distinguish individuals with colorectal cancer from those without. CCSA-2 is a distinct novel colon cancer marker identified using focused proteomics. Using an indirect ELISA on serum samples obtained from two institutions, we evaluated CCSA-2 as a serum-based colon cancer marker. A total of 111 serum samples from individuals who underwent colonoscopy and were subsequently diagnosed as either being normal or having hyperplastic polyps, nonadvanced adenomas, advanced adenomas, and colorectal cancer were evaluated. A diverse control population that consisted of 125 serum samples was also included in this study. Receiver operating characteristic analyses were used to measure the sensitivity and specificity of CCSA-2. CCSA-2 at a cutoff of 10.8 mug/mL has overall specificity of 78.4% [95% confidence interval (95% CI), 67.3-87.1%] and sensitivity of 97.3% (95% CI, 85.8-99.5%) in separating individuals with advanced adenomas and colorectal cancer from normal, hyperplastic, and nonadvanced adenoma populations. The receiver operating characteristic curve for CCSA-2 has an area under the curve of 0.90 (95% CI, 0.83-0.95). Our initial study shows that CCSA-2 is a potential serum-based marker for colon cancer detection with high sensitivity and specificity.

  14. Plasmodium falciparum kelch 13: a potential molecular marker for tackling artemisinin-resistant malaria parasites.

    PubMed

    Mita, Toshihiro; Tachibana, Shin-Ichiro; Hashimoto, Muneaki; Hirai, Makoto

    2016-01-01

    Although artemisinin combination therapies have been deployed as a first-line treatment for uncomplicated malaria in almost all endemic countries, artemisinin-resistant parasites have emerged and have gradually spread across the Greater Mekong subregions. There is growing concern that the resistant parasites may migrate to or emerge indigenously in sub-Saharan Africa, which might provoke a global increase in malaria-associated morbidity and mortality. Therefore, development of molecular markers that enable identification of artemisinin resistance with high sensitivity is urgently required to combat this issue. In 2014, a potential artemisinin-resistance responsible gene, Plasmodium falciparum kelch13, was discovered. Here, we review the genetic features of P. falciparum kelch13 and discuss its related resistant mechanisms and potential as a molecular marker.

  15. Endogenous prostaglandin E2 potentiates anti-inflammatory phenotype of macrophage through the CREB-C/EBP-β cascade.

    PubMed

    Na, Yi Rang; Jung, Daun; Yoon, Bo Ruem; Lee, Won Woo; Seok, Seung Hyeok

    2015-09-01

    Macrophages have important functions in tissue homeostasis, but the exact mechanisms regarding wide spectrum of macrophage phenotype remain unresolved. In this study, we report that mouse bone marrow derived naïve macrophages produce prostaglandin E2 (PGE2 ) endogenously, resulting in anti-inflammatory gene expression upon differentiation induced by macrophage colony stimulating factor (M-CSF). Cyclooxygenase (COX) inhibition by indomethacin reduced endogenous PGE2 production of macrophages and subsequently reduced arg1, IL10 and Mrc1, YmI and FizzI gene expressions. Of note, PGE2 phosphorylates CREB via EP2 and EP4 receptor ligation, thereby transcriptionally increasing C/EBP-β expression in BALB/c bone marrow derived macrophages. Activated CREB directly binds to the CREB-responsive element of the C/EBP-β promoter, such that PGE2 ultimately reinforces arg1, IL10 and Mrc1 gene expression. Cyclic AMP activator forskolin also phosphorylated CREB and induced the C/EBP-β cascade, but this was completely blocked by the PKA inhibitor, H89. Consequently, M-CSF grown macrophages inhibited T-cell proliferation but the inhibition ability was reduced when the COX is inhibited by indomethacin or macrophage C/EBP-β expression was decreased by siRNA transduction. Our results collectively describe the molecular basis for homeostatic macrophage differentiation by endogenous PGE2 .

  16. Recurrence quantification as potential bio-markers for diagnosis of pre-cancer

    NASA Astrophysics Data System (ADS)

    Mukhopadhyay, Sabyasachi; Pratiher, Sawon; Barman, Ritwik; Pratiher, Souvik; Pradhan, Asima; Ghosh, Nirmalya; Panigrahi, Prasanta K.

    2017-03-01

    In this paper, the spectroscopy signals have been analyzed in recurrence plots (RP), and extract recurrence quantification analysis (RQA) parameters from the RP in order to classify the tissues into normal and different precancerous grades. Three RQA parameters have been quantified in order to extract the important features in the spectroscopy data. These features have been fed to different classifiers for classification. Simulation results validate the efficacy of the recurrence quantification as potential bio-markers for diagnosis of pre-cancer.

  17. MMP13 is potentially a new tumor marker for breast cancer diagnosis.

    PubMed

    Chang, Hui-Jen; Yang, Ming-Je; Yang, Yu-Hsiang; Hou, Ming-Feng; Hsueh, Er-Jung; Lin, Shiu-Ru

    2009-11-01

    Within the past decade, the incidence of breast cancer in Taiwan has been rising year after year. Breast cancer is the first most prevalent cancer and the fourth leading cause of cancer-related deaths among women in Taiwan. The early stage of breast cancer not only have a wider range of therapeutic options, but also obtain a higher success rate of therapy than those with advanced breast cancer. A test for tumor markers is the most convenient method to screen for breast cancer. However, the tumor markers currently available for breast cancer detection include carcinoembryonic antigen (CEA), carbohydrate antigen 15.3 (CA15.3), and carbohydrate antigen 27.29 (CA27.29) exhibited certain limitations. Poor sensitivity and specificity greatly limits the diagnostic accuracy of these markers. This study aims to identify potential tumor markers for breast cancer. At first, we analyzed genes expression in infiltrating lobular carcinoma, metaplastic carcinoma, and infiltrating ductal carcinoma of paired specimens (tumor and normal tissue) from breast cancer patients using microarray technology. We selected 371 overexpressed genes in all of the three cell type. In advanced breast cancer tissue, we detected four genes MMP13, CAMP, COL10A1 and FLJ25416 from 25 overexpressed genes which encoded secretion protein more specifically for breast cancer than other genes. After validation with 15 pairs of breast cancer tissue and paired to normal adjacent tissues by membrane array and quantitative RT-PCR, we found MMP13 was 100% overexpressed and confirmed to be a secreted protein by Western blot analysis of the cell culture medium. The expression level of MMP13 was also measured by immunohistochemical staining. We suggest that MMP13 is a highly overexpressed secretion protein in breast cancer tissue. It has potential to be a new tumor marker for breast cancer diagnosis.

  18. Sperm midpiece apoptotic markers: impact on fertilizing potential in in vitro fertilization and intracytoplasmic sperm injection.

    PubMed

    Talarczyk-Desole, Joanna; Kotwicka, Małgorzata; Jendraszak, Magdalena; Pawelczyk, Leszek; Murawski, Marek; Jędrzejczak, Piotr

    2016-04-01

    The aim of this study was to investigate the relationship between apoptotic markers present in human spermatozoa, namely phosphatidylserine translocation (PST) from the inner to the outer layer of the cytomembrane and the active form of caspase-3 (c3) versus the fertilizing potential of male gametes in conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) models. A total of 116 male patients treated with their partners for infertility underwent basic semen analysis and an assessment of the presence of PST and the active c3 in sperm using flow cytometry. Forty patients underwent IVF, group A, while 76 patients underwent ICSI, group B. The fertilizing potential of the gametes was measured as the percentage of oocytes with pronuclei present after either procedure. PST and active c3 were identified in vital gametes, mainly in the midpiece area. Concentration, motility, morphology, and viability of spermatozoa strongly negatively correlated with both markers. In group A, a negative correlation between both markers and the success rate of conventional IVF was observed (r = -0.4, p = 0.04 for PST; r = -0.4, p = 0.02 for active c3, respectively). In group B, the success rate of ICSI did not correlate with either marker (r = -0.2, p = 0.85 for PST and r = 0.1, p = 0.51 for active c3). The two apoptotic markers localized in the sperm midpiece area may affect their function not only by decreasing basic andrologic parameters but also by reducing the probability of conception. Therefore, analysis of PST and active c3 in the sperm of patients undergoing infertility treatment should be recommended.

  19. Comprehensive urinary metabolomic profiling and identification of potential noninvasive marker for idiopathic Parkinson’s disease

    PubMed Central

    Luan, Hemi; Liu, Liang-Feng; Tang, Zhi; Zhang, Manwen; Chua, Ka-Kit; Song, Ju-Xian; Mok, Vincent C.T.; Li, Min; Cai, Zongwei

    2015-01-01

    Urine metabolic phenotyping has been associated with the development of Parkinson’s disease (PD). However, few studies using a comprehensive metabolomics approach have investigated the correlation between changes in the urinary markers and the progression of clinical symptoms in PD. A comprehensive metabolomic study with robust quality control procedures was performed using gas chromatography - mass spectrometry (GC - MS) and liquid chromatography - mass spectrometry (LC - MS) to characterize the urinary metabolic phenotypes of idiopathic PD patients at three stages (early, middle and advanced) and normal control subjects, with the aim of discovering potential urinary metabolite markers for the diagnosis of idiopathic PD. Both GC-MS and LC-MS metabolic profiles of idiopathic PD patients differed significantly from those of normal control subjects. 18 differentially expressed metabolites were identified as constituting a unique metabolic marker associated with the progression of idiopathic PD. Related metabolic pathway variations were observed in branched chain amino acid metabolism, glycine derivation, steroid hormone biosynthesis, tryptophan metabolism, and phenylalanine metabolism. Comprehensive, successive metabolomic profiling revealed changes in the urinary markers associated with progression of idiopathic PD. This profiling relies on noninvasive sampling, and is complementary to existing clinical modalities. PMID:26365159

  20. Discovery of potential DNA methylation markers for forensic tissue identification using bisulphite pyrosequencing.

    PubMed

    Vidaki, Athina; Giangasparo, Federica; Syndercombe Court, Denise

    2016-10-01

    The presence of specific body fluids at crime scenes could be linked with particular types of crime, therefore attributing a DNA profile to a specific tissue could increase the evidential significance of a match with a suspect. Current methodologies such as tissue-specific mRNA profiling are useful but drawbacks include low tissue specificity and applicability to degraded samples. In this study, the potential of 11 tissue-specific differentially methylated regions, initially identified following large-scale methylation analysis of whole blood, buccal cells and sperm, was explored in order to identify markers for blood, saliva and semen. Bisulphite pyrosequencing analysis supported previous findings, but tissue-specific differentially methylated regions for blood and buccal cells did not show enough specificity to be proposed as markers for blood and saliva, respectively. For some CpGs, a large inter-individual variation in methylation levels was also observed. Two of the semen markers (cg04382920 and cg11768416) were used for further validation on a large set of stains. These two semen-specific assays showed high sensitivity (as low as 50 pg) and stability. Future experiments will shed light on the usefulness of these markers in forensic casework. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Reference ranges for urinary concentrations and ratios of endogenous steroids, which can be used as markers for steroid misuse, in a Caucasian population of athletes.

    PubMed

    Van Renterghem, Pieter; Van Eenoo, Peter; Geyer, Hans; Schänzer, Wilhelm; Delbeke, Frans T

    2010-02-01

    The detection of misuse with naturally occurring steroids is a great challenge for doping control laboratories. Intake of natural anabolic steroids alters the steroid profile. Thus, screening for exogenous use of these steroids can be established by monitoring a range of endogenous steroids, which constitute the steroid profile, and evaluate their concentrations and ratios against reference ranges. Elevated values of the steroid profile constitute an atypical finding after which a confirmatory IRMS procedure is needed to unequivocally establish the exogenous origin of a natural steroid. However, the large inter-individual differences in urinary steroid concentrations and the recent availability of a whole range of natural steroids (e.g. dehydroepiandrosterone and androstenedione) which each exert a different effect on the monitored parameters in doping control complicate the interpretation of the current steroid profile. The screening of an extended steroid profile can provide additional parameters to support the atypical findings and can give specific information upon the steroids which have been administered. The natural concentrations of 29 endogenous steroids and 11 ratios in a predominantly Caucasian population of athletes were determined. The upper reference values at 97.5%, 99% and 99.9% levels were assessed for male (n=2027) and female (n=1004) populations. Monitoring minor metabolites and evaluation of concentration ratios with respect to their natural abundances could improve the interpretation of the steroid profile in doping analysis.

  2. Molecular Markers of Diabetic Retinopathy: Potential Screening Tool of the Future?

    PubMed Central

    Pusparajah, Priyia; Lee, Learn-Han; Abdul Kadir, Khalid

    2016-01-01

    Diabetic retinopathy (DR) is among the leading causes of new onset blindness in adults. Effective treatment may delay the onset and progression of this disease provided it is diagnosed early. At present retinopathy can only be diagnosed via formal examination of the eye by a trained specialist, which limits the population that can be effectively screened. An easily accessible, reliable screening biomarker of diabetic retinopathy would be of tremendous benefit in detecting the population in need of further assessment and treatment. This review highlights specific biomarkers that show promise as screening markers to detect early diabetic retinopathy or even to detect patients at increased risk of DR at the time of diagnosis of diabetes. The pathobiology of DR is complex and multifactorial giving rise to a wide array of potential biomarkers. This review provides an overview of these pathways and looks at older markers such as advanced glycation end products (AGEs), inflammatory markers, vascular endothelial growth factor (VEGF) as well as other newer proteins with a role in the pathogenesis of DR including neuroprotective factors such as brain derived neurotrophic factor (BDNF) and Pigment Epithelium Derived Factor (PEDF); SA100A12, pentraxin 3, brain natriuretic peptide, apelin 3, and chemerin as well as various metabolites such as lipoprotein A, folate, and homocysteine. We also consider the possible role of proteins identified through proteomics work whose levels are altered in the sera of patients with DR as screening markers though their role in pathophysiology remains to be characterized. The role of microRNA as a promising new screening marker is also discussed. PMID:27313539

  3. Molecular Markers of Diabetic Retinopathy: Potential Screening Tool of the Future?

    PubMed

    Pusparajah, Priyia; Lee, Learn-Han; Abdul Kadir, Khalid

    2016-01-01

    Diabetic retinopathy (DR) is among the leading causes of new onset blindness in adults. Effective treatment may delay the onset and progression of this disease provided it is diagnosed early. At present retinopathy can only be diagnosed via formal examination of the eye by a trained specialist, which limits the population that can be effectively screened. An easily accessible, reliable screening biomarker of diabetic retinopathy would be of tremendous benefit in detecting the population in need of further assessment and treatment. This review highlights specific biomarkers that show promise as screening markers to detect early diabetic retinopathy or even to detect patients at increased risk of DR at the time of diagnosis of diabetes. The pathobiology of DR is complex and multifactorial giving rise to a wide array of potential biomarkers. This review provides an overview of these pathways and looks at older markers such as advanced glycation end products (AGEs), inflammatory markers, vascular endothelial growth factor (VEGF) as well as other newer proteins with a role in the pathogenesis of DR including neuroprotective factors such as brain derived neurotrophic factor (BDNF) and Pigment Epithelium Derived Factor (PEDF); SA100A12, pentraxin 3, brain natriuretic peptide, apelin 3, and chemerin as well as various metabolites such as lipoprotein A, folate, and homocysteine. We also consider the possible role of proteins identified through proteomics work whose levels are altered in the sera of patients with DR as screening markers though their role in pathophysiology remains to be characterized. The role of microRNA as a promising new screening marker is also discussed.

  4. Cell-free methylation markers with diagnostic and prognostic potential in hepatocellular carcinoma

    PubMed Central

    Lu, Chang-Yi; Chen, Shih-Ya; Peng, Hui-Ling; Kan, Pu-Yeh; Chang, Wan-Chi; Yen, Chia-Jui

    2017-01-01

    Hepatocellular carcinoma (HCC) is a highly malignant tumor with poor prognosis and high mortality. There is a dearth of effective early diagnostic tools, so liver resection surgery and liver transplantation are the only effective medical treatments. The most commonly used marker for HCC detection is serum alpha fetoprotein (AFP), which has low sensitivity and specificity. Because aberrant DNA methylation of genes and miRNAs occurs early in most cancers, we explored whether circulating methylation markers could be promising clinical tools for HCC diagnosis. Using a whole-genome approach, we identified many hyper-methylated miRNAs in HCC. Furthermore, three abnormally methylated genes and one miRNA were combined to establish a methylation predictive model and tested for its diagnostic and prognostic potential in HCC. Using plasma samples, the predictive model exhibited high sensitivity and specificity (> 80%) for HBV-related HCC. Most importantly, nearly 75% of patients who could not be diagnosed with AFP at 20 ng/mL were detected by this model. Further, the predictive model exhibited an exceedingly high ability to predict 5-year overall survival in HCC patients. These data demonstrate the high diagnostic and prognostic potential of methylation markers in the plasma of HCC patients. PMID:28031532

  5. Biomonitoring results and cytogenetic markers among harbour workers with potential exposure to river silt aerosols

    PubMed Central

    Wegner, R; Radon, K; Heinrich-Ramm, R; Seemann, B; Riess, A; Koops, F; Poschadel, B; Szadkowski, D

    2004-01-01

    Background: Workers on dredgers and lighters on rivers are potentially exposed to a variety of substances. Aims: To determine the internal load of heavy metals and arsenic as well as levels of cytogenetic markers in workers exposed to river silt aerosols. Methods: One hundred exposed workers were examined up to eight times within three years. Additionally, 100 control workers were studied once. Blood samples were analysed for lead, mercury, and cadmium. Additionally, micronuclei frequency and sister chromatid exchange (SCE) rates were determined. Urinary samples were analysed for cadmium, mercury, nickel, chromium, and arsenic. Information on potential confounders, such as smoking habits and consumption of fish were assessed. Results: Apart from some increased concentrations of mercury in blood (maximum 14.6 µg/l) and arsenic in urine (maximum 356.5 µg/l) all measurements were within reference values. None of the exposure and effect markers were found to be significantly increased in exposed workers compared to non-exposed controls. In multiple linear regression models, mercury levels in blood as well as the concentration of arsenic in urine were strongly related to fish consumption. Cadmium levels in blood as well as urinary cadmium concentrations were strongly related to smoking habits. After adjusting for smoking habits, SCE rates were associated with cadmium levels in blood. Conclusion: Increased exposure levels or enhanced levels of cytogenetic markers were not found in workers exposed to river silt aerosols. However, cadmium exposure in blood was related to SCE frequency. PMID:14985520

  6. Biomonitoring results and cytogenetic markers among harbour workers with potential exposure to river silt aerosols.

    PubMed

    Wegner, R; Radon, K; Heinrich-Ramm, R; Seemann, B; Riess, A; Koops, F; Poschadel, B; Szadkowski, D

    2004-03-01

    Workers on dredgers and lighters on rivers are potentially exposed to a variety of substances. To determine the internal load of heavy metals and arsenic as well as levels of cytogenetic markers in workers exposed to river silt aerosols. One hundred exposed workers were examined up to eight times within three years. Additionally, 100 control workers were studied once. Blood samples were analysed for lead, mercury, and cadmium. Additionally, micronuclei frequency and sister chromatid exchange (SCE) rates were determined. Urinary samples were analysed for cadmium, mercury, nickel, chromium, and arsenic. Information on potential confounders, such as smoking habits and consumption of fish were assessed. Apart from some increased concentrations of mercury in blood (maximum 14.6 microg/l) and arsenic in urine (maximum 356.5 microg/l) all measurements were within reference values. None of the exposure and effect markers were found to be significantly increased in exposed workers compared to non-exposed controls. In multiple linear regression models, mercury levels in blood as well as the concentration of arsenic in urine were strongly related to fish consumption. Cadmium levels in blood as well as urinary cadmium concentrations were strongly related to smoking habits. After adjusting for smoking habits, SCE rates were associated with cadmium levels in blood. Increased exposure levels or enhanced levels of cytogenetic markers were not found in workers exposed to river silt aerosols. However, cadmium exposure in blood was related to SCE frequency.

  7. Chromogranin A – unspecific neuroendocrine marker. Clinical utility and potential diagnostic pitfalls

    PubMed Central

    Czarnywojtek, Agata; Fischbach, Jakub; Bączyk, Maciej; Ziemnicka, Katarzyna; Wrotkowska, Elżbieta; Gryczyńska, Maria; Ruchała, Marek

    2016-01-01

    Chromogranin A, despite a number of limitations, is still the most valuable marker of neuroendocrine tumors (NETs). Granins belong to the family of acidic proteins that constitute a major component of secretory granules of various endocrine and neuroendocrine cells, which are components of both the classical endocrine glands and the diffuse neuroendocrine system. These cells are a potential source of transformation into neuroendocrine tumors. The awareness of potential causes influencing the false results of its concentrations simplifies diagnosis and treatment. One of the disadvantages of this marker is its non-specificity and the existence of a number of pathological processes leading to an increase in its concentration, which often results in confusion and diagnostic difficulties. The molecular structure is characterized by a number of sites susceptible to the proteolytic activity of enzymes, resulting in the formation of a number of biologically active peptides. Presumably they act as precursors of active proteins. Chromogranin expression correlates with the amount of secretory vesicles in neuroendocrine cells. The peptide chain during biochemical changes becomes a precursor of biologically active proteins with a wide range of activities. There are a number of commercially available kits for the determination of chromogranin A, which differ in methodology. We present the evaluation of chromogranin A as a marker of neuroendocrine tumors in clinical practice and the possible factors that may affect the outcome of its concentration. PMID:26925113

  8. Analysis of potential markers for detection of submicroscopic lymph node metastases in breast cancer

    PubMed Central

    Merrie, A E H; Yun, K; Gunn, J; Phillips, L V; McCall, J L

    1999-01-01

    We have developed sensitive assays for cytokeratin (K) 8, 16, 19, stromelysin 3 (ST3), MUC1 and maspin mRNAs using reverse transcription polymerase chain reaction (RT-PCR) and used these to assess lymph node status in patients undergoing surgery for breast cancer. In addition the RT-PCR assays were tested against lymph nodes from non-cancer patients to determine their specificity. Despite high sensitivity RT-PCR assays for K8, K16, K19, ST3 and maspin were not found to be useful as markers of submicroscopic disease as transcripts of these genes were detected in the great majority of control lymph nodes tested. Expression of MUC1 was also not found to be useful as it was both insensitive and non-specific. The importance of assessing potential markers against an adequately sized control population is demonstrated, as failure to do so can lead to erroneous conclusions. © 1999 Cancer Research Campaign PMID:10471055

  9. Analysis of urinary nucleosides as potential cancer markers determined using LC-MS technique.

    PubMed

    Struck-Lewicka, Wiktoria; Kaliszan, Roman; Markuszewski, Michał Jan

    2014-12-01

    Nucleosides, the RNA metabolites, are well known as potential markers in various types of cancer. They are mainly detected in urine wherein their concentrations were found elevated in cancer patients. In order to determine the nucleosides' profile in urine with satisfactory sensitivity and accuracy, advanced analytical techniques should be applied involving mass spectrometry detection. In this work we overviewed actual possibilities in targeted and untargeted metabolomics studies of nucleosides and their analogues (cis-diol metabolites) using high performance liquid chromatography hyphenated with mass spectrometry detection. We focused on challenges and drawbacks using different types of ion sources and analyzers. The nucleosides' fragmentation patterns were also compared for the sake of their identification in biological samples. As applied analytical techniques allow for the metabolites' determination, statistical approach essential for evaluation of nucleosides as cancer markers was also reviewed. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Characterization of novel markers of senescence and their prognostic potential in cancer.

    PubMed

    Althubiti, M; Lezina, L; Carrera, S; Jukes-Jones, R; Giblett, S M; Antonov, A; Barlev, N; Saldanha, G S; Pritchard, C A; Cain, K; Macip, S

    2014-11-20

    Cellular senescence is a terminal differentiation state that has been proposed to have a role in both tumour suppression and ageing. This view is supported by the fact that accumulation of senescent cells can be observed in response to oncogenic stress as well as a result of normal organismal ageing. Thus, identifying senescent cells in in vivo and in vitro has an important diagnostic and therapeutic potential. The molecular pathways involved in triggering and/or maintaining the senescent phenotype are not fully understood. As a consequence, the markers currently utilized to detect senescent cells are limited and lack specificity. In order to address this issue, we screened for plasma membrane-associated proteins that are preferentially expressed in senescent cells. We identified 107 proteins that could be potential markers of senescence and validated 10 of them (DEP1, NTAL, EBP50, STX4, VAMP3, ARMX3, B2MG, LANCL1, VPS26A and PLD3). We demonstrated that a combination of these proteins can be used to specifically recognize senescent cells in culture and in tissue samples and we developed a straightforward fluorescence-activated cell sorting-based detection approach using two of them (DEP1 and B2MG). Of note, we found that expression of several of these markers correlated with increased survival in different tumours, especially in breast cancer. Thus, our results could facilitate the study of senescence, define potential new effectors and modulators of this cellular mechanism and provide potential diagnostic and prognostic tools to be used clinically.

  11. Concentrations of Pro-Inflammatory Cytokines Are Not Associated with Senescence Marker p16INK4a or Predictive of Intracellular Emtricitabine/Tenofovir Metabolite and Endogenous Nucleotide Exposures in Adults with HIV Infection

    PubMed Central

    Maas, Brian M.; Francis, Owen; Mollan, Katie R.; Lee, Cynthia; Cottrell, Mackenzie L.; Prince, Heather M. A.; Sykes, Craig; Trezza, Christine; Torrice, Chad; White, Nicole; Malone, Stephanie; Hudgens, Michael G.; Sharpless, Norman E.; Dumond, Julie B.

    2016-01-01

    Objectives As the HIV-infected population ages, the role of cellular senescence and inflammation on co-morbid conditions and pharmacotherapy is increasingly of interest. p16INK4a expression, a marker for aging and senescence in T-cells, is associated with lower intracellular concentrations of endogenous nucleotides (EN) and nucleos(t)ide reverse transcriptase inhibitors (NRTIs). This study expands on these findings by determining whether inflammation is contributing to the association of p16INK4a expression with intracellular metabolite (IM) exposure and endogenous nucleotide concentrations. Methods Samples from 73 HIV-infected adults receiving daily tenofovir/emtricitabine (TFV/FTC) with either efavirenz (EFV) or atazanavir/ritonavir (ATV/r) were tested for p16INK4a expression, and plasma cytokine and intracellular drug concentrations. Associations between p16INK4a expression and cytokine concentrations were assessed using maximum likelihood methods, and elastic net regression was applied to assess whether cytokines were predictive of intracellular metabolite/endogenous nucleotide exposures. Results Enrolled participants had a median age of 48 years (range 23–73). There were no significant associations between p16INK4a expression and cytokines. Results of the elastic net regression showed weak relationships between IL-1Ra and FTC-triphosphate and deoxyadenosine triphosphate exposures, and MIP-1β, age and TFV-diphosphate exposures. Conclusions In this clinical evaluation, we found no relationships between p16INK4a expression and cytokines, or cytokines and intracellular nucleotide concentrations. While inflammation is known to play a role in this population, it is not a major contributor to the p16INK4a association with decreased IM/EN exposures in these HIV-infected participants. PMID:28036343

  12. Molecular trophic markers in marine food webs and their potential use for coral ecology.

    PubMed

    Leal, Miguel Costa; Ferrier-Pagès, Christine

    2016-10-01

    Notable advances in ecological genomics have been driven by high-throughput sequencing technology and taxonomically broad sequence repositories that allow us to accurately assess species interactions with great taxonomic resolution. The use of DNA as a marker for ingested food is particularly relevant to address predator-prey interactions and disentangle complex marine food webs. DNA-based methods benefit from reductionist molecular approaches to address ecosystem scale processes, such as community structure and energy flow across trophic levels, among others. Here we review how molecular trophic markers have been used to better understand trophic interactions in the marine environment and their advantages and limitations. We focus on animal groups where research has been focused, such as marine mammals, seabirds, fishes, pelagic invertebrates and benthic invertebrates, and use case studies to illustrate how DNA-based methods unraveled food-web interactions. The potential of molecular trophic markers for disentangling the complex trophic ecology of corals is also discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. The potential utility of telomere-related markers for cancer diagnosis

    PubMed Central

    Heaphy, Christopher M; Meeker, Alan K

    2011-01-01

    Abstract The role telomeres and telomerase play in the initiation and progression of human cancers has been extensively evaluated. Telomeres are nucleoprotein complexes comprising the hexanucleotide DNA repeat sequence, TTAGGG and numerous telomere-associated proteins, including the six member Shelterin complex. The main function of the telomere is to stabilize the ends of the chromosomes. However, through multiple mechanisms, telomeres can become dysfunctional, which may drive genomic instability leading to the development of cancer. The majority of human cancers maintain, or actively lengthen, telomeres through up-regulation of the reverse transcriptase telomerase. Because there are significant differences in telomere length and telomerase activity between malignant and non-malignant tissues, many investigations have assessed the potential to utilize these molecular markers for cancer diagnosis. Here, we critically evaluate whether measurements of telomere lengths and telomerase levels may be clinically utilized as diagnostic markers in solid tumours, with emphasis on breast and prostate cancer as representative examples. Future directions focusing on the direct detection of dysfunctional telomeres are explored. New markers for telomere dysfunction may eventually prove clinically useful. PMID:21352473

  14. Diagnostic potential in prostate cancer of a panel of urinary molecular tumor markers.

    PubMed

    Talesa, Vincenzo N; Antognelli, Cinzia; Del Buono, Chiara; Stracci, Fabrizio; Serva, Maria R; Cottini, Emanuele; Mearini, Ettore

    2009-01-01

    Prostate cancer (PCa) is a heterogeneous, multifactorial and multifocal disease. Therefore, the search for a combination of assays using a panel of tumor markers is fundamental for a more precise and reliable diagnosis. In the present study we investigated the diagnostic value of five different genes, associated with PCa carcinogenesis, encoding for prostate-specific membrane antigen (PSMA), serine protease Hepsin, PCa antigen 3 (PCA3), UDP-N-acetyl-alpha-D-galatosamine transferase (GalNAC-T3) and prostate-specific antigen (PSA). Forty-four patients, with previously untreated, histologically verified PCa and forty-six patients with benign prostatic hyperplasia (BPH) were enrolled in this study. Absolute concentration of the transcript levels of each gene was calculated by quantitative Real-Time PCR analysis in urine sediments of men suffering from PCa or BPH after prostatic massage. The diagnostic value of a concomitant examination of these markers was evaluated by logistic regression analysis. We demonstrated that the diagnostic potential of the combined urinary PSA and PSMA level was significantly better than that of each singularly considered marker, including total serum PSA, the present gold standard test for PCa diagnosis.

  15. Oral keratinocyte stem/progenitor cells: specific markers, molecular signaling pathways and potential uses.

    PubMed

    Calenic, Bogdan; Greabu, Maria; Caruntu, Constantin; Tanase, Cristiana; Battino, Maurizio

    2015-10-01

    Oral keratinocyte stem cells reside in the basal layers of the oral epithelium, representing a minor population of cells with a great potential to self-renew and proliferate over the course of their lifetime. As a result of the potential uses of oral keratinocyte stem cells in regenerative medicine and the key roles they play in tissue homeostasis, inflammatory conditions, wound healing and tumor initiation and progression, intense scientific efforts are currently being undertaken to identify, separate and reprogram these cells. Although currently there is no specific marker that can characterize and isolate oral keratinocyte stem cells, several suggestions have been made. Thus, different stem/progenitor-cell subpopulations have been categorized based on combinations of positive and/or negative membrane-surface markers, which include integrins, clusters of differentiation and cytokeratins. Important advances have also been made in understanding the molecular pathways that govern processes such as self-renewal, differentiation, proliferation, wound healing and programmed cell death. A thorough understanding of stem-cell biology and the molecular players that govern cellular fate is paramount in the quest for using stem-cell-derived therapies in the treatment of various oral pathologies. The current review focuses on recent advances in understanding the molecular signaling pathways coordinating the behavior of these cells and in identifying suitable markers used for their isolation and characterization. Special emphasis will also be placed on the roles played by oral keratinocyte stem and progenitor cells in normal and diseased oral tissues and on their potential uses in the fields of general medicine and dentistry.

  16. Ramipril and Losartan Exert a Similar Long-Term Effect upon Markers of Heart Failure, Endogenous Fibrinolysis, and Platelet Aggregation in Survivors of ST-Elevation Myocardial Infarction: A Single Centre Randomized Trial

    PubMed Central

    Marinšek, Martin; Sinkovič, Andreja

    2016-01-01

    Introduction. Blocking the renin-angiotensin-aldosterone system in ST-elevation myocardial infarction (STEMI) patients prevents heart failure and recurrent thrombosis. Our aim was to compare the effects of ramipril and losartan upon the markers of heart failure, endogenous fibrinolysis, and platelet aggregation in STEMI patients over the long term. Methods. After primary percutaneous coronary intervention (PPCI), 28 STEMI patients were randomly assigned ramipril and 27 losartan, receiving therapy for six months with dual antiplatelet therapy (DAPT). We measured N-terminal proBNP (NT-proBNP), ejection fraction (EF), plasminogen-activator-inhibitor type 1 (PAI-1), and platelet aggregation by closure times (CT) at the baseline and after six months. Results. Baseline NT-proBNP ≥ 200 pmol/mL was observed in 48.1% of the patients, EF < 55% in 49.1%, and PAI-1 ≥ 3.5 U/mL in 32.7%. Six-month treatment with ramipril or losartan resulted in a similar effect upon PAI-1, NT-proBNP, EF, and CT levels in survivors of STEMI, but in comparison to control group, receiving DAPT alone, ramipril or losartan treatment with DAPT significantly increased mean CT (226.7 ± 80.3 sec versus 158.1 ± 80.3 sec, p < 0.05). Conclusions. Ramipril and losartan exert a similar effect upon markers of heart failure and endogenous fibrinolysis, and, with DAPT, a more efficient antiplatelet effect in long term than DAPT alone. PMID:27064499

  17. Chondrogenic potential of subpopulations of cells expressing mesenchymal stem cell markers derived from human synovial membranes.

    PubMed

    Arufe, M C; De la Fuente, A; Fuentes, I; de Toro, F J; Blanco, F J

    2010-11-01

    In this study we analyzed the chondrogenic potential of subpopulations of mesenchymal stem cells (MSCs) derived from human synovial membranes enriched for CD73, CD106, and CD271 markers. Subpopulations of human synovial membrane MSCs enriched for CD73, CD106, and CD271 markers were isolated using a cytometry sorter and characterized by flow cytometry for MSC markers. The expression of Sox9, Nanog, and Runx2 genes by these cells was measured by reverse transcriptase-polymerase chain reaction. The chondrogenesis of each subpopulation was assessed by culturing the cells in a defined medium to produce spontaneous spheroid formation and differentiation towards chondrocyte-like cells. The examination of the spheroids by histological and immunohistochemical analyses for collagen type II (COL2), aggrecan, collagen type I (COL1), metalloprotease 13 (MMP13), and collagen type X (COLX) levels were performed to assess their chondrogenesis capacity. The adipogenesis and osteogenesis potential of each subpopulation was determined using commercial media; the resulting cells were stained with oil red O or red alizarin to test the degree of differentiation. The subpopulations had different profiles of cells positive for the MSC markers CD44, CD69, CD73, CD90, and CD105 and showed different expression levels of the genes Sox9, Nanog, and Runx2 involved in chondrogenesis, undifferentiation, and osteoblastogenesis, respectively. Immunohistochemical analysis demonstrated that COL1, COL2, COLX, MMP13, and aggrecan were expressed in the spheroids as soon as 14 days of culture. The CD271(+) subpopulation expressed the highest levels of COL2 staining compared to the other subpopulations. CD105 and Runx2 were shown by immunohistochemistry and genetic analysis to have significantly higher expression CD271(+) subpopulation than the other subpopulations. Spheroids formed from CD271-enriched and CD73-enriched MSCs from normal human synovial membranes mimic the native cartilage extracellular

  18. Soluble Fas Ligand as a Potential Marker of Severity of Dengue Infection

    PubMed Central

    Zain, Nurfadly; Putra, Suhartono Taat; Zein, Umar; Hariman, Herman

    2017-01-01

    Background The apoptosis of microvascular endothelial cells causes plasma leakage in dengue haemorrhagic fever patients. The soluble Fas ligand is a protein with molecular weight of 40 kDa that acts as a mediator of apoptosis. This study aimed to prove whether soluble Fas ligand can be used as a potential marker to predict the severity of dengue infection by comparing the soluble Fas ligand levels in dengue fever (DF) and dengue haemorrhagic fever (DHF) patients early in the course of illness. Method This was a prospective study. It included 42 dengue patients (22 DF patients and 20 DHF patients) and 20 healthy people as a control group. The soluble Fas ligand was measured by the enzyme-linked immunosorbent assay (ELISA). Result Soluble Fas ligand was increased significantly (P < 0.001) in DHF patients (median = 130.19, IQR = 36.26) compared to DF patients (median = 104.73, IQR = 53.94) and the control group (median = 87.16, IQR = 24.91). Conclusion Soluble Fas ligand can be used as a potential marker to predict the severity of dengue infection in the early course of the illness. However, a larger sample size and further objective studies are needed to confirm these findings. PMID:28894401

  19. Soluble Fas Ligand as a Potential Marker of Severity of Dengue Infection.

    PubMed

    Zain, Nurfadly; Putra, Suhartono Taat; Zein, Umar; Hariman, Herman

    2017-03-01

    The apoptosis of microvascular endothelial cells causes plasma leakage in dengue haemorrhagic fever patients. The soluble Fas ligand is a protein with molecular weight of 40 kDa that acts as a mediator of apoptosis. This study aimed to prove whether soluble Fas ligand can be used as a potential marker to predict the severity of dengue infection by comparing the soluble Fas ligand levels in dengue fever (DF) and dengue haemorrhagic fever (DHF) patients early in the course of illness. This was a prospective study. It included 42 dengue patients (22 DF patients and 20 DHF patients) and 20 healthy people as a control group. The soluble Fas ligand was measured by the enzyme-linked immunosorbent assay (ELISA). Soluble Fas ligand was increased significantly (P < 0.001) in DHF patients (median = 130.19, IQR = 36.26) compared to DF patients (median = 104.73, IQR = 53.94) and the control group (median = 87.16, IQR = 24.91). Soluble Fas ligand can be used as a potential marker to predict the severity of dengue infection in the early course of the illness. However, a larger sample size and further objective studies are needed to confirm these findings.

  20. ABCG2 is a selectable marker for enhanced multilineage differentiation potential in periodontal ligament stem cells.

    PubMed

    Szepesi, Áron; Matula, Zsolt; Szigeti, Anna; Várady, György; Szabó, Gyula; Uher, Ferenc; Sarkadi, Balázs; Német, Katalin

    2015-01-15

    Periodontal ligament stem cells (PDLSCs) provide an important source for tissue regeneration and may become especially useful in the formation of osteogenic seeds. PDLSCs can be cultured, expanded, and differentiated in vitro; thus, they may be applied in the long-term treatment of the defects in the dental regions. Here we studied numerous potential markers allowing the selection of human PDLSCs with a maximum differentiation potential. We followed the expression of the ATP-binding cassette subfamily G member 2 (ABCG2) membrane transporter protein and isolated ABCG2-expressing cells by using a monoclonal antibody, recognizing the transporter at the cell surface in intact cells. The expression of the ABCG2 protein, corresponding to the so-called side-population phenotype in various tissue-derived stem cells, was found to be a useful marker for the selection of PDLSCs with enhanced osteogenic, chondrogenic, and adipogenic differentiation. These findings may have important applications in achieving efficient dental tissue regeneration by using stem cells from extracted teeth.

  1. ABCG2 Is a Selectable Marker for Enhanced Multilineage Differentiation Potential in Periodontal Ligament Stem Cells

    PubMed Central

    Szepesi, Áron; Matula, Zsolt; Szigeti, Anna; Várady, György; Szabó, Gyula; Uher, Ferenc; Sarkadi, Balázs

    2015-01-01

    Periodontal ligament stem cells (PDLSCs) provide an important source for tissue regeneration and may become especially useful in the formation of osteogenic seeds. PDLSCs can be cultured, expanded, and differentiated in vitro; thus, they may be applied in the long-term treatment of the defects in the dental regions. Here we studied numerous potential markers allowing the selection of human PDLSCs with a maximum differentiation potential. We followed the expression of the ATP-binding cassette subfamily G member 2 (ABCG2) membrane transporter protein and isolated ABCG2-expressing cells by using a monoclonal antibody, recognizing the transporter at the cell surface in intact cells. The expression of the ABCG2 protein, corresponding to the so-called side-population phenotype in various tissue-derived stem cells, was found to be a useful marker for the selection of PDLSCs with enhanced osteogenic, chondrogenic, and adipogenic differentiation. These findings may have important applications in achieving efficient dental tissue regeneration by using stem cells from extracted teeth. PMID:25101689

  2. Stimulation of insulin release by phospholipase D. A potential role for endogenous phosphatidic acid in pancreatic islet function.

    PubMed

    Metz, S A; Dunlop, M

    1990-09-01

    Although exogenous phosphatidic acid (PA) has been shown to promote insulin release, the effects of endogenous PA on endocrine function are largely unexplored. In order to generate PA in situ, intact adult-rat islets were treated with exogenous phospholipases of the D type (PLD), and their effects on phospholipid metabolism and on insulin release were studied in parallel. Chromatographically purified PLD from Streptomyces chromofuscus stimulated the accumulation of PA in [14C]arachidonate- or [14C]myristate-prelabelled islets, and also promoted insulin secretion over an identical concentration range. During 30 min incubations, insulin release correlated closely with the accumulation of [14C]arachidonate-labelled PA (r2 = 0.98; P less than 0.01) or [14C]myristate-labelled PA (r2 = 0.97; P less than 0.01). Similar effects were seen both in freshly isolated and in overnight-cultured intact islets. In contrast, PLDs (from cabbage or peanut) which do not support phospholipid hydrolysis at the pH of the extracellular medium also did not promote insulin release. The effects on secretion of the active PLD preparation were inhibited by modest cooling (to 30 degrees C); dantrolene or Co2+ also inhibited PLD-induced secretion without decreasing PLD-induced PA formation. Additionally, the removal of PLD left the subsequent islet responsiveness to glucose intact, further supporting an exocytotic non-toxic mechanism. PLD-induced insulin release did not appear to require influx of extracellular Ca2+, nor could the activation of protein kinase C clearly be implicated. During incubations of 30 min, PLD selectively generated PA; however, more prolonged incubations (60 min) also led to production of some diacyglycerol and free arachidonic acid concomitant with progressive insulin release. These data suggest that PLD activation has both rapid and direct effects (via PA) and more delayed, secondary, effects (via other effects of PA or the generation of other lipid signals). Taken in

  3. Plasma neuronal specific enolase: a potential stage diagnostic marker in human African trypanosomiasis

    PubMed Central

    Sternberg, Jeremy M.; Mitchell, Julia A.

    2014-01-01

    Background This study was carried out to determine the potential of neuronal specific enolase (NSE) as a stage diagnostic marker in human African trypanosomiasis. Methods Plasma and cerebrospinal fluid were obtained from a cohort of Trypanosoma brucei rhodesiense-infected patients and non-infected controls. Neuronal specific enolase concentrations were measured by ELISA and analysed in relation to diagnosis and disease-stage data. Results Plasma NSE concentration was significantly increased in late-stage patients (median 21 ng/ml), compared to the control (median 11 ng/ml), but not in early-stage patients (median 5.3 ng/ml). Cerebrospinal fluid NSE concentration did not vary between stages. Conclusion Plasma NSE is a potential stage diagnostic in this cohort and merits further investigation. PMID:24789741

  4. A potential role for endogenous microflora in dormancy release, cytokinin metabolism and the response to fluridone in Lolium rigidum seeds

    PubMed Central

    Goggin, Danica E.; Emery, R. J. Neil; Kurepin, Leonid V.; Powles, Stephen B.

    2015-01-01

    Background and Aims Dormancy in Lolium rigidum (annual ryegrass) seeds can be alleviated by warm stratification in the dark or by application of fluridone, an inhibitor of plant abscisic acid (ABA) biosynthesis via phytoene desaturase. However, germination and absolute ABA concentration are not particularly strongly correlated. The aim of this study was to determine if cytokinins of both plant and bacterial origin are involved in mediating dormancy status and in the response to fluridone. Methods Seeds with normal or greatly decreased (by dry heat pre-treatment) bacterial populations were stratified in the light or dark and in the presence or absence of fluridone in order to modify their dormancy status. Germination was assessed and seed cytokinin concentration and composition were measured in embryo-containing or embryo-free seed portions. Key Results Seeds lacking bacteria were no longer able to lose dormancy in the dark unless supplied with exogenous gibberellin or fluridone. Although these seeds showed a dramatic switch from active cytokinin free bases to O-glucosylated storage forms, the concentrations of individual cytokinin species were only weakly correlated to dormancy status. However, cytokinins of apparently bacterial origin were affected by fluridone and light treatment of the seeds. Conclusions It is probable that resident microflora contribute to dormancy status in L. rigidum seeds via a complex interaction between hormones of both plant and bacterial origin. This interaction needs to be taken into account in studies on endogenous seed hormones or the response of seeds to plant growth regulators. PMID:25471097

  5. Sequence-related amplified polymorphism (SRAP) markers: A potential resource for studies in plant molecular biology1

    PubMed Central

    Robarts, Daniel W. H.; Wolfe, Andrea D.

    2014-01-01

    In the past few decades, many investigations in the field of plant biology have employed selectively neutral, multilocus, dominant markers such as inter-simple sequence repeat (ISSR), random-amplified polymorphic DNA (RAPD), and amplified fragment length polymorphism (AFLP) to address hypotheses at lower taxonomic levels. More recently, sequence-related amplified polymorphism (SRAP) markers have been developed, which are used to amplify coding regions of DNA with primers targeting open reading frames. These markers have proven to be robust and highly variable, on par with AFLP, and are attained through a significantly less technically demanding process. SRAP markers have been used primarily for agronomic and horticultural purposes, developing quantitative trait loci in advanced hybrids and assessing genetic diversity of large germplasm collections. Here, we suggest that SRAP markers should be employed for research addressing hypotheses in plant systematics, biogeography, conservation, ecology, and beyond. We provide an overview of the SRAP literature to date, review descriptive statistics of SRAP markers in a subset of 171 publications, and present relevant case studies to demonstrate the applicability of SRAP markers to the diverse field of plant biology. Results of these selected works indicate that SRAP markers have the potential to enhance the current suite of molecular tools in a diversity of fields by providing an easy-to-use, highly variable marker with inherent biological significance. PMID:25202637

  6. Trehalose as an indicator of desiccation stress in Drosophila melanogaster larvae: A potential marker of anhydrobiosis

    SciTech Connect

    Thorat, Leena J.; Gaikwad, Sushama M.; Nath, Bimalendu B.

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer First report confirming anhydrobiosis in Drosophila melanogaster larvae. Black-Right-Pointing-Pointer Trehalose synthesis and accumulation in larvae that hydrolyzed on rehydration. Black-Right-Pointing-Pointer Trehalose synthesis in concert with the enzymes involved in trehalose metabolism. Black-Right-Pointing-Pointer Inhibition of trehalose hydrolysis in presence of a specific trehalase inhibitor. Black-Right-Pointing-Pointer Trehalose proposed as a reliable marker for biomonitoring of climate change studies. -- Abstract: In the current scenario of global climate change, desiccation is considered as one of the major environmental stressors for the biota exposed to altered levels of ambient temperature and humidity. Drosophila melanogaster, a cosmopolitan terrestrial insect has been chosen as a humidity-sensitive bioindicator model for the present study since its habitat undergoes frequent stochastic and/or seasonally aggravated dehydration regimes. We report here for the first time the occurrence of anhydrobiosis in D. melanogaster larvae by subjecting them to desiccation stress under laboratory conditions. Larvae desiccated for ten hours at <5% relative humidity could enter anhydrobiosis and could revive upon rehydration followed by resumption of active metabolism. As revealed by FTIR and HPLC analyzes, our findings strongly indicated the synthesis and accumulation of trehalose in the desiccating larvae. Biochemical measurements pointed out the desiccation-responsive trehalose metabolic pathway that was found to be coordinated in concert with the enzymes trehalose 6-phosphate synthase and trehalase. Further, an inhibitor-based experimental approach using deoxynojirimycin, a specific trehalase inhibitor, demonstrated the pivotal role of trehalose in larval anhydrobiosis of D. melanogaster. We therefore propose trehalose as a potential marker for the assessment of anhydrobiosis in Drosophila. The present findings thus add

  7. Evidence for endogenous formation of the hepatocarcinogen N-nitrosodihydrouracil in rats treated with dihydrouracil and sodium nitrite: a potential source of human hepatic DNA carboxyethylation.

    PubMed

    Wang, Mingyao; Cheng, Guang; Khariwala, Samir S; Bandyopadhyay, Dipankar; Villalta, Peter W; Balbo, Silvia; Hecht, Stephen S

    2013-10-25

    An earlier study demonstrated that hydrolysates of all human liver DNA samples analyzed contain the DNA adduct 7-(2'-carboxyethyl)guanine (7-CEGua) with an average level of 74.6 adducts per 10(9) nucleotides. One possible source of this DNA adduct would be endogenous nitrosation of the normal pyrimidine metabolites dihydrouracil (DHU) and β-ureidopropionic acid (β-UPA), yielding the corresponding nitroso compounds N-nitrosodihydrouracil, a potent hepatocarcinogen, and N-nitroso-β-ureidopropionic acid. Another potential source would be reaction of endogenously formed acrylic acid with DNA. We tested these hypotheses in a study in which rats were treated with NaNO2 in the drinking water, alone, or in combination with dietary DHU or β-UPA, or with acrylic acid in the drinking water, for either 2 or 4 weeks. Hepatic DNA from these rats was analyzed for 7-CEGua, using liquid chromatography-tandem mass spectrometry-selected reaction monitoring with confirmation by high resolution mass spectrometry. The results demonstrated consistent statistically significant increases of 7-CEGua in hepatic DNA of the rats treated with the combination of NaNO2 and DHU compared to the corresponding controls, while the other treatments gave variable results. These results support the hypothesis that endogenous nitrosation of DHU could be a major source of 7-CEGua in human hepatic DNA. Development of methodology for analysis of 7-CEGua in human leukocyte DNA is also reported, which will allow testing of this hypothesis in epidemiologic and clinical studies.

  8. Serum serotonin as unexpected potential marker for staging of experimental hepatocellular carcinoma.

    PubMed

    Abdel-Hamid, N M; Shehata, Dalia E; Abdel-Ghany, Ahmed A; Ragaa, Ahmed; Wahid, Ahmed

    2016-10-01

    Hepatocellular carcinoma (HCC) is the primary cancer of the liver. The present study aimed to assess the potential role of the endogenous regulators of angiogenesis like neurotransmitters, as possible HCC biomarkers. Five groups of rats were used in this study (8 rats per each): control healthy group (I), four intoxicated groups (II, III, IV, and V) used for induction of HCC with a single IP dose of diethylnitrosamine (DENA), 200mg/kg. Groups II, III, IV, and V were sacrificed after 8, 16, 24, and 32 weeks of DENA injection respectively. Serum levels of epinephrine, nor-epinephrine, serotonin, and dopamine of all animals were estimated using high performance liquid chromatography technique coupled with fluorescence detector (HPLC-FLD). Development of HCC was confirmed histopathologically. Our results showed a significant increase in 3 neurotransmitters (epinephrine, nor-epinephrine, and serotonin) in DENA intoxicated HCC rat model. Only serotonin exhibited a significant increase in early histological stage HCC development (16 weeks post DENA injection) in comparison to alpha-fetoprotein (AFP), (24 weeks post DENA injection). These results suggest that neurotransmitters (Epinephrine and Norepinephrine) may have a role as a biomarker for late histological stage HCC. Like AFP, while serotonin may be used for early stage HCC.

  9. Tyrosine kinase A receptor (trkA): a potential marker in epithelial ovarian cancer.

    PubMed

    Tapia, Verónica; Gabler, Fernando; Muñoz, Marcela; Yazigi, Roberto; Paredes, Alfonso; Selman, Alberto; Vega, Margarita; Romero, Carmen

    2011-04-01

    To evaluate the role of trkA receptor as a potential tumor marker in serous epithelial ovarian cancer and its relationship with the angiogenic factors expression as vascular endothelial growth factor (VEGF) and nerve growth factor (NGF). Additionally, to examine whether NGF and VEGF secreted by epithelial ovarian cancer (EOC) explants and from epithelial ovarian cancer cell line (A2780) are involved in the process of angiogenesis, such as cellular proliferation, migration and differentiation of the human endothelial cell line (EA.hy926). The mRNA levels of VEGF, NGF and trkA receptors were measured using PCR in 60 ovarian samples. Cellular localization and semi-quantitative estimation of VEGF, NGF, total trkA and p-trkA was performed using IHC in epithelial cells. NGF, total trkA and p-trkA protein were also evaluated in endothelial cells from the same tissues. Human endothelial cell line EA.hy926 was cultured with conditioned media obtained from both EOC explants and from the A2780 cell line, with or without NGF stimulus. Significantly higher levels of NGF, total trkA and p-trkA protein expressions were observed in epithelial and endothelial cells in poorly differentiated EOC versus normal ovary. Interestingly, the p-trkA receptor expression level showed the most significant difference and its presence was only found in borderline tumor and EOC samples indicating the importance of trkA receptor in EOC as a potential tumor marker. A significant increase in proliferation, migration and differentiation of EA.hy926 cells was observed with NGF, and this effect was significantly reverted when NGF was immuno-blocked and when a trkA inhibitor was used, showing that NGF is an important angiogenic factor in EOC by activating its trkA receptor. These results indicate that p-trkA may be considered as a new potential tumor marker in EOC, and that NGF may also act as a direct angiogenic factor in EOC. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. Cystatin C: a possible sensitive marker for detecting potential kidney injury after computed tomography coronary angiography.

    PubMed

    Takeuchi, Toyonari; Isobe, Satoshi; Sato, Kimihide; Kato, Mariko I; Kasai, Naho N; Ohyama, Hisato; Yoshikawa, Daiji; Ishii, Hideki; Matsubara, Tatsuaki; Murohara, Toyoaki

    2011-01-01

    Cystatin C (CyC) has recently been recognized as a sensitive marker for potential renal dysfunction. We investigated the role of CyC for evaluating potential kidney injury after computed tomography coronary angiography (CTCA). The CyC, serum creatinine (sCr), estimated glomerular filtration rate (eGFR), and blood urea nitrogen (BUN) levels were evaluated before and 1 day and 1 week after the procedure in 140 patients with preserved renal function referred for CTCA. The amount of unrestricted oral fluid intake was measured for 24 hours after CTCA. The relationship between the amount of oral fluid intake and the changes in each renal marker was compared. A strong correlation was observed between oral fluid volume and the changes in CyC (r = -0.80, P < 0.0001) as well as the changes in sCr (r = -0.54, P < 0.0001) and eGFR (r = 0.57, P < 0.0001), but a weak correlation was observed between oral fluid volume and the changes in BUN (r = -0.22, P = 0.03). A progressive rise in a mean level of CyC was observed. The percentage of diabetic history was greater (73% vs 40%, P < 0.001) and oral fluid volume was lower (1142 mL vs 2114 mL, P < 0.0001) in patients with a rise in CyC but without one in sCr than in those showing a rise in neither CyC nor sCr at 1 day postprocedure. Seventy-four (80%) of 92 patients with a rise in CyC at 1 day postprocedure showed a recovery to the baseline sCr levels at 1 week postprocedure, but only 26 (28%) showed a recovery to the baseline CyC levels at 1 week. Cystatin C is a more sensitive marker than sCr in evaluating the effects of oral fluid volume on renal function and in detecting potential kidney injury, especially in diabetic patients after CTCA.

  11. Urinary 5-Aminolevulinic Acid Concentrations as a Potential Tumor Marker for Colorectal Cancer Screening and Recurrence.

    PubMed

    Kamada, Yosuke; Murayama, Yasutoshi; Ota, Urara; Takahashi, Kiwamu; Arita, Tomohiro; Kosuga, Toshiyuki; Konishi, Hirotaka; Morimura, Ryo; Komatsu, Shuhei; Shiozaki, Atsushi; Kuriu, Yoshiaki; Ikoma, Hisashi; Nakanishi, Masayoshi; Ichikawa, Daisuke; Fujiwara, Hitoshi; Okamoto, Kazuma; Tanaka, Tohru; Otsuji, Eigo

    2016-05-01

    Tumor biomarkers, such as carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA19-9), are used to screen and monitor tumor recurrence in patients with colorectal cancer (CRC). 5-Aminolevulinic acid (5-ALA) is used in photodynamic diagnosis and therapy. Porphyrins produced by tumor cells are excreted in the urine after 5-ALA administration. In this study, we evaluated the use of porphyrins as novel tumor markers in urine samples from patients with CRC. Porphyrin metabolite concentrations were measured in urine samples of 33 patients with CRC, 16 patients with benign disease and 8 healthy adults, after 5-ALA administration. The porphyrin metabolite concentrations were significantly increased in the CRC group compared to the control group, while in CRC patients, the porphyrin metabolite concentrations in urine were significantly decreased after surgery. These results suggest that the measurement of porphyrin metabolites in urine may potentially serve as a new screening and recurrence marker for CRC. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  12. Identification of Meflin as a Potential Marker for Mesenchymal Stromal Cells

    PubMed Central

    Maeda, Keiko; Enomoto, Atsushi; Hara, Akitoshi; Asai, Naoya; Kobayashi, Takeshi; Horinouchi, Asuka; Maruyama, Shoichi; Ishikawa, Yuichi; Nishiyama, Takahiro; Kiyoi, Hitoshi; Kato, Takuya; Ando, Kenju; Weng, Liang; Mii, Shinji; Asai, Masato; Mizutani, Yasuyuki; Watanabe, Osamu; Hirooka, Yoshiki; Goto, Hidemi; Takahashi, Masahide

    2016-01-01

    Bone marrow-derived mesenchymal stromal cells (BM-MSCs) in culture are derived from BM stromal cells or skeletal stem cells. Whereas MSCs have been exploited in clinical medicine, the identification of MSC-specific markers has been limited. Here, we report that a cell surface and secreted protein, Meflin, is expressed in cultured MSCs, fibroblasts and pericytes, but not other types of cells including epithelial, endothelial and smooth muscle cells. In vivo, Meflin is expressed by immature osteoblasts and chondroblasts. In addition, Meflin is found on stromal cells distributed throughout the BM, and on pericytes and perivascular cells in multiple organs. Meflin maintains the undifferentiated state of cultured MSCs and is downregulated upon their differentiation, consistent with the observation that Meflin-deficient mice exhibit increased number of osteoblasts and accelerated bone development. In the bone and BM, Meflin is more highly expressed in primitive stromal cells that express platelet-derived growth factor receptor α and Sca-1 than the Sca-1-negative adipo-osteogenic progenitors, which create a niche for hematopoiesis. Those results are consistent with a decrease in the number of clonogenic colony-forming unit-fibroblasts within the BM of Meflin-deficient mice. These preliminary data suggest that Meflin is a potential marker for cultured MSCs and their source cells in vivo. PMID:26924503

  13. Assessment of Eccentric Exercise-Induced Oxidative Stress Using Oxidation-Reduction Potential Markers

    PubMed Central

    Stagos, Dimitrios; Goutzourelas, Nikolaos; Ntontou, Amalia-Maria; Kafantaris, Ioannis; Deli, Chariklia K.; Poulios, Athanasios; Jamurtas, Athanasios Z.; Bar-Or, David; Kouretas, Dimitrios

    2015-01-01

    The aim of the present study was to investigate the use of static (sORP) and capacity ORP (cORP) oxidation-reduction potential markers as measured by the RedoxSYS Diagnostic System in plasma, for assessing eccentric exercise-induced oxidative stress. Nineteen volunteers performed eccentric exercise with the knee extensors. Blood was collected before, immediately after exercise, and 24, 48, and 72 h after exercise. Moreover, common redox biomarkers were measured, which were protein carbonyls, thiobarbituric acid-reactive substances, total antioxidant capacity in plasma, and catalase activity and glutathione levels in erythrocytes. When the participants were examined as one group, there were not significant differences in any marker after exercise. However, in 11 participants there was a high increase in cORP after exercise, while in 8 participants there was a high decrease. Thus, the participants were divided in low cORP group exhibiting significant decrease in cORP after exercise and in high cORP group exhibiting significant increase. Moreover, only in the low cORP group there was a significant increase in lipid peroxidation after exercise suggesting induction of oxidative stress. The results suggested that high decreases in cORP values after exercise may indicate induction of oxidative stress by eccentric exercise, while high increases in cORP values after exercise may indicate no existence of oxidative stress. PMID:25874019

  14. Assessment of eccentric exercise-induced oxidative stress using oxidation-reduction potential markers.

    PubMed

    Stagos, Dimitrios; Goutzourelas, Nikolaos; Ntontou, Amalia-Maria; Kafantaris, Ioannis; Deli, Chariklia K; Poulios, Athanasios; Jamurtas, Athanasios Z; Bar-Or, David; Kouretas, Dimitrios

    2015-01-01

    The aim of the present study was to investigate the use of static (sORP) and capacity ORP (cORP) oxidation-reduction potential markers as measured by the RedoxSYS Diagnostic System in plasma, for assessing eccentric exercise-induced oxidative stress. Nineteen volunteers performed eccentric exercise with the knee extensors. Blood was collected before, immediately after exercise, and 24, 48, and 72 h after exercise. Moreover, common redox biomarkers were measured, which were protein carbonyls, thiobarbituric acid-reactive substances, total antioxidant capacity in plasma, and catalase activity and glutathione levels in erythrocytes. When the participants were examined as one group, there were not significant differences in any marker after exercise. However, in 11 participants there was a high increase in cORP after exercise, while in 8 participants there was a high decrease. Thus, the participants were divided in low cORP group exhibiting significant decrease in cORP after exercise and in high cORP group exhibiting significant increase. Moreover, only in the low cORP group there was a significant increase in lipid peroxidation after exercise suggesting induction of oxidative stress. The results suggested that high decreases in cORP values after exercise may indicate induction of oxidative stress by eccentric exercise, while high increases in cORP values after exercise may indicate no existence of oxidative stress.

  15. Senescence marker protein 30 (SMP30) serves as a potential prognostic indicator in hepatocellular carcinoma

    PubMed Central

    Mo, Zhijing; Zheng, Shunxin; Lv, Zhilue; Zhuang, Yuan; Lan, Xiuwan; Wang, Feng; Lu, Xiaoling; Zhao, Yongxiang; Zhou, Sufang

    2016-01-01

    Senescence marker protein 30 (SMP30) has been identified as a tumor-related molecule of hepatocellular carcinoma (HCC). Its clinical significance and underlying mechanisms in HCC tissues, however, remain largely unexplored. We have demonstrated a preferentially expressed SMP30 in normal liver using a tissue microarray. By employing real-time quantitative PCR, two tissue microarrays and Oncomine database analysis, we have also shown that the SMP30 in HCC tissues has significantly reduced when compared with that in paired adjacent non-tumor tissues (P = 0.0037). The reduced expression of SMP30 is very noticeably related to larger tumor size (P = 0.012), enhanced TNM (P = 0.009) and worse survival (P < 0.0001) in HCC patients. The analyses using Cox regression have indicated that the decreased SMP30 expression is an independent risk to the reduced overall survival rate of HCC patients (P = 0.001), and the down-regulation of SMP30 in HCC might be mediated by DNA methylation. Moreover, genes co-expressed with SMP30 may affect the prognosis through apoptotic process, biological adhesion and blood coagulation by PANTHER analyses. Our studies have indicated that the SMP30 may serve as a candidate of HCC clinical prognostic marker and a potential therapeutic target. PMID:27991558

  16. Marine-continental tephra correlations (Pantelleria, Italy, and Ionian Basin): the potential for Mediterranean marker horizons

    NASA Astrophysics Data System (ADS)

    Jordan, Nina

    2016-04-01

    Palaeo-environmental records from marine and terrestrial archives in the Mediterranean show broad-scale and millennial-scale climatic changes. Synchronising these records requires robust chronological control which may be achieved using isochronous tephra marker horizons. These need to be widespread and sufficiently unique in chemistry to be distinguished from each other. Pantelleria volcano, Italy, satisfies these criteria, with eruptions blanketing the Mediterranean Sea and being distinct from every other volcano in the region. This peralkaline volcano is already well-known for its 46 ka marker horizon (Y-6) but there is potential for extending correlations further back in time. Until recently, correlations were limited by scarce onshore glass data and few sediment cores covering sufficiently long time periods to compare with Pantelleria's >200 ka explosive volcanic history. Building on recent work that has established a detailed onshore stratigraphy, glass data are presented from Pantelleria and site 964 of ODP leg 160 which is situated ~400 km downwind from the volcano. New correlations can be established and previous suggestions are discussed in the light of this new data, representing a significant step forward in confident marine-continental tephra correlations.

  17. Quantification of plasma exosome is a potential prognostic marker for esophageal squamous cell carcinoma.

    PubMed

    Matsumoto, Yasunori; Kano, Masayuki; Akutsu, Yasunori; Hanari, Naoyuki; Hoshino, Isamu; Murakami, Kentaro; Usui, Akihiro; Suito, Hiroshi; Takahashi, Masahiko; Otsuka, Ryota; Xin, Hu; Komatsu, Aki; Iida, Keiko; Matsubara, Hisahiro

    2016-11-01

    Exosomes play important roles in cancer progression. Although its contents (e.g., proteins and microRNAs) have been focused on in cancer research, particularly as potential diagnostic markers, the exosome behavior and methods for exosome quantification remain unclear. In the present study, we analyzed the tumor-derived exosome behavior and assessed the quantification of exosomes in patient plasma as a biomarker for esophageal squamous cell carcinoma (ESCC). A CD63-GFP expressing human ESCC cell line (TE2-CD63-GFP) was made by transfection, and mouse subcutaneous tumor models were established. Fluorescence imaging was performed on tumors and plasma exosomes harvested from mice. GFP-positive small vesicles were confirmed in the plasma obtained from TE2-CD63-GFP tumor-bearing mice. Patient plasma was collected in Chiba University Hospital (n=86). Exosomes were extracted from 100 µl of the plasma and quantified by acetylcholinesterase (AChE) activity. The relationship between exosome quantification and the patient clinical characteristics was assessed. The quantification of exosomes isolated from the patient plasma revealed that esophageal cancer patients (n=66) expressed higher exosome levels than non-malignant patients (n=20) (P=0.0002). Although there was no correlation between the tumor progression and the exosome levels, exosome number was the independent prognostic marker and low levels of exosome predicted a poor prognosis (P=0.03). In conclusion, exosome levels may be useful as an independent prognostic factor for ESCC patients.

  18. Prevalence of polymorphisms in OPG, RANKL and RANK as potential markers for Charcot arthropathy development.

    PubMed

    Bruhn-Olszewska, Bożena; Korzon-Burakowska, Anna; Węgrzyn, Grzegorz; Jakóbkiewicz-Banecka, Joanna

    2017-03-29

    Charcot arthropathy is one of the most serious complications of diabetic foot syndrome that leads to amputation of the affected limb. Since there is no cure for Charcot arthropathy, early diagnosis and implementation preventive care are the best available treatment. However, diagnosis is hindered by obscure clinical picture of the disease and lack of molecular markers for its early detection. Results of recent research suggest that OPG-RANKL-RANK axis regulating bone metabolism can be associated with Charcot arthropathy and that SNPs in OPG gene are associated with the disease. Here we report the results of comprehensive analysis of ten SNPs in OPG, RANKL and RANK genes in 260 subjects divided into diabetes, neuropathy and Charcot arthropathy groups. Besides genotype analysis we performed linkage disequilibrium and hierarchical clustering to obtain information about correlation between SNPs. Our results show that OPG 245T/G (rs3134069) and OPG 1217C/T (rs3102734) polymorphisms co-occur in patients with Charcot arthropathy (r2 = 0.99). Moreover, hierarchical clustering revealed a characteristic profile of all SNPs in Charcot arthropathy and neuropathy, which is distinct from control group. Our results suggest that analysis of multiple SNPs can be used as potential marker of Charcot arthropathy and provide insight into possible molecular mechanisms of its development.

  19. Analysis of water soluble polysaccharides as a potential chemotaxonomic marker for landraces in Bixa orellana.

    PubMed

    Parimalan, Rangan; Mahendranath, Gondi; Giridhar, Parvatam

    2014-02-01

    Annatto tree (Bixa orellana L.) is native to Brazil and is now under cultivation in many parts of world for its reddish orange 'annatto' dye. There are three types of landraces in annatto and they are distinguished based on fruit shape i.e., ovate, conical and hemispherical, whose pigment yield differs. Since annatto pigment yield varies with landrace, it is necessary to characterize markers towards the identification of landraces. In this study, we characterized water soluble polysaccharides (WSP) of twigs from three landraces using size-exclusion chromatography (SEC), Fourier-transform Infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (NMR) and gas liquid chromatography (GLC) for their potential use as chemotaxonomic markers to distinguish the landraces. GLC analysis on WSP showed hemispherical type contained 38% rhamnose, while conical and ovate types contained 17% and 34% glucose, respectively. Thus, glucose and rhamnose content of WSP could be used to distinguish the three landraces. Further, differences in calculated molecular weight as revealed by SEC (281.8, 151.3 and 79.4 kDa for conical, hemispherical and ovate types, respectively) could also be used to distinguish the three landraces.

  20. Somatostatin receptor subtype 2 (sst₂) is a potential prognostic marker and a therapeutic target in medulloblastoma.

    PubMed

    Remke, Marc; Hering, Esther; Gerber, Nicolas U; Kool, Marcel; Sturm, Dominik; Rickert, Christian H; Gerß, Joachim; Schulz, Stefan; Hielscher, Thomas; Hasselblatt, Martin; Jeibmann, Astrid; Hans, Volkmar; Ramaswamy, Vijay; Taylor, Michael D; Pietsch, Torsten; Rutkowski, Stefan; Korshunov, Andrey; Monoranu, Carmelia-Maria; Frühwald, Michael C

    2013-08-01

    Neuroectodermal tumors in general demonstrate high and dense expression of the somatostatin receptor subtype 2 (sst₂). It controls proliferation of both normal and neoplastic cells. sst₂ has thus been suggested as a therapeutic target and prognostic marker for certain malignancies. To assess global expression patterns of sst 2 mRNA, we evaluated normal (n = 353) and tumor tissues (n = 340) derived from previously published gene expression profiling studies. These analyses demonstrated specific upregulation of sst 2 mRNA in medulloblastoma (p < 0.001). sst₂ protein was investigated by immunohistochemistry in two independent cohorts. Correlation of sst₂ protein expression with clinicopathological variables revealed significantly higher levels in medulloblastoma (p < 0.05) compared with CNS-PNET, ependymoma, or pilocytic astrocytoma. The non-SHH medulloblastoma subgroup tumors showed particularly high expression of sst₂, when compared to other tumors and normal tissues. Furthermore, we detected a significant survival benefit in children with tumors exhibiting high sst₂ expression (p = 0.02) in this screening set. A similar trend was observed in a validation cohort including 240 independent medulloblastoma samples. sst₂ is highly expressed in medulloblastoma and deserves further evaluation in the setting of prospective trials, given its potential utility as a prognostic marker and a therapeutic target.

  1. Evaluation of DNA methylation markers and their potential to predict human aging.

    PubMed

    Soares Bispo Santos Silva, Deborah; Antunes, Joana; Balamurugan, Kuppareddi; Duncan, George; Sampaio Alho, Clarice; McCord, Bruce

    2015-08-01

    We present epigenetic methylation data for two genetic loci, GRIA2, and NPTX2, which were tested for prediction of age from different donors of biofluids. We analyzed 44 saliva samples and 23 blood samples from volunteers with ages ranging from 5 to 72 years. DNA was extracted and bisulfite modified using commercial kits. Specific primers were used for amplification and methylation profiles were determined by pyrosequencing. Methylation data from both markers and their relationship with age were determined using linear regression analysis, which indicates a positive correlation between methylation and age. Older individuals tend to have increased methylation in both markers compared to younger individuals and this trend was more pronounced in the GRIA2 locus when compared to NPTX2. The epigenetic predicted age, calculated using a GRIA2 regression analysis model, was strongly correlated to chronological age (R(2) = 0.801), with an average difference of 6.9 years between estimated and observed ages. When using a NPTX2 regression model, we observed a lower correlation between predicted and chronological age (R(2) = 0.654), with an average difference of 9.2 years. These data indicate these loci can be used as a novel tool for age prediction with potential applications in many areas, including clinical and forensic investigations. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Mucosal-Associated Invariant T Cell Is a Potential Marker to Distinguish Fibromyalgia Syndrome from Arthritis

    PubMed Central

    Konno, Takahiko; Wakao, Rika; Fujita, Hiroko; Fujita, Hiroyoshi

    2015-01-01

    Background Fibromyalgia (FM) is defined as a widely distributed pain. While many rheumatologists and pain physicians have considered it to be a pain disorder, psychiatry, psychology, and general medicine have deemed it to be a syndrome (FMS) or psychosomatic disorder. The lack of concrete structural and/or pathological evidence has made patients suffer prejudice that FMS is a medically unexplained symptom, implying inauthenticity. Furthermore, FMS often exhibits comorbidity with rheumatoid arthritis (RA) or spondyloarthritis (SpA), both of which show similar indications. In this study, disease specific biomarkers were sought in blood samples from patients to facilitate objective diagnoses of FMS, and distinguish it from RA and SpA. Methods Peripheral blood mononuclear cells (PBMCs) from patients and healthy donors (HD) were subjected to multicolor flow cytometric analysis. The percentage of mucosal-associated invariant T (MAIT) cells in PBMCs and the mean fluorescent intensity (MFI) of cell surface antigen expression in MAIT cells were analyzed. Results There was a decrease in the MAIT cell population in FMS, RA, and SpA compared with HD. Among the cell surface antigens in MAIT cells, three chemokine receptors, CCR4, CCR7, and CXCR1, a natural killer (NK) receptor, NKp80, a signaling lymphocyte associated molecule (SLAM) family, CD150, a degrunulation marker, CD107a, and a coreceptor, CD8β emerged as potential biomarkers for FMS to distinguish from HD. Additionally, a memory marker, CD44 and an inflammatory chemokine receptor, CXCR1 appeared possible markers for RA, while a homeostatic chemokine receptor, CXCR4 deserved for SpA to differentiate from FMS. Furthermore, the drug treatment interruption resulted in alternation of the expression of CCR4, CCR5, CXCR4, CD27, CD28, inducible costimulatory molecule (ICOS), CD127 (IL-7 receptor α), CD94, NKp80, an activation marker, CD69, an integrin family member, CD49d, and a dipeptidase, CD26, in FMS. Conclusions

  3. Neck circumference as a potential marker of metabolic syndrome among college students1

    PubMed Central

    Pereira, Dayse Christina Rodrigues; de Araújo, Márcio Flávio Moura; de Freitas, Roberto Wagner Júnior Freire; Teixeira, Carla Regina de Souza; Zanetti, Maria Lúcia; Damasceno, Marta Maria Coelho

    2014-01-01

    OBJECTIVE: to relate neck circumference with metabolic syndrome and its criteria among college students. METHOD: cross-sectional study conducted with 702 college students in Fortaleza, CE, Brazil from September 2010 to June 2011. Socio-demographic data, waist circumference and neck circumference were collected together with blood pressure, fasting blood sugar, triglyceride levels, and HDL-C. RESULTS: 1.7% of the studied sample presented metabolic syndrome. Of these, 58.3% presented altered neck circumference (p<0.006). As neck circumference decreases, pressure levels improve (p<0.001). Additionally, college students with high fasting blood sugar (p=0.003) and high triglyceride levels (p<0.001) presented higher values of neck circumference. CONCLUSION: neck circumference is a potential predictive marker in the detection of metabolic syndrome and its components among college students. PMID:25591092

  4. Computer mouse movement patterns: A potential marker of mild cognitive impairment.

    PubMed

    Seelye, Adriana; Hagler, Stuart; Mattek, Nora; Howieson, Diane B; Wild, Katherine; Dodge, Hiroko H; Kaye, Jeffrey A

    2015-12-01

    Subtle changes in cognitively demanding activities occur in MCI but are difficult to assess with conventional methods. In an exploratory study, we examined whether patterns of computer mouse movements obtained from routine home computer use discriminated between older adults with and without MCI. Participants were 42 cognitively intact and 20 older adults with MCI enrolled in a longitudinal study of in-home monitoring technologies. Mouse pointer movement variables were computed during one week of routine home computer use using algorithms that identified and characterized mouse movements within each computer use session. MCI was associated with making significantly fewer total mouse moves (p<.01), and making mouse movements that were more variable, less efficient, and with longer pauses between movements (p<.05). Mouse movement measures were significantly associated with several cognitive domains (p's<.01-.05). Remotely monitored computer mouse movement patterns are a potential early marker of real-world cognitive changes in MCI.

  5. Adenosine deaminase complexing protein (ADCP): a transformation sensitive protein with potentials of a cancer marker.

    PubMed

    Herbschleb-Voogt, E; Ten Kate, J; Meera Khan, P

    1983-01-01

    Several observations by independent investigators in the past have indicated that adenosine deaminase complexing protein (ADCP), present in considerable quantities in certain human tissues, was absent or decreased in the cancers originated from them. During the present study, electrophoretic analysis of adenosine deaminase (ADA) isozymes and radioimmunoassay for ADCP in the primary fibroblasts and the transformed as well as certain tumor derived cell lines have demonstrated that ADCP present in large quantities in the primary cells was absent or nearly absent in the transformed or tumor-derived cell lines. Though the mechanisms involved are not yet clear, the above observations indicate that ADCP has the potentials of a useful marker in the studies on transformed cells and cancer tissues.

  6. Potential role of genetic markers in the management of kidney cancer.

    PubMed

    Junker, Kerstin; Ficarra, Vincenzo; Kwon, Eugene D; Leibovich, Bradley C; Thompson, R Houston; Oosterwijk, Egbert

    2013-02-01

    Kidney cancer is not a single entity but comprises a number of different types of cancer that occur in the kidney including renal cell tumours as the most common type. Four major renal cell tumour subtypes can be distinguished based on morphologic and genetic characteristics. To individualise therapy and to improve the prognosis in patients with renal cell tumours, accurate subtyping, definition of individual course of disease, and the prediction of therapy response are necessary. To discuss the potential role of genetic markers in the management of kidney cancer. A Medline search was conducted to identify original articles, review articles, and editorials addressing the role of genetic alterations in kidney cancer management. Keywords included kidney neoplasms, genetics, SNP, gene expression, miRNA, classification, diagnosis, drug therapy, prognosis, and therapy. The articles with the highest level of evidence were identified and critically reviewed. This review is the result of an interactive peer-reviewing process by an expert panel of co-authors. Each subtype is characterised by specific genetic, epigenetic, and expression patterns that potentially can be used to subclassify renal cell tumours in cases of ambivalent histopathology. Molecular signatures and single alterations in primary tumours are associated with aggressiveness and prognosis. Germline polymorphisms in specific genes encoding for metabolizing enzymes, efflux transporters, and drug targets seem to be associated with toxicity and response in patients receiving targeted therapy. Significant advances have been achieved in the molecular analysis of renal cancer. Validation of findings is greatly needed to implement genetic markers in the management of renal cancer. This should lead to improved diagnosis, prognosis, and personalised therapy in this heterogeneous disease. Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  7. Intracellular TCR-signaling pathway: novel markers for lymphoma diagnosis and potential therapeutic targets.

    PubMed

    Agostinelli, Claudio; Rizvi, Hasan; Paterson, Jennifer; Shende, Vishvesh; Akarca, Ayse U; Agostini, Elena; Fuligni, Fabio; Righi, Simona; Spagnolo, Sebastiano; Piccaluga, Pier Paolo; Clark, Edward A; Pileri, Stefano A; Marafioti, Teresa

    2014-10-01

    Despite the immunologic functions of T-cell receptor signaling molecules being extensively investigated, their potential as immunohistochemical markers has been poorly explored. With this background, we evaluated the expression of 5 intracellular proteins-GADS, DOK2, SKAP55, ITK, and PKCα-involved in T-cell receptor signaling in normal and neoplastic hematologic tissue samples, using antibodies raised against fixation-resistant epitopes of the 5 molecules. All 5 antibodies were associated with normal T-cell differentiation. GADS, DOK2, SKAP55, and ITK turned out to be T-cell lineage-specific markers in the setting of lymphoid and myeloid precursor neoplasms but showed differential expression in peripheral T-cell lymphoma (PTCL) subtypes, being detected in PTCL/not otherwise specified (NOS) and angioimmunoblastic T-cell lymphoma but negative in anaplastic large cell lymphoma (ALCL). Peripheral B-cell lymphomas were consistently negative for ITK, with occasional cases showing expression of DOK2 and SKAP55, and a proportion (47%) of hairy cell leukemias were GADS. Notably, PKCα highlighted a defective antigen in both PTCL/NOS (6%) and angioimmunoblastic T-cell lymphoma (10%), mostly negative in ALCL, and was aberrantly expressed in classical Hodgkin lymphoma (65%), Burkitt lymphoma (48%), and plasma cell myeloma (48%). In conclusion, all five molecules evaluated play a role in T-cell differentiation in normal and neoplastic tissues. They can be applied confidently to routine sections contributing primarily to assignment of T-lineage differentiation in the setting of hematopoietic precursor neoplasms (GADS/DOK2/SKAP55/ITK) and for the differential diagnosis between ALCL and PTCL/NOS (GADS/DOK2/SKAP55/ITK) or classical Hodgkin lymphoma (PKCα). Finally, association with specific tumor subtypes may have therapeutic potential.

  8. Parental potentiation of vocalization as a marker for filial bonds in infant animals.

    PubMed

    Shair, Harry N

    2014-12-01

    Maternal and paternal potentiation of vocalization are two parts of a promising model of early life social bonds that has been and can be a useful tool in research. Most mammalian infants vocalize when isolated. Interactions with adult females just before isolation have been found to increase vocalizations in several species. Interactions with littermates and other social stimuli do not. In guinea pigs and pigs, the response is specific to the dam. In rats and octagon degus, an unrelated adult female from the colony is sufficient. The presence of an intact adult male in the test chamber with dam-reared pups evokes behavioral inhibition, a fear response. Previous exposure to the male in the home cage, biparental rearing, dramatically transforms the response of the pup. The pup treats the adult male as it does its dam, including potentiation of vocalization during a subsequent isolation. This article outlines the methods, advantages, and disadvantages of parental potentiation as a research tool, as well as a brief review of the evidence supporting its use as a marker for filial attachment. Future research directions are outlined.

  9. Telangiectases in Scleroderma: A Potential Clinical Marker of Pulmonary Arterial Hypertension

    PubMed Central

    Shah, Ami A.; Wigley, Fredrick M.; Hummers, Laura K.

    2012-01-01

    Objective Clinical markers are needed to identify scleroderma patients at risk for pulmonary arterial hypertension (PAH) since early therapy may improve survival. We investigated whether increased numbers of telangiectases in scleroderma associate with measures of pulmonary vascular disease. Methods One hundred forty-seven consecutive adult patients with scleroderma were enrolled in this cross-sectional study and scored for the presence of matted telangiectases on 11 body areas. Per body area, telangiectases were scored as 0 if none were present, 1 if there were fewer than 10 telangiectases, and 2 if 10 or more telangiectases were counted. Linear regression analysis was performed to assess the association between right ventricular systolic pressure (RVSP) and telangiectasia score, adjusted for age, race, smoking status, scleroderma subtype, disease duration, and autoantibody status. Logistic regression analysis was performed with PAH by right-heart catheterization (RHC) as the dependent variable. Results The mean telangiectasia score was 6.0 (SD 4.5, range 0–20). RVSP and telangiectasia score were positively correlated (r = 0.271, p = 0.001). The mean RVSP increased by 10.9 mm Hg for every 10-point increase in telangiectasia score (95% CI 3.6–18.3 mm Hg, p = 0.004), adjusted for potential confounders. The adjusted relative odds of PAH by RHC were 12.4 for patients with a 10-point increase in telangiectasia score (95% CI 1.78–85.9, p = 0.01). Conclusion Increased numbers of telangiectases strongly associate with the presence of pulmonary vascular disease. Telangiectases may be a clinical marker of more widespread aberrant microvascular disease in scleroderma. PMID:19955048

  10. LINE-1 DNA methylation: A potential forensic marker for discriminating monozygotic twins.

    PubMed

    Xu, Jie; Fu, Guangping; Yan, Lina; Craig, Jeffery M; Zhang, Xiaojing; Fu, Lihong; Ma, Chunling; Li, Shujin; Cong, Bin

    2015-11-01

    Discriminating individuals within a pair of monozygotic (MZ) twins using genetic markers remains unresolved. This inability causes problems in criminal or paternity cases involving MZ twins as suspects or alleged fathers. Our previous study showed DNA methylation differences in interspersed repeat sequences such as Alu and LINE-1 within pairs of newborn MZ twins. To further evaluate the possible value of LINE-1 DNA methylation for discriminating MZ twins, this study investigated the LINE-1 DNA methylation of a large number of twins. We collected blood samples and buccal cell samples from 119 pairs of MZ and 57 pairs of dizygotic (DZ) twins. Genomic DNA was extracted and LINE-1 methylation level was detected using bisulfite pyrosequencing. The mean methylation level of the three CpG sites in the blood sample among the 176 unrelated individuals was 76.60% and 70.08% in buccal samples. This difference was significant, indicating the tissue specificity of LINE-1 DNA methylation. Among 119 pairs of MZ twins, 15 pairs could be discriminated according to the difference of CpG methylation level between them, which accounted for 12.61% of total number of MZ pairs. As for DZ twins, 10 pairs had significant differences between two individuals, which accounted for 17.54% of the total 57 DZ pairs. In conclusion, there are global DNA methylation differences within some healthy concordant monozygotic (MZ) twin pairs. LINE-1 DNA methylation might be a potential marker for helping to discriminate individuals within MZ twin pairs, and the tissue specificity must be considered in practice. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. S100B is a potential disease activity marker in non-segmental vitiligo.

    PubMed

    Speeckaert, Reinhart; Voet, Sofie; Hoste, Esther; van Geel, Nanja

    2017-02-14

    Vitiligo is a chronic skin condition characterized by progressive depigmentation of the skin. S100B is a damage-associated molecular pattern (DAMP) protein expressed in melanocytes, which has been proposed as a marker of melanocyte cytotoxicity. While the use of S100B as a biomarker in melanoma is well established, its association with vitiligo activity has not yet been investigated. Here, we show that S100B serum levels were significantly increased in patients with active non-segmental vitiligo and strongly correlated with the affected body surface area. Prospective follow-up showed a predictive value of serum S100B levels on disease progression. In vitro experiments using repeated freeze-thaw procedures demonstrated an intracellular upregulation of S100B in normal and vitiligo melanocytes prior to an extensive release in the environment. This phenomenon may explain the increased S100B serum values in the active phase of vitiligo. In a monobenzone-induced vitiligo mouse model we could show the potential of S100B inhibition as a therapeutic strategy in vitiligo. In conclusion, this report demonstrates the possible use of S100B as a biomarker for disease activity in vitiligo. Our data suggest that this DAMP protein could play a substantial role in the pathogenesis of vitiligo and may be a potential new target for treatment.

  12. Gene expression profiling of craniofacial fibrous dysplasia reveals ADAMTS2 overexpression as a potential marker.

    PubMed

    Zhou, Shang-Hui; Yang, Wen-Jun; Liu, Sheng-Wen; Li, Jiang; Zhang, Chun-Ye; Zhu, Yun; Zhang, Chen-Ping

    2014-01-01

    Fibrous dysplasia (FD) as an abnormal bone growth is one of the common fibro-osseous leasions (FOL) in oral and maxillofacial region, however, its etiology still remains unclear. Here, we performed gene expression profiling of FD using microarray analysis to explore the key molecule events in FD development, and develop potential diagnostic markers or therapeutic targets for FD. We found that 1,881 genes exhibited differential expression with more than two-fold changes in FD compared to normal bone tissues, including 1,200 upregulated genes and 681 downregulated genes. Pathway analysis indicated that obviously activated pathways are Ribosome and ECM-receptor interaction pathways; downregulated pathways are "Hepatitis C" and "cancer" signaling pathways. We further validated the expression of ADAMTS2, one of most differentiated expressed genes, by Immunohistochemistry (IHC) in 40 of FD cases. Results showed that ADAMTS2 was significantly overexpressed in FD tissues, but rarely expressed in normal bone tissues, suggesting that ADAMTS2 could be a potential biomarker for FD. Thus, this study uncovered differentially expressed candidate genes in FD, which provides pilot data for understanding FD pathogenesis, and developing novel biomarkers for diagnosis and targeting of FD.

  13. Ghrelin is a prognostic marker and a potential therapeutic target in breast cancer.

    PubMed

    Grönberg, Malin; Ahlin, Cecilia; Naeser, Ylva; Janson, Eva Tiensuu; Holmberg, Lars; Fjällskog, Marie-Louise

    2017-01-01

    Ghrelin and obestatin are gastrointestinal peptides, encoded by the same preproghrelin gene. Both are expressed in breast cancer tissue and ghrelin has been implicated in breast cancer tumorigenesis. Despite recent advances in breast cancer management the need for new prognostic markers and potential therapeutic targets in breast cancer remains high. We studied the prognostic impact of ghrelin and obestatin in women with node negative breast cancer. Within a cohort of women with breast cancer with tumor size ≤ 50 mm, no lymph node metastases and no initiation of adjuvant chemotherapy, 190 women were identified who died from breast cancer and randomly selected 190 women alive at the corresponding time as controls. Tumor tissues were immunostained with antibodies versus the peptides. Ghrelin expression was associated with better breast cancer specific survival in univariate analyses (OR 0.55, 95% CI 0.36-0.84) and in multivariate models, adjusted for endocrine treatment and age (OR 0.57, 95% CI 0.36-0.89). Obestatin expression was non-informative (OR 1.2, 95% CI 0.60-2.46). Ghrelin expression is independent prognostic factor for breast cancer death in node negative patients-halving the risk for dying of breast cancer. Our data implies that ghrelin could be a potential therapeutic target in breast cancer treatment.

  14. Molecular markers and imaging tools to identify malignant potential in Barrett's esophagus

    PubMed Central

    Bennett, Michael; Mashimo, Hiroshi

    2014-01-01

    Due to its rapidly rising incidence and high mortality, esophageal adenocarcinoma is a major public health concern, particularly in Western countries. The steps involved in the progression from its predisposing condition, gastroesophageal reflux disease, to its premalignant disorder, Barrett’s esophagus, and to cancer, are incompletely understood. Current screening and surveillance methods are limited by the lack of population-wide utility, incomplete sampling of standard biopsies, and subjectivity of evaluation. Advances in endoscopic ablation have raised the hope of effective therapy for eradication of high-risk Barrett’s lesions, but improvements are needed in determining when to apply this treatment and how to follow patients clinically. Researchers have evaluated numerous potential molecular biomarkers with the goal of detecting dysplasia, with varying degrees of success. The combination of biomarker panels with epidemiologic risk factors to yield clinical risk scoring systems is promising. New approaches to sample tissue may also be combined with these biomarkers for less invasive screening and surveillance. The development of novel endoscopic imaging tools in recent years has the potential to markedly improve detection of small foci of dysplasia in vivo. Current and future efforts will aim to determine the combination of markers and imaging modalities that will most effectively improve the rate of early detection of high-risk lesions in Barrett’s esophagus. PMID:25400987

  15. Evolutionary restoration potential evaluated through the use of a trait-linked genetic marker.

    PubMed

    Apgar, Travis M; Pearse, Devon E; Palkovacs, Eric P

    2017-06-01

    Human-driven evolution can impact the ecological role and conservation value of impacted populations. Most evolutionary restoration approaches focus on manipulating gene flow, but an alternative approach is to manipulate the selection regime to restore historical or desired trait values. Here we examined the potential utility of this approach to restore anadromous migratory behavior in coastal California steelhead trout (Oncorhynchus mykiss) populations. We evaluated the effects of natural and anthropogenic environmental variables on the observed frequency of alleles at a genomic marker tightly associated with migratory behavior across 39 steelhead populations from across California, USA. We then modeled the potential for evolutionary restoration at sites that have been impacted by anthropogenic barriers. We found that complete barriers such as dams are associated with major reductions in the frequency of anadromy-associated alleles. The removal of dams is therefore expected to restore anadromy significantly. Interestingly, accumulations of large numbers of partial barriers (passable under at least some flow conditions) were also associated with significant reductions in migratory allele frequencies. Restoration involving the removal of partial barriers could be evaluated alongside dam removal and fishway construction as a cost-effective tool to restore anadromous fish migrations. Results encourage broader consideration of in situ evolution during the development of habitat restoration projects.

  16. Endogenous ERP (Event Related Potential) Components Associated with Performance in Sonar Operators. 1. Reliability and Relation to Training.

    DTIC Science & Technology

    1986-12-31

    2), ERP component (N150, P200 , P400), EEG source (T3, T4, C3, and C4), and task (alternating checkerboard, background pattern, reversal pattern, and...support for the contention that the ERP components studied here are functions of hippocampal activity can be derived from the paper of Schmajuk (16...I AD-A1BZ 478 ENDJ f NOJJ ERP (JUENT RELATED POTENTIAL) COMPONDNUl 1/1 AS O C A TD WITH FEFO (U) NAVAL HEALT R8EARCH CETER UNLSSFE SAN DIEGO CA D J

  17. Potential of marker selection to increase prediction accuracy of genomic selection in soybean (Glycine max L.).

    PubMed

    Ma, Yansong; Reif, Jochen C; Jiang, Yong; Wen, Zixiang; Wang, Dechun; Liu, Zhangxiong; Guo, Yong; Wei, Shuhong; Wang, Shuming; Yang, Chunming; Wang, Huicai; Yang, Chunyan; Lu, Weiguo; Xu, Ran; Zhou, Rong; Wang, Ruizhen; Sun, Zudong; Chen, Huaizhu; Zhang, Wanhai; Wu, Jian; Hu, Guohua; Liu, Chunyan; Luan, Xiaoyan; Fu, Yashu; Guo, Tai; Han, Tianfu; Zhang, Mengchen; Sun, Bincheng; Zhang, Lei; Chen, Weiyuan; Wu, Cunxiang; Sun, Shi; Yuan, Baojun; Zhou, Xinan; Han, Dezhi; Yan, Hongrui; Li, Wenbin; Qiu, Lijuan

    Genomic selection is a promising molecular breeding strategy enhancing genetic gain per unit time. The objectives of our study were to (1) explore the prediction accuracy of genomic selection for plant height and yield per plant in soybean [Glycine max (L.) Merr.], (2) discuss the relationship between prediction accuracy and numbers of markers, and (3) evaluate the effect of marker preselection based on different methods on the prediction accuracy. Our study is based on a population of 235 soybean varieties which were evaluated for plant height and yield per plant at multiple locations and genotyped by 5361 single nucleotide polymorphism markers. We applied ridge regression best linear unbiased prediction coupled with fivefold cross-validations and evaluated three strategies of marker preselection. For plant height, marker density and marker preselection procedure impacted prediction accuracy only marginally. In contrast, for grain yield, prediction accuracy based on markers selected with a haplotype block analyses-based approach increased by approximately 4 % compared with random or equidistant marker sampling. Thus, applying marker preselection based on haplotype blocks is an interesting option for a cost-efficient implementation of genomic selection for grain yield in soybean breeding.

  18. Impact of aeration disturbances on endogenous phosphorus fractions and their algae growth potential from malodorous river sediment.

    PubMed

    Zhu, Jin; He, Yan; Wang, Jianhua; Qiao, Zhaochao; Wang, Yi; Li, Zhihong; Huang, Minsheng

    2017-03-01

    The present work assessed the impact of aeration disturbances on sediment-bound phosphorus fractions and their algae growth potential from a typical malodorous river. Phosphorus was sequentially extracted by a modified version of Hedley fractionation method. It was found that the mean contents of TP was 1476.1 ± 60.3 mg/kg, consisting mainly of dilute HCl-extractable P (52.6%) and NaOH-P (19.2%). The algae growth potential tests demonstrated that algae growth had varied P-level requirements for different P speciation and NaOH-P promoted algae growth remarkably and its promoting effect was positively related to its concentration. Additionally, intermittent overlying water aeration modes were recommended, and run 1 (7.0 mg/L, 12 h) was deemed as the optimized aerated mode in terms of its relatively low ecological risk and high P retention. It was noted that NaOH-P was most affected by aeration disturbance and exhibited marked increase with the elevated dissolved oxygen (DO) level whether for intermittent overlying water or sediment aeration. This research helps to gain improved understanding of the ecological risk on sediment P, and NaOH-P is recognized as one ecologically important P fraction in the sediments considering its relatively high proportion and bioavailability.

  19. Anabolic potential of bone mineral in human periosteal fibroblasts using steroid markers of healing.

    PubMed

    Suchak, A; Soory, M

    2013-05-01

    A deproteinized natural cancellous bone mineral (B) was studied in a cell culture model for its anabolic potential using two radiolabelled steroid substrates, 14C-testosterone (14C-T) and 14C-4-androstenedione (14C-4-A) independently; in the presence or absence of the anti-androgen finasteride (F) and minocycline (M). Culture medium was assayed for the biologically active metabolite 5 alpha-dihydrotestosterone (DHT) a marker of regenerative potential and wound healing. Confluent monolayer cultures of human periosteal fibroblasts were incubated in Eagle's minimum essential medium with each of the substrates 14C-T and 14C-4-A. Incubations were performed with previously established optimal concentrations of B5 (milligrams/ml), M25 (μg/ml) and F5 (μg/ml) alone and in combination (n=6) for 24h. The eluent was solvent extracted with ethyl acetate (2 ml x 2) and subjected to TLC in a benzene/acetone solvent system (4:1 v/v) for separation of metabolites; they were quantified using a radioisotope scanner. The yield of DHT was increased over controls in response to B and M with both substrates 14C-T and 14C-4-A by 1.7, 1.8-fold and 1.7, 1.6-fold respectively (n=6; p<0.001; one way ANOVA). Combined incubations of B and M resulted in similar yields. F inhibited DHT yields with both radiolabelled substrates by 2-3-fold (n=6; p<0.001) which was overcome by a combined incubation of F+B to values similar to those of controls (p<0.01). Documented pro-anabolic effects of minocycline were applicable as a standard for confirmation of responses to B. Significant increases in yields of DHT in response to B and M with both substrates indicate their anabolic potential in periosteal fibroblasts with implications for wound healing.

  20. Stress produces aversion and potentiates cocaine reward by releasing endogenous dynorphins in the ventral striatum to locally stimulate serotonin reuptake.

    PubMed

    Schindler, Abigail G; Messinger, Daniel I; Smith, Jeffrey S; Shankar, Haripriya; Gustin, Richard M; Schattauer, Selena S; Lemos, Julia C; Chavkin, Nicholas W; Hagan, Catherine E; Neumaier, John F; Chavkin, Charles

    2012-12-05

    Activation of the dynorphin/κ-opioid receptor (KOR) system by repeated stress exposure or agonist treatment produces place aversion, social avoidance, and reinstatement of extinguished cocaine place preference behaviors by stimulation of p38α MAPK, which subsequently causes the translocation of the serotonin transporter (SERT, SLC6A4) to the synaptic terminals of serotonergic neurons. In the present study we extend those findings by showing that stress-induced potentiation of cocaine conditioned place preference occurred by a similar mechanism. In addition, SERT knock-out mice did not show KOR-mediated aversion, and selective reexpression of SERT by lentiviral injection into the dorsal raphe restored the prodepressive effects of KOR activation. Kinetic analysis of several neurotransporters demonstrated that repeated swim stress exposure selectively increased the V(max) but not K(m) of SERT without affecting dopamine transport or the high-capacity, low-affinity transporters. Although the serotonergic neurons in the dorsal raphe project throughout the forebrain, a significant stress-induced increase in cell-surface SERT expression was only evident in the ventral striatum, and not in the dorsal striatum, hippocampus, prefrontal cortex, amygdala, or dorsal raphe. Stereotaxic microinjections of the long-lasting KOR antagonist norbinaltorphimine demonstrated that local KOR activation in the nucleus accumbens, but not dorsal raphe, mediated this stress-induced increase in ventral striatal surface SERT expression. Together, these results support the hypothesis that stress-induced activation of the dynorphin/KOR system produces a transient increase in serotonin transport locally in the ventral striatum that may underlie some of the adverse consequences of stress exposure, including the potentiation of the rewarding effects of cocaine.

  1. Stress produces aversion and potentiates cocaine reward by releasing endogenous dynorphins in the ventral striatum to locally stimulate serotonin reuptake

    PubMed Central

    Schindler, Abigail G.; Messinger, Daniel I.; Smith, Jeffrey S.; Shankar, Haripriya; Gustin, Richard M.; Schattauer, Selena S.; Lemos, Julia C.; Chavkin, Nicholas W.; Hagan, Catherine E.; Neumaier, John F.; Chavkin, Charles

    2012-01-01

    Activation of the dynorphin/kappa opioid receptor (KOR) system by repeated stress exposure or agonist treatment produces place aversion, social avoidance, and reinstatement of extinguished cocaine place preference behaviors by stimulation of p38α MAPK, which subsequently causes the translocation of the serotonin transporter (SERT, Slc6a4) to the synaptic terminals of serotonergic neurons. In the present study we extend those findings by showing that stress-induced potentiation of cocaine conditioned place preference occurred by a similar mechanism. In addition, SERT knockout mice did not show KOR-mediated aversion, and selective re-expression of SERT by lenti-viral injection into the dorsal raphe restored the prodepressive effects of KOR activation. Kinetic analysis of several neurotransporters demonstrated that repeated swim stress exposure selectively increased the Vmax but not Km of SERT without affecting dopamine transport or the high capacity, low affinity transporters. Although the serotonergic neurons in the dorsal raphe project throughout the forebrain, a significant stress-induced increase in cell-surface SERT expression was only evident in the ventral striatum, and not in the dorsal striatum, hippocampus, prefrontal cortex, amygdala, or dorsal raphe. Stereotaxic microinjections of the long-lasting KOR antagonist norBNI demonstrated that local KOR activation in the nucleus accumbens, but not dorsal raphe, mediated this stress-induced increase in ventral striatal surface SERT expression. Together, these results support the hypothesis that stress-induced activation of the dynorphin/KOR system produces a transient increase in serotonin transport locally in the ventral striatum that may underlie some of the adverse consequences of stress exposure, including the potentiation of the rewarding effects of cocaine. PMID:23223282

  2. Stimulating endogenous cardiac repair

    PubMed Central

    Finan, Amanda; Richard, Sylvain

    2015-01-01

    The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration, a combination of these approaches could ameliorate the overall repair process to incorporate the participation of multiple cellular players. PMID:26484341

  3. Identification and evaluation of potential forensic marker proteins in vaginal fluid by liquid chromatography/mass spectrometry.

    PubMed

    Igoh, Akihisa; Doi, Yusuke; Sakurada, Koichi

    2015-09-01

    Vaginal fluid is one of the most common body fluids found at crime scenes. Discriminating vaginal fluid from other body fluids is important in forensic science; however, few potential protein markers have been reported to date. Proteomic methods for identifying protein markers have gained attention, although few reports have applied this technology to forensic protein markers. Therefore, to identify characteristic vaginal proteins, we examined various body fluids (nasal secretions, saliva, urine, semen, vaginal fluids, and sweat) using liquid chromatography/electrospray ionization time-of-flight mass spectrometry and peptide mass fingerprinting. We identified three components (average molecular mass values 17,237 ± 2, 18,063 ± 2, and 15,075 ± 1) detectable only in vaginal samples: two human small proline-rich protein 3 (SPRR3) isoforms and a human fatty acid-binding protein 5 (FABP5) with an acetylated (+42) N-terminal region lacking the initiator methionine residue (-131). Using ELISA, these yielded markedly high average values in vaginal fluids. The mass spectra of these proteins were not detected in infant saliva but were detected in the vaginal fluid throughout the menstrual cycle. The results of forensic analysis (detection limit, mixed body fluid samples, casework samples, and blind samples) suggest that these proteins are potential forensic markers. In conclusion, high SPRR3 and FABP5 expression levels, which may be used as potential markers for vaginal fluid identification in forensic science, were detected in vaginal fluids from healthy adults.

  4. Oocytes express an endogenous red fluorescent protein in a stony coral, Euphyllia ancora: a potential involvement in coral oogenesis

    PubMed Central

    Shikina, Shinya; Chiu, Yi-Ling; Chung, Yi-Jou; Chen, Chieh-Jhen; Lee, Yan-Horn; Chang, Ching-Fong

    2016-01-01

    To date,the molecular and cellular mechanisms underlying coral sexual reproduction remain largely unknown. We then performed a differential screen to identify genes related to oogenesis in the stony coral Euphyllia ancora. We identified a clone encoding a novel red fluorescent protein cDNA of E. ancora (named EaRFP). Microscopic observation and quantitative RT-PCR revealed that EaRFP is almost exclusively expressed in the ovary of the adult coral. The combination of the ovarian-cell separation method and the RT-PCR analysis revealed that the oocytes, but not the ovarian somatic cells, are the cells expressing EaRFP. Immunohistochemical analysis revealed that the expression of EaRFP starts in the early stage of the oocyte and continues until the maturation period. Furthermore, recombinant EaRFP was shown to possess an H2O2 degradation activity. These results raise the possibility that EaRFP plays a role in protecting the oocytes from oxidative stress from the early to late stages of oogenesis. The present study provides not only the first evidence for the potential involvement of FPs in coral oogenesis but also an insight into a cellular strategy underlying coral sexual reproduction. PMID:27167722

  5. Metabolomics Profiling for Identification of Novel Potential Markers in Early Prediction of Preeclampsia

    PubMed Central

    Kuc, Sylwia; Koster, Maria P. H.; Pennings, Jeroen L. A.; Hankemeier, Thomas; Berger, Ruud; Harms, Amy C.; Dane, Adrie D.; Schielen, Peter C. J. I.; Visser, Gerard H. A.; Vreeken, Rob J.

    2014-01-01

    Objective The first aim was to investigate specific signature patterns of metabolites that are significantly altered in first-trimester serum of women who subsequently developed preeclampsia (PE) compared to healthy pregnancies. The second aim of this study was to examine the predictive performance of the selected metabolites for both early onset [EO-PE] and late onset PE [LO-PE]. Methods This was a case-control study of maternal serum samples collected between 8+0 and 13+6 weeks of gestation from 167 women who subsequently developed EO-PE n = 68; LO-PE n = 99 and 500 controls with uncomplicated pregnancies. Metabolomics profiling analysis was performed using two methods. One has been optimized to target eicosanoids/oxylipins, which are known inflammation markers and the other targets compounds containing a primary or secondary biogenic amine group. Logistic regression analyses were performed to predict the development of PE using metabolites alone and in combination with first trimester mean arterial pressure (MAP) measurements. Results Two metabolites were significantly different between EO-PE and controls (taurine and asparagine) and one in case of LO-PE (glycylglycine). Taurine appeared the most discriminative biomarker and in combination with MAP predicted EO-PE with a detection rate (DR) of 55%, at a false-positive rate (FPR) of 10%. Conclusion Our findings suggest a potential role of taurine in both PE pathophysiology and first trimester screening for EO-PE. PMID:24873829

  6. Pairwise diversity and tMRCA as potential markers for HIV infection recency

    PubMed Central

    Moyo, Sikhulile; Wilkinson, Eduan; Vandormael, Alain; Wang, Rui; Weng, Jia; Kotokwe, Kenanao P.; Gaseitsiwe, Simani; Musonda, Rosemary; Makhema, Joseph; Essex, Max; Engelbrecht, Susan; de Oliveira, Tulio; Novitsky, Vladimir

    2017-01-01

    Abstract Intrahost human immunodeficiency virus (HIV)-1 diversity increases linearly over time. We assessed the extent to which mean pairwise distances and the time to the most recent common ancestor (tMRCA) inferred from intrahost HIV-1C env sequences were associated with the estimated time of HIV infection. Data from a primary HIV-1C infection study in Botswana were used for this analysis (N = 42). A total of 2540 HIV-1C env gp120 variable loop region 1 to conserved region 5 (V1C5) of the HIV-1 envelope gp120 viral sequences were generated by single genome amplification and sequencing, with an average of 61 viral sequences per participant and 11 sequences per time point per participant. Raw pairwise distances were calculated for each time point and participant using the ape package in R software. The tMRCA was estimated using phylogenetic inference implemented in Bayesian Evolutionary Analysis by Sampling Trees v1.8.2. Pairwise distances and tMRCA were significantly associated with the estimated time since HIV infection (both P < 0.001). Taking into account multiplicity of HIV infection strengthened these associations. HIV-1C env-based pairwise distances and tMRCA can be used as potential markers for HIV recency. However, the tMRCA estimates demonstrated no advantage over the pairwise distances estimates. PMID:28178146

  7. Plasma DNA integrity index as a potential molecular diagnostic marker for breast cancer.

    PubMed

    Kamel, Azza M; Teama, Salwa; Fawzy, Amal; El Deftar, Mervat

    2016-06-01

    Plasma DNA integrity index is increased in various malignancies including breast cancer, the most common cancer in women worldwide; early detection is crucial for successful treatment. Current screening methods fail to detect many cases of breast cancer at an early stage. In this study, we evaluated the level of plasma DNA integrity index in 260 females (95 with breast cancer, 95 with benign breast lesions, and 70 healthy controls) to verify its potential value in discriminating malignant from benign breast lesions. The criteria of the American Joint Committee on Cancer were used for staging of breast cancer patients. DNA integrity index was measured by real-time PCR. DNA integrity index was significantly higher in breast cancer than in benign breast patients and healthy subjects (P = <0.001). DNA integrity index is correlated with TNM stage. Given 100 % specificity, the highest sensitivity achieved in detecting cancer group was 85.3 % at 0.55 DNA integrity index cutoff. In conclusion, the plasma DNA integrity index may be a promising molecular diagnostic marker of malignancy in breast lesions.

  8. The Impact of AD Drug Treatments on Event-Related Potentials as Markers of Disease Conversion

    PubMed Central

    Chapman, Robert M.; Porsteinsson, Anton P.; Gardner, Margaret N.; Mapstone, Mark; McCrary, John W.; Sandoval, Tiffany C.; Guillily, Maria D.; Reilly, Lindsey A.; DeGrush, Elizabeth

    2013-01-01

    This paper investigates how commonly prescribed pharmacologic treatments for Alzheimer’s disease (AD) affect Event-Related Potential (ERP) biomarkers as tools for predicting AD conversion in individuals with Mild Cognitive Impairment (MCI). We gathered baseline ERP data from two MCI groups (those taking AD medications and those not) and later determined which subjects developed AD (Convert->AD) and which subjects remained cognitively stable (Stable). We utilized a previously developed and validated multivariate system of ERP components to measure medication effects among these four subgroups. Discriminant analysis produced classification scores for each individual as a measure of similarity to each clinical group (Convert->AD, Stable), and we found a large significant main Group effect but no main AD Medications effect and no Group by Medications interaction. This suggested AD medications have negligible influence on this set of ERP components as weighted markers of disease progression. These results provide practical information to those using ERP measures as a biomarker to identify and track AD in individuals in a clinical or research setting. PMID:23905997

  9. Increased nuclear ?-catenin expression in oral potentially malignant lesions: A marker of epithelial dysplasia

    PubMed Central

    Rojas-Alcayaga, Gonzalo; Maturana, Andrea; Aitken, Juan-Pablo; Rojas, Carolina; Ortega, Ana-Verónica

    2015-01-01

    Background Deregulation of ?-catenin is associated with malignant transformation; however, its relationship with potentially malignant and malignant oral processes is not fully understood. The aim of this study was to determine and compare the nuclear ?-catenin expression in oral dysplasia and oral squamous cell carcinoma (OSCC). Material and Methods Cross sectional study. Immunodetection of ?-catenin was performed on 72 samples, with the following distribution: 21 mild dysplasia, 12 moderate dysplasia, severe dysplasia 3, 36 OSCC including 19 well differentiated, 15 moderately differentiated and 2 poorly differentiated. Through microscopic observation the number of positive cells per 1000 epithelial cells was counted. For the statistical analysis, the Kruskal Wallis test was used. Results Nuclear expression of ?-catenin was observed in all samples with severe and moderate dysplasia, with a median of 267.5, in comparison to mild dysplasia whose median was 103.75. Only 10 samples (27.7%) with OSCC showed nuclear expression, with statistically significant differences between groups (p < 0.05). Conclusions Our results are consistent with most of the reports which show increased presence of ?-catenin in severe and moderate dysplasia compared to mild dysplasia; however the expression of nuclear ?-catenin decreased after starting the invasive neoplastic process. This suggests a role for this protein in the progression of dysplasia and early malignant transformation to OSCC. Immunodetection of ?-catenin could be a possible immune marker in the detection of oral dysplasia. Key words:Oral squamous cell carcinoma (OSCC), ?-catenin, oral dysplasia. PMID:26241451

  10. Hypermethylation of the COX-2 gene is a potential prognostic marker for cervical cancer.

    PubMed

    Jo, Hoenil; Kang, Sokbom; Kim, Jae W; Kang, Gyeong H; Park, Noh H; Song, Yong S; Park, Sang Y; Kang, Soon B; Lee, Hyo P

    2007-06-01

    The aim of the present study was to evaluate the DNA hypermethylation profiles of 14 genes known to be associated with tumor behavior and their clinical significance in cervical cancer. The clinical features of 82 patients with stage IB cervical cancer were analyzed in terms of DNA hypermethylation of 14 genes (hMLH1, p16, COX-2, CDH1, APC, DAPK, MGMT, p14, RASSF1A, RUNX3, TIMP3, FHIT, THBS1, and HLTF). Of 14 genes investigated, only hypermethylation of COX-2 showed significant association with poor disease-free survival (P = 0.001). To further investigate an alteration in COX-2 expression by DNA hypermethylation, immunohistochemistry for COX-2 protein was performed in the cervical cancer tissues. We found no significant association between hypermethylation and expression patterns of the COX-2 gene. The present results suggest that DNA hypermethylation of the COX-2 gene may be a potential prognostic marker in early stage cervical cancer, the underlying mechanism of which is independent of gene silencing.

  11. Cytoglobin: a potential marker for adipogenic differentiation in preadipocytes in vitro.

    PubMed

    Doğan, Ayşegül; Demirci, Selami; Kıratlı, Binnur; Şahin, Fikrettin

    2017-02-01

    Obesity, mainly characterized by the excess fat storage, is a global health problem resulting in serious morbidity and mortality. Identification of molecular mechanisms in adipogenic differentiation pathway might lead to development of new strategies for diagnosis, prevention and therapy of obesity and associated diseases. Discovery of new genes and proteins in the differentiation pathway could help to understand the key specific regulators of the adipogenesis. Cytoglobin (Cygb), identified as a new globin family member protein, is expressed in various tissues. Although its interaction with oxygen and nitric oxide indicates the potential role in antioxidant pathways, the exact role remains unclear. In the current study, expression level of Cygb was determined in proliferating and differentiating 3T3-F442A cells by gene expression and protein expression analysis. Results revealed that Cygb expression up-regulated in differentiated cells in parallel with adipogenic differentiation markers; PPARγ, CEBPα and FABP4 expressions. Besides, Cygb overexpression in preadipocytes contributed to the adipogenic differentiation as verified by detection of higher lipid droplets and increased PPARγ, CEBPα and FABP4 expressions with respect to control cells. These findings will shed light on the unknown roles of Cygb in adipogenesis and obesity.

  12. Integrin α7 Is a Functional Marker and Potential Therapeutic Target in Glioblastoma.

    PubMed

    Haas, Tobias L; Sciuto, Maria Rita; Brunetto, Lidia; Valvo, Cecilia; Signore, Michele; Fiori, Micol E; di Martino, Simona; Giannetti, Stefano; Morgante, Liliana; Boe, Alessandra; Patrizii, Michele; Warnken, Uwe; Schnölzer, Martina; Ciolfi, Andrea; Di Stefano, Chiara; Biffoni, Mauro; Ricci-Vitiani, Lucia; Pallini, Roberto; De Maria, Ruggero

    2017-07-06

    Functionally relevant markers of glioblastoma stem-like cells (GSCs) have potential for therapeutic targeting to treat this aggressive disease. Here we used generation and screening of thousands of monoclonal antibodies to search for receptors and signaling pathways preferentially enriched in GSCs. We identified integrin α7 (ITGA7) as a major laminin receptor in GSCs and in primary high-grade glioma specimens. Analyses of mRNA profiles in comprehensive datasets revealed that high ITGA7 expression negatively correlated with survival of patients with both low- and high-grade glioma. In vitro and in vivo analyses showed that ITGA7 plays a key functional role in growth and invasiveness of GSCs. We also found that targeting of ITGA7 by RNAi or blocking mAbs impaired laminin-induced signaling, and it led to a significant delay in tumor engraftment plus a strong reduction in tumor size and invasion. Our data, therefore, highlight ITGA7 as a glioblastoma biomarker and candidate therapeutic target. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Calponin-h2: a potential serum marker for the early detection of human breast cancer?

    PubMed

    Debald, Manuel; Jin, Jian-Ping; Linke, Andrea; Walgenbach, Klaus-Jürgen; Rauch, Peter; Zellmer, Angela; Fimmers, Rolf; Kuhn, Walther; Hartmann, Gunther; Walgenbach-Brünagel, Gisela

    2014-11-01

    Early diagnosis is the key for the successful treatment of breast cancer. A serum marker for the early detection of breast cancer could significantly reduce breast cancer morbidity and mortality by bringing the time of diagnosis at an earlier and therefore still curable stage. So far, no biomarker for the early detection is available for the clinical routine. The aim of the present study was to evaluate the use of calponin-h2 as a blood-based biomarker for the early diagnosis of this disease. Using two monoclonal antibodies against calponin-h2, we developed a sandwich ELISA to analyze the serum levels of calponin-h2. In order to evaluate the diagnostic potential of this biomarker, patients with breast cancer (n = 76), benign diseases of the breast (n = 51) and healthy females (n = 24) were analyzed. Serum levels above 10 ng/ml were only observed in patients with breast cancer (n = 8; 10.5%). Further large-scale studies and preanalytic evaluations are necessary to clarify the definite role of calponin-h2 as a biomarker in breast cancer management.

  14. Oncogenic Fli-1 is a potential prognostic marker for the progression of epithelial ovarian cancer.

    PubMed

    Song, Wei; Hu, Lingyun; Li, Wei; Wang, Guanjun; Li, Yan; Yan, Lei; Li, Ailing; Cui, Jiuwei

    2014-06-12

    Ovarian cancer is the most lethal gynecologic malignancy, but its etiology remains poorly understood. This study investigated the role of Fli-1 in ovarian carcinogenesis and disease survival. Fli-1 protein expression was evaluated by immunohistochemistry in 104 primary epithelial ovarian cancer (EOC) patients with known follow-up data and 20 controls. Correlation between Fli-1 expression and clinical characteristics was evaluated with the logistic regression. Kaplan Meier analysis was used to assess the impact of Fli-1 expression on overall survival (OS) and disease-free survival (DFS). Cell proliferation and migration assay were used to explore the function of Fli-1 in ovarian cancer cells. Fli-1 was expressed in 74% cases and up-regulated in EOC tissues compared with normal control tissues (p< 0.05). The high expression of Fli-1 was significantly associated with advanced tumor stage, positive lymph nodal involvement, and poor OS and DFS (p< 0.05). Further analysis showed Fli-1 is an independent prognostic factor for OS and DFS. Down-regulation of Fli-1 inhibited cell proliferation but did not affect cell migration in SKOV3 cells. This study revealed that Fli-1 played an essential role in the development and progression of ovarian cancers. Its overexpression is intimately related to malignant phenotypes and poor clinical outcome, suggesting that Fli-1 is a potential prognostic marker and therapeutic molecular target in ovarian cancer.

  15. Assessment of volatile profile as potential marker of chilling injury of basil leaves during postharvest storage.

    PubMed

    Cozzolino, Rosaria; Pace, Bernardo; Cefola, Maria; Martignetti, Antonella; Stocchero, Matteo; Fratianni, Florinda; Nazzaro, Filomena; De Giulio, Beatrice

    2016-12-15

    The volatile profile of three sweet basil cultivars, "Italico a foglia larga", "Cammeo" and "Italiano classico", packaged in air at 4 or 12°C until 9days, was monitored by solid phase microextraction with GC-MS. Chilling injury (CI) score and electrolyte leakage were also assessed. In total, 71 volatile organic compounds (VOCs) were identified in the headspace of basil samples. A preliminary principal component analysis highlighted the dominant effect of the cultivar on VOCs profiles. Data analysis by post-transformation of projection to latent structures regression (ptPLS2) clarified the role played by time and temperature of storage. Temperature influenced the emission of volatiles during storage, with much lower total volatile emissions at 4°C compared to 12°C. Finally, a ptPLS2 regression model performed on VOCs and the two CI parameters allowed selection of 10 metabolites inversely correlated to both CI parameters, which can be considered potential markers of CI in basil leaves.

  16. Oxidized macrophage migration inhibitory factor is a potential new tissue marker and drug target in cancer

    PubMed Central

    Schinagl, Alexander; Thiele, Michael; Douillard, Patrice; Völkel, Dirk; Kenner, Lukas; Kazemi, Zahra; Freissmuth, Michael; Scheiflinger, Friedrich; Kerschbaumer, Randolf J.

    2016-01-01

    Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine, which was shown to be upregulated in cancers and to exhibit tumor promoting properties. Unlike other cytokines, MIF is ubiquitously present in the circulation and tissue of healthy subjects. We recently described a previously unrecognized, disease-related isoform of MIF, designated oxMIF, which is present in the circulation of patients with different inflammatory diseases. In this article, we report that oxMIF is also linked to different solid tumors as it is specifically expressed in tumor tissue from patients with colorectal, pancreatic, ovarian and lung cancer. Furthermore, oxMIF can be specifically targeted by a subset of phage display-derived fully human, monoclonal anti-MIF antibodies (mAbs) that were shown to neutralize pro-tumorigenic activities of MIF in vivo. We further demonstrate that anti-oxMIF mAbs sensitize human cancer cell lines (LNCaP, PC3, A2780 and A2780ADR) to the action of cytotoxic drugs (mitoxantrone, cisplatin and doxorubicin) in vitro and in an A2780 xenograft mouse model of ovarian cancer. We conclude that oxMIF is the disease related isoform of MIF in solid tumors and a potential new diagnostic marker and drug target in cancer. PMID:27636991

  17. Increased nuclear β-catenin expression in oral potentially malignant lesions: A marker of epithelial dysplasia.

    PubMed

    Reyes, Montserrat; Rojas-Alcayaga, Gonzalo; Maturana, Andrea; Aitken, Juan-Pablo; Rojas, Carolina; Ortega, Ana-Verónica

    2015-09-01

    Deregulation of β-catenin is associated with malignant transformation; however, its relationship with potentially malignant and malignant oral processes is not fully understood. The aim of this study was to determine and compare the nuclear β-catenin expression in oral dysplasia and oral squamous cell carcinoma (OSCC). Cross sectional study. Immunodetection of β-catenin was performed on 72 samples, with the following distribution: 21 mild dysplasia, 12 moderate dysplasia, severe dysplasia 3, 36 OSCC including 19 well differentiated, 15 moderately differentiated and 2 poorly differentiated. Through microscopic observation the number of positive cells per 1000 epithelial cells was counted. For the statistical analysis, the Kruskal Wallis test was used. Nuclear expression of β-catenin was observed in all samples with severe and moderate dysplasia, with a median of 267.5, in comparison to mild dysplasia whose median was 103.75. Only 10 samples (27.7%) with OSCC showed nuclear expression, with statistically significant differences between groups (p < 0.05). Our results are consistent with most of the reports which show increased presence of β-catenin in severe and moderate dysplasia compared to mild dysplasia; however the expression of nuclear β-catenin decreased after starting the invasive neoplastic process. This suggests a role for this protein in the progression of dysplasia and early malignant transformation to OSCC. Immunodetection of β-catenin could be a possible immune marker in the detection of oral dysplasia.

  18. Potential serodiagnostic markers for Q fever identified in Coxiella burnetii by immunoproteomic and protein microarray approaches

    PubMed Central

    2012-01-01

    Background Coxiella burnetii is the etiological agent of Q fever. The clinical diagnosis of Q fever is mainly based on several serological tests. These tests all need Coxiella organisms which are difficult and hazardous to culture and purify. Results An immunoproteomic study of C. burnetii Xinqiao strain isolated in China was conducted with the sera from experimentally infected BALB/c mice and Q fever patients. Twenty of whole proteins of Xinqiao recognized by the infection sera were identified by mass spectrometry. Nineteen of the 20 proteins were successfully expressed in Escherichia coli and used to fabricate a microarray which was probed with Q fever patient sera. As a result, GroEL, YbgF, RplL, Mip, OmpH, Com1, and Dnak were recognized as major seroreactive antigens. The major seroreactive proteins were fabricated in a small microarray and further analyzed with the sera of patients with rickettsial spotted fever, Legionella pneumonia or streptococcal pneumonia. In this analysis, these proteins showed fewer cross-reactions with the tested sera. Conclusions Our results demonstrate that these 7 Coxiella proteins gave a modest sensitivity and specificity for recognizing of Q fever patient sera, suggesting that they are potential serodiagnostic markers for Q fever. PMID:22420424

  19. Platelet–lymphocyte ratios: a potential marker for pulmonary tuberculosis diagnosis in COPD patients

    PubMed Central

    Chen, Guozhong; Wu, Chunling; Luo, Zhiying; Teng, Yiming; Mao, Suping

    2016-01-01

    Background In recent decades, morbidity and mortality have been found to be significantly increased in patients with chronic obstructive pulmonary disease (COPD) complicated with pulmonary tuberculosis (PTB). Platelet–lymphocyte ratio (PLR) is an indicator for inflammatory diseases. This study aims to investigate whether PLR could act as a potential marker for patients with COPD complicated with PTB. Methods In this retrospective study, laboratory characteristics of 87 COPD patients complicated with PTB (determined by Mycobacterium tuberculosis positive culture from sputum or bronchial lavage fluid) and 83 COPD patients (as the control group, determined by M. tuberculosis culture negativity from sputum or bronchial lavage fluid) were investigated. Data obtained on the day of admission were analyzed. Results PLR >216.82 was identified as the optimal cutoff value for discriminating COPD patients with PTB (sensitivity 92.4%, specificity 84.5%, positive-predictive value 91.6%, negative-predictive value 86.2%, and area under the curve [AUC] was 0.87) from patients with COPD alone. The AUC of PLR was significantly greater than that of neutrophil–lymphocyte count ratio (AUC, 0.74; 95% confidence interval, 0.67–0.81; P<0.01). Conclusion PLR could be developed as a valuable maker for identifying tuberculosis infection in COPD patients. PMID:27843310

  20. Potentials and Limitations of Guiding Liver Stereotactic Body Radiation Therapy Set-Up on Liver-Implanted Fiducial Markers

    SciTech Connect

    Wunderink, Wouter; Mendez Romero, Alejandra; Seppenwoolde, Yvette; Boer, Hans de; Levendag, Peter; Heijmen, Ben

    2010-08-01

    Purpose: We investigated the potentials and limitations of guiding liver stereotactic body radiation therapy (SBRT) set-up on liver-implanted fiducial markers. Methods and Materials: Twelve patients undergoing compression-supported SBRT in a stereotactic body frame received fluoroscopy at treatment preparation and before each treatment fraction. In fluoroscopic videos we localized the markers and diaphragm tip at expiration and the spine (measurements on free-breathing and abdominal compression). Day-to-day displacements, rotations (markers only), and deformations were determined. Marker guidance was compared to conventional set-up strategies in treatment set-up simulations. Results: For compression, day-to-day motion of markers with respect to their centers of mass (COM) was {sigma} = 0.9 mm (random error SD), {Sigma} = 0.4 mm (systematic error SD), and <2.1 mm (maximum). Consequently, assuming that markers were closely surrounding spherical tumors, marker COM-guided set-up would have required safety margins of {approx}2 mm. Using marker COM as the gold standard, other set-up methods (using no correction, spine registration, and diaphragm tip craniocaudal registration) resulted in set-up errors of 1.4 mm < {sigma} < 2.8 mm, 2.6 mm < {Sigma} < 5.1 mm, and 6.3 mm < max < 12.4 mm. Day-to-day intermarker motion of <16.7%, 2.2% median, and rotations between 3.5{sup o} and 7.2{sup o} were observed. For markers not surrounding the tumor, e.g., 5 cm between respective COMs, these changes could effect residual tumor set-up errors up to 8.4 mm, 1.1 mm median (deformations), and 3.1 mm to 6.3 mm (rotations). Compression did not systematically contribute to deformations and rotations, since similar results were observed for free-breathing. Conclusions: If markers can be implanted near and around the tumor, residual set-up errors by marker guidance are small compared to those of conventional set-up methods, allowing high-precision tumor radiation set-up. However, substantial

  1. The serum zinc concentration as a potential biological marker in patients with major depressive disorder.

    PubMed

    Styczeń, Krzysztof; Sowa-Kućma, Magdalena; Siwek, Marcin; Dudek, Dominika; Reczyński, Witold; Szewczyk, Bernadeta; Misztak, Paulina; Topór-Mądry, Roman; Opoka, Włodzimierz; Nowak, Gabriel

    2017-02-01

    Despite many clinical trials assessing the role of zinc in major depressive disorder (MDD), the conclusions still remain ambiguous. The aim of the present clinical study was to determine and comparison the zinc concentration in the blood of MDD patients (active stage or remission) and healthy volunteers (controls), as well as to discuss its potential clinical usefulness as a biomarker of the disease. In this study 69 patients with current depressive episode, 45 patients in remission and 50 controls were enrolled. The zinc concentration was measured by electrothermal atomic absorption spectrometry (ET AAS). The obtained results revealed, that the zinc concentration in depressed phase were statistically lower than in the healthy volunteers [0.89 vs. 1.06 mg/L, respectively], while the zinc level in patients achieve remission was not significantly different from the controls [1.07 vs. 1.06 mg/L, respectively]. Additionally, among the patients achieve remission a significant differences in zinc concentration between group with and without presence of drug-resistance in the previous episode of depression were observed. Also, patients in remission demonstrated correlation between zinc level and the average number of depressive episodes in the last year. Serum zinc concentration was not dependent on atypical features of depression, presence of psychotic symptoms or melancholic syndrome, age, age of onset or duration of disease, number of episodes in the life time, duration of the episode/remission and severity of depression measured by the Hamilton Rating Scale for Depression (HDRS), and the Montgomery-Asberg Depression Rating Scale (MADRS). Concluding, our findings confirm the correlation between zinc deficit present in the depressive episode, and are consistent with the majority of previous studies. These results may also indicate that serum zinc concentration might be considered as a potential biological marker of MDD.

  2. Role of CD248 as a potential severity marker in idiopathic pulmonary fibrosis.

    PubMed

    Bartis, Domokos; Crowley, Louise E; D'Souza, Vijay K; Borthwick, Lee; Fisher, Andrew J; Croft, Adam P; Pongrácz, Judit E; Thompson, Richard; Langman, Gerald; Buckley, Christopher D; Thickett, David R

    2016-04-14

    CD248 or Endosialin is a transmembrane molecule expressed in stromal cells binding to extracellular matrix (ECM) components. It has been previously implicated in kidney fibrosis, rheumatoid arthritis as well as in tumour-stromal interactions. This study investigates the role of CD248 in the pathogenesis of fibrotic diseases in Idiopathic Pulmonary Fibrosis (IPF). CD248 quantitative immunohistochemistry (IHC) was performed on lung samples from 22 IPF patients and its expression was assayed in cultured pulmonary fibroblasts and epithelial cells. Effects of CD248 silencing was evaluated on fibroblast proliferation and myofibroblast differentiation. IHC revealed strong CD248 expression in mesenchymal cells of normal lung structures such as pleura and adventitia but not in epithelium. Fibrotic areas showed markedly stronger staining than unaffected lung tissue. The extent of CD248 staining showed a significant negative correlation to lung function parameters FEV1, FVC, TLC, and TLCO (r2 > 0 · 35, p < 0 · 01). CD248 protein levels were significantly greater in IPF-derived lung fibroblasts vs normal lung fibroblasts (p < 0 · 01) and CD248 silencing significantly reduced the proliferation of lung fibroblasts, but did not affected myofibroblast differentiation. We conclude that CD248 overexpression is possibly involved in the pathogenesis of IPF and it has potential as a disease severity marker. Given that CD248 ligands are collagen type I, IV and fibronectin, we hypothesise that CD248 signalling represents a novel matrix-fibroblast interaction that may be a potential therapeutic target in IPF.

  3. [(11)C]-Acetoacetate PET imaging: a potential early marker for cardiac heart failure.

    PubMed

    Croteau, Etienne; Tremblay, Sébastien; Gascon, Suzanne; Dumulon-Perreault, Véronique; Labbé, Sébastien M; Rousseau, Jacques A; Cunnane, Stephen C; Carpentier, André C; Bénard, François; Lecomte, Roger

    2014-01-01

    The ketone body acetoacetate could be used as an alternate nutrient for the heart, and it also has the potential to improve cardiac function in an ischemic-reperfusion model or reduce the mitochondrial production of oxidative stress involved in cardiotoxicity. In this study, [(11)C]-acetoacetate was investigated as an early marker of intracellular damage in heart failure. A rat cardiotoxicity heart failure model was induced by doxorubicin, Dox(+). [(14)C]-Acetoacetate, a non-positron (β-) emitting radiotracer, was used to characterize the arterial blood input function and myocardial mitochondrial uptake. Afterward, [(11)C]-acetoacetate (β+) myocardial PET images were obtained for kinetic analysis and heart function assessment in control Dox(-) (n=15) and treated Dox(+) (n=6) rats. The uptake rate (K1) and myocardial clearance rate (k2or kmono) were extracted. [(14)C]-Acetoacetate in the blood was increased in Dox(+), from 2 min post-injection until the last withdrawal point when the heart was harvested, as well as the uptake in the heart and myocardial mitochondria (unpaired t-test, p <0.05). PET kinetic analysis of [(11)C]-acetoacetate showed that rate constants K1, k2 and kmono were decreased in Dox(+) (p <0.05) combined with a reduction of 24% of the left ventricular ejection fraction (p <0.001). Radioactive acetoacetate ex vivo analysis [(14)C], and in vivo kinetic [(11)C] studies provided evidence that [(11)C]-acetoacetate can assess heart failure Dox(+). Contrary to myocardial flow reserve (rest-stress protocol), [(11)C]-acetoacetate can be used to assess reduced kinetic rate constants without requirement of hyperemic stress response. The proposed [(11)C]-acetoacetate cardiac radiotracer in the investigation of heart disease is novel and paves the way to a potential role for [(11)C]-acetoacetate in cardiac pathophysiology. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Event-related potential markers of brain changes in preclinical familial Alzheimer disease

    PubMed Central

    Ally, B.A.; Celone, K.; McKeever, J.; Ruiz-Rizzo, A.L.; Lopera, F.; Stern, C.E.; Budson, A.E.

    2011-01-01

    Objectives: Event-related potentials (ERPs) can reflect differences in brain electrophysiology underlying cognitive functions in brain disorders such as dementia and mild cognitive impairment. To identify individuals at risk for Alzheimer disease (AD) we used high-density ERPs to examine brain physiology in young presymptomatic individuals (average age 34.2 years) who carry the E280A mutation in the presenilin-1 (PSEN1) gene and will go on to develop AD around the age of 45. Methods: Twenty-one subjects from a Colombian population with familial AD participated: 10 presymptomatic subjects positive for the PSEN1 mutation (carriers) and 11 siblings without the mutation (controls). Subjects performed a visual recognition memory test while 128-channel ERPs were recorded. Results: Despite identical behavioral performance, PSEN1 mutation carriers showed less positivity in frontal regions and more positivity in occipital regions, compared to controls. These differences were more pronounced during the 200–300 msec period. Discriminant analysis at this time interval showed promising sensitivity (72.7%) and specificity (81.8%) of the ERP measures to predict the presence of AD pathology. Conclusions: Presymptomatic PSEN1 mutation carriers show changes in brain physiology that can be detected by high-density ERPs. The relative differences observed showing greater frontal positivity in controls and greater occipital positivity in carriers indicates that control subjects may use frontally mediated processes to distinguish between studied and unstudied visual items, whereas carriers appear to rely more upon perceptual details of the items to distinguish between them. These findings also demonstrate the potential usefulness of ERP brain correlates as preclinical markers of AD. PMID:21775732

  5. Peripheral blood mononuclear cells: a potential source of homeostatic imbalance markers associated with obesity development.

    PubMed

    Oliver, Paula; Reynés, Bàrbara; Caimari, Antoni; Palou, Andreu

    2013-04-01

    Peripheral blood mononuclear cells (PBMC) have a great potential for nutrition and obesity studies. PBMC reflect the nutritional response of key organs involved in energy homeostasis maintenance, which is altered in the obese state. Here, we aimed to determine the usefulness of PBMC as a source of early markers of obesity. To that purpose, we analysed whether PBMC could reflect the insensitivity to changes in feeding conditions associated with obesity during the development of this pathology. Expression of key genes central to energy metabolism was measured by Q-PCR in PBMC samples of normoweight (control) and cafeteria-fed (obese) rats in feeding, fasting and refeeding conditions. Samples were obtained monthly from 2 (beginning of cafeteria diet-feeding) to 6 months of age. In general terms, expression of genes related to fatty acid synthesis (Fasn, Srebp1) and adipogenesis (Pparg) decreased with fasting and increased with refeeding. Conversely, the expression of a key gene regulating beta-oxidation (Cpt1a) and the gene for an orexigenic neuropeptide (Npy)-in accordance with their metabolic role-increased with fasting and decreased with refeeding. This expression pattern disappeared in obese rats, in which insensitivity to feeding conditions was observed after only 1 month of cafeteria diet-feeding. Thus, during development, PBMC accurately reflect nutritional regulation of energy homeostasic genes and the insensitivity to feeding associated with obesity, even in the earlier stages with a low degree of overweight. For this reason, this set of blood cells could constitute a potential source of biomarkers of early homeostatic imbalance which would be useful in nutrition studies that could help prevent the occurrence of obesity.

  6. FXYD5 is a Marker for Poor Prognosis and a Potential Driver for Metastasis in Ovarian Carcinomas

    PubMed Central

    Raman, Pichai; Purwin, Timothy; Pestell, Richard; Tozeren, Aydin

    2015-01-01

    Ovarian cancer (OC) is a leading cause of cancer mortality, but aside from a few well-studied mutations, very little is known about its underlying causes. As such, we performed survival analysis on ovarian copy number amplifications and gene expression datasets presented by The Cancer Genome Atlas in order to identify potential drivers and markers of aggressive OC. Additionally, two independent datasets from the Gene Expression Omnibus web platform were used to validate the identified markers. Based on our analysis, we identified FXYD5, a glycoprotein known to reduce cell adhesion, as a potential driver of metastasis and a significant predictor of mortality in OC. As a marker of poor outcome, the protein has effective antibodies against it for use in tissue arrays. FXYD5 bridges together a wide variety of cancers, including ovarian, breast cancer stage II, thyroid, colorectal, pancreatic, and head and neck cancers for metastasis studies. PMID:26494976

  7. Using marker pens on patients: a potential source of cross infection with MRSA.

    PubMed

    Tadiparthi, S; Shokrollahi, K; Juma, A; Croall, J

    2007-10-01

    Marker pens are widely used in surgery but pre-operative marking of patients may be a cause of bacterial cross-infection. Two experiments were performed to assess whether marking pens can be cause of cross-infection: (i) 26 indelible marker pens were collected from surgical wards for analysis; and (ii) 'fresh' as well as 'dry' (artificially dried by removing cap and exposing tip for 2 h) new permanent marker pens, and whiteboard marker pens were inoculated by dipping the tips into various concentrations of methicillin-resistant Staphylococcus aureus (MRSA). Each pen was inoculated onto 2 blood agar plates at 0 (immediately after inoculation) to 30 min at various intervals, 4 h and 24 h. The plates were incubated for 18 h at 35 degrees C in an incubator. Of 26 pens collected from the wards, 2 cultured Micrococci spp. (skin commensals). The constituents of new 'fresh' pen tips rapidly kill MRSA - in all cases by 4 h, but usually within minutes. At high inoculum concentrations, MRSA is not killed immediately. Dry marker pens harbour MRSA for at least 30 min and probably longer. Marker pens can act as fomites for nosocomial infection. The ethanol-based ink in permanent marker pens has a bactericidal action against MRSA that starts within seconds, and they are likely to be safe to use with a gap of at least 2 min between patients. Usually, harmless skin commensals are not pathogenic except in immunocompromised patients. Old or dried-out marker pens can harbour pathogens and should be discarded before attempted use on patients. We recommend disposable markers for the immunocompromised and patients with a known positive MRSA status.

  8. Using Marker Pens on Patients: a Potential Source of Cross Infection with MRSA

    PubMed Central

    Tadiparthi, S; Shokrollahi, K; Juma, A; Croall, J

    2007-01-01

    INTRODUCTION Marker pens are widely used in surgery but pre-operative marking of patients may be a cause of bacterial cross-infection. PATIENTS AND METHODS Two experiments were performed to assess whether marking pens can be cause of cross-infection: (i) 26 indelible marker pens were collected from surgical wards for analysis; and (ii) ‘fresh’ as well as ‘dry’ (artificially dried by removing cap and exposing tip for 2 h) new permanent marker pens, and whiteboard marker pens were inoculated by dipping the tips into various concentrations of methicillin-resistant Staphylococcus aureus (MRSA). Each pen was inoculated onto 2 blood agar plates at 0 (immediately after inoculation) to 30 min at various intervals, 4 h and 24 h. The plates were incubated for 18 h at 35°C in an incubator. RESULTS Of 26 pens collected from the wards, 2 cultured Micrococci spp. (skin commensals). The constituents of new ‘fresh’ pen tips rapidly kill MRSA – in all cases by 4 h, but usually within minutes. At high inoculum concentrations, MRSA is not killed immediately. Dry marker pens harbour MRSA for at least 30 min and probably longer. CONCLUSIONS Marker pens can act as fomites for nosocomial infection. The ethanol-based ink in permanent marker pens has a bactericidal action against MRSA that starts within seconds, and they are likely to be safe to use with a gap of at least 2 min between patients. Usually, harmless skin commensals are not pathogenic except in immunocompromised patients. Old or dried-out marker pens can harbour pathogens and should be discarded before attempted use on patients. We recommend disposable markers for the immunocompromised and patients with a known positive MRSA status. PMID:17959001

  9. Neuroglobin - a potential biological marker of retinal damage induced by LED light.

    PubMed

    Yu, Z-L; Qiu, S; Chen, X-C; Dai, Z-H; Huang, Y-C; Li, Y-N; Cai, R-H; Lei, H-T; Gu, H-Y

    2014-06-13

    Neuroglobin (NGB), a protein highly expressed in the retina, has been shown to be up-regulated to protect neurons from hypoxic and ischemic injuries. It exhibits neuroprotective functions and plays an important role in the survival of neurons. Recent studies show that light-emitting diode (LED) white light emitted significant amounts of blue light (short-wavelength), which may be harmful to retinal cells, but the studies about biomarkers for evaluating the damage from LED white light are still insufficient. In our study, we found that NGB levels in the retina showed a twofold increase and peaked at 1h after a 1-h exposure to blue light (453 nm) which did not cause damage to the retina. However, retinal damage was observed after 2h of blue-light irradiation, which induced an approximate sevenfold increase of NGB levels as confirmed by Western blot and RT-PCR analysis. Immunofluorescence study demonstrated that NGB was predominantly up-regulated in the ganglion cell layer (GCL), plexiform layer (PL) and photoreceptor layer (PRL). We also examined Ngb mRNA and protein expression in the damaged retina induced by light of other wavelengths given equal photon fluxes. The LED red light (625 nm), green light (527 nm) and blue light (453 nm) increased the expression of NGB and caused TdT-mediated dUTP nick-end labeling-positive cells, especially in the blue-light group. In addition, a negative correlation between NGB and rhodopsin was observed. These findings suggested that there was a correlation between NGB expression and the severity of the retinal damage, indicating NGB's potential function as a biological marker of retinal damage induced by LED light. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. SEL1L, an UPR response protein, a potential marker of colonic cell transformation.

    PubMed

    Ashktorab, Hassan; Green, William; Finzi, Giovanna; Sessa, Fausto; Nouraie, Mehdi; Lee, Edward L; Morgano, Annalisa; Moschetta, Antonio; Cattaneo, Monica; Mariani-Costantini, Renato; Brim, Hassan; Biunno, Ida

    2012-04-01

    SEL1L gene product is implicated in the endoplasmic reticulum (ER)-associated protein degradation and Unfolded Protein Response pathways. This gene and associated miRNAs have been indicated as predictive and prognostic markers of pancreatic cancer. Explore the role of SEL1L in colorectal cancer (CRC) progression. SEL1L expression was analysed immunohistochemically in 153 adenomas and 71 CRCs from African American and North Italian patients. The distribution of stained cells was determined by computing median and inter quartile range. The receiver operating characteristics plot was used as discriminate power of SEL1L expression, CRC diagnosis and the effects on patient survival. SEL1L was low in normal mucosa and confined to few scattered cells at the base crypt of the villi and in the foveolar glandular compartment. The highest levels were in Paneth cells within the lysosomes. The enterocytic progenitor cells and mature enterocytes showed less cytoplasmic staining. In CRCs, SEL1L expression significantly correlated with the progression from adenoma to carcinoma (P = 0.0001) being stronger in well-to-moderately differentiated cancers. No correlation was found with other clinicopathological characteristics or ethnicity. SEL1L expression is a potential CRC tissue biomarker since its expression is significantly higher in adenoma cells with respect to normal mucosa. The levels of expression decrease sensibly in undifferentiated CRC cancers. Interestingly, Paneth cells contain high levels of SEL1L protein that could indicate pre-neoplastic mucosa undergoing neoplastic transformation. Since SEL1L's major function lies within ER stress and active ERAD response, it may identify CRCs with differentiated secretory phenotype and acute cellular stress.

  11. MIC16 gene represents a potential novel genetic marker for population genetic studies of Toxoplasma gondii.

    PubMed

    Liu, Wen-Ge; Xu, Xiao-Pei; Chen, Jia; Xu, Qian-Ming; Luo, Si-Long; Zhu, Xing-Quan

    2016-06-08

    The zoonotic agent Toxoplasma gondii is distributed world-wide, and can infect a broad range of hosts including humans. Microneme protein 16 of T. gondii (TgMIC16) is responsible for binding to aldolase, and is associated with rhomboid cleavage and presence of trafficking signals during invasion. However, little is known of the TgMIC16 sequence diversity among T. gondii isolates from different hosts and geographical locations. In this study, we examined sequence variation in MIC16 gene among T. gondii isolates from different hosts and geographical regions. The entire genomic region of the MIC16 gene was amplified and sequenced, and phylogenetic relationship was reconstructed using Bayesian inference (BI) and maximum parsimony (MP) based on the MIC16 gene sequences. The results of sequence alignments showed two lengths of the sequence of MIC16 gene among all the examined 12 T. gondii strains: 4391 bp for strains TgCatBr5 and MAS, and 4394 bp for strains RH, TgPLH, GT1, PRU, QHO, PTG, PYS, GJS, CTG and TgToucan. Their A+T content ranged from 50.30 to 50.59 %. A total of 107 variable nucleotide positions (0.1-0.9 %) were identified, including 29 variations in 10 exons and 78 variations in 9 introns. Phylogenetic analysis of MIC16 sequences showed that typical genotypes (Type I, II and III) were able to be grouped into their respective genotypes. Moreover, the three major clonal lineages (Type I, II and III) can be differentiated by PCR-RFLP using restriction enzyme Pst I. Phylogenetic analysis and PCR-RFLP of the MIC16 locus among T. gondii isolates from different hosts and geographical regions allowed the differentiation of three major clonal lineages (Type I, II and III) into their respective genotypes, suggesting that MIC16 gene may provide a novel potential genetic marker for population genetic studies of T. gondii isolates.

  12. Adropin as a potential marker of enzyme-positive acute coronary syndrome.

    PubMed

    Aydin, Suna; Eren, Mehmet Nesimi; Yilmaz, Musa; Kalayci, Mehmet; Yardim, Meltem; Alatas, Omer Dogan; Kuloglu, Tuncay; Balaban, Huseyin; Cakmak, Tolga; Kobalt, Mehmet Ali; Çelik, Ahmet; Aydin, Suleyman

    Enzyme-positive acute coronary syndrome (EPACS) can cause injury to or death of the heart muscle owing to prolonged ischaemia. Recent research has indicated that in addition to liver and brain cells, cardiomyocytes also produce adropin. We hypothesised that adropin is released into the bloodstream during myocardial injury caused by acute coronary syndrome (ACS), so serum and saliva levels rise as the myocytes die. Therefore, it could be useful to investigate how ACS affects the timing and significance of adropin release in human subjects. Samples were taken over three days after admission, from 22 EPACS patients and 24 age- and gendermatched controls. The three major salivary glands (submandibular, sublingual and parotid) were immunohistochemically screened for adropin production, and serum and saliva adropin levels were measured by an enzyme-linked immunosorbent assay (ELISA). Salivary gland cells produce and secrete adropin locally. Serum adropin, troponin I, CK and CK-MB concentrations in the EPACS group became gradually higher than those in the control group up to six hours (p < 0.05), and troponin I continued to rise up to 12 hours after EPACS. The same relative increase in adropin level was observed in the saliva. Troponin I, CK and CK-MB levels started to decrease after 12 hours, while saliva and serum adropin levels started to decrease at six hours after EPACS. In samples taken four hours after EPACS, when the serum adropin value averaged 4.43 ng/ml, the receiver operating characteristic curve showed that the serum adropin concentration indicated EPACS with 91.7% sensitivity and 50% specificity, while when the cut-off adropin value in saliva was 4.12 ng/ml, the saliva adropin concentration indicated EPACS with 91.7% sensitivity and 57% specificity. In addition to cardiac troponin and CK-MB assays, measurement of adropin level in saliva and serum samples is a potential marker for diagnosing EPACS.

  13. Metabolomic profiling reveals potential markers and bioprocesses altered in bladder cancer progression.

    PubMed

    Putluri, Nagireddy; Shojaie, Ali; Vasu, Vihas T; Vareed, Shaiju K; Nalluri, Srilatha; Putluri, Vasanta; Thangjam, Gagan Singh; Panzitt, Katrin; Tallman, Christopher T; Butler, Charles; Sana, Theodore R; Fischer, Steven M; Sica, Gabriel; Brat, Daniel J; Shi, Huidong; Palapattu, Ganesh S; Lotan, Yair; Weizer, Alon Z; Terris, Martha K; Shariat, Shahrokh F; Michailidis, George; Sreekumar, Arun

    2011-12-15

    Although alterations in xenobiotic metabolism are considered causal in the development of bladder cancer, the precise mechanisms involved are poorly understood. In this study, we used high-throughput mass spectrometry to measure over 2,000 compounds in 58 clinical specimens, identifying 35 metabolites which exhibited significant changes in bladder cancer. This metabolic signature distinguished both normal and benign bladder from bladder cancer. Exploratory analyses of this metabolomic signature in urine showed promise in distinguishing bladder cancer from controls and also nonmuscle from muscle-invasive bladder cancer. Subsequent enrichment-based bioprocess mapping revealed alterations in phase I/II metabolism and suggested a possible role for DNA methylation in perturbing xenobiotic metabolism in bladder cancer. In particular, we validated tumor-associated hypermethylation in the cytochrome P450 1A1 (CYP1A1) and cytochrome P450 1B1 (CYP1B1) promoters of bladder cancer tissues by bisulfite sequence analysis and methylation-specific PCR and also by in vitro treatment of T-24 bladder cancer cell line with the DNA demethylating agent 5-aza-2'-deoxycytidine. Furthermore, we showed that expression of CYP1A1 and CYP1B1 was reduced significantly in an independent cohort of bladder cancer specimens compared with matched benign adjacent tissues. In summary, our findings identified candidate diagnostic and prognostic markers and highlighted mechanisms associated with the silencing of xenobiotic metabolism. The metabolomic signature we describe offers potential as a urinary biomarker for early detection and staging of bladder cancer, highlighting the utility of evaluating metabolomic profiles of cancer to gain insights into bioprocesses perturbed during tumor development and progression.

  14. Application of microsatellite markers as potential tools for traceability of Girgentana goat breed dairy products.

    PubMed

    Sardina, Maria Teresa; Tortorici, Lina; Mastrangelo, Salvatore; Di Gerlando, Rosalia; Tolone, Marco; Portolano, Baldassare

    2015-08-01

    In livestock, breed assignment may play a key role in the certification of products linked to specific breeds. Traceability of farm animals and authentication of their products can contribute to improve breed profitability and sustainability of animal productions with significant impact on the rural economy of particular geographic areas and on breed and biodiversity conservation. With the goal of developing a breed genetic traceability system for Girgentana dairy products, the aim of this study was to identify specific microsatellite markers able to discriminate among the most important Sicilian dairy goat breeds, in order to detect possible adulteration in Girgentana dairy products. A total of 20 microsatellite markers were analyzed on 338 individual samples from Girgentana, Maltese, and Derivata di Siria goat breeds. Specific microsatellite markers useful for traceability of dairy products were identified. Eight microsatellite markers showed alleles present at the same time in Maltese and Derivata di Siria and absent in Girgentana and, therefore, they were tested on DNA pools of the three breeds. Considering the electropherograms' results, only FCB20, SRCRSP5, and TGLA122 markers were tested on DNA samples extracted from cheeses of Girgentana goat breed. These three microsatellite markers could be applied in a breed genetic traceability system of Girgentana dairy products in order to detect adulteration due to Maltese and Derivata di Siria goat breeds. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Vitamin B12 as a potential compliance marker for fish intake.

    PubMed

    Scheers, Nathalie; Lindqvist, Helen; Langkilde, Anna Maria; Undeland, Ingrid; Sandberg, Ann-Sofie

    2014-09-01

    The aim of the present study was to investigate whether the following four markers: vitamin B12, selenium, vitamin D, and parvalbumin may be used as compliance markers for fish intake. Blood samples from a randomized cross-over herring intervention study (n = 32) were analysed by HPLC and immunochemistry. The criteria were that plasma or serum concentrations of candidate compliance markers after the herring diet should increase significantly compared to starting concentrations. In addition, the reference meat diet should not yield an increase in plasma concentration of the candidate marker. Vitamin B12 and selenium met the set criteria for indicating a correlation between the marker and fish intake with significant increases in serum concentrations at 8.9% (p = 0.008) and 4.6% (p = 0.02), respectively, after a 6-week herring intervention (5 meals a week). Parvalbumin and 25-hydroxy vitamin D3 levels did not increase significantly after the herring interventions. Vitamin B12 may be suitable as a compliance marker for fish intake. Although selenium also met the criteria, the change in selenium serum concentrations was small compared to the change in vitamin B12 levels.

  16. Endogenous Antibodies for Tumor Detection

    PubMed Central

    Rich, Barrie S.; Honeyman, Joshua N.; Darcy, David G.; Smith, Peter T.; Williams, Andrew R.; Lim, Irene Isabel P.; Johnson, Linda K.; Gönen, Mithat; Simon, Joel S.; LaQuaglia, Michael P.; Simon, Sanford M.

    2014-01-01

    The study of cancer immunology has provided diagnostic and therapeutic instruments through serum autoantibody biomarkers and exogenous monoclonal antibodies. While some endogenous antibodies are found within or surrounding transformed tissue, the extent to which this exists has not been entirely characterized. We find that in transgenic and xenograft mouse models of cancer, endogenous gamma immunoglobulin (IgG) is present at higher concentration in malignantly transformed organs compared to non-transformed organs in the same mouse or organs of cognate wild-type mice. The enrichment of endogenous antibodies within the malignant tissue provides a potential means of identifying and tracking malignant cells in vivo as they mutate and diversify. Exploiting these antibodies for diagnostic and therapeutic purposes is possible through the use of agents that bind endogenous antibodies. PMID:24875800

  17. Identification of Serum Monocyte Chemoattractant Protein-1 and Prolactin as Potential Tumor Markers in Hepatocellular Carcinoma

    PubMed Central

    Kumar, Rajneesh; Heah, Charmain; Utama, Andi; Tania, Navessa Padma; Li, Huihua; Tan, Sze Huey; Poo, Desmond; Choo, Su Pin; Chow, Wan Cheng; Tan, Chee Kiat; Toh, Han Chong

    2013-01-01

    Early diagnosis of hepatocellullar carcinoma (HCC) remains a challenge. The current practice of serum alpha-fetoprotein (AFP) measurement is inadequate. Here we utilized a proteomic approach to identify novel serum biomarkers for distinguishing HCC patients from non-cancer controls. We profiled the serum proteins in a group of 58 resectable HCC patients and 11 non-HCC chronic hepatitis B (HBV) carrier samples from the Singapore General Hospital (SGH) using the RayBio® L-Series 507 Antibody Array and found 113 serum markers that were significantly modulated between HCC and control groups. Selected potential biomarkers from this list were quantified using a multiplex sandwich enzyme-linked immunosorbent assay (ELISA) array in an expanded SGH cohort (126 resectable HCC patients and 115 non-HCC chronic HBV carriers (NC group)), confirming that serum prolactin and monocyte chemoattractant protein-1 (MCP-1) were significantly upregulated in HCC patients. This finding of serum MCP-1 elevation in HCC patients was validated in a separate cohort of serum samples from the Mochtar Riady Institute for Nanotechnology, Indonesia (98 resectable HCC, 101 chronic hepatitis B patients and 100 asymptomatic HBV/HCV carriers) by sandwich ELISA. MCP-1 and prolactin levels were found to correlate with AFP, while MCP-1 also correlated with disease stage. Subsequent receiver operating characteristic (ROC) analysis of AFP, prolactin and MCP-1 in the SGH cohort and comparing their area under the ROC curve (AUC) indicated that neither prolactin nor MCP-1 on their own performed better than AFP. However, the combination of AFP+MCP-1 (AUC, 0.974) had significantly superior discriminative ability than AFP alone (AUC, 0.942; p<0.001). In conclusion, prolactin and MCP-1 are overexpressed in HCC and are conveniently quantifiable in patients’ sera by ELISA. MCP-1 appears to be a promising complementary biomarker for HCC diagnosis and this MCP-1+AFP model should be further evaluated as potential

  18. Molybdenum (Mo) increases endogenous phenolics, proline and photosynthetic pigments and the phytoremediation potential of the industrially important plant Ricinus communis L. for removal of cadmium from contaminated soil.

    PubMed

    Hadi, Fazal; Ali, Nasir; Fuller, Michael Paul

    2016-10-01

    Cadmium (Cd) in agricultural soil negatively affects crops yield and compromises food safety. Remediation of polluted soil is necessary for the re-establishment of sustainable agriculture and to prevent hazards to human health and environmental pollution. Phytoremediation is a promising technology for decontamination of polluted soil. The present study investigated the effect of molybdenum (Mo) (0.5, 1.0 and 2.0 ppm) on endogenous production of total phenolics and free proline, plant biomass and photosynthetic pigments in Ricinus communis plants grown in Cd (25, 50 and 100 ppm) contaminated soils and the potential for Cd phytoextraction. Mo was applied via seed soaking, soil addition and foliar spray. Foliar sprays significantly increased plant biomass, Cd accumulation and bioconcentration. Phenolic concentrations showed significantly positive correlations with Cd accumulation in roots (R (2) = 0.793, 0.807 and 0.739) and leaves (R (2) = 0.707, 721 and 0.866). Similarly, proline was significantly positively correlated with Cd accumulation in roots (R (2) = 0.668, 0.694 and 0.673) and leaves (R (2) = 0.831, 0.964 and 0.930). Foliar application was found to be the most effective way to deliver Mo in terms of increase in plant growth, Cd accumulation and production of phenolics and proline.

  19. Multifunctional amaranth cystatin inhibits endogenous and digestive insect cysteine endopeptidases: A potential tool to prevent proteolysis and for the control of insect pests.

    PubMed

    Valdés-Rodríguez, Silvia; Galván-Ramírez, Juan Pablo; Guerrero-Rangel, Armando; Cedro-Tanda, Alberto

    2015-01-01

    In a previous study, the amaranth cystatin was characterized. This cystatin is believed to provide protection from abiotic stress because its transcription is induced in response to heat, drought, and salinity. It has also been shown that recombinant amaranth cystatin inhibits bromelain, ficin, and cysteine endopeptidases from fungal sources and also inhibits the growth of phytopathogenic fungi. In the present study, evidence is presented regarding the potential function of amaranth cystatin as a regulator of endogenous proteinases and insect digestive proteinases. During amaranth germination and seedling growth, different proteolytic profiles were observed at different pH levels in gelatin-containing SDS-PAGE. Most of the proteolytic enzymes detected at pH 4.5 were mainly inhibited by trans-epoxysuccinyl-leucyl amido(4-guanidino)butane (E-64) and the purified recombinant amaranth cystatin. Furthermore, the recombinant amaranth cystatin was active against insect proteinases. In particular, the E-64-sensitive proteolytic digestive enzymes from Callosobruchus maculatus, Zabrotes subfasciatus, and Acanthoscelides obtectus were inhibited by the amaranth cystatin. Taken together, these results suggest multiple roles for cystatin in amaranth, specifically during germination and seedling growth and in the protection of A. hypochondriacus against insect predation. Amaranth cystatin represents a promising tool for diverse applications in the control of insect pest and for preventing undesirable proteolytic activity.

  20. Induction of long-term potentiation and depression is reflected by corresponding changes in secretion of endogenous brain-derived neurotrophic factor

    PubMed Central

    Aicardi, Giorgio; Argilli, Emanuela; Cappello, Silvia; Santi, Spartaco; Riccio, Massimo; Thoenen, Hans; Canossa, Marco

    2004-01-01

    Neurotrophins play an important role in modulating activity-dependent neuronal plasticity. In particular, threshold levels of brain-derived neurotrophic factor (BDNF) are required to induce long-term potentiation (LTP) in acute hippocampal slices. Conversely, the administration of exogenous BDNF prevents the induction of long-term depression (LTD) in the visual cortex. A long-standing missing link in the analysis of this modulatory role of BDNF was the determination of the time-course of endogenous BDNF secretion in the same organotypic preparation in which LTP and LTD are elicited. Here, we fulfilled this requirement in slices of perirhinal cortex. Classical theta-burst stimulation patterns evoking LTP lasting >180 min elicited a large increase in BDNF secretion that persisted 5-12 min beyond the stimulation period. Weaker theta-burst stimulation patterns leading only to the initial phase of LTP (≈35 min) were accompanied by a smaller increase in BDNF secretion lasting <1 min. Sequestration of BDNF by TrkB-IgG receptor bodies prevented LTP. Low-frequency stimulations leading to LTD were accompanied by reductions in BDNF secretion that never lasted beyond the duration of the stimulation. PMID:15505222

  1. Electromagnetic field stimulation potentiates endogenous myelin repair by recruiting subventricular neural stem cells in an experimental model of white matter demyelination.

    PubMed

    Sherafat, Mohammad Amin; Heibatollahi, Motahareh; Mongabadi, Somayeh; Moradi, Fatemeh; Javan, Mohammad; Ahmadiani, Abolhassan

    2012-09-01

    Electromagnetic fields (EMFs) may affect the endogenous neural stem cells within the brain. The aim of this study was to assess the effects of EMFs on the process of toxin-induced demyelination and subsequent remyelination. Demyelination was induced using local injection of lysophosphatidylcholine within the corpus callosum of adult female Sprague-Dawley rats. EMFs (60 Hz; 0.7 mT) were applied for 2 h twice a day for 7, 14, or 28 days postlesion. BrdU labeling and immunostaining against nestin, myelin basic protein (MBP), and BrdU were used for assessing the amount of neural stem cells within the tissue, remyelination patterns, and tracing of proliferating cells, respectively. EMFs significantly reduced the extent of demyelinated area and increased the level of MBP staining within the lesion area on days 14 and 28 postlesion. EMFs also increased the number of BrdU- and nestin-positive cells within the area between SVZ and lesion as observed on days 7 and 14 postlesion. It seems that EMF potentiates proliferation and migration of neural stem cells and enhances the repair of myelin in the context of demyelinating conditions.

  2. Characterization of the osteogenic potential of mesenchymal stem cells from human periodontal ligament based on cell surface markers.

    PubMed

    Alvarez, Ruth; Lee, Hye-Lim; Wang, Cun-Yu; Hong, Christine

    2015-12-18

    Mesenchymal stem cell (MSC)-mediated therapy has been shown to be clinically effective in regenerating tissue defects. For improved regenerative therapy, it is critical to isolate homogenous populations of MSCs with high capacity to differentiate into appropriate tissues. The utilization of stem cell surface antigens provides a means to identify MSCs from various tissues. However, few surface markers that consistently isolate highly regenerative MSCs have been validated, making it challenging for routine clinical applications and making it all the more imperative to identify reliable surface markers. In this study, we used three surface marker combinations: CD51/CD140α, CD271, and STRO-1/CD146 for the isolation of homogenous populations of dental mesenchymal stem cells (DMSCs) from heterogeneous periodontal ligament cells (PDLCs). Fluorescence-activated cell sorting analysis revealed that 24% of PDLCs were CD51(+)/CD140α(+), 0.8% were CD271(+), and 2.4% were STRO-1(+)/CD146(+). Sorted cell populations were further assessed for their multipotent properties by inducing osteogenic and chondrogenic differentiation. All three subsets of isolated DMSCs exhibited differentiation capacity into osteogenic and chondrogenic lineages but with varying degrees. CD271(+) DMSCs demonstrated the greatest osteogenic potential with strong induction of osteogenic markers such as DLX5, RUNX2, and BGLAP. Our study provides evidence that surface marker combinations used in this study are sufficient markers for the isolation of DMSCs from PDLCs. These results provide important insight into using specific surface markers for identifying homogenous populations of DMSCs for their improved utilization in regenerative medicine.

  3. Aberrant expression of epithelial and neuroendocrine markers in alveolar rhabdomyosarcoma: a potentially serious diagnostic pitfall.

    PubMed

    Bahrami, Armita; Gown, Allen M; Baird, Geoffrey S; Hicks, M John; Folpe, Andrew L

    2008-07-01

    Alveolar rhabdomyosarcoma may be extremely difficult to distinguish from other primitive round cell neoplasms without ancillary immunohistochemistry and/or genetic study. Particularly in adults and in the head and neck locations, the differential diagnosis of alveolar rhabdomyosarcoma includes small cell carcinoma and neuroepithelial tumors, such as esthesioneuroblastoma. We have recently seen cases of genetically confirmed alveolar rhabdomyosarcoma, which were misdiagnosed owing to expression of cytokeratins and neuroendocrine markers. We studied a large group of well-characterized alveolar rhabdomyosarcomas for expression of such markers. Forty-four alveolar rhabdomyosarcomas (18 genetically confirmed) were retrieved from our archives and immunostained for wide-spectrum cytokeratin (OSCAR), low molecular weight cytokeratin (Cam5.2), synaptophysin, chromogranin A, and CD56 using commercially available antibodies. Cases were scored as 'negative', 'rare' (<5% positive cells), '1+' (5-25%), '2+' (26-50%) and '3+' (>51%). The tumors occurred in 23 males and 21 females at a mean age of 18 years (range, <1-64 years), and involved many sites. Fifty percent of cases (22 of 44) expressed wide-spectrum cytokeratin, and scored almost equally as rare, 1+, and 2+, but rarely 3+. Cam5.2 was positive in 52% (14 of 27). Forty-three percent of cases (16 of 37) expressed at least one of the specific neuroendocrine markers, 32% (12 of 37) expressed synaptophysin, 22% (eight of 36) expressed chromogranin A, and 11% expressed both. Expression of synaptophysin and chromogranin A was typically confined to rare cells but could be more widespread. Thirty-two percent of cases (12 of 37) expressed the wide-spectrum cytokeratin and at least one of the neuroendocrine markers, and 8% (three of 36) expressed cytokeratin and both neuroendocrine markers. CD56 expression was nearly ubiquitous. Aberrant expression of epithelial and neuroendocrine markers is relatively common in alveolar

  4. Testing the potential of a ribosomal 16S marker for DNA metabarcoding of insects

    PubMed Central

    Elbrecht, Vasco; Taberlet, Pierre; Dejean, Tony; Valentini, Alice; Usseglio-Polatera, Philippe; Beisel, Jean-Nicolas; Coissac, Eric; Boyer, Frederic

    2016-01-01

    Cytochrome c oxidase I (COI) is a powerful marker for DNA barcoding of animals, with good taxonomic resolution and a large reference database. However, when used for DNA metabarcoding, estimation of taxa abundances and species detection are limited due to primer bias caused by highly variable primer binding sites across the COI gene. Therefore, we explored the ability of the 16S ribosomal DNA gene as an alternative metabarcoding marker for species level assessments. Ten bulk samples, each containing equal amounts of tissue from 52 freshwater invertebrate taxa, were sequenced with the Illumina NextSeq 500 system. The 16S primers amplified three more insect species than the Folmer COI primers and amplified more equally, probably due to decreased primer bias. Estimation of biomass might be less biased with 16S than with COI, although variation in read abundances of two orders of magnitudes is still observed. According to these results, the marker choice depends on the scientific question. If the goal is to obtain a taxonomic identification at the species level, then COI is more appropriate due to established reference databases and known taxonomic resolution of this marker, knowing that a greater proportion of insects will be missed using COI Folmer primers. If the goal is to obtain a more comprehensive survey the 16S marker, which requires building a local reference database, or optimised degenerated COI primers could be more appropriate. PMID:27114891

  5. Copeptin - A potential endocrine surrogate marker of CCK-4-induced panic symptoms?

    PubMed

    Demiralay, Cüneyt; Agorastos, Agorastos; Yassouridis, Alexander; Jahn, Holger; Wiedemann, Klaus; Kellner, Michael

    2017-02-01

    Intravenous cholecystokinin-tetrapeptide (CCK-4) administration reliably and dose-dependently provokes panic anxiety in man, accompanied by adrenocorticotropic hormone (ACTH) and cortisol release. Preclinical findings suggest that behavioral and endocrine effects of CCK-4 are mediated via corticotropin-releasing hormone (CRH) release. Anxiogenic stimulation of the central CCK-receptors in man was shown to increase as well vasopressin (AVP), which acts synergistically with CRH as pituitary-adrenocortical axis stimulator during stress. Copeptin (CoP), the C-terminal part of pre-pro-AVP, is released in an equimolar ratio to AVP. It is more stable in the circulation and easier to determine than AVP and it was found to closely mirror the production of AVP. So far, CoP secretion has not been characterized during panic provocation. In 30 healthy male human subjects, we repeatedly measured CoP in plasma during a panic challenge and studied its correlation to Acute Panic Inventory (API) ratings and plasma ACTH and cortisol. CoP levels correlated positively with the increase in API ratings (r=0.41, p=0.03), while ACTH or cortisol did not (r=0.08, p=0.68 and r=0.12, p=0.53, respectively). CoP levels correlated also positively with ACTH (r=0.48, p=0.009) and cortisol (r=0.48, p=0.01) concentrations throughout the CCK-4 challenge. As expected, we found a positive correlation between plasma ACTH and cortisol levels (r=0.57, p=0.001). A vasopressinergic activation during CCK-4 induced panic was demonstrated, which was correlated positively to panic symptoms and pituitary-adrenocortical release. Our findings suggest a role of CoP as a potential surrogate marker of CCK-4 panic symptoms. Further studies are needed to replicate our results and to further clarify the role of CoP as a stress-sensitive hormone in different panic paradigms as well as in panic patients.

  6. Potential of Start Codon Targeted (SCoT) markers for DNA fingerprinting of newly synthesized tritordeums and their respective parents.

    PubMed

    Cabo, Sandra; Ferreira, Luciana; Carvalho, Ana; Martins-Lopes, Paula; Martín, António; Lima-Brito, José Eduardo

    2014-08-01

    Hexaploid tritordeum (H(ch)H(ch)AABB; 2n = 42) results from the cross between Hordeum chilense (H(ch)H(ch); 2n = 14) and cultivated durum wheat (Triticum turgidum ssp. durum (AABB; 2n = 28). Morphologically, tritordeum resembles the wheat parent, showing promise for agriculture and wheat breeding. Start Codon Targeted (SCoT) polymorphism is a recently developed technique that generates gene-targeted markers. Thus, we considered it interesting to evaluate its potential for the DNA fingerprinting of newly synthesized hexaploid tritordeums and their respective parents. In this study, 60 SCoT primers were tested, and 18 and 19 of them revealed SCoT polymorphisms in the newly synthesized tritordeum lines HT27 and HT22, respectively, and their parents. An analysis of the presence/absence of bands among tritordeums and their parents revealed three types of polymorphic markers: (i) shared by tritordeums and one of their parents, (ii) exclusively amplified in tritordeums, and (iii) exclusively amplified in the parents. No polymorphism was detected among individuals of each parental species. Three SCoT markers were exclusively amplified in tritordeums of lines HT22 and HT27, being considered as polyploidization-induced rearrangements. About 70% of the SCoT markers of H. chilense origin were not transmitted to the allopolyploids of both lines, and most of the SCoTs scored in the newly synthesized allopolyploids originated from wheat, reinforcing the potential use of tritordeum as an alternative crop.

  7. Absence of the Epithelial Glycocalyx As Potential Tumor Marker for the Early Detection of Colorectal Cancer

    PubMed Central

    Ramaker, Katrin; Bade, Steffen; Röckendorf, Niels; Meckelein, Barbara; Vollmer, Ekkehard; Schultz, Holger; Fröschle, Günter-Willi; Frey, Andreas

    2016-01-01

    Detection of cancer at an early stage is pivotal for successful treatment and long term survival, yet early diagnosis requires sensitive and specific markers that can be easily detected by screening procedures. Differences in the surface structure of tumor and healthy cells, if sufficiently pronounced and discernible, may serve that purpose. We analyzed the luminal surface of healthy and neoplastic human colorectal tissues for the presence and architecture of the glycocalyx—a dense network of highly glycosylated proteins—using transmission electron microscopy. The ultrastructural analyses showed that 93% of healthy mucosae were covered by an intact glycocalyx. Contrarily, on over 90% of the surface of neoplastic cells the glycocalyx was absent. The sensitivity and specificity of our marker “absence of a glycocalyx” are excellent, being 91% (83–96%) and 96% (89–99%) for adenocarcinomas and 94% (73–100%) and 92% (85–97%) for precancerous polyps (means and 95% confidence intervals). Using a cell culture model we could demonstrate that a particulate probe targeting a cell surface receptor usually concealed beneath the glycocalyx can bind selectively to glycocalyx-free areas of a tumor cell layer. We propose that the absence of a glycocalyx may serve as novel type of tumor marker. If the absence of the glycocalyx can be detected e.g. via binding of imaging probes to non-shielded surface receptors of anomalously differentiated cells, this tumor marker could be used to enable early diagnosis of colorectal cancer. PMID:28033349

  8. Carbohydrate-deficient transferrin in serum: a new marker of potentially harmful alcohol consumption reviewed.

    PubMed

    Stibler, H

    1991-12-01

    During the last 16 years an increasing number of studies have indicated a new diagnostic marker of alcohol abuse, unrelated to any of the conventional markers of alcoholism. This marker, now called carbohydrate-deficient transferrin, consists mainly of one or two isoforms of transferrin that are deficient in their terminal trisaccharides. Such isoforms have so far been detected by methods based on charge, i.e., isoelectric focusing, chromatofocusing, and anion-exchange chromatography of various designs combined with immunological detection techniques. This transferrin abnormality measures an accumulated effect of alcohol consumption, appearing after regular intake of 50-80 g of ethanol/day for at least one week and normalizing slowly during abstinence (half-life = about 15 days). To summarize all studies to date, approximately 2500 individuals have been examined, with a total clinical sensitivity of 82% and a specificity of 97%. False-positive results have only occasionally been reported: in a few patients with severe liver disease, usually primary biliary cirrhosis and chronic active hepatitis; in patients with genetic D variants of transferrin; and in patients with (and some carriers of) a recently identified inborn error of glycoprotein metabolism. The mechanism behind the transferrin abnormality is unknown but an acetaldehyde-mediated inhibition of glycosyl transfer has been suggested. Carbohydrate-deficient transferrin may thus offer a new possibility of diagnosing alcohol-related disorders. Its measurement is little affected by other conditions and, contrary to conventional markers of alcohol abuse, is apparently largely independent of concomitant liver disease.

  9. Identification of Apolipoprotein C-I as a Potential Wilms’ Tumor Marker after Excluding Inflammatory Factors

    PubMed Central

    Zhang, Junjie; Guo, Fei; Wang, Lei; Zhao, Wei; Zhang, Da; Yang, Heying; Yu, Jiekai; Niu, Lili; Yang, Fuquan; Zheng, Shu; Wang, Jiaxiang

    2014-01-01

    Wilms’ tumor is one of the most common malignant tumors observed in children, and its early diagnosis is important for late-stage treatment and prognosis. We previously screened and identified protein markers for Wilms’ tumor; however, these markers lacked specificity, and some were associated with inflammation. In the current study, serum samples from children with Wilms’ tumors were compared with those of healthy controls and patients with systemic inflammatory response syndrome (SIRS). After exclusion of factors associated with inflammation, specific protein markers for Wilms’ tumors were identified. After comparing the protein peak values obtained from all three groups, a protein with a m/z of 6438 Da was specified. Purification and identification of the target protein using high-pressure liquid chromatography (HPLC) and two-dimensional liquid chromatography-linearion trap mass spectrometry(2D-LC-LTQ-MS) mass spectrometry, respectively, revealed that it was apolipoprotein C-I (APO C-I). Thus, APO C-I is a specific protein marker for Wilms’ tumor. PMID:25222555

  10. Evaluation and Elucidation Studies of Natural Aglycones for Anticancer Potential using Apoptosis-Related Markers: An In silico Study.

    PubMed

    Akhtar, Salman; Khan, M Kalim A; Arif, Jamal M

    2016-10-05

    Exposure to exogenous and endogenous chemicals and subsequent cellular and molecular changes has been linked to enhanced cell proliferation and restricted apoptosis phenomenon. Though in the past decades numerous anticancer drugs inducing programmed cell death in cancer cells by targeting specific apoptotic markers have reached the market, they have been allied with unwanted side effects, ranging from mild to severe toxicity. With further understanding on the functional mechanism of p53 and MDM2 in apoptosis and in our continuous search for new and potent multi-target anticancer lead compounds, we have carried out molecular docking and inhibition studies of the selected aglycones along with selected anticancer leads, against the specific apoptotic and cell cycle markers using AutoDock Tools 4.0 and other computational softwares. The docking results have been analyzed in terms of binding energies (kcal/mol) and inhibition constant (µM). The study clearly proposes our aglycones [solanidine (Solanid-5-en-3β-ol), solasodine (Solasod-5-en-3β-ol), and tomatidine (5α-Tomatidan-3β-ol)] induce apoptosis by inhibiting the p53-MDM2 complex, p21(Waf1/Cip1), and Bcl-2 proteins, which were even found comparable with the anticancer drugs nutlin and/or halofuginone. The work further emphasizes that the individual molecular targets such as BAX and Bcl-2 may result in misleading data at any level; however, ratio of responses to BAX and Bcl-2 shall be considered for better clue about a compound to be pro- or anti-apoptotic.

  11. Geriatric forensics - Part 2 “Prevalence of elder abuse and their potential forensic markers among medical and dental patients”

    PubMed Central

    Mattoo, Khurshid A.; Garg, Rishabh; Kumar, Shalabh

    2015-01-01

    Context: This study is a continuation of the earlier studies and has been extended to investigate the potential forensic markers of elder abuse. Aims: To determine the prevalence of elder abuse in various outpatient departments (OPDs). To study the associated parameters related to the abuser and the abused. To determine the existence of potential forensic markers of elder abuse. Settings and Design: The subjects were randomly selected from the medical and the dental OPDs of the university. Materials and Methods: Eight hundred and thirty two elderly subjects in the age range 40-60 years were interviewed using a questionnaire to determine the existence of elder abuse. The subjects were investigated and examined for weight, nutrition and hydration, vital signs, habits, existing visual and auditory capabilities, medications, disclosure of wills/deeds, signs of depression, and documented cleanliness. The mini-mental state examination, the Geriatric Depression Scale, the Clock drawing test, and the Brief Psychiatric Rating Scale were used to determine the potential forensic markers. Statistical Analysis Used: Mean values in percentage were determined by dividing the number of determined subjects by the total number of subjects for that parameter. Results: About 37% in medical and 41% in dental OPDs were found to have suffered from abuse, mostly in the age group 60-70 years. Females received more abuse and a combination of son and daughter-in-law constituted most abusers. Various potential markers of elder abuse and neglect investigated among the elder abuse victims included depression (89%), signs of improper feeding (83%), changes in personal hygiene (69%), need for medical/dental treatment (78%), medication misuse (67%), changes in wills/deeds (26%), decubiti (10%), bruises (17%), skin tears (27%), and confusion (23%). Conclusions: Elder abuse exists in one or more forms in both medical and dental OPDs among both males and females in all age groups. PMID:26816460

  12. Orphan nuclear receptor Nurr1 as a potential novel marker for progression in human pancreatic ductal adenocarcinoma

    PubMed Central

    Ji, Li; Gong, Chen; Ge, Liangyu; Song, Linping; Chen, Fenfen; Jin, Chunjing; Zhu, Hongyan; Zhou, Guoxiong

    2017-01-01

    Nuclear receptor related-1 protein (Nurr1) is a novel orphan member of the nuclear receptor superfamily (the NR4A family) involved in tumorigenesis. The aim of the present study was to investigate the expression and possible function of Nurr1 in pancreatic ductal adenocarcinoma (PDAC). The expression pattern of Nurr1 protein was determined using immunohistochemical staining in 138 patients with PDAC. Elevated Nurr1 expression was more commonly observed in PDAC tissues and cell lines compared with healthy controls. Elevated expression was significantly associated with histological differentiation (P=0.041), lymph node metastasis (P=0.021), TNM classification of malignant tumors stage (P=0.031) and poor survival (P=0.001). Further experiments demonstrated that suppression of endogenous Nurr1 expression attenuated cell proliferation, migration and invasion, and induced apoptosis of PDAC cells. In conclusion, these results suggest that Nurr1 has an important role in the progression of PDAC and may be used as a novel marker for therapeutic targets. PMID:28352330

  13. Comparative study of osteogenic potential of a composite scaffold incorporating either endogenous bone morphogenetic protein-2 or exogenous phytomolecule icaritin: an in vitro efficacy study.

    PubMed

    Chen, S-H; Wang, X-L; Xie, X-H; Zheng, L-Z; Yao, D; Wang, D-P; Leng, Y; Zhang, G; Qin, L

    2012-08-01

    A local delivery system with sustained and efficient release of therapeutic agents from an appropriate carrier is desirable for orthopedic applications. Novel composite scaffolds made of poly (lactic-co-glycolic acid) with tricalcium phosphate (PLGA/TCP) were fabricated by an advanced low-temperature rapid prototyping technique, which incorporated either endogenous bone morphogenetic protein-2 (BMP-2) (PLGA/TCP/BMP-2) or phytomolecule icaritin (ICT) (PLGA/TCP/ICT) at low, middle and high doses. PLGA/TCP served as control. In vitro degradation, osteogenesis and release tests showed statistical differences among PLGA/TCP/ICT, PLGA/TCP and PLGA/TCP/BMP-2 groups, where PLGA/TCP/ICT had the desired slow release of bioactive icaritin in a dose-dependent manner, whereas there was almost no BMP-2 release from the PLGA/TCP/BMP-2 scaffolds. PLGA/TCP/ICT significantly increased more ALP activity, upregulated mRNA expression of osteogenic genes and enhanced calcium deposition and mineralization in rabbit bone marrow stem cells cultured on scaffolds compared with the other two groups. These results indicate the desired degradation rate, osteogenic capability and release property in PLGA/TCP/ICT composite scaffold, as icaritin preserved its bioactivity and structure after incorporation, while PLGA/TCP/BMP-2 did not show an initially expected osteogenic potential, owing to loss of the original bioactivity of BMP-2 during its incorporation and fabrication procedure. The results suggest that PLGA/TCP composite scaffolds incorporating osteogenic ICT might be a promising approach for bone tissue bioengineering and regeneration. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  14. The Human Endogenous Protection System against Cell-Free Hemoglobin and Heme Is Overwhelmed in Preeclampsia and Provides Potential Biomarkers and Clinical Indicators

    PubMed Central

    Johansson, Maria E.; Edström-Hägerwall, Anneli; Larsson, Irene; Jälmby, Maya; Hansson, Stefan R.; Åkerström, Bo

    2015-01-01

    Preeclampsia (PE) complicates 3–8% of all pregnancies and manifests clinically as hypertension and proteinuria in the second half of gestation. The pathogenesis of PE is not fully understood but recent studies have described the involvement of cell-free fetal hemoglobin (HbF). Hypothesizing that PE is associated with prolonged hemolysis we have studied the response of the cell-free Hb- and heme defense network. Thus, we have investigated the levels of cell-free HbF (both free, denoted HbF, and in complex with Hp, denoted Hp-HbF) as well as the major human endogenous Hb- and heme-scavenging systems: haptoglobin (Hp), hemopexin (Hpx), α1-microglobulin (A1M) and CD163 in plasma of PE women (n = 98) and women with normal pregnancies (n = 47) at term. A significant increase of the mean plasma HbF concentration was observed in women with PE. Plasma levels of Hp and Hpx were statistically significantly reduced, whereas the level of the extravascular heme- and radical scavenger A1M was significantly increased in plasma of women with PE. The Hpx levels significantly correlated with maternal blood pressure. Furthermore, HbF and the related scavenger proteins displayed a potential to be used as clinical biomarkers for more precise diagnosis of PE and are candidates as predictors of identifying pregnancies with increased risk of obstetrical complications. The results support that PE pathophysiology is associated with increased HbF-concentrations and an activation of the physiological Hb-heme defense systems. PMID:26368565

  15. Comparison of Breast Cancer to Healthy Control Tissue Discovers Novel Markers with Potential for Prognosis and Early Detection

    PubMed Central

    Schummer, Michèl; Green, Ann; Beatty, J. David; Karlan, Beth Y.; Karlan, Scott; Gross, Jenny; Thornton, Sean; McIntosh, Martin; Urban, Nicole

    2010-01-01

    This study was initiated to identify biomarkers with potential value for the early detection of poor-outcome breast cancer. Two sets of well-characterized tissues were utilized: one from breast cancer patients with favorable vs. poor outcome and the other from healthy women undergoing reduction mammaplasty. Over 46 differentially expressed genes were identified from a large list of potential targets by a) mining publicly available expression data (identifying 134 genes for quantitative PCR) and b) utilizing a commercial PCR array. Three genes show elevated expression in cancers with poor outcome and low expression in all other tissues, warranting further investigation as potential blood markers for early detection of cancers with poor outcome. Twelve genes showed lower expression in cancers with poor outcome than in cancers with favorable outcome but no differential expression between aggressive cancers and most healthy controls. These genes are more likely to be useful as prognostic tissue markers than as serum markers for early detection of aggressive disease. As a secondary finding was that, when histologically normal breast tissue was removed from a distant site in a breast with cancer, 7 of 38 specimens displayed a cancer-like expression profile, while the remaining 31 were genetically similar to the reduction mammaplasty control group. This finding suggests that some regions of ipsilateral histologically ‘normal’ breast tissue are predisposed to becoming malignant and that normal-appearing tissue with malignant signature might warrant treatment to prevent new primary tumors. PMID:20161755

  16. Comparison of breast cancer to healthy control tissue discovers novel markers with potential for prognosis and early detection.

    PubMed

    Schummer, Michèl; Green, Ann; Beatty, J David; Karlan, Beth Y; Karlan, Scott; Gross, Jenny; Thornton, Sean; McIntosh, Martin; Urban, Nicole

    2010-02-09

    This study was initiated to identify biomarkers with potential value for the early detection of poor-outcome breast cancer. Two sets of well-characterized tissues were utilized: one from breast cancer patients with favorable vs. poor outcome and the other from healthy women undergoing reduction mammaplasty. Over 46 differentially expressed genes were identified from a large list of potential targets by a) mining publicly available expression data (identifying 134 genes for quantitative PCR) and b) utilizing a commercial PCR array. Three genes show elevated expression in cancers with poor outcome and low expression in all other tissues, warranting further investigation as potential blood markers for early detection of cancers with poor outcome. Twelve genes showed lower expression in cancers with poor outcome than in cancers with favorable outcome but no differential expression between aggressive cancers and most healthy controls. These genes are more likely to be useful as prognostic tissue markers than as serum markers for early detection of aggressive disease. As a secondary finding was that, when histologically normal breast tissue was removed from a distant site in a breast with cancer, 7 of 38 specimens displayed a cancer-like expression profile, while the remaining 31 were genetically similar to the reduction mammaplasty control group. This finding suggests that some regions of ipsilateral histologically 'normal' breast tissue are predisposed to becoming malignant and that normal-appearing tissue with malignant signature might warrant treatment to prevent new primary tumors.

  17. DNA methylome profiling of maternal peripheral blood and placentas reveal potential fetal DNA markers for non-invasive prenatal testing.

    PubMed

    Xiang, Yuqian; Zhang, Junyu; Li, Qiaoli; Zhou, Xinyao; Wang, Teng; Xu, Mingqing; Xia, Shihui; Xing, Qinghe; Wang, Lei; He, Lin; Zhao, Xinzhi

    2014-09-01

    Utilizing epigenetic (DNA methylation) differences to differentiate between maternal peripheral blood (PBL) and fetal (placental) DNA has been a promising strategy for non-invasive prenatal testing (NIPT). However, the differentially methylated regions (DMRs) have yet to be fully ascertained. In the present study, we performed genome-wide comparative methylome analysis between maternal PBL and placental DNA from pregnancies of first trimester by methylated DNA immunoprecipitation-sequencing (MeDIP-Seq) and Infinium HumanMethylation450 BeadChip assays. A total of 36 931 DMRs and 45 804 differentially methylated sites (DMSs) covering the whole genome, exclusive of the Y chromosome, were identified via MeDIP-Seq and Infinium 450k array, respectively, of which 3759 sites in 2188 regions were confirmed by both methods. Not only did we find the previously reported potential fetal DNA markers in our identified DMRs/DMSs but also we verified fully the identified DMRs/DMSs in the validation round by MassARRAY EpiTYPER. The screened potential fetal DNA markers may be used for NIPT on aneuploidies and other chromosomal diseases, such as cri du chat syndrome and velo-cardio-facial syndrome. In addition, these potential markers may have application in the early diagnosis of placental dysfunction, such as pre-eclampsia.

  18. Synergistic effect of exogeneous and endogeneous electrostimulation on osteogenic differentiation of human mesenchymal stem cells seeded on silk scaffolds.

    PubMed

    Çakmak, Anıl S; Çakmak, Soner; White, James D; Raja, Waseem K; Kim, Kyungsook; Yiğit, Sezin; Kaplan, David L; Gümüşderelioğlu, Menemşe

    2016-04-01

    Bioelectrical regulation of bone fracture healing is important for many cellular events such as proliferation, migration, and differentiation. The aim of this study was to investigate the osteogenic differentiation potential of human mesenchymal stem cells (hMSCs) cultivated on silk scaffolds in response to different modes of electrostimulation (e.g., exogeneous and/or endogeneous). Endogeneous electrophysiology was altered through the use of monensin (10 nM) and glibenclamide (10 μM), along with external electrostimulation (60 kHz; 100-500 mV). Monensin enhanced the expression of early osteogenic markers such as alkaline phosphatase (ALP) and runt-related transcription factor 2 (RUNX-2). When exogeneous electrostimulation was combined with glibenclamide, more mature osteogenic marker upregulation based on bone sialoprotein expression (BSP) and mineralization was found. These results suggest the potential to exploit both exogeneous and endogeneous biophysical control of cell functions towards tissue-specific goals.

  19. Mirror-like slip surfaces in dolostone: natural and experimental constraints on a potential seismic marker

    NASA Astrophysics Data System (ADS)

    Fondriest, M.; Smith, S. A.; Di Toro, G.; Nielsen, S. B.

    2012-12-01

    The lack of clear geological markers of seismic faulting represents a major limitation in our current comprehension of earthquake physics. At present pseudotachylytes (i.e. friction-induced melts) are the only unambiguously identified indicator of ancient seismicity in exhumed fault zones, but pseudotachylytes are not found in many rock types, including carbonates. We report the occurrence of small-displacement, mirror-like slip surfaces from a fault zone cutting dolostones. A combination of field observations and rotary shear friction experiments suggests that such slip surfaces: 1) are formed only at seismic slip rates, and 2) could potentially be used to estimate power dissipation during individual slip events. The Foiana Line (FL) is a major NNE-SSW-trending sinistral transpressive fault in the Italian Southern Alps. The outcropping fault zone consists of a <300 m wide zone of heavily fractured ("pulverized") dolostones cut by a network of mirror-like slip surfaces. The slip surfaces have displacements ranging between 0.04 m and 0.5 m and their mirror-like appearance indicates that the wavelength of surface roughness is <1 μm. The slip surfaces have mainly dip-slip reverse kinematics and were exhumed from ~2 km depth. Resolved normal stress on the slip surfaces is estimated in the range 30-50 MPa. To understand how the mirror-like slip surfaces may have developed, slow- to high-velocity rotary-shear experiments using SHIVA (INGV, Rome) were performed on 3 mm thick layers of dolomite gouge (grain size <250 μm) collected from the FL. Tests were conducted using a purpose-built gouge sample holder at slip rates of 0.0001-1.13 m/s, normal stresses up to 26 MPa and displacements in the range 0.02-3.5 m. At seismic slip rates of 1.13 m/s the dolomite gouge shows a dramatic reduction of the friction coefficient (μ) from a peak value of ~0.7 to a steady-state value of ~0.25. The gouge starts to weaken above a threshold velocity in the range 0.19-0.49 m/s following a

  20. Existing and potentially novel functional markers of vitamin D status: a systematic review.

    PubMed

    Seamans, Kelly M; Cashman, Kevin D

    2009-06-01

    Although serum 25-hydroxyvitamin D [25(OH)D] is the currently accepted vitamin D status marker of choice, use of other biomarkers or functional endpoints have been suggested. The objective was to systematically review the effectiveness of 25(OH)D, parathyroid hormone (PTH), bone turnover markers, bone mineral density (BMD), and calcium absorption as biomarkers of vitamin D status. Methods included a structured search on Ovid MEDLINE, EMBASE (Ovid), and Cochrane CENTRAL; rigorous inclusion/exclusion criteria; data extraction; quality assessment; meta-analysis; and meta-regression. Thirty-six vitamin D supplementation randomized controlled trials (RCTs) and 4 before-after studies were included. Vitamin D supplementation significantly raised circulating 25(OH)D in all but one RCT, but the response was highly heterogeneous [weighted mean difference (WMD): 34.1 nmol/L; 95% CI: 28.9, 39.2; 32 RCTs; I2 = 97%). Vitamin D supplementation (without calcium) significantly lowered circulating PTH (WMD: -0.29 pmol/L; 95% CI: -0.56, -0.02; 11 RCTs; I2 = 29%), but this was not apparent in the presence of calcium supplementation. There was a suggestion that whole-body or lumbar spine BMD may be a useful biomarker in older people but not in adolescents. Bone turnover markers were not useful biomarkers of vitamin D status, but 4 before-after studies suggested that intestinal calcium absorption may respond to vitamin D status. This systematic review confirmed that circulating 25(OH)D is a robust and reliable marker of vitamin D status. Further research is needed to clarify which population subgroups show responses of PTH, BMD, and/or calcium absorption in response to changes in vitamin D status.

  1. Hypoxia in human colorectal adenocarcinoma: Comparison between extrinsic and potential intrinsic hypoxia markers

    SciTech Connect

    Goethals, Laurence; Debucquoy, Annelies; Perneel, Christiaan; Geboes, Karel; Ectors, Nadine; De Schutter, Harlinde; Penninckx, Freddy; McBride, William H.; Begg, Adrian C.; Haustermans, Karin M. . E-mail: karin.haustermans@uzleuven.be

    2006-05-01

    Purpose: To detect and quantify hypoxia in colorectal adenocarcinomas by use of pimonidazole and iododeoxyuridine (IdUrd) as extrinsic markers and carbonic anhydrase IX (CA IX), microvessel density (MVD), epidermal growth-factor receptor (EGFR), and vascular endothelial growth factor (VEGF) as intrinsic markers of hypoxia. Methods and Material: Twenty patients with an adenocarcinoma of the left colon and rectum treated by primary surgery were injected with pimonidazole and IdUrd. Serial sections of tumor biopsies were single stained for VEGF, EGFR, Ki67, and double stained for blood vessels in combination with either pimonidazole, IdUrd, or CA IX. Percentage of expression was scored as well as colocalization of pimonidazole with CA IX. Results: The median percentage of hypoxia, as judged by pimonidazole staining, was 16.7% (range, 0-52.4%). The expression of pimonidazole correlated inversely with the total MVD and endothelial cord MVD (R = -0.55, p = 0.01; R = -0.47, p = 0.04). Good colocalization was found between pimonidazole and CA IX in only 30% of tumors, with no correlation overall between pimonidazole and CA IX, VEGF, or EGFR or between the different intrinsic markers. Cells around some vessels (0.08-11%) were negative for IdUrd but positive for Ki 67, which indicated their lack of perfusion at the time of injection. Conclusion: Chronic and acute hypoxic regions are present in colorectal tumors, as shown by pimonidazole and IdUrd staining. Only in a minority of tumors did an association exist between the areas stained by pimonidazole and those positive for CA IX. Pimonidazole also did not correlate with expression of other putative intrinsic hypoxia markers (VEGF, EGFR)

  2. Identification of innovative potential quality markers in rocket and melon fresh-cut produce.

    PubMed

    Cavaiuolo, Marina; Cocetta, Giacomo; Bulgari, Roberta; Spinardi, Anna; Ferrante, Antonio

    2015-12-01

    Ready-to-eat fresh cut produce are exposed to pre- and postharvest abiotic stresses during the production chain. Our work aimed to identify stress responsive genes as new molecular markers of quality that can be widely applied to leaves and fruits and easily determined at any stage of the production chain. Stress responsive genes associated with quality losses were isolated in rocket and melon fresh-cut produce and their expression levels analyzed by quantitative real time PCR (qRT-PCR) at different time points after harvest at 20 °C and 4 °C. qRT-PCR results were supported by correlation analysis with physiological and biochemical determinations evaluated at the same conditions such as chlorophyll a fluorescence indices, total, reducing sugars, sucrose, ethylene, ascorbic acid, lipid peroxidation and reactive oxygen species. In both species the putative molecular markers increased their expression soon after harvest suggesting a possible use as novel and objective quality markers of fresh-cut produces.

  3. The potential of hypoxia markers as target for breast molecular imaging – a systematic review and meta-analysis of human marker expression

    PubMed Central

    2013-01-01

    Background Molecular imaging of breast cancer is a promising emerging technology, potentially able to improve clinical care. Valid imaging targets for molecular imaging tracer development are membrane-bound hypoxia-related proteins, expressed when tumor growth outpaces neo-angiogenesis. We performed a systematic literature review and meta-analysis of such hypoxia marker expression rates in human breast cancer to evaluate their potential as clinically relevant molecular imaging targets. Methods We searched MEDLINE and EMBASE for articles describing membrane-bound proteins that are related to hypoxia inducible factor 1α (HIF-1α), the key regulator of the hypoxia response. We extracted expression rates of carbonic anhydrase-IX (CAIX), glucose transporter-1 (GLUT1), C-X-C chemokine receptor type-4 (CXCR4), or insulin-like growth factor-1 receptor (IGF1R) in human breast disease, evaluated by immunohistochemistry. We pooled study results using random-effects models and applied meta-regression to identify associations with clinicopathological variables. Results Of 1,705 identified articles, 117 matched our selection criteria, totaling 30,216 immunohistochemistry results. We found substantial between-study variability in expression rates. Invasive cancer showed pooled expression rates of 35% for CAIX (95% confidence interval (CI): 26-46%), 51% for GLUT1 (CI: 40-61%), 46% for CXCR4 (CI: 33-59%), and 46% for IGF1R (CI: 35-70%). Expression rates increased with tumor grade for GLUT1, CAIX, and CXCR4 (all p < 0.001), but decreased for IGF1R (p < 0.001). GLUT1 showed the highest expression rate in grade III cancers with 58% (45-69%). CXCR4 showed the highest expression rate in small T1 tumors with 48% (CI: 28-69%), but associations with size were only significant for CAIX (p < 0.001; positive association) and IGF1R (p = 0.047; negative association). Although based on few studies, CAIX, GLUT1, and CXCR4 showed profound lower expression rates in normal breast tissue and benign

  4. Endogenous Ethylene Production Is a Potential Problem in the Measurement of Nitrogenase Activity Associated with Excised Corn and Sorghum Roots 1

    PubMed Central

    Sloger, Charles; van Berkum, Peter

    1988-01-01

    Endogenous ethylene production was evaluated as a source of ethylene during acetylene reduction assays with freshly collected roots of field-grown corn, Zea mays L. cv Funks G-4646, and sorghum, Sorghum bicolor (L.) Moench. cv CK-60A. Ethylene production was not detected when roots were incubated in air without acetylene. The presence of endogenous ethylene production was confirmed when roots were incubated anaerobically and in the presence of 40 millimolar sodium hydrosulfite. Ethylene oxidase activity was also associated with excised roots. The rate of ethylene oxidation was higher than the rates of ethylene accumulation during either acetylene reduction assays or anaerobic incubations. These results indicate that the procedure of incubating roots of grasses in air to monitor endogenous ethylene production is not a valid control in acetylene reduction studies with grasses. The presence of endogenous ethylene production during acetylene reduction assays was demonstrated by using either CO to inhibit nitrogenase activity or chloramphenicol to inhibit nitrogenase synthesis in freshly excised roots. PMID:16666249

  5. Pressure and oxygen debt on bypass - potential quality markers of perfusion?

    PubMed

    Poullis, Mike; Palmer, K; Al-Rawi, O; Johnson, I; Ridgeway, T

    2012-05-01

    No markers of quality of perfusion pressure and oxygen delivery during cardiopulmonary bypass (CPB), to complement rewarming rate, maximum temperature on rewarming, lowest haematocrit, and blood glucose, exist. Using the electronic acquisition of blood pressure on bypass (JOCAP system), the percentage of time perfusion pressure was below 30, 40, 50, 60 and 70 mmHg, average deviance, confidence interval, median, mode, standard deviation, variance, and average, maximum and cumulative oxygen debt were calculated. Numerous different readouts of achievement of maintenance of constant pressure on bypass and oxygen debt are now easily achievable with perfusion electronic data management systems. Mean, median, and mode offer poor discrimination of pressure control during CPB. Percentage of time perfusion pressure was below 30, 40, 50, 60 and 70 mmHg, average deviance, confidence interval, and standard deviation all have discriminatory power, but need clinical correlation for their significance. A composite score involving non-pressure readouts (e.g. oxygen delivery, arterial and venous saturations, and flow rates) may need to be integrated into any perfusion quality marker. Assessment of adequacy of constant perfusion pressure and oxygen delivery may allow the scientific evaluation of pressure and oxygen delivery on bypass for patients to be compared accurately. Currently, in studies involving CPB, blood pressure targets are stated with no quantitative assessment of adequacy of achievement of these targets. Electronic data monitoring during cardiopulmonary bypass, when correlated with clinical outcome, may help to provide a marker of quality of perfusion pressure during CPB and may, indeed, allow patient-specific perfusion pressure strategies to be developed.

  6. Plasma protoporphyrin IX following administration of 5-aminolevulinic acid as a potential tumor marker

    PubMed Central

    OTA, URARA; FUKUHARA, HIDEO; ISHIZUKA, MASAHIRO; ABE, FUMINORI; KAWADA, CHIAKI; TAMURA, KENJI; TANAKA, TOHRU; INOUE, KEIJI; OGURA, SHUN-ICHIRO; SHUIN, TARO

    2015-01-01

    Exogenously administered 5-aminolevulinic acid (ALA) is metabolized to protoporphyrin IX (PpIX), which specifically accumulates in cancer cells and emits red fluorescence by blue light irradiation. These phenomena are applied for the intraoperative diagnosis of cancer. Based on the fact that accumulated PpIX in cancer cells is exported extracellularly via the ATP-binding cassette transporter G2, we hypothesized that the measurement of plasma PpIX concentrations could be applied as a tumor marker for cancer screening. In the present study, the use of plasma samples from bladder cancer patients were evaluated as a tumor marker. ALA, 1.0 g, was orally administered to bladder cancer patients and healthy adults. The plasma concentration of PpIX was measured using a high-performance liquid chromatography system. The plasma PpIX concentration following ALA administration was significantly higher in bladder cancer patients than that in the healthy adults, suggesting the effectiveness of plasma PpIX analysis following ALA administration for cancer screening. Additionally, 4 h after ALA administration, plasma PpIX showed high sensitivity (94.4%) and high specificity (80.0%). PMID:26171183

  7. Statistical strategies to reveal potential vibrational markers for in vivo analysis by confocal Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Oliveira Mendes, Thiago de; Pinto, Liliane Pereira; Santos, Laurita dos; Tippavajhala, Vamshi Krishna; Téllez Soto, Claudio Alberto; Martin, Airton Abrahão

    2016-07-01

    The analysis of biological systems by spectroscopic techniques involves the evaluation of hundreds to thousands of variables. Hence, different statistical approaches are used to elucidate regions that discriminate classes of samples and to propose new vibrational markers for explaining various phenomena like disease monitoring, mechanisms of action of drugs, food, and so on. However, the technical statistics are not always widely discussed in applied sciences. In this context, this work presents a detailed discussion including the various steps necessary for proper statistical analysis. It includes univariate parametric and nonparametric tests, as well as multivariate unsupervised and supervised approaches. The main objective of this study is to promote proper understanding of the application of various statistical tools in these spectroscopic methods used for the analysis of biological samples. The discussion of these methods is performed on a set of in vivo confocal Raman spectra of human skin analysis that aims to identify skin aging markers. In the Appendix, a complete routine of data analysis is executed in a free software that can be used by the scientific community involved in these studies.

  8. Complement component C1q as potential diagnostic but not predictive marker of preeclampsia.

    PubMed

    Agostinis, Chiara; Stampalija, Tamara; Tannetta, Dionne; Loganes, Claudia; Vecchi Brumatti, Liza; De Seta, Francesco; Celeghini, Claudio; Radillo, Oriano; Sargent, Ian; Tedesco, Francesco; Bulla, Roberta

    2016-12-01

    We have previously found that C1q is constitutively expressed by invading trophoblast and endothelial cells of decidua and contributes to vascular and tissue remodeling. Based on these findings, we sought to determine whether there were changes in the circulating level of C1q that may be used as a diagnostic and predictive marker of preeclampsia. We measured the levels of C1q, C4, and complement activation products in serum or plasma of normal pregnant women and preeclamptic patients from different cohorts. We observed a marked decrease in the concentration of C1q associated with a reduced level of C4 in preeclamptic patients as compared to matched healthy pregnant woman but no significant difference in the circulating level of the activating products C5a and the soluble terminal complement complex sC5b-9. Analysis of serum samples collected at early phase of pregnancy from women who later developed preeclampsia failed to show a decrease in C1q level. The results of the present investigation demonstrate that low levels of C1q and C4 are associated with preeclampsia but cannot be used as predictive markers. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. MTHFR Gene Mutations: A Potential Marker of Late-Onset Alzheimer's Disease?

    PubMed

    Román, Gustavo C

    2015-01-01

    Recent epigenome-wide association studies have confirmed the importance of epigenetic effects mediated by DNA methylation in late-onset Alzheimer's disease (LOAD). Metabolic folate pathways and methyl donor reactions facilitated by B-group vitamins may be critical in the pathogenesis of LOAD. Methylenetetrahydrofolate reductase (MTHFR) gene mutations were studied in consecutive Alzheimer's Disease & Memory Clinic patients up to December 2014. DNA analyses of MTHFR-C667T and - A1298C homozygous and heterozygous polymorphisms in 93 consecutive elderly patients revealed high prevalence of MTHFR mutations (92.5%). Findings require confirmation in a larger series, but MTHFR mutations may become a LOAD marker, opening novel possibilities for prevention and treatment.

  10. VDAC3 As a Potential Marker of Mitochondrial Status Is Involved in Cancer and Pathology

    PubMed Central

    Reina, Simona; Guarino, Francesca; Magrì, Andrea; De Pinto, Vito

    2016-01-01

    VDAC3 is the least known isoform of the mammalian voltage-dependent anion selective channels of the outer mitochondrial membrane. It has been recently shown that cysteine residues of VDAC3 are found over-oxidized. The VDAC3 cysteine over-oxidation was associated with the oxidizing environment and the abundance of reactive oxygen species (ROS) in the intermembrane space. In this work, we have examined the role of VDAC3 in general pathogenic mechanisms at the basis of mitochondrial dysfunction and involving the mitochondrial quality control. Many of the diseases reported here, including cancer and viral infections, are often associated with significant changes in the intracellular redox state. In this sense, VDAC3 bearing oxidative modifications could become marker of the oxidative load in the mitochondria and part of the ROS signaling pathway. PMID:28066720

  11. Indoleamine 2,3-dioxygenase: As a potential prognostic marker and immunotherapeutic target for hepatocellular carcinoma

    PubMed Central

    Asghar, Kashif; Farooq, Asim; Zulfiqar, Bilal; Rashid, Muhammad Usman

    2017-01-01

    Tumor cells induce an immunosuppressive microenvironment which leads towards tumor immune escape. Understanding the intricacy of immunomodulation by tumor cells is essential for immunotherapy. Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme which mediates tumor immune escape in various cancers including hepatocellular carcinoma (HCC). IDO up-regulation in HCC may lead to recruitment of regulatory T-cells into tumor microenvironment and therefore inhibit local immune responses and promote metastasis. HCC associated fibroblasts stimulate natural killer cells dysfunction through prostaglandin E2 and subsequently IDO promotes favorable condition for tumor metastasis. IDO up-regulation induces immunosuppression and may enhance the risk of hepatitis C virus and hepatitis B virus induced HCC. Therefore, IDO inhibitors as adjuvant therapeutic agents may have clinical implications in HCC. This review proposes future prospects of IDO not only as a therapeutic target but also as a prognostic marker for HCC. PMID:28428708

  12. Free amino acids in the Arctic snow and ice core samples: Potential markers for paleoclimatic studies.

    PubMed

    Barbaro, Elena; Spolaor, Andrea; Karroca, Ornela; Park, Ki-Tae; Martma, Tõnu; Isaksson, Elisabeth; Kohler, Jack; Gallet, Jean Charles; Bjorkman, Mats P; Cappelletti, David; Spreen, Gunnar; Zangrando, Roberta; Barbante, Carlo; Gambaro, Andrea

    2017-12-31

    The role of oceanic primary production on climate variability has long been debated. Defining changes in past oceanic primary production can help understanding of the important role that marine algae have in climate variability. In ice core research methanesulfonic acid is the chemical marker commonly used for assessing changes in past primary production. However, other organic compounds such as amino acids, can be produced and emitted into the atmosphere during a phytoplankton bloom. These species can be transported and deposited onto the ice cap in polar regions. Here we investigate the correlation between the concentration of chlorophyll-a, marker of marine primary production, and amino acids present in an ice core. For the first time, free l- and d-amino acids in Arctic snow and firn samples were determined by a sensitive and selective analytical method based on liquid chromatography coupled with tandem mass spectrometry. The new method for the determination of free amino acids concentrations was applied to firn core samples collected on April 2015 from the summit of the Holtedahlfonna glacier, Svalbard (N 79'08.424, E 13'23.639, 1120m a.s.l.). The main results of this work are summarized as follows: (1) glycine, alanine and proline, were detected and quantified in the firn core samples; (2) their concentration profiles, compared with that of the stable isotope δ(18)O ratio, show a seasonal cycling with the highest concentrations during the spring and summer time; (3) back-trajectories and Greenland Sea chlorophyll-a concentrations obtained by satellite measurements were compared with the amino acids profile obtained from ice core samples, this provided further insights into the present results. This study suggests that the amino acid concentrations in the ice samples collected from the Holtedahlfonna glaciers could reflect changes in oceanic phytoplankton abundance. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Smoking-related DNA adducts as potential diagnostic markers of lung cancer: new perspectives.

    PubMed

    Grigoryeva, E S; Kokova, D A; Gratchev, A N; Cherdyntsev, E S; Buldakov, M A; Kzhyshkowska, J G; Cherdyntseva, N V

    2015-03-01

    In recent years, the new direction such as identification of informative circulating markers reflecting molecular genetic changes in the DNA of tumor cells was actively developed. Smoking-related DNA adducts are very promising research area, since they indicate high pathogenetic importance in the lung carcinogenesis and can be identified in biological samples with high accuracy and reliability using highly sensitive mass spectrometry methods (TOF/TOF, TOF/MS, MS/MS). The appearance of DNA adducts in blood or tissues is the result of the interaction of carcinogenic factors, such as tobacco constituents, and the body reaction which is determined by individual characteristics of metabolic and repair systems. So, DNA adducts may be considered as a cumulative mirror of heterogeneous response of different individuals to smoking carcinogens, which finally could determine the risk for lung cancer. This review is devoted to analysis of the role of DNA adducts in lung carcinogenesis in order to demonstrate their usefulness as cancer associated markers. Currently, there are some serious limitations impeding the widespread use of DNA adducts as cancer biomarkers, due to failure of standardization of mass spectrometry analysis in order to correctly measure the adduct level in each individual. However, it is known that all DNA adducts are immunogenic, their accumulation over some threshold concentration leads to the appearance of long-living autoantibodies. Thus, detection of an informative pattern of autoantibodies against DNA adducts using innovative multiplex ELISA immunoassay may be a promising approach to find lung cancer at an early stage in high-risk groups (smokers, manufacturing workers, urban dwellers).

  14. Expression Profiling of Ribosome Biogenesis Factors Reveals Nucleolin as a Novel Potential Marker to Predict Outcome in AML Patients

    PubMed Central

    Berger, Caroline M.; Perrial, Emeline; Plesa, Adriana; Thomas, Xavier; Mattei, Eve; Hayette, Sandrine; Saintigny, Pierre; Bouvet, Philippe; Diaz, Jean-Jacques; Dumontet, Charles

    2017-01-01

    Acute myeloid leukemia (AML) is a heterogeneous disease. Prognosis is mainly influenced by patient age at diagnosis and cytogenetic alterations, two of the main factors currently used in AML patient risk stratification. However, additional criteria are required to improve the current risk classification and better adapt patient care. In neoplastic cells, ribosome biogenesis is increased to sustain the high proliferation rate and ribosome composition is altered to modulate specific gene expression driving tumorigenesis. Here, we investigated the usage of ribosome biogenesis factors as clinical markers in adult patients with AML. We showed that nucleoli, the nucleus compartments where ribosome production takes place, are modified in AML by analyzing a panel of AML and healthy donor cells using immunofluorescence staining. Using four AML series, including the TCGA dataset, altogether representing a total of about 270 samples, we showed that not all factors involved in ribosome biogenesis have clinical values although ribosome biogenesis is increased in AML. Interestingly, we identified the regulator of ribosome production nucleolin (NCL) as over-expressed in AML blasts. Moreover, we found in two series that high NCL mRNA expression level was associated with a poor overall survival, particular in elderly patients. Multivariate analyses taking into account age and cytogenetic risk indicated that NCL expression in blast cells is an independent marker of reduced survival. Our study identifies NCL as a potential novel prognostic factor in AML. Altogether, our results suggest that the ribosome biogenesis pathway may be of interest as clinical markers in AML. PMID:28103300

  15. [Polymorphism of DNA nucleotide sequence as a source of enhancement of the discrimination potential of the STR-markers].

    PubMed

    Zemskova, E Yu; Timoshenko, T V; Leonov, S N; Ivanov, P L

    2016-01-01

    The objective of the present pilot investigation was to reveal and to study polymorphism of nucleotide sequence in the alleles of STR loci of human autosomal DNA with special reference to the role of this phenomenon as a source of the differences between homonymous allelic variants. The secondary objection was to evaluate the possibility of using the data thus obtained for the enhancement of the informative value of the forensic medical genotyping of STR loci by means of identification of single nucleotide polymorphisms (SNP) for the purpose of extending their allelic spectrum. The methodological basis of the study was constituted by the comprehensive amplified fragment length polymorphism (AFLP) analysis and amplified fragment sequence polymorphisms (AFSP) analysis of DNA with the use of the PLEX-ID^TM analytical mass-spectrometry platform (Abbot Molecular, USA). The study has demonstrated that polymorphism of DNA nucleotide sequence can be regarded as the possible source of enhancement of the discriminating potential of STR markers. It means that the analysis of polymorphism of DNA nucleotide sequence for genotyping AFLP-type markers of chromosomal DNA can considerably increase the effectiveness of their application as individualizing markers for the purpose of molecular genetic expertises.

  16. Expression Profiling of Ribosome Biogenesis Factors Reveals Nucleolin as a Novel Potential Marker to Predict Outcome in AML Patients.

    PubMed

    Marcel, Virginie; Catez, Frédéric; Berger, Caroline M; Perrial, Emeline; Plesa, Adriana; Thomas, Xavier; Mattei, Eve; Hayette, Sandrine; Saintigny, Pierre; Bouvet, Philippe; Diaz, Jean-Jacques; Dumontet, Charles

    2017-01-01

    Acute myeloid leukemia (AML) is a heterogeneous disease. Prognosis is mainly influenced by patient age at diagnosis and cytogenetic alterations, two of the main factors currently used in AML patient risk stratification. However, additional criteria are required to improve the current risk classification and better adapt patient care. In neoplastic cells, ribosome biogenesis is increased to sustain the high proliferation rate and ribosome composition is altered to modulate specific gene expression driving tumorigenesis. Here, we investigated the usage of ribosome biogenesis factors as clinical markers in adult patients with AML. We showed that nucleoli, the nucleus compartments where ribosome production takes place, are modified in AML by analyzing a panel of AML and healthy donor cells using immunofluorescence staining. Using four AML series, including the TCGA dataset, altogether representing a total of about 270 samples, we showed that not all factors involved in ribosome biogenesis have clinical values although ribosome biogenesis is increased in AML. Interestingly, we identified the regulator of ribosome production nucleolin (NCL) as over-expressed in AML blasts. Moreover, we found in two series that high NCL mRNA expression level was associated with a poor overall survival, particular in elderly patients. Multivariate analyses taking into account age and cytogenetic risk indicated that NCL expression in blast cells is an independent marker of reduced survival. Our study identifies NCL as a potential novel prognostic factor in AML. Altogether, our results suggest that the ribosome biogenesis pathway may be of interest as clinical markers in AML.

  17. Genome-wide association analysis of bacterial cold water disease resistance in rainbow trout reveals the potential of a hybrid approach between genomic selection and marker assisted selection

    USDA-ARS?s Scientific Manuscript database

    Genomic selection (GS) simultaneously incorporates dense SNP marker genotypes with phenotypic data from related animals to predict animal-specific genomic breeding value (GEBV), which circumvents the need to measure the disease phenotype in potential breeders. Marker assisted selection (MAS) involv...

  18. Label-free visualization of collagen in submucosa as a potential diagnostic marker for early detection of colorectal cancer

    NASA Astrophysics Data System (ADS)

    Qiu, Jingting; Yang, Yinghong; Jiang, Weizhong; Feng, Changyin; Chen, Zhifen; Guan, Guoxian; Zhu, Xiaoqin; Zhuo, Shuangmu; Chen, Jianxin

    2014-09-01

    The collagen signature in colorectal submucosa is changed due to remodeling of the extracellular matrix during the malignant process and plays an important role in noninvasive early detection of human colorectal cancer. In this work, multiphoton microscopy (MPM) was used to monitor the changes of collagen in normal colorectal submucosa (NCS) and cancerous colorectal submucosa (CCS). What's more, the collagen content was quantitatively measured. It was found that in CCS the morphology of collagen becomes much looser and the collagen content is significantly reduced compared to NCS. These results suggest that MPM has the ability to provide collagen signature as a potential diagnostic marker for early detection of colorectal cancer.

  19. Assessment of four molecular markers as potential DNA barcodes for red algae Kappaphycus Doty and Eucheuma J. Agardh (Solieriaceae, Rhodophyta).

    PubMed

    Tan, Ji; Lim, Phaik-Eem; Phang, Siew-Moi; Hong, Dang Diem; Sunarpi, H; Hurtado, Anicia Q

    2012-01-01

    DNA barcoding has been a major advancement in the field of taxonomy, seeing much effort put into the barcoding of wide taxa of organisms, macro and microalgae included. The mitochondrial-encoded cox1 and plastid-encoded rbcL has been proposed as potential DNA barcodes for rhodophytes, but are yet to be tested on the commercially important carrageenophytes Kappaphycus and Eucheuma. This study gauges the effectiveness of four markers, namely the mitochondrial cox1, cox2, cox2-3 spacer and the plastid rbcL in DNA barcoding on selected Kappaphycus and Eucheuma from Southeast Asia. Marker assessments were performed using established distance and tree-based identification criteria from earlier studies. Barcoding patterns on a larger scale were simulated by empirically testing on the commonly used cox2-3 spacer. The phylogeny of these rhodophytes was also briefly described. In this study, the cox2 marker which satisfies the prerequisites of DNA barcodes was found to exhibit moderately high interspecific divergences with no intraspecific variations, thus a promising marker for the DNA barcoding of Kappaphycus and Eucheuma. However, the already extensively used cox2-3 spacer was deemed to be in overall more appropriate as a DNA barcode for these two genera. On a wider scale, cox1 and rbcL were still better DNA barcodes across the rhodophyte taxa when practicality and cost-efficiency were taken into account. The phylogeny of Kappaphycus and Eucheuma were generally similar to those earlier reported. Still, the application of DNA barcoding has demonstrated our relatively poor taxonomic comprehension of these seaweeds, thus suggesting more in-depth efforts in taxonomic restructuring as well as establishment.

  20. Assessment of Four Molecular Markers as Potential DNA Barcodes for Red Algae Kappaphycus Doty and Eucheuma J. Agardh (Solieriaceae, Rhodophyta)

    PubMed Central

    Tan, Ji; Lim, Phaik-Eem; Phang, Siew-Moi; Hong, Dang Diem; Sunarpi, H.; Hurtado, Anicia Q.

    2012-01-01

    DNA barcoding has been a major advancement in the field of taxonomy, seeing much effort put into the barcoding of wide taxa of organisms, macro and microalgae included. The mitochondrial-encoded cox1 and plastid-encoded rbcL has been proposed as potential DNA barcodes for rhodophytes, but are yet to be tested on the commercially important carrageenophytes Kappaphycus and Eucheuma. This study gauges the effectiveness of four markers, namely the mitochondrial cox1, cox2, cox2-3 spacer and the plastid rbcL in DNA barcoding on selected Kappaphycus and Eucheuma from Southeast Asia. Marker assessments were performed using established distance and tree-based identification criteria from earlier studies. Barcoding patterns on a larger scale were simulated by empirically testing on the commonly used cox2-3 spacer. The phylogeny of these rhodophytes was also briefly described. In this study, the cox2 marker which satisfies the prerequisites of DNA barcodes was found to exhibit moderately high interspecific divergences with no intraspecific variations, thus a promising marker for the DNA barcoding of Kappaphycus and Eucheuma. However, the already extensively used cox2-3 spacer was deemed to be in overall more appropriate as a DNA barcode for these two genera. On a wider scale, cox1 and rbcL were still better DNA barcodes across the rhodophyte taxa when practicality and cost-efficiency were taken into account. The phylogeny of Kappaphycus and Eucheuma were generally similar to those earlier reported. Still, the application of DNA barcoding has demonstrated our relatively poor taxonomic comprehension of these seaweeds, thus suggesting more in-depth efforts in taxonomic restructuring as well as establishment. PMID:23285223

  1. Endogenous Klebsiella pneumoniae endophthalmitis.

    PubMed

    Yin, Wenpeng; Zhou, Haijiang; Li, Chunsheng

    2014-10-01

    Klebsiella pneumonia is a common human pathogen, and endogenous endophthalmitis is a vision-threatening infection presentedwith pain, redness, decreased vision acuity, and intraocular inflammation. Endogenous endophthalmitis caused by Klebsiella pneumoniae is uncommon and usually happens in patients with immunosuppression conditions. Diabetes is a predisposing risk factor, and liver abscess is a major source of Klebsiella pneumonia endogenous endophthalmitis (KPEE). Here, we report a case of KPEE in a patient who lost his vision in one eye after treatment.

  2. Inhibition of endogenous hydrogen sulfide production in clear-cell renal cell carcinoma cell lines and xenografts restricts their growth, survival and angiogenic potential

    PubMed Central

    Sonke, Eric; Verrydt, Megan; Postenka, Carl O.; Pardhan, Siddika; Willie, Chantalle J.; Mazzola, Clarisse R.; Hammers, Matthew D.; Pluth, Michael D.; Lobb, Ian; Power, Nicholas E.; Chambers, Ann F.; Leong, Hon S.; Sener, Alp

    2016-01-01

    Clear cell renal cell carcinoma (ccRCC) is characterized by Von Hippel–Lindau (VHL)-deficiency, resulting in pseudohypoxic, angiogenic and glycolytic tumours. Hydrogen sulfide (H2S) is an endogenously-produced gasotransmitter that accumulates under hypoxia and has been shown to be pro-angiogenic and cytoprotective in cancer. It was hypothesized that H2S levels are elevated in VHL-deficient ccRCC, contributing to survival, metabolism and angiogenesis. Using the H2S-specific probe MeRhoAz, it was found that H2S levels were higher in VHL-deficient ccRCC cell lines compared to cells with wild-type VHL. Inhibition of H2S-producing enzymes could reduce the proliferation, metabolism and survival of ccRCC cell lines, as determined by live-cell imaging, XTT/ATP assay, and flow cytometry respectively. Using the chorioallantoic membrane angiogenesis model, it was found that systemic inhibition of endogenous H2S production was able to decrease vascularization of VHL-deficient ccRCC xenografts. Endogenous H2S production is an attractive new target in ccRCC due to its involvement in multiple aspects of disease. PMID:26068241

  3. Endogenous Lunar Volatiles

    NASA Technical Reports Server (NTRS)

    McCubbin, F. M.; Liu, Y.; Barnes, J. J.; Boyce, J. W.; Day, J. M. D.; Elardo, S. M.; Hui, H.; Magna, T.; Ni, P.; Tartese, R.; hide

    2017-01-01

    The chapter will begin with an introduction that defines magmatic volatiles (e.g., H, F, Cl, S) versus geochemical volatiles (e.g., K, Rb, Zn). We will discuss our approach of understanding both types of volatiles in lunar samples and lay the ground work for how we will determine the overall volatile budget of the Moon. We will then discuss the importance of endogenous volatiles in shaping the "Newer Views of the Moon", specifically how endogenous volatiles feed forward into processes such as the origin of the Moon, magmatic differentiation, volcanism, and secondary processes during surface and crustal interactions. After the introduction, we will include a re-view/synthesis on the current state of 1) apatite compositions (volatile abundances and isotopic compositions); 2) nominally anhydrous mineral phases (moderately to highly volatile); 3) volatile (moderately to highly volatile) abundances in and isotopic compositions of lunar pyroclastic glass beads; 4) volatile (moderately to highly volatile) abundances in and isotopic compositions of lunar basalts; 5) volatile (moderately to highly volatile) abundances in and isotopic compositions of melt inclusions; and finally 6) experimental constraints on mineral-melt partitioning of moderately to highly volatile elements under lunar conditions. We anticipate that each section will summarize results since 2007 and focus on new results published since the 2015 Am Min review paper on lunar volatiles [9]. The next section will discuss how to use sample abundances of volatiles to understand the source region and potential caveats in estimating source abundances of volatiles. The following section will include our best estimates of volatile abundances and isotopic compositions (where permitted by available data) for each volatile element of interest in a number of important lunar reservoirs, including the crust, mantle, KREEP, and bulk Moon. The final section of the chapter will focus upon future work, outstanding questions

  4. Theory of Mind as a potential trait marker of schizophrenia: a family study.

    PubMed

    Pentaraki, A D; Stefanis, N C; Stahl, D; Theleritis, C; Toulopoulou, T; Roukas, D; Kaliora, S C; Chatzimanolis, I; Smyrnis, N; Russell, T; Kravariti, E; Murray, R M

    2012-01-01

    Although there is some evidence that Theory of Mind (ToM) deficits may be trait markers of schizophrenia it is not clear yet if ToM deficits are primary deficits, that is, to be independent of deficits in general intellectual abilities and executive function. The aim was to examine if ToM deficits may be trait markers of the illness and the effect of cognitive inhibition, general intellectual abilities and depression on ToM abilities of patients with schizophrenia and their unaffected parents. We assessed ToM abilities (first-order and second-order ToM stories, The Revised Eyes Test), cognitive inhibition (Stroop Task), general intellectual ability (Standard Progressive Matrices Test Plus) in patients with schizophrenia (N=21) and their unaffected fathers (N=21) and mothers (N=21) in comparison with healthy control families (healthy control males, N=21, healthy control fathers, N=21, healthy control mothers, N=21) Patients showed deficits in first-order ToM tasks but some of these deficits were mediated by general intellectual abilities. Impairments in cognitive inhibition mediated only patients' performance in The Revised Eyes Test. Patients showed deficits in second-order ToM stories independently of deficits in general intellectual abilities and cognitive inhibition. Unaffected parents did not show deficits in first-order ToM tasks, whereas they showed deficits in second-order ToM stories. However, the deficits that unaffected parents showed in second-order ToM stories were mediated by their deficits in general intellectual abilities, and there was an effect of remitted depression on the unaffected mothers' performance. The results suggest that intact neurocognitive and general intellectual abilities are necessary in order patients and their unaffected parents to pass successfully ToM tasks. Patients and their unaffected parents show ToM deficits but these deficits are not similar. Patients show ToM deficits but these deficits seem to be a component of the

  5. Gene Expression Changes in Developing Zebrafish as Potential Markers for Rapid Developmental Neurotoxicity Screening

    EPA Science Inventory

    Sparse information exists on many chemicals to guide developmental neurotoxicity (DNT) risk assessments. As DNT testing using rodents is laborious and expensive, alternative species such as zebrafish are being adapted for toxicity screening. Assessing the DNT potential of chem...

  6. Gene Expression Changes in Developing Zebrafish as Potential Markers for Rapid Developmental Neurotoxicity Screening

    EPA Science Inventory

    Sparse information exists on many chemicals to guide developmental neurotoxicity (DNT) risk assessments. As DNT testing using rodents is laborious and expensive, alternative species such as zebrafish are being adapted for toxicity screening. Assessing the DNT potential of chem...

  7. Reticulocyte hemoglobin equivalent as a potential marker for diagnosis of iron deficiency.

    PubMed

    Toki, Yasumichi; Ikuta, Katsuya; Kawahara, Yoshie; Niizeki, Noriyasu; Kon, Masayuki; Enomoto, Motoki; Tada, Yuko; Hatayama, Mayumi; Yamamoto, Masayo; Ito, Satoshi; Shindo, Motohiro; Kikuchi, Yoko; Inoue, Mitsutaka; Sato, Kazuya; Fujiya, Mikihiro; Okumura, Toshikatsu

    2017-07-01

    Evaluation of parameters relating to serum ferritin and iron is critically important in the diagnosis of iron deficiency anemia (IDA). The recent development of automated systems for hematology analysis has made it possible to measure reticulocyte hemoglobin equivalent (RET-He), which is thought to reflect iron content in reticulocytes, in the same sample used for complete blood count tests. If RET-He is, indeed, capable of evaluating iron deficiency (ID), it would be useful for immediate diagnosis of IDA. In the present study, we examined the usefulness of RET-He for diagnosis of ID. Blood samples were obtained from 211 patients. Anemia was defined as hemoglobin (Hb) level of <12 g/dL. Iron deficiency was defined as serum ferritin level of <12 ng/mL. Patients were classified into four groups: IDA, ID, control, and non-ID with anemia. Patients in the IDA group had significantly lower RET-He levels than those in the control group. RET-He correlated with serum ferritin in the IDA and ID groups. The area under the curve for RET-He was 0.902, indicating that RET-He facilitates the diagnosis of ID with high accuracy. RET-He changed in parallel with changes in Hb during iron administration for 21 IDA patients. Our results indicate that RET-He may be a clinically useful marker for determining ID in the general population.

  8. Antiphosphatidylserine/prothrombin antibodies (aPS/PT) as potential markers of antiphospholipid syndrome.

    PubMed

    Vlagea, Alexandru; Gil, Antonio; Cuesta, Maria V; Arribas, Florencia; Diez, Jesús; Lavilla, Paz; Pascual-Salcedo, Dora

    2013-06-01

    The antiphospholipid antibodies present in antiphospholipid syndrome (APS) are directed at a number of phospholipid-binding proteins: β2 glycoprotein I (β2GPI), prothrombin, and so on. Antibodies directed at β2GPI are accepted as a classification criterion for APS, while the presence of antiprothrombin antibodies is not. In the present article, we investigated the possible role of antiphosphatidylserine/prothrombin antibodies (aPS/PT) as marker of APS on a cohort of 295 individuals with APS (95 primary APS and 45 secondary APS) and APS-related diseases. We found aPS/PT to be highly associated with venous thrombosis (immunoglobulin G [IgG] aPS/PT odds ratio [OR], 7.44; 95% confidence interval [CI], 3.97-13.92 and IgM aPS/PT OR, 2.54; 95% CI, 1.35-4.77) and obstetric abnormalities (IgG aPS/PT OR, 2.37; 95% CI, 1.04-5.43), but not with arterial thrombosis. A very high degree of concordance between the concentration of aPS/PT and lupus anticoagulant activity was demonstrated. Therefore, we support the inclusion of aPS/PT determination as second-level assay to confirm APS classification.

  9. Imprecise vowel articulation as a potential early marker of Parkinson's disease: effect of speaking task.

    PubMed

    Rusz, Jan; Cmejla, Roman; Tykalova, Tereza; Ruzickova, Hana; Klempir, Jiri; Majerova, Veronika; Picmausova, Jana; Roth, Jan; Ruzicka, Evzen

    2013-09-01

    The purpose of this study was to analyze vowel articulation across various speaking tasks in a group of 20 early Parkinson's disease (PD) individuals prior to pharmacotherapy. Vowels were extracted from sustained phonation, sentence repetition, reading passage, and monologue. Acoustic analysis was based upon measures of the first (F1) and second (F2) formant of the vowels /a/, /i/, and /u/, vowel space area (VSA), F2i/F2u and vowel articulation index (VAI). Parkinsonian speakers manifested abnormalities in vowel articulation across F2u, VSA, F2i/F2u, and VAI in all speaking tasks except sustained phonation, compared to 15 age-matched healthy control participants. Findings suggest that sustained phonation is an inappropriate task to investigate vowel articulation in early PD. In contrast, monologue was the most sensitive in differentiating between controls and PD patients, with classification accuracy up to 80%. Measurements of vowel articulation were able to capture even minor abnormalities in speech of PD patients with no perceptible dysarthria. In conclusion, impaired vowel articulation may be considered as a possible early marker of PD. A certain type of speaking task can exert significant influence on vowel articulation. Specifically, complex tasks such as monologue are more likely to elicit articulatory deficits in parkinsonian speech, compared to other speaking tasks.

  10. The Potential of Genes and other Markers to Inform about Risk

    PubMed Central

    Pepe, Margaret S.; Gu, Jessie W.; Morris, Daryl E.

    2009-01-01

    Background Advances in biotechnology have raised expectations that biomarkers, including genetic profiles, will yield information to accurately predict outcomes for individuals. However, results to date have been disappointing. In addition, statistical methods to quantify the predictive information in markers have not been standardized. Methods We discuss statistical techniques to summarize predictive information including risk distribution curves and measures derived from them that relate to decision making. Attributes of these measures are contrasted with alternatives such as receiver operating characteristic curves, R-squared, percent reclassification and net reclassification index. Data are generated from simple models of risk conferred by genetic profiles for individuals in a population. Statistical techniques are illustrated and the risk prediction capacities of different risk models are quantified. Results Risk distribution curves are most informative and relevant to clinical practice. They show proportions of subjects classified into clinically relevant risk categories. In a population in which 10% have the outcome event and subjects are categorized as high risk if their risk exceeds 20%, we found to identify as high risk more than half of those destined to have an event, either 150 genes each with odds ratio of 1.5 or 250 genes each with odds ratio of 1.25 was required when the minor allele frequencies are 10%. We show that conclusions based on ROC curves may not be the same as conclusions based on risk distribution curves. Conclusions Many highly predictive genes will be required in order to identify substantial numbers of subjects at high risk. PMID:20160267

  11. Fecal but not serum calprotectin is a potential marker of GVHD after stem cell transplantation.

    PubMed

    Metafuni, Elisabetta; Giammarco, Sabrina; De Ritis, Daniela Giovanna; Rossi, Monica; De Michele, Teresa; Zuppi, Cecilia; Bacigalupo, Andrea P; Sica, Simona; Chiusolo, Patrizia

    2017-06-01

    Gastrointestinal graft-versus-host disease (GvHD) represents a life-threatening complication after stem cell transplantation. Differential diagnosis between gut GvHD and other causes of diarrhea after HSCT is still subjected to endoscopy and histological findings. The research for a reliable biomarker for gut GvHD might allow an early diagnosis of this condition and a consequent prompt treatment that could reduce unfavorable outcomes. Recently, fecal calprotectin was reported as reliable marker of gut involvement. We would evaluate if serum instead of fecal calprotectin could be considered a possible biomarker of gut GvHD. Serum calprotectin was measured in a cohort of 54 patients submitted to allogeneic stem cell transplantation using ELISA assay. For a subset of 21 patients, calprotectin serum levels were compared with fecal calprotectin detection. Contrary to fecal calprotectin, we found only a trend to high level of serum calprotectin for GvHD development and gut involvement, but statistical difference was not reached. Fecal but not serum calprotectin could be considered as possible biomarker for gut GvHD.

  12. Resistin as a potential marker of renal disease in lupus nephritis.

    PubMed

    Hutcheson, J; Ye, Y; Han, J; Arriens, C; Saxena, R; Li, Q-Z; Mohan, C; Wu, T

    2015-03-01

    Systemic lupus erythematosus (SLE) and lupus nephritis (LN) have strong concomitance with cardiovascular disease that cannot be explained fully by typical risk factors. We examined the possibility that serum or urine expression of adipokines may act as biomarkers for LN, as these proteins have been associated previously with cardiovascular disease as well as SLE. Antibody arrays were performed on serum and urine from lupus patients and matched controls using a cross-sectional study design. From the initial array-based screening data of 15 adipokines, adiponectin, leptin and resistin were selected for validation by enzyme-linked immunosorbent assay (ELISA). Correlations were determined between adipokine expression levels and measures of disease activity or lupus nephritis. The expression of adiponectin and resistin was increased in both sera and urine from LN patients, while leptin was increased in LN patient sera, compared to matched controls. Serum resistin, but not urine resistin, was correlated with measures of renal dysfunction in LN. Serum resistin expression may be useful as a marker of renal dysfunction in patients with LN, although longitudinal studies are warranted. Further studies are necessary to determine if resistin has functional consequences in LN. © 2014 British Society for Immunology.

  13. Structural chromosomal aberrations as potential risk markers in incident cancer patients.

    PubMed

    Vodenkova, Sona; Polivkova, Zdenka; Musak, Ludovit; Smerhovsky, Zdenek; Zoubkova, Hana; Sytarova, Sylvie; Kavcova, Elena; Halasova, Erika; Vodickova, Ludmila; Jiraskova, Katerina; Svoboda, Miroslav; Ambrus, Miloslav; Hemminki, Kari; Vodicka, Pavel

    2015-07-01

    Epidemiological prospective studies have shown that increased chromosomal aberrations (CAs) in peripheral blood lymphocytes may predict cancer risk. Here, we report CAs in newly diagnosed 101 colorectal, 87 lung and 158 breast cancer patients and corresponding healthy controls. Strong differences in distributions of aberrant cells (ACs), CAs, chromatid-type aberrations (CTAs) and chromosome-type aberrations (CSAs) were observed in lung and breast cancer patients as compared to healthy controls. In colorectal cancer (CRC) patients, only CTAs were significantly elevated. Binary logistic regression, adjusted for main confounders, indicates that all the analysed cytogenetic parameters along with smoking were significantly associated with breast and lung cancer risks. Significant differences in terminal deletions between breast cancer patients and corresponding female controls were recorded (0.39 vs. 0.18; P ≤ 0.05). We did not find any association of CAs with TNM (tumor nodus metastasis) stages or histopathological grade in either cancer type. CAs were neither associated with additional tumor characteristics-invasivity, ductal and lobular character, estrogene/progesterone receptors in breast tumors nor with non-small/small cell and bronchogenic/pulmonary types of lung tumors. Our study demonstrates that CAs serve as a predictive marker for breast and lung cancer, whereas only CTAs were elevated in incident CRC patients. © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Mutations in p53 as potential molecular markers for human breast cancer

    SciTech Connect

    Runnebaum, I.B.; Nagarajan, M.; Bowman, M.; Soto, D.; Sukumar, S. )

    1991-12-01

    Based on the high incidence of loss of heterozygosity for loci on chromosome 17p in the vicinity of the p53 locus in human breast tumors. The authors investigated the frequency and effects of mutations in the p53 tumor suppressor gene in mammary neoplasia. They examined the p53 gene in 20 breast cancer cell lines and 59 primary breast tumors. Northern blot analysis, immunoprecipitation, and nucleotide sequencing analysis revealed aberrant mRNA expression, over-expression of protein, and point mutations in the p53 gene in 50% of the cell line tested. A multiplex PCR assay was developed to search for deletions in the p53 genomic locus. Multiplex PCR of genomic DNA showed that up to 36% of primary tumors contained aberrations in the p53 locus. Mutations in exons 5-9 of the p53 gene were found in 10 out of 59 (17%) of the primary tumors studied by single-stranded conformation polymorphism analysis. They conclude that, compared to amplification of HER2/NEU, MYC, or INT2 oncogene loci, p53 gene mutations and deletions are the most frequently observed genetic change in breast cancer related to a single gene. Correlated to disease status, p53 gene mutations could prove to be a valuable marker for diagnosis and/or prognosis of breast neoplasia.

  15. Basal cytokeratin as a potential marker of low risk of invasion in ductal carcinoma in situ

    PubMed Central

    Aguiar, Fernando N.; Mendes, Henrique N.; Cirqueira, Cinthya S.; Bacchi, Carlos E.; Carvalho, Filomena M.

    2013-01-01

    OBJECTIVES: Biological markers that predict the development of invasive breast cancer are needed to improve personalized therapy for patients diagnosed with ductal carcinoma in situ. We investigated the role of basal cytokeratin 5/6 in the risk of invasion in breast ductal carcinoma in situ. METHODS: We constructed tissue microarrays using 236 ductal carcinoma in situ samples: 90 pure samples (group 1) and 146 samples associated with invasive carcinoma (group 2). Both groups had similar nuclear grades and were obtained from patients of similar ages. The groups were compared in terms of estrogen (ER) and progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) expression, cytokeratin 5/6 immunostaining, human epidermal growth factor receptor 1 (EGFR) membrane staining and molecular subtype, as indicated by their immunohistochemistry profiles. RESULTS: ER/PR-negative status was predictive of invasion, whereas HER2 superexpression and cytokeratin 5/6-positive status were negatively associated with invasion. Among the high-grade ductal carcinoma in situ cases, a triple-positive profile (positive for estrogen receptor, progesterone receptor, and HER2) and cytokeratin 5/6 expression by neoplastic cells were negatively associated with invasion. In the low-grade ductal carcinoma in situ subgroup, only cytokeratin 5/6 expression exhibited a negative association with the probability of invasion. CONCLUSION: The immunohistochemical expression of cytokeratin 5/6 by ductal carcinoma in situ epithelial cells may provide clinically useful information regarding the risk of progression to invasive disease. PMID:23778411

  16. A potential marker of bare metal stent restenosis: monocyte count - to- HDL cholesterol ratio.

    PubMed

    Ucar, Fatih Mehmet

    2016-10-03

    Oxidation and inflammation play significant roles in the pathogenesis of coronary artery diseases. Monocyte count to high-density lipoprotein (HDL) cholesterol ratio (MHR) is a new marker and has revealed as an indicator of inflammation in the literature. The present study aimed to search the effect of MHR on in-stent restenosis (ISR) in patients with stable or unstable angina pectoris undergoing bare-metal stent (BMS) implantation. A total of 468 consecutive stable or unstable angina pectoris patients (mean age 60.3 ± 10.1 and 70 % men) who had undergone successful BMS implantation were included the study. Serum samples were obtained before the procedure. The mean period between two coronary angiography procedures was 14 ± 7.9 months. The baseline MHR levels were significantly higher in patients that had ISR (odds ratio, 3.64; 95 % confidence interval, 2.45- 4.84; P < 0.001). Stent diameter, the time between the two coronary angiographic studies, uric acid and MHR levels emerged as independent predictors of ISR. Our results indicate that elevated MHR is an independent and powerful predictor of ISR in patients with stable or unstable angina pectoris who underwent successful BMS implantation.

  17. Potential markers and metabolic processes involved in the mechanism of radiation-induced heart injury.

    PubMed

    Slezak, Jan; Kura, Branislav; Babal, Pavel; Barancik, Miroslav; Ferko, Miroslav; Frimmel, Karel; Kalocayova, Barbora; Kukreja, Rakesh C; Lazou, Antigone; Mezesova, Lucia; Okruhlicova, Ludmila; Ravingerova, Tanya; Singal, Pawan K; Szeiffova Bacova, Barbara; Viczenczova, Csilla; Vrbjar, Norbert; Tribulova, Narcis

    2017-10-01

    Irradiation of normal tissues leads to acute increase in reactive oxygen/nitrogen species that serve as intra- and inter-cellular signaling to alter cell and tissue function. In the case of chest irradiation, it can affect the heart, blood vessels, and lungs, with consequent tissue remodelation and adverse side effects and symptoms. This complex process is orchestrated by a large number of interacting molecular signals, including cytokines, chemokines, and growth factors. Inflammation, endothelial cell dysfunction, thrombogenesis, organ dysfunction, and ultimate failing of the heart occur as a pathological entity - "radiation-induced heart disease" (RIHD) that is major source of morbidity and mortality. The purpose of this review is to bring insights into the basic mechanisms of RIHD that may lead to the identification of targets for intervention in the radiotherapy side effect. Studies of authors also provide knowledge about how to select targeted drugs or biological molecules to modify the progression of radiation damage in the heart. New prospective studies are needed to validate that assessed factors and changes are useful as early markers of cardiac damage.

  18. Personality traits as potential susceptibility markers: differential susceptibility to support among parents.

    PubMed

    Slagt, Meike; Dubas, Judith Semon; Denissen, Jaap J A; Deković, Maja; van Aken, Marcel A G

    2015-04-01

    In this study, we examined whether parents are differentially susceptible to support from their spouse and adolescent child depending on their personality traits, and whether differences in susceptibility to support among parents, in turn, are linked to the quality of support parents give to their children. Participants in this three-wave longitudinal study were 288 two-parent Dutch families with an adolescent child. Fathers were on average 43.9 years old (SD = 3.7 years), mothers were 41.7 years old (SD = 3.3 years), and adolescents (50% girls) were 14.5 years old (SD = 0.8 years). We found that the association between support from children toward their parents and subsequent support from parents toward their children was more pronounced for parents high on Openness, for better and for worse. Extraversion, Agreeableness, Conscientiousness, and Emotional Stability did not emerge as markers of differences in susceptibility. Also, parents did not differ in their susceptibility to support from their spouse, nor were differences in susceptibility found a year later when using data from a third wave. We found very modest support for differential susceptibility, only for Openness, and depending on the source of perceived support and on the timing of measurement.

  19. Oncofetal protein, IMP-3, a potential marker for prediction of postoperative peritoneal dissemination in gastric adenocarcinoma.

    PubMed

    Okada, Kaoru; Fujiwara, Yoshiyuki; Nakamura, Yurika; Takiguchi, Shuji; Nakajima, Kiyokazu; Miyata, Hiroshi; Yamasaki, Makoto; Kurokawa, Yukinori; Takahashi, Tsuyoshi; Mori, Masaki; Doki, Yuichiro

    2012-06-15

    The aim of this study was to determine the expression of insulin-like growth factor-II messenger RNA (mRNA)-binding protein-3 (IMP-3) and its clinical significance in gastric cancers, as well the prognostic value of its expression in the peritoneal lavage fluid after surgery. IMP-3 expression was examined by immunohistochemistry in 96 primary gastric tumors. IMP-3 mRNA expression in peritoneal lavage fluid obtained at laparotomy was determine by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Positive staining for IMP-3 was observed in 74% (71/96) of the tumors. IMP-3 expression in gastric tumors correlated significantly with worst overall survival (OS) and recurrence-free survival. Multivariate analyses identified pathological N stage and IMP-3 expression as significant independent prognostic factors for disease-free survival. Eight (28%) of 36 peritoneal lavage samples were cytologically negative but positive for IMP-3 mRNA expression by RT-PCR. The OS of patients with IMP-3-positive peritoneal lavage was significantly worse than of those with negative expression. IMP-3 expression in primary gastric tumors was an independent poor prognostic factor. IMP-3 mRNA expression in peritoneal lavage fluid was a predictor of recurrence after surgery in gastric cancer and a marker of poor prognosis. Copyright © 2011 Wiley Periodicals, Inc.

  20. MicroRNA-155 is a potential molecular marker of natural killer/T-cell lymphoma

    PubMed Central

    Huang, Ruixia; Li, Lifeng; Wang, Xinhua; Li, Ling; Fu, Xiaorui; Sun, Zhenchang; Li, Zhaoming; Chen, Qingjiang; Zhang, Mingzhi

    2016-01-01

    Natural killer/T-cell lymphoma (NKTCL) is characterized by its highly aggressive nature and rapid progression. MicroRNAs (miRNAs) play key roles in the development of NKTCL. We utilized next-generation Solexa high-throughput sequencing to compare miRNA expression in the SNK-6 and YTS NKTCL cell lines with expression in normal NK cells. We found that 195 miRNAs were upregulated in the SNK-6 cells and 286 miRNAs were upregulated in the YTS cells. Based on those results, we selected six miRNAs, including miRNA-155, and confirmed their expression using real-time polymerase chain reaction. Expression of miRNA-155 was higher in SNK-6 and YKS cells than in normal NK cells. We next determined the levels of miRNA-155 in the serum of healthy individuals and NKTCL patients, and correlated its expression with clinical parameters and inflammatory factors detected using enzyme-linked immunoabsorbent assays. Levels of miRNA-155 were higher in NKTCL patients’ serum than in serum from healthy individuals. miRNA-155 expression was higher in patients with stable or progressive disease (SD+PD) than in those with partial or complete remission (PR+CR). While further studies are needed to clarify the underlying molecular mechanisms, it appears miRNA-155 may be a molecular marker of NKTCL. PMID:27462776

  1. Assessment of coagulation and potential biochemical markers for hypercoagulability in canine hyperadrenocorticism.

    PubMed

    Pace, S L; Creevy, K E; Krimer, P M; Brainard, B M

    2013-01-01

    Anecdotal accounts and limited research suggest that dogs with spontaneous hyperadrenocorticism (HAC) are at risk of developing thromboembolic complications. Detailed description of coagulation status and identification of subsets of dogs at greatest risk would impact therapeutic recommendations for these patients. A subset of dogs with HAC will have a hypercoagulable tendency as identified by increased procoagulant activity, decreased fibrinolysis, or both. Objective 1: To document the existence of this hypercoagulable tendency in HAC dogs using assays of individual coagulation factors, fibrinolytic activity, and systemic coagulation. Objective 2: To evaluate clinical and biochemical markers in HAC dogs to identify a subset of HAC patients at increased risk of this hypercoagulable tendency. Seventeen dogs newly diagnosed with HAC. Prospective study. Medical history, physical examination findings, routine diagnostic tests, and comprehensive coagulation testing were performed at the time of HAC diagnosis. Coagulation parameters were assessed individually and as panels for each dog. Historical and clinical variables were correlated with coagulation parameters to identify risk factors. The majority (88.2%) of HAC dogs exhibited a hypercoagulable tendency. Abnormalities in 1 coagulation assay did not predict abnormalities in others. Duration of clinical signs of HAC did not predict hypercoagulability. Comorbid conditions or abnormal clinicopathologic parameters that predicted hypercoagulability were not identified. Although HAC dogs may demonstrate a hypercoagulable tendency individually and as a group, comorbid conditions or biochemical variables that would predict more severe coagulation abnormalities were not identified. Copyright © 2013 by the American College of Veterinary Internal Medicine.

  2. Investigating the potential of fluorescent fingerprint powders as a marker for blow fly larvae (Diptera: calliphoridae).

    PubMed

    Rosati, Jennifer Y; Robinson, Scott D; Devine, Richard

    2015-05-01

    Four fluorescent fingerprint powders (RedWop(™) , GreenWop(™) , Basic Yellow(™) , and Yellow Powder(™) ) were evaluated as a marker for blow fly larvae. Administration methods included ingestion (high vs. low concentration) or topical. Ingestion of high concentrations of Basic Yellow(™) and RedWop(™) caused higher larval mortality. Basic Yellow(™) delayed development and adult emergence while RedWop(™) and Yellow Powder(™) had a significant effect on particular stages of development, however, emergence time was not altered. Optimal administration is through ingestion at low concentration levels (<10%) or topically, with GreenWop(™) demonstrating minimal adverse effects. Optimum wavelength for discrimination between powders was 450 nm. This research can aid in investigative training to increase visibility of larval and pupal blow flies. It can also be used in entomological studies to differentiate between larval blow flies (or other dipteran) species or individuals to further understand complex interactions and behavior during larval development. © 2015 American Academy of Forensic Sciences.

  3. Nighttime fears of preschool children: a potential disposition marker for anxiety?

    PubMed

    Kushnir, Jonathan; Gothelf, Doron; Sadeh, Avi

    2014-02-01

    To examine if children who suffer from significant Nighttime Fears (NF) experience higher degree of general fears and behavioral problems and to explore whether effortful control mediates NF association with internalizing problems. One-hundred and nine preschool children (64 boys) between the ages 4 and 6years suffering from significant NF and 30 healthy children (16 boys) were evaluated using parental reports of behavioral problems [Child Behavior Checklist (CBCL)], parental and child report of fears [Fear Survey Revised for Parents (FSS-PC), Koala Fear Questionnaire (KFQ)], and a measure of effortful control derived from the Child Behavior Questionnaire (CBQ). Children with severe NF also suffer from an increased level of a wide variety of fears other than NF, and exhibit more behavioral problems than controls both on parental and children's measures of general fears, and main CBCL scale scores (Internalizing, Externalizing, Total score). Additionally, children with NF had lower abilities of effortful control (as manifested in CBQ attention and inhibitory control scales). Attention control mediated NF association to internalizing problems scale. NF may serve as a marker for anxiety vulnerability, and this vulnerability might be mediated by abnormal attentional control. Our finding also highlights the need for a more comprehensive assessment of behavioral problems, fears and anxiety phenomena among children referred with NF. © 2013.

  4. Protein O-fucosyltransferase 1: a potential diagnostic marker and therapeutic target for human oral cancer.

    PubMed

    Yokota, Satoshi; Ogawara, Katsunori; Kimura, Ryota; Shimizu, Fumie; Baba, Takao; Minakawa, Yasuyuki; Higo, Morihiro; Kasamatsu, Atsushi; Endo-Sakamoto, Yosuke; Shiiba, Masashi; Tanzawa, Hideki; Uzawa, Katsuhiro

    2013-12-01

    Protein O-fucosyltransferase 1 (POFUT1) is the enzyme that adds O-fucose through O-glycosidic linkage to conserved serine or threonine residues in the epidermal growth factor-like repeats of a number of cellular surface and secreted proteins. Our previous study using microarray technology showed that significant upregulation of POFUT1 occurs in oral squamous cell carcinoma (OSCC)-derived cell lines compared to human normal oral keratinocytes. The aim of the present study was to examine the status of POFUT1 mRNA and protein expression in OSCC-derived cell lines and human primary OSCCs. POFUT1 mRNA was upregulated significantly (P<0.05 for both comparisons) in five OSCC-derived cell lines and primary OSCCs using quantitative reverse transcriptase-polymerase chain reaction. Immunohistochemistry data indicated that POFUT1 protein expression levels were consistent with mRNA expression status in OSCC-derived cell lines and primary OSCCs. Furthermore, POFUT1 expression status was correlated significantly (P=0.048) with the primary tumor size. The proliferation of POFUT1 knockdown cells was inhibited significantly compared with that of control cells. These results indicated that POFUT1 expression can contribute to cancer progression and that POFUT1 may serve as a diagnostic marker and a therapeutic target for OSCCs.

  5. Antibodies to endothelial cells in systemic lupus erythematosus: a potential marker for nephritis and vasculitis.

    PubMed

    D'Cruz, D P; Houssiau, F A; Ramirez, G; Baguley, E; McCutcheon, J; Vianna, J; Haga, H J; Swana, G T; Khamashta, M A; Taylor, J C

    1991-08-01

    Using an ELISA, anti-endothelial cell antibodies (AECA) have been found in sera obtained at the time of renal biopsy in 46 out of 57 patients (81%) with systemic lupus erythematosus (SLE) and nephritis (mean binding index (BI) = 84% +/- 52.8) compared with 22 out of 50 SLE patients (44%) without nephritis (mean BI = 45% +/- 35.9). Seventy normal human sera had a mean BI of 10% +/- 9.8. The highest levels were seen in patients with diffuse proliferative glomerulonephritis (WHO grade IV) and in patients with proteinuria and nephrotic syndrome. When the biopsies were assessed for activity and chronicity scores, AECA were associated with active renal lesions (P less than 0.001). AECA levels correlated with low complement levels but not with anti-DNA antibodies to extractable nuclear antigens (ENA), anti-cardiolipin or anti-neutrophil cytoplasmic antibodies. The presence of AECA conferred a positive predictive value of 0.68 for the presence of nephritis. Twenty-five patients had active vasculitis at the time of assay and the highest AECA values were seen in patients with both nephritis and vasculitis. No correlation was seen with serum immunoglobulin levels and immune complexes did not bind significantly to the endothelial surface. The possible role of these antibodies as a marker in lupus nephritis is discussed.

  6. Maternal serum ADAM12s as a potential marker of trisomy 21 prior to 10 weeks of gestation.

    PubMed

    Spencer, Kevin; Vereecken, Annie; Cowans, Nicholas J

    2008-03-01

    ADAM12s (a disintegrin and metalloprotease) is a placenta-derived glycoprotein that is involved in growth and differentiation and has been shown to be a potential first-trimester and second-trimester marker of trisomy 21 and other aneuploides. Maternal ADAM12s concentrations show a considerable temporal variation with gestational age and in the initial study levels were found to be significantly reduced in the early first trimester. Here we study the levels prior to 10 weeks of gestation to establish further the effectiveness or otherwise of ADAM12s as an early screening marker. Samples collected as part of routine first-trimester screening were retrieved from storage. In total, ten samples from singleton pregnancies with trisomy 21 were identified and were collected between the 8th and 9th weeks of gestation-of these 80% had been identified by combined first-trimester screening. A series of 62 gestational age-matched samples from singleton pregnancies collected during the same period formed the control group. ADAM12s was measured by a new DELFIA assay incorporating two monoclonals (6E6 and 8F8). Results were expressed as multiples of the median (MoM). The median MoM ADAM12s at a median gestation of 9.3 weeks was 0.61 which was significantly lower than in the controls (p = 0.011) when compared by the Mann-Whitney test. The corresponding median pregnancy associated plasma protein (PAPP-A) was 0.30 and free beta-human chorionic gonadotropin (beta-hCG) 2.02. Combining the data from this study and from the only other published study with data prior to 10 weeks suggests that ADAM12s may have the potential as an early screening marker for trisomy 21, but may not be as reduced as first thought. Copyright (c) 2008 John Wiley & Sons, Ltd.

  7. Plasma miR-216a as a potential marker of pancreatic injury in a rat model of acute pancreatitis

    PubMed Central

    Kong, Xiang-Yu; Du, Yi-Qi; Li, Lei; Liu, Jian-Qiang; Wang, Guo-Kun; Zhu, Jia-Qi; Man, Xiao-Hua; Gong, Yan-Fang; Xiao, Li-Ning; Zheng, Yong-Zhi; Deng, Shang-Xin; Gu, Jun-Jun; Li, Zhao-Shen

    2010-01-01

    AIM: To study the potential value and specificity of plasma miR-216a as a marker for pancreatic injury. METHODS: Two rat models were applied in this article: L-arginine-induced acute pancreatitis was used as one model to explore the potential value of plasma miR-216a for detection of pancreatic injury; nonlethal sepsis induced in rats by single puncture cecal ligation and puncture (CLP) was used as the other model to evaluate the specificity of plasma miR-216a compared with two commonly used markers (amylase and lipase) for acute pancreatitis. Plasmas were sampled from rats at indicated time points and total RNA was isolated. Real-Time Quantitative reverse transcriptase-polymerase chain reaction was used to quantify miR-216a in plasmas. RESULTS: In the acute pancreatitis model, among five time points at which plasmas were sampled, miR-216a concentrations were significantly elevated 24 h after arginine administration and remained significantly increased until 48 h after operation (compared with 0 h time point, P < 0.01, Kruskal-Wallis Test). In the CLP model, plasma amylase and lipase, two commonly used biomarkers for acute pancreatitis, were significantly elevated 24 h after operation (compared with 0 h time point, P < 0.01 and 0.05 respectively, Pairwise Bonferroni corrected t-tests), while miR-216a remained undetectable among four tested time points. CONCLUSION: Our article showed for the first time that plasma miR-216a might serve as a candidate marker of pancreatic injury with novel specificity. PMID:20857533

  8. Short-term effects of air temperature on blood markers of coagulation and inflammation in potentially susceptible individuals.

    PubMed

    Schäuble, Claudia Luise; Hampel, Regina; Breitner, Susanne; Rückerl, Regina; Phipps, Richard; Diaz-Sanchez, David; Devlin, Robert B; Carter, Jacqueline D; Soukup, Joleen; Silbajoris, Robert; Dailey, Lisa; Koenig, Wolfgang; Cyrys, Josef; Geruschkat, Uta; Belcredi, Petra; Kraus, Ute; Peters, Annette; Schneider, Alexandra E

    2012-09-01

    Changes in air temperature are associated with an increase in cardiovascular events, but the role of procoagulant and proinflammatory blood markers is still poorly understood. The authors investigated the association between air temperature and fibrinogen, plasminogen activator inhibitor type 1, interleukin-6 and high-sensitivity C reactive protein in two potentially susceptible groups. This prospective panel study was conducted between March 2007 and December 2008 in Augsburg, Germany. The study population comprised 187 participants with type 2 diabetes mellitus or impaired glucose tolerance and 87 participants with genetic polymorphisms on the detoxification and inflammation pathways. Overall, 1766 repeated blood measurements were collected. Hourly meteorology data were available from a central measurement site. The association between temperature and blood markers was analysed with additive mixed models. For type 2 diabetes mellitus and impaired glucose tolerance participants, the authors observed immediate, lagged and cumulative increases in fibrinogen (range of percentage changes in geometric mean: 0.6%-0.8%) and plasminogen activator inhibitor type 1 (6.0%-10.1%) in association with a 5°C temperature decrement. Participants with a body mass index above 30 kg/m(2) as well as females showed particularly strong fibrinogen effects. In participants with the special genetic background, 5°C decreases in the 5-day average of temperature led to a change of 8.0% (95% CI 0.5% to 16.2%) in interleukin-6 and of -8.4% (95% CI -15.8% to -0.3%) in high-sensitivity C reactive protein, the latter driven by physically active individuals. The authors observed different temperature effects on blood markers in two potentially susceptible groups probably indicating varying underlying biological mechanisms. This study results might provide a link between temperature and cardiovascular events.

  9. The chloroplast DNA locus psbZ-trnfM as a potential barcode marker in Phoenix L. (Arecaceae).

    PubMed

    Ballardini, Marco; Mercuri, Antonio; Littardi, Claudio; Abbas, Summar; Couderc, Marie; Ludeña, Bertha; Pintaud, Jean-Christophe

    2013-12-30

    The genus Phoenix (Arecaceae) comprises 14 species distributed from Cape Verde Islands to SE Asia. It includes the economically important species Phoenix dactylifera. The paucity of differential morphological and anatomical useful characters, and interspecific hybridization, make identification of Phoenix species difficult. In this context, the development of reliable DNA markers for species and hybrid identification would be of great utility. Previous studies identified a 12 bp polymorphic chloroplast minisatellite in the trnG (GCC)-trnfM (CAU) spacer, and showed its potential for species identification in Phoenix. In this work, in order to develop an efficient DNA barcode marker for Phoenix, a longer cpDNA region (700 bp) comprising the mentioned minisatellite, and located between the psbZ and trnfM (CAU) genes, was sequenced. One hundred and thirty-six individuals, representing all Phoenix species except P. andamanensis,were analysed. The minisatellite showed 2-7 repetitions of the 12 bp motif, with 1-3 out of seven haplotypes per species. Phoenix reclinata and P. canariensis had species-specific haplotypes. Additional polymorphisms were found in the flanking regions of the minisatellite, including substitutions, indels and homopolymers. All this information allowed us to identify unambiguously eight out of the 13 species, and overall 80% of the individuals sampled. Phoenix rupicola and P. theophrasti had the same haplotype, and so had P. atlantica, P. dactylifera, and P. sylvestris (the "date palm complex" sensu Pintaud et al. 2013). For these species, additional molecular markers will be required for their unambiguous identification. The psbZ-trnfM (CAU) region therefore could be considered as a good basis for the establishment of a DNA barcoding system in Phoenix, and is potentially useful for the identification of the female parent in Phoenix hybrids.

  10. Volatile fingerprint of Brazilian defective coffee seeds: corroboration of potential marker compounds and identification of new low quality indicators.

    PubMed

    Toci, Aline T; Farah, Adriana

    2014-06-15

    In the present work, the volatile profiles of green and roasted Brazilian defective coffee seeds and their controls were characterised, totalling 159 compounds. Overall, defective seeds showed higher number and concentration of volatile compounds compared to those of control seeds, especially pyrazines, pyrroles and phenols. Corroborating our previous results, butyrolactone and hexanoic acid, previously considered as potential defective seeds' markers, were observed only in raw and roasted defective seeds, respectively, and not in control seeds. New compounds were suggested as potential defective seeds' markers: hexanoic acid (for raw and roasted defective seeds in general), butyrolactone (for raw defective seeds in general), and 3-ethyl-2-methyl-1,3-hexadiene (for raw black seeds); β-linalool and 2-butyl-3,5-dimethylpyrazine (for roasted defective seeds in general), and 2-pentylfuran (for roasted black seeds). Additional compounds suggested as low quality indicators were 2,3,5,6-tetramethylpyrazine,2,3-butanediol and 4-ethylguaiacol, β-linalool, 2-,3-dimethylbutyl butanoate, 2-phenylethyl acetate, 2,3-butanedione, hexanedioic acid, guaiacol, 2,3-dihydro-2-methyl-1H-benzopyrrol, 3-methylpiperidine, 2-pentylpiperidine, 3-octen-2-one, 2-octenal, 2-pentylfuran and 2-butyl-3-methylpyrazine.

  11. Are endogenous feline leukemia viruses really endogenous?

    PubMed

    Stewart, H; Jarrett, O; Hosie, M J; Willett, B J

    2011-10-15

    Full length endogenous feline leukemia virus (FeLV) proviruses exist within the genomes of many breeds of domestic cat raising the possibility that they may also exist in a transmissible exogenous form. Such viruses would share receptor usage with the recombinant FeLV-B subgroup, a viral subgroup that arises in vivo by recombination between exogenous subgroup A virus (FeLV-A) and endogenous FeLV. Accordingly, all isolates of FeLV-B made to date have contained a "helper" FeLV-A, consistent with their recombinatorial origin. In order to assess whether endogenous viruses are transmitted between cats, we examined primary isolates of FeLV for which the viral subgroup had been determined for the presence of a subgroup B virus that lacked an FeLV-A. Here we describe the identification of two primary field isolates of FeLV (2518 and 4314) that appeared to contain subgroup B virus only by classical interference assays, raising the possibility of between-host transmission of endogenous FeLV. Sequencing of the env gene and U3 region of the 3' long terminal repeat (LTR) confirmed that both viral genomes contained endogenous viral env genes. However the viral 3' LTRs appeared exogenous in origin with a putative 3' recombination breakpoint residing at the 3' end of the env gene. Further, the FeLV-2518 virions also co-packaged a truncated FeLV-A genome containing a defective env gene, termed FeLV-2518(A) whilst no helper subgroup A viral genome was detected in virions of FeLV-4314. The acquisition of an exogenous LTR by the endogenous FeLV in 4314 may have allowed a recombinant FeLV variant to outgrow an exogenous FeLV-A virus that was presumably present during first infection. Given time, a similar evolution may also occur within the 2518 isolate. The data suggest that endogenous FeLVs may be mobilised by acquisition of exogenous LTRs yielding novel viruses that type biologically as FeLV-B. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. [Screening and identification of apolipoprotein A-I as a potential marker for hepatoblastoma in children].

    PubMed

    Guo, Li-Hua; Zhao, Wei; Zhang, Jun-Jie; Zhang, Qian; Fan, Ying-Zhong; Wang, Jia-Xiang

    2016-12-01

    To screen and identify serum biomarkers for childhood hepatoblastoma (HB). The serum samples from 30 children with hepatoblastoma (HB), 20 children with systemic inflammatory response syndrome, and 20 normal children were treated with magnetic bead-based weak cation exchange chromatography. The platform of surface-enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS) was used to eliminate the interference of inflammatory factors and to screen out the differentially expressed proteins in serum between tumor group and normal group. After the purification and separation of target proteins were performed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, matrix-assisted laser desorption/ionization-time of flight-mass spectrometry was used to determine their amino acid sequences. The SwissProt database was searched for matched proteins. Finally, real-time PCR and ELISA were used to verify and measure the expression of target proteins. After SELDI-TOF-MS was used for screening and elimination of the interference of inflammatory factors, a differentially expression protein with a mass-to-charge ratio of 9 348 Da was found in serum between HB group and normal group, and the HB group had significantly lower expression of this protein than the normal group (p<0.05). This protein was identified as apolipoprotein A-1 (Apo A-I). Real-time PCR and ELISA verified the low mRNA and protein expression of Apo A-I in serum in the HB group and high expression in serum in the normal group. Apo A-I can be used as a non-inflammatory protein marker for HB and has a certain value in the early diagnosis of HB.

  13. Autoantibodies to Ca2+ binding protein Calnuc is a potential marker in colon cancer detection.

    PubMed

    Chen, Yao; Lin, Ping; Qiu, Suimin; Peng, Xuan-Xian; Looi, Koksun; Farquhar, Marilyn Gist; Zhang, Jian-Ying

    2007-05-01

    Calnuc is a calcium (Ca2+) binding protein found in both Golgi and cytoplasm, and it may play a role in G protein- and Ca2+-regulated signal transduction events. This study was designed to investigate the possibility of whether Calnuc protein might be a tumor-associated antigen (TAA) that induces autoantibody response in human cancers, and to evaluate the feasibility of the Calnuc antigen-antibody system as a marker in cancer detection. Purified full-length recombinant Calnuc protein was used as an antigen in enzyme-linked immunoassay and Western blotting for the detection of autoantibodies in cancers. Sera from 447 patients with 9 different types of cancer were analyzed. Although the frequency of autoantibody to Calnuc was found to be 4.7% in total groups of cancer, it was not significantly different to that of normal individuals (1.2%). However, the frequency of autoantibody to Calnuc in colon cancer (11.5%) was significantly higher than that in normal individuals (1.2%). The expression analysis of Calnuc in multiple colon cancer tissues by immunohistochemistry on tissue array further confirmed the high specificity of Calnuc in colon cancer. Of 69 colon cancer tissue specimens examined, 41 tissues (59.4%) overexpressed Calnuc, while normal colon tissues did not show any expression of Calnuc. The subcellular distribution analysis of Calnuc examined by subcellular fractionation and immunofluorescence indicates that Calnuc is a membrane associated protein and mostly distributed in Golgi, which is consistent with previous reports. With adding Calnuc into a TAA array (including p53, c-myc, cyclin B1, cyclin D1), the cumulative frequency of antibody to multiple TAAs in colon cancer was raised to 65.4% which is significantly higher than the cumulative frequency in normal individuals (6.1%). This indicates that a mini-array of multiple TAAs which includes Calnuc might provide a novel non-invasive approach to enhance antibody detection for colon cancer diagnosis.

  14. Arm Swing as a Potential New Prodromal Marker of Parkinson’s Disease

    PubMed Central

    Mirelman, Anat; Bernad-Elazari, Hagar; Thaler, Avner; Giladi-Yacobi, Eytan; Gurevich, Tanya; Gana-Weisz, Mali; Saunders-Pullman, Rachel; Raymond, Deborah; Doan, Nancy; Bressman, Susan B.; Marder, Karen S.; Alcalay, Roy N.; Rao, Ashwini K.; Berg, Daniela; Brockmann, Kathrin; Aasly, Jan; Waro, Bjørg Johanne; Tolosa, Eduardo; Vilas, Dolores; Pont-Sunyer, Claustre; Orr-Urtreger, Avi; Hausdorff, Jeffrey M.; Giladi, Nir

    2016-01-01

    Background Reduced arm swing is a well-known clinical feature of Parkinson’s disease (PD), often observed early in the course of the disease. We hypothesized that subtle changes in arm swing and axial rotation may also be detectable in the prodromal phase. Objective The purpose of this study was to evaluate the relationship between the LRRK2-G2019S mutation, arm swing, and axial rotation in healthy nonmanifesting carriers and noncarriers of the G2019S mutation and in patients with PD. Methods A total of 380 participants (186 healthy nonmanifesting controls and 194 PD patients) from 6 clinical sites underwent gait analysis while wearing synchronized 3-axis body-fixed sensors on the lower back and bilateral wrists. Participants walked for 1 minute under the following 2 conditions: (1) usual walking and (2) dual-task walking. Arm swing amplitudes, asymmetry, variability, and smoothness were calculated for both arms along with measures of axial rotation. Results A total of 122 nonmanifesting participants and 67 PD patients were carriers of the G2019S mutation. Nonmanifesting mutation carriers walked with greater arm swing asymmetry and variability and lower axial rotation smoothness under the dual task condition when compared with noncarriers (P < .04). In the nonmanifesting mutation carriers, arm swing asymmetry was associated with gait variability under dual task (P = .003). PD carriers showed greater asymmetry and variability of movement than PD noncarriers, even after controlling for disease severity (P < .009). Conclusions The G2019S mutation is associated with increased asymmetry and variability among nonmanifesting participants and patients with PD. Prospective studies should determine if arm swing asymmetry and axial rotation smoothness may be used as motor markers of prodromal PD. PMID:27430880

  15. Enhanced Laws textures: A potential MRI surrogate marker of hepatic fibrosis in a murine model.

    PubMed

    Li, Baojun; Jara, Hernan; Yu, Heishun; O'Brien, Michael; Soto, Jorge; Anderson, Stephan W

    2017-04-01

    To compare enhanced Laws textures derived from parametric proton density (PD) maps to other MRI surrogate markers (T2, PD, apparent diffusion coefficient (ADC)) in assessing degrees of liver fibrosis in an ex vivo murine model of hepatic fibrosis imaged using 11.7T MRI. This animal study was IACUC approved. Fourteen male, C57BL/6 mice were divided into control and experimental groups. The latter were fed a 3,5-dicarbethoxy-1,4-dihydrocollidine (DDC) supplemented diet to induce hepatic fibrosis. Ex vivo liver specimens were imaged using an 11.7T scanner, from which the parametric PD, T2, and ADC maps were generated from spin-echo pulsed field gradient and multi-echo spin-echo acquisitions. A sequential enhanced Laws texture analysis was applied to the PD maps: automated dual-clustering algorithm, optimal thresholding algorithm, global grayscale correction, and Laws texture features extraction. Degrees of fibrosis were independently assessed by digital image analysis (a.k.a. %Area Fibrosis). Scatterplot graphs comparing enhanced Laws texture features, T2, PD, and ADC values to degrees of fibrosis were generated and correlation coefficients were calculated. Hepatic fibrosis and the enhanced Laws texture features were strongly correlated with higher %Area Fibrosis associated with higher Laws textures (r=0.89). Without the proposed enhancements, only a moderate correlation was detected between %Area Fibrosis and unenhanced Laws texture features (r=0.70). Correlation also existed between %Area Fibrosis and ADC (r=0.86), PD (r=0.65), and T2 (r=0.66). Higher degrees of hepatic fibrosis are associated with increased Laws textures. The proposed enhancements could improve the accuracy of Laws texture features significantly. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Interleukin 2 as a potential cancer marker in patients after kidney transplantation.

    PubMed

    Witkowska, Agnieszka; Zywiec, Joanna; Strozik, Agnieszka; Gorczynska-Kosiorz, Sylwia; Trautsolt, Wanda; Strzalka-Mrozik, Barbara; Kimsa, Magdalena; Owczarek, Aleksander; Stępień, Beata; Mazurek, Urszula; Grzeszczak, Władysław; Gumprecht, Janusz

    2015-01-01

    Transplant recipients have a significantly greater incidence of cancer, compared with the general population, who are referred to immunosuppressive therapy as an additional malignancy risk factor. Therefore, there is a need to search for an easy in clinical practice neoplasm predictor, especially for this group of patients. A group of 74 (43M and 31F; aged 46.8 ± 12 years) kidney transplant recipients was investigated in a three-year follow-up study. During the time of observation, 7 patients were diagnosed with neoplasm (7.4 ± 1.5 years after transplantation). A serum level of IL2 (ELISA test) and mRNA level of IL1beta, IL10 and TNFalfa in peripheral mononuclear blood cells - PBMCs (QRT - PCR method) were measured in every year of observation. Analysis of variances and t-Student test were used in groups mean comparison: N - patients developing malignant neoplasm group (24 probes); M - set of probes from patients with malignancies at the moment of diagnosis (11 probes); P - set of probes from patients before developing malignant neoplasm (10 probes); C - control group of healthy transplant recipients (31 probes). Among the analyzed agents, only serum IL2 level differed between the analyzed groups, with higher values in the M compared with the P group (p<0.05) and with C group (p<0.01). There were no differences neither between N and C or P and C groups (p = 0.98), nor any correlation between IL2 and IL1b, IL2 and TNFalfa. The results may indicate that IL2 serum level might be consider as a useful late unspecific cancer marker, although larger studies should yield verification of this finding.

  17. Leukocytosis after routine cranial surgery: A potential marker for brain damage in intracranial surgery

    PubMed Central

    Agrawal, Deepak; Kurwale, Nilesh; Sharma, Bhawani Shankar

    2016-01-01

    Aims and Objectives: Leukocytosis after intracranial surgery may create concern about possible infection, especially when associated with fever. Knowledge of the expected degree of leukocytosis after surgery would assist in the interpretation of leukocytosis. It was hypothesized that the degree of leukocytosis after intracranial surgery correlated with the extent of brain damage inflicted during the surgery. Materials and Methods: In this prospective study conducted over 6 months, consecutive patients undergoing either elective resections of brain tumors (having significant collateral brain damage) or aneurysm clipping (with minimal collateral brain damage) were studied. Total blood leukocyte count was checked daily in the morning for the first five postoperative days in both the groups. The mean of the leukocyte count ratio (postoperative leukocyte count/preoperative leukocyte count) on each day was calculated for each group. Results: There were 76 patients, 46 in the test group and 30 controls. Both groups were well matched in age, sex, duration of surgery, and intraoperative fluid balance. The mean leukocyte count ratio on POD1 in the tumor group was significantly higher (1.87) as compared to 1.1 in the aneurysm group (P = 0.001). This difference in the leukocyte count ratio between the groups was maintained on the second and third postoperative days, with decreasing level of significance after the third day. Conclusions: This study shows that intraoperative brain injury is associated with leukocytosis in the immediate postoperative period. This can assist in the interpretation of leukocytosis after intracranial surgeries and could be a quantitative marker for brain injury in patients undergoing intracranial surgery. PMID:27057215

  18. Microglial CD206 Gene Has Potential as a State Marker of Bipolar Disorder

    PubMed Central

    Ohgidani, Masahiro; Kato, Takahiro A.; Haraguchi, Yoshinori; Matsushima, Toshio; Mizoguchi, Yoshito; Murakawa-Hirachi, Toru; Sagata, Noriaki; Monji, Akira; Kanba, Shigenobu

    2017-01-01

    The pathophysiology of bipolar disorder, especially the underlying mechanisms of the bipolarity between manic and depressive states, has yet to be clarified. Microglia, immune cells in the brain, play important roles in the process of brain inflammation, and recent positron emission tomography studies have indicated microglial overactivation in the brain of patients with bipolar disorder. We have recently developed a technique to induced microglia-like (iMG) cells from peripheral blood (monocytes). We introduce a novel translational approach focusing on bipolar disorder using this iMG technique. We hypothesize that immunological conditional changes in microglia may contribute to the shift between manic and depressive states, and thus we herein analyzed gene profiling patterns of iMG cells from three patients with rapid cycling bipolar disorder during both manic and depressive states, respectively. We revealed that the gene profiling patterns are different between manic and depressive states. The profiling pattern of case 1 showed that M1 microglia is dominant in the manic state compared to the depressive state. However, the patterns of cases 2 and 3 were not consistent with the pattern of case 1. CD206, a mannose receptor known as a typical M2 marker, was significantly downregulated in the manic state among all three patients. This is the first report to indicate the importance of shifting microglial M1/M2 characteristics, especially the CD206 gene expression pattern between depressive and manic states. Further translational studies are needed to dig up the microglial roles in the underlying biological mechanisms of bipolar disorder. PMID:28119691

  19. Possible human endogenous cryogens.

    PubMed

    Shido, Osamu; Sugimoto, Naotoshi

    2011-06-01

    Anapyrexia, which is a regulated fall in core temperature, is beneficial for animals and humans when the oxygen supply is limited, e.g., hypoxic, ischemic, or histotoxic hypoxia, since at low body temperature the tissues require less oxygen due to Q(10). Besides hypoxia, anapyrexia can be induced various exogenous and endogenous substances, named cryogens. However, there are only a few reports investigating endogenous cryogens in mammals. We have experienced one patient who suffered from severe hypothermia. The patient seemed to be excessively producing endogenous peptidergic cryogenic substances the molecular weight of which may be greater than 30 kDa. In animal studies, the patient's cryogen appeared to affect metabolic functions, including thermogenic threshold temperatures, and then to produce hypothermia. Since endogenous cryogenic substances may be regarded as useful tool in human activities, e.g., during brain hypothermia therapy or staying in a space station or spaceship, further studies may be needed to identify human endogenous cryogens.

  20. Marker-Trait Association for Biomass Yield of Potential Bio-fuel Feedstock Miscanthus sinensis from Southwest China.

    PubMed

    Nie, Gang; Huang, Linkai; Zhang, Xinquan; Taylor, Megan; Jiang, Yiwei; Yu, Xiaoqing; Liu, Xinchun; Wang, Xinyu; Zhang, Yajie

    2016-01-01

    As a great potential bio-fuel feedstock, the genus Miscanthus has been widely studied around the world, especially Miscanthus × giganteus owing to its high biomass yield in Europe and North America. However, the narrow genetic basis and sterile characteristics of M. × giganteus have become a limitation for utilization and adaptation to extreme climate conditions. In this study, we focused on one of the progenitors of M. × giganteus, Miscanthus sinensis, which was originally distributed in East Asia with abundant genetic resources and comparable biomass yield potential to M. × giganteus in some areas. A collection of 138 individuals was selected for conducting a 3-year trial of biomass production and analyzed by using 104 pairs of SRAP, ISAP, and SSR primers for genetic diversity as well as marker-trait association. Significant differences in biomass yield and related traits were observed among individuals. Tiller number, fresh biomass yield per plant and dry biomass yield per plant had a high level of phenotypic variation among individuals and the coefficient of variation were all above 40% in 2011, 2012, and 2013. The majority of the traits had a significant correlation with the biomass yield except for the length and width of flag leaves. Plant height was a highly stable trait correlated with biomass yield. A total of 1059 discernible loci were detected by markers across individuals. The population structure (Q) and cluster analyses identified three subpopulations in the collection and family relative kinship (K) represented high gene flow among M. sinensis populations from Southwest China. Model testing identified that Q+K was the best model for describing the associations between the markers and traits, compared to the simple linear, Q or K model. Using the Q+K model, 12 significant associations (P < 0.001) were identified including four markers with plant height and one with biomass yield. Such associations would serve an efficient tool for an early

  1. Marker-Trait Association for Biomass Yield of Potential Bio-fuel Feedstock Miscanthus sinensis from Southwest China

    PubMed Central

    Nie, Gang; Huang, Linkai; Zhang, Xinquan; Taylor, Megan; Jiang, Yiwei; Yu, Xiaoqing; Liu, Xinchun; Wang, Xinyu; Zhang, Yajie

    2016-01-01

    As a great potential bio-fuel feedstock, the genus Miscanthus has been widely studied around the world, especially Miscanthus × giganteus owing to its high biomass yield in Europe and North America. However, the narrow genetic basis and sterile characteristics of M. × giganteus have become a limitation for utilization and adaptation to extreme climate conditions. In this study, we focused on one of the progenitors of M. × giganteus, Miscanthus sinensis, which was originally distributed in East Asia with abundant genetic resources and comparable biomass yield potential to M. × giganteus in some areas. A collection of 138 individuals was selected for conducting a 3-year trial of biomass production and analyzed by using 104 pairs of SRAP, ISAP, and SSR primers for genetic diversity as well as marker-trait association. Significant differences in biomass yield and related traits were observed among individuals. Tiller number, fresh biomass yield per plant and dry biomass yield per plant had a high level of phenotypic variation among individuals and the coefficient of variation were all above 40% in 2011, 2012, and 2013. The majority of the traits had a significant correlation with the biomass yield except for the length and width of flag leaves. Plant height was a highly stable trait correlated with biomass yield. A total of 1059 discernible loci were detected by markers across individuals. The population structure (Q) and cluster analyses identified three subpopulations in the collection and family relative kinship (K) represented high gene flow among M. sinensis populations from Southwest China. Model testing identified that Q+K was the best model for describing the associations between the markers and traits, compared to the simple linear, Q or K model. Using the Q+K model, 12 significant associations (P < 0.001) were identified including four markers with plant height and one with biomass yield. Such associations would serve an efficient tool for an early

  2. Potential for Metabolomics-Based Markers of Exposure:Encouraging Evidence from Studies using Model Organisms

    EPA Science Inventory

    Genomic techniques (transcriptomics, proteomics, and metabolomics) have the potential to significantly improve the way chemical risk is managed in the 21st century. Indeed, a significant amount of research has been devoted to the use of these techniques to screen chemicals for h...

  3. Potential for Metabolomics-Based Markers of Exposure:Encouraging Evidence from Studies using Model Organisms

    EPA Science Inventory

    Genomic techniques (transcriptomics, proteomics, and metabolomics) have the potential to significantly improve the way chemical risk is managed in the 21st century. Indeed, a significant amount of research has been devoted to the use of these techniques to screen chemicals for h...

  4. Neospora caninum surface antigen (p40) is a potential diagnostic marker for cattle neosporosis

    USDA-ARS?s Scientific Manuscript database

    Neospora caninum is an intracellular protozoan that infects domestic and wild canids as well as many warm-blooded animals as shown by the isolation of viable parasites. The effectiveness of diagnostic tests for detecting specific antibodies against N. caninum is hampered by potential cross-reaction ...

  5. How biomarkers will change psychiatry. Part II: Biomarker selection and potential inflammatory markers of depression.

    PubMed

    Macaluso, Matthew; Drevets, Wayne C; Preskorn, Sheldon H

    2012-07-01

    Part I of this series defined biomarkers and discussed their current use in general medicine and their potential research and clinical utility in psychiatry. In this second column in the series, the authors first discuss the rationale for selecting a biomarker. The second half of the column discusses the potential use of inflammatory biomarkers in depression, with a specific focus on derivatives of the inflammatory biomarker, thromboxane, to illustrate how biomarkers can be developed for use in clinical practice. In the future, biomarkers are likely to become an integral component of psychiatric treatment, providing information about a patient's odds of developing an illness, the severity of illness, and level of response to therapeutic interventions.

  6. Potential Use of Salivary Markers for Longitudinal Monitoring of Inflammatory Immune Responses to Vaccination

    PubMed Central

    Garssen, Johan; Sandalova, Elena

    2016-01-01

    Vaccination, designed to trigger a protective immune response against infection, is a trigger for mild inflammatory responses. Vaccination studies can address the question of inflammation initiation, levels, and resolution as well as its regulation for respective studied pathogens. Such studies largely based on analyzing the blood components including specific antibodies and cytokines were usually constrained by number of participants and volume of collected blood sample. Hence, blood-based studies may not be able to cover the full dynamic range of inflammation responses induced by vaccination. In this review, the potential of using saliva in addition to blood for studying the kinetics of inflammatory response studies was assessed. Saliva sampling is noninvasive and has a great potential to be used for studies aimed at analysing the magnitude, time course, and variance in immune responses, including inflammation after vaccination. Based on a literature survey of inflammatory biomarkers that can be determined in saliva and an analysis of how these biomarkers could help to understand the mechanisms and dynamics of immune reactivity and inflammation, we propose that the saliva-based approach might have potential to add substantial value to clinical studies, particularly in vulnerable populations such as infants, toddlers, and ill individuals. PMID:27022211

  7. Genome-wide survey and analysis of microsatellites in the Pacific oyster genome: abundance, distribution, and potential for marker development

    NASA Astrophysics Data System (ADS)

    Wang, Jiafeng; Qi, Haigang; Li, Li; Zhang, Guofan

    2014-01-01

    Microsatellites are a ubiquitous component of the eukaryote genome and constitute one of the most popular sources of molecular markers for genetic studies. However, no data are currently available regarding microsatellites across the entire genome in oysters, despite their importance to the aquaculture industry. We present the first genome-wide investigation of microsatellites in the Pacific oyster Crassostrea gigas by analysis of the complete genome, resequencing, and expression data. The Pacific oyster genome is rich in microsatellites. A total of 604 653 repeats were identified, in average of one locus per 815 base pairs (bp). A total of 12 836 genes had coding repeats, and 7 332 were expressed normally, including genes with a wide range of molecular functions. Compared with 20 different species of animals, microsatellites in the oyster genome typically exhibited 1) an intermediate overall frequency; 2) relatively uniform contents of (A)n and (C)n repeats and abundant long (C)n repeats (≥24 bp); 3) large average length of (AG)n repeats; and 4) scarcity of trinucleotide repeats. The microsatellite-flanking regions exhibited a high degree of polymorphism with a heterozygosity rate of around 2.0%, but there was no correlation between heterozygosity and microsatellite abundance. A total of 19 462 polymorphic microsatellites were discovered, and dinucleotide repeats were the most active, with over 26% of loci found to harbor allelic variations. In all, 7 451 loci with high potential for marker development were identified. Better knowledge of the microsatellites in the oyster genome will provide information for the future design of a wide range of molecular markers and contribute to further advancements in the field of oyster genetics, particularly for molecular-based selection and breeding.

  8. Transgelin: a potentially useful diagnostic marker differentially expressed in triple-negative and non-triple-negative breast cancers.

    PubMed

    Rao, Deepthi; Kimler, Bruce F; Nothnick, Warren B; Davis, Marilyn K; Fan, Fang; Tawfik, Ossama

    2015-06-01

    Triple negative (TN) (estrogen receptor [ER], progesterone receptor [PR] and HER2-) are highly aggressive, rapidly growing, hormone-unresponsive tumors diagnosed at later stage that affect younger women with shorter overall survival. Most TN tumors are of the basal type. For the remainder, identification of target markers for effective treatment strategies remains a challenge. Transgelin (TGLN) is a 22-kd actin-binding protein of the calponin family. It is one of the earliest markers of smooth muscle differentiation. TGLN has been shown to have important biologic activities including regulating muscle fiber contractility, cell migration, and tumor suppression. We examined TGLN expression in the different molecular subtypes of breast cancer. TGLN expression was examined as a function of tumor size, grade, histologic type, lymph node status, patients' age and overall survival, ER, PR, HER2, and Ki-67 in 101 tumors that included 35 luminal A, 28 luminal B, 4 HER2, and 34 TN types. TGLN positivity (defined as 2+ or 3+) was associated with more aggressive tumors (10% of grade I/II tumors were TGLN+ versus 53% of grade III tumors; P < .001), high Ki-67 count, and low ER and PR expression (P < .001) but not with tumor size, age, or lymph node metastasis. TN (n = 34) tumors were 7.7 times more likely to be TGLN+ than non-TN (n = 67) tumors (77% versus 10%, respectively; P < .001). TGLN may be an excellent diagnostic marker of TN tumors and could be useful in stratification of patients. TGLN may also prove a potential target for future treatment strategies. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Assessment of Environmental and Hereditary Influence on Development of Pituitary Tumors Using Dermatoglyphic Traits and Their Potential as Screening Markers.

    PubMed

    Gradiser, Marina; Matovinovic Osvatic, Martina; Dilber, Dario; Bilic-Curcic, Ines

    2016-03-17

    The aim of this study was to assess environmental and hereditary influence on development of pituitary tumors using dermatoglyphic traits. The study was performed on 126 patients of both genders with pituitary tumors (60 non-functional and 66 functional pituitary tumor patients) in comparison to the control group of 400 phenotypically healthy individuals. Statistical analysis of quantitative and qualitative traits of digito-palmar dermatoglyphics was performed, and hormonal status was determined according to the standard protocols. Although we did not find markers that could specifically distinguish functional from non-functional tumors, we have found markers predisposing to the development of tumors in general (a small number of ridges between triradius of both hands, a smaller number of ridges between the triradius of c-d rc R), those for endocrine dysfunction (increased number of arches and reduced number of whorls, difference of pattern distribution in the I3 and I4 interdigital space), and some that could potentially be attributed to patients suffering from pituitary tumors (small number of ridges for variables FRR 5, smaller number of ridges in the FRL 4 of both hands and difference of pattern distribution at thenar of I1 and I2 interdigital space). The usage of dermatoglyphic traits as markers of predisposition of pituitary tumor development could facilitate the earlier detection of patients in addition to standard methods, and possibly earlier treatment and higher survival rate. Finally, our results are consistent with the hypothesis about multifactorial nature of pituitary tumor etiology comprised of both gene instability and environmental factors.

  10. Assessment of Environmental and Hereditary Influence on Development of Pituitary Tumors Using Dermatoglyphic Traits and Their Potential as Screening Markers

    PubMed Central

    Gradiser, Marina; Matovinovic Osvatic, Martina; Dilber, Dario; Bilic-Curcic, Ines

    2016-01-01

    The aim of this study was to assess environmental and hereditary influence on development of pituitary tumors using dermatoglyphic traits. The study was performed on 126 patients of both genders with pituitary tumors (60 non-functional and 66 functional pituitary tumor patients) in comparison to the control group of 400 phenotypically healthy individuals. Statistical analysis of quantitative and qualitative traits of digito-palmar dermatoglyphics was performed, and hormonal status was determined according to the standard protocols. Although we did not find markers that could specifically distinguish functional from non-functional tumors, we have found markers predisposing to the development of tumors in general (a small number of ridges between triradius of both hands, a smaller number of ridges between the triradius of c–d rc R), those for endocrine dysfunction (increased number of arches and reduced number of whorls, difference of pattern distribution in the I3 and I4 interdigital space), and some that could potentially be attributed to patients suffering from pituitary tumors (small number of ridges for variables FRR 5, smaller number of ridges in the FRL 4 of both hands and difference of pattern distribution at thenar of I1 and I2 interdigital space). The usage of dermatoglyphic traits as markers of predisposition of pituitary tumor development could facilitate the earlier detection of patients in addition to standard methods, and possibly earlier treatment and higher survival rate. Finally, our results are consistent with the hypothesis about multifactorial nature of pituitary tumor etiology comprised of both gene instability and environmental factors. PMID:26999178

  11. Biochemical markers and somatosensory evoked potentials in patients after cardiac arrest: the role of neurological outcome scores.

    PubMed

    Rana, Obaida R; Saygili, Erol; Schiefer, Johannes; Marx, Nikolaus; Schauerte, Patrick

    2011-06-15

    Biochemical markers, e.g. NSE or S100B, and somatosensory evoked potentials (SSEP) are considered promising candidates for neurological prognostic predictors in patients after cardiac arrest (CA). The Utstein Templates recommend the use of the Glasgow-Pittsburgh Cerebral Performance Categories (GP-CPC) to divide patients according to their neurological outcome. However, several studies investigating biochemical markers and SSEP are based on the Glasgow Outcome Score (GOS). We noticed that many studies failed to exclude patients who died without certified brain damage from patients classified as poor outcome, instead including all patients who died into this category. Therefore, we summarized the published NSE cut-off values and the derived sensitivity and specificity to predict poor outcome of those studies which only included patients with certified brain death in GOS-1 or GP-CPC-5 (group A) vs. those studies which did not differentiate between death from any cause or death due to primary brain damage (group B). On average, mean NSE cut-off values and sensitivity were higher (56 ± 35 ng/ml, 56 ± 18%) in group A than in group B (41 ± 17 ng/ml, 44 ± 25%), respectively. The specificity remained equally high in both groups. In analogy, the average sensitivity of SSEP to predict poor outcome was higher in group A (76 ± 11%) than in group B (50 ± 15%), while the specificity was similar in both groups. Conclusively, inclusion of deaths without certified brain damage after CA in neurological outcome studies will lead to underestimation of the prognostic power of biochemical or electrophysiological markers for brain damage. A modified GOS and GP-CPC score might help to avoid this bias.

  12. Hypochlorous Acid Converts the γ-Glutamyl Group of Glutathione Disulfide to 5-Hydroxybutyrolactam, a Potential Marker for Neutrophil Activation*

    PubMed Central

    Yuan, Wei; Wang, Yi; Heinecke, Jay W.; Fu, Xiaoyun

    2009-01-01

    In healthy cells, glutathione disulfide (GSSG) is rapidly reduced back to glutathione (GSH) by glutathione reductase to maintain redox status. The ratio of GSH/GSSG has been used as an indicator of oxidative stress. However, hypochlorous acid (HOCl) generated by the myeloperoxidase-H2O2-Cl− system of neutrophils converts GSH to irreversible oxidation products. Although several such products have been identified, yields of these compounds are very low in biological systems, and they cannot account quantitatively for thiol loss. In the current studies, we use liquid chromatography-mass spectrometry (LC-MS) to demonstrate that HOCl and chloramines oxidize GSSG to two irreversible products in high yield. The products, termed M-45 and M-90, are, respectively, 45 or 90 atomic mass units lighter than GSSG. The reaction pathway involves chloramine and aldehyde intermediates, and converts the γ-glutamyl residues of GSSG to 5-hydroxybutyrolactam. Importantly, M-45 and M-90 were resistant to reduction by glutathione reductase. Moreover, the monohydroxylbutyrolactam M-45 accounted for >90% of the endogenous GSH oxidation products generated by activated neutrophils. Because the reaction pathway involves chlorinating intermediates, hydroxylbutyrolactams are likely to be specific products of HOCl, which is generated only by myeloperoxidase. Therefore, our observations implicate M-45 as a potential biomarker for myeloperoxidase activity in vivo. PMID:19584048

  13. Immunocytochemical staining of endogenous nuclear proteins with the HIS-1 anti-poly-histidine monoclonal antibody: a potential source of error in His-tagged protein detection.

    PubMed

    Chilumuri, Amrutha; Markiv, Anatoliy; Milton, Nathaniel G N

    2014-07-01

    Histidine-tagged proteins are widely used in biochemical studies and frequently detected with antibodies specific for the histidine tag. Immunocytochemistry is widely used in studies with overexpressed proteins to determine cellular localization and in the case of histidine-tagged proteins can be carried out with anti-polyhistidine antibodies. Recent studies have suggested that polyhistidine sequences are present within a small number of human proteins and may direct expression to the nucleus and nuclear speckles compartments of the cell. In this study immunocytochemical staining of human SH-SY5Y neuroblastoma cell lines with the HIS-1 anti-polyhistidine monoclonal antibody were determined. Results showed that the HIS-1 anti-polyhistidine monoclonal antibody stained endogenous nuclear proteins in SH-SY5Y cells. The stained proteins were contained within the nuclear membrane, but were not directly linked to DNA. In a histidine-tagged catalase overexpressing cell line the HIS-1 anti-polyhistidine monoclonal antibody showed nuclear staining, whilst staining with the CAT-505 anti-catalase monoclonal antibody showed primarily cytoplasmic staining. These results suggest that anti-polyhistidine antibody staining shows significant cross-reactivity with endogenous nuclear proteins in SH-SY5Y neuroblastoma cells and may not be suitable for localization studies of histidine-tagged proteins. Immunocytochemical studies with anti-polyhistidine antibodies and localization of histidine-tagged proteins must be confirmed with protein specific antibodies or other methodology. Copyright © 2014 Elsevier GmbH. All rights reserved.

  14. The metabolic impact of methamphetamine on the systemic metabolism of rats and potential markers of methamphetamine abuse.

    PubMed

    Zheng, Tian; Liu, Linsheng; Shi, Jian; Yu, Xiaoyi; Xiao, Wenjing; Sun, Runbing; Zhou, Yahong; Aa, Jiye; Wang, Guangji

    2014-07-01

    Although the stimulating and psychotropic effects of methamphetamine (METH) on the nervous system are well documented, the impact of METH abuse on biological metabolism and the turnover of peripheral transmitters are poorly understood. Metabolomics has the potential to reveal the effect of METH abuse on systemic metabolism and potential markers suggesting the underlying mechanism of toxicity. In this study, male Sprague Dawley rats were intraperitoneally injected with METH at escalating doses of mg kg(-1) for 5 consecutive days and then were withdrawn for 2 days. The metabolites in the serum and urine were profiled and the systemic effects of METH on metabolic pathways were evaluated. Multivariate statistical analysis showed that METH caused distinct deviations, whereas the withdrawal of METH restored the metabolic patterns towards baseline. METH administration elevated energy metabolism, which was manifested by the distinct depletion of branched-chain amino acids, accelerated tricarboxylic-acid cycle and lipid metabolism, reduced serum glycerol-3-phosphate, and elevated serum and urinary 3-hydroxybutyrate and urinary glycerol. In addition to the increased serum levels of the excitatory amino acids glutamate and aspartate (the inhibitory neurotransmitters in the brain), a marked decline in serum alanine and glycine after METH treatment suggested the activation and decreased inhibition of the nervous system and hence elevated nervous activity. Withdrawal of METH for 2 days efficiently restored all but a few metabolites to baseline, including serum creatinine, citrate, 2-ketoglutarate, and urinary lactate. Therefore, these metabolites are potential markers of METH use, and they may be used to facilitate the diagnosis of METH abuse.

  15. Unique cyanide adduct in human serum albumin: potential as a surrogate exposure marker.

    PubMed

    Fasco, Michael J; Stack, Robert F; Lu, Shijun; Hauer, Charles R; Schneider, Erasmus; Dailey, Michael; Aldous, Kenneth M

    2011-04-18

    Cyanide (CN = HCN + CN(-)) is a renowned poison and neurotoxicant that is prevalent throughout the environment. Despite a plethora of studies conducted over the last half century, relatively little is known of its potential to cause adverse health outcomes at sublethal exposures. CN exposure is normally determined from blood, but because CN is rapidly metabolized and cleared from this compartment (t(1/2) < 1 h), it is common for several half-lives to have passed before blood samples are drawn for analysis. This variable, coupled with a very narrow toxic index and metabolic diversity within the human population, has rendered accurate assessment of CN exposure, and consequently any predictions of possible adverse health outcomes, highly problematic. Prior studies by us showed the potential of Cys-SCN adducts within human serum albumin (HSA) to act as retrospective surrogates of CN exposure. Here, we report the discovery of a stable, SCN adduct at Cys(567) formed by the reaction of CN with the C-terminal Cys(558)Cys(567) disulfide bond of HSA. Treatment of HSA purified from human serum with base in guanidine hydrochloride releases a readily detectable, uniquely modified, C-terminal-19-mer peptide from Cys(567)-SCN moieties in all the samples examined thus far. Inclusion of a HSA-Cys(567)-S(13)C(15)N labeled internal standard permits quantitation of the Cys(567)-SCN adduct by LC-MS/MS in selective reaction monitoring (SRM) of the surrogate peptide with high sensitivity and good precision. Reaction of CN in vitro with the Cys(558)Cys(567) disulfide bond in HSA is specific, rapid, and concentration dependent within a putative, physiologically relevant range. Data from various human sera demonstrate the potential usefulness of this adduct as a biomarker of CN exposure.

  16. Identification of species-specific nuclear insertions of mitochondrial DNA (numts) in gorillas and their potential as population genetic markers

    PubMed Central

    Clark Nicholas, Jonathan; Wildschutte Julia, Vera Halo; DiMattio, Kelly; Jensen-Seaman, Michael Ignatius; Anthony, Nicola Mary

    2014-01-01

    The first hyper-variable region (HV1) of the mitochondrial control region (MCR) has been widely used as a molecular tool in population genetics, but inadvertent amplification of nuclear translocated copies of mitochondrial DNA (numts) in gorillas has compromised the use of mitochondrial DNA in population genetic studies. At least three putative classes (I, II, III) of gorilla-specific HV1 MCR numts have been uncovered over the past decade. However, the number, size and location of numt loci in gorillas and other apes are completely unknown. Furthermore, little work to date has assessed the utility of numts as candidate population genetic markers. In the present study, we screened Bacterial Artificial Chromosome (BAC) genomic libraries in the chimpanzee and gorilla to compare patterns of mitochondrial-wide insertion in both taxa. We conducted an intensive BLAST search for numts in the gorilla genome and compared the prevalence of numt loci originating from the MCR with other great ape taxa. Additional gorilla-specific MCR numts were retrieved either through BAC library screens or using an anchored-PCR (A-PCR) amplification using genomic DNA from five unrelated gorillas. Locus-specific primers were designed to identify numt insertional polymorphisms and evaluate their potential as population genetic markers. Mitochondrial-wide surveys of chimpanzee and gorilla BACs showed that the number of numts does not differ between these two taxa. However, MCR numts are more abundant in chimpanzees than in other great apes. We identified and mapped 67 putative gorilla-specific numts, including two that contain the entire HV1 domain, cluster with sequences from two numt classes (I, IIb) and will likely co-amplify with mitochondrial sequences using most published HV1 primers. However, phylogenetic analysis coupled with post-hoc analysis of mitochondrial variation can successfully differentiate nuclear sequences. Insertional polymorphisms were evident in three out of five numts

  17. Mitosis Is a Source of Potential Markers for Screening and Survival and Therapeutic Targets in Cervical Cancer

    PubMed Central

    Espinosa, Ana María; Alfaro, Ana; Roman-Basaure, Edgar; Guardado-Estrada, Mariano; Palma, Ícela; Serralde, Cyntia; Medina, Ingrid; Juárez, Eligia; Bermúdez, Miriam; Márquez, Edna; Borges-Ibáñez, Manuel; Muñoz-Cortez, Sergio; Alcántara-Vázquez, Avissai; Alonso, Patricia; Curiel-Valdez, José; Kofman, Susana; Villegas, Nicolas; Berumen, Jaime

    2013-01-01

    The effect of preventive human papillomavirus (HPV) vaccination on the reduction of the cervical cancer (CC) burden will not be known for 30 years. Therefore, it’s still necessary to improve the procedures for CC screening and treatment. The objective of this study was to identify and characterize cellular targets that could be considered potential markers for screening or therapeutic targets. A pyramidal strategy was used. Initially the expression of 8,638 genes was compared between 43 HPV16-positive CCs and 12 healthy cervical epitheliums using microarrays. A total of 997 genes were deregulated, and 21 genes that showed the greatest deregulation were validated using qRT-PCR. The 6 most upregulated genes (CCNB2, CDC20, PRC1, SYCP2, NUSAP1, CDKN3) belong to the mitosis pathway. They were further explored in 29 low-grade cervical intraepithelial neoplasias (CIN1) and 21 high-grade CIN (CIN2/3) to investigate whether they could differentiate CC and CIN2/3 (CIN2+) from CIN1 and controls. CCNB2, PRC1, and SYCP2 were mostly associated with CC and CDC20, NUSAP1, and CDKN3 were also associated with CIN2/3. The sensitivity and specificity of CDKN3 and NUSAP1 to detect CIN2+ was approximately 90%. The proteins encoded by all 6 genes were shown upregulated in CC by immunohistochemistry. The association of these markers with survival was investigated in 42 CC patients followed up for at least 42 months. Only CDKN3 was associated with poor survival and it was independent from clinical stage (HR = 5.9, 95%CI = 1.4–23.8, p = 0.01). CDKN3 and NUSAP1 may be potential targets for the development of screening methods. Nevertheless, further studies with larger samples are needed to define the optimal sensitivity and specificity. Inhibition of mitosis is a well-known strategy to combat cancers. Therefore, CDKN3 may be not only a screening and survival marker but a potential therapeutic target in CC. However, whether it’s indispensable for tumor growth remains to be

  18. Identification of species-specific nuclear insertions of mitochondrial DNA (numts) in gorillas and their potential as population genetic markers.

    PubMed

    Soto-Calderón, Iván Darío; Clark, Nicholas Jonathan; Wildschutte, Julia Vera Halo; DiMattio, Kelly; Jensen-Seaman, Michael Ignatius; Anthony, Nicola Mary

    2014-12-01

    The first hyper-variable region (HV1) of the mitochondrial control region (MCR) has been widely used as a molecular tool in population genetics, but inadvertent amplification of nuclear translocated copies of mitochondrial DNA (numts) in gorillas has compromised the use of mitochondrial DNA in population genetic studies. At least three putative classes (I, II, III) of gorilla-specific HV1 MCR numts have been uncovered over the past decade. However, the number, size and location of numt loci in gorillas and other apes are completely unknown. Furthermore, little work to date has assessed the utility of numts as candidate population genetic markers. In the present study, we screened Bacterial Artificial Chromosome (BAC) genomic libraries in the chimpanzee and gorilla to compare patterns of mitochondrial-wide insertion in both taxa. We conducted an intensive BLAST search for numts in the gorilla genome and compared the prevalence of numt loci originating from the MCR with other great ape taxa. Additional gorilla-specific MCR numts were retrieved either through BAC library screens or using an anchored-PCR (A-PCR) amplification using genomic DNA from five unrelated gorillas. Locus-specific primers were designed to identify numt insertional polymorphisms and evaluate their potential as population genetic markers. Mitochondrial-wide surveys of chimpanzee and gorilla BACs showed that the number of numts does not differ between these two taxa. However, MCR numts are more abundant in chimpanzees than in other great apes. We identified and mapped 67 putative gorilla-specific numts, including two that contain the entire HV1 domain, cluster with sequences from two numt classes (I, IIb) and will likely co-amplify with mitochondrial sequences using most published HV1 primers. However, phylogenetic analysis coupled with post-hoc analysis of mitochondrial variation can successfully differentiate nuclear sequences. Insertional polymorphisms were evident in three out of five numts

  19. Measles Virus: Identification in the M Protein Primary Sequence of a Potential Molecular Marker for Subacute Sclerosing Panencephalitis.

    PubMed

    Kweder, Hasan; Ainouze, Michelle; Brunel, Joanna; Gerlier, Denis; Manet, Evelyne; Buckland, Robin

    2015-01-01

    Subacute Sclerosing Panencephalitis (SSPE), a rare lethal disease of children and young adults due to persistence of measles virus (MeV) in the brain, is caused by wild type (wt) MeV. Why MeV vaccine strains never cause SSPE is completely unknown. Hypothesizing that this phenotypic difference could potentially be represented by a molecular marker, we compared glycoprotein and matrix (M) genes from SSPE cases with those from the Moraten vaccine strain, searching for differential structural motifs. We observed that all known SSPE viruses have residues P64, E89, and A209 (PEA) in their M proteins whereas the equivalent residues for vaccine strains are either S64, K89, and T209 (SKT) as in Moraten or PKT. Through the construction of MeV recombinants, we have obtained evidence that the wt MeV-M protein PEA motif, in particular A209, is linked to increased viral spread. Importantly, for the 10 wt genotypes (of 23) that have had their M proteins sequenced, 9 have the PEA motif, the exception being B3, which has PET. Interestingly, cases of SSPE caused by genotype B3 have yet to be reported. In conclusion, our results strongly suggest that the PEA motif is a molecular marker for wt MeV at risk to cause SSPE.

  20. Measles Virus: Identification in the M Protein Primary Sequence of a Potential Molecular Marker for Subacute Sclerosing Panencephalitis

    PubMed Central

    Kweder, Hasan; Ainouze, Michelle; Brunel, Joanna; Gerlier, Denis

    2015-01-01

    Subacute Sclerosing Panencephalitis (SSPE), a rare lethal disease of children and young adults due to persistence of measles virus (MeV) in the brain, is caused by wild type (wt) MeV. Why MeV vaccine strains never cause SSPE is completely unknown. Hypothesizing that this phenotypic difference could potentially be represented by a molecular marker, we compared glycoprotein and matrix (M) genes from SSPE cases with those from the Moraten vaccine strain, searching for differential structural motifs. We observed that all known SSPE viruses have residues P64, E89, and A209 (PEA) in their M proteins whereas the equivalent residues for vaccine strains are either S64, K89, and T209 (SKT) as in Moraten or PKT. Through the construction of MeV recombinants, we have obtained evidence that the wt MeV-M protein PEA motif, in particular A209, is linked to increased viral spread. Importantly, for the 10 wt genotypes (of 23) that have had their M proteins sequenced, 9 have the PEA motif, the exception being B3, which has PET. Interestingly, cases of SSPE caused by genotype B3 have yet to be reported. In conclusion, our results strongly suggest that the PEA motif is a molecular marker for wt MeV at risk to cause SSPE. PMID:26587021

  1. LncRNA HOTAIR as Prognostic Circulating Marker and Potential Therapeutic Target in Patients with Tumor Diseases.

    PubMed

    Botti, Gerardo; Marra, Laura; Malzone, Maria Gabriella; Anniciello, Annamaria; Botti, Chiara; Franco, Renato; Cantile, Monica

    2017-01-01

    In the recent years the importance of the role played by non-coding RNA on the regulation of gene expression was increased by numerous studies. The research mainly focused on small ncRNAs, such as miRNAs, while the functions of long non-coding RNA (lncRNA) have been much less studied. lncRNAs can be transcribed from intergenic, intragenic or specific chromosomal regions. Compared to miRNAs, lncRNAs have a complex secondary and tertiary structure which allows to bind proteins, RNA, DNA and to carry out their regulatory functions. Several studies showed that extracellular ncRNAs can circulate in the blood of both healthy and diseased patients. Most of the circulating ncRNAs are included in lipid or lipoprotein vesicles, such as apoptotic bodies, macrovesicles or exosomes, in which they are highly stable. The presence of circulating ncRNAs in the blood of cancer patients versus normal subjects suggested the possibility that these molecules may represent new diagnostic markers. HOTAIR is a HOX transcript antisense RNA, located in the HOXC locus, able to repress transcription in the posterior region of the HOXD locus. HOTAIR has been involved in the evolution of several primary tumors, wherein increase of HOTAIR expression has endorsed invasion and metastasis. In this review, we describe the experimental evidences on the potential role as circulating marker of lncRNA HOTAIR.

  2. Chimeric foot-and-mouth disease viruses: evaluation of their efficacy as potential marker vaccines in cattle.

    PubMed

    Fowler, V L; Paton, D J; Rieder, E; Barnett, P V

    2008-04-07

    Previous work in pigs, has demonstrated that full protection against foot-and-mouth disease (FMD) can be achieved following vaccination with chimeric foot-and-mouth disease virus (FMDV) vaccines, in which the VP1 G-H loop had been substituted with that from another serotype. If proven to be effective in other economically important species such as cattle, such vaccine constructs could be trialed as potential marker vaccines. Here, we determine if G-H loop chimera FMDV vaccines can: (i) protect cattle from virus challenge and (ii) induce an antibody response that would enable the identification of infection, regardless of vaccination status. Inactivated, oil adjuvanated, chimeric vaccine constructs, based on the backbone sequence of the A(12)119 serotype virus, fully protected cattle from challenge 21 days post-vaccination. Differentiation assays developed for use in this study were able to identify sub-clinical infection, which in one vaccinated animal, persisted beyond day 32 post-challenge. This paper emphasises the importance of epitopes outside of the VP1 G-H loop for protective immunity in cattle, and demonstrates that chimeric FMDV vaccines could prove to be useful marker vaccines for the future.

  3. Investigation of cerebral microbleeds in multiple sclerosis as a potential marker of blood-brain barrier dysfunction.

    PubMed

    Eisele, Philipp; Alonso, Angelika; Griebe, Martin; Szabo, Kristina; Hennerici, Michael G; Gass, Achim

    2016-05-01

    In multiple sclerosis (MS) lesions blood-brain-barrier (BBB) breakdown is a common phenomenon delineating the phase of focal inflammation in developing MS lesions. In other pathologies like cerebral amyloid angiopathy or arteriosclerotic cerebral small vessel disease permanent cerebral microbleeds (CMB) have been shown to be sensitive markers indicating BBB dysfunction. We were interested in the potential role of T(2)*-weighted MRI and CMBs as BBB integrity markers in MS. A large cohort of 189 MS patients (179 relapsing remitting MS and 10 secondary progressive MS) was investigated on a 3T MRI system with conventional and T(2)*-weighted gradient echo MRI (T(2)*w) sequences. T(2)*w images were analysed for CMBs by experienced raters. None of the MS patients showed a CMB. On T(2)*w MRI the prevalence of CMBs is not higher in MS patients than what is to be expected in young healthy people. In contrast to pathologies with structural vascular changes like small vessel disease or cerebral amyloid angiopathy, CMBs are not seen in MS where the immune reaction is causing a functional change in the BBB. Copyright © 2016. Published by Elsevier B.V.

  4. Insight into Potential Probiotic Markers Predicted in Lactobacillus pentosus MP-10 Genome Sequence.

    PubMed

    Abriouel, Hikmate; Pérez Montoro, Beatriz; Casimiro-Soriguer, Carlos S; Pérez Pulido, Antonio J; Knapp, Charles W; Caballero Gómez, Natacha; Castillo-Gutiérrez, Sonia; Estudillo-Martínez, María D; Gálvez, Antonio; Benomar, Nabil

    2017-01-01

    Lactobacillus pentosus MP-10 is a potential probiotic lactic acid bacterium originally isolated from naturally fermented Aloreña green table olives. The entire genome sequence was annotated to in silico analyze the molecular mechanisms involved in the adaptation of L. pentosus MP-10 to the human gastrointestinal tract (GIT), such as carbohydrate metabolism (related with prebiotic utilization) and the proteins involved in bacteria-host interactions. We predicted an arsenal of genes coding for carbohydrate-modifying enzymes to modify oligo- and polysaccharides, such as glycoside hydrolases, glycoside transferases, and isomerases, and other enzymes involved in complex carbohydrate metabolism especially starch, raffinose, and levan. These enzymes represent key indicators of the bacteria's adaptation to the GIT environment, since they involve the metabolism and assimilation of complex carbohydrates not digested by human enzymes. We also detected key probiotic ligands (surface proteins, excreted or secreted proteins) involved in the adhesion to host cells such as adhesion to mucus, epithelial cells or extracellular matrix, and plasma components; also, moonlighting proteins or multifunctional proteins were found that could be involved in adhesion to epithelial cells and/or extracellular matrix proteins and also affect host immunomodulation. In silico analysis of the genome sequence of L. pentosus MP-10 is an important initial step to screen for genes encoding for proteins that may provide probiotic features, and thus provides one new routes for screening and studying this potentially probiotic bacterium.

  5. Insight into Potential Probiotic Markers Predicted in Lactobacillus pentosus MP-10 Genome Sequence

    PubMed Central

    Abriouel, Hikmate; Pérez Montoro, Beatriz; Casimiro-Soriguer, Carlos S.; Pérez Pulido, Antonio J.; Knapp, Charles W.; Caballero Gómez, Natacha; Castillo-Gutiérrez, Sonia; Estudillo-Martínez, María D.; Gálvez, Antonio; Benomar, Nabil

    2017-01-01

    Lactobacillus pentosus MP-10 is a potential probiotic lactic acid bacterium originally isolated from naturally fermented Aloreña green table olives. The entire genome sequence was annotated to in silico analyze the molecular mechanisms involved in the adaptation of L. pentosus MP-10 to the human gastrointestinal tract (GIT), such as carbohydrate metabolism (related with prebiotic utilization) and the proteins involved in bacteria–host interactions. We predicted an arsenal of genes coding for carbohydrate-modifying enzymes to modify oligo- and polysaccharides, such as glycoside hydrolases, glycoside transferases, and isomerases, and other enzymes involved in complex carbohydrate metabolism especially starch, raffinose, and levan. These enzymes represent key indicators of the bacteria’s adaptation to the GIT environment, since they involve the metabolism and assimilation of complex carbohydrates not digested by human enzymes. We also detected key probiotic ligands (surface proteins, excreted or secreted proteins) involved in the adhesion to host cells such as adhesion to mucus, epithelial cells or extracellular matrix, and plasma components; also, moonlighting proteins or multifunctional proteins were found that could be involved in adhesion to epithelial cells and/or extracellular matrix proteins and also affect host immunomodulation. In silico analysis of the genome sequence of L. pentosus MP-10 is an important initial step to screen for genes encoding for proteins that may provide probiotic features, and thus provides one new routes for screening and studying this potentially probiotic bacterium. PMID:28588563

  6. Potential novel markers to discriminate between active and latent tuberculosis infection in Chinese individuals.

    PubMed

    Bai, Xue-juan; Liang, Yan; Yang, You-rong; Feng, Jin-dong; Luo, Zhan-peng; Zhang, Jun-Xian; Wu, Xue-qiong

    2016-02-01

    Latent tuberculosis infection (LTBI) constitutes the main reservoir for reactivation tuberculosis. The finding of potential biomarkers for differentiating between TB and LTBI is very necessary. In this study, the immunological characteristics and potential diagnostic utility of Rv2029c, Rv2628 and Rv1813c proteins were assessed. These three proteins stimulated PBMCs from ELISPOT-positive LTBI subjects produced higher levels of IFN-γ in comparison with TB patients and ELISPOT-negative healthy subjects (p<0.05). BCG vaccination and non-TB respiratory disease had little influence on the immunological responses of Rv2029c and Rv2628 proteins (p>0.05). The LTBI diagnostic performance of Rv2029c was higher than Rv2628 and Rv1813c by ROC evaluation. But Rv2628 had much higher specificity than Rv2029c in active TB patients and uninfected healthy subjects. The IgG level against Rv1813c was higher in the TB group than in LTBI and uninfected healthy subjects (p<0.05). These results suggest that T cell response to Rv2628 and antibody against Rv1813c might be applicable as biomarkers to distinguish TB from LTBI and uninfected individuals.

  7. MYBL2 is a Potential Prognostic Marker that Promotes Cell Proliferation in Gallbladder Cancer.

    PubMed

    Liang, Hai-Bin; Cao, Yang; Ma, Qiang; Shu, Yi-Jun; Wang, Zheng; Zhang, Fei; Ye, Yuan-Yuan; Li, Huai-Feng; Xiang, Shan-Shan; Song, Xiao-Ling; Xu, Yi; Zhang, Yi-Chi; Bao, Run-Fa; Yuan, Rui-Yan; Zhang, Yi-Jian; Hu, Yun-Ping; Jiang, Lin; Li, Mao-Lan; Wang, Xu-An; Wu, Xiang-Song; Wu, Wen-Guang; Zhao, Shuai; Fand, Yong; Cui, Xiao-Peng; Lu, Yun-Shu; Zhou, Jian; Zheng, Lei; Gong, Wei; Liu, Ying-Bin

    2017-01-01

    Gallbladder cancer (GBC) is an aggressive and highly lethal biliary tract malignancy, with extremely poor prognosis. In the present study, we analyzed the potential involvement of MYBL2, a member of the Myb transcription factor family, in the carcinogenesis of human GBC. MYBL2 expression levels were measured in GBC and cholecystitis tissue specimens using quantitative real-time PCR (qRT-PCR) and immunohistochemical (IHC) assays. The effects of MYBL2 on cell proliferation and DNA synthesis were evaluated using Cell Counting Kit-8 assay (CCK-8), colony formation, and 5-ethynyl-2'-deoxyuridine (EdU) retention assay, flow cytometry analysis, western blot, and a xenograft model of GBC cells in nude mice. MYBL2 expression was increased in GBC tissues and associated with histological differentiation, tumour invasion, clinical stage and unfavourable overall survival in GBC patients. The downregulation of MYBL2 expression resulted in the inhibition of GBC cell proliferation, and DNA replication in vitro, and the growth of xenografted tumours in nude mice. Conversely, MYBL2 overexpression resulted in the opposite effects. MYBL2 overexpression promotes GBC cell proliferation through the regulation of the cell cycle at the S and G2/M phase transitions. Thus, MYBL2 could serve as a potential prognostic and therapeutic biomarker in GBC patients. © 2017 The Author(s)Published by S. Karger AG, Basel.

  8. ADHD and schizophrenia phenomenology: visual scanpaths to emotional faces as a potential psychophysiological marker?

    PubMed

    Marsh, Pamela J; Williams, Leanne M

    2006-01-01

    Commonalities in the clinical phenomenology and psychopharmacology of ADHD and schizophrenia are reviewed. The potential of psychostimulants to produce psychotic symptoms emphasizes the need for objective psychophysiological distinctions between these disorders. Impaired emotion perception in both disorders is discussed. It is proposed that visual scanpaths to facial expressions of emotion might prove a potentially useful psychophysiological distinction between ADHD and schizophrenia. There is consistent evidence that both facial affect recognition and scanpaths to facial expressions are impaired in schizophrenia, with emerging empirical evidence showing that facial affect recognition is impaired in ADHD also. Brain imaging studies show reduced activity in the medial prefrontal and limbic (amygdala) brain regions required to process emotional faces in schizophrenia, but suggest more localized loss of activity in these regions in ADHD. As amygdala activity in particular has been linked to effective visual scanning of face stimuli, it is postulated that condition-specific breakdowns in these brain regions that subserve emotional behavior might manifest as distinct scanpath aberrations to facial expressions of emotion in schizophrenia and ADHD.

  9. Differential proteomics of human seminal plasma: A potential target for searching male infertility marker proteins.

    PubMed

    Tomar, Anil Kumar; Sooch, Balwinder Singh; Singh, Sarman; Yadav, Savita

    2012-04-01

    The clinical fertility tests, available in the market, fail to define the exact cause of male infertility in almost half of the cases and point toward a crucial need of developing better ways of infertility investigations. The protein biomarkers may help us toward better understanding of unknown cases of male infertility that, in turn, can guide us to find better therapeutic solutions. Many clinical attempts have been made to identify biomarkers of male infertility in sperm proteome but only few studies have targeted seminal plasma. Human seminal plasma is a rich source of proteins that are essentially required for development of sperm and successful fertilization. This viewpoint article highlights the importance of human seminal plasma proteome in reproductive physiology and suggests that differential proteomics integrated with functional analysis may help us in searching potential biomarkers of male infertility.

  10. Mismatch negativity as a potential neurobiological marker of early-stage Alzheimer disease and vascular dementia.

    PubMed

    Jiang, Shixiang; Yan, Chang; Qiao, Zhengxue; Yao, Haiqian; Jiang, Shiquan; Qiu, Xiaohui; Yang, Xiuxian; Fang, Deyu; Yang, Yanjie; Zhang, Limei; Wang, Lina; Zhang, Liming

    2017-04-24

    Alzheimer's disease (AD) and vascular dementia (VD) are serious, irreversible forms of cognitive impairment, which means that an early diagnosis is essential to slow down their progression. One potential neurophysiological biomarker of these diseases is the mismatch negativity (MMN) event-related potentials (ERP) component, which reflects an automatic detection mechanism at the pre-attentive stages of information processing. We evaluated the auditory MMN response in individuals from two patient groups: those in the prodromal stages of AD (P-AD) and those in the prodromal stages of VD (P-VD). Thirty patients (15 P-AD patients and 15 P-VD patients) and 30 age-matched controls were recruited to undergo electrophysiological recordings during the presentation of an auditory deviant-standard-reverse oddball paradigm that was used to elicit genuine MMN responses. We show that over the frontal-central area, the mean amplitude of the MMN was significantly reduced in both the P-AD (p=0.017) and P-VD groups (p=0.013) compared with controls. The MMN peak latency in P-VD patients was significantly shorter than in controls (p=0.027). No MMN response differences between the P-AD and P-VD were found in either the frontal-central or the temporal areas. These results indicate that P-AD and P-VD patients exhibit impaired pre-attentive information processing mechanisms as revealed by the frontal-central area MMN response, which is associated with sensory memory and cognitive deficits. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Assessing cardiovascular risk in children with chronic kidney disease. B-type natriuretic peptide: a potential new marker.

    PubMed

    Ariceta, Gema; Brooks, Ellen R; Langman, Craig B

    2005-12-01

    Elevated plasma B-type natriuretic peptide (BNP) level is a hallmark of altered left ventricular (LV) structure and function. Measurement of circulating BNP has proved to be a sensitive and specific diagnostic test for congestive heart failure (CHF) and coronary syndrome in adults. Further, BNP levels constitute a strong predictive marker for future cardiovascular (CV) events. In high CV risk populations, such as adults with hypertension or chronic kidney disease (CKD), increased BNP predicts CV morbidity and mortality in symptomatic or asymptomatic patients. However, caution is needed in interpreting plasma BNP levels, as they increase with both age and decreased renal function. Despite increasing evidence of the value of BNP in the medical literature in adults, data in children are limited to those with congenital heart disease. It is appropriate to analyze the potential application of this tool in children with CKD, a well-known factor for CV disease.

  12. SOCS3 tyrosine phosphorylation as a potential bio-marker for myeloproliferative neoplasms associated with mutant JAK2 kinases

    PubMed Central

    Elliott, Joanne; Suessmuth, Yvonne; Scott, Linda M.; Nahlik, Krystyna; McMullin, Mary Frances; Constantinescu, Stefan N.; Green, Anthony R.; Johnston, James A.

    2009-01-01

    JAK2 V617F, identified in the majority of patients with myeloproliferative neoplasms, tyrosine phosphorylates SOCS3 and escapes its inhibition. Here, we demonstrate that the JAK2 exon 12 mutants described in a subset of V617F-negative MPN cases, also stabilize tyrosine phosphorylated SOCS3. SOCS3 tyrosine phosphorylation was also observed in peripheral blood mononuclear cells and granulocytes isolated from patients with JAK2 H538QK539L or JAK2 F537-K539delinsL mutations. JAK kinase inhibitors, which effectively inhibited the proliferation of cells expressing V617F or K539L, also caused a dose-dependent reduction in both mutant JAK2 and SOCS3 tyrosine phosphorylation. We propose, therefore, that SOCS3 tyrosine phosphorylation may be a novel bio-marker of myeloproliferative neoplasms resulting from a JAK2 mutation and a potential reporter of effective JAK2 inhibitor therapy currently in clinical development. PMID:19229050

  13. Identification of potential general markers of disease resistance in American oysters, Crassostrea virginica through gene expression studies.

    PubMed

    Nikapitiya, Chamilani; McDowell, Ian C; Villamil, Luisa; Muñoz, Pilar; Sohn, SaeBom; Gomez-Chiarri, Marta

    2014-11-01

    Several diseases have a significant impact on American oyster populations in the Atlantic coasts of North America. Knowledge about the responses of oysters to pathogenic challenge could help in identifying potential markers of disease resistance and biomarkers of the health status of an oyster population. A previous analysis of the transcriptome of resistant and susceptible American oysters in response to challenge with the bacterial pathogen Roseovarius crassostreae, as well as sequencing of suppression subtractive hybridization libraries from oysters challenged with the protozoan parasite Perkinsus marinus, provided a list of genes potentially involved in disease resistance or susceptibility. We investigated the patterns of inducible gene expression of several of these genes in response to experimental challenge with the oyster pathogens R. crassostreae, Vibrio tubiashii, and P. marinus. Oysters showing differential susceptibility to R. crassostreae demonstrated differential patterns of expression of genes coding for immune (serine protease inhibitor-1, SPI1) and stress-related (heat shock protein 70, HSP70; arginine kinase) proteins 30 days after challenge with this bacterial pathogen. Differential patterns of expression of immune (spi1, galectin and a matrix metalloproteinase) and stress-related (hsp70, histone H4, and arginine kinase) genes was observed in hemocytes from adult oysters challenged with P. marinus, but not with V. tubiashii. While levels of spi1 expression in hemocytes collected 8 and 21 days after P. marinus challenge were negatively correlated with parasite load in oysters tissues at the end of the challenge (62 days), levels of expression of hsp70 in hemocytes collected 1-day after challenge were positively correlated with oyster parasite load at 62 days. Our results confirm previous research on the role of serine protease inhibitor-1 in immunity and disease resistance in oysters. They also suggest that HSP70 and histone H4 could be used

  14. Eukaryotic elongation factor 2 is a prognostic marker and its kinase a potential therapeutic target in HCC.

    PubMed

    Pott, Leona L; Hagemann, Sascha; Reis, Henning; Lorenz, Kristina; Bracht, Thilo; Herold, Thomas; Skryabin, Boris V; Megger, Dominik A; Kälsch, Julia; Weber, Frank; Sitek, Barbara; Baba, Hideo A

    2017-02-14

    Hepatocellular carcinoma is a cancer with increasing incidence and largely refractory to current anticancer drugs. Since Sorafenib, a multikinase inhibitor has shown modest efficacy in advanced hepatocellular carcinoma additional treatments are highly needed. Protein phosphorylation via kinases is an important post-translational modification to regulate cell homeostasis including proliferation and apoptosis. Therefore kinases are valuable targets in cancer therapy. To this end we performed 2D differential gel electrophoresis and mass spectrometry analysis of phosphoprotein-enriched lysates of tumor and corresponding non-tumorous liver samples to detect differentially abundant phosphoproteins to screen for novel kinases as potential drug targets. We identified 34 differentially abundant proteins in phosphoprotein enriched lysates. Expression and distribution of the candidate protein eEF2 and its phosphorylated isoform was validated immunohistochemically on 78 hepatocellular carcinoma and non-tumorous tissue samples. Validation showed that total eEF2 and phosphorylated eEF2 at threonine 56 are prognostic markers for overall survival of HCC-patients. The activity of the regulating eEF2 kinase, compared between tumor and non-tumorous tissue lysates by in vitro kinase assays, is more than four times higher in tumor tissues. Functional analyzes regarding eEF2 kinase were performed in JHH5 cells with CRISPR/Cas9 mediated eEF2 kinase knock out. Proliferation and growth is decreased in eEF2 kinase knock out cells. eEF2 and phosphorylated eEF2 are prognostic markers for survival of hepatocellular carcinoma patients and the regulating eEF2 kinase is a potential drug target for tumor therapy.

  15. APRIL, a proliferation-inducing ligand, as a potential marker of lupus nephritis

    PubMed Central

    2012-01-01

    Introduction BLyS and APRIL are cytokines from the tumor necrosis factor family which play an important role in systemic lupus erythematosus (SLE). Previous works suggested an association between both molecules and SLE disease activity although their correlation with lupus nephritis is not known. We therefore assessed serum BLyS and APRIL in active lupus nephritis patients. Methods Serum samples from active lupus nephritis and at 6 months post-treatment were obtained. Serum levels of BLyS and APRIL (n = 47) as well as renal mRNA expression were measured. Serum levels of both molecules and clinical data (n = 27) were available at 6 months follow-up. All biopsy-proven lupus nephritis patients were treated with similar immunosuppressive drugs. Results Serum levels of APRIL were associated with proteinuria (Rs = 0.44, P value < 0.01) and degree of histological activity (Rs = 0.34; P value < 0.05) whereas BLyS levels were associated with complement levels (Rs = 0.46; P value < 0.01) and dosage of immunosuppressant. Interestingly, serum APRIL as well as its intrarenal mRNA levels were associated with resistance to treatment. From the receiver operating characteristic (ROC) analysis, high levels (> 4 ng/mL) of serum APRIL predicted treatment failure with a positive predictive value of 93 percent. Conclusion APRIL could be a potential biomarker for predicting difficult-to-treat cases of lupus nephritis. PMID:23171638

  16. Transcriptome sequencing of HER2-positive breast cancer stem cells identifies potential prognostic marker.

    PubMed

    Lei, Bo; Zhang, Xian-Yu; Zhou, Jia-Peng; Mu, Guan-Nan; Li, Yi-Wen; Zhang, You-Xue; Pang, Da

    2016-11-01

    In cancer stem cell theory, breast cancer stem cells (BCSCs) are postulated to be the root cause of recurrence and metastasis in breast cancer. Discovery of new biomarkers and development of BCSC-targeted therapy are practical issues that urgently need to be addressed in the clinic. However, few breast cancer stem cell targets are known. Given that there are few BCSCs, performing transcriptome sequencing on them thus far has not been possible. With the emergence of single-cell sequencing technology, we have now undertaken such a study. We prepared single-cell suspensions, which were sorted using flow cytometry from breast tumor tissue and adjacent normal breast tissue from two HER2-positive patients. We obtained BCSCs, breast cancer cells, mammary cells, and CD44(+) mammary cells. Transcriptome sequencing was then performed on these four cell types. Using bioinformatics, we identified 404 differentially expressed BCSC genes from the HER2-positive tumors and preliminary explored transcriptome characteristics of BCSCs. Finally, by querying a public database, we found that CA12 was a novel prognostic biomarker in HER2-positive breast cancer, which also had prognostic value in all breast cancer types. In conclusion, our results suggest that CA12 may be associated with BCSCs, especially HER2-positive BCSCs, and is a potential novel therapeutic target and biomarker.

  17. Potential of carotenoids in aquatic yeasts as a phylogenetically reliable marker and natural colorant for aquaculture.

    PubMed

    Ueno, Ryohei; Hamada-Sato, Naoko; Ishida, Masami; Urano, Naoto

    2011-01-01

    Apart from Xanthophyllomyces dendrorhous, pink colony-forming yeasts have not been examined as a pigmentation source in captive animals. In this study, aquatic yeasts were screened with a view to abundances of carotenoids. Phylogenetic analyses of these caroetnoid-rich yeasts based on large subunit ribosomal RNA gene (LSU rDNA) partial sequences showed that all belonged to the order Sporidiobolales. Both the qualitative and the quantitative differences in carotenoids between the yeasts appeared to be consistent with their phylogenetic affiliations. This information might be useful in the selection of pigment-rich yeasts containing specific carotenoids from a large number of strains. We also found, for the first time, the potential of a pigment-rich Rhodotorula strain as a colorant for aquaculture. The integuments of tilapia and carp fed the alkali-treated cells of strain Rhodotorula dairenensis Sag 17 were pigmented after 3 months of cultivation. The fish integuments retained the yeast carotenes shortly after the start of feeding, and were converted to the fish-specific xanthophylls in vivo.

  18. Serum β-glucuronidase as a potential colon cancer marker: a preliminary study.

    PubMed

    Waszkiewicz, Napoleon; Szajda, Sławomir Dariusz; Konarzewska-Duchnowska, Emilia; Zalewska-Szajda, Beata; Gałązkowski, Robert; Sawko, Anna; Nammous, Halim; Buko, Vyacheslav; Szulc, Agata; Zwierz, Krzysztof; Ładny, Jerzy Robert

    2015-04-08

    Colorectal cancer is characterized by high morbidity and mortality in developed countries. The lack of low-cost, easy-to-use screening diagnostic methods is one of the causes of late diagnosis of colorectal cancer. Beta-glucuronidase (GLU) is a lysosomal exoglycosidase involved in degradation of glycosaminoglycans of the cell membranes and extracellular matrix of normal and cancerous colon tissues. The aim of our research was to evaluate the activity of GLU in the serum of colorectal cancer and estimate its potential value in the diagnosis of colorectal cancer. Blood samples were collected from 21 patients with colorectal adenocarcinoma and 17 healthy subjects. GLU activity was determined by the colorimetric method of Marciniak et al. by measuring the amount of p-nitrophenol released from 4-nitrophenyl-beta-D-glucuronide, at λ = 405 nm. We found significantly greater activity of GLU (p<0.0001) in the serum of patients with colorectal cancer, as compared to the healthy subjects. The serum GLU activity significantly differentiates patients with colorectal cancer from healthy individuals. Serum GLU activity has diagnostic value and may be used in the diagnosis of colon adenocarcinoma.

  19. CFTR is a potential marker for nasopharyngeal carcinoma prognosis and metastasis

    PubMed Central

    Tu, Ziwei; Chen, Qu; Zhang, Jie Ting; Jiang, Xiaohua; Xia, Yunfei; Chan, Hsiao Chang

    2016-01-01

    While there is an increasing interest in the correlation of cystic fibrosis transmembrane conductance regulator (CFTR) and cancer incidence, the role of CFTR in nasopharyngeal carcinoma (NPC) development remains unknown. In this study, we aimed to explore the prognostic value of CFTR in NPC patients. The expression of CFTR was determined in NPC cell lines and tissues. Statistical analysis was utilized to evaluate the correlation between CFTR expression levels and clinicopathological characteristics and prognosis in 225 cases of NPC patients. The results showed that CFTR was down-regulated in NPC tissues and cell lines. Low expression of CFTR was correlated with advanced stage (p = 0.026), distant metastasis (p < 0.001) and poor prognosis (p < 0.01). Multivariate analysis identified CFTR as an independent prognostic factor (p = 0.003). Additionally, wound healing and transwell assays revealed that overexpression of CFTR inhibited NPC cell migration and invasion, whereas knockdown of CFTR promoted cell migration and invasion. Thus, the current study indicates that CFTR, as demonstrated to play an important role in tumor migration and invasion, may be used as a potential prognostic indicator in NPC. PMID:27769067

  20. Lysosomal enzymes in preterm infants with bronchopulmonary dysplasia: a potential diagnostic marker.

    PubMed

    Goi, G; Bairati, C; Massaccesi, L; Lombardo, A; Bonafè, L; Zanardo, V; Burlina, A

    1998-11-01

    Some lysosomal glycohydrolases (N-acetyl-beta-D-glucosaminidase and their major isoenzymes, beta-D-glucuronidase, alpha-D-galactosidase, beta-D-galactosidase and alpha-D-glucosidase) were investigated in the plasma of 36 preterm infants with respiratory distress, 11 of whom developed bronchopulmonary dysplasia (BPD), in order to evaluate the role of the lysosomal apparatus in the disease. Enzyme activity was assayed fluorimetrically; the major N-acetyl-beta-D-glucosaminidase (NAG) isoenzymes were separated using a routine chromatofocusing procedure; the diagnostic efficiency was evaluated by Bayes theorem. The mean levels of almost all glycohydrolases considered were significantly higher in BPD than in non-BPD infants. Among NAG major isoenzymes, an increase was found only in form A. No variation was evident in the plasma levels of glycohydrolases during dexamethasone therapy. Data from a retrospective analysis performed in all preterms considered, show that alpha-D-galactosidase and beta-D-galactosidase differentiate a posteriori BPD and non-BPD subjects. These enzymes, after a priori verification of their diagnostic potential in preterm infants at risk of BPD development, could acquire an important predictive value.

  1. MSRV pol sequence copy number as a potential marker of multiple sclerosis.

    PubMed

    Zawada, Mariola; Liwień, Izabela; Pernak, Monika; Januszkiewicz-Lewandowska, Danuta; Nowicka-Kujawska, Karina; Rembowska, Jolanta; Lewandowski, Krzysztof; Hertmanowska, Hanna; Wender, Mieczysław; Nowak, Jerzy

    2003-01-01

    Multiple sclerosis (MS) is a neurological disease in which demyelination in the brain and spinal cord is observed. The causal influence of bacterial/viral infections and genetic/immune factors in the etiology of multiple sclerosis is suggested. Multiple sclerosis-related retrovirus (MSRV) is one of the potential agents, which can lead to development of the disease. The aim of cytogenetic studies was assessment of MSRV pol sequence copy number in patients with MS compared to normal individuals. Cytogenetic slides with interphase nuclei and extended chromatin fibers were prepared from peripheral blood of 16 patients with MS and 10 healthy individuals. Fluorescence in situ hybridization (FISH) with biotinylated product of polymerase chain reaction was used in order to analyze MSRV pol sequence copy number in the examined material. Detection of MSRV pol probe was carried out by immunological reaction with avidin-fluorescein and biotinylated anti-avidin. MSRV pol sequence copy number was significantly greater in MS patients than in normal individuals. Using FISH technique to extended chromatin fibers, it was observed that MSRV pol exists as tandem repeats on various chromosomes. The increased number of MSRV pol sequence has been found on chromatin fibers of MS patients as compared to healthy controls.

  2. Salivary Acetylcholinesterase Activity Is Increased in Parkinson's Disease: A Potential Marker of Parasympathetic Dysfunction

    PubMed Central

    Fedorova, Tatyana; Knudsen, Cindy Soendersoe; Mouridsen, Kim; Nexo, Ebba; Borghammer, Per

    2015-01-01

    Introduction. Decreased salivary flow and xerostomia are frequent findings in Parkinson's disease (PD), possibly caused by alterations in the parasympathetic tonus. Here we explore salivary acetylcholinesterase (AChE) activity as a potential biomarker in PD. Methods. We measured salivary flow, AChE activity, and total protein concentration in 30 PD patients and 49 healthy controls. We also performed exploratory correlation analyses with disease duration, motor symptom severity, autonomic complaints, and other nonmotor symptoms. Results. PD patients displayed significantly decreased salivary flow rate, significantly increased salivary AChE activity, and total protein concentration. Importantly, the AChE activity/total protein ratio was significantly increased in PD patients, suggesting that increased AChE activity cannot be explained solely by upconcentration of saliva. The Unified PD Rating Scale (UPDRS) score displayed significant correlation with total salivary protein (P = 0.002) and near-significant correlation with salivary flow (P = 0.07). Color vision test scores were also significantly correlated with AChE activity (P = 0.04) and total protein levels (P = 0.002). Conclusion. Salivary AChE activity is increased in PD patients compared to healthy controls. Future studies are needed to elucidate whether this parameter reflects the extent of neuronal damage and parasympathetic denervation in the salivary glands of PD patients. PMID:25767737

  3. Gingival crevicular fluid flow rate and alkaline phosphatase level as potential marker of active tooth movement.

    PubMed

    Alfaqeeh, S A; Anil, S

    2014-06-01

    Gingival Crevicular Fluid (GCF) changes occur during orthodontic tooth movement and this could serve as a potential indicator to the response to active treatment. The objective of the study is to assess the changes in the GCF volume and the levels of Alkaline Phosphatase (ALP) during early phase of tooth movement. 20 patients requiring all first premolar extractions were selected and treated with conventional straight wire mechanotherapy. Canine retraction was done using Nitinol closed coil springs. Maxillary canine on one side acted as experimental site while the contralateral canine acted as control. GCF was collected from around the canines before initiation of retraction, 1 hour after initiating canine retraction, 1 day, 7 days, 14 days and 21 days. GCF volume and the ALP levels were estimated and compared with the control side. The results showed statistically significant changes in the GCF volume and ALP levels on the 7th, 14th and 21st days at the experimental sides. The peak in the activity occurred on the 14th day of initiation of retraction. The GCF volume and ALP levels did not show any significant variations at the control sites where no retraction was done. It can be concluded that GCF volume and ALP levels may serve as an indicator to assess tooth movement dynamics in orthodontic therapy. Based on the available data and further studies, ALP levels in GCF may aid in developing a reliable non-invasive chair side test for assessing the prognosis and progress of orthodontic therapy.

  4. Oncogenic histone methyltransferase EZH2: A novel prognostic marker with therapeutic potential in endometrial cancer

    PubMed Central

    Oki, Shinya; Sone, Kenbun; Oda, Katsutoshi; Hamamoto, Ryuji; Ikemura, Masako; Maeda, Daichi; Takeuchi, Makoto; Tanikawa, Michihiro; Mori-Uchino, Mayuyo; Nagasaka, Kazunori; Miyasaka, Aki; Kashiyama, Tomoko; Ikeda, Yuji; Arimoto, Takahide; Kuramoto, Hiroyuki; Wada-Hiraike, Osamu; Kawana, Kei; Fukayama, Masashi; Osuga, Yutaka; Fujii, Tomoyuki

    2017-01-01

    The histone methyltransferase EZH2, a key epigenetic modifier, is known to be associated with human tumorigenesis. However, the physiological importance of EZH2 and its clinical relevance in endometrial cancer remain unclear. Hence, in the present study, we investigated the expression and function of EZH2 in endometrial cancer. In a quantitative real-time PCR analysis of 11 endometrial cancer cell lines and 52 clinical endometrial cancer specimens, EZH2 was significantly overexpressed in cancer cells and tissues compared to that in corresponding normal control cells and tissues. Kaplan-Meier survival analysis using data of the TCGA RNA-seq database and tissue microarrays (TMAs) indicated that EZH2 overexpression is associated with endometrial cancer prognosis. In addition, knockdown of EZH2 using specific siRNAs resulted in growth suppression and apoptosis induction of endometrial cancer cells, accompanied by attenuation of H3K27 trimethylation. Consistent with these results, treatment with GSK126, a specific EZH2 inhibitor, suppressed endometrial cancer cell growth and decreased the number of cancer cell colonies. Furthermore, GSK126 showed additive effects with doxorubicin or cisplatin, which are conventional drugs for treatment of endometrial cancer. Further studies should explore the therapeutic potential of inhibiting EZH2 in patients with endometrial cancer. PMID:28418882

  5. MicroRNAs in plasma and cerebrospinal fluid as potential markers for Alzheimer's disease.

    PubMed

    Kiko, Takehiro; Nakagawa, Kiyotaka; Tsuduki, Tsuyoshi; Furukawa, Katsutoshi; Arai, Hiroyuki; Miyazawa, Teruo

    2014-01-01

    The development of Alzheimer's disease (AD) biomarkers remains an unmet challenge, and new approaches that can improve current AD biomarker strategies are needed. Recent reports suggested that microRNA (miRNA) profiling of biological fluids has emerged as a diagnostic tool for several pathologic conditions. In this study, we measured six candidate miRNAs (miR-9, miR-29a, miR-29b, miR-34a, miR-125b, and miR-146a) in plasma and cerebrospinal fluid (CSF) of AD and normal subjects by using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) to evaluate their potential usability as AD biomarkers. The qRT-PCR results showed that plasma miR-34a and miR-146a levels, and CSF miR-34a, miR-125b, and miR-146a levels in AD patients were significantly lower than in control subjects. On the other hand, CSF miR-29a and miR-29b levels were significantly higher than in control subjects. Our results provide a possibility that miRNAs detected in plasma and CSF can serve as biomarkers for AD.

  6. CFTR is a potential marker for nasopharyngeal carcinoma prognosis and metastasis.

    PubMed

    Tu, Ziwei; Chen, Qu; Zhang, Jie Ting; Jiang, Xiaohua; Xia, Yunfei; Chan, Hsiao Chang

    2016-11-22

    While there is an increasing interest in the correlation of cystic fibrosis transmembrane conductance regulator (CFTR) and cancer incidence, the role of CFTR in nasopharyngeal carcinoma (NPC) development remains unknown. In this study, we aimed to explore the prognostic value of CFTR in NPC patients. The expression of CFTR was determined in NPC cell lines and tissues. Statistical analysis was utilized to evaluate the correlation between CFTR expression levels and clinicopathological characteristics and prognosis in 225 cases of NPC patients. The results showed that CFTR was down-regulated in NPC tissues and cell lines. Low expression of CFTR was correlated with advanced stage (p = 0.026), distant metastasis (p < 0.001) and poor prognosis (p < 0.01). Multivariate analysis identified CFTR as an independent prognostic factor (p = 0.003). Additionally, wound healing and transwell assays revealed that overexpression of CFTR inhibited NPC cell migration and invasion, whereas knockdown of CFTR promoted cell migration and invasion. Thus, the current study indicates that CFTR, as demonstrated to play an important role in tumor migration and invasion, may be used as a potential prognostic indicator in NPC.

  7. Endogenous Pyrogen Physiology.

    ERIC Educational Resources Information Center

    Beisel, William R.

    1980-01-01

    Discusses the physiology of endogenous pyrogen (EP), the fever-producing factor of cellular origin. Included are: its hormone-like role, its molecular nature, bioassay procedures, cellular production and mechanisms of EP action. (SA)

  8. DNA damage marker phosphorylated histone H2AX is a potential predictive marker for progression of epithelial dysplasia of the oral cavity.

    PubMed

    Leung, Elaine Y; McMahon, Jeremy D; McLellan, Douglas R; Syyed, Nazlie; McCarthy, Caroline E; Nixon, Colin; Orange, Clare; Brock, Claire; Hunter, Keith D; Adams, Peter D

    2017-10-01

    To evaluate the relationships between immunohistochemical markers related to cellular senescence, cell proliferation and histological grade of epithelial dysplasia (OD) of the oral cavity. In addition, the predictive value of these markers for progression of OD was assessed. Retrospective immunohistochemical analyses were performed on 86 formalin-fixed paraffin-embedded specimens of OD and oral squamous cell carcinoma (OSCC) for Ki67, phosphorylated histone H2AX (γH2AX), p53, p16, trimethyl-histone H3 (Lys9) (H3K9me3) and cyclin D1 (CycD1). Three separate areas representing the highest severity of OD on each slide were annotated digitally by two independent pathologists. Mean automated histoscores of the selected markers were generated and compared to that of age-matched healthy controls (n = 24). Follow-up data of OD were retrieved and anonymized by a clinical team member and linked using unique participant identifiers. The median follow-up was 10.9 years (interquartile range: 10.1-11.5). Ki67 (P < 0.0001), γH2AX (P = 0.03) and p53 (P = 0.04) were increased significantly with higher histological grade of OD. γH2AX (P = 0.03), but not histological grade of OD (P = 0.73), was associated prospectively with disease progression. Using the median histoscore for γH2AX (median histoscore = 17) as a cut-off, histoscore ≥17 was associated with an increased risk of disease progression [hazard ratio (HR) = 3.15, 95% confidence interval (CI): 1.41-7.39, P = 0.0064]. Although proliferation marker Ki67, DNA damage/checkpoint markers γH2AX and p53 were increased in higher grade of OD, only γH2AX was predictive of disease progression. These observations may reflect the role of DNA replicative stress in the transformation from OD to OSCC. Larger studies should evaluate whether γH2AX can be used as a predictive marker of OD. © 2017 John Wiley & Sons Ltd.

  9. Expression of Potential Cancer Stem Cell Marker ABCG2 is Associated with Malignant Behaviors of Hepatocellular Carcinoma

    PubMed Central

    Luo, Weihuan; Jiao, Hongbo; Jiang, Chunping

    2013-01-01

    Background. Despite improvement in treatment, the prognosis of hepatocellular carcinoma (HCC) remains disastrous. Cancer stem cells (CSCs) may be responsible for cancer malignant behaviors. ATP-binding cassette, subfamily G, member 2 (ABCG2) is widely expressed in both normal and cancer stem cells and may play an important role in cancer malignant behaviors. Methods. The expression of ABCG2 in HCC tissues and SMMC-7721 cells was examined, and the relevance of ABCG2 expression with clinical characteristics was analyzed. ABCG2+ and ABCG2− cells were sorted, and the potential of tumorigenicity was determined. Expression level of ABCG2 was manipulated by RNA interference and overexpression. Malignant behaviors including proliferation, drug resistance, migration, and invasion were studied in vitro. Results. Expression of ABCG2 was found in a minor group of cells in HCC tissues and cell lines. ABCG2 expression showed tendencies of association with unfavorable prognosis factors. ABCG2 positive cells showed a superior tumorigenicity. Upregulation of ABCG2 enhanced the capacity of proliferation, doxorubicin resistance, migration, and invasion potential, while downregulation of ABCG2 significantly decreased these malignant behaviors. Conclusion. Our results indicate that ABCG2 is a potential CSC marker for HCC. Its expression level has a close relationship with tumorigenicity, proliferation, drug resistance, and metastasis ability. PMID:24194752

  10. Theta Burst Stimulation of the Cerebellum Modifies the TMS-Evoked N100 Potential, a Marker of GABA Inhibition

    PubMed Central

    2015-01-01

    Theta burst stimulation (TBS) of the cerebellum, a potential therapy for neurological disease, can modulate corticospinal excitability via the dentato-thalamo-cortical pathway, but it is uncertain whether its effects are mediated via inhibitory or facilitatory networks. The aim of this study was to investigate the effects of 30Hz cerebellar TBS on the N100 waveform of the TMS-evoked potential (TEP), a marker of intracortical GABAB-mediated inhibition. 16 healthy participants (aged 18–30 years; 13 right handed and 3 left handed) received 30Hz intermittent TBS (iTBS), continuous TBS (cTBS) or sham stimulation over the right cerebellum, in three separate sessions. The first 8 participants received TBS at a stimulus intensity of 80% of active motor threshold (AMT), while the remainder received 90% of AMT. Motor evoked potentials (MEP) and TEP were recorded before and after each treatment, by stimulating the first dorsal interosseus area of the left motor cortex. Analysis of the 13 right handed participants showed that iTBS at 90% of AMT increased the N100 amplitude compared to sham and cTBS, without significantly altering MEP amplitude. cTBS at 80% of active motor threshold decreased the N100 amplitude and cTBS overall reduced resting MEP amplitude. The study demonstrates effects of 30Hz cerebellar TBS on inhibitory cortical networks that may be useful for treatment of neurological conditions associated with dysfunctional intracortical inhibition. PMID:26529225

  11. Mathematically combined half-cell reduction potentials of low-molecular-weight thiols as markers of seed ageing.

    PubMed

    Birtić, Simona; Colville, Louise; Pritchard, Hugh W; Pearce, Stephen R; Kranner, Ilse

    2011-09-01

    The half-cell reduction potential of the glutathione disulphide (GSSG)/glutathione (GSH) redox couple appears to correlate with cell viability and has been proposed to be a marker of seed viability and ageing. This study investigated the relationship between seed viability and the individual half-cell reduction potentials (E(i)s) of four low-molecular-weight (LMW) thiols in Lathyrus pratensis seeds subjected to artificial ageing: GSH, cysteine (Cys), cysteinyl-glycine (Cys-Gly) and γ-glutamyl-cysteine (γ-Glu-Cys). The standard redox potential of γ-Glu-Cys was previously unknown and was experimentally determined. The E(i)s were mathematically combined to define a LMW thiol-disulphide based redox environment (E(thiol-disulphide)). Loss of seed viability correlated with a shift in E(thiol-disulphide) towards more positive values, with a LD(50) value of -0.90 ± 0.093 mV M (mean ± SD). The mathematical definition of E(thiol-disulphide) is envisaged as a step towards the definition of the overall cellular redox environment, which will need to include all known redox-couples.

  12. The human endogenous circadian system causes greatest platelet activation during the biological morning independent of behaviors.

    PubMed

    Scheer, Frank A J L; Michelson, Alan D; Frelinger, Andrew L; Evoniuk, Heather; Kelly, Erin E; McCarthy, Mary; Doamekpor, Lauren A; Barnard, Marc R; Shea, Steven A

    2011-01-01

    Platelets are involved in the thromboses that are central to myocardial infarctions and ischemic strokes. Such adverse cardiovascular events have day/night patterns with peaks in the morning (~9 AM), potentially related to endogenous circadian clock control of platelet activation. The objective was to test if the human endogenous circadian system influences (1) platelet function and (2) platelet response to standardized behavioral stressors. We also aimed to compare the magnitude of any effects on platelet function caused by the circadian system with that caused by varied standardized behavioral stressors, including mental arithmetic, passive postural tilt and mild cycling exercise. We studied 12 healthy adults (6 female) who lived in individual laboratory suites in dim light for 240 h, with all behaviors scheduled on a 20-h recurring cycle to permit assessment of endogenous circadian function independent from environmental and behavioral effects including the sleep/wake cycle. Circadian phase was assessed from core body temperature. There were highly significant endogenous circadian rhythms in platelet surface activated glycoprotein (GP) IIb-IIIa, GPIb and P-selectin (6-17% peak-trough amplitudes; p ≤ 0.01). These circadian peaks occurred at a circadian phase corresponding to 8-9 AM. Platelet count, ATP release, aggregability, and plasma epinephrine also had significant circadian rhythms but with later peaks (corresponding to 3-8 PM). The circadian effects on the platelet activation markers were always larger than that of any of the three behavioral stressors. These data demonstrate robust effects of the endogenous circadian system on platelet activation in humans--independent of the sleep/wake cycle, other behavioral influences and the environment. The 9 AM timing of the circadian peaks of the three platelet surface markers, including platelet surface activated GPIIb-IIIa, the final common pathway of platelet aggregation, suggests that endogenous circadian

  13. Molecular signature of salivary gland tumors: potential use as diagnostic and prognostic marker.

    PubMed

    Fonseca, Felipe Paiva; Sena Filho, Marcondes; Altemani, Albina; Speight, Paul M; Vargas, Pablo Agustin

    2016-02-01

    Salivary gland tumors are a highly heterogeneous group of lesions with diverse microscopic appearances and variable clinical behavior. The use of clinical and histological parameters to predict patient prognosis and survival rates has been of limited utility, and the search for new biomarkers that could not only aid in a better understanding of their pathogenesis but also be reliable auxiliaries for prognostic determination and useful diagnostic tools has been performed in the last decades with very exciting results. Hence, gene rearrangements such as CRTC1-MAML2 in mucoepidermoid carcinomas have shown excellent specificity, and more than that, it has been strongly correlated with low-grade tumors and consequently with an increased survival rate and better prognosis of patients affected by neoplasms carrying this translocation. Moreover, MYB-NFIB and EWSR1-ATF1 gene fusions were shown to be specifically found in cases of adenoid cystic carcinomas and hyalinizing clear cell carcinomas, respectively, in the context of salivary gland tumors, becoming reliable diagnostic tools for these entities and potential therapeutic targets for future therapeutic protocols. Finally, the identification of ETV6-NTRK3 in cases previously diagnosed as uncommon acinic cell carcinomas, cystadenocarcinomas, and adenocarcinomas not otherwise specified led to the characterization of a completely new and now widely accepted entity, including, therefore, mammary analogue secretory carcinoma in the list of well-recognized salivary gland carcinomas. Thus, further molecular investigations of salivary gland tumors are warranted, and the recognition of other genetic abnormalities can lead to the acknowledgment of new entities and the acquirement of reliable biomarkers.

  14. Cathepsin L and B as Potential Markers for Liver Fibrosis: Insights From Patients and Experimental Models

    PubMed Central

    Manchanda, Mansi; Das, Prasenjit; Gahlot, Gaurav P S; Singh, Ratnakar; Roeb, Elke; Roderfeld, Martin; Datta Gupta, Siddhartha; Saraya, Anoop; Pandey, R M; Chauhan, Shyam S

    2017-01-01

    OBJECTIVES: Cathepsin L (CTSL) and B (CTSB) have a crucial role in extracellular matrix (ECM) degradation and tissue remodeling, which is a prominent feature of fibrogenesis. The aim of this study was to determine the role and clinical significance of these cathepsins in liver fibrosis. METHODS: Hepatic histological CTSL and CTSB expression were assessed in experimental models of liver fibrosis, patients with liver cirrhosis, chronic viral hepatitis, and controls by real-time PCR and immunohistochemistry. Plasma levels of CTSL and CTSB were analyzed in 51 liver cirrhosis patients (Child–Pugh stages A, B and C) and 15 controls. RESULTS: Significantly enhanced CTSL mRNA (P=0.02) and protein (P=0.01) levels were observed in the liver of carbon tetrachloride-treated mice compared with controls. Similarly, hepatic CTSL and CTSB mRNA levels (P=0.02) were markedly increased in Abcb4−/− (ATP-binding cassette transporter knockout) mice compared with wild-type littermates. Elevated levels of CTSL and CTSB were also found in the liver (P=0.001) and plasma (P<0.0001) of patients with hepatic cirrhosis compared with healthy controls. Furthermore, CTSL and CTSB levels correlated well with the hepatic collagen (r=0.5, P=0.007; r=0.64, P=0.0001). CTSL and CTSB levels increased with the Child–Pugh stage of liver cirrhosis and correlated with total bilirubin content (r=0.4/0.2; P≤0.05). CTSL, CTSB, and their combination had a high diagnostic accuracy (area under the curve: 0.91, 0.89 and 0.96, respectively) for distinguishing patients from controls. CONCLUSIONS: Our data demonstrate the overexpression of CTSL and CTSB in patients and experimental mouse models, suggesting their potential as diagnostic biomarkers for chronic liver diseases. PMID:28617446

  15. A Preclinical Study of Laryngeal Motor-Evoked Potentials as a Marker Vagus Nerve Activation.

    PubMed

    Grimonprez, Annelies; Raedt, Robrecht; De Taeye, Leen; Larsen, Lars Emil; Delbeke, Jean; Boon, Paul; Vonck, Kristl

    2015-12-01

    Vagus nerve stimulation (VNS) is a treatment for refractory epilepsy and depression. Previous studies using invasive recording electrodes showed that VNS induces laryngeal motor-evoked potentials (LMEPs) through the co-activation of the recurrent laryngeal nerve and subsequent contractions of the laryngeal muscles. The present study investigates the feasibility of recording LMEPs in chronically VNS-implanted rats, using a minimally-invasive technique, to assess effective current delivery to the nerve and to determine optimal VNS output currents for vagal fiber activation. Three weeks after VNS electrode implantation, signals were recorded using an electromyography (EMG) electrode in the proximity of the laryngeal muscles and a reference electrode on the skull. The VNS output current was gradually ramped up from 0.1 to 1.0 mA in 0.1 mA steps. In 13/27 rats, typical LMEPs were recorded at low VNS output currents (median 0.3 mA, IQR 0.2-0.3 mA). In 11/27 rats, significantly higher output currents were required to evoke electrophysiological responses (median 0.7 mA, IQR 0.5-0.7 mA, p < 0.001). The latencies of these responses deviated significantly from LMEPs (p < 0.05). In 3/27 rats, no electrophysiological responses to simulation were recorded. Minimally invasive LMEP recordings are feasible to assess effective current delivery to the vagus nerve. Furthermore, our results suggest that low output currents are sufficient to activate vagal fibers.

  16. Visually Evoked Potential Markers of Concussion History in Patients with Convergence Insufficiency

    PubMed Central

    Poltavski, Dmitri; Lederer, Paul; Cox, Laurie Kopko

    2017-01-01

    ABSTRACT Purpose We investigated whether differences in the pattern visual evoked potentials exist between patients with convergence insufficiency and those with convergence insufficiency and a history of concussion using stimuli designed to differentiate between magnocellular (transient) and parvocellular (sustained) neural pathways. Methods Sustained stimuli included 2-rev/s, 85% contrast checkerboard patterns of 1- and 2-degree check sizes, whereas transient stimuli comprised 4-rev/s, 10% contrast vertical sinusoidal gratings with column width of 0.25 and 0.50 cycles/degree. We tested two models: an a priori clinical model based on an assumption of at least a minimal (beyond instrumentation’s margin of error) 2-millisecond lag of transient response latencies behind sustained response latencies in concussed patients and a statistical model derived from the sample data. Results Both models discriminated between concussed and nonconcussed groups significantly above chance (with 76% and 86% accuracy, respectively). In the statistical model, patients with mean vertical sinusoidal grating response latencies greater than 119 milliseconds to 0.25-cycle/degree stimuli (or mean vertical sinusoidal latencies >113 milliseconds to 0.50-cycle/degree stimuli) and mean vertical sinusoidal grating amplitudes of less than 14.75 mV to 0.50-cycle/degree stimuli were classified as having had a history of concussion. The resultant receiver operating characteristic curve for this model had excellent discrimination between the concussed and nonconcussed (area under the curve = 0.857; P < .01) groups with sensitivity of 0.92 and specificity of 0.80. Conclusions The results suggest a promising electrophysiological approach to identifying individuals with convergence insufficiency and a history of concussion. PMID:28609417

  17. Visually Evoked Potential Markers of Concussion History in Patients with Convergence Insufficiency.

    PubMed

    Poltavski, Dmitri; Lederer, Paul; Cox, Laurie Kopko

    2017-07-01

    We investigated whether differences in the pattern visual evoked potentials exist between patients with convergence insufficiency and those with convergence insufficiency and a history of concussion using stimuli designed to differentiate between magnocellular (transient) and parvocellular (sustained) neural pathways. Sustained stimuli included 2-rev/s, 85% contrast checkerboard patterns of 1- and 2-degree check sizes, whereas transient stimuli comprised 4-rev/s, 10% contrast vertical sinusoidal gratings with column width of 0.25 and 0.50 cycles/degree. We tested two models: an a priori clinical model based on an assumption of at least a minimal (beyond instrumentation's margin of error) 2-millisecond lag of transient response latencies behind sustained response latencies in concussed patients and a statistical model derived from the sample data. Both models discriminated between concussed and nonconcussed groups significantly above chance (with 76% and 86% accuracy, respectively). In the statistical model, patients with mean vertical sinusoidal grating response latencies greater than 119 milliseconds to 0.25-cycle/degree stimuli (or mean vertical sinusoidal latencies >113 milliseconds to 0.50-cycle/degree stimuli) and mean vertical sinusoidal grating amplitudes of less than 14.75 mV to 0.50-cycle/degree stimuli were classified as having had a history of concussion. The resultant receiver operating characteristic curve for this model had excellent discrimination between the concussed and nonconcussed (area under the curve = 0.857; P < .01) groups with sensitivity of 0.92 and specificity of 0.80. The results suggest a promising electrophysiological approach to identifying individuals with convergence insufficiency and a history of concussion.

  18. Hydrogen emission in meteors as a potential marker for the exogenous delivery of organics and water.

    PubMed

    Jenniskens, Peter; Mandell, Avram M

    2004-01-01

    We detected hydrogen Balmer-alpha (H(alpha)) emission in the spectra of bright meteors and investigated its potential use as a tracer for exogenous delivery of organic matter. We found that it is critical to observe the meteors with high enough spatial resolution to distinguish the 656.46 nm H(alpha) emission from the 657.46 nm intercombination line of neutral calcium, which was bright in the meteor afterglow. The H(alpha) line peak stayed in constant ratio to the atmospheric emissions of nitrogen during descent of the meteoroid. If all of the hydrogen originates in the Earth's atmosphere, the hydrogen atoms are expected to have been excited at T = 4400 K. In that case, we measured an H(2)O abundance in excess of 150 +/- 20 ppm at 80-90 km altitude (assuming local thermodynamic equilibrium in the air plasma). This compares with an expected <20 ppm from H(2)O in the gas phase. Alternatively, meteoric refractory organic matter (and water bound in meteoroid minerals) could have caused the observed H(alpha) emission, but only if the line is excited in a hot T approximately 10000 K plasma component that is unique to meteoric ablation vapor emissions such as Si(+). Assuming that the Si(+) lines of the Leonid spectrum would need the same hot excitation conditions, and a typical [H]/[C] = 1 in cometary refractory organics, we calculated an abundance ratio [C]/[Si] = 3.9 +/- 1.4 for the dust of comet 55P/Tempel-Tuttle. This range agreed with the value of [C]/[Si] = 4.4 measured for comet 1P/Halley dust. Unless there is 10 times more water vapor in the upper atmosphere than expected, we conclude that a significant fraction of the hydrogen atoms in the observed meteor plasma originated in the meteoroid.

  19. Hydrogen emission in meteors as a potential marker for the exogenous delivery of organics and water

    NASA Technical Reports Server (NTRS)

    Jenniskens, Peter; Mandell, Avram M.

    2004-01-01

    We detected hydrogen Balmer-alpha (H(alpha)) emission in the spectra of bright meteors and investigated its potential use as a tracer for exogenous delivery of organic matter. We found that it is critical to observe the meteors with high enough spatial resolution to distinguish the 656.46 nm H(alpha) emission from the 657.46 nm intercombination line of neutral calcium, which was bright in the meteor afterglow. The H(alpha) line peak stayed in constant ratio to the atmospheric emissions of nitrogen during descent of the meteoroid. If all of the hydrogen originates in the Earth's atmosphere, the hydrogen atoms are expected to have been excited at T = 4400 K. In that case, we measured an H(2)O abundance in excess of 150 +/- 20 ppm at 80-90 km altitude (assuming local thermodynamic equilibrium in the air plasma). This compares with an expected <20 ppm from H(2)O in the gas phase. Alternatively, meteoric refractory organic matter (and water bound in meteoroid minerals) could have caused the observed H(alpha) emission, but only if the line is excited in a hot T approximately 10000 K plasma component that is unique to meteoric ablation vapor emissions such as Si(+). Assuming that the Si(+) lines of the Leonid spectrum would need the same hot excitation conditions, and a typical [H]/[C] = 1 in cometary refractory organics, we calculated an abundance ratio [C]/[Si] = 3.9 +/- 1.4 for the dust of comet 55P/Tempel-Tuttle. This range agreed with the value of [C]/[Si] = 4.4 measured for comet 1P/Halley dust. Unless there is 10 times more water vapor in the upper atmosphere than expected, we conclude that a significant fraction of the hydrogen atoms in the observed meteor plasma originated in the meteoroid.

  20. Expression and potential clinical significance of urothelial cytodifferentiation markers in the exstrophic bladder.

    PubMed

    Rubenwolf, Peter C; Eder, Fabian; Ebert, Anne-Karoline; Hofstaedter, Ferdinand; Roesch, Wolfgang H

    2012-05-01

    We characterize the urothelium from patients with classic bladder exstrophy-epispadias complex for the expression of proteins associated with urothelial differentiation, and discuss a potential impact of urothelial phenotype on the structural and functional properties of the bladder template following bladder closure. From 2005 to 2010 bladder biopsies from 32 infants with bladder exstrophy-epispadias complex obtained at primary bladder closure were collected. After histological assessment immunochemistry was used to investigate the expression of uroplakin IIIa, cytokeratin differentiation restricted antigens CK13 and CK20, and tight junction protein claudin 4. Overall tissue morphology showed gross alterations with inflammatory, proliferative and metaplastic changes in most specimens. Sections of intact epithelium were present in 78% of biopsies. With respect to urothelial phenotype, CK13 was expressed in all specimens, whereas UPIIIa and CK20 were absent in 76% of the tissues examined. Of the biopsies 52% revealed an irregular expression pattern of tight junction protein Cl-4. This is the first study to our knowledge to characterize the urothelium from infants with bladder exstrophy-epispadias complex for the expression of urothelial differentiation associated antigens. Our findings suggest urothelial differentiation changes in a majority of exstrophic bladders, at least at primary bladder closure. Although the underlying etiology remains to be established, abnormal urothelial differentiation may result in a dysfunctional urothelial barrier with implications for the structural and functional properties of the bladder template. Despite the study limitations, our preliminary findings provide a platform for further investigation of the significance of the urothelium for the exstrophic bladder. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  1. Cholinergic muscarinic M4 receptor gene polymorphisms: a potential risk factor and pharmacogenomic marker for schizophrenia.

    PubMed

    Scarr, Elizabeth; Um, Jung Yoon; Cowie, Tiffany Frances; Dean, Brian

    2013-05-01

    Although schizophrenia is a widespread disorder of unknown aetiology, we have previously shown that muscarinic M4 receptor (CHRM4) expression is decreased in the hippocampus and caudate-putamen from subjects with the disorder, implicating the receptor in its pathophysiology. These findings led us to determine whether variation in the CHRM4 gene sequence was associated with an altered risk of schizophrenia by sequencing the CHRM4 gene from the brains of 76 people with the disorder and 74 people with no history of psychiatric disorders. In addition, because the CHRM4 is a potential target for antipsychotic drug development, we investigated whether variations in CHRM4 sequence were associated with final recorded doses of, and life-time exposure to, antipsychotic drugs. Gene sequencing identified two single nucleotide polymorphisms (SNPs; rs2067482 and rs72910092) in the CHRM4 gene. For rs2067482, our data suggested that both genotype (1341C/C; p = 0.05) and allele (C; p = 0.03) were associated with an increased risk of schizophrenia. In addition, there was a strong trend (p = 0.08) towards an association between CHRM4 sequence and increased lifetime exposure to antipsychotic drugs. Furthermore, there was a trend for people with the C allele to be prescribed benzodiazepines more frequently (p = 0.06) than those with the T allele. These data, albeit on small cohorts, are consistent with genetic variance at rs2067482 contributing to an altered risk of developing schizophrenia which requires more forceful pharmacotherapy to achieve a clinical response.

  2. Tissue microarray-based study of hepatocellular carcinoma validating SPIB as potential clinical prognostic marker.

    PubMed

    Ho, Yi-Jung; Lin, Yueh-Min; Huang, Yen-Chi; Yeh, Kun-Tu; Lin, Liang-In; Lu, Jeng-Wei

    2016-01-01

    Currently, the prognostic significance of SPIB protein overexpression in human hepatocellular carcinoma (HCC) is unclear. The aim of the present study was to investigate the level of SPIB expression in human HCC in order to determine possible correlations between SPIB expression and clinicopathological findings. The expression of SPIB proteins was detected using immunohistochemical staining in commercial multiple-tissue microarrays as a means of examining expression profiles in patients. Using online biomarker validation tool SurvExpress, we focused on the correlation between SPIB overexpression and survival as well as relapse-free survival (RFS). Results show that SPIB protein expression levels were significantly higher in colon, liver, and stomach tumors than in non-tumor tissues (p<0.05). SPIB overexpression in patients with HCC was also significantly higher than that of the normal samples (p<0.001). Among patients with liver disease, SPIB protein expression levels differ significantly according to the stage of liver disease, specifically between stages I, II, and III of HCC (p<0.05). SPIB expression was also shown to be significantly correlated with age (p=0.046) and histological grade (p=0.027). Furthermore, the SurvExpress analysis suggested that high SPIB and KI-67 mRNA expression were significantly associated with the poor survival of patients with HCC (p<0.05). Our results indicate that cross-talk in the expression of SPIB and KI-67 may be associated with poor prognosis and may potentially serve as a clinical prognostic indicator of HCC. This is the first time that such an association has been reported. Copyright © 2015 Elsevier GmbH. All rights reserved.

  3. Predictive value of bovine follicular components as markers of oocyte developmental potential.

    PubMed

    Matoba, Satoko; Bender, Katrin; Fahey, Alan G; Mamo, Solomon; Brennan, Lorraine; Lonergan, Patrick; Fair, Trudee

    2014-01-01

    The follicle is a unique micro-environment within which the oocyte can develop and mature to a fertilisable gamete. The aim of this study was to investigate the ability of a panel of follicular parameters, including intrafollicular steroid and metabolomic profiles and theca, granulosa and cumulus cell candidate gene mRNA abundance, to predict the potential of bovine oocytes to develop to the blastocyst stage in vitro. Individual follicles were dissected from abattoir ovaries, carefully ruptured under a stereomicroscope and the oocyte was recovered and individually processed through in vitro maturation, fertilisation and culture. The mean (±s.e.m.) follicular concentrations of testosterone (62.8±4.8 ngmL(-1)), progesterone (616.8±31.9 ngmL(-1)) and oestradiol (14.4±2.4 ngmL(-1)) were not different (P>0.05) between oocytes that formed (competent) or failed to form (incompetent) blastocysts. Principal-component analysis of the quantified aqueous metabolites in follicular fluid showed differences between oocytes that formed blastocysts and oocytes that degenerated; l-alanine, glycine and l-glutamate were positively correlated and urea was negatively correlated with blastocyst formation. Follicular fluid associated with competent oocytes was significantly lower in palmitic acid (P=0.023) and total fatty acids (P=0.031) and significantly higher in linolenic acid (P=0.036) than follicular fluid from incompetent oocytes. Significantly higher (P<0.05) transcript abundance of LHCGR in granulosa cells, ESR1 and VCAN in thecal cells and TNFAIP6 in cumulus cells was associated with competent compared with incompetent oocytes.

  4. Hydrogen emission in meteors as a potential marker for the exogenous delivery of organics and water

    NASA Technical Reports Server (NTRS)

    Jenniskens, Peter; Mandell, Avram M.

    2004-01-01

    We detected hydrogen Balmer-alpha (H(alpha)) emission in the spectra of bright meteors and investigated its potential use as a tracer for exogenous delivery of organic matter. We found that it is critical to observe the meteors with high enough spatial resolution to distinguish the 656.46 nm H(alpha) emission from the 657.46 nm intercombination line of neutral calcium, which was bright in the meteor afterglow. The H(alpha) line peak stayed in constant ratio to the atmospheric emissions of nitrogen during descent of the meteoroid. If all of the hydrogen originates in the Earth's atmosphere, the hydrogen atoms are expected to have been excited at T = 4400 K. In that case, we measured an H(2)O abundance in excess of 150 +/- 20 ppm at 80-90 km altitude (assuming local thermodynamic equilibrium in the air plasma). This compares with an expected <20 ppm from H(2)O in the gas phase. Alternatively, meteoric refractory organic matter (and water bound in meteoroid minerals) could have caused the observed H(alpha) emission, but only if the line is excited in a hot T approximately 10000 K plasma component that is unique to meteoric ablation vapor emissions such as Si(+). Assuming that the Si(+) lines of the Leonid spectrum would need the same hot excitation conditions, and a typical [H]/[C] = 1 in cometary refractory organics, we calculated an abundance ratio [C]/[Si] = 3.9 +/- 1.4 for the dust of comet 55P/Tempel-Tuttle. This range agreed with the value of [C]/[Si] = 4.4 measured for comet 1P/Halley dust. Unless there is 10 times more water vapor in the upper atmosphere than expected, we conclude that a significant fraction of the hydrogen atoms in the observed meteor plasma originated in the meteoroid.

  5. Growth Differentiation Factor-15 (GDF-15) is a potential marker of radiation response and radiation sensitivity.

    PubMed

    Sándor, Nikolett; Schilling-Tóth, Boglárka; Kis, Enikő; Benedek, Anett; Lumniczky, Katalin; Sáfrány, Géza; Hegyesi, Hargita

    2015-11-01

    We have investigated the importance of GDF-15 (secreted cytokine belonging to the TGF-β superfamily) in low and high dose radiation-induced cellular responses. A telomerase immortalized human fibroblast cell line (F11hT) was used in the experiments. A lentiviral system encoding small hairpin RNAs (shRNA) was used to establish GDF-15 silenced cells. Secreted GDF-15 levels were measured in culture medium by ELISA. Cell cycle analysis was performed by flow cytometry. The experiments demonstrated that in irradiated human fibroblasts GDF-15 expression increased with dose starting from 100mGy. Elevated GDF-15 expression was not detected in bystander cells. The potential role of GDF-15 in radiation response was investigated by silencing GDF-15 in immortalized human fibroblasts with five different shRNA encoded in lentiviral vectors. Cell lines with considerably reduced GDF-15 levels presented increased radiation sensitivity, while a cell line with elevated GDF-15 was more radiation resistant than wild type cells. We have investigated how the reduced GDF-15 levels alter the response of several known radiation inducible genes. In F11hT-shGDF-15 cells the basal expression level of CDKN1A was unaltered relative to F11hT cells, while GADD45A and TGF-β1 mRNA levels were slightly higher, and TP53INP1 was considerably reduced. The radiation-induced expression of TP53INP1 was lower in the silenced than in wild type fibroblast cells. Cell cycle analysis indicated that radiation-induced early G2/M arrest was abrogated in GDF-15 silenced cells. Moreover, radiation-induced bystander effect was less pronounced in GDF-15 silenced fibroblasts. In conclusion, the results suggest that GDF-15 works as a radiation inducible radiation resistance increasing factor in normal human fibroblast cells, acts by regulating the radiation-induced transcription of several genes and might serve as a radiation-induced early biomarker in exposed cells.

  6. Diffusion imaging changes in grey matter in Alzheimer's disease: a potential marker of early neurodegeneration.

    PubMed

    Weston, Philip S J; Simpson, Ivor J A; Ryan, Natalie S; Ourselin, Sebastien; Fox, Nick C

    2015-01-01

    Alzheimer's disease (AD) is recognized to have a long presymptomatic period, during which there is progressive accumulation of molecular pathology, followed by inexorable neuronal damage. The ability to identify presymptomatic individuals with evidence of neurodegenerative change, to stage their disease, and to track progressive changes will be important for early diagnosis and for prevention trials. Despite recent advances, particularly in magnetic resonance imaging, our ability to identify early neurodegenerative changes reliably is limited. The development of diffusion-weighted magnetic resonance imaging, which is sensitive to microstructural changes not visible with conventional volumetric techniques, has led to a number of diffusion imaging studies in AD; these have largely focused on white matter changes. However, in AD cerebral grey matter is affected very early, with pathological studies suggesting that grey matter changes predate those in white matter. In this article we review the growing number of studies that assess grey matter diffusivity changes in AD. Although use of the technique is still at a relatively early stage, results so far have been promising. Initial studies identified changes in diffusion measures in the hippocampi of patients with mild cognitive impairment, which predated macroscopic volume loss, with positive predictive value for progression to AD dementia. More recent studies have identified abnormalities in multiple neocortical areas (particularly the posterior cingulate) at various stages of disease progression. Studies of patients who carry genetic mutations predisposing to autosomal dominant familial AD have shown cortical and subcortical grey matter diffusivity changes several years before the expected onset of the first clinical symptoms. The technique is not without potential methodological difficulties, especially relating to partial volume effects, although recent advances appear to be reducing such issues. Going forward

  7. Potential use of iodine-123 metaiodobenzylguanidine radioaerosol as a marker of pulmonary neuroadrenergic function.

    PubMed

    Giordano, A; Calcagni, M L; Rossi, B; Fuso, L; Accardo, D; Valente, S; Pistelli, R; Franceschini, R; Troncone, L

    1997-01-01

    Iodine-123 metaiodobenzylguanidine (123I-MIBG) radioaerosol is of potential use in the investigation of the neuroadrenergic function of the lungs; however, before the method can be successfully employed the following issues need to be clarified: (1) Does the nebulization affect the radiochemical purity of 123I-MIBG? (2) Is the pulmonary distribution of inhaled 123I-MIBG homogeneous in normal subjects? (3) Does the pulmonary clearance of inhaled 123I-MIBG reflect the functional status of the neuroadrenergic system of the lungs? In this study we performed: (1) a chromatographic study of nebulized 123I-MIBG; (2) a quantitative evaluation of the lung distribution of 123I-MIBG radioaerosol in normal subjects as compared with that of technetium-99m diethylene triamine penta-acetic acid (99mTc-DTPA) and (3) an assessment of 123I-MIBG lung clearance both under control conditions and after pharmacologically induced beta-blockade, again compared with 99mTc-DTPA. For these purposes, eight normal subjects were divided randomly into an "MIBG group" and a "DTPA group" (four subjects each) and submitted to three scintigraphic studies each: a baseline study, and studies after the administration of a low (80 mg) and a high (160 mg) dose of propranolol. Radiochemical purity of nebulized 123I-MIBG ranged between 97.18% and 98.70%. The lung distribution of 123I-MIBG, as judged by the aerosol penetration index, was identical to that of 99mTc-DTPA under all study conditions. The 123I-MIBG clearance rate was slower than that of 99mTc-DTPA under baseline conditions (135+/-32 min vs 69+/-27 min, P<0.01) and increased significantly after propranolol administrations, while the 99mTc-DTPA clearance did not change. The following conclusions were drawn: (1) the nebulization does not affect the radiochemical purity of 123I-MIBG; (2) the lung distribution of 123I-MIBG is homogeneous in normal subjects; (3) the pulmonary clearance of 123I-MIBG reflects the functional status of the neuroadrenergic

  8. Genome-Wide Gene Expression Profile Analyses Identify CTTN as a Potential Prognostic Marker in Esophageal Cancer

    PubMed Central

    He, Wei; Wang, Jin; Jia, Yongxu; Sun, Yan; Tang, Senwei; Fu, Li; Qin, Yanru

    2014-01-01

    Aim Esophageal squamous cell carcinoma (ESCC) is one of the most common fatal malignances of the digestive tract. Its prognosis is poor mainly due to the lack of reliable markers for early detection and prognostic prediction. Here we aim to identify the molecules involved in ESCC carcinogenesis and those as potential markers for prognosis and as new molecular therapeutic targets. Methods We performed genome-wide gene expression profile analyses of 10 primary ESCCs and their adjacent normal tissues by cDNA microarrays representing 47,000 transcripts and variants. Candidate genes were then validated by semi quantitative reverse transcription-PCR (RT-PCR), tissue microarrays (TMAs) and immunohistochemistry (IHC) staining. Results Using an arbitrary cutoff line of signal log ratio of ≥1.5 or ≤−1.5, we observed 549 up-regulated genes and 766 down-regulated genes in ESCCs compared with normal esophageal tissues. The functions of 302 differentially expressed genes were associated with cell metabolism, cell adhesion and immune response. Several candidate deregulated genes including four overexpressed (CTTN, DMRT2, MCM10 and SCYA26) and two underexpressed (HMGCS2 and SORBS2) were subsequently verified, which can be served as biomarkers for ESCC. Moreover, overexpression of cortactin (CTTN) was observed in 126/198 (63.6%) of ESCC cases and was significantly associated with lymph node metastasis (P = 0.000), pathologic stage (P = 0.000) and poor survival (P<0.001) of ESCC patients. Furthermore, a significant correlation between CTTN overexpression and shorter disease-specific survival rate was found in different subgroups of ESCC patient stratified by the pathologic stage (P<0.05). Conclusion Our data provide valuable information for establishing molecules as candidates for prognostic and/or as therapeutic targets. PMID:24551190

  9. Genetic Structure and Inferences on Potential Source Areas for Bactrocera dorsalis (Hendel) Based on Mitochondrial and Microsatellite Markers

    PubMed Central

    Shi, Wei; Kerdelhué, Carole; Ye, Hui

    2012-01-01

    Bactrocera dorsalis (Diptera: Tephritidae) is mainly distributed in tropical and subtropical Asia and in the Pacific region. Despite its economic importance, very few studies have addressed the question of the wide genetic structure and potential source area of this species. This pilot study attempts to infer the native region of this pest and its colonization pathways in Asia. Combining mitochondrial and microsatellite markers, we evaluated the level of genetic diversity, genetic structure, and the gene flow among fly populations collected across Southeast Asia and China. A complex and significant genetic structure corresponding to the geographic pattern was found with both types of molecular markers. However, the genetic structure found was rather weak in both cases, and no pattern of isolation by distance was identified. Multiple long-distance dispersal events and miscellaneous host selection by this species may explain the results. These complex patterns may have been influenced by human-mediated transportation of the pest from one area to another and the complex topography of the study region. For both mitochondrial and microsatellite data, no signs of bottleneck or founder events could be identified. Nonetheless, maximal genetic diversity was observed in Myanmar, Vietnam and Guangdong (China) and asymmetric migration patterns were found. These results provide indirect evidence that the tropical regions of Southeast Asia and southern coast of China may be considered as the native range of the species and the population expansion is northward. Yunnan (China) is a contact zone that has been colonized from different sources. Regions along the southern coast of Vietnam and China probably served to colonize mainly the southern region of China. Southern coastal regions of China may also have colonized central parts of China and of central Yunnan. PMID:22615898

  10. Pulmonary neuroendocrine cells and neuroepithelial bodies in sudden infant death syndrome: potential markers of airway chemoreceptor dysfunction.

    PubMed

    Cutz, Ernest; Perrin, Donald G; Pan, Jie; Haas, Elisabeth A; Krous, Henry F

    2007-01-01

    Pulmonary neuroendocrine cells (PNEC), including neuroepithelial bodies (NEB), are amine- and peptide (for example, bombesin)-producing cells that function as hypoxia/hypercapnia-sensitive chemoreceptors that could be involved in the pathophysiology of sudden infant death syndrome (SIDS). We assessed morphometrically the frequency and size of PNEC/NEB in lungs of infants who died of SIDS (n = 21) and compared them to an equal number PNEC/NEB in lungs of age-matched control infants who died of accidental death or homicide, with all cases obtained from the San Diego SIDS/SUDC Research Project database. As a marker for PNEC/NEB we used an antibody against chromogranin A (CGA), and computer-assisted morphometric analysis was employed to determine the relative frequency of PNEC per airway epithelial area (% immunostained area, %IMS), the size of NEB, the number of nuclei/NEB, and the size of the NEB cells. The lungs of SIDS infants showed significantly greater %IMS of airway epithelium (2.72 +/- 0.28 [standard error of the mean, SEM] versus 1.88 +/- 0.24; P < 0.05) and larger NEB (1557 +/- 153 microm(2) versus 1151 +/- 106 microm(2); P < 0.05) compared to control infants. The size of NEB cells was also significantly increased in SIDS cases compared to the controls (180 +/- 6.39 microm(2) versus 157 +/- 8.0 microm(2); P < 0.05), indicating the presence of hypertrophy in addition to hyperplasia. Our findings support previous studies demonstrating hyperplasia of PNEC/NEB in lungs of infants who died of SIDS. These changes could be secondary to chronic hypoxia and/or could be attributable to maturational delay. Morphometric assessment and/or measurement of the secretory products of these cells (for example, CGA, bombesin) could provide a potential biological marker for SIDS.

  11. Association between Mutation and Expression of TP53 as a Potential Prognostic Marker of Triple-Negative Breast Cancer

    PubMed Central

    Kim, Ji-Yeon; Park, Kyunghee; Jung, Hae Hyun; Lee, Eunjin; Cho, Eun Yoon; Lee, Kwang Hee; Bae, Soo Youn; Lee, Se Kyung; Kim, Seok Won; Lee, Jeong Eon; Nam, Seok Jin; Ahn, Jin Seok; Im, Young-Hyuck; Park, Yeon Hee

    2016-01-01

    Purpose TP53, the most frequently mutated gene in breast cancer, is more frequently altered in HER2-enriched and basal-like breast cancer. However, no studies have clarified the role of TP53 status as a prognostic and predictive marker of triple-negative breast cancer (TNBC). Materials and Methods We performed p53 immunohistochemistry (IHC), nCounter mRNA expression assay, and DNA sequencing to determine the relationship between TP53 alteration and clinical outcomes of TNBC patients. Results Seventy-seven of 174 TNBC patients were found to harbor a TP53 mutation. Patients with missense mutations showed high protein expression in contrast to patients with deletion mutations (positivity of IHC: wild type vs. missense vs. deletion mutation, 53.6% vs. 89.8% vs. 25.0%, respectively; p < 0.001). TP53 mRNA expression was influenced by mutation status (mRNA expression [median]: wild type vs. missense vs. deletion mutation, 207.36± 132.73 vs. 339.61±143.21 vs. 99.53±99.57, respectively; p < 0.001). According to survival analysis, neither class of mutation nor protein or mRNA expression status had any impact on patient prognosis. In subgroup analysis, low mRNA expression was associated with poor prognosis in patients with a TP53 missense mutation (5-year distant recurrence-free survival [5Y DRFS]: low vs. high, 50.0% vs. 87.8%; p=0.009), while high mRNA expression with a TP53 deletion mutation indicated poor prognosis (5Y DRFS: low vs. high, 91.7% vs. 75.0%; p=0.316). Conclusion Association between TP53 mutation and expression indicates a potential prognostic marker of TNBC; hence both DNA sequencing and mRNA expression analysis may be required to predict the prognosis of TNBC patients. PMID:26910472

  12. Epigenetic regulation of CD271, a potential cancer stem cell marker associated with chemoresistance and metastatic capacity

    PubMed Central

    LI, SULAN; YUE, DONGLI; CHEN, XINFENG; WANG, LIPING; LI, JIEYAO; PING, YU; GAO, QUN; WANG, DAN; ZHANG, TENGFEI; LI, FENG; YANG, LI; HUANG, LAN; ZHANG, YI

    2015-01-01

    Cancer stem cells (CSCs) are considered to be the cause of tumor initiation, metastasis and recurrence. Additionally, CSCs are responsible for the failure of chemotherapy and radiotherapy. The isolation and identification of CSCs is crucial for facilitating the monitoring, therapy or prevention of cancer. We aimed to identify esophageal squamous cell carcinoma (ESCC) stem-like cells, the epigenetic mechanism and identify novel biomarkers for targeting ESCC CSCs. Sixty-three paired ESCC tissues and adjacent non-cancerous tissues were included in this study. CD271, which was identified as the CSC marker for melanoma, was assessed using quantitative PCR (qPCR). Using flow cytometry, we isolated CD271+ cells comprising 7.5% of cancer cells from the KYSE70 cell line. Sphere formation and anchorage-independent growth were analyzed in CD271+ and CD271− cancer cells, respectively. qPCR was used to detect stem-related genes and CCK-8 was performed to analyze the sensitivity to chemotherapy in the two groups. Bisulfite genomic sequencing was used to analyze the methylation status. CD271 expression was significantly higher in ESCC tissues than in adjacent non-cancerous tissues. Compared with CD271− cancer cells, CD271+ cancer cells showed a higher ability of sphere and colony formation, a high level expression of stem-related gene, and resistance to chemotherapy. The expression of CD271 was induced by a demethylation agent. In conclusion, CD271+ ESCC cells possess stem-like properties. CD271 can potentially act as a prognostic marker for ESCC, whose expression is regulated epigenetically. PMID:25351876

  13. Epigenetic regulation of CD271, a potential cancer stem cell marker associated with chemoresistance and metastatic capacity.

    PubMed

    Li, Sulan; Yue, Dongli; Chen, Xinfeng; Wang, Liping; Li, Jieyao; Ping, Yu; Gao, Qun; Wang, Dan; Zhang, Tengfei; Li, Feng; Yang, Li; Huang, Lan; Zhang, Yi

    2015-01-01

    Cancer stem cells (CSCs) are considered to be the cause of tumor initiation, metastasis and recurrence. Additionally, CSCs are responsible for the failure of chemotherapy and radiotherapy. The isolation and identification of CSCs is crucial for facilitating the monitoring, therapy or prevention of cancer. We aimed to identify esophageal squamous cell carcinoma (ESCC) stem-like cells, the epigenetic mechanism and identify novel biomarkers for targeting ESCC CSCs. Sixty-three paired ESCC tissues and adjacent non-cancerous tissues were included in this study. CD271, which was identified as the CSC marker for melanoma, was assessed using quantitative PCR (qPCR). Using flow cytometry, we isolated CD271+ cells comprising 7.5% of cancer cells from the KYSE70 cell line. Sphere formation and anchorage-independent growth were analyzed in CD271+ and CD271- cancer cells, respectively. qPCR was used to detect stem-related genes and CCK-8 was performed to analyze the sensitivity to chemotherapy in the two groups. Bisulfite genomic sequencing was used to analyze the methylation status. CD271 expression was significantly higher in ESCC tissues than in adjacent non-cancerous tissues. Compared with CD271- cancer cells, CD271+ cancer cells showed a higher ability of sphere and colony formation, a high level expression of stem-related gene, and resistance to chemotherapy. The expression of CD271 was induced by a demethylation agent. In conclusion, CD271+ ESCC cells possess stem-like properties. CD271 can potentially act as a prognostic marker for ESCC, whose expression is regulated epigenetically.

  14. Integration of zebrafish fin regeneration genes with expression data of human tumors in silico uncovers potential novel melanoma markers

    PubMed Central

    Hooks, Katarzyna B.; Khatib, Abdel-Majid

    2016-01-01

    Tissue regeneration requires expression of a large, unknown number of genes to initiate and maintain cellular processes such as proliferation, extracellular matrix synthesis, differentiation and migration. A unique model to simulate this process in a controlled manner is the re-growth of the caudal fin of zebrafish after amputation. Within this tissue stem cells differentiate into fibroblasts, epithelial and endothelial cells as well as melanocytes. Many genes implicated in the regeneration process are deregulated in cancer. We therefore undertook a systematic gene expression study to identify genes upregulated during the re-growth of caudal fin tissue. By applying a high stringency cut-off value of 4-fold change, we identified 54 annotated genes significantly overexpressed in regenerating blastema. Further bioinformatics data mining studies showed that 22 out of the 54 regeneration genes where overexpressed in melanoma compared to normal skin or other cancers. Whereas the role of TNC (tenascin C) and FN1 (fibronectin 1) in melanoma development is well documented, implication of MARCKS, RCN3, BAMBI, PEA3/ETV4 and the FK506 family members FKBP7, FKBP10 and FKBP11 in melanoma progression is unclear. Corresponding proteins were detected in melanoma tissue but not in normal skin. High expression of FKBP7, DPYSL5 and MDK was significantly associated with poor survival. We discuss a potential role of these novel melanoma genes, which have promising potential as new therapeutic targets or diagnostic markers. PMID:27689402

  15. The late positive potential as a marker of motivated attention to underweight bodies in girls with anorexia nervosa.

    PubMed

    Horndasch, Stefanie; Heinrich, Hartmut; Kratz, Oliver; Moll, Gunther H

    2012-12-01

    In anorexia nervosa (AN), aspects of motivational salience and reward are increasingly discussed. Event related potentials, particularly the late positive potential (LPP), have been investigated as a marker for motivational salience of stimuli, for example in addictive disorders. The aim of this study was to assess the LPP as a possible indicator of motivated attention towards disease-specific pictures of underweight female bodies in adolescents with AN in comparison to typically developing (TD) adolescent girls. 13 girls with AN and 18 TD adolescent girls (aged 12 to 18 years) viewed pictures of underweight, normal-weight and overweight women while EEG activity was recorded. An earlier (450-680 ms after stimulus onset) as well as a later time window (850-1250 ms after stimulus onset) of the LPP were examined for the different picture categories. Participants were also asked to rate subjective emotions (fear, disgust, happiness) elicited by the pictures. Subjective ratings showed no differential experience of emotions for the two groups. For AN patients, highest LPP amplitudes were found for underweight women in the earlier as well as in the later time window. In TD girls, highest amplitudes for pictures of overweight women were observed in the earlier time window. A differential LPP pattern for girls with AN and TD girls when viewing pictures of women's bodies of different weight categories was obtained. Highest amplitudes in AN patients for pictures of underweight women may reflect motivational significance of strongly underweight body shapes. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Moisture sorption as a potential condition marker for historic silks: noninvasive determination by near-infrared spectroscopy.

    PubMed

    Zhang, Xiaomei; Wyeth, Paul

    2007-02-01

    Given their ephemeral nature, the preservation of historic silks can be problematic. Rapid, on-site condition monitoring would offer significant benefits to conservators and museum curators concerned with continued access to collections. In this paper, near-infrared spectroscopy (NIR) is investigated as a noninvasive approach to the characterization of silk fabrics and particularly for determining the moisture content of silks as a potential age-related marker. Bands within the NIR spectrum of silk are assigned to contributions from water and the silk fibroin polymer. The water bands may be deconvolved to show separate contributions from bound and structural water. When silk is exposed to deuterium oxide, the water OH NIR bands are rapidly lost. The accompanying changes in the amide-related NIR absorptions reflect differential accessibility of regions within the semi-crystalline fibroin aggregate. NIR spectra were recorded while silk was maintained at a range of relative humidity; complementary gravimetry provided absolute reference data for moisture sorption. A single spectral parameter, the intensity of the water combination band, is sufficient to indicate the relative moisture content of silk and allows distinction of unaged and heat, light, and humidity aged silks. The results confirm that NIR has significant potential for on-site studies at collections in support of the preservation and access of our silk heritage.

  17. Evaluation of a 3A-truncated foot-and-mouth disease virus in pigs for its potential as a marker vaccine.

    PubMed

    Li, Pinghua; Lu, Zengjun; Bai, Xingwen; Li, Dong; Sun, Pu; Bao, Huifang; Fu, Yuanfang; Cao, Yimei; Chen, Yingli; Xie, Baoxia; Yin, Hong; Liu, Zaixin

    2014-05-01

    Foot-and-mouth disease (FMD) is a highly contagious and economically devastating disease of cloven-hoofed animals in the world. The disease can be effectively controlled by vaccination of susceptible animals with the conventional inactivated vaccine. However, one major concern of the inactivated FMD virus (FMDV) vaccine is that it does not allow serological discrimination between infected and vaccinated animals, and therefore interferes with serologic surveillance and the epidemiology of disease. A marker vaccine has proven to be of great value in disease eradication and control programs. In this study, we constructed a marker FMDV containing a deletion of residues 93 to 143 in the nonstructural protein 3A using a recently developed FMDV infectious cDNA clone. The marker virus, r-HN/3A93-143, had similar growth kinetics as the wild type virus in culture cell and caused a symptomatic infection in pigs. Pigs immunized with chemically inactivated marker vaccine were fully protected from the wild type virus challenge, and the potency of this marker vaccine was 10 PD50 (50% pig protective dose) per dose, indicating it could be an efficacious vaccine against FMDV. In addition, we developed a blocking ELISA targeted to the deleted epitope that could clearly differentiate animals infected with the marker virus from those infected with the wild type virus. These results indicate that a marker FMDV vaccine can be potentially developed by deleting an immunodominant epitope in NSP 3A.

  18. The Endogenous Exposome

    PubMed Central

    Nakamura, Jun; Mutlu, Esra; Sharma, Vyom; Collins, Leonard; Bodnar, Wanda; Yu, Rui; Lai, Yongquan; Moeller, Benjamin; Lu, Kun; Swenberg, James

    2014-01-01

    The concept of the Exposome, is a compilation of diseases and one’s lifetime exposure to chemicals, whether the exposure comes from environmental, dietary, or occupational exposures; or endogenous chemicals that are formed from normal metabolism, inflammation, oxidative stress, lipid peroxidation, infections, and other natural metabolic processes such as alteration of the gut microbiome. In this review, we have focused on the Endogenous Exposome, the DNA damage that arises from the production of endogenous electrophilic molecules in our cells. It provides quantitative data on endogenous DNA damage and its relationship to mutagenesis, with emphasis on when exogenous chemical exposures that produce identical DNA adducts to those arising from normal metabolism cause significant increases in total identical DNA adducts. We have utilized stable isotope labeled chemical exposures of animals and cells, so that accurate relationships between endogenous and exogenous exposures can be determined. Advances in mass spectrometry have vastly increased both the sensitivity and accuracy of such studies. Furthermore, we have clear evidence of which sources of exposure drive low dose biology that results in mutations and disease. These data provide much needed information to impact quantitative risk assessments, in the hope of moving towards the use of science, rather than default assumptions. PMID:24767943

  19. Microsatellite markers for the endangered Roanoke logperch, Percina rex (Percidae) and their potential utility for other darter species

    USGS Publications Warehouse

    Dutton, D.J.; Roberts, J.H.; Angermeier, P.L.; Hallerman, E.M.

    2008-01-01

    The Roanoke logperch (Percina rex Jordan and Evermann), an endangered fish, occurs in only six watersheds in the Roanoke and Chowan river drainages of Virginia, USA. The species' population genetic structure is poorly known. We developed 16 microsatellite markers that were reliably scorable and polymorphic P. rex. Markers were also screened in seven other darter species of the genus Percina. Most markers exhibited successful amplification and polymorphism in several species. These markers may therefore prove useful for population genetic studies in other darters, a diverse but highly imperiled group. ?? 2008 The Authors.

  20. Integrative miRNA and mRNA analysis in penile carcinomas reveals markers and pathways with potential clinical impact.

    PubMed

    Kuasne, Hellen; Barros-Filho, Mateus C; Busso-Lopes, Ariane; Marchi, Fábio A; Pinheiro, Maisa; Muñoz, Juan J M; Scapulatempo-Neto, Cristovam; Faria, Eliney F; Guimarães, Gustavo C; Lopes, Ademar; Trindade-Filho, José C S; Domingues, Maria Aparecida C; Drigo, Sandra A; Rogatto, Silvia R

    2017-02-28

    Penile carcinoma (PeCa) is an important public health issue in poor and developing countries, and has only recently been explored in terms of genetic and epigenetic studies. Integrative data analysis is a powerful method for the identification of molecular drivers involved in cancer development and progression. miRNA and mRNA expression profiles followed by integrative analysis were investigated in 23 PeCa and 12 non-neoplastic penile tissues (NPT). Expression levels of eight miRNAs and 10 mRNAs were evaluated in the same set of samples used for microarray and in a validation set of cases (PeCa = 36; NPT = 27). Eighty-one miRNAs and 2,697 mRNAs were identified as differentially expressed in PeCa. Integrative data analysis revealed 255 mRNAs potentially regulated by 68 miRNAs. Using RT-qPCR, eight miRNAs and nine transcripts were confirmed as altered in PeCa. We identified that MMP1, MMP12 and PPARG and hsa-miR-31-5p, hsa-miR-224-5p, and hsa-miR-223-3p were able to distinguish tumors from NPT with high sensitivity and specificity. Higher MMP1 expression was detected as a better predictor of lymph node metastasis than the clinical-pathological data. In addition, PPARG and EGFR were highlighted as potential pathways for targeted therapy in PeCa. The analysis based on HPV positivity (7 of 23 cases) revealed five miRNA and 13 mRNA differentially expressed. Although in a limited number of cases, HPV positive PeCa presented less aggressive phenotype in comparison with negative cases. Overall, an integrative analysis using mRNA and miRNA profiles revealed markers related with tumor development and progression. Furthermore, MMP1 expression level was a predictive marker for lymph node metastasis in patients with PeCa.

  1. Assessment of Potential Cross-Reactivity of Human Endogenous Matrix Metalloproteinases with Collagenase Clostridium histolyticum Antibodies in Human Sera Obtained from Patients with Dupuytren's Contracture

    PubMed Central

    Edkins, Thomas J.; Koller-Eichhorn, Roland; Alhadeff, Jack A.; Mayer, Ulrich; Faust, Heinrich

    2012-01-01

    Collagenase Clostridium histolyticum (CCH) contains a fixed ratio of class I (AUX-I) and class II (AUX-II) collagenases and is used as treatment for Dupuytren's contracture. These two Zn-dependent enzymes, produced by the Gram-positive bacterium Clostridium histolyticum, are related functionally to matrix metalloproteinases (MMPs) which, among other functions, degrade the extracellular matrix. Since AUX-I and AUX-II exhibit sequence similarities to human MMPs, we assessed MMP-1 (interstitial collagenase), MMP-2 (gelatinase A), MMP-3 (stromelysin 1), MMP-8 (collagenase 2), and MMP-13 (collagenase 3) for cross-reactivity with anti-AUX-I and anti-AUX-II antibodies in patient serum. Serum samples from 71 subjects enrolled in a long-term clinical study (58 males and 13 females; 63 ± 10 years old [mean ± standard error]) were evaluated for cross-reactivity with the five MMPs using the two validated enzyme-linked immunosorbent assays (ELISAs). Inhibition cutoff points for anti-AUX-I and anti-AUX-II antibodies were based on assay inhibition obtained with a nonspecific protein, bovine gamma globulin, which was tested for each clinical sample. No MMP cross-reactivity was found for any of the 71 clinical antibody-positive sera evaluated. Sequence identity assessments indicated minimal, nonmeaningful alignments of the MMPs and AUX-I/AUX-II. Furthermore, clinical adverse event assessments indicated no safety signals related to MMP inhibition. The bioanalytical results, sequence identity, and clinical assessments consistently did not demonstrate cross-reactivity between CCH antidrug antibodies and endogenous human matrix metalloproteinases. The results presented here suggest that treatment of Dupuytren's contracture patients with CCH does not lead to any clinical adverse events associated with MMP inhibition. PMID:22357647

  2. Health and endogenous growth.

    PubMed

    van Zon, A; Muysken, J

    2001-03-01

    The focus of endogenous growth theory on human capital formation and the physical embodiment of knowledge in people, suggests the integration of the growth supporting character of health production and the growth generating services of human capital accumulation in an endogenous growth framework. We show that a slow down in growth may be explained by a preference for health that is positively influenced by a growing income per head, or by an ageing population. Growth may virtually disappear for countries with high rates of decay of health, low productivity of the health-sector, or high rates of discount.

  3. Microsatellite Markers of Willow Species and Characterization of 11 Polymorphic Microsatellites for Salix eriocephala (Salicaceae), a Potential Native Species for Biomass Production in Canada.

    PubMed

    Lauron-Moreau, Aurélien; Pitre, Frédéric E; Brouillet, Luc; Labrecque, Michel

    2013-03-27

    Biomass produced from dedicated plantations constitutes a source of renewable energy and is expected to play an important role in several countries in the coming decades. The cultivation of woody crops such as willows therefore raises several environmental issues. In North America, several native willows are potentially interesting for biomass producers. Willow trees are diverse but few species used for environmental applications have been the object of molecular genetic studies. Based on the sequenced poplar genome, 24 microsatellite markers were assayed on five native North American willow species: Salix amygdaloides, S. discolor, S. eriocephala, S. interior and S. nigra. Polymorphic microsatellite markers were used to characterize the allele data on the shrub Salix eriocephala, a North American species with economic potential. Eleven markers amplified and confirmed the potential of this species. Analysis of samples from six populations in eastern Canada showed that all markers were variable as well as polymorphic in at least one population. The number of alleles per locus ranged from 1 to 9 (mean 2.95) and showed that these microsatellite markers can be used to assess genetic diversity of North American willow species.

  4. The chloroplast psbK-psbI intergenic region, a potential genetic marker for broad sectional relationships in Anthurium

    USDA-ARS?s Scientific Manuscript database

    Nuclear and chloroplast genetic markers have been extensively used for plant identification and molecular taxonomy studies. The efficacy of genetic markers to be used as DNA barcodes is under constant evaluation and improvement, with identification of new barcodes that provide greater resolution an...

  5. Soluble Endoglin (CD105) Serum Level as a Potential Marker in the Management of Head and Neck Paragangliomas.

    PubMed

    Litwiniuk, Małgorzata; Niemczyk, Kazimierz; Niderla-Bielińska, Justyna; Łukawska-Popieluch, Izabela; Grzela, Tomasz

    2017-10-01

    To assess the expression of endoglin in head and neck paragangliomas and the soluble endoglin level in serum of paraganglioma patients. Seven tumor samples of patients operated for cervical paraganglioma were assessed, as well as serum samples collected preoperatively, on days 4 and 28 postoperation. Serum level of endoglin in healthy controls was also determined. Tumor samples were subjected to immunofluorescent staining and examined with confocal microscope. The level of soluble endoglin in serum samples was examined using the immunoenzymatic assay (ELISA). Endoglin was highly expressed in all tumor samples. The level of soluble endoglin was significantly higher in paraganglioma patients compared to healthy controls and correlated with the tumor size. The serum level of s-endoglin was reduced after surgical excision of the tumor and remained stable after 4 weeks in all patients with complete resection of the tumor. Endoglin is an important factor in the pathophysiology of head and neck paragangliomas and may be a potential diagnostic and prognostic marker in these types of tumors.

  6. The mitochondrial genome of Euphausia superba (Prydz Bay) (Crustacea: Malacostraca: Euphausiacea) reveals a novel gene arrangement and potential molecular markers.

    PubMed

    Shen, Xin; Wang, Haiqing; Ren, Jianfeng; Tian, Mei; Wang, Minxiao

    2010-02-01

    Euphausiid krill are dominant organisms in the zooplankton population and play a central role in marine ecosystems. In this paper, we described the gene organization, gene rearrangement and codon usage in the mitochondrial genome of Euphausia superba Dana 1852 (sampling from Prydz Bay, PB). The mitochondrial genome of E. superba is more than 15,498 bp in length (partial non-coding region was not determined). Translocation of four tRNAs (trnL ( 1 ), trnL ( 2 ), trnW and trnI) and duplication of one tRNA (trnN) were founded in the mitochondrial genome of E. superba when comparing its genome with the pancrustacean ground pattern. To investigate the phylogenetic relationship within Malacostraca, phylogenetic trees based on currently available malacostracan mitochondrial genomes were built with the maximum likelihood and the Bayesian models. All analyses based on nucleotide and amino acid data strongly support the monophyly of Stomatopoda, Penaeidae, Caridea, and Brachyura, which is consistent with previous research. However, the taxonomic position of Euphausiacea within Malacostraca is unstable. From comparing the mitochondrial genome between E. superba (PB) and E. superba (sampling from Weddell Sea, WS), we found that nad2 gene contains maximal variation with 61 segregating sites, following by nad5 gene which has 12 segregating sites. Thus, nad2 and nad5 genes may be used as potential molecular markers to study the inherit diversity among different E. superba groups, which would be helpful to the exploitation and management of E. superba resources.

  7. Mining-related geochemical anomalies from 3500 to 2000 BP as potential stratigraphic markers for the base of the Anthropocene

    NASA Astrophysics Data System (ADS)

    Wagreich, Michael; Draganits, Erich

    2017-04-01

    Besides major issues and challenges in defining the Anthropocene as a formal chronostratigraphic unit of the Geological time scale, the questions of how and when to define the base of the Anthropocene are one of the major challenges. Lower stratigraphic boundaries of an (early) Anthropocene are strongly debated because of the diachronic character of anthropogenic signals from the Holocene to the Anthropocene. A first significant, partly synchronous and non-local signal for anthropogenic contamination provides the record of mining/smelting-related trace metal pollution in the northern hemisphere at 3500 - 2800 BP with a peak roughly at around 3000 BP, and the subsequent Roman lead peak at around 2000 BP. These events, as defined by lead enrichment and changes in lead isotope ratios, accompanied by other trace metal enrichments, are found in several types of geological archives, i.e. Arctic ice cores, European peat bogs, speleothems, fluvial, lake and marine records. Potential correlations and secondary markers may be present using tephrochronology, climate events, and magnetostratigraphy. Such a definition of the base of a formally defined (early) Anthropocene allows the use of a GSSP (Global Stratotype Section and Point) concept by using a point in a physical archive, and allows for a much larger quantity of anthropogenic strata as evidence for an Anthropocene chronostratigraphic unit than a base definition in the mid-20th century.

  8. Functional definition of the N450 event-related brain potential marker of conflict processing: a numerical stroop study.

    PubMed

    Szűcs, Dénes; Soltész, Fruzsina

    2012-03-27

    Several conflict processing studies aimed to dissociate neuroimaging phenomena related to stimulus and response conflict processing. However, previous studies typically did not include a paradigm-independent measure of either stimulus or response conflict. Here we have combined electro-myography (EMG) with event-related brain potentials (ERPs) in order to determine whether a particularly robust marker of conflict processing, the N450 ERP effect usually related to the activity of the Anterior Cingulate Cortex (ACC), is related to stimulus- or to response-conflict processing. EMG provided paradigm-independent measure of response conflict. In a numerical Stroop paradigm participants compared pairs of digits and pressed a button on the side where they saw the larger digit. 50% of digit-pairs were preceded by an effective cue which provided accurate information about the required response. 50% of trials were preceded by a neutral cue which did not communicate the side of response. EMG showed that response conflict was significantly larger in neutrally than in effectively cued trials. The N450 was similar when response conflict was high and when it was low. We conclude that the N450 is related to stimulus or abstract, rather than to response conflict detection/resolution. Findings may enable timing ACC conflict effects.

  9. Functional definition of the N450 event-related brain potential marker of conflict processing: a numerical stroop study

    PubMed Central

    2012-01-01

    Background Several conflict processing studies aimed to dissociate neuroimaging phenomena related to stimulus and response conflict processing. However, previous studies typically did not include a paradigm-independent measure of either stimulus or response conflict. Here we have combined electro-myography (EMG) with event-related brain potentials (ERPs) in order to determine whether a particularly robust marker of conflict processing, the N450 ERP effect usually related to the activity of the Anterior Cingulate Cortex (ACC), is related to stimulus- or to response-conflict processing. EMG provided paradigm-independent measure of response conflict. In a numerical Stroop paradigm participants compared pairs of digits and pressed a button on the side where they saw the larger digit. 50% of digit-pairs were preceded by an effective cue which provided accurate information about the required response. 50% of trials were preceded by a neutral cue which did not communicate the side of response. Results EMG showed that response conflict was significantly larger in neutrally than in effectively cued trials. The N450 was similar when response conflict was high and when it was low. Conclusions We conclude that the N450 is related to stimulus or abstract, rather than to response conflict detection/resolution. Findings may enable timing ACC conflict effects. PMID:22452924

  10. Piwil2 expressed in various stages of cervical neoplasia is a potential complementary marker for p16INK4a

    PubMed Central

    He, Gang; Chen, Li; Ye, Yin; Xiao, Yi; Hua, Keding; Jarjoura, David; Nakano, Toru; Barsky, Sanford H; Shen, Rulong; Gao, Jian-Xin

    2010-01-01

    Generally, cancers may undergo the developmental stages of benign proliferation, precancer and invasive cancer. Identification of biomarkers that are expressed throughout the developmental stages will facilitate detection, prevention and therapy of cancer. Piwil2, a member of AGO/PIWI family of proteins, has been suggested to be associated with tumor development. Here we reported that piwil2 can be detected by immunohistochemistry (IHC) in various stages of human cervical squamous cell carcinomas and adenocarcinomas. Interestingly, piwil2 was also detected in some metaplastic epithelial cells as well as histologically “normal” appearing tissues adjacent to malignant lesions. While all the premalignant and malignant lesions expressed varying levels of piwil2, p16INK4a (p16), a surrogate indicator of high-risk human papillomavirus (HR-HPV) infection, was detected in only 84.62% of the specimens. In Papanicolaou (Pap) test, piwil2 was also detected in atypical glandular cells (AGC), low-grade (LSIL) and high-grade squamous intraepithelial lesions (HSIL), whereas p16 was not always concomitantly detected in the same specimens. The results suggest that piwil2 might play important roles throughout the process of cervical cancer development and have the potential to be used as a complementary marker for p16INK4a. It is worth further study to improve the sensitivity and specificity of current screening methods for cervical cancers. PMID:20407605

  11. JMJD2B as a potential diagnostic immunohistochemical marker for hepatocellular carcinoma: a tissue microarray-based study.

    PubMed

    Lu, Jeng-Wei; Ho, Yi-Jung; Lin, Liang-In; Huang, Yen-Chi; Yeh, Kun-Tu; Lin, Yu-Hsiang; Lin, Yueh-Min; Tzeng, Tsai-Yu

    2015-01-01

    The purpose of this study was to examine JMJD2B expression in human hepatocellular carcinoma (HCC) and elucidate relationships between various expression patterns and clinicopathological parameters of HCC patients. Immunohistochemical techniques were performed to detect JMJD2B expression in a tissue microarray from patients with breast, cerebrum, colon, esophagus, kidney, liver, lung, prostate, stomach, and uterus cancers. We performed immunohistochemical staining of a multiple tissue array to examine the expression profile of JMJD2B. Our results demonstrate that JMJD2B protein levels were upregulated in malignant human tumors, including breast, colon, liver, and lung. Immunohistochemistry staining examination of liver tumor tissue microarray revealed that the expression of JMJD2B is significant according to the histological grade and TNM stage of liver tumor. Moreover, JMJD2B was also correlated with Ki-67 expression in HCC samples. These results reveal that JMJD2B is dramatically upregulated in HCC, making it a potential diagnostic marker for the further development of HCC treatment therapies. Copyright © 2014 Elsevier GmbH. All rights reserved.

  12. MFAP5 and TNNC1: Potential markers for predicting occult cervical lymphatic metastasis and prognosis in early stage tongue cancer.

    PubMed

    Yang, Xi; Wu, Kailiu; Li, Siyi; Hu, Longwei; Han, Jing; Zhu, Dongwang; Tian, Xuerui; Liu, Wei; Tian, Zhen; Zhong, Laiping; Yan, Ming; Zhang, Chenping; Zhang, Zhiyuan

    2017-01-10

    The purpose of this study is to identify candidate genes that could predict prognosis of early-stage tongue squamous cell carcinoma (TSCC) and its occult cervical lymphatic metastasis by large-scale gene expression profiling. Tumor tissue and matched normal mucosa samples were collected from patients with TSCC and analyzed with Affymetrix HTA2.0 high-density oligonucleotide array. Differentially expressed genes in TSCC with cervical lymph node metastasis (CLNM) were further analyzed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes for their functions and related pathways. A total of 107 differentially expressed genes (p < 0.05) were identified by microarray in TSCC samples with CLNM (n = 6) compared to those without CLNM (n = 6). Genes involved in the cell-matrix adherens junction and migration function including MFAP5, TNNC1, MGP, FBFBP1 and FBXO32 were selected and validated by RT-PCR in TSCC samples (n = 32). Of the five genes, MFAP5 and TNCC1 expressions were further validated by immohistochemistry (n = 61). The significant positive correlation between MFAP5 and TNNC1 expression (p<0.001) was observed. Notably, over-expression of MFAP5 and TNNC1 were correlated with CLNM, metastasis relapse-free survival and overall survival. Our findings indicated that MFAP5 and TNNC1 may be potential markers for predicting occult cervical lymphatic metastasis and prognosis of oral tongue carcinoma.

  13. Androgen receptor is a potential novel prognostic marker and oncogenic target in osteosarcoma with dependence on CDK11

    PubMed Central

    Liao, Yunfei; Sassi, Slim; Halvorsen, Stefan; Feng, Yong; Shen, Jacson; Gao, Yan; Cote, Gregory; Choy, Edwin; Harmon, David; Mankin, Henry; Hornicek, Francis; Duan, Zhenfeng

    2017-01-01

    Osteosarcoma is the most common bone cancer in children and adolescents. Previously, we have found that cyclin-dependent kinase 11 (CDK11) signaling was essential for osteosarcoma cell growth and survival. Subsequently, CDK11 siRNA gene targeting, expression profiling, and network reconstruction of differentially expressed genes were performed between CDK11 knock down and wild type osteosarcoma cells. Reconstructed network of the differentially expressed genes pointed to the AR as key to CDK11 signaling in osteosarcoma. CDK11 increased transcriptional activation of AR gene in osteosarcoma cell lines. AR protein was highly expressed in various osteosarcoma cell lines and patient tumor tissues. Tissue microarray analysis showed that the disease-free survival rate for patients with high-expression of AR was significantly shorter than for patients with low-expression of AR. In addition, AR gene expression knockdown via siRNA greatly inhibited cell growth and viability. Similar results were found in osteosarcoma cells treated with AR inhibitor. These findings suggest that CDK11 is involved in the regulation of AR pathway and AR can be a potential novel prognostic marker and therapeutic target for osteosarcoma treatment. PMID:28262798

  14. Investigation and Sensory Characterization of 1,4-Cineole: A Potential Aromatic Marker of Australian Cabernet Sauvignon Wine.

    PubMed

    Antalick, Guillaume; Tempère, Sophie; Šuklje, Katja; Blackman, John W; Deloire, Alain; de Revel, Gilles; Schmidtke, Leigh M

    2015-10-21

    This work reports the quantitation and sensory characterization of 1,4-cineole in red wine for the first time. A headspace-solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) method was developed to quantitate 1,4-cineole and 1,8-cineole in 104 commercial Australian red wines. 1,4-Cineole was detected in all of the wines analyzed, with concentrations ranging from 0.023 to 1.6 μg/L. An important varietal effect was observed, with concentrations of 1,4-cineole in Cabernet Sauvignon wines (mean of 0.6 ± 0.3 μg/L) significantly higher than in Shiraz (0.07 ± 0.04 μg/L) and Pinot Noir (0.2 ± 0.2 μg/L) wines. Regional variations of both cineole isomer concentrations have been measured between wines originating from different Australian regions. Sensory studies demonstrated that the addition of 0.54 μg/L 1,4-cineole in a Cabernet Sauvignon wine, to produce a final concentration of 0.63 μg/L, was perceived significantly by a sensory panel (p < 0.05). Descriptive analyses revealed that 1,4-cineole and 1,8-cineole may contribute to the hay, dried herbs, and blackcurrant aromas reported in Australian Cabernet Sauvignon wines and may be potential markers of regional typicality of these wines.

  15. The serum concentration of magnesium as a potential state marker in patients with diagnosis of bipolar disorder.

    PubMed

    Siwek, Marcin; Styczeń, Krzysztof; Sowa-Kućma, Magdalena; Dudek, Dominika; Reczyński, Witold; Szewczyk, Bernadeta; Misztak, Paulina; Opoka, Włodzimierz; Topór-Mądry, Roman; Nowak, Gabriel

    2015-01-01

    Few scientific reports indicate changes in the concentration of magnesium in the blood of patients with bipolar disorder (BD). So far very little studies concerning these issues have been conducted. Therefore, the aim of this study was to evaluate the serum magnesium level in patients with bipolar disorder (in different phases of the disease) in comparison to healthy volunteers. The study included 129 patients (58 subjects in depressive episode, 23 in manic episode and 48 patients in remission) with the diagnosis of bipolar disorder type I or II. The control group consisted of 50 healthy people. Magnesium concentration was measured using flame atomic absorption spectrometry (FAAS). Patients with a current depressive or manic/hypomanic episode had statistically significantly elevated serum magnesium levels compared to healthy volunteers. Moreover, a positive correlation between the duration of the manic/hypomanic episode and the relapse frequency in the last year was observed. The concentration of magnesium in patients in remission was unchanged in relation to the control group. Presented findings suggest a role of serum magnesium level as a potential state marker, reflecting the pathophysiological changes associated with acute episodes of bipolar disorder.

  16. Induction of hairy roots and characterization of peroxidase expression as a potential root growth marker in sesame.

    PubMed

    Chun, J-A; Lee, J-W; Yi, Y-B; Park, G-Y; Chung, C-H

    2009-01-01

    Using hypocotyl and cotyledon of sesame seedlings, hairy root cultures were established and cDNA coding for a peroxidase was cloned from the roots. The frequency of sesame hairy root formation was higher in hypocotyl (33.4%) than cotyledon (9.3%). Applicable levels of kanamycin and hygromycin as a selectable marker were 100 microg/mL and 30 microg/mL, respectively. The peroxidase cDNA showed relatively high sequence identity with and similarity to plant class III peroxidase family. The cDNA encoded polypeptide was identified with the presence of three sequence features: 1) the putative 4 disulfide bridges, 2) an ER-targeted signal sequence in the N-terminus, and 3) two triplets, NXS for glycosylation. A real-time RT-PCR exhibited an abrupt increase in the peroxidase transcription activity after 4-week cultures of the sesame hairy roots and its highest level in 6-week cultured hairy roots. In contrast, the growth pattern of sesame hairy roots showed a typical sigmoidal curve. The active hairy root growth began after 2-week culture and their stationary growth phase occurred after 5-week culture. These results suggested that the peroxidase expression patterns at its transcription level could be used a potential indicator signaling a message that there will be no longer active growth in hairy root cultures. The sesame peroxidase gene was differentially expressed in different tissues.

  17. Identification of Potential Transcriptomic Markers in Developing Ankylosing Spondylitis: A Meta-Analysis of Gene Expression Profiles

    PubMed Central

    Fang, Fang; Pan, Jian; Xu, Lixiao; Li, Gang; Wang, Jian

    2015-01-01

    The goal of this study was to identify potential transcriptomic markers in developing ankylosing spondylitis by a meta-analysis of multiple public microarray datasets. Using the INMEX (integrative meta-analysis of expression data) program, we performed the meta-analysis to identify consistently differentially expressed (DE) genes in ankylosing spondylitis and further performed functional interpretation (gene ontology analysis and pathway analysis) of the DE genes identified in the meta-analysis. Three microarray datasets (26 cases and 29 controls in total) were collected for meta-analysis. 905 consistently DE genes were identified in ankylosing spondylitis, among which 482 genes were upregulated and 423 genes were downregulated. The upregulated gene with the smallest combined rank product (RP) was GNG11 (combined RP = 299.64). The downregulated gene with the smallest combined RP was S100P (combined RP = 335.94). In the gene ontology (GO) analysis, the most significantly enriched GO term was “immune system process” (P = 3.46 × 10−26). The most significant pathway identified in the pathway analysis was antigen processing and presentation (P = 8.40 × 10−5). The consistently DE genes in ankylosing spondylitis and biological pathways associated with those DE genes identified provide valuable information for studying the pathophysiology of ankylosing spondylitis. PMID:25688367

  18. Investigation of in vivo potential of scorpion venom against skin tumorigenesis in mice via targeting markers associated with cancer development

    PubMed Central

    Al Asmari, Abdulrahman K; Khan, Abdul Quaiyoom

    2016-01-01

    Cancer is the leading cause of morbidity and mortality all over the world in spite of the advances made in its management. In this study, we investigated the in vivo anti-tumorigenic potential of the venom obtained from a medically important scorpion species Leiurus quinquestriatus on chemically induced skin cancer in mice. Animals were divided into five groups, with 13 animals in each group. All the treatments were given topically on the shaved dorsal surface of the skin. Animals in Group 1 received vehicle only (0.2 mL acetone). Moreover, 7,12-dimethylbenz[a]anthracene (DMBA, 400 nmol per mouse) was applied to all the animals in the remaining four groups. After 1 week, different concentrations of venom (17.5 μg, 35 μg, and 52.5 μg per animal) were applied to each animal in the Groups III–V. Thirty minutes after the application of venom, croton oil was applied on the same position where venom was administered to the animals of Groups III–V. Animals in Group II were treated as the positive control (without venom) and received croton oil as in Groups III–V. The findings of this study revealed that venom extract of L. quinquestriatus inhibits DMBA + croton oil-induced mouse skin tumor incidence and tumor multiplicity. Venom treatment also decreased the expression of proinflammatory cytokines. Immunohistochemistry results showed a downregulation of the expression of molecular markers such as Ki-67, nuclear factor kappa-B, cyclooxygenase-2, B-cell lymphoma-2, and vascular endothelial growth factor, in venom-treated animals. Our findings suggest that the venom of L. quinquestriatus possesses in vivo anticancer potential and may be used in the development of anticancer molecules. PMID:27799739

  19. Quantum dots based potential-resolution dual-targets electrochemiluminescent immunosensor for subtype of tumor marker and its serological evaluation.

    PubMed

    Liu, Xuan; Jiang, Hui; Fang, Yuan; Zhao, Wei; Wang, Nianyue; Zang, Guizhen

    2015-09-15

    The identification of subtypes of known tumor markers is of great importance for clinical diagnosis but still a great challenge in novel detection methodologies with simple operation and acceptable sensitivity. This work for the first time reported a quantum dots (QDs) based potential-resolved electrochemiluminescent (ECL) immunosensor to realize simultaneous detection of dual targets. Because of different surface microstructures, dimercaptosuccinic acid stabilized CdTe (DMSA-CdTe) QDs and TiO2 nanoparticles-glutathione stabilized CdTe (TiO2-GSH-CdTe) QDs composites showed a large difference of ECL peak potential (∼360 mV), which provided an access for potential-resolution detection. The ECL emission on indium tin oxide electrodes showed consistent strength during the cyclic scan, and intensity data were collected at -0.89 V and -1.25 V (vs Ag/AgCl) for DMSA-CdTe QDs and TiO2-GSH-CdTe QDs composites, respectively. The interface modification procedures of immunosensor construction were characterized by atomic force microscopy. The portion of Lens culinaris lectin affiliated isoform of alpha fetoprotein (AFP), AFP-L3%, in total AFP, is recently a novel criteria showing even higher sensitivity and specificity than AFP at the early stage of cancer. Combined with the enzyme cyclic amplification strategy, linear ranges for AFP-L3 and AFP dual-targets detection were 3.24 pg mL(-1)-32.4 ng mL(-1) and 1.0 pg mL(-1)-20 ng mL(-1), with limits of detection of 3.24 pg mL(-1) and 1.0 pg mL(-1), respectively. Compared with clinical detection data, the calculated portion of AFP-L3% by as-prepared immunosensor showed acceptable accuracy. These results open a new avenue for facile and rapid multiple-components detection based on the nano-ECL technique and provide a new clinical diagnosis platform for HCC.

  20. A novel strategy to rapidly explore potential chemical markers for the discrimination between raw and processed Radix Rehmanniae by UHPLC-TOFMS with multivariate statistical analysis.

    PubMed

    Li, Song-Lin; Song, Jing-Zheng; Qiao, Chun-Feng; Zhou, Yan; Qian, Keduo; Lee, Kuo-Hsiung; Xu, Hong-Xi

    2010-03-11

    In traditional Chinese medicine, raw and processed herbs are used to treat different diseases. Suitable chemical markers are crucial for the discrimination between raw and processed herbs. In this study, a novel strategy using UHPLC-TOFMS coupled with multivariate statistical analysis to rapidly explore potential chemical markers was proposed and validated. Using Radix Rehmanniae as a model herb, batches of raw and processed samples were determined by UHPLC-TOFMS. The datasets of t(R)-m/z pair, ion intensity and sample code were subjected to principal component analysis (PCA) and orthogonal partial least squared discriminant analysis (OPLS-DA) to holistically compare the difference between raw and processed samples. Once a clear cluster was found, extended statistics was performed to generate S-plot, in which the variables (t(R)-m/z pair) contributing most to the difference were clearly indicated as points at the two ends of "S", and the components that correlate to these ions should be the processing-induced transformed components. These transformed components could be regarded as the potential chemical markers that can be used to distinguish between raw and processed herbs. The identity of the potential markers can be identified by comparing the mass/UV spectra and retention time with that of reference compounds and/or tentatively assigned by matching empirical molecular formula with that of the known compounds published. Using this proposed strategy, leonuride or its isomer and 5-(alpha-d-glucopyranosyl-(1-6)-alpha-d-glucopyranosyloxymethyl)-2-furancarboxaldehyde were rapidly explored as the most characteristic markers of raw and processed Radix Rehmanniae, respectively. This newly proposed strategy can not only be used to explore chemical markers but also to investigate the chemical transforming mechanisms underlying traditional herb processing. Copyright 2009 Elsevier B.V. All rights reserved.

  1. Resolvin D2 is a potent endogenous inhibitor for transient receptor potential subtype V1/A1, inflammatory pain, and spinal cord synaptic plasticity in mice: distinct roles of resolvin D1, D2, and E1.

    PubMed

    Park, Chul-Kyu; Xu, Zhen-Zhong; Liu, Tong; Lü, Ning; Serhan, Charles N; Ji, Ru-Rong

    2011-12-14

    Inflammatory pain such as arthritic pain is typically treated with opioids and cyclo-oxygenase-2 inhibitors with well known side effects. Transient receptor potential subtype vanilloid 1 (TRPV1) and TRP ankyryn 1 (TRPA1) contribute importantly to the genesis of inflammatory pain via both peripheral mechanisms (peripheral sensitization) and spinal cord mechanisms (central sensitization). Although these TRP channels have been intensively studied, little is known about their endogenous inhibitors. Recent studies have demonstrated that the endogenous lipid mediators resolvins (RvE1 and RvD1), derived from ω-3 unsaturated fatty acids, are potent inhibitors for inflammatory pain, without noticeable side effects. However, the molecular mechanisms underlying resolvins' distinct analgesic actions in mice are unclear. RvD2 is a novel family member of resolvins. Here we report that RvD2 is a remarkably potent inhibitor of TRPV1 (IC(50) = 0.1 nm) and TRPA1 (IC(50) = 2 nm) in primary sensory neurons, whereas RvE1 and RvD1 selectively inhibited TRPV1 (IC(50) = 1 nm) and TRPA1 (IC(50) = 9 nm), respectively. Accordingly, RvD2, RvE1, and RvD1 differentially regulated TRPV1 and TRPA1 agonist-elicited acute pain and spinal cord synaptic plasticity [spontaneous EPSC (sEPSC) frequency increase]. RvD2 also abolished inflammation-induced sEPSC increases (frequency and amplitude), without affecting basal synaptic transmission. Intrathecal administration of RvD2 at very low doses (0.01-1 ng) prevented formalin-induced spontaneous pain. Intrathecal RvD2 also reversed adjuvant-induced inflammatory pain without altering baseline pain and motor function. Finally, intrathecal RvD2 reversed C-fiber stimulation-evoked long-term potentiation in the spinal cord. Our findings suggest distinct roles of resolvins in regulating TRP channels and identify RvD2 as a potent endogenous inhibitor for TRPV1/TRPA1 and inflammatory pain.

  2. A potential novel spontaneous preterm birth gene, AR, identified by linkage and association analysis of X chromosomal markers.

    PubMed

    Karjalainen, Minna K; Huusko, Johanna M; Ulvila, Johanna; Sotkasiira, Jenni; Luukkonen, Aino; Teramo, Kari; Plunkett, Jevon; Anttila, Verneri; Palotie, Aarno; Haataja, Ritva; Muglia, Louis J; Hallman, Mikko

    2012-01-01

    Preterm birth is the major cause of neonatal mortality and morbidity. In many cases, it has severe life-long consequences for the health and neurological development of the newborn child. More than 50% of all preterm births are spontaneous, and currently there is no effective prevention. Several studies suggest that genetic factors play a role in spontaneous preterm birth (SPTB). However, its genetic background is insufficiently characterized. The aim of the present study was to perform a linkage analysis of X chromosomal markers in SPTB in large northern Finnish families with recurrent SPTBs. We found a significant linkage signal (HLOD = 3.72) on chromosome locus Xq13.1 when the studied phenotype was being born preterm. There were no significant linkage signals when the studied phenotype was giving preterm deliveries. Two functional candidate genes, those encoding the androgen receptor (AR) and the interleukin-2 receptor gamma subunit (IL2RG), located near this locus were analyzed as candidates for SPTB in subsequent case-control association analyses. Nine single-nucleotide polymorphisms (SNPs) within these genes and an AR exon-1 CAG repeat, which was previously demonstrated to be functionally significant, were analyzed in mothers with preterm delivery (n = 272) and their offspring (n = 269), and in mothers with exclusively term deliveries (n = 201) and their offspring (n = 199), all originating from northern Finland. A replication study population consisting of individuals born preterm (n = 111) and term (n = 197) from southern Finland was also analyzed. Long AR CAG repeats (≥ 26) were overrepresented and short repeats (≤ 19) underrepresented in individuals born preterm compared to those born at term. Thus, our linkage and association results emphasize the role of the fetal genome in genetic predisposition to SPTB and implicate AR as a potential novel fetal susceptibility gene for SPTB.

  3. A Potential Novel Spontaneous Preterm Birth Gene, AR, Identified by Linkage and Association Analysis of X Chromosomal Markers

    PubMed Central

    Karjalainen, Minna K.; Huusko, Johanna M.; Ulvila, Johanna; Sotkasiira, Jenni; Luukkonen, Aino; Teramo, Kari; Plunkett, Jevon; Anttila, Verneri; Palotie, Aarno; Haataja, Ritva; Muglia, Louis J.; Hallman, Mikko

    2012-01-01

    Preterm birth is the major cause of neonatal mortality and morbidity. In many cases, it has severe life-long consequences for the health and neurological development of the newborn child. More than 50% of all preterm births are spontaneous, and currently there is no effective prevention. Several studies suggest that genetic factors play a role in spontaneous preterm birth (SPTB). However, its genetic background is insufficiently characterized. The aim of the present study was to perform a linkage analysis of X chromosomal markers in SPTB in large northern Finnish families with recurrent SPTBs. We found a significant linkage signal (HLOD  = 3.72) on chromosome locus Xq13.1 when the studied phenotype was being born preterm. There were no significant linkage signals when the studied phenotype was giving preterm deliveries. Two functional candidate genes, those encoding the androgen receptor (AR) and the interleukin-2 receptor gamma subunit (IL2RG), located near this locus were analyzed as candidates for SPTB in subsequent case-control association analyses. Nine single-nucleotide polymorphisms (SNPs) within these genes and an AR exon-1 CAG repeat, which was previously demonstrated to be functionally significant, were analyzed in mothers with preterm delivery (n = 272) and their offspring (n = 269), and in mothers with exclusively term deliveries (n = 201) and their offspring (n = 199), all originating from northern Finland. A replication study population consisting of individuals born preterm (n = 111) and term (n = 197) from southern Finland was also analyzed. Long AR CAG repeats (≥26) were overrepresented and short repeats (≤19) underrepresented in individuals born preterm compared to those born at term. Thus, our linkage and association results emphasize the role of the fetal genome in genetic predisposition to SPTB and implicate AR as a potential novel fetal susceptibility gene for SPTB. PMID:23227263

  4. Urinary leukotriene E4 concentrations as a potential marker of inflammation in dogs with inflammatory bowel disease.

    PubMed

    Im Hof, M; Schnyder, M; Hartnack, S; Stanke-Labesque, F; Luckschander, N; Burgener, I A

    2012-01-01

    Inflammatory bowel disease (IBD) and food-responsive diarrhea (FRD) are chronic enteropathies of dogs (CCE) that currently can only be differentiated by their response to treatment after exclusion of other diseases. In humans, increased urinary concentrations of leukotriene E4 (LTE4) have been associated with active IBD. To evaluate urinary LTE4 concentrations in dogs with IBD, FRD, and healthy controls, and to assess correlation of urinary LTE4 concentrations with the canine IBD activity index (CIBDAI) scores. Eighteen dogs with IBD, 19 dogs with FRD, and 23 healthy control dogs. In this prospective study, urine was collected and CIBDAI scores were calculated in client-owned dogs with IBD and those with FRD. Quantification of LTE4 in urine was performed by liquid chromatography-tandem mass spectrometry and corrected to creatinine. Urinary LTE4 concentrations were highest in dogs with IBD (median 85.2 pg/mg creatinine [10th-90th percentiles 10.9-372.6]) followed by those with FRD (median 31.2 pg/mg creatinine [10th-90th percentiles 6.2-114.5]) and control dogs (median 21.1 pg/mg creatinine [10th-90th percentiles 9.1-86.5]). Urinary LTE4 concentrations were higher in dogs with IBD than in control dogs (P = .011), but no significant difference between IBD and FRD was found. No correlation was found between urinary LTE4 concentrations and CIBDAI. The higher urinary LTE4 concentrations in dogs with IBD suggest that cysteinyl leukotriene pathway activation might be a component of the inflammatory process in canine IBD. Furthermore, urinary LTE4 concentrations are of potential use as a marker of inflammation in dogs with CCE. Copyright © 2012 by the American College of Veterinary Internal Medicine.

  5. Date prints on stranded macroplastics: Exploring the potential of marine litter assemblages as chronological markers in recent coastal deposit

    NASA Astrophysics Data System (ADS)

    Sander, L.

    2016-12-01

    Plastic is a collective term describing a group of synthetic materials developed from the early 1900s onward. The mass production of plastics began in the 1950s and already in the 1970s, the magnitude of plastic pollution has been recognized as an issue of concern for the global marine environment. Today, it is no longer a rare event to encounter plastic fragments and objects in modern coastal deposits. The presence of any form of plastic holds in itself a chronological indication (i.e. the deposit is younger than the invention of plastic). Larger items can be surveyed as discrete objects and allow the retrieval of more precise, though indirect age-information, such as production-date prints (i.e. the deposit is younger than the encountered litter item). The potential of this approach was tested in an investigation into the spatial distribution of stranded macroplastics in recent overwash deposits in SW Denmark. An amount of >110 georeferenced surface samples containing date prints were surveyed in summer 2015. Objects with ages from the late 1970s until 2014 were encountered. The distribution of the litter was clearly non-random in relation to overwash morphology, and based on the collected samples, it was possible to reconstruct indication on both the timing and the extent of extreme events since the 1990s. These observations were cross-compared with a dense time series of satellite images and orthophotos. It is proposed that an improved interpretation of indications from the plastic record may be obtained by broader surveys including additional parameters, such as the exact location, elevation, chemical composition, assemblage, origin, product design, decay, fracturing or the colonization by marine sessile organisms, from all encountered macroplastic objects. If calibrated properly, the plastic assemblages may serve as fast, cheap and reliable chronological markers in recent coastal deposits.

  6. Gross cystic disease fluid protein 15 in stratum corneum is a potential marker of decreased eccrine sweating for atopic dermatitis.

    PubMed

    Kamiya, Koji; Sakabe, Jun-Ichi; Yamaguchi, Hayato; Suzuki, Takahiro; Yatagai, Tsuyoshi; Aoshima, Masahiro; Ito, Taisuke; Tokura, Yoshiki

    2015-01-01

    It is well known that eccrine sweating is attenuated in patients with atopic dermatitis (AD). We have reported by using proteome analysis that gross cystic disease fluid protein 15 (GCDFP15), a substance secreted from eccrine sweat glands, is decreased in tape-stripped stratum corneum (SC) samples from AD patients. The aim of this study was to evaluate GCDFP15 production by eccrine glands with SC samples and to assess sweating in AD. SC samples were obtained from 51 healthy control (HC) and 51 AD individuals. Sweat samples were from 18 HC and 12 AD subjects. GCDFP15 was quantified by ELISA. By immunohistochemistry, the expression of GCDFP15 in eccrine glands was examined in normal and AD skin specimens. To identify GCDFP15-producing cells, double immunofluorescence staining for GCDFP15 and S100 protein was performed in frozen sections. To address the mechanism underlying the decreased eccrine sweating in AD patients, we examined the expression of cholinergic receptor M3 (CHRM3), a receptor for acetylcholine-induced sweating, in eccrine sweat glands. The amounts of GCDFP15 in the SC extracts were significantly lower in AD than HC (P < 0.0001). The sweat samples from AD patients also had lower levels of GCDFP15 concentration (P < 0.05). Immunohistochemistry showed positive GCDFP15 staining in the eccrine gland secretory cells and the ductal and acrosyringial lumen in normal skin, but AD lacked clear staining. Immunofluorescence staining revealed that GCDFP15 was co-expressed with S100 protein, suggesting that the clear cell of eccrine glands produces GCDFP15. Finally, we found that the expression of CHRM3 was depressed in AD, suggesting contribution to the low sweating. The SC of AD patients contains a low amount of GCDFP15 due to both low sweating and low GCDFP15 concentration in the sweat. GCDFP15 in SC is a potential marker for dysregulated sweating in AD.

  7. Evaluation of bovine zona pellucida characteristics in polarized light as a prognostic marker for embryonic developmental potential.

    PubMed

    Koester, M; Mohammadi-Sangcheshmeh, A; Montag, M; Rings, F; Schimming, T; Tesfaye, D; Schellander, K; Hoelker, M

    2011-06-01

    It has previously been demonstrated that zona pellucida imaging of human oocytes using polarized light microscopy is a clinically applicable method for the noninvasive assessment of oocyte quality. This study was designed to investigate whether zona pellucida characteristics of bovine oocytes and zygotes in polarized light may similarly serve as a useful marker for developmental competence in bovine reproductive biotechnologies. Zona birefringence intensity parameters of 2862 oocytes/zygotes were objectively evaluated with an automatic analysis system and correlated with oocyte/zygote quality. In detail, immature oocytes of good quality assessed with brilliant cresyl blue staining showed significantly lower zona birefringence than poor-quality counterparts (P<0.001). After in vitro maturation and classification according to maturational status, the birefringence intensity parameters were significantly different in those oocytes that reached metaphase II compared with arrested stages (P<0.001). Following either parthenogenetic activation or IVF with subsequent in vitro culture in a well-of-the-well system until day 9, superior development as determined by cleavage, blastocyst formation, and hatching ability was associated with lower zona birefringence intensity parameters. When early zygote-stage embryos were selected and assorted in groups based on zona birefringence (high/medium/low), the group of embryos derived from high-birefringence zygotes displayed a significantly compromised developmental potential compared with low-birefringence zygotes. These results clearly show that developmentally competent bovine oocytes/zygotes exhibit lower zona birefringence intensity parameters. Therefore, birefringence imaging of zona pellucida is a suitable technique to predict bovine preimplantation embryo development.

  8. [Provoking endogenous psychoses].

    PubMed

    Trostorff, S V

    1988-05-01

    For six forms of endogenous psychosis, causal agencies were sought to establish endogenous, physical, and mental provocation. Endocrine causes were found most frequently, 17.5%, in mixed bipolar disorders, followed by cycloid psychoses, 8.5%, which in this respect appear to be closer to the mixed bipolar psychoses, than the unipolar forms at 4.4%. Among the physical causes, the difference in affective psychoses is not particularly great. Cycloid psychoses head the list at 9%. Among the mental causes, pure phase psychoses account for the greatest number, 12.7%, by a wide margin. The three unsystematic forms of schizophrenia revealed a slender link with their causes. Clear distinctions among the causes of the six forms were thus demonstrated.

  9. Modeling of the total antioxidant capacity of rooibos (Aspalathus linearis) tea infusions from chromatographic fingerprints and identification of potential antioxidant markers.

    PubMed

    Orzel, Joanna; Daszykowski, Michal; Kazura, Malgorzata; de Beer, Dalene; Joubert, Elizabeth; Schulze, Alexandra E; Beelders, Theresa; de Villiers, André; Malherbe, Christiaan J; Walczak, Beata

    2014-10-31

    Models to predict the total antioxidant capacity (TAC) of rooibos tea infusions from their chromatographic fingerprints and peak table data (content of individual phenolic compounds), obtained using HPLC with diode array detection, were developed in order to identify potential antioxidant markers. Peak table data included the content of 12 compounds, namely phenylpyruvic acid-2-O-glucoside, aspalathin, nothofagin, isoorientin, orientin, ferulic acid, quercetin-3-O-robinobioside, vitexin, hyperoside, rutin, isovitexin and isoquercitrin. The TAC values, measured using the oxygen radical absorbance capacity (ORAC) and DPPH radical scavenging assays, could be predicted from the peak table data or the chromatographic fingerprints (prediction errors 9-12%) using partial least squares (PLS) regression. Prediction models created from samples of only two production years could additionally be used to predict the TAC of samples from another production year (prediction errors<13%) indicating the robustness of the models in a quality control environment. Furthermore, the uninformative variable elimination (UVE)-PLS method was used to identify potential antioxidant markers for rooibos infusions. All individual phenolic compounds that were quantified were selected as informative variables, except vitexin, while UVE-PLS models developed from chromatographic fingerprints indicated additional antioxidant markers, namely (S)-eriodictyol-6-C-glucoside, (R)-eriodictyol-6-C-glucoside, aspalalinin and two unidentified compounds. The potential antioxidant markers should be validated prior to use in quality control of rooibos tea.

  10. Endogenous Pyrogen Physiology

    DTIC Science & Technology

    1980-01-01

    Intracerebroventricular injection of rats: a sensitive directed to the photoreceptor system for phototaxis of the proto- assay method for endogenous...spinal heating and cooling and photobiologists. The remainder of the book is devoted to the eye. intracerebroventricular injections of monoamines and...photobehavior and vision discussed, such as histamine /antihistamines, cough remedies, of invertebrates. h i e nd slep-aids and laxatives. The few citations

  11. Endogeneity in High Dimensions

    PubMed Central

    Fan, Jianqing; Liao, Yuan

    2014-01-01

    Most papers on high-dimensional statistics are based on the assumption that none of the regressors are correlated with the regression error, namely, they are exogenous. Yet, endogeneity can arise incidentally from a large pool of regressors in a high-dimensional regression. This causes the inconsistency of the penalized least-squares method and possible false scientific discoveries. A necessary condition for model selection consistency of a general class of penalized regression methods is given, which allows us to prove formally the inconsistency claim. To cope with the incidental endogeneity, we construct a novel penalized focused generalized method of moments (FGMM) criterion function. The FGMM effectively achieves the dimension reduction and applies the instrumental variable methods. We show that it possesses the oracle property even in the presence of endogenous predictors, and that the solution is also near global minimum under the over-identification assumption. Finally, we also show how the semi-parametric efficiency of estimation can be achieved via a two-step approach. PMID:25580040

  12. Harnessing endogenous stem/progenitor cells for tendon regeneration

    PubMed Central

    Lee, Chang H.; Lee, Francis Y.; Tarafder, Solaiman; Kao, Kristy; Jun, Yena; Yang, Guodong; Mao, Jeremy J.

    2015-01-01

    Current stem cell–based strategies for tissue regeneration involve ex vivo manipulation of these cells to confer features of the desired progenitor population. Recently, the concept that endogenous stem/progenitor cells could be used for regenerating tissues has emerged as a promising approach that potentially overcomes the obstacles related to cell transplantation. Here we applied this strategy for the regeneration of injured tendons in a rat model. First, we identified a rare fraction of tendon cells that was positive for the known tendon stem cell marker CD146 and exhibited clonogenic capacity, as well as multilineage differentiation ability. These tendon-resident CD146+ stem/progenitor cells were selectively enriched by connective tissue growth factor delivery (CTGF delivery) in the early phase of tendon healing, followed by tenogenic differentiation in the later phase. The time-controlled proliferation and differentiation of CD146+ stem/progenitor cells by CTGF delivery successfully led to tendon regeneration with densely aligned collagen fibers, normal level of cellularity, and functional restoration. Using siRNA knockdown to evaluate factors involved in tendon generation, we demonstrated that the FAK/ERK1/2 signaling pathway regulates CTGF-induced proliferation and differentiation of CD146+ stem/progenitor cells. Together, our findings support the use of endogenous stem/progenitor cells as a strategy for tendon regeneration without cell transplantation and suggest this approach warrants exploration in other tissues. PMID:26053662

  13. Harnessing endogenous stem/progenitor cells for tendon regeneration.

    PubMed

    Lee, Chang H; Lee, Francis Y; Tarafder, Solaiman; Kao, Kristy; Jun, Yena; Yang, Guodong; Mao, Jeremy J

    2015-07-01

    Current stem cell-based strategies for tissue regeneration involve ex vivo manipulation of these cells to confer features of the desired progenitor population. Recently, the concept that endogenous stem/progenitor cells could be used for regenerating tissues has emerged as a promising approach that potentially overcomes the obstacles related to cell transplantation. Here we applied this strategy for the regeneration of injured tendons in a rat model. First, we identified a rare fraction of tendon cells that was positive for the known tendon stem cell marker CD146 and exhibited clonogenic capacity, as well as multilineage differentiation ability. These tendon-resident CD146+ stem/progenitor cells were selectively enriched by connective tissue growth factor delivery (CTGF delivery) in the early phase of tendon healing, followed by tenogenic differentiation in the later phase. The time-controlled proliferation and differentiation of CD146+ stem/progenitor cells by CTGF delivery successfully led to tendon regeneration with densely aligned collagen fibers, normal level of cellularity, and functional restoration. Using siRNA knockdown to evaluate factors involved in tendon generation, we demonstrated that the FAK/ERK1/2 signaling pathway regulates CTGF-induced proliferation and differentiation of CD146+ stem/progenitor cells. Together, our findings support the use of endogenous stem/progenitor cells as a strategy for tendon regeneration without cell transplantation and suggest this approach warrants exploration in other tissues.

  14. Determining the potential of desmoglein 3 as a sensitive and specific immunohistochemical marker for the detection of micrometastasis in patients with primary oral squamous cell carcinoma

    PubMed Central

    Spadigam, Anita; Dhupar, Anita

    2016-01-01

    Aim of the study Despite advances in surgical and radiotherapy techniques, the presence of lymph node metastasis drastically decreases the survival rate of patients with primary oral squamous cell carcinoma (OSCC). Thus the accurate pathological staging of the neck is critical. Desmoglein 3 (DSG3), a desmosomal cadherin protein is said to be highly expressed in head and neck squamous cell carcinoma (HNSCC) and in metastatic cervical lymph nodes, but absent in non-invaded nodes. With an aim to improve the sensitivity of tumour cell detection, we investigated the potential of DSG3 as an immunohistochemical marker for the detection of occult lymph node metastasis in patients with primary OSCC. Material and methods Forty-seven lymph node specimens from 10 patients who underwent neck dissection for primary OSCC were immunostained with DSG3. Results The DSG3 positivity was noted in the six positive lymph nodes. However, when using DSG3 as an immunohistochemical marker, no additional micrometastatic deposits were evident in the histologically negative nodes. Interestingly, tumour marker DSG3-positive macrophages could be identified within the subcapsular sinuses, medullary sinuses, and the interfollicular areas. Conclusions Our findings suggest that although DSG3 is overexpressed in HNSCC, it is not specific and may not prove to be a potent immunohistochemical marker to detect micrometastasis. The role of tumour marker-positive macrophages within the lymph nodes needs to be investigated further.

  15. Development of simple sequence repeat markers in persimmon (Diospyros L.) and their potential use in related species.

    PubMed

    Yang, Y; Jing, Z B; Ruan, X F; Cheng, J M

    2015-01-30

    Persimmon (Diospyros L.) is an economically important fruit in the world, and it has been recognized as a healthy nutrient supply for human consumption. In this study, 14 microsatellite markers were developed from an AG/TC and AC/TG-enriched genomic library of Chinese persimmon Mopanshi. Twelve polymorphic markers were selected in 4 related species; these markers showed transferability to the 4 related persimmon species. In addition, 10 simple sequence repeat (SSR) markers were used to detect the genetic diversity among 51 persimmon accessions from China, Japan, and Korea. A total of 57 polymorphic bands with an average of 5.7 bands per primer pair were observed. According to cluster analysis and principal coordinate analysis, all persimmon accessions could be divided into 4 groups. A close relationship existed between D. kaki and D. oleifera, and D. glaucifolia and D. lotus. Jinzaoshi could be considered a separate species of persimmon. These new SSR markers provide tools for evaluating genetic relatedness among different persimmon species.

  16. Lipocalin 2 (LCN2) is a promising target for cholangiocarcinoma treatment and bile LCN2 level is a potential cholangiocarcinoma diagnostic marker

    PubMed Central

    Chiang, Kun-Chun; Yeh, Ta-Sen; Wu, Ren-Chin; Pang, Jong-Hwei S.; Cheng, Chi-Tung; Wang, Shang-Yu; Juang, Horng-Heng; Yeh, Chun-Nan

    2016-01-01

    Cholangiocarcinoma (CCA) is a devastating disease due to resistance to traditional chemotherapies and radiotherapies. New therapeutic strategies against CCA are urgently needed. This study investigated the role of lipocalin-2 (LCN2) in human cholangiocarcinoma as a potential therapeutic target and diagnostic marker. So far, the role of LCN2 in cancer is still controversial and studies regarding the role of LCN2 in CCA are limited. LCN2 knockdown inhibited CCA cell growth in vitro and in vivo through induction of cell cycle arrest at G0/G1 phases and decreased metastatic potential due to repression of epithelial-mesenchymal transition (EMT). Overexpression of LCN2 in CCA cells increased cell metastatic potential. We showed for the first time that the N-myc downstream regulated gene 1 (NDRG1) and NDRG2, known as tumor suppressor genes, are negatively regulated by LCN2 in CCA cells. LCN2 concentration in bile was higher in patients with CCA than that in patients with gallstones, with a cutoff value of 20.08 ng/ml making this a potential diagnostic marker. Higher LCN2 expression was associated with worse survival in patients with CCA. LCN2 is a promising target for CCA treatment and bile LCN2 level is a potential diagnostic marker for CCA. PMID:27782193

  17. Post-stimulus endogenous and exogenous oscillations are differentially modulated by task difficulty

    PubMed Central

    Li, Yun; Lou, Bin; Gao, Xiaorong; Sajda, Paul

    2013-01-01

    We investigate the modulation of post-stimulus endogenous and exogenous oscillations when a visual discrimination is made more difficult. We use exogenous frequency tagging to induce steady-state visually evoked potentials (SSVEP) while subjects perform a face-car discrimination task, the difficulty of which varies on a trial-to-trial basis by varying the noise (phase coherence) in the image. We simultaneously analyze amplitude modulations of the SSVEP and endogenous alpha activity as a function of task difficulty. SSVEP modulation can be viewed as a neural marker of attention toward/away from the primary task, while modulation of post-stimulus alpha is closely related to cortical information processing. We find that as the task becomes more difficult, the amplitude of SSVEP decreases significantly, approximately 250–450 ms post-stimulus. Significant changes in endogenous alpha amplitude follow SSVEP modulation, occurring at approximately 400–700 ms post-stimulus and, unlike the SSVEP, the alpha amplitude is increasingly suppressed as the task becomes less difficult. Our results demonstrate simultaneous measurement of endogenous and exogenous oscillations that are modulated by task difficulty, and that the specific timing of these modulations likely reflects underlying information processing flow during perceptual decision-making. PMID:23386819

  18. Summary of impact markers and potential impact mechanisms for the YDB impact event at 12.9 ka

    NASA Astrophysics Data System (ADS)

    Bunch, T. E.; Schultz, P. H.; Wittke, J. H.; West, A.; Kennett, J.; Kennett, D. J.

    2009-12-01

    Until the announcements of a possible impact event (Firestone et al. 2007; Kennett et al., 2009a; 2009b) at the beginning of the Younger Dryas (YD) around 12.9 ka, the KT impact layer (KTB) that resulted from the Chicxulub impact at 65 mya was the only geological boundary layer known to contain coeval peaks in various impact markers, including diamonds. Here, we compare impact markers from the KTB, YD boundary layer (YDB), and the 1908 Tunguska airburst layer (TAL). First order markers, related to impact and biomass burning, include: magnetic spherules, carbon spherules, nanodiamonds (cubic and lonsdaleite), iridium anomalies, charcoal, fullerenes (with high 3He to 4He ratio), grape-like soot, and widespread extinctions. Observations and analytical data for the YDB are consistent with all of the KTB markers, while the last three markers are unknown or inconclusive for the Tunguska layer. Selected markers for cratering events, e.g, Chicxulub, are: a visible crater, shocked minerals, impact breccia, and microtektites. None of these are known for the YD event or Tunguska. The discussion here is limited to possible origins of the impact markers and not with impact consequences (climate change, extinctions, etc.). Several origins may account for impact materials in the YDB: (1) An extraordinary accretion of micrometeorites (Pinter and Ishman, 2008). However, this is inconsistent with YDB carbon spherule compositions, including the large concentrations of nanodiamonds found embedded in those carbon spherules. (2) Oblique impact(s) into the Laurentide Ice Sheet. This model is consistent with the lack of a visible crater and apparent lack of cratering markers (above), and yet also provides for shock production of the many cubic nanodiamonds and lonsdaleite found in the YDB. (3) Impact-induced aerial burst. e.g, Boslough and Crawford (2007); Shuvalov (2008). The lack of high shock pressures in an aerial detonation does not necessarily preclude the formation of cubic and

  19. Proteomic analysis allows for early detection of potential markers of metabolic impairment in very young obese children

    PubMed Central

    2014-01-01

    Apo A1 (IR vs. non-IR). Assays routinely used in the clinical setting (ELISA/kinetic nephelometry), only partially confirmed the changes observed by proteomic analysis (ApoA1 and haptoglobin). Conclusion Proteomic analysis can allow for the identification of potential new candidate biomarkers as a complement to routinely used assays to detect initial changes in serum markers of inflammation and lipid metabolism impairment in young obese children. PMID:24949022

  20. Monoclonal antibodies raised to paraffin wax embedded archival tissue; feasibility study of their potential to detect novel antigenic markers.

    PubMed

    Moran, E; Larkin, A; Cleary, I; Barnes, C; Kennedy, S M; Kelehan, P; Clynes, M

    1998-10-01

    A study to determine the feasibility of using archival paraffin wax embedded tissue to generate monoclonal antibodies is described. Specifically, monoclonal antibodies were raised to paraffin wax embedded normal human kidney tissue to test the possibility of producing antibodies to such tissue samples prior to attempting generation of antibodies to valuable archival tissue. Multiple sections (10 x 5 microm) were pooled and dewaxed as for immunohistochemical procedures and combined with Freund's adjuvant for immunization of BALB/c mice in vivo. Immunized spleen cells were fused with SP2 myeloma cells and subsequent clones screened on paraffin wax embedded normal human kidney sections, a range of cell lines and normal mouse tissue. Supernatants from 11 wells (from a total of 90 wells screened) showed different staining patterns on sections of paraffin wax embedded kidney. One clone, 1/11C, (isotype IgG1) which exhibited strong staining on all kidney tubules by immunohistochemical studies (glomeruli interstitium and vessels were unstained) and identified a band at 52 kDa on immunoblots of dewaxed kidney tissue (as used for immunogen) was chosen for further characterization. Immunoblotting of five mammalian cell lines showed differential expression of this 52 kDa band (distinct expression on 3/5, weak expression on 2/5 cell lines) whereas, all cell lines displayed a band at 44 kDa and a third band at 70 kDa was observed on 2/5 cell lines. In mouse tissue extracts, the 52 kDa band was identified in kidney tissue only (not in the lung, liver or spleen) with the 44 kDa and 70 kDa bands weakly expressed in all tissues. This preliminary investigation of a novel approach to identifying possible new antigenic markers or producing monoclonal antibodies which react better to known antigens on sections of paraffin wax embedded tissue showed that this method is feasible. The need to have a comprehensive screening system in place and the ability to identify potentially useful

  1. Can melatonin be used as a marker for neonatal sepsis?

    PubMed

    El-Mashad, Abdel-Rahman; Elmahdy, Heba; El-Dib, Mohamed; Elbatch, Manal; Aly, Hany

    2016-09-01

    Melatonin, an indolamine endogenously produced by pineal body, has important role as an anti-oxidant, anti-inflammatory and anti-apoptotic. Whether melatonin concentration changes in neonatal sepsis and whether it can be used as a marker of sepsis is unknown. The objective of this study is to evaluate melatonin concentration in the serum as a marker for neonatal sepsis and compare it to standard markers. We prospectively studied 40 neonates: 20 diagnosed with late neonatal sepsis and 20 healthy neonates as a control group. Markers of sepsis and melatonin concentration were compared between both groups. The sepsis groups had significantly increased immature to total neutrophils ratio (I/T ratio), and high sensitivity C-reactive protein (HsCRP), and decreased platelet count. Melatonin concentration was increased in sepsis group when compared to control group (27.2 ± 3.3 versus 11.4 ± 3.2 pg/ml, p = 0.001), and positively correlated with HsCRP (r = 0.952, p = 0.001) and I/T ratio (r = 0.326, p = 0.015). Combining melatonin to HsCRP increased sensitivity and specificity to detect neonatal sepsis to 97.3 and 93.3%, respectively. Endogenous melatonin concentration is increased in late neonatal sepsis and can potentially be used as a marker for sepsis especially when combined with CRP.

  2. HMGB1: Endogenous Danger Signaling

    PubMed Central

    Klune, John R; Dhupar, Rajeev; Cardinal, Jon; Billiar, Timothy R; Tsung, Allan

    2008-01-01

    While foreign pathogens and their products have long been known to activate the innate immune system, the recent recognition of a group of endogenous molecules that serve a similar function has provided a framework for understanding the overlap between the inflammatory responses activated by pathogens and injury. These endogenous molecules, termed alarmins, are normal cell constituents that can be released into the extracellular milieu during states of cellular stress or damage and subsequently activate the immune system. One nuclear protein, High mobility group box-1 (HMGB1), has received particular attention as fulfilling the functions of an alarmin by being involved in both infectious and non-infectious inflammatory conditions. Once released, HMGB1 signals through various receptors to activate immune cells involved in the immune process. Although initial studies demonstrated HMGB1 as a late mediator of sepsis, recent findings indicate HMGB1 to have an important role in models of non-infectious inflammation, such as autoimmunity, cancer, trauma, and ischemia reperfusion injury. Furthermore, in contrast to its pro-inflammatory functions, there is evidence that HMGB1 also has restorative effects leading to tissue repair and regeneration. The complex functions of HMGB1 as an archetypical alarmin are outlined here to review our current understanding of a molecule that holds the potential for treatment in many important human conditions. PMID:18431461

  3. Human endogenous retroviruses and cancer

    PubMed Central

    Gonzalez-Cao, María; Iduma, Paola; Karachaliou, Niki; Santarpia, Mariacarmela; Blanco, Julià; Rosell, Rafael

    2016-01-01

    Human endogenous retroviruses (HERVs) are retroviruses that infected human genome millions of years ago and have persisted throughout human evolution. About 8% of our genome is composed of HERVs, most of which are nonfunctional because of epigenetic control or deactivating mutations. However, a correlation between HERVs and human cancer has been described and many tumors, such as melanoma, breast cancer, germ cell tumors, renal cancer or ovarian cancer, express HERV proteins, mainly HERV-K (HML6) and HERV-K (HML2). Although the causative role of HERVs in cancer is controversial, data from animal models demonstrated that endogenous retroviruses are potentially oncogenic. HERV protein expression in human cells generates an immune response by activating innate and adaptive immunities. Some HERV-derived peptides have antigenic properties. For example, HERV-K (HML-6) encodes the HER-K MEL peptide recognized by CD8+ lymphocytes. In addition, HERVs are two-edged immunomodulators. HERVs show immunosuppressive activity. The presence of genomic retroviral elements in host-cell cytosol may activate an interferon type I response. Therefore, targeting HERVs through cellular vaccines or immunomodulatory drugs combined with checkpoint inhibitors is attracting interest because they could be active in human tumors. PMID:28154780

  4. Endogenous Inhibitors of Kidney Inflammation

    PubMed Central

    Trostel, Jessica; Garcia, Gabriela E.

    2015-01-01

    Although inflammation is the physiological response to pathogen invasion and tissue damage, it can also be responsible for significant tissue damage. Therefore, the inflammatory response must be carefully regulated to prevent critical inflammatory damage to vital organs. Typically, local endogenous regulatory mechanisms adjust the magnitude of the response such that the injurious condition is resolved and homeostasis is mantained. Humoral mechanisms that restrain or inhibit inflammation include glucocorticoid hormones, anti-inflammatory cytokines such as IL-10 and transforming growth factor-β (TGF-β), and soluble cytokine receptors; other mediators facilitate tissue healing, like lipoxins and resolvins. There is growing evidence that inflammation plays a critical role in the development and progression of heart disease, cancer, stroke, diabetes, kidney diseases, sepsis, and several fibroproliferative disorders. Consequently, understanding the mechanisms that regulate inflammation may offer therapeutic targets for inhibiting the progression of several diseases. In this article, we review the significance of several novel endogenous anti-inflammatory mediators in the protection from kidney injury and the potential of these regulatory molecules as therapeutic targets for treatment of kidney inflammatory diseases. PMID:26779569

  5. Endogeneity in prison risk classification.

    PubMed

    Shermer, Lauren O'Neill; Bierie, David M; Stock, Amber

    2013-10-01

    Security designation tools are a key feature of all prisons in the United States, intended as objective measures of risk that funnel inmates into security levels-to prison environments varying in degree of intrusiveness, restriction, dangerousness, and cost. These tools are mostly (if not all) validated by measuring inmates on a set of characteristics, using scores from summations of that information to assign inmates to prisons of varying security level, and then observing whether inmates assumed more risky did in fact offend more. That approach leaves open the possibility of endogeneity--that the harsher prisons are themselves bringing about higher misconduct and thus biasing coefficients assessing individual risk. The current study assesses this potential bias by following an entry cohort of inmates to more than 100 facilities in the Federal Bureau of Prisons (BOP) and exploiting the substantial variation in classification scores within a given prison that derive from systematic overrides of security-level designations for reasons not associated with risk of misconduct. By estimating pooled models of misconduct along with prison-fixed effects specifications, the data show that a portion of the predictive accuracy thought associated with the risk-designation tool used in BOP was a function of facility-level contamination (endogeneity).

  6. Acylcarnitines as markers of exercise-associated fuel partitioning, xenometabolism, and potential signals to muscle afferent neurons

    USDA-ARS?s Scientific Manuscript database

    With insulin-resistance or type 2 diabetes mellitus, mismatches between mitochondrial fatty acid fuel delivery and oxidative phosphorylation/tricarboxylic acid cycle activity may contribute to inordinate accumulation of short- or medium-chain acylcarnitine fatty acid derivatives (markers of incomple...

  7. Short-term Effects of Air Temperature on Blood Markers of Coagulation and Inflammation in Potentially Susceptible Individuals

    EPA Science Inventory

    Objectives: Changes in air temperature are associated with an increase in cardiovascular events, but the role of pro-coagulant and pro-inflammatory blood markers is still poorly understood. We investigated the association between air temperature and fibrinogen, plasminogen act...

  8. Short-term Effects of Air Temperature on Blood Markers of Coagulation and Inflammation in Potentially Susceptible Individuals

    EPA Science Inventory

    Objectives: Changes in air temperature are associated with an increase in cardiovascular events, but the role of pro-coagulant and pro-inflammatory blood markers is still poorly understood. We investigated the association between air temperature and fibrinogen, plasminogen act...

  9. Negative regulatory element associated with potentially functional promoter and enhancer elements in the long terminal repeats of endogenous murine leukemia virus-related proviral sequences

    SciTech Connect

    Ch'ang, L.Y.; Yang, W.K.; Myer, F.E.; Yang, D.M.

    1989-06-01

    Three series of recombinant DNA clones were constructed, with the bacterial chloramphenical acetyltransferase (CAT) gene as a quantitative indicator, to examine the activities of promoter and enhancer sequence elements in the 5' long terminal repeat (LTR) of murine leukemia virus (MuLV)-related proviral sequences isolated from the mouse genome. Transient CAT expression was determined in mouse NIH 3T3, human HT1080, and mink CCL64 cultured cells transfected with the LTR-CAT constructs. The 700-base pair (bp) LTRs of three polytropic MuLV-related proviral clones and the 750-bp LTRs of four modified polytropic proviral clones, in complete structures either with or without the adjacent downstream sequences, all showed very little or negligible activities for CAT expression, while ecotropic MuLV LTRs were highly active. The MuLV-related LTRs were divided into three portions and examined separately. The 3' portion of the MuLV-related LTRs that contains the CCAAC and TATAA boxes was found to be a functional promoter, being about one-half to one-third as active as the corresponding portion of the ecotropic MuLV LTRs. A MboI-Bg/II fragment, representing the distinct 190- to 200-pb inserted segment in the middle, was found to be a potential enhancer, especially when examined in combination with the simian virus 40 promoter in CCL64 cells. A PstI-MboI fragment of the 5' portion, which contains the protein-binding motifs on the enhancer segment as well as the upstream LTF sequences, showed moderate enhancer activities in CCL6 cells but was virtually inactive in NIH 3T3 cells and HT1080 cells; addition of this fragment to the ecotropic LTR-CAT constructs depressed CAT expression.

  10. Dental pulp stem cells express tendon markers under mechanical loading and are a potential cell source for tissue engineering of tendon-like tissue

    PubMed Central

    Chen, Yu-Ying; He, Sheng-Teng; Yan, Fu-Hua; Zhou, Peng-Fei; Luo, Kai; Zhang, Yan-Ding; Xiao, Yin; Lin, Min-Kui

    2016-01-01

    Postnatal mesenchymal stem cells have the capacity to differentiate into multiple cell lineages. This study explored the possibility of dental pulp stem cells (DPSCs) for potential application in tendon tissue engineering. The expression of tendon-related markers such as scleraxis, tenascin-C, tenomodulin, eye absent homologue 2, collagens I and VI was detected in dental pulp tissue. Interestingly, under mechanical stimulation, these tendon-related markers were significantly enhanced when DPSCs were seeded in aligned polyglycolic acid (PGA) fibre scaffolds. Furthermore, mature tendon-like tissue was formed after transplantation of DPSC-PGA constructs under mechanical loading conditions in a mouse model. This study demonstrates that DPSCs could be a potential stem cell source for tissue engineering of tendon-like tissue. PMID:27811845

  11. Dental pulp stem cells express tendon markers under mechanical loading and are a potential cell source for tissue engineering of tendon-like tissue.

    PubMed

    Chen, Yu-Ying; He, Sheng-Teng; Yan, Fu-Hua; Zhou, Peng-Fei; Luo, Kai; Zhang, Yan-Ding; Xiao, Yin; Lin, Min-Kui

    2016-12-16

    Postnatal mesenchymal stem cells have the capacity to differentiate into multiple cell lineages. This study explored the possibility of dental pulp stem cells (DPSCs) for potential application in tendon tissue engineering. The expression of tendon-related markers such as scleraxis, tenascin-C, tenomodulin, eye absent homologue 2, collagens I and VI was detected in dental pulp tissue. Interestingly, under mechanical stimulation, these tendon-related markers were significantly enhanced when DPSCs were seeded in aligned polyglycolic acid (PGA) fibre scaffolds. Furthermore, mature tendon-like tissue was formed after transplantation of DPSC-PGA constructs under mechanical loading conditions in a mouse model. This study demonstrates that DPSCs could be a potential stem cell source for tissue engineering of tendon-like tissue.

  12. Endogenic nortestosterone in cattle?

    PubMed

    de Brabander, H F; van Hende, J; Batjoens, P; Hendriks, L; Raus, J; Smets, F; Pottie, G; van Ginkel, L; Stephany, R W

    1994-12-01

    When residues of nortestosterone (NT) were found in the urine of cattle, racehorses or bodybuilders, exogenic administration was thought to be proven. In previous literature, no records were found of the endogenic presence of this molecule. In the horse-racing world, Houghton and Courthot found that NT is normally present in the urine of the stallion. Belgian and Dutch researchers found that NT is also present in the urine and edible parts of the intact boar. Vandenbroeck et al. (1991) suggested the endogenous presence of NT (in the beta form) in the pregnant cow. Meyer (1992) reported the presence of NT (in the alpha form) in relatively high amounts in the urine of the cow peri-partum and the neo-natal calf. These observations may have important consequences for veterinary meat inspection in the EU. Therefore, in Belgium a large scale experiment was set up in co-operation with the EU Community Reference Laboratory (RIVM). In this paper the present state of the results in this area is presented. A large number of urine samples (> 50) of pregnant non-treated cows were collected and analysed by gas chromatography-mass spectrometry (GC-MS) in 4 different laboratories. Further samples (> 100) were taken, but only analysed in one laboratory. The results proved clearly that NT may indeed be detectable in the alpha form in the urine of pregnant cows, from at least 2 months, but most probably from 4-5 months before partus.

  13. Transcriptome analysis of cattle muscle identifies potential markers for skeletal muscle growth rate and major cell types.

    PubMed

    Guo, Bing; Greenwood, Paul L; Cafe, Linda M; Zhou, Guanghong; Zhang, Wangang; Dalrymple, Brian P

    2015-03-13

    This study aimed to identify markers for muscle growth rate and the different cellular contributors to cattle muscle and to link the muscle growth rate markers to specific cell types. The expression of two groups of genes in the longissimus muscle (LM) of 48 Brahman steers of similar age, significantly enriched for "cell cycle" and "ECM (extracellular matrix) organization" Gene Ontology (GO) terms was correlated with average daily gain/kg liveweight (ADG/kg) of the animals. However, expression of the same genes was only partly related to growth rate across a time course of postnatal LM development in two cattle genotypes, Piedmontese x Hereford (high muscling) and Wagyu x Hereford (high marbling). The deposition of intramuscular fat (IMF) altered the relationship between the expression of these genes and growth rate. K-means clustering across the development time course with a large set of genes (5,596) with similar expression profiles to the ECM genes was undertaken. The locations in the clusters of published markers of different cell types in muscle were identified and used to link clusters of genes to the cell type most likely to be expressing them. Overall correspondence between published cell type expression of markers and predicted major cell types of expression in cattle LM was high. However, some exceptions were identified: expression of SOX8 previously attributed to muscle satellite cells was correlated with angiogenesis. Analysis of the clusters and cell types suggested that the "cell cycle" and "ECM" signals were from the fibro/adipogenic lineage. Significant contributions to these signals from the muscle satellite cells, angiogenic cells and adipocytes themselves were not as strongly supported. Based on the clusters and cell type markers, sets of five genes predicted to be representative of fibro/adipogenic precursors (FAPs) and endothelial cells, and/or ECM remodelling and angiogenesis were identified. Gene sets and gene markers for the analysis of

  14. Marker vaccine potential of a foot-and-mouth disease virus with a partial VP1 G-H loop deletion.

    PubMed

    Fowler, V L; Knowles, N J; Paton, D J; Barnett, P V

    2010-04-26

    Previous work in cattle and pigs demonstrated that protection against foot-and-mouth disease (FMD) could be achieved following vaccination with chimeric foot-and-mouth disease virus (FMDV) vaccines, in which the VP1 G-H loop had been substituted with that from another serotype. This indicated that the VP1 G-H loop may not be essential for the protection of natural hosts against FMDV. If this could be substantiated there would be potential to develop FMD marker vaccines, characterised by the absence of this region. Here, we investigate the serological responses to vaccination with a virus with a partial VP1 G-H loop deletion in order to determine the likelihood of achieving protection and the potential of this virus as a marker vaccine. Inactivated, oil adjuvanted, vaccines, consisting of chemically inactivated virus with or without a partially deleted VP1 G-H loop, were used to immunise cattle. Serum was collected on days 0, 7, 14 and 21 and antibody titres calculated using the virus neutralisation test (VNT) to estimate the likelihood of protection. We predict a good likelihood that cattle vaccinated with a vaccine characterised by a partial VP1 G-H loop would be protected against challenge with the same virus containing the VP1 G-H loop. We also present evidence on the potential of such a construct to act as a marker vaccine, when used in conjunction with a novel serological test.