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  1. Medline search engine for finding genetic markers with biological significance.

    Science.gov (United States)

    Xuan, Weijian; Wang, Pinglang; Watson, Stanley J; Meng, Fan

    2007-09-15

    Genome-wide high density SNP association studies are expected to identify various SNP alleles associated with different complex disorders. Understanding the biological significance of these SNP alleles in the context of existing literature is a major challenge since existing search engines are not designed to search literature for SNPs or other genetic markers. The literature mining of gene and protein functions has received significant attention and effort while similar work on genetic markers and their related diseases is still in its infancy. Our goal is to develop a web-based tool that facilitates the mining of Medline literature related to genetic studies and gene/protein function studies. Our solution consists of four main function modules for (1) identification of different types of genetic markers or genetic variations in Medline records (2) distinguishing positive versus negative linkage or association between genetic markers and diseases (3) integrating marker genomic location data from different databases to enable the retrieval of Medline records related to markers in the same linkage disequilibrium region (4) and a web interface called MarkerInfoFinder to search, display, sort and download Medline citation results. Tests using published data suggest MarkerInfoFinder can significantly increase the efficiency of finding genetic disorders and their underlying molecular mechanisms. The functions we developed will also be used to build a knowledge base for genetic markers and diseases. The MarkerInfoFinder is publicly available at: http://brainarray.mbni.med.umich.edu/brainarray/datamining/MarkerInfoFinder.

  2. The significance of markers in the diagnosis of endometrial cancer

    Directory of Open Access Journals (Sweden)

    Monika M. Żyła

    2016-11-01

    Full Text Available Endometrial cancer is one of the most common cancers experienced by women throughout the world. It is also the most common malignancy within the female reproductive system, representing 37.7% of all disorders. The incidence increases with age, and is diagnosed most frequently in women between 45 and 65 years old. In the last few years, numerous studies have been performed to identify tumour biomarkers. Biomarkers include not only protein routinely used as tumour markers but also genes and chromosomes. The limiting factor in the use of markers in the diagnosis of endometrial cancer is their lack of specificity. However, specific markers for endometrial cancer are the subject of much research attention. Although moderately elevated levels of markers are present in a number of inflammatory or non-malignant diseases, significantly increased levels of markers indicate the development of cancer. Recently, research has been focused on the identification of molecular changes leading to different histological subtypes of endometrial cancer. In this paper the authors reviewed several currently investigated markers. Progress in these investigations is very important in the diagnostics and treatment of endometrial cancer. In particular, the identification of novel mutations and molecular profiles should enhance our ability to personalise adjuvant treatment with genome-guided targeted therapy.

  3. The significance of markers in the diagnosis of endometrial cancer

    Science.gov (United States)

    Żyła, Monika M.; Wilczyński, Jacek R.; Kostrzewa, Marta; Księżakowska-Łakoma, Kinga; Nowak, Marek; Stachowiak, Grzegorz; Szyłło, Krzysztof

    2016-01-01

    Endometrial cancer is one of the most common cancers experienced by women throughout the world. It is also the most common malignancy within the female reproductive system, representing 37.7% of all disorders. The incidence increases with age, and is diagnosed most frequently in women between 45 and 65 years old. In the last few years, numerous studies have been performed to identify tumour biomarkers. Biomarkers include not only protein routinely used as tumour markers but also genes and chromosomes. The limiting factor in the use of markers in the diagnosis of endometrial cancer is their lack of specificity. However, specific markers for endometrial cancer are the subject of much research attention. Although moderately elevated levels of markers are present in a number of inflammatory or non-malignant diseases, significantly increased levels of markers indicate the development of cancer. Recently, research has been focused on the identification of molecular changes leading to different histological subtypes of endometrial cancer. In this paper the authors reviewed several currently investigated markers. Progress in these investigations is very important in the diagnostics and treatment of endometrial cancer. In particular, the identification of novel mutations and molecular profiles should enhance our ability to personalise adjuvant treatment with genome-guided targeted therapy. PMID:27980530

  4. Potential blood-based markers of celiac disease.

    Science.gov (United States)

    Bragde, Hanna; Jansson, Ulf; Fredrikson, Mats; Grodzinsky, Ewa; Söderman, Jan

    2014-10-09

    Blood-based diagnostics has the potential to simplify the process of diagnosing celiac disease (CD). Although high levels of autoantibodies against tissue transglutaminase (anti-TG2) are strongly indicative of active CD, several other scenarios involve a need for additional blood-based CD markers. We investigated the levels of messenger RNA (mRNA) in whole blood (n = 49) and protein in plasma (n = 22) from cases with active CD (n = 20), with confirmed CD and normalized histology (n = 15), and without a CD diagnosis (n = 14). Group differences were analyzed using Kruskal-Wallis one-way analysis of variance by ranks. We also investigated correlations between levels of potential markers, histopathology according to the modified Marsh scale, and CD risk gradient based on HLA type, using Spearman rank correlation. The relation between HLA-DQ2 gene dose effect and the expression levels of selected blood-based markers was investigated using the Mann-Whitney U test. Finally, the diagnostic performance of anti-TG2, potential blood-based CD markers, and logistic regression models of combined markers was evaluated using receiver operating characteristic (ROC) curve analysis. CXCL11 protein levels and TNFRSF9 and TNFSF13B mRNA levels were identified as potential CD markers. These are all affected by or involved in the regulation of the NF-κB complex. CXCL11 protein levels and IL21 and IL15 mRNA levels were correlated with histopathology according to the modified Marsh scale, as were the established CD markers. HLA genotype risk and HLA-DQ2 gene dose effect did not show any significant relations with either the potential CD markers or the established CD markers. ROC curve analysis revealed a slight, non-significant increase in the area under the curve for the combined use of anti-TG2 and different constellations of potential blood-based CD markers compared to anti-TG2 alone. The CD markers identified in this study further emphasize the significance of

  5. Antibody Arrays Identify Potential Diagnostic Markers of Hepatocellular Carcinoma

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    Brian J. Peter

    2008-01-01

    Full Text Available Hepatocellular carcinoma (HCC is the third leading cause of cancer deaths worldwide. Effective treatment of HCC patients is hampered by the lack of sensitive and specific diagnostic markers of HCC. Alpha-fetoprotein (AFP, the currently used HCC marker, misses 30%–50% of HCC patients, who therefore remain undiagnosed and untreated. In order to identify novel diagnostic markers that can be used individually or in combination with AFP, we used an antibody array platform to detect the levels of candidate proteins in the plasma of HCC patients (n = 48 and patients with chronic hepatitis B or C viral infections (n = 19 (both of which are the major risk factors of HCC. We identified 7 proteins that significantly differentiate HCC patients from hepatitis patients (p < 0.05 (AFP, CTNNB, CSF1, SELL, IGFBP6, IL6R, and VCAM1.Importantly, we also identified 8 proteins that significantly differentiate HCC patients with ‘normal’ levels of AFP (<20 ng/ml from hepatitis patients (p < 0.05 (IL1RN, IFNG, CDKN1A, RETN, CXCL14, CTNNB, FGF2, and SELL. These markers are potentially important complementary markers to AFP. Using an independent immunoassay method in an independent group of 23 HCC patients and 22 hepatitis patients, we validated that plasma levels of CTNNB were significantly higher in the HCC group (p = 0.020. In conclusion, we used an antibody array platform to identify potential circulating diagnostic markers of HCC, some of which may be valuable when used in combination with AFP. The clinical utility of these newly identified HCC diagnostic markers needs to be systematically evaluated.

  6. Markers of Collagen Remodeling Detect Clinically Significant Fibrosis in Chronic Hepatitis C Patients

    DEFF Research Database (Denmark)

    Nielsen, Mette J; Kazankov, Konstantin; Leeming, Diana J

    2015-01-01

    as potential biomarkers for clinically significant and advanced fibrosis. METHODS: Specific protein fragments of matrix metalloprotease degraded type I, III, IV and VI collagen (C1M, C3M, C4M, C6M) and type III and IV collagen formation (Pro-C3 and P4NP7S) were assessed in plasma from 403 chronic hepatitis C...... patients by specific ELISAs. Patients were stratified according to Metavir Fibrosis stage; F0 (n = 46), F1 (n = 161), F2 (n = 95), F3 (n = 44) and F4 (n = 33) based on liver biopsy. RESULTS: Pro-C3 was significantly elevated in patients with significant fibrosis (≥F2) compared to F0-F1 (p... the markers C3M, C4M, C6M and P4NP7S were significantly elevated in patients with advanced fibrosis (≥F3) compared to F0-F2 (p

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  9. Potential of marker-assisted selection for Tobacco mosaic ...

    African Journals Online (AJOL)

    memory

    Potential of marker-assisted selection for Tobacco mosaic tobamovirus resistance in tobacco breeding. Memory Mazarire1,2, Edmore Gasura1* and Dahlia Garwe2. 1Department of Crop Science, University of Zimbabwe, P.O Box MP167, Mount Pleasant, Harare, Zimbabwe. 2Kutsaga Research Station, Airport Ring Road, ...

  10. Sequence-Related Amplified Polymorphism (SRAP Markers: A Potential Resource for Studies in Plant Molecular Biology

    Directory of Open Access Journals (Sweden)

    Daniel W. H. Robarts

    2014-07-01

    Full Text Available 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.

  11. Glycan Markers as Potential Immunological Targets in Circulating Tumor Cells.

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    Wang, Denong; Wu, Lisa; Liu, Xiaohe

    2017-01-01

    We present here an experimental approach for exploring a new class of tumor biomarkers that are overexpressed by circulating tumor cells (CTCs) and are likely targetable in immunotherapy against tumor metastasis. Using carbohydrate microarrays, anti-tumor monoclonal antibodies (mAbs) were scanned against a large panel of carbohydrate antigens to identify potential tumor glycan markers. Subsequently, flow cytometry and fiber-optic array scanning technology (FAST) were applied to determine whether the identified targets are tumor-specific cell-surface markers and are, therefore, likely suitable for targeted immunotherapy. Finally, the tumor glycan-specific antibodies identified were validated using cancer patients' blood samples for their performance in CTC-detection and immunotyping analysis. In this article, identifying breast CTC-specific glycan markers and targeting mAbs serve as examples to illustrate this tumor biomarker discovery strategy.

  12. Potential blood-based markers of celiac disease

    OpenAIRE

    Bragde, Hanna; Jansson, Ulf; Fredrikson, Mats; Grodzinsky, Ewa; Soederman, Jan

    2014-01-01

    Background Blood-based diagnostics has the potential to simplify the process of diagnosing celiac disease (CD). Although high levels of autoantibodies against tissue transglutaminase (anti-TG2) are strongly indicative of active CD, several other scenarios involve a need for additional blood-based CD markers. Methods We investigated the levels of messenger RNA (mRNA) in whole blood (n?=?49) and protein in plasma (n?=?22) from cases with active CD (n?=?20), with confirmed CD and normalized hist...

  13. Evaluation and prognostic significance of ACAT1 as a marker of prostate cancer progression.

    Science.gov (United States)

    Saraon, Punit; Trudel, Dominique; Kron, Ken; Dmitromanolakis, Apostolos; Trachtenberg, John; Bapat, Bharati; van der Kwast, Theodorus; Jarvi, Keith A; Diamandis, Eleftherios P

    2014-04-01

    Prostate cancer is the second leading cause of cancer-related death among men in North America. While a majority of prostate cancer cases remain indolent, subsets of patients develop aggressive cancers, which may lead to death. The current methods of detection include digital rectal examination and the serum PSA test. However, due to lack of specificity, neither of these approaches is able to accurately discriminate between indolent and aggressive cancer, which is why there is a need for additional prognostic factors. Previously, we identified enzymes of the ketogenic pathway, particularly ACAT1, to be elevated in aggressive prostate cancer. In the current study, we assessed the diagnostic and prognostic potential of ACAT1 by analyzing its expression using immunohistochemistry on a tissue microarray consisting of 251 clinically localized prostate cancer patients who have undergone radical prostatectomy. Using quantitative digital imaging software, we found that ACAT1 expression was significantly greater in cancerous cores compared to adjacent benign cores (P cancers versus GS≤6 cancers (P cancers versus GS7 cancers (P = 0.001), as well as pT3/pT4 versus pT2 cancers (P = 0.001). In addition, ACAT1 predicted biochemical recurrence in univariate (HR, 1.81, CI = 1.13-2.9, P = 0.0128), and multivariate models (HR, 1.69, CI = 1.01-2.81, P = 0.0431) including pre-operative PSA level, Gleason score and pathological stage. In univariate time-to-recurrence analysis, ACAT1 expression predicted recurrence in ERG negative cases (P = 0.0025), whereas ERG positive cases did not display any differences. Taken together, these findings indicate that ACAT1 expression could serve as a potential prognostic marker in prostate cancer, specifically in differentiating indolent and aggressive forms of cancer. © 2013 Wiley Periodicals, Inc.

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

    Science.gov (United States)

    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.

  15. Serum cathepsin H as a potential prognostic marker in patients with colorectal cancer

    DEFF Research Database (Denmark)

    Schweiger, A; Christensen, Ib Jarle; Nielsen, Hans Jørgen

    2005-01-01

    Cathepsin H is a lysosomal cysteine protease that may participate in tumor progression. In order to evaluate its potential as a prognostic marker, its protein levels were measured by ELISA in preoperative sera from 324 patients with colorectal cancer. The level of cathepsin H was significantly...

  16. Prognostic significance of new immunohistochemical markers in refractory classical Hodgkin lymphoma: a study of 59 cases.

    Directory of Open Access Journals (Sweden)

    Danielle Canioni

    Full Text Available Although most classical Hodgkin lymphoma patients are cured, a significant minority fail after primary therapy and may die as result of their disease. To date, there is no consensus on biological markers that add value to usual parameters (which comprise the International Prognostic Score used at diagnosis to predict outcome. We evaluated 59 patients (18 with primary refractory or early relapse disease and 41 responders for bcl2, Ki67, CD20, TiA1 and c-kit expression by semi-quantitative immunohistochemical study and correlated the results with the response to treatment.The results showed that expression of bcl2 and CD20 in Hodgkin and Reed Sternberg cells, and expression of TiA1 in micro-environmental lymphocytes, and c-kit positive mast cells in microenvironment, were independent prognostic markers. These novel cHL markers could be used in association with clinical parameters to identify newly diagnosed patients with favorable or unfavorable prognosis and to better tailor treatment for different risk groups.

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

    Science.gov (United States)

    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.

  18. Gene transcripts as potential diagnostic markers for allergic contact dermatitis

    DEFF Research Database (Denmark)

    Hansen, Malene Barré; Skov, Lone; Menné, Torkil

    2005-01-01

    The standard procedure for diagnosing allergic contact dermatitis is to perform a patch test. Because this has several disadvantages, the development of a new in vitro test system would be of immense value. Gene transcripts that distinguish allergics from non-allergics may have the potential to s...... widely available. The 26 differentially expressed genes identified in this study may potentially function as diagnostic markers for contact sensitivity....... to serve as the molecular basis for such a diagnostic tool. In this study, we use the microarray technology in the identification of differentially expressed genes in allergen-stimulated peripheral blood mononuclear cells (PBMCs) from 3 chromium-allergic patients versus 3 healthy controls. Using...

  19. The macrophage activation marker sCD163 combined with markers of the Enhanced Liver Fibrosis (ELF) score predicts clinically significant portal hypertension in patients with cirrhosis

    DEFF Research Database (Denmark)

    Sandahl, T D; McGrail, R; Møller, Holger Jon

    2016-01-01

    BACKGROUND: Noninvasive identification of significant portal hypertension in patients with cirrhosis is needed in hepatology practice. AIM: To investigate whether the combination of sCD163 as a hepatic inflammation marker and the fibrosis markers of the Enhanced Liver Fibrosis score (ELF) can pre...

  20. Serum Advanced Oxidation Protein Products in Oral Squamous Cell Carcinoma: Possible Markers of Diagnostic Significance

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    Abhishek Singh Nayyar

    2013-07-01

    Full Text Available Background: The aim of this study was to measure the concentrations (levels ofserum total proteins and advanced oxidation protein products as markers of oxidantmediated protein damage in the sera of patients with oral cancers.Methods: The study consisted of the sera analyses of serum total protein andadvanced oxidation protein products’ levels in 30 age and sex matched controls, 60patients with reported pre-cancerous lesions and/or conditions and 60 patients withhistologically proven oral squamous cell carcinoma. One way analyses of variance wereused to test the difference between groups. To determine which of the two groups’ meanswere significantly different, the post-hoc test of Bonferroni was used. The results wereaveraged as mean ± standard deviation. In the above test, P values less than 0.05 weretaken to be statistically significant. The normality of data was checked before thestatistical analysis was performed.Results: The study revealed statistically significant variations in serum levels ofadvanced oxidation protein products (P<0.001. Serum levels of total protein showedextensive variations; therefore the results were largely inconclusive and statisticallyinsignificant.Conclusion: The results emphasize the need for more studies with larger samplesizes to be conducted before a conclusive role can be determined for sera levels of totalprotein and advanced oxidation protein products as markers both for diagnosticsignificance and the transition from the various oral pre-cancerous lesions and conditionsinto frank oral cancers.

  1. [Circular RNA in human disease and their potential clinic significance].

    Science.gov (United States)

    Chen, Yonghua; Li, Cheng; Tan, Chunlu; Mai, Gang; Liu, Xubao

    2017-02-10

    Circular RNAs (circ RNAs) are a novel type of RNA that, unlike linear RNAs, form a covalently closed continuous loop and are highly represented in the eukaryotic transcriptome. They share a stable structure, high expression and often exhibit tissue/developmental-stage-specific expression. Emerging evidence indicates that circRNAs might play important roles in human disease, such as cancer, neurological disorders and atherosclerotic vascular disease risk. The huge potentials of circRNAs are recently being discovered from the laboratory to the clinic. CircRNAs might be developed as a potential novel and stable biomarker and potential drugs used in disease diagnosis and treatment. Here, we review the current understanding of the roles of circRNAs in human disease and their potential clinic significance in disease.

  2. Markers of potential malignancy in chronic hyperplastic candidiasis.

    Science.gov (United States)

    Darling, Mark R; McCord, Christina; Jackson-Boeters, Linda; Copete, Maria

    2012-08-01

    To examine the presence of markers associated with malignancy, including p53, p21 cyclin-dependent kinase inhibitor 1A, murine double minutes-2, and others, in chronic hyperplastic candidiasis. Immunohistochemical methods were used to examine the expression of p53, murine double minutes-2, p21 cyclin-dependent kinase inhibitor 1A, metallothionein, and proliferating cell nuclear antigen in 42 chronic hyperplastic candidiasis lesions and 11 non-infected control tissues. Terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling was used to examine apoptosis, which was correlated with p53 expression. These markers were measured in lesions of chronic hyperplastic candidiasis that did not show any epithelial dysplasia or histological signs of malignancy. p53 scores were higher in chronic hyperplastic candidiasis than in controls (P = 0.0046). Murine double-minutes 2 levels were not elevated. p21 cyclin-dependent kinase inhibitor 1A was increased in parabasal (P hyperplastic candidiasis lesions showed a similar basal/parabasal metallothionein staining pattern to that seen in normal squamous epithelium. Proliferating cell nuclear antigen was increased (P = 0.0007), as was apoptosis (P = 0.0033). Increased p53 in oral chronic hyperplastic candidiasis suggests an increased potential for malignant change in the epithelium, above that of normal tissues. Further functional investigation is required, as well as clinical follow-up studies. © 2012 Blackwell Publishing Asia Pty Ltd.

  3. Impaired pitch identification as a potential marker for depression.

    Science.gov (United States)

    Schwenzer, Michael; Zattarin, Eva; Grözinger, Michael; Mathiak, Klaus

    2012-04-19

    Impaired auditory performance has been considered as marker for depression. The present study tested whether pitch perception is affected in depression and whether the impairment is task-specific or reflects global dysfunction. Twelve depressive in-patients and 12 non-depressive participants, half of the sample women, volunteered. The participants performed pitch identification using a four-choice reaction task, pitch contour perception, and pitch discrimination. During pitch identification but not during pitch contour perception or pitch discrimination, depressive patients responded less accurate than non-depressive participants (F = 3.3, p = 0.047). An analysis of covariates revealed that only female but not male depressive patients identified pitches poorly (Z = -2.2, p = 0.025) and inaccurate pitch identification correlated with high scores in the Beck Depression Inventory in women (r = -0.8, p = 0.001) but not in men (r = -0.1, p = 0.745). Patients did not differ from controls in reaction time or responsiveness. Impaired pitch perception in depression is task-specific. Therefore, cognitive deficits in depression are circumscribed and not global. Reduced pitch identification in depression was associated with female sex. We suggest that impaired pitch identification merits attention as a potential marker for depression in women.

  4. Impaired pitch identification as a potential marker for depression

    Directory of Open Access Journals (Sweden)

    Schwenzer Michael

    2012-04-01

    Full Text Available Abstract Background Impaired auditory performance has been considered as marker for depression. The present study tested whether pitch perception is affected in depression and whether the impairment is task-specific or reflects global dysfunction. Methods Twelve depressive in-patients and 12 non-depressive participants, half of the sample women, volunteered. The participants performed pitch identification using a four-choice reaction task, pitch contour perception, and pitch discrimination. Results During pitch identification but not during pitch contour perception or pitch discrimination, depressive patients responded less accurate than non-depressive participants (F = 3.3, p = 0.047. An analysis of covariates revealed that only female but not male depressive patients identified pitches poorly (Z = −2.2, p = 0.025 and inaccurate pitch identification correlated with high scores in the Beck Depression Inventory in women (r = −0.8, p = 0.001 but not in men (r = −0.1, p = 0.745. Patients did not differ from controls in reaction time or responsiveness. Conclusions Impaired pitch perception in depression is task-specific. Therefore, cognitive deficits in depression are circumscribed and not global. Reduced pitch identification in depression was associated with female sex. We suggest that impaired pitch identification merits attention as a potential marker for depression in women.

  5. Markers of stem cells in human ovarian granulosa cells: is there a clinical significance in ART?

    Directory of Open Access Journals (Sweden)

    Varras Michail

    2012-11-01

    Full Text Available Abstract Background The purpose of the study was to determine the incidence of gene expression of Oct-4 and DAZL, which are typical markers for stem cells, in human granulosa cells during ovarian stimulation in women with normal FSH levels undergoing IVF or ICSI and to discover any clinical significance of such expression in ART. Methods Twenty one women underwent ovulation induction for IVF or ICSI and ET with standard GnRH analogue-recombinant FSH protocol. Infertility causes were male and tubal factor. Cumulus–mature oocyte complexes were denuded separately and granulosa cells were analyzed for each patient separately using quantitative reverse-transcription–polymerase chain reaction analysis for Oct-4 and DAZL gene expression with G6PD gene as internal standard. Results G6PD and Oct-4 mRNA was detected in the granulosa cells in 47.6% (10/21. The median of Oct-4 mRNA/G6PD mRNA was 1.75 with intra-quarteral range from 0.10 to 98.21. The OCT-4 mRNA expression was statistically significantly correlated with the number of oocytes retrieved; when the Oct-4 mRNA expression was higher, then more than six oocytes were retrieved (p=0.037, Wilcoxon rank-sum. No detection of DAZL mRNA was found in granulosa cells. There was no additional statistically significant correlation between the levels of Oct-4 expression and FSH basal levels or estradiol peak levels or dosage of FSH for ovulation induction. No association was found between the presence or absence of Oct-4 mRNA expression in granulosa cells and ovarian response to gonadotropin stimulation. Also, no influence on pregnancy was observed between the presence or absence of Oct-4 mRNA expression in granulosa cells or to its expression levels accordingly. Conclusions Expression of OCT-4 mRNA, which is a typical stem cell marker and absence of expression of DAZL mRNA, which is a typical germ cell marker, suggest that a subpopulation of luteinized granulosa cells in healthy ovarian follicles (47

  6. Heparanase, a potential marker for premalignant oral cavity cancer.

    Science.gov (United States)

    Leiser, Yoav; Shilo, Dekel; Abu El Naaj, Imad; Rachmiel, Adi

    2014-01-01

    In the past we have shown that the heparanase gene expression significantly correlates to oral cancer patient survival. Our aim was to study heparanase expression in all stages of carcinogenesis. Heparanase expression (mRNA and protein), as well as its enzymatic activity were studied separately in the nucleus and cytoplasm of both normal and cancerous cells using an in vivo oral cancer mouse model. Heparanase nuclear expression was associated with normal tissue; at the time carcinogenesis is initiated heparanase translocates to the cytoplasm and increases protein expression and enzymatic activity, as the cancer progresses. Heparanase overall expression is increased in cancer formation from premalignant to invasive squamous cell carcinoma (SCC). Heparanase is suggested to be a prognostic and diagnostic marker for oral premalignant lesions which could have a major impact on future prognosis and diagnosis of SCC of the oral cavity. Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  7. Beta blocker dose and markers of sympathetic activation in heart failure patients: interrelationships and prognostic significance.

    Science.gov (United States)

    Cohen-Solal, Alain; Jacobson, Arnold F; Piña, Ileana L

    2017-11-01

    Extent of cardiac sympathetic activation can be estimated from physiological parameters, blood biomarkers, and imaging findings. This study examined the prognostic value of three markers of sympathetic activity and their relationship to beta blocker dose in heart failure patients. A post hoc analysis of 858 heart failure subjects in the ADMIRE-HF trial was performed. Variables related to sympathetic activity were plasma norepinephrine, baseline heart rate, the heart to mediastinum (H/M) ratio of 123 I-mIBG uptake, and beta blocker dose. Univariate and multivariate analyses for occurrence of mortality (all-cause and cardiac) and arrhythmic events were performed. Beta blocker dose was significantly related to age, heart rate, b-type natriuretic peptide (negatively), body mass index, body weight and plasma norepinephrine. Univariate predictors of all-cause and cardiac mortality were baseline heart rate (χ2  = 4.5, P = 0.029 and χ2  = 5 .2, P = 0.022, respectively), plasma norepinephrine level (χ2  = 8.9, P = 0.0006 and χ2  = 8.6, P = 0.003, respectively), and H/M (χ = 22.4, P 67 b.p.m. was associated with significantly higher cardiac mortality. Higher beta blocker dose was associated with lower mortality, but of the variables associated with sympathetic activity examined, cardiac 123 I-mIBG uptake was the most powerful prognostic marker in heart failure patients. Elevated heart rate was associated with greater risk for cardiac death. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

  8. Significant association of rheumatoid arthritis-related inflammatory markers with non-surgical periodontal therapy.

    Science.gov (United States)

    Yang, Ning-Ya; Wang, Chen-Ying; Chyuan, I-Tsu; Wu, King-Jean; Tu, Yu-Kang; Chang, Ching-Wen; Hsu, Ping-Ning; Kuo, Mark Yen-Ping; Chen, Yi-Wen

    2017-11-22

    Chronic periodontitis (CP) and rheumatoid arthritis (RA) are the most common chronic inflammatory diseases and their immunopathogenesis is similar. The aim of this study was to evaluate the effect of non-surgical periodontal treatment on the serum levels of RA-related inflammatory markers in patients with chronic periodontitis. Thirty-one Taiwanese adults with CP were included. Demographics and periodontal parameters, including probing depth, clinical attachment level, and number of remaining teeth in the oral cavity, were recorded. All subjects received non-surgical periodontal treatment such as scaling and subgingival root planing. Serum samples were collected before and after the treatment. Serum levels of anti-citrullinated protein antibodies (ACPA), rheumatoid factor, tumor necrosis factor-α (TNF-α), C-reactive protein, interleukin-1β (IL-1β), and Interleukin-6 (IL-6) were measured using an enzyme-linked immunosorbent assay. Non-surgical periodontal treatment significantly reduced the serum ACPA (p = 0.015) and TNF-α levels (p = 0.026) in CP patients, particularly in patients with generalized CP. Furthermore, there was a significant and positive correlation between the number of extracted teeth and the reduction in the serum ACPA (p = 0.05) and IL-1β levels (p = 0.029) after non-surgical periodontal treatment. Non-surgical periodontal therapy may aid in the control of RA-related inflammatory markers in patients with CP. A large-scale study with well-defined populations is needed to clarify the benefit of non-surgical periodontal therapy. Copyright © 2017. Published by Elsevier B.V.

  9. Calprotectin is a potential prognostic marker for polycystic ovary syndrome.

    Science.gov (United States)

    Chen, Shouzhen; Jiang, Mei; Ding, Tao; Wang, Junmei; Long, Ping

    2017-03-01

    Background Calprotectin is an antimicrobial, calcium and zinc-binding heterocomplex protein and has been proposed as a marker to rule out inflammatory conditions. The aim of this study was to evaluate the role of calprotectin in the diagnosis of polycystic ovary syndrome and to investigate the association between calprotectin and insulin resistance. Methods A total of 41 females with polycystic ovary syndrome and 54 age-matched without polycystic ovary syndrome were eligible for the study. Serum concentration of calprotectin was determined using enzyme-linked immunosorbent assay. Clinical characteristics, hormone and metabolic parameters were evaluated in each subject. The predictive value of serum calprotectin was assessed using receiver operating characteristic curves. Correlations between the serum calprotectin concentrations and insulin resistance were examined using Spearman's correlation. Results We found that the serum calprotectin concentrations were significantly higher in polycystic ovary syndrome compared with the non-polycystic ovary syndrome group ( P polycystic ovary syndrome diagnosis. A significant positive correlation was found between the serum calprotectin and insulin resistance. Conclusions These results suggest that calprotectin might be a useful adjunct in the diagnosis of polycystic ovary syndrome, especially those with insulin resistance.

  10. Functional significance of the emotion-related late positive potential

    Directory of Open Access Journals (Sweden)

    Stephen B.R.E. Brown

    2012-02-01

    Full Text Available The late positive potential (LPP is an event-related potential component over visual cortical areas that is modulated by the emotional intensity of a stimulus. However, the functional significance of this neural modulation remains elusive. We conducted two experiments in which we studied the relation between LPP amplitude, subsequent perceptual sensitivity to a non-emotional stimulus (Experiment 1 and visual cortical excitability, as reflected by P1/N1 components evoked by this stimulus (Experiment 2. During the LPP modulation elicited by unpleasant stimuli, perceptual sensitivity and the P1 component were not affected. In contrast, we found some evidence for a decreased N1 amplitude during the LPP modulation, and consistent negative (but nonsignificant across-subject correlations between the magnitudes of the LPP modulation and corresponding changes in d-prime or P1/N1 amplitude. The results provide preliminary evidence that the LPP reflects a global inhibition of ongoing activity in visual cortex, resulting in the selective survival of activity associated with the processing of the emotional stimulus.

  11. Cell-free nucleic acids as potential markers for preeclampsia.

    Science.gov (United States)

    Hahn, S; Rusterholz, C; Hösli, I; Lapaire, O

    2011-02-01

    Preeclampsia is one of the leading causes of maternal and fetal/neonatal mortality and morbidity worldwide. Therefore, widely applicable and affordable tests are needed to make an early diagnosis before the occurrence of the clinical symptoms. Circulating cell-free nucleic acids in plasma and serum are novel biomarkers with promising clinical applications in different medical fields, including prenatal diagnosis. Quantitative changes of cell-free fetal (cff)DNA in maternal plasma as an indicator for impending preeclampsia have been reported in different studies, using real-time quantitative PCR for the male-specific SRY or DYS 14 loci. In case of early onset preeclampsia, elevated levels may be already seen in the first trimester. The increased levels of cffDNA before the onset of symptoms may be due to hypoxia/reoxygenation within the intervillous space leading to tissue oxidative stress and increased placental apoptosis and necrosis. In addition to the evidence for increased shedding of cffDNA into the maternal circulation, there is also evidence for reduced renal clearance of cffDNA in preeclampsia. As the amount of fetal DNA is currently determined by quantifying Y-chromosome specific sequences, alternative approaches such as the measurement of total cell-free DNA or the use of gender-independent fetal epigenetic markers, such as DNA methylation, offer a promising alternative. Cell-free RNA of placental origin might be another potentially useful biomarker for screening and diagnosis of preeclampsia in clinical practice. Fetal RNA is associated with subcellular placental particles that protect it from degradation. Its levels are ten-fold higher in pregnant women with preeclampsia compared to controls. In conclusion, through the use of gender-independent sequences, the universal incorporation of fetal nucleic acids into routine obstetric care and into screening or diagnostic settings using combined markers may soon become a reality. Effort has now to be put into

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

    Science.gov (United States)

    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

  13. Strong slime production is a marker of clinical significance in Staphylococcus epidermidis isolated from intravascular catheters.

    Science.gov (United States)

    Mateo, M; Maestre, J R; Aguilar, L; Giménez, M J; Granizo, J J; Prieto, J

    2008-04-01

    Biofilm production was assessed in 52 Staphylococcus epidermidis isolates from the catheters of 52 patients with catheter-related bloodstream infections (CR-BSI) and compared with 14 isolates from the skin of healthy volunteers by spectrophotometry. The isolates were classified as non- (G1), weak- (G2) or strong- (G3) slime producers based on optical density, and as producers and non-producers based on the results of the Congo red agar test. Differences (p = 0.012) in the proportion of G1, G2 and G3 among the isolates were found between catheter and healthy skin strains: there was a higher percentage of G1 types among the healthy skin strains (35.7 vs. 11.5%; p = 0.046) and a higher percentage of G3 types among the catheter isolates (44.2 vs. 0%; p = 0.001). No significant differences were found with the Congo red agar test. G3 is a phenotypic marker for CR-BSI.

  14. Potential significance of physiological and pharmacological glucocorticoids in early pregnancy.

    Science.gov (United States)

    Michael, Anthony E; Papageorghiou, Aris T

    2008-01-01

    Despite extensive studies of the developmental consequences of increased glucocorticoid exposure in mid- to late pregnancy, relatively little is known regarding the significance of glucocorticoids in early pregnancy. The objective of this review was to consider potential roles for this family of corticosteroids that might relate to early pregnancy. Although this is a narrative review, 249 source articles addressing potential effects of glucocorticoids on aspects of early pregnancy and development (published between 1997 and 2007) were identified using a systematic literature search. Additional articles (115) were identified if cited by the primary reference articles identified in the systematic phase of the review. Much of the evidence to implicate glucocorticoids in early pregnancy comes from studies of steroid receptors and the 11beta-hydroxysteroid dehydrogenase enzymes, which modulate cortisol action in the endometrium/decidua, trophoblast, placenta and embryo/fetus. The evidence reviewed suggests that in early pregnancy the actions of glucocorticoids are balanced between positive effects that would promote pregnancy (e.g. stimulation of hCG secretion, suppression of uterine natural killer cells, and promotion of trophoblast growth/invasion) versus adverse effects that would be expected to compromise the pregnancy (e.g. inhibition of cytokine-prostaglandin signalling, restriction of trophoblast invasion following up-regulation of plasminogen activation inhibitor-1, induction of apoptosis, and inhibition of embryonic and placental growth). Glucocorticoids exert many actions that could impact both negatively and positively on key aspects of early pregnancy. These steroids may also be implicated in obstetric complications, including intra-uterine growth restriction, pre-term labour, pre-eclampsia and chorio-aminionitis.

  15. Impaired pitch identification as a potential marker for depression

    National Research Council Canada - National Science Library

    Schwenzer, Michael; Zattarin, Eva; Grözinger, Michael; Mathiak, Klaus

    2012-01-01

    Impaired auditory performance has been considered as marker for depression. The present study tested whether pitch perception is affected in depression and whether the impairment is task-specific or reflects global dysfunction...

  16. Potential predictive markers of chemotherapy resistance in stage III ovarian serous carcinomas

    Directory of Open Access Journals (Sweden)

    Olsson Björn

    2009-10-01

    Full Text Available Abstract Background Chemotherapy resistance remains a major obstacle in the treatment of women with ovarian cancer. Establishing predictive markers of chemoresponse would help to individualize therapy and improve survival of ovarian cancer patients. Chemotherapy resistance in ovarian cancer has been studied thoroughly and several non-overlapping single genes, gene profiles and copy number alterations have been suggested as potential markers. The objective of this study was to explore genetic alterations behind chemotherapy resistance in ovarian cancer with the ultimate aim to find potential predictive markers. Methods To create the best opportunities for identifying genetic alterations of importance for resistance, we selected a homogenous tumor material concerning histology, stage and chemotherapy. Using high-resolution whole genome array comparative genomic hybridization (CGH, we analyzed the tumor genomes of 40 fresh-frozen stage III ovarian serous carcinomas, all uniformly treated with combination therapy paclitaxel/carboplatin. Fisher's exact test was used to identify significant differences. Subsequently, we examined four genes in the significant regions (EVI1, MDS1, SH3GL2, SH3KBP1 plus the ABCB1 gene with quantitative real-time polymerase chain reaction (QPCR to evaluate the impact of DNA alterations on the transcriptional level. Results We identified gain in 3q26.2, and losses in 6q11.2-12, 9p22.3, 9p22.2-22.1, 9p22.1-21.3, Xp22.2-22.12, Xp22.11-11.3, and Xp11.23-11.1 to be significantly associated with chemotherapy resistance. In the gene expression analysis, EVI1 expression differed between samples with gain versus without gain, exhibiting higher expression in the gain group. Conclusion In conclusion, we detected specific genetic alterations associated with resistance, of which some might be potential predictive markers of chemotherapy resistance in advanced ovarian serous carcinomas. Thus, further studies are required to validate

  17. Estimation of Radiative Efficiency of Chemicals with Potentially Significant Global Warming Potential

    Data.gov (United States)

    U.S. Environmental Protection Agency — The set of commercially available chemical substances in commerce that may have significant global warming potential (GWP) is not well defined. Although there are...

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

    Science.gov (United States)

    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.

  19. Clinical significance of markers of collagen metabolism in rheumatic mitral valve disease.

    Science.gov (United States)

    Banerjee, Tanima; Mukherjee, Somaditya; Ghosh, Sudip; Biswas, Monodeep; Dutta, Santanu; Pattari, Sanjib; Chatterjee, Shelly; Bandyopadhyay, Arun

    2014-01-01

    Rheumatic Heart Disease (RHD), a chronic acquired heart disorder results from Acute Rheumatic Fever. It is a major public health concern in developing countries. In RHD, mostly the valves get affected. The present study investigated whether extracellular matrix remodelling in rheumatic valve leads to altered levels of collagen metabolism markers and if such markers can be clinically used to diagnose or monitor disease progression. This is a case control study comprising 118 subjects. It included 77 cases and 41 healthy controls. Cases were classified into two groups- Mitral Stenosis (MS) and Mitral Regurgitation (MR). Carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP), total Matrix Metalloproteinase-1(MMP-1) and Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) were assessed. Histopathology studies were performed on excised mitral valve leaflets. A p value marker (AUC = 0.95; 95% CI = 0.91-0.99; p459 ng/mL for PICP provided 91% sensitivity, 90% specificity and a likelihood ratio of 9 in diagnosing RHD. Histopathology analysis revealed inflammation, scarring, neovascularisation and extensive leaflet fibrosis in diseased mitral valve. Levels of collagen metabolism markers correlated with echocardiographic parameters for RHD diagnosis.

  20. The Clinical Significance of DC-SIGN and DC-SIGNR, which Are Novel Markers Expressed in Human Colon Cancer

    Science.gov (United States)

    Chen, Kai; Chen, Zhe; Sun, Zhigang; Zhang, Zhuqing; Ding, Dongbing; Ren, Shuangyi; Zuo, Yunfei

    2014-01-01

    Background Colon cancer has always been diagnosed at a late stage, which is associated with poor prognosis. The currently used serum tumor markers CEA and CA19-9 display low sensitivity and specificity and may not have diagnostic value in early stage colon cancer. Thus, there is an urgent need to identify novel serum biomarkers for use in the early detection of colon cancer. Methods In this study, the expression of DC-SIGN and DC-SIGNR in serum was detected by enzyme-linked immunosorbent assay (ELISA). DC-SIGN and DC-SIGNR expression was detected in cancer tissues by immunohistochemistry (IHC). Results The level of sDC-SIGN was lower in patients than in the healthy controls, while the level of sDC-SIGNR in patients was higher than in the healthy controls. Both sDC-SIGN and sDC-SIGNR had diagnostic significances for cancer patients, and the combined diagnosis of these two markers was higher than both of them alone. Furthermore, there were significant differences between both sDC-SIGN and sDC-SIGNR in stage I/II patients and the healthy controls. Moreover, high sDC-SIGN level was accompanied with the long survival time. Additionally, DC-SIGNR was negative in the cancer foci and matched normal colon tissues but was weakly positive between the cancer foci. DC-SIGN staining was faint in matched normal colon tissues, strong in the tumor stroma and the invasive margin of colon cancer tissues, and negatively correlated with the sDC-SIGN level in serum from the same patient. Interestingly, the percent survival of patients with a DC-SIGN mean density of>0.001219 (the upper 95% confidence interval of matched normal colon tissues) was higher than for all other patients. Conclusion DC-SIGN and DC-SIGNR are blood-based molecular markers that can potentially be used for the diagnosis of early stage patients. Moreover, expression of DC-SIGN in serum and cancer tissues may affect the survival time for colon cancer patients. PMID:25504222

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

    Science.gov (United States)

    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…

  2. Multiplex polymerase chain reaction of genetic markers for detection of potentially pathogenic environmental Legionella pneumophila isolates

    Directory of Open Access Journals (Sweden)

    Arvind Valavane

    2017-01-01

    Interpretation & conclusions: The findings of this study showed the presence of gene markers of pathogenic potential of the bacterium L. pneumophila. However, the genomic constitution of the environmental isolates should be correlated with clinical isolates to prove their pathogenic potential. Rapid diagnostic methods such as multiplex PCR reported here, for elucidating gene markers, could help in future epidemiological studies of bacterium L. pneumophila.

  3. LRIG1 as a potential novel marker for neoplastic transformation in ocular surface squamous neoplasia.

    Science.gov (United States)

    Nagata, Maho; Nakamura, Takahiro; Sotozono, Chie; Inatomi, Tsutomu; Yokoi, Norihiko; Kinoshita, Shigeru

    2014-01-01

    The leucine rich repeats and immunoglobulin-like protein 1 (LRIG1) is a newly discovered negative regulator of epidermal growth factor receptor (EGFR) and a proposed tumor suppressor. It is not universally downregulated in human cancers, and its role in neoplastic transformation and tumorigenesis is not well-documented. In this study, we show the expression of LRIG1 as a novel potential marker for neoplastic transformation in ocular-surface squamous neoplasia (OSSN). The following two groups were included in this study: 1) benign group (3 cases; 1 with papilloma and 2 with dysplasia) and 2) malignant group (3 cases with squamous cell carcinoma (SCC)). In both groups, immunofluorescence analysis was firstly performed for keratins 4, 12, 13, and 15 to characterize the state of differentiation, and for Ki67 to evaluate the proliferation activity. Subsequently, LRIG1 and EGFR expression was analyzed. Either keratin 4 and/or 13, both non-keratinized epithelial cell markers, were generally expressed in both groups, except for 1 severe SCC case. Keratin 15, an undifferentiated basal cell marker, was more strongly expressed in the malignant cases than in the benign cases. The Ki67 index was significantly higher (Pbasal epithelial cells in normal corneal epithelial tissue. Interestingly, LRIG1 was expressed throughout the epithelium in all the benign cases. In contrast, its expression was limited or totally disappeared in the malignant cases. Inversely, EGFR staining was faintly expressed in the benign cases, yet strongly expressed in the malignant cases. Malignant tissue with proliferative potential presented EGFR overexpression and inverse downregulation of LRIG1, consistent with LRIG1 being a suppressor of neoplastic transformation by counteracting the tumor growth property of EGFR. Our findings indicate that downregulation of LRIG1 is possibly a novel potential marker of transformation and tumorigenesis in OSSN cases.

  4. LRIG1 as a potential novel marker for neoplastic transformation in ocular surface squamous neoplasia.

    Directory of Open Access Journals (Sweden)

    Maho Nagata

    Full Text Available The leucine rich repeats and immunoglobulin-like protein 1 (LRIG1 is a newly discovered negative regulator of epidermal growth factor receptor (EGFR and a proposed tumor suppressor. It is not universally downregulated in human cancers, and its role in neoplastic transformation and tumorigenesis is not well-documented. In this study, we show the expression of LRIG1 as a novel potential marker for neoplastic transformation in ocular-surface squamous neoplasia (OSSN. The following two groups were included in this study: 1 benign group (3 cases; 1 with papilloma and 2 with dysplasia and 2 malignant group (3 cases with squamous cell carcinoma (SCC. In both groups, immunofluorescence analysis was firstly performed for keratins 4, 12, 13, and 15 to characterize the state of differentiation, and for Ki67 to evaluate the proliferation activity. Subsequently, LRIG1 and EGFR expression was analyzed. Either keratin 4 and/or 13, both non-keratinized epithelial cell markers, were generally expressed in both groups, except for 1 severe SCC case. Keratin 15, an undifferentiated basal cell marker, was more strongly expressed in the malignant cases than in the benign cases. The Ki67 index was significantly higher (P<0.002 in the malignant group (33.2% than in the benign group (10.9%. LRIG1 expression was limited to basal epithelial cells in normal corneal epithelial tissue. Interestingly, LRIG1 was expressed throughout the epithelium in all the benign cases. In contrast, its expression was limited or totally disappeared in the malignant cases. Inversely, EGFR staining was faintly expressed in the benign cases, yet strongly expressed in the malignant cases. Malignant tissue with proliferative potential presented EGFR overexpression and inverse downregulation of LRIG1, consistent with LRIG1 being a suppressor of neoplastic transformation by counteracting the tumor growth property of EGFR. Our findings indicate that downregulation of LRIG1 is possibly a novel

  5. Impaired pitch identification as a potential marker for depression

    OpenAIRE

    Schwenzer Michael; Zattarin Eva; Grözinger Michael; Mathiak Klaus

    2012-01-01

    Abstract Background Impaired auditory performance has been considered as marker for depression. The present study tested whether pitch perception is affected in depression and whether the impairment is task-specific or reflects global dysfunction. Methods Twelve depressive in-patients and 12 non-depressive participants, half of the sample women, volunteered. The participants performed pitch identification using a four-choice reaction task, pitch contour perception, and pitch discrimination. R...

  6. Association mapping to discover significant marker-trait associations for resistance against fusarium wilt variant 2 in pigeonpea [Cajanus cajan (L.) Millspaugh] using SSR markers.

    Science.gov (United States)

    Patil, Prakash G; Dubey, Jyotirmay; Bohra, Abhishek; Mishra, R K; Saabale, P R; Das, Alok; Rathore, Meenal; Singh, N P

    2017-08-01

    Pigeonpea production is severely constrained by wilt disease caused by Fusarium udum. In the current study, we discover the putative genomic regions that control resistance response to variant 2 of fusarium wilt using association mapping approach. The association panel comprised of 89 diverse pigeonpea genotypes including seven varieties, three landraces and 79 germplasm lines. The panel was screened rigorously for 3 consecutive years (2013-14, 2014-15 and 2015-2016) against variant 2 in a wilt-sick field. A total of 65 pigeonpea specific hypervariable SSR markers (HASSRs) were screened representing seven linkage groups and 29 scaffolds of the pigeonpea genome. A total of 181 alleles were detected, with average values of gene diversity and polymorphism information content (PIC) of 0.55 and 0.47, respectively. Further analysis using model based (STRUCTURE) and distance based (clustering) approaches separated the entire pigeonpea collection into two distinct subgroups (K = 2). The marker trait associations (MTAs) were established based on three-year wilt incidence data and SSR dataset using a unified mixed linear model. Consequently, six SSR markers were identified, which were significantly associated with wilt resistance and explained up to 6% phenotypic variance (PV) across the years. Among these SSRs, HASSR18 was found to be the most stable and significant, accounting for 5-6% PV across the years. To the best of our knowledge, this is the first report of identification of favourable alleles for resistance to variant 2 of Fusarium udum in pigeonpea using association mapping. The SSR markers identified here will greatly facilitate marker assisted resistance breeding against fusarium wilt in pigeonpea.

  7. Iraq`s significant hydrocarbon potential remains relatively undeveloped

    Energy Technology Data Exchange (ETDEWEB)

    AL-Gailani, M. [GeoDesign Ltd., Kingston-upon-Thames (United Kingdom)

    1996-07-29

    Iraq is probably one of the least explored countries in the Middle East, despite the fact that it possesses one of the richest hydrocarbon basins in the world almost on a par to Saudi Arabia`s potential, if not more. The aim of this article is to state the facts about Iraq and focus on the huge but untapped and undeveloped hydrocarbon resources to the international oil community. Perhaps it is best to start by describing briefly the sedimentary and tectonic elements responsible for accumulating such large hydrocarbon resources. The paper describes the basin, tectonic elements, structural anomalies, deep drilling, source rocks, reservoir rocks, characteristics, and new reserves.

  8. Intermittent Feeding Schedules—Behavioural Consequences and Potential Clinical Significance

    Directory of Open Access Journals (Sweden)

    Michelle Murphy

    2014-03-01

    Full Text Available Food availability and associated sensory cues such as olfaction are known to trigger a range of hormonal and behavioural responses. When food availability is predictable these physiological and behavioural responses can become entrained to set times and occur in anticipation of food rather than being dependent on the food-related cues. Here we summarise the range of physiological and behavioural responses to food when the time of its availability is unpredictable, and consider the potential to manipulate feeding patterns for benefit in metabolic and mental health.

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

    Directory of Open Access Journals (Sweden)

    Guita Rubinsky-Elefant

    2011-04-01

    Full Text Available 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.

  10. Significance Of 30 KD Protein As A Diagnostic Marker In CSF Of tuberculour Meningits

    Directory of Open Access Journals (Sweden)

    Kashyap R.S

    2001-01-01

    Full Text Available Tuberculous meningitis (TBM is a sub acute or chronic inflammation of the cerebral meninges caused by tubercule bacilli, the diagnosis for which is still very intricate. To establish a rapid diagnosis, we used Sodium dodecyl suplhate polyacrylamide gel electrophoresis (SDS-PAGE for the detection of marker protein in CSF specific to TBM patients. CSF was collected by standard lumbar puncture technique. Polyclonal antibody was raised against sonicated M.tuberculosis of H37RV in rabbit. 145 CSF samples were collected for this study over a period of two and half years which included 44 suspected and one proven case of TBM. In this communication we have investigated for a possible presence of a marker protein(s in cerebrospinal fluid (CSF of TBM patients. Two bands, a 30kd and a 14kd were detected. The 30kd band was observed in 92% cases of TBM patients. The 14kd band was not much of diagnostic importance since it was found in only about 45%. None of the control group patients had these protein bands. The 30 kd protein band either disappeared or became faint on anti-TB medication. To evaluate whether the eluted 30 kd protein was a mycobacterium tuberculosis product, gel retardation assay was also performed. The 30kd protein did not react with the polyclonal antisera. The CSF biochemical picture correlated well with the presence of this protein band. This study suggests that 30kd protein band observed in CSF is not a Mycobacterium product and is not only an important diagnostic marker for early diagnosis of TBM but may also be useful for monitoring the post treatment phase.

  11. Advances in Carcinogenic Metal Toxicity and Potential Molecular Markers

    Directory of Open Access Journals (Sweden)

    Preeyaporn Koedrith

    2011-12-01

    Full Text Available 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.

  12. Advances in carcinogenic metal toxicity and potential molecular markers.

    Science.gov (United States)

    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.

  13. Advances in Carcinogenic Metal Toxicity and Potential Molecular Markers

    Science.gov (United States)

    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

  14. Breath acetone as a potential marker in clinical practice.

    Science.gov (United States)

    Ruzsányi, Veronika; Péter Kalapos, Miklós

    2017-06-01

    In recent decades, two facts have changed the opinion of researchers about the function of acetone in humans. Firstly, it has turned out that acetone cannot be regarded as simply a waste product of metabolism, because there are several pathways in which acetone is produced or broken down. Secondly, methods have emerged making possible its detection in exhaled breath, thereby offering an attractive alternative to investigation of blood and urine samples. From a clinical point of view the measurement of breath acetone levels is important, but there are limitations to its wide application. These limitations can be divided into two classes, technical and biological limits. The technical limits include the storage of samples, detection threshold, standardization of clinical settings, and the price of instruments. When considering the biological ranges of acetone, personal factors such as race, age, gender, weight, food consumption, medication, illicit drugs, and even profession/class have to be taken into account to use concentration information for disorders. In some diseases such as diabetes mellitus and lung cancer, as well as in nutrition-related behavior such as starvation and ketogenic diet, breath acetone has been extensively examined. At the same time, there is a lack of investigations in other cases in which ketosis is also evident, such as in alcoholism or an inborn error of metabolism. In summary, the detection of acetone in exhaled breath is a useful and promising tool for diagnosis and it can be used as a marker to follow the effectiveness of treatments in some disorders. However, further endeavors are needed for clarification of the exact distribution of acetone in different body compartments and evaluation of its complex role in humans, especially in those cases in which a ketotic state also occurs.

  15. Estimation of Radiative Efficiency of Chemicals with Potentially Significant Global Warming Potential

    Science.gov (United States)

    The set of commercially available chemical substances in commerce that may have significant global warming potential (GWP) is not well defined. Although there are currently over 200 chemicals with high GWP reported by the Intergovernmental Panel on Climate Change, World Meteorological Organization, or Environmental Protection Agency, there may be hundreds of additional chemicals that may also have significant GWP. Evaluation of various approaches to estimate radiative efficiency (RE) and atmospheric lifetime will help to refine GWP estimates for compounds where no measured IR spectrum is available. This study compares values of RE calculated using computational chemistry techniques for 235 chemical compounds against the best available values. It is important to assess the reliability of the underlying computational methods for computing RE to understand the sources of deviations from the best available values. Computed vibrational frequency data is used to estimate RE values using several Pinnock-type models. The values derived using these models are found to be in reasonable agreement with reported RE values (though significant improvement is obtained through scaling). The effect of varying the computational method and basis set used to calculate the frequency data is also discussed. It is found that the vibrational intensities have a strong dependence on basis set and are largely responsible for differences in computed values of RE in this study. Deviations of

  16. Cyclin A and cyclin D1 as significant prognostic markers in colorectal cancer patients

    Directory of Open Access Journals (Sweden)

    Mahmoud Moustafa

    2004-09-01

    Full Text Available Abstract Background Colorectal cancer is a common cancer all over the world. Aberrations in the cell cycle checkpoints have been shown to be of prognostic significance in colorectal cancer. Methods The expression of cyclin D1, cyclin A, histone H3 and Ki-67 was examined in 60 colorectal cancer cases for co-regulation and impact on overall survival using immunohistochemistry, southern blot and in situ hybridization techniques. Immunoreactivity was evaluated semi quantitatively by determining the staining index of the studied proteins. Results There was a significant correlation between cyclin D1 gene amplification and protein overexpression (concordance = 63.6% and between Ki-67 and the other studied proteins. The staining index for Ki-67, cyclin A and D1 was higher in large, poorly differentiated tumors. The staining index of cyclin D1 was significantly higher in cases with deeply invasive tumors and nodal metastasis. Overexpression of cyclin A and D1 and amplification of cyclin D1 were associated with reduced overall survival. Multivariate analysis shows that cyclin D1 and A are two independent prognostic factors in colorectal cancer patients. Conclusions Loss of cell cycle checkpoints control is common in colorectal cancer. Cyclin A and D1 are superior independent indicators of poor prognosis in colorectal cancer patients. Therefore, they may help in predicting the clinical outcome of those patients on an individual basis and could be considered important therapeutic targets.

  17. Salivary TNF-alpha: A potential marker of periodontal destruction

    Directory of Open Access Journals (Sweden)

    Pritma Singh

    2014-01-01

    Full Text Available Aims and Objectives: (1 To evaluate the effect of type 2 diabetes mellitus on salivary TNF-α level in chronic periodontitis. (2 To evaluate the effect of smoking on salivary TNF-α level in chronic periodontitis. (3 To compare and correlate TNF-α level with the healthy individuals. Materials and Methods: Subjects aged 30-35 years were included for the study and divided into four groups as a group of 20 systemically and periodontally healthy individuals (group I, a group of 20 subjects with pocket probing depth (PPD ≥5 mm and clinical attachment loss (CAL of ≥2 mm (group II, a group of 20 diabetic subjects (of more than 5 years with periodontal parameters as of group II as (group III and a group of 20 subjects smoking (≥10 cigarettes a day with periodontal parameters of group II as (group IV. Periodontal parameters of PPD, CAL, gingival index (GI, and plaque index (PI were measured using standard indices and criteria. Three milliliter of unstimulated saliva was taken and salivary TNF-α determined by using ELISA technique (Quantikine Human total TNF-A immunoassay kit. Results: Data revealed highest mean TNF-α in group III followed by group IV, group II, and group I. Mean TNF-α of both group III (76.1% and group IV (48.8% was significantly higher as compared to group I (P 0.05 and a significant negative correlation was observed between CAL and TNF-α in group IV. Conclusion: Our study clearly underlines a profound impact of diabetes and smoking on salivary TNF-α in chronic periodontitis subjects in comparison to healthy subjects. Moreover, diabetes status increased TNF-α significantly in comparison to smoking in chronic periodontitis patients.

  18. Salivary TNF-alpha: A potential marker of periodontal destruction.

    Science.gov (United States)

    Singh, Pritma; Gupta, Narender Dev; Bey, Afshan; Khan, Saif

    2014-05-01

    (1) To evaluate the effect of type 2 diabetes mellitus on salivary TNF-α level in chronic periodontitis. (2) To evaluate the effect of smoking on salivary TNF-α level in chronic periodontitis. (3) To compare and correlate TNF-α level with the healthy individuals. Subjects aged 30-35 years were included for the study and divided into four groups as a group of 20 systemically and periodontally healthy individuals (group I), a group of 20 subjects with pocket probing depth (PPD) ≥5 mm and clinical attachment loss (CAL) of ≥2 mm (group II), a group of 20 diabetic subjects (of more than 5 years) with periodontal parameters as of group II as (group III) and a group of 20 subjects smoking (≥10 cigarettes a day) with periodontal parameters of group II as (group IV). Periodontal parameters of PPD, CAL, gingival index (GI), and plaque index (PI) were measured using standard indices and criteria. Three milliliter of unstimulated saliva was taken and salivary TNF-α determined by using ELISA technique (Quantikine Human total TNF-A immunoassay kit). Data revealed highest mean TNF-α in group III followed by group IV, group II, and group I. Mean TNF-α of both group III (76.1%) and group IV (48.8%) was significantly higher as compared to group I (P 0.05) and a significant negative correlation was observed between CAL and TNF-α in group IV. Our study clearly underlines a profound impact of diabetes and smoking on salivary TNF-α in chronic periodontitis subjects in comparison to healthy subjects. Moreover, diabetes status increased TNF-α significantly in comparison to smoking in chronic periodontitis patients.

  19. Dysphonations in infant cry: A potential marker for health status

    Science.gov (United States)

    Abbs, Katlin J.

    Sudden infant death syndrome (SIDS) is defined as an unexplained death in an infant's first year of life. Risk factors for SIDS include maternal smoking, sex, and infant sleep positioning, among others. The current study analyzed dysphonations in the cries of 32 infants 24-66 hours after birth. Dysphonations are acoustic characteristics of cries and include frequency shift (FS), harmonic doubling (HD), biphonation (BP), and noise (N). An interaction effect was found, male infants whose mothers smoked during pregnancy (maternal smoking status) had a significantly lower percent of dysphonations than male infants whose mothers did not smoke during pregnancy (no maternal smoking status). No significant main effects were found for the factors maternal smoking status, sex, infant positioning, or partition. In addition, the types of dysphonations were consistently distributed across groups with noise being the most commonly occurring dysphonation followed by harmonic doubling, frequency shift and then biphonation. It is hypothesized that differences in number and type of dysphonations may either be an effect of differences in infant arousal and/or developmental differences. A lower number of dysphonations seen in male infants with mothers who smoked during pregnancy may suggest a lowered arousal state, which may be associated with the occurrence of SIDS.

  20. Mast Cells as a Potential Prognostic Marker in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Gianluigi Taverna

    2013-01-01

    Full Text Available Despite years of intensive investigation that has been made in understanding prostate cancer, it remains one of the major men’s health issues and the leading cause of death worldwide. It is now ascertained that prostate cancer emerges from multiple spontaneous and/or inherited alterations that induce changes in expression patterns of genes and proteins that function in complex networks controlling critical cellular events. It is now accepted that several innate and adaptive immune cells, including T- and B-lymphocytes, macrophages, natural killer cells, dendritic cells, neutrophils, eosinophils, and mast cells (MCs, infiltrate the prostate cancer. All of these cells are irregularly scattered within the tumor and loaded with an assorted array of cytokines, chemokines, and inflammatory and cytotoxic mediators. This complex framework reflects the diversity in tumor biology and tumor-host interactions. MCs are well-established effector cells in Immunoglobulin-E (Ig-E associated immune responses and potent effector cells of the innate immune system; however, their clinical significance in prostate cancer is still debated. Here, these controversies are summarized, focusing on the implications of these findings in understanding the roles of MCs in primary prostate cancer.

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

    Science.gov (United States)

    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.

  2. Estimation of Radiative Efficiency of Chemicals with Potentially Significant Global Warming Potential.

    Science.gov (United States)

    Betowski, Don; Bevington, Charles; Allison, Thomas C

    2016-01-19

    Halogenated chemical substances are used in a broad array of applications, and new chemical substances are continually being developed and introduced into commerce. While recent research has considerably increased our understanding of the global warming potentials (GWPs) of multiple individual chemical substances, this research inevitably lags behind the development of new chemical substances. There are currently over 200 substances known to have high GWP. Evaluation of schemes to estimate radiative efficiency (RE) based on computational chemistry are useful where no measured IR spectrum is available. This study assesses the reliability of values of RE calculated using computational chemistry techniques for 235 chemical substances against the best available values. Computed vibrational frequency data is used to estimate RE values using several Pinnock-type models, and reasonable agreement with reported values is found. Significant improvement is obtained through scaling of both vibrational frequencies and intensities. The effect of varying the computational method and basis set used to calculate the frequency data is discussed. It is found that the vibrational intensities have a strong dependence on basis set and are largely responsible for differences in computed RE values.

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

    Science.gov (United States)

    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.

  4. Neural differentiation potential of human bone marrow-derived mesenchymal stromal cells: misleading marker gene expression

    Directory of Open Access Journals (Sweden)

    Montzka Katrin

    2009-03-01

    Full Text Available Abstract Background In contrast to pluripotent embryonic stem cells, adult stem cells have been considered to be multipotent, being somewhat more restricted in their differentiation capacity and only giving rise to cell types related to their tissue of origin. Several studies, however, have reported that bone marrow-derived mesenchymal stromal cells (MSCs are capable of transdifferentiating to neural cell types, effectively crossing normal lineage restriction boundaries. Such reports have been based on the detection of neural-related proteins by the differentiated MSCs. In order to assess the potential of human adult MSCs to undergo true differentiation to a neural lineage and to determine the degree of homogeneity between donor samples, we have used RT-PCR and immunocytochemistry to investigate the basal expression of a range of neural related mRNAs and proteins in populations of non-differentiated MSCs obtained from 4 donors. Results The expression analysis revealed that several of the commonly used marker genes from other studies like nestin, Enolase2 and microtubule associated protein 1b (MAP1b are already expressed by undifferentiated human MSCs. Furthermore, mRNA for some of the neural-related transcription factors, e.g. Engrailed-1 and Nurr1 were also strongly expressed. However, several other neural-related mRNAs (e.g. DRD2, enolase2, NFL and MBP could be identified, but not in all donor samples. Similarly, synaptic vesicle-related mRNA, STX1A could only be detected in 2 of the 4 undifferentiated donor hMSC samples. More significantly, each donor sample revealed a unique expression pattern, demonstrating a significant variation of marker expression. Conclusion The present study highlights the existence of an inter-donor variability of expression of neural-related markers in human MSC samples that has not previously been described. This donor-related heterogeneity might influence the reproducibility of transdifferentiation protocols as

  5. ATF1 and RAS in exosomes are potential clinical diagnostic markers for cervical cancer.

    Science.gov (United States)

    Shi, Yanhua; Wang, Wei; Yang, Baozhi; Tian, Hongge

    2017-10-01

    Cervical cancer is one of the most common cancers among women worldwide. It is highly lethal yet can be treated when found in early stage. Thus, early detection is of significant important for early diagnosis of cervical cancer. Exosomes have been used as biomarkers in clinical diagnosis. It is unknown that whether blood exosomes associated with cervical cancer can be detected and if these exosomes can accurately represent the developmental stage of cervical cancer. Mouse models were made out of a relapsed cervical cancer patient's tumour sample for original and recurrent cervical cancer, and gene analysis in both tumours and exosomes in these mouse models were performed. We found that activating transcription factor 1 (ATF1) and RAS genes were significantly up-regulated in tumours of both primary and recurrent cervical cancer mouse model, and they can also be detected in the blood exosomes of the mouse model. Our results indicated that ATF1 and RAS could be potential candidate biomarkers for cervical cancer in early diagnosis. ATF1 and RAS genes were found significantly elevated in tumours of primary and recurrent cervical cancer mouse model, and they were also detected in the blood exosomes. Therefore, ATF1 and RAS could be used as a diagnostic marker for cervical cancer in the future. Copyright © 2017 John Wiley & Sons, Ltd.

  6. An immunohistochemical study and review of potential markers of human intestinal M cells

    Directory of Open Access Journals (Sweden)

    NACS Wong

    2009-06-01

    Full Text Available M cells are found in intestinal follicle associated epithelium. Studies into the physiological and pathological roles of human M cells have been hampered by the lack of well-substantiated, specific markers for these cells. A critical literature review suggests the following molecules may potentially serve as such markers: CK7, FcaR (CD89, S100, CD1a, CD21, CD23, sialyl Lewis A, and cathepsin E. Normal ileum, appendix and colorectum were studied using paraffinembedded, formalin-fixed tissue and immunohistochemistry for these 8 markers. Cathepsin E immunohistochemistry was also performed on cases of colorectal adenocarcinoma, colorectal adenoma, colorectal hyperplastic/metaplastic polyp, lymphocytic colitis, collagenous colitis, pseudomembranous colitis and active ulcerative colitis. Of the 8 markers tested, only cathepsin E appeared to be specific to follicle associated epithelium (expressed by cells with and without M cell morphology and follicular crypt epithelium; this specificity was limited to the colorectum. Focal epithelial expression of cathepsin E was seen in adenocarcinoma, adenoma, hyperplastic/metaplastic polyp, ulcerative colitis and pseudomembranous colitis. In conclusion, cathepsin E is a specific marker of normal colorectal follicle associated epithelium and follicular crypt epithelium though is not specific to M cells within these compartments. None of the other 7 markers studied is exclusively expressed by human M cells.

  7. The comparison of thrombocytosis and platelet-lymphocyte ratio as potential prognostic markers in colorectal cancer

    DEFF Research Database (Denmark)

    Baranyai, Zsolt; Krzystanek, Marcin; Josa, Valeria

    2014-01-01

    The aim of the present study was to analyse the preoperative platelet count and the platelet-lymphocyte ratio (PLR) in patients with colorectal cancer (CRC) of different stages and with hepatic metastasis of CRC (mCRC) and to compare these factors as potential prognostic markers. Clinicopathologi...

  8. Potential hydrophobic protein markers of breast cancer in Malaysian Chinese, Malay and Indian patients.

    Science.gov (United States)

    Liang, Seng; Singh, Manjit; Gam, Lay-Harn

    Breast cancer is a leading cause of worldwide mortality in females. In Malaysia, breast cancer is the most commonly diagnosed cancer in women. Of these, the Chinese had the most number of breast cancer cases, followed by the Indian and the Malay. The most common type of breast cancer is infiltrating ductal carcinoma (IDC). A proteomic approach was used to identify protein profile changes in cancerous tissues compared with the normal tissues, the tissues were collected from patients of three different ethnicities, i.e. Chinese, Malay and Indian. Ten differentially expressed hydrophobic proteins were identified. We had evaluated the potential of these proteins as biomarker for infiltrating ducal carcinoma (IDC) and the ethnic-specific expression of these proteins was also determined. The data showed that peroxiredoxin-2, heat shock protein 60, protein disulfide isomerase and calreticulin may serve as ethnic-related potential markers for either one or combination of Chinese, Malay and Indian cohorts as their expression levels were significantly high in the cancerous tissues compared to the normal tissues in the ethnic group tested.

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

    National Research Council Canada - National Science Library

    Adams, Arthur; van Brussel, Aram S A; Vermeulen, Jeroen F; Mali, Willem P Th M; van der Wall, Elsken; van Diest, Paul J; Elias, Sjoerd G

    2013-01-01

    .... 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...

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

    Science.gov (United States)

    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.

  11. Aminoacylase 3 Is a New Potential Marker and Therapeutic Target in Hepatocellular Carcinoma.

    Science.gov (United States)

    Tsirulnikov, Kirill; Duarte, Sergio; Ray, Anamika; Datta, Nakul; Zarrinpar, Ali; Hwang, Lin; Faull, Kym; Pushkin, Alexander; Kurtz, Ira

    2018-01-01

    Ras proteins (HRas, KRas and NRas) are common oncogenes that require membrane association for activation. Previous approaches to block/inhibit Ras membrane association were unsuccessful for cancer treatment in human clinical studies. In the present study we utilized a new approach to decrease Ras membrane association in hepatocellular carcinoma (HCC) cell lines via inhibition of an enzyme aminoacylase 3 (AA3; EC 3.5.1.114). AA3 expression was significantly elevated in the livers of HCC patients and HCC cell lines. Treatment of HepG2 cells with AA3 inhibitors, and HepG2 and HuH7 with AA3 siRNA significantly decreased Ras membrane association and was toxic to these HCC cell lines. AA3 inhibitors also increased the levels of N-acetylfarnesylcysteine (NAFC) and N-acetylgeranylgeranylcysteine (NAGGC) in HepG2 and Huh7 cell lines. We hypothesized that AA3 deacetylates NAFC and NAGGC, and generated farnesylcysteine (FC) and geranylgeranylcysteine (GGC) that are used in HCC cells for the regeneration of farnesylpyrophosphate and geranylgeranylpyrophosphate providing the prenyl (farnesyl or geranylgeranyl) group for Ras prenylation required for Ras membrane association. This was confirmed experimentally where purified human AA3 was capable of efficiently deacetylating NAFC and NAGGC. Our findings suggest that AA3 inhibition may be an effective approach in the therapy of HCC and that elevated AA3 expression in HCC is potentially an important diagnostic marker.

  12. Metabolomics of osteoarthritis: emerging novel markers and their potential clinical utility.

    Science.gov (United States)

    Zhai, Guangju; Randell, Edward W; Rahman, Proton

    2018-01-24

    OA is a multifactorial and progressive disease with no cure yet. Substantial efforts have been made and several biochemical and genetic markers have been reported, but neither alone nor in combination is adequate to identify early OA changes or determine disease progression with sufficient predictive values. Recent advances in metabolomics and its application to the study of OA have led to elucidation of involvement of several metabolic pathways and new specific metabolic markers for OA. Some of these metabolic pathways affect amino acid metabolism, including branched chain amino acids and arginine, and phospholipid metabolism involving conversion of phosphatidylcholine to lysophosphatidylcholine. These metabolic markers appear to be clinically actionable and may potentially improve the clinical management of OA patients. In this article, we review the recent studies of metabolomics of OA, discuss those novel metabolic markers and their potential clinical utility, and indicate future research directions in the field. © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

    Directory of Open Access Journals (Sweden)

    Chenuil Anne

    2010-09-01

    Full Text Available Abstract 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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  16. Neospora caninum surface antigen (p40) is a potential diagnostic marker for cattle neosporosis.

    Science.gov (United States)

    He, Pengfei; Li, Jianhua; Gong, Pengtao; Liu, Chengwu; Zhang, Guocai; Yang, Ju; Tuo, Wenbin; Yang, Bintong; Zhang, Xichen

    2013-05-01

    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 with other Coccidia. So, there is currently an urgent need for a sensitive and specific diagnostic assay for detecting N. caninum in animals. The N. caninum 40-kD surface antigen (p40), similar to NcSAG1 and NcSRS2, was shown to belong to surface antigen super family and thus represents an excellent marker for the diagnosis of neosporosis. In order to test the hypothesis, recombinant Ncp40 (rNcp40) was expressed in Escherichia coli, and an indirect ELISA test was developed using recombinant NCp40 antigen for N. caninum serodiagnosis. The antigen used in this study did not have cross-reactivity with anti-Toxoplasma gondii serum. Anti-p40 antibodies were detected by ELISA in the sera of Yellow cattle and were compared with (IFAT). Optimal sensitivity and specificity (98.2 and 98.6 %) were identified by IFAT. Additionally, 37 positive sera of T. gondii were detected and there was no significant difference with the negative serum of N. caninum. The rNcp40 ELISA developed here provides a specific and sensitive assay for detecting neosporosis in cattle.

  17. RECQL1 DNA repair helicase: a potential therapeutic target and a proliferative marker against ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Sakiko Sanada

    Full Text Available OBJECTIVE: This study analyzed the clinicopathological correlation between ovarian cancer (OC and RECQL1 DNA helicase to assess its therapeutic potential. METHODS: Surgically resected OC from 118 retrospective cases, for which paraffin blocks and all clinical data were complete, were used in this study. RECQL1 and Ki-67 immunostaining were performed on sections to correlate RECQL1 staining with subtype and patient survival. Ten OC and two normal cell lines were then examined for RECQL1 expression and were treated with siRNA against RECQL1 to assess its effect on cell proliferation. RESULTS: Of the 118 cases of adenocarcinoma (50, serous; 26, endometrioid; 21, clear cell; 15, mucinous; 6, other histology, 104 (90% showed varying levels of RECQL1 expression in the nuclei of OC cells. The Cox hazards model confirmed that diffuse and strong staining of RECQL1 was correlated with histological type. However, RECQL1 expression did not correlate with overall patient survival or FIGO stage. In vitro, RECQL1 expression was exceptionally high in rapidly growing OC cell lines, as compared with normal cells. Using a time-course analysis of RECQL1-siRNA transfection, we observed a significant inhibition in cell proliferation. CONCLUSIONS: RECQL1 DNA helicase is a marker of highly proliferative cells. RECQL1-siRNA may offer a new therapeutic strategy against various subtypes of OC, including platinum-resistant cancers, or in recurrent cancers that gain platinum resistance.

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

    Science.gov (United States)

    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.

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

    OpenAIRE

    Gr?nberg, Malin; Ahlin, Cecilia; Naeser, Ylva; Janson, Eva Tiensuu; Holmberg, Lars; Fj?llskog, 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...

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

    Directory of Open Access Journals (Sweden)

    Chen G

    2016-11-01

    Full Text Available Guozhong Chen, Chunling Wu, Zhiying Luo, Yiming Teng, Suping Mao Department of Respiratory Medicine, Yiwu Central Hospital, Yiwu, Zhejiang Province, People’s Republic of China 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. Keywords: platelet to lymphocyte ratio, pulmonary tuberculosis, chronic obstructive pulmonary disease

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

    Science.gov (United States)

    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.

  2. Clinicopathological and molecular significance of Sumolyation marker (ubiquitin conjugating enzyme 9 (UBC9)) expression in breast cancer of black women.

    Science.gov (United States)

    Agboola, A O J; Musa, A A; Ayoade, B A; Banjo, A A; Anunobi, C C; Deji-Agboola, A M; Rakha, E A; Nolan, C; Ellis, I O; Green, A R

    2014-01-01

    The majority of breast cancers (BC) in Nigerian women are triple negative and show breast cancer-associated gene 1 (BRCA1) deficiency as well as the basal like phenotype, with a high mortality rate. In contrast to the well-defined predictive factors for the hormonal therapy, there is a paucity of information on the BRCA1 deficiency breast tumor biology, particularly among African women. BRCA1 Sumoylation (UBC9) has been speculated to be involved in the ER transcription activity, BRCA1 deficiency and triple negative BC. We therefore hypothesized that UBC9, a SUMOylation marker, may have contributed to the aggressive nature of BRCA1 tumor phenotype observed in Nigerian women. This study investigated the immunoprofiles of UBC9 in tissue microarray (TMA) of 199 Nigerian women and correlated their protein expression with clinical outcome, pathological responses and the expression of other biomarkers to demonstrate the functional significance in Nigerian women. The protein expression of UBC9, as compared with other biomarkers, showed an inverse correlation with steroid hormones (ER, progesterone (PgR)), BRCA1, p27, p21 and MDM4, and a positive correlation with triple negative, basal cytokeratins (CK14 and CK5/6), epidermal growth factor receptor (EGFR), basal-like breast cancer phenotype, p53, phosphoinositide-3-kinases (PI3KCA), placental cadherin, (P-cadherin) and BRCA1 regulators (metastasis tumor antigen-1 (MTA1). Survival analysis showed that those tumors positive for UBC9 expression had a significantly poorer breast cancer-specific survival (BCSS) as compared with those showing negative expression. UBC9 remained an independent predictor of outcome for BCSS. This study demonstrates that UBC9 appears to play an important role in the tumor biology of Nigerian women. Therefore, a novel UBC9 targeted therapy in black women with BC could enhance a better patient outcome. Copyright © 2013 Elsevier GmbH. All rights reserved.

  3. Exosomal proteins as potential diagnostic markers in advanced non-small cell lung carcinoma

    DEFF Research Database (Denmark)

    Jakobsen, Kristine Raaby; Paulsen, Birgitte Sandfeld; Bæk, Rikke

    2015-01-01

    control subjects based on the differential display of exosomal protein markers. Methods: Plasma was isolated from 109 NSCLC patients with advanced stage (IIIa–IV) disease and 110 matched control subjects initially suspected of having cancer, but diagnosed to be cancer free. The Extracellular Vesicle Array......-derived vesicles displaying various proteins on their membrane surfaces. In addition, they are readily available in blood samples where they constitute potential biomarkers of human diseases, such as cancer. Here, we examine the potential of distinguishing non-small cell lung carcinoma (NSCLC) patients from...

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

    Directory of Open Access Journals (Sweden)

    Priyia ePusparajah

    2016-06-01

    Full Text Available 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.

  5. Aortic and Mitral Calcification Is Marker of Significant Carotid and Limb Atherosclerosis in Patients with First Acute Coronary Syndrome.

    Science.gov (United States)

    Sannino, Anna; Losi, Maria-Angela; Giugliano, Giuseppe; Canciello, Grazia; Toscano, Evelina; Giamundo, Alessandra; Scudiero, Fernando; Brevetti, Linda; Scudiero, Laura; Prastaro, Maria; Perrino, Cinzia; Perrone-Filardi, Pasquale; Galderisi, Maurizio; Trimarco, Bruno; Esposito, Giovanni

    2015-12-01

    Atherosclerosis is a systemic disease and coronary artery disease is frequently associated with peripheral artery disease. As aortic and mitral valvular calcification (VC) share some etiopathogenetic mechanisms with atherosclerosis, we analyzed the risk profile and the echocardiographic characteristics of patients admitted for first acute coronary syndrome (ACS) to investigate whether the presence of VC could be a marker of asymptomatic hemodynamically significant peripheral atherosclerosis. A total of 151 patients admitted for ACS without previous history of cardiovascular disease were consecutively enrolled. The presence of VC was identified by echocardiography; a carotid stenosis ≥50% by ultrasound identified carotid artery disease (CarAD); an ankle-brachial index ≤0.9 or ≥1.4 identified lower extremity artery disease (LEAD). Significant peripheral atherosclerosis was defined by the presence of CarAD and/or LEAD. Peripheral atherosclerosis was diagnosed in 82 (54.3%) patients; isolated CarAD in 24, isolated LEAD in 20, both diseases in 38 patients. VC was present in 103 (68.2%) patients. By multivariate analysis, age (OR = 1.059, 95% CI 1.007-1.113, P = 0.025), diabetes mellitus (OR = 5.068, 95% CI 1.480-17.351, P = 0.010), VC (OR = 7.422, 95% CI 2.421-22.880, P < 0.001), and multivessel CAD (OR = 3.317, 95% CI 1.281-8.586, P = 0.013) were the only independent predictors of having peripheral atherosclerosis. C-statistic for VC was not inferior to that obtained by age (0.728, 95% CI 0.649-0.797 vs. 0.800, 95% CI 0.727-0.861, P = 0.101) and to that obtained by the combination of multivessel CAD with diabetes (0.750; 95% CI 0.673-0.817, P = 0.635), and, furthermore, it was higher than that obtained by diabetes alone (0.620, 95% CI 0.538-0.698, P = 0.036). Ruling out the presence of significant peripheral atherosclerosis should be routinely considered in patients with ACS showing VC at echocardiography. © 2015, Wiley Periodicals, Inc.

  6. Comparative mitogenomic analysis of mirid bugs (Hemiptera: Miridae and evaluation of potential DNA barcoding markers

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    Juan Wang

    2017-08-01

    Full Text Available The family Miridae is one of the most species-rich families of insects. To better understand the diversity and evolution of mirids, we determined the mitogenome of Lygus pratenszs and re-sequenced the mitogenomes of four mirids (i.e., Apolygus lucorum, Adelphocoris suturalis, Ade. fasciaticollis and Ade. lineolatus. We performed a comparative analysis for 15 mitogenomic sequences representing 11 species of five genera within Miridae and evaluated the potential of these mitochondrial genes as molecular markers. Our results showed that the general mitogenomic features (gene content, gene arrangement, base composition and codon usage were well conserved among these mirids. Four protein-coding genes (PCGs (cox1, cox3, nad1 and nad3 had no length variability, where nad5 showed the largest size variation; no intraspecific length variation was found in PCGs. Two PCGs (nad4 and nad5 showed relatively high substitution rates at the nucleotide and amino acid levels, where cox1 had the lowest substitution rate. The Ka/Ks values for all PCGs were far lower than 1 (<0.59, but the Ka/Ks values of cox1-barcode sequences were always larger than 1 (1.34 –15.20, indicating that the 658 bp sequences of cox1 may be not the appropriate marker due to positive selection or selection relaxation. Phylogenetic analyses based on two concatenated mitogenomic datasets consistently supported the relationship of Nesidiocoris + (Trigonotylus + (Adelphocoris + (Apolygus + Lygus, as revealed by nad4, nad5, rrnL and the combined 22 transfer RNA genes (tRNAs, respectively. Taken sequence length, substitution rate and phylogenetic signal together, the individual genes (nad4, nad5 and rrnL and the combined 22 tRNAs could been used as potential molecular markers for Miridae at various taxonomic levels. Our results suggest that it is essential to evaluate and select suitable markers for different taxa groups when performing phylogenetic, population genetic and species identification

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

    Science.gov (United States)

    Adams, Arthur; van Brussel, Aram S A; Vermeulen, Jeroen F; Mali, Willem P Th M; van der Wall, Elsken; van Diest, Paul J; Elias, Sjoerd G

    2013-11-10

    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. 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. 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 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 breast tissue and benign breast disease (p markers as breast cancer molecular imaging targets. Although specificity is promising, combining targets would be necessary for optimal sensitivity. These data could help guide the choice of imaging targets for tracer development depending on the envisioned clinical application.

  8. Serpin peptidase inhibitor clade A member 1 as a potential marker for malignancy in insulinomas.

    Science.gov (United States)

    de Sá, Sandra Valéria; Corrêa-Giannella, Maria Lúcia; Machado, Márcio Carlos; Krogh, Karin; de Almeida, Madson Queiroz; Albergaria Pereira, Maria Adelaide; Coelho Siqueira, Sheila Aparecida; Patzina, Rosely Antunes; Ibuki, Felícia Satie; Sogayar, Mari Cleide; Machado, Marcel Cerqueira César; Giannella-Neto, Daniel

    2007-09-15

    The biological behavior of insulinomas cannot be predicted based on histopathologic criteria in which the diagnosis of malignancy is confirmed by the presence of metastases. In this study, microarray and quantitative real-time reverse transcription-PCR were applied to identify differentially expressed genes between malignant and nonmalignant insulinomas to search for useful biomarkers to recognize the metastatic potential of insulinomas. Code Link human bioarrays were used to analyze differences in approximately 20,000 genes between six well-differentiated endocrine tumors of benign behavior compared with one well-differentiated endocrine carcinoma (WDEC) and three metastases of endocrine carcinomas (MEC). Quantitative real-time reverse transcription-PCR was used to validate differential expressions of five genes in a series of 35 sporadic insulinomas. Serpin peptidase inhibitor clade A member 1 (SERPINA1; alpha-1-antitrypsin) expression, identified as up-regulated in malignant insulinomas, was also evaluated by immunohistochemistry. Analysis of microarray data resulted in 230 differentially expressed genes. Gene Ontology analysis identified serine-type endopeptidase activity and serine-type endopeptidase inhibitor activity as pathways presenting significant differential expression. Protease serine 2 and complement factor B (from serine-type endopeptidase activity pathway) were respectively confirmed as up-regulated in well-differentiated endocrine tumors of benign behavior (WDET) and in WDEC/MEC. Angiotensinogen and SERPINA1 (from serine-type endopeptidase inhibitor activity pathway) were confirmed as up-regulated in WDEC/MEC. SERPINA1 was shown to be expressed in 85.7% of malignant versus 14.3% of nonmalignant insulinomas by immunohistochemistry. Our data are consistent to the possibility that SERPINA1 is a marker of malignancy in insulinomas. Given the widespread availability of antibody anti-alpha-1-antitrypsin in pathology services, SERPINA1 expression

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

    Science.gov (United States)

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

    Science.gov (United States)

    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. Clinical Significance of Inflammatory Markers in Polycystic Ovary Syndrome: Their Relationship to Insulin Resistance and Body Mass Index

    Directory of Open Access Journals (Sweden)

    Nervana Samy

    2009-01-01

    Full Text Available Background: Women with polycystic ovary syndrome (PCOS have an increased prevalence of insulin resistance (IR and related disorders. Elevated serum levels of high sensitivity CRP (hs-CRP, interleukin-6 (IL-6 and tumor necrosis factor α (TNF-α reflect low-grade chronic inflammation and have been associated with several insulin-resistant states; they are useful cardiovascular risk markers. The objective of this study was to investigate whether soluble inflammatory markers are altered in PCOS focusing on its relationship with obesity and indexes of insulin resistance.

  12. Alcohol dehydrogenase: A potential new marker for diagnosis of intestinal ischemia using rat as a model

    Science.gov (United States)

    Gumaste, Upendra R; Joshi, Mukund M; Mourya, Devendra T; Barde, Pradip V; Shrivastav, Ghanshyam K; Ghole, Vikram S

    2005-01-01

    AIM: Intestinal ischemia (Ii) is an abdominal emergency due to blockade of the superior mesenteric artery resulting in 60-100% mortality if diagnosed late. Changes in several biochemical parameters such as D (-)-lactate, Creatinine kinase isoenzymes and lactate dehydrogenase suggested for early diagnosis, lack specificity and sensitivity. Therefore a biochemical parameter with greater sensitivity needs to be identified. METHODS: Wistar male rats were randomly assigned into two groups; control sham operated (n = 24) and ischemic test (n = 24) group. Superior mesenteric arterial occlusion was performed in the ischemic test group for 1 h. Alcohol dehydrogenase (ADH) was estimated in blood from portal vein, right ventricle of heart, dorsal aorta (DA) and inferior vena cava (IVC). The Serum glutamic acid pyruvate transaminase (SGPT) was also estimated in blood from portal vein and right ventricle of heart. RESULTS: A significant increase (P<0.001) in the levels of ADH in both portal blood as well as heart blood of the test group (232.72±99.45 EU and 250.85±95.14 EU, respectively) as compared to the control group (46.39±21.69 EU and 65.38±30.55 EU, respectively) were observed. Similarly, increased levels of ADH were observed in blood samples withdrawn from DA and IVC in test animals (319.52±80.14 EU and 363.90±120.68 EU, respectively) as compared to the control group (67.68±63.22 EU and 72.50±58.45 EU, respectively). However, in test animals there was significant increase in SGPT in portal blood (P = 0.054) without much increase in heart blood. CONCLUSION: Significant increase in the levels of ADH in portal and heart blood within 1 h of SMA occlusion without increase in SGPT in heart blood, suggests that the origin of ADH is from ischemic intestine and not from liver. Similarly, raised ADH levels were found in DA and IVC as well. IVC blood does represent peripheral blood sample. A raised level of ADH in test animals confirms it to be a potential marker in the

  13. Identification and potential use of a molecular marker for rust resistance in common bean.

    Science.gov (United States)

    Miklas, P N; Stavely, J R; Kelly, J D

    1993-02-01

    The Up 2 gene of common bean (Phaseolus Vulgaris L.) is an important source of dominant genetic resistance to the bean rust pathogen [Uromyces appendiculatus (Pers. ex Pers.) Unger var 'appendiculatus' [syn U. Phaseoli (Reben) Wint.]. Up 2 in combination with other rust resistance genes may be used to obtain potentially stable genetic resistance. It is difficult, however, to combine rust resistance genes effective against a single race due to epistatic interactions that frequently occur between them. A strategy that employed bulked DNA samples formed separately from the DNA of three BC6F2 individuals with Up 2 and three without Up 2 as contrasting near-isogenic lines (NILs) was used to identify random amplified polymorphic DNA fragments (RAPDs) tightly linked to the Up 2 locus. Only 1 of 931 fragments amplified by 167 10-mer primers of arbitrary sequence in the polymerase chain reaction (PCR) was polymorphic. The RAPD marker (OA141100) amplified by the 5'-TCTGTGCTGG-3' primer was repeatable and its presence and absence easy to score. No recombination was observed between OA141100 and the dominant Up 2 allele within a segregating BC6F2 population of 84 individuals. This result suggests that OA141100 and Up 2 are tightly linked. Andean and Mesoamerican bean germ plasm, with and without the Up 2 allele, were assayed for the presence of OA141100. Apparently, the marker is of Andean origin because all Andean lines, with or without the Up 2 allele, contained the marker, and the marker was absent in all Mesoamerican germ plasm except the lines to which Up-2 had been purposely transferred. These results suggest that OA141100 will be most useful for pyramiding Up 2 with other rust resistance genes into germ plasm of Mesoamerican origin where the marker does not traditionally exist. The use of bulked DNA samples may have concentrated resources toward the identification of RAPDs that were tightly linked to the target locus. Marker-based selection may provide an alternative to

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

    Science.gov (United States)

    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.

  15. Screening of Genes Specifically Expressed in Males of Fenneropenaeus chinensis and Their Potential as Sex Markers

    Directory of Open Access Journals (Sweden)

    Shihao Li

    2013-01-01

    Full Text Available The androgenic gland (AG, playing an important role in sex differentiation of male crustacean, is a target candidate to understand the mechanism of male development and to mine male-specific sex markers. An SSH library (designated as male reproduction-related tissues—SSH library, MRT-SSH library for short was constructed using cDNA from tissues located at the basal part of the 5th pereiopods, including AG and part of spermatophore sac, as tester, and the cDNA from the basal part of the 4th pereiopods of these male shrimp as driver. 402 ESTs from the SSH library were sequenced and assembled into 48 contigs and 104 singlets. Twelve contigs and 14 singlets were identified as known genes. The proteins encoded by the identified genes were categorized, according to their proposed functions, into neuropeptide hormone and hormone transporter, RNA posttranscriptional regulation, translation, cell growth and death, metabolism, genetic information processing, signal transduction/transport, or immunity-related proteins. Eleven highly expressed contigs in the SSH library were selected for validation of the MRT-SSH library and screening sex markers of shrimp. One contig, specifically expressed in male shrimp, had a potential to be developed as a transcriptomic sex marker in shrimp.

  16. V-amylose structural characteristics, methods of preparation, significance, and potential applications

    CSIR Research Space (South Africa)

    Obiro, WC

    2012-02-01

    Full Text Available , and postprandial hyperglycaemia in diabetics. Various aspects of V-amylose structure, methods of preparation, factors that affect its formation, and the significance and potential applications of the V-amylose complexes are reviewed....

  17. Wound healing potentials of Thevetia peruviana: Antioxidants and inflammatory markers criteria

    Directory of Open Access Journals (Sweden)

    Nazneen Rahman

    2017-10-01

    Full Text Available Thevetia peruviana is a medicinal plant used in the treatment of external wounds, infected area, ring worms, tumours etc. in traditional system of medicine. The aim of the study was to evaluate the wound healing potentials of T. peruviana leaves hexane (LH and fruit rind (FW water extracts and to prove the folkloric claims. The antimicrobial, antioxidant and anti-inflammatory potentials could be important strategies in defining potent wound healing drug. Based on these approaches the current study was designed using incision, excision and dead space wound models with the biochemical, antioxidant enzymes and inflammatory marker analysis. The fruit rind water extract showed highest WBS of 1133 ± 111.4 g. The extracts in excision model retrieved the excised wound i.e. complete healing of wound at day 14. The hydroxyproline content of FW and LH treated dry granuloma tissue was increased to 65.73 ± 3.2 mg/g and 53.66 ± 0.38 mg/g, accompanied by elevations of hexosamine and hexauronic acid with upregulation of GSH, catalase, SOD, peroxidase and the down regulation of the inflammatory marker (NO and oxidative stress marker (LPO in wet granulation tissue was documented. Conclusively, both the extracts showed enhanced WBS, rate of wound contraction, skin collagen tissue development, and early epithelisation. Therapeutic wound healing effect was further proven by reduced free radicals and inflammatory makers associated with enhanced antioxidants and connective tissue with histological evidence of more collagen formation. The present research could establish T. peruviana as potential source of effective wound healing drugs.

  18. ABCG2 is a potential marker of tumor-initiating cells in breast cancer.

    Science.gov (United States)

    Sicchieri, Renata Danielle; da Silveira, Willian Abraham; Mandarano, Larissa Raquel Mouro; de Oliveira, Tatiane Mendes Gonçalves; Carrara, Hélio Humberto Angotti; Muglia, Valdair Francisco; de Andrade, Jurandyr Moreira; Tiezzi, Daniel Guimarães

    2015-12-01

    The existence of tumor-initiating cells (TICs) within solid tumors has been hypothesized to explain tumor heterogeneity and resistance to cancer therapy. In breast cancer, the expression of CD44 and CD24 and the activity of aldehyde dehydrogenase 1 (ALDH1) can be used to selectively isolate a cell population enriched in TICs. However, the ideal marker to identify TICs has not been established. The aim of this study was to evaluate the expression of novel potential markers for TIC in breast carcinoma. We prospectively analyzed the expression of CD44, CD24, ABCG2, and CXCR4, and the activity of ALDH1 by using flow cytometry in 48 invasive ductal carcinomas from locally advanced and metastatic breast cancer patients who were administered primary chemotherapy. A mammosphere assay was employed in 30 samples. The relationship among flow cytometric analyses, ABCG2 gene expression, and clinical and pathological responses to therapy was analyzed. The GSE32646 database was analyzed in silico to identify genes associated with tumors with low and high ABCG2 expression. We observed that the presence of ABCG2(+) cells within the primary tumor was the only marker to predict the formation of mammospheres in vitro (R (2) = 0.15, p = 0.029). Quantitative polymerase chain reaction (qPCR) revealed a positive correlation between ABCG2 expression and the presence of ABCG2(+) cells within the primary tumor. The expression of ABCG2 was predictive of the response to neoadjuvant chemotherapy in our experiments and in the GSE32646 dataset (p = 0.04 and p = 0.002, respectively). The in silico analysis demonstrated that ABCG2(Up) breast cancer samples have a slower cell cycle and a higher expression of membrane proteins but a greater potential for chromosomal instability, metastasis, immune evasion, and resistance to hypoxia. Such genetic characteristics are compatible with highly aggressive and resistant tumors. Our results support the hypothesis that the presence of ABCG2

  19. Retinal vessel caliber as a potential marker of treatment outcome in patients with proliferative diabetic retinopathy

    DEFF Research Database (Denmark)

    Vergmann, Anna Stage; Torp, Thomas Lee; Lundberg, Kristian

    , CRVE and the arterio-venous (AV) ratio. All measurements were performed by a certified grader. Results: Median age and duration of diabetes were 52 years and 20 years, respectively, and 65% were male. Median HbA1c was 63 mmol/mol, and the blood pressure was 155/82 mmHg. There were no differences......Title of abstract: Retinal vessel caliber as a potential marker of treatment outcome in patients with proliferative diabetic retinopathy Design of study: Three months prospective, interventional clinical study. Purpose: The retinal vascular tree can be measured non-invasively and summarized...

  20. Compound motor action potential duration and latency are markers of recurrent laryngeal nerve injury.

    Science.gov (United States)

    Bhatt, Neel K; Park, Andrea M; Al-Lozi, Mohammad T; Gale, Derrick C; Paniello, Randal C

    2017-08-01

    Compound motor action potential (CMAP) can quantitatively evaluate innervation following injury to the recurrent laryngeal nerve (RLN) in canines. CMAP duration (the total time of CMAP) and latency (the time between the nerve impulse and the onset of action potentials) have not been assessed following RLN injury. Animal study. Twelve canine hemilaryngeal preparations were investigated. Baseline CMAP duration and latency were derived. Group A (n = 5) underwent RLN stretch injury, and group B (n = 7) underwent RLN transection/repair. The change in CMAP duration and latency was assessed between the baseline and 6-month measurements using receiver operator characteristic (ROC) curves for each group individually and combined. Six months following injury, transection/repair injuries had the most significant increase in CMAP duration (2.8 ± 0.6 ms vs. 4.2 ± 0.8 ms, difference 1.4 ms 95% confidence interval [CI]: 0.43 to 2.40) and latency (2.6 ± 0.5 ms vs. 5.6 ± 1.5 ms, difference 3.0 ms 95% CI: 1.65 to 4.38). Stretch injuries also caused an increase in CMAP duration (2.3 ± 0.8 ms vs. 3.0 ± 0.6 ms, difference 0.7 ms 95% CI: -0.49 to 1.77) and latency (2.5 ± 0.8 ms vs. 4.7 ± 1.5 ms, difference 2.3 95% CI: 0.76 to 3.80). Using ROC curves, CMAP duration and latency differentiated between the baseline control and RLN injury at 6 months (area under the curve = 0.78 and 0.98, respectively). CMAP duration and latency are both quantitative measures that may have clinical utility as markers of RLN injury. CMAP latency had superior discrimination between injured and uninjured RLNs. Increased CMAP duration and latency may be explained by incomplete myelination and focal conduction block. NA. Laryngoscope, 127:1855-1860, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  1. Generalised convulsive status epilepticus in Singapore: clinical outcomes and potential prognostic markers.

    Science.gov (United States)

    Rathakrishnan, Rahul; Sidik, Novalia Purnama; Huak, Chan Yiong; Wilder-Smith, Einar P

    2009-04-01

    To study the characteristics, outcomes and prognostic markers of convulsive status epilepticus (SE) in Singapore. 62 adult admissions to the National University Hospital Singapore from 2002 to 2005 were studied. Ethnicity, history of epilepsy, educational subnormality, neuroimaging, seizure duration, length of stay, Modified Rankin Scale (MRS) pre and post discharge, blood glucose, creatine kinase, potassium, white cell and platelet count were recorded. An MRS> or =3 at discharge was defined as a poor outcome. ROCs of significant variables were plotted to identify the best test cut-offs. Mean age was 59.2 years (range 20-94). 75.9% patients had epilepsy. Mean length of stay was 14 days (range 1-75). Univariate analyses revealed age (p=0.01, OR 1.075, 95% CI 1.030-1.122), length of stay in ICU (p=0.03, OR 1.299, 95% CI 1.014-1.665) and hospital (p=0.014, OR 1.203, 95% CI 1.038-1.393) and hyperglycemia (p=0.045, OR 1.327, 95% CI 1.007-1.750) associated with poor outcome. Test cut-off values for prognostic markers were established: age> or =55 years (ROC 0.790, sensitivity 72.3, specificity 85.7, PPV9 4.4%, NPV 48.8%) and serum glucose> or =7 mmol/L (ROC 0.737, sensitivity 72.3, specificity 80.0, PPV 93.5%, NPV 36.4%). A discriminant model using these variables was then constructed with probability scores for poor outcome. Age, hyperglycemia and length of stay in hospital influenced outcome from convulsive SE in the local population with hyperglycemia being a novel prognostic marker. Some prognostic markers cited in the literature differed, highlighting the possibility that these indicators may vary across population groups.

  2. Crystal structure of human esterase D: a potential genetic marker of retinoblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Dong; Li, Yang; Song, Gaojie; Zhang, David; Shaw, Neil; Liu, Zhi-Jie; (Chinese Aca. Sci.)

    2009-07-10

    Retinoblastoma (RB), a carcinoma of the retina, is caused by mutations in the long arm of chromosome 13, band 13q14. The esterase D (ESD) gene maps at a similar location as the RB gene locus and therefore serves as a potential marker for the prognosis of retinoblastoma. Because very little is known about the structure and function of ESD, we determined the 3-dimensional structure of the enzyme at 1.5 {angstrom} resolution using X-ray crystallography. ESD shows a single domain with an {alpha}/{beta}-hydrolase fold. A number of insertions are observed in the canonical {alpha}/{beta}-hydrolase fold. The active site is located in a positively charged, shallow cleft on the surface lined by a number of aromatic residues. Superimposition studies helped identify the typical catalytic triad residues -- Ser-153, His264, and Asp230 -- involved in catalysis. Mutagenesis of any of the catalytic triad residues to alanine abolished the enzyme activity. Backbone amides of Leu54 and Met150 are involved in the formation of the oxyanion hole. Interestingly, a M150A mutation increased the enzyme activity by 62%. The structure of human ESD determined in this study will aid the elucidation of the physiological role of the enzyme in the human body and will assist in the early diagnosis of retinoblastoma. Wu, D., Li, Y., Song, G., Zhang, D., Shaw, N., Liu, Z. J. Crystal structure of human esterase D: a potential genetic marker of retinoblastoma.

  3. [THE SOMATIC MUTATIONS AND ABERRANT METHYLATION AS POTENTIAL GENETIC MARKERS OF URINARY BLADDER CANCER].

    Science.gov (United States)

    Mikhailenko, D S; Kushlinskii, N E

    2016-02-01

    All around the world, more than 330 thousands cases of bladder cancer are registered annually hence representing actual problem of modern oncology. Still in demand are search and characteristic of new molecular markers of bladder cancer detecting in tumor cells from urinary sediment and having high diagnostic accuracy. The studies of last decade, especially using methods of genome-wide sequencing, permitted to receive a large amount of experimental data concerning development and progression of bladder cancer The review presents systematic analysis of publications available in PubMed data base mainly of last five years. The original studies of molecular genetic disorders under bladder cancer and meta-analyzes were considered This approach permitted to detected the most common local alterations of DNA under bladder cancer which can be detected using routine genetic methods indifferent clinical material and present prospective interest for development of test-systems. The molecular genetic markers of disease can be activating missense mutations in 7 and 10 exons of gene of receptor of growth factor of fibroblasts 3 (FGFR3), 9 and 20 exons of gene of Phosphatidylinositol-4,5-bi-phosphate-3-kinase (PIK3CA) and mutation in -124 and -146 nucleotides in promoter of gene of catalytic subunit telomerase (TERT). The development of test-systems on the basis of aberrant methylation of CpG-islets of genes-suppressors still is seemed as a difficult task because of differences in pattern of methylation of different primary tumors at various stages of clonal evolution of bladder cancer though they can be considered as potential markers.

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

    Energy Technology Data Exchange (ETDEWEB)

    Thorat, Leena J. [Centre for Advanced Studies, Department of Zoology, University of Pune, Pune 411007 (India); Gaikwad, Sushama M. [Division of Biochemical Sciences, National Chemical Laboratory, Pune 411008 (India); Nath, Bimalendu B., E-mail: bbnath@unipune.ac.in [Centre for Advanced Studies, Department of Zoology, University of Pune, Pune 411007 (India)

    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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  8. Galectin-3 as a marker and potential therapeutic target in breast cancer.

    Science.gov (United States)

    Zhang, Hao; Luo, Minna; Liang, Xi; Wang, Dan; Gu, Xin; Duan, Chao; Gu, Huizi; Chen, Guanglei; Zhao, Xinhan; Zhao, Zuowei; Liu, Caigang

    2014-01-01

    Galectin-3 has a relatively high level of expression in triple-negative breast cancers and is a potential marker for this disease. However, the clinical and prognostic implications of galectin-3 expression in breast cancer remain unclear. We examined mastectomy specimens from 1086 breast cancer cases and matching, adjacent non-cancerous tissues using immunohistochemistry. Overall, triple-negative breast cancers expressed galectin-3 more strongly than did other breast cancers types (63.59% vs 21.36%, P = 0.001). Galectin-3 expression was not found to be an independent prognostic factor for breast cancer by Cox regression analysis, but was associated with chemotherapeutic resistance. Apoptosis was only weakly induced by arsenic trioxide (ATO) treatment in galectin-3-positive breast cancer cells (MDA-MB-231 and MCF-7), although ATO treatment up-regulated galectin-3 expression. Knockdown of galectin-3 in MDA-MB-231 cells sensitized them to killing by ATO. These findings support a possible role for galectin-3 as a marker for triple-negative breast cancer progression and as a therapeutic target in combination with ATO treatment, although the mechanisms that underlie this synergy require further investigation.

  9. Galectin-3 as a marker and potential therapeutic target in breast cancer.

    Directory of Open Access Journals (Sweden)

    Hao Zhang

    Full Text Available Galectin-3 has a relatively high level of expression in triple-negative breast cancers and is a potential marker for this disease. However, the clinical and prognostic implications of galectin-3 expression in breast cancer remain unclear. We examined mastectomy specimens from 1086 breast cancer cases and matching, adjacent non-cancerous tissues using immunohistochemistry. Overall, triple-negative breast cancers expressed galectin-3 more strongly than did other breast cancers types (63.59% vs 21.36%, P = 0.001. Galectin-3 expression was not found to be an independent prognostic factor for breast cancer by Cox regression analysis, but was associated with chemotherapeutic resistance. Apoptosis was only weakly induced by arsenic trioxide (ATO treatment in galectin-3-positive breast cancer cells (MDA-MB-231 and MCF-7, although ATO treatment up-regulated galectin-3 expression. Knockdown of galectin-3 in MDA-MB-231 cells sensitized them to killing by ATO. These findings support a possible role for galectin-3 as a marker for triple-negative breast cancer progression and as a therapeutic target in combination with ATO treatment, although the mechanisms that underlie this synergy require further investigation.

  10. Kaempferitrin from Uncaria guianensis (Rubiaceae) and its potential as a chemical marker for the species

    Energy Technology Data Exchange (ETDEWEB)

    Valente, Ligia M.M.; Liechocki, Sally; Barboza, Rodolfo S.; Paixao, Djavan da [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Inst. de Quimica], e-mail: valente@iq.ufrj.br; Bizarri, Carlos H.B.; Almeida, M. Beatriz S.; Benevides, Paulo J.C.; Siani, Antonio C. [Fundacao Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, RJ (Brazil). Inst. de Tecnologia em Farmacos; Magalhaes, Alvicler [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Inst. de Quimica

    2009-07-01

    Uncaria tomentosa (Willd.) DC. and U. guianensis (Aubl.) Gmel., known as cat's claw, are large woody vines native to the Amazonian and Central American rain forests. The species contain, in different proportions, indole and oxindole alkaloids, triterpenoid glycosides, sterols and proanthocyanidins. U. tomentosa can be chemically identified by its oxindole alkaloid profile and content, whereas U. guianensis has no satisfactorily established chemical markers. This work describes, for the first time, the isolation of kaempferol-3,7-O-(a)-dirhamnoside (kaempferitrin) in Uncaria species. Screening for this compound in leaves, stems or bark of both species through TLC and HPLC-DAD-MS showed the presence of kaempferitrin only in the leaves and stems of U. guianensis, at a ratio almost thirty six times greater in the leaves than in the stems. These results reveal the selectivity of U. guianensis to produce this bioactive flavonoid glycoside, and suggest this compound as a potential chemical marker for the species.(author)

  11. Mucosal-associated invariant T cell is a potential marker to distinguish fibromyalgia syndrome from arthritis.

    Directory of Open Access Journals (Sweden)

    Chie Sugimoto

    Full Text Available 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.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.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.Combined with the currently available

  12. Genotyping in the MHC locus: potential for defining predictive markers in sarcoidosis

    Directory of Open Access Journals (Sweden)

    Seitzer Ulrike

    2001-10-01

    Full Text Available Abstract In sarcoidosis, host genetic factors are discussed as contributing to disease susceptibility and course. Since tumor necrosis factor (TNF-α is a central mediator of granuloma formation and since elevated TNF-α levels are found during active phases of sarcoidosis, genetic polymorphisms correlating with influences on TNF-α levels are of special interest. The complete sequencing of the MHC region and the increase in the number of identified gene polymorphisms in this locus associated with TNF-α production offer the opportunity of detecting new genes associated with sarcoidosis and perhaps of defining disease-associated haplotypes that bear the potential of serving as predictive markers for this disease.

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

    Science.gov (United States)

    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.

  14. CCNA1 promoter methylation: a potential marker for grading Papanicolaou smear cervical squamous intraepithelial lesions.

    Science.gov (United States)

    Chujan, Suthipong; Kitkumthorn, Nakarin; Siriangkul, Sumalee; Mutirangura, Apiwat

    2014-01-01

    From our previous study, we established that cyclin A1 (CCNA1) promoter methylation is strongly correlated with multistep progression of HPV-associated cervical cancer, suggesting potential use as a diagnostic maker of disease. The purpose of the present study was to assess the prevalence of CCNA1 promoter methylation in residual cervical cells isolated from liquid-based cytology that underwent hrHPV DNA screening for cervical cancer, and then to evaluate this marker for diagnostic accuracy using parameters like sensitivity, specificity, predictive values and likelihood ratio. In this retrospective study, histopathology was used as the gold standard method with specimens separated into the following groups: negative (n=31), low- grade squamous intraepithelial lesions (LSIL, n=34) and high-grade squamous intraepithelial lesions or worse (HSIL+, n=32). The hrHPV was detected by Hybrid Capture 2 (HC2) and CCNA1 promoter methylation was examined by CCNA1 duplex methylation specific PCR. The results showed the frequencies of CCNA1 promoter methylation were 0%, 5.88% and 83.33%, while the percentages of hrHPV were 66.67%, 82.35% and 100% in the negative, LSIL and HSIL+ groups, respectively. Although hrHPV infection showed high frequency in all three groups, it could not differentiate between the different groups and grades of precancerous lesions. In contrast, CCNA1 promoter methylation clearly distinguished between negative/LSIL and HSIL+, with high levels of all statistic parameters. CCNA1 promoter methylation is a potential marker for distinguishing between histologic negative/LSIL and HSIL+using cervical cytology samples.

  15. Stathmin protein level, a potential predictive marker for taxane treatment response in endometrial cancer.

    Directory of Open Access Journals (Sweden)

    Henrica M J Werner

    Full Text Available Stathmin is a prognostic marker in many cancers, including endometrial cancer. Preclinical studies, predominantly in breast cancer, have suggested that stathmin may additionally be a predictive marker for response to paclitaxel. We first evaluated the response to paclitaxel in endometrial cancer cell lines before and after stathmin knock-down. Subsequently we investigated the clinical response to paclitaxel containing chemotherapy in metastatic endometrial cancer in relation to stathmin protein level in tumors. Stathmin level was also determined in metastatic lesions, analyzing changes in biomarker status on disease progression. Knock-down of stathmin improved sensitivity to paclitaxel in endometrial carcinoma cell lines with both naturally higher and lower sensitivity to paclitaxel. In clinical samples, high stathmin level was demonstrated to be associated with poor response to paclitaxel containing chemotherapy and to reduced disease specific survival only in patients treated with such combination. Stathmin level increased significantly from primary to metastatic lesions. This study suggests, supported by both preclinical and clinical data, that stathmin could be a predictive biomarker for response to paclitaxel treatment in endometrial cancer. Re-assessment of stathmin level in metastatic lesions prior to treatment start may be relevant. Also, validation in a randomized clinical trial will be important.

  16. Development of a novel assay to quantify serum human telomerase reverse transcriptase messenger RNA and its significance as a tumor marker for hepatocellular carcinoma.

    Science.gov (United States)

    Miura, Norimasa; Maruyama, Shigeo; Oyama, Kenji; Horie, Yutaka; Kohno, Michimori; Noma, Eijiro; Sakaguchi, Seigo; Nagashima, Miki; Kudo, Masatoshi; Kishimoto, Yukihiro; Kawasaki, Hironaka; Hasegawa, Junichi; Shiota, Goshi

    2007-01-01

    Currently available tumor markers for hepatocellular carcinoma (HCC) are alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive AFP (AFP-L3), and Des-gamma-carboxy prothrombin (DCP). However, their positive rate can not surpass abdominal ultrasonography (US) as modalities to detect small HCC at early stage, resulting in a possible delay of its diagnosis. There is a need to develop an additional sensitive marker to improve the early detection of HCC. We here introduced a newly developed quantitative detection method for serum hTERT mRNA, which has a clinical significance in HCC diagnosis. Briefly, we examined its sensitivity and specificity in HCC diagnosis, clinical significance in comparison with other tumor markers, and its correlations with the clinical parameters. Serum hTERT mRNA showed higher values in patients with HCC than those with chronic liver diseases. hTERT mRNA expression independently correlated with clinical parameters such as differentiation degree (p < 0.001). The sensitivity/specificity of hTERT mRNA in HCC diagnosis showed 88.2/70.0%. hTERT mRNA proved to be expectedly superior to AFP mRNA , AFP and DCP in HCC diagnosis. Importantly, hTERT mRNA in serum correlated with that in HCC tissue. Thus, we report that serum hTERT mRNA is a novel and available marker for HCC diagnosis. Copyright 2007 S. Karger AG, Basel.

  17. Oxidative damage markers are significantly associated with the carotid artery intima-media thickness after controlling for conventional risk factors of atherosclerosis in men.

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    Jin-Ha Yoon

    Full Text Available This study aimed to assess the association between oxidative damage markers and carotid artery intima-media thickness (CIMT after controlling for conventional risk factors of atherosclerosis in multiple logistic regression models.Fifty-one case male participants (CIMT ≥ 0.9 mm were enrolled during their visits to Korean Genomic Rural Cohort Study of Wonju centers between May 1 and August 31, 2011, along with 51 control participants (CIMT < 0.9 mm selected using frequency matching by age group. The levels of oxidative damage markers, 8-hydroxy-2'-deoxyquuanosine (8-OHdG, malondialdehyde (MDA, and 8-iso-prostaglandin F2α (Isoprostane, were measured. Conditional logistic regression models were used to evaluate relative relationships between the oxidative damage markers and the risk of high CIMT.The markers of oxidative lipid (Isoprostane and MDA and DNA (8-OHdG damage were associated with CIMT after controlling for the conventional risk factors, including age, low density lipoprotein, body mass index, smoking history, alcohol consumption, and metabolic syndrome (ORs [95% CI] for Isoprostane: 3rd tertile, 8.47 [2.59-27.67]; for MDA: 3rd tertile, 8.47 [2.59-27.67]; for 8-OHdG: 3rd tertile, 5.58 [1.79-17.33]. When all the oxidative damage markers were incorporated in the same logistic regression model, only Isoprostane was significantly related to CIMT (OR [95% CI]: 4.22 [1.31-13.53] in 2nd tertile and 14.21 [3.34-60.56] in 3rd tertile.In this nested case-control study, the oxidative damage markers of lipid and DNA were associated with CIMT even after controlling for the conventional risk factors of cardiovascular diseases.

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

    Science.gov (United States)

    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 (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.

  19. Antimicrobial-Resistance Genetic Markers in Potentially Pathogenic Gram Positive Cocci Isolated from Brazilian Soft Cheese.

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    Resende, Juliana Alves; Fontes, Cláudia Oliveira; Ferreira-Machado, Alessandra Barbosa; Nascimento, Thiago César; Silva, Vânia Lúcia; Diniz, Cláudio Galuppo

    2018-01-16

    Although most Brazilian dairy products meet high technological standards, there are quality issues regarding milk production, which may reduce the final product quality. Several microbial species may contaminate milk during manufacture and handling. If antimicrobial usage remains uncontrolled in dairy cattle, the horizontal transfer of antimicrobial resistance genes in foodstuffs may be of particular concern for both food producers and dairy industry. This study focused on the evaluation of putative Gram positive cocci in Minas cheese and of antimicrobial and biocide resistance genes among the isolated bacteria. Representative samples of 7 different industrially trademarked Minas cheeses (n = 35) were processed for selective culture and isolation of Gram positive cocci. All isolated bacteria were identified by DNA sequencing of the 16S rRNA gene. Antimicrobial resistance genes were screened by PCR. Overall, 208 strains were isolated and identified as follows: Enterococcus faecalis (47.6%), Macrococcus caseolyticus (18.3%), Enterococcus faecium (11.5%), Enterococcus caseliflavus (7.7%), Staphylococcus haemolyticus (7.2%), Staphylococcus aureus (4.3%), Staphylococcus epidermidis (2.9%), and Enterococcus hirae (0.5%). The genetic markers mecA (78.0%) and smr (71.4%) were the most prevalent, but others were also detected, such as blaZ (65.2%), msrA (60.9%), msrB (46.6%), linA (54.7%), and aacA-aphD (47.6%). The occurrence of opportunist pathogenic bacteria harboring antimicrobial resistance markers in the cheese samples are of special concern, since these bacteria are not considered harmful contaminating agents according to the Brazilian sanitary regulations. However, they are potentially pathogenic bacteria and the cheese may be considered a reservoir for antimicrobial resistance genes available for horizontal transfer through the food chain, manufacturing personnel and consumers. © 2018 Institute of Food Technologists®.

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

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    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.

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

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    Malin Grönberg

    Full Text Available 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.

  2. The Y4-RNA fragment, a potential diagnostic marker, exists in saliva

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    Tatsuya Ishikawa

    2017-06-01

    Full Text Available The 94-nt full-length Y4-RNA is thought to have roles in the initiation of DNA replication and RNA quality control. Although its 31/32-nt fragment also exists abundantly in plasma, little is known about its physiological role. Since the 31/32-nt Y4-RNA fragment in sera is reported to be more abundant in patients with coronary artery disease than healthy persons, the fragment may have a potential for a diagnostic and/or prognostic biomarker for some diseases regardless of its functionality. As a step toward further investigation of its potential utility, we examined if the 31/32-nt Y4-RNA fragment also exists in saliva that can be obtained noninvasively, and showed that, in addition to the 31/32-nt fragment, 14- and 11-nt Y4-RNA fragments are present in all saliva RNA samples from four healthy persons. We established a PCR method to accurately quantitate the amount of the 31/32-nt Y4-RNA fragment, and estimated its amount in saliva of healthy persons to be 0.06 ± 0.04 fmol per nanogram of saliva RNA. We also tried to develop an easier quantitation method using a DNA molecular beacon. Keywords: Y4-RNA fragment, Saliva RNA, Diagnostic/prognostic marker, Next-generation sequencing, RT-PCR, Molecular beacon

  3. Serum p53 antibody as a potential tumor marker in extrahepatic cholangiocarcinoma.

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    Okada, Rei; Shimada, Hideaki; Otsuka, Yuichiro; Tsuchiya, Masaru; Ishii, Jun; Katagiri, Toshio; Maeda, Tetsuya; Kubota, Yoshihisa; Nemoto, Tetsuo; Kaneko, Hironori

    2017-12-01

    Only a few studies have evaluated the clinicopathological significance of the p53 protein expression and s-p53-Abs level in patients with cholangiocarcinoma. We therefore analyzed the clinicopathological and prognostic significance of s-p53-Abs in patients with extrahepatic cholangiocarcinoma. We prospectively evaluated s-p53-Abs levels before and after surgery in 61 patients with extrahepatic cholangiocarcinoma to determine the relationship between clinicopathological factors and the prognostic significance of s-p53-Abs. Among a total of 61 primary extrahepatic cholangiocarcinoma cases, 23% were positive for s-p53-Abs. Combination of s-p53-Abs with the conventional serum markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) significantly increased the rate of positive extrahepatic cholangiocarcinoma cases (57% for CEA and/or CA19-9 vs. 75% for CEA and/or CA19-9 and/or s-p53-Abs, P = 0.035). There were no significant differences in clinicopathological factors between the p53-seropositive and p53-seronegative patients. An immunohistochemical analysis showed the presence of significant associations between the intensity (P = 0.003) and extent (P = 0.001) of p53 immunoreactivity and p53-seropositivitly. Although s-p53-Abs was not a significant prognostic factor for the survival in either univariate or multivariate analyses, p53 immunoreactivity was independently associated with a poor survival. Among patients positive for s-p53-Abs before surgery, the s-p53-Abs levels were reduced after surgery in most. These findings suggested that s-p53-Abs might be associated with p53 immunoreactivity. In addition, s-p53-Abs may be useful for a diagnosis, but was not useful for predicting tumor recurrence or the survival. This study was registered as UMIN000014530.

  4. Candidate SNP Markers of Chronopathologies Are Predicted by a Significant Change in the Affinity of TATA-Binding Protein for Human Gene Promoters.

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    Ponomarenko, Petr; Rasskazov, Dmitry; Suslov, Valentin; Sharypova, Ekaterina; Savinkova, Ludmila; Podkolodnaya, Olga; Podkolodny, Nikolay L; Tverdokhleb, Natalya N; Chadaeva, Irina; Ponomarenko, Mikhail; Kolchanov, Nikolay

    2016-01-01

    Variations in human genome (e.g., single nucleotide polymorphisms, SNPs) may be associated with hereditary diseases, their complications, comorbidities, and drug responses. Using Web service SNP_TATA_Comparator presented in our previous paper, here we analyzed immediate surroundings of known SNP markers of diseases and identified several candidate SNP markers that can significantly change the affinity of TATA-binding protein for human gene promoters, with circadian consequences. For example, rs572527200 may be related to asthma, where symptoms are circadian (worse at night), and rs367732974 may be associated with heart attacks that are characterized by a circadian preference (early morning). By the same method, we analyzed the 90 bp proximal promoter region of each protein-coding transcript of each human gene of the circadian clock core. This analysis yielded 53 candidate SNP markers, such as rs181985043 (susceptibility to acute Q fever in male patients), rs192518038 (higher risk of a heart attack in patients with diabetes), and rs374778785 (emphysema and lung cancer in smokers). If they are properly validated according to clinical standards, these candidate SNP markers may turn out to be useful for physicians (to select optimal treatment for each patient) and for the general population (to choose a lifestyle preventing possible circadian complications of diseases).

  5. Candidate SNP Markers of Chronopathologies Are Predicted by a Significant Change in the Affinity of TATA-Binding Protein for Human Gene Promoters

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    Petr Ponomarenko

    2016-01-01

    Full Text Available Variations in human genome (e.g., single nucleotide polymorphisms, SNPs may be associated with hereditary diseases, their complications, comorbidities, and drug responses. Using Web service SNP_TATA_Comparator presented in our previous paper, here we analyzed immediate surroundings of known SNP markers of diseases and identified several candidate SNP markers that can significantly change the affinity of TATA-binding protein for human gene promoters, with circadian consequences. For example, rs572527200 may be related to asthma, where symptoms are circadian (worse at night, and rs367732974 may be associated with heart attacks that are characterized by a circadian preference (early morning. By the same method, we analyzed the 90 bp proximal promoter region of each protein-coding transcript of each human gene of the circadian clock core. This analysis yielded 53 candidate SNP markers, such as rs181985043 (susceptibility to acute Q fever in male patients, rs192518038 (higher risk of a heart attack in patients with diabetes, and rs374778785 (emphysema and lung cancer in smokers. If they are properly validated according to clinical standards, these candidate SNP markers may turn out to be useful for physicians (to select optimal treatment for each patient and for the general population (to choose a lifestyle preventing possible circadian complications of diseases.

  6. Matrix metalloproteinase 3 polymorphisms as a potential marker of enhanced susceptibility to lung cancer in chronic obstructive pulmonary disease subjects

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    Kamil Brzóska

    2014-09-01

    Full Text Available [b]Introduction and objective[/b]. Chronic obstructive pulmonary disease (COPD is often accompanied by lung cancer. Among the genes that may play a role in the occurrence of COPD and lung cancer are those encoding the proteolytic enzymes, such as matrix metalloproteinases (MMPs and their tissue inhibitors. The objective of this study was to find MMPs-associated markers useful in the identification of COPD subjects with increased susceptibility to developing lung cancer. [b]Materials and methods[/b]. We compared the frequency of single nucleotide polymorphisms in genes coding for matrix proteinases ([i]MMP1, MMP2, MMP3, MMP9, MMP12[/i] as well as tissue inhibitor of metalloproteinases ([i]TIMP1[/i] in two groups of subjects: COPD patients (54 subjects and COPD patients diagnosed for lung cancer occurrence (53 subjects.The levels of the respective proteins in blood serum were also analyzed. [b]Results[/b]. The frequencies of 2 genotypes, [i]MMP3[/i] rs3025058 and MMP3 rs678815, were significantly different between the studied groups. In both cases, more heterozygotes and less homozygotes (both types were observed in the COPD group than in the COPD + cancer group. A significantly higher TIMP1 level in blood serum was observed in the COPD + cancer group than in the COPD group. There were no statistically significant differences in[i] MMPs[/i] blood levels between the studied groups. In addition, no genotype-associated differences in [i]TIMP1[/i] or[i] MMPs[/i] blood levels were observed. [b]Conclusions[/b]. Homozygocity for [i]MMP3[/i] rs3025058 and rs678815 polymorphisms is a potential marker of enhanced susceptibility to lung cancer development among COPD subjects.

  7. Prostate-specific membrane antigen expression is a potential prognostic marker in endometrial adenocarcinoma.

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    Mhawech-Fauceglia, Paulette; Smiraglia, Dominic J; Bshara, Wiam; Andrews, Christopher; Schwaller, Juerg; South, Stacey; Higgs, Donald; Lele, Shashikant; Herrmann, Francois; Odunsi, Kunle

    2008-03-01

    The aim of this study was to determine the role of prostate-specific membrane antigen (PSMA) as a prognostic marker in endometrial adenocarcinoma (EAC) and to explore whether its down-regulation could be due to epigenetic mechanism. First, we examined the expression and the prognostic value of PSMA by semiquantitative reverse transcription-PCR and immunohistochemistry in EAC tissue samples. Second, to explore the role of CpG methylation in down-regulation PSMA in EAC, we evaluated PSMA CpG island methylation using methylation-specific PCR in cells lines and in a subset of patients' samples. Furthermore, association of the status of tumor methylation to the clinical and histologic variables was also evaluated. Higher PSMA mRNA levels were associated with stage I (P = 0.046) and PSMA protein intensity by immunohistochemistry (P = 0.032). In multivariate analysis, loss of PSMA expression was associated with a worse disease-free survival (P = 0.02). PSMA was methylated in prostate cell lines (DU145 and PC3) and endometrial cell lines. In addition, PSMA was methylated in 5 of 18 samples (all 5 had low PSMA mRNA value). There was a significant association between PSMA methylation and loss of protein expression by immunohistochemistry and PSMA-RNA level with P value of 0.036 and 0.011, respectively. In addition, there was an association between PSMA methylation and tumor size (P = 0.025). In summary, (a) PSMA is underexpressed in advanced stage EAC, (b) loss of PSMA expression can be considered as a prognostic marker in patients with EAC, and (c) loss of PSMA expression in a subset of EAC cases could be due to epigenetic silencing.

  8. Assessment of Tools for Marker-Assisted Selection in a Marine Commercial Species: Significant Association between MSTN-1 Gene Polymorphism and Growth Traits

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    Irma Sánchez-Ramos

    2012-01-01

    Full Text Available Growth is a priority trait from the point of view of genetic improvement. Molecular markers linked to quantitative trait loci (QTL have been regarded as useful for marker-assisted selection in complex traits as growth. Polymorphisms have been studied in five candidate genes influencing growth in gilthead seabream (Sparus aurata: the growth hormone (GH, insulin-like growth factor-1 (IGF-1, myostatin (MSTN-1, prolactin (PRL, and somatolactin (SL genes. Specimens evaluated were from a commercial broodstock comprising 131 breeders (from which 36 males and 44 females contributed to the progeny. In all samples eleven gene fragments, covering more than 13,000 bp, generated by PCR-RFLP, were analyzed; tests were made for significant associations between these markers and growth traits. ANOVA results showed a significant association between MSTN-1 gene polymorphism and growth traits. Pairwise tests revealed several RFLPs in the MSTN-1 gene with significant heterogeneity of genotypes among size groups. PRL and MSTN-1 genes presented linkage disequilibrium. The MSTN-1 gene was mapped in the centromeric region of a medium-size acrocentric chromosome pair.

  9. Assessment of tools for marker-assisted selection in a marine commercial species: significant association between MSTN-1 gene polymorphism and growth traits.

    Science.gov (United States)

    Sánchez-Ramos, Irma; Cross, Ismael; Mácha, Jaroslav; Martínez-Rodríguez, Gonzalo; Krylov, Vladimir; Rebordinos, Laureana

    2012-01-01

    Growth is a priority trait from the point of view of genetic improvement. Molecular markers linked to quantitative trait loci (QTL) have been regarded as useful for marker-assisted selection in complex traits as growth. Polymorphisms have been studied in five candidate genes influencing growth in gilthead seabream (Sparus aurata): the growth hormone (GH), insulin-like growth factor-1 (IGF-1), myostatin (MSTN-1), prolactin (PRL), and somatolactin (SL) genes. Specimens evaluated were from a commercial broodstock comprising 131 breeders (from which 36 males and 44 females contributed to the progeny). In all samples eleven gene fragments, covering more than 13,000 bp, generated by PCR-RFLP, were analyzed; tests were made for significant associations between these markers and growth traits. ANOVA results showed a significant association between MSTN-1 gene polymorphism and growth traits. Pairwise tests revealed several RFLPs in the MSTN-1 gene with significant heterogeneity of genotypes among size groups. PRL and MSTN-1 genes presented linkage disequilibrium. The MSTN-1 gene was mapped in the centromeric region of a medium-size acrocentric chromosome pair.

  10. Theta Burst Stimulation of the Cerebellum Modifies the TMS-Evoked N100 Potential, a Marker of GABA Inhibition.

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    Allanah Harrington

    Full Text Available 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.

  11. Expression of Potential Cancer Stem Cell Marker ABCG2 is Associated with Malignant Behaviors of Hepatocellular Carcinoma

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    Guang Zhang

    2013-01-01

    Full Text Available 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.

  12. Novel Peptide Marker Corresponding to Salivary Protein gSG6 Potentially Identifies Exposure to Anopheles Bites

    Science.gov (United States)

    Poinsignon, Anne; Cornelie, Sylvie; Mestres-Simon, Montserrat; Lanfrancotti, Alessandra; Rossignol, Marie; Boulanger, Denis; Cisse, Badara; Sokhna, Cheikh; Arcà, Bruno; Simondon, François; Remoue, Franck

    2008-01-01

    Background In order to improve malaria control, and under the aegis of WHO recommendations, many efforts are being devoted to developing new tools for identifying geographic areas with high risk of parasite transmission. Evaluation of the human antibody response to arthropod salivary proteins could be an epidemiological indicator of exposure to vector bites, and therefore to risk of pathogen transmission. In the case of malaria, which is transmitted only by anopheline mosquitoes, maximal specificity could be achieved through identification of immunogenic proteins specific to the Anopheles genus. The objective of the present study was to determine whether the IgG response to the Anopheles gambiae gSG6 protein, from its recombinant form to derived synthetic peptides, could be an immunological marker of exposure specific to Anopheles gambiae bites. Methodology/Principal Findings Specific IgG antibodies to recombinant gSG6 protein were observed in children living in a Senegalese area exposed to malaria. With the objective of optimizing Anopheles specificity and reproducibility, we designed five gSG6-based peptide sequences using a bioinformatic approach, taking into consideration i) their potential antigenic properties and ii) the absence of cross-reactivity with protein sequences of other arthropods/organisms. The specific anti-peptide IgG antibody response was evaluated in exposed children. The five gSG6 peptides showed differing antigenic properties, with gSG6-P1 and gSG6-P2 exhibiting the highest antigenicity. However, a significant increase in the specific IgG response during the rainy season and a positive association between the IgG level and the level of exposure to Anopheles gambiae bites was significant only for gSG6-P1. Conclusions/Significance This step-by-step approach suggests that gSG6-P1 could be an optimal candidate marker for evaluating exposure to Anopheles gambiae bites. This marker could be employed as a geographic indicator, like remote sensing

  13. Microarray-based identification of CUB-domain containing protein 1 as a potential prognostic marker in conventional renal cell carcinoma.

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    Awakura, Yasuo; Nakamura, Eijiro; Takahashi, Takeshi; Kotani, Hirokazu; Mikami, Yoshiki; Kadowaki, Tadashi; Myoumoto, Akira; Akiyama, Hideo; Ito, Noriyuki; Kamoto, Toshiyuki; Manabe, Toshiaki; Nobumasa, Hitoshi; Tsujimoto, Gozoh; Ogawa, Osamu

    2008-12-01

    Renal cell carcinoma (RCC) is characterized by a variable and unpredictable clinical course. Thus, accurate prediction of the prognosis is important in clinical settings. We conducted microarray-based study to identify a novel prognostic marker in conventional RCC. The present study included the patients surgically treated at Kyoto University Hospital. Gene expression profiling of 39 samples was carried out to select candidate prognostic markers. Quantitative real-time PCR of 65 samples confirmed the microarray experiment results. Finally, we evaluated the significance of potential markers at their protein expression level by immunohistochemically analyzing 230 conventional RCC patients. Using expression profiling analysis, we identified 14 candidate genes whose expression levels predicted unfavorable disease-specific survival. Next, we examined the expression levels of nine candidate genes by quantitative real-time PCR and selected CUB-domain containing protein 1 (CDCP1) for further immunohistochemical analysis. Positive staining for CDCP1 inversely correlated with disease-specific and recurrence-free survivals. In multivariate analysis including clinical/pathological factors, CDCP1 staining was a significant predictor of disease-specific and recurrence-free survivals. We identified CDCP1 as a potential prognostic marker for conventional RCC. Further studies might be required to confirm the prognostic value of CDCP1 and to understand its function in RCC progression.

  14. Effect of smoking on potential salivary markers of periodontal disease: A clinical and biochemical study

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    Narender Dev Gupta

    2016-01-01

    Full Text Available Introduction: Tobacco smoking exerts a harmful effect on the periodontal tissues manifested by periodontal pockets, attachment loss, and periodontal bone loss. Various factors contribute to the deleterious periodontal effects of smoking, including alteration of both microbial and host response factors. Moreover, smoking may exert effects throughout the cytokine network. Aims: The aim of this study was to evaluate the influence of smoking on periodontal biomarkers possibly related to the development of periodontitis including inflammatory mediators and pro-inflammatory cytokines in saliva. Materials and Methods: A total of sixty subjects aged 30–55 years were included in the study and divided into three groups: systemically and periodontally healthy individuals (Group 1, subjects with pocket probing depth (PPD ≥5 mm and clinical attachment loss (CAL of ≥2 mm (Group 2, and a subjects smoking (≥10 cigarettes a day with periodontal parameters of Group 2 (Group 3. Periodontal parameters of PPD, CAL, gingival index (GI, and plaque index were measured using standard indices and criteria. Three milliliters of unstimulated saliva was taken, and salivary tumor necrosis factor-alpha (TNF-α and matrix metalloproteinase-8 (MMP-8 were determined using ELISA technique. Results: The mean GI was lowest for Group 3, but the mean probing depth of Group 3 (4.93 ± 0.41 was highest. The mean TNF-α level of Group 3 was significantly different and higher as compared to Group 1 and Group 2 (24.32 ± 8.32 ng/ml vs. 6.43 ± 2.65 ng/ml, q = 16.14; P< 0.001. Similarly, the mean MMP-8 level of Group 3 (461.71 ± 58.01 ng/ml was significantly different (P < 0.001 and higher as compared to Group 1 (192.96 ± 134.89 ng/ml and Group 2 (347.83 ± 206.72 ng/ml. Both markers showed positive and significant correlation with their periodontal status. Conclusion: Our study clearly indicates a profound effect of smoking on salivary markers of periodontal disease (TNF-α and

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

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    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.

  16. Plasma Serotonin in Heart Failure: Possible Marker and Potential Treatment Target.

    Science.gov (United States)

    Selim, Ahmed M; Sarswat, Nitasha; Kelesidis, Iosif; Iqbal, Muhammad; Chandra, Ramesh; Zolty, Ronald

    2017-05-01

    The relationship between heart failure (HF) and the serotonergic system has been established in animal studies. However, data on human plasma serotonin level in HF and its significance over the course of the disease is lacking. Serotonin levels were measured in 173 patients (108 males, 65 females), 116 were stable HF and 40 were acute decompensated HF patients. The normal control group included 17 healthy volunteers with no known medical or psychiatric conditions. Patients receiving medications affecting serotonin receptors and those with pulmonary hypertension were excluded. All patients, except for those in the decompensated group, were on stable doses of HF medications. Plasma serotonin levels were significantly elevated in decompensated HF patients compared with stable patients (P=0.002). Higher plasma serotonin levels were associated with worse HF symptoms (NYHA class) and the presence of systolic dysfunction, and was borderline associated with low peak oxygen consumption during cardiopulmonary exercise testing (P=0.055). These results were independent of age, gender, race, hypertension, diabetes, renal failure, weight, coronary artery disease (CAD), atrial fibrillation and medication use. Serotonin is a marker for decompensation in patients with chronic heart failure. Higher serotonin levels were associated with worse HF symptoms and systolic dysfunction. Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  17. Serum inhibin B in polycystic ovary syndrome as a potential marker of ovarian dysfunction

    Directory of Open Access Journals (Sweden)

    Ćetković Aleksandar

    2008-01-01

    Full Text Available INTRODUCTION Polycystic ovary syndrome (PCOS is one of the most common causes of anovulation, infertility and hyperandrogenism, and the prevalence of this condition in women of reproductive is 5-10%. The growth of early ovarian antral follicles is arrested and dominant follicle selection is disturbed in this syndrome. OBJECTIVE The aim of this study is to investigate whether inhibin B serum concentrations represent the extent of ovarian abnormalities in patients with PCOS. METHOD Inhibin B serum concentrations on the third day of spontaneous menstrual cycle and other endocrine characteristics were compared between 20 patients with PCOS and 19 healthy women in the control group. RESULTS Inhibin B concentrations were not significantly different between women with PCOS and women in the control group. In patients with PCOS there was statistically significant correlation between serum inhibin B and LH (r=0.514; p=0.021. There were no positive correlations between inhibin B and others endocrine parameters in patients with PCOS (FSH, E2, T, androstenedione. CONCLUSION Inhibin B serum concentrations on the third day of spontaneous menstrual cycle in women with PCOS are not different from the concentrations in healthy women. Serum Inhibin B levels in patients with PCOS are only slightly correlated with the endocrine markers of the disease so it could not represent the magnitude of ovarian dysfunction in this syndrome.

  18. [Sleep disorder, a potential early diagnostic marker for psychiatric and neurodegenerative diseases].

    Science.gov (United States)

    Chen, Yan-Mei; Qin, Dong-Dong; Jiang, Hui-Hui; Hu, Xin-Tian; Ma, Yuan-Ye

    2011-02-01

    Sleep/circadian timing depends on several neurotransmitter systems, including 5-HT, NE, DA, Ach, GABA, etc. These neurotransmitter systems play critical roles in mental, emotional and cognitive functions in the brain. Dysfunctions of these systems not only result in sleep disorder, but are also related to many psychiatric and neurodegenerative diseases. Sleep disruption is tightly associated with an increased susceptibility to a broad range of psychiatric and neurodegenerative diseases, such as depression and Parkinson diseases. Non-human primates, especially the rhesus monkey is an excellent biomedical model for human sleep and CNS diseases. Establishing nonhuman primates' model of mental disorders and monitoring the sleep changes during the development of the model will help us to know more about the relationships between sleep disorder and psychiatric and neurodegenerative diseases. Sleep disorder as an early marker for psychiatric and neurodegenerative diseases would permit early intervention of these diseases and draw attention to the potential therapeutic benefits of normalizing sleep rhythms in individuals with brain pathologies.

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

    Science.gov (United States)

    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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. A hierarchy of event-related potential markers of auditory processing in disorders of consciousness

    Directory of Open Access Journals (Sweden)

    Steve Beukema

    2016-01-01

    Full Text Available Functional neuroimaging of covert perceptual and cognitive processes can inform the diagnoses and prognoses of patients with disorders of consciousness, such as the vegetative and minimally conscious states (VS;MCS. Here we report an event-related potential (ERP paradigm for detecting a hierarchy of auditory processes in a group of healthy individuals and patients with disorders of consciousness. Simple cortical responses to sounds were observed in all 16 patients; 7/16 (44% patients exhibited markers of the differential processing of speech and noise; and 1 patient produced evidence of the semantic processing of speech (i.e. the N400 effect. In several patients, the level of auditory processing that was evident from ERPs was higher than the abilities that were evident from behavioural assessment, indicating a greater sensitivity of ERPs in some cases. However, there were no differences in auditory processing between VS and MCS patient groups, indicating a lack of diagnostic specificity for this paradigm. Reliably detecting semantic processing by means of the N400 effect in passively listening single-subjects is a challenge. Multiple assessment methods are needed in order to fully characterise the abilities of patients with disorders of consciousness.

  1. Marker-based standardization and investigation of nutraceutical potential of Indian propolis.

    Science.gov (United States)

    Sadhana, Nanaware; Lohidasan, Sathiyanarayanan; Mahadik, Kakasaheb Ramoo

    2017-11-01

    Propolis, a resinous material collected by honey bees from various plants, has been explored globally for its medicinal and nutritional properties. However, research over Indian propolis is at infancy. This study was designed to investigate nutraceutical potential of Indian propolis. In the present study, propolis extract was standardized with respect to markers caffeic acid phenethyl ester, caffeic acid, galangin, luteolin, curcumin, apigenin, pinocembrin and quercetin by new high-performance thin-layer chromatographic (HPTLC) methods. The physico-chemical analysis, residues analysis and in vitro antioxidant activity analysis were performed. Nutraceutical value was examined in terms of fats, fibers, minerals, proteins, polysaccharides, total carbohydrates, and energy value. The developed HPTLC methods were found to be simple, reliable accurate, and the validation parameters were within the limits of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use guidelines. Macerated ethanolic extract of propolis (MEEP) was found to have polyphenolic content of (20.99 ± 0.24) mg/g and flavonoids content of (8.39 ± 0.04) mg/g. MEEP was found to comprise of (283.33 ± 51.31) g/kg fats, (30.07 ± 7.30) g/kg fibers, (102.56 ± 2.84) g/kg proteins and (389.36 ± 57.50) g/kg carbohydrate with a calorie value of (38 409.33 ± 6 169.80) kJ/kg. It was found that Indian propolis exhibited high nutraceutical value and showed absence of pesticides and heavy metals. The MEEP showed in vitro antioxidant activity with inhibitory concentration of (12.24 ± 4.64) μg/mL. The present work explores Indian propolis as a potential nutritious candidate. The proposed analytical methods can be applied in future screening of the quality of Indian propolis.

  2. Global gene expression profiling reveals SPINK1 as a potential hepatocellular carcinoma marker.

    Directory of Open Access Journals (Sweden)

    Aileen Marshall

    Full Text Available Liver cirrhosis is the most important risk factor for hepatocellular carcinoma (HCC but the role of liver disease aetiology in cancer development remains under-explored. We investigated global gene expression profiles from HCC arising in different liver diseases to test whether HCC development is driven by expression of common or different genes, which could provide new diagnostic markers or therapeutic targets.Global gene expression profiling was performed for 4 normal (control livers as well as 8 background liver and 7 HCC from 3 patients with hereditary haemochromatosis (HH undergoing surgery. In order to investigate different disease phenotypes causing HCC, the data were compared with public microarray repositories for gene expression in normal liver, hepatitis C virus (HCV cirrhosis, HCV-related HCC (HCV-HCC, hepatitis B virus (HBV cirrhosis and HBV-related HCC (HBV-HCC. Principal component analysis and differential gene expression analysis were carried out using R Bioconductor. Liver disease-specific and shared gene lists were created and genes identified as highly expressed in hereditary haemochromatosis HCC (HH-HCC were validated using quantitative RT-PCR. Selected genes were investigated further using immunohistochemistry in 86 HCC arising in liver disorders with varied aetiology. Using a 2-fold cut-off, 9 genes were highly expressed in all HCC, 11 in HH-HCC, 270 in HBV-HCC and 9 in HCV-HCC. Six genes identified by microarray as highly expressed in HH-HCC were confirmed by RT qPCR. Serine peptidase inhibitor, Kazal type 1 (SPINK1 mRNA was very highly expressed in HH-HCC (median fold change 2291, p = 0.0072 and was detected by immunohistochemistry in 91% of HH-HCC, 0% of HH-related cirrhotic or dysplastic nodules and 79% of mixed-aetiology HCC.HCC, arising from diverse backgrounds, uniformly over-express a small set of genes. SPINK1, a secretory trypsin inhibitor, demonstrated potential as a diagnostic HCC marker and should be

  3. Ameliorative potential of gingerol: Promising modulation of inflammatory factors and lipid marker enzymes expressions in HFD induced obesity in rats.

    Science.gov (United States)

    Brahma Naidu, Parim; Uddandrao, V V Sathibabu; Ravindar Naik, Ramavat; Suresh, Pothani; Meriga, Balaji; Begum, Mustapha Shabana; Pandiyan, Rajesh; Saravanan, Ganapathy

    2016-01-05

    Obesity, generally linked to hyperlipidemia, has been occurring of late with distressing alarm and has now become a global phenomenon casting a huge economic burden on the health care system of countries around the world. The present study investigated the effects of gingerol over 30 days on the changes in HFD-induced obese rats in marker enzymes of lipid metabolism such as fatty-acid synthase (FAS), Acetyl CoA Carboxylase (ACC), Carnitine Palmitoyl Transferase-1(CPT-1), HMG co-A Reductase (HMGR), Lecithin Choline Acyl Transferase (LCAT) and Lipoprotein Lipase (LPL) and inflammatory markers (TNF-α and IL-6). The rats were treated orally with gingerol (75 mg kg(-1)) once daily for 30 days with a lorcaserin-treated group (10 mg kg(-1)) included for comparison. Changes in body weight, glucose, insulin resistance and expressions of lipid marker enzymes and inflammatory markers in tissues were observed in experimental rats. The administration of gingerol resulted in a significant reduction in body weight gain, glucose and insulin levels, and insulin resistance, which altered the activity, expressions of lipid marker enzymes and inflammatory markers. It showed that gingerol had significantly altered these parameters when compared with HFD control rats. This study confirms that gingerol prevents HFD-induced hyperlipidemia by modulating the expression of enzymes important to cholesterol metabolism. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Novel peptide marker corresponding to salivary protein gSG6 potentially identifies exposure to Anopheles bites.

    Science.gov (United States)

    Poinsignon, Anne; Cornelie, Sylvie; Mestres-Simon, Montserrat; Lanfrancotti, Alessandra; Rossignol, Marie; Boulanger, Denis; Cisse, Badara; Sokhna, Cheikh; Arcà, Bruno; Simondon, François; Remoue, Franck

    2008-06-25

    In order to improve malaria control, and under the aegis of WHO recommendations, many efforts are being devoted to developing new tools for identifying geographic areas with high risk of parasite transmission. Evaluation of the human antibody response to arthropod salivary proteins could be an epidemiological indicator of exposure to vector bites, and therefore to risk of pathogen transmission. In the case of malaria, which is transmitted only by anopheline mosquitoes, maximal specificity could be achieved through identification of immunogenic proteins specific to the Anopheles genus. The objective of the present study was to determine whether the IgG response to the Anopheles gambiae gSG6 protein, from its recombinant form to derived synthetic peptides, could be an immunological marker of exposure specific to Anopheles gambiae bites. Specific IgG antibodies to recombinant gSG6 protein were observed in children living in a Senegalese area exposed to malaria. With the objective of optimizing Anopheles specificity and reproducibility, we designed five gSG6-based peptide sequences using a bioinformatic approach, taking into consideration i) their potential antigenic properties and ii) the absence of cross-reactivity with protein sequences of other arthropods/organisms. The specific anti-peptide IgG antibody response was evaluated in exposed children. The five gSG6 peptides showed differing antigenic properties, with gSG6-P1 and gSG6-P2 exhibiting the highest antigenicity. However, a significant increase in the specific IgG response during the rainy season and a positive association between the IgG level and the level of exposure to Anopheles gambiae bites was significant only for gSG6-P1. This step-by-step approach suggests that gSG6-P1 could be an optimal candidate marker for evaluating exposure to Anopheles gambiae bites. This marker could be employed as a geographic indicator, like remote sensing techniques, for mapping the risk of malaria. It could also represent

  5. Novel peptide marker corresponding to salivary protein gSG6 potentially identifies exposure to Anopheles bites.

    Directory of Open Access Journals (Sweden)

    Anne Poinsignon

    2008-06-01

    Full Text Available In order to improve malaria control, and under the aegis of WHO recommendations, many efforts are being devoted to developing new tools for identifying geographic areas with high risk of parasite transmission. Evaluation of the human antibody response to arthropod salivary proteins could be an epidemiological indicator of exposure to vector bites, and therefore to risk of pathogen transmission. In the case of malaria, which is transmitted only by anopheline mosquitoes, maximal specificity could be achieved through identification of immunogenic proteins specific to the Anopheles genus. The objective of the present study was to determine whether the IgG response to the Anopheles gambiae gSG6 protein, from its recombinant form to derived synthetic peptides, could be an immunological marker of exposure specific to Anopheles gambiae bites.Specific IgG antibodies to recombinant gSG6 protein were observed in children living in a Senegalese area exposed to malaria. With the objective of optimizing Anopheles specificity and reproducibility, we designed five gSG6-based peptide sequences using a bioinformatic approach, taking into consideration i their potential antigenic properties and ii the absence of cross-reactivity with protein sequences of other arthropods/organisms. The specific anti-peptide IgG antibody response was evaluated in exposed children. The five gSG6 peptides showed differing antigenic properties, with gSG6-P1 and gSG6-P2 exhibiting the highest antigenicity. However, a significant increase in the specific IgG response during the rainy season and a positive association between the IgG level and the level of exposure to Anopheles gambiae bites was significant only for gSG6-P1.This step-by-step approach suggests that gSG6-P1 could be an optimal candidate marker for evaluating exposure to Anopheles gambiae bites. This marker could be employed as a geographic indicator, like remote sensing techniques, for mapping the risk of malaria. It could

  6. DNA Microarray Analysis Identifies CKS2 and LEPR as Potential Markers of Meningioma Recurrence

    Science.gov (United States)

    Menghi, Francesca; Orzan, Francesca N.; Eoli, Marica; Farinotti, Mariangela; Maderna, Emanuela; Pisati, Federica; Bianchessi, Donatella; Valletta, Lorella; Lodrini, Sandro; Galli, Giuseppe; Anghileri, Elena; Pellegatta, Serena; Pollo, Bianca

    2011-01-01

    Meningiomas are the most frequent intracranial tumors. Surgery can be curative, but recurrences are possible. We performed gene expression analyses and loss of heterozygosity (LOH) studies looking for new markers predicting the recurrence risk. We analyzed expression profiles of 23 meningiomas (10 grade I, 10 grade II, and 3 grade III) and validated the data using quantitative polymerase chain reaction (qPCR). We performed LOH analysis on 40 meningiomas, investigating chromosomal regions on 1p, 9p, 10q, 14q, and 22q. We found 233 and 268 probe sets to be significantly down- and upregulated, respectively, in grade II or III meningiomas. Genes downregulated in high-grade meningiomas were overrepresented on chromosomes 1, 6, 9, 10, and 14. Based on functional enrichment analysis, we selected LIM domain and actin binding 1 (LIMA1), tissue inhibitor of metalloproteinases 3 (TIMP3), cyclin-dependent kinases regulatory subunit 2 (CKS2), leptin receptor (LEPR), and baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) for validation using qPCR and confirmed their differential expression in the two groups of tumors. We calculated ΔCt values of CKS2 and LEPR and found that their differential expression (C-L index) was significantly higher in grade I than in grade II or III meningiomas (p < .0001). Interestingly, the C-L index of nine grade I meningiomas from patients who relapsed in <5 years was significantly lower than in grade I meningiomas from patients who did not relapse. These findings indicate that the C-L index may be relevant to define the progression risk in meningioma patients, helping guide their clinical management. A prospective analysis on a larger number of cases is warranted. PMID:21948653

  7. Update on the potential significance of psammoma bodies in lung adenocarcinoma from a modern perspective.

    Science.gov (United States)

    Miyake, Akio; Okudela, Koji; Matsumura, Mai; Hideaki, Mitsui; Arai, Hiromasa; Umeda, Shigeaki; Yamanaka, Shoji; Ishikawa, Yoshihiro; Tajiri, Michihiko; Ohashi, Kenichi

    2017-09-12

    Psammoma bodies are concentrically lamellated microscopic structures made of calcium. They are commonly observed in papillary carcinomas of the thyroid gland and serous papillary adenocarcinomas of the ovary, but are also occasionally detected in lung adenocarcinomas. Only one study, published in 1972, has systematically described the significance of psammoma bodies in lung adenocarcinomas. The aim of this study was to update the significance of psammoma bodies in lung adenocarcinomas from a modern perspective. Psammoma bodies were detected in 7.2% (59/822) of the adenocarcinomas examined, among which the papillary (20.3%, 12/59) and acinar (44.1%, 26/59) histological subtypes, with the feature of a terminal respiratory unit (91.5%, 54/59), were dominant. Malignant potential (cell growth activity measured by Ki67 labelling, lymph node metastasis, and postoperative survival) did not significantly differ between adenocarcinomas with and without psammoma bodies. On the basis of cytogenetic features, adenocarcinomas with psammoma bodies were preferentially affected by tyrosine kinase inhibitor (TKI)-targetable driver mutations [EGFR (69.8%, 37/53), ALK (13.2%, 7/53), and ROS1 (1.9%, 1/53)]. Multivariate analyses confirmed that psammoma bodies may constitute an independent predictor for these mutations, particularly EGFR and ALK mutations. Psammoma bodies may predict a favourable response of lung adenocarcinomas to TKIs. © 2017 John Wiley & Sons Ltd.

  8. New risk markers may change the HeartScore risk classification significantly in one-fifth of the population

    DEFF Research Database (Denmark)

    Olsen, M H; Hansen, T W; Christensen, M K

    2008-01-01

    The study aim was to determine whether urine albumin/creatinine ratio (UACR), high-sensitivity C-reactive protein (hsCRP) or N-terminal pro-brain natriuretic peptide (Nt-proBNP) added to risk prediction based on HeartScore and history of diabetes or cardiovascular disease. A Danish population......CRP in subjects with low-moderate risk and UACR and Nt-proBNP in subjects with known diabetes of cardiovascular disease changed HeartScore risk classification significantly in 19% of the population....... sample of 2460 individuals was divided in three groups: 472 subjects receiving cardiovascular medication or having history of diabetes, prior myocardial infarction or stroke, 559 high-risk subjects with a 10-year risk of cardiovascular death above 5% as estimated by HeartScore, and 1429 low-moderate risk...

  9. Circulating Inflammatory Mediators as Potential Prognostic Markers of Human Colorectal Cancer.

    Directory of Open Access Journals (Sweden)

    Giuseppe Di Caro

    Full Text Available Cytokines and chemokines in the tumor microenvironment drive metastatic development and their serum levels might mirror the ongoing inflammatory reaction at the tumor site. Novel highly sensitive tools are needed to identify colorectal cancer patients at high risk of recurrence that should be more closely monitored during post-surgical follow up. Here we study whether circulating inflammatory markers might be used to predict recurrence in CRC patients.Circulating levels of the inflammatory cytokines IL-1, IL-6, IL-10, TNFalpha, CCL2, CXCL8, VEGF and the acute phase protein Pentraxin-3 were measured by ELISA in preoperative serum samples prospectively collected from a cohort of sixty-nine patients undergoing surgical resection for stage 0-IV CRC and associated with post-operative disease recurrence.Cox multivariate analysis showed that combined high levels (≥ROC cut off-value of CXCL8, VEGF and Pentraxin3 were associated with increased risk of disease recurrence [HR: 14.28; 95%CI: (3.13-65.1] independently of TNM staging. Kaplan-Meier analysis showed that CXCL8, VEGF and Pentraxin3 levels were significantly associated with worse survival (P<0.001.Circulating inflammatory mediators efficiently predicted postoperative recurrence after CRC surgery. Therefore, this study suggest that their validation in large-scale clinical trials may help in tailoring CRC post-surgical management.

  10. The potential of microRNAs as biofluid markers of neurodegenerative diseases – a systematic review

    DEFF Research Database (Denmark)

    Danborg, Pia B; Simonsen, Anja H; Waldemar, Gunhild

    2014-01-01

    MicroRNAs (miRNA) are biological molecules transcribed from non-protein coding regions of the genome, participating in regulating cellular processes. MiRNAs in biofluids may possess neurodegenerative disease biomarker potential for screening tests, differential diagnosis and disease progression...... monitoring. This systematic review clarifies biomarker potential of miRNAs detected in biofluids of neurodegenerative disease patients. Thirty-three and ten miRNAs displayed significant expression between patients with multiple sclerosis and Alzheimer's disease, respectively, compared to healthy controls...

  11. Toward better assessment of tornado potential in typhoons: Significance of considering entrainment effects for CAPE

    Science.gov (United States)

    Sueki, Kenta; Niino, Hiroshi

    2016-12-01

    The characteristics of typhoons that spawned tornadoes (tornadic typhoons: TTs) in Japan from 1991 to 2013 were investigated by composite analysis using the Japanese 55 year Reanalysis and compared with those of typhoons that did not spawn tornadoes (nontornadic typhoons: NTs). We found that convective available potential energy (CAPE), which considers the effects of entrainment (entraining CAPE: E-CAPE), and storm-relative environmental helicity (SREH) are significantly large in the northeast quadrant of TTs where tornadoes frequently occur and that E-CAPE and SREH in that quadrant for TTs are larger than those for NTs. On the other hand, ordinary CAPE without entrainment does not account for the spatial distribution of tornado occurrences nor does it distinguish TTs from NTs. E-CAPE is sensitive to humidity in the midtroposphere; thus, it is effective for detecting a conditionally unstable layer up to about 550 hPa, which is distinctive of TTs.

  12. Identifying potentially induced seismicity and assessing statistical significance in Oklahoma and California

    CERN Document Server

    McClure, Mark; Chiu, Kitkwan; Ranganath, Rajesh

    2016-01-01

    In this study, we develop a statistical method for identifying induced seismicity from large datasets and apply the method to decades of wastewater disposal and seismicity data in California and Oklahoma. The method is robust against a variety of potential pitfalls. The study regions are divided into gridblocks. We use a longitudinal study design, seeking associations between seismicity and wastewater injection along time-series within each gridblock. The longitudinal design helps control for non-random application of wastewater injection. We define a statistical model that is flexible enough to describe the seismicity observations, which have temporal correlation and high kurtosis. In each gridblock, we find the maximum likelihood estimate for a model parameter that relates induced seismicity hazard to total volume of wastewater injected each year. To assess significance, we compute likelihood ratio test statistics in each gridblock and each state, California and Oklahoma. Resampling is used to empirically d...

  13. Induced KCNQ1 autoimmunity accelerates cardiac repolarization in rabbits: potential significance in arrhythmogenesis and antiarrhythmic therapy.

    Science.gov (United States)

    Li, Jin; Maguy, Ange; Duverger, James Elber; Vigneault, Patrick; Comtois, Philippe; Shi, Yanfen; Tardif, Jean-Claude; Thomas, Dierk; Nattel, Stanley

    2014-11-01

    Autoantibodies directed against various cardiac receptors have been implicated in cardiomyopathy and heart rhythm disturbances. In a previous study among patients with dilated cardiomyopathy, autoantibodies targeting the cardiac voltage-gated KCNQ1 K(+) channel were associated with shortened corrected QT intervals (QTc). However, the electrophysiologic actions of KCNQ1 autoimmunity have not been assessed experimentally in a direct fashion. The purpose of this study was to investigate the cardiac electrophysiologic effects of KCNQ1 autoantibody production induced by vaccination in a rabbit model. Rabbits were immunized with KCNQ1 channel peptide. ECG recordings were obtained during a 1-month follow-up period. Rabbits then underwent in vivo electrophysiologic study, after which cardiomyocytes were isolated for analysis of slow delayed rectifier current (IKs) and action potential properties via patch-clamp. KCNQ1-immunized rabbits exhibited shortening of QTc compared to sham-immunized controls. Reduced ventricular effective refractory periods and increased susceptibility to ventricular tachyarrhythmia induction were noted in KCNQ1-immunized rabbits upon programmed ventricular stimulation. Action potential durations were shortened in cardiomyocytes isolated from KCNQ1-immunized rabbits compared to the sham group. IKs step and tail current densities were enhanced after KCNQ1 immunization. Functional and structural changes of the heart were not observed. The potential therapeutic significance of KCNQ1 immunization was then explored in a dofetilide-induced long QT rabbit model. KCNQ1 immunization prevented dofetilide-induced QTc prolongation and attenuated long QT-related arrhythmias. Induction of KCNQ1 autoimmunity accelerates cardiac repolarization and increases susceptibility to ventricular tachyarrhythmia induction through IKs enhancement. On the other hand, vaccination against KCNQ1 ameliorates drug-induced QTc prolongation and might be useful therapeutically to

  14. Development of genomic SSR and potential EST-SSR markers in ...

    African Journals Online (AJOL)

    PRECIOUS

    2009-11-16

    SSR markers in Bupleurum chinense DC. Chun Sui, Jian-He Wei*, Shi-Lin Chen, Huai-Qiong Chen and Cheng-Min Yang. Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences (CAMS) and ...

  15. Semi-targeted metabolomic approaches to validate potential markers of health for micronutrients: Analytical perspectives

    NARCIS (Netherlands)

    Bayle, M.L.; Wopereis, S.; Bouwman, J.; Ommen, B. van; Scalbert, A.; Pujos-Guillot, E.

    2012-01-01

    Recommended dietary allowances for micronutrients fluctuate noticeably within European Union countries. The Network of Excellence EURRECA (EURopean micronutrient RECommendations Aligned) aims at harmonising micronutrient intake recommendations through population groups. The lack of proper markers of

  16. Serum Sphingolipids Level as a Novel Potential Marker for Early Detection of Human Myocardial Ischaemic Injury

    Directory of Open Access Journals (Sweden)

    Emmanuel Eroume A Egom

    2013-06-01

    Full Text Available Background: Ventricular tachyarrhythmias are the most common and often the first manifestation of coronary heart disease and lead to sudden cardiac death. Early detection/identification of acute myocardial ischaemic injury at risk for malignant ventricular arrhythmias in patients remains an unmet medical need. In the present study, we examined the sphingolipids level after transient cardiac ischaemia following temporary coronary artery occlusion during percutaneous coronary intervention (PCI in patients and determined the role of sphingolipids level as a novel indicator for early detection of human myocardial ischaemic injury.Methods and Results:Venous samples were collected from either the coronary sinus (n=7 or femoral vein (n=24 from 31 patients aged 40-73 years-old at 1, 5 min and 12h, following elective PCI. Plasma sphingolipids levels were assessed by HPLC. At 1 min coronary sinus levels of sphingosine 1-phosphate (S1P, sphingosine (SPH and sphinganine (SA were increased by 314%, 115% and 614%, respectively (n=7, while peripheral blood levels increased by 79%, 68% and 272% (n=24. By 5 min, coronary sinus S1P and SPH levels increased further (720%, 117%, as did peripheral levels of S1P alone (792%. Where troponin T was detectable at 12 h (10 of 31, a strong correlation was found with peak S1P (R2=0.818; P<0.0001. Conclusion: For the first time, we demonstrate the behaviour of plasma sphingolipids following transient cardiac ischaemia in humans. The observation supports the important role of sphingolipids level as a potential novel marker of transient or prolonged myocardial ischaemia.

  17. Identification of Potential Transcriptomic Markers in Developing Ankylosing Spondylitis: A Meta-Analysis of Gene Expression Profiles

    Science.gov (United States)

    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. A comparison of prognostic significance of strong ion gap (SIG) with other acid-base markers in the critically ill: a cohort study.

    Science.gov (United States)

    Ho, Kwok M; Lan, Norris S H; Williams, Teresa A; Harahsheh, Yusra; Chapman, Andrew R; Dobb, Geoffrey J; Magder, Sheldon

    2016-01-01

    This cohort study compared the prognostic significance of strong ion gap (SIG) with other acid-base markers in the critically ill. The relationships between SIG, lactate, anion gap (AG), anion gap albumin-corrected (AG-corrected), base excess or strong ion difference-effective (SIDe), all obtained within the first hour of intensive care unit (ICU) admission, and the hospital mortality of 6878 patients were analysed. The prognostic significance of each acid-base marker, both alone and in combination with the Admission Mortality Prediction Model (MPM0 III) predicted mortality, were assessed by the area under the receiver operating characteristic curve (AUROC). Of the 6878 patients included in the study, 924 patients (13.4 %) died after ICU admission. Except for plasma chloride concentrations, all acid-base markers were significantly different between the survivors and non-survivors. SIG (with lactate: AUROC 0.631, confidence interval [CI] 0.611-0.652; without lactate: AUROC 0.521, 95 % CI 0.500-0.542) only had a modest ability to predict hospital mortality, and this was no better than using lactate concentration alone (AUROC 0.701, 95 % 0.682-0.721). Adding AG-corrected or SIG to a combination of lactate and MPM0 III predicted risks also did not substantially improve the latter's ability to differentiate between survivors and non-survivors. Arterial lactate concentrations explained about 11 % of the variability in the observed mortality, and it was more important than SIG (0.6 %) and SIDe (0.9 %) in predicting hospital mortality after adjusting for MPM0 III predicted risks. Lactate remained as the strongest predictor for mortality in a sensitivity multivariate analysis, allowing for non-linearity of all acid-base markers. The prognostic significance of SIG was modest and inferior to arterial lactate concentration for the critically ill. Lactate concentration should always be considered regardless whether physiological, base excess or physical-chemical approach

  19. Significance of the evaluation of the tissue proliferation specific marker (TPS) and the carcinoembryonal antigen (CEA) in patients with ulcerative colitis and adenocarcinoma.

    Science.gov (United States)

    Krauss, Hanna; Ignyś, Iwona; Kopczyński, Zygmunt; Piatek, Jacek

    2002-01-01

    The aim of our research was to evaluate TPS concentration as a marker of proliferative processes and the levels of CEA in children and adults with ulcerative colitis (UC) and in adults with colorectal adenocarcinoma (AC), to find out if there is any interdependence between TPS and CEA concentrations in these patients and to evaluate the usefulness of TPS as a marker of neoplastic risk in patients with UC. The study was carried out in 3 groups of patients: Group I consisted of 15 children, ages 10-18, treated for UC; Group II, 22 adults, ages 23-40, treated for UC; and Group III, 14 patients, ages 40-60, in whom AC was diagnosed. In Group II, the mean TPS concentration was significantly higher than in Group I (pGroup III, adults with AC, the mean TPS concentration was 1074.00+/-1356.87 U/l. Thus there was a statistically significant difference between TPS concentrations in adults with UC and adults with AC (pgroups with UC. However, a statistically significant difference occurred between CEA concentrations in children and adults with UC and the group of adults with AC (peffectiveness.

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

    Science.gov (United States)

    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.

  1. Enhanced Laws textures: A potential MRI surrogate marker of hepatic fibrosis in a murine model.

    Science.gov (United States)

    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 (T 2 , 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, T 2 , 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, T 2 , 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 T 2 (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.

  2. Side of dental anomalies and taurodontism as potential clinical markers for cleft subphenotypes.

    Science.gov (United States)

    Küchler, Erika Calvano; da Motta, Luise Gomes; Vieira, Alexandre Rezende; Granjeiro, José Mauro

    2011-01-01

    The aim of this work was to investigate in more detail the dental clinical features that could serve to define subphenotypes of oral clefts. Dental records of oral cleft subjects from a group of 164 cases were examined, and 157 were included in this study. In addition, 65 families with two or more siblings born with clefts and 30 control families were evaluated to determine whether dental phenotypes were sporadic. Type of oral cleft and dental phenotypes (tooth agenesis, supernumerary teeth, taurodontism, dental transposition, and microdontia) outside the cleft area were investigated. Association of dental anomalies with preferential subtypes of cleft (subphenotype) was assessed. A total of 74 subjects presented at least one developmental dental anomaly. Tooth agenesis was the most common dental anomaly (28.6%), followed by taurodontism (15.2%). Supernumerary teeth were associated with cleft palate only (p  =  .05). The absence of maxillary left lateral incisors was significantly associated with unilateral right cleft lip (p  =  .02). Bilateral clefts were strongly associated with bilateral dental anomalies (p taurodontism (odds ratio  =  3.95; 95% confidence interval, 2.28 to 6.82). Tooth agenesis, microdontic upper lateral incisors, and supernumerary teeth were most commonly found in unaffected siblings and parents of children born with clefts in comparison with families with no family history of clefts (p  =  .01). The preferential associations between specific cleft types with dental phenotypes suggest dental anomalies can be used as clinical markers to define the subphenotype isolated cleft lip and palate.

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

    Directory of Open Access Journals (Sweden)

    Vasco Elbrecht

    2016-04-01

    Full Text Available 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.

  4. Marker chromosomes.

    Science.gov (United States)

    Rao, Kiran Prabhaker; Belogolovkin, Victoria

    2013-04-01

    Marker chromosomes are a morphologically heterogeneous group of structurally abnormal chromosomes that pose a significant challenge in prenatal diagnosis. Phenotypes associated with marker chromosomes are highly variable and range from normal to severely abnormal. Clinical outcomes are very difficult to predict when marker chromosomes are detected prenatally. In this review, we outline the classification, etiology, cytogenetic characterization, and clinical consequences of marker chromosomes, as well as practical approaches to prenatal diagnosis and genetic counseling.

  5. Further significant effects of eldecalcitol on bone resorption markers and bone mineral density in postmenopausal osteoporosis patients having undergone long-term bisphosphonate treatment.

    Science.gov (United States)

    Iba, Kousuke; Sonoda, Tomoko; Takada, Junichi; Dohke, Takayuki; Yamashita, Toshihiko

    2017-03-01

    We investigated whether eldecalcitol has further significant effects on bone metabolic markers and bone mineral density (BMD) in osteoporosis patients having undergone long-term bisphosphonate treatment. Eldecalcitol treatment was initiated in 48 postmenopausal osteoporosis patients who had undergone bisphosphonate treatment with or without alfacalcidol treatment for more than 2 years (average period 6.3 years). Age, height, weight, total muscle volume, total fat volume, estimated glomerular filtration rate, and BMD at the lumbar spine, total hip, and distal third of the radius were measured as background data for each patient. Serum alkaline phosphatase, tartrate-resistant acid phosphatase 5b, calcium, and phosphate levels were measured at the baseline and 3 and 12 months after the initiation of eldecalcitol treatment, and BMD was measured at the baseline and 12 months after the initiation of eldecalcitol treatment. Tartrate-resistant acid phosphatase 5b level was significantly decreased at 3 and 12 months after the initiation of eldecalcitol treatment in comparison with the baseline level. There were no significant changes in alkaline phosphatase, calcium, or phosphate levels in comparison with the baseline levels. In addition, the lumbar spine BMD at 12 months after the initiation of treatment was significantly increased in comparison with the baseline level, although no significant changes in BMD at the total hip and distal third of the radius were observed. Eldecalcitol demonstrated significant effects in additionally decreasing the level of the bone resorption marker tartrate-resistant acid phosphatase 5b and increasing BMD at the lumbar spine, even in osteoporosis patients having undergone long-term bisphosphonate treatment.

  6. 3-Hydroxylysine, a potential marker for studying radical-induced protein oxidation

    DEFF Research Database (Denmark)

    Morin, B; Bubb, W A; Davies, Michael Jonathan

    1998-01-01

    albumin (BSA) and human low-density lipoprotein (LDL)] and diseased human tissues (atherosclerotic plaques and lens cataractous proteins). This work was aimed at investigating oxidized lysine as a sensitive marker for protein oxidation, as such residues are present on protein surfaces, and are therefore...... hydroxylysines are however useful markers, with HPLC analysis of 9-fluorenylmethyl chloroformate (FMOC) derivatives providing a sensitive and accurate method for quantitative measurement. Hydroxylysines have been detected in the hydrolysates of peptides (Gly-Lys-Gly and Lys-Val-Ile-Leu-Phe) and proteins (BSA...... with globular proteins such as BSA. Hydroxylysines, and particularly 3-hydroxylysine, may therefore be sensitive and useful markers of radical-mediated protein oxidation in biological systems....

  7. CXCL10/IP10 is a novel potential in vitro marker of TB infection

    Directory of Open Access Journals (Sweden)

    Ilaria Sauzullo

    2009-06-01

    Full Text Available Introduction IFN-γ is a pivotal cytokine in the immune response to Myc. tuberculosis, infact this is the key cytokine produced in response to antigens specific following tuberculosis exposure causing either active or latent tuberculosis (TB and this observation forms the basis of interferon gamma release assay (IGRA, but there are alternative or additional cytokines and chemokines that could be used to improve detection of Myc. tuberculosis infection.The aim of this study was to evaluate the diagnostic utility of chemokine CXCL10/IP-10 as biomarker of active TB and to compare the results with classical QuantiFERON-Gold assay . Methods CXCL10/IP-10 and IFN-γ responses to stimulation with ESAT-6 and CFP-10 were evaluated in 21 patients with active tuberculosis and in 6 healthy unexposed subjects with no history of TB or TB contact were used as controls healthy controls. QuantiFERON-TB Gold (QFT-G, Cellestis was used for the measurement of IFN-γ levels; CXCL10/IP-10 was detected by ELISA (R&D Systems . Results Of the 21 TB patients included, 11 had a QFT-G positive and 10 had negative QFT-G results.All QFT-G positive patients had increased levels of CXCL10/IP-10 (median, pg/ml in both ESAT-6 and CFP-10 stimulated samples patients compared to healthy controls (1807 and 1111 vs 251 and 188 of controls, respectively (p<0.001 for both. The patients with active TB and QFT-G negative exhibited higher concentrations of CXCL10/IP-10 following antigen stimulation (837 pg/ml for ESAT-6;1674 pg/ml for CFP-10 (p<0.001. Conclusion Our study showed that in all patients with active TB, the CXCL10/IP-10 is expressed in higher amounts than IFN-γ following Myc. tuberculosis antigen-specific stimulation, and CXCL10/IP-10 appeared to be even more sensitive than QuantiFERON TB-Gold in TB patients with negative IFN-γ response. The measurement of chemokine CXCL10/IP-10, although not specific for tuberculosis, may have potential as an alternative or additional marker

  8. Mining-related geochemical anomalies from 3500 to 2000 BP as potential stratigraphic markers for the base of the Anthropocene

    Science.gov (United States)

    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.

  9. Rare human papillomavirus 16 E6 variants reveal significant oncogenic potential

    Directory of Open Access Journals (Sweden)

    Tommasino Massimo

    2011-06-01

    Full Text Available Abstract The aim of this study was to determine whether low prevalence human papillomavirus (HPV 16 E6 variants differ from high prevalence types in their functional abilities. We evaluated functions relevant to carcinogenesis for the rarely-detected European variants R8Q, R10G and R48W as compared to the commonly detected L83V. Human immortalized keratinocytes (NIKS stably transduced with the E6 variants were used in most functional assays. Low and high prevalence E6 variants displayed similar abilities in abrogation of growth arrest and inhibition of p53 elevation induced by actinomycin D. Differences were detected in the abilities to dysregulate stratification and differentiation of NIKS in organotypic raft cultures, modulate detachment induced apoptosis (anoikis and hyperactivate Wnt signaling. No distinctive phenotype could be assigned to include all rare variants. Like L83V, raft cultures derived from variants R10G and R48W similarly induced hyperplasia and aberrantly expressed keratin 5 in the suprabasal compartment with significantly lower expression of keratin 10. Unlike L83V, both variants, and particularly R48W, induced increased levels of anoikis upon suspension in semisolid medium. R8Q induced a unique phenotype characterized by thin organotypic raft cultures, low expression of keratin 10, and high expression of keratins 5 and 14 throughout all raft layers. Interestingly, in a reporter based assay R8Q exhibited a higher ability to augment TCF/β-catenin transcription. The data suggests that differences in E6 variant prevalence in cervical carcinoma may not be related to the carcinogenic potential of the E6 protein.

  10. Development and significance of RAPD-SCAR markers for the identification of Litchi chinensis Sonn. by improved RAPD amplification and molecular cloning

    Directory of Open Access Journals (Sweden)

    Jingliang Cheng

    2015-01-01

    Conclusions: This study developed stable SCAR markers for the identification of L. chinensis by the cloning of the improved RAPD fragments. Combining RAPD and SCAR markers provides a simple and reliable tool for the genetic characterization of plant species.

  11. Potential vegetation markers – analytical pyrolysis of modern plant species representative of Neolithic SE Spain

    NARCIS (Netherlands)

    Schellekens, J.; Barbera, G.G.; Buurman, P.

    2013-01-01

    A selection of plant species that may have been relevant for the Neolithic in the SW Mediterranean have been characterised with pyrolysis gas chromatography mass spectrometry (pyrolysis–GC/MS) in search for molecular vegetation markers. Roots and aerial parts were analysed separately for the

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

    Directory of Open Access Journals (Sweden)

    Katrin Ramaker

    Full Text Available 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.

  13. Translation elongation factor 1-α gene as a potential taxonomic and identification marker in dermatophytes

    NARCIS (Netherlands)

    Mirhendi, Hossein; Makimura, Koichi; de Hoog, G Sybren; Rezaei-Matehkolaei, Ali; Najafzadeh, Mohammad Javad; Umeda, Yoshiko; Ahmadi, Bahram

    2014-01-01

    Intra- and interspecies variations of the translation elongation factor 1-α (Tef-1α) gene were evaluated as a new identification marker in a wide range of dermatophytes, which included 167 strains of 30 species. An optimized pan-dermatophyte primer pair was designed, and the target was sequenced.

  14. Neurone-specific enolase and N-acetyl-aspartate as potential peripheral markers of ischaemic stroke

    NARCIS (Netherlands)

    Stevens, H; Jakobs, C; de Jager, AEJ; Cunningham, RT; Korf, J

    Background After stroke, brain-specific proteins (including neurone-specific enolase) leak into the blood. The question addressed in the present study was whether N-acetyl-aspartate (amino acid derivative localized in cerebral neurones) could also serve as a peripheral marker of ischaemic damage.

  15. Development of genomic SSR and potential EST-SSR markers in ...

    African Journals Online (AJOL)

    Nineteen genomic SSR markers were developed using inter-simple sequence repeat (ISSR)- suppression PCR technique in Bupleurum chinense DC., a widely used Chinese medicinal plant. A total of 126 alleles were detected across 22 individual plants of B. chinense DC. f. octoradiatum (Bunge) Shan et Sheh, with an ...

  16. Pregnancy-associated microRNAs in plasma as potential molecular markers of ectopic pregnancy.

    Science.gov (United States)

    Miura, Kiyonori; Higashijima, Ai; Mishima, Hiroyuki; Miura, Shoko; Kitajima, Michio; Kaneuchi, Masanori; Yoshiura, Koh-Ichiro; Masuzaki, Hideaki

    2015-05-01

    To investigate cell-free pregnancy-associated microRNAs as molecular markers for the diagnosis of ectopic pregnancy. Laboratory study using human plasma samples. Research unit in a university hospital. Plasma samples from 18 women with ectopic pregnancies (EP group), 12 women with spontaneous abortion (SA group), and 26 normal women with singleton pregnancies (NP group). Total RNAs containing small RNA molecules extracted from 1.2 mL of plasma. Plasma concentrations of cell-free microRNAs measured by quantitative real-time reverse-transcriptase polymerase chain reaction. Plasma concentrations of cell-free pregnancy-associated microRNAs (miR-323-3p, miR-515-3p, miR-517a, miR-517c, and miR-518b) and serum concentration of human chorionic gonadotropin (hCG) were confirmed to have statistically significantly different plasma or serum concentrations in women with EP, SA, or NP. There was no statistically significant difference in the plasma concentrations of cell-free miR-21 between the three groups. By correlation coefficient analysis, no relationship was detected between serum hCG levels and plasma cell-free miR-517c, miR-515-3p, miR-517a, miR-518b, miR-323-3p, or miR-21 levels. Plasma concentrations of cell-free miR-517a could distinguish EP/SA from NP, yielding an area under the curve of 0.9654 (95% confidence interval, 0.9172-1.0). Plasma concentrations of cell-free miR-323-3p could distinguish EP from SA, yielding an area under the curve of 0.7454 (95% confidence interval, 0.5558-0.9349). Cell-free pregnancy-associated microRNAs have potential as molecular markers of ectopic pregnancy. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  17. Complete mitochondrial genomes of Taenia multiceps, T. hydatigena and T. pisiformis: additional molecular markers for a tapeworm genus of human and animal health significance

    Science.gov (United States)

    2010-01-01

    Background Mitochondrial genomes provide a rich source of molecular variation of proven and widespread utility in molecular ecology, population genetics and evolutionary biology. The tapeworm genus Taenia includes a diversity of tapeworm parasites of significant human and veterinary importance. Here we add complete sequences of the mt genomes of T. multiceps, T. hydatigena and T. pisiformis, to a data set of 4 published mtDNAs in the same genus. Seven complete mt genomes of Taenia species are used to compare and contrast variation within and between genomes in the genus, to estimate a phylogeny for the genus, and to develop novel molecular markers as part of an extended mitochondrial toolkit. Results The complete circular mtDNAs of T. multiceps, T. hydatigena and T. pisiformis were 13,693, 13,492 and 13,387 bp in size respectively, comprising the usual complement of flatworm genes. Start and stop codons of protein coding genes included those found commonly amongst other platyhelminth mt genomes, but the much rarer initiation codon GTT was inferred for the gene atp6 in T. pisiformis. Phylogenetic analysis of mtDNAs offered novel estimates of the interrelationships of Taenia. Sliding window analyses showed nad6, nad5, atp6, nad3 and nad2 are amongst the most variable of genes per unit length, with the highest peaks in nucleotide diversity found in nad5. New primer pairs capable of amplifying fragments of variable DNA in nad1, rrnS and nad5 genes were designed in silico and tested as possible alternatives to existing mitochondrial markers for Taenia. Conclusions With the availability of complete mtDNAs of 7 Taenia species, we have shown that analysis of amino acids provides a robust estimate of phylogeny for the genus that differs markedly from morphological estimates or those using partial genes; with implications for understanding the evolutionary radiation of important Taenia. Full alignment of the nucleotides of Taenia mtDNAs and sliding window analysis suggests

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

    Science.gov (United States)

    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

  19. Immunofluorescent analysis of testicular biopsies with germ cell and Sertoli cell markers shows significant MVH negative germ cell depletion with older age at orchiopexy.

    Science.gov (United States)

    Li, Ruili; Thorup, Jorgen; Sun, Cong; Cortes, Dina; Southwell, Bridget; Hutson, John

    2014-02-01

    Undescended testis is the most common defect in male newborns. This condition is associated with increased risks of infertility and testicular malignancy due to abnormal germ cell development in the testes. Early surgery may limit such risks. We analyzed germ cell development vs age at orchiopexy using a germ cell marker and a Sertoli cell marker on testicular biopsies. A total of 22 testicular biopsies at orchiopexy in 20 patients 5 to 24.5 months old were fixed and embedded in paraffin. Sections were processed and labeled with AMH antibody for Sertoli cells and MVH antibody for germ cells for immunofluorescent histochemical analysis. Confocal images were counted using ImageJ (National Institutes of Health, Bethesda, Maryland) for germ cells and testicular tubules. The data were analyzed using linear regression. Sertoli cells were clearly distinguished from MVH positive and negative germ cells located centrally or on basement membranes of tubules. Percentage of tubules with MVH negative germ cells significantly decreased with increasing age at orchiopexy (β = -0.03, p = 0.03). Total tubular numbers and "empty" tubules without germ cells significantly increased with age at orchiopexy (β = 1.15, p = 0.02 and β = 0.44, p = 0.04, respectively). AMH antibody distinguished Sertoli cells from germ cells, and MVH antibody distinguished 2 types of germ cells at different developmental stages. Biopsy at orchiopexy in older patients showed significant germ cell depletion. These results lend support to early surgery to optimize germ cell number. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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

    OpenAIRE

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

    2017-01-01

    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 associa...

  1. Serum β-glucuronidase as a potential colon cancer marker: a preliminary study

    Directory of Open Access Journals (Sweden)

    Napoleon Waszkiewicz

    2015-04-01

    Full Text Available 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.

  2. Matrix metalloproteinase-9 genotype as a potential genetic marker for abdominal aortic aneurysm.

    Science.gov (United States)

    Duellman, Tyler; Warren, Christopher L; Peissig, Peggy; Wynn, Martha; Yang, Jay

    2012-10-01

    Degradation of extracellular matrix support in the large abdominal arteries contribute to abnormal dilation of aorta, leading to abdominal aortic aneurysms, and matrix metalloproteinase-9 (MMP-9) is the predominant enzyme targeting elastin and collagen present in the walls of the abdominal aorta. Previous studies have suggested a potential association between MMP-9 genotype and abdominal aortic aneurysm, but these studies have been limited only to the p-1562 and (CA) dinucleotide repeat microsatellite polymorphisms in the promoter region of the MMP-9 gene. We determined the functional alterations caused by 15 MMP-9 single-nucleotide polymorphisms (SNPs) reported to be relatively abundant in the human genome through Western blots, gelatinase, and promoter-reporter assays and incorporated this information to perform a logistic-regression analysis of MMP-9 SNPs in 336 human abdominal aortic aneurysm cases and controls. Significant functional alterations were observed for 6 exon SNPs and 4 promoter SNPs. Genotype analysis of frequency-matched (age, sex, history of hypertension, hypercholesterolemia, and smoking) cases and controls revealed significant genetic heterogeneity exceeding 20% observed for 6 SNPs in our population of mostly white subjects from Northern Wisconsin. A step-wise logistic-regression analysis with 6 functional SNPs, where weakly contributing confounds were eliminated using Akaike information criteria, gave a final 2 SNP (D165N and p-2502) model with an overall odds ratio of 2.45 (95% confidence interval, 1.06-5.70). The combined approach of direct experimental confirmation of the functional alterations of MMP-9 SNPs and logistic-regression analysis revealed significant association between MMP-9 genotype and abdominal aortic aneurysm.

  3. MicroRNA Levels as Prognostic Markers for the Differentiation Potential of Human Mesenchymal Stromal Cell Donors.

    Science.gov (United States)

    Georgi, Nicole; Taipaleenmaki, Hanna; Raiss, Christian C; Groen, Nathalie; Portalska, Karolina Janaeczek; van Blitterswijk, Clemens; de Boer, Jan; Post, Janine N; van Wijnen, Andre J; Karperien, Marcel

    2015-08-15

    The ability of human mesenchymal stromal/stem cells (hMSCs) to differentiate into various mesenchymal cell lineages makes them a promising cell source for the use in tissue repair strategies. Since the differentiation potential of hMSCs differs between donors, it is necessary to establish biomarkers for the identification of donors with high differentiation potential. In this study, we show that microRNA (miRNA) expression levels are effective for distinguishing donors with high differentiation potential from low differentiation potential. Twenty hMSC donors were initially tested for marker expression and differentiation potential. In particular, the chondrogenic differentiation potential was evaluated on the basis of histological matrix formation, mRNA expression levels of chondrogenic marker genes, and quantitative glycosaminoglycan deposition. Three donors out of twenty were identified as donors with high chondrogenic potential, whereas nine showed moderate and eight showed low chondrogenic potential. Expression profiles of miRNAs involved in chondrogenesis and cartilage homeostasis were used for the distinction between high-performance hMSCs and low-performance hMSCs. Global mRNA expression profiles of the donors before the onset of chondrogenic differentiation revealed minor differences in gene expression between low and high chondrogenic performers. However, analysis of miRNA expression during a 7-day differentiation period identified miR-210 and miR-630 as positive regulators of chondrogenesis. In contrast, miR-181 and miR-34a, which are negative regulators of chondrogenesis, were upregulated during differentiation in low-performing donors. In conclusion, profiling of hMSC donors for a specific panel of miRNAs may have a prognostic value for selecting donors with high differentiation potential to improve hMSC-based strategies for tissue regeneration.

  4. Screening of Genes Specifically Expressed in Males of Fenneropenaeus chinensis and Their Potential as Sex Markers

    OpenAIRE

    Li, Shihao; Li, Fuhua; Xie, Yusu; Wang, Bing; Wen, Rong; Zhang, Chengsong; Yu, Kuijie; Xiang, Jianhai

    2013-01-01

    The androgenic gland (AG), playing an important role in sex differentiation of male crustacean, is a target candidate to understand the mechanism of male development and to mine male-specific sex markers. An SSH library (designated as male reproduction-related tissues—SSH library, MRT-SSH library for short) was constructed using cDNA from tissues located at the basal part of the 5th pereiopods, including AG and part of spermatophore sac, as tester, and the cDNA from the basal part of the 4th ...

  5. Serum YKL-40, a potential new marker of disease activity in patients with inflammatory bowel disease

    DEFF Research Database (Denmark)

    Vind, Ida; Johansen, J S; Price, P A

    2003-01-01

    BACKGROUND: YKL-40 is secreted by macrophages and neutrophils and is a growth factor for vascular endothelial cells and fibroblasts. Elevated serum concentrations of YKL-40 are found in patients with diseases characterized by inflammation or ongoing fibrosis. The aim of this study was to seek ass...... were found between serum YKL-40 and CRP, albumin and leucocytes. CONCLUSIONS: Serum YKL-40 is elevated in patients with active IBD and may be complementary to inflammatory markers and clinical characteristics in the assessment of disease activity....

  6. Serum YKL-40, a potential new marker of disease activity in patients with inflammatory bowel disease

    DEFF Research Database (Denmark)

    Vind, Ida; Johansen, J S; Price, P A

    2003-01-01

    BACKGROUND: YKL-40 is secreted by macrophages and neutrophils and is a growth factor for vascular endothelial cells and fibroblasts. Elevated serum concentrations of YKL-40 are found in patients with diseases characterized by inflammation or ongoing fibrosis. The aim of this study was to seek...... were found between serum YKL-40 and CRP, albumin and leucocytes. CONCLUSIONS: Serum YKL-40 is elevated in patients with active IBD and may be complementary to inflammatory markers and clinical characteristics in the assessment of disease activity....

  7. Soluble CD36 and risk markers of insulin resistance and atherosclerosis are elevated in polycystic ovary syndrome and significantly reduced during pioglitazone treatment

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Højlund, Kurt; Andersen, Marianne

    2008-01-01

    during insulin stimulation in PCOS patients and control subjects (n = 44). sCD36 and oxLDL were significant independent predictors of glucose and lipid metabolism, whereas hsCRP and IL-6 showed no significant contribution. Following pioglitazone treatment, insulin sensitivity increased, whereas sCD36 (3......OBJECTIVE: We investigated the relation between soluble CD36 (sCD36), risk markers of atherosclerosis and body composition, and glucose and lipid metabolism in polycystic ovary syndrome (PCOS). RESEARCH DESIGN AND METHODS: Thirty PCOS patients were randomized to 30 mg/day pioglitazone or placebo......: sCD36 (2.87 relative units [0.88-9.36] vs. 1.67 relative units [0.72-3.89]), oxLDL (44.9 units/l [26.9-75.1] vs. 36.1 units/l [23.4-55.5]), and hsCRP (0.26 mg/dl [0.03-2.41] vs. 0.12 mg/dl [0.02-0.81]) were significantly increased in PCOS patients versus control subjects (geometric mean +/- 2 SD...

  8. Potential toxicity of flavonoids and other dietary phenolics: significance for their chemopreventive and anticancer properties.

    Science.gov (United States)

    Galati, Giuseppe; O'Brien, Peter J

    2004-08-01

    Flavonoids, including isoflavones, are natural components in our diet and, with the burgeoning interest in alternative medicine, are increasingly being ingested by the general population. Plant phenolics, which form moieties on flavonoid rings, such as gallic acid, are also widely consumed. Several beneficial properties have been attributed to these dietary compounds, including antioxidant, anti-inflammatory, and anticarcinogenic effects. Flavonoid preparations are marketed as herbal medicines or dietary supplements for a variety of alleged nontoxic therapeutic effects. However, they have yet to pass controlled clinical trials for efficacy, and their potential for toxicity is an understudied field of research. This review summarizes the current knowledge regarding potential dietary flavonoid/phenolic-induced toxicity concerns, including their pro-oxidant activity, mitochondrial toxicity (potential apoptosis-inducing properties), and interactions with drug-metabolizing enzymes. Their chemopreventive activity in animal in vivo experiments may result from their ability to inhibit phase I and induce phase II carcinogen metabolizing enzymes that initiate carcinogenesis. They also inhibit the promotion stage of carcinogenesis by inhibiting oxygen radical-forming enzymes or enzymes that contribute to DNA synthesis or act as ATP mimics and inhibit protein kinases that contribute to proliferative signal transduction. Finally, they may prevent tumor development by inducing tumor cell apoptosis by inhibiting DNA topoisomerase II and p53 downregulation or by causing mitochondrial toxicity, which initiates mitochondrial apoptosis. While most flavonoids/phenolics are considered safe, flavonoid/phenolic therapy or chemopreventive use needs to be assessed as there have been reports of toxic flavonoid-drug interactions, liver failure, contact dermatitis, hemolytic anemia, and estrogenic-related concerns such as male reproductive health and breast cancer associated with dietary

  9. Expression level of chromodomain Y (CDY: potential marker for prediction of sperm recovery in non-obstructive azoospermia

    Directory of Open Access Journals (Sweden)

    Neda Heydarian

    2016-06-01

    Full Text Available Background: The availability of testis specific genes will be of help in choosing the most promising biomarkers for the detection of testicular sperm retrieval in patients with non-obstructive azoospermia (NOA. Testis specific chromodomain protein Y 1 (CDY1 is a histone acetyltransferase which concentrates in the round spermatid nucleus, where histone hyperacetylation occurs and causes the replacement of histones by the sperm-specific DNA packaging proteins, TNPs and PRMs. Objective: The aim was to evaluate CDY1 gene as a marker for predicting of successful sperm retrieval in NOA patients. Materials and Methods: This research was conducted on 29 patients with NOA who had undergone testicular sperm extraction (TESE procedure. NOA patients were subdivided into patients with successful sperm retrieval (NOA+, n=12 and patients with unsuccessful sperm retrieval (NOA-, n=17. Relative expression of CDY1 gene and chromatin incorporation of CDY1 protein were measured by quantitative real-time polymerase chain reaction (qRT-PCR and ELISA assay, respectively. Results: Quantification of mRNA relative expression and incorporation of CDY1 protein in chromatin showed significant lower expressions and protein levels of CDY1 in testis tissues of NOA- in comparison to NOA+ group. Conclusion: The findings in this study demonstrated a correlation between the low levels of CDY1 function and unsuccessful sperm recovery in the testicular tissues of NOA- compared to NOA+ patients. Therefore, it can be reasonable to consider CDY1 as a potential biomarker for predicting the presence of spermatozoa, although the claim needs more samples to be confirmed.

  10. Significance of antioxidant potential of plants and its relevance to therapeutic applications.

    Science.gov (United States)

    Kasote, Deepak M; Katyare, Surendra S; Hegde, Mahabaleshwar V; Bae, Hanhong

    2015-01-01

    Oxidative stress has been identified as the root cause of the development and progression of several diseases. Supplementation of exogenous antioxidants or boosting endogenous antioxidant defenses of the body is a promising way of combating the undesirable effects of reactive oxygen species (ROS) induced oxidative damage. Plants have an innate ability to biosynthesize a wide range of non-enzymatic antioxidants capable of attenuating ROS- induced oxidative damage. Several in vitro methods have been used to screen plants for their antioxidant potential, and in most of these assays they revealed potent antioxidant activity. However, prior to confirming their in vivo therapeutic efficacy, plant antioxidants have to pass through several physiopharmacological processes. Consequently, the findings of in vitro and in vivo antioxidant potential assessment studies are not always the same. Nevertheless, the results of in vitro assays have been irrelevantly extrapolated to the therapeutic application of plant antioxidants without undertaking sufficient in vivo studies. Therefore, we have briefly reviewed the physiology and redox biology of both plants and humans to improve our understanding of plant antioxidants as therapeutic entities. The applications and limitations of antioxidant activity measurement assays were also highlighted to identify the precise path to be followed for future research in the area of plant antioxidants.

  11. DISORDERED PORPHYRIN METABOLISM: A POTENTIAL BIOLOGICAL MARKER FOR AUTISM RISK ASSESSMENT

    Science.gov (United States)

    Heyer, Nicholas J.; Echeverria, Diana; Woods, James S.

    2011-01-01

    Autism (AUT) is a complex neurodevelopmental disorder that, together with Asperger Syndrome and Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS), comprises the expanded classification of autistic spectrum disorder (ASD). The heterogeneity of ASD underlies the need to identify biomarkers or clinical features that can be employed to identify meaningful subtypes of ASD, define specific etiologies, and inform intervention and treatment options. Previous studies have shown that disordered porphyrin metabolism, manifested principally as significantly elevated urinary concentrations of pentacarboxyl- (penta) and copro- porphyrins, is commonly observed among some children with ASD. Here, we extend these observations by specifically evaluating penta and copro porphyrins as biological indicators of ASD among 76 male children comprising 30 with validated AUT, 14 with PDD-NOS and 32 neurotypical (NT) controls. ASD children (AUT and PDD-NOS) had higher mean urinary penta (p porphyrin measures are strong predictors of both AUT and PDD-NOS and support the potential clinical utility of urinary porphyrin measures for identifying a subgroup of ASD subjects in whom disordered porphyrin metabolism may be a salient characteristic. PMID:22298513

  12. MSRV pol sequence copy number as a potential marker of multiple sclerosis.

    Science.gov (United States)

    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.

  13. Cerebrospinal fluid metabolomic profiling in tuberculous and viral meningitis: Screening potential markers for differential diagnosis.

    Science.gov (United States)

    Li, Zihui; Du, Boping; Li, Jing; Zhang, Jinli; Zheng, Xiaojing; Jia, Hongyan; Xing, Aiying; Sun, Qi; Liu, Fei; Zhang, Zongde

    2017-03-01

    Tuberculous meningitis (TBM) is the most severe and frequent form of central nervous system tuberculosis. The current lack of efficient diagnostic tests makes it difficult to differentiate TBM from other common types of meningitis, especially viral meningitis (VM). Metabolomics is an important tool to identify disease-specific biomarkers. However, little metabolomic information is available on adult TBM. We used (1)H nuclear magnetic resonance-based metabolomics to investigate the metabolic features of the CSF from 18 TBM and 20 VM patients. Principal component analysis and orthogonal signal correction-partial least squares-discriminant analysis (OSC-PLS-DA) were applied to analyze profiling data. Metabolites were identified using the Human Metabolome Database and pathway analysis was performed with MetaboAnalyst 3.0. The OSC-PLS-DA model could distinguish TBM from VM with high reliability. A total of 25 key metabolites that contributed to their discrimination were identified, including some, such as betaine and cyclohexane, rarely reported before in TBM. Pathway analysis indicated that amino acid and energy metabolism was significantly different in the CSF of TBM compared with VM. Twenty-five key metabolites identified in our study may be potential biomarkers for TBM differential diagnosis and are worthy of further investigation. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Oncogenic histone methyltransferase EZH2: A novel prognostic marker with therapeutic potential in endometrial cancer.

    Science.gov (United States)

    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

    2017-06-20

    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.

  15. A Preclinical Study of Laryngeal Motor-Evoked Potentials as a Marker Vagus Nerve Activation.

    Science.gov (United States)

    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 vagus nerve. Furthermore, our results suggest that low output currents are sufficient to activate vagal fibers.

  16. The role of microRNAs in colorectal liver metastasis: Important participants and potential clinical significances.

    Science.gov (United States)

    Wang, Dongxu; Liu, Jie; Huo, Tingting; Tian, Yaowen; Zhao, Lei

    2017-06-01

    Colorectal cancer is one of the most common cancers in the world, and liver metastasis is the leading direct cause of cancer-related deaths in colorectal cancer. MicroRNA is involved in tumor metastasis in many aspects; mounting studies have shown that microRNAs play important roles in colorectal liver metastasis. Although lots of reviews about the association between microRNAs and colorectal cancer metastasis have been published, the reviews specifically focusing on microRNAs and colorectal liver metastasis are still lacking in the literature. To address this issue, here, we summarize the underlying mechanisms of microRNAs in colorectal liver metastasis and explore their potential clinical applications in this aspect.

  17. Cocoa bioactive compounds: significance and potential for the maintenance of skin health.

    Science.gov (United States)

    Scapagnini, Giovanni; Davinelli, Sergio; Di Renzo, Laura; De Lorenzo, Antonino; Olarte, Hector Hugo; Micali, Giuseppe; Cicero, Arrigo F; Gonzalez, Salvador

    2014-08-11

    Cocoa has a rich history in human use. Skin is prone to the development of several diseases, and the mechanisms in the pathogenesis of aged skin are still poorly understood. However, a growing body of evidence from clinical and bench research has begun to provide scientific validation for the use of cocoa-derived phytochemicals as an effective approach for skin protection. Although the specific molecular and cellular mechanisms of the beneficial actions of cocoa phytochemicals remain to be elucidated, this review will provide an overview of the current literature emphasizing potential cytoprotective pathways modulated by cocoa and its polyphenolic components. Moreover, we will summarize in vivo studies showing that bioactive compounds of cocoa may have a positive impact on skin health.

  18. Immunofluorescence Analysis of Testicular Biopsies With Germ Cell and Sertoli Cell Markers Shows Significant MVH Negative Germ Cell Depletion With Older Age of Orchidopexy

    DEFF Research Database (Denmark)

    Li, Ruili; Thorup, Jørgen Mogens; Sun, Cong

    2014-01-01

    Undescended testis is the most common defect in newborn boys. It is associated with increased risks of infertility and testicular malignancy due to abnormal germ cell development in these testes. Early surgery may limit such risks. The aim of our study was to analyse germ cell development verses...... age of orchidopexy using a germ cell marker and a Sertoli cell marker on testicular biopsies....

  19. Significance of Matrix Metalloproteinase 9 Expression as Supporting Marker to Cytokeratin 19 mRNA in Sentinel Lymph Nodes in Breast Cancer Patients

    Directory of Open Access Journals (Sweden)

    Marek Murawski

    2016-04-01

    Full Text Available One-step nucleic acid amplification (OSNA detects and quantifies, with the use of a polymerase chain reaction, the presence of cytokeratin 19 mRNA in sentinel lymph nodes. The main advantage of the OSNA assay is the avoidance of second surgery in case of positive sentinel lymph node diagnosis. The objective of this study was to evaluate the significance of matrix metalloproteinase 9 expression by immunohistochemistry as supporting marker to cytokeratin 19 mRNA in sentinel lymph nodes in breast cancer patients and to relate this expression with clinicopathological data. This study was conducted on fresh sentinel lymph nodes obtained from 40 patients with tumors classified as carcinoma of no special type. The presence of metastatic cells in the slices of lymph nodes was evaluated by immunohistochemistry using antibodies for CK19 and MMP-9. Expression of CK19 and MMP-9 in lymph nodes was also confirmed by means of Western blot analysis. Results indicated that the strongest correlation with CK19 mRNA was displayed by MMP-9, CK19 (by immunohistochemistry, IHC, and nodal metastases (p < 0.001. Higher histological grading also positively correlated with CK19 mRNA, however that correlation was less significant. Since MMP-9 shows very strong correlation with CK19 mRNA in breast carcinoma of no special type metastases, expression of MMP-9 in sentinel lymph nodes should be considered as useful method whenever OSNA analysis is not available.

  20. Modulation of age-related changes in oxidative stress markers and energy status in the rat heart and hippocampus: a significant role for ozone therapy.

    Science.gov (United States)

    El-Sawalhi, Maha M; Darwish, Hebatallah A; Mausouf, Mohamed N; Shaheen, Amira A

    2013-08-01

    Oxidative stress emerges as a key player in the ageing process. Controlled ozone administration is known to promote an oxidative preconditioning or adaptation to oxidative stress. The present study investigated whether prophylactic ozone administration could interfere with the age-related changes in the heart and the hippocampus of rats. Four groups of rats, aged about 3 months old, were used. Group 1 (Prophylactic ozone group) received ozone/oxygen mixture by rectal insufflations (0.6 mg/kg) twice/week for the first 3 months, then once/week till the age of 15 months. Group 2 (Oxygen group) received oxygen as vehicle for ozone in a manner similar to group 1. Group 3 (Aged control group) was kept without any treatment until the age of 15 months. A fourth group of rats (Adult control group) was evaluated at 3 months of age to provide baseline data. Ozone alleviated age-associated redox state imbalance as evidenced by reduction of lipid and protein oxidation markers, lessening of lipofuscin deposition, restoration of glutathione levels in both tissues and normalization of glutathione peroxidase activity in the heart tissue. Ozone also mitigated age-associated energy failure in the heart and the hippocampus, improved cardiac cytosolic Ca(2+) homeostasis and restored the attenuated Na(+) , K(+) -ATPase activity in the hippocampus of aged rats. These data provide new evidence concerning the anti-ageing potential of prophylactic ozone administration. Copyright © 2012 John Wiley & Sons, Ltd.

  1. Transcriptome analysis of cattle muscle identifies potential markers for skeletal muscle growth rate and major cell types.

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  3. Components of Cell-Matrix Linkage as Potential New Markers for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Navdaev, Alexey; Eble, Johannes A., E-mail: eble@med.uni-frankfurt.de [Center for Molecular Medicine, Deptartment Vascular Matrix Biology, Excellence Cluster Cardio-Pulmonary System, Frankfurt University Hospital, Theodor-Stern-Kai 7, 60590 Frankfurt am Main (Germany)

    2011-02-25

    Prostate cancer is one of the most common tumor diseases worldwide. Often being non-aggressive, prostate tumors in these cases do not need immediate treatment. However, about 20% of diagnosed prostate cancers tend to metastasize and require treatment. Existing diagnostic methods may fail to accurately recognize the transition of a dormant, non-aggressive tumor into highly malignant prostate cancer. Therefore, new diagnostic tools are needed to improve diagnosis and therapy of prostate carcinoma. This review evaluates existing methods to diagnose prostate carcinoma, such as the biochemical marker prostate-specific antigen (PSA), but also discusses the possibility to use the altered expression of integrins and laminin-332 in prostate carcinomas as diagnostic tools and therapeutic targets of prostate cancer.

  4. Evaluation of the antibody response to Anopheles salivary antigens as a potential marker of risk of malaria.

    Science.gov (United States)

    Remoue, Franck; Cisse, Badara; Ba, Fatou; Sokhna, Cheikh; Herve, Jean-Pierre; Boulanger, Denis; Simondon, François

    2006-04-01

    The evaluation of human immune responses to arthropod bites may be a useful marker of exposure to vector-borne diseases, with applications to malaria, the most serious parasitic infection in humans. The specific antibody (Ab) IgG response to saliva obtained from Anopheles gambiae mosquitoes was evaluated in young children from an area of seasonal malaria transmission in Senegal. Specific IgG was higher in children who developed clinical Plasmodium falciparum malaria within the 3 months that followed than in those who did not (P<0.05), and it increased significantly (P<0.0001) with the level of Anopheles exposure, as evaluated by conventional entomological methods. These results suggest that evaluation of antisalivary Ab responses could be a useful approach for identifying a marker for the risk of malaria transmission.

  5. Antibiotic Resistance Genetic Markers and Integrons in White Soft Cheese: Aspects of Clinical Resistome and Potentiality of Horizontal Gene Transfer.

    Science.gov (United States)

    de Paula, Ana Caroline L; Medeiros, Julliane D; de Azevedo, Analice C; de Assis Chagas, Jéssica M; da Silva, Vânia L; Diniz, Cláudio G

    2018-02-19

    Antibiotic resistance poses an important threat to global public health and has become a challenge to modern medicine. The occurrence of antibiotic-resistant bacteria in a broad range of foods has led to a growing concern about the impact that food may have as a reservoir of antibiotic resistance genes. Considering Minas Frescal Cheese (MFC)-a typical Brazilian white soft cheese-and its economic and cultural values, in this study, medically relevant antimicrobial-resistance genetic markers (AR genes) were screened, and the occurrence of integrons were evaluated in manufactured MFC using culture-independent approaches. Through a fingerprinting analysis, the tested MFCs were brand-clustered, indicating reproducibility along the production chain. A common core of resistance markers in all brands evaluated and related antimicrobials such as β-lactams, tetracyclines, quinolones, and sulfonamide was detected. Several other markers, including efflux pumps and aminoglycosides-resistance were distributed among brands. Class 1 and 2 integrons were observed, respectively, in 77% and 97% of the samples. The presence of AR genes is of special interest due to their clinical relevance. Taken together, the data may suggest that the production chain of MFC might contribute to the spread of putative drug-resistant bacteria, which could greatly impact human health. Furthermore, detection of class 1 and class 2 integrons in MFC has led to discussions about resistance gene spread in this traditional cheese, providing evidence of potential horizontal transfer of AR genes to human gut microbiota.

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

    Science.gov (United States)

    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.

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

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    Virginie Marcel

    Full Text Available 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.

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

    Science.gov (United States)

    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 δ18O 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.

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

    Science.gov (United States)

    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).

  10. Discordant vs. concordant left bundle branch block: A potential clinical significance.

    Science.gov (United States)

    Khalil, Jalkh; Bernard, Abi Saleh; Maurice, Khoury; Zaheer, Yousef; Marwan, Refaat; Abdallah, Rebeiz; Samir, Alam; Hadi, Skouri

    2016-01-01

    LBBB in heart failure patients has prognostic significance. Subtypes of LBBB (concordant and discordant) have not been considered when considering management. The aim of this study is to explore the clinical difference between the two subtypes. 216 patients with LBBB were included and categorized into concordant (LBBBC) and discordant (LBBBD) groups. Of the 216 patients (age 69.13±11.7; 56% male 44% female), 133 (61.5%) were LBBBD and 83 (38.5%) were LBBBC. LBBBD patients presented with lower LVEF (mean 36% vs 51%; P<0.001), wider QRS (mean 160 ms vs 151 ms; P<0.001), larger LA (mean 45 cm(2) vs 40 cm(2); P<0.001), moderate to severe mitral and tricuspid regurgitation (17% vs 3%; P<0.05, 10% vs 1%; P<0.05 respectively), CKD (41% vs 18%; P<0.001), COPD (4.6% vs 0%; P<0.01), CAD (67% vs 36%; P<0.001), and CABG (39% vs 16%; P<0.001). LBBBD is significantly associated with worse cardiac function and clinical characteristics. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. FLT3 Mutation as a Significant Prognostic Marker in de novo Acute Myeloid Leukemia Patients: Incidence, Distribution and Association with Cytogenetic Findings in a Study from South India

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    Santhi Sarojam

    2014-10-01

    Full Text Available Background: Fms-like tyrosine kinase 3 is a tyrosine kinase receptor that plays an important role in proliferation and differentiation of hematopoietic stem cells. Internal tandem duplication and tyrosine kinase domain mutation are the two most common types of fms-like tyrosine kinase 3 mutations frequently reported in acute myeloid leukemia associated with pathogenesis of this disease. The present study investigates the prevalence and distribution pattern in different acute myeloid leukemia sub- and cytogenetic groups, the association with clinical parameters and the prognostic importance of these mutations in acute myeloid leukemia patients from South India. Methods:Mutation analysis was performed in 276 de novo acute myeloid leukemia patients by polymerase chain reaction restriction fragment length polymorphism using specific restriction enzymes followed by sequencing to confirm the mutations. Kaplan-Meier survival analysis was performed to detect the prognosis. Results: Fms-like tyrosine kinase 3 internal tandem duplication mutations were observed in 20%, tyrosine kinase domain mutation in 4% and dual mutations in 0.3% of the analyzed cases. The internal tandem duplication mutations ranged from 15-107 nucleotides with the majority at the juxta membrane domain of the receptor. Three types of tyrosine kinase domain point mutations were identified: D835Y, D835H and D835V. We observed a significant association between fms-like tyrosine kinase 3 mutations and increased WBC and LDH counts (P<0.001 and blast percentage but not with age, gender and FAB subtypes. A significant association with normal karyotype was observed for the mutants (P=0.002. Survival analysis revealed that the fms-like tyrosine kinase 3 gene mutation was a negative prognostic marker for acute myeloid leukemia patients. The risk stratified analysis showed the mutation to be a risk factor for the intermediate karyotype group, especially for those with normal cytogenetics

  12. Aquaculture: a rapidly growing and significant source of sustainable food? Status, transitions and potential.

    Science.gov (United States)

    Little, D C; Newton, R W; Beveridge, M C M

    2016-08-01

    The status and potential of aquaculture is considered as part of a broader food landscape of wild aquatic and terrestrial food sources. The rationale and resource base required for the development of aquaculture are considered in the context of broader societal development, cultural preferences and human needs. Attention is drawn to the uneven development and current importance of aquaculture globally as well as its considerable heterogeneity of form and function compared with established terrestrial livestock production. The recent drivers of growth in demand and production are examined and the persistent linkages between exploitation of wild stocks, full life cycle culture and the various intermediate forms explored. An emergent trend for sourcing aquaculture feeds from alternatives to marine ingredients is described and the implications for the sector with rapidly growing feed needs discussed. The rise of non-conventional and innovative feed ingredients, often shared with terrestrial livestock, are considered, including aquaculture itself becoming a major source of marine ingredients. The implications for the continued expected growth of aquaculture are set in the context of sustainable intensification, with the challenges that conventional intensification and emergent integration within, and between, value chains explored. The review concludes with a consideration of the implications for dependent livelihoods and projections for various futures based on limited resources but growing demand.

  13. Biliverdin reductase: new features of an old enzyme and its potential therapeutic significance.

    Science.gov (United States)

    Florczyk, Urszula M; Jozkowicz, Alicja; Dulak, Jozef

    2008-01-01

    Biliverdin reductase (BVR) was known for a long time solely as an enzyme converting biliverdin to bilirubin, the major physiological antioxidant. Recent years revealed unique features of this protein which are not related to its reductase activity. The most intriguing and surprising finding is its dual-specificity kinase character. As such serine/threonine/tyrosine kinase BVR is involved in regulation of glucose metabolism or in control of cell growth and apoptosis. In consequence, it may play a role in pathogenesis of many diseases, such as diabetes or cancers. Moreover, in the nucleus BVR, being a leucine zipper-like DNA binding protein, can act as a transcription factor for activator protein 1 (AP-1)-regulated genes. It has been shown that BVR modulates ATF-2 and HO-1 expression, what suggests its potential role in control of AP-1 and cAMP-regulated genes. In conclusion, BVR together with its substrate, biliverdin, and product, bilirubin, are revealed to be important players in cellular signal transduction pathways, gene expression and oxidative response. These features make BVR unusually interesting and unique among all enzymes characterized to date.

  14. Hydrogen emission in meteors as a potential marker for the exogenous delivery of organics and water

    Science.gov (United States)

    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 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.

  15. Oxidative stress markers and antioxidant potential of wheat treated with phytohormones under salinity stress

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    Nasser A.M. Barakat

    2011-12-01

    Full Text Available The interactive effects 0.5 mM indole acetic acid or 0.1 mM of salicylic acid as shoot spraying on NaCl wheat stressed plant organs (spike, shoot and root grown in pot experiment under different salinity levels (0, 50, 100, 150 and 200 mM NaCl were studied. The antioxidant enzymes as catalase, peroxidase and ascorbate peroxidase, photosynthetic pigments, reducing sugar, proteins, amino acids, and proline contents in spike, shoot and root of salinity stressed plants were the most affected parameters specially at high salinity levels (150-200 mM NaCl.Treatments with 0.5 mM indole acetic acid or 0.1 mM of salicylic acid as shoot spraying on NaCl wheat stressed plant organs mitigated the harmful effect of NaCl. To conclude the phytohormone indole acetic acid or salicylic acid improved salt tolerance in stressed wheat by significantly activated catalase, peroxidase, and ascorbate peroxidase, increased photosynthetic pigments and enhancing the accumulation of nontoxic metabolites (sugars, proteins, amino acid and free proline as a protective adaptation mechanism in different wheat organs. However, the magnitude of increase was more pronounced in salicylic acid treated plants than in indole acetic acid treated ones, and the spike was more accumulator organ of non toxic metabolites compared to shoot and root. Thus salicylic acid and/or indole acetic acid treatments prevents the deleterious effects of salinity stressed wheat and could be adopted as a potential growth regulator or antioxidant to improve growth particularly under moderate NaCl salinity levels, wheat plant respond positively to SA foliar application than IAA application.

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

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    Ji Tan

    Full Text Available 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.

  17. A new hero emerges: another exceptional mammalian spine and its potential adaptive significance.

    Science.gov (United States)

    Stanley, William T; Robbins, Lynn W; Malekani, Jean M; Mbalitini, Sylvestre Gambalemoke; Migurimu, Dudu Akaibe; Mukinzi, Jean Claude; Hulselmans, Jan; Prévot, Vanya; Verheyen, Erik; Hutterer, Rainer; Doty, Jeffrey B; Monroe, Benjamin P; Nakazawa, Yoshinori J; Braden, Zachary; Carroll, Darin; Peterhans, Julian C Kerbis; Bates, John M; Esselstyn, Jacob A

    2013-10-23

    The hero shrew's (Scutisorex somereni) massive interlocking lumbar vertebrae represent the most extreme modification of the vertebral column known in mammals. No intermediate form of this remarkable morphology is known, nor is there any convincing theory to explain its functional significance. We document a new species in the heretofore monotypic genus Scutisorex; the new species possesses cranial and vertebral features representing intermediate character states between S. somereni and other shrews. Phylogenetic analyses of DNA sequences support a sister relationship between the new species and S. somereni. While the function of the unusual spine in Scutisorex is unknown, it gives these small animals incredible vertebral strength. Based on field observations, we hypothesize that the unique vertebral column is an adaptation allowing these shrews to lever heavy or compressive objects to access concentrated food resources inaccessible to other animals.

  18. Complementary Therapies for Significant Dysfunction from Tinnitus: Treatment Review and Potential for Integrative Medicine

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    Ruth Q. Wolever

    2015-01-01

    Full Text Available Tinnitus is a prevalent and costly chronic condition; no universally effective treatment exists. Only 20% of patients who report tinnitus actually seek treatment, and when treated, most patients commonly receive sound-based and educational (SBE therapy. Additional treatment options are necessary, however, for nonauditory aspects of tinnitus (e.g., anxiety, depression, and significant interference with daily life and when SBE therapy is inefficacious or inappropriate. This paper provides a comprehensive review of (1 conventional tinnitus treatments and (2 promising complementary therapies that have demonstrated some benefit for severe dysfunction from tinnitus. While there has been no systematic study of the benefits of an Integrative Medicine approach for severe tinnitus, the current paper reviews emerging evidence suggesting that synergistic combinations of complementary therapies provided within a whole-person framework may augment SBE therapy and empower patients to exert control over their tinnitus symptoms without the use of medications, expensive devices, or extended programs.

  19. EXPRESSION OF NeuGc ON PIG CORNEAS AND ITS POTENTIAL SIGNIFICANCE IN PIG CORNEAL XENOTRANSPLANTATION

    Science.gov (United States)

    Lee, Whayoung; Miyagawa, Yuko; Long, Cassandra; Ekser, Burcin; Walters, Eric; Ramsoondar, Jagdeece; Ayares, David; Tector, A. Joseph; Cooper, David K. C.; Hara, Hidetaka

    2016-01-01

    Purpose Pigs expressing neither galactose-α1,3-galactose (Gal) nor N-glycolylneuraminic acid (NeuGc) take xenotransplantation one step closer to the clinic. Our aims were (i) to document the lack of NeuGc expression on corneas and aortas, and cultured endothelial cells (aortic [AECs]; corneal [CECs]) of GTKO/NeuGcKO pigs, and (ii) to investigate whether the absence of NeuGc reduced human antibody binding to the tissues and cells. Methods Wild-type (WT), GTKO, and GTKO/NeuGcKO pig were used for the study. Human tissues and cultured cells were negative controls. Immunofluorescence staining was performed using anti-Gal and anti-NeuGc antibodies, and to determine human IgM and IgG binding to tissues. Flow cytometric analysis was used to determine Gal and NeuGc expression on cultured CECs and AECs and to measure human IgM/IgG binding to these cells. Results Both Gal and NeuGc were detected on WT pig corneas and aortas. Although GTKO pigs expressed NeuGc, neither human nor GTKO/NeuGcKO pigs expressed Gal or NeuGc. Human IgM/IgG binding to corneas and aortas from GTKO and GTKO/NeuGcKO pigs was reduced compared to binding to WT pigs. Human antibody binding to GTKO/NeuGcKO AECs was significantly less than to GTKO AECs, but there was no significant difference in binding between GTKO and GTKO/NeuGcKO CECs. Conclusions The absence of NeuGc on GTKO aortic tissue and AECs is associated with reduced human antibody binding, and possibly will provide better outcome in clinical xenotransplantation using vascularized organs. For clinical corneal xenotransplantation, the absence of NeuGc expression on GTKO/NeuGcKO pig corneas may not prove an advantage over GTKO corneas. PMID:26418433

  20. Sweet waste extract uptake by a mosquito vector: Survival, biting, fecundity responses, and potential epidemiological significance.

    Science.gov (United States)

    Dieng, Hamady; Satho, Tomomitsu; Abang, Fatimah; Meli, Nur Khairatun Khadijah Binti; Ghani, Idris A; Nolasco-Hipolito, Cirilo; Hakim, Hafijah; Miake, Fumio; Ahmad, Abu Hassan; Noor, Sabina; Zuharah, Wan Fatma; Ahmad, Hamdan; Majid, Abdul Hafiz A; Morales Vargas, Ronald E; Morales, Noppawan P; Attrapadung, Siriluck; Noweg, Gabriel Tonga

    2017-05-01

    In nature, adult mosquitoes typically utilize nectar as their main energy source, but they can switch to other as yet unidentified sugary fluids. Contemporary lifestyles, with their associated unwillingness to consume leftovers and improper disposal of waste, have resulted in the disposal of huge amounts of waste into the environment. Such refuse often contains unfinished food items, many of which contain sugar and some of which can collect water from rain and generate juices. Despite evidence that mosquitoes can feed on sugar-rich suspensions, semi-liquids, and decaying fruits, which can be abundant in garbage sites, the impacts of sweet waste fluids on dengue vectors are unknown. Here, we investigated the effects of extracts from some familiar sweet home waste items on key components of vectorial capacity of Aedes aegypti. Adult mosquitoes were fed one of five diets in this study: water (WAT); sucrose (SUG); bakery product (remnant of chocolate cake, BAK); dairy product (yogurt, YOG); and fruit (banana (BAN). Differences in survival, response time to host, and egg production were examined between groups. For both males and females, maintenance on BAK extract resulted in marked survival levels that were similar to those seen with SUG. Sweet waste extracts provided better substrates for survival compared to water, but this superiority was mostly seen with BAK. Females maintained on BAK, YOG, and BAN exhibited shorter response times to a host compared to their counterparts maintained on SUG. The levels of egg production were equivalent in waste extract- and SUG-fed females. The findings presented here illustrate the potential of sweet waste-derived fluids to contribute to the vectorial capacity of dengue vectors and suggest the necessity of readdressing the issue of waste disposal, especially that of unfinished sweet foods. Such approaches can be particularly relevant in dengue endemic areas where rainfall is frequent and waste collection infrequent. Copyright

  1. The significance and export potential of Serbian economy with special reference to condition of livestock

    Directory of Open Access Journals (Sweden)

    Madžar Lidija

    2014-01-01

    Full Text Available With respect to the availability of significant human and natural resources, as well as the achieved level of production and processing, agriculture is the key economic activity of the Republic of Serbia. However, as a result of the transition process, the agriculture of the Republic of Serbia operates in extremely unstable, unpredictable and unfavorable conditions. It is therefore characterized by an unchanged production structure, primarily in capital-intensive production. Animal Husbandry in Serbia, together with farming, represents an essential branch of the agriculture. Serbian livestock occupies an important place in the national economy because it creates a greatvalue-added by engaging natural and human resources. Although this activity has a chance to grow into a significant agricultural industry, the volume of livestock during the last two decades has been constantly decreasing in the amount of 2-3% per annum. The aim of the research is to examine the causes of the reduced share of national agriculture and livestock in the gross domestic product (GDP of the country, as well as the cause of the tendency of gradual and persistent reduction and livestock crisis. Data from the paper, for the most part, are based on the Agricultural Census 2012. It should be noted that, due to different definition concepts, data obtained by the latest Census of Agriculture are not fully comparable with the data obtained in the former regular statistical surveys. Census of family farms and farms of entrepreneurs was conducted through interviews. The study also applied statistical analysis methods of current and interval time series data, as well as the method of the considered variables comparison. This paper, first, discusses the importance of agriculture and its foreign trade position in the Serbian national economy. Furthermore, attention is paid to the current state of the domestic livestock and its geographical distribution by statistically defined

  2. Intensive induction is effective in selected octogenarian acute myeloid leukemia patients: prognostic significance of karyotype and selected molecular markers used in the European LeukemiaNet classification.

    Science.gov (United States)

    Wetzler, Meir; Mrózek, Krzysztof; Kohlschmidt, Jessica; Dombret, Hervé; Döhner, Hartmut; Pilorge, Sylvain; Krug, Utz; Carroll, Andrew J; Larson, Richard A; Marcucci, Guido; Hiddemann, Wolfgang; Büchner, Thomas; Bloomfield, Clara D

    2014-02-01

    We investigated whether octogenarian patients with acute myeloid leukemia enrolled onto Cooperative Group clinical trials and treated with intensive induction therapy could be cured, and whether karyotype and selected molecular markers had any prognostic significance in these patients. Among 138 patients with cytogenetic information, normal karyotype was the most common (47.1%) followed by complex karyotype (14.5%) and sole +8 (9.4%). Among these patients, the relapse-free survival rate at 1 year was 37% and 13% at 3 years, and the respective overall survival rates were 24% and 8%. Whereas the 90 patients who survived beyond 30 days had the same relapse-free survival rates, their 1-year and 3-year overall survival rates were 36% and 11%, respectively. Of the 66 patients surviving beyond 30 days who could be classified into European LeukemiaNet genetic groups, those in the intermediate-I group had better overall survival than patients in the adverse group (P=0.01). Among patients with cytogenetically normal acute myeloid leukemia who were tested for the European LeukemiaNet-associated molecular alterations, FLT3-internal tandem duplication and NPM1 mutations, it was found that FLT3-internal tandem duplication (detected in 29% of patients) did not associate with overall survival (P=0.31), whereas NPM1 mutations (30%) were associated with a significantly longer overall survival (P=0.002). We conclude that intensive induction is effective and indicated in selected octogenarians with acute myeloid leukemia, that their overall survival varies among the European LeukemiaNet genetic groups and that NPM1 mutations may be of prognostic significance among octogenarian patients with cytogenetically normal acute myeloid leukemia.

  3. Significant improvement in dynamic visual acuity after cataract surgery: a promising potential parameter for functional vision.

    Science.gov (United States)

    Ao, Mingxin; Li, Xuemin; Huang, Chen; Hou, Zhiqiang; Qiu, Weiqiang; Wang, Wei

    2014-01-01

    Dynamic visual acuity (DVA) is a relatively independent parameter for evaluating the ability to distinguish details of a moving target. The present study has been designed to discuss the extent to which age-related cataract impacts DVA in elderly individuals and to determine whether it could be restored after bilateral phacoemulsification combined with intraocular lens implantation surgery. Twenty-six elderly cataract patients scheduled for binocular cataract surgery and 30 elderly volunteers without cataract were enrolled in the study. DVA at 15, 30, 60 and 90 degree per second (dps) was assessed, and velocity-dependent visual acuity decreases between consecutive speed levels were calculated. Compared with the control group, the patient group exhibited significantly worse DVA performance at all speed levels (pDVA performance at every speed level in the patient group clearly improved (pDVA was more pronounced than the improvement in static visual acuity (p15 dps = 0.001 and pDVA was more severe than its effects on static visual acuity. After cataract surgery, not only static vision of the patients was restored markedly, but also the dynamic vision. DVA could be an important adjunct to the current evaluation system of functional vision, thereby meriting additional attention in clinical assessment.

  4. Qualitative ubiquitome unveils the potential significances of protein lysine ubiquitination in hyphal growth of Aspergillus nidulans.

    Science.gov (United States)

    Chu, Xin-Ling; Feng, Ming-Guang; Ying, Sheng-Hua

    2016-02-01

    Protein ubiquitination is an evolutionarily conserved post-translational modification process in eukaryotes, and it plays an important role in many biological processes. Aspergillus nidulans, a model filamentous fungus, contributes to our understanding of cellular physiology, metabolism and genetics, but its ubiquitination is not completely revealed. In this study, the ubiquitination sites in the proteome of A. nidulans were identified using a highly sensitive mass spectrometry combined with immuno-affinity enrichment of the ubiquitinated peptides. The 4816 ubiquitination sites were identified in 1913 ubiquitinated proteins, accounting for 18.1% of total proteins in A. nidulans. Bioinformatic analysis suggested that the ubiquitinated proteins associated with a number of biological functions and displayed various sub-cellular localisations. Meanwhile, seven motifs were revealed from the ubiquitinated peptides, and significantly over-presented in the different pathways. Comparison of the enriched functional catalogues indicated that the ubiquitination functions divergently during growth of A. nidulans and Saccharomyces cerevisiae. Additionally, the proteins in A. nidulans-specific sub-category (cell growth/morphogenesis) were subjected to the protein interaction analysis which demonstrated that ubiquitination is involved in the comprehensive protein interactions. This study presents a first proteomic view of ubiquitination in the filamentous fungus, and provides an initial framework for exploring the physiological roles of ubiquitination in A. nidulans.

  5. Racial Disparities in Clinically Significant Prostate Cancer Treatment: The Potential Health Information Technology Offers.

    Science.gov (United States)

    Bickell, Nina A; Lin, Jenny J; Abramson, Sarah R; Hoke, Gerald P; Oh, William; Hall, Simon J; Stock, Richard; Fei, Kezhen; McAlearney, Ann Scheck

    2018-01-01

    Black men are more likely to die as a result of prostate cancer than white men, despite effective treatments that improve survival for clinically significant prostate cancer. We undertook this study to identify gaps in prostate cancer care quality, racial disparities in care, and underlying reasons for poorer quality care. We identified all black men and random age-matched white men with Gleason scores ≥ 7 diagnosed between 2006 and 2013 at two urban hospitals to determine rates of treatment underuse. Underuse was defined as not receiving primary surgery, cryotherapy, or radiotherapy. We then interviewed treating physicians about the reasons for underuse. Of 359 black and 282 white men, only 25 (4%) experienced treatment underuse, and 23 (92%) of these were black. Most (78%) cases of underuse were due to system failures, where treatment was recommended but not received; 38% of these men continued receiving care at the hospitals. All men with treatment underuse due to system failures were black. Treatment rates of prostate cancer are high. Yet, racial disparities in rates and causes of underuse remain. Only black men experienced system failures, a type of underuse amenable to health information technology-based solutions. Institutions are missing opportunities to use their health information technology capabilities to reduce disparities in cancer care.

  6. Nanoparticle-enhanced electrical impedance detection and its potential significance in image tomography.

    Science.gov (United States)

    Liu, Ran; Jin, Cuiyun; Song, Fengjuan; Liu, Jing

    2013-01-01

    The conductivity and permittivity of tumors are known to differ significantly from those of normal tissues. Electrical impedance tomography (EIT) is a relatively new imaging method for exploiting these differences. However, the accuracy of data capture is one of the difficult problems urgently to be solved in the clinical application of EIT technology. A new concept of EIT sensitizers is put forward in this paper with the goal of expanding the contrast ratio of tumor and healthy tissue to enhance EIT imaging quality. The use of nanoparticles for changing tumor characteristics and determining the infiltration vector for easier detection has been widely accepted in the biomedical field. Ultra-pure water, normal saline, and gold nanoparticles, three kinds of material with large differences in electrical characteristics, are considered as sensitizers and undergo mathematical model analysis and animal experimentation. Our preliminary results suggest that nanoparticles are promising for sensitization work. Furthermore, in experimental and simulation results, we found that we should select different sensitizers for the detection of different types and stages of tumor.

  7. Theileriosis in six dogs in South Africa and its potential clinical significance

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    Chantal T. Rosa

    2014-02-01

    Full Text Available Theileriosis is a tick-borne disease caused by a piroplasma of the genus Theileria that can causeanaemia and thrombocytopenia. Its clinical importance for dogs’ remains poorly understood,as only some develop clinical signs. In this study, physical and laboratory findings, treatment and outcomes of six client-owned diseased dogs presented at the Onderstepoort Veterinary Academic Hospital are described retrospectively. In the dogs, Theileria species (n = 4and Theileria equi (n = 2 were detected by a polymerase chain reaction (PCR-reverse blothybridisation assay in blood samples, whilst PCR for Babesia, Anaplasma and Ehrlichia were negative. The most common physical findings were pale mucous membranes (five out of six dogs, bleeding tendencies (five out of six dogs and lethargy (three out of six dogs. All dogs were thrombocytopenic [median 59.5 x 109/L (range 13–199] and five out of six dogs were anaemic [median haematocrit 18% (range 5–32]. Bone marrow core biopsies performed in two dogs showed myelofibrosis. Theileriosis was treated with imidocarb dipropionate and the suspected secondary immune-mediated haematological disorders with prednisolone and azathioprine. Five dogs achieved clinical cure and post-treatment PCR performed in three out of five dogs confirmed absence of circulating parasitaemia. An immune-mediated response to Theileria species is thought to result in anaemia and/or thrombocytopenia in diseased dogs with theileriosis. A bleeding tendency, most likely secondary to thrombocytopenia and/or thrombocytopathy, was the most significant clinical finding in these cases. The link between thrombocytopenia, anaemia and myelofibrosis in theileriosis requires further investigation and theileriosis should be considered a differential diagnosis for dogs presenting with anaemia and/or thrombocytopenia in endemic tick-borne disease areas.

  8. The significance of SAR remote sensing in volcano-geology for hazard and resource potential mapping

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    Saepuloh, Asep; Bakker, Erwin; Suminar, Wulan

    2017-07-01

    Geological mapping at volcanic terrain is crucial for providing accurate information related to the distribution of volcanic products and volcano-related structures. The volcano-geology map is basis information, not only for hazard mitigation related to volcanic activity, but also for resource exploration as well as scientific purposes. Therefore, the accurate detection and observation of volcanic products and their genetics are necessary for volcano-geology mapping. The classical problem at Torrid Zone such as cloud, dense vegetation, heavy weathering, and erosion usually hamper the detection and observation of volcanic products and their structures. Moreover, the stratigraphic of volcanic products generally follows paleo-topography which was buried by the products. Overcoming the problem, we exploited the applicability of remotely sensed data to provide the great assistance for field based observations at volcanic field in Indonesia. The Geomorphologic and Structural Features (GSF) of the Synthetic Aperture Radar (SAR) are the selected parameters to define the distribution of the volcanic products. We explained about the significant of SAR identification to detect and interpret volcano-geology parameters such as eruption centers, volcanic products, depositional mechanisms, and volcanic structures especially at complex of volcanoes. The fall and flowing mechanisms controlled the depositional process were also analyzed to obtain the genetic of volcanic products. For young volcanoes, the quantitative techniques based on SAR surface roughness and polarized signatures are effective to identify volcanic formations and their sources. However, for old volcanoes the visual analyses of GSF is superior to identify the volcanic units and structures. We selected two volcanic complexes at Mts. Guntur and Malabar in West Java (Indonesia) presenting the young and old volcanic field characteristics under Torrid Zone condition.

  9. Granulocyte macrophage - colony stimulating factor (GM-CSF) significantly enhances articular cartilage repair potential by microfracture.

    Science.gov (United States)

    Truong, M-D; Choi, B H; Kim, Y J; Kim, M S; Min, B-H

    2017-08-01

    To investigate whether granulocyte macrophage-colony stimulating factor (GM-CSF) can be used to increase the number of mesenchymal stem cells (MSCs) in blood clots formed by microfracture arthroplasty (MFX) and whether it can improve the therapeutic outcome for cartilage repair. Thirty-six New Zealand white rabbits were divided into four groups: (1) control, (2) GM-CSF, (3) MFX, and (4) GM-CSF + MFX. GM-CSF was administrated intravenously (IV) at 10 μg/kg body weight 20 min before the MFX surgery. The repaired tissues were retrieved and examined by histological observation, quantitative assessment, and biochemical assays at 4, 8, and 12 weeks after treatment. The number of MSCs was measured in the blood clots by the colony forming unit-fibroblast (CFU-F) assay. The kinetic profile and distribution of GM-CSF in vivo was also evaluated by near-Infrared (NIR) fluorescence imaging and enzyme-linked immune sorbent assay. In the histological observations and chemical assays examined at 4, 8, and 12 weeks, the MFX after GM-CSF administration showed better cartilage repair than the one without GM-CSF. The CFU-F assay showed a significantly larger amount of MSCs present in the blood clots of the GM-CSF + MFX group than in the blood clots of the other groups. The blood concentration of GM-CSF peaked at 10 min and decreased back to almost the initial level after a couple of hours. GM-CSF was distributed in many organs including the bone marrow but was not observed clearly in the joint cavity. Intravenous administration of GM-CSF together with MFX could be a promising therapeutic protocol to enhance the repair of cartilage defects. Copyright © 2017. Published by Elsevier Ltd.

  10. Marker-Based Estimates Reveal Significant Nonadditive Effects in Clonally Propagated Cassava (Manihot esculenta): Implications for the Prediction of Total Genetic Value and the Selection of Varieties

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    Wolfe, Marnin D.; Kulakow, Peter; Rabbi, Ismail Y.; Jannink, Jean-Luc

    2016-01-01

    In clonally propagated crops, nonadditive genetic effects can be effectively exploited by the identification of superior genetic individuals as varieties. Cassava (Manihot esculenta Crantz) is a clonally propagated staple food crop that feeds hundreds of millions. We quantified the amount and nature of nonadditive genetic variation for three key traits in a breeding population of cassava from sub-Saharan Africa using additive and nonadditive genome-wide marker-based relationship matrices. We then assessed the accuracy of genomic prediction for total (additive plus nonadditive) genetic value. We confirmed previous findings based on diallel crosses that nonadditive genetic variation is significant for key cassava traits. Specifically, we found that dominance is particularly important for root yield and epistasis contributes strongly to variation in cassava mosaic disease (CMD) resistance. Further, we showed that total genetic value predicted observed phenotypes more accurately than additive only models for root yield but not for dry matter content, which is mostly additive or for CMD resistance, which has high narrow-sense heritability. We address the implication of these results for cassava breeding and put our work in the context of previous results in cassava, and other plant and animal species. PMID:27587297

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

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    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

  12. Significant improvement in dynamic visual acuity after cataract surgery: a promising potential parameter for functional vision.

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    Mingxin Ao

    Full Text Available PURPOSE: Dynamic visual acuity (DVA is a relatively independent parameter for evaluating the ability to distinguish details of a moving target. The present study has been designed to discuss the extent to which age-related cataract impacts DVA in elderly individuals and to determine whether it could be restored after bilateral phacoemulsification combined with intraocular lens implantation surgery. METHODS: Twenty-six elderly cataract patients scheduled for binocular cataract surgery and 30 elderly volunteers without cataract were enrolled in the study. DVA at 15, 30, 60 and 90 degree per second (dps was assessed, and velocity-dependent visual acuity decreases between consecutive speed levels were calculated. RESULTS: Compared with the control group, the patient group exhibited significantly worse DVA performance at all speed levels (p<0.001, and the decreases in velocity-dependent visual acuity were more serious in the patient group at the intervals of 0-15 dps (p<0.001, 15-30 dps (p = 0.007 and 30-60 dps (p = 0.008. Postoperatively, DVA performance at every speed level in the patient group clearly improved (p<0.001 and recovered to levels compatible to the control group. The decrease in visual acuity with increasing speed was less pronounced than during the preoperative phase (p0-15 dps = 0.001, p15-30 dps<0.001 and p30-60 dps = 0.001 and became similar to that of the control group. The postoperative visual benefit regarding DVA was more pronounced than the improvement in static visual acuity (p15 dps = 0.001 and p<0.001 at 30 dps, 60 dps and 90 dps. CONCLUSIONS: The impact of age-related cataract on DVA was more severe than its effects on static visual acuity. After cataract surgery, not only static vision of the patients was restored markedly, but also the dynamic vision. DVA could be an important adjunct to the current evaluation system of functional vision, thereby meriting additional attention in clinical assessment.

  13. State and trait markers of emotionally charged visual event-related potentials (P300) in drug-naïve schizophrenia.

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    Mori, Keiichiro; Morita, Kiichiro; Shoji, Yoshihisa; Matsuoka, Toshimasa; Fujiki, Ryo; Uchimura, Naohisa

    2012-06-01

    In the present study, we investigated the changes in P3 component in the emotionally charged visual event-related potentials (ERP) in 30 drug-naïve schizophrenic patients for up to 1 year. Visual oddball event-related potential was recorded from six recording sites for crying baby or smiling baby photographs. ERP were recorded before the treatment (session 1 [S1]), after 3 months (session 2 [S2]), and after 12 months (session 3 [S3]), as well as in 30 healthy subjects. Before taking medicine, there were no significant differences in the P300 amplitude between viewing photographs of a crying and a smiling baby. The P300 amplitude was significantly larger at S2 and S3 than at S1 for a crying baby, while there was no significant difference among sessions for a smiling baby after medication. A significant difference of the P300 amplitude was only observed between S3 and healthy subjects for a smiling baby. The P300 latency only when viewing a smiling face became significantly longer at S3 than those at S1 and S2. A significant negative correlation was obtained between the P300 amplitude changes upon viewing crying faces and negative syndrome score changes at the Pz site. The P300 amplitude induced by crying-face stimuli may be a state marker and the P300 amplitude caused by smiling-face stimuli may be a trait marker during recovery in schizophrenic patients. Atypical antipsychotic medications may be useful and may recover cognitive function reflected by the emotionally charged visual P300 components in schizophrenic patients. © 2012 The Authors. Psychiatry and Clinical Neurosciences © 2012 Japanese Society of Psychiatry and Neurology.

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

    Science.gov (United States)

    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.

  15. Intraindividual variability across cognitive tasks as a potential marker for prodromal Alzheimer’s disease

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    Andrea Maria Kälin

    2014-07-01

    Full Text Available Recent studies have shown that increased cognitive intraindividual variability (IIV across accuracy scores from tests representing different cognitive domains (across-domain IIV might indicate prodromal Alzheimer’s disease (AD. Although IIV has been proposed to index cognitive control processes, IIV across accuracy scores from cognitive control tasks (within-domain IIV has not been examined in healthy controls subjects (HCS, mild cognitive impairment (MCI and AD patients in a single comparative study. This study examines the discriminative properties of within-domain IIV, and across-domain IIV in 149 HCS, 31 MCI and 26 AD. Three tasks representing different cognitive domains were identified to calculate across-domain IIV. Three other tasks representing cognitive control were identified to calculate within-domain IIV. The intraindividual standard deviation (ISD was calculated across accuracy scores. To compare IIV between groups, ANCOVAs with the covariates age, gender, education, and mean performance were computed. IIV scores in general were higher in AD vs. HCS (p< 0.01. Only across-domain IIV was higher in AD vs. MCI (p=0.001, and only within-domain IIV was higher in MCI vs. HCS (p=0.05. Within-domain IIV may constitute a cognitive marker for the detection of prodromal AD at the MCI stage, whereas across-domain IIV may detect beginning AD at the MCI stage.

  16. Human AP Endonuclease 1: A Potential Marker for the Prediction of Environmental Carcinogenesis Risk

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    Jae Sung Park

    2014-01-01

    Full Text Available Human apurinic/apyrimidinic endonuclease 1 (APE1 functions mainly in DNA repair as an enzyme removing AP sites and in redox signaling as a coactivator of various transcription factors. Based on these multifunctions of APE1 within cells, numerous studies have reported that the alteration of APE1 could be a crucial factor in development of human diseases such as cancer and neurodegeneration. In fact, the study on the combination of an individual’s genetic make-up with environmental factors (gene-environment interaction is of great importance to understand the development of diseases, especially lethal diseases including cancer. Recent reports have suggested that the human carcinogenic risk following exposure to environmental toxicants is affected by APE1 alterations in terms of gene-environment interactions. In this review, we initially outline the critical APE1 functions in the various intracellular mechanisms including DNA repair and redox regulation and its roles in human diseases. Several findings demonstrate that the change in expression and activity as well as genetic variability of APE1 caused by environmental chemical (e.g., heavy metals and cigarette smoke and physical carcinogens (ultraviolet and ionizing radiation is likely associated with various cancers. These enable us to ultimately suggest APE1 as a vital marker for the prediction of environmental carcinogenesis risk.

  17. PTEN: A potential prognostic marker in virus-induced hepatocellular carcinoma.

    Science.gov (United States)

    Khalid, Ayesha; Hussain, Tabinda; Manzoor, Sobia; Saalim, Muhammad; Khaliq, Saba

    2017-06-01

    PTEN is the second most frequently mutated tumor suppresser gene in cancers after p53. Genetic and epigenetic alterations in the PTEN gene and its regulatory regions have been reported in various studies. PTEN is a crucial downregulator of the pro-survival phosphoinositide 3-kinase/Akt/mammalian target of rapamycin pathway and also suppresses insulin signaling. Failure to regulate these pathways leads to increase in cell proliferation and migration which in turn promotes tumorigenesis. PTEN underexpression is mediated by a variety of cytokines and stress kinases which seem to collectively induce the RAS/mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway. In the context of hepatocellular carcinoma, reduced expression of PTEN is seen in nearly half of the cases on average. In some cases, PTEN has been observed to be either mutated or methylated which can also lead to reduced expression or in some cases, complete loss of expression. On the cellular level, PTEN is also a target in the pathogenic pathway of hepatitis C virus core protein and hepatitis B virus X protein. These viruses appear to alter PTEN regulation and pro-apoptotic ability to enhance the process of tumor formation. In perspective of the crucial role PTEN plays in balancing proliferation and apoptosis, we propose PTEN as a valuable marker in the diagnosis, assessment of tumor grade, and disease stage in hepatocellular carcinoma patients.

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

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    Fernando N. Aguiar

    2013-05-01

    Full Text Available 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.

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

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    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.

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

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    Marco Ballardini

    2013-12-01

    Full Text Available 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.

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

    Science.gov (United States)

    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. Copyright © 2014. Published by Elsevier Ltd.

  2. The potential for a suite of isotope and chemical markers to differentiate sources of nitrate contamination: a review.

    Science.gov (United States)

    Fenech, C; Rock, L; Nolan, K; Tobin, J; Morrissey, A

    2012-05-01

    Nitrate is naturally found within the environment as part of the nitrogen cycle. However, anthropogenic inputs have greatly increased nitrate loads within ground and surface waters. This has had a severe impact on aquatic ecosystems and has given rise to health considerations in humans and livestock. Therefore, the identification of nitrate sources is important in preserving water quality and achieving sustainability of our water resources. Nitrate sources can be determined based on the nitrate nitrogen (N) and oxygen (O) isotopic compositions (δ(15)N, δ(18)O). However, sewage and manure have overlapping δ(15)N and δ(18)O values making their differentiation on this basis problematic. The specific differentiation between sources of faecal contamination is of particular importance, because the risk to humans is usually considered higher from human faecal contamination (sewage) than from animal faecal contamination. This review summarises the current state of knowledge in using isotope tracers to differentiate various nitrate sources and identifies potential chemical tracers for differentiating sewage and manure. In particular, an in depth review of the current state of knowledge regarding the necessary considerations in using chemical markers, such as pharmaceuticals and food additives, to differentiate sewage and manure sources of nitrate contamination will be given, through an understanding of their use, occurrence and fate, in order to identify the most suitable potential chemical markers. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Perioperative NT-proBNP level: Potential prognostic markers in children undergoing congenital heart disease surgery.

    Science.gov (United States)

    Qu, Jiangbo; Liang, Huiying; Zhou, Na; Li, Lijuan; Wang, Yanfei; Li, Jianbin; Cui, Yanqin

    2017-08-01

    To assess the relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) levels at different time points and early outcome, and to evaluate the reliability of NT-proBNP level as a predictor of early outcome after surgery in a large series of children with congenital heart disease (CHD). A retrospective observational study involving 363 consecutive children with CHD was used. Plasma NT-proBNP records were obtained for each patient before and 1, 12, and 36 hours after surgery. The specificity, sensitivity, and prediction value of NT-proBNP in predicting early postoperative outcomes were determined. Analyses confirmed that time-varying NT-proBNP level, particularly 1-hour postoperative levels, had prognostic value on the prediction of prolonged duration of mechanical ventilation, intensive care unit (ICU) stay, and inotropic therapy. Joint modeling analyses of a linear mixed effects model for NT-proBNP from before to 36 hours after surgery and generalized linear models for the duration of the mechanical ventilation, ICU stay, and inotropic therapy showed that a 1% increase in NT-proBNP was associated with 5.5%, 3.9%, and 3.5% relative increases in expected duration of mechanical ventilation, ICU stay, and inotropic therapy, respectively; related P values were .001, .001, and .01, respectively. After CHD surgery, the perioperative NT-proBNP levels might be powerful markers to identify subjects at higher risk for worse outcome. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  4. Potential therapeutic impact of omega-3 long chain-polyunsaturated fatty acids on inflammation markers in Duchenne muscular dystrophy: A double-blind, controlled randomized trial.

    Science.gov (United States)

    Rodríguez-Cruz, Maricela; Cruz-Guzmán, Oriana Del Rocío; Almeida-Becerril, Tomás; Solís-Serna, Alan Donovan; Atilano-Miguel, Salvador; Sánchez-González, Juan Raúl; Barbosa-Cortés, Lourdes; Ruíz-Cruz, Eugenia Dolores; Huicochea, Juan Carlos; Cárdenas-Conejo, Alan; Escobar-Cedillo, Rosa Elena; Yam-Ontiveros, Carlos Alberto; Ricárdez-Marcial, Edgar F

    2017-09-23

    Duchenne Muscular Dystrophy (DMD) is the most frequent dystrophy in childhood generated by a deficiency in dystrophin. DMD is a neuromuscular disease and its clinical course comprises chronic inflammation and gradual muscle weakness. Supplementation of omega-3 long chain-Polyunsaturated Fatty Acids (ω-3 long chain-PUFA) reduces inflammatory markers in various disorders. The goal of this research was to analyze the influence of ω-3 long chain-PUFA intake on gene expression and blood inflammatory markers in boys with DMD. In a placebo-controlled, double. Blind, randomized trial, boys with DMD (n = 36) consumed 2.9 g/day of ω-3 long chain-PUFA or sunflower oil as control, in capsules, for a period of 6 months. Blood was analyzed at baseline and at months 1, 2, 3, and 6 of supplementation for expression of inflammatory markers in leukocytes and serum. There was high adherence to capsule intake (control: 95.3% ± 7.2%, and ω-3 long chain-PUFA: 97.4% ± 3.7% at month 6). Enrichment of EicosaPentaenoic Acid (EPA) and DocosaHexaenoic Acid (DHA) in erythrocytes increased significantly in patients supplemented with ω-3 long chain-PUFA compared with the placebo group during the 6 months of supplementation. Messenger RNA (mRNA) of the Nuclear Factor kappa beta (NF-κB) and its target genes InterLeukin 1 beta (IL-1β) and IL-6 was downregulated significantly (p chain-PUFA for 6 months, compared to the placebo group. Omega-3 long chain-PUFA intake decreased the serum IL-1β (-59.5%; p = 0.011) and IL-6 (-54.8%; p = 0.041), and increased the serum IL-10 (99.9%, p chain-PUFA 2.9 g/day is well-tolerated, has a beneficial reductive effect on proinflammatory markers, and increases an anti-inflammatory marker, indicating that ω-3 long chain-PUFA could have a potential therapeutic impact on chronic inflammation in DMD. This research is registered at clinicaltrials.gov (NCT018264229). Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and

  5. Neospora caninum surface antigen (p40) is a potential diagnostic marker for cattle neosporosis

    Science.gov (United States)

    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 ...

  6. Clinical and prognostic significance of aberrant T-cell marker expression in 225 cases of de novo diffuse large B-cell lymphoma and 276 cases of other B-cell lymphomas

    Science.gov (United States)

    Tsuyama, Naoko; Ennishi, Daisuke; Yokoyama, Masahiro; Baba, Satoko; Asaka, Reimi; Mishima, Yuko; Terui, Yasuhito; Hatake, Kiyohiko; Takeuchi, Kengo

    2017-01-01

    Expression of T-cell markers, generally investigated for immunophenotyping of T-cell lymphomas, is also observed in several types of B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL). We previously reported that CD5 expression in DLBCL is an inferior prognostic factor in the era of rituximab. However, data regarding the frequencies, histological relevance, and prognostic importance of T-cell markers other than CD5 are currently unavailable. In the present study, we comprehensively evaluated the expression of T-cell markers (CD2, CD3, CD4, CD5, CD7, and CD8) in 501 B-cell lymphomas, including 225 DLBCLs, by flow cytometry and subsequent immunohistochemistry. T-cell markers other than CD5, such as CD2, CD4, CD7, and CD8, were expressed in 27 (5%) patients, and notably, all of these cases were classified as large B-cell lymphoma subtypes: 25 DLBCLs and 2 intravascular large B-cell lymphomas. CD5 and other T-cell markers were expressed in 15% (31/225) and 10% (25/225) of DLBCL cases, respectively. Five of them co-expressed CD5 and other T-cell markers. Retrospectively analyzing the prognostic relevance of T-cell markers in 169 patients with primary DLBCL treated with rituximab-based chemotherapy, we showed that only CD5 was a strong predictor of poor survival. This study provides information about the occurrence of T-cell markers other than CD5 in B-cell lymphomas, their frequent histological subtypes, and their prognostic significance in DLBCL. CD5 was reconfirmed as a negative prognostic marker in DLBCL patients receiving rituximab-inclusive chemotherapy, whereas T-cell markers other than CD5 were found to have no impact on clinicopathological and survival analyses. PMID:28380441

  7. Genome-wide survey and analysis of microsatellites in the Pacific oyster genome: abundance, distribution, and potential for marker development

    Science.gov (United States)

    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. SSR mining in coffee tree EST databases: potential use of EST-SSRs as markers for the Coffea genus.

    Science.gov (United States)

    Poncet, Valérie; Rondeau, Myriam; Tranchant, Christine; Cayrel, Anne; Hamon, Serge; de Kochko, Alexandre; Hamon, Perla

    2006-11-01

    Expressed sequence tags (ESTs) from Coffea canephora leaves and fruits were used to search for types and frequencies of simple sequence repeats (EST-SSRs) with a motif length of 1-6 bp. From a non-redundant (NR) EST set of 5,534 potential unigenes, 6.8% SSR-containing sequences were identified, with an average density of one SSR every 7.73 kb of EST sequences. Trinucleotide repeats were found to be the most abundant (34.34%), followed by di- (25.75%) and hexa-nucleotide (22.04%) motifs. The development of unique genic SSR markers was optimized by a computational approach which allowed us to eliminate redundancy in the original EST set and also to test the specificity of each pair of designed primers. Twenty-five EST-SSRs were developed and used to evaluate cross-species transferability in the Coffea genus. The orthology was supported by the amplicon sequence similarity and the amplification patterns. The >94% identity of flanking sequences revealed high sequence conservation across the Coffea genus. A high level of polymorphic loci was obtained regardless of the species considered (from 75% for C. liberica to 86% for C. canephora). Moreover, the polymorphism revealed by EST-SSR was similar to that exposed by genomic SSR. It is concluded that Coffea ESTs are a valuable resource for microsatellite mining. EST-SSR markers developed from C. canephora sequences can be easily transferred to other Coffea species for which very little molecular information is available. They constitute a set of conserved orthologous markers, which would be ideal for assessing genetic diversity in coffee trees as well as for cross-referencing transcribed sequences in comparative genomics studies.

  9. Potential protein post-translational modification in ERp57: A phenotype marker for male fertility

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    Viroj Wiwanitkit

    2010-01-01

    Full Text Available Background : In protein expression, post-translational modification is an important process. It is also an important process in human reproductive science. ERp57 is a molecule that is mentioned for post-translational modification. ERp57 is a component of human sperm acrosome proteins. However, the data on post-translational modifications of ERp57 is limited. Aim: The aim of this work is to assess potential protein post-translational modifications in ERp57 protein. Settings and Design : A descriptive computational bioinformatics study. Materials and Methods : In this work, potential protein post-translational modifications in ERp57 protein were assessed via a standard bioinformatics technique. Statistical Analysis Used : Bioinformatics analysis. Results : There are three post-translational modifications within ERp57 from bioinformatics analysis. Conclusion : This new knowledge can be useful for better realization on molecular process of male infertility.

  10. Potential protein post-translational modification in ERp57: A phenotype marker for male fertility

    OpenAIRE

    Viroj Wiwanitkit

    2010-01-01

    Background : In protein expression, post-translational modification is an important process. It is also an important process in human reproductive science. ERp57 is a molecule that is mentioned for post-translational modification. ERp57 is a component of human sperm acrosome proteins. However, the data on post-translational modifications of ERp57 is limited. Aim: The aim of this work is to assess potential protein post-translational modifications in ERp57 protein. Settings and Design : A desc...

  11. Potential Use of Salivary Markers for Longitudinal Monitoring of Inflammatory Immune Responses to Vaccination

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    Pei Wen Lim

    2016-01-01

    Full Text Available 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.

  12. The metabolic impact of methamphetamine on the systemic metabolism of rats and potential markers of methamphetamine abuse.

    Science.gov (United States)

    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.

  13. Identification of species-specific nuclear insertions of mitochondrial DNA (numts) in gorillas and their potential as population genetic markers

    Science.gov (United States)

    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

  14. Measles Virus: Identification in the M Protein Primary Sequence of a Potential Molecular Marker for Subacute Sclerosing Panencephalitis

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    Hasan Kweder

    2015-01-01

    Full Text Available 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.

  15. A computational procedure for functional characterization of potential marker genes from molecular data: Alzheimer's as a case study

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    Barla Annalisa

    2011-07-01

    Full Text Available Abstract Background A molecular characterization of Alzheimer's Disease (AD is the key to the identification of altered gene sets that lead to AD progression. We rely on the assumption that candidate marker genes for a given disease belong to specific pathogenic pathways, and we aim at unveiling those pathways stable across tissues, treatments and measurement systems. In this context, we analyzed three heterogeneous datasets, two microarray gene expression sets and one protein abundance set, applying a recently proposed feature selection method based on regularization. Results For each dataset we identified a signature that was successively evaluated both from the computational and functional characterization viewpoints, estimating the classification error and retrieving the most relevant biological knowledge from different repositories. Each signature includes genes already known to be related to AD and genes that are likely to be involved in the pathogenesis or in the disease progression. The integrated analysis revealed a meaningful overlap at the functional level. Conclusions The identification of three gene signatures showing a relevant overlap of pathways and ontologies, increases the likelihood of finding potential marker genes for AD.

  16. Measles Virus: Identification in the M Protein Primary Sequence of a Potential Molecular Marker for Subacute Sclerosing Panencephalitis

    Science.gov (United States)

    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

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

    NARCIS (Netherlands)

    A. Vidaki (Athina); F. Giangasparo (Federica); D. Syndercombe-Court (Denise)

    2016-01-01

    textabstractThe 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

  18. Expressions and clinical significance of autophagy-related markers Beclin1, LC3, and EGFR in human cervical squamous cell carcinoma

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    Hu YF

    2015-08-01

    Full Text Available Yun-Feng Hu,1 Xia Lei,2 Hong-Yi Zhang,3 Jun-wei Ma,1 Wei-wei Yang,1 Min-lin Chen,1 Jie Cui,1,4 Hong Zhao1 1Department of Oncology, 2Department of Gynecology, 3Department of Urology, Yan’an University Affiliated Hospital, Yan’an, Shaanxi Province, People’s Republic of China; 4Department of Oncology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of China Purpose: We aimed to investigate the expression of EGFR and the autophagy-related markers Beclin1 and LC3 in cervical cancer.Methods: Beclin1, LC3, and EGFR expression were analyzed in 80 samples of cervical squamous cell carcinoma (SCC, 40 samples of high-grade cervical intraepithelial neoplasia (CIN, and 40 samples of normal cervical tissues by immunohistochemistry. The protein expression rates were analyzed with χ2 and Fisher’s exact tests. Differences in overall survival (OS were determined using the Kaplan–Meier method and log-rank tests.Results: Cervical cancer, high-grade CIN, and normal cervical epithelial cells expressed Beclin1 in 26.2%, 77.5%, and 82.5% of patients, respectively, and expressed LC3 in 28.8%, 70.0%, and 75.0% of patients, respectively. There was a significant difference between cervical SCC and high-grade CIN or normal cervical epithelial cells (P=0.000. Cervical cancer cells, high-grade CIN cells, and normal cervical epithelial cells expressed EGFR in 68.8%, 62.5%, and 12.5% of patients, respectively. There was a significant difference between cervical SCC or high-grade CIN and normal cervical epithelial cells (P=0.000. No significant association between Beclin1 or LC3 or EGFR expression and various clinicopathological parameters was observed in cervical SCC. There was no significant correlation between Beclin1, LC3, EGFR expression, and 5-year OS rates of cervical SCC patients. Beclin1- or LC3-negativity with EGFR-positivity in cervical SCC was associated with a higher Federation International of

  19. Metabolomic Profiling Reveals Potential Markers and Bioprocesses Altered in Bladder Cancer Progression

    OpenAIRE

    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

    2011-01-01

    While alterations in xenobiotic metabolism are considered causal in the development of bladder cancer (BCa), 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 BCa. This metabolic signature distinguished both normal and benign bladder from BCa. Exploratory analyses of this metabolomic signature in urine showed ...

  20. Clinical significance of half-lives of tumor markers α-fetoprotein and des-γ-carboxy prothrombin after hepatectomy for hepatocellular carcinoma.

    Science.gov (United States)

    Tsukamoto, Masayo; Nitta, Hidetoshi; Imai, Katsunori; Higashi, Takaaki; Nakagawa, Shigeki; Okabe, Hirohisa; Arima, Kota; Kaida, Takayoshi; Taki, Katsunobu; Hashimoto, Daisuke; Chikamoto, Akira; Ishiko, Takatoshi; Beppu, Toru; Baba, Hideo

    2017-08-10

    The prognostic significance of the half-lives (HLs) of α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) in patients undergoing hepatectomy for hepatocellular carcinoma (HCC) is unclear. We evaluated the HLs of AFP and DCP in a cohort of such patients. This study included data on 202 patients with HCC who underwent curative hepatectomy and had preoperative AFP concentrations ≥100 ng/mL or DCP ≥200 mAU/mL. We calculated the HLs of AFP and DCP from their values just before and 1 month after hepatectomy. We identified three groups: a normalization group, tumor marker concentrations within normal range 1 month post-hepatectomy; a long group, HL of AFP ≥7 days or DCP ≥4 days; and a short group, remaining patients. We evaluated associations between HL and prognosis. Three-year recurrence-free survival (RFS) in the normalization (n = 70), short (n = 71), and long groups (n = 61) was 41.3%, 46.0%, and 16.8%, respectively (P = 0.002). Five-year overall survival (OS) of normalization, short, and long groups was 72.6, 70.6 and 43.8%, respectively (P = 0.002). Multivariate analysis revealed that long HL is an independent risk factor for poor RFS (hazard ratio [HR] 2.21, P = 0.0006) and poor OS (HR 2.70, P = 0.004). The extrahepatic recurrence rate was 21.3% (13/61) in the long group, which is higher than in the normalization group (8.6%, 6/70) (P = 0.04) and short group (9.9%, 7/71) (P = 0.07). Post-hepatectomy HLs of AFP and DCP are predictors of long-term outcome in patients with HCC. © 2017 The Japan Society of Hepatology.

  1. Glut1 and Glut3 as Potential Prognostic Markers for Oral Squamous Cell Carcinoma

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    Fernanda Rocha Rojas Ayala

    2010-04-01

    Full Text Available We associated clinical-pathological features of 142 OSCC with the expression pattern of GLUT1 and GLUT3 in order to estimate their prognostic value. Methods: Clinical-pathological features and overall survival data of 142 patients with Oral Squamous Cell Carcinoma (OSCC were retrospectively reviewed from A.C.Camargo hospital records. A tissue microarray (TMA was built for the immunohistochemical (IHC analysis of GLUT 1 and GLUT 3. IHC results were evaluated according to the staining pattern and number of positive cells. Results: GLUT 1 was over expressed in 50.3% of OSSC cases showing membrane staining pattern. However, nuclear expression was observed in 49.7% of the analyzed cases. GLUT 3 over expression was detected in 21.1% of OSCC cases. The pattern of GLUT 1 expression showed significant association with alcohol consumption (p = 0.004. Positive cell membrane GLUT 3 protein expression was associated with advanced clinic-staging of tumours (p = 0.005 as well as with vascular embolization (p = 0.005. Positive expression of GLUT 3 was associated with unfavorable free-disease survival (p = 0.021. Conclusion: GLUT1 and GLUT3 protein expression evaluated by immunohistochemistry are, significantly, indicators of poor prognosis outcome in oral squamous cell carcinoma, probably due to the enhanced glycolytic metabolism of more aggressive neoplastic cells.

  2. A combination of plasma DAO and citrulline levels as a potential marker for acute mesenteric ischemia

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    Rıdvan Çakmaz

    2013-03-01

    Full Text Available Introduction: There is no valid and reliable diagnostic test for early diagnosis of acute mesenteric ischemia (AMI. The aim of this study was to measure the plasma levels of diamine oxidase (DAO and citrulline in AMI to gain insight into its early diagnosis. Material and methods: A total of 21 Wistar albino rats were divided into three groups, that is, control group, short-term ischemia group, and prolonged ischemia group. The superior mesenteric artery was occluded for 15 min in the short-term ischemia group and for 12 h in the prolonged ischemia group. Twelve hours later, the experiment was terminated and plasma DAO and citrulline levels were measured. Intestinal tissue was evaluated for the histopathological changes. Results: Compared to the control group, the short-term and prolonged ischemia groups showed significant increases in the plasma levels of DAO, whereas the plasma citrulline levels decreased significantly. Prolonged ischemia caused a larger increase in the plasma DAO levels and a larger decrease in the plasma citrulline levels compared to the short-term ischemia (p=0.011 and p=0.021, respectively. Intestinal damage was shown to develop more in the prolonged ischemia group (p=0.001. Conclusion: In the early period of AMI, the plasma DAO levels increase while citrulline levels decrease, and the extent of these changes depends on the duration of ischemia.

  3. Homocysteine as a potential biochemical marker for depression in elderly stroke survivors

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    Michaela C. Pascoe

    2012-04-01

    Full Text Available Background: Elderly stroke survivors have been reported to be at risk of malnutrition and depression. Vitamin B-related metabolites such as methylmalonic acid and homocysteine have been implicated in depression. Objective: We conducted a study exploring the relationship between homocysteine and post-stroke depression. Design: Three methodologies were used: Observational cohort study of elderly Swedish patients (n=149 1.5 years post-stroke, assessed using Diagnostic and Statistical Manual of Mental Disorders, Montgomery Åsberg Depression Rating Scale and serum blood levels of methylmalonic acid and homocysteine. Results: Homocysteine significantly correlated with depressive symptomatology in stroke survivors (β = 0.18*. Individuals with abnormal levels of methylmalonic acid and homocysteine were almost twice more likely to show depressive symptomatology than those with normal levels (depressive symptoms 22%; no depressive symptoms 12%. Comparison of methylmalonic acid and homocysteine levels with literature data showed fewer stroke survivors had vitamin deficiency than did reference individuals (normal range 66%; elevated 34%. Conclusions: Homocysteine is significantly associated with depressive symptomatology in elderly Swedish stroke survivors.

  4. Potential of carotenoids in aquatic yeasts as a phylogenetically reliable marker and natural colorant for aquaculture.

    Science.gov (United States)

    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.

  5. Oxidation-reduction potential as a new marker for oxidative stress: Correlation to male infertility

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    Ashok Agarwal

    2017-11-01

    Full Text Available Male infertility affects men worldwide. Oxidative stress (OS, characterized by an overabundance of reactive oxygen species (ROS or a deficiency of antioxidants, is one of the major causes of male infertility. OS causes damage at the molecular level, which impairs lipids, proteins, and DNA. The cyclic cascade of redox reactions weakens sperm function which leads to poor semen parameters and eventual sterility. There is a need for advanced diagnostic tests that can quickly and accurately detect OS. Most commonly used assays can only measure single constituents of OS. However, the MiOXSYS System introduces a new strategy to detect OS by measuring the oxidation-reduction potential (ORP--a direct evaluation of the redox balance between ROS and antioxidants. The MiOXSYS System has shown promise as a diagnostic tool in the evaluation of male infertility. This review explores the concept of ORP, details the principle of the MiOXSYS System, and summarizes the findings in clinical studies that support ORP measurement in semen.

  6. Ulex europeus agglutinin-I binding as a potential prognostic marker in ovarian cancer.

    Science.gov (United States)

    Blonski, Katharina; Milde-Langosch, Karin; Bamberger, Ana-Maria; Osterholz, Tina; Utler, Christian; Berger, Jürgen; Löning, Thomas; Schumacher, Udo

    2007-01-01

    Ovarian cancer represents the malignant tumour of the female genital tract with the worst prognosis, mainly caused by early intraperitoneal spread. Cell-to-cell and cell-to-matrix interactions play a functionally important role in this spread and are both mediated by the cell membrane. Changes in the glycosylation of the cell membrane, as detected by lectin histochemistry, are sometimes associated with a poor prognosis. The expression of lectin binding of 164 ovarian cancer patients was analysed and the staining results were correlated with the clinical data of the patients. The univariate and multivariate statistical analysis revealed an independent prognostic significance for Ulex europeus agglutinin-I (UEA-I) binding. These findings indicate that UEA-I binding can serve as a prognostic factor in ovarian cancer.

  7. Serum alkaline phosphatase: a potential marker in the progression of periodontal disease in cirrhosis patients.

    Science.gov (United States)

    Jaiswal, Gagan; Deo, Vikas; Bhongade, Manohar; Jaiswal, Shraddha

    2011-04-01

    As a consequence of their liver dysfunction, cirrhotic patients have elevated levels of serum alkaline phosphatase (ALP). Increased ALP activity is seen in periodontal tissues during the progression of periodontitis. The present study was carried out to compare ALP levels in cirrhosis patients with and without periodontitis and to correlate ALP levels with the severity of periodontitis. Both the test and control groups consisted of 30 liver cirrhosis patients with or without periodontitis. The parameters recorded were modified OHI-S Index, Gingival Index (GI), and clinical attachment level (CAL). All patients underwent standardized panoramic radiographs to assess alveolar bone height. The total serum ALP was determined with the kinetic method (R.A 50). Alveolar bone loss (ABL) was 1.62 ± 0.32 mm in the test group and 0.28 ± 0.04 mm in the control group. Mean clinical attachment level (CAL) for the test group was greater than the control group: 2.34 ± 0.67 mm and 0.43 ± 0.14 mm, respectively. The mean serum alkaline phosphatase level in the test group was higher (39.94 ± 3.34) than the control group (29.42 ± 6.11) and the differences was statistically significant (P > .05). When comparison was made between age group (20 to 40 years and 41 to 60 years), the older age group liver cirrhosis patients exhibited significantly higher values for bone loss, clinical attachment level, and serum ALP level. There is strong positive correlation between periodontal breakdown and serum alkaline phosphatase level in liver cirrhosis patients.

  8. Investigation of potential early Histologic markers of pediatric inflammatory bowel disease.

    Science.gov (United States)

    Bass, Julie A; Friesen, Craig A; Deacy, Amanda D; Neilan, Nancy A; Bracken, Julia M; Shakhnovich, Valentina; Singh, Vivekanand

    2015-10-13

    Early manifestations of pediatric inflammatory bowel disease (IBD) can be relatively nonspecific. Initial mucosal biopsies may not be conclusive, delaying the diagnosis until subsequent biopsies demonstrate typical histologic features of IBD. We hypothesized that certain inflammatory cell types may be utilized as early histologic indicators of IBD in children. A retrospective analysis compared histologic findings from initially inconclusive or negative endoscopic studies in 22 patients who were subsequently diagnosed with IBD (after diagnostic endoscopy) to those of 20 comparison patients with functional abdominal pain matched for age, gender, and study type. A pediatric pathologist, blinded to study group, reviewed biopsies for histologic abnormalities. Eosinophil densities were obtained from the stomach, duodenum, and rectosigmoid areas. Immunohistochemistry (IHC) staining for tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-9 (MMP-9) was performed on the stomach and rectosigmoid areas. Gastritis and colonic crypt distortion were present in the IBD group at a greater rate (61 % vs. 22 %, p = 0.020; 34 % vs. 4 %, p = 0.008, respectively). Peak and mean eosinophil densities in the rectosigmoid area were greater in the IBD group (17.0/hpf vs. 5.0/hpf, p = 0.0063; 12.3/hpf vs. 4.2/hpf, p = 0.0106, respectively). TNF-α and MMP-9 staining did not reveal any significant differences. Our data suggests that significantly greater inflammation in the stomach, crypt distortion in the colon, and eosinophilia in the rectosigmoid distinguished the IBD group from the comparison group at the time of the initial endoscopic evaluation.

  9. The Transferrin Receptor: A Potential Molecular Imaging Marker for Human Cancer

    Directory of Open Access Journals (Sweden)

    Dagmar Högemann-Savellano

    2003-11-01

    Full Text Available Noninvasive imaging of differences between the molecular properties of cancer and normal tissue has the potential to enhance the detection of tumors. Because overexpression of endogenous transferrin receptor (TfR has been qualitatively described for various cancers and is presumably due to malignant transformation of cells, TfR may represent a suitable target for application of molecular imaging technologies to increase detection of smaller tumors. In the work reported here, investigation into the biology of this receptor using electron microscopy has demonstrated that iron oxide particles targeted to TfR are internalized and accumulate in lysosomal vesicles within cells. Biochemical analysis of the interaction of imaging probes with cells overexpressing the TfR demonstrated that the extent of accumulation, and therefore probe efficacy, is dependent on the nature of the chemical cross-link between transferrin and the iron oxide particle. These data were utilized to design and synthesize an improved imaging probe. Experiments demonstrate that the novel magnetic resonance imaging (MRI probe is sensitive enough to detect small differences in endogenous TfR expression in human cancer cell lines. Quantitative measurement of TfR overexpression in a panel of 27 human breast cancer patients demonstrated that 74% of patient cancer tissues overexpressed the TfR and that the sensitivity of the new imaging agent was suitable to detect TfR overexpression in greater than 40% of these cases. Based on a biochemical and cell biological approach, these studies have resulted in the synthesis and development of an improved MRI probe with the best in vitro and in vivo imaging properties reported to date.

  10. Anti-fibrotic potential of aMatthiola arabicaisothiocyanates rich fraction: impact on oxidative stress, inflammatory and fibrosis markers.

    Science.gov (United States)

    Mohammed, E D; El-Naga, R N; Lotfy, R A; Al-Gendy, A A; El-Demerdash, E

    2017-10-01

    The present study is the first one to investigate the glucosinolates (GLS) profile and anti-fibrotic effect of isothiocyanates (ITCs) rich fraction of Matthiola arabica (Brassicaceae) using an experimental model of liver fibrosis in rats. Five GLS (ethyl glucosinolate, gluconapin, glucodehydroerucin, glucoerucin and glucoraphanin) were identified by gas liquid chromatography-mass spectrometric (GLC-MS) analysis of their hydrolysis products, produced by the natural autolysis and exogenous myrosinase hydrolysis using one and two units of the enzyme. Spectrophotometric determination of the total intact GLS revealed that content in the fresh sample was 1.8 times higher than in the dry one. ITCs rich fraction was prepared by natural autolysis of the fresh aerial part. Male albino rats were given carbon tetrachloride (CCl4) (0.5 ml/kg, twice a week) and/or ITCs -rich fraction (30 mg/ kg, three times a week) for six weeks. Liver function, different oxidative stress, inflammatory and fibrosis markers were investigated. Treatment of animals with ITCs rich fraction significantly counteracted the changes in liver function induced by CCl4. Histopathological examination under both light and electron microscope showed the anti-fibrotic effect of ITCs rich fraction. This finding was confirmed with the markedly improved liver fibrosis markers with ITCs rich fraction co-treatment. In elucidation of anti-fibrotic mechanisms of ITCs rich fraction, the significant glutathione depletion and lipid peroxidation caused by CCl4 intoxication was restored by ITCs rich fraction co-treatment. Besides, ITCs rich fraction showed an anti-inflammatory effect through its ability to counteract the significant increase in nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2) expression, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) levels in liver tissue that caused by CCl4 intoxication. These findings indicate that ITCs-rich fraction of M. arabica possesses a promising anti

  11. Expansion and characterization of ventral mesencephalic precursor cells: effect of mitogens and investigation of FA1 as a potential dopaminergic marker

    DEFF Research Database (Denmark)

    Jensen, Pia; Bauer, Matthias; Jensen, Charlotte H

    2007-01-01

    Methods for identification and in vitro expansion of ventral mesencephalic dopaminergic precursor cells are of interest in the search for transplantable neurons for cell therapy in Parkinson's disease (PD). We investigated the potential use of fibroblast growth factor 2 (FGF2) and fibroblast growth...... factor 8 (FGF8) for expansion of such dopaminergic precursor cells, and fetal antigen-1 (FA1), a secreted neuronal protein of unknown function, as a non-invasive dopaminergic marker. Tissue from embryonic day (ED) 12 rat ventral mesencephalon was dissociated mechanically and cultured for 4 days...... in the presence of FGF2, FGF8, or without mitogens (control). After mitogen withdrawal and addition of 0.5% bovine serum, cells were differentiated for 6 days. Before differentiation, significantly more cells incorporated BrdU in cultures exposed to FGF2 (19-fold; P

  12. Frontal Lobe Hemodynamic Responses to Painful Stimulation: A Potential Brain Marker of Nociception.

    Science.gov (United States)

    Aasted, Christopher M; Yücel, Meryem A; Steele, Sarah C; Peng, Ke; Boas, David A; Becerra, Lino; Borsook, David

    2016-01-01

    The purpose of this study was to use functional near-infrared spectroscopy (fNIRS) to examine patterns of both activation and deactivation that occur in the frontal lobe in response to noxious stimuli. The frontal lobe was selected because it has been shown to be activated by noxious stimuli in functional magnetic resonance imaging studies. The brain region is located behind the forehead which is devoid of hair, providing a relative ease of placement for fNIRS probes on this area of the head. Based on functional magnetic resonance imaging studies showing blood-oxygenation-level dependent changes in the frontal lobes, we evaluated functional near-infrared spectroscopy measures in response to two levels of electrical pain in awake, healthy human subjects (n = 10; male = 10). Each subject underwent two recording sessions separated by a 30-minute resting period. Data collected from 7 subjects were analyzed, containing a total of 38/36 low/high intensity pain stimuli for the first recording session and 27/31 pain stimuli for the second session. Our results show that there is a robust and significant deactivation in sections of the frontal cortices. Further development and definition of the specificity and sensitivity of the approach may provide an objective measure of nociceptive activity in the brain that can be easily applied in the surgical setting.

  13. Effect of clay nanoparticles on model lung surfactant: a potential marker of hazard from nanoaerosol inhalation.

    Science.gov (United States)

    Kondej, Dorota; Sosnowski, Tomasz R

    2016-03-01

    This work investigates influence of different aluminosillicate nanoparticles (NPs) which are found in air in selected workplaces on the properties of the phospholipid (DPPC) monolayer at air-saline interface considered as ex vivo model of the lung surfactant (LS). The measurements were done under physiological-like conditions (deformable liquid interface at 37 °C) for NP concentrations matching the calculated lung doses after exposure in the working environment. Measured surface pressure-area (π-A) isotherms and compressibility curves demonstrated NP-induced changes in the structure and mechanical properties of the lipid monolayer. It was shown that hydrophilic nanomaterials (halloysite and bentonite) induced concentration-dependent impairment of DPPC's ability of attaining high surface pressures on interfacial compression, suggesting a possibility of reduction of physiological function of natural LS. Hydrophobic montmorillonites affected DPPC monolayer in the opposite way; however, they significantly changed the mechanical properties of the air-liquid interface during compression. The results support the hypothesis of possible reduction or even degradation of the natural function of the lung surfactant induced by particle-phospholipid interactions after inhalation of nanoclays. Presented data do not only supplement the earlier results obtained with another LS model (animal-derived surfactant in oscillating bubble experiments) but also offer an explanation of physicochemical mechanisms responsible for detrimental effects which arise after deposition of inhaled nanomaterials on the surface of the respiratory system.

  14. TBX2 subfamily suppression in lung cancer pathogenesis: a high-potential marker for early detection

    Science.gov (United States)

    Khalil, Athar A.; Sivakumar, Smruthy; Lucas, Frances Anthony San; McDowell, Tina; Lang, Wenhua; Tabata, Kazuhiro; Fujimoto, Junya; Yatabe, Yasushi; Spira, Avrum; Scheet, Paul; Nemer, Georges; Kadara, Humam

    2017-01-01

    The TBX2 subfamily (TBXs 2, 3, 4 and 5) transactivates or represses genes involved in lung organogenesis. Yet TBX2 subfamily expression in pathogenesis of non-small cell lung cancer (NSCLC), the most common lung malignancy, remains elusive. We sought to probe the expression profile of the TBX2 subfamily in early phases of NSCLC. Expression of TBX2 subfamily was analyzed in datasets of pan-normal specimens as well as NSCLCs and normal lung tissues. TBX2 subfamily expression in matched normal lungs, premalignant hyperplasias and NSCLCs was profiled by transcriptome sequencing. TBX2 subfamily expression was evaluated in the cancerization field consisting of matched NSCLCs and adjacent cytologically-normal airways relative to distant normal lungs and in a dataset of normal bronchial samples from smokers with indeterminate nodules suspicious for malignancy. Statistical analysis was performed using R. TBX2 subfamily expression was markedly elevated in normal lungs relative to other organ-specific normal tissues. Expression of the TBXs was significantly suppressed in NSCLCs relative to normal lungs (P cancer status (P cancer detection in high-risk smokers. PMID:28978111

  15. [Ocular melanoma: immunohistochemical evaluation of the potentially predictive markers of prognosis. Preliminary results].

    Science.gov (United States)

    Poitevin, J; Venteo, L; Guillou, P J; Rabah Benabbas, S; Ducasse, A; Pluot, M

    2006-05-01

    To study the characteristics of certain biological parameters, many of which have been recently discovered, to assess their possible contribution to the prognosis of ocular melanoma. and methods: 25 patients with ocular and orbital melanoma treated at the Reims Regional Hospital since 1993 were included in the retrospective study. The surgical specimens were put in formalin 10%, then in paraffin. Five proteins were analyzed retrospectively: topoisomerase I, topoisomerase IIalpha, ICBP90, Ki67, and P53 on 200 cells per case. Of the 25 tumors from 14 men and 11 women, 15 were iris and ciliary body melanomas and ten choroidal melanomas. Histopathologic analysis showed 12 spindle-cell-type melanomas, seven epithelioid-cell-type melanomas and six mixed-cell-type melanomas. The immunohistochemical study found a significant difference in distribution between the cellular types for the topoisomerase IIalpha and Ki67 antibodies. Eight patients had metastasis, six of whom died. The metastasis came from three mixed-cell-type melanomas, three epithelioid-cell-type melanomas, and two spindle-cell-type melanomas. On the other hand, six cases of sclera infiltration were discovered among these eight patients. Several prognostic factors seem to be involved in the progression of melanoma: sclera infiltration seems to be essential in our study. Its rate seems to increase with the tumor size and in epithelioid-cell-type melanomas. The correlation between the different immunomarkers and the appearance of metastasis has not yet been verified.

  16. Altered platelet indices as potential markers of severe and complicated malaria caused by Plasmodium vivax: a cross-sectional descriptive study.

    Science.gov (United States)

    Leal-Santos, Fábio A; Silva, Soraya B R; Crepaldi, Natasha P; Nery, Andréia F; Martin, Thamires O G; Alves-Junior, Eduardo R; Fontes, Cor J F

    2013-12-27

    This study described altered platelet indices in patients with acute malaria caused by Plasmodium vivax and determined whether these alterations are associated with warning signs of severe and complicated malaria. A total of 186 patients attending the Malaria Clinic at the University Hospital from the Federal University of Mato Grosso, Brazil, between 2008 and 2013 were included in this study. After parasitological confirmation of exclusive infection by P. vivax, blood cell counts and platelet indices were determined. Disease gravity was evaluated on the basis of classic signs of Plasmodium falciparum severe malaria, including severe anemia, or by changes in serum levels of glucose, bilirubin, aminotransferases and creatinine at the time of the patient's admission. Patients with a longer duration of symptoms or those identified as primo infected were considered potential candidates for evolution into the severe form of malaria. The mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) values exhibited significant variability. A significant inverse relationship was observed between parasitaemia and PCT. Patients with warning signs for evolution into severe disease, with primo infection, or presenting with symptoms for over three days had the highest MPV and PDW. The adjusted analyses showed the presence of warning signs for the development of severe and complicated malaria remained independently linked to elevated MPV and PDW. Altered platelet indices should be analysed as potential markers for the severity of malaria caused by P. vivax. Future studies with appropriate methodology for prognostic evaluation could confirm the potential use of these indices in clinical practice.

  17. [Value of plasma microRNAs has-let-7d and has-let-7e as potential molecular markers in workers with occupational exposure to mercury].

    Science.gov (United States)

    Guo, J; Zhang, H Q; Ding, E M; Bai, Y; Zhu, B L

    2017-10-20

    Objective: To investigate whether plasma microRNAs has-let-7d and has-let-7e can be used as potential molecular markers for workers with occupational exposure to mercury. Methods: October 2013, the workers with occupational exposure to mercury who worked in a mercury thermometer factory and participated in occupational health examination were selected as subjects, and biological samples and basic data were collected. The subjects were divided into chronic mercury poisoning group,mercury absorption group,and control group,with 30 individuals in each group. AmicroRNA microarray combined with RT-qPCR was used to measure the expression of has-let-7d and has-let-7e in the three groups, the receiver operating characteristic(ROC)curve was used to analyze the values of has-let-7d and has-let-7e in the diagnosis of occupational chronic mercury poisoning,a software platform was used to predict target genes. Gene ontology enrichment analysis and KEGG pathway analysis were also performed. Results: Compared with the control group, the chronic mercury poisoning group and the mercury absorption group had significant increases in the expression of has-let-7d and has-let-7e(P<0.05). The areas under the ROC curve for microRNAs has-let-7d and has-let-7e in the diagnosis of occupational chronic mercury poisoning were 0.912(95% confidence interval[CI]0.843-0.981)and 0.908(95%CI0.837-0.979),respectively,and there was a significant difference between them(P<0.001). Conclusion: Plasma microRNAs has-let-7d and has-let-7e can be used as potential molecular markers for workers with occupational exposure to mercury.

  18. Stage-specific embryonic antigen-3 (SSEA-3) and β3GalT5 are cancer specific and significant markers for breast cancer stem cells.

    Science.gov (United States)

    Cheung, Sarah K C; Chuang, Po-Kai; Huang, Han-Wen; Hwang-Verslues, Wendy W; Cho, Candy Hsin-Hua; Yang, Wen-Bin; Shen, Chia-Ning; Hsiao, Michael; Hsu, Tsui-Ling; Chang, Chuan-Fa; Wong, Chi-Huey

    2016-01-26

    The discovery of cancer stem cells (CSCs), which are responsible for self-renewal and tumor growth in heterogeneous cancer tissues, has stimulated interests in developing new cancer therapies and early diagnosis. However, the markers currently used for isolation of CSCs are often not selective enough to enrich CSCs for the study of this special cell population. Here we show that the breast CSCs isolated with CD44(+)CD24(-/lo)SSEA-3(+) or ESA(hi)PROCR(hi)SSEA-3(+) markers had higher tumorigenicity than those with conventional markers in vitro and in vivo. As few as 10 cells with CD44(+)CD24(-/lo)SSEA-3(+) formed tumor in mice, compared with more than 100 cells with CD44(+)CD24(-/lo). Suppression of SSEA-3 expression by knockdown of the gene encoding β-1,3-galactosyltransferase 5 (β3GalT5) in the globo-series pathway, led to apoptosis in cancer cells specifically but had no effect on normal cells. This finding is further supported by the analysis of SSEA-3 and the two related globo-series epitopes SSEA4 and globo-H in stem cells (embryonic stem cells and induced pluripotent stem cells) and various normal and cancer cells, and by the antibody approach to target the globo-series glycans and the late-stage clinical trials of a breast cancer vaccine.

  19. Evaluation of a 3A-truncated foot-and-mouth disease virus in pigs for its potential as a marker vaccine

    Science.gov (United States)

    2014-01-01

    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. PMID:24885414

  20. Prolactin-induced protein as a potential therapy response marker of adjuvant chemotherapy in breast cancer patients.

    Science.gov (United States)

    Jablonska, Karolina; Grzegrzolka, Jedrzej; Podhorska-Okolow, Marzenna; Stasiolek, Mariusz; Pula, Bartosz; Olbromski, Mateusz; Gomulkiewicz, Agnieszka; Piotrowska, Aleksandra; Rys, Janusz; Ambicka, Aleksandra; Ong, Siew Hwa; Zabel, Maciej; Dziegiel, Piotr

    2016-01-01

    Many studies are dedicated to exploring the molecular mechanisms of chemotherapy-resistance in breast cancer (BC). Some of them are focused on searching for candidate genes responsible for this process. The aim of this study was typing the candidate genes associated with the response to standard chemotherapy in the case of invasive ductal carcinoma. Frozen material from 28 biopsies obtained from IDC patients with different responses to chemotherapy were examined using gene expression microarray, Real-Time PCR (RT-PCR) and Western blot (WB). Based on the microarray results, further analysis of candidate gene expression was evaluated in 120 IDC cases by RT-PCR and in 224 IDC cases by immunohistochemistry (IHC). The results were correlated with clinical outcome and molecular subtype of the BC. Gene expression microarray revealed Prolactin-Induced Peptide (PIP) as a single gene differentially expressed in BC therapy responder or non-responder patients (p <0.05). The level of PIP expression was significantly higher in the BC therapy responder group than in the non-responder group at mRNA (p=0.0092) and protein level (p=0.0256). Expression of PIP mRNA was the highest in estrogen receptor positive (ER+) BC cases (p=0.0254) and it was the lowest in triple negative breast cancer (TNBC) (p=0.0336). Higher PIP mRNA expression was characterized by significantly longer disease free survival (DFS, p=0.0093), as well as metastasis free survival (MFS, p=0.0144). Additionally, PIP mRNA and PIP protein expression levels were significantly higher in luminal A than in other molecular subtypes and TNBC. Moreover significantly higher PIP expression was observed in G1, G2 vs. G3 cases (p=0.0027 and p=0.0013, respectively). Microarray analysis characterized PIP gene as a candidate for BC standard chemotherapy response marker. Analysis of clinical data suggests that PIP may be a good prognostic and predictive marker in IDC patients. Higher levels of PIP were related to longer DFS and MFS

  1. Quantitative Proteomics Analysis by Isobaric Tags for Relative and Absolute Quantitation Identified Lumican as a Potential Marker for Acute Aortic Dissection

    Directory of Open Access Journals (Sweden)

    Guorong Gu

    2011-01-01

    Full Text Available Acute aortic dissection (AAD is a serious vascular disease. Currently the diagnosis relies on clinical and radiological means whereas serum biomarkers are lacking. The purpose of this study was to identify potential serum biomarkers for AAD using isobaric tags for relative and absolute quantitation (iTRAQ approach. A total of 120 serum samples were collected from three groups: AAD patients (n=60, patients with acute myocardial infarction (AMI, n=30, and healthy volunteers (n=30, whereas the first 10 samples from each group were used for iTRAQ analysis. Using iTRAQ approach, a total of 174 proteins were identified as significantly different between AAD patients and healthy subjects. Among them, forty-six proteins increased more than twofold, full-scale analysis using serum sample for the entire 120 subjects demonstrated that Lumican level was significantly increased relative to control and AMI samples. Further, Lumican level correlated with time from onset to admission in AAD but not AMI samples. Using iTRAQ approach, our study showed that Lumican may be a potential AAD-related serum marker that may assist the diagnosis of AAD.

  2. Personal significance is encoded automatically by the human brain: an event-related potential study with ringtones.

    Science.gov (United States)

    Roye, Anja; Jacobsen, Thomas; Schröger, Erich

    2007-08-01

    In this human event-related brain potential (ERP) study, we have used one's personal--relative to another person's--ringtone presented in a two-deviant passive oddball paradigm to investigate the long-term memory effects of self-selected personal significance of a sound on the automatic deviance detection and involuntary attention system. Our findings extend the knowledge of long-term effects usually reported in group-approaches in the domains of speech, music and environmental sounds. In addition to the usual mismatch negativity (MMN) and P3a component elicited by deviants in contrast to standard stimuli, we observed a posterior ERP deflection directly following the MMN for the personally significant deviant only. This specific impact of personal significance started around 200 ms after sound onset and involved neural generators that were different from the mere physical deviance detection mechanism. Whereas the early part of the P3a component was unaffected by personal significance, the late P3a was enhanced for the ERPs to the personal significant deviant suggesting that this stimulus was more powerful in attracting attention involuntarily. Following the involuntary attention switch, the personally significant stimulus elicited a widely-distributed negative deflection, probably reflecting further analysis of the significant sound involving evaluation of relevance or reorienting to the primary task. Our data show, that the personal significance of mobile phone and text message technology, which have developed as a major medium of communication in our modern world, prompts the formation of individual memory representations, which affect the processing of sounds that are not in the focus of attention.

  3. Sucrose acetate isobutyrate-based nanogels as liquid fiducial tissue markers with potential use in image guided radiotherapy

    DEFF Research Database (Denmark)

    Bruun, Linda Maria; Schaarup-Jensen, Henrik; Jølck, Rasmus Irming

    The poster presents the development of a liquid fiducial tissue marker based on sucrose acetate isobutyrate (SAIB) and uniform, coated gold nanoparticles (AuNPs). The PNIPAM-coated AuNP-SAIB gel provided high CT contrast and high in vivo stability and was assessed to be a suitable tissue marker f...

  4. The chloroplast psbK-psbI intergenic region, a potential genetic marker for broad sectional relationships in Anthurium

    Science.gov (United States)

    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. Candidate SNP Markers of Familial and Sporadic Alzheimer's Diseases Are Predicted by a Significant Change in the Affinity of TATA-Binding Protein for Human Gene Promoters

    Directory of Open Access Journals (Sweden)

    Petr Ponomarenko

    2017-07-01

    Full Text Available While year after year, conditions, quality, and duration of human lives have been improving due to the progress in science, technology, education, and medicine, only eight diseases have been increasing in prevalence and shortening human lives because of premature deaths according to the retrospective official review on the state of US health, 1990-2010. These diseases are kidney cancer, chronic kidney diseases, liver cancer, diabetes, drug addiction, poisoning cases, consequences of falls, and Alzheimer's disease (AD as one of the leading pathologies. There are familial AD of hereditary nature (~4% of cases and sporadic AD of unclear etiology (remaining ~96% of cases; i.e., non-familial AD. Therefore, sporadic AD is no longer a purely medical problem, but rather a social challenge when someone asks oneself: “What can I do in my own adulthood to reduce the risk of sporadic AD at my old age to save the years of my lifespan from the destruction caused by it?” Here, we combine two computational approaches for regulatory SNPs: Web service SNP_TATA_Comparator for sequence analysis and a PubMed-based keyword search for articles on the biochemical markers of diseases. Our purpose was to try to find answers to the question: “What can be done in adulthood to reduce the risk of sporadic AD in old age to prevent the lifespan reduction caused by it?” As a result, we found 89 candidate SNP markers of familial and sporadic AD (e.g., rs562962093 is associated with sporadic AD in the elderly as a complication of stroke in adulthood, where natural marine diets can reduce risks of both diseases in case of the minor allele of this SNP. In addition, rs768454929, and rs761695685 correlate with sporadic AD as a comorbidity of short stature, where maximizing stature in childhood and adolescence as an integral indicator of health can minimize (or even eliminate the risk of sporadic AD in the elderly. After validation by clinical protocols, these candidate SNP

  6. Candidate SNP Markers of Familial and Sporadic Alzheimer's Diseases Are Predicted by a Significant Change in the Affinity of TATA-Binding Protein for Human Gene Promoters

    Science.gov (United States)

    Ponomarenko, Petr; Chadaeva, Irina; Rasskazov, Dmitry A.; Sharypova, Ekaterina; Kashina, Elena V.; Drachkova, Irina; Zhechev, Dmitry; Ponomarenko, Mikhail P.; Savinkova, Ludmila K.; Kolchanov, Nikolay

    2017-01-01

    While year after year, conditions, quality, and duration of human lives have been improving due to the progress in science, technology, education, and medicine, only eight diseases have been increasing in prevalence and shortening human lives because of premature deaths according to the retrospective official review on the state of US health, 1990-2010. These diseases are kidney cancer, chronic kidney diseases, liver cancer, diabetes, drug addiction, poisoning cases, consequences of falls, and Alzheimer's disease (AD) as one of the leading pathologies. There are familial AD of hereditary nature (~4% of cases) and sporadic AD of unclear etiology (remaining ~96% of cases; i.e., non-familial AD). Therefore, sporadic AD is no longer a purely medical problem, but rather a social challenge when someone asks oneself: “What can I do in my own adulthood to reduce the risk of sporadic AD at my old age to save the years of my lifespan from the destruction caused by it?” Here, we combine two computational approaches for regulatory SNPs: Web service SNP_TATA_Comparator for sequence analysis and a PubMed-based keyword search for articles on the biochemical markers of diseases. Our purpose was to try to find answers to the question: “What can be done in adulthood to reduce the risk of sporadic AD in old age to prevent the lifespan reduction caused by it?” As a result, we found 89 candidate SNP markers of familial and sporadic AD (e.g., rs562962093 is associated with sporadic AD in the elderly as a complication of stroke in adulthood, where natural marine diets can reduce risks of both diseases in case of the minor allele of this SNP). In addition, rs768454929, and rs761695685 correlate with sporadic AD as a comorbidity of short stature, where maximizing stature in childhood and adolescence as an integral indicator of health can minimize (or even eliminate) the risk of sporadic AD in the elderly. After validation by clinical protocols, these candidate SNP markers may

  7. Immuno-Detection of C3a, a C3 Complement Activated Product in Mastitis Milk, a Potential Diagnostic Marker

    Directory of Open Access Journals (Sweden)

    Thanislass Jacob

    2017-02-01

    Full Text Available The sub-clinical form of mastitis is difficult to detect and causes huge economic loss to the dairy industry. It has become a threat to public health at large, thus there is a need for definite diagnosis of the disease. Therefore, this study was undertaken to identify the novel diagnostic marker for the detection of the sub-clinical form of mastitis. Two-dimensional gel analysis of the whey protein fraction of normal and mastitis milk samples revealed the presence of proteose peptone component 3 precursor, Trypsin precursor, complement component-C3, Ig heavy chain precursors and a C-type lectin domain as differentially expressed protein during the early stage of mastitis. Of these proteins identified, complement component-C3 was tested for its diagnostic potential. Western blot analysis of the milk whey of sub-clinical mastitis cases (M+, M++ & M+++ identified the accumulation of C3a, an activated product of complement component-C3. Further, the hemolytic activity of the above milk whey samples positively correlated with the somatic cell count. As C3a is already reported as an anaphylotoxic agent, it chemo tactically attracts lymphocytes at the site of inflammation, the detection of which in the milk whey can be of diagnostic importance for sub-clinical mastitis.

  8. The mitochondrial genome of Euphausia superba (Prydz Bay) (Crustacea: Malacostraca: Euphausiacea) reveals a novel gene arrangement and potential molecular markers.

    Science.gov (United States)

    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.

  9. Recombinant VP1 protein as a potential marker for the diagnosis of acute hepatitis A virus infection.

    Science.gov (United States)

    da Silva Junior, Haroldo Cid; da Silva, Edimilson Domingos; Lewis-Ximenez de Souza Rodrigues, Lia Laura; Medeiros, Marco Alberto

    2017-07-01

    Since hepatitis A virus (HAV) production is time-consuming and expensive, the use of recombinant proteins may represent an alternative source of antigens for diagnostic purposes. The present study aimed to express, purify and evaluate the potential of recombinant VP1 protein (rVP1) as a marker for the diagnosis of acute HAV infection. The rVP1 was expressed and purified successfully from Escherichia coli. The purified rVP1 was used to establish an in-house enzyme-linked immunosorbent assay (ELISA-rVP1) for detection of IgM antibodies in sera from HAV-positive patients. For a cut-off point of 0.351, the sensitivity and specificity of ELISA-rVP1 were 100.0% and 95.0%, respectively. These results indicate that rVP1 may be a useful antigen for detection of IgM antibodies against HAV. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. The potential of molecular markers to improve interventions through the natural history of oesophageal squamous cell carcinoma.

    Science.gov (United States)

    da Costa, Nathalia Meireles; Soares Lima, Sheila Coelho; de Almeida Simão, Tatiana; Ribeiro Pinto, Luis Felipe

    2013-08-14

    EC (oesophageal cancer) is one of the ten most frequent and fatal tumours worldwide and ESCC (oesophageal squamous cell carcinoma) accounts for about 80% of the cases. The first symptoms of ESCC arise late during the progression of the disease and, therefore, the diagnosis is usually done in advanced stages. This leads to an inefficient treatment and consequently to a poor prognosis. Thus, a comprehensive knowledge of ESCC biology is of major importance to identify risk factors, especially in high-incidence areas and biomarkers which could enable ESCC prevention and interventions throughout the natural history of the disease. In this review, we present the current knowledge regarding ESCC aetiology as well as the different genetic and epigenetic alterations already described in this tumour. We also discuss how these alterations could be used to anticipate ESCC diagnosis as well as how they can help improving treatment. A molecular natural history of the disease is proposed pointing out potential markers that may improve interventions at different points of ESCC development. Only when the different layers of complexity behind this tumour are elucidated, it will be possible to successfully perform prevention at different levels.

  11. Choice of xenogenic-free expansion media significantly influences the myogenic differentiation potential of human bone marrow-derived mesenchymal stromal cells.

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    Brun, Juliane; Abruzzese, Tanja; Rolauffs, Bernd; Aicher, Wilhelm K; Hart, Melanie L

    2016-03-01

    Mesenchymal stromal cells (MSCs) have great potential for use in cell-based therapies for restoration of structure and function of many tissue types including smooth muscle. We compared proliferation, immunophenotype, differentiation capability and gene expression of bone marrow-derived MSCs expanded in different media containing human serum, plasma and platelet lysate in combination with commonly used protocols for myogenic, osteogenic, chondrogenic and adipogenic differentiation. Moreover, we developed a xenogenic-free protocol for myogenic differentiation of MSCs. Expansion of MSCs in media complemented with serum, serum + platelet lysate or plasma + platelet lysate were multipotent because they differentiated toward four mesenchymal (myogenic, osteogenic, chondrogenic, adipogenic) lineages. Addition of platelet lysate to expansion media increased the proliferation of MSCs and their expression of CD146. Incubation of MSCs in medium containing human serum or plasma plus 5% human platelet lysate in combination with smooth muscle cell (SMC)-inducing growth factors TGFβ1, PDGF and ascorbic acid induced high expression of ACTA2, TAGLN, CNN1 and/or MYH11 contractile SMC markers. Osteogenic, adipogenic and chondrogenic differentiations served as controls. Our study provides novel data on the myogenic differentiation potential of human MSCs toward the SMC lineage using different xenogenic-free cell culture expansion media in combination with distinct differentiation medium compositions. We show that the choice of expansion medium significantly influences the differentiation potential of human MSCs toward the smooth muscle cell, as well as osteogenic, adipogenic and chondrogenic lineages. These results can aid in designing studies using MSCs for tissue-specific therapeutic applications. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  12. Investigation of in vivo potential of scorpion venom against skin tumorigenesis in mice via targeting markers associated with cancer development

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    Al Asmari AK

    2016-10-01

    Full Text Available Abdulrahman K Al Asmari, Abdul Quaiyoom Khan Research Centre, Prince Sultan Military Medical City, Riyadh, Saudi Arabia Abstract: 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 antitumorigenic 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. Keywords: Leiurus quinquestriatus, skin cancer, apoptosis, immunosuppression

  13. Clinical significance and therapeutic potential of prostate cancer antigen-1/ALKBH3 in human renal cell carcinoma.

    Science.gov (United States)

    Hotta, Kiyohiko; Sho, Masayuki; Fujimoto, Kiyohide; Shimada, Keiji; Yamato, Ichiro; Anai, Satoshi; Harada, Hiroshi; Tsujikawa, Kazutake; Konishi, Noboru; Shinohara, Nobuo; Nakajima, Yoshiyuki

    2015-08-01

    Prostate cancer antigen-1 (PCA-1)/ALKBH3 has been recently identified in human prostate cancer and its expression is correlated with disease progression and prognosis. However, the precise role and function of PCA-1/ALKBH3 in human malignancies are largely unknown. In the present study, we investigated the clinical significance and therapeutic potential of PCA-1/ALKBH3 in renal cell carcinoma (RCC). PCA-1/ALKBH3 expression was examined by immunohistochemistry in 101 RCC patients who underwent radical or partial nephrectomy. Its expression was positively correlated with advanced pathological T- and M-factors and TNM stage (T, P<0.05; M, P<0.01; TNM, P<0.01, respectively). In the prognostic analysis, PCA-1/ALKBH3-negative patients with RCC had a significantly better prognosis than PCA-1/ALKBH3-positive patients (5-year survival rate, 92.9 vs. 75.9%, respectively; P<0.05). Next, the therapeutic potential of targeting PCA-1/ALKBH3 was further evaluated by small interfering RNA method using a human RCC cell line (CAKI-1). We found that PCA-1/ALKBH3 knockdown significantly inhibited the growth of CAKI-1 cells compared with the control (P<0.001). Furthermore, knockdown of PCA-1 induced apoptosis in CAKI-1 cells, as assessed by poly(ADP-ribose) polymerase-cleavage assays. We demonstrated for the first time that PCA-1/ALKBH3 expression has a significant prognostic impact on patient prognosis in RCC. Furthermore, its knockdown has a therapeutic efficacy on RCC. Taken together, both our clinical and experimental data strongly suggest that PCA-1/ALKBH3 may be functionally important and a novel molecular target for human RCC.

  14. Identification of Rubisco rbcL and rbcS in Camellia oleifera and their potential as molecular markers for selection of high tea oil cultivars.

    Science.gov (United States)

    Chen, Yongzhong; Wang, Baoming; Chen, Jianjun; Wang, Xiangnan; Wang, Rui; Peng, Shaofeng; Chen, Longsheng; Ma, Li; Luo, Jian

    2015-01-01

    Tea oil derived from seeds of Camellia oleifera Abel. is high-quality edible oil in China. This study isolated full-length cDNAs of Rubisco subunits rbcL and rbcS from C. oleifera. The rbcL has 1,522 bp with a 1,425 bp coding region, encoding 475 amino acids; and the rbcS has 615 bp containing a 528 bp coding region, encoding 176 amino acids. The expression level of the two genes, designated as Co-rbcL and Co-rbcS, was determined in three C. oleifera cultivars: Hengchong 89, Xianglin 1, and Xianglin 14 whose annual oil yields were 546.9, 591.4, and 657.7 kg ha(-1), respectively. The Co-rbcL expression in 'Xianglin 14' was significantly higher than 'Xianglin 1', and 'Xianglin 1' was greater than 'Hengchong 89'. The expression levels of Co-rbcS in 'Xianglin 1' and 'Xianglin 14' were similar but were significantly greater than in 'Hengchong 89'. The net photosynthetic rate of 'Xianglin 14' was significantly higher than 'Xianglin 1', and 'Xianglin 1' was higher than 'Hengchong 89'. Pearson's correlation analysis showed that seed yields and oil yields were highly correlated with the expression level of Co-rbcL at P rbcL in particular could potentially be molecular markers for early selection of high oil yield cultivars. In combination with the measurement of net photosynthetic rates, the early identification of potential high oil production cultivars would significantly shorten plant breeding time and increase breeding efficiency.

  15. PYGOPUS2 expression in prostatic adenocarcinoma is a potential risk stratification marker for PSA progression following radical prostatectomy.

    Science.gov (United States)

    Kao, Kenneth R; Popadiuk, Paul; Thoms, John; Aoki, Satoko; Anwar, Shahgul; Fitzgerald, Emily; Andrews, Phillip; Voisey, Kim; Gai, Luis; Challa, Satya; He, Zhijian; Gonzales-Aguirre, Paola; Simmonds, Andrea; Popadiuk, Catherine

    2017-09-18

    Prostate cancer (PrCa) is the most frequently diagnosed non-cutaneous cancer in men. Without clear pathological indicators of disease trajectory at diagnosis, management of PrCa is challenging, given its wide-ranging manifestation from indolent to highly aggressive disease. This study examines the role in PrCa of the Pygopus (PYGO)2 chromatin effector protein as a risk stratification marker in PrCa. RNA expression was performed in PrCa cell lines using Northern and RT-PCR analyses. Protein levels were assessed using immunoblot and immunofluorescence. Immunohistochemistry was performed on tissue microarrays constructed from radical prostatectomies with 5-year patient follow-up data including Gleason score tumour staging, margin and lymph node involvement and prostate serum antigen (PSA) levels. Biochemical recurrence (BR) was defined as a postoperative PSA level of >0.2 nL. Univariate and multivariate analyses were performed using SAS and Kaplan-Meier curves using graphPad (Prism). In vitro depletion of PYGO2 by RNAi in both androgen receptor positive and negative PrCa cell lines attenuated growth and reduced Ki67 and 47S rRNA expression, while PYGO2 protein was localised to the nuclei of tumours as determined by immunohistochemistry. High expression levels of PYGO2 in tumours (n=156) were correlated with BR identified as PSA progression, after 7-year follow-up independent of other traditional risk factors. Most importantly, high PYGO2 levels in intermediate grade tumours suggested increased risk of recurrence over those with negative or weak expression. Our data suggest that elevated PYGO2 expression in primary prostate adenocarcinoma is a potential risk factor for BR. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  16. Date prints on stranded macroplastics: Exploring the potential of marine litter assemblages as chronological markers in recent coastal deposit

    Science.gov (United States)

    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.

  17. Scalp-recorded evoked potentials as a marker for afferent nerve impulse in clinical vagus nerve stimulation.

    Science.gov (United States)

    Usami, Kenichi; Kawai, Kensuke; Sonoo, Masahiro; Saito, Nobuhito

    2013-07-01

    Vagus nerve stimulation (VNS) is a palliative treatment for drug resistant epilepsy for which the efficacy and safety are well established. Accumulating evidence suggests that ascending vagal signals modulate abnormal cortical excitability via various pathways. However, there is no direct evidence for an ascending conduction of neural impulses in a clinical case of VNS. We recorded and analyzed the short-latency components of the vagus nerve (VN) evoked potential (EP) from the viewpoint of determining whether or not it is a marker for the ascending neural conduction. EPs within 20 ms were prospectively recorded simultaneously from a surgical wound in the neck and at multiple scalp sites during implantation surgery in 25 patients with drug-resistant epilepsy. Electrical stimulation was delivered using the clinical VNS Therapy system. A recording was made before and after a muscle relaxant was administered, when changing the rostrocaudal position of stimulation, or when stimulating the ansa cervicalis instead of the VN. The short-latency components consisted of four peaks. The early component around 3 ms, which was most prominent in A1-Cz, remained unchanged after muscle relaxation while the later peaks disappeared. Rostral transition of the stimulation resulted in an earlier shift of the early component. The estimated conduction velocity was 27.4 ± 10.2 m/s. Stimulation of the ansa cervicalis induced no EP. The early component was regarded as directly resulting from ascending neural conduction of A fibers of the VN, probably originating around the jugular foramen. Recording of VN-EP might document the cause of treatment failure in some patients. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Zero Valent Iron Significantly Enhances Methane Production from Waste Activated Sludge by Improving Biochemical Methane Potential Rather Than Hydrolysis Rate

    Science.gov (United States)

    Liu, Yiwen; Wang, Qilin; Zhang, Yaobin; Ni, Bing-Jie

    2015-02-01

    Anaerobic digestion has been widely applied for waste activated sludge (WAS) treatment. However, methane production from anaerobic digestion of WAS is usually limited by the slow hydrolysis rate and/or poor biochemical methane potential of WAS. This work systematically studied the effects of three different types of zero valent iron (i.e., iron powder, clean scrap and rusty scrap) on methane production from WAS in anaerobic digestion, by using both experimental and mathematical approaches. The results demonstrated that both the clean and the rusty iron scrap were more effective than the iron powder for improving methane production from WAS. Model-based analysis showed that ZVI addition significantly enhanced methane production from WAS through improving the biochemical methane potential of WAS rather than its hydrolysis rate. Economic analysis indicated that the ZVI-based technology for enhancing methane production from WAS is economically attractive, particularly considering that iron scrap can be freely acquired from industrial waste. Based on these results, the ZVI-based anaerobic digestion process of this work could be easily integrated with the conventional chemical phosphorus removal process in wastewater treatment plant to form a cost-effective and environment-friendly approach, enabling maximum resource recovery/reuse while achieving enhanced methane production in wastewater treatment system.

  19. The potential use of 29 kDa protein as a marker of pathogenicity and diagnosis of symptomatic infections with Blastocystis hominis.

    Science.gov (United States)

    Abou Gamra, Maha M; Elwakil, Hala S; El Deeb, Hala K; Khalifa, Khalifa E; Abd Elhafiz, Hala E

    2011-05-01

    The present study was performed to characterize the protein profiles of Blastocystis hominis isolates from symptomatic and asymptomatic individuals by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting using sera from symptomatic and asymptomatic patients. The presence of immunogenic bands associated with pathogenicity or of diagnostic potentials was also evaluated. The study comprised 80 individuals classified into four groups, 20 each: symptomatic blastocystosis (G1), asymptomatic blastocystosis (G2), other parasitic infections (G3), and healthy control subjects (G4). SDS-PAGE analysis of individual antigens form symptomatic and asymptomatic B. hominis isolates revealed similar and distinctive antigenic bands with significant differences in two high (123.5 and 112.3 kDa) and few low molecular weight bands (48.5, 38, 42.3, and 35.5 kDa). Immunoblotting was performed using symptomatic and asymptomatic antigen pools with sera of the four studied groups. It was found that anti-B. hominis IgG reacted with nine protein bands ranging from 100 to 18 kDa of the symptomatic antigen pool. There was a significant difference between G1 and G2 in the recognition of 64, 56, 38, and 29 kDa antigen bands. Also, anti-B. hominis IgG reacted with five protein bands ranging from 56 to 12 kDa of asymptomatic antigen pool. There was a significant difference between G1 and G2 in the recognition of 29 kDa antigen band. These findings suggest the potential use of the 29-kDa antigen as marker of pathogenicity and implicate its use in the diagnosis and differentiation between symptomatic and asymptomatic blastocystosis.

  20. Ultra-structural cell distribution of the melanoma marker iodobenzamide: improved potentiality of SIMS imaging in life sciences

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    Papon Janine

    2004-04-01

    Full Text Available Abstract Background Analytical imaging by secondary ion mass spectrometry (SIMS provides images representative of the distribution of a specific ion within a sample surface. For the last fifteen years, concerted collaborative research to design a new ion microprobe with high technical standards in both mass and lateral resolution as well as in sensitivity has led to the CAMECA NanoSims 50, recently introduced onto the market. This instrument has decisive capabilities, which allow biological applications of SIMS microscopy at a level previously inaccessible. Its potential is illustrated here by the demonstration of the specific affinity of a melanoma marker for melanin. This finding is of great importance for the diagnosis and/or treatment of malignant melanoma, a tumour whose worldwide incidence is continuously growing. Methods The characteristics of the instrument are briefly described and an example of application is given. This example deals with the intracellular localization of an iodo-benzamide used as a diagnostic tool for the scintigraphic detection of melanic cells (e.g. metastasis of malignant melanoma. B16 melanoma cells were injected intravenously to C57BL6/J1/co mice. Multiple B16 melanoma colonies developed in the lungs of treated animals within three weeks. Iodobenzamide was injected intravenously in tumour bearing mice six hours before sacrifice. Small pieces of lung were prepared for SIMS analysis. Results Mouse lung B16 melanoma colonies were observed with high lateral resolution. Cyanide ions gave "histological" images of the cell, representative of the distribution of C and N containing molecules (e.g. proteins, nucleic acids, melanin, etc. while phosphorus ions are mainly produced by nucleic acids. Iodine was detected only in melanosomes, confirming the specific affinity of the drug for melanin. No drug was found in normal lung tissue. Conclusion This study demonstrates the potential of SIMS microscopy, which allows the

  1. Application of thresholds of potential concern and limits of acceptable change in the condition assessment of a significant wetland.

    Science.gov (United States)

    Rogers, Kerrylee; Saintilan, Neil; Colloff, Matthew J; Wen, Li

    2013-10-01

    We propose a framework in which thresholds of potential concern (TPCs) and limits of acceptable change (LACs) are used in concert in the assessment of wetland condition and vulnerability and apply the framework in a case study. The lower Murrumbidgee River floodplain (the 'Lowbidgee') is one of the most ecologically important wetlands in Australia and the focus of intense management intervention by State and Federal government agencies. We used a targeted management stakeholder workshop to identify key values that contribute to the ecological significance of the Lowbidgee floodplain, and identified LACs that, if crossed, would signify the loss of significance. We then used conceptual models linking the condition of these values (wetland vegetation communities, waterbirds, fish species and the endangered southern bell frog) to measurable threat indicators, for which we defined a management goal and a TPC. We applied this framework to data collected across 70 wetland storages', or eco-hydrological units, at the peak of a prolonged drought (2008) and following extensive re-flooding (2010). At the suggestion of water and wetland mangers, we neither aggregated nor integrated indices but reported separately in a series of chloropleth maps. The resulting assessment clearly identified the effect of rewetting in restoring indicators within TPC in most cases, for most storages. The scale of assessment was useful in informing the targeted and timely management intervention and provided a context for retaining and utilising monitoring information in an adaptive management context.

  2. IGF2BP3 as a potential tissue marker for the diagnosis of esophageal high-grade intraepithelial neoplasia

    Directory of Open Access Journals (Sweden)

    Zhang JJ

    2017-08-01

    Full Text Available Jingjing Zhang,1,* Qing Ji,2,* Chunhua Jiao,3,* Lihua Ren,4 Ye Zhao,4 Yanfang Chen,4 Ruihua Shi,4 Yadong Feng4 1State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, 2Department of Emergency, Jingjiang People’s Hospital, Jingjiang, 3Department of Gastroenterology, First Affiliated Hospital with Nanjing Medical University, 4Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China *These authors contributed equally to this work Background: The clinical significance of insulin-like growth factor-II mRNA-binding protein-3 (IGF2BP3 in esophageal high-grade intraepithelial neoplasia (HGIN is not clear. This study was designed to characterize the expression of IGF2BP3 in HGIN. Patients and methods: IGF2BP3 expression was evaluated by Western blot analyses in 12 cases and by immunohistochemistry (IHC in 112 cases. The associations between IGF2BP3 expression in HGIN and the clinicopathological parameters were examined. Results: Moderate to strong IGF2BP3 expression was present in HGIN samples. Using IHC, it was found that IGF2BP3 was positive in 68 (60.71% cases. Intense IHC of IGF2BP3 in HGIN was associated with a deeper lesion depth, and the lesion depth was the only predictor of the positive expression of IGF2BP3. Conclusion: Our results suggested that IGF2BP3 may be a supplementary tissue marker for preoperative diagnosis of HGIN. Keywords: esophageal squamous cell carcinoma, precancerous lesion, immunohistochemistry detection, early diagnosis

  3. Potential diagnostic significance of HSP90, ACS/TMS1, and L-plastin in the identification of melanoma.

    Science.gov (United States)

    Strickler, Allen G; Vasquez, Juan G; Yates, Nathan; Ho, Jonhan

    2014-12-01

    Melanoma is one of the deadliest cancers, yet it remains a diagnostic and prognostic challenge. The lack of effective treatment modalities compounds this challenge. Characterizing the molecular mechanisms leading to the development of melanoma is the first step to understanding the pathophysiology of melanoma. Numerous molecular studies have helped us understand critical changes that occur in the transition from a benign nevus to melanoma. However, many of these processes remain undiscovered. The goal of the current project was to characterize the proteomes of benign nevi and malignant melanomas using proteomic methods, with confirmation by immunohistochemical analysis. Using tandem mass spectrometry, we identified proteins potentially involved in melanoma pathogenesis. Several of the identified proteins have known roles in oncogenesis, melanogenesis, or both. We selected Hsp90-β, apoptosis-associated speck-like protein containing a CARD (ASC/TMS1), and L-plastin from these to analyze nevi and melanoma samples by immunohistochemical analysis. Hsp90-β and ASC/TMS1 staining was higher in melanoma when compared with nevi, whereas L-plastin protein expression was not significantly different between cells of these tumor types; however, it was expressed in the inflammatory milieu of melanoma. ACS/TMS1 showed staining in normal and junctional melanocytes, as well as in superficial nevomelanocytes, but deeper dermal nevomelanocytes gradually lost expression. This study helps validate the use of proteomics to aid in characterizing protein differences between nevi and melanomas and also underscores the importance of correlating proteomic results with histomorphology to understand the context of the information. The proteins in the current study may hold potential in differentiating between melanoma and benign nevi in diagnostically challenging cases.

  4. Effects of low-dose rate γ-irradiation combined with simulated microgravity on markers of oxidative stress, DNA methylation potential, and remodeling in the mouse heart.

    Directory of Open Access Journals (Sweden)

    John W Seawright

    Full Text Available Space travel is associated with an exposure to low-dose rate ionizing radiation and the microgravity environment, both of which may lead to impairments in cardiac function. We used a mouse model to determine short- and long-term cardiac effects to simulated microgravity (hindlimb unloading; HU, continuous low-dose rate γ-irradiation, or a combination of HU and low-dose rate γ-irradiation.Cardiac tissue was obtained from female, C57BL/6J mice 7 days, 1 month, 4 months, and 9 months following the completion of a 21 day exposure to HU or a 21 day exposure to low-dose rate γ-irradiation (average dose rate of 0.01 cGy/h to a total of 0.04 Gy, or a 21 day simultaneous exposure to HU and low-dose rate γ-irradiation. Immunoblot analysis, rt-PCR, high-performance liquid chromatography, and histology were used to assess inflammatory cell infiltration, cardiac remodeling, oxidative stress, and the methylation potential of cardiac tissue in 3 to 6 animals per group.The combination of HU and γ-irradiation demonstrated the strongest increase in reduced to oxidized glutathione ratios 7 days and 1 month after treatment, but a difference was no longer apparent after 9 months. On the other hand, no significant changes in 4-hydroxynonenal adducts was seen in any of the groups, at the measured endpoints. While manganese superoxide dismutase protein levels decreased 9 months after low-dose γ-radiation, no changes were observed in expression of catalase or Nrf2, a transcription factor that determines the expression of several antioxidant enzymes, at the measured endpoints. Inflammatory marker, CD-2 protein content was significantly decreased in all groups 4 months after treatment. No significant differences were observed in α-smooth muscle cell actin protein content, collagen type III protein content or % total collagen.This study has provided the first and relatively broad analysis of small molecule and protein markers of oxidative stress, T

  5. Effects of low-dose rate γ-irradiation combined with simulated microgravity on markers of oxidative stress, DNA methylation potential, and remodeling in the mouse heart.

    Science.gov (United States)

    Seawright, John W; Samman, Yusra; Sridharan, Vijayalakshmi; Mao, Xiao Wen; Cao, Maohua; Singh, Preeti; Melnyk, Stepan; Koturbash, Igor; Nelson, Gregory A; Hauer-Jensen, Martin; Boerma, Marjan

    2017-01-01

    Space travel is associated with an exposure to low-dose rate ionizing radiation and the microgravity environment, both of which may lead to impairments in cardiac function. We used a mouse model to determine short- and long-term cardiac effects to simulated microgravity (hindlimb unloading; HU), continuous low-dose rate γ-irradiation, or a combination of HU and low-dose rate γ-irradiation. Cardiac tissue was obtained from female, C57BL/6J mice 7 days, 1 month, 4 months, and 9 months following the completion of a 21 day exposure to HU or a 21 day exposure to low-dose rate γ-irradiation (average dose rate of 0.01 cGy/h to a total of 0.04 Gy), or a 21 day simultaneous exposure to HU and low-dose rate γ-irradiation. Immunoblot analysis, rt-PCR, high-performance liquid chromatography, and histology were used to assess inflammatory cell infiltration, cardiac remodeling, oxidative stress, and the methylation potential of cardiac tissue in 3 to 6 animals per group. The combination of HU and γ-irradiation demonstrated the strongest increase in reduced to oxidized glutathione ratios 7 days and 1 month after treatment, but a difference was no longer apparent after 9 months. On the other hand, no significant changes in 4-hydroxynonenal adducts was seen in any of the groups, at the measured endpoints. While manganese superoxide dismutase protein levels decreased 9 months after low-dose γ-radiation, no changes were observed in expression of catalase or Nrf2, a transcription factor that determines the expression of several antioxidant enzymes, at the measured endpoints. Inflammatory marker, CD-2 protein content was significantly decreased in all groups 4 months after treatment. No significant differences were observed in α-smooth muscle cell actin protein content, collagen type III protein content or % total collagen. This study has provided the first and relatively broad analysis of small molecule and protein markers of oxidative stress, T-lymphocyte infiltration, and

  6. Clinicopathological significance and potential drug target of CDH1 in breast cancer: a meta-analysis and literature review

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    Huang R

    2015-09-01

    Full Text Available Ruixue Huang,* Ping Ding,* Fei Yang*Department of Occupational and Environmental Health, School of Public Health, Central South University, Changsha, Hunan, People’s Republic of China*All authors contributed equally to this workAbstract: CDH1, as a tumor suppressor gene, contributes sporadic breast cancer (BC progression. However, the association between CDH1 hypermethylation and BC, and its clinicopathological significance remains unclear. We conducted a meta-analysis to investigate the relationship between the CDH1 methylation profile and the major clinicopathological features. A detailed literature was searched through the electronic databases PubMed, Web of Science™, and EMBASE™ for related research publications. The data were extracted and assessed by two reviewers independently. Odds ratios (ORs with corresponding confidence intervals (CIs were calculated and summarized respectively. The frequency of CDH1 methylation was significantly higher in invasive ductal carcinoma than in normal breast tissues (OR =5.83, 95% CI 3.76–9.03, P<0.00001. CDH1 hypermethylation was significantly higher in estrogen receptor (ER-negative BC than in ER-positive BC (OR =0.62, 95% CI 0.43–0.87, P=0.007. In addition, we found that the CDH1 was significantly methylated in HER2-negative BC than in HER2-positive BC (OR =0.26, 95% CI 0.15–0.44, P<0.00001. However, CDH1 methylation frequency was not associated with progesterone receptor (PR status, or with grades, stages, or lymph node metastasis of BC patients. Our results indicate that CDH1 hypermethylation is a potential novel drug target for developing personalized therapy. CDH1 hypermethylation is strongly associated with ER-negative and HER2-negative BC, respectively, suggesting CDH1 methylation status could contribute to the development of novel therapeutic approaches for the treatment of ER-negative or HER2-negative BC with aggressive tumor biology.Keywords: methylation, estrogen receptor, HER2

  7. The role of BRAF V600E mutation as a potential marker for prognostic stratification of papillary thyroid carcinoma: a long-term follow-up study.

    Science.gov (United States)

    Daliri, Mahdi; Abbaszadegan, Mohammad Reza; Bahar, Mostafa Mehrabi; Arabi, Azadeh; Yadollahi, Mona; Ghafari, Azar; Taghehchian, Negin; Zakavi, Seyed Rasoul

    2014-01-01

    Abstract Papillary carcinoma is the most prevalent malignancy of thyroid gland, and its incidence has been recently increased. The BRAF(V600E) mutation is the most frequent genetic alteration in papillary thyroid carcinoma (PTC). The role of BRAF(V600E) mutation as a potential prognostic factor has been controversially reported in different studies, with short-term follow-up. In this study, we evaluated the role of BRAF(V600E) mutation as a potential marker for prognostic stratification of patients with PTC in long-term follow-up. We studied 69 PTC patients with a mean follow-up period of 63.9 months (median: 60 m). The BRAF(V600E) mutation was analyzed by PCR-single-strand conformational polymorphism and sequencing. The correlation between the presence or absence of the BRAF(V600E) mutation, clinicopathological features and prognosis of PTC patients were studied. The BRAF(V600E) mutation was found in 28 of 69 (40.6%) PTC patients, and it was significantly more frequent in older patients (p history of radiation exposure (p = 0.037). Incomplete response to treatment in PTC patients was significantly correlated with certain clinicopathological characteristics (follow-up time, distant metastases, advanced stage, first thyroglobulin (fTg) level, history of reoperation and external radiotherapy and delay in iodine therapy) but it was not related to the presence of BRAF(V600E) mutation. Prevalence of BRAF(V600E) mutation was 40.6% in patients with papillary thyroid cancer in northeast of Iran. The BRAF(V600E) mutation was associated with older age and advanced tumor stage but was not correlated with incomplete response during follow-up.

  8. Summary of impact markers and potential impact mechanisms for the YDB impact event at 12.9 ka

    Science.gov (United States)

    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

  9. Usefulness of field potential as a marker of embryonic stem cell-derived cardiomyocytes, and endpoint analysis of embryonic stem cell test.

    Science.gov (United States)

    Koseki, Naoteru; Deguchi, Jiro; Yamada, Toru; Funabashi, Hitoshi; Seki, Takaki

    2010-12-01

    The embryonic stem cell test (EST) is a validated method and a useful screening tool for drug discovery. EST requires microscopic observation of beating cells to be considered cardiomyocytes as an endpoint assay. However, this procedure is time-consuming and limits the throughput performance. Instead of microscopic observation, we previously established a novel assay method based on cardiac field potential as an endpoint. However, cardiac specificity of this field potential is not yet clarified, because beating cells have not been rigorously evaluated as skeletal or cardiomyocyte. Here, we investigated the relationships between field potential, beating, and cardiac troponin T (cTnT) expression, selected as a cardiomyocyte-specific marker, and evaluated suitability of the field potential as a marker for cardiomyocyte in vehicle or 5-fluorouracil treated embryo bodies. Embryoid bodies of mouse embryonic stem cells (D3) were differentiated in a chamber with multi-electrode array for 5 days, and field potential and beating were measured at the end of differentiation. In addition, these chambers were immunohistochemically stained with anti-cTnT antibody, and the correlation between field potential, beating, and cTnT expression was examined. These results indicated the area of field potential or beating mainly coincided with that of cTnT expression. 5-fluorouracil treatment decreased not only the number of field potential detecting electrodes and beating area, but also cTnT expression, and the area of these parameters was also nearly identical. These results indicate that field potential can be used as a suitable cardiac differentiation marker, and can be a promising parameter of EST.

  10. Physiologic responses and gene diversity indicate olive alternative oxidase as a potential source for markers involved in efficient adventitious root induction.

    Science.gov (United States)

    Santos Macedo, Elisete; Cardoso, Hélia G; Hernández, Alejandro; Peixe, Augusto A; Polidoros, Alexios; Ferreira, Alexandre; Cordeiro, António; Arnholdt-Schmitt, Birgit

    2009-12-01

    Olive (Olea europaea L.) trees are mainly propagated by adventitious rooting of semi-hardwood cuttings. However, efficient commercial propagation of valuable olive tree cultivars or landraces by semi-hardwood cuttings can often be restricted by a low rooting capacity. We hypothesize that root induction is a plant cell reaction linked to oxidative stress and that activity of stress-induced alternative oxidase (AOX) is importantly involved in adventitious rooting. To identify AOX as a source for potential functional marker sequences that may assist tree breeding, genetic variability has to be demonstrated that can affect gene regulation. The paper presents an applied, multidisciplinary research approach demonstrating first indications of an important relationship between AOX activity and differential adventitious rooting in semi-hardwood cuttings. Root induction in the easy-to-root Portuguese cultivar 'Cobrançosa' could be significantly reduced by treatment with salicyl-hydroxamic acid, an inhibitor of AOX activity. On the contrary, treatment with H2O2 or pyruvate, both known to induce AOX activity, increased the degree of rooting. Recently, identification of several O. europaea (Oe) AOX gene sequences has been reported from our group. Here we present for the first time partial sequences of OeAOX2. To search for polymorphisms inside of OeAOX genes, partial OeAOX2 sequences from the cultivars 'Galega vulgar', 'Cobrançosa' and 'Picual' were cloned from genomic DNA and cDNA, including exon, intron and 3'-untranslated regions (3'-UTRs) sequences. The data revealed polymorphic sites in several regions of OeAOX2. The 3'-UTR was the most important source for polymorphisms showing 5.7% of variability. Variability in the exon region accounted 3.4 and 2% in the intron. Further, analysis performed at the cDNA from microshoots of 'Galega vulgar' revealed transcript length variation for the 3'-UTR of OeAOX2 ranging between 76 and 301 bp. The identified polymorphisms and 3'-UTR

  11. Evaluation of potential prognostic value of Bmi-1 gene product and selected markers of proliferation (Ki-67 and apoptosis (p53 in the neuroblastoma group of tumors

    Directory of Open Access Journals (Sweden)

    Katarzyna Taran

    2016-02-01

    Full Text Available Introduction: Cancer in children is a very important issue in pediatrics. The least satisfactory treatment outcome occurs among patients with clinically advanced neuroblastomas. Despite much research, the biology of this tumor still remains unclear, and new prognostic factors are sought. The Bmi-1 gene product is a currently highly investigated protein which belongs to the Polycomb group (PcG and has been identified as a regulator of primary neural crest cells. It is believed that Bmi‑1 and N-myc act together and are both involved in the pathogenesis of neuroblastoma. The aim of the study was to assess the potential prognostic value of Bmi-1 protein and its relations with mechanisms of proliferation and apoptosis in the neuroblastoma group of tumors.Material/Methods: 29 formalin-fixed and paraffin-embedded neuroblastoma tissue sections were examined using mouse monoclonal antibodies anti-Bmi-1, anti-p53 and anti-Ki-67 according to the manufacturer’s instructions.Results: There were found statistically significant correlations between Bmi-1 expression and tumor histology and age of patients.Conclusions: Bmi-1 seems to be a promising marker in the neuroblastoma group of tumors whose expression correlates with widely accepted prognostic parameters. The pattern of BMI-1 expression may indicate that the examined protein is also involved in maturation processes in tumor tissue.

  12. Levels of vaspin and omentin-1 in gingival crevicular fluid as potential markers of inflammation in patients with chronic periodontitis and type 2 diabetes mellitus.

    Science.gov (United States)

    Bozkurt Doğan, Şeyma; Öngöz Dede, Figen; Ballı, Umut; Sertoğlu, Erdim

    2016-01-01

    The aims of the present study were to determine the levels of vaspin and omentin-1 in gingival crevicular fluid (GCF) in patients with chronic periodontitis (CP) with and without type 2 diabetes mellitus (T2DM), and to evaluate GCF vaspin and omentin-1 levels after non-surgical periodontal therapy. The study included 60 subjects: 15 systemically and periodontally healthy individuals, 15 periodontally healthy patients with T2DM, 15 systemically healthy patients with CP, and 15 patients with both CP and T2DM. GCF and clinical periodontal parameters were examined at the baseline and 6 weeks after periodontal therapy. Levels of vaspin, omentin-1 and tumor necrosis factor-alpha (TNF-α) were measured by ELISA, and their relative ratios were calculated. GCF vaspin and TNF-α levels were significantly higher in the CP groups than in the periodontally healthy groups (P periodontally healthy groups (P periodontal therapy influenced the GCF levels of both vaspin and omentin-1 in the CP groups. Our results suggest that the levels of vaspin and omentin-1 in GCF could have potential application as inflammatory markers of diabetes, periodontal disease and treatment outcome. (J Oral Sci 58, 379-389, 2016).

  13. Androgen and oestrogen receptors as potential prognostic markers for patients with ductal carcinoma in situ treated with surgery and radiotherapy.

    Science.gov (United States)

    Ravaioli, Sara; Tumedei, Maria Maddalena; Foca, Flavia; Maltoni, Roberta; Rocca, Andrea; Massa, Ilaria; Pietri, Elisabetta; Bravaccini, Sara

    2017-11-28

    Ductal carcinoma in situ (DCIS) is a heterogeneous disease that has been investigated less extensively than invasive breast cancer. Women with DCIS are mainly treated with conservative surgery almost exclusively followed by radiotherapy. However, as radiation treatment is not always effective, the search for biomarkers capable of identifying DCIS lesions that could progress to invasive cancer is ongoing. Although conventional biomarkers have been thoroughly studied in invasive tumours, little is known about the role played by androgen receptor (AR), widely expressed in DCIS. A series of 42 DCIS patients treated with quadrantectomy and radiotherapy were followed for a period of up to 95 months. Of these, 11 had recurrent DCIS or progressed to invasive cancer. All tumours were analysed for clinical pathological features. Conventional biomarkers and androgen receptor expression were determined by immunohistochemistry. Our results showed that AR was higher in tumours of relapsed patients than non-relapsed patients (P value: 0.0005). Conversely, oestrogen receptor (ER) was higher, albeit not significantly, in non-relapsed patients than in relapsed patients. AR/ER ratio was considerably different in the two subgroups (P value: 0.0033). Area under the curve (AUC) values were 0.85 for AR and 0.80 for the AR/ER ratio. These preliminary results highlight the potentially important role of both AR and the AR/ER ratio as prognostic markers in DCIS. © 2017 The Authors. International Journal of Experimental Pathology © 2017 International Journal of Experimental Pathology.

  14. Comparative sperm protein profiling in bulls differing in fertility and identification of phosphatidylethanolamine-binding protein 4, a potential fertility marker.

    Science.gov (United States)

    Somashekar, L; Selvaraju, S; Parthipan, S; Patil, S K; Binsila, B K; Venkataswamy, M M; Karthik Bhat, S; Ravindra, J P

    2017-09-01

    This study aimed to identify sperm proteomic signatures regulating sperm functions and fertility by: (i) comparing the sperm electrophoretic protein profiles and identifying the differentially abundant proteins among breeding bulls differing in fertility status and (ii) elucidating the possible role of one of the identified novel proteins, PEBP4 on sperm function and fertility. The grouping of bulls as fertile (n = 6) and low fertile (n = 6) was performed based on bull fertility index and infertile (n = 6) based on semen rejection rate (>33%). The sperm motility, fructolysis index, acrosomal reaction, intracellular calcium levels, and seminal plasma fructose and calcium levels were studied among fertility groups. The differentially expressed sperm proteins observed in single- and two-dimensional gel electrophoresis (2DE) were identified using Nano-LC-MS/MS. In the fertile bulls, the expression levels of calmodulin (CALM1), spermadhesinZ13 (SPADH2), and phosphatidylethanolamine-binding protein 4 (PEBP4) were significantly (p sperm fructose uptake was observed. Further, PEBP4 was localized in elongated spermatids, Leydig cells, excurrent duct system, and principal piece of spermatozoa. These findings suggest a crucial role for the PEBP4 protein in spermiogenesis, epididymal sperm maturation, and sperm motility. This first study in bovine indicates the positive association of PEBP4 in regulating sperm maturation, functions, and fertility and could be a potential marker for predicting semen quality and fertility. © 2017 American Society of Andrology and European Academy of Andrology.

  15. Acylcarnitines as markers of exercise-associated fuel partitioning, xenometabolism, and potential signals to muscle afferent neurons

    Science.gov (United States)

    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...

  16. Pretreatment levels of urinary deoxypyridinoline as a potential marker in patients with prostate cancer with or without bone metastasis

    NARCIS (Netherlands)

    Wymenga, L. F.; Groenier, K.; Schuurman, J.; Boomsma, J. H.; Elferink, R. O.; Mensink, H. J.

    2001-01-01

    OBJECTIVE: To assess the predictive role of the bone markers alkaline phosphatase (ALP) and urinary deoxypyridinoline (DPD), as indicators of bone turnover, at baseline in patients with prostate cancer. PATIENTS, SUBJECTS AND METHODS: Urinary DPD, serum ALP and prostate-specific antigen (PSA) were

  17. N-acetyl-beta-D-hexosaminidase and its isoenzymes A and B in blood serum and urine, as a potential colon cancer markers.

    Science.gov (United States)

    Szajda, Sławomir Dariusz; Borzym-Kluczyk, Małgorzata; Snarska, Jadwiga; Puchalski, Zbigniew; Zwierz, Krzysztof

    2009-01-01

    Evaluation of N-acetyl-beta-D-hexosaminidase (HEX), and its isoenzymes A (HEX A) and B (HEX B) activity in blood serum and urine as potential markers of colorectal cancer. The study was performed in blood serum and urine of 32 patients with adenocarcinoma, 6 with adenocarcinoma mucinosum of the colon, and 20 healthy people. The activity of HEX, HEX A and HEX B was determined in blood serum and urine by spectrophotometric method of Marciniak et al. The concentration of CEA was determined in blood serum by immunoenzymatic method (MEIA). The concentration of protein was assessed by the Lowry method, whereas the concentration of creatinine in urine by the Jaffe method (without deproteinization). A significant increase in the concentration of HEX, HEX A and HEX B activity was proved in serum and urine of patients with colon adenocarcinoma. In patients with colon adenocarcinoma mucinosum, the higher activity of HEX was revealed in blood serum compared to healthy people, and the significantly higher activity of HEX and HEX B expressed as pKat/mg of creatinine, was found in urine. We observe a significant increase in the activity of HEX, HEX A and HEX B expressed in pKat/mg of creatinine was found in urine of patients bearing tumor of diameter 6.0-7.0 cm in comparison to patients with tumor of diameter 4.0-5.0 cm. The present study results suggest that determination of HEX, HEX A and HEX B activity in blood serum and urine may be used to detect colon cancer in its early stages. However, the use of HEX, HEX A and HEX B activity in oncological diagnostics requires further studies on a larger group of patients.

  18. [Somatosensory evoked potentials and biochemical markers of neuronal deficits in patients undergoing carotid endarterectomy under regional anesthesia].

    Science.gov (United States)

    Schneemilch, C E; Ludwig, S; Ulrich, A; Halloul, Z; Hachenberg, T

    2007-06-01

    Carotid endarterectomy (CEA) remains the standard procedure for primary and secondary prevention of stroke. Somato-sensory evoked potentials (SEP) are frequently used in carotid endarterectomy under general anaesthesia and recommended for monitoring cerebral functions. The aim of the study was to compare changes in SEP and serum levels of S-100 beta protein and neuron-specific enolase (NSE) with perioperative clinical neurological deficits in patients undergoing regional anaesthesia (RA). After approval of the ethics committee of the Otto-von-Guericke-University, Magdeburg fifty patients undergoing elective CEA under RA were prospectively investigated. RA was performed by combined deep and superficial cervical plexus blockade. SEP was monitored continuously during the surgical procedure. A more of 50 % decrease of potentials (N 20 / P 25 amplitude) compared to potentials before clamping was considered to be significant. Arterial blood samples were collected preoperatively, before declamping and on the first postoperative day to determine serum levels of S-100 beta and NSE. 12 patients developed intraoperatively neurological deficits with carotid clamping. The symptoms were transient and regressed in one minute after shunting. One patient was discharged with persistent hemiparesis. In 8 of 12 patients (66 %) with neurological deficits a more of 50 % decrease of potentials was observed. In one patient with loss of consciousness and hemiparesis changes in SEP or decrease in N 20 / P 25 amplitude were absent. Decrease in amplitude was in patients with intraoperative neurological deficits with 78 % versus 34 % in patients without any deficits significantly reduced (p = 0.01). The sensitivity of monitoring was 67 % at a specificity of 74 %. Serum levels of S-100 beta increased before declamping between patients with and without any neurological deficits significantly (p = 0.02). On the first postoperative day, increased levels of S-100 beta correlated with decrease in

  19. Expression of HIF-1α and Markers of Angiogenesis Are Not Significantly Different in Triple Negative Breast Cancer Compared to Other Breast Cancer Molecular Subtypes: Implications for Future Therapy.

    Directory of Open Access Journals (Sweden)

    Lamis Yehia

    Full Text Available Triple negative breast cancer lacks estrogen, progesterone and epidermal growth factor receptors rendering it refractory to available targetedtherapies. TNBC is associated with central fibrosis and necrosis, both indicators of tumor hypoxia. Hypoxia inducible factor 1α is up-regulated under hypoxia and its expression is associated with induction of angiogenesis resulting in proliferation, aggressive tumor phenotype and metastasis. In this study we evaluate the potential use of HIF-1α as aTNBC-specific marker.62 TNBC, 64 HER2+, and 64 hormone-receptors positive breast cancer cases were evaluated for central fibrosis and necrosis, HIF-1α, HIF-1β, VEGFR3, CD31 expression and microvessel density. RNA extraction from paraffin-embedded samples, followed by quantitative real-time polymerase chain reaction (qRT-PCR evaluation of HIF-1α and VEGF transcripts was performed on 54 cases (18 from each subtype.HIF-1α protein was expressed in 35.5% TNBC, 45.3% HER2+and 25.0% ER+/PR+ (p = 0.055; χ2 test. PCRanalysis of subgroup of breast cancers, 84.2% expressed HIF-1α protein and its transcripts, while only 66.7% expressed VEGF transcripts simultaneously with the HIF-1α protein and its transcripts. Central fibrosis and necrosis was highest in TNBC (p = 0.015; χ2 test, while MVD was comparable among all groups (p = 0.928; χ2 test. VEGFR3 was highest in TNBC expressing HIF-1α. HIF-1β protein was expressed in 32.0% of HIF-1α(+, and in (44.3% of HIF-1α(- breast cancer cases (p = 0.033; χ2 test. Moreover, HIF-1α expression in cases with central fibrosis and necrosis was highest in the HER2+ followed by the TNBC (p = 0.156; χ2 test.A proportion of TNBC express HIF-1α but not in a significantly different manner from other breast cancer subtypes. The potential of anti-HIF-1α targeted therapy is therefore not a candidate for exclusive use in TNBC, but should be considered in all breast cancers, especially in the setting of clinically aggressive or

  20. Expression of HIF-1α and Markers of Angiogenesis Are Not Significantly Different in Triple Negative Breast Cancer Compared to Other Breast Cancer Molecular Subtypes: Implications for Future Therapy.

    Science.gov (United States)

    Yehia, Lamis; Boulos, Fouad; Jabbour, Mark; Mahfoud, Ziyad; Fakhruddin, Najla; El-Sabban, Marwan

    2015-01-01

    Triple negative breast cancer lacks estrogen, progesterone and epidermal growth factor receptors rendering it refractory to available targetedtherapies. TNBC is associated with central fibrosis and necrosis, both indicators of tumor hypoxia. Hypoxia inducible factor 1α is up-regulated under hypoxia and its expression is associated with induction of angiogenesis resulting in proliferation, aggressive tumor phenotype and metastasis. In this study we evaluate the potential use of HIF-1α as aTNBC-specific marker. 62 TNBC, 64 HER2+, and 64 hormone-receptors positive breast cancer cases were evaluated for central fibrosis and necrosis, HIF-1α, HIF-1β, VEGFR3, CD31 expression and microvessel density. RNA extraction from paraffin-embedded samples, followed by quantitative real-time polymerase chain reaction (qRT-PCR) evaluation of HIF-1α and VEGF transcripts was performed on 54 cases (18 from each subtype). HIF-1α protein was expressed in 35.5% TNBC, 45.3% HER2+and 25.0% ER+/PR+ (p = 0.055; χ2 test). PCRanalysis of subgroup of breast cancers, 84.2% expressed HIF-1α protein and its transcripts, while only 66.7% expressed VEGF transcripts simultaneously with the HIF-1α protein and its transcripts. Central fibrosis and necrosis was highest in TNBC (p = 0.015; χ2 test), while MVD was comparable among all groups (p = 0.928; χ2 test). VEGFR3 was highest in TNBC expressing HIF-1α. HIF-1β protein was expressed in 32.0% of HIF-1α(+), and in (44.3%) of HIF-1α(-) breast cancer cases (p = 0.033; χ2 test). Moreover, HIF-1α expression in cases with central fibrosis and necrosis was highest in the HER2+ followed by the TNBC (p = 0.156; χ2 test). A proportion of TNBC express HIF-1α but not in a significantly different manner from other breast cancer subtypes. The potential of anti-HIF-1α targeted therapy is therefore not a candidate for exclusive use in TNBC, but should be considered in all breast cancers, especially in the setting of clinically aggressive or

  1. Phosphorylated neurofilament H (pNF-H) as a potential diagnostic marker for neurological disorders in horses.

    Science.gov (United States)

    Intan-Shameha, A R; Divers, Thomas J; Morrow, Jennifer K; Graves, Amy; Olsen, Emil; Johnson, Amy L; Mohammed, Hussni O

    2017-10-01

    The current study aimed at the investigating the potential use of phosphorylated neurofilament H (pNF-H) as a diagnostic biomarker for neurologic disorders in the horse. Paired serum and cerebrospinal fluid (CSF) samples (n=88) and serum only (n=30) were obtained from horses diagnosed with neurologic disorders and clinically healthy horses as control. The neurologic horses consisted of equine protozoal myeloencephalitis (EPM) (38 cases) and cervical vertebral malformation (CVM) (23 cases). Levels of pNF-H were determined using an ELISA. The correlation between CSF and serum concentrations of pNF-H was evaluated using Spearman's Rank test and the significance of the difference among the groups was assessed using a nonparametric test. Horses had higher pNF-H levels in the CSF than serum. Horses afflicted with EPM had significantly higher serum pNF-H levels in comparison to controls or CVM cases. The correlation between CSF and serum pNF-H levels was poor in both the whole study population and among subgroups of horses included in the study. There was significant association between the likelihood of EPM and the concentrations of pNF-H in either the serum or CSF. These data suggest that pNF-H could be detected in serum and CSF samples from neurologic and control horses. This study demonstrated that pNF-H levels in serum and CSF have the potential to provide objective information to help in the early diagnosis of horses afflicted with neurologic disorders. Published by Elsevier Ltd.

  2. MicroRNA-4639 Is a Regulator of DJ-1 Expression and a Potential Early Diagnostic Marker for Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Yimeng Chen

    2017-07-01

    Full Text Available Parkinson’s disease (PD is the second most common neurodegenerative disorder and has profound impacts on the daily lives of patients. However, there is a lack of effective biomarkers for early diagnosis, and the mechanisms of PD pathogenesis remain obscure. microRNAs (miRNAs are post-transcriptional gene regulators and can be easily detected in plasma, which suggests a promising role as diagnostic markers. Here, we aimed to explore a peripheral biomarker, which not only can be applied for early diagnosis of PD but also has the potential to be a therapeutic target. Through miRNA microarray screening and further validation in plasma from 169 sporadic PD patients, 170 healthy controls, and 60 essential tremor (ET patients, hsa-miR-4639-5p level was identified to be significantly up-regulated in PD patients. Also, it was able to discriminate between early PD patients (disease duration ≤2 years or Hoehn and Yahr stage 1–2.5 and healthy controls. Furthermore, hsa-miR-4639-5p was shown to negatively regulate DJ-1 (PARK7, a well-known PD-related gene, in the post-transcriptional level. Abnormal up-regulation of hsa-miR-4639-5p caused down-regulation of DJ-1 protein level, leading to severe oxidative stress and neuronal death. In conclusion, hsa-miR-4639-5p has the potential to be a peripheral diagnostic biomarker and therapeutic target for early PD.

  3. Aberrant Promoter Methylation of Protocadherin8 (PCDH8) in Serum is a Potential Prognostic Marker for Low Gleason Score Prostate Cancer.

    Science.gov (United States)

    Lin, Ying-Li; Li, Yan-Li; Ma, Jian-Guo

    2017-10-13

    BACKGROUND PCDH8 is a newly-discovered suppressor gene that is frequently inactivated by aberrant methylation in several human cancers, including prostate cancer. The identification of PCDH8 methylation can be used as a potential predictive biomarker. Prostate cancer patients with high Gleason score are considered as being at high risk for tumor recurrence and progression, and adjuvant therapy is often routinely performed in clinical practice. In the present study, we did not measure the methylation of PCDH8 in these patients. The main purpose of the present study was to evaluate the clinical significance of PCDH8 methylation in serum of prostate cancer patients with low Gleason score. MATERIAL AND METHODS PCDH8 methylation in serum samples of 117 patients and 47 controls was checked by methylation-specific PCR (MSP). Then, we correlated PCDH8 methylation status with the clinicopathological parameters of prostate cancer patients with low Gleason score and patient outcomes. RESULTS We found that PCDH8 was more frequently methylated in serum samples of patients with prostate cancer than in controls. PCDH8 methylation was correlated with advanced clinical stage (P=0.021), higher level of preoperative PSA (P=0.008), and positive lymph node metastasis (P=0.010). Moreover, patients with PCDH8 methylation had worse biochemical recurrence (BCR)-free survival (PGleason score were: PCDH8 methylation in serum (Exp (B)=3.147, 95% CI: 1.152-7.961, P=0.007), clinical stage (Exp (B)=2.53, 95% CI: 1.032-4.763, P=0.025) and lymph node status (Exp (B)=1.476, 95% CI: 1.107-4.572, P=0.042). CONCLUSIONS Our study indicated that PCDH8 methylation in serum occurred frequently in prostate cancer patients and was correlated with risk factors for poor outcome. The methylation of PCDH8 in serum is a potential predictive marker for prostate cancer patients with low Gleason score after surgery.

  4. Short-Term High Fat Intake Does Not Significantly Alter Markers of Renal Function or Inflammation in Young Male Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Catherine Crinigan

    2015-01-01

    Full Text Available Chronic high fat feeding is correlated with diabetes and kidney disease. However, the impact of short-term high fat diets (HFD is not well-understood. Six weeks of HFD result in indices of metabolic syndrome (increased adiposity, hyperglycemia, hyperinsulinemia, hyperlipidemia, hyperleptinemia, and impaired endothelium-dependent vasodilation compared to rats fed on standard chow. The hypothesis was that short-term HFD would induce early signs of renal disease. Young male Sprague-Dawley rats were fed either HFD (60% fat or standard chow (5% fat for six weeks. Morphology was determined by measuring changes in renal mass and microstructure. Kidney function was measured by analyzing urinary protein, creatinine, and hydrogen peroxide (H2O2 concentrations, as well as plasma cystatin C concentrations. Renal damage was measured through assessment of urinary oxDNA/RNA concentrations as well as renal lipid peroxidation, tumor necrosis factor alpha (TNFα, and interleukin 6 (IL-6. Despite HFD significantly increasing adiposity and renal mass, there was no evidence of early stage kidney disease as measured by changes in urinary and plasma biomarkers as well as histology. These findings suggest that moderate hyperglycemia and inflammation produced by short-term HFD are not sufficient to damage kidneys or that the ketogenic HFD may have protective effects within the kidneys.

  5. Twelve potential fibrosis markers to differentiate mild liver fibrosis from cirrhosis in patients infected with chronic hepatitis C genotype 1

    DEFF Research Database (Denmark)

    Andersen, E S; Ruhwald, M; Mössner, Belinda Klemmensen

    2011-01-01

    Information about the stage of liver fibrosis is important for managing patients with chronic hepatitis C (CHC). The aim of this study was to evaluate 12 plasma markers for differentiating no/mild liver fibrosis from cirrhosis among patients with CHC genotype 1. Transient elastography was used...... to assess the stage of fibrosis for the patients included in the study. Forty patients were included (21 cirrhotic). Plasma levels of tumor necrosis factor-α (TNF-α), interleukin 8 (IL-8), interferon-γ inducible protein-10 (IP-10), monocyte chemotactic protein-1 (MCP-1), soluble urokinase-type plasminogen....... In conclusion, several of the investigated markers showed promise for differentiating cirrhosis from no/mild fibrosis among patients with CHC genotype 1....

  6. Basal late sodium current is a significant contributor to the duration of action potential of guinea pig ventricular myocytes.

    Science.gov (United States)

    Song, Yejia; Belardinelli, Luiz

    2017-05-01

    In cardiac myocytes, an enhancement of late sodium current ( I N aL ) under pathological conditions is known to cause prolongation of action potential duration (APD). This study investigated the contribution of I N aL under basal, physiological conditions to the APD Whole-cell I N aL and the APD of ventricular myocytes isolated from healthy adult guinea pigs were measured at 36°C. The I N aL inhibitor GS967 or TTX was applied to block I N aL The amplitude of basal I N aL and the APD at 50% repolarization in myocytes stimulated at a frequency of 0.17 Hz were -0.24 ± 0.02 pA/pF and 229 ± 6 msec, respectively. GS967 (0.01-1  μ mol/L) concentration dependently reduced the basal I NaL by 18 ± 3-82 ± 4%. At the same concentrations, GS967 shortened the APD by 9 ± 2 to 25 ± 1%. Similarly, TTX at 0.1-10  μ mol/L decreased the basal I NaL by 13 ± 1-94 ± 1% and APD by 8 ± 1-31 ± 2%. There was a close correlation ( R 2  = 0.958) between the percentage inhibition of I N aL and the percentage shortening of APD caused by either GS967 or TTX MTSEA (methanethiosulfonate ethylammonium, 2 mmol/L), a Na V 1.5 channel blocker, reduced the I NaL by 90 ± 5%, suggesting that the Na V 1.5 channel isoform is the major contributor to the basal I NaL KN-93 (10  μ mol/L) and AIP (2  μ mol/L), blockers of CaMKII, moderately reduced the basal I NaL Thus, this study provides strong evidence that basal endogenous I NaL is a significant contributor to the APD of cardiac myocytes. In addition, the basal I NaL of guinea pig ventricular myocytes is mainly generated from Na V 1.5 channel isoform and is regulated by CaMKII. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  7. Prognostic Significance of Melanoma Differentiation and Trans-Differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Maddodi, Nityanand; Setaluri, Vijayasaradhi, E-mail: setaluri@wisc.edu [Department of Dermatology, University of Wisconsin School of Medicine and Public Health, 1300 University Avenue, B25, Madison WI 53706 (United States)

    2010-05-26

    Cutaneous malignant melanomas share a number of molecular attributes such as limitless replicative potential that define capabilities acquired by most malignancies. Accordingly, much effort has been focused on evaluating and validating protein markers related to these capabilities to function as melanoma prognostic markers. However, a few studies have also highlighted the prognostic value of markers that define melanocytic differentiation and the plasticity of melanoma cells to trans-differentiate along several other cellular pathways. Here, we provide a comprehensive review and evaluation of the prognostic significance of melanocyte-lineage markers such as MITF and melanogenic proteins, as well as markers of vascular epithelial and neuronal differentiation.

  8. Assessment of eosinophil peroxidase as a potential diagnostic and prognostic marker in dogs with inflammatory bowel disease.

    Science.gov (United States)

    Bastan, Idil; Robinson, Nicholas A; Ge, Xiao Na; Rendahl, Aaron K; Rao, Savita P; Washabau, Robert J; Sriramarao, P

    2017-01-01

    OBJECTIVE To evaluate a method for identifying intact and degranulated eosinophils in the small intestine of dogs with inflammatory bowel disease (IBD) by use of a monoclonal antibody (mAb) against eosinophil peroxidase (EPX). ANIMALS 11 untreated dogs with IBD, 5 dogs with IBD treated with prednisolone, and 8 control dogs with no clinical evidence of gastrointestinal tract disease and no immunosuppressive treatment. PROCEDURES 4-μm-thick sections of paraffin-embedded tissues from necropsy specimens were immunostained with EPX mAb. Stained intact and degranulated eosinophils in consecutive microscopic fields (400X magnification) of the upper (villus tips) and lower (between the muscularis mucosae and crypts) regions of the lamina propria of the jejunum were manually counted. RESULTS Compared with control and treated IBD dogs, untreated IBD dogs had a significantly higher number of degranulated eosinophils in the lower region of the lamina propria. However, no significant differences were detected in the number of intact eosinophils in this region among groups. In the upper region of the lamina propria, untreated IBD dogs had a significantly higher number of degranulated and intact eosinophils, compared with control and treated IBD dogs. Number of degranulated and intact eosinophils did not differ significantly between control and treated IBD dogs. CONCLUSIONS AND CLINICAL RELEVANCE Immunohistologic analysis with EPX mAb yielded prominent granule staining that allowed reliable morphological identification of degranulated and intact eosinophils, which may provide a strategy for quantitative and selective evaluation of eosinophils in gastrointestinal biopsy specimens and a potential method to diagnose IBD and evaluate treatment outcome.

  9. Aviation and the environment : aviation's effects on the global atmosphere are potentially significant and expected to grow

    Science.gov (United States)

    2000-02-01

    Concerns about global warming are focusing increasingly on the contribution of human activities, including aviation. Jet aircraft are among many sources of greenhouse gases-gases that can trap heat, potentially increasing the temperature of the earth...

  10. Development of Potential Pharmacodynamic and Diagnostic Markers for Anti-IFN-α Monoclonal Antibody Trials in Systemic Lupus Erythematosus.

    Science.gov (United States)

    Yao, Yihong; Higgs, Brandon W; Morehouse, Chris; de Los Reyes, Melissa; Trigona, Wendy; Brohawn, Philip; White, Wendy; Zhang, Jianliang; White, Barbara; Coyle, Anthony J; Kiener, Peter A; Jallal, Bahija

    2009-11-17

    To identify potential pharmacodynamic biomarkers to guide dose selection in clinical trials using anti-interferon-alpha (IFN-α) monoclonal antibody (mAb) therapy for systemic lupus erythematosus (SLE), we used an Affymetrix human genome array platform and identified 110 IFN-α/β-inducible transcripts significantly upregulated in whole blood (WB) of 41 SLE patients. The overexpression of these genes was confirmed prospectively in 54 additional SLE patients and allowed for the categorization of the SLE patients into groups of high, moderate, and weak overexpressers of IFN-α/β-inducible genes. This approach could potentially allow for an accurate assessment of drug target neutralization in early trials of anti-IFN-α mAb therapy for SLE. Furthermore, ex vivo stimulation of healthy donor peripheral blood mononuclear cells with SLE patient serum and subsequent neutralization with anti-IFN-α mAb or anti-IFN-α receptor mAb showed that anti-IFN-α mAb has comparable effects of neutralizing the overexpression of type I IFN-inducible genes as that of anti-IFNAR mAb. These results suggest that IFN-α, and not other members of type I IFN family in SLE patients, is mainly responsible for the induction of type I IFN-inducible genes in WB of SLE patients. Taken together, these data strengthen the view of IFN-α as a therapeutic target for SLE.

  11. Novel potential predictive markers of sunitinib outcomes in long-term responders versus primary refractory patients with metastatic clear-cell renal cell carcinoma.

    Science.gov (United States)

    Puente, Javier; Laínez, Nuria; Dueñas, Marta; Méndez-Vidal, María José; Esteban, Emilio; Castellano, Daniel; Martinez-Fernández, Mónica; Basterretxea, Laura; Juan-Fita, María José; Antón, Luis; León, Luis; Lambea, Julio; Pérez-Valderrama, Begoña; Vázquez, Sergio; Suarez, Cristina; Del Muro, Xavier Garcia; Gallardo, Enrique; Maroto, José Pablo; Samaniego, M Luz; Suárez-Paniagua, Beatriz; Sanz, Julián; Paramio, Jesús M

    2017-05-02

    Several potential predictive markers of efficacy of targeted agents in patients with metastatic renal cell carcinoma (mRCC) have been identified. Interindividual heterogeneity warrants further investigation. Multicenter, observational, retrospective study in patients with clear-cell mRCC treated with sunitinib. Patients were classified in two groups: long-term responders (LR) (progression-free survival (PFS)≥22 months and at least stable disease), and primary refractory (PR) (progressive disease within 3-months of sunitinib onset). Objectives were to compare baseline clinical factors in both populations and to correlate tumor expression of selected signaling pathways components with sunitinib PFS. 123 patients were analyzed (97 LR, 26 PR). In the LR cohort, overall response rate was 79% and median duration of best response was 30 months. Median PFS and overall survival were 43.2 (95% confidence intervals[CI]:37.2-49.3) and 63.5 months (95%CI:55.1-71.9), respectively. At baseline PR patients had a significantly lower proportion of nephrectomies, higher lactate dehydrogenase and platelets levels, lower hemoglobin, shorter time to and higher presence of metastases, and increased Fuhrman grade. Higher levels of HEYL, HEY and HES1 were observed in LR, although only HEYL discriminated populations significantly (AUC[ROC]=0.704; cut-off=34.85). Increased levels of hsa-miR-27b, hsa-miR-23b and hsa-miR-628-5p were also associated with prolonged survival. No statistical significant associations between hsa-miR-23b or hsa-miR-27b and the expression of c-Met were found. Certain mRCC patients treated with sunitinib achieve extremely long-term responses. Favorable baseline hematology values and longer time to metastasis may predict longer PFS. HEYL, hsa-miR-27b, hsa-miR-23b and hsa-miR-628-5p could be potentially used as biomarkers of sunitinib response.

  12. Bioinformatics analysis for evaluation of the diagnostic potentialities of miR-19b, -125b and -205 as liquid biopsy markers of prostate cancer

    Science.gov (United States)

    Bryzgunova, O. E.; Lekchnov, E. A.; Zaripov, M. M.; Yurchenko, Yu. B.; Yarmoschuk, S. V.; Pashkovskaya, O. A.; Rykova, E. Yu.; Zheravin, A. A.; Laktionov, P. P.

    2017-09-01

    Presence of tumor-derived cell-free miRNA in biological fluids as well as simplicity and robustness of cell-free miRNA quantification makes them suitable markers for cancer diagnostics. Based on previously published data demonstrating diagnostic potentialities of miR-205 in blood and miR-19b as well as miR-125b in urine of prostate cancer patients, bioinformatics analysis was carried out to follow their involvement in prostate cancer development and select additional miRNA-markers for prostate cancer diagnostics. Studied miRNAs are involved in different signaling pathways and regulate a number of genes involved in cancer development. Five of their targets (CCND1, BRAF, CCNE1, CCNE2, RAF1), according to the STRING database, act as part of the same signaling pathway. RAF1 is regulated by miR-19b and miR-125b, and it was shown to be involved in prostate cancer development by DIANA and STRING databases. Thus, other microRNAs regulating RAF1 expression such as miR-16, -195, -497, and -7 (suggested by DIANA, TargetScan, MiRTarBase and miRDB databases) can potentially be regarded as prostate cancer markers.

  13. Candidate SNP markers of aggressiveness-related complications and comorbidities of genetic diseases are predicted by a significant change in the affinity of TATA-binding protein for human gene promoters.

    Science.gov (United States)

    Chadaeva, Irina V; Ponomarenko, Mikhail P; Rasskazov, Dmitry A; Sharypova, Ekaterina B; Kashina, Elena V; Matveeva, Marina Yu; Arshinova, Tatjana V; Ponomarenko, Petr M; Arkova, Olga V; Bondar, Natalia P; Savinkova, Ludmila K; Kolchanov, Nikolay A

    2016-12-28

    Aggressiveness in humans is a hereditary behavioral trait that mobilizes all systems of the body-first of all, the nervous and endocrine systems, and then the respiratory, vascular, muscular, and others-e.g., for the defense of oneself, children, family, shelter, territory, and other possessions as well as personal interests. The level of aggressiveness of a person determines many other characteristics of quality of life and lifespan, acting as a stress factor. Aggressive behavior depends on many parameters such as age, gender, diseases and treatment, diet, and environmental conditions. Among them, genetic factors are believed to be the main parameters that are well-studied at the factual level, but in actuality, genome-wide studies of aggressive behavior appeared relatively recently. One of the biggest projects of the modern science-1000 Genomes-involves identification of single nucleotide polymorphisms (SNPs), i.e., differences of individual genomes from the reference genome. SNPs can be associated with hereditary diseases, their complications, comorbidities, and responses to stress or a drug. Clinical comparisons between cohorts of patients and healthy volunteers (as a control) allow for identifying SNPs whose allele frequencies significantly separate them from one another as markers of the above conditions. Computer-based preliminary analysis of millions of SNPs detected by the 1000 Genomes project can accelerate clinical search for SNP markers due to preliminary whole-genome search for the most meaningful candidate SNP markers and discarding of neutral and poorly substantiated SNPs. Here, we combine two computer-based search methods for SNPs (that alter gene expression) {i} Web service SNP_TATA_Comparator (DNA sequence analysis) and {ii} PubMed-based manual search for articles on aggressiveness using heuristic keywords. Near the known binding sites for TATA-binding protein (TBP) in human gene promoters, we found aggressiveness-related candidate SNP markers

  14. Castration attenuates myelin repair following lysolecithin induced demyelination in rat optic chiasm: an evaluation using visual evoked potential, marker genes expression and myelin staining.

    Science.gov (United States)

    Sherafat, Mohammad Amin; Javan, Mohammad; Mozafari, Sabah; Mirnajafi-Zadeh, Javad; Motamedi, Fereshteh

    2011-10-01

    Multiple sclerosis (MS) is a demyelinating disease that affects the central nervous system. MS is the most common neurological disorder in young adults with a greater incidence among females. Male gonadal hormones have a protective effect on neural system development and myelin maturation. In this study, we investigate the effect of castration on lysolecithin-induced demyelination and remyelination processes using visual evoked potentials, in addition to measuring the expressions of Olig2, MBP, Nogo-A and GFAP mRNAs as oligodendrocyte or astrocyte markers; and histological assessments by myelin-specific staining. We observed more expanded demyelination with delayed repair process in castrated rats. Expression levels of the aforementioned marker genes confirmed histological and electrophysiological observations. Our results showed a pivotal role for endogenous male hormones in the context of demyelinating insults. It may also account for the different prognosis of MS between male and female genders and provide new insights for therapeutic treatments.

  15. Gene expression changes in phosphorus deficient potato (Solanum tuberosum L. leaves and the potential for diagnostic gene expression markers.

    Directory of Open Access Journals (Sweden)

    John P Hammond

    Full Text Available BACKGROUND: There are compelling economic and environmental reasons to reduce our reliance on inorganic phosphate (Pi fertilisers. Better management of Pi fertiliser applications is one option to improve the efficiency of Pi fertiliser use, whilst maintaining crop yields. Application rates of Pi fertilisers are traditionally determined from analyses of soil or plant tissues. Alternatively, diagnostic genes with altered expression under Pi limiting conditions that suggest a physiological requirement for Pi fertilisation, could be used to manage Pifertiliser applications, and might be more precise than indirect measurements of soil or tissue samples. RESULTS: We grew potato (Solanum tuberosum L. plants hydroponically, under glasshouse conditions, to control their nutrient status accurately. Samples of total leaf RNA taken periodically after Pi was removed from the nutrient solution were labelled and hybridised to potato oligonucleotide arrays. A total of 1,659 genes were significantly differentially expressed following Pi withdrawal. These included genes that encode proteins involved in lipid, protein, and carbohydrate metabolism, characteristic of Pi deficient leaves and included potential novel roles for genes encoding patatin like proteins in potatoes. The array data were analysed using a support vector machine algorithm to identify groups of genes that could predict the Pi status of the crop. These groups of diagnostic genes were tested using field grown potatoes that had either been fertilised or unfertilised. A group of 200 genes could correctly predict the Pi status of field grown potatoes. CONCLUSIONS: This paper provides a proof-of-concept demonstration for using microarrays and class prediction tools to predict the Pi status of a field grown potato crop. There is potential to develop this technology for other biotic and abiotic stresses in field grown crops. Ultimately, a better understanding of crop stresses may improve our management

  16. Soluble adhesion molecules as markers for sepsis and the potential pathophysiological discrepancy in neonates, children and adults

    Science.gov (United States)

    2014-01-01

    Sepsis is a severe and life-threatening systemic inflammatory response to infection that affects all populations and age groups. The pathophysiology of sepsis is associated with aberrant interaction between leukocytes and the vascular endothelium. As inflammation progresses, the adhesion molecules that mediate these interactions become shed from cell surfaces and accumulate in the blood as soluble isoforms that are being explored as potential prognostic disease biomarkers. We critically review the studies that have tested the predictive value of soluble adhesion molecules in sepsis pathophysiology with emphasis on age, as well as the underlying mechanisms and potential roles for inflammatory shedding. Five soluble adhesion molecules are associated with sepsis, specifically, E-selectin, L-selectin and P-selectin, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. While increased levels of these soluble adhesion molecules generally correlate well with the presence of sepsis, their degree of elevation is still poorly predictive of sepsis severity scores, outcome and mortality. Separate analyses of neonates, children and adults demonstrate significant age-dependent discrepancies in both basal and septic levels of circulating soluble adhesion molecules. Additionally, a range of both clinical and experimental studies suggests protective roles for adhesion molecule shedding that raise important questions about whether these should positively or negatively correlate with mortality. In conclusion, while predictive properties of soluble adhesion molecules have been researched intensively, their levels are still poorly predictive of sepsis outcome and mortality. We propose two novel directions for improving clinical utility of soluble adhesion molecules: the combined simultaneous analysis of levels of adhesion molecules and their sheddases; and taking age-related discrepancies into account. Further attention to these issues may provide better

  17. Potential of Start Codon Targeted (SCoT Markers to Estimate Genetic Diversity and Relationships among Chinese Elymus sibiricus Accessions

    Directory of Open Access Journals (Sweden)

    Junchao Zhang

    2015-04-01

    Full Text Available Elymus sibiricus as an important forage grass and gene pool for improving cereal crops, that is widely distributed in West and North China. Information on its genetic diversity and relationships is limited but necessary for germplasm collection, conservation and future breeding. Start Codon Targeted (SCoT markers were used for studying the genetic diversity and relationships among 53 E. sibiricus accessions from its primary distribution area in China. A total of 173 bands were generated from 16 SCoT primers, 159 bands of which were polymorphic with the percentage of polymorphic bands (PPB of 91.91%. Based upon population structure analysis five groups were formed. The cluster analysis separated the accessions into two major clusters and three sub-clusters, similar to results of principal coordinate analysis (PCoA. The molecular variance analysis (AMOVA showed that genetic variation was greater within geographical regions (50.99% than between them (49.01%. Furthermore, the study also suggested that collecting and evaluating E. sibiricus germplasm for major geographic regions and special environments broadens the available genetic base and illustrates the range of variation. The results of the present study showed that SCoT markers were efficient in assessing the genetic diversity among E. sibiricus accessions.

  18. The development and mapping of functional markers in Fragaria and their transferability and potential for mapping in other genera.

    Science.gov (United States)

    Sargent, D J; Rys, A; Nier, S; Simpson, D W; Tobutt, K R

    2007-01-01

    We have developed 46 primer pairs from exon sequences flanking polymorphic introns of 23 Fragaria gene sequences and one Malus sequence deposited in the EMBL database. Sequencing of a set of the PCR products amplified with the novel primer pairs in diploid Fragaria showed the products to be homologous to the sequences from which the primers were originally designed. By scoring the segregation of the 24 genes in two diploid Fragaria progenies FV x FN (F. vesca x F. nubicola F(2)) and 815 x 903BC (F. vesca x F. viridis BC(1)) 29 genetic loci at discrete positions on the seven linkage groups previously characterised could be mapped, bringing to 35 the total number of known function genes mapped in Fragaria. Twenty primer pairs, representing 14 genes, amplified a product of the expected size in both Malus and Prunus. To demonstrate the applicability of these gene-specific loci to comparative mapping in Rosaceae, five markers that displayed clear polymorphism between the parents of a Malus and a Prunus mapping population were selected. The markers were then scored and mapped in at least one of the two additional progenies.

  19. Prolactin-induced protein as a potential therapy response marker of adjuvant chemotherapy in breast cancer patients

    Science.gov (United States)

    Jablonska, Karolina; Grzegrzolka, Jedrzej; Podhorska-Okolow, Marzenna; Stasiolek, Mariusz; Pula, Bartosz; Olbromski, Mateusz; Gomulkiewicz, Agnieszka; Piotrowska, Aleksandra; Rys, Janusz; Ambicka, Aleksandra; Ong, Siew Hwa; Zabel, Maciej; Dziegiel, Piotr

    2016-01-01

    Many studies are dedicated to exploring the molecular mechanisms of chemotherapy-resistance in breast cancer (BC). Some of them are focused on searching for candidate genes responsible for this process. The aim of this study was typing the candidate genes associated with the response to standard chemotherapy in the case of invasive ductal carcinoma. Frozen material from 28 biopsies obtained from IDC patients with different responses to chemotherapy were examined using gene expression microarray, Real-Time PCR (RT-PCR) and Western blot (WB). Based on the microarray results, further analysis of candidate gene expression was evaluated in 120 IDC cases by RT-PCR and in 224 IDC cases by immunohistochemistry (IHC). The results were correlated with clinical outcome and molecular subtype of the BC. Gene expression microarray revealed Prolactin-Induced Peptide (PIP) as a single gene differentially expressed in BC therapy responder or non-responder patients (p G1, G2 vs. G3 cases (p=0.0027 and p=0.0013, respectively). Microarray analysis characterized PIP gene as a candidate for BC standard chemotherapy response marker. Analysis of clinical data suggests that PIP may be a good prognostic and predictive marker in IDC patients. Higher levels of PIP were related to longer DFS and MFS but not with OS. PMID:27293986

  20. Visual event-related potentials as markers of hyperarousal in Gulf War Illness: evidence against a stress-related etiology

    Science.gov (United States)

    Tillman, Gail D.; Calley, Clifford S.; Green, Timothy A.; Buhl, Virginia I.; Biggs, Melanie M.; Spence, Jeffrey S.; Briggs, Richard W.; Haley, Robert W.; Kraut, Michael A.; Hart, John

    2012-01-01

    An exaggerated response to emotional stimuli is among the many symptoms widely reported by veterans of the 1991 Persian Gulf War. These symptomologies have been attributed to damage and dysfunction associated with deployment-related exposures. We collected event-related potential data from 22 veterans meeting Haley criteria for Gulf War (GW) Syndromes 1-3 and from 8 matched GW veteran controls, who were deployed but not symptomatic, while they performed a visual three-condition oddball task where images authenticated to be associated with the 1991 Persian Gulf War were the distractor stimuli. Hyperarousal reported by ill veterans was significantly greater than that by control veterans, but this was not paralleled by higher amplitude P3a in their ERP responses to GW-related distractor stimuli. Whereas previous studies of PTSD patients have shown higher amplitude P3b responses to target stimuli that are placed amid trauma-related nontarget stimuli, ill veterans in this study showed P3b amplitudes to target stimuli—placed amid GW-related nontarget stimuli—that were significantly lower than those of the control group. Hyperarousal scores reliably predicted P3b, but not P3a, amplitudes. Although many factors may contribute to P3b amplitude differences—most notably depression and poor sleep quality, symptoms that are prevalent in the GW syndrome groups—our findings in context of previous studies on this population are consistent with the contention that dysfunction in cholinergic and dopaminergic neurotransmitter systems, and in white matter and basal ganglia may be contributing to impairments in GW veterans. PMID:23149040

  1. The pain threshold of high-threshold mechanosensitive receptors subsequent to maximal eccentric exercise is a potential marker in the prediction of DOMS associated impairment

    Science.gov (United States)

    Simon, Perikles; König, Matthias; Vogt, Lutz; Banzer, Winfried

    2017-01-01

    Background Delayed-onset muscle soreness (DOMS) refers to dull pain and discomfort in people after participating in exercise, sport or recreational physical activities. The aim of this study was to detect underlying mechanical thresholds in an experimental model of DOMS. Methods Randomised study to detect mechanical pain thresholds in a randomised order following experimentally induced DOMS of the non-dominant arm in healthy participants. Main outcome was the detection of the pressure pain threshold (PPT), secondary thresholds included mechanical detection (MDT) and pain thresholds (MPT), pain intensity, pain perceptions and the maximum isometric voluntary force (MIVF). Results Twenty volunteers (9 female and 11 male, age 25.2 ± 3.2 years, weight 70.5 ± 10.8 kg, height 177.4 ± 9.4 cm) participated in the study. DOMS reduced the PPT (at baseline 5.9 ± 0.4 kg/cm2) by a maximum of 1.5 ± 1.4 kg/cm2 (-24%) at 48 hours (p < 0.001). This correlated with the decrease in MIVF (r = -0.48, p = 0.033). Whereas subjective pain was an indicator of the early 48 hours, the PPT was still present after 72 hours (r = 0.48, p = 0.036). Other mechanical thresholds altered significantly due to DOMS, but did show no clinically or physiologically remarkable changes. Conclusions Functional impairment following DOMS seems related to the increased excitability of high-threshold mechanosensitive nociceptors. The PPT was the most valid mechanical threshold to quantify the extent of dysfunction. Thus PPT rather than pain intensity should be considered a possible marker indicating the athletes’ potential risk of injury. PMID:28985238

  2. The pain threshold of high-threshold mechanosensitive receptors subsequent to maximal eccentric exercise is a potential marker in the prediction of DOMS associated impairment.

    Directory of Open Access Journals (Sweden)

    Johannes Fleckenstein

    Full Text Available Delayed-onset muscle soreness (DOMS refers to dull pain and discomfort in people after participating in exercise, sport or recreational physical activities. The aim of this study was to detect underlying mechanical thresholds in an experimental model of DOMS.Randomised study to detect mechanical pain thresholds in a randomised order following experimentally induced DOMS of the non-dominant arm in healthy participants. Main outcome was the detection of the pressure pain threshold (PPT, secondary thresholds included mechanical detection (MDT and pain thresholds (MPT, pain intensity, pain perceptions and the maximum isometric voluntary force (MIVF.Twenty volunteers (9 female and 11 male, age 25.2 ± 3.2 years, weight 70.5 ± 10.8 kg, height 177.4 ± 9.4 cm participated in the study. DOMS reduced the PPT (at baseline 5.9 ± 0.4 kg/cm2 by a maximum of 1.5 ± 1.4 kg/cm2 (-24% at 48 hours (p < 0.001. This correlated with the decrease in MIVF (r = -0.48, p = 0.033. Whereas subjective pain was an indicator of the early 48 hours, the PPT was still present after 72 hours (r = 0.48, p = 0.036. Other mechanical thresholds altered significantly due to DOMS, but did show no clinically or physiologically remarkable changes.Functional impairment following DOMS seems related to the increased excitability of high-threshold mechanosensitive nociceptors. The PPT was the most valid mechanical threshold to quantify the extent of dysfunction. Thus PPT rather than pain intensity should be considered a possible marker indicating the athletes' potential risk of injury.

  3. Potential markers of aggressive behavior: the fear of other persons' laughter and its overlaps with mental disorders.

    Directory of Open Access Journals (Sweden)

    Elisabeth M Weiss

    Full Text Available BACKGROUND: Anecdotal evidence suggested that some outbreaks of aggression and violence may be related to a fear of being laughed at and ridiculed. The present study examined the potential association of the fear of other persons' laughter (gelotophobia with emotion-related deficits predisposing for aggression, anger and aggression proneness, and its overlaps with relevant mental disorders. METHODOLOGY/PRINCIPAL FINDINGS: Gelotophobic individuals were compared to a non-phobic control group with respect to emotion regulation skills and strategies, alexithymia, anger proneness, and aggressive behavior. Social phobia was diagnosed using the Structural Clinical Interview (SCID-I for DSM IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Additionally, the SCID-II modules for Cluster A Personality Disorders, which includes schizoid, paranoid, and schizotypal personality disorder were administered to all participants. The findings show that gelotophobia is associated with deficits in the typical handling of an individual's own affective states, greater anger proneness and more aggressive behavior according to self-report as compared to non-phobic individuals. 80% of the subjects in the gelotophobia group had an additional diagnosis of social phobia and/or Cluster A personality disorder. The additional diagnoses did not predict additional variance of anger or aggressive behavior as compared to gelotophobia alone. CONCLUSIONS/SIGNIFICANCE: Features related to aggression and violence that are inherent in mental disorders such as social phobia and Cluster A personality disorders may be particularly evident in the symptom of fear of other persons' laughter.

  4. Glycogen phosphorylase BB as a potential marker of cardiac toxicity in patients treated with anthracyclines for acute leukemia.

    Science.gov (United States)

    Horacek, J M; Jebavy, L; Vasatova, M; Pudil, R; Tichy, M; Jakl, M; Maly, J

    2013-01-01

    The aim of the presented study was to assess plasma glycogen phosphorylase BB (GPBB) concentrations in acute leukemia patients treated with anthracycline containing chemotherapy. Anthracyclines represent the highest risk for development of cardiotoxicity. GPBB belongs to proposed biomarkers of cardiac injury with a very limited experience in this context. Totally, 24 adult patients with acute leukemia were enrolled. Plasma GPBB concentrations were measured by ELISA at diagnosis (before chemotherapy), after first chemotherapy with anthracyclines and 6 months after the completion of treatment. The cut-off value for GPBB positivity was 10.00 µg/L as recommended by the manufacturer. Before chemotherapy, the mean plasma GPBB concentration was 5.25±3.81 µg/L, increased above the cut-off in 1 patient (4.2 %). After the first chemotherapy, the mean GPBB was 6.61±5.54 µg/L, positive in 7 (29.2 %) patients. Six months after treatment, the mean GPBB was 10.06±11.41 µg/L, positive in 8 (33.3 %) patients. Six months after treatment, we found a significant correlation between elevation in GPBB and diastolic left ventricular dysfunction on echocardiography (r=0.621; pfuture is not clear and will be evaluated during the follow-up. Further studies are needed to define the potential role of GPBB and other biomarkers in the assessment of chemotherapy-induced cardiotoxicity (Ref. 21). Text in PDF www.elis.sk.

  5. Antiphosphatidylserine/prothrombin antibodies (aPS/PT) as potential diagnostic markers and risk predictors of venous thrombosis and obstetric complications in antiphospholipid syndrome.

    Science.gov (United States)

    Shi, Hui; Zheng, Hui; Yin, Yu-Feng; Hu, Qiong-Yi; Teng, Jia-Lin; Sun, Yue; Liu, Hong-Lei; Cheng, Xiao-Bing; Ye, Jun-Na; Su, Yu-Tong; Wu, Xin-Yao; Zhou, Jin-Feng; Norman, Gary L; Gong, Hui-Yun; Shi, Xin-Ming; Peng, Yi-Bing; Wang, Xue-Feng; Yang, Cheng-De

    2017-11-22

    The aim of the study was to determine the prevalence and clinical associations of antiphosphatidylserine/prothrombin antibodies (aPS/PT) with thrombosis and pregnancy loss in Chinese patients with antiphospholipid syndrome (APS) and seronegative APS (SNAPS). One hundred and eighty six Chinese patients with APS (67 primary, 119 secondary), 48 with SNAPS, 176 disease controls (79 systemic lupus erythematosus [SLE], 29 Sjogren's syndrome [SS], 30 ankylosing spondylitis [AS], 38 rheumatoid arthritis [RA]) and 90 healthy donors were examined. IgG and IgM aPS/PT, IgG/IgM/IgA anticardiolipin (aCL) and IgG/IgM/IgA anti-β2-glycoprotein I (anti-β2GPI) antibodies were tested by ELISA. One hundred and sixty (86.0%) of APS patients were positive for at least one aPS/PT isotype. One hundred and thirty five (72.6%) were positive for IgG aPS/PT, 124/186 (66.7%) positive for IgM aPS/PT and 99 (53.2%) positive for both. Approximately half of the SNAPS patients were positive for IgG and/or IgM aPS/PT. Highly significant associations between IgG aPS/PT and venous thrombotic events (odds ratio [OR]=6.72) and IgG/IgM aPS/PT and pregnancy loss (OR=9.44) were found. Levels of IgM aPS/PT were significantly different in APS patients with thrombotic manifestations and those with fetal loss (p=0.014). The association between IgG/IgM aPS/PT and lupus anticoagulant (LAC) was highly significant (pLAC-positive specimens were positive for IgG and/or IgM aPS/PT, suggesting aPS/PT is an effective option when LAC testing is not available. Anti-PS/PT antibody assays demonstrated high diagnostic performance for Chinese patients with APS, detected some APS patients negative for criteria markers and may serve as potential risk predictors for venous thrombosis and obstetric complications.

  6. Clinical and virological factors influencing the performance of a NS1 antigen-capture assay and potential use as a marker of dengue disease severity.

    Directory of Open Access Journals (Sweden)

    Veasna Duong

    2011-07-01

    Full Text Available BACKGROUND: Detection of dengue NS1 antigen in acute infection has been proposed for early diagnosis of dengue disease. The aim of this study was to evaluate the clinical and virological factors influencing the performance of the Platelia NS1 Ag kit (BioRad and to assess the potential use of NS1 antigen and dengue viral loads as markers of dengue disease severity. METHODOLOGY/PRINCIPAL FINDINGS: Blood specimens were collected from patients hospitalized at the Kampong Cham hospital during the 2006 and 2007 dengue epidemics in Cambodia. Dengue infection was confirmed in 243/339 symptomatic patients and in 17 asymptomatic individuals out of 214 household members tested. Overall sensitivity and specificity of Platelia NS1 Ag kit were 57.5% and 100% respectively. NS1 Ag assay combined with IgM antibody capture ELISA significantly increased the sensitivity for dengue diagnosis. NS1 Ag positivity rate was found significantly higher in DF than in DHF/DSS, in primary than in secondary infections, in patients with a high viremia (>5 log/mL and in patients infected with DENV-1. In asymptomatic individuals, the NS1 Ag capture sensitivity tends to be lower than that in symptomatic patients. Milder disease severity was observed independently in patients with RNA copy number >5 log10 cDNA equivalents/mL or in high level of NS1 antigen ratio or in DENV-1 infection. CONCLUSIONS: Overall sensitivity of NS1 Ag detection kit varied widely across the various forms of dengue infection or disease. Sensitivity was highest in patients sampled during the first 3 days after onset of fever, in patients with primary infection, DENV-1 infection, with high level of viremia and in DF rather than DHF/DSS. In asymptomatic patients, RT-PCR assay has proved to be more sensitive than NS1 antigen detection. The NS1 antigen level correlated significantly with viremia and a low NS1 antigen ratio was associated with more severe disease.

  7. Identification by a differential proteomic approach of heat shock protein 27 as a potential marker of atherosclerosis

    DEFF Research Database (Denmark)

    Martin-Ventura, Jose Luis; Duran, Mari Carmen; Blanco-Colio, Luis Miguel

    2004-01-01

    BACKGROUND: We hypothesized that normal and pathological vessel walls display a differential pattern of secreted proteins. We have recently set up the conditions for comparing secretomes from carotid atherosclerotic plaques and control arteries using a proteomic approach to assess whether...... differentially secreted proteins could represent markers for atherosclerosis. METHODS AND RESULTS: Normal endartery segments and different regions of endarterectomy pieces (noncomplicated/complicated plaques) were incubated in protein-free medium, and the released proteins were analyzed by 2D electrophoresis (2......-DE). Among the differently secreted proteins, we have identified heat shock protein-27 (HSP27). Surprisingly, compared with control arteries, HSP27 release was drastically decreased in atherosclerotic plaques and barely detectable in complicated plaque supernatants. HSP27 was expressed primarily...

  8. DNA barcoding in the cycadales: testing the potential of proposed barcoding markers for species identification of cycads.

    Science.gov (United States)

    Sass, Chodon; Little, Damon P; Stevenson, Dennis Wm; Specht, Chelsea D

    2007-11-07

    Barcodes are short segments of DNA that can be used to uniquely identify an unknown specimen to species, particularly when diagnostic morphological features are absent. These sequences could offer a new forensic tool in plant and animal conservation-especially for endangered species such as members of the Cycadales. Ideally, barcodes could be used to positively identify illegally obtained material even in cases where diagnostic features have been purposefully removed or to release confiscated organisms into the proper breeding population. In order to be useful, a DNA barcode sequence must not only easily PCR amplify with universal or near-universal reaction conditions and primers, but also contain enough variation to generate unique identifiers at either the species or population levels. Chloroplast regions suggested by the Plant Working Group of the Consortium for the Barcode of Life (CBoL), and two alternatives, the chloroplast psbA-trnH intergenic spacer and the nuclear ribosomal internal transcribed spacer (nrITS), were tested for their utility in generating unique identifiers for members of the Cycadales. Ease of amplification and sequence generation with universal primers and reaction conditions was determined for each of the seven proposed markers. While none of the proposed markers provided unique identifiers for all species tested, nrITS showed the most promise in terms of variability, although sequencing difficulties remain a drawback. We suggest a workflow for DNA barcoding, including database generation and management, which will ultimately be necessary if we are to succeed in establishing a universal DNA barcode for plants.

  9. Biochemical and proteomic analyses of the physiological response induced by individual housing in gilts provide new potential stress markers.

    Science.gov (United States)

    Marco-Ramell, Anna; Arroyo, Laura; Peña, Raquel; Pato, Raquel; Saco, Yolanda; Fraile, Lorenzo; Bendixen, Emøke; Bassols, Anna

    2016-11-25

    The objective assessment of animal stress and welfare requires proper laboratory biomarkers. In this work, we have analyzed the changes in serum composition in gilts after switching their housing, from pen to individual stalls, which is generally accepted to cause animal discomfort. Blood and saliva samples were collected a day before and up to four days after changing the housing system. Biochemical analyses showed adaptive changes in lipid and protein metabolism after the housing switch, whereas cortisol and muscular markers showed a large variability between animals. 2D-DIGE and iTRAQ proteomic approaches revealed variations in serum protein composition after changing housing and diet of gilts. Both techniques showed alterations in two main homeostatic mechanisms: the innate immune and redox systems. The acute phase proteins haptoglobin, apolipoprotein A-I and α1-antichymotrypsin 3, and the antioxidant enzyme peroxiredoxin 2 were found differentially expressed by 2D-DIGE. Other proteins related to the innate immune system, including lactotransferrin, protegrin 3 and galectin 1 were also identified by iTRAQ, as well as oxidative stress enzymes such as peroxiredoxin 2 and glutathione peroxidase 3. Proteomics also revealed the decrease of apolipoproteins, and the presence of intracellular proteins in serum, which may indicate physical injury to tissues. Housing of gilts in individual stalls and diet change increase lipid and protein catabolism, oxidative stress, activate the innate immune system and cause a certain degree of tissue damage. We propose that valuable assays for stress assessment in gilts may be based on a score composed by a combination of salivary cortisol, lipid metabolites, innate immunity and oxidative stress markers and intracellular proteins.

  10. DNA barcoding in the cycadales: testing the potential of proposed barcoding markers for species identification of cycads.

    Directory of Open Access Journals (Sweden)

    Chodon Sass

    Full Text Available Barcodes are short segments of DNA that can be used to uniquely identify an unknown specimen to species, particularly when diagnostic morphological features are absent. These sequences could offer a new forensic tool in plant and animal conservation-especially for endangered species such as members of the Cycadales. Ideally, barcodes could be used to positively identify illegally obtained material even in cases where diagnostic features have been purposefully removed or to release confiscated organisms into the proper breeding population. In order to be useful, a DNA barcode sequence must not only easily PCR amplify with universal or near-universal reaction conditions and primers, but also contain enough variation to generate unique identifiers at either the species or population levels. Chloroplast regions suggested by the Plant Working Group of the Consortium for the Barcode of Life (CBoL, and two alternatives, the chloroplast psbA-trnH intergenic spacer and the nuclear ribosomal internal transcribed spacer (nrITS, were tested for their utility in generating unique identifiers for members of the Cycadales. Ease of amplification and sequence generation with universal primers and reaction conditions was determined for each of the seven proposed markers. While none of the proposed markers provided unique identifiers for all species tested, nrITS showed the most promise in terms of variability, although sequencing difficulties remain a drawback. We suggest a workflow for DNA barcoding, including database generation and management, which will ultimately be necessary if we are to succeed in establishing a universal DNA barcode for plants.

  11. Genetic Variability and Population Structure of the Potential Bioenergy Crop Miscanthus sinensis (Poaceae in Southwest China Based on SRAP Markers

    Directory of Open Access Journals (Sweden)

    Gang Nie

    2014-08-01

    Full Text Available The genus Miscanthus has great potential as a biofuel feedstock because of its high biomass, good burning quality, environmental tolerance, and good adaptability to marginal land. In this study, the genetic diversity and the relationship of 24 different natural Miscanthus sinensis populations collected from Southwestern China were analyzed by using 33 pairs of Sequence Related Amplified Polymorphism (SRAP primers. A total of 688 bands were detected with 646 polymorphic bands, an average of 19.58 polymorphic bands per primer pair. The average percentage of polymorphic loci (P, gene diversity (H, and Shannon’s diversity index (I among the 24 populations are 70.59%, 0.2589, and 0.3836, respectively. The mean value of total gene diversity (HT was 0.3373 ± 0.0221, while the allelic diversity within populations (HS was 0.2589 ± 0.0136 and the allelic diversity among populations (DST was 0.0784. The mean genetic differentiation coefficient (Gst = 0.2326 estimated from the detected 688 loci indicated that there was 76.74% genetic differentiation within the populations, which is consistent with the results from Analysis of Molecular Variance (AMOVA analysis. Based upon population structure and phylogenetic analysis, five groups were formed and a special population with mixed ancestry was inferred indicating that human-mediated dispersal may have had a significant effect on population structure of M. sinensis. Evaluating the genetic structure and genetic diversity at morphological and molecular levels of the wild M. sinensis in Southwest China is critical to further utilize the wild M. sinensis germplasm in the breeding program. The results in this study will facilitate the biofuel feedstock breeding program and germplasm conservation.

  12. Presence of CTX gene cluster in environmental non-O1/O139 Vibrio cholerae and its potential clinical significance

    Directory of Open Access Journals (Sweden)

    B Bakhshi

    2012-01-01

    Full Text Available Purpose: The aim of this study was to understand the epidemiological linkage of clinical and environmental isolates of Vibrio cholerae and to determine their genotypes and virulence genes content. Materials and Methods: A total of 60 V. cholerae strains obtained from clinical specimens (n = 40 and surface waters (n = 20 were subjected to genotyping using PFGE and determination of their virulence-associated gene clusters. Result: PCR analysis showed the presence of chromosomally located hly and RTX genetic elements in 100% and 90% of the environmental isolates, respectively. The phage-mediated genetic elements such as CTX, TLC and VPI were detected in 5% of the environmental isolates suggesting that the environmental isolates cannot acquire certain mobile gene clusters. A total of 4 and 18 pulsotypes were obtained among the clinical and environmental V. cholerae isolates, respectively. Non-pathogenic environmentally isolated V. cholerae constituted a distinct cluster with one single non-O1, non-O139 strain (EP6 carrying the virulence genes similar to the epidemic strains. This may suggest the possible potential of conversion of non-pathogenic to a pathogenic environmental strain. Conclusions: The emergence of a single environmental isolate in our study containing the pathogenicity genes amongst the diverse non-pathogenic environmental isolates needs to be further studied in the context of V. cholerae pathogenicity sero-coversion.

  13. The Madeira Archipelago As a Significant Source of Marine-Derived Actinomycete Diversity with Anticancer and Antimicrobial Potential.

    Science.gov (United States)

    Prieto-Davó, Alejandra; Dias, Tiago; Gomes, Sofia E; Rodrigues, Sara; Parera-Valadez, Yessica; Borralho, Pedro M; Pereira, Florbela; Rodrigues, Cecilia M P; Santos-Sanches, Ilda; Gaudêncio, Susana P

    2016-01-01

    Marine-derived actinomycetes have demonstrated an ability to produce novel compounds with medically relevant biological activity. Studying the diversity and biogeographical patterns of marine actinomycetes offers an opportunity to identify genera that are under environmental pressures, which may drive adaptations that yield specific biosynthetic capabilities. The present study describes research efforts to explore regions of the Atlantic Ocean, specifically around the Madeira Archipelago, where knowledge of the indigenous actinomycete diversity is scarce. A total of 400 actinomycetes were isolated, sequenced, and screened for antimicrobial and anticancer activities. The three most abundant genera identified were Streptomyces, Actinomadura, and Micromonospora. Phylogenetic analyses of the marine OTUs isolated indicated that the Madeira Archipelago is a new source of actinomycetes adapted to life in the ocean. Phylogenetic differences between offshore (>100 m from shore) and nearshore (diverse bacterial strains. Novel phylotypes from chemically rich marine actinomycete groups like MAR4 and the genus Salinispora were isolated. Anticancer and antimicrobial assays identified Streptomyces, Micromonospora, and Salinispora as the most biologically active genera. This study illustrates the importance of bioprospecting efforts at unexplored regions of the ocean to recover bacterial strains with the potential to produce novel and interesting chemistry.

  14. The Madeira Archipelago as a significant source of marine-derived actinomycete diversity with anticancer and antimicrobial potential

    Directory of Open Access Journals (Sweden)

    Alejandra Prieto-Davo

    2016-10-01

    Full Text Available Marine-derived actinomycetes have demonstrated an ability to produce novel compounds with medically relevant biological activity. Studying the diversity and biogeographical patterns of marine actinomycetes offers an opportunity to identify genera that are under environmental pressures, which may drive adaptations that yield specific biosynthetic capabilities. The present study describes research efforts to explore regions of the Atlantic Ocean, specifically around the Madeira Archipelago, where knowledge of the indigenous actinomycete diversity is scarce. A total of 400 actinomycetes were isolated, sequenced and screened for antimicrobial and anticancer activities. The three most abundant genera identified were Streptomyces, Actinomadura and Micromonospora. Phylogenetic analyses of the marine OTUs isolated indicated that the Madeira Archipelago is a new source of actinomycetes adapted to life in the ocean. Phylogenetic differences between offshore (>100m from shore and nearshore (<100m from shore populations illustrates the importance of sampling offshore in order to isolate new and diverse bacterial strains. Novel phylotypes from chemically rich marine actinomycete groups like MAR4 and the genus Salinispora were isolated. Anticancer and antimicrobial assays identified Streptomyces, Micromonospora and Salinispora as the most biologically active genera. This study illustrates the importance of bioprospecting efforts at unexplored regions of the ocean to recover bacterial strains with the potential to produce novel and interesting chemistry.

  15. The Madeira Archipelago As a Significant Source of Marine-Derived Actinomycete Diversity with Anticancer and Antimicrobial Potential

    Science.gov (United States)

    Prieto-Davó, Alejandra; Dias, Tiago; Gomes, Sofia E.; Rodrigues, Sara; Parera-Valadez, Yessica; Borralho, Pedro M.; Pereira, Florbela; Rodrigues, Cecilia M. P.; Santos-Sanches, Ilda; Gaudêncio, Susana P.

    2016-01-01

    Marine-derived actinomycetes have demonstrated an ability to produce novel compounds with medically relevant biological activity. Studying the diversity and biogeographical patterns of marine actinomycetes offers an opportunity to identify genera that are under environmental pressures, which may drive adaptations that yield specific biosynthetic capabilities. The present study describes research efforts to explore regions of the Atlantic Ocean, specifically around the Madeira Archipelago, where knowledge of the indigenous actinomycete diversity is scarce. A total of 400 actinomycetes were isolated, sequenced, and screened for antimicrobial and anticancer activities. The three most abundant genera identified were Streptomyces, Actinomadura, and Micromonospora. Phylogenetic analyses of the marine OTUs isolated indicated that the Madeira Archipelago is a new source of actinomycetes adapted to life in the ocean. Phylogenetic differences between offshore (>100 m from shore) and nearshore (< 100 m from shore) populations illustrates the importance of sampling offshore in order to isolate new and diverse bacterial strains. Novel phylotypes from chemically rich marine actinomycete groups like MAR4 and the genus Salinispora were isolated. Anticancer and antimicrobial assays identified Streptomyces, Micromonospora, and Salinispora as the most biologically active genera. This study illustrates the importance of bioprospecting efforts at unexplored regions of the ocean to recover bacterial strains with the potential to produce novel and interesting chemistry. PMID:27774089

  16. Identification of altered plasma proteins by proteomic study in valvular heart diseases and the potential clinical significance.

    Directory of Open Access Journals (Sweden)

    Ge Gao

    Full Text Available BACKGROUND: Little is known about genetic basis and proteomics in valvular heart disease (VHD including rheumatic (RVD and degenerative (DVD valvular disease. The present proteomic study examined the hypothesis that certain proteins may be associated with the pathological changes in the plasma of VHD patients. METHODS AND RESULTS: Differential protein analysis in the plasma identified 18 differentially expressed protein spots and 14 corresponding proteins or polypeptides by two-dimensional electrophoresis and mass spectrometry in 120 subjects. Two up-regulated (complement C4A and carbonic anhydrase 1 and three down-regulated proteins (serotransferrin, alpha-1-antichymotrypsin, and vitronectin were validated by ELISA in enlarging samples. The plasma levels (n = 40 for each of complement C4A in RVD (715.8±35.6 vs. 594.7±28.2 ng/ml, P = 0.009 and carbonic anhydrase 1 (237.70±15.7 vs. 184.7±10.8 U/L, P = 0.007 in DVD patients were significantly higher and that of serotransferrin (2.36±0.20 vs. 2.93±0.16 mg/ml, P = 0.025 and alpha-1-antichymotrypsin (370.0±13.7 vs. 413.0±11.6 µg/ml, P = 0.019 in RVD patients were significantly lower than those in controls. The plasma vitronectin level in both RVD (281.3±11.0 vs. 323.2±10.0 µg/ml, P = 0.006 and DVD (283.6±11.4 vs. 323.2±10.0 µg/ml, P = 0.011 was significantly lower than those in normal controls. CONCLUSIONS: We have for the first time identified alterations of 14 differential proteins or polypeptides in the plasma of patients with various VHD. The elevation of plasma complement C4A in RVD and carbonic anhydrase 1 in DVD and the decrease of serotransferrin and alpha-1-antichymotrypsin in RVD patients may be useful biomarkers for these valvular diseases. The decreased plasma level of vitronectin - a protein related to the formation of valvular structure - in both RVD and DVD patients might indicate the possible genetic deficiency in these patients.

  17. Identification of altered plasma proteins by proteomic study in valvular heart diseases and the potential clinical significance.

    Science.gov (United States)

    Gao, Ge; Xuan, Chao; Yang, Qin; Liu, Xiao-Cheng; Liu, Zhi-Gang; He, Guo-Wei

    2013-01-01

    Little is known about genetic basis and proteomics in valvular heart disease (VHD) including rheumatic (RVD) and degenerative (DVD) valvular disease. The present proteomic study examined the hypothesis that certain proteins may be associated with the pathological changes in the plasma of VHD patients. Differential protein analysis in the plasma identified 18 differentially expressed protein spots and 14 corresponding proteins or polypeptides by two-dimensional electrophoresis and mass spectrometry in 120 subjects. Two up-regulated (complement C4A and carbonic anhydrase 1) and three down-regulated proteins (serotransferrin, alpha-1-antichymotrypsin, and vitronectin) were validated by ELISA in enlarging samples. The plasma levels (n = 40 for each) of complement C4A in RVD (715.8±35.6 vs. 594.7±28.2 ng/ml, P = 0.009) and carbonic anhydrase 1 (237.70±15.7 vs. 184.7±10.8 U/L, P = 0.007) in DVD patients were significantly higher and that of serotransferrin (2.36±0.20 vs. 2.93±0.16 mg/ml, P = 0.025) and alpha-1-antichymotrypsin (370.0±13.7 vs. 413.0±11.6 µg/ml, P = 0.019) in RVD patients were significantly lower than those in controls. The plasma vitronectin level in both RVD (281.3±11.0 vs. 323.2±10.0 µg/ml, P = 0.006) and DVD (283.6±11.4 vs. 323.2±10.0 µg/ml, P = 0.011) was significantly lower than those in normal controls. We have for the first time identified alterations of 14 differential proteins or polypeptides in the plasma of patients with various VHD. The elevation of plasma complement C4A in RVD and carbonic anhydrase 1 in DVD and the decrease of serotransferrin and alpha-1-antichymotrypsin in RVD patients may be useful biomarkers for these valvular diseases. The decreased plasma level of vitronectin - a protein related to the formation of valvular structure - in both RVD and DVD patients might indicate the possible genetic deficiency in these patients.

  18. Reduced content of chloroatranol and atranol in oak moss absolute significantly reduces the elicitation potential of this fragrance material

    DEFF Research Database (Denmark)

    Andersen, Flemming; Andersen, Kirsten H; Bernois, Armand

    2015-01-01

    BACKGROUND: Oak moss absolute, an extract from the lichen Evernia prunastri, is a valued perfume ingredient but contains extreme allergens. OBJECTIVES: To compare the elicitation properties of two preparations of oak moss absolute: 'classic oak moss', the historically used preparation, and 'new oak...... moss', with reduced contents of the major allergens atranol and chloroatranol. PATIENTS/MATERIALS/METHODS: The two preparations were compared in randomized double-blinded repeated open application tests and serial dilution patch tests in 30 oak moss-sensitive volunteers and 30 non-allergic control...... subjects. RESULTS: In both test models, new oak moss elicited significantly less allergic contact dermatitis in oak moss-sensitive subjects than classic oak moss. The control subjects did not react to either of the preparations. CONCLUSIONS: New oak moss is still a fragrance allergen, but elicits less...

  19. Short communication: Effect of commercial or depurinized milk diet on plasma advanced oxidation protein products, cardiovascular markers, and bone marrow CD34+ stem cell potential in rat experimental hyperuricemia.

    Science.gov (United States)

    Kocic, Gordana; Sokolovic, Dusan; Jevtovic, Tatjana; Cvetkovic, Tatjana; Veljkovic, Andrej; Kocic, Hristina; Stojanovic, Svetlana; Jovanovic, Aneta; Jovanovic, Jelena; Zivkovic, Petar

    2014-11-01

    Cardiovascular repair and myocardial contractility may be improved by migration of bone marrow stem cells (BMSC) and their delivery to the site of injury, a process known as BMSC homing. The aim of our study was to examine the dietary effect of a newly patented depurinized milk (DP) that is almost free of uric acid and purine and pyrimidine compounds compared with a standard commercial 1.5% fat UHT milk diet or allopurinol therapy in rat experimental hyperuricemia. Bone marrow stem cell potential (BMCD34(+), CD34-postive bone marrow cells), plasma oxidative stress parameters [advanced oxidation protein products, AOPP) and thiobarbituric acid reactive substances (TBARS)], myocardial damage markers [creatine phosphokinase (CPK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH)], plasma cholesterol, and high-density lipoprotein cholesterol were investigated. The DP milk diet significantly increased the number of BMCD34(+) stem cells compared with commercial UHT milk. Allopurinol given alone also increased the number of BMCD34(+). Hyperuricemia caused a significant increase in all plasma enzyme markers for myocardial damage (CPK, LDH, and AST). A cardioprotective effect was achieved with allopurinol but almost equally with DP milk and more than with commercial milk. Regarding plasma AOPP, TBARS, and cholesterol levels, the most effective treatment was DP milk. In conclusion, the protective role of a milk diet on cardiovascular function may be enhanced through the new depurinized milk diet, which may improve cardiovascular system function via increased bone marrow stem cell regenerative potential, decreased plasma oxidative stress parameters, and decreased levels of myocardial damage markers and cholesterol. New dairy technology strategies focused on eliminating harmful milk compounds should be completely nontoxic. Novel milk products should be tested for their ability to improve tissue repair and function. Copyright © 2014 American Dairy Science

  20. Functional significance of thermosensitive transient receptor potential melastatin channel 8 (TRPM8) expression in immortalized human corneal endothelial cells.

    Science.gov (United States)

    Mergler, Stefan; Mertens, Charlotte; Valtink, Monika; Reinach, Peter S; Székely, Violeta Castelo; Slavi, Nefeli; Garreis, Fabian; Abdelmessih, Suzette; Türker, Ersal; Fels, Gabriele; Pleyer, Uwe

    2013-11-01

    Human corneal endothelial cells (HCEC) maintain appropriate tissue hydration and transparency by eliciting net ion transport coupled to fluid egress from the stroma into the anterior chamber. Such activity offsets tissue swelling caused by stromal imbibition of fluid. As corneal endothelial (HCE) transport function is modulated by temperature changes, we probed for thermosensitive transient receptor potential melastatin 8 (TRPM8) functional activity in immortalized human corneal endothelial cells (HCEC-12) and freshly isolated human corneal endothelial cells (HCEC) as a control. This channel is either activated upon lowering to 28 °C or by menthol, eucalyptol and icilin. RT-PCR and quantitative real-time PCR (qPCR) verified TRPM8 gene expression. Ca(2+) transients induced by either menthol (500 μmol/l), eucalyptol (3 mmol/l), or icilin (2-60 μmol/l) were identified using cell fluorescence imaging. The TRP channel blocker lanthanum III chloride (La(3+), 100 μmol/l) as well as the TRPM8 blockers BCTC (10 μmol/l) and capsazepine (CPZ, 10 μmol/l) suppressed icilin-induced Ca(2+) increases. In and outward currents induced by application of menthol (500 μmol/l) or icilin (50 μmol/l) were detected using the planar patch-clamp technique. A thermal transition from room temperature to ≈ 18 °C led to Ca(2+) increases that were inhibited by a TRPM8 blocker BCTC (10 μmol/l). Other thermosensitive TRP pathways whose heterogeneous Ca(2+) response patterns are suggestive of other Ca(2+) handling pathways were also detected upon strong cooling (≈10 °C). Taken together, functional TRPM8 expression in HCEC-12 and freshly dissociated HCEC suggests that HCE function can adapt to thermal variations through activation of this channel subtype. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Caffeinated energy drink consumption among adolescents and potential health consequences associated with their use: a significant public health hazard.

    Science.gov (United States)

    De Sanctis, Vincenzo; Soliman, Nada; Soliman, Ashraf T; Elsedfy, Heba; Di Maio, Salvatore; El Kholy, Mohamed; Fiscina, Bernadette

    2017-08-23

    improve our understanding of potential negative consequences of caffeinated energy drinks on health.

  2. GATA3: a multispecific but potentially useful marker in surgical pathology: a systematic analysis of 2500 epithelial and nonepithelial tumors.

    Science.gov (United States)

    Miettinen, Markku; McCue, Peter A; Sarlomo-Rikala, Maarit; Rys, Janusz; Czapiewski, Piotr; Wazny, Krzysztof; Langfort, Renata; Waloszczyk, Piotr; Biernat, Wojciech; Lasota, Jerzy; Wang, Zengfeng

    2014-01-01

    neuroendocrine tumors. Mesenchymal tumors were only sporadically positive, except epithelia of biphasic synovial sarcomas. GATA3 is a useful marker in the characterization of not only mammary and urothelial but also renal and germ cell tumors, mesotheliomas, and paragangliomas. The multiple specificities of GATA3 should be taken into account when using this marker to detect metastatic mammary or urothelial carcinomas.

  3. Oral cancer risk and molecular markers.

    Science.gov (United States)

    Chimenos-Küstner, Eduardo; Font-Costa, Imma; López-López, José

    2004-01-01

    The clinical appearance and, especially, the degree of dysplasia that may be shown by pre-cancerous lesions in the oral cavity suggest a potential for malignisation. An increasing number of studies are seeking new, more specific markers that would help to determine the degree of cell alteration and enable a better understanding of the degree of malignant degeneration of these cells. The present review considers the most recent findings for these markers, grouping them into families: tumour growth markers; markers of tumour suppression and anti-tumour response; angiogenesis markers; markers of tumour invasion and metastatic potential; cell surface markers; intracellular markers; markers derived from arachidonic acid; and enzymatic markers.

  4. Toxicological significance of renal Bcrp: Another potential transporter in the elimination of mercuric ions from proximal tubular cells

    Energy Technology Data Exchange (ETDEWEB)

    Bridges, Christy C., E-mail: bridges_cc@mercer.edu; Zalups, Rudolfs K.; Joshee, Lucy

    2015-06-01

    Secretion of inorganic mercury (Hg{sup 2+}) from proximal tubular cells into the tubular lumen has been shown to involve the multidrug resistance-associated protein 2 (Mrp2). Considering similarities in localization and substrate specificity between Mrp2 and the breast cancer resistance protein (Bcrp), we hypothesize that Bcrp may also play a role in the proximal tubular secretion of mercuric species. In order to test this hypothesis, the uptake of Hg{sup 2+} was examined initially using inside-out membrane vesicles containing Bcrp. The results of these studies suggest that Bcrp may be capable of transporting certain conjugates of Hg{sup 2+}. To further characterize the role of Bcrp in the handling of mercuric ions and in the induction of Hg{sup 2+}-induced nephropathy, Sprague–Dawley and Bcrp knockout (bcrp{sup −/−}) rats were exposed intravenously to a non-nephrotoxic (0.5 μmol·kg{sup −1}), a moderately nephrotoxic (1.5 μmol·kg{sup −1}) or a significantly nephrotoxic (2.0 μmol·kg{sup −1}) dose of HgCl{sub 2}. In general, the accumulation of Hg{sup 2+} was greater in organs of bcrp{sup −/−} rats than in Sprague–Dawley rats, suggesting that Bcrp may play a role in the export of Hg{sup 2+} from target cells. Within the kidney, cellular injury and necrosis was more severe in bcrp{sup −/−} rats than in controls. The pattern of necrosis, which was localized in the inner cortex and the outer stripe of the outer medulla, was significantly different from that observed in Mrp2-deficient animals. These findings suggest that Bcrp may be involved in the cellular export of select mercuric species and that its role in this export may differ from that of Mrp2. - Highlights: • Bcrp may mediate transport of mercury out of proximal tubular cells. • Hg-induced nephropathy was more severe in Bcrp knockout rats. • Bcrp and Mrp2 may differ in their ability to transport Hg.

  5. The thymidine kinase-1 as a potential tumor marker: structure, function, activity in normal and malignant tissues

    Directory of Open Access Journals (Sweden)

    N. S. Sergeeva

    2017-01-01

    Full Text Available In the review the role of the thymidine kinase (TK to ensure the replication of DNA de novo and spare (salvage the way in health and activate alternate ways in carcinogenesis is described. The structure of cytoplasmic TK (TК-1, also called fetal, and the level of regulation of its activity in the cells and their change during the cell cycle is described. Considering the data about the absence of TK-1 in resting (G0 cells, TK-1 is positioned as a marker of proliferating cells, which activity is recorded from late G1 phase, peaking in S-phase, it is stored in the G2 and mitosis, quickly decreasing to undetectable levels in the early G1 phase. Data on the expression TK-1 (as compared with Ki-67 and PCNA (proliferating cell nuclear antigen in tumor tissues (colorectal, breast, cervical, lung, renal, prostate and ovarian cancer, as well as some benign and precancerous pathological processes in relation to the clinical and diagnostic features of these processes are systemized. These data suggest that the proliferative index studies on TK-1 (antibody to the domain HRA-210 should be used together with Ki-67 and PCNA, for a more complete assessment of the proliferative status of malignant tumors and pre-cancerous and benign conditions, with the aim of prognosis of the tumor process and treatment planning.

  6. Brucella melitensis VirB12 recombinant protein is a potential marker for serodiagnosis of human brucellosis.

    Science.gov (United States)

    Mirkalantari, Shiva; Zarnani, Amir-Hassan; Nazari, Mahboobeh; Irajian, Gholam Reza; Amirmozafari, Nour

    2017-03-03

    The numerous drawbacks of current serological tests for diagnosis of brucellosis which mainly results from cross reactivity with LPS from other gram-negative bacteria have generated an increasing interest to find more specific non-LPS antigens. Previous studies had indicated that Brucella VirB12 protein, a cell surface protein and component of type IV secretion system, induces antibody response during animal infection. However, this protein has not yet been tested as a serological diagnostic marker in human brucellosis. Recombinant VirB12 protein was prepared and evaluated the efficacy of it in an indirect enzyme-linked immunosorbent assay (ELISA) for brucellosis with sera collected from different region of Iran and the results were compared with a commercial ELISA kit. Sera from human brucellosis patients strongly reacted to the purified recombinant VirB12. The sensitivity, specificity, accuracy, negative predictive value and positive predictive value of recombinant VirB12-based ELISA related to the commercial-ELISA method were 87.8, 94, 90, 80 and 96.6% respectively. We concluded that antigenic VirB12 have a property value that can be considered as a candidate for using in serodiagnostic tests for human brucellosis.

  7. Survey and analysis of microsatellites from transcript sequences in Phytophthora species: frequency, distribution, and potential as markers for the genus

    Directory of Open Access Journals (Sweden)

    Barreto Emiliano

    2006-09-01

    Full Text Available Abstract Background Members of the genus Phytophthora are notorious pathogens with world-wide distribution. The most devastating species include P. infestans, P. ramorum and P. sojae. In order to develop molecular methods for routinely characterizing their populations and to gain a better insight into the organization and evolution of their genomes, we used an in silico approach to survey and compare simple sequence repeats (SSRs in transcript sequences from these three species. We compared the occurrence, relative abundance, relative density and cross-species transferability of the SSRs in these oomycetes. Results The number of SSRs in oomycetes transcribed sequences is low and long SSRs are rare. The in silico transferability of SSRs among the Phytophthora species was analyzed for all sets generated, and primers were selected on the basis of similarity as possible candidates for transferability to other Phytophthora species. Sequences encoding putative pathogenicity factors from all three Phytophthora species were also surveyed for presence of SSRs. However, no correlation between gene function and SSR abundance was observed. The SSR survey results, and the primer pairs designed for all SSRs from the three species, were deposited in a public database. Conclusion In all cases the most common SSRs were trinucleotide repeat units with low repeat numbers. A proportion (7.5% of primers could be transferred with 90% similarity between at least two species of Phytophthora. This information represents a valuable source of molecular markers for use in population genetics, genetic mapping and strain fingerprinting studies of oomycetes, and illustrates how genomic databases can be exploited to generate data-mining filters for SSRs before experimental validation.

  8. Midkine is a potential novel marker for malignant mesothelioma with different prognostic and diagnostic values from mesothelin.

    Science.gov (United States)

    Ak, Guntulu; Tada, Yuji; Shimada, Hideaki; Metintas, Selma; Ito, Masaaki; Hiroshima, Kenzo; Tagawa, Masatoshi; Metintas, Muzaffer

    2017-03-23

    We evaluated possible diagnostic and prognostic values of serum midkine in malignant pleural mesothelioma in comparison with those of serum mesothelin, a well-established diagnostic biomarker. Serum mesothelin and midkine levels were determined with an enzyme-linked immunosorbent assay. We examined specimens from 95 Turkish cases with malignant pleural mesothelioma, 56 metastatic cancers to pleura, 27 other types of benign pleural diseases and 20 benign asbestos pleurisy. The cut-off values were 1.5 nmol/L for mesothelin and 421 pg/mL for midkine. Sensitivity and specificity of mesothelin were 51.6 and 71.4%, 51.6 and 85.2%, and 51.6 and 85% for differentiating mesothelioma from metastatic cancers to pleura, other benign pleural diseases and benign asbestos pleurisy, respectively. Sensitivity and specificity of midkine were 61.1 and 41.1%, 61.1 and 48.1%, and 61.1 and 75% to distinguish mesothelioma from metastatic cancers to pleura, other benign pleural diseases and benign asbestos pleurisy, respectively. Combination of both biomarkers did not improve the differential diagnostic efficacy. Mesothelin levels were elevated in the epitheloid type and in the advanced cases, but were not related to the prognosis. In contrast, elevated baseline levels of midkine were independently associated with a poor prognosis of mesothelioma patients after adjusting for the stage, the histological subtypes and treatment schedules (HR = 1.84; 95% CI: 1.09-3.09) (p = 0.022). Serum mesothelin showed moderate sensitivity and high specificity to differentiate malignant pleural mesothelioma from metastatic malignancy to pleura and from benign pleural diseases. In contrast, midkine was a useful marker for predicting prognosis of mesothelioma patients.

  9. A mixture of oleic, erucic and conjugated linoleic acids modulates cerebrospinal fluid inflammatory markers and improve somatosensorial evoked potential in X-linked adrenoleukodystrophy female carriers.

    Science.gov (United States)

    Cappa, Marco; Bizzarri, Carla; Petroni, Anna; Carta, Gianfranca; Cordeddu, Lina; Valeriani, Massimiliano; Vollono, Catello; De Pasquale, Loredana; Blasevich, Milena; Banni, Sebastiano

    2012-09-01

    X-linked adrenoleukodystrophy is a rare inherited demyelinating disorder characterized by an abnormal accumulation of very long chain fatty acids, mainly hexacosanoic acid (26:0), due to a mutation of the gene encoding for a peroxisomal membrane protein. The only available, and partially effective, therapeutic treatment consists of dietary intake of a 4:1 mixture of triolein and trierucin, called Lorenzo's oil (LO), targeted to inhibit the elongation of docosanoic acid (22:0) to 26:0. In this study we tested whether, besides inhibiting elongation, an enhancement of peroxisomal beta oxidation induced by conjugated linoleic acid (CLA), will improve somatosensory evoked potentials and modify inflammatory markers in adrenoleukodystrophy females carriers. We enrolled five heterozygous women. They received a mixture of LO (40 g/day) with CLA (5 g/day) for 2 months. The therapeutic efficacy was evaluated by the means of plasma levels of 26:0, 26:0/22:0 ratio, modification of cerebrospinal fluid (CSF) inflammatory markers and somatosensory evoked potentials. Changes of fatty acid profile, and in particular CLA incorporation, were also evaluated in CSF and plasma. The results showed that CLA promptly passes the blood brain barrier and the mixture was able to lower both 26:0 and 26:0/22:0 ratio in plasma. The mixture improved somatosensory evoked potentials, which were previously found unchanged or worsened with dietary LO alone, and reduced IL-6 levels in CSF in three out of five patients. Our data suggest that the synergic activity of CLA and LO, by enhancing peroxisomal beta-oxidation and preventing 26:0 formation, improves the somatosensory evoked potentials and reduces neuroinflammation.

  10. Urinary cystatin C as a potential risk marker for cardiovascular disease and chronic kidney disease in patients with obesity and metabolic syndrome.

    Science.gov (United States)

    Satoh-Asahara, Noriko; Suganami, Takayoshi; Majima, Takafumi; Kotani, Kazuhiko; Kato, Yasuhisa; Araki, Rika; Koyama, Kazunori; Okajima, Taiichiro; Tanabe, Makito; Oishi, Mariko; Himeno, Akihiro; Kono, Shigeo; Sugawara, Akira; Hattori, Masakazu; Ogawa, Yoshihiro; Shimatsu, Akira

    2011-02-01

    Obesity and metabolic syndrome (MS) increase the risk of cardiovascular disease (CVD), chronic kidney disease (CKD), and all-cause mortality. Serum cystatin C (S-CysC), a marker of GFR, has been shown to be associated with CVD and CKD. This study was designed to elucidate the association of urinary CysC (U-CysC), a marker of renal tubular dysfunction, with CVD and CKD risk factors in patients with obesity and MS. The U-CysC-creatinine ratio (UCCR) was examined in 343 Japanese obese outpatients enrolled in the multi-centered Japan Obesity and Metabolic Syndrome Study. UCCR was positively correlated with urine albumin-creatinine ratio (UACR) and S-CysC and negatively correlated with estimated GFR (eGFR). Among obese patients, UCCR was significantly higher in MS patients than in non-MS patients. UCCR had significant correlations with the number of components of MS and arterial stiffness, all of which are CVD predictors, similarly to UACR (Peffect of weight reduction on renal tubular dysfunction. This study demonstrates that UCCR is significantly associated with renal dysfunction, the severity of MS, arterial stiffness, and weight change in obese patients. The data of this study suggest that U-CysC could serve as a CVD and CKD risk factor in patients with obesity and MS.

  11. Identification of alpha-1 acid glycoprotein (AGP) as a potential marker of impaired growth in the newborn piglet

    Science.gov (United States)

    Two studies were conducted to investigate the relationship between the circulating levels of the acute phase proteins haptoglobin (HP) and alpha 1 acid glycoprotein (AGP) and growth potential in neonatal pigs. In runts, the circulating level of AGP, but not HP in serum of newborn piglets was higher...

  12. Potential of maize single-cross hybrids for extraction of inbred lines using the mean components and mixed models with microsatellite marker information.

    Science.gov (United States)

    Balestre, M; Von Pinho, R G; Souza, J C; Machado, J C

    2008-10-21

    The present study examined the importance of mean (m+a' and d) components in the performance of single-cross hybrids for the formation of new populations and determined the contribution of the mixed model (best linear unbiased predictor of random effects, BLUP) method associated with molecular markers for the choice of crosses to obtain interpopulation hybrids. Ten single-cross commercial hybrids of different companies were used for this purpose, producing all possible double-cross hybrids through a complete diallel. The hybrids were evaluated in 15 locations in the agricultural year 2005/2006, using randomized complete block design with three repetitions. In three of these locations, estimates of m+a' and d were obtained. DNA was extracted from the single-cross hybrids and 20 SSR primers were used, nine of which were linked to QTL for yield. There was no correlation between m+a' of the single-cross hybrids with general combining ability (r = -0.15) inferring that populations with lines with high means do not always produce good hybrids. Also, it was observed that the correlation between the genetic distances with specific combining ability varied from 0.31 to 0.80 in the inter-group hybrids, while in the intra-group hybrids these estimates were low and non-significant. The heritability value obtained by BLUP was high and greater than that obtained by ordinary least squares (h(2) = 0.95 and 0.86), confirming the greater selection accuracy by the BLUP method. There were no differences between the accuracy values obtained with microsatellite information and without this information, inferring that there was no advantage of progenitor information on balanced data. It can be concluded that the estimate m+a' should not be used as a deciding parameter about the potential for extracting lines from a given population. The heritability and accuracy values obtained by BLUP allow the inference that it is possible to predict success in the choice of progenitors to obtain

  13. Acylcarnitines as markers of exercise-associated fuel partitioning, xenometabolism, and potential signals to muscle afferent neurons.

    Science.gov (United States)

    Zhang, Jie; Light, Alan R; Hoppel, Charles L; Campbell, Caitlin; Chandler, Carol J; Burnett, Dustin J; Souza, Elaine C; Casazza, Gretchen A; Hughen, Ronald W; Keim, Nancy L; Newman, John W; Hunter, Gary R; Fernandez, Jose R; Garvey, W Timothy; Harper, Mary-Ellen; Fiehn, Oliver; Adams, Sean H

    2017-01-01

    What is the central question of this study? Does improved metabolic health and insulin sensitivity following a weight-loss and fitness intervention in sedentary, obese women alter exercise-associated fuel metabolism and incomplete mitochondrial fatty acid oxidation (FAO), as tracked by blood acylcarnitine patterns? What is the main finding and its importance? Despite improved fitness and blood sugar control, indices of incomplete mitochondrial FAO increased in a similar manner in response to a fixed load acute exercise bout; this indicates that intramitochondrial muscle FAO is inherently inefficient and is tethered directly to ATP turnover. 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 incomplete long-chain fatty acid oxidation (FAO)]. We reasoned that incomplete FAO in muscle would be ameliorated concurrent with improved insulin sensitivity and fitness following a ∼14 week training and weight-loss intervention in obese, sedentary, insulin-resistant women. Contrary to this hypothesis, overnight-fasted and exercise-induced plasma C4-C14 acylcarnitines did not differ between pre- and postintervention phases. These metabolites all increased robustly with exercise (∼45% of pre-intervention peak oxygen consumption) and decreased during a 20 min cool-down. This supports the idea that, regardless of insulin sensitivity and fitness, intramitochondrial muscle β-oxidation and attendant incomplete FAO are closely tethered to absolute ATP turnover rate. Acute exercise also led to branched-chain amino acid acylcarnitine derivative patterns suggestive of rapid and transient diminution of branched-chain amino acid flux through the mitochondrial branched-chain ketoacid dehydrogenase complex. We confirmed our prior novel observation

  14. Pregnancy associated plasma protein A, a potential marker for vulnerable plaque in patients with non-ST-segment elevation acute coronary syndrome

    DEFF Research Database (Denmark)

    Iversen, Kasper K; Teisner, Ane S; Teisner, Borge

    2009-01-01

    OBJECTIVES: To describe the presence and time-related pattern of circulating pregnancy associated plasma protein A (PAPP-A) levels in patients with non ST-segment elevation acute coronary syndrome (NSTE-ACS). DESIGN AND METHODS: Consecutively admitted patients (N=573) with clinical signs of NSTE......-ACS were included. Blood samples for analysis of PAPP-A were drawn at admission and every 6-8 h until levels of biomarkers of myocardial necrosis showed a consistent decrease. RESULTS: High-risk NSTE-ACS was diagnosed in 123 patients (23%). Significantly more patients with high-risk NSTE-ACS (63%) had...... detectable PAPP-A than did those with low-risk NSTE-ACS (49%) (PPAPP-A concentrations were significantly associated with typical angina at admission, significant ST-depressions on the ECG, multivessel disease and presence of high-risk NSTE-ACS. CONCLUSION: PAPP-A seems to be a marker ischaemia both...

  15. Polymorphism rs2073618 of the osteoprotegerin gene as a potential marker of subclinical carotid atherosclerosis in Caucasians with type 2 diabetes mellitus.

    Science.gov (United States)

    Pleskovič, Aleš; Ramuš, Sara Mankoč; Pražnikar, Zala Jenko; Šantl Letonja, Marija; Cokan Vujkovac, Andreja; Gazdikova, Katarina; Caprnda, Martin; Gaspar, Ludovit; Kruzliak, Peter; Petrovič, Daniel

    2017-08-01

    The OPG/RANKL/RANK (osteoprotegerin/receptor-activator of nuclear factor κB ligand/receptor-activator of nuclear factor κB) axis has been recently linked to the development of atherosclerosis and plaque destabilization. We have investigated whether polymorphism rs2073618 of the OPG gene is associated with subclinical markers of carotid atherosclerosis in subjects with type 2 diabetes mellitus (T2DM). 595 subjects with T2DM were enrolled in the cross-sectional study. Subclinical markers of carotid atherosclerosis (carotid intima media thickness, plaque thickness, and plaques presence) were assessed with ultrasound at the time of recruitment. Genotyping for rs2073618 (a missense variant located in exon I of the OPG gene) was performed, and OPG serum levels were determined by ELISA. Compared to the GG genotype, the CC genotype of the rs2073618 polymorphism had a significantly increased risk for the presence of carotid plaque (OR = 2.54, 95 % CI = 1.22-5.28, p = 0.01). No statistically significant difference could be detected (p = 0.68) upon comparing median values of serum OPG levels among studied genotype groups in subjects with T2DM. Multivariable linear regression analyses in T2DM subjects demonstrated that GC and CC genotypes (p = 0.03 and p = 0.003), together with statin therapy (p = 0.009), were independent predictors of the number of carotid segments with plaques. Despite the fact that OPG rs2073618 genotypes failed to predict the serum OPG levels as there was no statistical difference among compared genotypes, our results demonstrate that the rs2073618 polymorphism could be a possible genetic marker for the prediction of increased risk for carotid plaque burden as a measure of advanced subclinical atherosclerosis in T2DM subjects.

  16. Pituitary tumor transforming gene and insulin-like growth factor 1 receptor expression and immunohistochemical measurement of Ki-67 as potential prognostic markers of pituitary tumors aggressiveness.

    Science.gov (United States)

    Sánchez-Tejada, Laura; Sánchez-Ortiga, Ruth; Moreno-Pérez, Oscar; Montañana, Carmen Fajardo; Niveiro, Maria; Tritos, Nicholas A; Alfonso, Antonio M Picó

    2013-01-01

    The ability to predict recurrence of pituitary adenoma (PA) after surgery may be helpful to determine follow-up frequency and the need for adjuvant treatment. The purpose of this study was to assess the prognostic capacity of pituitary tumor transforming gene (PTTG), insulin-like growth factor 1 receptor (IGF1R), and Ki-67. In this retrospective study, the normalized copy number (NCN) of PTIG and IGF1R mRNA was measured using RT-PCR, and the Ki-67 index was measured by immunohistochemistry in 46 PA samples. Clinical data, histological subtype, and radiographic characteristics were collected to assess associations between variables and tumor behavior. Progression of tumor remnants and its association to markers was also studied in 14 patients with no adjuvant treatment after surgery followed up for 46±36 months. Extrasellar tumors had a lower PTTG expression as compared to sellar tumors (0.065 [1st-3rd quartile: 0.000-0.089] NCN vs. 0.135 [0.105-0.159] NCN, p=0.04). IGF1R expression changed depending on histological subtype (p=0.014), and was greater in tumor with remnant growth greater than 20% during follow-up (10.69±3.84 NCN vs. 5.44±3.55 NCN, p=0.014). Our results suggest that the IGF1R is a more helpful molecular marker than PTTG in PA management. Ki-67 showed no association to tumor behavior. However, the potential of these markers should be established in future studies with standardized methods and on larger samples. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  17. Serum Levels of Asymmetric Dimethylarginine and Apelin as Potential Markers of Vascular Endothelial Dysfunction in Early Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Manuela Di Franco

    2012-01-01

    Full Text Available Objectives. Impaired endothelial function represents the early stage of atherosclerosis, which is typically associated with systemic inflammatory diseases like rheumatoid arthritis (RA. As modulators of endothelial nitric oxide synthase expression, asymmetric-dimethylarginine (ADMA and apelin might be measured in the blood of RA patients to detect early atherosclerotic changes. We conducted a prospective, case-control study to investigate serum ADMA and apelin profiles of patients with early-stage RA (ERA before and after disease-modifying antirheumatic drug (DMARD therapy. Methods. We enrolled 20 consecutively diagnosed, treatment-naïve patients with ERA and 20 matched healthy controls. Serum ADMA and apelin levels and the 28-joint disease activity scores (DAS28 were assessed before and after 12 months of DMARDs treatment. All patients underwent ultrasonographic assessment for intima-media tickness (IMT evaluation. Results. In the ERA group, ADMA serum levels were significantly higher than controls at baseline (P=0.007 and significantly decreased after treatment (P=0.012 versus controls. Baseline serum apelin levels were significantly decreased in this group (P=0.0001 versus controls, but they were not significantly altered by treatment. IMT did not show significant changes. Conclusions. ERA is associated with alterations of serum ADMA and apelin levels, which might be used as biomarkers to detect early endothelial dysfunction in these patients.

  18. Construction of Bacillus thuringiensis wild-type S76 and Cry- derivatives expressing a green fluorescent protein: two potential marker organisms to study bacteria-plant interactions.

    Science.gov (United States)

    Parente, Ana Flávia; Silva-Pereira, Ildinete; Baldani, José Ivo; Tibúrcio, Victor Hugo da Silva; Báo, Sônia Nair; De-Souza, Marlene T

    2008-09-01

    Collectively, the species Bacillus thuringiensis, Bacillus cereus, and Bacillus anthracis represent microorganisms of high economic, medical, and biodefense importance. Although the genetic correlation and pathogenic characteristics have been extensively dissected, the ecological properties of these three species in their natural environments remain poorly understood. Thus, a tractable marker for detecting these bacteria under specific environmental and physiological conditions is a valuable tool. With this purpose, a plasmid (pAD43-25) carrying a functional gfp gene sequence (gfpmut3A) was introduced into the wild-type strain Bacillus thuringiensis subsp. kurstaki S76, which bears approximately 11 plasmids, allowing constitutive synthesis of green fluorescent protein (GFP) during vegetative growth (strain S76GFP+). Additionally, this vector was transferred to a plasmid-cured (Cry-) B. thuringiensis host. Bright green cells were detected by fluorescence microscopy in both recombinants by 2 h after inoculation in liquid medium and could be seen throughout the remaining cultivation time until complete sporulation was accomplished. For strain S76GFP+ protein profile and plasmid DNA analyses indicate, respectively, that this recombinant maintained Cry proteins expression and resident plasmid outline. Thus, in addition to the potential of strain S76GFP+ as a marker organism in bacteria--plant interaction studies, the production and stability of active GFPmut3a make this unique expression system a useful experimental model to study adaptive changes of host-plasmid as well as plasmid-plasmid relationships in a population of cells stressed by the production of a recombinant protein.

  19. Mapping of proteomic lysate of a MCF-7 cancer cell line for the identification of potential markers for breast cancer

    Directory of Open Access Journals (Sweden)

    V. E. Shevchenko

    2012-01-01

    Full Text Available Mass spectrometric mapping of proteomic lysate of a MCF-7 cancer cell line was carried out, which identified 153 proteins having molecular weights of 5000 to 630000 Da, a high proportion of which was cytoplasmic and nuclear proteins. The latter accounted for 60 % of their total number whereas the proportion of extracellular and membrane proteins constituted 13 %. After using some selection criteria to analyze the findings, the authors present a list of 31 potential biomarkers and describe 12 promising breast anticancer therapeutic targets.

  20. Characterisation of potential virulence markers in Aeromonas caviae isolated from polluted and unpolluted aquatic environments in Morocco

    DEFF Research Database (Denmark)

    Imziln, Boujama; Krovacek, Karel; Baloda, Suraj B.

    1998-01-01

    .406) than those isolated from raw sewage (PVI = 0.175) or those from river waters (PVI = 0.09). These results suggest that stabilisation pond systems used for sewage purification under arid climate conditions in Marrakech, may have selected potentially enteropathogenic A. caviae strains.......A total of 100 Aeromonas caviae strains isolated from river waters (38 isolates), raw sewage (30 isolates) and effluents of stabilisation ponds (i.e. treated sewage; 32 isolates) in Marrakech, Morocco, were tested for the presence of putative virulence factors to delineate differences, if any...

  1. 8-C N-ethyl-2-pyrrolidinone substituted flavan-3-ols as the marker compounds of Chinese dark teas formed in the post-fermentation process provide significant antioxidative activity.

    Science.gov (United States)

    Wang, Weinan; Zhang, Liang; Wang, Shu; Shi, Shepo; Jiang, Yong; Li, Ning; Tu, Pengfei

    2014-01-01

    Phytochemical investigation of the aqueous extract of pu-erh tea afforded eight novel 8-C N-ethyl-2-pyrrolidinone substituted flavan-3-ols (puerins I-VIII) by (1)H, (13)C, two-dimensional nuclear magnetic resonance (NMR) and high-performance liquid chromatography with diode array detection and electrospray ionization mass spectrometry (HPLC-DAD-ESI/MS) analysis. Comparative chemical analysis of green tea, black tea and Chinese dark teas confirmed that these compounds were the marker compounds of Chinese dark teas. Furthermore, fungal fermentation was indispensable for the biosynthesis of these novel compounds. Through single fungal fermentation, it was proved that catechins and theanine were the precursors of puerins I-VIII. HPLC-DAD-ESI/MS analysis elucidated the biosynthetic pathway for puerins I-VIII. Puerins I-IV have potential protective effects for the human micro-vascular endothelial cells (HMEC) injury induced by hydrogen dioxide compared to other tea polyphenols. 8-C N-ethyl-2-pyrrolidinone substituted flavan-3-ols could be used in the quality control and authentication of Chinese dark teas. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Integrative miRNA and mRNA analysis in penile carcinomas reveals markers and pathways with potential clinical impact

    DEFF Research Database (Denmark)

    Kuasne, Hellen; Barros-Filho, Mateus Camargo; Busso-Lopes, Ariane F

    2017-01-01

    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...

  3. Fructose-bisphosphate aldolase a is a potential metastasis-associated marker of lung squamous cell carcinoma and promotes lung cell tumorigenesis and migration.

    Directory of Open Access Journals (Sweden)

    Sha Du

    Full Text Available Fructose-bisphosphate aldolase A (ALDOA is a key enzyme in glycolysis and is responsible for catalyzing the reversible conversion of fructose-1,6-bisphosphate to glyceraldehydes-3-phosphate and dihydroxyacetone phosphate. ALDOA contributes to various cellular functions such as muscle maintenance, regulation of cell shape and mobility, striated muscle contraction, actin filament organization and ATP biosynthetic process. Here, we reported that ALDOA is a highly expressed in lung squamous cell carcinoma (LSCC and its expression level is correlated with LSCC metastasis, grades, differentiation status and poor prognosis. Depletion of ALDOA expression in the lung squamous carcinoma NCI-H520 cells reduces the capabilities of cell motility and tumorigenesis. These data suggest that ALDOA could be a potential marker for LSCC metastasis and a therapeutic target for drug development.

  4. Fructose-bisphosphate aldolase a is a potential metastasis-associated marker of lung squamous cell carcinoma and promotes lung cell tumorigenesis and migration.

    Science.gov (United States)

    Du, Sha; Guan, Zhuzhu; Hao, Lihong; Song, Yang; Wang, Lan; Gong, Linlin; Liu, Lu; Qi, Xiaoyu; Hou, Zhaoyuan; Shao, Shujuan

    2014-01-01

    Fructose-bisphosphate aldolase A (ALDOA) is a key enzyme in glycolysis and is responsible for catalyzing the reversible conversion of fructose-1,6-bisphosphate to glyceraldehydes-3-phosphate and dihydroxyacetone phosphate. ALDOA contributes to various cellular functions such as muscle maintenance, regulation of cell shape and mobility, striated muscle contraction, actin filament organization and ATP biosynthetic process. Here, we reported that ALDOA is a highly expressed in lung squamous cell carcinoma (LSCC) and its expression level is correlated with LSCC metastasis, grades, differentiation status and poor prognosis. Depletion of ALDOA expression in the lung squamous carcinoma NCI-H520 cells reduces the capabilities of cell motility and tumorigenesis. These data suggest that ALDOA could be a potential marker for LSCC metastasis and a therapeutic target for drug development.

  5. Photodynamic Therapy of Established Prostatic Adenocarcinoma with TOOKAD: A Biphasic Apparent Diffusion Coefficient Change as Potential Early MRI Response Marker

    Directory of Open Access Journals (Sweden)

    Vicki Plaks

    2004-05-01

    Full Text Available The goal of this study was to examine the use of diffusion-weighted magnetic resonance imaging (DW-MRI for the assessment of early progression of photodamage induced by Pd-bacteriopheophorbide (TOOKAD-based photodynamic therapy (PDT. TOOKAD is a novel second-generation photosensitizer for PDT of solid tumors developed in our laboratory and presently under clinical trials for prostate cancer (PC therapy. Using the subcutaneous human prostate adenocarcinoma WISH-PC14 xenografts in nude mice as a model, a unique biphasic change in the apparent diffusion coefficient (ADC was observed within the first 24 hours post-PDT, with initial decrease followed by an increase in ADC. Using DW-MRI, this phenomenon enables the detection of successful tumor response to PDT within 7 hours posttreatment. This process was validated by direct, histological, immunohistochemical examinations and also by evaluation of serum prostate-specific antigen (PSA levels that decreased significantly already 7 hours posttreatment. In vitro studies of multicellular cell spheroids confirmed a PDT-induced decrease in ADC, suggesting that lipid peroxidation (LPO significantly contributes to ADC decline observed after PDT. These results demonstrate that TOOKAD-based PDT successfully eradicates prostate adenocarcinoma xenografts and suggests DW-MRI to be useful for the detection of early tumor response and treatment outcome in the clinical setting.

  6. Metabolic profiling reveals potential metabolic markers associated with Hypoxia Inducible Factor-mediated signalling in hypoxic cancer cells.

    Science.gov (United States)

    Armitage, Emily G; Kotze, Helen L; Allwood, J William; Dunn, Warwick B; Goodacre, Royston; Williams, Kaye J

    2015-10-28

    Hypoxia inducible factors (HIFs) plays an important role in oxygen compromised environments and therefore in tumour survival. In this research, metabolomics has been applied to study HIFs metabolic function in two cell models: mouse hepatocellular carcinoma and human colon carcinoma, whereby the metabolism has been profiled for a range of oxygen potentials. Wild type cells have been compared to cells deficient in HIF signalling to reveal its effect on cellular metabolism under normal oxygen conditions as well as low oxygen, hypoxic and anoxic environments. Characteristic responses to hypoxia that were conserved across both cell models involved the anti-correlation between 2-hydroxyglutarate, 2-oxoglutarate, fructose, hexadecanoic acid, hypotaurine, pyruvate and octadecenoic acid with 4-hydroxyproline, aspartate, cysteine, glutamine, lysine, malate and pyroglutamate. Further to this, network-based correlation analysis revealed HIF specific pathway responses to each oxygen condition that were also conserved between cell models. From this, 4-hydroxyproline was revealed as a regulating hub in low oxygen survival of WT cells while fructose appeared to be in HIF deficient cells. Pathways surrounding these hubs were built from the direct connections of correlated metabolites that look beyond traditional pathways in order to understand the mechanism of HIF response to low oxygen environments.

  7. Identification of potential breast cancer markers in nipple discharge by protein profile analysis using two-dimensional nano-liquid chromatography/nanoelectrospray ionization-mass spectrometry.

    Science.gov (United States)

    Kurono, Sadamu; Kaneko, Yuka; Matsuura, Nariaki; Oishi, Haruki; Noguchi, Shinzaburo; Kim, Seung Jin; Tamaki, Yasuhiro; Aikawa, Takao; Kotsuma, Yoshikazu; Inaji, Hideo; Matsuura, Shuji

    2016-05-01

    This research aimed to establish a diagnostic technique for breast cancer using nipple discharge (ND), with the objective of preventive diagnosis. ND has been proposed as a source of secreted proteomes that reflect early pathological changes in the ductal-lobular epithelial microenvironment, and could thus provide breast-specific cancer biomarkers that could be accessed noninvasively as a new clinical diagnostic technique. Minute amounts of ND from patients with and without breast cancer (n = 19 and 12, respectively) were collected at the hospital and kept frozen until just before use. They were analyzed using high-pH RP peptide fractionations/low-pH RP 2D nano-LC/ESI-MS/MS. Biomarker candidates were also investigated using Western blot analysis and sandwich ELISA on ND and/or sera. We found distinct tendencies in protein expression and three candidate breast cancer biomarkers (carbonic anhydrase 2, catalase, and peroxiredoxin-2) whose levels differed significantly between ND specimens from patients with and without breast cancer. These tendencies in protein expression and markers provide new ways to identify breast cancer patients. Therefore, RP/RP 2D LC/MS/MS analyses of ND and the above three markers are supported as a new breast cancer diagnostic technique. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Salivary mRNA markers having the potential to detect oral squamous cell carcinoma segregated from oral leukoplakia with dysplasia.

    Science.gov (United States)

    Michailidou, Evangelia; Tzimagiorgis, Georgios; Chatzopoulou, Fani; Vahtsevanos, Konstantinos; Antoniadis, Konstantinos; Kouidou, Sofia; Markopoulos, Anastasios; Antoniades, Dimitrios

    2016-08-01

    In the current study the presence of extracellular IL-1B, IL-8, OAZ and SAT mRNAs in the saliva was evaluated as a tool in the early detection of oral squamous cell carcinoma. 34 patients with primary oral squamous cell carcinoma stage T1N0M0/T2N0M0, 20 patients with oral leukoplakia and dysplasia (15 patients with mild dysplasia and 5 with severe dysplasia/in situ carcinoma) and 31 matched healthy-control subjects were included in the study. The presence of IL-1B, IL-8, OAZ and SAT mRNA was evaluated in extracellular RNA isolated from saliva samples using sequence-specific primers and real-time RT-PCR. ROC curve analysis was used to estimate the ability of the biomarkers to detect oral squamous cell carcinoma patients. The data reveal that the combination of these four biomarkers provides a good predictive probability of up to 80% (AUC=0.799, p=0.002) for patients with oral squamous cell carcinoma but not patients suffering from oral leukoplakia with dysplasia. Moreover, the combination of only the two biomarkers (SAT and IL-8) also raises a high predictive ability of 75.5% (AUC=0.755, p=0.007) approximately equal to the four biomarkers suggesting the use of the two biomarkers only in the prediction model for oral squamous cell carcinoma patients limiting the economic and health cost in half. SAT and IL-8 mRNAs are present in the saliva in high quality and quantity, with a good discriminatory ability for oral squamous cell carcinoma patients only but not for patients with oral leukoplakia and dysplasia an oral potentially malignant disorder. Copyright © 2016. Published by Elsevier Ltd.

  9. Comparative genotyping of Clostridium thermocellum strains isolated from biogas plants: genetic markers and characterization of cellulolytic potential.

    Science.gov (United States)

    Koeck, Daniela E; Zverlov, Vladimir V; Liebl, Wolfgang; Schwarz, Wolfgang H

    2014-07-01

    Clostridium thermocellum is among the most prevalent of known anaerobic cellulolytic bacteria. In this study, genetic and phenotypic variations among C. thermocellum strains isolated from different biogas plants were determined and different genotyping methods were evaluated on these isolates. At least two C. thermocellum strains were isolated independently from each of nine different biogas plants via enrichment on cellulose. Various DNA-based genotyping methods such as ribotyping, RAPD (Random Amplified Polymorphic DNA) and VNTR (Variable Number of Tandem Repeats) were applied to these isolates. One novel approach - the amplification of unknown target sequences between copies of a previously discovered Random Inserted Mobile Element (RIME) - was also tested. The genotyping method with the highest discriminatory power was found to be the amplification of the sequences between the insertion elements, where isolates from each biogas plant yielded a different band pattern. Cellulolytic potentials, optimal growth conditions and substrate spectra of all isolates were characterized to help identify phenotypic variations. Irrespective of the genotyping method used, the isolates from each individual biogas plant always exhibited identical patterns. This is suggestive of a single C. thermocellum strain exhibiting dominance in each biogas plant. The genotypic groups reflect the results of the physiological characterization of the isolates like substrate diversity and cellulase activity. Conversely, strains isolated across a range of biogas plants differed in their genotyping results and physiological properties. Both strains isolated from one biogas plant had the best specific cellulose-degrading properties and might therefore achieve superior substrate utilization yields in biogas fermenters. Copyright © 2014 Elsevier GmbH. All rights reserved.

  10. Investigation of a potential scintigraphic marker of apoptosis: radioiodinated Z-Val-Ala-DL-Asp(O-methyl)-fluoromethyl ketone

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    Haberkorn, Uwe E-mail: uwe_haberkorn@med.uni-heidelberg.de; Kinscherf, Ralf; Krammer, Peter H.; Mier, Walter; Eisenhut, Michael

    2001-10-01

    The imaging of apoptosis represents an attractive diagnostic goal in the area of tumor therapy, degenerative diseases and organ transplantation. Since caspases play a key role during the early period of the intracellular signal cascade of cells undergoing apoptosis we considered benzyloxycarbonyl-Val-Ala-DL-Asp(O-methyl)-fluoromethyl ketone [Z-VAD-fmk], a pan-caspase inhibitor, as a potential apoptosis imaging agent. Applying the Tl(TFA){sub 3}/[{sup 131}I]iodide method Z-VAD-fmk was successfully labeled at the benzyloxycarbonyl protecting group. The success of radioiodination, however, depended on the presence of carrier iodide resulting in specific radioactivities of 2.6 GBq/{mu}mol and the formation of a mixture of the 2- and 4-iodophenyl derivative (61%) which could not be separated by HPLC. Uptake measurements were performed with Morris hepatoma cells (MH3924Atk8) which showed expression of the Herpes Simplex Virus thymidine kinase (HSVtk) gene. Apoptosis was induced by treatment of the cells with 25 {mu}M ganciclovir. The TUNEL assay revealed 1.3{+-}0.3 and 23{+-}1.1% apoptotic cells immediately and 24 h after therapy, respectively. A two-fold increase of [{sup 131}I]IZ-VAD-fmk uptake was found at the end of treatment with the HSVtk/suicide system which constantly remained elevated for the following 4 hours. The slow cellular influx and lack of uptake saturation of [{sup 131}I]IZ-VAD-fmk are evidence for simple diffusion as transport mechanism. In addition, the absolute cellular uptake of [{sup 131}I]IZ-VAD-fmk was found to be low. This quality was related to the rather high lipophilicity of [{sup 131}I]IZ-VAD-fmk causing unspecific binding to macromolecules in the medium. Instead of using an inhibitor, synthetic caspase substrates are currently investigated which may accumulate in the apoptotic cell by metabolic trapping thereby enhancing the imaging signal.

  11. NY-ESO-1 expression in hepatocellular carcinoma: A potential new marker for early recurrence after surgery.

    Science.gov (United States)

    Xu, Heng; Gu, Na; Liu, Zhao-Bo; Zheng, Min; Xiong, Fang; Wang, Si-Ying; Li, Ning; Lu, Jun

    2012-01-01

    NY-ESO-1 belongs to the cancer testis antigens (CTA) family, and is identified in a variety of tumors. Certain studies have demonstrated that NY-ESO-1 predicts tumor recurrence and treatment response. No reports are currently available regarding the correlation between NY-ESO-1 and the recurrence of hepatocellular carcinoma (HCC) following surgery. The purpose of the present study was to evaluate the association between NY-ESO-1 and relapse of HCC and to explore the possible mechanisms for this correlation. A total of 120 HCC patients were analyzed for the expression of NY-ESO-1 by immunohistochemistry (IHC). A stable NY-ESO-1 over-expressed HepG2 cell line (ESO-HepG2) was established to determine the biological effects of NY-ESO-1 on cell proliferation, cell cycle and migration by using the xCELLigence DP system, flow cytometry and xCELLigence SP system. NY-ESO-1 was positive in 28 of 120 (23.3%) HCC tumor tissues. NY-ESO-1 was not detectable in adjacent normal liver tissues. A close correlation was found between NY-ESO-1 expression and the recurrence of HCC following surgery (P=0.007). Kaplan-Meier analysis showed a shorter recurrence-free survival (RFS) for patients positive for NY-ESO-1 (log-rank test, P=0.003). The Cox regression model demonstrated that NY-ESO-1 expression was a significant independent predictor for the recurrence of HCC following curative surgery (P=0.022). Compared with HepG2 cells, ESO-HepG2 cells have increased migration but not proliferation ability. In conclusion, NY-ESO-1 expression is associated with worse HCC outcome following surgery, and the mechanism for this finding may be that NY-ESO-1 increases tumor cell migration.

  12. Analyses of Potential Predictive Markers and Response to Targeted Therapy in Patients with Advanced Clear-cell Renal Cell Carcinoma

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    Yan Song

    2015-01-01

    Full Text Available Background: Vascular endothelial growth factor-targeted agents are standard treatments in advanced clear-cell renal cell carcinoma (ccRCC, but biomarkers of activity are lacking. The aim of this study was to investigate the association of Von Hippel-Lindau (VHL gene status, vascular endothelial growth factor receptor (VEGFR or stem cell factor receptor (KIT expression, and their relationships with characteristics and clinical outcome of advanced ccRCC. Methods: A total of 59 patients who received targeted treatment with sunitinib or pazopanib were evaluated for determination at Cancer Hospital and Institute, Chinese Academy of Medical Sciences between January 2010 and November 2012. Paraffin-embedded tumor samples were collected and status of the VHL gene and expression of VEGFR and KIT were determined by VHL sequence analysis and immunohistochemistry. Clinical-pathological features were collected and efficacy such as response rate and Median progression-free survival (PFS and overall survival (OS were calculated and then compared based on expression status. The Chi-square test, the Kaplan-Meier method, and the Lon-rank test were used for statistical analyses. Results: Of 59 patients, objective responses were observed in 28 patients (47.5%. The median PFS was 13.8 months and median OS was 39.9 months. There was an improved PFS in patients with the following clinical features: Male gender, number of metastatic sites 2 or less, VEGFR-2 positive or KIT positive. Eleven patients (18.6% had evidence of VHL mutation, with an objective response rate of 45.5%, which showed no difference with patients with no VHL mutation (47.9%. VHL mutation status did not correlate with either overall response rate (P = 0.938 or PFS (P = 0.277. The PFS was 17.6 months and 22.2 months in VEGFR-2 positive patients and KIT positive patients, respectively, which was significantly longer than that of VEGFR-2 or KIT negative patients (P = 0.026 and P = 0.043. Conclusion

  13. Application of δ13c Values Recorded in Neoproterozoic Marine Dolomite As a Marker for Global Correlations: Significance of Major δ13c Variations for the Carbon Cycle Based on Studies of Modern Dolomite Precipitating Environments

    Science.gov (United States)

    McKenzie, J. A.; Bontognali, T. R. R.; Bahniuk, A.; Vasconcelos, C.

    2014-12-01

    Since the early Paleozoic, the average bulk δ13C value of marine carbonates has remained relatively positive varying between 0 and +4‰ with distinctive positive excursions that are associated with global changes in the carbon cycle. Unlike the Phanerozoic δ13C data for marine limestones, a major δ13C excursion has been recorded in a globally deposited Neoproterozoic marine dolomite formation, known as the cap dolostone. This excursion with δ13C values ranging systematically between -3 and -5‰ represents a global chronstratigraphic marker used to correlate the end of the major Marinoan glaciation at 636 Ma1. Does this excursion signify a primary seawater value and how might it be interpreted as a primary carbon cycle signal, considering the widespread distribution of the cap dolostone? Studies of modern dolomite precipitating environments, such as supratidal sabkhas of Abu Dhabi, U.A.E. and Qatar and coastal hypersaline lagoons of Rio de Janiero State, Brazil, indicate that microbial activity or the biological products, thereof, influence or mediate mineral formation. The precipitating solutions are sourced from normal seawater, which has experienced variable stages of concentration through evaporative processes. Comparison of δ13C values of sabkha dolomite with that formed in the hypersaline lagoons reveals that the former are always rather positive (approx. +2 to +7 ‰), whereas the latter are always negative (approx. -5‰ to -11‰). During very early diagenesis, the original δ13C value of the initial precipitate is not necessarily retained, indicating that synsedimentary processes can alter the carbon signal prior to burial and later diagenesis. However, the potential for very early lithification of microbial dolomite promotes the preservation of original δ13C values, which, thus, can be useful for evaluation of the ancient carbon cycle. 1Halverson, G.P. et al., 2005. Toward a Neoproterozoic composite carbon-isotope record, GSA Bulletin, v. 117, p

  14. Physical Fitness Measures as Potential Markers of Low Cognitive Function in Japanese Community-Dwelling Older Adults without Apparent Cognitive Problems

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    Kenji Narazaki, Eri Matsuo, Takanori Honda, Yu Nofuji, Koji Yonemoto, Shuzo Kumagai

    2014-09-01

    Full Text Available Detecting signs of cognitive impairment as early as possible is one of the most urgent challenges in preventive care of dementia. It has still been unclear whether physical fitness measures can serve as markers of low cognitive function, a sign of cognitive impairment, in older people free from dementia. The aim of the present study was to examine an association between each of five physical fitness measures and global cognition in Japanese community-dwelling older adults without apparent cognitive problems. The baseline research of the Sasaguri Genkimon Study was conducted from May to August 2011 in Sasaguri town, Fukuoka, Japan. Of the 2,629 baseline subjects who were aged 65 years or older and not certified as individuals requiring nursing care by the town, 1,552 participants without apparent cognitive problems (Mini-Mental State Examination score ≥24 were involved in the present study (59.0% of the baseline subjects, median age: 72 years, men: 40.1%. Global cognitive function was measured by the Japanese version of the Montreal Cognitive Assessment. Handgrip strength, leg strength, sit-to-stand rate, gait speed, and one-leg stand time were examined as physical fitness measures. In multiple linear regression analyses, each of the five physical fitness measures was positively associated with the Montreal Cognitive Assessment score after adjusting for age and sex (p < 0.001. These associations were preserved after additional adjustment for years of formal education, body mass index, and other confounding factors (p < 0.001. The present study first demonstrated the associations between multiple aspects of physical fitness and global cognitive function in Japanese community-dwelling older people without apparent cognitive problems. These results suggest that each of the physical fitness measures has a potential as a single marker of low cognitive function in older populations free from dementia and thereby can be useful in community

  15. Transcription analysis in the MeLiM swine model identifies RACK1 as a potential marker of malignancy for human melanocytic proliferation

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    Vincent-Naulleau Silvia

    2008-04-01

    Full Text Available Abstract Background Metastatic melanoma is a severe disease. Few experimental animal models of metastatic melanoma exist. MeLiM minipigs exhibit spontaneous melanoma. Cutaneous and metastatic lesions are histologically similar to human's. However, most of them eventually spontaneously regress. Our purpose was to investigate whether the MeLiM model could reveal markers of malignancy in human melanocytic proliferations. Results We compared the serial analysis of gene expression (SAGE between normal pig skin melanocytes and melanoma cells from an early pulmonary metastasis of MeLiM minipigs. Tag identification revealed 55 regulated genes, including GNB2L1 which was found upregulated in the melanoma library. In situ hybridisation confirmed GNB2L1 overexpression in MeLiM melanocytic lesions. GNB2L1 encodes the adaptor protein RACK1, recently shown to influence melanoma cell lines tumorigenicity. We studied the expression of RACK1 by immunofluorescence and confocal microscopy in tissues specimens of normal skin, in cutaneous and metastatic melanoma developped in MeLiM minipigs and in human patients. In pig and human samples, the results were similar. RACK1 protein was not detected in normal epidermal melanocytes. By contrast, RACK1 signal was highly increased in the cytoplasm of all melanocytic cells of superficial spreading melanoma, recurrent dermal lesions and metastatic melanoma. RACK1 partially colocalised with activated PKCαβ. In pig metastases, additional nuclear RACK1 did not associate to BDNF expression. In human nevi, the RACK1 signal was low. Conclusion RACK1 overexpression detected in situ in human melanoma specimens characterized cutaneous and metastatic melanoma raising the possibility that RACK1 can be a potential marker of malignancy in human melanoma. The MeLiM strain provides a relevant model for exploring mechanisms of melanocytic malignant transformation in humans. This study may contribute to a better understanding of melanoma

  16. CPM Is a Useful Cell Surface Marker to Isolate Expandable Bi-Potential Liver Progenitor Cells Derived from Human iPS Cells

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    Taketomo Kido

    2015-10-01

    Full Text Available To develop a culture system for large-scale production of mature hepatocytes, liver progenitor cells (LPCs with a high proliferation potential would be advantageous. We have found that carboxypeptidase M (CPM is highly expressed in embryonic LPCs, hepatoblasts, while its expression is decreased along with hepatic maturation. Consistently, CPM expression was transiently induced during hepatic specification from human-induced pluripotent stem cells (hiPSCs. CPM+ cells isolated from differentiated hiPSCs at the immature hepatocyte stage proliferated extensively in vitro and expressed a set of genes that were typical of hepatoblasts. Moreover, the CPM+ cells exhibited a mature hepatocyte phenotype after induction of hepatic maturation and also underwent cholangiocytic differentiation in a three-dimensional culture system. These results indicated that hiPSC-derived CPM+ cells share the characteristics of LPCs, with the potential to proliferate and differentiate bi-directionally. Thus, CPM is a useful marker for isolating hiPSC-derived LPCs, which allows development of a large-scale culture system for producing hepatocytes and cholangiocytes.

  17. Clinical significance of epithelial mesenchymal transition (EMT) in chronic obstructive pulmonary disease (COPD): potential target for prevention of airway fibrosis and lung cancer.

    Science.gov (United States)

    Sohal, Sukhwinder Singh; Mahmood, Malik Quasir; Walters, Eugene Haydn

    2014-12-01

    Unfortunately, the research effort directed into chronic obstructive pulmonary disease (COPD) has been disproportionately weak compared to its social importance, and indeed it is the least researched of all common chronic conditions. Tobacco smoking is the major etiological factor. Only 25% of smokers will develop "classic" COPD; in these vulnerable individuals the progression of airways disease to symptomatic COPD occurs over two or more decades. We know surprisingly little about the pathobiology of COPD airway disease, though small airway fibrosis and obliteration are likely to be the main contributors to physiological airway dysfunction and these features occur earlier than any subsequent development of emphysema. One potential mechanism contributing to small airway fibrosis/obliteration and change in extracellular matrix (ECM) is epithelial mesenchymal transition (EMT), so called Type-II EMT. When associated with angiogenesis (Type-III EMT) it may well also be a link with the development of lung (airway) cancer which is closely associated with COPD. Active EMT in COPD may help to explain why lung cancer is so common in smokers and also the core pathophysiology of small airway fibrosis. Better understanding may lead to new markers for incipient neoplasia, and better preventive management of patients. There is serious need to understand key components of airway EMT in smokers and COPD, and to demarcate novel drug targets for the prevention of lung cancer and airway fibrosis, as well as better secondary management of COPD. Since over 90% of human cancer arises in epithelia and the involvement of EMT in all of these may be a central paradigm, insights gained in COPD may have important generalizable value.

  18. A pilot study on potential plasma hypoxia markers in the radiotherapy of non-small cell lung cancer. Osteopontin, carbonic anhydrase IX and vascular endothelial growth factor

    Energy Technology Data Exchange (ETDEWEB)

    Ostheimer, C.; Bache, M.; Guettler, A.; Vordermark, D. [Martin-Luther-University Halle-Wittenberg, Department of Radiation Oncology, Halle (Saale) (Germany); Kotzsch, M. [Technical University Dresden, Department of Pathology, Dresden (Germany)

    2014-03-15

    Hypoxic radioresistance plays a critical role in the radiotherapy of cancer and adversely impacts prognosis and treatment response. This prospective study investigated the interrelationship and the prognostic significance of several hypoxia-related proteins in non-small cell lung cancer (NSCLC) patients treated by radiotherapy ± chemotherapy. Pretreatment osteopontin (OPN), vascular endothelial growth factor (VEGF) and carbonic anhydrase IX (CA IX) plasma levels were determined by ELISA in 55 NSCLC (M0) patients receiving 66 Gy curative-intent radiotherapy or chemoradiation. Marker correlation, association with clinicopathological parameters and the prognostic value of a biomarker combination was evaluated. All biomarkers were linearly correlated and linked to different clinical parameters including lung function, weight loss (OPN), gross tumor volume (VEGF) and T stage (CA IX). High OPN (p = 0.03), VEGF (p = 0.02) and CA IX (p = 0.04) values were significantly associated with poor survival. Double marker combination additively increased the risk of death by a factor of 2 and high plasma levels of the triple combination OPN/VEGF/CA IX yielded a 5.9-fold risk of death (p = 0.009). The combined assessment of OPN/VEGF/CA IX correlated independently with prognosis (p = 0.03) in a multivariate Cox regression model including N stage, T stage and GTV. This pilot study suggests that a co-detection augments the prognostic value of single markers and that the integration of OPN, VEGF and CA IX into a hypoxic biomarker profile for the identification of patients with largely hypoxic and radioresistant tumors should be further evaluated. (orig.) [German] Hypoxische Radioresistenz spielt eine kritische Rolle in der Radiotherapie maligner Tumoren und beeinflusst Prognose und Therapieansprechen negativ. Diese prospektive Studie untersuchte den Zusammenhang und die prognostische Bedeutung einiger hypoxieassoziierter Proteine bei Patienten mit nicht-kleinzelligem Bronchialkarzinom

  19. MR spectroscopy of intracranial tuberculomas: A singlet peak at 3.8 ppm as potential marker to differentiate them from malignant tumors

    Science.gov (United States)

    Alfaro, David; Martinot, Carlos; Fayed, Nicolas; Gaskill-Shipley, Mary

    2015-01-01

    Purpose The diagnosis of intracranial tuberculomas is often challenging. Our purpose is to describe the most common metabolic patterns of tuberculomas by MR spectroscopy (MRS) with emphasis on potential specific markers. Methods Single-voxel MRS short echo time was performed in 13 cases of tuberculomas proven by histology and/or response to anti-mycobacterial therapy. For comparison MRS was also performed in 19 biopsy-proven malignant tumors (13 high-grade gliomas and six metastasis). Presence of metabolic peaks was assessed visually and categorical variables between groups were compared using chi-square. Metabolite ratios were compared using Mann-Whitney test and diagnostic accuracy of the metabolite ratios was compared using receiver-operating characteristic (ROC) curves analysis. Results Spectroscopic peaks representing lipids and glutamate/glutamine (Glx) as well as a peak at ∼3.8 ppm were well defined in 77% (10/13), 77% (10/13) and 69% (nine of 13) of tuberculomas, respectively. Lipid and Glx peaks were also present in most of the malignant lesions, 79% (15/19) and 74% (14/19) respectively. However, a peak at ∼3.8 ppm was present in only 10% (two of 19) of the tumor cases (p < 0.001). Higher Cho/Cr and mI/Cr ratios helped discriminate malignant lesions with an area under the ROC curve of 0.86 (SE: 0.078, p < 0.002, CI: 0.7–1) and 0.8 (SE: 0.1, p < 0.009, CI: 0.6–1), respectively. Threshold values between 1.7–1.9 for Cho/Cr and 0.8–0.9 for mI/Cr provided high specificity (91% for both metabolites) and adequate sensitivity (75% and 80%, respectively) for discrimination of malignant lesions. Conclusion A singlet peak at ∼3.8 ppm is present in the majority of tuberculomas and absent in most malignant tumors, potentially a marker to differentiate these lesions. The assignment of the peak is difficult from our analysis; however, guanidinoacetate (Gua) is a possibility. Higher Cho/Cr and mI/Cr ratios should favor malignant lesions

  20. Isolation and characterization of CD276+/HLA-E+ human subendocardial mesenchymal stem cells from chronic heart failure patients: analysis of differentiative potential and immunomodulatory markers expression.

    Science.gov (United States)

    Anzalone, Rita; Corrao, Simona; Lo Iacono, Melania; Loria, Tiziana; Corsello, Tiziana; Cappello, Francesco; Di Stefano, Antonino; Giannuzzi, Pantaleo; Zummo, Giovanni; Farina, Felicia; La Rocca, Giampiero

    2013-01-01

    Mesenchymal stem cells (MSCs) are virtually present in all postnatal organs as well as in perinatal tissues. MSCs can be differentiated toward several mature cytotypes and interestingly hold potentially relevant immunomodulatory features. Myocardial infarction results in severe tissue damage, cardiomyocyte loss, and eventually heart failure. Cellular cardiomyoplasty represents a promising approach for myocardial repair. Clinical trials using MSCs are underway for a number of heart diseases, even if their outcomes are hampered by low long-term improvements and the possible presence of complications related to cellular therapy administration. Therefore, elucidating the presence and role of MSCs that reside in the post-infarct human heart should provide essential alternatives for therapy. In the current article we show a novel method to reproducibly isolate and culture MSCs from the subendocardial zone of human left ventricle from patients undergoing heart transplant for post-infarct chronic heart failure (HSE-MSCs, human subendocardial mesenchymal stem cells). By using both immunocytochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR), we demonstrated that these cells do express key MSCs markers and do express heart-specific transcription factors in their undifferentiated state, while lacking strictly cardiomyocyte-specific proteins. Moreover, these cells do express immunomodulatory molecules that should disclose their further potential in immune modulation processes in the post-infarct microenvironment. Another novel datum of potentially relevant interest is the expression of cardiac myosin heavy chain at nucclear level in HSE-MSCs. Standard MSCs trilineage differentiation experiments were also performed. The present paper adds new data on the basic biological features of heart-resident MSCs that populate the organ following myocardial infarction. The use of heart-derived MSCs to promote in-organ repair or as a cellular source for cardiomyoplasty

  1. Evaluation of peripheral serotonin content and α2-adrenergic receptor function as potential markers for life-long recurrent depressive disorder by using methodological improvements.

    Science.gov (United States)

    Aleksovski, Boris; Novotni, Antoni; Vujović, Viktorija; Rendevski, Vladimir; Manusheva, Nensi; Neceva, Violeta; Filipce, Ana; Risteski, Aleksandar; Aleksovski, Vasko; Gjorgoski, Icko

    2017-12-07

    We aimed to evaluate the role and the relations between peripheral platelet serotonin content, blood plasma serotonin concentration and the function of platelet α 2 -adrenergic receptors (α 2 -AR) as potential state or trait biomarkers for recurrent depressive disorder (RDD). 26 drug-free patients with life-long RDD and 31 healthy controls were included in the study. Several methodological improvements in blood collection and platelet isolation were implemented following the present standards in Haematology and Light transmission aggregometry. Our results have shown lower platelet serotonin content, higher plasma serotonin concentration and desensitization of platelet α 2 -AR in patients with RDD. The variables were found heterogeneous and mainly influenced by the clinical characteristics of the current episode. High amplitude of the α 2 -AR correlated with severe anxious symptoms and high platelet serotonin content (as well as low plasma serotonin levels) were associated with psychotic symptoms. The evaluated peripheral markers reflect only state (but not trait) abnormalities in patients with current severe episode of RDD. The observed peripheral α 2 -AR and serotonin abnormalities are mutually not related and they are probably triggered by different mechanisms.

  2. Proteomic Analysis of Plasma-Purified VLDL, LDL, and HDL Fractions from Atherosclerotic Patients Undergoing Carotid Endarterectomy: Identification of Serum Amyloid A as a Potential Marker

    Directory of Open Access Journals (Sweden)

    Antonio J. Lepedda

    2013-01-01

    Full Text Available Apolipoproteins are very heterogeneous protein family, implicated in plasma lipoprotein structural stabilization, lipid metabolism, inflammation, or immunity. Obtaining detailed information on apolipoprotein composition and structure may contribute to elucidating lipoprotein roles in atherogenesis and to developing new therapeutic strategies for the treatment of lipoprotein-associated disorders. This study aimed at developing a comprehensive method for characterizing the apolipoprotein component of plasma VLDL, LDL, and HDL fractions from patients undergoing carotid endarterectomy, by means of two-dimensional electrophoresis (2-DE coupled with Mass Spectrometry analysis, useful for identifying potential markers of plaque presence and vulnerability. The adopted method allowed obtaining reproducible 2-DE maps of exchangeable apolipoproteins from VLDL, LDL, and HDL. Twenty-three protein isoforms were identified by peptide mass fingerprinting analysis. Differential proteomic analysis allowed for identifying increased levels of acute-phase serum amyloid A protein (AP SAA in all lipoprotein fractions, especially in LDL from atherosclerotic patients. Results have been confirmed by western blotting analysis on each lipoprotein fraction using apo AI levels for data normalization. The higher levels of AP SAA found in patients suggest a role of LDL as AP SAA carrier into the subendothelial space of artery wall, where AP SAA accumulates and may exert noxious effects.

  3. Dickkopf-3 As a New Potential Marker for Neoangiogenesis in Colorectal Cancer: Expression in Cancer Tissue and Adjacent Non-Cancerous Tissue

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    Matthias Zitt

    2008-01-01

    Full Text Available Gene expression of Dickkopf-3 (Dkk-3 has been shown to be upregulated in tumor endothelium of colorectal cancer (CRC. For the first time, we analyzed Dkk-3 protein expression in CRC and its potential as a marker for neoangiogenesis. We used tissue microarrays (TMAs to investigate Dkk-3 in microvessels of 403 CRC samples, 318 appropriate adjacent non-cancerous samples and 127 normal colorectal samples. Of cancer samples with CD31-positive microvessels, 67.7% were positive for Dkk-3. Dkk-3 staining was demonstrated in endothelial cells of all microvessels in nearly all cases. Dkk-3-positive samples showed a higher mean microvessel count than did Dkk-3-negative samples (P=0.001. Dkk-3 expression increased with rising numbers of microvessels per sample (P<0.0001. In adjacent samples with CD31-positive microvessels, 56% were Dkk-3-positive in all microvessels. Similar to cancer samples, Dkk-3-positive adjacent samples had a higher mean microvessel count than did Dkk-3-negative samples (P<0.0001, and Dkk-3 expression also increased with rising numbers of microvessels (P<0.0001. All microvessels in normal mucosa samples were negative for Dkk-3.

  4. Development and validation of allele-specific SNP/indel markers for eight yield-enhancing genes using whole-genome sequencing strategy to increase yield potential of rice, Oryza sativa L.

    Science.gov (United States)

    Kim, Sung-Ryul; Ramos, Joie; Ashikari, Motoyuki; Virk, Parminder S; Torres, Edgar A; Nissila, Eero; Hechanova, Sherry Lou; Mauleon, Ramil; Jena, Kshirod K

    2016-12-01

    Rice is one of the major staple foods in the world, especially in the developing countries of Asia. Its consumption as a dietary source is also increasing in Africa. To meet the demand for rice to feed the increasing human population, increasing rice yield is essential. Improving the genetic yield potential of rice is one ideal solution. It is imperative to introduce the identified yield-enhancing gene(s) into modern rice cultivars for the rapid improvement of yield potential through marker-assisted breeding. We report the development of PCR-gel-based markers for eight yield-related functional genes (Gn1a, OsSPL14, SCM2, Ghd7, DEP1, SPIKE, GS5, and TGW6) to introduce yield-positive alleles from the donor lines. Six rice cultivars, including three each of donor and recipient lines, respectively, were sequenced by next-generation whole-genome sequencing to detect DNA polymorphisms between the genotypes. Additionally, PCR products containing functional nucleotide polymorphism (FNP) or putative FNPs for yield-related genes were sequenced. DNA polymorphisms discriminating yield-positive alleles and non-target alleles for each gene were selected through sequence analysis and the allele-specific PCR-gel-based markers were developed. The markers were validated with our intermediate breeding lines produced from crosses between the donors and 12 elite indica rice cultivars as recipients. Automated capillary electrophoresis was tested and fluorescence-labeled SNP genotyping markers (Fluidigm SNP genotyping platform) for Gn1a, OsSPL14, Ghd7, GS5, and GS3 genes were developed for high-throughput genotyping. The SNP/indel markers linked to yield related genes functioned properly in our marker-assisted breeding program with identified high yield potential lines. These markers can be utilized in local favorite rice cultivars for yield enhancement. The marker designing strategy using both next generation sequencing and Sanger sequencing methods can be used for suitable marker

  5. Candidate SNP Markers of Gender-Biased Autoimmune Complications of Monogenic Diseases Are Predicted by a Significant Change in the Affinity of TATA-Binding Protein for Human Gene Promoters

    Science.gov (United States)

    Ponomarenko, Mikhail P.; Arkova, Olga; Rasskazov, Dmitry; Ponomarenko, Petr; Savinkova, Ludmila; Kolchanov, Nikolay

    2016-01-01

    Some variations of human genome [for example, single nucleotide polymorphisms (SNPs)] are markers of hereditary diseases and drug responses. Analysis of them can help to improve treatment. Computer-based analysis of millions of SNPs in the 1000 Genomes project makes a search for SNP markers more targeted. Here, we combined two computer-based approaches: DNA sequence analysis and keyword search in databases. In the binding sites for TATA-binding protein (TBP) in human gene promoters, we found candidate SNP markers of gender-biased autoimmune diseases, including rs1143627 [cachexia in rheumatoid arthritis (double prevalence among women)]; rs11557611 [demyelinating diseases (thrice more prevalent among young white women than among non-white individuals)]; rs17231520 and rs569033466 [both: atherosclerosis comorbid with related diseases (double prevalence among women)]; rs563763767 [Hughes syndrome-related thrombosis (lethal during pregnancy)]; rs2814778 [autoimmune diseases (excluding multiple sclerosis and rheumatoid arthritis) underlying hypergammaglobulinemia in women]; rs72661131 and rs562962093 (both: preterm delivery in pregnant diabetic women); and rs35518301, rs34166473, rs34500389, rs33981098, rs33980857, rs397509430, rs34598529, rs33931746, rs281864525, and rs63750953 (all: autoimmune diseases underlying hypergammaglobulinemia in women). Validation of these predicted candidate SNP markers using the clinical standards may advance personalized medicine. PMID:27092142

  6. (SSR) markers

    African Journals Online (AJOL)

    uwerhiavwe

    Variability was observed for six ... rapid increase in climate change, so there is need to develop high yielding ... the past decade including assessment of genetic diversity in maize ... The SSR gel images and marker data were processed using.

  7. Gastroprotective potential of Buddleja scordioides Kunth Scrophulariaceae infusions; effects into the modulation of antioxidant enzymes and inflammation markers in an in vivo model.

    Science.gov (United States)

    Díaz-Rivas, J O; Herrera-Carrera, E; Gallegos-Infante, J A; Rocha-Guzmán, N E; González-Laredo, R F; Moreno-Jiménez, M R; Ramos-Gómez, M; Reynoso-Camacho, R; Larrosa-Pérez, M; Gallegos-Corona, M A

    2015-07-01

    A common plant used to treat several gastric disorders is Buddleja scordioides Kunth, commonly known as salvilla. To detect inflammatory markers, in order to evaluate the gastroprotective potential of salvilla infusions, as this could have beneficial impact on the population exposed to gastric ulcers and colitis. The present work attempted infusions were prepared with B. scordioides (1% w/w) lyophilized and stored. Total phenolic content and GC-MS analysis were performed. Wistar rats were divided into five groups (n=8), a negative vehicle control, an indomethacin group, and three experimental groups, named preventive, curative, and suppressive. All rats were sacrificed under deep ether anesthesia (6h) after the last oral administration of indomethacin/infusion. The rat stomachs were promptly excised, weighed, and chilled in ice-cold and 0.9% NaCl. Histological analysis, nitrites quantification and immunodetection assays were done. B. scordioides infusions markedly reduced the visible hemorrhagic lesions induced by indomethacin in rat stomachs, also showed down-regulation of COX2, IL-8 and TNFα and up-regulation of COX-1 with a moderate down-regulation of NFkB and lower amount of nitrites. However, this behavior was dependent on the treatment, showing most down-regulation of COX-2, TNFα and IL-8 in the curative treatment; more down-regulation of NF-kB in the preventive treatment; and more up-regulation of COX-1 for the suppressor and preventive treatments. The anti-inflammatory potential of B. scordioides infusions could be related with the presence of polyphenols as quercetin in the infusion and how this one is consumed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Circulating oxysterol metabolites as potential new surrogate markers in patients with hormone receptor-positive breast cancer: Results of the OXYTAM study.

    Science.gov (United States)

    Dalenc, Florence; Iuliano, Luiggi; Filleron, Thomas; Zerbinati, Chiara; Voisin, Maud; Arellano, Cécile; Chatelut, Etienne; Marquet, Pierre; Samadi, Mohammad; Roché, Henri; Poirot, Marc; Silvente-Poirot, Sandrine

    2017-05-01

    Accumulating evidence indicates that cholesterol oxygenation products, also known as oxysterols (OS), are involved in breast cancer (BC) promotion. The impact of Tam, as well as aromatase inhibitors (AI), an alternative BC endocrine therapy (ET), on OS metabolism in patients is currently unknown. We conducted a prospective clinical study in BC patients receiving Tam (n=15) or AI (n=14) in adjuvant or in metastatic settings. The primary end point was the feasibility of detecting and quantifying 11 different OS in the circulation of patients before and after 28days of treatment with Tam or AI. Key secondary end points were the measurements of variations in the concentrations of OS according to differences between patients and treatments. OS profiling in the serum of patients was determined by gas chromatography coupled to mass spectrometry. OS profiling was conducted in all patients both at baseline and during treatment regimens. An important inter-individual variability was observed for each OS. Interestingly 5,6β-epoxycholesterol relative concentrations significantly increased in the entire population (p=0.0109), while no increase in Cholestane-triol (CT) levels was measured. Interestingly, we found that, in contrast to AI, Tam therapy significantly decreased blood levels of 24-hydroxycholesterol (24-HC), 7α-HC and 25-HC (a tumor promoter) (p=0.0007, p=0.0231 and p=0.0231, respectively), whereas 4β-HC levels increased (p=0.0010). Interestingly, levels of 27-HC (a tumor promoter) significantly increased in response to AI (p=0.0342), but not Tam treatment. According to these results, specific OS are promising candidate markers of Tam and AI efficacy. Thus, further clinical investigations are needed to confirm the use of oxysterols as biomarkers of both prognosis and/or the efficacy of ET. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Temporal course of pregnancy-associated plasma protein-A in angioplasty-treated ST-elevation myocardial infarction patients and potential significance of concomitant heparin administration

    DEFF Research Database (Denmark)

    Terkelsen, Christian J; Oxvig, Claus; Nørgaard, Bjarne L

    2009-01-01

    Pregnancy-associated plasma protein-A (PAPP-A) is a putative plaque instability marker. In acute coronary syndromes, the disrupted culprit plaque contains abundant PAPP-A, and circulating PAPP-A levels predict clinical outcomes. Determinants of circulating PAPP-A levels, however, are not fully...

  10. Whole-genome association analysis of pork meat pH revealed three significant regions and several potential genes in Finnish Yorkshire pigs.

    Science.gov (United States)

    Verardo, Lucas L; Sevón-Aimonen, Marja-Liisa; Serenius, Timo; Hietakangas, Ville; Uimari, Pekka

    2017-02-13

    One of the most commonly used quality measurements of pork is pH measured 24 h after slaughter. The most probable mode of inheritance for this trait is oligogenic with several known major genes, such as PRKAG3. In this study, we used whole-genome SNP genotypes of over 700 AI boars; after a quality check, 42,385 SNPs remained for association analysis. All the boars were purebred Finnish Yorkshire. To account for relatedness of the animals, a pedigree-based relationship matrix was used in a mixed linear model to test the effect of SNPs on pH measured from loin. A bioinformatics analysis was performed to identify the most promising genes in the significant regions related to meat quality. Genome-wide association study (GWAS) revealed three significant chromosomal regions: one on chromosome 3 (39.9 Mb-40.1 Mb) and two on chromosome 15 (58.5 Mb-60.5 Mb and 132 Mb-135 Mb including PRKAG3). A conditional analysis with a significant SNP in the PRKAG3 region, MARC0083357, as a covariate in the model retained the significant SNPs on chromosome 3. Even though linkage disequilibrium was relatively high over a long distance between MARC0083357 and other significant SNPs on chromosome 15, some SNPs retained their significance in the conditional analysis, even in the vicinity of PRKAG3. The significant regions harbored several genes, including two genes involved in cyclic AMP (cAMP) signaling: ADCY9 and CREBBP. Based on functional and transcription factor-gene networks, the most promising candidate genes for meat pH are ADCY9, CREBBP, TRAP1, NRG1, PRKAG3, VIL1, TNS1, and IGFBP5, and the key transcription factors related to these genes are HNF4A, PPARG, and Nkx2-5. Based on SNP association, pathway, and transcription factor analysis, we were able to identify several genes with potential to control muscle cell homeostasis and meat quality. The associated SNPs can be used in selection for better pork. We also showed that post-GWAS analysis reveals important information about the

  11. Dual-specificity tyrosine-regulated kinase 2 is a suppressor and potential prognostic marker for liver metastasis of colorectal cancer.

    Science.gov (United States)

    Ito, Daisuke; Yogosawa, Satomi; Mimoto, Rei; Hirooka, Shinichi; Horiuchi, Takashi; Eto, Ken; Yanaga, Katsuhiko; Yoshida, Kiyotsugu

    2017-08-01

    Colorectal cancer is a common cancer and a leading cause of cancer-related death worldwide. The liver is a dominant metastatic site for patients with colorectal cancer. Molecular mechanisms that allow colorectal cancer cells to form liver metastases are largely unknown. Activation of epithelial-mesenchymal transition is the key step for metastasis of cancer cells. We recently reported that dual-specificity tyrosine-regulated kinase 2 (DYRK2) controls epithelial-mesenchymal transition in breast cancer and ovarian serous adenocarcinoma. The aim of this study is to clarify whether DYRK2 regulates liver metastases of colorectal cancer. We show that the ability of cell invasion and migration was abrogated in DYRK2-overexpressing cells. In an in vivo xenograft model, liver metastatic lesions were markedly diminished by ectopic expression of DYRK2. Furthermore, we found that patients whose liver metastases expressed low DYRK2 levels had significantly worse overall and disease-free survival. Given the findings that DYRK2 regulates cancer cell metastasis, we concluded that the expression status of DYRK2 could be a predictive marker for liver metastases of colorectal cancer. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  12. Expression of the Matrix Metalloproteases 2, 14, 24, and 25 and Tissue Inhibitor 3 as Potential Molecular Markers in Advanced Human Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Sol de la Peña

    2014-01-01

    Full Text Available Background. During progression of gastric cancer (GC, degradation of the extracellular matrix is mediated by the matrix metalloproteases (MMPs and their tissue inhibitors (TIMPs: changes in the expression of these have been related to unfavorable prognosis in GC. Objective. To analyze the expression of certain MMPs and TIMPs in chronic superficial gastritis (SG and GC. Methods. The expression of MMPs and TIMPs was determined using qRT-PCR; the expression was classified, using threshold cycle (CT values, as very high (CT≤25, high (CT=26–30, moderate (CT=31–35, low (CT=36–39, or not detected (CT=40. Strength of association was estimated between the proteins, which were detected by Western blot, and the risk of developing GC. Results. We found a high expression of MMP1, MMP2, MMP14, TIMP1, and TIMP3; moderate one of MMP9 and MMP25, and low one of MMP13 and MMP24 in both tissues. In absolute mRNA levels, significant differences were found in expression of MMP2, MMP24, and MMP25, which are overexpressed in GC compared with SG. The presence of the proteins MMP-14 and TIMP-3 was associated with the risk of developing GC. Conclusions. We consider that MMP2, MMP24, and MMP25 and the proteins MMP-14 and TIMP-3 could be candidates for prognostic molecular markers in GC.

  13. Apoplastic water fraction and rehydration techniques introduce significant errors in measurements of relative water content and osmotic potential in plant leaves.

    Science.gov (United States)

    Arndt, Stefan K; Irawan, Andi; Sanders, Gregor J

    2015-12-01

    Relative water content (RWC) and the osmotic potential (π) of plant leaves are important plant traits that can be used to assess drought tolerance or adaptation of plants. We estimated the magnitude of errors that are introduced by dilution of π from apoplastic water in osmometry methods and the errors that occur during rehydration of leaves for RWC and π in 14 different plant species from trees, grasses and herbs. Our data indicate that rehydration technique and length of rehydration can introduce significant errors in both RWC and π. Leaves from all species were fully turgid after 1-3 h of rehydration and increasing the rehydration time resulted in a significant underprediction of RWC. Standing rehydration via the petiole introduced the least errors while rehydration via floating disks and submerging leaves for rehydration led to a greater underprediction of RWC. The same effect was also observed for π. The π values following standing rehydration could be corrected by applying a dilution factor from apoplastic water dilution using an osmometric method but not by using apoplastic water fraction (AWF) from pressure volume (PV) curves. The apoplastic water dilution error was between 5 and 18%, while the two other rehydration methods introduced much greater errors. We recommend the use of the standing rehydration method because (1) the correct rehydration time can be evaluated by measuring water potential, (2) overhydration effects were smallest, and (3) π can be accurately corrected by using osmometric methods to estimate apoplastic water dilution. © 2015 Scandinavian Plant Physiology Society.

  14. Eosinophil granule proteins ECP and EPX as markers for a potential early-stage inflammatory lesion in female genital schistosomiasis (FGS)

    DEFF Research Database (Denmark)

    Ramarokoto, Charles Emile; Kildemoes, Anna M. O.; Randrianasolo, Bodo Sahondra

    2014-01-01

    BACKGROUND: Genital granulomas induced by Schistosoma haematobium eggs can manifest as different lesion types visible by colposcopy; rubbery papules (RP), homogenous sandy patches (HSP) and grainy sandy patches (GSP). Pronounced tissue eosinophilia is a candidate marker for active S. haematobium ...

  15. Differences in Virulence Markers between Helicobacter pylori Strains from Iraq and Those from Iran: Potential Importance of Regional Differences in H. pylori-Associated Disease▿

    Science.gov (United States)

    Hussein, Nawfal R.; Mohammadi, Marjan; Talebkhan, Yeganeh; Doraghi, Masoumeh; Letley, Darren P.; Muhammad, Merdan K.; Argent, Richard H.; Atherton, John C.

    2008-01-01

    Helicobacter pylori causes peptic ulceration and gastric adenocarcinoma; the latter is common in Iran but not in Iraq. We hypothesized that more virulent H. pylori strains may be found in Iran than in Iraq and so compared established and newly described virulence factors in strains from these countries. We studied 59 unselected dyspeptic patients from Iran and 49 from Iraq. cagA was found in similar proportions of strains from both countries (76% in Iran versus 71% in Iraq) and was significantly associated with peptic ulcer disease in Iraq (P ≤ 0.01) but not in Iran. cagA alleles encoding four or more tyrosine phosphorylation motifs were found in 12% of the Iranian strains but none of the Iraqi strains (P = 0.02). There were no significant differences in the vacA signal-, middle-, or intermediate-region types between Iranian and Iraqi strains. Among the strains from Iran, vacA genotypes showed no specific peptic ulcer associations, but among the strains from Iraq, vacA i1 strains were associated with gastric ulcer (P ≤ 0.02), mimicking their previously demonstrated association with gastric cancer in Iran. dupA was found in similar proportions of Iranian and Iraqi strains (38% and 32%, respectively) and was associated with peptic ulceration in Iraqi patients (P ≤ 0.01) but not Iranian patients. H. pylori strains from Iraq and Iran possess virulence factors similar to those in Western countries. The presence of cagA with more phosphorylation motifs in Iranian strains may contribute to the higher incidence of gastric cancer. However, the association between strain virulence markers and disease in Iraq but not Iran suggests that other host and environmental factors may be more important in the disease-prone Iranian population. PMID:18353934

  16. Four variants in transferrin and HFE genes as potential markers of iron deficiency anaemia risk: an association study in menstruating women

    Directory of Open Access Journals (Sweden)

    Arroyo-Pardo Eduardo

    2011-10-01

    Full Text Available Abstract Background Iron deficiency anaemia is a worldwide health problem in which environmental, physiologic and genetic factors play important roles. The associations between iron status biomarkers and single nucleotide polymorphisms (SNPs known to be related to iron metabolism were studied in menstruating women. Methods A group of 270 Caucasian menstruating women, a population group at risk of iron deficiency anaemia, participated in the study. Haematological and biochemical parameters were analysed and 10 selected SNPs were genotyped by minisequencing assay. The associations between genetic and biochemical data were analysed by Bayesian Model Averaging (BMA test and decision trees. Dietary intake of a representative subgroup of these volunteers (n = 141 was assessed, and the relationship between nutrients and iron biomarkers was also determined by linear regression. Results Four variants, two in the transferrin gene (rs3811647, rs1799852 and two in the HFE gene (C282Y, H63D, explain 35% of the genetic variation or heritability of serum transferrin in menstruating women. The minor allele of rs3811647 was associated with higher serum transferrin levels and lower transferrin saturation, while the minor alleles of rs1799852 and the C282Y and H63D mutations of HFE were associated with lower serum transferrin levels. No association between nutrient intake and iron biomarkers was found. Conclusions In contrast to dietary intake, these four SNPs are strongly associated with serum transferrin. Carriers of the minor allele of rs3811647 present a reduction in iron transport to tissues, which might indicate higher iron deficiency anaemia risk, although the simultaneous presence of the minor allele of rs1799852 and HFE mutations appear to have compensatory effects. Therefore, it is suggested that these genetic variants might potentially be used as markers of iron deficiency anaemia risk.

  17. Age-specific gene expression signatures for breast tumors and cross-species conserved potential cancer progression markers in young women.

    Science.gov (United States)

    Colak, Dilek; Nofal, Asmaa; Albakheet, Albandary; Nirmal, Maimoona; Jeprel, Hatim; Eldali, Abdelmoneim; Al-Tweigeri, Taher; Tulbah, Asma; Ajarim, Dahish; Malik, Osama Al; Inan, Mehmet S; Kaya, Namik; Park, Ben H; Bin Amer, Suad M

    2013-01-01

    Breast cancer in young women is more aggressive with a poorer prognosis and overall survival compared to older women diagnosed with the disease. Despite recent research, the underlying biology and molecular alterations that drive the aggressive nature of breast tumors associated with breast cancer in young women have yet to be elucidated. In this study, we performed transcriptomic profile and network analyses of breast tumors arising in Middle Eastern women to identify age-specific gene signatures. Moreover, we studied molecular alterations associated with cancer progression in young women using cross-species comparative genomics approach coupled with copy number alterations (CNA) associated with breast cancers from independent studies. We identified 63 genes specific to tumors in young women that showed alterations distinct from two age cohorts of older women. The network analyses revealed potential critical regulatory roles for Myc, PI3K/Akt, NF-κB, and IL-1 in disease characteristics of breast tumors arising in young women. Cross-species comparative genomics analysis of progression from pre-invasive ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) revealed 16 genes with concomitant genomic alterations, CCNB2, UBE2C, TOP2A, CEP55, TPX2, BIRC5, KIAA0101, SHCBP1, UBE2T, PTTG1, NUSAP1, DEPDC1, HELLS, CCNB1, KIF4A, and RRM2, that may be involved in tumorigenesis and in the processes of invasion and progression of disease. Array findings were validated using qRT-PCR, immunohistochemistry, and extensive in silico analyses of independently performed microarray datasets. To our knowledge, this study provides the first comprehensive genomic analysis of breast cancer in Middle Eastern women in age-specific cohorts and potential markers for cancer progression in young women. Our data demonstrate that cancer appearing in young women contain distinct biological characteristics and deregulated signaling pathways. Moreover, our integrative genomic and cross

  18. Simultaneous detection of multiple mRNA markers CK19, CEA, c-Met, Her2/neu and hMAM with membrane array, an innovative technique with a great potential for breast cancer diagnosis.

    Science.gov (United States)

    Chen, Chung-Chi; Hou, Ming-Feng; Wang, Jaw-Yuan; Chang, Tsai-Wang; Lai, Dan-Yu; Chen, Yi-Fang; Hung, Sung-Yu; Lin, Shiu-Ru

    2006-08-28

    The objective of this study was mainly to develop and evaluate a membrane array-based method simultaneously detecting the expression levels of a multiple mRNA marker panel in the peripheral blood for used in complementary breast cancer diagnosis. The mRNA markers employed included cytokeratin 19 (CK-19), carcinoembryonic antigen (CEA), c-Met, Her2/neu, and mammaglobin (hMAM). The specimens of peripheral blood were collected from 80 healthy women and 102 female patients with breast cancer. The expression levels of molecular markers were evaluated by real-time Q-PCR and membrane array. Data obtained from real-time Q-PCR and membrane array were subjected to linear regression analysis, revealing that there was a high degree of correlation between the results of these two methods (r=0.979, Pmembrane array assay with a combined panel of five mRNA markers was demonstrated to achieve sensitivity of 80.6%, and specificity of 83.8% for breast cancer detection, much higher than those of analysis of single marker. In addition, we demonstrated that the membrane array method could detect circulating cancer cells at a density as low as five cancer cells per 1 ml of blood. The analysis of correlation between the outcome of membrane array and clinicopathological characteristics indicated that overexpression of the multiple marker panel was significantly correlated with tumor size (P=0.030) and TNM stage (0.009). In conclusion, the detection of circulating cancer cells by means of membrane array simultaneously monitoring five mRNA markers could significantly enhance the sensitivity and specificity for cancer cell detection.

  19. Marker-assisted identification of restorer gene(s) in iso-cytoplasmic restorer lines of WA cytoplasm in rice and assessment of their fertility restoration potential across environments.

    Science.gov (United States)

    Kumar, Amit; Bhowmick, Prolay Kumar; Singh, Vikram Jeet; Malik, Manoj; Gupta, Ashish Kumar; Seth, R; Nagarajan, M; Krishnan, S Gopala; Singh, Ashok Kumar

    2017-10-01

    Iso-cytoplasmic restorers possess the same male sterile cytoplasm as the cytoplasmic male sterile (CMS) lines, thereby minimizing the potential cyto-nuclear conflict in the hybrids. Restoration of fertility of the wild abortive CMS is governed by two major genes namely, Rf3 and Rf4. Therefore, assessing the allelic status of these restorer genes in the iso-cytoplasmic restorers using molecular markers will not only help in estimating the efficiency of these genes either alone or in combination, in fertility restoration in the hybrids in different environments, but will also be useful in determining the efficacy of these markers. In the present study, the efficiency of molecular markers in identifying genotypes carrying restorer allele of the gene(s) Rf3 and Rf4, restoring male fertility of WA cytoplasm in rice was assessed in a set of 100 iso-cytoplasmic rice restorers using gene linked as well as candidate gene based markers. In order to validate the efficacy of markers in identifying the restorers, a sub-set of selected 25 iso-cytoplasmic rice restorers were crossed with four different cytoplasmic male sterile lines namely, IR 79156A, IR 58025A, Pusa 6A and RTN 12A, and the pollen and spikelet fertility of the F1s were evaluated at three different locations. Marker analysis showed that Rf4 was the predominant fertility restorer gene in the iso-cytoplasmic restorers and Rf3 had a synergistic effect on fertility restoration. The efficiency of gene based markers, DRCG-RF4-14 and DRRM-RF3-10 for Rf4 (87%) and Rf3 (84%) genes was higher than respective gene-linked SSR markers RM6100 (80%) and RM3873 (82%). It is concluded that the gene based markers can be effectively used in identifying fertility restorer lines obviating the need for making crosses and evaluating the F1s. Though gene based markers are more efficient, there is a need to identify functional polymorphisms which can provide 100% efficiency. Three iso-cytoplasmic restorers namely, PRR 300, PRR 363 and

  20. Full-length soluble CD147 promotes MMP-2 expression and is a potential serological marker in detection of hepatocellular carcinoma

    Science.gov (United States)

    2014-01-01

    Background As a surface glycoprotein, CD147 is capable of stimulating the production of matrix metalloproteinases (MMPs) from neighboring fibroblasts. The aim of the present study is to explore the role of soluble CD147 on MMPs secretion from hepatocellular carcinoma (HCC) cells, and to investigate the diagnostic value of serum soluble CD147 in the HCC detection. Methods We identified the form of soluble CD147 in cell culture supernate of HCC cells and serum of patients with HCC, and explored the role of soluble CD147 on MMPs secretion. Serum CD147 levels were detected by the enzyme-linked immunosorbent assay, and the value of soluble CD147 as a marker in HCC detection was analyzed. Results Full length soluble CD147 was presented in the culture medium of HCC cells and serum of patients with HCC. The extracellular domain of soluble CD147 promoted the expression of CD147 and MMP-2 from HCC cells. Knockdown of CD147 markedly diminished the up-regulation of CD147 and MMP-2 which induced by soluble CD147. Soluble CD147 activated ERK, FAK, and PI3K/Akt pathways, leading to the up-regulation of MMP-2. The level of soluble CD147 in serum of patients with HCC was significantly elevated compared with healthy individuals (P Soluble CD147 levels were found to be associated with HCC tumor size (P = 0.007) and Child-Pugh grade (P = 0.007). Moreover, soluble CD147 showed a better performance in distinguishing HCC compared with alpha-fetoprotein. Conclusions The extracellular domain of soluble CD147 enhances the secretion of MMP-2 from HCC cells, requiring the cooperation of membrane CD147 and activation of ERK, FAK, and PI3K/Akt signaling. The measurement of soluble CD147 may offer a useful approach in diagnosis of HCC. PMID:24996644

  1. (SSR) markers

    African Journals Online (AJOL)

    HP-PROBOOK

    2016-10-05

    Oct 5, 2016 ... Cluster analysis was constructed using DARwin program version 6.0. Forty eight (48) coconut individuals were clustered into three groups. Key words: Coconut palm (Cocos nucifera ... markers, cluster analysis, diversity. INTRODUCTION ... industry in Kenya (Muhammed et al., 2013). Furthermore, the slow ...

  2. (SRAP) markers

    African Journals Online (AJOL)

    STORAGESEVER

    2009-06-03

    Jun 3, 2009 ... are a very powerful tool for characterization and genetic diversity estimation. Many molecular marker techniques have been successfully used in identification and genetic diversity analysis in mulberry, such as RAPD (Xiang et al., 1995; Feng et al., 1996; Zhao and Pan, 2004),. AFLP (Sharma and Sharma, ...

  3. (SSR) markers

    African Journals Online (AJOL)

    SAM

    2014-07-30

    Jul 30, 2014 ... and attempt crosses for genetic improvement of the crop. Key words: Capsicum, genetic diversity, molecular characterization, simple sequence repeats (SSR) markers. INTRODUCTION. Chilli pepper (Capsicum annuum L.) (Solanaceae) has a chromosome number 2n=2x=24. It is indigenous to South.

  4. (SSR) markers

    African Journals Online (AJOL)

    Yomi

    2012-04-03

    Apr 3, 2012 ... Oilseed rape (Brassica napus L.) is an important oilseed crop worldwide. The objective of this research was to study the genetic diversity and relationships of B. napus accessions using simple sequence repeat (SSR). A set of 217 genotypes was characterized using 37 SSR markers of mapping on the B.

  5. (RAPD) markers

    African Journals Online (AJOL)

    Administrator

    2011-09-21

    Sep 21, 2011 ... Biotechnol. Biotechnol. Equip.14: 16-18. Belaj A, Satovic Z, Cipriani G, Baldoni L, Testolin R, Rallo L, Trujillo I. (2003). Comparative study of the discriminating capacity of RAPD,. AFLP and SSR markers and of their effectiveness in establishing genetic relationships in olive. Theor. Appl. Genet. 107: 736-744 ...

  6. Genipin-structured peptide-polysaccharide nanoparticles with significantly improved resistance to harsh gastrointestinal environments and their potential for oral delivery of polyphenols.

    Science.gov (United States)

    Hu, Bing; Xie, Minhao; Zhang, Chen; Zeng, Xiaoxiong

    2014-12-24

    Genipin-cross-linked caseinophosphopeptide (CPP)-chitosan (CS) nanoparticles (smaller than 300 nm) showed significantly improved stability and adjustable release profile in the gastrointestinal (GI) tract. Optimal purification of the nanoparticles was established by centrifugation to terminate the cross-linking reaction, which was further confirmed and characterized by FT-IR. Results from transmission electron microscopy (TEM), dynamic light scattering (DLS), and electrophoretic mobility (ζ-potential) measurements revealed that genipin cross-linking significantly prevented the bursting of the CPP-CS nanoparticles in simulated stomach acid and their precipitation under neutral intestinal environment. Pepsin showed little impact on the nanoparticle colloid stability; however, trypsin induced their aggregations. Genipin cross-linking slowed the burst release of (-)-epigallocatechin-3-gallate (EGCG) from the nanoparticles. The EGCG-loaded nanoparticles showed strong cytotoxicity against cancer cells; meanwhile, the net nanoparticles demonstrated high biocompatibility. The findings in the present work provide fundamental information for the rational design of biopolymer nanoparticles as an effective delivery systems for polyphenols.

  7. Multiple Brain Markers are Linked to Age-Related Variation in Cognition

    Science.gov (United States)

    Hedden, Trey; Schultz, Aaron P.; Rieckmann, Anna; Mormino, Elizabeth C.; Johnson, Keith A.; Sperling, Reisa A.; Buckner, Randy L.

    2016-01-01

    Age-related alterations in brain structure and function have been challenging to link to cognition due to potential overlapping influences of multiple neurobiological cascades. We examined multiple brain markers associated with age-related variation in cognition. Clinically normal older humans aged 65–90 from the Harvard Aging Brain Study (N = 186) were characterized on a priori magnetic resonance imaging markers of gray matter thickness and volume, white matter hyperintensities, fractional anisotropy (FA), resting-state functional connectivity, positron emission tomography markers of glucose metabolism and amyloid burden, and cognitive factors of processing speed, executive function, and episodic memory. Partial correlation and mediation analyses estimated age-related variance in cognition shared with individual brain markers and unique to each marker. The largest relationships linked FA and striatum volume to processing speed and executive function, and hippocampal volume to episodic memory. Of the age-related variance in cognition, 70–80% was accounted for by combining all brain markers (but only ∼20% of total variance). Age had significant indirect effects on cognition via brain markers, with significant markers varying across cognitive domains. These results suggest that most age-related variation in cognition is shared among multiple brain markers, but potential specificity between some brain markers and cognitive domains motivates additional study of age-related markers of neural health. PMID:25316342

  8. Tumor Markers: An Overview

    Directory of Open Access Journals (Sweden)

    Ajay G Nayak

    2010-01-01

    Full Text Available Oral cancer is a potentially fatal disease that has been the bane of clinicians throughout the world. Though various modalities of management exist, early detection still provides the best hope for any cancer patient Advances in molecular diagnosis have led to a plethora of choices being available in the fight against cancer. Abnormal cellular products elucidated from malignant cells can be detected and measured in various body tissues and fluids and constitute tumor markers. The various clinical applications and their limitations are covered in the brief overview to help the oral medicine specialist understand the relevant advances made in the field of tumor markers.

  9. The potential use of lithium as a marker for the assessment of the sources of dietary salt : cooking studies and physiological experiments in men

    NARCIS (Netherlands)

    Sanchez-Castillo, C P; Seidell, J; James, W.P.T.

    Lithium was investigated for its possible use as a marker for identifying the various sources of NaCl in the diet. Micromolar concentrations of lithium can be detected in various vegetables, tap water and also in urine specimens of adult volunteers. The lithium content of vegetables varied from 6.1

  10. Potential markers for early diagnostics of Colorectal cancer and Inflammatory bowel disease in humans : intestinal microorganisms and immune system (teammates or rivals)

    Czech Academy of Sciences Publication Activity Database

    Horák, P.; Kučerová, Petra; Červinková, Monika

    2017-01-01

    Roč. 1, č. 2 (2017), s. 59-64 E-ISSN 2560-8304 R&D Projects: GA MŠk(CZ) LO1609 Institutional support: RVO:67985904 Keywords : colorectal cancer * inflammatory bowel disease * immune markers Subject RIV: EB - Genetics ; Molecular Biology

  11. Clinical prospective study of biochemical markers and evoked potentials for identifying adverse neurological outcome after thoracic and thoracoabdominal aortic aneurysm surgery.

    NARCIS (Netherlands)

    Lases, E.C.; Schepens, M.A.; Haas, F.J.L.M.; Aarts, L.P.H.J.; Beek, H.T. ter; Dongen, E. van; Siegers, H.P.; Tweel, I. van de; Boezeman, E.H.

    2005-01-01

    BACKGROUND: Neurological deficit after repair of a thoracic or thoracoabdominal aortic aneurysm (TAA/TAAA) remains a devastating complication. The aim of our study was to investigate the clinical value of biochemical markers [S-100B, neurone-specific enolase (NSE) and lactate dehydrogenase (LD)],

  12. Development of new microsatellite markers for Salvia officinalis L. and its potential use in conservation-genetic studies of narrow endemic Salvia brachyodon Vandas.

    Science.gov (United States)

    Radosavljević, Ivan; Satovic, Zlatko; Jakse, Jernej; Javornik, Branka; Greguraš, Danijela; Jug-Dujaković, Marija; Liber, Zlatko

    2012-01-01

    Nine new microsatellite markers (SSR) were isolated from Salvia officinalis L. A total of 125 alleles, with 8 to 21 alleles per locus, were detected in a natural population from the east Adriatic coast. The observed heterozygosity, expected heterozygosity, and polymorphic information content ranged from 0.46 to 0.83, 0.73 to 0.93 and 0.70 to 0.92, respectively. New microsatellite markers, as well as previously published markers, were tested for cross-amplification in Salvia brachyodon Vandas, a narrow endemic species known to be present in only two localities on the Balkan Peninsula. Out of 30 microsatellite markers tested on the natural S. brachyodon population, 15 were successfully amplified. To obtain evidence of recent bottleneck events in the populations of both species, observed genetic diversity (H(E)) was compared to the expected genetic diversity at mutation-drift equilibrium (H(EQ)) and calculated from the observed number of alleles using a two-phased mutation model (TPM). Recent bottleneck events were detected only in the S. brachyodon population. This result suggests the need to reconsider the current threat category of this endemic species.

  13. Cardiac MRI. Diagnostic gain of an additional axial SSFP chest sequence for the detection of potentially significant extracardiac findings in the cardiac MRI examination setting

    Energy Technology Data Exchange (ETDEWEB)

    Roller, F.C.; Schneider, C.; Krombach, G.A. [University Hospital Giessen (Germany). Dept. Radiology; Schuhbaeck, A. [University Hospital Giessen (Germany). Dept. Cardiology; Rolf, A. [Kerckhoff Hospital Bad Nauheim (Germany). Dept. Cardiology

    2014-01-15

    Purpose: Cardiac MRI (CMRI) is an effective method for imaging of the heart. The aim of our study was to assess whether an axial chest sequence in addition to the standard CMR examination setting has advantages in the detection of potentially significant extracardiac findings (PSEF). Materials and Methods: 400 consecutive patients were imaged at 1.5 T for clinical reasons. In addition to the standard long and short-axis views, an axial SSFP sequence was obtained covering the thorax from the lung apex to the diaphragm. All sequences were separately evaluated for PSEF. Results: A total of 25 PSEF were diagnosed in 400 patients, including 16 pleural effusions, a pulmonary fibrosis, a spondylodiscitis, ascites, lymphadenopathies, relapse of a mamma carcinoma, growth of adrenal glands metastases and diaphragmatic elevation. All 25 PSEF were detected by reading survey sequences. 24 of the 25 PSEF were detected by the additional SSFP chest sequence as well as the CINE sequences. Conclusion: In our study the additional axial SSFP chest sequence didn't show a benefit in the detection of PSEF. With the survey sequences we were able to detect all PSEF. We conclude that survey images should be assessed for additional findings. (orig.)

  14. The Carbon and Global Warming Potential Impacts of Organic Farming: Does It Have a Significant Role in an Energy Constrained World?

    Directory of Open Access Journals (Sweden)

    Ralph C. Martin

    2011-01-01

    Full Text Available About 130 studies were analyzed to compare farm-level energy use and global warming potential (GWP of organic and conventional production sectors. Cross cutting issues such as tillage, compost, soil carbon sequestration and energy offsets were also reviewed. Finally, we contrasted E and GWP data from the wider food system. We concluded that the evidence strongly favours organic farming with respect to whole-farm energy use and energy efficiency both on a per hectare and per farm product basis, with the possible exception of poultry and fruit sectors. For GWP, evidence is insufficient except in a few sectors, with results per ha more consistently favouring organic farming than GWP per unit product. Tillage was consistently a negligible contributor to farm E use and additional tillage on organic farms does not appear to significantly deplete soil C. Energy offsets, biogas, energy crops and residues have a more limited role on organic farms compared to conventional ones, because of the nutrient and soil building uses of soil organic matter, and the high demand for organic foods in human markets. If farm E use represents 35% of total food chain E use, improvements shown of 20% or more in E efficiency through organic farm management would reduce food-chain E use by 7% or more. Among other food supply chain stages, wholesale/retail (including cooling and packaging and processing often each contribute 30% or more to total food system E. Thus, additional improvements can be obtained with reduced processing, whole foods and food waste minimization.

  15. Gangliosides as a potential new class of stem cell markers: the case of GD1a in human bone marrow mesenchymal stem cells[S

    OpenAIRE

    Bergante, Sonia; Torretta, Enrica; Creo, Pasquale; Sessarego, Nadia; Papini, Nadia; Piccoli, Marco; Fania, Chiara; Cirillo, Federica; Conforti, Erika; Ghiroldi, Andrea; Tringali, Cristina; Venerando, Bruno; Ibatici, Adalberto; Gelfi, Cecilia; Tettamanti, Guido

    2014-01-01

    Owing to their exposure on the cell surface and the possibility of being directly recognized with specific antibodies, glycosphingolipids have aroused great interest in the field of stem cell biology. In the search for specific markers of the differentiation of human bone marrow mesenchymal stem cells (hBMSCs) toward osteoblasts, we studied their glycosphingolipid pattern, with particular attention to gangliosides. After lipid extraction and fractionation, gangliosides, metabolically 3H-label...

  16. Development of new polymorphic microsatellite markers for three closely related plant-pathogenic Phytophthora species using 454-pyrosequencing and their potential applications.

    Science.gov (United States)

    Schoebel, Corine N; Jung, Esther; Prospero, Simone

    2013-10-01

    Phytophthora spp. (oomycetes) are causal agents of devastating diseases on a high number of crops, ornamentals, and native plants worldwide. Neutral molecular markers are increasingly being used to investigate the genetic population structure and possible pathways of spread of different plant pathogens, including Phytophthora spp. In this study, polymorphic microsatellite markers were developed for three species of the former Phytophthora citricola species complex-namely, P. multivora, P. plurivora, and P. pini (P. citricola I)-using the 454-pyrosequencing technique. In total, 35 polymorphic microsatellite loci were found and further characterized: 11 for P. plurivora, 16 for P. multivora, and 8 for P. pini. Microsatellites with dinucleotide motifs repeated 6 to 10 times were the most common for all three species. On average, 65 alleles per species and 5.3 alleles per locus were detected. Most loci were characterized by a low observed heterozygosity, which might be due to the homothallic mating system of the three Phytophthora spp. targeted. Cross amplification of the newly developed markers was tested on 17 Phytophthora spp. belonging to five different internal transcribed spacer clades. Transferability success was generally low and decreased with increasing genetic distance from the species to the three target species. A set of four loci was selected to easily discriminate P. plurivora, P. multivora, and P. pini on the basis of presence or absence of a polymerase chain reaction amplicon on an agarose gel.

  17. Expression of Lipid Peroxidation Markers in the Tear Film and Ocular Surface of Patients with Non-Sjogren Syndrome: Potential Biomarkers for Dry Eye Disease.

    Science.gov (United States)

    Choi, Won; Lian, Cui; Ying, Li; Kim, Ga Eon; You, In Cheon; Park, Soo Hyun; Yoon, Kyung Chul

    2016-09-01

    To investigate the expression of lipid peroxidation markers in the tear film and ocular surface and their correlation with disease severity in patients with dry eye disease. The concentrations of hexanoyl-lysine (HEL), 4-hydroxy-2-nonenal (HNE), and malondialdehyde (MDA) were measured with enzyme-linked immunosorbent assays in tears obtained from 44 patients with non-Sjogren syndrome dry eye and 33 control subjects. The correlations between the marker levels and the tear film and ocular surface parameters, including tear film break-up time (BUT), Schirmer tear value, tear clearance rate, keratoepitheliopathy scores, corneal sensitivity, conjunctival goblet cell density, and symptom score, were analyzed. The expression of the lipid peroxidation markers HEL, 4-HNE, and MDA in the conjunctiva was evaluated using immunohistochemistry. The concentrations of HEL, 4-HNE, and MDA were 279.84 ± 69.98 nmol/L, 0.02 ± 0.01 μg/mL, and 3.80 ± 1.05 pmol/mg in control subjects and 283.21 ± 89.67 nmol/L (p = 0.97), 0.20 ± 0.03 μg/mL (p tear value, tear clearance rate, keratoepitheliopathy scores, conjunctival goblet cell density, and symptom score (p tear film and ocular surface of patients with dry eye. The levels correlate with various tear film and ocular surface parameters and may reflect the severity of dry eye disease.

  18. THE THYMIDINE KINASE-1(TK-1 AS A POTENTIAL TUMOR MARKER: SERUM LEVELS IN SERUM OF PATIENTS WITH SOLID AND SYSTEM MALIGNANCE NEOPLASMS

    Directory of Open Access Journals (Sweden)

    N. S. Sergeeva

    2017-01-01

    Full Text Available The review summarizes the results of studies of levels and/or activity in the blood serum of a metabolic marker thymidine kinase-1 (TK-1 of proliferating cells in patients with lymphoproliferative diseases (LPD and malignant neopasms (NM.Comparison of the data in the literature in some cases have been difficult due to the fundamentally different methods of detection the activity or concentration of TK-1, used by authors, even despite the presence of relatively high (but not absolute correlation between these parameters (maximum 0.8.Many clinical and laboratory studies have shown levels of correlation and/or TK-1 activity with clinical stages and different types of LPD and solid MN and can serve as a prognostic factor for overall and recurrence-free survival of patients. When solid MN shown that the activity of TK-1 accurately reflects the proliferative status of tumor.A comparison of the dynamics of TC-1 in the process of chemotherapy and its clinical efficacy, different authors have received fundamentally different results: in some cases the marker reduction was associated with treatment efficacy, and in part of publications they show that the clinically relevant effects of the treatment observed increase in the marker after the first chemotherapy.The entire set of received data demonstrates the relevance of the further development of the algorithm use of TK-1 in oncology practice.

  19. Clinical Implications of Intestinal Stem Cell Markers in Colorectal Cancer

    DEFF Research Database (Denmark)

    Espersen, Maiken Lise Marcker; Olsen, Jesper; Linnemann, Dorte

    2015-01-01

    Colorectal cancer (CRC) still has one of the highest incidence and mortality rate among cancers. Therefore, improved differential diagnostics and personalized treatment are still needed. Several intestinal stem cell markers have been found to be associated with CRC and might have a prognostic...... and predictive significance in CRC patients. This review provides an overview of the intestinal stem cell markers leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), B cell–specific Moloney murine leukemia virus insertion site 1 (BMI1), Musashi1 (MSI1), and sex-determining region y-box 9 (SOX9......) and their implications in human CRC. The exact roles of the intestinal stem cell markers in CRC development and progression remain unclear; however, high expression of these stem cell markers have a potential prognostic significance and might be implicated in chemotherapy resistance...

  20. A potential species-specific molecular marker suggests interspecific hybridization between sibling species Littorina arcana and L. saxatilis (Mollusca, Caenogastropoda) in natural populations.

    Science.gov (United States)

    Mikhailova, Natalia A; Gracheva, Yulia A; Backeljau, Thierry; Granovitch, Andrey I

    2009-12-01

    Three sister species of rough periwinkles, viz. Littorina saxatilis (Olivi 1792), L. arcana (Hannaford Ellis 1978) and L. compressa (Jeffreys 1865) from the Barents Sea (Russia), the White Sea (Russia) and the Norwegian Sea (Norway) were studied. The identification of two sibling species L. saxatilis and L. arcana is often difficult as both species have extremely similar shell morphology and reproductive systems. Only mature females can be unambiguously distinguished, with a jelly gland present in female L. arcana, but which is replaced by a brood pouch containing developing embryos in L. saxatilis. No clear-cut diagnostic features have been found to discriminate between males or juveniles of the two species. The very first diagnostic DNA marker (DNA fragment A2.8, 271 bp length) for L. arcana and L. saxatilis separation was developed. The marker was derived from apparently species-specific L. arcana DNA fragments obtained via Random Amplified Polymorphic DNA (RAPD) analysis. This fragment was cloned and sequenced, whereupon specific primers were designed and the amplification was surveyed in a large number of morphologically well-identified females of both species. Subsequently, the specific DNA marker was used for the identification of male L. arcana and partners in copulating pairs. In this way, we obtained evidence of possible interspecific hybridization between the sibling species L. arcana and L. saxatilis living in sympatry in natural populations: the presence of A2.8 fragment in 12% of morphologically well identified L. saxatilis females and its absence in 14% of morphologically well identified L. arcana females. The A2.8 fragment never amplified in L. saxatilis from sites without L. arcana. The A2.8 fragment did not amplify in L. compressa, not even in microsympatric populations, and we did not observe interspecific copulations between L. arcana and L. compressa.

  1. THE ECONOMIC EVALUATION AND SIGNIFICANCE OF AN EARLY RELOCATION VERSUS COMPLETE DESTRUCTION BY A POTENTIAL TSUNAMI OF A COASTAL CITY IN ECUADOR

    Directory of Open Access Journals (Sweden)

    Fabian Rodriguez

    2016-01-01

    Full Text Available The coastal part of continental Ecuador is highly vulnerable for tsunami hazards as shown in the past two centuries. In order to avoid future devastating destructions in a given part in the coastline, we have estimated the economic effects of a potential future tsunami for one small Pacific town in Ecuador in order to analyze such potential cost of damages and compare it with a proposed resettlement value of the entire town. In past, most of the known resettlement projects have been realized as result of a natural disaster or a planning infrastructure such as hydro-electrical plants. Yet, in this study, we have considered to propose to policy makers and other authorities to take into account that a resettlement plan should be realized prior an impact by one the most deadly natural hazard. The results include four different scenarios of economic losses as a result of a potential tsunami, using human losses as the only variable that vary. Potential economic losses vary from 441 US$ up to 620 US$ millions, when compared to a potential resettlement and associated costs based on the four scenarios. The B/C ratio is favorable to town resettlement as Government’s preventing policy favoring an intelligent reduction and prevention of vulnerability and loss of human life.

  2. Visual evoked potential and magnetic resonance imaging are more effective markers of multiple sclerosis progression than laser polarimetry with variable corneal compensation

    Directory of Open Access Journals (Sweden)

    Ema eKantorová

    2014-01-01

    Full Text Available Backround: The aim of our study was to assess the role of laser polarimetry and visual evoked potentials as potential biomarkers of disease progression in multiple sclerosis (MS. Participants: A total of 41 patients with MS (82 eyes and 22 age-related healthy volunteers (44 eyes completed the study. MS patients were divided into two groups, one (ON with a history of optic neuritis (17 patients, 34 eyes and another group (NON without it (24 patients, 48 eyes. The MS patients and controls underwent laser polarimetry (GDx examination of the retinal nerve fibre layer (RNFL. In the MS group we also examined: Kurtzke Expanded disability status scale (EDSS, the duration of the disorder, visual evoked potentials (VEP – latency and amplitude – and conventional brain MRI. Results: In the MS group, brain atrophy and new T2 brain lesions in MRI correlated with both VEP latencies and amplitudes. Separate comparisons revealed VEP latency testing to be less sensitive in ON than in NON patients. In ON patients, VEP amplitudes correlated mildly with brain atrophy (r =-0.15 and strongly with brain new MRI lesions (r = -0.8. In NON patients, highly significant correlation of new MRI brain lesions with VEP latencies (r = 0.63, r = 0.6, and amplitudes ( r = -0.3, r = -4.2 was found. EDSS also correlated with brain atrophy in this group (r = 0.5. Our study did not find a correlation of GDx measures with MRI tests. The GDx method was not able to detect whole brain demyelinisation and the degeneration process, but was only able to reveal the involvement of optic nerves in ON and NON patients.Conclusions: In our study, we found that both methods (VEP and GDx can be used for detection of optic nerve damage, but VEP was found to be superior in evaluating whole brain demyelinisation and axonal degeneration. Both VEP and MRI, but not GDx, have an important role in monitoring disease progression in MS patients, independent of the ON history.

  3. Association of genetic polymorphism -670A>G in the Fas gene and serum markers AST platelet ratio index, AST/ALT with significant fibrosis and cirrhosis in chronic hepatitis C.

    Science.gov (United States)

    Deghady, Akram; Abdou, Alaa; El-Neanaey, Wafaa Ahmed; Diab, Iman

    2012-06-01

    This study was carried out to evaluate the association of genetic polymorphism -670A>G in the promoter of Fas gene as well as serum biomarkers aspartate aminotransferase (AST) platelet ratio index (APRI) and AST/alanine aminotransferase (ALT) with significant fibrosis and cirrhosis in chronic hepatitis C patients. Seventy-nine patients with chronic hepatitis C in addition to 80 age- and sex-matched healthy controls were evaluated for genetic polymorphism -670A>G of Fas gene by polymerase chain reaction-restriction fragment length polymorphism and serum biomarkers APRI and AST/ALT in relation to significant fibrosis and cirrhosis diagnosed by liver biopsy. Genetic polymorphism -670A>G in Fas gene was associated with significant liver fibrosis and cirrhosis. Heterozygous mutation was found in 11.4% of patients and 10% of controls, while homozygous mutation was found only in 7.6% of patients. Odds ratio (OR) was statistically not significant (OR=1.93, 95% confidence interval=0.76-4.92). Mean values of APRI and AST/ALT were significantly higher in patients with (F3-F4) compared with those with (F0-F2). (p-value polymorphism -670A>G of Fas gene was associated with significant fibrosis and cirrhosis in chronic hepatitis C patients. APRI and AST/ALT are independent predictors for significant fibrosis. APRI showed a better sensitivity than AST/ALT for prediction of significant fibrosis. Moreover, APRI can be used as an index to exclude liver cirrhosis without performing liver biopsy.

  4. Draft genome sequence of Talaromyces islandicus (“Penicillium islandicum”) WF-38-12, a neglected mold with significant biotechnological potential

    DEFF Research Database (Denmark)

    Schafhauser, Thomas; Wibberg, Daniel; Rückert, Christian

    2015-01-01

    Talaromyces (Penicillium) islandicus is a common mold found in stored rice or cereals. It has a highly versatile metabolism characterized by the secretion of numerous biopolymer degrading enzymes, mycotoxins, and anthraquinones that altogether offer a broad range of potential industrial applicati......Talaromyces (Penicillium) islandicus is a common mold found in stored rice or cereals. It has a highly versatile metabolism characterized by the secretion of numerous biopolymer degrading enzymes, mycotoxins, and anthraquinones that altogether offer a broad range of potential industrial...

  5. Injectable iodine-125 labeled tissue marker for radioactive localization of non-palpable breast lesions

    DEFF Research Database (Denmark)

    Schaarup-Jensen, Henrik; Jensen, Andreas Ingemann; Hansen, Anders Elias

    2018-01-01

    through thin hypodermic needles (≥27G), the marker holds great promise for clinical application, since patient discomfort is reduced significantly compared to current methods. Statement of Significance. A new type of tissue marker for local administration to non-palpable breast tumors has been developed......We have developed a 125I-radiolabeled injectable fiducial tissue marker with the potential to replace current methods used for surgical guidance of non-palpable breast tumors. Methods in routine clinical use today such as radioactive seed localization, radio-guided occult lesion localization...... and wire-guided localization suffers from limitations that this injectable fiducial tissue marker offers solutions to. The developed 125I-radiolabeled injectable fiducial tissue marker is based on highly viscous sucrose acetate isobutyrate. The marker was readily inserted in NMRI mice and proved...

  6. Evaluation of MCT1, MCT4 and CD147 Genes in Peripheral Blood Cells of Breast Cancer Patients and Their Potential Use as Diagnostic and Prognostic Markers.

    Science.gov (United States)

    Luz, Maria Cláudia de B; Perez, Matheus M; Azzalis, Ligia A; Sousa, Luiz Vinícius de A; Adami, Fernando; Fonseca, Fernando L A; Alves, Beatriz da C A

    2017-03-23

    Patients with breast cancer-the deadliest cancer among women-are at constant risk of developing metastasis. Oxidative stress and hypoxia are common feature of tumor cells that can proliferate even in a resultant metabolic acidosis. Despite the low extracellular pH, intracellular pH of tumor cells remains relatively normal, or even more alkaline due to the action of a membrane protein family known as monocarboxylate transporters (MCTs). The objective of this study was to verify the diagnostic and prognostic value of MCT1, MCT4 and CD147 in tumor and peripheral blood samples of patients with breast cancer undergoing chemotherapic treatment. Differential expression of MCT1, MCT4 and CD147 obtained by qPCR was determined by 2-ΔΔCq method between biological samples (tumor and serial samples of peripheral) of patients (n = 125) and healthy women (n = 25). tumor samples with higher histological grades have shown higher expression of these markers; this higher expression was also observed in blood samples obtained at diagnosis of patients when compared to healthy women and in patients with positive progression of the disease (metastasis development). markers studied here could be a promising strategy in routine laboratory evaluations as breast cancer diagnosis and prognosis.

  7. Potential role of pNF-H, a biomarker of axonal damage in the central nervous system, as a predictive marker of chemotherapy-induced cognitive impairment.

    Science.gov (United States)

    Natori, Akina; Ogata, Toru; Sumitani, Masahiko; Kogure, Takamichi; Yamauchi, Teruo; Yamauchi, Hideko

    2015-03-15

    Chemotherapy-induced cognitive impairment (CICI) is a clinically significant problem. Previous studies using magnetic resonance imaging indicated structural changes in the cerebral white matter of patients with CICI. Phosphorylated neurofilament heavy subunit (pNF-H), a major structural protein in axons, was recently reported to be elevated in the serum of patients with some central nervous system disorders. We performed a cross-sectional analysis of neuropsychological test results and serum pNF-H levels in patients undergoing adjuvant chemotherapy for breast cancer. Our hypothesis was that CICI is accompanied by axonal damage that can be detected by elevated serum pNF-H levels. Seventy-six patients with early breast cancer in various phases of treatment (naïve to chemotherapy; after one, three, or seven cycles of chemotherapy; or with a history of chemotherapy) were assessed by self-administered neuropsychological tests and a single pNF-H measurement. The χ(2) and Mann-Whitney tests were used for statistical analysis. Increased pNF-H levels were observed in 28.8% of the patients who underwent chemotherapy, but in none of the chemotherapy-naïve patients or patients with a history of chemotherapy. The pNF-H-positive rate increased significantly in proportion to the number of chemotherapy cycles (one cycle, 5.0%; three cycles, 31.6%; seven cycles, 55.0%; P pNF-H level in patients undergoing chemotherapy for breast cancer increased in a cumulative dose-dependent manner, suggesting its potential application as a biomarker of neural damage after chemotherapy. ©2015 American Association for Cancer Research.