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Sample records for enolase synaptophysin chromogranin

  1. Early fetal acquisition of the chromaffin and neuronal immunophenotype by human adrenal medullary cells. An immunohistological study using monoclonal antibodies to chromogranin A, synaptophysin, tyrosine hydroxylase, and neuronal cytoskeletal proteins.

    NARCIS (Netherlands)

    Molenaar, W M; Lee, V M; Trojanowski, J Q

    1990-01-01

    The development of chromaffin and neuronal features in the adrenal medulla was studied in normal human fetuses with gestational ages (GAs) of 6-34 weeks. Monoclonal antibodies specific for chromogranin A, synaptophysin, and tyrosine hydroxylase; for different subunits and phosphoisoforms of

  2. Chromogranins - new sensitive markers for neuroendocrine tumors

    International Nuclear Information System (INIS)

    Eriksson, B.; Arnberg, H.; Oeberg, K.; Hellman, U.; Lundqvist, G.; Wernstedt, C.; Wilander, E.; Uppsala Hospital; Uppsala Hospital

    1989-01-01

    Chromogranins A, B and C, proteins that are costored and coreleased with peptides and amines, have been identified in a variety of endocrine and nervous tissues, both normal and neoplastic. We examined the secretion of chromogranin A and chromogranin A+B by hormone-producing tumors in patients with endocrine pancreatic tumors (EPT), carcinoid tumors, pheochromocytomas and small cell lung cancer (SCLC). Radioimmunoassay (RIA) of the plasma/serum concentrations of chromogranin A+B showed a greater sensitivity than RIA of chromogranin A alone. All patients with EPT, carcinoids and pheochromocytomas had increased levels of chromogranin A+B, whereas a small number of the patients (5/18 with EPT and 1/3 with pheochromocytomas) had normal levels of chromogranin A. Also in immunocytochemical stainings, our polyclonal antiserum detecting both chromogranin A and B showed a greater sensitivity than other available antisera against chromogranin A, B and C. (orig.)

  3. Chromogranin B and Secretogranin II in transgenic mice overexpressing human APP751 with the London (V717I) and Swedish (K670M/N671L) mutations and in Alzheimer patients.

    Science.gov (United States)

    Willis, Michael; Prokesch, Manuela; Hutter-Paier, Birgit; Windisch, Manfred; Stridsberg, Mats; Mahata, Sushil K; Kirchmair, Rudolf; Wietzorrek, Georg; Knaus, Hans-Günther; Jellinger, Kurt; Humpel, Christian; Marksteiner, Josef

    2008-03-01

    Chromogranin B and secretogranin II are major soluble constituents of large dense core vesicles of presynaptic structures and have been found in neuritic plaques of Alzheimer patients. We examined the distribution and expression of these peptides in both transgenic mice over expressing human amyloid-beta protein precursor APP751 with the London (V717I) and Swedish (K670M/N671L) mutations and in human post-mortem brain. In transgenic mice, the number of amyloid-beta plaques and chromogranin immunopositive plaques increased from 6 to 12 months. About 60% of amyloid-beta plaques were associated with chromogranin B and about 40% with secretogranin II. Chromogranin immunoreactivity appeared mainly as swollen dystrophic neurites. Neither synaptophysin- nor glial fibrillary acidic protein- immunoreactivity was expressed in chromogranin immunoreactive structures at any timepoint. Density of chromogranin peptides in hippocampal structures did not change in transgenic animals at any timepoint, even though animals had a poorer performance in the Morris water maze task. In conclusion, our findings in transgenic animals partly resembled findings in Alzheimer patients. Chromogranin peptides were associated with amyloid-beta plaques, but were not reduced in specific brain areas as previously reported by our group. Therefore specific changes of chromogranin peptides observed in Alzheimer patients can be related to amyloid-beta pathology only.

  4. Aberrant intermediate filament and synaptophysin expression is a frequent event in malignant melanoma: an immunohistochemical study of 73 cases.

    Science.gov (United States)

    Romano, Ryan C; Carter, Jodi M; Folpe, Andrew L

    2015-08-01

    Malignant melanomas are known to express vimentin, among other intermediate filaments. Though anomalous keratin expression by malignant melanoma has been reported, its frequency is not well-established and this phenomenon is not well-known. We have seen in consultation a number of malignant melanomas with anomalous expression of keratin, other intermediate filaments, or synaptophysin, and therefore studied a large group of primary and metastatic melanomas to determine the frequency of these events. About 73 cases of malignant melanoma (22 primaries and 51 metastases) from 71 patients (51 male, 20 female; mean 59 years, range 17-87 years) were retrieved from our archives. Prior diagnoses were confirmed by re-review of hematoxylin and eosin sections and relevant (e.g., S100 protein, HMB45, Melan-A, and tyrosinase) immunohistochemical studies. Available sections were immunostained for keratin (OSCAR and AE1/AE3 antibodies), desmin, neurofilament protein, glial fibrillary acidic protein, synaptophysin, and chromogranin A. Not all cases could be tested for all markers. Cases were predominantly epithelioid (48/73, 66%) or spindle cell/desmoplastic (25/73, 34%). S100 protein, Melan-A, HMB45, and tyrosinase were positive in 60/65 (92%), 34/64 (53%), 30/60 (50%), 25/48 (52%) of cases, respectively. All five S100-protein-negative cases expressed at least one of the other melanocytic markers: Melan-A (two of four, 50%), HMB45 (two of three, 67%), and tyrosinase (one of two, 50%). All cases expressed at least one melanocytic marker. Cases were positive for keratin (OSCAR, 17/61, 28%; AE1/AE3, 16/40, 40%), desmin (11/47, 24%), neurofilament protein (5/31, 16%), glial fibrillary acidic protein (3/32, 9%), and synaptophysin (10/34, 29%), typically only in a minority of cells. Chromogranin was negative (0/32, 0%). Altogether 9/73 cases (12%) showed expression of >1 intermediate filament. All S100-protein-negative melanomas showed anomalous intermediate filament expression (keratin

  5. Making sense of chromogranin A in heart disease

    DEFF Research Database (Denmark)

    Gøtze, Jens Peter; Alehagen, Urban; Flyvbjerg, Allan

    2013-01-01

    Chromogranin A is an acidic protein present in secretory granules of neuroendocrine cells. In plasma, chromogranin A is an important marker of neuroendocrine tumours. Chromogranin A measurement has gained interest in cardiovascular disease, because increased plasma concentrations are associated...... with risk of clinical deterioration and death in patients with acute coronary syndromes or chronic heart failure. Cardiac chromogranin A is stored in atrial granules with cardiac natriuretic peptides—the principal cardiac hormones associated with systemic homoeostasis of water and blood pressure. Expression...

  6. Crystal structure of enolase from Drosophila melanogaster.

    Science.gov (United States)

    Sun, Congcong; Xu, Baokui; Liu, Xueyan; Zhang, Zhen; Su, Zhongliang

    2017-04-01

    Enolase is an important enzyme in glycolysis and various biological processes. Its dysfunction is closely associated with diseases. Here, the enolase from Drosophila melanogaster (DmENO) was purified and crystallized. A crystal of DmENO diffracted to 2.0 Å resolution and belonged to space group R32. The structure was solved by molecular replacement. Like most enolases, DmENO forms a homodimer with conserved residues in the dimer interface. DmENO possesses an open conformation in this structure and contains conserved elements for catalytic activity. This work provides a structural basis for further functional and evolutionary studies of enolase.

  7. Chromogranin A in the mammalian heart

    DEFF Research Database (Denmark)

    Hansen, Lasse H.; Darkner, Stine; Svendsen, Jesper H.

    2017-01-01

    Aim: To investigate whether chromogranin A (CgA) is secreted from the heart into circulation.  Materials & methods: Porcine cardiac tissue was analyzed for the presence of CgA-derived glycopeptides using a global O-glycoproteomic strategy. Blood was sampled from the femoral vein, right atrium...... from the heart (coronary sinus [795 pmol/l] vs left atrium [678 pmol/l]; p heart could be established (p = 0.6366).  Conclusion: The cardiac atria express but do not secrete CgA into circulation in patients with atrial disease....

  8. Neocortical synaptophysin asymmetry and behavioral lateralization in chimpanzees (Pan troglodytes)

    DEFF Research Database (Denmark)

    Sherwood, Chet C; Duka, Tetyana; Stimpson, Cheryl D

    2010-01-01

    Although behavioral lateralization is known to correlate with certain aspects of brain asymmetry in primates, there are limited data concerning hemispheric biases in the microstructure of the neocortex. In the present study, we investigated whether there is asymmetry in synaptophysin-immunoreacti......Although behavioral lateralization is known to correlate with certain aspects of brain asymmetry in primates, there are limited data concerning hemispheric biases in the microstructure of the neocortex. In the present study, we investigated whether there is asymmetry in synaptophysin...... density. In contrast, puncta densities were symmetrical in right-handed chimpanzees. These findings support the conclusion that synapse asymmetry is modulated by lateralization of skilled motor behavior in chimpanzees....

  9. The multifaceted roles of Leptospira enolase.

    Science.gov (United States)

    Salazar, Natália; Souza, Matilde Costa Lima de; Biasioli, Amanda Gameiro; Silva, Ludmila Bezerra da; Barbosa, Angela Silva

    A previous study had demonstrated that Leptospira enolase is secreted extracellularly by a yet unknown mechanism and reassociates with the bacterial membrane. Surface-anchored leptospiral enolase displays plasminogen binding activity. In this work, we explored the consequences of this interaction and also assessed whether Leptospira enolase might display additional moonlighting functions by interacting with other host effector proteins. We first demonstrated that enolase-bound plasminogen is converted to its active form, plasmin. The protease plasmin targets human fibrinogen and vitronectin, but not the complement proteins C3b and C5. Leptospira enolase also acts as an immune evasion protein by interacting with the negative complement regulators C4b binding protein and factor H. Once bound to enolase, both regulators remain functional as cofactors of factor I, mediating cleavage of C4b and C3b. In conclusion, enolase may facilitate leptospiral survival and dissemination, thus contributing to bacterial virulence. The identification and characterization of moonlighting proteins is a growing field of bacterial pathogenesis, as these multifaceted proteins may represent potential future therapeutic targets to fight bacterial infections. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  10. Chromogranin A as a biomarker in cardiovascular disease

    DEFF Research Database (Denmark)

    Goetze, Jens P; Alehagen, Urban; Flyvbjerg, Allan

    2014-01-01

    with acute coronary syndromes or chronic heart failure. In this article, we summarize the current clinical data on chromogranin A as a biomarker in cardiovascular disease from high-risk conditions; for example, obesity, hypertension and diabetes, to overt heart failure. Biological activity of the various......Chromogranin A is known as an important marker of neuroendocrine tumors. In cardiovascular medicine, however, chromogranin A measurement has only recently gained interest, since increased concentrations in the circulation are associated with risk of clinical worsening and death in patients...

  11. Limitations of Chromogranin A in clinical practice.

    Science.gov (United States)

    Marotta, Vincenzo; Nuzzo, Vincenzo; Ferrara, Teresa; Zuccoli, Alfonso; Masone, Milena; Nocerino, Lorenzo; Del Prete, Michela; Marciello, Francesca; Ramundo, Valeria; Lombardi, Gaetano; Vitale, Mario; Colao, Annamaria; Faggiano, Antongiulio

    2012-03-01

    Usefulness of circulating Chromogranin A (CgA) for the diagnosis of neuroendocrine tumors (NEN) is controversial. The aim of the present study was to assess the actual role of this marker as diagnostic tool. Serum blood samples were obtained from 42 subjects affected with NEN, 120 subjects affected with non-endocrine neoplasias (non-NEN) and 100 non-neoplastic subjects affected with benign nodular goitre (NNG). Determination of CgA was performed by means of immunoradiometric assay. The CgA levels among NEN-patients were not significantly different from NNG and non-NEN subjects. The Receiver operating characteristic (ROC) curves analysis failed to identify a feasible cut-off value for the differential diagnosis between NEN and the other conditions. Serum CgA is not helpful for the first-line diagnosis of NEN.

  12. Structure of synaptophysin: a hexameric MARVEL-domain channel protein.

    Science.gov (United States)

    Arthur, Christopher P; Stowell, Michael H B

    2007-06-01

    Synaptophysin I (SypI) is an archetypal member of the MARVEL-domain family of integral membrane proteins and one of the first synaptic vesicle proteins to be identified and cloned. Most all MARVEL-domain proteins are involved in membrane apposition and vesicle-trafficking events, but their precise role in these processes is unclear. We have purified mammalian SypI and determined its three-dimensional (3D) structure by using electron microscopy and single-particle 3D reconstruction. The hexameric structure resembles an open basket with a large pore and tenuous interactions within the cytosolic domain. The structure suggests a model for Synaptophysin's role in fusion and recycling that is regulated by known interactions with the SNARE machinery. This 3D structure of a MARVEL-domain protein provides a structural foundation for understanding the role of these important proteins in a variety of biological processes.

  13. CHROMOGRANIN A DETECTION IN SALIVA OF TYPE 2 DIABETES PATIENTS

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    Martine Soell

    2010-02-01

    Full Text Available Chromogranin A is present in secretion granules of nerve, endocrine and immune cells and is a precursor of several peptides with antibacterial and antifungal properties at micromolar concentrations.Our aim in this prospective, double blind study, was to determine the expression of chromogranin A and its peptides at protein level in saliva of type 2 diabetic patients and thereby to obtain a new non-invasive diagnostic means for the future.Saliva was taken from 30 type 2 diabetic patients and 30 healthy individuals at the same time interval in the morning without any oral stimuli. Circadianic periodics in protein productions have been avoided. The presence of chromogranin A and its derived peptides was determined in whole saliva, after centrifugation at 40C for 12 min at 14 000 rpm, by SDS-PAGE electrophoresis and Immunoblotting (Western Blot. To ensure same protein concentrations Bradford protein quantification assay has been performed before.For the first time, we have determined an overexpression of chromogranin A in saliva of diabetic patients in 100% of the individuals.Chromogranin A, a circulating biomarker for epithelial tumours, is also overexpressed in saliva of type 2 diabetic patients. To confirm our results, more studies with a large amount of patients is necessary.

  14. Chromogranin A Detection in Saliva of Type 2 Diabetes Patients

    Directory of Open Access Journals (Sweden)

    Martine Soell

    2010-02-01

    Full Text Available Chromogranin A is present in secretion granules of nerve, endocrine and immune cells and is a precursor of several peptides with antibacterial and antifungal properties at micromolar concentrations.Our aim in this prospective, double blind study, was to determine the expression of chromogranin A and its peptides at protein level in saliva of type 2 diabetic patients and thereby to obtain a new non-invasive diagnostic means for the future.Saliva was taken from 30 type 2 diabetic patients and 30 healthy individuals at the same time interval in the morning without any oral stimuli. Circadianic periodics in protein productions have been avoided. The presence of chromogranin A and its derived peptides was determined in whole saliva, after centrifugation at 4°C for 12 min at 14 000 rpm, by SDS-PAGE electrophoresis and Immunoblotting (Western Blot. To ensure same protein concentrations Bradford protein quantification assay has been performed before.For the first time, we have determined an overexpression of chromogranin A in saliva of diabetic patients in 100% of the individuals.Chromogranin A, a circulating biomarker for epithelial tumours, is also overexpressed in saliva of type 2 diabetic patients. To confirm our results, more studies with a large amount of patients is necessary.

  15. Elevated serum levels of Chromogranin A in hepatocellular carcinoma.

    Science.gov (United States)

    Biondi, Antonio; Malaguarnera, Giulia; Vacante, Marco; Berretta, Massimiliano; D'Agata, Velia; Malaguarnera, Michele; Basile, Francesco; Drago, Filippo; Bertino, Gaetano

    2012-01-01

    During the past three decades, the incidence of hepatocellular carcinoma in the United States has tripled. The neuroendocrine character has been observed in some tumor cells within some hepatocellular carcinoma nodules and elevated serum chromogranin A also been reported in patients with hepatocellular carcinoma. The aim of this work was to investigate the role of serum concentration of chromogranin A in patients with hepatocellular carcinoma at different stages. The study population consisted of 96 patients (63 males and 33 females age range 52-84) at their first hospital admission for hepatocellular carcinoma. The control group consisted of 35 volunteers (20 males and 15 females age range 50-80). The hepatocellular carcinoma patients were stratified according the Barcelona-Clinic Liver Cancer classification. Venous blood samples were collected before treatment from each patients before surgery, centrifuged to obtain serum samples and stored at -80° C until assayed. The chromogranin A serum levels were elevated (> 100 ng/ml) in 72/96 patients with hepatocellular carcinoma. The serum levels of chromogranin A were significantly correlated (p<0.05) with alpha-fetoprotein. In comparison with controls, the hepatocellular carcinoma patients showed a significant increase (p<0.001) vs controls. The chromogranin A levels in the Barcelona staging of hepatocellular carcinoma was higher in stage D compared to stage C (p<0.01), to stage B (p<0.001), and to stage A (p<0.001). Molecular markers, such as chromogranin A, could be very useful tools for hepatocellular carcinoma diagnosis. However the molecular classification should be incorporated into a staging scheme, which effectively separated patients into groups with homogeneous prognosis and response to treatment, and thus serves to aid in the selection of appropriate therapy.

  16. Post-translational processing of synaptophysin in the rat retina is disrupted by diabetes.

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    Travis S D'Cruz

    Full Text Available Synaptophysin, is an abundant presynaptic protein involved in synaptic vesicle recycling and neurotransmitter release. Previous work shows that its content is significantly reduced in the rat retina by streptozotocin (STZ-diabetes. This study tested the hypothesis that STZ-diabetes alters synaptophysin protein turnover and glycosylation in the rat retina. Whole explant retinas from male Sprague-Dawley rats were used in this study. Rats were made diabetic by a single intraperitoneal STZ injection (65 mg/kg body weight in 10 mM sodium citrate, pH 4.5. mRNA translation was measured using a (35S-methionine labeling assay followed by synaptophysin immunoprecipitation and autoradiography. A pulse-chase study was used to determine the depletion of newly synthesized synaptophysin. Depletion of total synaptophysin was determined after treatment with cycloheximide. Mannose rich N-glycosylated synaptophysin was detected by treating retinal lysates with endoglycosidase H followed by immunoblot analysis. Synaptophysin mRNA translation was significantly increased after 1 month (p<0.001 and 2 months (p<0.05 of STZ-diabetes, compared to age-matched controls. Newly synthesized synaptophysin degradation was significantly accelerated in the retina after 1 and 2 months of diabetes compared to controls (p<0.05. Mannose rich glycosylated synaptophysin was significantly increased after 1 month of STZ-diabetes compared to controls (p<0.05.These data suggest that diabetes increases mRNA translation of synaptophysin in the retina, resulting in an accumulation of mannose rich glycosylated synaptophysin, a transient post-translational state of the protein. This diabetes-induced irregularity in post-translational processing could explain the accelerated degradation of retinal synaptophysin in diabetes.

  17. Detection of chromogranins A and B in endocrine tissues with radioactive and biotinylated oligonucleotide probes

    International Nuclear Information System (INIS)

    Lloyd, R.V.; Jin, L.; Fields, K.

    1990-01-01

    We analyzed the distribution of chromogranins A and B in normal and neoplastic endocrine tissues with secretory granules using 35 S-labeled and biotin-labeled oligonucleotide probes by in situ hybridization (ISH). Both radioactive and nonradioactive probes detected messenger RNAs (mRNAs) in frozen and paraffin tissue sections. Endocrine tissues with variable immunoreactivities for chromogranin A protein, such as small-cell lung carcinomas, neuroblastomas, insulinomas, and parathyroid adenomas, expressed the mRNA for chromogranins A and B in most cells. Some technical problems with the biotinylated probes included nonspecific nuclear staining and endogenous alkaline phosphatase, which was not completely abolished by levamisole pretreatment. A differential distribution of chromogranins A and B was seen in pituitary prolactinomas, which expressed abundant chromogranin B but not chromogranin A mRNAs, and in parathyroid adenomas, which expressed abundant chromogranin A but only small amounts of chromogranin B mRNAs. These results indicate that ISH can be used to detect chromogranins A and B in endocrine tissues with radioactive and biotinylated oligonucleotide probes and that the mRNAs for chromogranin A and B are demonstrable in some tumors even when the chromogranin proteins cannot be detected by immunohistochemistry

  18. Detection of chromogranins A and B in endocrine tissues with radioactive and biotinylated oligonucleotide probes

    Energy Technology Data Exchange (ETDEWEB)

    Lloyd, R.V.; Jin, L.; Fields, K. (Univ. of Michigan, Ann Arbor (USA))

    1990-01-01

    We analyzed the distribution of chromogranins A and B in normal and neoplastic endocrine tissues with secretory granules using {sup 35}S-labeled and biotin-labeled oligonucleotide probes by in situ hybridization (ISH). Both radioactive and nonradioactive probes detected messenger RNAs (mRNAs) in frozen and paraffin tissue sections. Endocrine tissues with variable immunoreactivities for chromogranin A protein, such as small-cell lung carcinomas, neuroblastomas, insulinomas, and parathyroid adenomas, expressed the mRNA for chromogranins A and B in most cells. Some technical problems with the biotinylated probes included nonspecific nuclear staining and endogenous alkaline phosphatase, which was not completely abolished by levamisole pretreatment. A differential distribution of chromogranins A and B was seen in pituitary prolactinomas, which expressed abundant chromogranin B but not chromogranin A mRNAs, and in parathyroid adenomas, which expressed abundant chromogranin A but only small amounts of chromogranin B mRNAs. These results indicate that ISH can be used to detect chromogranins A and B in endocrine tissues with radioactive and biotinylated oligonucleotide probes and that the mRNAs for chromogranin A and B are demonstrable in some tumors even when the chromogranin proteins cannot be detected by immunohistochemistry.

  19. Metal ion effects on enolase activity

    International Nuclear Information System (INIS)

    Lee, M.E.; Nowak, T.

    1986-01-01

    Most metal binding studies with yeast enolase suggest that two metals per monomer are required for catalytic activity. The functions of metal I and metal II have not been unequivocally defined. In a series of kinetic experiments where the concentration of MgII is kept constant at subsaturating levels (1mM), the addition of MnII or of ZnII gives a hyperbolic decrease in activity. The final velocity of these mixed metal systems is the same velocity obtained with either only MnII or ZnII respectively. The concentration of MnII (40 μM) or of Zn (2μM) which gives half maximal effect in the presence of (1mM) MgII is approximately the same as the Km' value for MnII (9μM) or ZnII (3μM) respectively. Direct binding of MnII to enolase in the absence and presence of MgII shows that MnII and MgII compete for the same metal site on enolase. In the presence of 2-phosphoglycerate (2-PGA) and MgII, only a single site is occupied by MnII. Results suggest MnII at site I and MgII at site II. PRR and high resolution 1 H and 31 P NMR studies of enzyme-ligand complexes containing MnII and MgII and MnII are consistent with this model. 31 P measurements allow a measure of the equilibrium constant (0.36) for enolase. Saturation transfer measurements yield net rate constants (k/sub f/ = 0.49s -1 ; k/sub r/ = 1.3s -1 ) for the overall reaction. These values are smaller than k/sub cat/ (38s -1 ) measured under analogous conditions. The cation at site I appears to determine catalytic activity

  20. Glycosylated Chromogranin A: Potential Role in the Pathogenesis of Heart Failure.

    Science.gov (United States)

    Ottesen, Anett H; Christensen, Geir; Omland, Torbjørn; Røsjø, Helge

    2017-12-01

    Endocrine and paracrine factors influence the cardiovascular system and the heart by a number of different mechanisms. The chromogranin-secretogranin (granin) proteins seem to represent a new family of proteins that exerts both direct and indirect effects on cardiac and vascular functions. The granin proteins are produced in multiple tissues, including cardiac cells, and circulating granin protein concentrations provide incremental prognostic information to established risk indices in patients with myocardial dysfunction. In this review, we provide recent data for the granin proteins in relation with cardiovascular disease, and with a special focus on chromogranin A and heart failure. Chromogranin A is the most studied member of the granin protein family, and shorter, functionally active peptide fragments of chromogranin A exert protective effects on myocardial cell death, ischemia-reperfusion injury, and cardiomyocyte Ca 2+ handling. Granin peptides have also been found to induce angiogenesis and vasculogenesis. Protein glycosylation is an important post-translational regulatory mechanism, and we recently found chromogranin A molecules to be hyperglycosylated in the failing myocardium. Chromogranin A hyperglycosylation impaired processing of full-length chromogranin A molecules into physiologically active chromogranin A peptides, and patients with acute heart failure and low rate of chromogranin A processing had increased mortality compared to other acute heart failure patients. Other studies have also demonstrated that circulating granin protein concentrations increase in parallel with heart failure disease stage. The granin protein family seems to influence heart failure pathophysiology, and chromogranin A hyperglycosylation could directly be implicated in heart failure disease progression.

  1. Primary Small Cell Neuroendocrine Carcinoma of Vagina: A Rare Case Report

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    Jignasa N. Bhalodia

    2011-01-01

    Full Text Available Primary small cell neuroendocrine carcinoma of vagina is an extremely rare disease. There have been only 26 previously reported cases in literature. Here, we report a case of primary small cell neuroendocrine carcinoma of vagina. Immunohistochemistry (IHC showed tumor cells positive for synaptophysin, chromogranin, and neuron-specific enolase (NSE.

  2. LEVELS OF NEUROSPECIFIC ENOLASE AND ENOLASE-SPECIFIC AUTOANTIBODIES IN BLOOD SERUM OF THE PATIENTS WITH AUTOIMMUNE THYROPATIES

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    N. N. Tsybikov

    2010-01-01

    Full Text Available The patients with autoimmune thyroiditis and various functional states of thyroid gland, and diffuse toxic goiter with pronounced thyrotoxicosis were studied for neurospecific enolase and enolase-specific autoantibodies levels in blood serum. Increased concentrations of neurospecific enolase and specific autoantibodies were revealed in all groups of the patients. A conclusion was drawn that nervous system may be involved into pathological process during development of thyropaties.

  3. Carbon Partitioning in Green Algae (Chlorophyta and the Enolase Enzyme

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    Jürgen E. W. Polle

    2014-08-01

    Full Text Available The exact mechanisms underlying the distribution of fixed carbon within photoautotrophic cells, also referred to as carbon partitioning, and the subcellular localization of many enzymes involved in carbon metabolism are still unknown. In contrast to the majority of investigated green algae, higher plants have multiple isoforms of the glycolytic enolase enzyme, which are differentially regulated in higher plants. Here we report on the number of gene copies coding for the enolase in several genomes of species spanning the major classes of green algae. Our genomic analysis of several green algae revealed the presence of only one gene coding for a glycolytic enolase [EC 4.2.1.11]. Our predicted cytosolic localization would require export of organic carbon from the plastid to provide substrate for the enolase and subsequent re-import of organic carbon back into the plastids. Further, our comparative sequence study of the enolase and its 3D-structure prediction may suggest that the N-terminal extension found in green algal enolases could be involved in regulation of the enolase activity. In summary, we propose that the enolase represents one of the crucial regulatory bottlenecks in carbon partitioning in green algae.

  4. Parallel expression of synaptophysin and evoked neurotransmitter release during development of cultured neurons

    DEFF Research Database (Denmark)

    Ehrhart-Bornstein, M; Treiman, M; Hansen, Gert Helge

    1991-01-01

    Primary cultures of GABAergic cerebral cortex neurons and glutamatergic cerebellar granule cells were used to study the expression of synaptophysin, a synaptic vesicle marker protein, along with the ability of each cell type to release neurotransmitter upon stimulation. The synaptophysin expression...... by quantitative immunoblotting and light microscope immunocytochemistry, respectively. In both cell types, a close parallelism was found between the temporal pattern of development in synaptophysin expression and neurotransmitter release. This temporal pattern differed between the two types of neurons....... The cerebral cortex neurons showed a biphasic time course of increase in synaptophysin content, paralleled by a biphasic pattern of development in their ability to release [3H]GABA in response to depolarization by glutamate or elevated K+ concentrations. In contrast, a monophasic, approximately linear increase...

  5. Characterization of the interaction of yeast enolase with polynucleotides.

    Science.gov (United States)

    al-Giery, A G; Brewer, J M

    1992-09-23

    Yeast enolase is inhibited under certain conditions by DNA. The enzyme binds to single-stranded DNA-cellulose. Inhibition was used for routine characterization of the interaction. The presence of the substrate 2-phospho-D-glycerate reduces inhibition and binding. Both yeast enolase isozymes behave similarly. Impure yeast enolase was purified by adsorption onto a single-stranded DNA-cellulose column followed by elution with substrate. Interaction with RNA, double-stranded DNA, or degraded DNA results in less inhibition, suggesting that yeast enolase preferentially binds single-stranded DNA. However, yeast enolase is not a DNA-unwinding protein. The enzyme is inhibited by the short synthetic oligodeoxynucleotides G6, G8 and G10 but not T8 or T6, suggesting some base specificity in the interaction. The interaction is stronger at more acid pH values, with an apparent pK of 5.6. The interaction is prevented by 0.3 M KCl, suggesting that electrostatic factors are important. Histidine or lysine reverse the inhibition at lower concentrations, while phosphate is still more effective. Binding of single-stranded DNA to enolase reduces the reaction of protein histidyl residues with diethylpyrocarbonate. The inhibition of yeast enolase by single-stranded DNA is not total, and suggests the active site is not directly involved in the interaction. Binding of substrate may induce a conformational change in the enzyme that interferes with DNA binding and vice versa.

  6. Surface-expressed enolases of Plasmodium and other pathogens

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    Anil Kumar Ghosh

    2011-08-01

    Full Text Available Enolase is the eighth enzyme in the glycolytic pathway, a reaction that generates ATP from phosphoenol pyruvate in cytosolic compartments. Enolase is essential, especially for organisms devoid of the Krebs cycle that depend solely on glycolysis for energy. Interestingly, enolase appears to serve a separate function in some organisms, in that it is also exported to the cell surface via a poorly understood mechanism. In these organisms, surface enolase assists in the invasion of their host cells by binding plasminogen, an abundant plasma protease precursor. Binding is mediated by the interaction between a lysine motif of enolase with Kringle domains of plasminogen. The bound plasminogen is then cleaved by specific proteases to generate active plasmin. Plasmin is a potent serine protease that is thought to function in the degradation of the extracellular matrix surrounding the targeted host cell, thereby facilitating pathogen invasion. Recent work revealed that the malaria parasite Plasmodium also expresses surface enolase, and that this feature may be essential for completion of its life cycle. The therapeutic potential of targeting surface enolases of pathogens is discussed.

  7. Inhibition of purified enolases from oral bacteria by fluoride.

    Science.gov (United States)

    Guha-Chowdhury, N; Clark, A G; Sissons, C H

    1997-04-01

    Enolase activity in strains of oral streptococci previously has been found to be inhibited by 50% (Ki) by fluoride concentrations ranging from 50 to 300 microM or more in the presence of 0.5 to 1.0 mM inorganic phosphate ions. In this study, enolase was extracted and partly purified by a two-step process from five oral bacterial species and the effect of fluoride on the kinetics of enolase examined. The molecular weight of the putative enolase proteins was 46-48 kDa. The Vmax values ranged from 20 to 323 IU/mg and K(m) for glycerate-2-phosphate from 0.22 to 0.74 mM. Enolase activity was inhibited competitively by fluoride, with Ki values ranging from 16 to 54 microM in the presence of 5 mM inorganic phosphate ions. Ki values for phosphate ranged from 2 to 8 mM. The enolase from Streptococcus sanguis ATCC 10556 was more sensitive to fluoride (Ki = 16 +/- 2) than was enolase from Streptococcus salivarius ATCC 10575 (Ki = 19 +/- 2) or Streptococcus mutans NCTC 10449 (Ki = 40 +/- 4) and all three streptococcal strains were more sensitive to fluoride than either Actinomyces naeslundii WVU 627 (Ki = 46 +/- 6) or Lactobacillus rhamnosus ATCC 7469 (Ki = 54 +/- 6) enolases. The levels of fluoride found to inhibit the streptococcal enolases in this study are much lower than previously reported and are likely to be present in plaque, especially during acidogenesis, and could exert an anti-glycolytic effect.

  8. The surging role of Chromogranin A in cardiovascular homeostasis

    Science.gov (United States)

    Tota, Bruno; Angelone, Tommaso; Cerra, Maria

    2014-08-01

    Together with Chromogranin B and Secretogranins, Chromogranin A (CGA) is stored in secretory (chromaffin) granules of the diffuse neuroendocrine system and released with noradrenalin and adrenalin. Co-stored within the granule together with neuropeptideY, cardiac natriuretic peptide hormones, several prohormones and their proteolytic enzymes, CGA is a multifunctional protein and a major marker of the sympatho-adrenal neuroendocrine activity. Due to its partial processing to several biologically active peptides, CGA appears an important pro-hormone implicated in relevant modulatory actions on endocrine, cardiovascular, metabolic, and immune systems through both direct and indirect sympatho-adrenergic interactions. As a part of this scenario, we here illustrate the emerging role exerted by the full-length CGA and its three derived fragments, i.e. Vasostatin 1, catestatin and serpinin, in the control of circulatory homeostasis with particular emphasis on their cardio-vascular actions under both physiological and physio-pathological conditions. The Vasostatin 1- and catestatin-induced cardiodepressive influences are achieved through anti-beta-adrenergic-NO-cGMP signalling, while serpinin acts like beta1-adrenergic agonist through AD-cAMP-independent NO signalling. On the whole, these actions contribute to wide our knowledge regarding the sympatho-chromaffin control of the cardiovascular system and its highly integrated “whip-brake” networks.

  9. [Effect of piperine on 5-HT and synaptophysin expression of rats with irritable bowel syndrome].

    Science.gov (United States)

    Wu, Shu-Juan; Wang, Ren-Ye; Xue, Ji-Xiong; Pan, Jian-Chun

    2013-12-01

    This study is to explore the amelioration of piperine on chronic acute combining stress rat with depression-like behavior, visceral sensitivity, and its effect on the expression of serotonin (5-HT) and synaptophysin. Forty two SD rats were divided into seven groups: blank group, model group, piperine (12.5, 25, 50 and 100 mgkg-1, ig) and imipramine (10 mgkg-1, ip) groups. The rat model of irritable bowel syndrome was established by chronic acute combining stress, and then to evaluate depression-like behavior and visceral sensitivity. The expressions of 5-HT and synaptophysin in the hippocampus and colon were determined by high performance liquid chromatography (HPLC) and Western blotting, respectively. The duration of immobility of IBS rat in the forced swimming test had been significantly increased, the sucrose consumption of IBS rat had been reduced and visceral sensitivity was obviously elevated in the IBS model group as compared with those in the normal control group (P<0.05, P<0.01). As compared with those in the normal control group, the expression of 5-HT significantly decreased, 5-HIAA/5-HT ratio significantly increased in the hippocampus of IBS model group (P<0.05), but opposite presentations were noted in the colon (P<0.05). As compared with that in the normal control group, the synaptophysin expression in the hippocampus decreased significantly but obviously increased in the colon (P<0.05). Piperine improved the behavior of IBS rats, and reversed the levels of 5-HT and 5-HIAA, and 5-HIAA/5-HT proportion in the hippocampus and colon (P<0.05); besides, they significantly reverse the synaptophysin level in the hippocampus and colon (P<0.05). The presence of depression and visceral sensitivity had been changed in IBS rats, with abnormal expression of 5-HT and synaptophysin in the brain-gut system. Piperine can ameliorate the changes of the behavior and regulation of serotonin and synaptophysin expression in IBS rat model.

  10. Factors associated with elevated serum chromogranin A levels in patients with autoimmune gastritis.

    Science.gov (United States)

    Kalkan, Çağdaş; Karakaya, Fatih; Soykan, İrfan

    2016-11-01

    Chromogranin A is an important tool in the diagnosis of neuroendocrine tumors. Autoimmune gastritis is an autoimmune disorder marked by hypergastrinemia, which stimulates enterochromaffin-like cell proliferation. Chromogranin A is also elevated in autoimmune gastritis patients with a different level of increase in each patient. The goal of this study is to explore constituents that influence serum chromogranin A levels in autoimmune gastritis patients. One hundred and eighty-eight autoimmune gastritis patients and 20 patients with type I gastric carcinoid tumors were analyzed retrospectively and compared to 110 functional dyspepsia patients in terms of factors that might affect serum chromogranin A levels. The mean serum chromogranin A level was 171.17±67.3 ng/mL in autoimmune gastritis patients (n=62) without enterochromaffin-like cell hyperplasia, and 303.3±102.82 ng/mL in patients (n=126) with enterochromaffin-like cell hyperplasia (pgastritis were the presence of ECL cell hyperplasia and serum gastrin levels. Serum chromogranin A levels maybe helpful in distinguishing autoimmune gastritis patients and gastric carcinoid type I from the control group, but not useful in the differentiation of individuals with autoimmune gastritis from patients with gastric carcinoids.

  11. CLINICAL VALUE OF CHROMOGRANIN A IN GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS

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    N. V. Lyubimova

    2015-01-01

    Full Text Available Background: Neuroendocrine tumors (NET is a heterogeneous group of neoplasms characterized by hypersecretion of biologically active sub- stances that manifests by specific syndromes and determines the clinical course of the disease. The most common NET types are those of gastrointestinal tract. The obligatory biochemical marker used in the examination of NET patients is chromogranin A (CgA.Aim: Evaluation of the CgA value for diagnostics and monitoring of gastrointestinal NETs.Materials and methods: A comparative study of plasma CgA levels was performed in 146 patients with gastroenteropancreatic neuroendocrine tu- mors and 66 healthy individuals using the enzyme immunoassay “Chromogranin A ELISA kit” (Dako A/S, Denmark.Results: CgA levels were significantly higher in patients with NETs of all localizations, such as pancreas, stomach, gut, small and large bowel, than in the healthy subjects (р < 0.000001. In NET patients, CgA secretion was highly variable, with the highest value in the group of patients with gastric NETs (102000 U/l. The highest CgA medians were detected in patients with small intestinal (183.9 U/l, colon (148.4 U/l and pancreatic (135.9 U/l NETs. There was an association between CgA secretion and extension or activity of NETs, with the highest median values in patients with hepatic metastases (395 U/l and those with carcinoid syndrome (352 U/l. The clinical significance of CgA as a NET marker was assessed using the cut-off value of 33 U/l, calculated according to the results in the control group. Overall diagnostic sensitivity of CgA in NET patients was high (85.8% with a specificity of 98.5%. Conclusion: The results obtained confirm a high sensitivity of CgA as a NET marker whose determination helps to improve accuracy of diagnostics and to assess NET prevalence.

  12. A chromogranin A ELISA absent of an apparent high-dose hook effect observed in other chromogranin A ELISAs.

    Science.gov (United States)

    Erickson, J Alan; Grenache, David G

    2016-01-15

    Routine testing for chromogranin A (CgA) using an established commercial ELISA revealed an apparent high-dose hook effect in approximately 15% of specimens. Investigations found the same effect in two additional ELISAs. We hypothesized that a CgA derived peptide(s) at high concentrations was responsible but experiments were inconclusive. Here we describe the analytical performance characteristics of the Chromoa™ CgA ELISA that did not display the apparent high-dose hook effect. Performance characteristics of the Chromoa ELISA were assessed. The reference interval was established utilizing healthy volunteers. Specimens producing the apparent high-dose hook effect in other assays were evaluated using the Chromoa ELISA. The limit of detection was 8ng/ml. Linearity was acceptable (slope=1.04, intercept=18.1 and r(2)=0.997). CVs were ≤4.6 and ≤9.3% for repeatability and within-laboratory imprecision, respectively. CgA was stable at ambient and refrigerated temperatures for a minimum of two and 14days, respectively. An upper reference interval limit of 95ng/ml was established. Specimens demonstrating the apparent high-dose hook effect in other ELISAs did not exhibit the phenomenon using the Chromoa ELISA. The Chromoa ELISA demonstrates acceptable performance for quantifying serum CgA. The apparent high-dose hook effect exhibited in other ELISAs was absent using the Chromoa assay. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Pituitary oncocytoma presenting as Cushing′s disease

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    M K Garg

    2013-01-01

    Full Text Available A 19-year-old girl presented with classical features of Cushing′s syndrome. Endocrinal evaluation was consistent with pituitary source of ACTH; but imaging showed normal pituitary. Bilateral inferior petrosal sinus sampling confirmed the diagnosis. A successful remission was achieved after adenomectomy by transphenoidal route. Histopathological examination was consistent with pituitary oncocytoma and immunohistochemistry was positive for synaptophysin, chromogranin, neuron specific enolase, S-100, ACTH, prolactin, and GH.

  14. Purification and properties of enolase of human erythrocytes

    NARCIS (Netherlands)

    Hoorn, R.K.J.; Flikweert, J.P.; Staal, Gerard E.J.

    1974-01-01

    1. 1. Human erythrocyte enolase (2-phospho-D-glycerate hydrolyase, EC 4.2.1.11) was purified I000-fold. 2. 2. The pH-optimum was at pH 6.5. The molecular weight, estimated by gel filtration, was found to be 95,000 ± 5,000. 3. 3. Electrophoresis on agar-agarose at pH 8.5 and 6.4 showed only one

  15. Progress in the biological function of alpha-enolase

    Directory of Open Access Journals (Sweden)

    Hong Ji

    2016-03-01

    Full Text Available Alpha-enolase (ENO1, also known as 2-phospho-D-glycerate hydrolase, is a metalloenzyme that catalyzes the conversion of 2-phosphoglyceric acid to phosphoenolpyruvic acid in the glycolytic pathway. It is a multifunctional glycolytic enzyme involved in cellular stress, bacterial and fungal infections, autoantigen activities, the occurrence and metastasis of cancer, parasitic infections, and the growth, development and reproduction of organisms. This article mainly reviews the basic characteristics and biological functions of ENO1.

  16. Effect of site-directed mutagenesis of His373 of yeast enolase on some of its physical and enzymatic properties.

    Science.gov (United States)

    Brewer, J M; Glover, C V; Holland, M J; Lebioda, L

    1997-06-20

    The X-ray structure of yeast enolase shows His373 interacting with a water molecule also held by residues Glu168 and Glu211. The water molecule is suggested to participate in the catalytic mechanism (Lebioda, L. and Stec, B. (1991) Biochemistry 30, 2817-2822). Replacement of His373 with asparagine (H373N enolase) or phenylalanine (H373F enolase) reduces enzymatic activity to ca. 10% and 0.0003% of the native enzyme activity, respectively. H373N enolase exhibits a reduced Km for the substrate, 2-phosphoglycerate, and produces the same absorbance changes in the chromophoric substrate analogues TSP1 and AEP1, relative to native enolase. H373F enolase binds AEP less strongly, producing a smaller absorbance change than native enolase, and reacts very little with TSP. H373F enolase dissociates to monomers in the absence of substrate; H373N enolase subunit dissociation is less than H373F enolase but more than native enolase. Substrate and Mg2+ increase subunit association in both mutants. Differential scanning calorimetric experiments indicate that the interaction with substrate that stabilizes enolase to thermal denaturation involves His373. We suggest that the function of His373 in the enolase reaction may involve hydrogen bonding rather than acid/base catalysis, through interaction with the Glu168/Glu211/H2O system, which produces removal or addition of hydroxyl at carbon-3 of the substrate.

  17. Polychlorinated biphenyls alter expression of alpha-synuclein, synaptophysin and parkin in the rat brain

    DEFF Research Database (Denmark)

    Malkiewicz, Katarzyna; Mohammed, Roma; Folkesson, Ronnie

    2006-01-01

    Polychlorinated Biphenyls (PCBs)-induced changes in synaptic transmission are one of the effects of their neurotoxicity but the mechanism remains unknown. We assessed the in vivo effects of the PCBs mixture, Aroclor 1254 on the expression of neuronal proteins that are involved in the synaptic...... function and/or are associated with neurodegeneration. Wistar rats were treated orally with repeated doses of Aroclor 1254 and the levels of soluble alpha-synuclein, parkin, synaptophysin and amyloid precursor protein (APP) in the brain were determined by Western blotting. The results showed that Aroclor...... did not cause changes in the expression and processing of APP but at a dose 100 microg/g/day repeated for 6 days caused a decrease in the expression of alpha-synuclein in the cerebellum, cortex, hippocampus and hypothalamus of the animals sacrificed 2 days after treatment. The decrease in alpha...

  18. The primary structures of two yeast enolase genes. Homology between the 5' noncoding flanking regions of yeast enolase and glyceraldehyde-3-phosphate dehydrogenase genes.

    Science.gov (United States)

    Holland, M J; Holland, J P; Thill, G P; Jackson, K A

    1981-02-10

    Segments of yeast genomic DNA containing two enolase structural genes have been isolated by subculture cloning procedures using a cDNA hybridization probe synthesized from purified yeast enolase mRNA. Based on restriction endonuclease and transcriptional maps of these two segments of yeast DNA, each hybrid plasmid contains a region of extensive nucleotide sequence homology which forms hybrids with the cDNA probe. The DNA sequences which flank this homologous region in the two hybrid plasmids are nonhomologous indicating that these sequences are nontandemly repeated in the yeast genome. The complete nucleotide sequence of the coding as well as the flanking noncoding regions of these genes has been determined. The amino acid sequence predicted from one reading frame of both structural genes is extremely similar to that determined for yeast enolase (Chin, C. C. Q., Brewer, J. M., Eckard, E., and Wold, F. (1981) J. Biol. Chem. 256, 1370-1376), confirming that these isolated structural genes encode yeast enolase. The nucleotide sequences of the coding regions of the genes are approximately 95% homologous, and neither gene contains an intervening sequence. Codon utilization in the enolase genes follows the same biased pattern previously described for two yeast glyceraldehyde-3-phosphate dehydrogenase structural genes (Holland, J. P., and Holland, M. J. (1980) J. Biol. Chem. 255, 2596-2605). DNA blotting analysis confirmed that the isolated segments of yeast DNA are colinear with yeast genomic DNA and that there are two nontandemly repeated enolase genes per haploid yeast genome. The noncoding portions of the two enolase genes adjacent to the initiation and termination codons are approximately 70% homologous and contain sequences thought to be involved in the synthesis and processing messenger RNA. Finally there are regions of extensive homology between the two enolase structural genes and two yeast glyceraldehyde-3-phosphate dehydrogenase structural genes within the 5

  19. Identification and characterization of a novel protective antigen, Enolase of Streptococcus suis serotype 2.

    Science.gov (United States)

    Zhang, Anding; Chen, Bo; Mu, Xiaofeng; Li, Ran; Zheng, Pei; Zhao, Yaxin; Chen, Huanchun; Jin, Meilin

    2009-02-25

    Streptococcus suis serotype 2 (SS2) is a porcine and human pathogen with adhesive and invasive properties. The absence of suitable vaccine or virulent marker can be the bottleneck to control SS2 infection. In the present study, a novel immunogenic Enolase identified in the previous study was inducibly overexpressed in Escherichia coli, and the purified recombinant protein could elicit a significant humoral antibody response and confer efficient immunity against challenge with lethal dose of SS2 or SS7 infection in mouse model. The roles Enolase plays in pathogenicity of SS2 were also explored as reasons for which Enolase could be a protective antigen. The Enolase was an in vivo-induced antigen confirmed by the real-time PCR and could adhere to the Hep-2 cells by the indirect immunofluorescent assay and the inhibition assay. These suggested that Enolase could play important roles in pathogenicity and may serve as a novel vaccine candidate against SS2 infection.

  20. Sarcocystis neurona: molecular characterization of enolase domain I region and a comparison to other protozoa.

    Science.gov (United States)

    Bolten, K E; Marsh, A E; Reed, S M; Dubey, J P; Toribio, R E; Saville, W J A

    2008-09-01

    Sarcocystis neurona causes protozoal myeloencephalitis and has the ability to infect a wide host range in contrast to other Sarcocystis species. In the current study, five S. neurona isolates from a variety of sources, three Sarcocystis falcatula, one Sarcocystis dasypi/S. neurona-like isolate, and one Besnoitia darlingi isolate were used to compare the enolase 2 gene segment containing the domain I region to previously sequenced enolase genes from Neospora caninum, Neospora hughesi, Toxoplasma gondii, Plasmodium falciparum, and Trypanosoma cruzi; enolase 2 segment containing domain I region is highly conserved amongst these parasites of veterinary and medical importance. Immunohistochemistry results indicates reactivity of T. gondii enolase 1 and 2 antibodies to S. neurona merozoites and metrocytes, but no reactivity of anti-enolase 1 to the S. neurona bradyzoite stage despite reactivity to T. gondii bradyzoites, suggesting expression differences between organisms.

  1. An evaluation of chromogranin A versus gastrin and progastrin in gastrinoma diagnosis and control

    DEFF Research Database (Denmark)

    Rehfeld, Jens F; Bardram, Linda; Hilsted, Linda

    2014-01-01

    AIM: The value of chromogranin A (CgA) versus gastrin and progastrin in diagnosis and control of gastrinoma patients is not settled because the peptides circulate as variable mixtures. We have addressed this complexity using defined sequence-specific assays. PATIENTS & METHODS: Six assays were......-amidated gastrins have high diagnostic value except for singular patients in whom only progastrin was elevated. By contrast, CgA measurements are not valid in diagnosis or control of gastrinomas....

  2. Tooth loss early in life suppresses neurogenesis and synaptophysin expression in the hippocampus and impairs learning in mice.

    Science.gov (United States)

    Kubo, Kin-Ya; Murabayashi, Chika; Kotachi, Mika; Suzuki, Ayumi; Mori, Daisuke; Sato, Yuichi; Onozuka, Minoru; Azuma, Kagaku; Iinuma, Mitsuo

    2017-02-01

    Tooth loss induced neurological alterations through activation of a stress hormone, corticosterone. Age-related hippocampal morphological and functional changes were accelerated by early tooth loss in senescence-accelerated mouse prone 8 (SAMP8). In order to explore the mechanism underlying the impaired hippocampal function resulting from early masticatory dysfunction due to tooth loss, we investigated the effects of early tooth loss on plasma corticosterone levels, learning ability, neurogenesis, and synaptophysin expression in the hippocampus later in life of SAMP8 mice. We examined the effects of tooth loss soon after tooth eruption (1 month of age) on plasma corticosterone levels, learning ability in the Morris water maze, newborn cell proliferation, survival and differentiation in the hippocampal dentate gyrus, and synaptophysin expression in the hippocampus of aged (8 months of age) SAMP8 mice. Aged mice with early tooth loss exhibited increased plasma corticosterone levels, hippocampus-dependent learning deficits in the Morris water maze, decreased cell proliferation, and cell survival in the dentate gyrus, and suppressed synaptophysin expression in the hippocampus. Newborn cell differentiation in the hippocampal dentate gyrus, however, was not affected by early tooth loss. These findings suggest that learning deficits in aged SAMP8 mice with tooth loss soon after tooth eruption are associated with suppressed neurogenesis and decreased synaptophysin expression resulting from increased plasma corticosterone levels, and that long-term tooth loss leads to impaired cognitive function in older age. Copyright © 2016. Published by Elsevier Ltd.

  3. The P413L chromogranin B variation in French patients with sporadic amyotrophic lateral sclerosis.

    Science.gov (United States)

    Blasco, Hélène; Corcia, Philippe; Veyrat-Durebex, Charlotte; Coutadeur, Cathleen; Fournier, Clémentine; Camu, William; Gordon, Paul; Praline, Julien; Andres, Christian R; Vourc'h, Patrick

    2011-05-01

    Chromogranins interact with mutant forms of superoxide dismutase 1 (SOD1) responsible for a portion of familial amyotrophic lateral sclerosis (ALS). A particular variation (P413L) in the chromogranin B gene, CHGB, has been recently associated with an earlier age at onset in both familial and sporadic ALS. The aim of our study was to evaluate the P413L chromogranin variation in French patients with sporadic amyotrophic lateral sclerosis. We developed a High Resolution DNA Melting (HRM) protocol to analyse the P413L variation in the CHGB gene in 540 French patients with sporadic ALS and 504 controls. The clinical characteristics of patients were analysed in relation to their genotype. Results showed that our study on a large cohort of French-Caucasian patients with SALS and controls failed to confirm an increased frequency of the 413L variant in SALS patients. This frequency was 5.3% in the SALS population and 5.5% in the control group. Moreover, we did not observe a previous observation of a difference of age at onset between T-allele carriers and non-carriers (median age of onset 60.4 vs. 62.0 years of age, respectively). Thus, our findings do not support the 413L variant of rs742710 as a risk factor for sporadic ALS in the French population.

  4. Molecular characterization of enolase gene from Taenia multiceps.

    Science.gov (United States)

    Li, W H; Qu, Z G; Zhang, N Z; Yue, L; Jia, W Z; Luo, J X; Yin, H; Fu, B Q

    2015-10-01

    Taenia multiceps is a cestode parasite with its larval stage, known as Coenurus cerebralis, mainly encysts in the central nervous system of sheep and other livestocks. Enolase is a key glycolytic enzyme and represents multifunction in most organisms. In the present study, a 1617bp full-length cDNA encoding enolase was cloned from T. multiceps and designated as TmENO. A putative encoded protein of 433 amino acid residues that exhibited high similarity to helminth parasites. The recombinant TmENO protein (rTmENO) showed the catalytic and plasminogen-binding characteristics after the TmENO was subcloned and expressed in the pET30a(+) vector. The TmENO gene was transcribed during the adult and larval stages and was also identified in both cyst fluid and as a component of the adult worms and the metacestode by western blot analysis. Taken together, our results will facilitate further structural characterization for TmENO and new potential control strategies for T. multiceps. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Increased synaptophysin is involved in inflammation-induced heat hyperalgesia mediated by cyclin-dependent kinase 5 in rats.

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    Hong-Hai Zhang

    Full Text Available Mechanisms associated with cyclin-dependent kinase 5 (Cdk5-mediated heat hyperalgesia induced by inflammation remain undefined. This study was designed to examine whether Cdk5 mediates heat hyperalgesia resulting from peripheral injection of complete Freund's adjuvant (CFA in the spinal dorsal horns of rats by interacting with synaptophysin, a well known membrane protein mediating the endocytosis-exocytosis cycle of synaptic vesicles as a molecular marker associated with presynaptic vesicle membranes. The role of Cdk5 in mediating synaptophysin was examined through the combined use of behavioral approaches, imaging studies, and immunoprecipitation following CFA-induced inflammatory pain. Results showed that Cdk5 colocalized with both synaptophysin and soluble N-ethylmaleimide-sensitive factor (NSF attachment protein receptors (SNAREs consisting of VAMP-2, SNAP-25, and syntaxin 1A in spinal dorsal horn of rats. Increased synaptophysin expression of spinal cord horn neurons post intraplantar injection of CFA coincided with increased duration of heat hyperalgesia lasting from 6 h to 3 d. Intrathecal administration of roscovitine, a Cdk5 specific inhibitor, significantly depressed synaptophysin expression during peak heat hyperalgesia and heat hyperalgesia induced by peripheral injection of CFA. Data presented in this report indicated that calpain activity was transiently upregulated 6 h post CFA-treatment despite previous reports suggesting that calpain was capable of cleaving p35 into p25. Results from previous studies obtained by other laboratories demonstrated that significant changes in p35 expression levels within spinal cord horn neurons were not observed in the CFA-treated inflammatory pain model although significant upregulation of Cdk5 kinase was observed between 2 h to 7 d. Therefore, generation of p25 occurred in a calpain-independent fashion in a CFA-treated inflammatory pain model. Our results demonstrated that increased synaptophysin

  6. The interaction of streptococcal enolase with canine plasminogen: the role of surfaces in complex formation.

    Directory of Open Access Journals (Sweden)

    Vinod Balhara

    Full Text Available The enolase from Streptococcus pyogenes (Str enolase F137L/E363G is a homo-octamer shaped like a donut. Plasminogen (Pgn is a monomeric protein composed of seven discrete separated domains organized into a lock washer. The enolase is known to bind Pgn. In past work we searched for conditions in which the two proteins would bind to one another. The two native proteins in solution would not bind under any of the tried conditions. We found that if the structures were perturbed binding would occur. We stated that only the non-native Str enolase or Pgn would interact such that we could detect binding. We report here the results of a series of dual polarization interferometry (DPI experiments coupled with atomic force microscopy (AFM, isothermal titration calorimetry (ITC, dynamic light scattering (DLS, and fluorescence. We show that the critical condition for forming stable complexes of the two native proteins involves Str enolase binding to a surface. Surfaces that attract Str enolase are a sufficient condition for binding Pgn. Under certain conditions, Pgn adsorbed to a surface will bind Str enolase.

  7. Enzymatic function of loop movement in enolase: preparation and some properties of H159N, H159A, H159F, and N207A enolases.

    Science.gov (United States)

    Brewer, John M; Glover, Claiborne V C; Holland, Michael J; Lebioda, Lukasz

    2003-05-01

    The hypothesis that His159 in yeast enolase moves on a polypeptide loop to protonate the phosphoryl of 2-phosphoglycerate to initiate its conversion to phosphoenolpyruvate was tested by preparing H159N, H159A, and H159F enolases. These have 0.07%-0.25% of the native activity under standard assay conditions and the pH dependence of maximum velocities of H159A and H159N mutants is markedly altered. Activation by Mg2+ is biphasic, with the smaller Mg2+ activation constant closer to that of the "catalytic" Mg2+ binding site of native enolase and the larger in the mM range in which native enolase is inhibited. A third Mg2+ may bind to the phosphoryl, functionally replacing proton donation by His159. N207A enolase lacks an intersubunit interaction that stabilizes the closed loop(s) conformation when 2-phosphoglycerate binds. It has 21% of the native activity, also exhibits biphasic Mg2+ activation, and its reaction with the aldehyde analogue of the substrate is more strongly inhibited than is its normal enzymatic reaction. Polypeptide loop(s) closure may keep a proton from His159 interacting with the substrate phosphoryl oxygen long enough to stabilize a carbanion intermediate.

  8. Synaptophysin 1 Clears Synaptobrevin 2 from the Presynaptic Active Zone to Prevent Short-Term Depression

    Directory of Open Access Journals (Sweden)

    Rajit Rajappa

    2016-02-01

    Full Text Available Release site clearance is an important process during synaptic vesicle (SV recycling. However, little is known about its molecular mechanism. Here we identify self-assembly of exocytosed Synaptobrevin 2 (Syb2 and Synaptophysin 1 (Syp1 by homo- and hetero-oligomerization into clusters as key mechanisms mediating release site clearance for preventing cis-SNARE complex formation at the active zone (AZ. In hippocampal neurons from Syp1 knockout mice, neurons expressing a monomeric Syb2 mutant, or after acute block of the ATPase N-ethylmaleimide-sensitive factor (NSF, responsible for cis-SNARE complex disassembly, we found strong frequency-dependent short-term depression (STD, whereas retrieval of Syb2 by compensatory endocytosis was only affected weakly. Defects in Syb2 endocytosis were stimulus- and frequency-dependent, indicating that Syp1 is not essential for Syb2 retrieval, but for its efficient clearance upstream of endocytosis. Our findings identify an SV protein as a release site clearance factor.

  9. Chromogranin A is present in and released by fish endocrine tissue

    International Nuclear Information System (INIS)

    Deftos, L.J.; Bjoernsson, B.T.; Burton, D.W.; O'Connor, D.T.; Copp, D.H.

    1987-01-01

    Chromogranin A (CgA) is a protein that is present in many mammalian endocrine cells and co-secreted with their resident hormones. The authors have demonstrated the presence of CgA by immunohistology in the ultimobranchial glands and corpuscles of Stannius of rainbow trout. CgA was also detected by radioimmunoassay in the medium of incubated coho salmon ultimobranchial glands. Their observations demonstrate the presence of CgA in endocrine glands of evolutionarily divergent species. These observations are consistent with the hypothesis that CgA participates in the secretory process of a wide variety of hormones. 18 references, 1 figure, 1 table

  10. Multifunctional roles of enolase in Alzheimer's disease brain: beyond altered glucose metabolism.

    Science.gov (United States)

    Butterfield, D Allan; Lange, Miranda L Bader

    2009-11-01

    Enolase enzymes are abundantly expressed, cytosolic carbon-oxygen lyases known for their role in glucose metabolism. Recently, enolase has been shown to possess a variety of different regulatory functions, beyond glycolysis and gluconeogenesis, associated with hypoxia, ischemia, and Alzheimer's disease (AD). AD is an age-associated neurodegenerative disorder characterized pathologically by elevated oxidative stress and subsequent damage to proteins, lipids, and nucleic acids, appearance of neurofibrillary tangles and senile plaques, and loss of synapse and neuronal cells. It is unclear if development of a hypometabolic environment is a consequence of or contributes to AD pathology, as there is not only a significant decline in brain glucose levels in AD, but also there is an increase in proteomics identified oxidatively modified glycolytic enzymes that are rendered inactive, including enolase. Previously, our laboratory identified alpha-enolase as one the most frequently up-regulated and oxidatively modified proteins in amnestic mild cognitive impairment (MCI), early-onset AD, and AD. However, the glycolytic conversion of 2-phosphoglycerate to phosphoenolpyruvate catalyzed by enolase does not directly produce ATP or NADH; therefore it is surprising that, among all glycolytic enzymes, alpha-enolase was one of only two glycolytic enzymes consistently up-regulated from MCI to AD. These findings suggest enolase is involved with more than glucose metabolism in AD brain, but may possess other functions, normally necessary to preserve brain function. This review examines potential altered function(s) of brain enolase in MCI, early-onset AD, and AD, alterations that may contribute to the biochemical, pathological, clinical characteristics, and progression of this dementing disorder.

  11. The H159A mutant of yeast enolase 1 has significant activity.

    Science.gov (United States)

    Brewer, J M; Holland, M J; Lebioda, L

    2000-10-05

    The function of His159 in the enolase mechanism is disputed. Recently, Vinarov and Nowak (Biochemistry (1999) 38, 12138-12149) prepared the H159A mutant of yeast enolase 1 and expressed this in Escherichia coli. They reported minimal (ca. 0.01% of the native value) activity, though the protein appeared to be correctly folded, according to its CD spectrum, tryptophan fluorescence, and binding of metal ion and substrate. We prepared H159A enolase using a multicopy plasmid and expressed the enzyme in yeast. Our preparations of H159A enolase have 0.2-0.4% of the native activity under standard assay conditions and are further activated by Mg(2+) concentrations above 1 mM to 1-1.5% of the native activity. Native enolase 1 (and enolase 2) are inhibited by such Mg(2+) concentrations. It is possible that His159 is necessary for correct folding of the enzyme and that expression in E. coli leads to largely misfolded protein. Copyright 2000 Academic Press.

  12. Identification and characterization of Taenia solium enolase as a plasminogen-binding protein.

    Science.gov (United States)

    Ayón-Núñez, Dolores A; Fragoso, Gladis; Espitia, Clara; García-Varela, Martín; Soberón, Xavier; Rosas, Gabriela; Laclette, Juan P; Bobes, Raúl J

    2018-06-01

    The larval stage of Taenia solium (cysticerci) is the causal agent of human and swine cysticercosis. When ingested by the host, T. solium eggs are activated and hatch in the intestine, releasing oncospheres that migrate to various tissues and evolve into cysticerci. Plasminogen (Plg) receptor proteins have been reported to play a role in migration processes for several pathogens. This work is aimed to identify Plg-binding proteins in T. solium cysticerci and determine whether T. solium recombinant enolase (rTsEnoA) is capable of specifically binding and activating human Plg. To identify Plg-binding proteins, a 2D-SDS-PAGE ligand blotting was performed, and recognized spots were identified by MS/MS. Seven proteins from T. solium cysticerci were found capable of binding Plg: fascicilin-1, fasciclin-2, enolase, MAPK, annexin, actin, and cytosolic malate dehydrogenase. To determine whether rTsEnoA binds human Plg, a ligand blotting was performed and the results were confirmed by ELISA both in the presence and absence of εACA, a competitive Plg inhibitor. Finally, rTsEnoA-bound Plg was activated to plasmin in the presence of tPA. To better understand the evolution of enolase isoforms in T. solium, a phylogenetic inference analysis including 75 enolase amino acid sequences was conducted. The origin of flatworm enolase isoforms, except for Eno4, is independent of their vertebrate counterparts. Therefore, herein we propose to designate tapeworm protein isoforms as A, B, C, and 4. In conclusion, recombinant enolase showed a strong plasminogen binding and activating activity in vitro. T. solium enolase could play a role in parasite invasion along with other plasminogen-binding proteins. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Chromogranin A

    Science.gov (United States)

    ... PF4 Antibody Hepatitis A Testing Hepatitis B Testing Hepatitis C Testing HER2/neu Herpes Testing High-sensitivity C-reactive Protein (hs-CRP) Histamine Histone Antibody HIV Antibody and HIV Antigen (p24) HIV Antiretroviral Drug Resistance Testing, Genotypic HIV Viral Load HLA Testing HLA- ...

  14. Plasma chromogranin A levels are increased in a small portion of patients with hereditary head and neck paragangliomas

    NARCIS (Netherlands)

    van Duinen, Nicolette; Kema, Ido P.; Romijn, Johannes A.; Corssmit, Eleonora P. M.

    2011-01-01

    The majority of patients with head and neck paragangliomas (HNPGL) have biochemically silent tumours. Chromogranin A (CgA) is a tumour marker for neuroendocrine tumours. To assess the role of CgA as a tumour marker in patients with hereditary HNPGL. We included 95 consecutive patients with

  15. Plasma chromogranin A levels are increased in a small portion of patients with hereditary head and neck paragangliomas

    NARCIS (Netherlands)

    van Duinen, Nicolette; Kema, Ido P.; Romijn, Johannes A.; Corssmit, Eleonora P. M.

    P>Context The majority of patients with head and neck paragangliomas (HNPGL) have biochemically silent tumours. Chromogranin A (CgA) is a tumour marker for neuroendocrine tumours. Objective To assess the role of CgA as a tumour marker in patients with hereditary HNPGL. Patients and Methods We

  16. Yeast enolase: mechanism of activation by metal ions.

    Science.gov (United States)

    Brewer, J M

    1981-01-01

    Yeast enolase as prepared by current procedures is inherently chemically homogeneous, though deamidation and partial denaturation can produce electrophoretically distinct forms. A true isozyme of the enzyme exists but does not survive the purification procedure. The chemical sequence for both has been established. The enzyme behaves in solution like a compact, nearly spherical molecule of moderate hydration. Strong intramolecular forces maintain the structure of the individual subunits. The enzyme as isolated is dimeric. If dissociated in the presence of magnesium ions and substrate, then the subunits are active, but if the dissociation occurs in the absence of metal ions, they are inactive until they have reassociated and undergone a first order "annealing" process. Magnesium (II) enhances association. The interaction between the subunits is hydrophobic in character. The enzyme can bind up to 2 mol of most metal ions in "conformational" sites which then allows up to 2 mol of substrate or some substrate analogue to bind. This is not sufficient for catalysis, but conformational metal ions do more than just allow substrate binding. A change in the environment of the metal ions occurs on substrate or substrate analogue binding. There is an absolute correlation between the occurrence of a structural change undergone by the 3-amino analogue of phosphoenolpyruvate and whether the metal ions produce any level of enzymatic activity. For catalysis, two more moles of metal ions, called "catalytic", must bind. There is evidence that the enzymatic reaction involves a carbanion mechanism. It is likely that two more moles of metal ion can bind which inhibit the reaction. The requirement for 2 mol of metal ion per subunit which contribute in different ways to catalysis is exhibited by a number of other enzymes.

  17. NEUROSPECIFIC ENOLASE IN DIAGNOSTICS FOR PERINATAL DAMAGE TO THE CENTRAL NERVOUS SYSTEM IN PREMATURE INFANTS

    Directory of Open Access Journals (Sweden)

    E.G. Novopol'tseva

    2010-01-01

    Full Text Available Neurospecific enolase is an endoenzyme of the central nervous system (CNS present in neurons of the brain and peripheral neuraltissue. This is currently the only known general marker of all differentiated neurons. The article illustrates the results of determining this enzyme in premature infants with fetal infections and assessment of their importance as a marker of damage to CNS in this group of children. A high level of neurospecific enolase in children with infectious and inflammatory diseases is not only the marker of damage to blood-brain barrier, but also reflects the nature of damage (hypoxia, intoxication, inflammation. This parameter in premature infants with various pathologies may serve as a degree of perinatal damage severity, and along with other parameters, determine the performed therapy tactics. Key words: neurospecific enolase, marker of CNS damage, perinatal damage, children. (Pediatric Pharmacology. – 2010; 7(3:66-70

  18. Synaptophysin and the dopaminergic system in hippocampus are involved in the protective effect of rutin against trimethyltin-induced learning and memory impairment.

    Science.gov (United States)

    Zhang, Lei; Zhao, Qi; Chen, Chun-Hai; Qin, Qi-Zhong; Zhou, Zhou; Yu, Zheng-Ping

    2014-09-01

    This study aimed to investigate the protective effect of rutin against trimethyltin-induced spatial learning and memory impairment in mice. This study focused on the role of synaptophysin, growth-associated protein 43 and the action of the dopaminergic system in mechanisms associated with rutin protection and trimethyltin-induced spatial learning and memory impairment. Cognitive learning and memory was measured by Morris Water Maze. The expression of synaptophysin and growth-associated protein 43 in hippocampus was analyzed by western blot. The concentrations of dopamine, homovanillic acid, and dihyroxyphenylacetic acid in hippocampus were detected using reversed phase high-performance liquid chromatography with electrochemical detection. Trimethyltin-induced spatial learning impairment showed a dose-dependent mode. Synaptophysin but not growth-associated protein 43 was decreased in the hippocampus after trimethyltin administration. The concentration of dopamine decreased, while homovanillic acid increased in the hippocampus after trimethyltin administration. Mice pretreated with 20 mg/kg of rutin for 7 consecutive days exhibited improved water maze performance. Moreover, rutin pretreatment reversed the decrease of synaptophysin expression and dopamine alteration. These results suggest that rutin may protect against spatial memory impairment induced by trimethyltin. Synaptophysin and the dopaminergic system may be involved in trimethyltin-induced neuronal damage in hippocampus.

  19. Homology modeling of Leishmania donovani enolase and its molecular interaction with novel inhibitors

    Directory of Open Access Journals (Sweden)

    Jay Prakash Mahato

    2017-01-01

    Full Text Available Introduction: The treatment of Indian tropical disease such as kala-azar is likely to be troublesome to the clinicians as AmpB- and miltefosine-resistant Leishmania donovani has been reported. The rationale behind designed a novel inhibitors of model of L. donovani enolase and performing a binding study with its inhibitors to gain details of the interaction between protein residues and ligand molecules. Methods and Materials: The L. donovani enolase model consists of two typical domains. The N-terminal one contains three-stranded antiparallel β-sheets, followed by six α-helices. The C-terminal domain composes of eleven-stranded mixed α/β-barrel with connectivity. The first α-helix within the C-terminal domain, H7, and the second β-strand, S7, of the barrel domain was arranged in an antiparallel fashion compared to all other α-helices and β-strands. The root-mean-square deviation between predicted model and template is 0.4 Å. The overall conformation of L. donovani enolase model is similar to those of Trypanosoma cruzi enolase and Streptococcus pneumoniae enolase crystal structures. Result: The key amino acid residues within the docking complex model involved in the interaction between model enolase structure and ligand molecule are Lys70, Asn165, Ala168, Asp17, and Asn213. Conclusion: Our theoretical prediction may lead to the establishment of prophylactic and therapeutic approaches for the treatment of kala-azar. This biomedical informatics analysis will help us to combat future kala-azar.

  20. Amyloid-β acts as a regulator of neurotransmitter release disrupting the interaction between synaptophysin and VAMP2.

    Directory of Open Access Journals (Sweden)

    Claire L Russell

    Full Text Available It is becoming increasingly evident that deficits in the cortex and hippocampus at early stages of dementia in Alzheimer's disease (AD are associated with synaptic damage caused by oligomers of the toxic amyloid-β peptide (Aβ42. However, the underlying molecular and cellular mechanisms behind these deficits are not fully understood. Here we provide evidence of a mechanism by which Aβ42 affects synaptic transmission regulating neurotransmitter release.We first showed that application of 50 nM Aβ42 in cultured neurones is followed by its internalisation and translocation to synaptic contacts. Interestingly, our results demonstrate that with time, Aβ42 can be detected at the presynaptic terminals where it interacts with Synaptophysin. Furthermore, data from dissociated hippocampal neurons as well as biochemical data provide evidence that Aβ42 disrupts the complex formed between Synaptophysin and VAMP2 increasing the amount of primed vesicles and exocytosis. Finally, electrophysiology recordings in brain slices confirmed that Aβ42 affects baseline transmission.Our observations provide a necessary and timely insight into cellular mechanisms that underlie the initial pathological events that lead to synaptic dysfunction in Alzheimer's disease. Our results demonstrate a new mechanism by which Aβ42 affects synaptic activity.

  1. Mobility of creatine phosphokinase and beta-enolase in cultured muscle cells

    OpenAIRE

    Arrio-Dupont, M.; Foucault, G.; Vacher, M.; Douhou, A.; Cribier, S.

    1997-01-01

    The diffusion of beta-enolase and creatine phosphokinase in muscle cells has been studied by modulated fringe pattern photobleaching. Beta-enolase is mobile in the sarcoplasm. At 20 degrees C, the diffusion coefficient is 13.5 +/- 2.5 microm2 s(-1) in the cytosol and 56 microm2 s(-1) in aqueous media. As in the case of dextrans of the same hydrodynamic radius, its mobility is hindered by both the crowding of the fluid phase of the cytoplasm and the screening effect due to myofilaments. A frac...

  2. Stopped-flow studies of the reaction of D-tartronate semialdehyde-2-phosphate with human neuronal enolase and yeast enolase 1.

    Science.gov (United States)

    Brewer, John M; McKinnon, Jared S; Phillips, Robert S

    2010-03-05

    We determined the kinetics of the reaction of human neuronal enolase and yeast enolase 1 with the slowly-reacting chromophoric substrate D-tartronate semialdehyde phosphate (TSP), each in tris (tris (hydroxymethyl) aminomethane) and another buffer at several Mg2+ concentrations, 50 or 100 microM, 1 mM and 30 mM. All data were biphasic, and could be satisfactorily fit, assuming either two successive first-order reactions or two independent first-order reactions. Higher Mg2+ concentrations reduce the relative magnitude of the slower reaction. The results are interpreted in terms of a catalytically significant interaction between the two subunits of these enzymes. Copyright (c) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  3. Increased chromogranin A cell density in the large intestine of patients with irritable bowel syndrome after receiving dietary guidance

    OpenAIRE

    Mazzawi, Tarek; Gundersen, Doris Irene; Hausken, Trygve; El-Salhy, Magdy

    2015-01-01

    The large intestine contains five types of endocrine cells that regulate its functions by sensing its luminal contents and releasing specific hormones. Chromogranin A (CgA) is a common marker for the gastrointestinal endocrine cells, and it is abnormal in irritable bowel syndrome (IBS) patients. Most IBS patients relate their symptoms to certain food elements. The present study investigated the effect of dietary guidance on the total endocrine cells of the large intestine as detected by CgA i...

  4. The identification of a sequence related to apicomplexan enolase from Sarcocystis neurona.

    Science.gov (United States)

    Wilson, A P; Thelen, J J; Lakritz, J; Brown, C R; Marsh, A E

    2004-11-01

    Equine protozoal myeloencephalitis (EPM) is a neurological disease caused by Sarcocystis neurona, an apicomplexan parasite. S. neurona is also associated with EPM-like diseases in marine and small mammals. The mechanisms of transmission and ability to infect a wide host range remain obscure; therefore, characterization of essential proteins may provide evolutionary information allowing the development of novel chemotherapeutics that target non-mammalian biochemical pathways. In the current study, two-dimensional electrophoresis and matrix-assisted laser desorption ionization-time of flight (MALDI-ToF) mass spectrometry were combined to characterize and identify an enolase protein from S. neurona based on peptide homology to the Toxoplasma gondii protein. Enolase is thought to be a vestigial, non-photosynthetic protein resulting from an evolutionary endosymbiosis event of an apicomplexan ancestor with green algae. Enolase has also been suggested to play a role in parasite stage conversion for T. gondii. Characterization of this protein in S. neurona and comparison to other protozoans indicate a biochemical similarity of S. neurona enolase to other tissue-cyst forming coccidians that cause encephalitis.

  5. Increased serum neuron specific enolase concentrations in patients with hyperglycemic cortical ischemic stroke

    NARCIS (Netherlands)

    Elting, JW; De Keyser, J; Sulter, G.

    1998-01-01

    A detrimental effect of hyperglycemia in ischemic brain has been demonstrated in laboratory experiments and it has been found that hyperglycemia in ischemic stroke is a predictor of poor outcome. We determined serum neuron specific enolase (NSE) concentrations in 41 consecutive patients with a

  6. Genetic and proteomic evidences support the localization of yeast enolase in the cell surface

    DEFF Research Database (Denmark)

    López-Villar, Elena; Monteoliva, Lucía; Larsen, Martin Røssel

    2006-01-01

    Although enolase, other glycolytic enzymes, and a variety of cytoplasmic proteins lacking an N-terminal secretion signal have been widely described as located at the cell surface in yeast and in mammalian cells, their presence in this external location is still controversial. Here, we report that...

  7. The structure of bradyzoite-specific enolase from Toxoplasma gondii reveals insights into its dual cytoplasmic and nuclear functions

    Energy Technology Data Exchange (ETDEWEB)

    Ruan, Jiapeng [Northwestern University, 320 E. Superior Street, Morton 7-601, Chicago, IL 60611 (United States); Mouveaux, Thomas [Université Lille Nord de France, (France); Light, Samuel H.; Minasov, George; Anderson, Wayne F. [Northwestern University, 320 E. Superior Street, Morton 7-601, Chicago, IL 60611 (United States); Tomavo, Stanislas [Université Lille Nord de France, (France); Ngô, Huân M., E-mail: h-ngo@northwestern.edu [Northwestern University, 320 E. Superior Street, Morton 7-601, Chicago, IL 60611 (United States); BrainMicro LLC, 21 Pendleton Street, New Haven, CT 06511 (United States)

    2015-03-01

    The second crystal structure of a parasite protein preferentially enriched in the brain cyst of T. gondii has been solved at 2.75 Å resolution. Bradyzoite enolase 1 is reported to have differential functions as a glycolytic enzyme and a transcriptional regulator in bradyzoites. In addition to catalyzing a central step in glycolysis, enolase assumes a remarkably diverse set of secondary functions in different organisms, including transcription regulation as documented for the oncogene c-Myc promoter-binding protein 1. The apicomplexan parasite Toxoplasma gondii differentially expresses two nuclear-localized, plant-like enolases: enolase 1 (TgENO1) in the latent bradyzoite cyst stage and enolase 2 (TgENO2) in the rapidly replicative tachyzoite stage. A 2.75 Å resolution crystal structure of bradyzoite enolase 1, the second structure to be reported of a bradyzoite-specific protein in Toxoplasma, captures an open conformational state and reveals that distinctive plant-like insertions are located on surface loops. The enolase 1 structure reveals that a unique residue, Glu164, in catalytic loop 2 may account for the lower activity of this cyst-stage isozyme. Recombinant TgENO1 specifically binds to a TTTTCT DNA motif present in the cyst matrix antigen 1 (TgMAG1) gene promoter as demonstrated by gel retardation. Furthermore, direct physical interactions of both nuclear TgENO1 and TgENO2 with the TgMAG1 gene promoter are demonstrated in vivo using chromatin immunoprecipitation (ChIP) assays. Structural and biochemical studies reveal that T. gondii enolase functions are multifaceted, including the coordination of gene regulation in parasitic stage development. Enolase 1 provides a potential lead in the design of drugs against Toxoplasma brain cysts.

  8. Beneficial effects of environmental enrichment on behavior, stress reactivity and synaptophysin/BDNF expression in hippocampus following early life stress.

    Science.gov (United States)

    Dandi, Εvgenia; Kalamari, Aikaterini; Touloumi, Olga; Lagoudaki, Rosa; Nousiopoulou, Evangelia; Simeonidou, Constantina; Spandou, Evangelia; Tata, Despina A

    2018-06-01

    Exposure to environmental enrichment can beneficially influence the behavior and enhance synaptic plasticity. The aim of the present study was to investigate the mediated effects of environmental enrichment on postnatal stress-associated impact with regard to behavior, stress reactivity as well as synaptic plasticity changes in the dorsal hippocampus. Wistar rat pups were submitted to a 3 h maternal separation (MS) protocol during postnatal days 1-21, while another group was left undisturbed. On postnatal day 23, a subgroup from each rearing condition (maternal separation, no-maternal separation) was housed in enriched environmental conditions until postnatal day 65 (6 weeks duration). At approximately three months of age, adult rats underwent behavioral testing to evaluate anxiety (Elevated Plus Maze), locomotion (Open Field Test), spatial learning and memory (Morris Water Maze) as well as non-spatial recognition memory (Novel Object Recognition Test). After completion of behavioral testing, blood samples were taken for evaluation of stress-induced plasma corticosterone using an enzyme-linked immunosorbent assay (ELISA), while immunofluorescence was applied to evaluate hippocampal BDNF and synaptophysin expression in dorsal hippocampus. We found that environmental enrichment protected against the effects of maternal separation as indicated by the lower anxiety levels and the reversal of spatial memory deficits compared to animals housed in standard conditions. These changes were associated with increased BDNF and synaptophysin expression in the hippocampus. Regarding the neuroendocrine response to stress, while exposure to an acute stressor potentiated corticosterone increases in maternally-separated rats, environmental enrichment of these rats prevented this effect. The current study aimed at investigating the compensatory role of enriched environment against the negative outcomes of adverse experiences early in life concurrently on emotional and cognitive

  9. Release Pattern of Salivary Chromogranin A in Pediatric Subjects with Obstructive Sleep Apnea

    Directory of Open Access Journals (Sweden)

    Heung-Ku Lee

    2014-12-01

    Full Text Available Background and Objective Sleep-disordered breathing (SDB is associated with activation of the stress response, including the autonomic nervous system. Salivary chromogranin A (sCgA is considered a valuable indicator of sympathoadrenal activity. We examined the relationship between sCgA and polysomnography (PSG parameters. Methods In this prospective study, we enrolled 103 children who underwent a physical examination and fully attended in-lab PSG. Saliva was collected at night before PSG and in the early morning after PSG. Results The subjects (n = 103 were divided into control [n = 41, apnea-hypopnea index (AHI ≤ 1] and obstructive sleep apnea syndrome (OSAS; n = 62, AHI > 1 groups. The OSAS group was subdivided into mild (1 < AHI ≤ 5, moderate (5 < AHI ≤ 10, and severe (10 < AHI groups. There was no significant difference in the sCgA parameters between the control and OSAS groups. No significant difference was observed in sCgA parameters between the control group and OSAS subgroups (mild, moderate, and severe. No circadian rhythm was detected in sCgA secretion, and no difference in sCgA concentrations was measured at the two time points. Conclusions Our findings suggest that sCgA secretion was not influenced by OSAS severity and no definitive circadian rhythm was detected in pediatric subjects. Further study is needed to establish whether there is a circadian rhythm in pediatric subjects.

  10. Chromogranin A levels in the cerebrospinal fluid of patients with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Verde, Federico; Steinacker, Petra; Oeckl, Patrick; Weishaupt, Jochen H; Rosenbohm, Angela; Silani, Vincenzo; Ludolph, Albert C; Otto, Markus

    2018-07-01

    Chromogranin A (CgA) is a protein found in large dense-core vesicles of neuroendocrine cells and neurons and regulating secretion. A relevance to amyotrophic lateral sclerosis (ALS) was suggested as its overexpression accelerates disease onset in model systems and it interacts with mutant forms of SOD1. Recently, increased cerebrospinal fluid (CSF) CgA levels have been reported in ALS patients relative to controls. With the aim of confirming this finding, we measured CgA and phosphorylated neurofilament heavy chain (pNFH), an established ALS biomarker, in the CSF of 32 ALS patients and 32 disease controls. ALS patients had clearly increased pNFH levels (p < 0.0001), while CgA levels were only modestly lower relative to controls (p = 0.0265), with wide value overlap and consequently poor discriminative performance. CgA did not correlate with any disease parameters among ALS patients. Our findings suggest that CgA is not a promising clinical biomarker for ALS. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Automated two-site immunofluorescent assay for the measurement of serum chromogranin A.

    Science.gov (United States)

    Popovici, Théodora; Moreira, Baptiste; Schlageter, Marie-Hélène; Bories, Phuong-Nhi

    2014-01-01

    Chromogranin A (CgA) is the best-characterized biological marker common to neuroendocrine tumours and is therefore recommended for their diagnosis. The measurement of serum CgA is of great importance for reaching an early diagnosis and thus reducing the delay before treatment is instigated. The Kryptor CgA assay is the first fully automated assay available. The aim of this study was to evaluate its analytical performance. The imprecision and linearity of the Kryptor CgA assay were evaluated. This assay was compared with the Cis Bio CgA RIA assay in 78 serum samples. Its clinical utility was assessed in serum from 229 patients. The study performed on imprecision of Kryptor measurements showed intra- and inter-run CVs ≤ 5%. The study of linearity showed a satisfactory recovery rate for CgA concentrations up to 1200 μg/L. The Kryptor and RIA assays agreed well on the basis of the cut-off values provided by the two manufacturers. The Bland and Altman plot of the values obtained (range: 20-5560 μg/L) provided a mean difference of -10.1 μg/L (SD: 116). The clinical sensitivities of Kryptor CgA for diagnosis of pheochromocytoma and paraganglioma (n 20) and gastroenteropancreatic NETs (n 17) were respectively 100 and 94%. The Kryptor assay for CgA shows reliable analytical and clinical characteristics and allows a fast delivery of results. © 2013.

  12. Serum chromogranin A concentration in hyperthyroidism before and after medical treatment.

    Science.gov (United States)

    Al-Shoumer, Kamal A S; Vasanthy, Bagavathy A

    2009-07-01

    The aim was to evaluate changes in chromogranin A (CgA) concentration in hyperthyroidism and to assess its metabolic correlations. We studied CgA levels in hyperthyroidism. First, 38 hyperthyroid patients matched with 86 normal controls were studied after an overnight fast. Second, 30 if the 38 patients were followed up for 6 months with medical antithyroid drug therapy (carbimazole). In the first study, after 10-12 h overnight fasting, blood was collected for measurement of CgA, glucose, insulin, intact proinsulin, and thyroid function. These variables were remeasured in the second study for the patients after attainment of euthyroidism with the antithyroid drug carbimazole for 6 months. Pretreatment CgA level was significantly higher in patients compared with controls. CgA levels dropped significantly to levels similar to those of controls after antithyroid therapy. Although baseline and follow-up fasting glucose, insulin, and intact proinsulin demonstrated similar pattern of CgA changes before and after medical treatment, CgA did not correlate with any of them. However, CgA levels demonstrated a significant positive correlation with free T(3) and free T(4) only. These studies demonstrate that untreated hyperthyroidism is associated with elevated CgA level that changes in parallel to thyroid status. It is therefore possible to use CgA concentration as a potential marker of disease activity in hyperthyroidism.

  13. Black tea aroma inhibited increase of salivary chromogranin-A after arithmetic tasks.

    Science.gov (United States)

    Yoto, Ai; Fukui, Natsuki; Kaneda, Chisa; Torita, Shoko; Goto, Keiichi; Nanjo, Fumio; Yokogoshi, Hidehiko

    2018-01-24

    Growing attention has been paid to the effects of food flavor components on alleviating negative brain functions caused by stressful lifestyles. In this study, we investigated the alleviating effect of two kinds of black tea aromas on physical and psychological stress induced by the Uchida-Kraepelin test, based on salivary chromogranin-A (CgA) levels as a stress marker and subjective evaluations (Profile of Mood States). Compared with the water exposure control, inhaling black tea aroma (Darjeeling and Assam in this study) induced lower salivary CgA concentration levels after 30 min of mental stress load tasks. This anti-stress effect of black tea aroma did not differ between the two tea types even though the concentration of the anti-stress components in the Darjeeling tea aroma was higher than that in the Assam aroma. However, Darjeeling tea aroma tended to decrease the tension and/or anxiety score immediately after the first exposure. Inhaling black tea aroma may diminish stress levels caused by arithmetic mental stress tasks, and Darjeeling tea aroma tended to improve mood before mental stress load.

  14. a7 nicotinic receptor agonism mitigates phencyclidine-induced changes in synaptophysin and Arc gene expression in the mouse prefrontal cortex

    DEFF Research Database (Denmark)

    Thomsen, Morten S; Hansen, Henrik H; Mikkelsen, Jens D

    2010-01-01

    Repeated phencyclidine (PCP) administration in mice reproduces several histopathological features of schizophrenia, such as reduced synaptophysin and parvalbumin mRNA expression in the frontal cortex. These changes can be prevented by co-administering the a7 nicotinic acetylcholine receptor (n...

  15. α7 nicotinic receptor agonism mitigates phencyclidine-induced changes in synaptophysin and Arc gene expression in the mouse prefrontal cortex

    DEFF Research Database (Denmark)

    Thomsen, Morten S; Hansen, Henrik H; Mikkelsen, Jens D

    2010-01-01

    Repeated phencyclidine (PCP) administration in mice reproduces several histopathological features of schizophrenia, such as reduced synaptophysin and parvalbumin mRNA expression in the frontal cortex. These changes can be prevented by co-administering the α7 nicotinic acetylcholine receptor (n...

  16. Crystallization and preliminary X-ray analysis of 2,3-diketo-5-methylthiopentyl-1-phosphate enolase from Bacillus subtilis

    International Nuclear Information System (INIS)

    Tamura, Haruka; Ashida, Hiroki; Koga, Shogo; Saito, Yohtaro; Yadani, Tomonori; Kai, Yasushi; Inoue, Tsuyoshi; Yokota, Akiho; Matsumura, Hiroyoshi

    2009-01-01

    Crystals of the 45.1 kDa functional form of 2,3-diketo-5-methylthiopentyl-1-phosphate enolase from B. subtilis diffracted to 2.30 Å resolution. 2,3-Diketo-5-methylthiopentyl-1-phosphate enolase (DK-MTP-1P enolase) from Bacillus subtilis was crystallized using the hanging-drop vapour-diffusion method. Crystals grew using PEG 3350 as the precipitant at 293 K. The crystals diffracted to 2.3 Å resolution at 100 K using synchrotron radiation and were found to belong to the monoclinic space group P2 1 , with unit-cell parameters a = 79.3, b = 91.5, c = 107.0 Å, β = 90.8°. The asymmetric unit contained four molecules of DK-MTP-1P enolase, with a V M value of 2.2 Å 3 Da −1 and a solvent content of 43%

  17. In silico-based identification of human α-enolase inhibitors to block cancer cell growth metabolically

    Science.gov (United States)

    Lung, Jrhau; Chen, Kuan-Liang; Hung, Chien-Hui; Chen, Chih-Cheng; Hung, Ming-Szu; Lin, Yu-Ching; Wu, Ching-Yuan; Lee, Kuan-Der; Shih, Neng-Yao; Tsai, Ying Huang

    2017-01-01

    Unlimited growth of cancer cells requires an extensive nutrient supply. To meet this demand, cancer cells drastically upregulate glucose uptake and metabolism compared to normal cells. This difference has made the blocking of glycolysis a fascinating strategy to treat this malignant disease. α-enolase is not only one of the most upregulated glycolytic enzymes in cancer cells, but also associates with many cellular processes or conditions important to cancer cell survival, such as cell migration, invasion, and hypoxia. Targeting α-enolase could simultaneously disturb cancer cells in multiple ways and, therefore, is a good target for anticancer drug development. In the current study, more than 22 million chemical structures meeting the criteria of Lipinski’s rule of five from the ZINC database were docked to α-enolase by virtual screening. Twenty-four chemical structures with docking scores better than that of the enolase substrate, 2-phosphoglycerate, were further screened by the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties prediction. Four of them were classified as non-mutagenic, non-carcinogenic, and capable of oral administration where they showed steady interactions to α-enolase that were comparable, even superior, to the currently available inhibitors in molecular dynamics (MD) simulation. These compounds may be considered promising leads for further development of the α-enolase inhibitors and could help fight cancer metabolically. PMID:29180852

  18. Chromogranin A as circulating marker for diagnosis and management of neuroendocrine neoplasms: more flaws than fame.

    Science.gov (United States)

    Marotta, Vincenzo; Zatelli, Maria Chiara; Sciammarella, Concetta; Ambrosio, Maria Rosaria; Bondanelli, Marta; Colao, Annamaria; Faggiano, Antongiulio

    2018-01-01

    Owing to the heterogeneity of neuroendocrine neoplasms (NENs), the availability of reliable circulating markers is critical for improving diagnostics, prognostic stratification, follow-up and definition of treatment strategy. This review is focused on chromogranin A (CgA), a hydrophilic glycoprotein present in large dense core vesicles of neuroendocrine cells. Despite being long identified as the most useful NEN-related circulating marker, clinical application of CgA is controversial. CgA assays still lack standardization, thus hampering not only clinical management but also the comparison between different analyses. In the diagnostic setting, clinical utility of CgA is limited as hampered by (a) the variety of oncological and non-oncological conditions affecting marker levels, which impairs specificity; (b) the fact that 30-50% of NENs show normal CgA, which impairs sensitivity. Regarding the prognostic phase, there is prospective evidence which demonstrates that advanced NENs secreting CgA have poorer outcome, as compared with those showing non-elevated marker levels. Although the identification of cut-offs allowing a proper risk stratification of CgA-secreting patients has not been performed, this represents the most important clinical application of the marker. By contrast, based on prospective studies, the trend of elevated circulating CgA does not represent a valid indicator of morphological evolution and has therefore no utility for the follow-up phase. Ultimately, current knowledge about the role of the marker for the definition of treatment strategy is poor and is limited by the small number of available studies, their prevalent retrospective nature and the absence of control groups of untreated subjects. © 2018 Society for Endocrinology.

  19. Oral Immunization Against Candidiasis Using Lactobacillus casei Displaying Enolase 1 from Candida albicans

    OpenAIRE

    Shibasaki, Seiji; Karasaki, Miki; Tafuku, Senji; Aoki, Wataru; Sewaki, Tomomitsu; Ueda, Mitsuyoshi

    2014-01-01

    Abstract Candidiasis is a common fungal infection that is prevalent in immunocompromised individuals. In this study, an oral vaccine against Candida albicans was developed by using the molecular display approach. Enolase 1 protein (Eno1p) of C. albicans was expressed on the Lactobacillus casei cell surface by using poly-gamma-glutamic acid synthetase complex A from Bacillus subtilis as an anchoring protein. The Eno1p-displaying L. casei cells were used to immunize mice, which were later chall...

  20. Significance of the enzymatic properties of yeast S39A enolase to the catalytic mechanism.

    Science.gov (United States)

    Brewer, J M; Glover, C V; Holland, M J; Lebioda, L

    1998-04-02

    The S39A mutant of yeast enolase (isozyme 1), prepared by site-directed mutagenesis, has a relative Vmax of 0.01% and an activation constant for Mg2+ ca. 10-fold higher, compared with native enzyme. It is correctly folded. There is little effect of solvent viscosity on activity. We think that the loop Ser36-His43 fails to move to the 'closed' position upon catalytic Mg2+ binding, weakening several electrostatic interactions involved in the mechanism.

  1. Identification and functional characterization of alpha-enolase from Taenia pisiformis metacestode.

    Science.gov (United States)

    Zhang, Shaohua; Guo, Aijiang; Zhu, Xueliang; You, Yanan; Hou, Junling; Wang, Qiuxia; Luo, Xuenong; Cai, Xuepeng

    2015-04-01

    Enolase belongs to glycolytic enzymes with moonlighting functions. The role of enolase in Taenia species is still poorly understood. In this study, the full length of cDNA encoding for Taenia pisiformis alpha-enolase (Tpeno) was cloned from larval parasites and soluble recombinant Tpeno protein (rTpeno) was produced. Western blot indicated that both rTpeno and the native protein in excretion-secretion antigens from the larvae were recognized by anti-rTpeno monoclonal antibodies (MAbs). The primary structure of Tpeno showed the presence of a highly conserved catalytic site for substrate binding and an enolase signature motif. rTpeno enzymatic activities of catalyzing the reversible dehydration of 2-phosphoglycerate (2-PGA) to phosphoenolpyruvate (PEP) and vice versa were shown to be 30.71 ± 2.15 U/mg (2-PGA to PEP) and 11.29 ± 2.38 U/mg (PEP to 2-PGA), respectively. Far-Western blotting showed that rTpeno could bind to plasminogen, however its binding ability was inhibited by ϵ-aminocaproic acid (ϵACA) in a competitive ELISA test. Plasminogen activation assay showed that plasminogen bound to rTpeno could be converted into active plasmin using host-derived activators. Immunohistochemistry and immunofluorescence indicated that Tpeno was distributed in the bladder wall of the metacestode and the periphery of calcareous corpuscles. In addition, a vaccine trial showed that the enzyme could produce a 36.4% protection rate in vaccinated rabbits against experimental challenges from T. pisiformis eggs. These results suggest that Tpeno with multiple functions may play significant roles in the migration, growth, development and adaptation of T. pisiformis for survival in the host environment. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Correlative study between neuron-specific enolase and blood sugar level in ischemic stroke patients

    OpenAIRE

    Pandey, Aparna; Saxena, Kiran; Verma, Meena; Bharosay, Anuradha

    2011-01-01

    Background: A study to investigate the level of the neurobiochemical marker, Neuron-Specific Enolase (NSE), at the time of admission and its correlation with the blood sugar level in ischemic stroke patients. Patients and Methods: We investigated 90 patients with complete stroke who were admitted to the Stroke Unit of the Department of Neurology at Sri Aurobindo Institute of Medical Sciences. NSE was measured with commercially available quantitative ′sandwich′ enzyme-linked immunosorbent assa...

  3. Balance and coordination training, but not endurance training, enhances synaptophysin and neurotrophin-3 immunoreactivity in the lumbar spinal cord after sciatic nerve crush.

    Science.gov (United States)

    Bonetti, Leandro Viçosa; Ilha, Jocemar; Schneider, Ana Paula Krauthein; Barbosa, Silvia; Faccioni-Heuser, Maria Cristina

    2016-04-01

    Numerous rehabilitation treatments have been shown to be useful for peripheral and central restoration after (PNI). After sciatic nerve crush, we investigated 4 weeks of endurance training (ET) and balance and coordination training (BCT) with sciatic function index, hind-paw stride length, and spinal cord dorsal horn synaptophysin and neurotrophin-3 immunoreactivity. Our results demonstrated no significant differences between the non-trained (NT), ET, and BCT groups in sciatic functional index, and in stride-length analysis, but the ET showed higher values compared with the NT group. Synaptophysin immunoreactivity was higher in the BCT group compared with the NT group, and neurotrophin-3 immunoreactivity in the BCT group was greater compared with the other groups. BCT can positively affect spinal cord plasticity after a (PNI), and these modifications are important in the rehabilitation process. © 2015 Wiley Periodicals, Inc.

  4. In vivo imaging of chromogranin A-positive endocrine tumours by three-step monoclonal antibody targeting

    International Nuclear Information System (INIS)

    Siccardi, A.G.; Paganelli, G.; Pontiroli, A.E.; Pelagi, M.; Magnani, P.; Viale, G.; Faglia, G.; Fazio, F.

    1996-01-01

    The detection of chromogranins (Cg) by immunohistochemistry and serology represents a new in vitro diagnostic tool for endocrine tumours. We have recently reported on the feasibility of targeting chromogranin A (CgA) for in vivo detection of pituitary adenomas by immunoscintigraphy (ISG). The scintigraphic procedure, based on an anti-CgA monoclonal antibody and on the avidin-biotin three-step method (Cg-3S-ISG), was evaluated on a group of 29 consecutive patients with known or suspected endocrine tumours other than pituitary adenomas, i.e. medullary thyroid carcinoma, carcinoid, insulinoma and parathormone- or ACTH-producing tumours. Primary tumours (10) and recurrences (16) were visualised in 26 patients, whereas conventional imaging techniques (planar radiography, computerised tomography, magnetic resonance imaging and ultrasonography) failed to detect the tumour sites in ten of the same (Cg-3S-ISG-positive) patients. Therefore, these preliminary results indicate that Cg-3S-ISG, the first immunological method able to detect endocrine tumours in vivo, has a higher diagnostic accuracy than conventional imaging techniques (93.1% compared with 65.5%). (orig.). With 3 figs., 1 tab

  5. Immunoreactive neuron-specific enolase (NSE) is expressed in testicular carcinoma-in-situ

    DEFF Research Database (Denmark)

    Kang, J L; Rajpert-De Meyts, E; Skakkebaek, N E

    1996-01-01

    Neuron-specific enolase (NSE) is a well-known marker of tumours that have neuroendocrine origin. High levels of NSE have also been described in various types of testicular germ cell neoplasms, particularly in seminomas. To evaluate the presence of NSE in testicular carcinoma-in situ (CIS), a prei...... are evidence against a relationship between NSE and N-myc in testicular germ cell tumours. The high expression of NSE in CIS and overt germ cell tumours may be due to the increased gene dosage effect associated with the overrepresentation of isochromosome 12p....

  6. Evolution of Enzymatic Activities in the Enolase Superfamily: D-Mannonate Dhydratase from Novosphingobium aromaticivorans

    Energy Technology Data Exchange (ETDEWEB)

    Rakus,J.; Fedorov, A.; Fedorov, E.; Glasner, M.; Vick, J.; Babbitt, P.; Almo, S.; Gerlt, J.

    2007-01-01

    The d-mannonate dehydratase (ManD) function was assigned to a group of orthologous proteins in the mechanistically diverse enolase superfamily by screening a library of acid sugars. Structures of the wild type ManD from Novosphingobium aromaticivorans were determined at pH 7.5 in the presence of Mg2+ and also in the presence of Mg2+ and the 2-keto-3-keto-d-gluconate dehydration product; the structure of the catalytically active K271E mutant was determined at pH 5.5 in the presence of the d-mannonate substrate. As previously observed in the structures of other members of the enolase superfamily, ManD contains two domains, an N-terminal a+{beta} capping domain and a ({beta}/a)7{beta}-barrel domain. The barrel domain contains the ligands for the essential Mg2+, Asp 210, Glu 236, and Glu 262, at the ends of the third, fourth, and fifth {beta}-strands of the barrel domain, respectively. However, the barrel domain lacks both the Lys acid/base catalyst at the end of the second {beta}-strand and the His-Asp dyad acid/base catalyst at the ends of the seventh and sixth {beta}-strands, respectively, that are found in many members of the superfamily. Instead, a hydrogen-bonded dyad of Tyr 159 in a loop following the second {beta}-strand and Arg 147 at the end of the second {beta}-strand are positioned to initiate the reaction by abstraction of the 2-proton. Both Tyr 159 and His 212, at the end of the third {beta}-strand, are positioned to facilitate both syn-dehydration and ketonization of the resulting enol intermediate to yield the 2-keto-3-keto-d-gluconate product with the observed retention of configuration. The identities and locations of these acid/base catalysts as well as of cationic amino acid residues that stabilize the enolate anion intermediate define a new structural strategy for catalysis (subgroup) in the mechanistically diverse enolase superfamily. With these differences, we provide additional evidence that the ligands for the essential Mg2+ are the only

  7. Expression, purification, crystallization and preliminary X-ray studies of Lactobacillus jensenii enolase

    Energy Technology Data Exchange (ETDEWEB)

    Harris, Paul T.; Raghunathan, Kannan; Spurbeck, Rachel R.; Arvidson, Cindy G.; Arvidson, Dennis N. (MSU)

    2010-09-02

    Recombinant Lactobacillus jensenii enolase fused to a C-terminal noncleavable His tag was expressed in Escherichia coli, purified and crystallized by sitting-drop vapor diffusion. A complete data set was collected to 3.25 {angstrom} resolution. The crystals belonged to space group I4, with unit-cell parameters a = b = 145.31, c = 99.79 {angstrom}. There were two protein subunits in the asymmetric unit, which gave a Matthews coefficient V{sub M} of 2.8 {angstrom}{sup 3} Da{sup -1}, corresponding to 55.2% solvent content.

  8. Mobility of creatine phosphokinase and beta-enolase in cultured muscle cells.

    Science.gov (United States)

    Arrio-Dupont, M; Foucault, G; Vacher, M; Douhou, A; Cribier, S

    1997-11-01

    The diffusion of beta-enolase and creatine phosphokinase in muscle cells has been studied by modulated fringe pattern photobleaching. Beta-enolase is mobile in the sarcoplasm. At 20 degrees C, the diffusion coefficient is 13.5 +/- 2.5 microm2 s(-1) in the cytosol and 56 microm2 s(-1) in aqueous media. As in the case of dextrans of the same hydrodynamic radius, its mobility is hindered by both the crowding of the fluid phase of the cytoplasm and the screening effect due to myofilaments. A fraction of creatine phosphokinase is mobile in the sarcoplasm. Its diffusion coefficient in the cytosol, 4.5 +/- 1 microm2 s(-1), is lower than that of the dextran of equivalent size. The other fraction (20 to 50%) is very slightly mobile, with an apparent diffusion coefficient varying from 0.0035 to 0.043 microm2 s(-1). This low mobility might be attributed to exchange between free and bound creatine phosphokinase. The bound fraction of the endogenous enzyme was localized by immunocytofluorescence on the cultured muscle cells. Our results favor a localization of bound cytosolic creatine phosphokinase on the M-line and a diffuse distribution in all myotubes.

  9. Correlative study between neuron-specific enolase and blood sugar level in ischemic stroke patients

    Directory of Open Access Journals (Sweden)

    Aparna Pandey

    2011-01-01

    Full Text Available Background: A study to investigate the level of the neurobiochemical marker, Neuron-Specific Enolase (NSE, at the time of admission and its correlation with the blood sugar level in ischemic stroke patients. Patients and Methods: We investigated 90 patients with complete stroke who were admitted to the Stroke Unit of the Department of Neurology at Sri Aurobindo Institute of Medical Sciences. NSE was measured with commercially available quantitative ′sandwich′ enzyme-linked immunosorbent assay kits obtained from R and D Systems. Hyperglycemia was defined as blood glucose concentration ≥ 7 mmol / L, and measured using the glucose oxidase method immediately. Results: Significantly increased NSE and lipid profile levels were found in ischemic stroke patients as compared to the control. Hyperglycemic ischemic stroke patients had increased levels of NSE, lipid profile, and National Institute of Health stroke scale scores (NIHSS score compared to normoglycemic ischemic stroke patients. In addition the serum NSE level of hyperglycemic stroke patients was also positively correlated with the blood sugar level (r = 0.734 P < 0.001. Conclusions: Hyperglycemia predicts an increased risk of poor outcome after ischemic stroke and it is reflected by a significantly increased level of Neuron-Specific Enolase.

  10. Stability of the octameric structure affects plasminogen-binding capacity of streptococcal enolase.

    Directory of Open Access Journals (Sweden)

    Amanda J Cork

    Full Text Available Group A Streptococcus (GAS is a human pathogen that has the potential to cause invasive disease by binding and activating human plasmin(ogen. Streptococcal surface enolase (SEN is an octameric α-enolase that is localized at the GAS cell surface. In addition to its glycolytic role inside the cell, SEN functions as a receptor for plasmin(ogen on the bacterial surface, but the understanding of the molecular basis of plasmin(ogen binding is limited. In this study, we determined the crystal and solution structures of GAS SEN and characterized the increased plasminogen binding by two SEN mutants. The plasminogen binding ability of SENK312A and SENK362A is ~2- and ~3.4-fold greater than for the wild-type protein. A combination of thermal stability assays, native mass spectrometry and X-ray crystallography approaches shows that increased plasminogen binding ability correlates with decreased stability of the octamer. We propose that decreased stability of the octameric structure facilitates the access of plasmin(ogen to its binding sites, leading to more efficient plasmin(ogen binding and activation.

  11. Age-related changes in the hippocampus (loss of synaptophysin and glial-synaptic interaction) are modified by systemic treatment with an NCAM-derived peptide, FGL.

    Science.gov (United States)

    Ojo, Bunmi; Rezaie, Payam; Gabbott, Paul L; Davies, Heather; Colyer, Frances; Cowley, Thelma R; Lynch, Marina; Stewart, Michael G

    2012-07-01

    Altered synaptic morphology, progressive loss of synapses and glial (astrocyte and microglial) cell activation are considered as characteristic hallmarks of aging. Recent evidence suggests that there is a concomitant age-related decrease in expression of the presynaptic protein, synaptophysin, and the neuronal glycoprotein CD200, which, by interacting with its receptor, plays a role in maintaining microglia in a quiescent state. These age-related changes may be indicative of reduced neuroglial support of synapses. FG Loop (FGL) peptide synthesized from the second fibronectin type III module of neural cell adhesion molecule (NCAM), has previously been shown to attenuate age-related glial cell activation, and to 'restore' cognitive function in aged rats. The mechanisms by which FGL exerts these neuroprotective effects remain unclear, but could involve regulation of CD200, modifying glial-synaptic interactions (affecting neuroglial 'support' at synapses), or impacting directly on synaptic function. Light and electron microscopic (EM) analyses were undertaken to investigate whether systemic treatment with FGL (i) alters CD200, synaptophysin (presynaptic) and PSD-95 (postsynaptic) immunohistochemical expression levels, (ii) affects synaptic number, or (iii) exerts any effects on glial-synaptic interactions within young (4 month-old) and aged (22 month-old) rat hippocampus. Treatment with FGL attenuated the age-related loss of synaptophysin immunoreactivity (-ir) within CA3 and hilus (with no major effect on PSD-95-ir), and of CD200-ir specifically in the CA3 region. Ultrastructural morphometric analyses showed that FGL treatment (i) prevented age-related loss in astrocyte-synaptic contacts, (ii) reduced microglia-synaptic contacts in the CA3 stratum radiatum, but (iii) had no effect on the mean number of synapses in this region. These data suggest that FGL mediates its neuroprotective effects by regulating glial-synaptic interaction. Copyright © 2011 Elsevier Inc. All

  12. Preparation by site-directed mutagenesis and characterization of the E211Q mutant of yeast enolase 1.

    Science.gov (United States)

    Sangadala, V S; Glover, C V; Robson, R L; Holland, M J; Lebioda, L; Brewer, J M

    1995-08-16

    The published 'charge shuttle' mechanism of enolase (Lebioda, L. and Stec, B. (1991) Biochemistry 30, 2817-2822) assigns Glu-211 the task of orienting a water molecule that serves as the catalytic base which removes the proton from carbon-2 of the substrate. We prepared the E211Q mutant of yeast enolase 1 by site-directed mutagenesis. It appears to be folded correctly and to respond similarly to many of the normal ligands of enolase: it is stabilized against thermal denaturation by conformational Mg2+ and by Mg2+ and substrate and binds the chromophoric substrate analogue D-tartronate semialdehyde-2-phosphate (TSP) with affinity comparable to that of the native enzyme. However, it has only 0.01% (10(-4)) of the activity of native enolase under standard assay conditions and does not exhibit significantly more activity at various pH values or higher concentrations of substrate and Mg2+. Its ability to produce the form of enzyme-bound and reacted TSP that absorbs at shorter wavelengths is greatly slowed, while the longer wavelength absorbing form is produced rapidly. Overall, these observations are consistent with the hypothetical mechanism.

  13. Proinflammatory Cytokines, Enolase and S-100 as Early Biochemical Indicators of Hypoxic-Ischemic Encephalopathy Following Perinatal Asphyxia in Newborns

    Directory of Open Access Journals (Sweden)

    Verónica Chaparro-Huerta

    2017-02-01

    Conclusion: The role of cytokines after hypoxic-ischemic insult has been determined in studies of transgenic mice that support the use of these molecules as candidate biomarkers. Similarly, S-100 and enolase are considered promising candidates because these markers have been correlated with tissue damage in different experimental models.

  14. Gamma-enolase: a well-known tumour marker, with a less-known role in cancer

    Science.gov (United States)

    Vizin, Tjasa; Kos, Janko

    2015-01-01

    Background Gamma-enolase, known also as neuron-specific enolase (NSE), is an enzyme of the glycolytic pathway, which is expressed predominantly in neurons and cells of the neuroendocrine system. As a tumour marker it is used in diagnosis and prognosis of cancer; however, the mechanisms enrolling it in malignant progression remain elusive. As a cytoplasmic enzyme gamma-enolase is involved in increased aerobic glycolysis, the main source of energy in cancer cells, supporting cell proliferation. However, different cellular localisation at pathophysiological conditions, proposes other cellular engagements. Conclusions The C-terminal part of the molecule, which is not related to glycolytic pathway, was shown to promote survival of neuronal cells by regulating neuronal growth factor receptor dependent signalling pathways, resulting also in extensive actin cytoskeleton remodelling. This additional function could be important also in cancer cells either to protect cells from stressful conditions and therapeutic agents or to promote tumour cell migration and invasion. Gamma-enolase might therefore have a multifunctional role in cancer progression: it supports increased tumour cell metabolic demands, protects tumour cells from stressful conditions and promotes their invasion and migration. PMID:26401126

  15. Gamma-enolase: a well-known tumour marker, with a less-known role in cancer

    International Nuclear Information System (INIS)

    Vizin, Tjasa; Kos, Janko

    2015-01-01

    Gamma-enolase, known also as neuron-specific enolase (NSE), is an enzyme of the glycolytic pathway, which is expressed predominantly in neurons and cells of the neuroendocrine system. As a tumour marker it is used in diagnosis and prognosis of cancer; however, the mechanisms enrolling it in malignant progression remain elusive. As a cytoplasmic enzyme gamma-enolase is involved in increased aerobic glycolysis, the main source of energy in cancer cells, supporting cell proliferation. However, different cellular localisation at pathophysiological conditions, proposes other cellular engagements. The C-terminal part of the molecule, which is not related to glycolytic pathway, was shown to promote survival of neuronal cells by regulating neuronal growth factor receptor dependent signalling pathways, resulting also in extensive actin cytoskeleton remodelling. This additional function could be important also in cancer cells either to protect cells from stressful conditions and therapeutic agents or to promote tumour cell migration and invasion. Gamma-enolase might therefore have a multifunctional role in cancer progression: it supports increased tumour cell metabolic demands, protects tumour cells from stressful conditions and promotes their invasion and migration

  16. Surface displaced alfa-enolase of Lactobacillus plantarum is a fibronectin binding protein

    Directory of Open Access Journals (Sweden)

    Muscariello Lidia

    2009-02-01

    Full Text Available Abstract Background Lactic acid bacteria of the genus Lactobacillus and Bifidobacterium are one of the most important health promoting groups of the human intestinal microbiota. Their protective role within the gut consists in out competing invading pathogens for ecological niches and metabolic substrates. Among the features necessary to provide health benefits, commensal microorganisms must have the ability to adhere to human intestinal cells and consequently to colonize the gut. Studies on mechanisms mediating adhesion of lactobacilli to human intestinal cells showed that factors involved in the interaction vary mostly among different species and strains, mainly regarding interaction between bacterial adhesins and extracellular matrix or mucus proteins. We have investigated the adhesive properties of Lactobacillus plantarum, a member of the human microbiota of healthy individuals. Results We show the identification of a Lactobacillus plantarum LM3 cell surface protein (48 kDa, which specifically binds to human fibronectin (Fn, an extracellular matrix protein. By means of mass spectrometric analysis this protein was identified as the product of the L. plantarum enoA1 gene, coding the EnoA1 alfa-enolase. Surface localization of EnoA1 was proved by immune electron microscopy. In the mutant strain LM3-CC1, carrying the enoA1 null mutation, the 48 kDa adhesin was not anymore detectable neither by anti-enolase Western blot nor by Fn-overlay immunoblotting assay. Moreover, by an adhesion assay we show that LM3-CC1 cells bind to fibronectin-coated surfaces less efficiently than wild type cells, thus demonstrating the significance of the surface displaced EnoA1 protein for the L. plantarum LM3 adhesion to fibronectin. Conclusion Adhesion to host tissues represents a crucial early step in the colonization process of either pathogens or commensal bacteria. We demonstrated the involvement of the L. plantarum Eno A1 alfa-enolase in Fn-binding, by studying

  17. Evolution of Enzymatic Activities in the Enolase Superfamily: L-Rhamnonate Dehydratase

    Energy Technology Data Exchange (ETDEWEB)

    Rakus,J.; Fedorov, A.; Fedorov, E.; Glaner, M.; Hubbard, B.; Delli, J.; Babbitt, P.; Almo, S.; Gerlt, J.

    2008-01-01

    The l-rhamnonate dehydratase (RhamD) function was assigned to a previously uncharacterized family in the mechanistically diverse enolase superfamily that is encoded by the genome of Escherichia coli K-12. We screened a library of acid sugars to discover that the enzyme displays a promiscuous substrate specificity: l-rhamnonate (6-deoxy-l-mannonate) has the 'best' kinetic constants, with l-mannonate, l-lyxonate, and d-gulonate dehydrated less efficiently. Crystal structures of the RhamDs from both E. coli K-12 and Salmonella typhimurium LT2 (95% sequence identity) were obtained in the presence of Mg2+; the structure of the RhamD from S. typhimurium was also obtained in the presence of 3-deoxy-l-rhamnonate (obtained by reduction of the product with NaBH4). Like other members of the enolase superfamily, RhamD contains an N-terminal a + {beta} capping domain and a C-terminal ({beta}/a)7{beta}-barrel (modified TIM-barrel) catalytic domain with the active site located at the interface between the two domains. In contrast to other members, the specificity-determining '20s loop' in the capping domain is extended in length and the '50s loop' is truncated. The ligands for the Mg2+ are Asp 226, Glu 252 and Glu 280 located at the ends of the third, fourth and fifth {beta}-strands, respectively. The active site of RhamD contains a His 329-Asp 302 dyad at the ends of the seventh and sixth {beta}-strands, respectively, with His 329 positioned to function as the general base responsible for abstraction of the C2 proton of l-rhamnonate to form a Mg2+-stabilized enediolate intermediate. However, the active site does not contain other acid/base catalysts that have been implicated in the reactions catalyzed by other members of the MR subgroup of the enolase superfamily. Based on the structure of the liganded complex, His 329 also is expected to function as the general acid that both facilitates departure of the 3-OH group in a syn-dehydration reaction and

  18. Cannabidiol normalizes caspase 3, synaptophysin, and mitochondrial fission protein DNM1L expression levels in rats with brain iron overload: implications for neuroprotection.

    Science.gov (United States)

    da Silva, Vanessa Kappel; de Freitas, Betânia Souza; da Silva Dornelles, Arethuza; Nery, Laura Roesler; Falavigna, Lucio; Ferreira, Rafael Dal Ponte; Bogo, Maurício Reis; Hallak, Jaime Eduardo Cecílio; Zuardi, Antônio Waldo; Crippa, José Alexandre S; Schröder, Nadja

    2014-02-01

    We have recently shown that chronic treatment with cannabidiol (CBD) was able to recover memory deficits induced by brain iron loading in a dose-dependent manner in rats. Brain iron accumulation is implicated in the pathogenesis of neurodegenerative diseases, including Parkinson's and Alzheimer's, and has been related to cognitive deficits in animals and human subjects. Deficits in synaptic energy supply have been linked to neurodegenerative diseases, evidencing the key role played by mitochondria in maintaining viable neural cells and functional circuits. It has also been shown that brains of patients suffering from neurodegenerative diseases have increased expression of apoptosisrelated proteins and specific DNA fragmentation. Here, we have analyzed the expression level of brain proteins involved with mitochondrial fusion and fission mechanisms (DNM1L and OPA1), the main integral transmembrane protein of synaptic vesicles (synaptophysin), and caspase 3, an apoptosis-related protein, to gain a better understanding of the potential of CBD in restoring the damage caused by iron loading in rats. We found that CBD rescued iron-induced effects, bringing hippocampal DNM1L, caspase 3, and synaptophysin levels back to values comparable to the control group. Our results suggest that iron affects mitochondrial dynamics, possibly trigging synaptic loss and apoptotic cell death and indicate that CBD should be considered as a potential molecule with memory-rescuing and neuroprotective properties to be used in the treatment of cognitive deficits observed in neurodegenerative disorders.

  19. [Development of the Human Olfactory Bulbs in the Prenatal Ontogenesis: an Immunochistochemical Study with Markers of Presynaptic Terminals (anti-SNAP-25, -Synapsin-I, -Synaptophysin)].

    Science.gov (United States)

    Kharlamova, A S; Barabanov, V M; Saveliev, S V

    2015-01-01

    We provide the data of the olfactory bulbs (OB) development in the human fetuses on the stages from 8 week to birth. Immunochistochemical markers of presynaptic terminals (anti-SNAP-25, -synapsin-I, -synaptophysin) were used to evaluate the maturation of the OB. Differentiation of the OB layers begins from periphery, which implicitly evidences that growth of the olfactory nerves fibers induses not only anatomical differentiation of the OB, but also differentiation of its functional layers. The sites of the developing glomerulus are revealed using the immunochistochemical prosedure on the stage before distinct glomerulus can be identified with common histological procedure. OB conductive system demonstrates immunoreactivity with the antibodies to the presynaptic proteins on the all stages from 10-11 weeks of fetus development. Four stages of the OB development are described. All functional layers of the OB are mature at the 22-weeks stage. Further differentiation of the OB neuroblasts, including lamina formation of the internal granular leyer, glomerular layer development, OB growth continue after 20-22 weeks stage until 38-40 weeks of the fetus develoment. Patterns of the immunoreactivity with antibodies to SNAP-25, synapsin-I and synaptophysin are completely appropriate to those of adult's OB on the 38-40 weeks of the prenatal development. Complete maturity of the human OB is achived at 38-40 weeks of the prenatal development.

  20. Oral Immunization Against Candidiasis Using Lactobacillus casei Displaying Enolase 1 from Candida albicans.

    Science.gov (United States)

    Shibasaki, Seiji; Karasaki, Miki; Tafuku, Senji; Aoki, Wataru; Sewaki, Tomomitsu; Ueda, Mitsuyoshi

    2014-01-01

    Candidiasis is a common fungal infection that is prevalent in immunocompromised individuals. In this study, an oral vaccine against Candida albicans was developed by using the molecular display approach. Enolase 1 protein (Eno1p) of C. albicans was expressed on the Lactobacillus casei cell surface by using poly-gamma-glutamic acid synthetase complex A from Bacillus subtilis as an anchoring protein. The Eno1p-displaying L. casei cells were used to immunize mice, which were later challenged with a lethal dose of C. albicans. The data indicated that the vaccine elicited a strong IgG response and increased the survival rate of the vaccinated mice. Furthermore, L. casei acted as a potent adjuvant and induced high antibody titers that were comparable to those induced by strong adjuvants such as the cholera toxin. Overall, the molecular display method can be used to rapidly develop vaccines that can be conveniently administered and require minimal processing.

  1. An X-ray absorption spectroscopy study of the interactions of Ni2+ with yeast enolase.

    Science.gov (United States)

    Wang, S; Scott, R A; Lebioda, L; Zhou, Z H; Brewer, J M

    1995-05-15

    An x-ray absorption spectroscopy (XAS) study was carried out at pH 7.6 on solutions of Ni2+ and yeast enolase depleted of its physiological cofactor (Mg2+) in the presence or absence of substrate/product, the very strongly bound competitive inhibitor 2-phosphonoacetohydroxamate and Mg2+. Both "conformational" and "catalytic" Ni2+ are distorted octahedral in coordination, in agreement with several spectroscopic studies but in contrast to the coordination in the crystal at pH 6.0. The data are consistent with direct coordination of what must be the catalytic Ni2+ to the phosphate of the substrate, in agreement with some previous data but in disagreement with recent interpretations by other workers. The ligands around the metal ions obtained from the x-ray structure give simulated XAS spectra in good agreement with the observed spectra.

  2. Surface display of Clonorchis sinensis enolase on Bacillus subtilis spores potentializes an oral vaccine candidate.

    Science.gov (United States)

    Wang, Xiaoyun; Chen, Wenjun; Tian, Yanli; Mao, Qiang; Lv, Xiaoli; Shang, Mei; Li, Xuerong; Yu, Xinbing; Huang, Yan

    2014-03-10

    Clonorchis sinensis (C. sinensis) infections remain the common public health problem in freshwater fish consumption areas. New effective prevention strategies are still the urgent challenges to control this kind of foodborne infectious disease. The biochemical importance and biological relevance render C. sinensis enolase (Csenolase) as a potential vaccine candidate. In the present study, we constructed Escherichia coli/Bacillus subtilis shuttle genetic engineering system and investigated the potential of Csenolase as an oral vaccine candidate for C. sinensis prevention in different immunization routes. Our results showed that, compared with control groups, both recombinant Csenolase protein and nucleic acid could induce a mixed IgG1/IgG2a immune response when administrated subcutaneously (Psinensis infection. Csenolase derived oral vaccine conferred worm reduction rate and egg reduction rate at 60.07% (Psinensis prevention. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Five year remission of GHRH secreting bronchial neuroendocrine tumor with symptoms of acromegaly. Utility of chromogranin A in the monitoring of the disease

    International Nuclear Information System (INIS)

    Bolanowski, M.; Zatonska, K.; Kos-Kudla, B.; Rzeszutko, M.; Marciniak, M.

    2006-01-01

    Acromegaly is usually caused by excess GH (growth hormone) secretion by pituitary adenoma. Extremely rare (< 1% of cases) acromegaly can be a result of ectopic GHRH (growth hormone releasing hormone) secretion by bronchial tubes, lung, pancreatic or intestinal tumor. The aim of this description is to present the case of successfully treated acromegaly caused by ectopic GHRH secretion by bronchial neuroendocrine tumor and the usefulness of chromogranin A assay in the disease monitoring. The diagnosis of acromegaly in 61-year old woman was based on typical clinical picture and elevated GH and IGF-1(insulin-like growth factor-1) levels. MRI (magnetic resonance imaging) images revealed no tumor in the pituitary but only the pituitary enlargement. Moreover, the right lung tumor (10 cm size) and elevated GHRH level were documented. The secretion of GH, IGF-1 and GHRH were normalized and progression of acromegaly was stopped after the carcinoid tumor surgery. Currently, 5 year after surgery, acromegaly is still in the remission, as the normal levels of GH, IGF-1, chromogranin A and normal chest and pituitary images confirm. The authors emphasize usefulness of measurement of chromogranin A concentration for the evaluation of the tumor remission in case the routine GHRH assay is not accessible. (authors)

  4. Primary structure of bovine pituitary secretory protein I (chromogranin A) deduced from the cDNA sequence

    International Nuclear Information System (INIS)

    Ahn, T.G.; Cohn, D.V.; Gorr, S.U.; Ornstein, D.L.; Kashdan, M.A.; Levine, M.A.

    1987-01-01

    Secretory protein I (SP-I), also referred to as chromogranin A, is an acidic glycoprotein that has been found in every tissue of endocrine and neuroendocrine origin examined but never in exocrine or epithelial cells. Its co-storage and co-secretion with peptide hormones and neurotransmitters suggest that it has an important endocrine or secretory function. The authors have isolated cDNA clones from a bovine pituitary λgt11 expression library using an antiserum to parathyroid SP-I. The largest clone (SP4B) hybridized to a transcript of 2.1 kilobases in RNA from parathyroid, pituitary, and adrenal medulla. Immunoblots of bacterial lysates derived from SP4B lysognes demonstrated specific antibody binding to an SP4B/β-galactosidase fusion protein (160 kDa) with a cDNA-derived component of 46 kDa. Radioimmunoassay of the bacterial lystates with SP-I antiserum yielded parallel displacement curves of 125 I-labeled SP-I by the SP4B lysate and authentic SP-I. SP4B contains a cDNA of 1614 nucleotides that encodes a 449-amino acid protein (calculated mass, 50 kDa). The nucleotide sequences of the pituitary SP-I cDNA and adrenal medullary SP-I cDNAs are nearly identical. Analysis of genomic DNA suggests that pituitary, adrenal, and parathyroid SP-I are products of the same gene

  5. Increased Chromogranin A Cell Density in the Large Intestine of Patients with Irritable Bowel Syndrome after Receiving Dietary Guidance

    Directory of Open Access Journals (Sweden)

    Tarek Mazzawi

    2015-01-01

    Full Text Available The large intestine contains five types of endocrine cells that regulate its functions by sensing its luminal contents and releasing specific hormones. Chromogranin A (CgA is a common marker for the gastrointestinal endocrine cells, and it is abnormal in irritable bowel syndrome (IBS patients. Most IBS patients relate their symptoms to certain food elements. The present study investigated the effect of dietary guidance on the total endocrine cells of the large intestine as detected by CgA in 13 IBS patients. Thirteen control subjects were also included. Each patient received three sessions of dietary guidance. Colonoscopies were performed on controls and patients (at baseline and at 3–9 months after receiving guidance. Biopsy samples from the colon and rectum were immunostained for CgA and quantified by computerized image analysis. The densities of CgA cells in the total colon (mean ± SEM among the controls and the IBS patients before and after receiving dietary guidance were 83.3±10.1, 38.6±3.7, and 64.7±4.2 cells/mm2, respectively (P=0.0004, and were unchanged in the rectum. In conclusion, the increase in CgA cell density after receiving dietary guidance may reflect a change in the densities of the large intestinal endocrine cells causing an improvement in the IBS symptoms.

  6. Effect of laughter on salivary flow rates and levels of chromogranin A in young adults and elderly people.

    Science.gov (United States)

    Toda, Masahiro; Ichikawa, Hiroe

    2012-11-01

    Salivary chromogranin A (CgA) levels and salivary flow rates were measured to evaluate the stress relief effect of laughter on the young and the elderly. Thirty healthy volunteers (15 aged 20-25 years; 15 aged 62-83 years) performed a serial arithmetic task for 15 min and then watched a comedy video for 30 min. On a different day, as a control, they watched a non-humorous video after performing a task similar to the first one. Saliva samples were collected immediately before and after the arithmetic task, 30 min after completing the task (immediately after watching the film), and 30 min after watching the film (60 min after completing mental task). Salivary CgA levels were determined by enzyme-linked immunosorbent assay. In the elderly group, salivary flow rates, which had declined by the end of the arithmetic task, were statistically significantly higher after watching the comedy video. In the young group, salivary CgA levels, which had increased by the end of the task, had statistically significantly declined after watching the comedy video. No such post-task changes were apparent in control results; in the young group, there was a statistically significant interprotocol difference in salivary CgA levels. These findings suggest that laughter may relieve stress, particularly in the young people.

  7. Primary structure of bovine pituitary secretory protein I (chromogranin A) deduced from the cDNA sequence

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, T.G.; Cohn, D.V.; Gorr, S.U.; Ornstein, D.L.; Kashdan, M.A.; Levine, M.A.

    1987-07-01

    Secretory protein I (SP-I), also referred to as chromogranin A, is an acidic glycoprotein that has been found in every tissue of endocrine and neuroendocrine origin examined but never in exocrine or epithelial cells. Its co-storage and co-secretion with peptide hormones and neurotransmitters suggest that it has an important endocrine or secretory function. The authors have isolated cDNA clones from a bovine pituitary lambdagt11 expression library using an antiserum to parathyroid SP-I. The largest clone (SP4B) hybridized to a transcript of 2.1 kilobases in RNA from parathyroid, pituitary, and adrenal medulla. Immunoblots of bacterial lysates derived from SP4B lysognes demonstrated specific antibody binding to an SP4B/..beta..-galactosidase fusion protein (160 kDa) with a cDNA-derived component of 46 kDa. Radioimmunoassay of the bacterial lystates with SP-I antiserum yielded parallel displacement curves of /sup 125/I-labeled SP-I by the SP4B lysate and authentic SP-I. SP4B contains a cDNA of 1614 nucleotides that encodes a 449-amino acid protein (calculated mass, 50 kDa). The nucleotide sequences of the pituitary SP-I cDNA and adrenal medullary SP-I cDNAs are nearly identical. Analysis of genomic DNA suggests that pituitary, adrenal, and parathyroid SP-I are products of the same gene.

  8. Stability for Function Trade-Offs in the Enolase Superfamily 'Catalytic Module'

    Energy Technology Data Exchange (ETDEWEB)

    Nagatani, R.A.; Gonzalez, A.; Shoichet, B.K.; Brinen, L.S.; Babbitt, P.C.; /UC, San Francisco /SLAC, SSRL

    2007-07-12

    Enzyme catalysis reflects a dynamic interplay between charged and polar active site residues that facilitate function, stabilize transition states, and maintain overall protein stability. Previous studies show that substituting neutral for charged residues in the active site often significantly stabilizes a protein, suggesting a stability trade-off for functionality. In the enolase superfamily, a set of conserved active site residues (the ''catalytic module'') has repeatedly been used in nature in the evolution of many different enzymes for the performance of unique overall reactions involving a chemically diverse set of substrates. This catalytic module provides a robust solution for catalysis that delivers the common underlying partial reaction that supports all of the different overall chemical reactions of the superfamily. As this module has been so broadly conserved in the evolution of new functions, we sought to investigate the extent to which it follows the stability-function trade-off. Alanine substitutions were made for individual residues, groups of residues, and the entire catalytic module of o-succinylbenzoate synthase (OSBS), a member of the enolase superfamily from Escherichia coli. Of six individual residue substitutions, four (K131A, D161A, E190A, and D213A) substantially increased protein stability (by 0.46-4.23 kcal/mol), broadly consistent with prediction of a stability-activity trade-off. The residue most conserved across the superfamily, E190, is by far the most destabilizing. When the individual substitutions were combined into groups (as they are structurally and functionally organized), nonadditive stability effects emerged, supporting previous observations that residues within the module interact as two functional groups within a larger catalytic system. Thus, whereas the multiple-mutant enzymes D161A/E190A/D213A and K131A/K133A/D161A/E190A/D213A/K235A (termed 3KDED) are stabilized relative to the wild-type enzyme (by 1

  9. Evolution of Enzymatic Activities in the Enolase Superfamily: L-Fuconate Dehydratase from Xanthomonas campestris

    Energy Technology Data Exchange (ETDEWEB)

    Yew,W.; Fedorov, A.; Fedorov, E.; Rakus, J.; Pierce, R.; Almo, S.; Gerlt, J.

    2006-01-01

    Many members of the mechanistically diverse enolase superfamily have unknown functions. In this report the authors use both genome (operon) context and screening of a library of acid sugars to assign the L-fuconate dehydratase (FucD) function to a member of the mandelate racemase (MR) subgroup of the superfamily encoded by the Xanthomonas campestris pv. campestris str. ATCC 33913 genome (GI: 21233491). Orthologues of FucD are found in both bacteria and eukaryotes, the latter including the rTS beta protein in Homo sapiens that has been implicated in regulating thymidylate synthase activity. As suggested by sequence alignments and confirmed by high-resolution structures in the presence of active site ligands, FucD and MR share the same active site motif of functional groups: three carboxylate ligands for the essential Mg2+ located at the ends of th third, fourth, and fifth-strands in the (/)7-barrel domain (Asp 248, Glu 274, and Glu 301, respectively), a Lys-x-Lys motif at the end of the second-strand (Lys 218 and Lys 220), a His-Asp dyad at the end of the seventh and sixth-strands (His 351 and Asp 324, respectively), and a Glue at the end of the eighth-strand (Glu 382). The mechanism of the FucD reaction involves initial abstraction of the 2-proton by Lys 220, acid catalysis of the vinylogous-elimination of the 3-OH group by His 351, and stereospecific ketonization of the resulting 2-keto-3-deoxy-L-fuconate product. Screening of the library of acid sugars revealed substrate and functional promiscuity: In addition to L-fuconate, FucD also catalyzes the dehydration of L-galactonate, D-arabinonate, D-altronate, L-talonate, and D-ribonate. The dehydrations of L-fuconate, L-galactonate, and D-arabinonate are initiated by abstraction of the 2-protons by Lys 220. The dehydrations of L-talonate and D-ribonate are initiated by abstraction of the 2-protons by His 351; however, protonation of the enediolate intermediates by the conjugate acid of Lys 220 yields L

  10. Human alpha-enolase from endothelial cells as a target antigen of anti-endothelial cell antibody in Behçet's disease.

    Science.gov (United States)

    Lee, Kwang Hoon; Chung, Hae-Shin; Kim, Hyoung Sup; Oh, Sang-Ho; Ha, Moon-Kyung; Baik, Ja-Hyun; Lee, Sungnack; Bang, Dongsik

    2003-07-01

    To identify and recombine a protein of the human dermal microvascular endothelial cell (HDMEC) that specifically reacts with anti-endothelial cell antibody (AECA) in the serum of patients with Behçet's disease (BD), and to evaluate the usefulness of this protein in BD. The proteomics technique, with 2-dimensional gel electrophoresis and matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry, was used to identify and recombine HDMEC antigen. Western blotting and enzyme-linked immunosorbent assay (ELISA) of recombinant protein isolated by gene cloning were performed on serum from healthy controls, patients with BD, and patients with other rheumatic diseases (rheumatoid arthritis, systemic lupus erythematosus, and Wegener's granulomatosis). Eighteen of 40 BD patients had serum IgM antibody to HDMEC antigen. The purified protein that reacted with AECA in BD patient sera was found to be alpha-enolase by 2-dimensional gel electrophoresis followed by immunoblotting and MALDI-TOF mass spectrometry. Recombinant alpha-enolase protein was isolated and refined by gene cloning. On Western blots, AECA-positive IgM from the sera of patients with active BD reacted strongly with recombinant human alpha-enolase. BD patient sera positive for anti-alpha-enolase did not react with human gamma-enolase. On dot-blotting, reactivity to human alpha-enolase was detected only in the IgM-positive group. Fifteen of the 18 AECA-positive sera that were positive for the HDMEC antigen showed reactivity to recombinant alpha-enolase IgM antibody by ELISA. The alpha-enolase protein is the target protein of serum AECA in BD patients. This is the first report of the presence of IgM antibodies to alpha-enolase in endothelial cells from the serum of BD patients. Although further studies relating this protein to the pathogenesis of BD will be necessary, alpha-enolase and its antibody may prove useful in the development of new diagnostic and treatment modalities in BD.

  11. Salivary function impairment in type 2 Diabetes patients associated with concentration and genetic polymorphisms of chromogranin A.

    Science.gov (United States)

    Kogawa, Evelyn Mikaela; Grisi, Daniela Corrêa; Falcão, Denise Pinheiro; Amorim, Ingrid Aquino; Rezende, Taia Maria Berto; da Silva, Izabel Cristina Rodrigues; Silva, Osmar Nascimento; Franco, Octávio Luiz; de Amorim, Rivadávio Fernandes Batista

    2016-11-01

    The purpose of this study was to evaluate the effect of type 2 diabetes mellitus (T2DM) on salivary function impairments according to glycemic control status and subsequently compare the concentration of chromogranin A (CHGA) with its genetic profile. Thirty-six patients with controlled T2DM, 36 with poorly controlled T2DM, and 38 nondiabetic subjects underwent salivary flow rate measurements by means of unstimulated labial (ULS), unstimulated whole (UWS), and stimulated whole saliva (SWS) collections. CHGA concentrations were determined in saliva and plasma with ELISA, and two CHGA polymorphisms (T-415C and Glu264Asp) were analyzed by polymerase chain reaction-restriction fragment length polymorphism. T2DM patients presented significantly lower ULS and UWS flow rates regardless of glycemic control status compared to controls (P = 0.002 and P = 0.027, respectively). The SWS flow rate in the poorly controlled T2DM was the lowest among the groups (P = 0.026). Significantly higher plasma and salivary CHGA levels were found in T2DM groups (P = 0.019 and P diabetics and control subjects when associated with lower salivary flow and higher salivary CHGA production (P salivary glands. However, poorly controlled T2DM has the most influence on SWS flow rates. Our findings indicate an association between plasma and salivary CHGA levels and T2DM patients. Furthermore, the results suggest that CGHA polymorphisms might be associated with salivary gland hypofunction and higher salivary CHGA production in T2DM patients. Nevertheless, further epidemiological studies are required to elucidate this clinical implication. Salivary impairments and high levels of CHGA are associated with T2DM patients. In addition, CGHA polymorphisms might be associated with salivary gland hypofunction and higher salivary CHGA production in T2DM patients. This could be a significant insight to establish a role for salivary CHGA as a potential clinical biomarker to T2DM.

  12. Differential expression of secretogranin II and chromogranin A genes in the female rat pituitary through sexual maturation and estrous cycle

    International Nuclear Information System (INIS)

    Anouar, Y.; Duval, J.

    1991-01-01

    Secretogranin II (SgII) is a protein of pituitary secretory granules released by LHRH-stimulated gonadotrope cells. Estrogens and androgens are modulators of SgII release. Experiments were performed to determine the regulation of expression of the SgII gene in the female rat pituitary, during sexual maturation and according to the estrous cycle. Age- and cycle-related changes in SgII mRNA content were estimated through cytoplasmic slot blot; SgII content was determined by western blotting; maturation of the protein was controlled through [35S]sulfate labeling. Variations in chromogranin A (CgA), another protein of secretory granules, were analyzed in the same experimental conditions to assess the specificity of SgII regulation. The pituitary SgII concentration increased between days 7 and 21 (2.2-fold) and then declined to the initial 7-day-old value. Simultaneously, the CgA concentration went through a maximum between days 14 and 21 and then strongly dropped to barely detectable levels in the adult pituitary. The SgII mRNA concentration followed roughly the same pattern as the protein. Moreover, the sulfation level remained constant between days 14 and 60. These results demonstrated a regulatory mechanism operating, during sexual maturation, on the SgII gene and not on the protein processing or on storage/release steps. In the 4-day cycling females, the pituitary SgII mRNA and protein contents were the lowest during estrus. They then increased to their highest values in diestrus II. Moreover, the sulfation level of SgII was significantly higher during estrus than during any other stage. Due to its low content level, variations in pituitary CgA could not be demonstrated during the cycle

  13. Catecholamines, cardiac natriuretic peptides and chromogranin A: evolution and physiopathology of a 'whip-brake' system of the endocrine heart.

    Science.gov (United States)

    Tota, Bruno; Cerra, Maria Carmela; Gattuso, Alfonsina

    2010-09-15

    In the past 50 years, extensive evidence has shown the ability of vertebrate cardiac non-neuronal cells to synthesize and release catecholamines (CA). This formed the mindset behind the search for the intrinsic endocrine heart properties, culminating in 1981 with the discovery of the natriuretic peptides (NP). CA and NP, co-existing in the endocrine secretion granules and acting as major cardiovascular regulators in health and disease, have become of great biomedical relevance for their potent diagnostic and therapeutic use. The concept of the endocrine heart was later enriched by the identification of a growing number of cardiac hormonal substances involved in organ modulation under normal and stress-induced conditions. Recently, chromogranin A (CgA), a major constituent of the secretory granules, and its derived cardio-suppressive and antiadrenergic peptides, vasostatin-1 and catestatin, were shown as new players in this framework, functioning as cardiac counter-regulators in 'zero steady-state error' homeostasis, particularly under intense excitatory stimuli, e.g. CA-induced myocardial stress. Here, we present evidence for the hypothesis that is gaining support, particularly among human cardiologists. The actions of CA, NP and CgA, we argue, may be viewed as a hallmark of the cardiac capacity to organize 'whip-brake' connection-integration processes in spatio-temporal networks. The involvement of the nitric oxide synthase (NOS)/nitric oxide (NO) system in this configuration is discussed. The use of fish and amphibian paradigms will illustrate the ways that incipient endocrine-humoral agents have evolved as components of cardiac molecular loops and important intermediates during evolutionary transitions, or in a distinct phylogenetic lineage, or under stress challenges. This may help to grasp the old evolutionary roots of these intracardiac endocrine/paracrine networks and how they have evolved from relatively less complicated designs. The latter can also be used

  14. Changes in salivary chromogranin A levels in adults with atopic dermatitis are correlated with changes in their condition.

    Science.gov (United States)

    Cai, Liang; Kaneko, Sakae; Morita, Eishin

    2018-05-01

    Stress-induced scratching is an issue in patients with adult atopic dermatitis (AD). Symptoms of stress-induced AD are common in clinical practise. Salivary chromogranin A (CgA) level has research value as a possible index related to a patient's psychological stress. Using saliva, which is easily collectable, we compared two assessments of the severities of AD and stress with the levels of stress proteins in the saliva of 30 patients with AD in the Department of Dermatology of Shimane University between April 2015 and May 2017. The severities of AD and stress were assessed using the Scoring Atopic Dermatitis (SCORAD) score and State-Trait Anxiety Inventory score, respectively. Additionally, the assessments included those of personality using the Tokyo University Egogram (TEG)-II score and quality of life using the Dermatology Life Quality Index score. Simultaneously, we measured their salivary CgA levels. The change in salivary CgA per protein in patients with AD was correlated with their changes in SCORAD score (correlation coefficient, r = 0.596, P = 0.001) and objective SCORAD (r = 0.608, P < 0.001). The changes in CgA per protein correlated with those in TEG-II A (r = 0.370, P = 0.022), while the changes in SCORAD score correlated with those in DLQI (r = 0.309, P = 0.048). Our results suggest that changes in a patient's condition are reflective of the changes in the patient's stress. The changes in salivary CgA level in patients with AD correlated with the changes in their condition. © 2018 Japanese Dermatological Association.

  15. Chromogranin A cell density in the large intestine of Asian and European patients with irritable bowel syndrome.

    Science.gov (United States)

    El-Salhy, Magdy; Patcharatrakul, Tanisa; Hatlebakk, Jan Gunnar; Hausken, Trygve; Gilja, Odd Helge; Gonlachanvit, Sutep

    Patients with irritable bowel syndrome (IBS) in Asia show distinctive differences from those in the western world. The gastrointestinal endocrine cells appear to play an important role in the pathophysiology of IBS. The present study aimed at studying the density of chromogranin A (CgA) cells in the large intestine of Thai and Norwegian IBS patients. Thirty Thai IBS patients and 20 control subjects, and 47 Norwegian IBS patients and 20 control subjects were included. A standard colonoscopy was performed in both the patients and controls, and biopsy samples were taken from the colon and the rectum. The biopsy samples were stained with hematoxylin-eosin and immunostained for CgA. The density of CgA cells was determined by computerized image analysis. In the colon and rectum, the CgA cell densities were far higher in both IBS and healthy Thai subjects than in Norwegians. The colonic CgA cell density was lower in Norwegian IBS patients than in controls, but did not differ between Thai IBS patients and controls. In the rectum, the CgA cell densities in both Thai and Norwegian patients did not differ from those of controls. The higher densities of CgA cells in Thai subjects than Norwegians may be explained by a higher exposure to infections at childhood and the development of a broad immune tolerance, by differences in the intestinal microbiota, and/or differing diet habits. The normal CgA cell density in Thai IBS patients in contrast to that of Norwegians may be due to differences in pathophysiology.

  16. Evaluation of anxiety and salivary chromogranin a secretion in women receiving breast conserving surgery followed by radiation therapy

    International Nuclear Information System (INIS)

    Seki-Nakamura, Kaori; Maebayashi, Katsuya; Nasu-Izumi, Sachiko; Akimoto, Tetsuo; Mitsuhashi, Norio

    2011-01-01

    We conducted a prospective study to assess the anxiety and salivary Chromogranin A (CgA), which is considered to be a biomarker of the stress response, in outpatients receiving breast conserving surgery followed by radiation therapy (RT) to the whole breast. Fifty consecutive patients who received whole-breast RT were enrolled in this study. The anxiety levels were measured by the State-Trait Anxiety Inventory (STAI) at the beginning of RT (baseline), 30 Gy, completion of RT, and 1 and 3 months after RT. Salivary CgA levels were also measured at the same time. The mean state anxiety score for all patients was 46.16 with a standard error (SE) of 1.57 at the beginning of RT (baseline) which continued to decline during and after RT. It reached its lowest score with 36.34±1.56 at 3 months after RT (p<0.0001). The mean trait anxiety score for all patients was 43.10±1.54 at baseline and remained constant during RT but began to decline after completion of RT and reached a low level at 3 months after RT (p=0.0021). The mean salivary CgA concentration for all patients demonstrated no consistent trends over time, but at 30 Gy the concentration showed a significant decreasing pattern (p=0.0473). Salivary CgA concentrations and state anxiety and trait anxiety scores at all time points showed no correlation. The mean anxiety scores measured by State Trait Anxiety Inventory (STAI) showed no positive correlation with salivary CgA concentration for breast cancer patients undergoing radiation therapy following breast conserving surgery. (author)

  17. Fasciola gigantica enolase is a major component of worm tegumental fraction protective against sheep fasciolosis.

    Science.gov (United States)

    Mahana, N; Abd-Allah, H A-S; Salah, M; Tallima, H; El Ridi, R

    2016-06-01

    Infection of cattle and sheep with the parasite Fasciola gigantica is a cause of important economic losses throughout Asia and Africa. Many of the available anthelmintics have undesirable side effects, and the parasite may acquire drug resistance as a result of mass and repeated treatments of livestock. Accordingly, the need for developing a vaccine is evident. Triton-soluble surface membrane and tegumental proteins (TSMTP) of 60, 32, and 28 kDa previously shown to elicit protective immunity in mice against challenge F. gigantica infection were found to be strongly immunogenic in sheep eliciting vigorous specific antibody responses to a titer>1:16,000 as assessed by enzyme-linked immunosorbent assay. Furthermore, the 60 kDa fraction induced production of antibodies able to bind to the surface membrane of newly excysted juvenile flukes and mediate their attrition in antibody-dependent complement- and cell-mediated cytotoxicity assays, and significant (PFasciola hepatica enolase, suggesting that a fasciolosis vaccine might be effective against both tropical and temperate liver flukes. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Homology models guide discovery of diverse enzyme specificities among dipeptide epimerases in the enolase superfamily

    Science.gov (United States)

    Lukk, Tiit; Sakai, Ayano; Kalyanaraman, Chakrapani; Brown, Shoshana D.; Imker, Heidi J.; Song, Ling; Fedorov, Alexander A.; Fedorov, Elena V.; Toro, Rafael; Hillerich, Brandan; Seidel, Ronald; Patskovsky, Yury; Vetting, Matthew W.; Nair, Satish K.; Babbitt, Patricia C.; Almo, Steven C.; Gerlt, John A.; Jacobson, Matthew P.

    2012-01-01

    The rapid advance in genome sequencing presents substantial challenges for protein functional assignment, with half or more of new protein sequences inferred from these genomes having uncertain assignments. The assignment of enzyme function in functionally diverse superfamilies represents a particular challenge, which we address through a combination of computational predictions, enzymology, and structural biology. Here we describe the results of a focused investigation of a group of enzymes in the enolase superfamily that are involved in epimerizing dipeptides. The first members of this group to be functionally characterized were Ala-Glu epimerases in Eschericiha coli and Bacillus subtilis, based on the operon context and enzymological studies; these enzymes are presumed to be involved in peptidoglycan recycling. We have subsequently studied more than 65 related enzymes by computational methods, including homology modeling and metabolite docking, which suggested that many would have divergent specificities;, i.e., they are likely to have different (unknown) biological roles. In addition to the Ala-Phe epimerase specificity reported previously, we describe the prediction and experimental verification of: (i) a new group of presumed Ala-Glu epimerases; (ii) several enzymes with specificity for hydrophobic dipeptides, including one from Cytophaga hutchinsonii that epimerizes D-Ala-D-Ala; and (iii) a small group of enzymes that epimerize cationic dipeptides. Crystal structures for certain of these enzymes further elucidate the structural basis of the specificities. The results highlight the potential of computational methods to guide experimental characterization of enzymes in an automated, large-scale fashion. PMID:22392983

  19. Circulating autoantibodies to phosphorylated α-enolase are a hallmark of pancreatic cancer.

    Science.gov (United States)

    Tomaino, Barbara; Cappello, Paola; Capello, Michela; Fredolini, Claudia; Sperduti, Isabella; Migliorini, Paola; Salacone, Paola; Novarino, Anna; Giacobino, Alice; Ciuffreda, Libero; Alessio, Massimo; Nisticò, Paola; Scarpa, Aldo; Pederzoli, Paolo; Zhou, Weidong; Petricoin Iii, Emanuel F; Liotta, Lance A; Giovarelli, Mirella; Milella, Michele; Novelli, Francesco

    2011-01-07

    Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis and no diagnostic markers have, as of yet, been defined. In PDAC patients, α-enolase (ENOA) is up-regulated and elicits the production of autoantibodies. Here, we analyzed the autoantibody response to post-translational modifications of ENOA in PDAC patients. ENOA isolated from PDAC tissues and cell lines was characterized by two-dimensional electrophoresis (2-DE) Western blot (WB), revealing the expression of six different isoforms (named ENOA1,2,3,4,5,6) whereas only 4 isoforms (ENOA3,4,5,6) were detectable in normal tissues. As assessed by 2-DE WB, 62% of PDAC patients produced autoantibodies to the two more acidic isoforms (ENOA1,2) as opposed to only 4% of controls. Mass spectrometry showed that ENOA1,2 isoforms were phosphorylated on serine 419. ROC analysis demonstrated that autoantibodies to ENOA1,2 usefully complement the diagnostic performance of serum CA19.9 levels, achieving approximately 95% diagnostic accuracy in both advanced and resectable PDAC. Moreover, the presence of autoantibodies against ENOA1,2 correlated with a significantly better clinical outcome in advanced patients treated with standard chemotherapy. In conclusion, our results demonstrate that ENOA phosphorylation is associated with PDAC and induces specific autoantibody production in PDAC patients that may have diagnostic value.

  20. Neuron- specific enolase level in patients with metabolic syndrome and its value forecasting acute stroke

    Directory of Open Access Journals (Sweden)

    Oral Ospanov

    2018-03-01

    Full Text Available Background Patients with metabolic syndrome are at a greater risk of experiencing a cerebrovascular event. Several studies show that patients with metabolic syndrome have asymptomatic ischemic brain injury. In this case, there is a need for rapid determination of asymptomatic brain lesions and prediction of acute stroke. Aims The aim of the study was to determine the neuron-specific enolase (NSE serum level in patients with metabolic syndrome and the value of this level for forecasting acute stroke. Methods The study used the following information to determine metabolic syndrome: waist circumference, total cholesterol, triglycerides, high-density lipoprotein cholesterol, blood pressure, and blood glucose. Doppler sonography mapping of the brachiocephalic trunk was held to determine the percentage of the carotid artery stenosis. To determine asymptomatic ischemic brain injury, the NSE serum marker was measured. Statistical processing of the measurements was performed using the H test and the Mann–Whitney test. The possible link between MS and NSE were determined by logistic regression analysis. Mathematical modeling was performed using logistic regression. Results There are statistically significant differences in NSE concentrations in groups with metabolic syndrome and ischemic stroke patients. This assertion is confirmed by logistic regression analysis, which revealed the existence of a relationship between metabolic syndrome and increased concentration of NSE. Conclusion Patients with metabolic syndrome have an increased concentration of NSE. This indicates the presence of asymptomatic ischemic neuronal damage. A prognostic model for determining the probability that patients with metabolic syndrome will have an acute stroke was developed.

  1. Co-purification of arrestin like proteins with alpha-enolase from bovine myocardial tissues and the possible role in heart diseases as an autoantigen

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    Mirshahi, M., E-mail: massoud.mirshahi@inserm.fr; Le Marchand, S.

    2015-05-08

    Aim: Previously, we reported that visual arrestin co-purified with glycolytic enzymes. The aim of this study was to analyze the co-purification of arrestin like proteins (ALP) in bovine cardiac tissues with enolases. Methods: The soluble extract of bovine myocardial tissues from different regions such as left and right atriums and ventricles of the bovine heart (n = 3) was analyzed by ACA-34 gel filtration, immuno-affinity column, SDS-PAGE, ELISA, western blot and a sandwich immune assay for quantification of ALP and sequence analysis. Results: We observed that; 1) The cardiac muscle contained a 50 kDa ALP at a concentration of 751 pg/mg of soluble protein extract, 2) ALP purified, by immunoaffinity, contained alpha-enolase of 48 kDa confirmed by protein sequence analysis; 3) Cardiomyocyte cells exposed to anti arrestin and anti enolase monoclonal antibodies showed decreased proliferation in vitro, 4) High level of autoantibodies were detected by ELISA (3.57% for arrestin and 9.12% for α-enolase) in serum of patients with infarcted heart disease. Conclusion: We suggest a possible interaction between ALP and alpha-enolases yielding a complex that may be involved in the induction of cardiac autoimmune diseases. - Highlights: • We examine a possible interaction between arrestin like protein and alpha-enolases in cardiomyocyte. • We demonstrated the effect of antibodies against arrestin and enolase on cardiomyocyte cell proliferation. • We suggest that this proteins complex may be involved in the induction of cardiac autoimmune diseases.

  2. Malignant Range Elevation of Serum Chromogranin A due to Inadvertent Use of Proton Pump Inhibitor in a Subject with Pancreatic Incidentaloma

    Directory of Open Access Journals (Sweden)

    Usman Hammawa Malabu

    2011-01-01

    Full Text Available We present a case of highly elevated tenfold rise of serum chromogranin A in a young, morbidly obese, hypertensive female being investigated for pancreatic mass, weight loss, and elevated ESR. Following extensive noninvasive investigations, an ultrasound-guided pancreatic biopsy confirmed benign haemorrhagic cyst. A clue to the etiology of the hyperchromogranin A was the elevated serum gastrin level leading to suspicion of proton pump inhibitor administration confirmed by admittance to its use. Withdrawal of the medication led to dramatic resolution of the neuroendocrine tumor marker.

  3. Carbohydrate metabolism of Xylella fastidiosa: Detection of glycolytic and pentose phosphate pathway enzymes and cloning and expression of the enolase gene

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    Facincani Agda Paula

    2003-01-01

    Full Text Available The objective of this work was to assess the functionality of the glycolytic pathways in the bacterium Xylella fastidiosa. To this effect, the enzymes phosphoglucose isomerase, aldolase, glyceraldehyde-3-phosphate dehydrogenase and pyruvate kinase of the glycolytic pathway, and glucose 6-phosphate dehydrogenase of the Entner-Doudoroff pathway were studied, followed by cloning and expression studies of the enolase gene and determination of its activity. These studies showed that X. fastidiosa does not use the glycolytic pathway to metabolize carbohydrates, which explains the increased duplication time of this phytopatogen. Recombinant enolase was expressed as inclusion bodies and solubilized with urea (most efficient extractor, Triton X-100, and TCA. Enolase extracted from X. fastidiosa and from chicken muscle and liver is irreversibly inactivated by urea. The purification of enolase was partial and resulted in a low yield. No enzymatic activity was detected for either recombinant and native enolases, aldolase, and glyceraldehyde-3-phosphate dehydrogenase, suggesting that X. fastidiosa uses the Entner-Doudoroff pathway to produce pyruvate. Evidence is presented supporting the idea that the regulation of genes and the presence of isoforms with regulation patterns might make it difficult to understand the metabolism of carbohydrates in X. fastidiosa.

  4. Neuron-specific enolase is a useful maker of neuroendocrine origin in pheochromocytoma cell culture

    International Nuclear Information System (INIS)

    Abelin, N.; Dahia, P.L.M.; Martin, R.; Kato, S.; Toledo, S.P.A.

    1994-01-01

    Neuron-specific enolase (NSE) has been used as a marker for neuroendocrine tumors either in immunocytochemical studies or in serum measurements. In this paper NSE levels were determined in cultured pheochromocytoma cells to test whether it is also a useful marker in cell culture of tumors derived from neuroendocrine system. Cultured pheochromocytoma cells came from a primary explant and were grown in RPMI supplemented with 20% fetal calf serum, 100 μg/mL ampicillin and 100 μ/mL streptomycin. NSE was measured in culture medium and cell homogenates. Samples from different pheochromocytoma cultures were analyzed and compared to normal cultured fibroblast cells derived from human skin. NSE was measured by a commercially available radioimmunoassay kit. NSE levels were higher in cell homogenates as compared to those in culture medium, reaching levels as high as 6-fold in the former in TE cell line (26.46 ng/mL and 4.39 ng/mL, respectively). Serial measurements in culture medium from TE cell line evidenced decreasing values in subsequential subcultures (from 9.24 ng/mL during primary explant to 1.7 ng/mL in the tenth subculture). In cultured normal fibroblasts, NSE levels in cultured media were definitely lower than those obtained from pheochromocytoma cultures. These preliminary data suggest that NSE may be a useful marker of neuroendocrine derived tumors, such as pheochromocytoma, in culture. Thus, the simplicity and availability of NSE radioimmunoassay provides an alternative to catecholamine measurement to better characterize pheochromocytoma cell lines in culture, with the advantage of faster result at lower costs. (author). 18 refs, 2 tabs

  5. Serum neuron specific enolase - a novel indicator for neuropsychiatric systemic lupus erythematosus?

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    Hawro, T; Bogucki, A; Krupińska-Kun, M; Maurer, M; Woźniacka, A

    2015-12-01

    Neuropsychiatric (NP) lupus, a common manifestation of systemic lupus erythematosus (SLE), is still insufficiently understood, in part, because of the lack of specific biomarkers. Neuron specific enolase (NSE), an important neuronal glycolytic enzyme, shows increased serum levels following acute brain injury, and decreased serum levels in several chronic disorders of the nervous system, including multi infarct dementia, multiple sclerosis and depression. The aim of the study was to evaluate serum NSE levels in SLE patients with and without nervous system involvement, and in healthy controls, and to assess the correlation of NSE serum levels of patients with neuropsychiatric systemic lupus erythematosus (NPSLE) with clinical parameters. The study comprised 47 SLE patients and 28 controls. SLE activity was assessed using the Systemic Lupus Activity Measure (SLAM). A neurologist and a psychiatrist examined all patients. NP involvement was diagnosed according to strict NPSLE criteria proposed by Ainiala and coworkers, as modification to American College of Rheumatology (ACR) nomenclature and case definitions. NSE serum levels were determined by use of an immunoassay. Mean NSE serum concentrations in patients with NPSLE were significantly lower than in non-NPSLE patients (6.3 ± 2.6 µg/L vs. 9.7 ± 3.3 µg/L, p < 0.01) and in controls (8.8 ± 3.3 µg/L, p < 0.05). There were significant negative correlations between NSE serum levels and SLE activity (r = -0.42, p < 0.05) and the number of NPSLE manifestations diagnosed (-0.37; p = 0.001). Decreased serum concentrations of NSE may reflect chronic neuronal damage with declined metabolism of the nervous tissue in patients with NPSLE. © The Author(s) 2015.

  6. The relationship between neuron-specific enolase and prognosis of patients with acute traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Yun-yang LIU

    2015-03-01

    Full Text Available Objective To investigate the relationship between neuron-specific enolase (NSE levels in serum and cerebrospinal fluid (CSF of patients with acute traumatic brain injury (TBI and the prognosis of TBI patients.  Methods A total of 89 patients with acute TBI were divided into light, medium, heavy and severe TBI groups based on admission Glasgow Coma Scale (GCS score. Serum NSE expression levels were detected in all cases and NSE levels in CSF were detected in 18 cases within 12 h after TBI. The expression levels of serum NSE in 20 normal people, except cases of lung disease and nervous system damage, were detected as a control group. Results Compared with the control group, serum NSE expression levels of patients in each TBI group were elevated (P < 0.05, for all, and the NSE levels in severe and heavy TBI groups were higher than that in medium and light groups (P < 0.05, for all. The serum NSE expression levels of patients with cerebral contusion were higher than that of patients with diffuse axonal injury (DAI, P = 0.025, subdural hematoma (P = 0.031 and epidural hematoma (P = 0.021. Serum NSE expression levels were negatively correlated with GCS score (rs = - 0.327, P = 0.024 and Glasgow Outcome Scale (GOS score (rs = - 0.252, P = 0.049. The NSE expression levels of CSF in severe and heavy TBI patients were higher than that of serum (P = 0.039, 0.031.  Conclusions NSE expression changes can be evaluated as an auxiliary indicator in reflecting the degree of acute TBI, typing diagnosis and prognostic evaluation, and NSE levels of CSF is more sensitive than that of serum. DOI: 10.3969/j.issn.1672-6731.2015.03.013

  7. Changes in small intestinal chromogranin A-immunoreactive cell densities in patients with irritable bowel syndrome after receiving dietary guidance.

    Science.gov (United States)

    Mazzawi, Tarek; El-Salhy, Magdy

    2016-05-01

    Chromogranin A (CgA) is a common marker for enteroendocrine cells in the gut, and CgA-immunoreactive cell densities are abnormal in patients with irritable bowel syndrome (IBS). The majority of patients with IBS report that their symptoms develop after consuming certain foodstuffs. In the present study, we investigated the effects of dietary guidance on the total enteroendocrine cell densities in the small intestine, as detected by CgA. A total of 14 patients with IBS underwent a gastroscopy with duodenal biopsies and 11 of them also underwent a colonoscopy, with biopsy samples obtained from the ileum. Fourteen control subjects were also included. Each patient received 3 sessions of dietary guidance. Gastroscopies and colonoscopies were performed on both the controls and patients with IBS (at baseline and at 3-9 months after receiving guidance). Biopsy samples obtained from the duodenum and ileum were immunostained for CgA using the avidin-biotin complex (ABC) method and were quantified using computerized image analysis. The density of CgA-immunoreactive cells in the duodenum (mean ± SEM values) in the control subjects was 235.9 ± 31.9 cells/mm2; in the patients with IBS, the density was 36.9 ± 9.8 and 103.7 ± 16.9 cells/mm2 before and after they received dietary guidance, respectively (P=0.007). The density of CgA-immunoreactive cells in the ileum in the control subjects was 47.4 ± 8.3 cells/mm2; in the patients with IBS, the density was 48.4 ± 8.1 and 17.9 ± 4.4 cells/mm2, before and after they received dietary guidance, respectively (P=0.0006). These data indicate that changes in CgA-immunoreactive cell densities in patients with IBS after receiving dietary guidance may reflect a change in the densities of the small intestinal enteroendocrine cells, which may contribute to an improvement in the IBS symptoms.

  8. Presence of chromogranin-derived antimicrobial peptides in plasma during coronary artery bypass surgery and evidence of an immune origin of these peptides.

    Science.gov (United States)

    Tasiemski, Aurélie; Hammad, Hamida; Vandenbulcke, Franck; Breton, Christophe; Bilfinger, Thomas J; Pestel, Joel; Salzet, Michel

    2002-07-15

    Chromogranin A (CGA) and chromogranin B (CGB) are acidic proteins stored in secretory organelles of endocrine cells and neurons. In addition to their roles as helper proteins in the packaging of peptides, they may serve as prohormones to generate biologically active peptides such as vasostatin-1 and secretolytin. These molecules derived from CGA and CGB, respectively, possess antimicrobial properties. The present study demonstrates that plasmatic levels of both vasostatin-1 and secretolytin increase during surgery in patients undergoing cardiopulmonary bypass (CPB). Vasostatin-1 and secretolytin, initially present in plasma at low levels, are released just after skin incision. Consequently, they can be added to enkelytin, an antibacterial peptide derived from proenkephalin A, for the panoply of components acting as a first protective barrier against hypothetical invasion of pathogens, which may occur during surgery. CGA and CGB, more commonly viewed as markers for endocrine and neuronal cells, were also found to have an immune origin. RNA messengers coding for CGB were amplified by reverse transcription-polymerase chain reaction in human monocytes, and immunocytochemical analysis by confocal microscopy revealed the presence of CGA or CGB or both in monocytes and neutrophils. A combination of techniques including confocal microscopic analysis, mass spectrometry measurement, and antibacterial tests allowed for the identification of the positive role of interleukin 6 (IL-6) in the secretolytin release from monocytes in vitro. Because IL-6 release is known to be strongly enhanced during CPB, we suggest a possible relationship between IL-6 and the increased level of secretolytin in patients undergoing CPB.

  9. Lack of association between the P413L variant of chromogranin B and ALS risk or age at onset: a meta-analysis.

    Science.gov (United States)

    Yang, Xinglong; Li, Shimei; Xing, Dongmei; Li, Peiyun; Li, Ci; Qi, Ling; Xu, Yanming; Ren, Hui

    2018-02-01

    Amyotrophic lateral sclerosis (ALS), the most common motor neuron disease, is thought to result from interaction of genetic and environmental risk factors. Whether the potentially functional exonic P413L variant in the chromogranin B gene influences ALS risk and age at onset is controversial. We meta-analysed or other studies assessing the association between the P413L variant and ALS risk or age at ALS onset indexed in Web of Science, PubMed, Embase, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed databases. Five case-control studies were analysed, involving 2639 patients with sporadic ALS, 201 with familial ALS and 3381 controls. No association was detected between risk of either ALS type and the CT + TT genotype or T-allele of the P413L variant. Age at ALS onset was similar between carriers and non-carriers of the T-allele. The available evidence suggests that the P413L variant of chromogranin B is not associated with ALS risk or age at ALS onset. These results should be validated in large, well-designed studies.

  10. Proinflammatory Cytokines, Enolase and S-100 as Early Biochemical Indicators of Hypoxic-Ischemic Encephalopathy Following Perinatal Asphyxia in Newborns.

    Science.gov (United States)

    Chaparro-Huerta, Verónica; Flores-Soto, Mario Eduardo; Merin Sigala, Mario Ernesto; Barrera de León, Juan Carlos; Lemus-Varela, María de Lourdes; Torres-Mendoza, Blanca Miriam de Guadalupe; Beas-Zárate, Carlos

    2017-02-01

    Estimation of the neurological prognosis of infants suffering from perinatal asphyxia and signs of hypoxic-ischemic encephalopathy is of great clinical importance; however, it remains difficult to satisfactorily assess these signs with current standard medical practices. Prognoses are typically based on data obtained from clinical examinations and neurological tests, such as electroencephalography (EEG) and neuroimaging, but their sensitivities and specificities are far from optimal, and they do not always reliably predict future neurological sequelae. In an attempt to improve prognostic estimates, neurological research envisaged various biochemical markers detectable in the umbilical cord blood of newborns (NB). Few studies examining these biochemical factors in the whole blood of newborns exist. Thus, the aim of this study was to determine the expression and concentrations of proinflammatory cytokines (TNF-α, IL-1β and IL-6) and specific CNS enzymes (S-100 and enolase) in infants with perinatal asphyxia. These data were compared between the affected infants and controls and were related to the degree of HIE to determine their utilities as biochemical markers for early diagnosis and prognosis. The levels of the proinflammatory cytokines and enzymes were measured by enzyme-linked immunosorbent assay (ELISA) and Reverse Transcription polymerase chain reaction (RT-PCR). The expression and serum levels of the proinflammatory cytokines, enolase and S-100 were significantly increased in the children with asphyxia compared with the controls. The role of cytokines after hypoxic-ischemic insult has been determined in studies of transgenic mice that support the use of these molecules as candidate biomarkers. Similarly, S-100 and enolase are considered promising candidates because these markers have been correlated with tissue damage in different experimental models. Copyright © 2016. Published by Elsevier B.V.

  11. Limbic encephalitis associated with anti-NH2-terminal of α-enolase antibodies

    Science.gov (United States)

    Kishitani, Toru; Matsunaga, Akiko; Ikawa, Masamichi; Hayashi, Kouji; Yamamura, Osamu; Hamano, Tadanori; Watanabe, Osamu; Tanaka, Keiko; Nakamoto, Yasunari; Yoneda, Makoto

    2017-01-01

    Abstract Several types of autoantibodies have been reported in autoimmune limbic encephalitis (LE), such as antibodies against the voltage-gated potassium channel (VGKC) complex including leucine-rich glioma inactivated 1 (LGI1). We recently reported a patient with autoimmune LE and serum anti-NH2-terminal of α-enolase (NAE) antibodies, a specific diagnostic marker for Hashimoto encephalopathy (HE), who was diagnosed with HE based on the presence of antithyroid antibodies and responsiveness to immunotherapy. This case suggests that LE patients with antibodies to both the thyroid and NAE could be diagnosed with HE and respond to immunotherapy. The aim of this study was to clarify the clinicoimmunological features and efficacy of immunotherapy in LE associated with anti-NAE antibodies to determine whether the LE is a clinical subtype of HE. We examined serum anti-NAE antibodies in 78 LE patients with limbic abnormality on magnetic resonance imaging and suspected HE based on positivity for antithyroid antibodies. Nineteen of the 78 patients had anti-NAE antibodies; however, 5 were excluded because they were double positive for antibodies to the VGKC complex including LGI1. No antibodies against the N-methyl-D-aspartate receptor (NMDAR), contactin-associated protein 2 (Caspr2), γ-aminobutyric acid-B receptor (GABABR), or α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) were detected in the 19 patients. Among the remaining 14 who were positive only for anti-NAE antibodies, the median age was 62.5 (20–83) years, 9 (64%) were women, and 8 (57%) showed acute onset, with less than 2 weeks between onset and admission. Consciousness disturbance (71%) and memory disturbance (64%) were frequently observed, followed by psychiatric symptoms (50%) and seizures (43%). The frequency of these symptoms significantly differed between the acute- and subacute-onset groups. Abnormalities in cerebrospinal fluid and electroencephalogram were commonly observed (92

  12. Biological Variation and Reference Change Value Data for Serum Neuron-Specific Enolase in a Turkish Population.

    Science.gov (United States)

    Matyar, Selcuk; Goruroglu Ozturk, Ozlem; Ziyanoglu Karacor, Esin; Yuzbasioglu Ariyurek, Sedefgul; Sahin, Gulhan; Kibar, Filiz; Yaman, Akgun; Inal, Tamer

    2016-11-01

    Neuron-specific enolase (NSE) is a recognized biomarker for the assessment of cerebral injury in neurological disorders. This study aims to report a definitive assessment of the biological variation (BV) components of this biomarker, including within-subject BV (CVI), between-subject BV (CVG), index of individuality (II), and reference change value (RCV), in a cohort of Turkish participants using an experimental protocol. Six blood specimens were collected from each of the 13 apparently healthy volunteers (seven women, six men; ranging in age from 23 to 36) on the same day, every 2 weeks for 2 months. Serum specimens were stored at -20°C until analysis. Neuron-specific enolase levels were evaluated in serum samples using an electrochemiluminescence (ECLIA) immunoassay kit with a Roche Cobas e 411 auto-analyser. ANOVA test was used to calculate the variations. The CVI and CVG for NSE were 21.5% and 28.8%, respectively. Analytical variation (CVA) was calculated as 10.2%. Additionally, II and RCV were calculated as 0.74 and 66% (95% confident interval, CI), respectively. As the performance index (PI) was found to be less than 2 (PI = 0.95), it is concluded that the NSE measurements have a desirable performance for analytical imprecision. Since the II was found to be less than 1 (II: 0.74), the reference values will be of little use. Thus, RCV would provide better information for deciding whether a significant change has occurred. © 2016 Wiley Periodicals, Inc.

  13. Biomarkers S100B and neuron-specific enolase predict outcome in hypothermia-treated encephalopathic newborns*.

    Science.gov (United States)

    Massaro, An N; Chang, Taeun; Baumgart, Stephen; McCarter, Robert; Nelson, Karin B; Glass, Penny

    2014-09-01

    To evaluate if serum S100B protein and neuron-specific enolase measured during therapeutic hypothermia are predictive of neurodevelopmental outcome at 15 months in children with neonatal encephalopathy. Prospective longitudinal cohort study. A level IV neonatal ICU in a freestanding children's hospital. Term newborns with moderate to severe neonatal encephalopathy referred for therapeutic hypothermia during the study period. Serum neuron-specific enolase and S100B were measured at 0, 12, 24, and 72 hours of hypothermia. Of the 83 infants enrolled, 15 (18%) died in the newborn period. Survivors were evaluated by the Bayley Scales of Infant Development-II at 15 months. Outcomes were assessed in 49 of 68 survivors (72%) at a mean age of 15.2 ± 2.7 months. Neurodevelopmental outcome was classified by Bayley Scales of Infant Development-II Mental Developmental Index and Psychomotor Developmental Index scores, reflecting cognitive and motor outcomes, respectively. Four-level outcome classifications were defined a priori: normal = Mental Developmental Index/Psychomotor Developmental Index within 1 SD (> 85), mild = Mental Developmental Index/Psychomotor Developmental Index less than 1 SD (70-85), moderate/severe = Mental Developmental Index/Psychomotor Developmental Index less than 2 SD (encephalopathy are associated with neurodevelopmental outcome at 15 months. These putative biomarkers of brain injury may help direct care during therapeutic hypothermia.

  14. Chromogranin A as a Biochemical Marker for Neuroendocrine Tumors: A Single Center Experience at Royal Hospital, Oman

    Directory of Open Access Journals (Sweden)

    Elham S. Al-Risi

    2017-09-01

    Full Text Available Objectives: To evaluate the significance of serum chromogranin A (CgA status in patients with and without different neuroendocrine tumors (NETs by conducting a retrospective assessment of the diagnostic utility and limitations of CgA as a biomarker for NETs in a tertiary care hospital in Oman. Methods: We conducted a retrospective analysis of CgA requests referred to the Clinical Biochemistry Laboratory, Royal Hospital, Oman over a 24-month period (April 2012 to March 2014. During this time, 302 CgA tests for 270 patients (119 males and 151 females; age range 11–86 years and mean±standard deviation (SD 44.0±18.0 years, were requested. Of these CgA tests, 245 tests were performed for 245 patients investigated for the diagnosis of NETs, and 57 CgA tests were performed for 25 patients with diagnosed NETs who were undergoing follow-up. Serum CgA levels were analyzed using the enzyme-linked immunosorbent assay based on a cut-off value of 22 IU/L. Results: Of the 302 CgA tests reviewed, 197 (65.2% were within the quoted normal range; however, 105 (34.8% had CgA > 22 IU/L. Of the 245 patients with first-line CgA, 38 patients (15.5% had NET that included carcinoid, pheochromocytoma, pancreatic NET, adrenal adenoma, prostatic adenocarcinoma, gastrointestinal NET, medullary thyroid carcinoma, Schwannoma, lung small cell carcinoma, parathyroid adenoma, and pituitary macroadenoma. The mean±SD of CgA in these patients with NETs was 205.0±172.0 IU/L. Meanwhile, there were 45 (18.3% patients with CgA > 22 IU/L (83.0±116.0 IU/L who did not have NETs. The conditions/diseases included: essential hypertension, chronic kidney disease, heart failure, peptic ulcer, chronic diarrhea, use of proton pump inhibitors, and other chronic diseases (hypothyroidism, asthma, diabetes mellitus. Of the 25 patients with known NET who were followed-up, there were 57 CgA results (29 with CgA ≤ 22 IU/L and 28 with CgA > 22 IU/L. The overall clinical sensitivity of CgA in the

  15. [Chromogranin A derived peptide CGA47-66 inhibits hyper-permeability of blood brain barrier in mice with sepsis].

    Science.gov (United States)

    Zeng, Yan; Zhang, Dan; Jiang, Liping; Wei, Fu; Xu, Shan

    2016-02-01

    To explore the effect of chromofungin (CHR), a chromogranin A (CGA) derived peptide CGA47-66, on hyper-permeability of blood brain barrier in septic mice. 120 healthy male C57BL/6 mice were randomly divided into groups, with 12 mice in each group. Seventy-two mice were used for dynamic observation of the contents of water and Evan blue (EB) in brain tissue after being treated with lipopolysaccharide (LPS). Another 48 mice were divided into normal saline control group (NS group), LPS induced sepsis model group (LPS group), low-dose CHR pretreatment group (CL+LPS group), and high-dose CHR pretreatment group (CH+LPS group). The septic model was reproduced by intraperitoneal injection of 10 mg/kg LPS 0.1 mL, and the mice in NS group was given equal volume of normal saline. The mice in CL+LPS group and CH+LPS group were intraperitoneally injected with 15.5 μg/kg and 77.5 μg/kg CHR 10 minutes before LPS injection. Six hours after LPS injection, 4 mL/kg of 2% EB was injected via caudal vein, the contents of water and EB in brain tissue were determined, and EB immune fluorescence in brain tissue was determined to assess the changes in permeability of blood brain barrier. Brain pathology was observed with hematoxylin and eosin (HE) staining. With the extension of time after LPS injection, the contents of water and EB in brain tissue were gradually increased, and the time of difference with statistical significance appeared earlier when compared with that of control group in the contents of water than that in EB contents (3 hours and 6 hours, respectively). The contents of water and EB in brain tissue in LPS group were significantly increased as compared with NS group [water content: (79.77±0.62)% vs. (78.28±0.44)%, P water and EB contents in brain tissue induced by LPS, and the effect was more significant in CH+LPS group [water content: (78.15±0.73)% vs. (79.77±0.62)%, EB (μg/g): 7.09±2.59 vs. 13.87±4.50, both P leakage in LPS group was more marked than that of NS

  16. Pancreatic metastasis in a case of small cell lung carcinoma: Diagnostic role of fine-needle aspiration cytology and immunocytochemistry

    Directory of Open Access Journals (Sweden)

    Dilip K Das

    2011-01-01

    Full Text Available Small cell lung carcinoma represents a group of highly malignant tumors giving rise to early and widespread metastasis at the time of diagnosis. However, the pancreas is a relatively infrequent site of metastasis by this neoplasm, and there are only occasional reports on its fine needle aspiration (FNA cytology diagnosis. A 66-year-old man presented with extensive mediastinal lymphadenopathy and a mass in the pancreatic tail. Ultrasound-guided FNA smears from the pancreatic mass contained small, round tumor cells with extensive nuclear molding. The cytodiagnosis was metastatic small cell carcinoma. Immunocytochemical staining showed that a variable number of neoplastic cell were positive for cytokeratin, chromogranin A, neurone-specific enolase and synaptophysin but negative for leukocyte common antigen. The trans-bronchial needle aspiration was non-diagnostic, but biopsy was suspicious of a small cell carcinoma. This case represents a rare metastatic lesion in the pancreas from small cell lung carcinoma, diagnosed by FNA cytology.

  17. Neuroendocrine carcinoma of the mammary gland in a dog.

    Science.gov (United States)

    Nakahira, R; Michishita, M; Yoshimura, H; Hatakeyama, H; Takahashi, K

    2015-01-01

    A 10-year-old female border collie was presented with a mass (2 cm diameter) in the fifth mammary gland. The mass was located in the subcutis and the cut surface was grey-white in colour. Microscopically, the mass was composed of tumour cells arranged in nests of various sizes separated by delicate fibrovascular stroma. The tumour cells had small, round hypochromatic nuclei and abundant cytoplasm. Metastases were observed in the inguinal lymph node. Immunohistochemically, most tumour cells expressed cytokeratin (CK) 20, chromogranin A, neuron-specific enolase, synaptophysin and oestrogen receptor-β, but not low molecular weight CK (CAM5.2), p63 and insulin. Ultrastructurally, the tumour cells contained a large number of electron-dense granules corresponding to neuroendocrine granules. Based on these findings, this case was diagnosed as a neuroendocrine carcinoma of the mammary gland. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Early detection of response in small cell bronchogenic carcinoma by changes in serum concentrations of creatine kinase, neuron specific enolase, calcitonin, ACTH, serotonin and gastrin releasing peptide

    DEFF Research Database (Denmark)

    Bork, E; Hansen, M; Urdal, P

    1988-01-01

    Creatine kinase (CK-BB), neuron specific enolase (NSE), ACTH, calcitonin, serotonin and gastrin releasing peptide (GRP) were measured in serum or plasma before and immediately after initiation of treatment in patients with small cell lung cancer (SCC). Pretherapeutic elevated concentrations of CK...

  19. Korelasi Peningkatan Kadar Neuron Spesific Enolase dengan Derajat Keparahan dan Luaran Fungsional Pasien Stroke Infark Aterotrombotik Akut

    Directory of Open Access Journals (Sweden)

    Neti Sri Wardiyani

    2010-06-01

    Full Text Available Neuronal damage and decreasing aerobic glicolysis process in ischaemic stroke are caused by lowering level of blood glucose. The amount of neuronal intrasitoplasmic glicolytic enolase enzyme, also known as neuron specific enolase, increases in blood circulation because it is not used anymore in damage neuron. So the mechanism failure in blood-brain barrier, as result of neuronal and cell membrane damage, causes NSE diffusion to extracellular and cerebrospinal fluid, then NSE level increases in blood serum and cerebrospinal fluid in acute cerebral infarction. Elevating NSE level is also connected with infarct volume and the extent of brain damage. The aim of this study was to evaluate connection between upgrading NSE serum level in acute atherothrombotic-stroke infarction patients, level of stroke incompatibility, and functional outcome. The method of study was observational analytic with kohort study. Subjects of study were divided into case group consisted of acute atherothrombotic-stroke infarction patients and control group consisted the healthy person. The data was collected in Hasan Sadikin Hospital between February to August 2008. Evaluating patients was performed to get descriptions on NSE serum level, level stroke incompability measuring by NIHSS scoring at the first time entering the hospital, and Barthel index scoring at seventh day of treatment. This study was analyzed by bivariat analysis using Mann Whitney statistic test and Pearson correlation test. There were 43 patients in each group. There was a significantly difference in NSE serum level on case group (mean was 11.41 [5.07] ng/mL in comparison to those on control group (mean was 8.93 [3.03] ng/mL, p=0.019 . There was a significantly correlation between raising NSE serum level on case group and level of stroke incompatibility measuring by NIHSS scoring and also with functional outcome according to Barthel index scoring. The highest accuration value of NSE serum level was 12 ng

  20. The Cloning and Characterization of the Enolase2 Gene of Gekko japonicus and Its Polyclonal Antibody Preparation

    Directory of Open Access Journals (Sweden)

    Mei Liu

    2013-04-01

    Full Text Available The enolase2 gene is usually expressed in mature neurons and also named neuron specific enolase (NSE. In the present study, we first obtained the NSE gene cDNA sequence by using the RACE method based on the expressed sequence tag (EST fragment from the cDNA library of Gekko japonicus and identified one transcript of about 2.2 kb in central nervous system of Gekko japonicus by Northern blotting. The open reading frame of NSE is 1305 bp, which encodes a 435 amino-acid protein. We further investigated the multi-tissue expression pattern of NSE by RT-PCR and found that the expression of NSE mRNA was very high in brain, spinal cord and low in heart, while it was not detectable in other tissues. The real-time quantitative PCR was used to investigate the time-dependent change in the expression of the NSE mRNA level after gecko spinal cord transection and found it significantly increased at one day, reaching its highest level three days post-injury and then decreasing at the seventh day of the experiment. The recombinant plasmid of pET-32a-NSE was constructed and induced to express His fused NSE protein. The purified NSE protein was used to immunize rabbits to generate polyclonal antisera. The titer of the antiserum was more than 1:65536 determined by ELISA. Western blotting showed that the prepared antibody could specifically recognize the recombinant and endogenous NSE protein. The result of immunohistochemistry revealed that positive signals were present in neurons of the brain and the spinal cord. This study provided the tools of cDNA and polyclonal antibody for studying NSE function in Gekko japonicus.

  1. A T4SS Effector Targets Host Cell Alpha-Enolase Contributing to Brucella abortus Intracellular Lifestyle.

    Science.gov (United States)

    Marchesini, María I; Morrone Seijo, Susana M; Guaimas, Francisco F; Comerci, Diego J

    2016-01-01

    Brucella abortus , the causative agent of bovine brucellosis, invades and replicates within cells inside a membrane-bound compartment known as the Brucella containing vacuole (BCV). After trafficking along the endocytic and secretory pathways, BCVs mature into endoplasmic reticulum-derived compartments permissive for bacterial replication. Brucella Type IV Secretion System (VirB) is a major virulence factor essential for the biogenesis of the replicative organelle. Upon infection, Brucella uses the VirB system to translocate effector proteins from the BCV into the host cell cytoplasm. Although the functions of many translocated proteins remain unknown, some of them have been demonstrated to modulate host cell signaling pathways to favor intracellular survival and replication. BPE123 (BAB2_0123) is a B. abortus VirB-translocated effector protein recently identified by our group whose function is yet unknown. In an attempt to identify host cell proteins interacting with BPE123, a pull-down assay was performed and human alpha-enolase (ENO-1) was identified by LC/MS-MS as a potential interaction partner of BPE123. These results were confirmed by immunoprecipitation assays. In bone-marrow derived macrophages infected with B. abortus , ENO-1 associates to BCVs in a BPE123-dependent manner, indicating that interaction with translocated BPE123 is also occurring during the intracellular phase of the bacterium. Furthermore, ENO-1 depletion by siRNA impaired B. abortus intracellular replication in HeLa cells, confirming a role for α-enolase during the infection process. Indeed, ENO-1 activity levels were enhanced upon B. abortus infection of THP-1 macrophagic cells, and this activation is highly dependent on BPE123. Taken together, these results suggest that interaction between BPE123 and host cell ENO-1 contributes to the intracellular lifestyle of B. abortus .

  2. APP with Kunitz type protease inhibitor domain (KPI) correlates with neuritic plaque density but not with cortical synaptophysin immunoreactivity in Alzheimer's disease and non-demented aged subjects: a multifactorial analysis.

    Science.gov (United States)

    Zhan, S S; Sandbrink, R; Beyreuther, K; Schmitt, H P

    1995-01-01

    The formation of beta A4 amyloid protein in neuritic plaques in Alzheimer's disease (AD) and advanced age is a complex process that involves a number of both cellular and molecular mechanisms, the interrelations of which are not yet completely understood. We have examined quantitatively, in AD and aged controls an extended spectrum of amyloid plaque-related cellular and molecular factors and the cortical synaptophysin immunoreactivity (synaptic density) in order to check for interrelations between them by multifactorial analysis. In 3 cases of senile dementia of the Alzheimer type (SDAT) aged 72, 80 and 82 years, and 9 controls aged 43-88 (mean age 65) years, the cortical synaptophysin immunoreactivity was assessed, together with the numbers of neurons, astrocytes and microglial cells, senile plaques, of tangle-bearing neurons, and the amount of beta A4 amyloid precursor protein (APP) with and without the Kunitz type serine protease inhibitor (KPI) domain. The main results were: APP including the KPI domain (KPI-APP) correlated with the number of neuritic plaques, regardless of whether they occurred in SDAT or non-demented controls. There was no significant difference in the amount of KPI-APP between SDAT and controls. Conversely, APP695 (without KPI) was significantly reduced in SDAT. KPI-APP did not correlate with the synaptophysin immunoreactivity (RGVA), while APP695 showed a significant correlation with the latter in all evaluations. It also correlated with the neuron counts, which was not true for KPI-APP. These results support previous findings indicating that KPI-APP is an important local factor for amyloid deposition in the neuritic plaques, both in AD and in non-demented aged people. On the contrary, KPI-APP does not seem to be significantly involved in the mechanisms of synaptic change outside of the plaques.

  3. Identification of enolases and aldolases as important fish allergens in cod, salmon and tuna: component resolved diagnosis using parvalbumin and the new allergens.

    Science.gov (United States)

    Kuehn, A; Hilger, C; Lehners-Weber, C; Codreanu-Morel, F; Morisset, M; Metz-Favre, C; Pauli, G; de Blay, F; Revets, D; Muller, C P; Vogel, L; Vieths, S; Hentges, F

    2013-07-01

    The majority of fish-allergic patients are sensitized to parvalbumin, known to be the cause of important IgE cross-reactivity among fish species. Little is known about the importance of fish allergens other than parvalbumin. The aim of this study was to characterize hitherto undefined fish allergens in three commonly consumed fish species, cod, salmon and tuna, and to evaluate their importance for in vitro IgE-diagnosis in addition to parvalbumin and fish gelatin. Sixty-two patients were diagnosed by clinical history, skin prick tests and specific IgE to fish extracts. Two new fish allergens from cod, salmon and tuna were identified by microsequencing. These proteins were characterized by immunoblot, ELISA and mediator release assay. Purified parvalbumin, enolase, aldolase and fish gelatin were used for quantification of specific IgE in ELISA. Parvalbumin and two other allergens of 50 and 40 kDa were detected in IgE-immunoblots of cod, salmon and tuna extracts by most patient sera. The 50 and 40 kDa proteins were identified as beta-enolase and fructose-bisphosphate aldolase A respectively. Both purified enzymes showed allergenic activity in the mediator release assay. Indeed, 72.6% of the patients were sensitized to parvalbumin, 20% of these had specific IgE to salmon parvalbumin only. IgE to enolases were found in 62.9% (0.5-95.0 kUA /L), to aldolases in 50.0% (0.4-26.0 kUA /L) and to fish gelatin in 19.3% (0.4-20.0 kUA /L) of the patients. Inter-species cross-reactivity, even though limited, was found for enolases and aldolases by IgE-inhibition ELISA. Fish enolase and aldolase have been identified as important new fish allergens. In fish allergy diagnosis, IgE to enolase and aldolase are especially relevant when IgE to parvalbumin are absent. © 2013 John Wiley & Sons Ltd.

  4. The Energetics of Streptococcal Enolase Octamer Formation: The Quantitative Contributions of the Last Eight Amino Acids at the Carboxy-Terminus.

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    Jack A Kornblatt

    Full Text Available The enolase produced by Streptococcus pyogenes is a homo-octamer whose overall shape resembles that of a donut. The octamer is best described as a tetramer of dimers. As such, it contains two types of interfaces. The first is common to almost all enolases as most enolases that have been studied are dimers. The second is unique to the octamers and includes residues near the carboxy-terminus. The primary sequence of the enolase contains 435 residues with an added 19 as an N-terminal hexahistine tag. We have systematically truncated the carboxy-terminus, individually removing the first 8 residues. This gave rise to a series of eight structures containing respectively, 435, 434, 433, 432, 431, 430, 429 and 427 residues. The truncations cause the protein to gradually dissociate from octamers to enzymatically inactive monomers with very small amounts of intermediate tetramers and dimers. We have evaluated the contributions of the missing residues to the monomer/octamer equilibrium using a combination of analytical ultracentrifugation and activity assays. For the dissociation reaction, octamer 8 monomer truncation of all eight C-terminal residues resulted in a diminution in the standard Gibbs energy of dissociation of about 59 kJ/mole of octamer relative to the full length protein. Considering that this change is spread over eight subunits, this translates to a change in standard Gibbs interaction energy of less than 8 kJ/mole of monomer distributed over the eight monomers. The resulting proteins, containing 434, 433, 432, 431, 430, 429 and 427 residues per monomer, showed intermediate free energies of dissociation. Finally, three other mutations were introduced into our reference protein to establish how they influenced the equilibrium. The main importance of this work is it shows that for homo-multimeric proteins a small change in the standard Gibbs interaction energy between subunits can have major physiological effects.

  5. Serum Neuron-Specific Enolase, Biogenic Amino-Acids and Neurobehavioral Function in Lead-Exposed Workers from Lead-Acid Battery Manufacturing Process

    OpenAIRE

    K Ravibabu; T Barman; HR Rajmohan

    2015-01-01

    Background: The interaction between serum neuron-specific enolase (NSE), biogenic amino-acids and neurobehavioral function with blood lead levels in workers exposed to lead form lead-acid battery manufacturing process was not studied. Objective: To evaluate serum NSE and biogenic amino-acids (dopamine and serotonin) levels, and neurobehavioral performance among workers exposed to lead from lead-acid storage battery plant, and its relation with blood lead levels (BLLs). Methods: In a c...

  6. Baseline plasma chromogranin A levels in patients with well-differentiated neuroendocrine tumors of the pancreas: A potential predictor of postoperative recurrence.

    Science.gov (United States)

    Nanno, Yoshihide; Toyama, Hirochika; Matsumoto, Ippei; Otani, Kyoko; Asari, Sadaki; Goto, Tadahiro; Ajiki, Tetsuo; Zen, Yoh; Fukumoto, Takumi; Ku, Yonson

    The present study aimed to elucidate prognostic values of baseline plasma chromogranin A (CgA) concentrations in patients with resectable, well-differentiated pancreatic neuroendocrine tumors (PNETs). Preoperative CgA levels in 21 patients with PNET were correlated with clinicopathological factors and patients' survival. Plasma CgA levels ranged 2.9-30.8 pmol/mL (median 6.0), and were significantly elevated in patients with post-operative recurrence (P = 0.004). Using the receiver operating characteristic curve, the optimal cutoff value to predict tumor recurrence was determined as 17.0 pmol/mL. This threshold identified patients with recurrence with 60% sensitivity, 100% specificity, and 90% overall accuracy. Patients with higher CgA levels showed worse recurrence-free survival than those with low CgA levels, both in total (P < 0.001) and in G2 patients (P = 0.020). Combined plasma CgA concentrations and WHO grading may assist in better stratification of PNET patients in terms of the risk of recurrence. Copyright © 2016. Published by Elsevier B.V.

  7. Salivary chromogranin A levels correlate with disease severity but do not reflect anxiety or personality of adult patients with atopic dermatitis.

    Science.gov (United States)

    Kaneko, Sakae; Liu, Lijuan; Kakamu, Takeyasu; Minami-Hori, Masako; Morita, Eishin

    2017-08-01

    Stress-induced scratching is an issue in patients with adult atopic dermatitis (AD). Although itching and stress are believed to be intimately related, no objective index is available; therefore, most evaluations are subjective. Using saliva, which is easily collected, we investigated the degree to which AD severity and patient stress levels are reflected in stress proteins in the saliva. Here, we evaluated the severity (Scoring Atopic Dermatitis [SCORAD] score), stress (State-Trait Anxiety Index [STAI] score), personality (Tokyo University Egogram [TEG] II score) and quality of life (Dermatology Life Quality Index [DLQI] score) of 51 patients with AD who were examined in the Department of Dermatology of Shimane University between April and December 2015. We collected saliva and measured salivary chromogranin A (CgA), amylase and cortisol. The amount of salivary CgA per protein in patients with AD was correlated with their SCORAD score (r = 0.458, P < 0.001). There was no correlation between cortisol or amylase levels and SCORAD score. SCORAD score was correlated with DLQI (r = 0.390, P = 0.006). CgA per protein was correlated with DLQI (r = 0.393, P = 0.004). There was no correlation between scores for the anxiety component of the STAI, TEG II or DLQI. Our results suggested that patients with more severe AD may have high stress levels. The personalities of these patients with AD tended to involve elevated anxiety levels. © 2017 Japanese Dermatological Association.

  8. Computation-Facilitated Assignment of Function in the Enolase Superfamily: A Regiochemically Distinct Galactarate Dehydratase from Oceanobacillus iheyensis†

    Science.gov (United States)

    Rakus, John F.; Kalyanaraman, Chakrapani; Fedorov, Alexander A.; Fedorov, Elena V.; Mills-Groninger, Fiona P.; Toro, Rafael; Bonanno, Jeffrey; Bain, Kevin; Sauder, J. Michael; Burley, Stephen K.; Almo, Steven C.; Jacobson, Matthew P.; Gerlt, John A.

    2009-01-01

    The structure of an uncharacterized member of the enolase superfamily from Oceanobacillus iheyensis (GI: 23100298; IMG locus tag Ob2843; PDB Code 2OQY) was determined by the New York SGX Research Center for Structural Genomics (NYSGXRC). The structure contained two Mg2+ ions located 10.4 Å from one another, with one located in the canonical position in the (β/α)7β-barrel domain (although the ligand at the end of the fifth β-strand is His, unprecedented in structurally characterized members of the superfamily); the second is located in a novel site within the capping domain. In silico docking of a library of mono- and diacid sugars to the active site predicted a diacid sugar as a likely substrate. Activity screening of a physical library of acid sugars identified galactarate as the substrate (kcat = 6.8 s−1, KM = 620 μM; kcat/KM = 1.1 × 104 M−1 s−1), allowing functional assignment of Ob2843 as galactarate dehydratase (GalrD-II) The structure of a complex of the catalytically impaired Y90F mutant with Mg2+ and galactarate allowed identification of a Tyr 164-Arg 162 dyad as the base that initiates the reaction by abstraction of the α-proton and Tyr 90 as the acid that facilitates departure of the β-OH leaving group. The enzyme product is 2-keto-3-deoxy-D-threo-4,5-dihydroxyadipate, the enantiomer of the product obtained in the GalrD reaction catalyzed by a previously characterized bifunctional L-talarate/galactarate dehydratase (TalrD/GalrD). On the basis of the different active site structures and different regiochemistries, we recognize that these functions represent an example of apparent, not actual, convergent evolution of function. The structure of GalrD-II and its active site architecture allow identification of the seventh functionally and structurally characterized subgroup in the enolase superfamily. This study provides an additional example that an integrated sequence/structure-based strategy employing computational approaches is a viable

  9. Label-free electrochemical immunoassay for neuron specific enolase based on 3D macroporous reduced graphene oxide/polyaniline film.

    Science.gov (United States)

    Zhang, Qi; Li, Xiaoyan; Qian, Chunhua; Dou, Li; Cui, Feng; Chen, Xiaojun

    2018-01-01

    The content of neuron specific enolase (NSE) in serum is considered to be an essential indicator of small cell lung cancer (SCLC). Here, a novel label-free electrochemical immunoassay for the detection of NSE based on the three dimensionally macroporous reduced graphene oxide/polyaniline (3DM rGO/PANI) film has been proposed. The 3DM rGO/PANI film was constructed by electrochemical co-deposition of GO and aniline into the interspaces of a sacrificial silica opal template modified Au slice. During the co-deposition, GO was successfully reduced by aniline and PANI could be deposited on the surfaces of rGO sheets. The ratio of rGO and PANI in the composite was also optimized to achieve the maximum electrochemical performance. The 3DM rGO/PANI composite provided larger specific surface area for the antibody immobilization, exhibited enhanced conductivity for electron transfer, and more important was that PANI acted as the electroactive probe for indicating the NSE concentration. Under the optimal conditions, a linear current response of PANI to NSE concentration was obtained over 0.5 pg mL -1 -10.0 ng mL -1 with a detection limit of 0.1 pg mL -1 . Moreover, the immunosensor showed excellent selectivity, good stability, satisfactory reproducibility and regeneration, and was employed to detect NSE in clinical serum specimens. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Influence of intracerebral exposure to enriched uranium on neutron specific enolase and interleukin-1 β content in neonatal rats

    International Nuclear Information System (INIS)

    Gu Guixiong; Zhu Shoupeng; Wang Liuyi; Yang Shuqin; Zhu Lingli

    2001-01-01

    Objective: To examine biochemically the injurious effects of enriched uranium 235 U on developing brain of neonatal rats. Methods: Neonatal rats were irradiated with single injection of 2 μl enriched uranium into the left lateral ventricle of the brain at postnatal day 1 ( 235 U, respectively. The micro-autoradiographic tracing was performed, somatic growth and neuro-behavior development of neonatal rats were examined by determination of multiple parameters, and the neuron specific enolase (NSE) and interleukin-1 β(IL-1 β) levels in brains were determined with radioimmunoassay. Results: The radionuclides were mainly accumulated in the neuronal nucleus, and autoradiographic tracks appeared in the cytoplasm and inter- cellular space. Neonatal rats showed delayed growth and abnormal neuro-behavior. The changes of NSE, IL-1 β in cerebellum, cerebral cortex, hippocampus, diencephalons showed a dose-dependent relationship that when the dose of irradiation was increased, the levels of NSE was decreased and the IL-1 β was increased. Conclusion: The nerve cell of developing brain of neonatal rats is sensitive, fragile and compensable to injurious effects of α-irradiation from enriched uranium

  11. Serial measurement of neuron specific enolase improves prognostication in cardiac arrest patients treated with hypothermia: A prospective study

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    Storm Christian

    2012-01-01

    Full Text Available Abstract Background Neuron specific enolase (NSE has repeatedly been evaluated for neurological prognostication in patients after cardiac arrest. However, it is unclear whether current guidelines for NSE cutoff levels also apply to cardiac arrest patients treated with hypothermia. Thus, we investigated the prognostic significance of absolute NSE levels and NSE kinetics in cardiac arrest patients treated with hypothermia. Methods In a prospective study of 35 patients resuscitated from cardiac arrest, NSE was measured daily for four days following admission. Outcome was assessed at ICU discharge using the CPC score. All patients received hypothermia treatment for 24 hours at 33°C with a surface cooling device according to current guidelines. Results The cutoff for absolute NSE levels in patients with unfavourable outcome (CPC 3-5 72 hours after cardiac arrest was 57 μg/l with an area under the curve (AUC of 0.82 (sensitivity 47%, specificity 100%. The cutoff level for NSE kinetics in patients with unfavourable outcome (CPC 3-5 was an absolute increase of 7.9 μg/l (AUC 0.78, sensitivity 63%, specificity 100% and a relative increase of 33.1% (AUC 0.803, sensitivity 67%, specificity 100% at 48 hours compared to admission. Conclusion In cardiac arrest patients treated with hypothermia, prognostication of unfavourable outcome by NSE kinetics between admission and 48 hours after resuscitation may be superior to prognostication by absolute NSE levels.

  12. Inflammation-induced reversible switch of the neuron-specific enolase promoter from Purkinje neurons to Bergmann glia.

    Science.gov (United States)

    Sawada, Yusuke; Konno, Ayumu; Nagaoka, Jun; Hirai, Hirokazu

    2016-06-13

    Neuron-specific enolase (NSE) is a glycolytic isoenzyme found in mature neurons and cells of neuronal origin. Injecting adeno-associated virus serotype 9 (AAV9) vectors carrying the NSE promoter into the cerebellar cortex is likely to cause the specific transduction of neuronal cells, such as Purkinje cells (PCs) and interneurons, but not Bergmann glia (BG). However, we found BG-predominant transduction without PC transduction along a traumatic needle tract for viral injection. The enhancement of neuroinflammation by the co-application of lipopolysaccharide (LPS) with AAV9 significantly expanded the BG-predominant area concurrently with the potentiated microglial activation. The BG-predominant transduction was gradually replaced by the PC-predominant transduction as the neuroinflammation dissipated. Experiments using glioma cell cultures revealed significant activation of the NSE promoter due to glucose deprivation, suggesting that intracellularly stored glycogen is metabolized through the glycolytic pathway for energy. Activation of the glycolytic enzyme promoter in BG concurrently with inactivation in PC may have pathophysiological significance for the production of lactate in activated BG and the utilization of lactate, which is provided by the BG-PC lactate shuttle, as a primary energy resource in injured PCs.

  13. Long-term effects of enriched environment following neonatal hypoxia-ischemia on behavior, BDNF and synaptophysin levels in rat hippocampus: Effect of combined treatment with G-CSF.

    Science.gov (United States)

    Griva, Myrsini; Lagoudaki, Rosa; Touloumi, Olga; Nousiopoulou, Evangelia; Karalis, Filippos; Georgiou, Thomas; Kokaraki, Georgia; Simeonidou, Constantina; Tata, Despina A; Spandou, Evangelia

    2017-07-15

    Increasing evidence shows that exposure to an enriched environment (EE) is neuroprotective in adult and neonatal animal models of brain ischemia. However, the mechanisms underlying this effect remain unclear. The aim of the current study was to investigate whether post-weaning EE would be effective in preventing functional deficits and brain damage by affecting markers of synaptic plasticity in a neonatal rat model of hypoxia-ischemia (HI). We also examined the possibility that granulocyte-colony stimulating factor (G-CSF), a growth factor with known neuroprotective effects in a variety of experimental brain injury models, combined with EE stimulation could enhance the potential beneficial effect of EE. Seven-day-old Wistar rats of either sex were subjected to permanent ligation of the left common carotid artery followed by 60min of hypoxia (8% O 2 ) and immediately after weaning (postnatal day 21) were housed in enriched conditions for 4weeks. A group of enriched-housed rats had been treated with G-CSF immediately after HI for 5 consecutive days (50μg/kg/day). Behavioral examination took place approximately at three months of age and included assessments of learning and memory (Morris water maze) as well as motor coordination (Rota-Rod). Infarct size and hippocampal area were estimated following behavioral assessment. Synaptic plasticity was evaluated based on BDNF and synaptophysin expression in the dorsal hippocampus. EE resulted in recovery of post-HI motor deficits and partial improvement of memory impairments which was not accompanied by reduced brain damage. Increased synaptophysin expression was observed in the contralateral to carotid ligation hemisphere. Hypoxia-ischemia alone or followed by enriched conditions did not affect BDNF expression which was increased only in enriched-housed normal rats. The combined therapy of G-CSF and EE further enhanced cognitive function compared to EE provided as monotherapy and prevented HI-induced brain damage by

  14. Concordance between results of somatostatin receptor scintigraphy with 111In-DOTA-DPhe1-Tyr3-octreotide and chromogranin A assay in patients with neuroendocrine tumours

    International Nuclear Information System (INIS)

    Rodrigues, Margarida; Gabriel, Michael; Heute, Dirk; Putzer, Daniel; Virgolini, Irene; Griesmacher, Andrea

    2008-01-01

    Somatostatin receptor scintigraphy (SRS) and chromogranin A (CgA) assay have successfully been implemented in the clinical work-up and management of neuroendocrine tumour (NET) patients. However, there is still a lack of studies comparing results in these patients. Our aim was to compare directly in NET patients SRS and CgA assay results with special regard to tumour features such as grade of malignancy, primary origin, disease extent and function. One hundred twenty consecutive patients with histological confirmed NETs were investigated with 111 In-DOTA-DPhe 1 -Tyr 3 -octreotide ( 111 In-DOTA-TOC) SRS and CgA immunoradiometric assay. Tumours were classified by cell characteristics [well-differentiated NETs, well-differentiated neuroendocrine carcinomas, poorly differentiated neuroendocrine carcinomas (PDNECs)], primary origin (foregut, midgut, hindgut, undetermined), disease extent (limited disease, metastases, primary tumour and metastases) and functionality (secretory, nonsecretory). SRS was positive in 107 (89%) patients; CgA levels were increased in 95 (79%) patients. Overall, concordance between SRS and CgA results was found in 84 patients. Positive SRS but normal CgA level were found in 24 patients, with higher prevalence (p 111 In-DOTA-TOC SRS proved to be more sensitive than CgA in NETs patients. Tumour differentiation, disease extent and presence of liver metastases impact both SRS and CgA results, whereas nonsecretory activity is a negative predictor of only CgA increase. PDNECs and hindgut origin of tumours predispose to discrepancies with negative SRS but increased CgA levels. (orig.)

  15. Concordance between results of somatostatin receptor scintigraphy with 111In-DOTA-DPhe 1-Tyr 3-octreotide and chromogranin A assay in patients with neuroendocrine tumours.

    Science.gov (United States)

    Rodrigues, Margarida; Gabriel, Michael; Heute, Dirk; Putzer, Daniel; Griesmacher, Andrea; Virgolini, Irene

    2008-10-01

    Somatostatin receptor scintigraphy (SRS) and chromogranin A (CgA) assay have successfully been implemented in the clinical work-up and management of neuroendocrine tumour (NET) patients. However, there is still a lack of studies comparing results in these patients. Our aim was to compare directly in NET patients SRS and CgA assay results with special regard to tumour features such as grade of malignancy, primary origin, disease extent and function. One hundred twenty consecutive patients with histological confirmed NETs were investigated with (111)In-DOTA-DPhe(1)-Tyr(3)-octreotide ((111)In-DOTA-TOC) SRS and CgA immunoradiometric assay. Tumours were classified by cell characteristics [well-differentiated NETs, well-differentiated neuroendocrine carcinomas, poorly differentiated neuroendocrine carcinomas (PDNECs)], primary origin (foregut, midgut, hindgut, undetermined), disease extent (limited disease, metastases, primary tumour and metastases) and functionality (secretory, nonsecretory). SRS was positive in 107 (89%) patients; CgA levels were increased in 95 (79%) patients. Overall, concordance between SRS and CgA results was found in 84 patients. Positive SRS but normal CgA level were found in 24 patients, with higher prevalence (p<0.05) in patients with nonsecretory tumours. Conversely, negative SRS but CgA level increased were seen in 12 patients, with higher proportion (p<0.05) in patients with PDNECs and tumours of hindgut origin. Overall, (111)In-DOTA-TOC SRS proved to be more sensitive than CgA in NETs patients. Tumour differentiation, disease extent and presence of liver metastases impact both SRS and CgA results, whereas nonsecretory activity is a negative predictor of only CgA increase. PDNECs and hindgut origin of tumours predispose to discrepancies with negative SRS but increased CgA levels.

  16. Seahorse-derived peptide suppresses invasive migration of HT1080 fibrosarcoma cells by competing with intracellular α-enolase for plasminogen binding and inhibiting uPA-mediated activation of plasminogen.

    Science.gov (United States)

    Kim, Yong-Tae; Kim, Se-kwon; Jeon, You-Jin; Park, Sun Joo

    2014-12-01

    α-Enolase is a glycolytic enzyme and a surface receptor for plasminogen. α-Enolase-bound plasminogen promotes tumor cell invasion and cancer metastasis by activating plasmin and consequently degrading the extracellular matrix degradation. Therefore, α-enolase and plasminogen are novel targets for cancer therapy. We found that the amino acid sequence of a peptide purified from enzymatic hydrolysates of seahorse has striking similarities to that of α-enolase. In this study, we report that this peptide competes with cellular α-enolase for plasminogen binding and suppresses urokinase plasminogen activator (uPA)-mediated activation of plasminogen, which results in decreased invasive migration of HT1080 fibrosarcoma cells. In addition, the peptide treatment decreased the expression levels of uPA compared to that of untreated controls. These results provide new insight into the mechanism by which the seahorse-derived peptide suppresses invasive properties of human cancer cells. Our findings suggest that this peptide could emerge as a potential therapeutic agent for cancer.

  17. Plasma autoantibodies against heat shock protein 70, enolase 1 and ribonuclease/angiogenin inhibitor 1 as potential biomarkers for cholangiocarcinoma.

    Directory of Open Access Journals (Sweden)

    Rucksak Rucksaken

    Full Text Available The diagnosis of cholangiocarcinoma (CCA is often challenging, leading to poor prognosis. CCA arises via chronic inflammation which may be associated with autoantibodies production. This study aims to identify IgG antibodies directed at self-proteins and tumor-associated antigens. Proteins derived from immortalized cholangiocyte cell line (MMNK1 and CCA cell lines (M055, M214 and M139 were separated using 2-dimensional electrophoresis and incubated with pooled plasma of patients with CCA and non-neoplastic controls by immunoblotting. Twenty five immunoreactive spots against all cell lines-derived proteins were observed on stained gels and studied by LC-MS/MS. Among these, heat shock protein 70 (HSP70, enolase 1 (ENO1 and ribonuclease/angiogenin inhibitor 1 (RNH1 obtained the highest matching scores and were thus selected for further validation. Western blot revealed immunoreactivity against HSP70 and RNH1 in the majority of CCA cases and weakly in healthy individuals. Further, ELISA showed that plasma HSP70 autoantibody level in CCA was significantly capable to discriminate CCA from healthy individuals with an area under the receiver operating characteristic curve of 0.9158 (cut-off 0.2630, 93.55% sensitivity and 73.91% specificity. Plasma levels of IgG autoantibodies against HSP70 were correlated with progression from healthy individuals to cholangitis to CCA (r = 0.679, P<0.001. In addition, circulating ENO1 and RNH1 autoantibodies levels were also significantly higher in cholangitis and CCA compared to healthy controls (P<0.05. Moreover, the combinations of HSP70, ENO1 or RNH1 autoantibodies positivity rates improved specificity to over 78%. In conclusion, plasma IgG autoantibodies against HSP70, ENO1 and RNH1 may represent new diagnostic markers for CCA.

  18. Immune response induced by oral delivery of Bacillus subtilis spores expressing enolase of Clonorchis sinensis in grass carps (Ctenopharyngodon idellus).

    Science.gov (United States)

    Jiang, Hongye; Chen, Tingjin; Sun, Hengchang; Tang, Zeli; Yu, Jinyun; Lin, Zhipeng; Ren, Pengli; Zhou, Xinyi; Huang, Yan; Li, Xuerong; Yu, Xinbing

    2017-01-01

    Clonorchiasis, caused by the consumption of raw or undercooked freshwater fish containing infective metacercariae of Clonorchis sinensisis (C.sinensis), remains a common public health problem. New effective prevention strategies are still urgent to control this food-borne infectious disease. The previous studies suggested Bacillus subtilis (B. subtilis) spores was an ideal vaccines delivery system, and the C.sinensis enolase (CsENO) was a potential vaccine candidate against clonorchiasis. In the current study, we detected CsENO-specific IgM levels by ELISA in sera, intestinal mucus and skin mucus in grass carps (Ctenopharyngodon idella) through oral administration with B. subtilis spores surface expressing CsENO. In addition, immune-related genes expression was also measured by qRT-PCR. Grass carps orally treated with B. subtilis spores or normal forages were used as controls. The results of ELISA manifested that specific IgM levels of grass carps in CsENO group in sera, intestine mucus and skin mucus almost significantly increased from week 4 post the first oral administration when compared to the two control groups. The levels of specific IgM reached its peak in intestine mucus firstly, then in sera, and last in skin mucus. qRT-PCR results showed that 5 immune-related genes expression had different degree of rising trend in CsENO group when compared to the two control groups. Our study demonstrated that orally administrated with B. subtilis spores expressing CsENO induced innate and adaptive immunity, systemic and local mucosal immunity, and humoral and cellular immunity. Our work may pave the way to clarify the exact mechanisms of protective efficacy elicited by B. subtilis spores expressing CsENO and provide new ideas for vaccine development against C. sinensis infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Serological response and diagnostic value of recombinant candida cell wall protein enolase, phosphoglycerate kinase and β- glucosidase

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    Zhengxin eHe

    2015-09-01

    Full Text Available There are no specific signs and symtoms for invasive candidiasis (IC, which makes its diagnosis a challenge. Efforts have been made for decades to establish serological assays for rapid diagnosis of invasive candidiasis, but none of them have found widespread clinical use. Using a systemic candiasis murine model, serological response to recombinant proteins of enolase (rEno1, phosphoglycerate kinase (rPgk1 and β-glucosidase (rBgl2 were evaluated and rEno1 was found to possess the strongest immunoreactivity, followed by rPgk1 and rBgl2. Likewise, IgG antibody titers to rEno1, rPgk1 and rBgl2 in the positive sera of proven IC patients were determined by ELISA. Results show anti-rEno1 antibody possesses the highest titer, followed by rPgk1 and rBgl2. Antibodies against rEno1, rPgk1 and rBgl2 were detected by ELISA tests in a group of 52 proven IC patients or 50 healthy subjects, The sensitivity, specificity, positive and negative predictive values were 88.5%, 90.0%, 90.2%, and 88.2% for anti-rEno1 detection, 86.5%, 92.0%, 91.8% and 86.8% for anti-rPgk1 detection, and 80.8%, 90.0%, 89.4% and 81.8% for anti-rBgl2 detection, respectively. The data clearly demonstrate that the recombinant proteins of Eno1, Pgk1 and Bgl2 are promising candidates for IC serodiagnosis. There’s great possibility that the recombinant Eno1 will be more applicable in serodiagnosis and vaccine research on account of its strong serological response.

  20. Research of the serum level of neuron-specific enolase in children with various types of seizure

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    WANG Chun

    2012-10-01

    Full Text Available Objective To explore the relevance between the level changes of serum neuron-specific enolase (NSE and neuronal damage in various seizure types of children with epilepsy. Methods According to the classification criteria of seizure types formulated by International League Against Epilepsy (ILAE in 1981, 190 children with epilepsy were enrolled including tonic-clonic seizure group (41 cases, tonic seizure group (34 cases, clonic seizure group (22 cases, myoclonic seizure group (12 cases, atonic seizure group (17 cases, absence seizure group (22 cases, simple partial seizure group (21 cases and complex partial seizure group (21 cases, and 64 healthy children were enrolled as control group. The long-range vedio-electroencephalogram (VEEG was operated and the blood samples were collected from these cases within 72 h after their seizures. Results The serum NSE levels of epileptic children were significantly higher than control group (P = 0.000. Among these seizure groups, serum NSE in myoclonic seizure group [(32.42 ± 6.62 ng/ml] was significantly higher than the other types, except for tonic-clonic seizure group (P = 0.062. There was no significant difference among the other types (P > 0.05, for all. According to rank correlation analysis, there was positive corrlation between serum NSE levels and VEEG abnormal intensity (rs = 0.613, P = 0.000. Conclusion The serum NSE were markedly increased in children with epilepsy after seizures, suggesting that a certain degree of neuronal damage may result from seizures; the higher NSE levels were, the more serious neuronal damage caused by epileptiform discharges was. The serum NSE levels in myoclonic seizure group and tonic-clonic seizure group were significantly higher than other seizure types, indicating the two kinds of seizures may result in greater neuronal damage.

  1. Diagnostic utility of neuron specific enolase (NSE) in serum and pleural fluids from patients with lung cancer and tuberculosis

    International Nuclear Information System (INIS)

    Alam, J.M.; Baig, J.A.; Asghar, S.S.; Mahmood, S.R.; Ansari, M.A.; Jamil, S.

    2010-01-01

    Several past and recent investigations have focused on the determination of tumor markers in pleural fluids to assess their Usefulness as less invasive replacement method of diagnosis. In this regard, few studies have dealt with the determination of the tumor marker, neuron specific enolase (NSE), in pleural fluids of patients suffering from both benign and malignant diseases such as non small cell lung carcinoma( NSCLC), small cell lung carcinoma( SCLC) and tuberculosis. Therefore, the present study was undertaken to establish the diagnostic utility of NSE in malignant condition by assessing levels in serum and pleural fluids of patients with lung cancer and by comparing it with a benign pulmonary disease of tuberculosis. Pleural fluids were obtained from 22 patients with carcinomatous pleurisy due to SCLC, 11 patients with carcinomatous pleurisy due to non-small cell lung cancer, and 30 patients with tuberculosis pleurisy for comparison purpose. Determination of NSE levels was performed by ECL technology according to the manufacturer's instructions. NSE levels of pleural fluids from SCLC patients were significantly elevated( P<0.0001) when compared with pleural fluids from NSCLC and tuberculosis patients. Moreover, pleural fluids of all 30 tuberculosis patients and 11 NSCLC patients showed moderate significance ( P< O.05 and P < 0.01, respectively) when compared with each other. In addition, cumulative results of NSE levels from SCLC and NSCLC combined also showed high significance (P<0.001) as compared to pleural fluids of tuberculosis patients and moderate significance (P<0.01) when compared with serum levels of both malignant and benign groups. It is concluded that determination of NSE levels in pleural fluids of lung cancer patients noted to be an effective diagnostic tool to differentiate carcinomatous pleurisy due to SCLC from those occurring due to NSCLC and tuberculosis. Further studies with larger group of patients are under progress to further establish

  2. Prophylactic Injection of Recombinant Alpha-Enolase Reduces Arthritis Severity in the Collagen-Induced Arthritis Mice Model.

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    Clément Guillou

    Full Text Available To evaluate the ability of the glycolytic enzyme alpha-enolase (ENO1 or its immunodominant peptide (pEP1 to reduce the severity of CIA in DBA/1 mice when injected in a prophylactic way.Mice were treated with mouse ENO1 or pEP1 one day prior to collagen II immunization. Clinical assessment was evaluated using 4 parameters (global and articular scores, ankle thickness and weight. Titers of serum anti-ENO1, anti-cyclic citrullinated peptides (anti-CCP and anti-CII (total IgG and IgG1/IgG2a isotypes antibodies were measured by ELISA at different time-points. Disease activity was assessed by histological analysis of both anterior and hind paws at the end of experimentation.Prophylactic injection of 100 μg of ENO1 reduced severity of CIA. Serum levels of anti-CII antibodies were reduced in ENO1-treated mice. Concordantly, ENO1-treated mice joints presented less severe histological signs of arthritis. ENO1 did not induce a shift toward a Th2 response since IgG1/IgG2a ratio of anti-CII antibodies remained unchanged and IL-4 serum levels were similar to those measured in the control group.Pre-immunization with ENO1 or its immunodominant peptide pEP1 reduces CIA severity at the clinical, immunological and histological levels. Effects of pEP1 were less pronounced. This immunomodulatory effect is associated with a reduction in anti-CII antibodies production but is not due to a Th1/Th2 shift.

  3. Prophylactic Injection of Recombinant Alpha-Enolase Reduces Arthritis Severity in the Collagen-Induced Arthritis Mice Model

    Science.gov (United States)

    Guillou, Clément; Derambure, Céline; Fréret, Manuel; Verdet, Mathieu; Avenel, Gilles; Golinski, Marie-Laure; Sabourin, Jean-Christophe; Loarer, François Le; Adriouch, Sahil; Boyer, Olivier; Lequerré, Thierry; Vittecoq, Olivier

    2015-01-01

    Objective To evaluate the ability of the glycolytic enzyme alpha-enolase (ENO1) or its immunodominant peptide (pEP1) to reduce the severity of CIA in DBA/1 mice when injected in a prophylactic way. Methods Mice were treated with mouse ENO1 or pEP1 one day prior to collagen II immunization. Clinical assessment was evaluated using 4 parameters (global and articular scores, ankle thickness and weight). Titers of serum anti-ENO1, anti-cyclic citrullinated peptides (anti-CCP) and anti-CII (total IgG and IgG1/IgG2a isotypes) antibodies were measured by ELISA at different time-points. Disease activity was assessed by histological analysis of both anterior and hind paws at the end of experimentation. Results Prophylactic injection of 100 μg of ENO1 reduced severity of CIA. Serum levels of anti-CII antibodies were reduced in ENO1-treated mice. Concordantly, ENO1-treated mice joints presented less severe histological signs of arthritis. ENO1 did not induce a shift toward a Th2 response since IgG1/IgG2a ratio of anti-CII antibodies remained unchanged and IL-4 serum levels were similar to those measured in the control group. Conclusions Pre-immunization with ENO1 or its immunodominant peptide pEP1 reduces CIA severity at the clinical, immunological and histological levels. Effects of pEP1 were less pronounced. This immunomodulatory effect is associated with a reduction in anti-CII antibodies production but is not due to a Th1/Th2 shift. PMID:26302382

  4. Discovery of a novel target for the dysglycemic chromogranin A fragment pancreastatin: interaction with the chaperone GRP78 to influence metabolism.

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    Nilima Biswas

    Full Text Available RATIONALE: The chromogranin A-derived peptide pancreastatin (PST is a dysglycemic, counter-regulatory peptide for insulin action, especially in liver. Although previous evidence for a PST binding protein has been reported, such a receptor has not been identified or sequenced. METHODS AND RESULTS: We used ligand affinity to purify the PST target, with biotinylated human PST (hCHGA273-301-amide as "bait" and mouse liver homogenate as "prey", and identified GRP78 (a.k.a. "78 kDa Glucose Regulated Protein", HSPA5, BIP as a major interacting partner of PST. GRP78 belongs to the family of heat shock proteins (chaperones, involved in several cellular processes including protein folding and glucose metabolism. We analyzed expression of GRP78 in the absence of PST in a mouse knockout model lacking its precursor CHGA: hepatic transcriptome data revealed global over-expression of not only GRP78 but also other heat shock transcripts (of the "adaptive UPR" in CHGA(-/- mice compared to wild-type (+/+. By contrast, we found a global decline in expression of hepatic pro-apoptotic transcripts in CHGA(-/- mice. GRP78's ATPase enzymatic activity was dose-dependently inhibited by PST (IC50∼5.2 µM. PST also inhibited the up-regulation of GRP78 expression during UPR activation (by tunicamycin in hepatocytes. PST inhibited insulin-stimulated glucose uptake in adipocytes, and increased hepatic expression of G6Pase (the final step in gluconeogenesis/glycogenolysis. In hepatocytes not only PST but also other GRP78-ATPase inhibitors (VER-155008 or ADP increased G6Pase expression. GRP78 over-expression inhibited G6Pase expression in hepatocytes, with partial restoration by GRP78-ATPase inhibitors PST, VER-155008, or ADP. CONCLUSIONS: Our results indicate that an unexpected major hepatic target of PST is the adaptive UPR chaperone GRP78. PST not only binds to GRP78 (in pH-dependent fashion, but also inhibits GRP78's ATPase enzymatic activity, and impairs its biosynthetic

  5. Cerebellar hemangioblastomas: A study of the immunoprofile of neoplastic stromal component

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    Tasić Desanka

    2004-01-01

    Full Text Available Background. Central nervous system hemangioblastomas (HBs are uncommon highly vascularized tumors that are predominantly found in the cerebellum. They occur sporadically or in association with von Hippel-Lindau (VHL disease. HBs are of unknown histogenesis, and the origin of stromal cells is still a subject of debate. The aim of this study was to investigate the immunoprofile of neoplastic stromal component, and to determine whether the profile of the expression of immunomarkers used can contribute to the elucidation of the histogenesis of HBs. Methods. A series of eight cerebellar HBs were histochemically examined for the detection of mast cells and immunohistochemically for the expression of factor VIII-related antigen (FVIII-RAg, CD34, vimentin, factor XIIIa (FXIIIa, S-100 protein, glial fibrillary acidic protein (GFAP, neuron-specific enolase (NSE neurofilaments (NF, synaptophysin, chromogranin, and somatostatin. Results. Mast cells were present in all hemangioblastomas, and were particularly abundant in one tumor. Immunohistochemically, intense reactivity for vimentin and NSE in the stromal cells was constantly seen. Immunoreactivity with S-100 protein and FXIIIa was variable, but generally many HBs stromal cells were negative for these markers. However, stromal cells were uniformly negative for FVIII-RAg in all HBs investigated. They were negative for CD34 GFAP, NF, synaptophysin, chromogranin, as well as somatostatin. GFAP-positivity of the occasional stromal type cells, located only peripherally, was interpreted as "pseudopositivity". Conclusion. The immunoprofile of neoplastic stromal component in this study suggested a possible origin from undifferentiated multipotential mesenchymal cells. High expression of NSE (glycolytic and hypoxia-inducible enzyme in the HBs stromal cells might be related to the loss of the VHL protein function.

  6. The prognostic value of serum neuron-specific enolase in traumatic brain injury: systematic review and meta-analysis.

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    Feng Cheng

    Full Text Available BACKGROUND: Several studies have suggested that neuron-specific enolase (NSE in serum may be a biomarker of traumatic brain injury. However, whether serum NSE levels correlate with outcomes remains unclear. The purpose of this review was to evaluate the prognostic value of serum NSE protein after traumatic brain injury. METHODS: PubMed and Embase were searched for relevant studies published up to October 2013. Full-text publications on the relationship of NSE to TBI were included if the studies concerned patients with closed head injury, NSE levels in serum after injury, and Glasgow Outcome Scale (GOS or Extended GOS (GOSE scores or mortality. Study design, inclusion criteria, assay, blood sample collection time, NSE cutoff, sensitivity and specificity of NSE for mortality prediction (if sufficient information was provided to calculate these values, and main outcomes were recorded. RESULTS: Sixteen studies were eligible for the current meta-analysis. In the six studies comparing NSE concentrations between TBI patients who died and those who survived, NSE concentrations correlated with mortality (M.D. 0.28, 95% confidence interval (CI, 0.21 to 0.34; I2 55%. In the eight studies evaluating GOS or GOSE, patients with unfavorable outcomes had significantly higher NSE concentrations than those with favorable outcomes (M.D. 0.24, 95% CI, 0.17 to 0.31; I2 64%. From the studies providing sufficient data, the pooled sensitivity and specificity for mortality were 0.79 and 0.50, and 0.72 and 0.66 for unfavorable neurological prognosis, respectively. The areas under the SROC curve (AUC of NSE concentrations were 0.73 (95% CI, 0.66-0.80 for unfavorable outcome and 0.76 (95% CI, 0.62-0.90 for mortality. CONCLUSIONS: Mortality and unfavorable outcome were significantly associated with greater NSE concentrations. In addition, NSE has moderate discriminatory ability to predict mortality and neurological outcome in TBI patients. The optimal discrimination cutoff

  7. Limbic encephalitis associated with anti-NH2-terminal of α-enolase antibodies: A clinical subtype of Hashimoto encephalopathy.

    Science.gov (United States)

    Kishitani, Toru; Matsunaga, Akiko; Ikawa, Masamichi; Hayashi, Kouji; Yamamura, Osamu; Hamano, Tadanori; Watanabe, Osamu; Tanaka, Keiko; Nakamoto, Yasunari; Yoneda, Makoto

    2017-03-01

    Several types of autoantibodies have been reported in autoimmune limbic encephalitis (LE), such as antibodies against the voltage-gated potassium channel (VGKC) complex including leucine-rich glioma inactivated 1 (LGI1). We recently reported a patient with autoimmune LE and serum anti-NH2-terminal of α-enolase (NAE) antibodies, a specific diagnostic marker for Hashimoto encephalopathy (HE), who was diagnosed with HE based on the presence of antithyroid antibodies and responsiveness to immunotherapy. This case suggests that LE patients with antibodies to both the thyroid and NAE could be diagnosed with HE and respond to immunotherapy. The aim of this study was to clarify the clinicoimmunological features and efficacy of immunotherapy in LE associated with anti-NAE antibodies to determine whether the LE is a clinical subtype of HE.We examined serum anti-NAE antibodies in 78 LE patients with limbic abnormality on magnetic resonance imaging and suspected HE based on positivity for antithyroid antibodies. Nineteen of the 78 patients had anti-NAE antibodies; however, 5 were excluded because they were double positive for antibodies to the VGKC complex including LGI1. No antibodies against the N-methyl-D-aspartate receptor (NMDAR), contactin-associated protein 2 (Caspr2), γ-aminobutyric acid-B receptor (GABABR), or α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) were detected in the 19 patients. Among the remaining 14 who were positive only for anti-NAE antibodies, the median age was 62.5 (20-83) years, 9 (64%) were women, and 8 (57%) showed acute onset, with less than 2 weeks between onset and admission. Consciousness disturbance (71%) and memory disturbance (64%) were frequently observed, followed by psychiatric symptoms (50%) and seizures (43%). The frequency of these symptoms significantly differed between the acute- and subacute-onset groups. Abnormalities in cerebrospinal fluid and electroencephalogram were commonly observed (92% for both

  8. A differential scanning calorimetric study of the effects of metal ions, substrate/product, substrate analogues and chaotropic anions on the thermal denaturation of yeast enolase 1.

    Science.gov (United States)

    Brewer, J M; Wampler, J E

    2001-03-14

    The thermal denaturation of yeast enolase 1 was studied by differential scanning calorimetry (DSC) under conditions of subunit association/dissociation, enzymatic activity or substrate binding without turnover and substrate analogue binding. Subunit association stabilizes the enzyme, that is, the enzyme dissociates before denaturing. The conformational change produced by conformational metal ion binding increases thermal stability by reducing subunit dissociation. 'Substrate' or analogue binding additionally stabilizes the enzyme, irrespective of whether turnover is occurring, perhaps in part by the same mechanism. More strongly bound metal ions also stabilize the enzyme more, which we interpret as consistent with metal ion loss before denaturation, though possibly the denaturation pathway is different in the absence of metal ion. We suggest that some of the stabilization by 'substrate' and analogue binding is owing to the closure of moveable polypeptide loops about the active site, producing a more 'closed' and hence thermostable conformation.

  9. Stopped-flow studies of changes in fluorescence of 8-anilino-1-naphthalene sulfonic acid caused by magnesium and salt binding to yeast enolase.

    Science.gov (United States)

    Brewer, J M

    1976-12-11

    Stopped-flow studies of magnesium and salt (potassium chloride and acetate) effects on yeast enolase were carried out by following 8-anilino-1-naphthalenesulfonic acid fluorescence changes. The fluorescence changes appear to be largely caused by subunit association and dissociation, though there is evidence in some reactions for large changes in fluorescence occurring within the dead time of the stopped-flow measurements. These data are combined with measurements of initial enzyme activity after incubation in various solvents with or without magnesium to obtain subunit association and dissociation rates. From these, it is concluded that magnesium and the salts act by directly changing the affinities of the subunits for each other, apparently by producing a rapid change in protein conformation.

  10. Neuron-Specific Enolase Is Correlated to Compromised Cerebral Metabolism in Patients Suffering from Acute Bacterial Meningitis; An Observational Cohort Study

    DEFF Research Database (Denmark)

    Bartek, Jiri; Thelin, Eric Peter; Ghatan, Per Hamid

    2016-01-01

    between day 1 (0-24 h) and day 3 (48-72 h) after admission to the NICU (p = 0.0001). No correlation between MD parameters or biomarkers and outcome was found. CONCLUSION: In this observational cohort study, we were able to show that cerebral metabolism is frequently affected in patients with ABM...... in combination with serum samples of biomarkers indicating brain tissue injury, S100B and Neuron Specific Enolase (NSE), additional information might be provided. The aim of this study was to evaluate biomarkers in serum and MD parameters in patients with ABM. METHODS: From a prior study on patients (n = 52......) with a confirmed ABM and impaired consciousness (GCS ≤ 9, or GCS = 10 combined with lumbar spinal opening pressure > 400 mmH2O), a subgroup of patients (n = 21) monitored with intracerebral MD and biomarkers was included in the present study. All patients were treated in the NICU with intracranial pressure (ICP...

  11. Early detection of response in small cell bronchogenic carcinoma by changes in serum concentrations of creatine kinase, neuron specific enolase, calcitonin, ACTH, serotonin and gastrin releasing peptide

    DEFF Research Database (Denmark)

    Bork, E; Hansen, M; Urdal, P

    1988-01-01

    Creatine kinase (CK-BB), neuron specific enolase (NSE), ACTH, calcitonin, serotonin and gastrin releasing peptide (GRP) were measured in serum or plasma before and immediately after initiation of treatment in patients with small cell lung cancer (SCC). Pretherapeutic elevated concentrations of CK...... stage patients and 71% in limited stage patients. Frequent initial monitoring of the substances showed an increase in the concentrations of pretherapeutic elevated CK-BB and NSE on day 1 or 2 followed by a sharp decrease within 1 week. These changes were correlated to objective clinical response...... determined within 4-8 weeks. The results indicate that serum CK-BB and NSE are potential markers for SCC at the time of diagnosis and that changes in the concentrations during the first course of cytostatic therapy are promising as biochemical tests for early detection of response to chemotherapy....

  12. Functional and Structural Characterization of a Novel HLA-DRB1*04:01-Restricted α-Enolase T Cell Epitope in Rheumatoid Arthritis

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    Christina Gerstner

    2016-11-01

    Full Text Available Antibodies to citrullinated proteins, common in rheumatoid arthritis (RA patients, are strongly associated to a specific set of HLA-DR alleles including HLA-DRB1*04:01, *04:04, and *01:01. Here, we first demonstrate that autoantibody levels toward the dominant citrullinated B cell epitope from α-enolase are significantly elevated in HLA-DRB1*04:01-positive RA patients. Furthermore, we identified α-enolase-derived T cell epitopes and demonstrated that native and citrullinated versions of several peptides bind with different affinities to HLA-DRB1*04:01, *04:04, and *01:01. The citrulline residues in the eight identified peptides are distributed throughout the entire length of the presented epitopes and more specifically, localized at peptide positions p-2, p2, p4, p6, p7, p10, and p11. Importantly, in contrast to its native version peptide 26 (TSKGLFRAAVPSGAS, the HLA-DRB1*04:01-restricted citrullinated peptide Cit26 (TSKGLFCitAAVPSGAS elicited significant functional T cell responses in primary cells from RA patients. Comparative analysis of the crystal structures of HLA-DRB1*04:01 in complex with peptide 26 or Cit26 demonstrated that the posttranslational modification did not alter the conformation of the peptide. And since citrullination is the only structural difference between the two complexes, this indicates that the neo-antigen Cit26 is recognized by T cells with high specificity to the citrulline residue.

  13. The level of neuron-specific enolase and S-100 protein in the cerebrospinal fluid of patients with acute bacterial meningitis

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    A. V. Sokhan

    2016-08-01

    Full Text Available Aim. To evaluate the diagnostic and prognostic role of neuron-specific enolase (NSE and S-100 protein levels in cerebrospinal fluid (CSF of patients with acute bacterial meningitis in the course of the disease. Materials and Methods. 54 cases of acute bacterial meningitis were analyzed, among them – 26 with pneumococcal and 28 with meningococcal etiology. Patients were divided into groups depending on the severity and etiology of disease. In addition to routine laboratory methods, we analyzed the CSF levels of S-100 protein and NSE at admission and after 10 – 12 days of treatment. 12 patients with acute respiratory infections and meningism were examined as a comparison group. Results. In all patients with acute bacterial meningitis CSF NSE and protein S-100 levels were significantly higher than in the control group (P <0,05. CSF neuro specific proteins level was in direct dependence on severity of the disease, and in patients with severe disease was significantly higher than in patients with moderate severity and in the control group (P <0,01. After 10 – 12 days of treatment, the level of the NSE and S-100 protein decreased, but in severe cases was still higher than in the control group (P <0,05. Conclusions. Increased cerebrospinal fluid NSE and S – 100 protein levels shows the presence and value of neurons and glial cells damage in patients with acute bacterial meningitis. CSF S-100 protein and neuron-specific enolase levels help to determine the severity of neurons destruction and glial cells in patients with acute bacterial meningitis. Level of neurospecific protein is in direct proportion to the severity of the disease and is the highest in patients with severe cases (P<0,05. It confirms the diagnostic and prognostic value of CSF neurospecific protein determination in patients with bacterial meningitis.

  14. Identification and Function Analysis of enolase Gene NlEno1 from Nilaparvata lugens (Stål) (Hemiptera:Delphacidae)

    Science.gov (United States)

    Wang, Wei-Xia; Li, Kai-Long; Chen, Yang; Lai, Feng-Xiang; Fu, Qiang

    2015-01-01

    The enolase [EC 4.2.1.11] is an essential enzyme in the glycolytic pathway catalyzing the conversion of 2-phosphoglycerate (2-PGE) to phosphoenolpyruvate (PEP). In this study, a full-length cDNA encoding α-enolase was cloned from rice brown planthopper (Nilaparvata lugens) and is provisionally designated as NlEno1. The cDNA sequence of NlEno1 was 1,851 bp with an open reading frame (ORF) of 1,305 bp and encoding 434 amino acids. The deduced protein shares high identity of 80–87% with ENO1-like protein from Hemiptera, Diptera, and Lepidoptera speices. The NlEno1 showed the highest mRNA expression level in hemolymph, followed by fat body, salivary gland, ovaries and egg, and showed trace mRNA levels in testis. The mRNA of NlEno1 showed up-regulated level in virulent N. lugens population Mudgo, IR56 and IR42 when compared with TN1 population. Injection of double-stranded RNA (dsRNA) of NlEno1 into the adults significantly down-regulated the NlEno1 mRNA level along with decreased eggs and offspring. Moreover, injection of NlEno1-dsRNA decreased mRNA level of Vitellogenin (Vg) gene. These results showed that the NlEno1, as a key glycolytic enzyme, may play roles in regulation of fecundity and adaptation of N. lugens to resistant rice varieties. PMID:26056319

  15. Evolution of Enzymatic Activities in the Enolase Superfamily: Stereochemically Distinct Mechanisms in Two Families of cis,cis-Muconate Lactonizing Enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, A.; Fedorov, A; Fedorov, E; Schnoes, A; Glasner, M; Burley, S; Babbitt, P; Almo, S; Gerlt, J

    2009-01-01

    The mechanistically diverse enolase superfamily is a paradigm for elucidating Nature's strategies for divergent evolution of enzyme function. Each of the different reactions catalyzed by members of the superfamily is initiated by abstraction of the a-proton of a carboxylate substrate that is coordinated to an essential Mg2+. The muconate lactonizing enzyme (MLE) from Pseudomonas putida, a member of a family that catalyzes the syn-cycloisomerization of cis,cis-muconate to (4S)-muconolactone in the e-ketoadipate pathway, has provided critical insights into the structural bases for evolution of function within the superfamily. A second, divergent family of homologous MLEs that catalyzes anti-cycloisomerization has been identified. Structures of members of both families liganded with the common (4S)-muconolactone product (syn, Pseudomonas fluorescens, gi 70731221; anti, Mycobacterium smegmatis, gi 118470554) document that the conserved Lys at the end of the second e-strand in the (e/a)7e-barrel domain serves as the acid catalyst in both reactions. The different stereochemical courses (syn and anti) result from different structural strategies for determining substrate specificity: although the distal carboxylate group of the cis,cis-muconate substrate attacks the same face of the proximal double bond, opposite faces of the resulting enolate anion intermediate are presented to the conserved Lys acid catalyst. The discovery of two families of homologous, but stereochemically distinct, MLEs likely provides an example of 'pseudoconvergent' evolution of the same function from different homologous progenitors within the enolase superfamily, in which different spatial arrangements of active site functional groups and substrate specificity determinants support catalysis of the same reaction.

  16. Evolution of Enzymatic Activities in the Enolase Superfamily: Stereochemically Distinct Mechanisms in Two Families of cis,cis-Muconate Lactonizing Enzymes†

    Science.gov (United States)

    Sakai, Ayano; Fedorov, Alexander A.; Fedorov, Elena V.; Schnoes, Alexandra M.; Glasner, Margaret E.; Brown, Shoshana; Rutter, Marc E.; Bain, Kevin; Chang, Shawn; Gheyi, Tarun; Sauder, J. Michael; Burley, Stephen K.; Babbitt, Patricia C.; Almo, Steven C.; Gerlt, John A.

    2009-01-01

    The mechanistically diverse enolase superfamily is a paradigm for elucidating Nature’s strategies for divergent evolution of enzyme function. Each of the different reactions catalyzed by members of the superfamily is initiated by abstraction of the α-proton of a carboxylate substrate that is coordinated to an essential Mg2+. The muconate lactonizing enzyme (MLE) from Pseudomonas putida, a member of a family that catalyzes the syn-cycloisomerization of cis,cis-muconate to (4S)-muconolactone in the β-ketoadipate pathway, has provided critical insights into the structural bases for evolution of function within the superfamily. A second, divergent family of homologues MLEs that catalyzes anti-cycloisomerization has been identified. Structures of members of both families liganded with the common (4S)-muconolactone product (syn, Pseudomonas fluorescens, GI:70731221; anti, Mycobacterium smegmatis, GI:118470554) document that the conserved Lys at the end of the second β-strand in the (β/α)7β-barrel domain serves as the acid catalyst in both reactions. The different stereochemical courses (syn and anti) result from different structural strategies for determining substrate specificity: although the distal carboxylate group of the cis,cis-muconate substrate attacks the same face of the proximal double bond, opposite faces of the resulting enolate anion intermediate are presented to the conserved Lys acid catalyst. The discovery of two families of homologous, but stereochemically distinct, MLEs likely provides an example of “pseudoconvergent” evolution of the same function from different homologous progenitors within the enolase superfamily, in which different spatial arrangements of active site functional groups and substrate specificity determinants support catalysis of the same reaction. PMID:19220063

  17. Evaluating the prognosis and degree of brain injury by combined S-100 protein and neuron specific enolase determination

    Institute of Scientific and Technical Information of China (English)

    Xihua Wang; Xinding Zhang

    2006-01-01

    Background:S-100 and neuron specific enolase(NSE)possess the characteristics of specific distribution in brain and relative stable content.Some studies suggest that combined detection of the both is of very importance for evaluating the degree of brain injury.OBJECTIVE: To observe the changes of S-100 protein and NSE levels at different time points after acute brain injury,and evaluate the values of combined detection detection of the both for different injury degrees,pathological changes and prognosis.DESIGN: Case-control observation SETTING: Department of Neurosurgery,Second Affiliated Hospital,Lanzhou University.PARTICIPANTS:Thirty-four inpatients with brain injury,19 males and 15 females,aged 15 to 73 years.who received treatment between September 2005 and May 2006 in the Department of Neurosurgery. Second Affiliated Hospital,Lanzhou University,were recruited.The patients were admitted to hospital at 24 hours after brain injury.After admission,skull CT confirmed that they suffered from brain injury.Following Glasgow coma score(GCS)on admission,the patients were assigned into 3 groups:severe group(GCS 3 to 8 points,n=15).moderate group(GCS 9 to 12 points,n=8)and mild group(GCS 13 to 15 points,n=11).Following Glasgow outcome scale(GOS)at 3 months after brain injury,the patients were assigned into good outcome group (GOS 4 to 5 points,good recovery and moderate disability included,n=19)and poor outcome group(GOS 1 to 3 points,severe disability,vegetative state and death,n=15).Ten subjects who received health examination concurrently were chosen as normal control group,including 6 males and 4 females,aged(45.4±14.3)years.In our laboratory,the normal level of NSE was≤15.2 ng/L,and that of S100 was≤0.105 μg/L.METHODS:①Blood samples of control group were collected when the subjects received health examination Blood samples of patients with brain injury were collected at 24 hours,3,7 and 14 days after injury.According to the instructions of NSE and S-100 kits

  18. Replacement of Ser108 in Plasmodium falciparum enolase results in weak Mg(II) binding: role of a parasite-specific pentapeptide insert in stabilizing the active conformation of the enzyme.

    Science.gov (United States)

    Dutta, Sneha; Mukherjee, Debanjan; Jarori, Gotam K

    2015-06-01

    A distinct structural feature of Plasmodium falciparum enolase (Pfeno) is the presence of a five amino acid insert -104EWGWS108- that is not found in host enolases. Its conservation among apicomplexan enolases has raised the possibility of its involvement in some important physiological function(s). Deletion of this sequence is known to lower k(cat)/K(m), increase K(a) for Mg(II) and convert dimer into monomers (Vora HK, Shaik FR, Pal-Bhowmick I, Mout R & Jarori GK (2009) Arch Biochem Biophys 485, 128-138). These authors also raised the possibility of the formation of an H-bond between Ser108 and Leu49 that could stabilize the apo-Pfeno in an active closed conformation that has high affinity for Mg(II). Here, we examined the effect of replacement of Ser108 with Gly/Ala/Thr on enzyme activity, Mg(II) binding affinity, conformational states and oligomeric structure and compared it with native recombinant Pfeno. The results obtained support the view that Ser108 is likely to be involved in the formation of certain crucial H-bonds with Leu49. The presence of these interactions can stabilize apo-Pfeno in an active closed conformation similar to that of Mg(II) bound yeast enolase. As predicted, S108G/A-Pfeno variants (where Ser108-Leu49 H-bonds are likely to be disrupted) were found to exist in an open conformation and had low affinity for Mg(II). They also required Mg(II) induced conformational changes to acquire the active closed conformational state essential for catalysis. The possible physiological relevance of apo-Pfeno being in such an active state is discussed. © 2015 FEBS.

  19. Structure of the first representative of Pfam family PF04016 (DUF364) reveals enolase and Rossmann-like folds that combine to form a unique active site with a possible role in heavy-metal chelation

    International Nuclear Information System (INIS)

    Miller, Mitchell D.; Aravind, L.; Bakolitsa, Constantina; Rife, Christopher L.; Carlton, Dennis; Abdubek, Polat; Astakhova, Tamara; Axelrod, Herbert L.; Chiu, Hsiu-Ju; Clayton, Thomas; Deller, Marc C.; Duan, Lian; Feuerhelm, Julie; Grant, Joanna C.; Han, Gye Won; Jaroszewski, Lukasz; Jin, Kevin K.; Klock, Heath E.; Knuth, Mark W.; Kozbial, Piotr; Krishna, S. Sri; Kumar, Abhinav; Marciano, David; McMullan, Daniel; Morse, Andrew T.; Nigoghossian, Edward; Okach, Linda; Reyes, Ron; Bedem, Henry van den; Weekes, Dana; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Elsliger, Marc-André; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

    2010-01-01

    The crystal structure of the first representative of DUF364 family reveals a combination of enolase N-terminal-like and C-terminal Rossmann-like folds. Analysis of the interdomain cleft combined with sequence and genome context conservation among homologs, suggests a unique catalytic site likely involved in the synthesis of a flavin or pterin derivative. The crystal structure of Dhaf4260 from Desulfitobacterium hafniense DCB-2 was determined by single-wavelength anomalous diffraction (SAD) to a resolution of 2.01 Å using the semi-automated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). This protein structure is the first representative of the PF04016 (DUF364) Pfam family and reveals a novel combination of two well known domains (an enolase N-terminal-like fold followed by a Rossmann-like domain). Structural and bioinformatic analyses reveal partial similarities to Rossmann-like methyltransferases, with residues from the enolase-like fold combining to form a unique active site that is likely to be involved in the condensation or hydrolysis of molecules implicated in the synthesis of flavins, pterins or other siderophores. The genome context of Dhaf4260 and homologs additionally supports a role in heavy-metal chelation

  20. Immunohistochemical localization of gastrin-releasing peptide, neuronal nitric oxide synthase and neurone-specific enolase in the uterus of the North American opossum, Didelphis virginiana.

    Science.gov (United States)

    Kumano, A; Sasaki, M; Budipitojo, T; Kitamura, N; Krause, W J; Yamada, J

    2005-08-01

    The present study has demonstrated the immunohistochemical localization of gastrin-releasing peptide (GRP), neuronal nitric oxide synthase (nNOS) and neurone-specific enolase (NSE) in the uterus of the North American opossum. Although the presence of GRP, nNOS and NSE has been reported recently in the uterus of eutherian species this is the first description of these peptides in a metatherian species. Metatherian mammals are of interest because in these species it is the prolonged lactation phase of development that is the period of primary reproductive investment rather than intrauterine development as is true of eutherian mammals. The opossum, like other marsupial species, has a very abbreviated gestation period which in Didelphis lasts only 12.5 days. GRP was localized in the cytoplasm of cells forming the surface lining epithelium and the glandular epithelium of the opossum endometrium late in pregnancy, at 11.5 days of gestation. Likewise, immunoreactivities of nNOS and NSE were found primarily within the epithelial cells of the endometrium at 11.5 days of gestation. As these peptides and enzymes appear primarily at the time of establishment of the yolk sac placenta (between day 10 and day 12.5 gestation), the present results strongly suggest that these factors may play a fundamental role in the placentation of the opossum.

  1. The biomarkers neuron-specific enolase and S100b measured the day following admission for severe accidental hypothermia have high predictive values for poor outcome

    DEFF Research Database (Denmark)

    Wiberg, Sebastian; Kjaergaard, Jesper; Kjærgaard, Benedict

    2017-01-01

    was analyzed for NSE and S100b. Follow-up was conducted after 30days and poor neurologic outcome was defined as a Cerebral Performance Category (CPC) score of 3-5. The predictive value of NSE and S100b was assessed as the area under the receiver-operating characteristics curve (AUC). RESULTS: A total of 34......AIM: The aim of the present study was to assess the ability of the biomarkers neuron-specific enolase (NSE) and S100 calcium-binding protein b (S100b) to predict mortality and poor neurologic outcome after 30days in patients admitted with severe accidental hypothermia. METHODS: Consecutive patients...... in 30 unconscious and/or sedated patients. NSE and S100b achieved AUCs of 0.93 and 0.88, respectively, for prediction of 30day mortality and AUCs of 0.88 and 0.87, respectively, for prediction of poor neurologic outcome. CONCLUSIONS: In patients remaining unconscious the day following admission...

  2. Serum neuron-specific enolase, biogenic amino-acids and neurobehavioral function in lead-exposed workers from lead-acid battery manufacturing process.

    Science.gov (United States)

    Ravibabu, K; Barman, T; Rajmohan, H R

    2015-01-01

    The interaction between serum neuron-specific enolase (NSE), biogenic amino-acids and neurobehavioral function with blood lead levels in workers exposed to lead form lead-acid battery manufacturing process was not studied. To evaluate serum NSE and biogenic amino-acids (dopamine and serotonin) levels, and neurobehavioral performance among workers exposed to lead from lead-acid storage battery plant, and its relation with blood lead levels (BLLs). In a cross-sectional study, we performed biochemical and neurobehavioral function tests on 146 workers exposed to lead from lead-acid battery manufacturing process. BLLs were assessed by an atomic absorption spectrophotometer. Serum NSE, dopamine and serotonin were measured by ELISA. Neurobehavioral functions were assessed by CDC-recommended tests---simple reaction time (SRT), symbol digit substitution test (SDST), and serial digit learning test (SDLT). There was a significant correlation (r 0.199, pSDLT and SRT had also a significant positive correlation (r 0.238, p<0.01). NSE had a negative correlation (r -0.194, p<0.05) with serotonin level. Multiple linear regression analysis revealed that both SRT and SDST had positive significant associations with BLL. SRT also had a positive significant association with age. Serum NSE cannot be used as a marker for BLL. The only domain of neurobehavioral function tests that is affected by increased BLL in workers of lead-acid battery manufacturing process is that of the "attention and perception" (SDST).

  3. Determination of serum neuron specific enolase and glutathion S transferases levels in patients with acute cerebral infarction and its clinical significance

    International Nuclear Information System (INIS)

    Guo Jianyi; Lu Tianhe; Bao Yanmei

    2002-01-01

    Objective: To evaluate the variation of serum neuron specific enolase (NSE) and glutathion S transferases (GST) levels in patients with cerebral infarction and its clinical significance. Methods: The serum levels of NSE in cerebral infarction patients were determined with immunoradiometric assay (IRMA), and the serum level of GST were determined by enzyme immuno sandwich assay (ELISA). Results: Serum NSE levels linked in patients were significantly higher (p<0.01) and GST serum levels were significantly lower (p < 0.01) within 3 days after onset of disease than those at two weeks and those in the controls. There was a positive correlation between serum NSE levels and neurological deficit scores (p < 0.001) and a negative correlation with serum GST levels (p < 0.05). There was also a close relationship between the serum NSE levels and the volume of infarction (p < 0.001). Conclusion: There was a close relationship between the Serum levels of NSE, GST and clinical features of Patients in the early stage of cerebral infarction

  4. Enolase 1 (ENO1 and protein disulfide-isomerase associated 3 (PDIA3 regulate Wnt/β-catenin-driven trans-differentiation of murine alveolar epithelial cells

    Directory of Open Access Journals (Sweden)

    Kathrin Mutze

    2015-08-01

    Full Text Available The alveolar epithelium represents a major site of tissue destruction during lung injury. It consists of alveolar epithelial type I (ATI and type II (ATII cells. ATII cells are capable of self-renewal and exert progenitor function for ATI cells upon alveolar epithelial injury. Cell differentiation pathways enabling this plasticity and allowing for proper repair, however, are poorly understood. Here, we applied proteomics, expression analysis and functional studies in primary murine ATII cells to identify proteins and molecular mechanisms involved in alveolar epithelial plasticity. Mass spectrometry of cultured ATII cells revealed a reduction of carbonyl reductase 2 (CBR2 and an increase in enolase 1 (ENO1 and protein disulfide-isomerase associated 3 (PDIA3 protein expression during ATII-to-ATI cell trans-differentiation. This was accompanied by increased Wnt/β-catenin signaling, as analyzed by qRT-PCR and immunoblotting. Notably, ENO1 and PDIA3, along with T1α (podoplanin; an ATI cell marker, exhibited decreased protein expression upon pharmacological and molecular Wnt/β-catenin inhibition in cultured ATII cells, whereas CBR2 levels were stabilized. Moreover, we analyzed primary ATII cells from mice with bleomycin-induced lung injury, a model exhibiting activated Wnt/β-catenin signaling in vivo. We observed reduced CBR2 significantly correlating with surfactant protein C (SFTPC, whereas ENO1 and PDIA3 along with T1α were increased in injured ATII cells. Finally, siRNA-mediated knockdown of ENO1, as well as PDIA3, in primary ATII cells led to reduced T1α expression, indicating diminished cell trans-differentiation. Our data thus identified proteins involved in ATII-to-ATI cell trans-differentiation and suggest a Wnt/β-catenin-driven functional role of ENO1 and PDIA3 in alveolar epithelial cell plasticity in lung injury and repair.

  5. Metabolic syndrome and its components with neuron-specific enolase: a cross-sectional study in large health check-up population in China.

    Science.gov (United States)

    Wang, Shu-Yi; Zha, Xiao-Juan; Zhu, Xin-Ying; Li, Wen-Bo; Ma, Jun; Wu, Ze-Wei; Wu, Huan; Jiang, Ming-Fei; Wen, Yu-Feng

    2018-04-10

    This study was aimed at investigating the relationship between neuron-specific enolase (NSE) and components of metabolic syndrome (MS). Cross-sectional study. Chinese health check-up population. 40 684 health check-up people were enrolled in this study from year 2014 to 2016. OR and coefficient for MS. The percentage of abnormal NSE and MS was 26.85% and 8.85%, respectively. There were significant differences in sex, body mass index, drinking habit, triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), blood pressure and MS between low-NSE and high-NSE groups. In logistic regression analysis, elevated NSE was present in MS, higher body mass index, hypertriglyceridaemia, hypertension and low-HDL groups. Stepwise linear analysis showed a negative correlation between NSE and fasting blood glucose (FBG) (<6.0 mmol/L), and a positive correlation between NSE and TGs (<20 mmol/L), systolic blood pressure (75-200 mm Hg), HDL-C (0.75-2.50 mmol/L), diastolic blood pressure (<70 mm Hg) and FBG (6.00-20.00 mmol/L). Furthermore, MS was positively correlated with NSE within the range of 2.00-7.50 ng/mL, but had a negative correlation with NSE within the range of 7.50-23.00 ng/mL. There are associations between NSE with MS and its components. The result suggests that NSE may be a potential predictor of MS. Further research could be conducted in discussing the potential mechanism involved. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  6. Serum Neuron-Specific Enolase, Biogenic Amino-Acids and Neurobehavioral Function in Lead-Exposed Workers from Lead-Acid Battery Manufacturing Process

    Directory of Open Access Journals (Sweden)

    K Ravibabu

    2015-01-01

    Full Text Available Background: The interaction between serum neuron-specific enolase (NSE, biogenic amino-acids and neurobehavioral function with blood lead levels in workers exposed to lead form lead-acid battery manufacturing process was not studied. Objective: To evaluate serum NSE and biogenic amino-acids (dopamine and serotonin levels, and neurobehavioral performance among workers exposed to lead from lead-acid storage battery plant, and its relation with blood lead levels (BLLs. Methods: In a cross-sectional study, we performed biochemical and neurobehavioral function tests on 146 workers exposed to lead from lead-acid battery manufacturing process. BLLs were assessed by an atomic absorption spectrophotometer. Serum NSE, dopamine and serotonin were measured by ELISA. Neurobehavioral functions were assessed by CDC-recommended tests—simple reaction time (SRT, symbol digit substitution test (SDST, and serial digit learning test (SDLT. Results: There was a significant correlation (r 0.199, p<0.05 between SDST and BLL. SDLT and SRT had also a significant positive correlation (r 0.238, p<0.01. NSE had a negative correlation (r –0.194, p<0.05 with serotonin level. Multiple linear regression analysis revealed that both SRT and SDST had positive significant associations with BLL. SRT also had a positive significant association with age. Conclusion: Serum NSE cannot be used as a marker for BLL. The only domain of neurobehavioral function tests that is affected by increased BLL in workers of lead-acid battery manufacturing process is that of the “attention and perception” (SDST.

  7. Effect of Memantine on Serum Levels of Neuron-Specific Enolase and on the Glasgow Coma Scale in Patients With Moderate Traumatic Brain Injury.

    Science.gov (United States)

    Mokhtari, Majid; Nayeb-Aghaei, Hossein; Kouchek, Mehran; Miri, Mir Mohammad; Goharani, Reza; Amoozandeh, Arash; Akhavan Salamat, Sina; Sistanizad, Mohammad

    2018-01-01

    Traumatic brain injury (TBI) is a major cause of disability and death globally. Despite significant progress in neuromonitoring and neuroprotection, pharmacological interventions have failed to generate favorable results. We examined the effect of memantine on serum levels of neuron-specific enolase (NSE), a marker of neuronal damage, and the Glasgow Coma Scale (GCS) in patients with moderate TBI. Patients were randomly assigned to the control group (who received standard TBI management) and the treatment group (who, alongside their standard management, received enteral memantine 30 mg twice daily for 7 days). Patients' clinical data, GCS, findings of head computed tomography, and serum NSE levels were collected during the study. Forty-one patients were randomized into the control and treatment groups, 19 and 22 patients respectively. Baseline characteristics and serum NSE levels were not significantly different between the 2 groups. The mean serum NSE levels for the memantine and the control groups on day 3 were 7.95 ± 2.86 and 12.33 ± 7.09 ng/mL, respectively (P = .05), and on day 7 were 5.03 ± 3.25 and 10.04 ± 5.72 ng/mL, respectively (P = .003). The mean GCS on day 3 was 12.3 ± 2.0 and 10.9 ± 1.9 in the memantine and control groups, respectively (P = .03). Serum NSE levels and GCS changes were negatively correlated (r = -0.368, P = .02). Patients with moderate TBI who received memantine had significantly reduced serum NSE levels by day 7 and marked improvement in their GCS scores on day 3 of the study. © 2017, The American College of Clinical Pharmacology.

  8. Tumors of the endocrine/neuroendocrine system: an overview.

    Science.gov (United States)

    Erlandson, R A; Nesland, J M

    1994-01-01

    For the sake of discussion, the markedly diversified tumors of the endocrine/neuroendocrine system are classified as those originating in classic epithelial endocrine organs (eg, adrenal cortical adenomas), from the diffuse endocrine cells (eg, jejunal carcinoid tumors), or from clusters of these cells (eg, islet cell tumors); and those arising from neurosecretory neurons (eg, neuroblastoma) or paraganglia (eg, carotid body tumor). Although traditional transmission electron microscopy is useful for identifying neurosecretory or endosecretory granules as such, with few exceptions (eg, insulin-containing granules with a complex paracrystalline core) it is not possible to ascribe a granule type (size, shape, or ultrastructure) to a distinct nosologic entity or secretory product because of their overlapping fine structures in different cell types. Immunoelectron microscopy methods utilizing colloidal gold-labeled secondary antibodies can be used to localize virtually any antigen (peptide or neuroamine) to a specific neurosecretory or endosecretory granule or other cell structure. General endocrine/neuroendocrine cell markers such as neuron-specific enolase, the chromogranins, and synaptophysin are useful in identifying neuroendocrine differentiation in a neoplasm using routine immunohistochemical procedures. The current relevance of the APUD concept of Pearse as well as the biologic importance of endocrine/neuroendocrine secretory products such as bombesin and insulinlike growth factors also are discussed.

  9. Endoscopic Management of a Primary Duodenal Carcinoid Tumor

    Directory of Open Access Journals (Sweden)

    Albin Abraham

    2012-03-01

    Full Text Available Carcinoids are rare, slow-growing tumors originating from a variety of different neuroendocrine cell types. They are identified histologically by their affinity for silver salts and by positive reactions to neuroendocrine markers such as neuron-specific enolase, synaptophysin and chromogranin. They can present with various clinical symptoms and are difficult to diagnose. We present the case of a 43-year-old woman who was referred for evaluation of anemia. Upper endoscopy showed a duodenal bulb mass around 1 cm in size. Histopathological and immunohistochemistry staining were consistent with the diagnosis of a carcinoid tumor. Further imaging and endoscopic studies showed no other synchronous carcinoid lesions. Endoscopic ultrasound (EUS revealed a 1 cm lesion confined to the mucosa and no local lymphadenopathy. Successful endoscopic mucosal resection of the mass was performed. Follow-up surveillance 6 months later with EUS and Octreoscan revealed no new lesions suggestive of recurrence. No consensus guidelines exist for the endoscopic management of duodenal carcinoid tumors. However, endoscopic resection is safe and preferred for tumors measuring 1 cm or less with no evidence of invasion of the muscularis layer.

  10. Carcinoid tumor of the verumontanum (colliculus seminalis of the prostatic urethra with a coexisting prostatic adenocarcinoma: a case report

    Directory of Open Access Journals (Sweden)

    Werahera Priya N

    2010-01-01

    Full Text Available Abstract Introduction Urethral carcinoid tumors are very rare tumors with only four cases described in the literature. Case presentation We present the case of a 61-year-old man with a primary carcinoid tumor of the verumontanum (colliculis seminalis portion of the prostatic urethra with a coexisting prostatic adenocarcinoma. In addition to whole mount hematoxylin and eosin staining, special immunoperoxidase staining specific for chromogranin A, neuron specific enolase, synaptophysin, pan-cytokeratin and PSA, and a special combined staining for racemase (α-methyl CoA antigen and p63 antigen were performed. A review of the literature is included. A single focus of invasive prostatic adenocarcinoma was identified in the periphery of the mid-left, posterior quadrant of the prostate. Approximately 17 mm from this adenocarcinoma, within the verumontanum of the prostatic urethra, there was a 3 mm maximal dimension carcinoid tumor. Conclusion Based on different histological features and antigenic profiles, we concluded that the two tumors were distinct.

  11. Granular cell tumors of the urinary bladder

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    Kayani Naila

    2007-03-01

    Full Text Available Abstract Background Granular cell tumors (GCTs are extremely rare lesions of the urinary bladder with only nine cases being reported in world literature of which one was malignant. Generally believed to be of neural origin based on histochemical, immunohistochemical, and ultrastructural studies; they mostly follow a clinically benign course but are commonly mistaken for malignant tumors since they are solid looking, ulcerated tumors with ill-defined margins. Materials and methods We herein report two cases of GCTs, one benign and one malignant, presenting with gross hematuria in a 14- and a 47-year-old female, respectively. Results Histopathology revealed characteristic GCTs with positive immunostaining for neural marker (S-100 and negative immunostaining for epithelial (cytokeratin, Cam 5.2, AE/A13, neuroendocrine (neuron specific enolase, chromogranin A, and synaptophysin and sarcoma (desmin, vimentin markers. The benign tumor was successfully managed conservatively with transurethral resection alone while for the malignant tumor, radical cystectomy, hysterectomy with bilateral salpingo-oophorectomy, anterior vaginectomy, plus lymph node dissection was done. Both cases show long-term disease free survival. Conclusion We recommend careful pathologic assessment for establishing the appropriate diagnosis and either a conservative or aggressive surgical treatment for benign or localized malignant GCT of the urinary bladder, respectively.

  12. Clinicopathological characteristics of head and neck Merkel cell carcinomas.

    Science.gov (United States)

    Knopf, Andreas; Bas, Murat; Hofauer, Benedikt; Mansour, Naglaa; Stark, Thomas

    2017-01-01

    There are still controversies about the therapeutic strategies and subsequent outcome in head and neck Merkel cell carcinoma. Clinicopathological data of 23 Merkel cell carcinomas, 93 cutaneous head and neck squamous cell carcinomas (HNSCCs), 126 malignant melanomas, and 91 primary parotid gland carcinomas were comprehensively analyzed. Merkel cell carcinomas were cytokeratin 20 (CK20)/neuron-specific enolase (NSE)/chromogranin A (CgA)/synaptophysin (Syn)/thyroid transcription factor-1 (TTF-1)/MIB1 immunostained. All Merkel cell carcinomas underwent wide local excision. Parotidectomy/neck dissection was performed in 40%/33% cutaneous Merkel cell carcinoma and 100%/100% in parotid gland Merkel cell carcinoma. Five-year recurrence-free interval (RFI)/overall survival (OS) was significantly higher in malignant melanoma (81/80%) than in cutaneous Merkel cell carcinoma/HNSCC. Interestingly, 5-year RFI/OS was significantly higher in Merkel cell carcinoma (61%/79%) than in HNSCC (33%/65%; p Merkel cell carcinoma and parotid gland carcinomas, nor in the immunohistochemical profile. Five-year RFI/OS was significantly better in cutaneous Merkel cell carcinoma when compared with TNM classification matched HNSCC. Five-year RFI/OS was comparable in parotid gland Merkel cell carcinoma and other primary parotid gland malignancies. © 2016 Wiley Periodicals, Inc. Head Neck 39: 92-97, 2017. © 2016 Wiley Periodicals, Inc.

  13. Concordance between results of somatostatin receptor scintigraphy with {sup 111}In-DOTA-DPhe{sup 1}-Tyr{sup 3}-octreotide and chromogranin A assay in patients with neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, Margarida [Medical University of Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); Hietzing Hospital, Institute of Nuclear Medicine, Vienna (Austria); Gabriel, Michael; Heute, Dirk; Putzer, Daniel; Virgolini, Irene [Medical University of Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); Griesmacher, Andrea [Medical University of Innsbruck, Central Institute of Medical and Chemical Laboratory Diagnostics, Innsbruck (Austria)

    2008-10-15

    Somatostatin receptor scintigraphy (SRS) and chromogranin A (CgA) assay have successfully been implemented in the clinical work-up and management of neuroendocrine tumour (NET) patients. However, there is still a lack of studies comparing results in these patients. Our aim was to compare directly in NET patients SRS and CgA assay results with special regard to tumour features such as grade of malignancy, primary origin, disease extent and function. One hundred twenty consecutive patients with histological confirmed NETs were investigated with {sup 111}In-DOTA-DPhe{sup 1}-Tyr{sup 3}-octreotide ({sup 111}In-DOTA-TOC) SRS and CgA immunoradiometric assay. Tumours were classified by cell characteristics [well-differentiated NETs, well-differentiated neuroendocrine carcinomas, poorly differentiated neuroendocrine carcinomas (PDNECs)], primary origin (foregut, midgut, hindgut, undetermined), disease extent (limited disease, metastases, primary tumour and metastases) and functionality (secretory, nonsecretory). SRS was positive in 107 (89%) patients; CgA levels were increased in 95 (79%) patients. Overall, concordance between SRS and CgA results was found in 84 patients. Positive SRS but normal CgA level were found in 24 patients, with higher prevalence (p<0.05) in patients with nonsecretory tumours. Conversely, negative SRS but CgA level increased were seen in 12 patients, with higher proportion (p < 0.05) in patients with PDNECs and tumours of hindgut origin. Overall, {sup 111}In-DOTA-TOC SRS proved to be more sensitive than CgA in NETs patients. Tumour differentiation, disease extent and presence of liver metastases impact both SRS and CgA results, whereas nonsecretory activity is a negative predictor of only CgA increase. PDNECs and hindgut origin of tumours predispose to discrepancies with negative SRS but increased CgA levels. (orig.)

  14. Paraganglioma of the thyroid gland: A case report

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    Filipović Aleksandar

    2014-01-01

    Full Text Available Introduction. Thyroid paraganglioma is a very rare malignant neuroendocrine tumor. Immunohistochemical features of thyroid paraganglioma are helpful for the diagnosis. Case report. A 69-year-old female came to hospital with the presence of a growing thyroid nodule of the left lobe. Ultrasonic neck examination showed 5 cm hypoechoic nodule in the left thyroid lobe. Thyroid scintigraphy showed a big cold nodule in the left lobe. Computed tomography (CT scan showed left lobe thyroid tumor with tracheal deviation on the right site. Extended total thyroidectomy was done. Intraoperative consultation with the pathologist confirmed thyroid cancer. The pathologist diagnosed thyroid paraganglioma on the base of immuohistochemical investigation. This thyroid paraganglioma was positive for neuron-specific enolase, chomogranin A, synaptophysin, and S-100 protein highlighted the sustentacular cells. Tumor cells were nega-tive for thyroglobulin, epithelial membrane antigen, cytokeratin, calcitonin, and carcinoembryonic. After the surgery the patient was treated with chemotherapy, peptide receptor radionuclide therapy, and permanent TSH suppressive therapy. The patient was followed with measurements of thyroid hormone and serum neuron-specific enolase, chromogranin A level, every 6 months. Gastroscopy, colonoscopy, chest and abdomen CT scan as well as further tests (chest x-ray, ultrasound of the neck, and whole body octreotide scintigraphy were done. No primary neuroendocrine tumor in digestive sistem or in the chest was found. After more than 3 years the patient has no evidence of the recurrent disease. Conclusion. Radical resection of thyroid paraganglioma, followed by chemotherapy and peptide receptor radionuclide therapy, should be considered the treatment of choice in patients with thyroid gland paraganglioma.

  15. Merkel cell carcinoma with an unusual immunohistochemical profile

    Directory of Open Access Journals (Sweden)

    L. Pilloni

    2009-12-01

    Full Text Available The clinical and morphological picture of Merkel cell carcinoma (MCC may be rather challenging; therefore, the immunohistochemical profile plays a relevant role in confirming the microscopic diagnosis. A panel of antibodies including cytokeratins 20, 7 and epithelial membrane antigen, and neuronspecific enolase is used in confirming the morphological diagnosis of MCC. The majority of MCCs express CK20 and are CK7-negative. Herein, we present a case of primary cutaneous neuroendocrine carcinoma with an atypical immunohistochemical pattern. A 83-years old woman presented with a painless plaque, red to violaceous in colour, located in the leg. The skin tumor was excided, formalin-fixed and paraffinembedded. Tissue sections were immunostained with a panel of antibodies routinely utilized in complex primary skin tumors for evidencing epithelial and neuroendocrine differentiation of tumor cells. The neuroendocrine differentiation of tumor cells was evidenced by their immunoreactivity for synaptophysin, chromograninA and neuron-specific enolase. Tumor cells also showed diffuse cytoplasmic staining for CK7. No immunoreactivity was detected for CK20 and thyroid transcription factor-1. Our data, together with previous rare reports of CK20-/CK7+ MCCs, lay stress on the importance of routinely utilizing a panel of antibodies in the differential diagnosis of complex primary carcinomas of the skin and may have important implications in expanding the differential diagnosis of skin tumors. In particular, caution should be taken in excluding the diagnosis of MCC only on the basis of the absence of reactivity of tumor cells for CK20, favouring the wrong diagnosis of less aggressive skin tumors.

  16. Alpha-enolase (ENO1 controls alpha v/beta 3 integrin expression and regulates pancreatic cancer adhesion, invasion, and metastasis

    Directory of Open Access Journals (Sweden)

    Moitza Principe

    2017-01-01

    Full Text Available Abstract Background We have previously shown that in pancreatic ductal adenocarcinoma (PDA cells, the glycolytic enzyme alpha-enolase (ENO1 also acts as a plasminogen receptor and promotes invasion and metastasis formation. Moreover, ENO1 silencing in PDA cells induces oxidative stress, senescence and profoundly modifies PDA cell metabolism. Although anti-ENO1 antibody inhibits PDA cell migration and invasion, little is known about the role of ENO1 in regulating cell-cell and cell-matrix contacts. We therefore investigated the effect of ENO1 silencing on the modulation of cell morphology, adhesion to matrix substrates, cell invasiveness, and metastatic ability. Methods The membrane and cytoskeleton modifications that occurred in ENO1-silenced (shENO1 PDA cells were investigated by a combination of confocal microscopy and atomic force microscopy (AFM. The effect of ENO1 silencing was then evaluated by phenotypic and functional experiments to identify the role of ENO1 in adhesion, migration, and invasion, as well as in senescence and apoptosis. The experimental results were then validated in a mouse model. Results We observed a significant increase in the roughness of the cell membrane due to ENO1 silencing, a feature associated with an impaired ability to migrate and invade, along with a significant downregulation of proteins involved in cell-cell and cell-matrix adhesion, including alpha v/beta 3 integrin in shENO1 PDA cells. These changes impaired the ability of shENO1 cells to adhere to Collagen I and IV and Fibronectin and caused an increase in RGD-independent adhesion to vitronectin (VN via urokinase plasminogen activator receptor (uPAR. Binding of uPAR to VN triggers integrin-mediated signals, which result in ERK1-2 and RAC activation, accumulation of ROS, and senescence. In shENO1 cancer cells, the use of an anti-uPAR antibody caused significant reduction of ROS production and senescence. Overall, a decrease of in vitro and in vivo cell

  17. Constructing disease-specific gene networks using pair-wise relevance metric: Application to colon cancer identifies interleukin 8, desmin and enolase 1 as the central elements

    Directory of Open Access Journals (Sweden)

    Jiang Wei

    2008-08-01

    Full Text Available Abstract Background With the advance of large-scale omics technologies, it is now feasible to reversely engineer the underlying genetic networks that describe the complex interplays of molecular elements that lead to complex diseases. Current networking approaches are mainly focusing on building genetic networks at large without probing the interaction mechanisms specific to a physiological or disease condition. The aim of this study was thus to develop such a novel networking approach based on the relevance concept, which is ideal to reveal integrative effects of multiple genes in the underlying genetic circuit for complex diseases. Results The approach started with identification of multiple disease pathways, called a gene forest, in which the genes extracted from the decision forest constructed by supervised learning of the genome-wide transcriptional profiles for patients and normal samples. Based on the newly identified disease mechanisms, a novel pair-wise relevance metric, adjusted frequency value, was used to define the degree of genetic relationship between two molecular determinants. We applied the proposed method to analyze a publicly available microarray dataset for colon cancer. The results demonstrated that the colon cancer-specific gene network captured the most important genetic interactions in several cellular processes, such as proliferation, apoptosis, differentiation, mitogenesis and immunity, which are known to be pivotal for tumourigenesis. Further analysis of the topological architecture of the network identified three known hub cancer genes [interleukin 8 (IL8 (p ≈ 0, desmin (DES (p = 2.71 × 10-6 and enolase 1 (ENO1 (p = 4.19 × 10-5], while two novel hub genes [RNA binding motif protein 9 (RBM9 (p = 1.50 × 10-4 and ribosomal protein L30 (RPL30 (p = 1.50 × 10-4] may define new central elements in the gene network specific to colon cancer. Gene Ontology (GO based analysis of the colon cancer-specific gene network and

  18. Constructing disease-specific gene networks using pair-wise relevance metric: application to colon cancer identifies interleukin 8, desmin and enolase 1 as the central elements.

    Science.gov (United States)

    Jiang, Wei; Li, Xia; Rao, Shaoqi; Wang, Lihong; Du, Lei; Li, Chuanxing; Wu, Chao; Wang, Hongzhi; Wang, Yadong; Yang, Baofeng

    2008-08-10

    With the advance of large-scale omics technologies, it is now feasible to reversely engineer the underlying genetic networks that describe the complex interplays of molecular elements that lead to complex diseases. Current networking approaches are mainly focusing on building genetic networks at large without probing the interaction mechanisms specific to a physiological or disease condition. The aim of this study was thus to develop such a novel networking approach based on the relevance concept, which is ideal to reveal integrative effects of multiple genes in the underlying genetic circuit for complex diseases. The approach started with identification of multiple disease pathways, called a gene forest, in which the genes extracted from the decision forest constructed by supervised learning of the genome-wide transcriptional profiles for patients and normal samples. Based on the newly identified disease mechanisms, a novel pair-wise relevance metric, adjusted frequency value, was used to define the degree of genetic relationship between two molecular determinants. We applied the proposed method to analyze a publicly available microarray dataset for colon cancer. The results demonstrated that the colon cancer-specific gene network captured the most important genetic interactions in several cellular processes, such as proliferation, apoptosis, differentiation, mitogenesis and immunity, which are known to be pivotal for tumourigenesis. Further analysis of the topological architecture of the network identified three known hub cancer genes [interleukin 8 (IL8) (p approximately 0), desmin (DES) (p = 2.71 x 10(-6)) and enolase 1 (ENO1) (p = 4.19 x 10(-5))], while two novel hub genes [RNA binding motif protein 9 (RBM9) (p = 1.50 x 10(-4)) and ribosomal protein L30 (RPL30) (p = 1.50 x 10(-4))] may define new central elements in the gene network specific to colon cancer. Gene Ontology (GO) based analysis of the colon cancer-specific gene network and the sub-network that

  19. Neuron-Specific Enolase Is Correlated to Compromised Cerebral Metabolism in Patients Suffering from Acute Bacterial Meningitis; An Observational Cohort Study.

    Directory of Open Access Journals (Sweden)

    Jiri Bartek

    Full Text Available Patients suffering from acute bacterial meningitis (ABM with a decreased level of consciousness have been shown to have an improved clinical outcome if treated with an intracranial pressure (ICP guided therapy. By using intracranial microdialysis (MD to monitor cerebral metabolism in combination with serum samples of biomarkers indicating brain tissue injury, S100B and Neuron Specific Enolase (NSE, additional information might be provided. The aim of this study was to evaluate biomarkers in serum and MD parameters in patients with ABM.From a prior study on patients (n = 52 with a confirmed ABM and impaired consciousness (GCS ≤ 9, or GCS = 10 combined with lumbar spinal opening pressure > 400 mmH2O, a subgroup of patients (n = 21 monitored with intracerebral MD and biomarkers was included in the present study. All patients were treated in the NICU with intracranial pressure (ICP guided therapy. Serum biomarkers were obtained at admission and every 12 hours. The MD parameters glucose, lactate, pyruvate and glycerol were analyzed. Outcome was assessed at 12-55 months after discharge from hospital. Mann-Whitney U-Test and Wilcoxon matched-pairs signed rank test were applied.The included patients had a mean GCS of 8 (range, 3-10 on admission and increased ICP (>20 mmHg was observed in 62% (n = 13/21 of the patients. Patients with a lactate:pyruvate ratio (LPR >40 (n = 9/21, 43% had significantly higher peak levels of serum NSE (p = 0.03, with similar, although non-significant observations made in patients with high levels of glycerol (>500 μmol/L, p = 0.11 and those with a metabolic crisis (Glucose 25, p = 0.09. No associations between serum S100B and MD parameters were found. Furthermore, median MD glucose levels decreased significantly between day 1 (0-24 h and day 3 (48-72 h after admission to the NICU (p = 0.0001. No correlation between MD parameters or biomarkers and outcome was found.In this observational cohort study, we were able to show

  20. Single versus Serial Measurements of Neuron-Specific Enolase and Prediction of Poor Neurological Outcome in Persistently Unconscious Patients after Out-Of-Hospital Cardiac Arrest - A TTM-Trial Substudy

    DEFF Research Database (Denmark)

    Wiberg, Sebastian; Hassager, Christian; Stammet, Pascal

    2017-01-01

    were included from sites participating in the TTM-trial biobank sub study. NSE was measured at 24, 48 and 72 hours after ROSC and follow-up was concluded after 180 days. The primary end point was poor neurological function or death defined by a cerebral performance category score (CPC-score) of 3 to 5...... of the biomarker neuron-specific enolase (NSE) in combination with other predictors of outcome in patients admitted after out-of-hospital cardiac arrest (OHCA). This study sought to investigate the ability of NSE to predict poor outcome in patients remaining unconscious at day three after OHCA. In addition....... RESULTS: A total of 685 (73%) patients participated in the study. At day three after OHCA 63 (9%) patients had died and 473 (69%) patients were not awake. In these patients, a single NSE measurement at 48 hours predicted poor outcome with an area under the receiver operating characteristics curve (AUC...

  1. Enolasa específica de neurona en dos recién nacidos con depresión ligera al nacer Neuron- specific Enolase in two newborns presenting with moderate depression at birth

    Directory of Open Access Journals (Sweden)

    Raisa Bu-Coifiu Fanego

    2009-03-01

    Full Text Available INTRODUCCIÓN. La enolasa específica de neurona es una isoenzima que se vierte al torrente sanguíneo después de un episodio de daño neuronal. En los procesos de hipoxia neonatal estos valores enzimáticos en suero suelen estar alterados. El objetivo del presente artículo fue estudiar la enolasa específica de neurona en suero de 2 recién nacidos con Apgar bajo y determinar si, en el seguimiento durante un año, dichos pacientes presentaban trastornos del desarrollo psicomotor. MÉTODOS. Se tomaron muestras de suero al momento del nacimiento y a las 72 h siguientes. Se determinaron los niveles de enolasa específica de neurona por un método inmunoenzimático de tipo ELISA. Cada muestra fue evaluada por el método de reacción en cadena de la polimerasa para citomegalovirus, en el Instituto de Inmunología de Wuersburg (Alemania. También se cuantificaron anticuerpos contra citomegalovirus de clase IgM e IgG, en el Laboratorio de Neuroquímica de la Universidad Georg August de Goettingen (Alemania. Se recogieron los datos clínicos de interés de cada recién nacido y al año se citaron a estos pacientes y se les realizó un examen físico para evaluar su neurodesarrollo. RESULTADOS. Las cifras de enolasa estuvieron incrementadas tanto al nacimiento como a las 72 h, con anticuerpos anticitomegalovirus de clase IgG que fueron transferidos de la madre a través de la placenta. No se encontró presencia de este virus en el momento del nacimiento. En el examen físico y neurológico realizado al año se constató que los niños evolucionaban satisfactoriamente hasta esa fecha. CONCLUSIONES. Se recomienda extender el estudio hasta los 3 años de vida y aumentar el número de pacientes estudiados, con énfasis en aquellos casos cuyo Apgar es menor de 5 a los 5 min del nacimiento.INTRODUCTION: Neuron-specific Enolase of is an isoenzyme present in blood stream after a neuronal damage episode. In processes of neonatal hypoxia, these enzymatic values

  2. Rare case of left adrenal cortical carcinoma with level 3 inferior vena ...

    African Journals Online (AJOL)

    K. Jain

    2017-05-02

    May 2, 2017 ... carcinoma with no renal parenchymal invasion and the immuno-histochemistry showing it to be positive for synaptophysin, inhibin and KI-67 (15%) while negative for chromogranin, pan cytokeratin and CD-10 receptors. Patient then received 3 weekly 6 cycles of adriamycin and cisplatin chemotherapy.

  3. Cardiac, renal, and neurological benefits of preoperative levosimendan administration in patients with right ventricular dysfunction and pulmonary hypertension undergoing cardiac surgery: evaluation with two biomarkers neutrophil gelatinase-associated lipocalin and neuronal enolase

    Directory of Open Access Journals (Sweden)

    Guerrero-Orriach JL

    2016-04-01

    Full Text Available José Luis Guerrero-Orriach,1 Daniel Ariza-Villanueva,1 Ana Florez-Vela,1 Lourdes Garrido-Sánchez,2,3 María Isabel Moreno-Cortés,1 Manuel Galán-Ortega,1 Alicia Ramírez-Fernández,1 Juan Alcaide Torres,3 Concepción Santiago Fernandez,3 Isabel Navarro Arce,1 José María Melero-Tejedor,4 Manuel Rubio-Navarro,1 José Cruz-Mañas1 1Department of Cardio-Anaesthesiology, University Hospital Virgen de la Victoria, Málaga, Spain; 2CIBER Fisiología de la Obesidad y Nutrición (CIBEROBN, Instituto de Salud Carlos III, Málaga, Spain; 3Department of Nutrition and Endocrinology, Instituto de Investigaciones Biomédicas de Málaga (IBIMA, University Hospital Virgen de la Victoria, Málaga, Spain; 4Department of Cardiovascular Surgery, University Hospital Virgen de la Victoria, Málaga, Spain Purpose: To evaluate if the preoperative administration of levosimendan in patients with right ventricular (RV dysfunction, pulmonary hypertension, and high perioperative risk would improve cardiac function and would also have a protective effect on renal and neurological functions, assessed using two biomarkers neutrophil gelatinase-associated lipocalin (N-GAL and neuronal enolase. Methods: This is an observational study. Twenty-seven high-risk cardiac patients with RV dysfunction and pulmonary hypertension, scheduled for cardiac valve surgery, were prospectively followed after preoperative administration of levosimendan. Levosimendan was administered preoperatively on the day before surgery. All patients were considered high risk of cardiac and perioperative renal complications. Cardiac function was assessed by echocardiography, renal function by urinary N-GAL levels, and the acute kidney injury scale. Neuronal damage was assessed by neuron-specific enolase levels. Results: After surgery, no significant variations were found in mean and SE levels of N-GAL (14.31 [28.34] ng/mL vs 13.41 [38.24] ng/mL, neuron-specific enolase (5.40 [0.41] ng/mL vs 4.32 [0.61] ng

  4. Morphometric evaluation of NB84, synaptophysin and AgNOR is useful for the histological diagnosis and prognosis in peripheral neuroblastic tumors (pNTs A avaliação morfométrica de NB84, sinaptofisina e AgNOR é útil para o dignóstico histológico e prognóstico dos tumores neuroblásticos periféricos (pNTs

    Directory of Open Access Journals (Sweden)

    Aparecida de Cássia Carvalho

    2007-01-01

    Full Text Available OBJECTIVE: To study the importance of NB84, synaptophysin and AgNOR and explore the quantitative association of these factors with diagnosis and outcome as well as the association between NB84 and AgNOR and other tumor and stromal factors in twenty-eight peripheral neuroblastic tumors. METHODS: We assessed AgNORs, NB84, synaptophysin and several other markers in tumor tissues from 28 patients with primary neuroblastic tumors. The treatment included: surgery for stage 1, chemotherapy and bone marrow transplantation for most of stages 3 and 4. Histochemistry, immunohistochemistry and morphometry were used to evaluate the amount of tumor staining for AgNOR, NB84 and synaptophysin; the outcome for our study was survival time until death due to recurrent neuroblastic tumors. RESULTS: Only stage (pOBJETIVO: Estudar a importância dos marcadores NB84 e AgNOR e explorar as relações quantitativas entre esses marcadores com o diagnóstico e prognóstico assim como as relações entre NB84 e AgNOR e outros marcadores tumorais e estromais em 28 tumores neuroblásticos periféricos. MÉTODOS: Examinamos AgNOR, NB84 e sinaptofisina e vários outros marcadores em tecidos tumorais de vinte e oito pacientes com tumors neuroblásticos primários. Tratamento dos pacientes incluiu: cirurgia para o estágio 1, quimioterapia e transplante de medula óssea para a maioria dos pacientes nos estágios 3 e 4. Utilizamos histoquímica, imunohistoquímica e morfometria para avaliar a intensidade e extensão de expressão do AgNOR, NB84 e sinaptofisina, tendo o prognóstico dos pacientes incluído o tempo de sobrevida até a morte por recurrência dos tumores neuroblásticos. RESULTADOS: Estadiamento (p<0.01, AgNOR (p<0.01, NB84 (p<0.01 e sinaptofisina (p=0.01 foram marcadores independents de sobrevida. CONCLUSÕES: A determinação dos marcadores NB84 e sinaptofisina mostrou-se como uma ferramenta útil no diagnóstico dos tumors neuroblásticos periféricos; a associa

  5. Clinical significance of combined determination of serum neuron-specific enolase (NSE), tumor necrosis factor-α (TNF-α) and lipid-associated sialic acid (LSA) in patients with lung cancer

    International Nuclear Information System (INIS)

    Wu Wei; Yao Dengfu; Qiu Liwei; Wu Xinghua

    2003-01-01

    Objective: To explore the expression and the diagnostic value of determining serum neuron-specific enolase (NSE), tumor necrosis factor-α (TNF-α) and lipid-associated sialic acid (LSA) in patients with lung cancer. Methods: The concentrations of NSE, TNF-α and LSA were measured in 78 patients with lung cancer and 32 patients with benign lung diseases as well as 109 controls by enzymelinked immunosorbent assay (ELISA) and chemical assay respectively. Results: The levels of NSE (19.78 ± 12.10 ng/ml), TNF-α (135.64 ± 49.01 pg/ml) and LSA (106 ± 0.31 ng/ml) were significantly higher in patients with lung cancer than those in patients with benign lung diseases (NSE 7.56 ± 3.41 ng/ml, TNF-α 84.70 ± 24.89 pg/ml, LSA 0.78 ± 0.18 mg/ml) and controls (NSE 8.01 ± 2.81 ng/ml, TNF-α 71.25 ± 13.50 pg/ml, LSA 0.70 ± 0.13 ng/ml) (all p < 0.01). Conclusion: The present data suggest that the syntheses of NSE, TNF-α and LSA increase in patients with lung cancer and combined determination of NSE, TNF-α and LSA be helpful to diagnosis of lung cancer

  6. Immunocytochemistry in the diagnosis of small blue cell tumours of ...

    African Journals Online (AJOL)

    The retrieved blocks were cut and stained with antibodies to desmin, leucocyte common antigen, cytokeratin, chromogranin, neuron-specific-enolase, vimentin and neurofilament using the avidin-biotin technique as previously described. Results: Of the 25 cases studied 24 (96%) gave interpretable immunostaining reaction ...

  7. Differential expression of syntaxin-1 and synaptophysin in the ...

    Indian Academy of Sciences (India)

    Unknown

    expression of this synaptic vesicle protein roughly corres- ponds to the morphological development of synapses in the rat retina: in the OPL, synapses appear at around PD 5 and in the IPL at around PD 10–11 (Weidman and Kuwa- bara 1968, 1969). Several studies in other parts of the central nervous system have reported ...

  8. Differential expression of syntaxin-1 and synaptophysin in the ...

    Indian Academy of Sciences (India)

    Unknown

    In this study, the expression of both proteins was examined in the developing human retina and compared with .... human retina nor the state of synaptogenesis in the fetal human retina beyond 15 ... 2.1 Tissue samples. Human fetuses were ...

  9. Canine mammary minute oncocytomas with neuroendocrine differentiation associated with multifocal acinar cell oncocytic metaplasia.

    Science.gov (United States)

    Nagahara, Rei; Kimura, Masayuki; Itahashi, Megu; Sugahara, Go; Kawashima, Masashi; Murayama, Hirotada; Yoshida, Toshinori; Shibutani, Makoto

    2016-11-01

    Two solitary and minute tumors of 1 and 1.5 mm diameter were identified by microscopy in the left fourth mammary gland of a 13-year-old female Labrador Retriever dog, in addition to multiple mammary gland tumors. The former tumors were well circumscribed and were composed of small-to-large polyhedral neoplastic oncocytes with finely granular eosinophilic cytoplasm, and were arranged in solid nests separated by fine fibrovascular septa. Scattered lumina of variable sizes containing eosinophilic secretory material were evident. Cellular atypia was minimal, and no mitotic figures were visible. One tumor had several oncocytic cellular foci revealing cellular transition, with perivascular pseudorosettes consisting of columnar epithelial cells surrounding the fine vasculature. Scattered foci of mammary acinar cell hyperplasia showing oncocytic metaplasia were also observed. Immunohistochemically, the cytoplasm of neoplastic cells of the 2 microtumors showed diffuse immunoreactivity to anti-cytokeratin antibody AE1/AE3, and finely granular immunoreactivity for 60-kDa heat shock protein, mitochondrial membrane ATP synthase complex V beta subunit, and chromogranin A. One tumor also had oncocytic cellular foci forming perivascular pseudorosettes showing cellular membrane immunoreactivity for neural cell adhesion molecule. The tumors were negative for smooth muscle actin, neuron-specific enolase, vimentin, desmin, S100, and synaptophysin. Ultrastructural observation confirmed the abundant mitochondria in the cytoplasm of both neoplastic and hyperplastic cells, the former cells also having neuroendocrine granule-like electron-dense bodies. From these results, our case was diagnosed with mammary oncocytomas accompanied by neuroendocrine differentiation. Scattered foci of mammary oncocytosis might be related to the multicentric occurrence of these oncocytomas. © 2016 The Author(s).

  10. Gastric neuroendocrine carcinomas in bearded dragons (Pogona vitticeps).

    Science.gov (United States)

    Ritter, J M; Garner, M M; Chilton, J A; Jacobson, E R; Kiupel, M

    2009-11-01

    This article describes a newly recognized highly malignant neoplastic entity in young bearded dragons (Pogona vitticeps), gastric neuroendocrine carcinomas, which readily metastasize. Ten bearded dragons with histories of anorexia (8), vomiting (3), hyperglycemia (2), and anemia (3) were included in this study. All animals had neoplastic masses in their stomach, with metastasis to the liver. Microscopically, 6 of these neuroendocrine carcinomas were well-differentiated and 4 were poorly differentiated. For further characterization, immunohistochemistry for protein gene product 9.5, neuron-specific enolase, endorphin, chromogranins A and B, synaptophysin, somatostatin, insulin, glucagon, gastrin, pancreatic polypeptide, and vasoactive intestinal peptide was performed on 5 animals. Because only immunolabeling for somatostatin was consistently observed in all neoplasms, a diagnosis of somatostatinoma was made for these 5 bearded dragons. Some neoplasms also exhibited multihormonal expression. Electron microscopy performed on 1 tumor confirmed the presence of neuroendocrine granules within neoplastic cells. Gastric neuroendocrine carcinomas, and specifically somatostatinomas, have not been previously reported in bearded dragons, or other reptiles, and may be underdiagnosed due to inconsistent, ambiguous clinical signs. In humans, pancreatic somatostatinomas are associated with a syndrome of hypersomatostatinemia, which includes hyperglycemia, weight loss, and anemia, as observed in some of these bearded dragons. Somatostatinomas in humans are commonly associated with neurofibromatosis type 1 (Von Recklinghausen's disease), caused by a mutation in the tumor suppressor gene NF1, which results in decreased expression of neurofibromin. In all 5 animals examined, neoplasms exhibited decreased neurofibromin expression compared with control tissues, suggesting that decreased functional neurofibromin may play a role in the pathogenesis of somatostatinomas in bearded dragons.

  11. Merkel Cell Carcinoma of the Buccal Mucosa and Lower Lip.

    Science.gov (United States)

    Islam, Mohammed N; Chehal, Hardeep; Smith, Molly Housley; Islam, Sarah; Bhattacharyya, Indraneel

    2018-06-01

    Merkel cell carcinoma (MCC) is an uncommon relatively aggressive neuroendocrine dermal neoplasm first described in 1972 as a tumor of the sun exposed skin. Although most MCC affect the skin of the head and neck, rare primarily oral mucosal cases have been documented. Merkel cells are nondendritic neuroendocrine cells that are found not only in the skin but also the oral mucosa and give rise to MCC. Neuroendocrine cells may be found as aggregates in organs or as diffuse or isolated cells within organs and their epithelial lining. They contain peptide hormones and biogenic amines and occur in two forms: dendritic, which are not associated with nerve fibers and non-dendritic, which are associated with nerve fibers. Merkel cells as well as MCC express simple epithelium-type Cytokeratins (8, 18, 19, 20), neurosecretory substances; chromogranin A, synaptophysin, neuron-specific enolase (NSE), adhesion molecules, and villin (intermediate filament). Though weakly, they also express neural markers such as S-100 protein. Cytokeratin 20, and Cluster of differentiation 56, are the two key diagnostic markers for Merkel cells and MCC. Etiology includes UV radiation, the recently described Merkel cell polyomavirus, and long term systemic immunosuppression. The cutaneous and mucosal variants of MCC are considered aggressive tumors with a high risk for local recurrence and metastasis and should be considered in the differential diagnosis of head and neck mucosal lesions. We present two cases of primary Merkel cell carcinoma, one on the buccal mucosa and the other on the lower lip, and discuss the salient histologic, immunohistochemical and clinical features.

  12. Oral delivery of Bacillus subtilis spore expressing enolase of Clonorchis sinensis in rat model: induce systemic and local mucosal immune responses and has no side effect on liver function.

    Science.gov (United States)

    Yu, Jinyun; Chen, Tingjin; Xie, Zhizhi; Liang, Pei; Qu, Honglin; Shang, Mei; Mao, Qiang; Ning, Dan; Tang, Zeli; Shi, Mengchen; Zhou, Lina; Huang, Yan; Yu, Xinbing

    2015-07-01

    Caused by the consumption of raw or undercooked freshwater fish containing infective metacercariae of Clonorchis sinensis, human clonorchiasis remains a major public health problem in China. In previous study, we had expressed enolase from C. sinensis (CsENO) on the surface of Bacillus subtilis spore and the recombinant spore induced a pronounced protection in terms of reduced worm burden and eggs per gram feces, suggesting B. subtilis spore as an ideal vehicle for antigen delivery by oral treatment and CsENO as a promising vaccine candidate against clonorchiasis. In the current study, we detected CsENO-specific IgG and IgA levels both in serum and in intestinal mucus from rats orally administrated with B. subtilis spore surface expressing CsENO by ELISA. Lysozyme levels in serum and in intestinal mucus were analyzed too. In addition, IgA-secreting cells in intestine epithelium of the rats were detected by immunohistochemistry assay. The intestinal villi lengths of duodenum, jejunum, and ileum were also measured. Rats orally treated with B. subtilis spore or normal saline were used as controls. Our results showed that, compared with the control groups, oral administration of B. subtilis spore expressing CsENO induced both systemic and local mucosal immune response. The recombinant spores also enhanced non-specific immune response in rats. The spores had no side effect on liver function. Moreover, it might facilitate food utilization and digestion of the rats. Our work will pave the way to clarify the involved mechanisms of protective efficacy elicited by B. subtilis spore expressing CsENO and encourage us to carry out more assessment trails of the oral treated spore to develop vaccine against clonorchiasis.

  13. Non increased neuron-specific enolase concentration in cerebrospinal fluid during first febrile seizures and a year follow-up in pediatric patients No incrementos en la concentración de enolasa específica de neurona en el líquido cefalorraquídeo durante el primer ataque febril y al año en pacientes pediátricos

    Directory of Open Access Journals (Sweden)

    ALBERTO J. DORTA-CONTRERAS

    1998-09-01

    Full Text Available Febrile seizures are the commonest acute neurological disorder of early childhood. Studies suggested that febrile seizures are previous acute events from a more serious neurological problem. Due to neuron-specific enolase is generally accepted as a marker for neuropathological processes in the brain, 16 pediatric patients were studied during their first seizures and a year after it. Neuron-specific enolase in cerebrospinal fluid and blood were analysed by an immune enzyme assay. Non pathological neuron-specific enolase values were obtained in both periods in the group of patients. There were no significative differences when paired series statistics test was performed with 95% of confidence. Neuron-specific enolase appears not to be a marker for febrile seizures because its concentration not be increased in cerebrospinal fluid in this group of patients.Los ataques febriles constituyen el trastorno neurológico agudo más común en la infancia temprana. Existen estudios que sugieren que los ataques febriles son eventos agudos previos a problemas neurológicos más severos. Debido a que la enolasa específica de neurona está aceptada generalmente como marcador de procesos neuropatológicos en el cerebro, se estudiaran 16 pacientes pediátricos durante su primer ataque y al año de este. La enolasa específica de neurona en el líquido cefalorraquídeo y sangre fue analizada por una prueba inmunoenzimática. No se obtuvieron valores patológicos de enolasa específica de neurona en ambos períodos en el grupo de pacientes. No hubo diferencias significativas al aplicar el test de series apareadas con un 95% de confianza. La enolasa específica de neurona parece no ser un marcador para ataques febriles porque su concentración no se incrementa en este grupo de pacientes.

  14. Association of levels of antibodies against citrullinated cyclic peptides and citrullinated α-enolase in chronic and aggressive periodontitis as a risk factor of Rheumatoid arthritis: a case control study.

    Science.gov (United States)

    Reichert, Stefan; Schlumberger, Wolfgang; Dähnrich, Cornelia; Hornig, Nora; Altermann, Wolfgang; Schaller, Hans-Günter; Schulz, Susanne

    2015-08-29

    Periodontal disease could be a risk factor for rheumatoid arthritis (RA). It is assumed that the bacterial strain Porphyromonas gingivalis mediates citrullination of host peptides and thereby the generation of RA-associated autoantibodies in genetically predisposed individuals. For that reason non-RA individuals who suffered from generalized aggressive (GAgP, N = 51) and generalized chronic periodontitis (GChP, N = 50) were investigated regarding the occurrence of antibodies against citrullinated cyclic peptides (anti-CCP) and citrullinated α-enolase peptide-1 (anti-CEP-1) in comparison to non-RA non-periodontitis controls (N = 89). Furthermore, putative associations between infections with five periodontopathic bacteria or expression of certain human leucocyte antigens (HLA) to these autoantibodies were investigated. The presence of anti-CCP and anti-CEP-1 in plasma samples was conducted with enzyme linked immunosorbent assay. Subgingival plaque specimens were taken from the deepest pocket of each quadrant and pooled. For detection of DNA of five periodontopathic bacteria PCR with sequence specific oligonucleotides was carried out. Low resolution HLA typing was carried out with PCR with sequence specific primers. Differences between patients and controls were assessed using Chi square test with Yates correction or Fisher`s exact test if the expected number n in one group was GChP and two controls (2.2%, pFisher = 0.662) were positive for anti-CEP-1 whereas no study participant was anti-CCP positive. Individuals with P. gingivalis were slightly more often anti-CEP-1 positive in comparison to individuals without P. gingivalis (3.2 vs. 1.1%, pFisher = 0.366). Carrier of HLA-DQB1*06 or the HLA combination DRB1*13; DRB3*; DQB1*06 were slightly more anti-CEP-1 positive (6.1 and 4.3%) than no carriers (0.7 and 0%, pFisher 0.053). GAgP and GChP and the presence of periodontopathic bacteria are not associated with an increased risk for occurrence of anti-CCP and anti

  15. [Pheochromocytoma--pathohistologic and immunohistochemical aspects].

    Science.gov (United States)

    Tatić, Svetislav; Havelka, Marija; Paunović, Ivan; Bozić, Vesna; Diklic, Aleksandar; Brasanac, Dimitrije; Janković, Radovan; Jancić-Zguricas, Marija

    2002-07-01

    Pheochromocytoma originates in chromaffin cells of the adrenal medulla. Its incidence is similar in both sexes and most frequent between the ages of thirty and fifty. Multiple and bilateral pheochromocytomas constitute 5 to 10 percent of all cases. Pheochromocytoma occurs sporadically or is related to family syndromes such as: syndrome of multiple endocrine neoplasia--MEN IIA and IIB, neurofibromatosis (von Recklinghausen's disease), von Hippel-Lindau's disease, Sturge-Weber's syndrome, and tuberous sclerosis. Cases in a family usually occur at a younger age and are mostly bilateral and with more aggressive biological behaviour. The aim of the study was to make histomorphological and immunohistochemical analyses of 52 pheochromocytomas. These cases are the surgical material from the Centre of Endocrine Surgery, Institute of Endocrinology, Diabetes, and Metabolic Disorders, Clinical Centre of Serbia, Belgrade, over the period from 1974 to 1997. Frozen and fixed sections, which were cut from paraffinembedded material and stained by both hematoxylin-eosin and PAS, were used in order to make pathohistological diagnoses. The expression of chromogranin A, S-100 protein and ACTH was examined using the PAP method, while neuronspecific enolase (NSE), synaptophysin and neurofilament were examined by the APAAP method with appropriate antibodies (DAKO). The patients were between 4 and 65 years of age (average age 38.5) and there were 28 females (63.64%) and 16 males (36.36%). The largest pheochromocytoma had the diameter of 12 cm, and weight of pheochromocytomas in question was from 13.5 to 370 grams, the average weight being 83.4 grams. On gross examination, the tumours proved to be well-defined, either by fibrous capsule, or by adrenocortical tissue. The cross-sections of tumours were mainly of pale red-grayish colour, and showed numerous foci of necrosis, haemorrhage and cystic softening. Histological appearance of pheochromocytomas was with significant irregularities in

  16. Solid and papillary neoplasm of the pancreas

    DEFF Research Database (Denmark)

    Jørgensen, L J; Hansen, A B; Burcharth, F

    1992-01-01

    In two cases of solid and papillary neoplasm of the pancreas (SPN), positive staining for argyrophil granules, chromogranin-A, neuron-specific enolase, chymotrypsin, alpha 1-antitrypsin, vimentin, cytokeratin, and estrogen receptors was present. Ultrastructurally, neurosecretory as well as zymoge......In two cases of solid and papillary neoplasm of the pancreas (SPN), positive staining for argyrophil granules, chromogranin-A, neuron-specific enolase, chymotrypsin, alpha 1-antitrypsin, vimentin, cytokeratin, and estrogen receptors was present. Ultrastructurally, neurosecretory as well...... as zymogenlike granules were demonstrated. Measurements of mean nuclear volume and volume-corrected mitotic index discriminated between SPN and well-differentiated ductal adenocarcinoma of the pancreas, with notably lower values being seen in SPN. Silver-stained nucleolar organizer region counts showed wide...

  17. Biomarkers of epileptic seizures and epilepsy

    Directory of Open Access Journals (Sweden)

    Bogdan Lorber

    2013-07-01

    Full Text Available The purpose of this article is to review biological markers, their importance and usefulness in the diagnosis of epileptic seizure or epilepsy. Assessed are also their prognostic value, their use in the evaluation of antiepileptic therapy effect and some other useful properties. The article reviews prolactin, neuron specific enolase, S–100 protein, creatin kinase, laminin, matrix metalloproteinase, nesfatin–1, ghrelin, obestatin and chromogranin A. The authors stress the need for further research studies in this area.

  18. Differential expression of the neural cell adhesion molecule NCAM 140 in human pituitary tumors

    OpenAIRE

    Aletsee-Ufrecht, M. C.; Langley, O. K.; Gratzl, O.; Gratzl, Manfred

    1990-01-01

    We have analyzed the expression of the intracellular marker protein neuron specific enolase (NSE), synaptophysin (SYN) and of the cell surface marker NCAM (neural cell adhesion molecule) in both normal human hypophysis and in pituitary adenomas in order to explore their potential use as diagnostic tools. All adenomas (4 prolactinomas, 3 growth hormone (GH) producing adenomas and 4 inactive adenomas) showed SYN and NSE immunoreactivity on tissue sections and this was confirmed by immunoblots. ...

  19. Expression of Selected Markers in Immunohistochemical Diagnosis of Canine and Human Testicular Tumours

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    Ciaputa Rafał

    2015-04-01

    Full Text Available Immunohistochemical profiles of the most common canine testicular tumours, including the Leydig cell tumours, seminomas, and Sertoli cell tumours were analysed, and the results were compared with those obtained in the corresponding types of human testicular neoplasms. The expressions of vimentin, von Willebrand factor (FVIII, chromogranin A, synaptophysin, and MCM3 were quantified. In the case of Sertoli cell tumours, only canine ones were analysed, since this type of tumour is very rarely diagnosed in men. The expression of the analysed proteins in the testicular tumours was similar. The von Willebrand factor exhibited the strongest expression in Leydig cell tumours in dogs and men, while vimentin was expressed more strongly in dogs (96.7% had an intensity at +++ than in men (62.5% had +++ in the Leydigioma. The immunoexpression of MCM3 in seminomas was high in both men and dogs – 90% +++ and 100% +++ respectively. The lack of chromogranin A and synaptophysin was observed in almost 100% of seminomas in men and dogs. This differed from the results obtained for Leydigioma, where chromogranin A was expressed in 70% of dogs at +++ and in 100% of men at ++++. The results may indicate that the antibodies were selected correctly. Their analysis and interpretation provides valuable information concerning the nature of the studied tumours.

  20. Accesion number Protein name ENOA_MOUSE Alpha-enolase ...

    Indian Academy of Sciences (India)

    Sandra Feijoo Bandin

    Mitochondrial inner membrane protein. CMC1_MOUSE. Calcium-binding mitochondrial carrier protein Aralar1. CMC2_MOUSE. Calcium-binding mitochondrial carrier protein Aralar2. Biological process. Metabolic process. Glycolysis. Lipid metabolism. Respiratory electron transport chain. Others. Calcium ion homeostasis.

  1. A Rare Combination of Ovarian and Uterine Leiomyomas with Goblet Cell Carcinoid of the Appendix

    Directory of Open Access Journals (Sweden)

    Abdulrahman F. Al-Shaikh

    2015-01-01

    Full Text Available We present a case of the rare combination of unilateral ovarian leiomyoma, uterine leiomyoma, and goblet cell carcinoid tumor of the appendix in a premenopausal woman who presented with right iliac pain. Immunohistochemistry study for desmin (muscle marker and chromogranin and synaptophysin (neuroendocrine markers confirmed immunophenotyping origin. Interestingly, both tumors showed positive reaction for estrogen receptor. To our knowledge, such a combination has not been reported previously in the literature. In this paper, the pathogenesis and differential diagnosis of both types of tumors are discussed.

  2. Triple composite tumor of stomach: A rare combination of alpha fetoprotein positive hepatoid adenocarcinoma, tubular adenocarcinoma and large cell neuroendocrine carcinoma

    Directory of Open Access Journals (Sweden)

    Lipika Lipi

    2014-01-01

    Full Text Available A 50-year-old male patient presented with pain abdomen of 6 months duration. Computed tomography scan revealed a large mass in the stomach occluding the lumen. Histopathology revealed a triple composite tumor comprising of tubular adenocarcinoma arising on a background of high-grade dysplasia, hepatoid adenocarcinoma (positive for Hep Par-1 and alpha fetoprotein and large cell neuroendocrine carcinoma (positive for synaptophysin and chromogranin with nodal metastasis.Triple composite tumors are distinctly rare with few reports in literature.

  3. Pleomorphic (giant cell) carcinoma of the intestine. An immunohistochemical and electron microscopic study

    DEFF Research Database (Denmark)

    Bak, Martin; Teglbjaerg, P S

    1989-01-01

    reaction for neuron-specific enolase (NSE) was found in three tumors and a positive reaction for chromogranin was found in one tumor. On electron microscopic study, intracytoplasmic whorls of intermediate filaments were seen in the perinuclear area. Dense core "neurosecretory" granules were rarely seen......Pleomorphic (giant cell) carcinomas have been described in the lungs, thyroid, pancreas, and gallbladder. Two pleomorphic carcinomas of the small bowel and two of the large bowel are presented. On light microscopic study, the carcinomas were solid, without squamous or glandular differentiation...

  4. MIA PaCa-2 and PANC-1 - pancreas ductal adenocarcinoma cell lines with neuroendocrine differentiation and somatostatin receptors.

    Science.gov (United States)

    Gradiz, Rui; Silva, Henriqueta C; Carvalho, Lina; Botelho, Maria Filomena; Mota-Pinto, Anabela

    2016-02-17

    Studies using cell lines should always characterize these cells to ensure that the results are not distorted by unexpected morphological or genetic changes possibly due to culture time or passage number. Thus, the aim of this study was to describe those MIA PaCa-2 and PANC-1 cell line phenotype and genotype characteristics that may play a crucial role in pancreatic cancer therapeutic assays, namely neuroendocrine chemotherapy and peptide receptor radionuclide therapy. Epithelial, mesenchymal, endocrine and stem cell marker characterization was performed by immunohistochemistry and flow cytometry, and genotyping by PCR, gene sequencing and capillary electrophoresis. MIA PaCa-2 (polymorphism) expresses CK5.6, AE1/AE3, E-cadherin, vimentin, chromogranin A, synaptophysin, SSTR2 and NTR1 but not CD56. PANC-1 (pleomorphism) expresses CK5.6, MNF-116, vimentin, chromogranin A, CD56 and SSTR2 but not E-cadherin, synaptophysin or NTR1. MIA PaCA-1 is CD24(-), CD44(+/++), CD326(-/+) and CD133/1(-), while PANC-1 is CD24(-/+), CD44(+), CD326(-/+) and CD133/1(-). Both cell lines have KRAS and TP53 mutations and homozygous deletions including the first 3 exons of CDKN2A/p16(INK4A), but no SMAD4/DPC4 mutations or microsatellite instability. Both have neuroendocrine differentiation and SSTR2 receptors, precisely the features making them suitable for the therapies we propose to assay in future studies.

  5. Analysis of Clinicopathological Features and Prognostic Factors in 39 Cases of Bladder Neuroendocrine Carcinoma.

    Science.gov (United States)

    Zhou, Hui-Hui; Liu, Li-Yan; Yu, Guo-Hua; Qu, Gui-Mei; Gong, Pei-You; Yu, Xiao; Yang, Ping

    2017-08-01

    Through analysis and summarization of clinicopathological features, immunohistochemical expression, pathological diagnostic criteria, prognostic and other factors in patients suffering from bladder neuroendocrine carcinoma (BNEC), a better understanding of BNEC could be achieved to provide solid evidence for clinicopathology and prognosis. The clinicopathological data of 39 cases of BNEC with up to 5-year follow-up data (median follow-up=650 days) were analyzed retrospectively based on immunohistochemical staining. Survival analyses were carried out using the Kaplan-Meier method and tested with the log-rank method. Multivariate Cox regression analysis was adopted to screen independent risk factors affecting patients' survival. In these 39 cases of BNEC, there were 26 cases of male patients, 13 female, with the proportion of male to female being 2:1. The ages of onset ranged from 44 to 86, with the median age being 62 and the average age 61.97 years, respectively. Histologically, referring to the WHO standard of neuroendocrine lung tumor classification, there were 7 cases of typical carcinoid tumors, 8 atypical carcinoid, 12 small-cell carcinomas and 12 large-cell carcinomas. In these cases there were 11 cases of featured urothelium carcinomas and 9 cases of adenocarcinomas. Immunohistochemical staining showed that, in these 39 cases of BNEC, the positive expression for the neuroendocrinic markers, including neural cell adhesion molecule 56 (CD56), synaptophysin (Syn), chromogranin A (CgA), neuron-specific enolase (NSE), thyroid transcription factor-1 (TTF-1), cytokeratin (CK) and cytokeratin 7 (CK7), accounted for 39/39, 27/39, 18/39, 39/39, 19/39, 10/39 and 8/39, respectively. In contrast, cytokeratin 20 (CK20), protein 63 (P63), human melanoma black 45 (HMB45), S-lfln protein 100 (S-100) and leukocyte common antigen (LCA) were all negatively expressed. During the follow-up period, 12 patients died. The 1-, 3- and 5-year overall survival (OS) rates were 76.92%, 74

  6. CARCINOID TUMOR OF THE DUODENUM: a rare tumor at an unusual site. Case series from a single institution

    Directory of Open Access Journals (Sweden)

    Jaques WAISBERG

    2013-03-01

    Full Text Available Context Duodenal carcinoids are extremely rare, and their characteristics and biological behavior have not been fully elucidated. Objective To analyze the clinicopathological characteristics of patients with resected duodenal carcinoids. Methods Twenty patients (12 females and 8 males were investigated. Their average age was 66.4 ± 5.8 years old (43 to 88 years old. The data corresponding to the clinical picture, diagnosis, treatment, and prognosis of patients with duodenal carcinoid tumors subjected to resection over a period of 18 years (1993-2011 were analyzed. Results The most common symptoms were dyspepsia (50% and epigastric pain (45% followed by weight loss (10% and vomiting (5%. Carcinoid syndrome was not observed in any patient. The lesion was located on the first part of the duodenum in 15 (75% patients, the second part in 4 (20% patients, and the third part in 1 (5% patient. The diagnosis of a carcinoid tumor was established through an endoscopic excision biopsy in 19 (95% patients and an histopathological examination of the surgical specimen in 1 (5% patient. The average tumor size was 1.1 cm ± 0.4 cm (0.3 cm to 6.0 cm. Nineteen (95% patients were initially treated by endoscopic resection of the duodenal lesion. One patient (5%, whose tumor was on the third part of the duodenum underwent a duodenectomy of the third and fourth duodenal parts and duodenojejunal anastomosis. The duodenal carcinoid resection margin was involved in four (20% patients. Four (20% patients were subjected to a partial gastrectomy to fully remove the lesion. The tumor was restricted to the submucosal layer in 16 (80% cases, and it penetrated into the muscular layer in 4 (20% cases. All patients exhibited positive chromogranin A, neuron-specific enolase, and/or synaptophysin immunostaining. The average duration of the follow-up period was 39.6 months (3 to 96 months. Twelve (60% of the 20 cases in this series are alive without any evidence of active

  7. Clinical and Pathologic Study of Feline Merkel Cell Carcinoma With Immunohistochemical Characterization of Normal and Neoplastic Merkel Cells.

    Science.gov (United States)

    Dohata, A; Chambers, J K; Uchida, K; Nakazono, S; Kinoshita, Y; Nibe, K; Nakayama, H

    2015-11-01

    The authors herein describe the morphologic and immunohistochemical features of normal Merkel cells as well as the clinicopathologic findings of Merkel cell carcinoma in cats. Merkel cells were characterized as vacuolated clear cells and were individually located in the epidermal basal layer of all regions examined. Clusters of Merkel cells were often observed adjacent to the sinus hair of the face and carpus. Immunohistochemically, Merkel cells were positive for cytokeratin (CK) 20, CK18, p63, neuron-specific enolase, synaptophysin, and protein gene product 9.5. Merkel cell carcinoma was detected as a solitary cutaneous mass in 3 aged cats (13 to 16 years old). On cytology, large lymphocyte-like cells were observed in all cases. Histologic examinations of surgically resected tumors revealed nests of round cells separated by various amounts of a fibrous stroma. Tumor cells were commonly immunopositive for CK20, CK18, p63, neuron-specific enolase, and synaptophysin, representing the characteristics of normal Merkel cells. © The Author(s) 2015.

  8. Synchronous primary carcinoid tumor and primary adenocarcinoma arising within mature cystic teratoma of horseshoe kidney: a unique case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Perepletchikov Aleksandr M

    2009-06-01

    teratomatous cyst wall showed strong staining for smooth muscle actin, and weak staining for carbonic anhydrase IX, CD99, chromogranin and synaptophysin. The adenocarcinoma component was strongly positive for cytokeratin 7 and pancytokeratin, weakly positive for synaptophysin and CD56, and negative for carbonic anhydrase IX, CD99, CDX2, chromogranin, cytokeratin 20 and smooth muscle actin. The carcinoid tumor component was strongly positive for CD56, chromogranin and synaptophysin, weakly positive for pancytokeratin, and negative for carbonic anhydrase IX, CD99, CDX2, cytokeratin 7, cytokeratin 20 and smooth muscle actin. She received no adjuvant therapy and is alive without evidence of disease six months after diagnosis and surgery. Conclusion This unique and first case herein presented with synchronous primary carcinoid tumor and primary adenocarcinoma arising within mature cystic teratoma of horseshoe kidney emphasizes the need for thorough sectioning and entire submission for histologic evaluation of mature cystic teratomas, in order to avoid missing multiple additional histogenetically distinct neoplasms.

  9. Neuroendocrine carcinoma of the ampulla of Vater causing ectopic adrenocorticotropic hormone-dependent Cushing's syndrome.

    Science.gov (United States)

    Kato, Akihisa; Hayashi, Kazuki; Naitoh, Itaru; Seno, Kyoji; Okada, Yukiko; Ban, Tesshin; Kondo, Hiromu; Nishi, Yuji; Umemura, Shuichiro; Hori, Yasuki; Natsume, Makoto; Joh, Takashi

    2016-07-01

    Ectopic adrenocorticotropic hormone (ACTH) is rarely secreted by neuroendocrine tumors. Although neuroendocrine tumors may occur at any site in the gastrointestinal system, they very rarely occur in the ampulla of Vater and have a poor prognosis. The present study described the first Cushing's syndrome as a result of ectopic ACTH arising from the ampulla of Vater neuroendocrine carcinoma. A 69-year-old female was admitted with clinical features of Cushing's syndrome, confirmed biochemically by hypokalemia, and elevated levels of ACTH and cortisol. In further investigations, a tumor of the ampulla of Vater and liver metastases were detected. Pathological analysis of the biopsy confirmed a neuroendocrine carcinoma, which was immunohistochemically positive for chromogranin A, synaptophysin, cluster of differentiation 56 and ACTH. Therefore, the present study diagnosed a functional and metastatic neuroendocrine carcinoma of the ampulla of Vater with ectopic ACTH production causing Cushing's syndrome. The patient succumbed to mortality 4 months later, despite administration of combined chemotherapy with irinotecan and cisplatin.

  10. Small cell type neuroendocrine carcinoma colliding with squamous cell carcinoma at esophagus

    Science.gov (United States)

    Yang, Luoluo; Sun, Xun; Zou, Yabin; Meng, Xiangwei

    2014-01-01

    Collision tumor is an extremely rare tumor which defined as the concrescence of two distinct primaries neoplasms. We report here a case of collision tumor at lower third esophagus composed of small cell type neuroendocrine carcinoma (NEC), which is an very rare, highly aggressive and poorly prognostic carcinoma and squamous cell carcinoma (SqCC). In our case, pathologically, the small cell carcinoma display the characteristic of small, round, ovoid or spindle-shaped tumor cells with scant cytoplasm, which colliding with a moderately differentiated squamous cell carcinoma. Immunohistochemical staining demonstrated positive activities for CD56, synaptophysin, 34βE12, CK 5/6, ki-67 (70%-80%), but negative for CD99, chromogranin A, and TTF-1. Accurate diagnosis was made base on these findings. PMID:24817981

  11. A Primary Pulmonary Glomus Tumor: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Yasushi Ariizumi

    2012-01-01

    Full Text Available A case of a glomus tumor originating from the lung is reported. A 43-year-old female had undergone resection of a right lung tumor following a clinical diagnosis of carcinoid, sclerosing hemangioma, or other sarcoma. Histologically, the tumor comprised uniform small round to oval cells with centrally located nucleus, a clear cytoplasm, and apparent cell borders. The tumor also showed a focally hemangiopericytomatous pattern with irregularly branching or dilated vessels. Electron microscopy revealed smooth muscle differentiation of the tumor cells. Immunostaining further revealed that the tumor cells expressed smooth muscle actin, h-caldesmon, muscle specific actin (HHF-35, but not cytokeratin, epithelial membrane antigen, synaptophysin, or chromogranin A. Based on these findings, a diagnosis of primary pulmonary glomus tumor was established. Glomus tumors of the lung are very rare and only 21 cases have been reported to date. The histological features of the present tumor and the relevant literature are discussed.

  12. Goblet cell carcinoid: Case report

    Directory of Open Access Journals (Sweden)

    Ulaş Alabalık

    2013-03-01

    Full Text Available The mixt endocrine-exocrine carcinoma of the appendix,being a rare tumor, makes up a very little part of all gastrointestinalsystem tumors. These tumors are thought tobe the intermediary tumors taking place between adenocarcinomasand endocrine tumors. Generally they areseen in the 5th -6th decades equally in males and females.Being very characteristic, the histomorphological pictureof goblet cell carcinoid consists of atypical epithelial cellswith conspicuous nucleoli that make small abortive glandsdemonstrating scattered nests under surface epitheliumand containing Goblet cells. The tumor exhibits transmuralspread producing mucin pools designating positiveimmunoreaction histochemically with musicarmenstain. In addition to CEA and keratin expressions, thereis neuroendocrine differentiation that may be illustratedboth immunohistochemically and ultrastructurally. In ourcase, under the appendix epithelium we determined atumor that was formed by gland structures lined by mucinousepithelial cells with conspicuous nucleoli, growingforward to the muscle layer and seeming invasive. Weestablished that the tumor expressed PanCK, synaptophysin,chromogranin and CEA in immunohistochemicalstudy and stained positively with PAS, PAS-AB andmusicarmen in histochemical study. We considered thecase as goblet cell carcinoid when clinical, histopathological,histochemical and immunohistochemical data wereassessed together. In the time interval 2 years after theoperation, any recurrence and/or metastase was not determined.Key words: Goblet cell carcinoid, CEA, chromogranin A,PAS-AB, musicarmen

  13. Duodenal neuroendocrine tumor and the onset of severe diabetes mellitus in a US veteran

    Directory of Open Access Journals (Sweden)

    Lauren Murray

    2016-01-01

    Full Text Available Objective: Neuroendocrine tumors are neoplasms derived from endocrine cells, most commonly occurring in the gastrointestinal tract. Duodenal neuroendocrine tumors are rare tumors averaging 1.2–1.5 cm, and most are asymptomatic. Common presentation is abdominal pain, upper gastrointestinal bleed, constipation, anemia, and jaundice. Methods: An adult, Black, male patient with newly diagnosed diabetes mellitus presented to the emergency department with elevated liver function test and fatigue. Results: Magnetic resonance cholangiopancreatography demonstrated a large obstructing mass (3.6 cm × 4.4 cm × 3 cm within the second and third portions of the duodenum at the ampulla. Esophagogastroduodenoscopy demonstrated an ulcerated duodenal mass that was biopsied. Immunohistochemical stains were positive for synaptophysin, chromogranin B, and CK7. Chromogranin A was in normal range. Post-Whipple procedure demonstrated a 5.5 cm × 4.1 cm × 2.9 cm duodenal mass with invasion of the subserosal tissue of the small intestine, a mitotic rate of 2 per high-power field, and antigen Ki-67 of 2%–5%. Conclusion: This case raises the question as to if the patient developed diabetes mellitus due to the tumor size and location or if the new onset of diabetes was coincidental. This case also demonstrates the importance of a proficient history and physical.

  14. Spontaneous regression in an ulcerated CK7 positive Merkel cell carcinoma

    Directory of Open Access Journals (Sweden)

    Anza Khader

    2015-01-01

    Full Text Available Merkel cell carcinoma is an aggressive and frequently lethal tumor of the elderly, associated with sun exposure and immunosuppression which is less common in the dark-skinned. We report the case of a 40-year-old woman who presented with multiple slowly progressive, mildly itchy ulcerated plaques of size ranging from 2 × 3 cm to 5 × 7 cm on the left knee of 1 year duration. Skin biopsy showed diffuse dermal infiltration by small round cells with molding of cells and lymphocyte infiltration. The cells stained positive for cytokeratin (CK 20, CK7, neuron-specific enolase, and chromogranin. The skin lesions underwent spontaneous regression within 1 month of skin biopsy and have not recurred during the past 2 years. The immune mechanisms triggered by biopsy possibly explain the spontaneous regression.

  15. Microscopic colitis in Egyptian population: study of some contributing factors and role of chromogranin A as a diagnostic marker

    Directory of Open Access Journals (Sweden)

    Mohamed S Gomaa

    2017-01-01

    Conclusion The initial results of our study revealed that MC is not an uncommon disease, and there was a significant correlation between using NSAID and proton pump inhibitor and smoking, with cases proved to have MC.

  16. RNAi-mediated silencing of enolase confirms its biological importance in Clonorchis sinensis.

    Science.gov (United States)

    Wang, Xiaoyun; Chen, Wenjun; Tian, Yanli; Huang, Yan; Li, Xuerong; Yu, Xinbing

    2014-04-01

    Clonorchis sinensis (C. sinensis) infection is still a common public health problem in freshwater fish consumption areas in Asian countries. More molecular evidence are required to speed up the prevention strategies to control this kind of infectious disease. In the present study, to confirm the biological importance of Csenolase followed by our previous observations of the key metabolic enzyme, we explored the RNA silence effect of the Csenolase-derived RNA interference (RNAi) in C. sinensis. The extramembranous region aa105-226 was selected as the target sequence of RNA silence. Csenolase-derived double strand RNA (dsRNA-Csenolase, 366 bp) was synthetized and delivered into C. sinensis by soaking approach. The penetration of dsRNA into adult worms and metacercariae was tracked using fluorescently labeled RNA. Western blotting and qRT-PCR experiments were performed to determine dsRNA-Csenolase-silencing effect. Our results showed that, after incubating for 120 h, dsRNA-Csenolase could effectively target and downregulate the expression of Csenolase in both adult worms (P sinensis adult worms (P sinensis, allowing further applications in identifying functional genes in C. sinensis.

  17. S-100b and neuron-specific enolase in patients with fulminant hepatic failure

    DEFF Research Database (Denmark)

    Strauss, Gitte Irene; Christiansen, Michael; Møller, Kirsten

    2001-01-01

    , the cerebral flux of S-100b and NSE was measured. We included 35 patients with FHF, 6 patients with acute on chronic liver disease (AOCLD), 13 patients with cirrhosis of the liver without hepatic encephalopathy, and 8 healthy subjects. Blood samples were obtained from catheters placed in the radial artery...

  18. Release of erythropoietin and neuron-specific enolase after breath holding in competing free divers

    DEFF Research Database (Denmark)

    Kjeld, Thomas; Jattu, T; Nielsen, Henrik

    2015-01-01

    , and troponin T. Venous blood samples were obtained from 17 competing free divers before and 3 h after sessions of static apnea and underwater swimming. The heart was evaluated by echocardiography. Static apnea for 293 ± 78 s (mean ± SD) and subsequent 88 ± 21 m underwater swimming increased plasma...

  19. Catalase and alpha-enolase : two novel granulocyte autoantigens in inflammatory bowel disease (IBD)

    NARCIS (Netherlands)

    Roozendaal, C; Zhao, MH; Horst, G; Lockwood, CM; Kleibeuker, JH; Limburg, PC; Nelis, GF; Kallenberg, CGM

    1998-01-01

    In IBD, the target antigens of anti-neutrophil cytoplasmic autoantibodies (ANCA) have not been fully identified, which limits the analysis of the diagnostic significance as well as of the possible pathophysiological role of these antibodies. In this study, we identify the target antigens of ANCA in

  20. Catalase and alpha-enolase: two novel granulocyte autoantigens in inflammatory bowel disease (IBD)

    NARCIS (Netherlands)

    Roozendaal, C.; Zhao, M.H.; Lockwood, C.M.; Kleibeuker, Jan; Limburg, Piet; Nelis, G.F.; Kallenberg, Cees; Horst, G.

    1998-01-01

    In IBD, the target antigens of anti-neutrophil cytoplasmic autoantibodies (ANCA) have not been fully identified, which limits the analysis of the diagnostic significance as well as of the possible pathophysiological role of these antibodies. In this study, we identify the target antigens of ANCA in

  1. Primary male neuroendocrine adenocarcinoma involving the nipple simulating Merkel cell carcinoma - a diagnostic pitfall.

    Science.gov (United States)

    Mecca, Patricia; Busam, Klaus

    2008-02-01

    Male breast cancer is a rare entity accounting for Nipple skin/subcutaneous tumors in men are even rarer. Likewise, true neuroendocrine carcinoma of the breast, defined as > 50% of tumor cells staining for either chromogranin or synaptophysin, is not a common entity, usually occurring in older women. We present the case of a 70-year-old man with a slowly growing nipple mass that had enlarged over the previous 1.5 years. The histology consisted of nests, trabeculae and sheets of basaloid cells with rare abortive gland formation and a pushing edge. The case was originally misdiagnosed as a Merkel cell carcinoma, based largely on histologic morphology. Strong staining for synaptophysin (in greater than 50% of cells), CD56, keratins AE1 : AE3 and Cam 5.2, as well as estrogen receptor and progesterone receptor was noted. Myoepithelial cells within in situ areas were identified using stains for calponin and 4A4, supporting a primary mammary duct origin. Additionally, a substantial portion of cells stained for Gross Cystic Disease Fluid Protein-15 (GCDFP-15), confirming some overlap with sweat duct differentiation. To the best of our knowledge, although reported in the male breast, no case of primary nipple neuroendocrine carcinoma in a male patient has been reported in the literature. The gender of the patient and association with the skin of the chest wall probably contributed to the original misdiagnosis of Merkel cell carcinoma in this patient.

  2. Fetal presentation of congenital fibrosarcoma of the meninges: case report and literature review.

    Science.gov (United States)

    Marguet, Florent; Bergogne, Lise; Laurent, Nicole; Rousseau, Thierry; Laquerrière, Annie

    2015-01-01

    Congenital infantile fibrosarcoma (CIFS) exceptionally occurs in the meninges, with no cases reported before or at birth. We report herein a meningeal CIFS diagnosed in a fetus at 40 weeks of gestation (WG). A 24-year-old pregnant woman was referred to the obstetrics department for vaginal bleeding. A severe right hydrocephalus due to a large tumor invading the left hemisphere and ventricles was discovered in the fetus, and medical termination of the pregnancy was achieved. Histological examination revealed a highly cellular spindle or ovoid shaped cell proliferation organized in interlacing bundles; it was diffusely positive for vimentin, and scarcely for SMA (smooth muscle actin). NFs (neurofilaments), NeuN, S100 protein, desmin, GFAP (glial fibrillary acidic protein), Olig2, chromogranin, synaptophysin, CD31, CD34, BCL2, and EMA (epithelial membrane antigen) antibodies were negative. Ki67 antibody labeled 20% of the nuclei. A reverse transcription polymerase chain reaction assay was performed to detect the gene fusion ETV6-NTRK3 transcript. Despite negative results, it was concluded to be a CIFS of the meninges. CIFS of the meninges during the fetal period has never been reported. Its diagnosis is based on immunohistochemistry, and, whenever possible, on the detection of the reciprocal translocation t (12;15) resulting in the gene fusion ETV6-NTRK3. Its prognosis depends on rapid growth and local invasiveness leading to cerebral structure damage.

  3. A rare case with synchronous gastric gastrointestinal stromal tumor, pancreatic neuroendocrine tumor, and uterine leiomyoma.

    Science.gov (United States)

    Arabadzhieva, Elena; Yonkov, Atanas; Bonev, Sasho; Bulanov, Dimitar; Taneva, Ivanka; Vlahova, Alexandrina; Dikov, Tihomir; Dimitrova, Violeta

    2016-11-15

    Although gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, they comprise less than 1% of all gastrointestinal tumors. Neuroendocrine tumors (NET) of the gastro-enteropancreatic system are also rare, representing about 2% of all gastrointestinal neoplasms. Pancreatic localization of NET is extremely uncommon-these tumors are only 1-5% of all pancreatic cancers. We describe an unusual case with triple tumor localization-a gastric tumor, a formation in the pancreas, which involves the retroperitoneal space, and a uterine leiomyoma. The exact diagnosis was confirmed with immunohistochemical study after surgical treatment of the patient. Distal pancreatic resection, splenectomy, partial gastrectomy, omentectomy, and hysterectomy were performed. The histological examination proved an epithelioid type of gastric GIST. Immunostaining showed focal positive expression of c-kit and no mitotic figures per 50 HPF. Histology of the pancreatic and retroperitoneal formation proved a well-differentiated NET with origin from the islets of Langerhans. The immunohistochemical study demonstrated co-expression of chromogranin A and synaptophysin. This is the fourth case published so far of a patient with synchronous pancreatic NET and gastric GIST. The main objective of the study is to present a unique case because we have not found any reports for coexistence of the described three types of neoplasm, as in our patient, and we hope that it will be valuable in the future investigations about the genesis, diagnosis, and treatment of these types of tumors.

  4. Carcinome neuroendocrine thymique: à propos d’un cas et revue de la littérature

    Science.gov (United States)

    Ramahandrisoa, Andriatsihoarana Voahary Nasandratriniavo; Hasiniatsy, Nomeharisoa Rodrigue Emile; Refeno, Valéry; Vololonantenaina, Clairette Raharisolo; Rakotoarisoa, Andriamihaja Jean Claude; Rakotovao, Hanitrala Jean Louis; Rafaramino, Florine

    2017-01-01

    Les tumeurs neuroendocrines thymiques (TNET) sont rares, de pronostic mal connu. L'objectif est de rapporter un cas de TNET et discuter la difficulté diagnostique et thérapeutique en milieu à faibles ressources. Un homme de 60 ans présentait une douleur thoracique, une toux grasse et un amaigrissement récent. Le scanner thoracique révélait une masse tissulaire médiastinale antérieure. L'histologie définitive obtenue quatre mois après la biopsie par médiastinotomie antérieure montrait une TNET bien différenciée, avec marquage intense à la chromogranine et à la synaptophysine. La recherche d'autres tumeurs neuroendocrines et le bilan d'extension étaient négatifs. La tumeur était inextirpable d'emblée et la radiothérapie indisponible. Le patient a reçu deux lignes de chimiothérapie première. Avec un recul de 16 mois, le patient était asymptomatique, mais en progression tumorale. Le diagnostic de TNET peut être retardé quand l'examen immunohistochimique n'est pas réalisé en routine. La chimiothérapie apporte une amélioration des symptômes en situation palliative. PMID:28451004

  5. Pituitary null cell adenoma in a domestic llama (Lama glama).

    Science.gov (United States)

    Chalkley, M D; Kiupel, M; Draper, A C E

    2014-07-01

    Pituitary gland neoplasia has been reported rarely in camelids. A 12-year-old neutered male llama (Lama glama) presented with lethargy, inappetence and neurological signs. On physical examination, the llama was mentally dull and exhibited compulsive pacing and circling to the left. Complete blood count and serum biochemistry revealed haemoconcentration, mild hypophosphataemia, hyperglycaemia, hypercreatininaemia and hyperalbuminaemia. Humane destruction was elected due to rapid clinical deterioration and poor prognosis. Post-mortem examination revealed a pituitary macroadenoma and bilateral internal hydrocephalus. Microscopically, the pituitary tumour was composed of neoplastic chromophobic pituitary cells. Ultrastructural studies revealed similar neoplastic cells to those previously described in human null cell adenomas. Immunohistochemically, the neoplastic cells were strongly immunoreactive for neuroendocrine markers (synaptophysin and chromogranin A), but did not exhibit immunoreactivity for epithelial, mesenchymal, neuronal and all major pituitary hormone markers (adrenocorticotropic hormone, follicle stimulating hormone, growth hormone, luteinizing hormone, melanocyte-stimulating hormone, prolactin and thyroid stimulating hormone), consistent with the diagnosis of a pituitary null cell adenoma. This is the first report of pituitary neoplasia in a llama. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Surgical treatment of a rare primary renal carcinoid tumor with liver metastasis

    Directory of Open Access Journals (Sweden)

    Rowland Randall G

    2008-04-01

    Full Text Available Abstract Background Carcinoid tumors are characteristically low grade malignant neoplasms with neuroendocrine differentiation that arise in various body sites, most commonly the lung and gastrointestinal tract, but less frequently the kidneys, breasts, ovaries, testes, prostate and other locations. We report a case of a carcinoid of renal origin with synchronous single liver metastases on radiological studies. Case presentation A 45 year-old patient who presented with abdominal pain was found on CT scan to have lesions in the right ovary, right kidney, and left hepatic lobe. CA-125, CEA, and CA 19-9 were within normal limits, as were preoperative liver function tests and renal function. Biopsy of the liver mass demonstrated metastatic neuroendocrine tumor. At laparotomy, the patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy, radical right nephrectomy with lymphadenectomy, and left hepatectomy. Pathology evaluation reported a right ovarian borderline serous tumor, well-differentiated neuroendocrine carcinoma of the kidney (carcinoid with 2 positive retroperitoneal lymph nodes, and a single liver metastasis. Immunohistochemistry revealed that this lesion was positive for synaptophysin and CD56, but negative for chromogranin as well as CD10, CD7, and CD20, consistent with a well-differentiated neuroendocrine tumor. She is doing well one year after her initial surgery, with no evidence of tumor recurrence. Conclusion Early surgical intervention, together with careful surveillance and follow-up, can achieve successful long-term outcomes in patients with this rare malignancy.

  7. Neuroendocrine Carcinoma of the Stomach: A Case Study

    Directory of Open Access Journals (Sweden)

    Keisuke Kubota

    2011-01-01

    Full Text Available Gastric neuroendocrine carcinomas are rare and have a poor prognosis, and the diagnostic criteria for this disease have recently changed. We herein report a case of sporadic gastric neuroendocrine carcinoma. A 75-year-old man was referred to our hospital with epigastric pain. Endoscopic examination revealed a localized ulcerative lesion (diameter, 4 cm at the upper stomach. The diagnosis on biopsy was neuroendocrine carcinoma. Total gastrectomy with D2 lymphadenectomy, splenectomy, and cholecystectomy was performed. Pathologically, the tumor infiltrated the subserosal layer, and 6/49 lymph nodes were involved. The tumor was uniform in shape and arranged in a rosette-like structure to form solid nests, with medium-sized, round-to-cuboid-shaped tumor cells and intense mitosis 46/10 HPF. It was positive for synaptophysin and chromogranin A, and the Ki-67 labeling index was 70–80%. The diagnosis of neuroendocrine carcinoma was made according to the WHO 2010 criteria. The patient was followed up for three years without recurrence.

  8. Neoplasm carcinoid: Description of a case

    International Nuclear Information System (INIS)

    Carrillo, Luis; Abarca, Jaysoom; Penaherrera, Vicente; Legarda, Eduardo

    2004-01-01

    We describe a case of small bowel obstruction associated with a carcinoid neoplasm of the ileum in a 78 year old man who was presented with abdominal pain, vomiting, and a mass in right lower quadrant. Carcinoids are neuroendocrine neoplasm originating in multiple locations throughout the body human. About 75% of such neoplasm are located within the gastrointestinal tract and are capable of rpoducing various peptides. Their clinical course is often indolent but can also be aggressive and resistant to therapy. The incidence of these tumours is approximately 2.5 in 100.000 people per year. The former classification system of fore gut, midgut and hind gut tumors is still used in clinical routine. Determination of the histopathology of carcinoid tumors is of utmost importance and involves specific immunohistochemical staining for chromogranin A, synaptophysin, serotonin and gastrin. New localization procedures include somatostatin receptor scintigraphy and positron emission tomography. Surgery remains the cornerstone of treatment and provides the only chance of a cure. Other cytoreductive procedures include radiofrequency ablation, laser treatment and chemo embolization. New therapies, such as ling acting somatostatin analogs, together with further development of tumor targeted treatments, will come into clinical use in the near future. (The author)

  9. Primary Small Cell Carcinoma of the Stomach Successfully Treated With Cisplatin and Etoposide

    Directory of Open Access Journals (Sweden)

    Shu-Chen Kuo

    2009-11-01

    Full Text Available We report a 44-year-old man with primary gastric small cell carcinoma who showed a remarkable response to chemotherapy specific for pulmonary small cell carcinoma. The patient had been admitted to another local hospital because of intermittent epigastralgia. An upper gastrointestinal examination there revealed an ulcerative tumor, 5 cm in diameter, on the lesser curvature side of the cardia, and endoscopic biopsy reported adenocarcinoma. Computed tomography revealed a mass over the lesser curvature of the stomach and some enlarged regional lymph nodes. Radical total gastrectomy, lymph node dissection, Roux-en-Y esophagojejunostomy and splenectomy were performed at our hospital. Pathology revealed gastric mucosa infiltrated by small-sized tumor cells with scanty cytoplasm and hyperchromatic nuclei. Immunohisto- chemically, the tumor cells were positive for synaptophysin, chromogranin A, and CD56. Primary gastric small cell carcinoma was diagnosed. The postoperative course, complicated by shock due to bleeding, wound infection and intra-abdominal abscess, took more than 2 months to resolve. Follow-up computed tomography showed tumor recurrence with multiple enlarged lymph nodes in the aortocaval region and hepatic hilum. The patient received palliative chemotherapy consisting of cisplatin 80 mg/m2 on day 1 and etoposide 80 mg/m2 on days 1–3 every 28 days, and had partial response to the chemotherapy, with a progression-free survival of 10 months. Chemotherapy with cisplatin and etoposide used for small cell carcinoma of the lung is a good treatment for gastric small cell carcinoma.

  10. Adolescent Neuroblastoma of Lower Limb

    Directory of Open Access Journals (Sweden)

    Rajeshwari K

    2013-04-01

    Full Text Available Neuroblastoma is an embryonic tumour of neural crest origin, commonly seen in children with upper abdomen involvement. Rarely neuroblastomas present in adolescents and adults involving lower limb. Histopathologically neuroblastoma of lower limb can be confused with other small round cell tumour especially with Ewing's sarcoma and rhabdomyosarcoma. A 16 year old male presented with 15x11cm swelling, pain and multiple discharging sinuses of right leg since 4 months. Routine haematological and biochemical analysis were within normal limits. Radiology of right leg showed large soft tissue swelling encompassing the pathological fracture of tibia and bowing of fibula. Fine needle aspiration of the swelling revealed malignant small round cell tumour. Histopathology revealed poorly differentiated neuroblastoma of lower limb. The immunohistochemistry of Synaptophysin and Chromogranin were positive and CD 99 was negative. Neuroblastoma diagnosed at unusual site with uncommon age has poor prognosis. Hence, one must keep in mind the differential diagnosis of neuroblastoma as one of the differential diagnosis in evaluating the soft tissue tumours of lower limb.

  11. FNAB cytology of extra-cranial metastasis of glioblastoma multiforme may resemble a lung primary: A diagnostic pitfall

    Directory of Open Access Journals (Sweden)

    Dincer HE

    2005-01-01

    Full Text Available Abstract Background As extra-cranial metastasis of glioblastoma multiforme (GBM is rare, it may create a diagnostic dilemma especially during interpretation of fine needle aspiration biopsy (FNAB cytology. Case presentation We present transbronchial FNAB findings in a 62-year-old smoker with lung mass clinically suspicious for a lung primary. The smears of transbronchial FNAB showed groups of cells with ill-defined cell margins and cytological features overlapping with poorly differentiated non-small cell carcinoma. The tumor cells demonstrated lack of immunoreactivity for cytokeratin, thyroid transcription factor-1, and usual neuroendocrine markers, synaptophysin and chromogranin in formalin-fixed cellblock sections. However, they were immunoreactive for the other neuroendocrine immunomarker, CD56, suggesting neural nature of the cells. Further scrutiny of clinical details revealed a history of GBM, 13 months status-post surgical excision with radiation therapy and systemic chemotherapy. The tumor recurred 7 months earlier and was debulked surgically and with intra-cranial chemotherapy. Additional evaluation of tumor cells for glial fibrillary acidic protein (GFAP immunoreactivity with clinical details resulted in final interpretation of metastatic GBM. Conclusion Lack of clinical history and immunophenotyping may lead to a diagnostic pitfall with possible misinterpretation of metastatic GBM as poorly differentiated non-small cell carcinoma of lung in a smoker.

  12. A case report of metastatic neuroendocrine carcinoma of the right adrenal gland successfully treated with chemotherapy and surgery.

    Science.gov (United States)

    Ochiai, Toshiya; Komiyama, Sosuke; Ikoma, Hisashi; Kubota, Takeshi; Nakanishi, Masayoshi; Ichikawa, Daisuke; Kikuchi, Shojiro; Fujiwara, Hitoshi; Sakakura, Chohei; Kokuba, Yukihito; Sonoyama, Teruhisa; Otsuji, Eigo

    2010-08-01

    Poorly differentiated neuroendocrine carcinoma has a poor prognosis, especially when associated with distant metastasis. A 60-year-old man was admitted to a private hospital because of dyspnea at work in 2007. Computed tomography revealed lung infarction and a right adrenal tumor sized 12 cm in diameter that was tightly compressed against the inferior vena cava (IVC). Moreover, multiple lymph node metastases around the celiac axis and a solitary liver metastasis at the lateral segment were observed. Thus, we planned chemotherapy without surgery. We selected a combination therapy of irinotecan (CPT-11) and cisplatin (CDDP) (i.e., IP therapy): administration of CDDP [60 mg/m(2) body surface area (BSA)] on day 1 plus CPT-11 (80 mg/m(2)) BSA on days 1 and 8. Thereafter, this protocol was repeated at 3-week intervals. After 15 months of this chemotherapy strategy, the whole lesions showed a partial response by RECIST. The primary tumor had shrunk to 4.2 cm in diameter. In November 2008, we planned surgery to perform resection of the whole lesions. Histological diagnosis of the specimen was a poorly differentiated neuroendocrine carcinoma based on the immunostaining features, i.e., synaptophysin- and chromogranin positive. There were no viable tumor cells at the dissected lymph nodes or at the liver tumor. After surgery, CPT-11 administration was continued. The patient has remained well for 9 months without recurrence.

  13. Ependymoma and Carcinoid Tumor Associated with Ovarian Mature Cystic Teratoma in a Patient with Multiple Endocrine Neoplasia I

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    Reed Spaulding

    2014-01-01

    Full Text Available Ovarian teratomas rarely undergo new neoplastic transformation and account for a small percentage of malignant ovarian germ cell neoplasms. Here we report a case of a 51-year-old woman with multiple endocrine neoplasia type I (MEN I who was found to have an ependymoma and neuroendocrine tumor (trabecular carcinoid associated with mature cystic teratoma of her left ovary. The ependymoma component displayed cells with round nuclei and occasional small nucleoli which were focally arranged in perivascular pseudorosettes and true rosettes. Rare mitoses were identified. No necrosis was present. Immunohistochemical staining was positive for S-100 and GFAP. The Ki67 proliferation index was very low (2-3%. In contrast, the endocrine tumor component was composed of small uniform cells with eosinophilic cytoplasm, round nuclei, and speckled chromatin. Immunohistochemical staining was positive for synaptophysin and focally positive for chromogranin. This rare case illustrates that MEN I may have an influence on the pathogenesis of ovarian teratomas as they undergo malignant transformation.

  14. Hirschsprung′s disease diagnosis: Comparison of immunohistochemical, hematoxilin and eosin staining

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    Memarzadeh Mehrdad

    2009-01-01

    Full Text Available Background : The diagnosis of Hirschsprung′s disease (HD is based on the absence of ganglion cells. In hemotoxilin and eosin (H and E as well as acetylcholine esterase staining there are limitations in the diagnosis of immature ganglion cells in neonates. Methods : In this prospective study, 54 biopsies taken from suspected HD patients (five mucosal specimens and 49 full thickness specimens were studied. In the laboratory, after preparing sections of paraffin embedded tissues, H and E staining slides were compared with immunohistochemical (IHC staining including: S100, NSE, CD117, CD56, Cathepsin D, Vimentin, BCL2, GFAP, Synaptophysin and chromogranin. Results : The study revealed 30 negative (absence of ganglion cells cases (55.5%, 17 positive cases (31.04% and seven suspected cases (12.9% of ganglion cells on the H and E staining. On IHC staining with CD56 and Cathepsin D, all of the 17 positive cases detected through H and E, were confirmed for having ganglion cells and out of 30 cases reported negative on H and E staining, 28(93.3% were reported negative and two (6.7% positive by IHC staining. Of the seven suspected cases H and E staining, IHC staining detectedganglion cells only in five slides; two remained negative. Conclusions : IHC staining using CD56 and Cathepsin D improved the accuracy of diagnosis in HD when used in addition to H and E staining technique, especially for negative or suspicious slides.

  15. Hirschsprung's disease diagnosis: Comparison of immunohistochemical, hematoxilin and eosin staining

    Science.gov (United States)

    Memarzadeh, Mehrdad; Talebi, Ardeshir; Edalaty, Masod; Hosseinpour, Mehrdad; Vahidi, Nasrin

    2009-01-01

    Background: The diagnosis of Hirschsprung's disease (HD) is based on the absence of ganglion cells. In hemotoxilin and eosin (H and E) as well as acetylcholine esterase staining there are limitations in the diagnosis of immature ganglion cells in neonates. Methods: In this prospective study, 54 biopsies taken from suspected HD patients (five mucosal specimens and 49 full thickness specimens) were studied. In the laboratory, after preparing sections of paraffin embedded tissues, H and E staining slides were compared with immunohistochemical (IHC) staining including: S100, NSE, CD117, CD56, Cathepsin D, Vimentin, BCL2, GFAP, Synaptophysin and chromogranin. Results: The study revealed 30 negative (absence of ganglion cells) cases (55.5%), 17 positive cases (31.04%) and seven suspected cases (12.9%) of ganglion cells on the H and E staining. On IHC staining with CD56 and Cathepsin D, all of the 17 positive cases detected through H and E, were confirmed for having ganglion cells and out of 30 cases reported negative on H and E staining, 28(93.3%) were reported negative and two (6.7%) positive by IHC staining. Of the seven suspected cases H and E staining), IHC staining detectedganglion cells only in five slides; two remained negative. Conclusions: IHC staining using CD56 and Cathepsin D improved the accuracy of diagnosis in HD when used in addition to H and E staining technique, especially for negative or suspicious slides. PMID:20671847

  16. Neuroendocrine and squamous colonic composite carcinoma: Case report with molecular analysis

    Institute of Scientific and Technical Information of China (English)

    Sabrina C Wentz; Cindy Vnencak-Jones; William V Chopp

    2011-01-01

    Composite colorectal carcinomas are rare. There are a modest number of cases in the medical literature, with even fewer cases describing composite carcinoma with neuroendocrine and squamous components. There are to our knowledge no reports of composite carcinoma molecular alterations. We present a case of composite carcinoma of the splenic flexure in a 33 year-old Cau casian male to investigate the presence and prognos tic significance of molecular alterations in rare colonic carcinoma subtypes. Formalin-fixed paraffin-embedded (FFPE) tissue was hematoxylin and eosin- and mucicar-mine-stained according to protocol, and immuno-stained with cytokeratin (CK)7, CK20, CDX2, AE1/AE3, chromo-granin-A and synaptophysin. DNA was extracted from FFPE tissues and molecular analyses were performedaccording to lab-developed methods, followed by capil lary electrophoresis. Hematoxylin and eosin staining showed admixed neuroendocrine and keratinized squa mous cells. Positive nuclear CDX2 expression confirmed intestinal derivation. CK7 and CK20 were negative. Neuroendocrine cells stained positively for synaptophy sin and AE1/AE3 and negatively for chromogranin and mucicarmine. Hepatic metastases showed a similar im munohistochemical profile. Molecular analysis revealed a G13D KRAS mutation. BRAF mutational testing was negative and microsatellite instability was not detected. The patient had rapid disease progression on chemo therapy and died 60 d after presentation. Although the G13D KRAS mutation normally predicts an intermediate outcome, the aggressive tumor behavior suggests other modifying factors in rare types of colonic carcinomas.

  17. Basaloid carcinoma of the pancreas--clinicopathological presentation and oncogenetic snapshot of a rare entity.

    Science.gov (United States)

    Szasz, A Marcell; Szirtes, Ildiko; Tihanyi, Balazs; Barkaszi, Bernadett; Baranyai, Zsolt; Tihanyi, Tibor; Harsanyi, Laszlo; Timar, Jozsef; Kulka, Janina

    2015-02-01

    We report a case of basaloid pancreatic carcinoma with clinical, pathological, and genomic data. The 73-year-old male patient had jaundice, acholic stool, diarrhea, weight loss, and a large, painless gall bladder. His GGT was highly elevated. The pancreatic head contained a tumor, which was resected by partial pancreatoduodenectomy with pancreato-gastric anastomosis, cholecystectomy, and lymphadenectomy. On gross examination, a 3.8-cm white firm nodule was found, which microscopically was composed of basaloid cell nests with a less than usual desmoplastic stromal background and focally PANIN. Immunohistochemical profile displayed strong CK5/6, CK19, p63, EGFR, vimentin, and evident CK14 expression and absence of expression of CK7, chromogranin, synaptophysin, and BRCA1. A high Ki-67 index and p53 expression were noted. Sequencing of the most frequent 46 oncogenes with ionTorrent (AmpliSeq PCR) method identified PIK3CA, KRAS, and TP53 genes as drivers and variants of the FGFR3, PDGFRA, KIT, KDR, EGFR, RET, and ATM genes. The tumor we report displays histopathological appearances similar to the previously described case and a genomic landscape fitting to the general population of pancreatic carcinomas. We hypothesize that this tumor may belong to the group of DNA damage repair-deficient pancreatic carcinoma subgroup.

  18. Primary clear cell ductal adenocarcinoma of the pancreas: A case report and clinicopathologic literature review

    Directory of Open Access Journals (Sweden)

    Yashpal Modi

    2014-01-01

    Full Text Available We present a very rare, interesting case of a carcinoma of the pancreas with predominantly abundant clear cell morphology. According to the WHO classification, primary clear cell carcinoma of the pancreas is classified as a rare "miscellaneous" carcinoma. The tumor was observed in the distal body and tail of the pancreas of a 74-year-old woman. The histopathology of tumor cells showed well-defined cell membranes, clear cytoplasm, and prominent cell boundaries. Immunohistochemical (IHC staining showed positive reactions to antibodies against vimentin, cytokeratin 7 (CK-7, mucicarmine (MUC-1, periodic acid-Schiff (PAS, periodic acid-Schiff with diastase (PASD, carcinoembryonic antigen (CEA, and Carbohydrate Antigen 19-9 (CA 19-9. On the other hand, IHC staining was negative for alpha-fetoprotein (AFP, cytokeratin 20 (CK-20, HMB45, chromogranin, and synaptophysin. The patient was subsequently diagnosed with a primary solid-type pancreatic clear cell carcinoma with hepatic metastasis. Herein, we report this rare case and include a review of the current literature of this tumor.

  19. Can Archival Tissue Reveal Answers to Modern Research Questions?: Computer-Aided Histological Assessment of Neuroblastoma Tumours Collected over 60 Years

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    Albert Chetcuti

    2014-02-01

    Full Text Available Despite neuroblastoma being the most common extracranial solid cancer in childhood, it is still a rare disease. Consequently, the unavailability of tissue for research limits the statistical power of studies. Pathology archives are possible sources of rare tissue, which, if proven to remain consistent over time, could prove useful to research of rare disease types. We applied immunohistochemistry to investigate whether long term storage caused any changes to antigens used diagnostically for neuroblastoma. We constructed and quantitatively assessed a tissue microarray containing neuroblastoma archival material dating between 1950 and 2007. A total of 119 neuroblastoma tissue cores were included spanning 6 decades. Fourteen antibodies were screened across the tissue microarray (TMA. These included seven positive neuroblastoma diagnosis markers (NB84, Chromogranin A, NSE, Ki-67, INI1, Neurofilament Protein, Synaptophysin, two anticipated to be negative (S100A, CD99, and five research antibodies (IL-7, IL-7R, JAK1, JAK3, STAT5. The staining of these antibodies was evaluated using Aperio ImageScope software along with novel pattern recognition and quantification algorithms. This analysis demonstrated that marker signal intensity did not decrease over time and that storage for 60 years had little effect on antigenicity. The construction and assessment of this neuroblastoma TMA has demonstrated the feasibility of using archival samples for research.

  20. Primary Small Cell Carcinoma of the Esophagus: Clinico- pathological Features and Therapeutic Options.

    Science.gov (United States)

    Nevárez, Andrea; Saftoiu, A; Bhutani, M S

    2011-01-01

    Primary esophageal small cell carcinoma (SmCC) is a rare disease with a poor prognosis despite agressive multimodality combination treatment. This article presents the case of a 76-year old women diagnosed with pimary esophageal SmCC. The diagnosis was established by upper gastrointestinal endoscopy with biopsies that confirmed an esophageal SmCC positive to synaptophysin, chromogranin, CD56, TTF-1, and cytokeratin 8/18. Further staging procedures included CT, PET and EUS, followed by combination chemotherapy and radiotherapy. Restaging was then performed, again with PET and CT of the thorax, abdomen and pelvis. This was then followed by salvage esophagectomy due to the presence of residual tumor. Surgical pathology confirmed a 3 cm SmCC, with invasion of the submucosa and lymphovascular invasion. In conclusion, the article describes the rare occurrence of esophageal SmCC, together with the algorithm of diagnosis and staging based on state-of-the-art imaging methods. This was followed by combination chemoradiotherapy and surgical esophagectomy as the standard of care in this aggressive disease.

  1. Schwannoma of the adrenal gland

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    Anunayi Jeshtadi

    2014-07-01

    Full Text Available Visceral schwannomas are extremely rare and are usually discov-ered incidentally on USG/CT-Scan. Primary schwannomas of the adrenal gland are extremely uncommon. It has been theorized that they originate from Schwann cells that insulate the nerve fi-bers innervating the adrenal medulla. Histopathological examina-tion coupled with immunohistochemistry provides the definitive diagnosis. A 55 year old normotensive female presented with pain in the right loin since 5 months. Her renal parameters were normal. Contrast enhanced computed tomography of abdomen showed a well delineated 6.5 x 5cms mass at upper pole of her right kidney. 24-hour urinary metanephrine was slightly elevated (3.07mg/24hrs. A decline in Serum cortisol levels was observed following a dexamethasone suppression test (18.89nmol/l. Histopathological examination revealed a spindle cell tumor. Immunohistochemistry showed strong and diffuse positive staining for S-100 with negative expression for CD-117, desmin, CD-34, HMB-45, synaptophysin, chromogranin, cytokeratin, and SMA. Ki-67 index was 2%.A diagnosis of cellular schwannoma of adrenal gland was confirmed.

  2. [Neuroendocrine carcinoma of the urinary bladder. A case report].

    Science.gov (United States)

    Aragón-Tovar, Anel Rogelio; Pineda-Rodríguez, Marco Elí; Puente-Gallegos, Francisco Edgardo; Zavala-Pompa, Angel

    2014-01-01

    Small cell carcinoma of the urinary bladder is an infrequent lesion. We present the case of a 68-year-old male who arrived at the emergency room with a history of 24-h gross hematuria. Imaging studies show a urinary bladder tumor with a 218 cc volume that during a 20-day period increased to 426 cc. Histopathological images with hematoxylin-eosin show an infiltrating solid mass with uneven borders. It is composed of neoplastic cells with evident nuclei predominance and scant cytoplasm (small cells). Chromogranin immunohistochemical staining shows a diffusely positive cytoplasmic granular pattern on neoplastic cells. High molecular weight cytokeratin staining shows a negative pattern on neoplastic cells along with a positive pattern on reporsurrounding normal urothelium. Tumoral mass is positive for synaptophysin and CD-56 and negative for CK-7 and CK-20. Patient therapy was based on radiation plus chemotherapy. Small cell carcinoma of the urinary bladder represents 0.35-0.70% of urinary bladder tumors. Histological and immunohistochemical identification are key elements in the diagnosis. Treatment approach is based on cisplatin-based chemotherapy plus radical cystectomy, except when metastatic disease is present.

  3. A Case of Primary Gastric Small-Cell Carcinoma in an Elderly Patient

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    Fa-Chang Yu

    2012-03-01

    Full Text Available We report a case of primary small-cell carcinoma of the stomach in a 75-year-old man. The patient was admitted to our hospital with a 1-week history of intermittent tarry stool. An upper gastrointestinal examination revealed a large stage A2 ulcer in the greater curvature of the body of the stomach, and pathological findings from biopsy specimens revealed small-cell carcinoma. The tumor cells were small-sized, composed of hyperchromatic nuclei with scant cytoplasm, and stained positive for cytokeratin, synaptophysin, and chromogranin A. The patient was diagnosed with primary small-cell carcinoma of the stomach. He declined further evaluation and received palliative management. This is a rare carcinoma of the stomach, with aggressive manifestations and a poor prognosis. The mean survival of patients with primary gastric small-cell carcinoma is reported to be 7 months. The choice of treatment for this disease is still controversial. This rare gastric tumor should be listed in the differential diagnosis of gastric carcinoma in the elderly.

  4. Neuroendocrine tumors of the gallbladder: a case report and review of the literature

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    Mezi Silvia

    2011-07-01

    Full Text Available Abstract Introduction Primary gallbladder neuroendocrine tumors are extremely rare, representing 0.2% of all neuroendocrine tumors. The diagnosis is incidental in most cases. Case presentation We describe the case of a 57-year-old Caucasian man who underwent laparoscopic cholecystectomy for the evaluation of a gallbladder polyp that had been incidentally detected by ultasonography. Histologically, his lesion was composed of monomorphic cells that contained small round nuclei and that were organized in small nodular, trabecular, and acinar structures. His cells were positive for chromogranin A and synaptophysin, and a diagnosis of "typical" carcinoid of the gallbladder was made. His post-operative computerized axial tomography, 111In-pentetreotide scintigraphy, and hormone-specific marker results were negative. He is disease-free 45 months after surgical treatment. Conclusions Characteristic pathological findings of the gallbladder neuroendocrine tumors predict the prognosis. Whereas classical carcinoids of the gallbladder only rarely have a metastatic or invasive phenotype, the "atypical" variants are more aggressive and are associated with a poorer prognosis. Given the difficulty in distinguishing between benign and malignant lesions in the pre-surgical setting, we tend to consider each polypoid-like lesion of the gallbladder to be a high-risk lesion if it is larger than 1 cm and, as a result, to emphasize the need for cholecystectomy in all cases, relying on the pathological and immunohistochemistry analyses for the final diagnosis.

  5. Primary minute mucinous adenocarcinoma of vermiform appendix arising from appendiceal diverticulosis

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    Tadashi Terada, MD, PhD

    2015-03-01

    Full Text Available Primary mucinous adenocarcinoma (MA of vermiform appendix is extremely rare; only three cases have been reported in the English literature. A 77-year-old man presented with abdominal pain, and was diagnosed with acute appendicitis. Appendectomy was performed. The resected appendix showed submucosal swelling measuring 0.7×0.6×0.6 cm in the tip of appendix. The appendix showed inflammation and numerous diverticuloses. Microscopically, the submucosal swelling was a mucin lake in which adenocarcinoma cells were floating. The adenocarcinoma cells were MA in 80% and signet-ring cell carcinoma in 20%. The carcinoma cells were located in the submucosa, muscular layer and subserosa, sparing the mucosa. No apparent lymphovascular permeation was seen. The surgical margins were negative for tumor cells. The non-tumorous appendix shows numerous diverticulosis, diverticulitis, and appendicitis. Immunohistochemically, the tumor cells were positive for CK CAM5.2, CK AE1/3, CK8, CK18, CK19, CK20, EMA, CEA, CA19-9, MUC1, MUC2, MUC5AC, MUC6, NCAM, p53 and Ki-67 (labeling index = 23%. The tumor cells were negative for CK34BE12, CD5, CK6, CK7, NSE, chromogranin, synaptophysin, CA125, KIT, and PDGFRA. No metastasis has been seen 2.5 years after the operation.

  6. Intramural Ganglion Structures in Esophageal Atresia: A Morphologic and Immunohistochemical Study

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    Biagio Zuccarello

    2009-01-01

    Full Text Available Introduction and Aim. Disorders of esophageal motility causing dysphagia and gastroesophageal reflux are frequent in survivors to esophageal atresia (EA and distal tracheoesophageal fistula (TEF. The aim of the present study was to investigate the histologic and immunohistochemical features in both esophageal atretic segments to further understand the nature of the motor disorders observed in these patients. Material and Methods. Esophageal specimens from 12 newborns with EA/TEF and 5 newborns dead of unrelated causes were examined. The specimens were fixed in 5% buffered formalin, included in paraffin and cut in 5 micron sections that were stained with hematoxilin and eosin (H and E, and immunohistochemical stainings for Actin, S-100 protein, Neurofilament, Neuron-Specific-Enolase, Chromogranin A and Peripherin were evaluated under the microscope. Results. In controls, the distribution of the neural elements was rather homogenous at both levels of the esophagus. In contrast, the atretic segments showed quantitative and qualitative differences between them with sparser nervous tissue in the distal one in comparison with the proximal one and with controls. Conclusions. These results further support the assumption that histomorphological alterations of the muscular and nervous elements within the esophageal wall might contribute to esophageal dysmotility in patients surviving neonatal operations for EA/TEF.

  7. Surgical Control of a Primary Hepatic Carcinoid Tumor: A Case Report

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    Norio Yokoigawa

    2009-04-01

    Full Text Available We report a primary hepatic carcinoid tumor occurring in a 47-year-old man. The patient consulted our hospital complaining of epigastralgia. Abdominal ultrasonography, computed tomography scanning, and magnetic resonance imaging showed a large mass in the right lobe of the liver. FDG-PET revealed 18F-FDG uptake by the right hepatic lobe. The tumor was a solid mass with cystic components, approximately 15 cm in diameter. We conducted an extended right lobectomy of the liver. The resected specimen was a solid tumor with cystic components and hemorrhagic lesion. Microscopic findings showed that the tumor cells had round nuclei and formed trabecular patterns. Immunohistologically, tumor cells were stained positive for chromogranin A, neuron specific enolase, CD56, and S-100. Careful examinations before and after the operation revealed no other possible origin of the tumor. Based on these findings, the tumor was diagnosed as a primary hepatic carcinoid. This is a report of a rare case of a primary hepatic carcinoid tumor with a discussion of several other relevant reports.

  8. Characterization and uptake of radiolabelled meta-iodobenzylguanidine (MIBG) in a human neuroblastoma heterotransplant model in athymic rats

    International Nuclear Information System (INIS)

    Nilsson, S.; Paahlman, S.; Arnberg, H.; Letocha, H.; Westlin, J.E.

    1993-01-01

    Cells from an established human neuroblastoma cell line, SH-SY5Y, were demonstrated to grow and form solid tumours in nude rats. This cell line, which is an adrenergic subclone of the SK-N-SH cell line, has previously been used in differentiation model studies. The tumours retained the neuronal phenotype of the cultured cells, as evidenced by the expression of neuron-specific enolase (NSE) and chromogranin A + B. The transcription factor Isl-1, a protein expressed in subsets of neurons and endocrine cells as well as in neuroblastoma cells, was also expressed in the transplanted tumours, thus further verifying the retained phenotype of the cells under in vivo conditions. At scintigraphy utilizing 123 I-MIBG the optimal tumour/background ratio was obtained 20 h after injection. The assessment of tissue/serum ratios showed the highest uptake in the spleen (0.067% per gram of inj. activity), neuroblastoma tumours (0.067% per gram of inj. activity) and in the adrenals (0.065% per gram of inj. activity). (orig.)

  9. Characterization and uptake of radiolabelled meta-iodobenzylguanidine (MIBG) in a human neuroblastoma heterotransplant model in athymic rats

    Energy Technology Data Exchange (ETDEWEB)

    Nilsson, S. (Dept. of Oncology, Univ. Hospital, Uppsala (Sweden)); Paahlman, S. (Dept. of Pathology, Univ. Hospital, Uppsala (Sweden)); Arnberg, H. (Dept. of Oncology, Univ. Hospital, Uppsala (Sweden)); Letocha, H. (Dept. of Oncology, Univ. Hospital, Uppsala (Sweden)); Westlin, J.E. (Dept. of Oncology, Univ. Hospital, Uppsala (Sweden))

    1993-01-01

    Cells from an established human neuroblastoma cell line, SH-SY5Y, were demonstrated to grow and form solid tumours in nude rats. This cell line, which is an adrenergic subclone of the SK-N-SH cell line, has previously been used in differentiation model studies. The tumours retained the neuronal phenotype of the cultured cells, as evidenced by the expression of neuron-specific enolase (NSE) and chromogranin A + B. The transcription factor Isl-1, a protein expressed in subsets of neurons and endocrine cells as well as in neuroblastoma cells, was also expressed in the transplanted tumours, thus further verifying the retained phenotype of the cells under in vivo conditions. At scintigraphy utilizing [sup 123]I-MIBG the optimal tumour/background ratio was obtained 20 h after injection. The assessment of tissue/serum ratios showed the highest uptake in the spleen (0.067% per gram of inj. activity), neuroblastoma tumours (0.067% per gram of inj. activity) and in the adrenals (0.065% per gram of inj. activity). (orig.).

  10. Characterization of Insulin-Immunoreactive Cells and Endocrine Cells Within the Duct System of the Adult Human Pancreas.

    Science.gov (United States)

    Li, Rong; Zhang, Xiaoxi; Yu, Lan; Zou, Xia; Zhao, Hailu

    2016-01-01

    The adult pancreatic duct system accommodates endocrine cells that have the potential to produce insulin. Here we report the characterization and distribution of insulin-immunoreactive cells and endocrine cells within the ductal units of adult human pancreas. Sequential pancreas sections from 12 nondiabetic adults were stained with biomarkers of ductal epithelial cells (cytokeratin 19), acinar cells (amylase), endocrine cells (chromogranin A; neuron-specific enolase), islet hormones (insulin, glucagon, somatostatin, pancreatic polypeptide), cell proliferation (Ki-67), and neogenesis (CD29). The number of islet hormone-immunoreactive cells increased from large ducts to the terminal branches. The insulin-producing cells outnumbered endocrine cells reactive for glucagon, somatostatin, or pancreatic polypeptide. The proportions of insulin-immunoreactive count compared with local islets (100% as a baseline) were 1.5% for the main ducts, 7.2% for interlobular ducts, 24.8% for intralobular ducts, 67.9% for intercalated ducts, and 348.9% for centroacinar cells. Both Ki-67- and CD29-labeled cells were predominantly localized in the terminal branches around the islets. The terminal branches also showed cells coexpressing islet hormones and cytokeratin 19. The adult human pancreatic ducts showed islet hormone-producing cells. The insulin-reactive cells predominantly localized in terminal branches where they may retain potential capability for β-cell neogenesis.

  11. Neuroendocrine Tumor, Well Differentiated, of the Breast: A Relatively High-Grade Case in the Histological Subtype

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    Shogo Tajima

    2013-01-01

    Full Text Available Primary neuroendocrine carcinoma of the breast is a rare entity, comprising <1% of breast carcinomas. Described here is the case of a 78-year-old woman who developed an invasive tumor in the left breast measuring 2.0 cm x 1.5 cm x 1.2 cm. The tumor was composed of only endocrine elements in the invasive part. It infiltrated in a nested fashion with no tubular formation. Intraductal components were present both inside and outside of the invasive portion. Almost all carcinoma cells consisting of invasive and intraductal parts were positive for synaptophysin and neuron-specific enolase. According to the World Health Organization classification 2012, this tumor was subclassified as neuroendocrine tumor, well-differentiated. Among the subgroup, this tumor was relatively high-grade because it was grade 3 tumor with a few mitotic figures. Vascular and lymphatic permeation and lymph node metastases were noted. In the lymph nodes, the morphology of the tumor was similar to the primary site. No distant metastasis and no relapse was seen for one year after surgery. The prognosis of neuroendocrine carcinomas is thought to be worse than invasive mammary carcinomas, not otherwise specified. Therefore, immunohistochemistry for neuroendocrine markers is important in the routine practice to prevent overlooking neuroendocrine carcinomas.

  12. Immunohistochemical evaluation of neuroreceptors in healthy and pathological temporo-mandibular joint.

    Science.gov (United States)

    Favia, Gianfranco; Corsalini, Massimo; Di Venere, Daniela; Pettini, Francesco; Favia, Giorgio; Capodiferro, Saverio; Maiorano, Eugenio

    2013-01-01

    A study was performed on the articular disk and periarticular tissues of the temporo-mandibular joint (TMJ) with immunohistochemical techniques to give evidence to the presence of neuroreceptors (NRec) in these sites. The study was carried out on tissue samples obtained from 10 subjects without TMJ disease and from 7 patients with severe TMJ arthritis and arthrosis. We use antibodies directed against following antigens: Gliofibrillary Acidic Protein (GFAP), Leu-7, Myelin Basic Protein (MBP), Neurofilaments 68 kD (NF), Neuron Specific Enolase (NSE), S-100 protein (S-100) and Synaptophysin (SYN). This study revealed that Ruffini's-like, Pacini's-like and Golgi's-like receptors can be demonstrated in TMJ periarticular tissues and that free nervous endings are present in the subsynovial tissues but not within the articular disk. We observed elongated cytoplamic processes of chondrocytes that demonstrated strong S-100 immunoreactivity but they were unreactive with all other antibodies. These cytoplamic processes were more abundant and thicker in the samples obtained from patients with disease TMJ. The results of this study confirm that different Nrec are detectable in TMJ periarticular tissues but they are absent within the articular disk. In the latter site, only condrocytic processes are evident, especially in diseased TMJ, and they might have been confused with nervous endings in previous morphological studies. Nevertheless the absence of immunoreactivity for NF, NSE and SYN proves that they are not of neural origin.

  13. Effects of all-trans-retinoic acid on human SH-SY5Y neuroblastoma as in vitro model in neurotoxicity research.

    Science.gov (United States)

    Cheung, Yuen-Ting; Lau, Way Kwok-Wai; Yu, Man-Shan; Lai, Cora Sau-Wan; Yeung, Sze-Chun; So, Kwok-Fai; Chang, Raymond Chuen-Chung

    2009-01-01

    Human neuroblastoma SH-SY5Y is a dopaminergic neuronal cell line which has been used as an in vitro model for neurotoxicity experiments. Although the neuroblastoma is usually differentiated by all-trans-retinoic acid (RA), both RA-differentiated and undifferentiated SH-SY5Y cells have been used in neuroscience research. However, the changes in neuronal properties triggered by RA as well as the subsequent responsiveness to neurotoxins have not been comprehensively studied. Therefore, we aim to re-evaluate the differentiation property of RA on this cell line. We hypothesize that modulation of signaling pathways and neuronal properties during RA-mediated differentiation in SH-SY5Y cells can affect their susceptibility to neurotoxins. The differentiation property of RA was confirmed by showing an extensive outgrowth of neurites, increased expressions of neuronal nuclei, neuron specific enolase, synaptophysin and synaptic associated protein-97, and decreased expression of inhibitor of differentiation-1. While undifferentiated SH-SY5Y cells were susceptible to 6-OHDA and MPP+, RA-differentiation conferred SH-SY5Y cells higher tolerance, potentially by up-regulating survival signaling, including Akt pathway as inhibition of Akt removed RA-induced neuroprotection against 6-OHDA. As a result, the real toxicity cannot be revealed in RA-differentiated cells. Therefore, undifferentiated SH-SY5Y is more appropriate for studying neurotoxicity or neuroprotection in experimental Parkinson's disease research.

  14. Caracterização da enolase de Paracoccidioides brasiliensis e identificação proteômica de novas moléculas

    OpenAIRE

    Marcos, Caroline Maria [UNESP

    2011-01-01

    Paracoccidioides brasiliensis é um importante patógeno humano que causa a paracoccidioidomicose (PCM), uma micose sistêmica com ampla distribuição na América Latina. A adesão e invasão de células são eventos cruciais envolvidos na infecção e disseminação do patógeno. Além disso, patógenos utilizam suas moléculas de superfície para se ligar aos componentes da matriz extracelular para estabelecer a infecção. Uma proteína antigênica de P. brasiliensis foi isolada de géis de eletroforese bidimens...

  15. Role of Caveolin 1, E-Cadherin, Enolase 2 and PKCalpha on resistance to methotrexate in human HT29 colon cancer cells

    DEFF Research Database (Denmark)

    Selga, Elisabet; Morales Torres, Christina; Noé, Véronique

    2008-01-01

    , a list of 3-fold differentially expressed genes with a p-value multiple testing correction (Benjamini and Hochberg false discovery rate) was generated. RT-Real-time PCR was used to validate the expression levels of selected genes and copy-number was determined by qPCR. Functional......ABSTRACT: BACKGROUND: Methotrexate is one of the earliest cytotoxic drugs used in cancer therapy, and despite the isolation of multiple other folate antagonists, methotrexate maintains its significant role as a treatment for different types of cancer and other disorders. The usefulness of treatment...

  16. Elevated levels of 14-3-3 proteins, serotonin, gamma enolase and pyruvate kinase identified in clinical samples from patients diagnosed with colorectal cancer

    Czech Academy of Sciences Publication Activity Database

    Dowling, P.; Hughes, D. J.; Larkin, A.M.; Meiller, J.; Henry, M.; Meleady, P.; Lynch, V.; Pardini, B.; Naccarati, A.; Levý, M.; Vodička, Pavel; Neary, P.; Clynes, M.

    2015-01-01

    Roč. 441, feb. (2015), s. 133-141 ISSN 0009-8981 Institutional support: RVO:68378041 Keywords : biomarkers * colorectal cancer * proteomics * mass spectrometry * 14-3-3 proteins * pyruvate kinase Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.799, year: 2015

  17. Goblet cell carcinoids: characteristics of a Danish cohort of 83 patients.

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    Ingrid Holst Olsen

    Full Text Available Appendiceal goblet cell carcinoids (GCCs exhibit neuroendocrine and adenocarcinoma features.Analysis of demography, pathology, prognostic markers, treatment and survival in 83 GCC patients (f/m: 56/27 diagnosed 1992-2013.Median age for f/m was 59/58 years, respectively, and similar for localized and disseminated disease. At diagnosis 54 patients had localized appendiceal disease (f/m: 29/25. According to TNM 24% had Stage I, 70% had Stage II and 6% had Stage III. Twenty-nine patients had disseminated disease (f/m: 27/2. Chromogranin A, synaptophysin and p53 were positive in >90%. Serotonin was positive in 70%. Median Ki67 index was 32% (6-75% and higher in Tang group C (50% compared to group A (30%; p<0.0001, and group B (30%; p<0.004. All patients had surgery. Sixty-three (76% had radical resections including all patients with localized disease. Median OS was 83 months. The 1-, 5- and 10-year survival rates were 90%, 58%, and 38%, respectively. For localized disease OS was 164 months and 1-, 5- and 10-year survival rates were 100%, 80%, and 55%, respectively. For disseminated disease OS was 19 months and 1-, 5- and 10-year survival rates were 73%, 18% and 6%, respectively. The 1-, 5- and 10 year-survival rates for f/m were 87%/96%, 49%/76% and 31%/57%, respectively (p = 0.02. According to the Tang classification group A, B, and C OS was 118, 83 and 20 months, respectively (p = 0.0002.The Tang classification was found to be a significant prognostic factor, while the Ki67 index was not. Localized GCCs occurred equally in males and females, while disseminated GCCs were mostly seen in females. Median age of patients with localized disease and disseminated disease was identical. Cox regression analysis found Stage IV, focally positive synaptophysin and non-radical surgery as strongest negative prognostic factors.

  18. Reevaluation and reclassification of resected lung carcinomas originally diagnosed as squamous cell carcinoma using immunohistochemical analysis

    Science.gov (United States)

    Kadota, Kyuichi; Nitadori, Jun-ichi; Rekhtman, Natasha; Jones, David R.; Adusumilli, Prasad S.; Travis, William D.

    2015-01-01

    Currently, non-small cell lung carcinomas are primarily classified by light microscopy. However, recent studies have shown that poorly-differentiated tumors are more accurately classified by immunohistochemistry. In this study, we investigated the use of immunohistochemical analysis in reclassifying lung carcinomas that were originally diagnosed as squamous cell carcinoma. Tumor slides and blocks were available for histologic evaluation, and tissue microarrays were constructed from 480 patients with resected lung carcinomas originally diagnosed as squamous cell carcinoma between 1999 and 2009. Immunohistochemistry for p40, p63, thyroid transcription factor-1 (TTF-1; clone SPT24 and 8G7G3/1), Napsin A, Chromogranin A, Synaptophysin, and CD56 were performed. Staining intensity (weak, moderate, or strong) and distribution (focal or diffuse) were also recorded. Of all, 449 (93.5%) patients were confirmed as having squamous cell carcinomas; the cases were mostly diffusely positive for p40 and negative for TTF-1 (8G7G3/1). Twenty cases (4.2%) were reclassified as adenocarcinoma since they were positive for TTF-1 (8G7G3/1 or SPT24) with either no or focal p40 expression, and all of them were poorly-differentiated with squamoid morphology. In addition, 1 case was reclassified as adenosquamous carcinoma, 4 cases as large cell carcinoma, 4 cases as large cell neuroendocrine carcinoma, and 2 cases as small cell carcinoma. In poorly-differentiated non-small cell lung carcinomas, an accurate distinction between squamous cell carcinoma and adenocarcinoma cannot be reliably determined by morphology alone and requires immunohistochemical analysis, even in resected specimens. Our findings suggest that TTF-1 8G7G3/1 may be better suited as the primary antibody in differentiating adenocarcinoma from squamous cell carcinoma. PMID:25871623

  19. Immunohistochemical characterization of glandular elements in glandular cardiac myxoma: Study of six cases

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    Devajit Nath

    2017-01-01

    Full Text Available Back ground: Glandular cardiac myxoma has varying clinical presentation with uncertain histogenesis and debatable immunohistochemical profile. Glandular epithelial differentiations are rare phenomenon known to be present as an intrinsic component of the tumor. The origin of the glands has been attributed to epithelial differentiation of a totipotent cardiomyogenic precursor cells or the entrapped foregut rests in the tumor. Materials and Methods: Retrospective study includes six cases of glandular cardiac myxoma collected over a perior of 4 years. Sections were examined to define the histogenesis, histological and immunohistochemical profile of the glandular elements. Results: Incidence of glandular cardiac myxoma was 6.6% with a male to female ratio of 1:2.Mean age was 49.9 years. Left atrium was the commonest site. Five were sporadic and one was familial. Chest pain and dyspnea were the commonest clinical symptoms. Histologically all myxoma showed well formed glandular structures with typical myxomatous area. No atypia, mitosis or necrosis was identified in the glandular elements. Markers in six cases of glandular cardiac myxoma were immunopositive for CK7, CK 19, EMA, CEA, focally for E-cadherin while immunonegative for CK20, Chromogranin, Synaptophysin, calretenin, vimentin, B-catenin, TTF-1 and GCDFP-15 favoring enteric differentiation. Conclusion: Glandular cardiac myxoma is a rare entity which shows characteristics similar to those of classical cardiac myxoma with benign glandular elements showing enteric differentiation. Complete surgical excision is the treatment of choice with good prognosis. It is important to recognize this entity to avoid an erroneous diagnosis of metastatic adenocarcinoma.

  20. Tumeur de Frantz: deux nouveaux cas

    Science.gov (United States)

    Bellarbi, Salma; Sina, Mohamed; Jahid, Ahmed; Zouaidia, Fouad; Bernoussi, Zakia; Mahassini, Najat

    2013-01-01

    A travers cet article, nous détaillons les caractéristiques clinico-pathologiques et discutons l'histogenèse de la tumeur de Frantz. Deux patients opérés pour tumeur de Frantz. Ils ont eu un traitement chirurgical seul. L'étude morphologique était couplée à un examen immuno-histochimique (IHC) utilisant les anticorps anti CD10, anti- vimentine, anti-énolase neuronale spécifique (NSE), anti-synaptophysine, anti-chromogranine A et anti-cytokératine. Un immuno-marquage à l'anti-oestrogène et l'anti-progestérone a été réalisé dans un cas. Il s'agissait d'une femme âgée de 45ans et d'un garçon de 12 ans. Les aspects échographiques et scannographiques étaient non spécifiques. Une exérèse chirurgicale complète a été réalisée dans les deux cas. L'analyse histologique évoquait une tumeur de Frantz. Le diagnostic a été retenu après étude immuno-histohimique. L'évolution était favorable sans récidive avec respectivement un recul de 18 et 16 mois. La tumeur de Frantz est une entité rare. Son diagnostic repose sur l'examen anatomopathologique complété par l'étude immuno-histochimique. Son pronostic est excellent après résection chirurgicale. PMID:23503717

  1. Pleomorphic xanthoastrocytoma with anaplastic features: one case report and review of literature

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    Cui-yun SUN

    2014-12-01

    Full Text Available Objective To investigate the clinicopathological features of pleomorphic xanthoastrocytoma with anaplastic features (PXA-A.  Methods The clinical manifestations, imaging, histopathological features, and immunophenotype were analyzed in one case of PXA-A, and relevant literatures were reviewed. Results The patient was a 58-year-old woman. MRI examination revealed a parenchyma mass with irregularly long T1 and long T2 signal in right temporal lobe and basal ganglia region. The border was clear and peritumoral edema was inconspicuous. The mesocephalon and right ventricle were compressed, and the midline was shifted to left. Enhanced MRI showed multiple flaky and nodular enhancement. Histologically, tumor cells showed remarkable cellular pleomorphism, and they were composed of mononuclear cells, multinuclear giant tumor cells, frothy tumor cells and spindle cells. Eosinophilic granular bodies and intranuclear inclusions were seen. Tumor cells in partial regions were intensively arranged, with obvious atypia. Immunohistochemical analysis showed immunoreactivity of the cells to glial fibrillary acidic protein (GFAP, Vimentin (Vim, S-100 protein (S-100, neuronal nuclei (NeuN and P53. The cells showed a negative reaction for synaptophysin (Syn, chromogranin A (CgA, neurofilament protein (NF, CD34 and isocitrate dehydrogenase 1 (IDH1. The Ki-67 label index was 8.20% .  Conclusions PXA-A is a rare tumor. The imaging features can offer a few diagnostic cues. However, a definite diagnosis depends on the histological and immunohistochemical features. doi: 10.3969/j.issn.1672-6731.2014.12.013

  2. Relationship between clinical characteristics and survival of gastroenteropancreatic neuroendocrine neoplasms: A single-institution analysis (1995–2012 in South China

    Directory of Open Access Journals (Sweden)

    Wang Yu-hong

    2012-11-01

    Full Text Available Abstract Background Gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN is the most common type of neuroendocrine tumors accounting for 65–75% of neuroendocrine neoplasms (NENs. Given the fact that there are few studies on GEP-NENs among Chinese patients, we performed a retrospective study in South China. Methods Totally 178 patients with GEP-NENs treated at the First Affiliated Hospital of Sun Yat-sen University between January 1995 and May 2012 were analyzed retrospectively. Results Pancreas was found the most common site of involvement (34.8%. 149 patients (83.7% presented as non-functional tumors with non-specific symptoms such as abdominal pain (33.7%; carcinoid syndrome was not found in this study. Several methods are useful for localization of GEP-NENs, yielding varied detection rates from 77.8% to 98.7%. Positive rates of chromogranin A (CgA and synaptophysin (Syn immunhistochemically were 69.1% and 90.2%, respectively. 87 patients (51.5% had G1 tumors, 31(18.3% G2 tumors and 51 (30.2% G3 tumors. Neuroendocrine tumor (NET, neuroendocrine carcinoma (NEC and mixed adenoendocrine carcinoma (MANEC were 69.8%, 27.2% and 3.0%, respectively. 28.1% of patients presented with distant disease. Surgery was performed in 152 (85.4% patients, and overall 5-year survival rate was 54.5%. Functionality, G1 grading and NET classification were associated with favorable prognosis in univariate analysis. Distant metastasis contributed to unfavorable prognosis of these tumors. Conclusions Nonfunctional tumors with non-specific symptoms account for the majority of GEP-NENs. Diagnosis depends on pathological classification. Multidisciplinary treatments could help improve the outcome.

  3. Re-epithelialization resulted from prostate basal cells in canine prostatic urethra may represent the ideal healing method after two-micron laser resection of the prostate

    Directory of Open Access Journals (Sweden)

    Ying Cao

    2015-01-01

    Full Text Available The purpose of this study is to characterize the re-epithelialization of wound healing in canine prostatic urethra and to evaluate the effect of this re-epithelialization way after two-micron laser resection of the prostate (TmLRP. TmLRP and partial bladder neck mucosa were performed in 15 healthy adult male crossbred canines. Wound specimens were harvested at 3 days, and 1, 2, 3, and 4 weeks after operation, respectively. The histopathologic characteristics were observed by hematoxylin and eosin staining. The expression of cytokeratin 14 (CK14, CK5, CK18, synaptophysin (Syn, chromogranin A (CgA, uroplakin, transforming growth factor-β1 (TGF-β1 , and TGF-β type II receptor in prostatic urethra wound were examined by immunohistochemistry and real-time polymerase chain reaction, respectively. Van Gieson staining was performed to determine the expression of collagen fibers in prostatic urethra and bladder neck would. The results showed that the re-epithelialization of the prostatic urethra resulted from the mobilization of proliferating epithelial cells from residual prostate tissue under the wound. The proliferating cells expressed CK14, CK5, but not CK18, Syn, and CgA and re-epithelialize expressed uroplakin since 3 weeks. There were enhanced TGF-β1 and TGF-β type II receptor expression in proliferating cells and regenerated cells, which correlated with specific phases of re-epithelialization. Compared with the re-epithelialization of the bladder neck, re-epithelialization of canine prostatic urethra was faster, and the expression of collagen fibers was relatively low. In conclusion, re-epithelialization in canine prostatic urethra resulted from prostate basal cells after TmLRP and this re-epithelialization way may represent the ideal healing method from anatomic repair to functional recovery after injury.

  4. [Paraneoplastic Cushing's syndrome, a real diagnostic and therapeutic challenge: A case report and literature review].

    Science.gov (United States)

    Meftah, A; Moumen, A; Massine El Hammoumi, M; Hajhouji, S; El Jadi, H; Anas Guerboub, A; Elmoussaoui, S; Mayaudon, H; Hassane Kabiri, E; Hakkou, K; Belmejdoub, G

    2015-12-01

    Paraneoplastic Cushing's syndrome is a rare cause of endogenous hypercortisolism attributable to ectopic ACTH secretion by non-pituitary tumors. Imaging and biochemical results are often inconclusive and differential diagnosis with Cushing's disease can then be challenging. Moreover, these tumors may be occult and difficult to find and thus the need of new imaging tools such as (18)FDG-PET scan and (18)DOPA-PET scan. We report a 50-year-old man who presented with very aggressive clinical features related to Cushing's syndrome. Biological work-up confirmed the hypercortisolism and was consistent with an ectopic ACTH secretion. Conventional localization techniques failed to show any tumor and bilateral adrenalectomy was performed because of life-threatening complications. Two years later, thoracic computed tomography reveals an 11 mm mass in the left lower pulmonary lobe, (18)FDG-PET scan found a non-specific mild hypermetabolism of the lung nodule, and the (18)DOPA-PET scan confirmed the high uptake of this nodule suggesting an endocrine carcinoma. Histology confirmed a typical carcinoid tumor. The tumor cells stained positive for ACTH, CD56, chromogranin and synaptophysin. This case illustrates the dilemma between the need for morphological diagnosis of the ectopic ACTH source and control of the life-threatening hypercortisolism. (18)FDG-PET scan and (18)DOPA-PET scan should be considered early as a secondary diagnostic tool when conventional imagery fails to show any tumor. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  5. The Genetic Landscape of Breast Carcinomas with Neuroendocrine Differentiation

    Science.gov (United States)

    Marchiò, Caterina; Geyer, Felipe C; Ng, Charlotte KY; Piscuoglio, Salvatore; De Filippo, Maria R; Cupo, Marco; Schultheis, Anne M; Lim, Raymond S; Burke, Kathleen A; Guerini-Rocco, Elena; Papotti, Mauro; Norton, Larry; Sapino, Anna; Weigelt, Britta; Reis-Filho, Jorge S

    2016-01-01

    Neuroendocrine breast carcinomas (NBCs) account for 2–5% of all invasive breast cancers and are histologically similar to neuroendocrine tumours from other sites. They typically express oestrogen receptor (ER), are HER2-negative and of luminal 'intrinsic' subtype. Here we sought to define the mutational profile of NBCs, and to investigate whether NBCs and common forms of luminal (ER+/HER2-) breast cancer display distinct repertoires of somatic mutations. Eighteen ER+/HER2- NBCs, defined as harbouring >50% of tumour cells expressing chromogranin A and/or synaptophysin, and matched normal tissue were microdissected and subjected to massively parallel sequencing targeting all exons of 254 genes most frequently mutated in breast cancer and/or related to DNA repair. Their mutational repertoire was compared to that of ER+/HER2- (n=240), PAM50-defined luminal breast cancers (n=209 luminal A; n=111 luminal B) and invasive lobular carcinomas (n=127) from The Cancer Genome Atlas. NBCs were found to harbour a median of 4.5 (range 1-11) somatic mutations, similar to that of luminal B breast cancers (median=3, range 0-17) but significantly higher than that of luminal A breast cancers (median=3, range 0-18, p=0.02). The most frequently mutated genes were GATA3, FOXA1, TBX3, ARID1A (3/18, 17%), and PIK3CA, AKT1, CDH1 (2/18, 11%). NBCs less frequently harboured PIK3CA mutations than common forms of ER+/HER2, luminal A and invasive lobular carcinomas (pcancers. No TP53 somatic mutations were detected in NBCs. Compared to common forms of luminal breast cancers, NBCs display a distinctive repertoire of somatic mutations featuring lower frequency of TP53 and PIK3CA mutations, and enrichment for FOXA1, TBX3 mutations, and akin to neuroendocrine tumours from other sites, ARID1A mutations. PMID:27925203

  6. Isoform 1 of TPD52 (PC-1) promotes neuroendocrine transdifferentiation in prostate cancer cells

    KAUST Repository

    Moritz, Tom

    2016-02-05

    The tumour protein D52 isoform 1 (PC-1), a member of the tumour protein D52 (TPD52) protein family, is androgen-regulated and prostate-specific expressed. Previous studies confirmed that PC-1 contributes to malignant progression in prostate cancer with an important role in castration-resistant stage. In the present work, we identified its impact in mechanisms leading to neuroendocrine (NE) transdifferentiation. We established for long-term PC-1 overexpression an inducible expression system derived from the prostate carcinoma cell line LNCaP. We observed that PC-1 overexpression itself initiates characteristics of neuroendocrine cells, but the effect was much more pronounced in the presence of the cytokine interleukin-6 (IL-6). Moreover, to our knowledge, this is the first report that treatment with IL-6 leads to a significant upregulation of PC-1 in LNCaP cells. Other TPD52 isoforms were not affected. Proceeding from this result, we conclude that PC-1 overexpression enhances the IL-6-mediated differentiation of LNCaP cells into a NE-like phenotype, noticeable by morphological changes and increased expression of typical NE markers, like chromogranin A, synaptophysin or beta-3 tubulin. Immunofluorescent staining of IL-6-treated PC-1-overexpressing LNCaP cells indicates a considerable PC-1 accumulation at the end of the long-branched neuron-like cell processes, which are typically formed by NE cells. Additionally, the experimentally initiated NE transdifferentiation correlates with the androgen receptor status, which was upregulated additively. In summary, our data provide evidence for an involvement of PC-1 in NE transdifferentiation, frequently associated with castration resistance, which is a major therapeutic challenge in the treatment of advanced prostate cancer.

  7. Primary signet-ring cell carcinoma of vermiform appendix clinically and pathologically presenting as acute appendicitis

    Directory of Open Access Journals (Sweden)

    Tadashi Terada, MD, PhD

    2014-03-01

    Full Text Available Primary signet-ring cell carcinoma (SRCC of vermiform appendix is extremely rare; only three cases have been reported in the English literature. An 89-year-old man suddenly presented right lower abdominal pain, and transferred to a hospital, where he was diagnosed with acute appendicitis by physical data, blood data, and CT. He was further transferred to our hospital for emergency operation. Physical examination showed positive abdominal pain, Blunberg sign, and Rosenstein sign. Blood test showed leukocytosis and increased C-reactive protein. An appendectomy was performed. Gross examination during operation showed inflamed appendix, appendiceal adhesion, and acute peritonitis. Gross pathological examination showed no apparent tumor, but the proximal appendix showed wall thickening and luminal occlusion. The appendix was cut into three sections, and was observed under microscopically. Nests of carcinoma cells were seen in the proximal appendix. The carcinoma was composed of SRCC (70% and mucinous carcinoma (30%. The size of carcinoma was 6 × 7 mm. The carcinoma cells invaded into muscular layer. No lymphovascular permeation was seen. The cut margins were negative for carcinoma cells. Immunohistochemically, SRCC cells were positive for cytokeratin (CK AE1/3, CK CAM5.2, CK8, CK18, CK19, CK20, EMA, CEA, CA19-9, p53, Ki-67 (labeling = 30%, CDX2, MUC2, and MUC5AC. They were negative for CK34PE1, CK5/6, CK7, CK14, p63, vimentin, TTF-1, MUC1, MUC 5AC, NSE, synaptophysin, chromogranin, and CD56. No further treatments were performed, because the appendiceal carcinoma was small, the surgical margins were negative and the patient was very old. He was followed up by various imaging modalities. No recurrence or metastasis is found 17 months after the operation.

  8. Initial Case Reports of Cancer in Naked Mole-rats (Heterocephalus glaber).

    Science.gov (United States)

    Delaney, M A; Ward, J M; Walsh, T F; Chinnadurai, S K; Kerns, K; Kinsel, M J; Treuting, P M

    2016-05-01

    Naked mole-rats (NMRs;Heterocephalus glaber) are highly adapted, eusocial rodents renowned for their extreme longevity and resistance to cancer. Because cancer has not been formally described in this species, NMRs have been increasingly utilized as an animal model in aging and cancer research. We previously reported the occurrence of several age-related diseases, including putative pre-neoplastic lesions, in zoo-housed NMR colonies. Here, we report for the first time 2 cases of cancer in zoo-housed NMRs. In Case No. 1, we observed a subcutaneous mass in the axillary region of a 22-year-old male NMR, with histologic, immunohistochemical (pancytokeratin positive, rare p63 immunolabeling, and smooth muscle actin negative), and ultrastructural characteristics of an adenocarcinoma possibly of mammary or salivary origin. In Case No. 2, we observed a densely cellular, poorly demarcated gastric mass of polygonal cells arranged in nests with positive immunolabeling for synaptophysin and chromogranin indicative of a neuroendocrine carcinoma in an approximately 20-year-old male NMR. We also include a brief discussion of other proliferative growths and pre-cancerous lesions diagnosed in 1 zoo colony. Although these case reports do not alter the longstanding observation of cancer resistance, they do raise questions about the scope of cancer resistance and the interpretation of biomedical studies in this model. These reports also highlight the benefit of long-term disease investigations in zoo-housed populations to better understand naturally occurring disease processes in species used as models in biomedical research. © The Author(s) 2016.

  9. Paraganglioma of the urinary bladder: a clinicopathologic spectrum of a series of 14 cases emphasizing diagnostic dilemmas.

    Science.gov (United States)

    Menon, Santosh; Goyal, Pankaj; Suryawanshi, Pallavi; Tongaonkar, Hemant; Joshi, Amit; Bakshi, Ganesh; Desai, Sangeeta

    2014-01-01

    Paraganglioma (PG) of the urinary bladder is a rare neuroendocrine neoplasm, accounting for bladder tumours. Distinction from urothelial carcinoma is imperative as management and prognosis vary markedly. In this report, we describe our experience with the histopathology of paragangliomas of the urinary bladder with emphasis on the histologic features that have led to their being misdiagnosed as conventional urothelial cancer and, most importantly, those that will help pathologists recognize this rare tumor of the bladder. All cases of PG of urinary bladder diagnosed at our institute from 2002-2012 were retrieved and diagnosis confirmed in accordance with WHO classification. Clinical and treatment details were obtained from hospital medical records. Fourteen cases of PG of urinary bladder including 5 consult cases were analysed. These included 11 transurethral resections ± partial cystectomies, 2 partial cystectomies and 1 radical cystectomy. Two out of the 5 consult cases had been submitted with a diagnosis of urothelial carcinoma and 1 with that of a rhabdomyosarcoma. Age ranged from 15-84 years (median, 43 years) with a male to female ratio of 1:2.5. Presenting symptoms were haematuria, dysuria and flank pain; only 1 case had antecedent hypertension. Histologically, typical 'zellballen' (72%), diffuse (21%) and ribbon-like (7%) growth patterns amidst a richly vascularised stroma were seen. Muscularis propria invasion and necrosis was present in 72% and 21%, respectively. Substantial cautery artifacts led to misdiagnosis in the 3 erroneous cases. Tumour cells were positive for chromogranin, synaptophysin; sustentacular cells were S-100 positive. Follow up was available in 6 patients; median follow-up was 29 months (8-120 months). One patient developed distant metastasis in cervical lymph node 10 years after diagnosis; remaining were alive without evidence of disease. Paraganglioma of the urinary bladder is a rare tumor and may be misdiagnosed as urothelial cancer

  10. Relationship between clinical characteristics and survival of gastroenteropancreatic neuroendocrine neoplasms: A single-institution analysis (1995-2012) in South China.

    Science.gov (United States)

    Wang, Yu-Hong; Lin, Yuan; Xue, Ling; Wang, Jin-Hui; Chen, Min-Hu; Chen, Jie

    2012-11-29

    Gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) is the most common type of neuroendocrine tumors accounting for 65-75% of neuroendocrine neoplasms (NENs). Given the fact that there are few studies on GEP-NENs among Chinese patients, we performed a retrospective study in South China. Totally 178 patients with GEP-NENs treated at the First Affiliated Hospital of Sun Yat-sen University between January 1995 and May 2012 were analyzed retrospectively. Pancreas was found the most common site of involvement (34.8%). 149 patients (83.7%) presented as non-functional tumors with non-specific symptoms such as abdominal pain (33.7%); carcinoid syndrome was not found in this study. Several methods are useful for localization of GEP-NENs, yielding varied detection rates from 77.8% to 98.7%. Positive rates of chromogranin A (CgA) and synaptophysin (Syn) immunhistochemically were 69.1% and 90.2%, respectively. 87 patients (51.5%) had G1 tumors, 31(18.3%) G2 tumors and 51 (30.2%) G3 tumors. Neuroendocrine tumor (NET), neuroendocrine carcinoma (NEC) and mixed adenoendocrine carcinoma (MANEC) were 69.8%, 27.2% and 3.0%, respectively. 28.1% of patients presented with distant disease. Surgery was performed in 152 (85.4%) patients, and overall 5-year survival rate was 54.5%. Functionality, G1 grading and NET classification were associated with favorable prognosis in univariate analysis. Distant metastasis contributed to unfavorable prognosis of these tumors. Nonfunctional tumors with non-specific symptoms account for the majority of GEP-NENs. Diagnosis depends on pathological classification. Multidisciplinary treatments could help improve the outcome.

  11. Current Treatments for Surgically Resectable, Limited-Stage, and Extensive-Stage Small Cell Lung Cancer.

    Science.gov (United States)

    Stinchcombe, Thomas E

    2017-12-01

    The prevalence of small cell lung cancer (SCLC) has declined in the U.S. as the prevalence of tobacco use has declined. However, a significant number of people in the U.S. are current or former smokers and are at risk of developing SCLC. Routine histological or cytological evaluation can reliably make the diagnosis of SCLC, and immunohistochemistry stains (thyroid transcription factor-1, chromogranin, synaptophysin, and CD56) can be used if there is uncertainty about the diagnosis. Rarely do patients present with SCLC amendable to surgical resection, and evaluation requires a meticulous workup for extra-thoracic metastases and invasive staging of the mediastinum. Resected patients require adjuvant chemotherapy and/or thoracic radiation therapy (TRT), and prophylactic cranial radiation (PCI) should be considered depending on the stage. For limited-stage disease, concurrent platinum-etoposide and TRT followed by PCI is the standard. Thoracic radiation therapy should be started early in treatment, and can be given twice daily to 45 Gy or once daily to 60-70 Gy. For extensive-stage disease, platinum-etoposide remains the standard first-line therapy, and the standard second-line therapy is topotecan. Preliminary studies have demonstrated the activity of immunotherapy, and the response rate is approximately 10-30% with some durable responses observed. Rovalpituzumab tesirine, an antibody drug conjugate, has shown promising activity in patients with high delta-like protein 3 tumor expression (approximately 70% of patients with SCLC). The emergence of these and other promising agents has rekindled interest in drug development in SCLC. Several ongoing trials are investigating novel agents in the first-line, maintenance, and second-line settings. This review will provide an update on the standard therapies for surgically resected limited-stage small cell lung cancer and extensive-stage small cell lung cancer that have been investigated in recent clinical trials. © Alpha

  12. Treatment of a Patient with Merkel Cell Skin Carcinoma Using Radiation Therapy - A Case Report.

    Science.gov (United States)

    Petrov, Andrej; Kraleva, Slavica; Kubelka-Sabit, Katerina; Petrova, Deva

    2018-04-15

    Merkel cell carcinoma (MCC) is a rare, very aggressive tumour. The pathogenesis remains unclear, but UV radiation, immunosuppression, and the presence of Merkel cell polyomavirus in the tumour genome appear to have a key role. Merkel cell carcinoma is a highly aggressive tumour that often has a lethal end. A patient at 93 years of age comes for an examination by a dermatologist due to a rapidly growing nodular tumour growth in the forehead area. A tumour was about 3 cm in size. It had no signs of basal-cell carcinoma, no arborising vascularisation, no pigmentations on dermoscopy. Clinically, an eventual Merkel cell carcinoma was considered for the patient, but other primary skin tumours had to be excluded, as well as the possibility that regarding the patient's age, it may be a metastatic deposit. A skin biopsy was performed, as well as H-E examination and immunohistochemical analyses (positive CD56, positivity of neuroendocrine markers synaptophysin, chromogranin) which were in favour of Merkel cell carcinoma of the skin. After setting the diagnosis, our patient was treated with therapy which led to a complete withdrawal of a tumour. However, after 3 months the patient had repeated relapse of a tumour at the same site on the forehead and metastases in the retroauricular lymph nodes bilaterally. It shows that the radiotherapy as monotherapy has a great effect on the removal of the tumour formation, but unfortunately, it has no impact on lesion recurrence. It is also compatible with the literature data. In many adult patients, as our case suggests, radiotherapy could be a good palliative treatment opportunity that should be considered, as well as a combination of radiation therapy with other oncologic therapeutic options.

  13. Contribution of Human papillomavirus in neuroendocrine tumors from a series of 10,575 invasive cervical cancer cases.

    Science.gov (United States)

    Alejo, Maria; Alemany, Laia; Clavero, Omar; Quiros, Beatriz; Vighi, Susana; Seoud, Muhieddine; Cheng-Yang, Chou; Garland, Suzanne M; Juanpere, Nuria; Lloreta, Josep; Tous, Sara; Klaustermeier, Jo Ellen; Quint, Wim; Bosch, F Xavier; de Sanjosé, Silvia; Lloveras, Belen

    2018-06-01

    Neuroendocrine tumors (NET) of the cervix are rare tumors with a very aggressive course. The human papillomavirus (HPV) has been linked to its etiology. The objective of this study is to describe HPV prevalence and genotype distribution of NET. Forty-nine tumors with histological neuroendocrine features were identified among 10,575 invasive cervical cancer (ICC) cases from an international study. HPV DNA detection was done using SPF10/DEIA /LiPA 25 system. Immunohistochemical (IHC) staining for neuroendocrine markers (chromogranin A, synaptophysin, CD56) and for p16 INK4a as a surrogate for HPV transforming infection was performed. In 13 samples with negative IHC for all 3 neuroendocrine markers studied, it was possible to conduct electron microscopy (EM). NET represented 0.5% of the total ICC series and HPV was detected in 42 out of 49 samples (85.7%, 95%CI:72.8%,94.1%). HPV16 was the predominant type (54.8%), followed by HPV18 (40.5%). p16 INK4a overexpression was observed in 38/44 cases (86.4%). Neuroendocrine IHC markers could be demonstrated in 24/37 (64.9%) cases. EM identified neuroendocrine granules in 8 samples with negative IHC markers. Our data confirms the association of cervical NET with HPV and p16 INK4a overexpression. Specifically, HPV16 and 18 accounted together for over 95% of the HPV positive cases. Current HPV vaccines could largely prevent these aggressive tumors. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Peripheral primitive neuroectodermal tumor of the urinary bladder in an Arab woman with history of squamous cell carcinoma: a case report.

    Science.gov (United States)

    Al Meshaan, Mohd Khaled; Nayef, Marwan; Kwaider, Talal; Otto, Wolfgang; Katchy, Ken C

    2009-04-29

    Peripheral primitive neuroectodermal tumors of the urinary bladder are rare and tend to occur in an older age group than do their counterparts in bones and soft tissue. We report a case of peripheral primitive neuroectodermal tumor of the urinary bladder in a 67-year-old woman of Arab origin. She had undergone transurethral resection followed by chemotherapy because of pulmonary metastasized muscle-invasive squamous cell carcinoma of the bladder in 2005. One year later, she first presented with a history of repeated hematuria in our institution. Performing cystoscopy any tumor could be detected. Control cystoscopy two months later showed a tumor mass of 3 cm in diameter at another location than described for the first tumor. After perforating by transurethral resection partial bladder resection had to be done. Tissue specimen after pathological analysis revealed a peripheral primitive neuroectodermal tumor with tumor cells reactive to cluster of differentiation 99, neuron-specific enolase and S100 protein and stained negative for other markers such as cytokeratins, epithelial membrane antigen, desmin, smooth muscle actin, chromogranin and leucocyte common antigen. Staging computerized tomography was especially free from any hint on organ metastasis, but the patient died due to a cardiac problem only a few months later. To the best of our knowledge, we report the eighth case of bladder peripheral primitive neuroectodermal tumors in literature and the first concerning an Arab patient. It is also the first presentation of a peripheral primitive neuroectodermal tumor patient with a history of squamous cell carcinoma of the bladder. As in other cases, expression of single-chain-type 1 glycoprotein and neural markers was positive and the disease was at an advanced stage at the time of diagnosis.

  15. Solid pseudopapillary neoplasm of the pancreas in children: a 15-year experience and the identification of a unique immunohistochemical marker.

    Science.gov (United States)

    Laje, Pablo; Bhatti, Tricia R; Adzick, N Scott

    2013-10-01

    To review our 15-year experience in the management of children with solid pseudopapillary neoplasm (SPPN) of the pancreas at a single pediatric institution, to delineate a unique immunohistochemical marker for SPPN, and to analyze cumulative data on this rare entity in the literature. We did a retrospective analysis of the demographic data, clinical presentation, immunohistochemical characteristics, surgical approach, and long-term outcomes of all patients diagnosed with SPPN between 1997 and 2012. There were 6 patients in the series, 5 females and 1 male. Median age at presentation and at surgery was 15 years (11-18 years). Abdominal pain was the presenting symptom in 5 cases and jaundice in 1 case. Two patients had a pancreatic head tumor and underwent a pylorus-preserving pancreaticoduodenectomy. Two patients had the tumor in the pancreatic tail and underwent a distal pancreatectomy with splenectomy. Two patients had the tumor in the pancreatic body and underwent a distal pancreatectomy with splenectomy in one case and with preservation of the spleen in the other. All tumors were completely resected with pathologic margins free of disease. The median maximum diameter was 6.8 cm (3 to 15 cm). On immunohistochemistry the tumors exhibited different combinations of non-specific markers like chromogranin, vimentin and neuron-specific enolase, but all tumors showed the highly SPPN-specific paranuclear dot-like immunoreactivity pattern for CD99 in the solid as well as in the pseudopapillary areas. No patient had metastasis at presentation. Median follow-up was 6.5 years (6 months to 15 years). There were no recurrences, no long-term metastasis, and all patients are disease-free. Our series supports the concept that complete resection is necessary to achieve the best possible long-term results. Additionally, we demonstrate that SPPN exhibits a very unique immunostaining pattern for CD99 that is present in all cases. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. A Delphic consensus assessment: imaging and biomarkers in gastroenteropancreatic neuroendocrine tumor disease management

    Directory of Open Access Journals (Sweden)

    Kjell Oberg

    2016-09-01

    Full Text Available The complexity of the clinical management of neuroendocrine neoplasia (NEN is exacerbated by limitations in imaging modalities and a paucity of clinically useful biomarkers. Limitations in currently available imaging modalities reflect difficulties in measuring an intrinsically indolent disease, resolution inadequacies and inter-/intra-facility device variability and that RECIST (Response Evaluation Criteria in Solid Tumors criteria are not optimal for NEN. Limitations of currently used biomarkers are that they are secretory biomarkers (chromogranin A, serotonin, neuron-specific enolase and pancreastatin; monoanalyte measurements; and lack sensitivity, specificity and predictive capacity. None of them meet the NIH metrics for clinical usage. A multinational, multidisciplinary Delphi consensus meeting of NEN experts (n = 33 assessed current imaging strategies and biomarkers in NEN management. Consensus (>75% was achieved for 78% of the 142 questions. The panel concluded that morphological imaging has a diagnostic value. However, both imaging and current single-analyte biomarkers exhibit substantial limitations in measuring the disease status and predicting the therapeutic efficacy. RECIST remains suboptimal as a metric. A critical unmet need is the development of a clinico-biological tool to provide enhanced information regarding precise disease status and treatment response. The group considered that circulating RNA was better than current general NEN biomarkers and preliminary clinical data were considered promising. It was resolved that circulating multianalyte mRNA (NETest had clinical utility in both diagnosis and monitoring disease status and therapeutic efficacy. Overall, it was concluded that a combination of tumor spatial and functional imaging with circulating transcripts (mRNA would represent the future strategy for real-time monitoring of disease progress and therapeutic efficacy.

  17. Incidence and prognostic value of serotonin secretion in pancreatic neuroendocrine tumours.

    Science.gov (United States)

    Zandee, Wouter T; van Adrichem, Roxanne C; Kamp, Kimberly; Feelders, Richard A; van Velthuysen, Marie-Louise F; de Herder, Wouter W

    2017-08-01

    Serotonin secretion occurs in approximately 1%-4% of patients with a pancreatic neuroendocrine tumour (PNET), but the incidence is not well defined. The aim of this study was to determine the incidence of serotonin secretion with and without carcinoid syndrome and the prognostic value for overall survival (OS). Data were collected from 255 patients with a PNET if 24-hours urinary 5-hydroxyindoleacetic acid excretion (5-HIAA) was assessed. Patients were diagnosed with serotonin secretion if 24-hours urinary 5-HIAA excretion was more than 3× the upper limit of normal (ULN) of 50 μmol/24 hours during follow-up. The effect of serotonin secretion on OS was estimated with uni- and multivariate analyses using a Cox regression. Two (0.8%) patients were diagnosed with carcinoid syndrome, and another 20 (7.8%) had a serotonin-secreting PNET without symptoms. These patients mostly had ENETS stage IV disease with high chromogranin A (CgA). Serotonin secretion was a negative prognostic factor in univariate analysis (HR 2.2, 95% CI: 1.27-3.81), but in multivariate analysis, only CgA>10× ULN (HR: 1.81, 95% CI: 1.10-2.98) and neuron-specific enolase (NSE) >ULN (HR: 3.51, 95% CI: 2.26-5.46) were predictors for OS. Immunohistochemical staining for serotonin was positive in 28.6% of serotonin-secreting PNETs (one with carcinoid syndrome) and negative in all controls. Carcinoid syndrome is rare in patients with a PNET, but serotonin secretion occurs often. This is a negative prognostic factor for OS, but after correction for CgA and NSE, it is no longer a predictor and probably only a "not-so innocent bystander" in patients with high tumour burden. © 2017 John Wiley & Sons Ltd.

  18. Clinicopathologic and radiologic features of extraskeletal myxoid chondrosarcoma: a retrospective study of 40 Chinese cases with literature review.

    Science.gov (United States)

    Shao, Rui; Lao, I Weng; Wang, Lei; Yu, Lin; Wang, Jian; Fan, Qinhe

    2016-08-01

    The aim of this study is to describe the clinicopathologic and radiologic features of 40 cases of extraskeletal myxoid chondrosarcoma (EMC) from China. There were 25 males and 15 females (sex ratio, 1.7:1). Apart from an adolescent, all patients were adults with a median age of 49years. Twenty-four tumors (60%) occurred in the lower limb and limb girdles, especially the thigh, followed by the upper limb and limb girdles (20%) and trunk (10%). Other less commonly involved locations included the head and neck, sacrococcygeal region, and perineum. Tumors ranged in size from 1.5 to 19cm (mean, 7cm). By radiology, they appeared as hypoattenuated or isoattenuated masses on computed tomography with hyperintense signal on T2-weighted magnetic resonance imaging. Intralesional hypointense septa were present in most cases. Of the 40 tumors, 30 belonged to the classic subtype, whereas 9 cases were cellular, and 1 case had a rhabdoid phenotype. Tumor cells showed variable expression of synaptophysin (36%), S-100 protein (29%), epithelial membrane antigen (11%), and neuron-specific enolase (7%). Ki-67 index was remarkably higher in the cellular variant (mean, 30%). EWSR1-related rearrangement was detected in 12 of 14 cases tested by fluorescence in situ hybridization using break-apart probes. The overall 5- and 7-year survival was 71% and 60%, respectively. Awareness of the imaging features may help pathologists in the diagnosis of EMC. Fluorescence in situ hybridization also serves as a useful diagnostic tool for EMC, especially in the distinction from its mimics. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Clinical analysis of primary primitive neuroectodermal tumors in the female genital tract.

    Science.gov (United States)

    Xiao, Changji; Zhao, Jing; Guo, Peng; Wang, Dan; Zhao, Dachun; Ren, Tong; Yang, Jiaxin; Shen, Keng; Lang, Jinghe; Xiang, Yang; Cui, Quancai

    2014-03-01

    The aim of the study was to investigate the clinical manifestations, diagnosis, treatment, and prognosis of primitive neuroectodermal tumors (PNETs) in the female genital tract. From April 2001 to May 2013, the clinicopathologic characteristics, treatments, outcomes, and prognosis of 11 patients with PNET in the female genital tract were analyzed retrospectively at our hospital. The location of PNET in the 11 patients presented here included vulva (2 patients), cervix (2 patients), uterus and its ligament (5 patients), and the ovaries (2 patients). Ages ranged from 18 to 59 years (median, 31 years).The main clinical manifestations of PNET in the female genital tract are irregular vaginal bleeding (6 patients), pelvic mass, uterine enlargement, and rapidly increasing vulvar mass (8 patients), and vulvar pain and lower abdominal pain (5 patients). The CA125 levels of 8 patients were elevated before the operations and reduced to normal when the diseases were controlled, while the levels increased as the tumor was progressive. Results for the most commonly used immunohistochemistry studies revealed CD99 in 11 of the 11 tumors, synaptophysin in 6 of the 7 positive tumors, and neuron-specific enolase in 6 of the 6 tumors. Ten patients underwent surgical resection. Nine of them underwent preoperative or/and postoperative combination chemotherapy. The follow-up of 10 patients were available and ranged from 1 to 145 months (median, 30.5 months), 3 of whom experiencing recurrence. Primitive neuroectodermal tumor is very rare and can originate from any part of the female genital tract. The tumors had different manifestations but the same pathologic features. CA125 may be an important marker for prognosis and follow-up of PNET of the female internal genital tract.

  20. Neuron-Specific Enolase as a Predictor of Death or Poor Neurological Outcome After Out-of-Hospital Cardiac Arrest and Targeted Temperature Management at 33°C and 36°C

    DEFF Research Database (Denmark)

    Stammet, Pascal; Collignon, Olivier; Hassager, Christian

    2015-01-01

    levels were assessed in blood samples obtained 24, 48, and 72 h after return of spontaneous circulation. The primary outcome was neurological outcome at 6 months using the cerebral performance category score. RESULTS: NSE was a robust predictor of neurological outcome in a baseline variable......-adjusted model, and target temperature did not significantly affect NSE values. Median NSE values were 18 ng/ml versus 35 ng/ml, 15 ng/ml versus 61 ng/ml, and 12 ng/ml versus 54 ng/ml for good versus poor outcome at 24, 48, and 72 h, respectively (p ... with areas under the receiver-operating curve of 0.85 and 0.86, respectively. High NSE cutoff values with false positive rates ≤5% and tight 95% confidence intervals were able to reliably predict outcome. CONCLUSIONS: High, serial NSE values are strong predictors of poor outcome after OHCA. Targeted...

  1. Diagnosis of extraskeletal myxoid chondrosarcoma in the thigh using EWSR1-NR4A3 gene fusion: a case report.

    Science.gov (United States)

    Kobayashi, Hiroki; Kikuta, Kazutaka; Sekita, Tetsuya; Susa, Michiro; Nishimoto, Kazumasa; Sasaki, Aya; Kameyama, Kaori; Sugita, Shintaro; Hasegawa, Tadashi; Nakamura, Masaya; Matsumoto, Morio; Morioka, Hideo

    2016-11-10

    Extraskeletal myxoid chondrosarcoma is a rare soft tissue sarcoma that has unusual ultrastructural and molecular features. However, unlike other soft tissue sarcomas, it does not have specific clinical symptoms or radiological features, which can make its diagnosis difficult. Nevertheless, extraskeletal myxoid chondrosarcoma has a rare gene fusion (EWSR1-NR4A3) that is useful for making a differential diagnosis. A 43-year-old Japanese man presented with a soft tissue mass in his right thigh. A physical examination and radiography revealed a large soft tissue mass. During magnetic resonance imaging, the mass exhibited isointensity on T1-weighted images and high intensity on T2-weighted images, as well as gadolinium enhancement at the side edge of the partition structure. Thus, we considered a possible diagnosis of a malignant myxoid soft tissue tumor, such as myxoid liposarcoma, myxofibrosarcoma, or metastatic carcinomas, including myoepithelial tumor and neuroendocrine tumor, and performed an incisional biopsy to make a definitive diagnosis. The pathological findings revealed a lobulated tumor with a myxoid structure and atypical spindle-shaped cells that created eosinophilic cord-like forms. Immunohistochemistry revealed that the tumor was positive for S-100 and negative for synaptophysin, chromogranin A, and pan keratin (AE1/AE3). The percentage of Ki-67 was 10 % in the hot spot area. Based on these clinicopathological findings, we initially considered the possibility of a myxoid liposarcoma, although we did not observe any lipoblasts. Therefore, we considered the possibility of an extraskeletal myxoid chondrosarcoma. As this tumor is very rare, we searched for the EWSR1-NR4A3 gene fusion using fluorescence in situ hybridization, which confirmed the diagnosis of extraskeletal myxoid chondrosarcoma. Positron emission tomography-computed tomography did not identify any obvious metastases, and we performed radical resection of our patient's vastus medialis and

  2. Sellar/suprasellar extraventricular neurocytoma

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    Li ZHANG

    2018-01-01

    Full Text Available Objective To explore the clinicopathological features of extraventricular neurocytoma located in the sellar/suprasellar region. Methods The clinical manifestations, neuroimaging, histopathological, immunohistochemical and molecular genetic features were retrospectively analyzed in one case of sellar/suprasellar extraventricular neurocytoma, and the related literatures were reviewed. Results A 27-year-old female presented with intermittent headache, accompanied by blurred vision for 5 months. Head MRI demonstrated a mass with a well-defined margin measuring 3.80 cm × 2.50 cm × 3.40 cm located in the sellar/suprasellar region. The tumor showed isointense to hyperintense signals on T1WI and hyper-hypointense mixed signals on T2WI, and slightly hyperintense signal on diffusion-weighted imaging (DWI. The pituitary was not shown. A transsphenoidal sellar tumor resection, cerebrospinal fluid (CSF rhinorrhea repairing and optic decompression were performed. The mass was lightly yellow and tough with abundant blood supply and filled with old hemorrhage. The pituitary tissue was pushed to the left rear. Microscopy examination showed a diffuse invasive growth pattern with neuropil background in some area. The tumor cells were uniform on size and shape with round to oval, exquisite and hyperchromatic nuclei. No mitosis was found. Immunohistochemical staining showed the tumor cells were positive for neuronal nuclei (NeuN and thyroid transcription factor-1 (TTF-1 in nuclei, calretinin (CR in nuclei and cytoplasm, synaptophysin (Syn, chromogranin A (CgA, E-cadherin, matrix metalloproteinase-9 (MMP-9 in cytoplasm, and focally positive for S-100 protein (S-100 in nuclei, and neurofilament protein (NF, cytokeratin 8 (CK8 and vimentin (Vim in cytoplasm. The Ki-67 labeling index was about 3%. The tumor tissue was negative for reticular fiber staining. Molecular genetic analysis showed that isocitrate dehydrogenasel (IDH gene was not mutated, and 1p/19q was intact

  3. Malignant extra-adrenal pancreatic paraganglioma: case report and literature review

    International Nuclear Information System (INIS)

    Al-Jiffry, Bilal O; AlNemary, Yasir; Khayat, Samah H; Haiba, Moutaz; Hatem, Mohammed

    2013-01-01

    Pancreatic paragangliomas are rare tumors, with only 16 reported cases to date. One of these cases demonstrates metastasis to lymph node, while another case was functional, however, none of these cases showed malignant and large, pancreatic paraganglioma with marked invasion. Also another unique feature was the age of our patient compared to the average reported ages in published literature (42–85 years). A 19-year-old woman presented with a one-year history of intermittent abdominal pain. Physical examination showed a palpable mass in the right upper abdomen, but initial laboratory results were within normal ranges; tumor markers (CEA, AFP, and CA19-9) were negative. An abdominal and pelvic computed tomography (CT) scan showed a well-defined retroperitoneal para-aortic mass. The CT scan revealed that the surrounding lymph nodes were not enlarged, but the liver showed evidence of parenchymal infiltration. Intraoperatively, a large, firm tumor originating from the head of pancreas was found pushing on the caudate hepatic lobe and the inferior vena cava (IVC). The tumor was resected through a pancreaticoduodenectomy, involving segment VI of the liver and a small segment of the IVC. The blood pressure spiked (>220 mm Hg) when the tumor was manipulated during the operation. The final pathology report showed a 9-cm tumor with lymphovascular invasions; immunohistochemistry was positive for synaptophysin and chromogranin. All resection margins were negative and 1/15 lymph nodes was positive for metastasis. Post-operative recovery was unremarkable. One month after discharge, the patient was re-admitted with abdominal pain and found to have an abdominal collection at the resection site, which was drained under CT guidance. She received a therapeutic dose of I 131 -metaiodobenzylguanidine (MIBG). Follow-ups showed the absence of recurrence, and she has remained disease free. This patient was an extraordinary example of a rare tumor. Even more remarkable was that the tumor

  4. Morphology and Function of the Lamb Ileum following Preterm Birth

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    Tracey J. Flores

    2018-01-01

    Full Text Available BackgroundFor infants born moderately/late preterm (32–37 weeks of gestation, immaturity of the intestine has the potential to impact both short- and long-term gastrointestinal function. The aim of this study conducted in sheep was to compare the morphology and smooth muscle contractility of the ileum in term and late preterm lambs.Materials and methodsLambs delivered preterm (132 days gestation; n = 7 or term (147 days gestation; n = 9 were milk-fed after birth and euthanased at 2 days of age. A segment of distal ileum was collected for analysis of the length and cellular composition of the villi and crypts, smooth muscle width and contractility, and mRNA expression of the cell markers Ki67, lysozyme, mucin 2, synaptophysin, chromogranin A, olfactomedin 4, axis inhibition protein 2, and leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5.ResultsThere was no difference in the proportion of inflammatory, proliferating, apoptotic, enterocyte, or goblet cells between groups, but preterm lambs exhibited a significant upregulation of the stem cell marker LGR5 (p = 0.01. Absolute villus height (term: 1,032 ± 147 µm, preterm: 651 ± 52 µm; p < 0.0001 and crypt depth (term: 153 ± 11 µm, preterm: 133 ± 17 µm; p = 0.01 were significantly shorter in the preterm ileums, with a trend (p = 0.06 for a reduction in muscularis externa width. There was no difference between groups in the contractile response to acetylcholine, but peak contractility in response to bradykinin (p = 0.02 and angiotensin II (p = 0.03 was significantly greater in the preterm lambs.ConclusionFindings demonstrate that the crypt-villus units are shorter in the ileum of late preterm offspring, but functionally mature with an equivalent cellular composition and normal contractile response to acetylcholine compared with term offspring. The exaggerated contractility to inflammatory mediators evident in the

  5. Primitive Neuroectodermal Tumors of the Female Genital Tract: A Morphologic, Immunohistochemical, and Molecular Study of 19 Cases.

    Science.gov (United States)

    Chiang, Sarah; Snuderl, Matija; Kojiro-Sanada, Sakiko; Quer Pi-Sunyer, Ariadna; Daya, Dean; Hayashi, Tohru; Bosincu, Luisanna; Ogawa, Fumihiro; Rosenberg, Andrew E; Horn, Lars-Christian; Wang, Lu; Iafrate, A John; Oliva, Esther

    2017-06-01

    Primary primitive neuroectodermal tumor (PNET) of the female genital tract is rare, and its proper classification remains unclear. The clinical, histologic, and immunophenotypic features as well as EWSR1 rearrangement status of 19 gynecologic PNETs, including 10 ovarian, 8 uterine, and 1 vulvar tumors, are herein reported. Patient age ranged from 12 to 68 years, with a median age of 20 and 51 years among those with ovarian and uterine PNETs, respectively. Morphologic features of central nervous system (CNS) tumors were seen in 15 PNETs, including 9 medulloblastomas, 3 ependymomas, 2 medulloepitheliomas, and 1 glioblastoma, consistent with central PNET. The remaining 4 PNETs were composed entirely of undifferentiated small round blue cells and were classified as Ewing sarcoma/peripheral PNET. Eight PNETs were associated with another tumor type, including 5 ovarian mature cystic teratomas, 2 endometrial low-grade endometrioid carcinomas, and a uterine carcinosarcoma. By immunohistochemistry, 17 PNETs expressed at least 1 marker of neuronal differentiation, including synaptophysin, NSE, CD56, S100, and chromogranin in 10, 8, 14, 8, and 1 tumors, respectively. GFAP was positive in 4 PNETs, all of which were of central type. Membranous CD99 and nuclear Fli-1 staining was seen in 10 and 16 tumors, respectively, and concurrent expression of both markers was seen in both central and Ewing sarcoma/peripheral PNETs. All tumors expressed vimentin, whereas keratin cocktail (CAM5.2, AE1/AE3) staining was only focally present in 4 PNETs. Fluorescence in situ hybridization was successful in all cases and confirmed EWSR1 rearrangement in 2 of 4 tumors demonstrating morphologic features of Ewing sarcoma/peripheral PNET and concurrent CD99 and Fli-1 expression. In conclusion, central and Ewing sarcoma/peripheral PNETs may be encountered in the female genital tract with central PNETs being more common. Central PNETs show a spectrum of morphologic features that overlaps with CNS

  6. Proximal-type epithelioid sarcoma of pharynx: A case report with immunohistochemical study

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    Tadashi Terada, M.D., Ph.D.

    2015-06-01

    Full Text Available Epithelioid sarcoma (ES usually occurs in extremities. ES shows characteristic granulomatous morphologies, and its prognosis is not so poor. Proximal-type ES (PT-ES is a variant of ES, and is characterized by central locations, severe atypical features, and poor prognosis. Both ES and PT-ES histologically show epithelial and sarcomatous patterns, and immunohistochemically express both vimentin and cytokeratins. A 77-year-old man presented with sore throat. The laryngoscope revealed a large polypoid tumor (4 × 3 × 4 cm in upper pharynx, and a large biopsy was taken. The biopsy showed malignant epithelioid and spindle tumor cells. There were no apparent transitions between normal epithelial cells and tumor cells. The tumor consisted of malignant epithelioid and spindle cells with marked anaplasia. The tumor showed marked infiltrative features and lymphovascular permiations. Mitotic figures, atypical mitosis, and necrotic areas were present. No apparent features of sarcomas were seen. No rhabdoid cells were seen. Immunohistochemically, the malignant cells were positive for vimentin (3+, diffuse, CK AE1/3 (1+, focal, CK CAM5.2 (1+, diffuse, CK8 (1+, focal, CK18 (1+, focal, CD20 (1+, focal, p53 (3+, 84%, Ki-67 (labeling = 94%, CD68 (2+, only focal, and anti-trypsin (2+, only focal. They were negative for CK34BE12, CK5, CK6, CK7, CK14, CK19, CD99, CEA, CA19-9, CA125, EMA, S100 protein, NCAM, NSE, synaptophysin, chromogranin, α-smooth muscle actin, smooth muscle actin, desmin, CD34, CD31, CD45, D2-40, factor-VIII-related antigen, HMB-45, Melan-A, myoglobin, MDM2, CDK4, KIT, and PDGFRA. The author diagnosed this pharyngeal tumor as PT-ES, but the author cannot completely exclude the possibility of sarcomatoid carcinoma. The prognosis of patient was poor; the patient died of carcinomatosis 2 years after the manifestation.

  7. Adult medulloblastoma with myogenic differentiation

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    Xia-ling ZHANG

    2015-09-01

    Full Text Available Objective To explore the clinicopathological features of adult medulloblastoma with myogenic differentiation and to discuss clinicopathological differentiations from relevant tumors, so as to improve the ability of diagnosing and differentiating this kind of tumor. Methods The clinical manifestations, imaging, pathological features and immunohistochemical features of one case of adult medulloblastoma with myogenic differentiation were analyzed, and related literatures were reviewed. Results A 32-year-old female patient presented with repeated distortion of mouth and facial numbness for over 6 years. T1WI showed a mixed-signal lesion in the cerebellar vermis and dorsal part of brainstem, and protruded toward the fourth ventricle. Enhanced T1WI showed a round strengthened nodule in the lesion. During operation, it was seen that the tumor arised in cerebellar vermis, projected into the fourth ventricle and invaded brainstem. On microscopy examination, it was found that oval nuclei tumor cells were distributed in sheet or scattered patterns, and neuroblastic rosettes were observed. Abundant and eosinophilic cytoplasm, eccentrically placed and atypical nuclei containing hyperchromatic chromatin or prominent nucleoli in the tumor could be displayed. Mitoses were frequently seen. The tumor also presented with fresh and old hemorrhage in some place. Immunohistochemical staining showed that tumor cells were diffusely positive for integrase interactor 1 (INI1, synaptophysin (Syn, chromogranin A (CgA, human internexin neuronal intermediate filament protein α (INα, neurofilament protein (NF, Nestin (Nes, β-catenin and P53, and partly positive for desmin (Des, neuronal nuclei (NeuN and S-100 protein (S-100, but negative for glial fibrillary acidic protein (GFAP, oligodendrocyte transcription factor-2 (Olig-2, CD99, pan cytokeratin (PCK, epithelial membrane antigen (EMA, MyoD1, myogenin, muscle-specific actin (MSA and smooth muscle actin (SMA. Ki-67

  8. NEW CLASSIFICATION AND DIAGNOSIS OF APPENDICEAL CARCINOID TUMORS

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    Vuka Katić

    2012-03-01

    Full Text Available Carcinoid tumours are rare lesions that belong to the APUDoma category having the capacity of Amine Precursor Uptake and Decarboxylase. Gastrointestinal system comprises 90% of all carcinoids in the body and they are the most common type of primary malignant lesions of the appendix. New WHO classification of gastrointestinal carcinoids, diagnostic dilemmas of some carcinoid variants and, sometimes unpredictable prognosis are the reasons for the following study: clinical, macro- and microscopical as well as cytochemical and immunocytochemical examination of the vermiform appendix carcinoids, surgically removed from 16 patients. The appendectomy was induced by acute appendicitis or tumorous mass, without carcinoid syndrome. After two-day fixation in 10% formaldehyde, routinelly processed and embedded in paraffin, laboratory sections were stained with H&E, Fontana-Masson’s, Grimelius’, FIF and ABPAS methods. ABC method has been used for immunohistochemical examination. The antibodies for Chromogranin A, NSE, Synaptophysin, Cytokeratin 7, S-100 protein, Ki67 and CEA (primary antibodies and ABC (secondary antibody (Dako Kopenhagen were tested. The patients had no carcinoid syndrome. The most frequent was classic appendiceal carcinoid, well differentiated - NETG1 (8 cases, without metastases; goblet cell carcinoids were rare (3 cases, one case with liver metastases. The second case of goblet cell carcinoid was associated with cystadenoma papillare mucinosum, complicated by pseudomixoma peritonei and the third case was limited only to appendiceal wall. The patient with liver metastases died five months after appendectomy. The patient with goblet cell carcinoid associated with papillary mucinous cystadenoma and complicated by pseudomixoma peritonei had re-operation with both partial cecal and right ovarial resection, associated with washing the peritoneal cavity. The patient was feeling well during six years from the second operation. Based on our

  9. Sinonasal malignancies with neuroendocrine differentiation: Case series and review of literature

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    Menon Santosh

    2010-01-01

    Full Text Available Primary sinonasal tumors with neuroendocrine differentiation (SCND are uncommon tumors with considerable overlap of histological features. Based on their neuroendocrine differentiation they can be sub categorized into sinonasal undifferentiated carcinoma (SNUC, sinonasal neuroendocrine carcinoma (SNEC, esthesioneuroblastoma (ENB and small cell carcinoma (SmCC. The natural history and biological behavior varies in this group of tumors. Hence the histo-morphological diagnosis coupled with grading/staging is important for the prognostication of these tumors. Aim : To study the clinicopathological characteristics of sinonasal neuroendocrine malignancies at our institute. Material and Methods : We searched our institute′s pathology database for the period from 2002 to 2007, for the four subcategories of sinonasal tumors with neuroendocrine differentiation. Morphological and immunohistochemical features were studied and, grading, staging was done in accordance with standard criteria. The clinical treatment and follow- up data were retrieved from the case files in available cases. Results : A total of 37 cases were retrieved from our database which include 14 cases of SNUC, 14 cases of ENB and nine cases of SNEC. The cases of SNUC were immunopositive for cytokeratin, epithelial membrane antigen and weakly for neuron-specific enolase. SNEC showed strong reactivity with epithelial and neuroendocrine markers whereas ENB demonstrated immunoreactivity to synaptophysisn and chromogranin strongly, with weak to negative expression of epithelial markers. All cases of SNUC and SNEC were of high grade and stage whereas 50% of ENB cases were of grade II but high stage tumors. Most of the SNUC and SNEC patients had been treated with multimodality treatment regimens including upfront chemotherapy followed by surgery and loco- regional radiation. In contrast, ENB patients had undergone surgical extirpation followed by radiation therapy in majority of cases. With

  10. Survival improvement in patients with disseminated medullary thyroid carcinoma treated with 131I-MIBG therapy

    International Nuclear Information System (INIS)

    Mihaljevic, I.; Topuzovi, N.; Snajder, D.

    2015-01-01

    Full text of publication follows. Introduction and aim: The aim of this paper is to present our experience of 131 I-MIBG therapy in the cases of aggressive form of medullary thyroid carcinoma (MTC) with local and distant metastases. MTC is an uncommon thyroid tumor, accounting from 3-5% of all thyroid malignancies, and arises from para-follicular C cells which produce calcitonin (CT). Prognosis of MTC is related to tumor extension at disease detection, but long-term survival in patients with disseminated MTC is still unsatisfactory. Methods: 4 female patients with metastatic MTC (63, 69 and 2 patients aged 73 years), which already underwent total thyroidectomy and selective neck dissection, received therapy with 100 mCi 131 I-MIBG in our Institute. Patients had widespread disease with neck recurrences (all 4 cases), liver and bone metastases (2 cases) and lung metastases (1 case). All those patients received the therapy twice, second one 3 months up to 1 year after the first cycle. After therapy, whole body scintigraphy was performed; tumor marker levels (CT, carcinoembryonic antigen - CEA, neuron specific enolase - NSE, chromogranin A - CgA and pro-gastrin releasing peptide - pro-GRP) were measured before and after therapy. Results: in one patient we observed a slight decrease in CT level after first MIBG therapy, in another one a slight decrease in CEA serum level, and no lung metastases were visible on whole body scan after second 131 I-MIBG therapy. In one of the two remaining cases there was a significant decrease in CT serum level only after neck dissection. In all cases the patients reported an improvement in subjective symptom reduction. Conclusion: 131 I-MIBG therapy could provide additional benefit to patients with MTC and could improve overall survival, but more patient should be treated in order to define the true potential of the therapy. The aim of this paper is to present our experience of 131 I-MIBG therapy in the cases of aggressive form of

  11. Dual Paraneoplastic Endocrine Syndromes Heralding Onset of Extrapulmonary Small Cell Carcinoma: A Case Report and Narrative Review

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    Jill B. Feffer

    2018-04-01

    Full Text Available ObjectiveExtrapulmonary small cell carcinoma (EPSCC is rare and frequent metastases at presentation can complicate efforts to identify a site of origin. In particular, SCC comprises <1% of prostate cancers and has been implicated in castration resistance.MethodsClinical, laboratory, imaging, and pathology data are presented.ResultsA 56-year-old man with locally advanced prostate adenocarcinoma on androgen deprivation therapy presented with a clogged nephrostomy tube. Laboratory results included calcium 13.8 mg/dL (8.5–10.5 mg/dL, albumin 3.6 g/dL (3.5–5 mg/dL, and potassium 2.8 mmol/L (3.5–5.2 mmol/L. Hypercalcemia investigation revealed intact PTH 19 pg/mL (16–87 pg/mL, 25-OH vitamin D 15.7 ng/mL (>30 ng/mL, and PTH-related peptide (PTHrP 63.4 pmol/L (<2.3 pmol/L. Workup for hypokalemia yielded aldosterone 5.3 ng/dL (<31 ng/dL, renin 0.6 ng/mL/h (0.5–4 ng/mL/h, and 6:00 a.m. cortisol 82 µg/dL (6.7–22.6 µg/dL with ACTH 147 pg/mL (no ref. range. High-dose Dexamethasone suppression testing suggested ACTH-dependent ectopic hypercortisolism. Contrast-enhanced CT findings included masses in the liver and right renal pelvis, a heterogeneous enlarged mass in the region of the prostate invading the bladder, bilateral adrenal thickening, and lytic lesions in the pelvis and spine. Liver biopsy identified epithelioid malignancy with Ki proliferation index 98% and immunohistochemical staining positive for synaptophysin and neuron-specific enolase, compatible with high-grade small cell carcinoma. Staining for ACTH was negative; no stain for CRH was available. Two weeks after chemotherapy, 6:00 a.m. cortisol normalized and CT scans showed universal improvement.ConclusionExtensive literature details paraneoplastic syndromes associated with SCC, but we report the first case of EPSCC diagnosed due to onset of dual paraneoplastic syndromes.

  12. AcEST: DK961770 [AcEST

    Lifescience Database Archive (English)

    Full Text Available Gamma-enolase OS=Gallus gallus GN=ENO2 PE=2... 55 2e-09 sp|Q9W7L0|ENOA_PYTRG Alpha-enolase OS=Python regius...FEFFMD 79 E+ID A Y + +I +DVAA EF+ D Sbjct: 229 EAIDKAGYTDKIVIGMDVAASEFYRD 254 >sp|Q9W7L0|ENOA_PYTRG Alpha-enolase OS=Python

  13. Chemical mechanism of the fluoride-inhibition of fermentation

    Energy Technology Data Exchange (ETDEWEB)

    Warburg, O; Christian, W

    1941-08-01

    Among the fluoride-sensitive fermentation elements, enolase is the most sensitive. An investigation was made, quantitatively, of fluoride inhibition for chemically pure magnesium-enolase using an optical enolase test. Data show that the effective compound for fluoride inhibition is a complex magnesium-fluoro-phosphate and that the magnesium-fluoro-phosphate inhibits fermentation by combining proportionally to its concentration with the ferment-protein in a dissociating manner.

  14. Autoimmunity against a glycolytic enzyme as a possible cause for persistent symptoms in Lyme disease.

    Science.gov (United States)

    Maccallini, Paolo; Bonin, Serena; Trevisan, Giusto

    2018-01-01

    Some patients with a history of Borrelia burgdorferi infection develop a chronic symptomatology characterized by cognitive deficits, fatigue, and pain, despite antibiotic treatment. The pathogenic mechanism that underlines this condition, referred to as post-treatment Lyme disease syndrome (PTLDS), is currently unknown. A debate exists about whether PTLDS is due to persistent infection or to post-infectious damages in the immune system and the nervous system. We present the case of a patient with evidence of exposure to Borrelia burgdorferi sl and a long history of debilitating fatigue, cognitive abnormalities and autonomic nervous system issues. The patient had a positive Western blot for anti-basal ganglia antibodies, and the autoantigen has been identified as γ enolase, the neuron-specific isoenzyme of the glycolytic enzyme enolase. Assuming Borrelia own surface exposed enolase as the source of this autoantibody, through a mechanism of molecular mimicry, and given the absence of sera reactivity to α enolase, a bioinformatical analysis was carried out to identify a possible cross-reactive conformational B cell epitope, shared by Borrelia enolase and γ enolase, but not by α enolase. Taken that evidence, we hypothesize that this autoantibody interferes with glycolysis in neuronal cells, as the physiological basis for chronic symptoms in at least some cases of PTLDS. Studies investigating on the anti-γ enolase and anti-Borrelia enolase antibodies in PTLDS are needed to confirm our hypotheses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Ectopic corticotroph syndrome

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    Penezić Zorana

    2004-01-01

    located nuclei. Stromal tissue was scanty, and mitotic figures were infrequent. Tumor cells were immunoreactive for synaptophysin, neuron-specific enolase, and ACTH. The postoperative course was uneventful and the patient was discharged on glucocorticoid supplementation. Signs of Cushing's syndrome were in regression, and patient remained normotensive and normoglycaemic without therapy. DISCUSSION A multitude of normal nonpituitary cells from different organs and tissues have been shown to express the POMC gene from which ACTH is derived. The tumors most commonly associated the ectopic ACTH syndrome arise from neuroendocrine tissues, APUD cells. POMC gene expression in non-pituitary cells differs from that in pituitary cells both qualitatively and quantitatively [8], Aggressive tumors, like small cell cancer of the lung (SCCL preferentially release intact POMC, whereas carcinoids rather overprocess the precursor, releasing ACTH and smaller peptides like CLIP. Some tumors associated with ectopic ACTH syndrome express other markers of neuroendocrine differentiation like two specific prohormone convertases (PCs. Assessment of vasopressin (V3 receptor gene expression in ACTH-producing nonpituitary tumors revealed bronchial carcinoid as a particular subset of tumors where both V3 receptor and POMC gene may be expressed in pattern indistinguishable from that in corticotroph adenoma [9]. In most, but not all, patients with ectopic ACTH syndrome, cortisol is unresponsive to high-dose dexamethason suppression test, what is used as diagnostic tool. It is not clear if the primary resistance resulted from structural abnormality of the native glucocorticoid receptor (GR, a low level of expression, or some intrinsic property of the cell line [9]. It appears that ectopic ACTH syndrome is made of two different entities. When it is because of highly differentiated tumors, with highest level of pituitary-like POMC mRNA, expressing PCs, high level of V3 receptors and GR, like bronchial

  16. Metabolic Host Responses to Malarial Infection during the Intraerythrocytic Developmental Cycle

    Science.gov (United States)

    2016-08-08

    supply for other biological processes in the RBC. In contrast to the relatively high PGK flux, we obtained zero ratios for diphosphoglycerate ...iRBCs; DPGase, diphosphoglycerate phosphatase; DPGM, diphosphoglycero mutase; ENO, enolase; FBA, fructose bisphosphate aldolase; GAPD, glyceraldehyde-3...1107 kb) Abbreviations cRBC, cocultured uninfected RBCs; DPGase, diphosphoglycerate phosphatase; DPGM, diphosphoglycero mutase; ENO, enolase; FAD

  17. ATP Production in Chlamydomonas reinhardtii Flagella by Glycolytic Enzymes

    DEFF Research Database (Denmark)

    Mitchell, Beth F; Pedersen, Lotte B; Feely, Michael

    2005-01-01

    reside in the detergent-soluble (membrane + matrix) compartments. We further show that axonemal enolase is a subunit of the CPC1 central pair complex and that reduced flagellar enolase levels in the cpc1 mutant correlate with the reduced flagellar ATP concentrations and reduced in vivo beat frequencies...

  18. Backgrounds of origin and character of structural changes in testicles of coalminers of Donbass region

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    Yu. V. Danilov

    2014-04-01

    Full Text Available Introduction. For the verification of Chernobyl factor that influences the structure of testicles of Chernobyl accident liquidators that reside in Donbass region it is necessary to establish pre-existing morphological changes due to harmful work conditions in coal mines. The analytical survey of existing literature indicates the lack of actual data on this question. Purpose – to establish mechanisms of changes in morphological and functional states of testicles of coal miners by complex of qualitative and quantitative histological and immunohistochemical studies for further development of differential diagnostic criteria of verification of the Chernobyl impact factor on liquidators of CNPP accident. Material and methods. Testicles withdrawn during forensic medical examination of 57 persons (control group – 30, miners - 27 at ages of 35-45 were taken as the material. Pathohistological research was conducted according to standard methodology. Mice monoclonal antibodies were used to CD34, collаgen type IV, PCNA, chromogranin A and synaptophysine (DAKO. The preparations were studied under Olympus AX70 (Japan microscope with the use of AnalySIS Pro 3.2 program (SoftImaging Firm, Germany. The morphometric estimation of parenchyma and stroma condition included the determination of 29 parameters in testicles. The results of the research. A comparative morphological study of testicular tissue of the miner group allows us to ascertain the presence of expressed dystrophic and atrophic processes in parenchyma, which correlates with the intensity and partial depletion of function of the interstitial tissue of testes, worsening of microcirculation, expressed development of venous stasis. Against the background of growing average size and proportions of stroma this leads to the increased ratio of vascular and tubular, vascular and epithelial, stromal and parenchymal components. Consequence of malfunctioning in sperm maturation is the increase in the

  19. Carcinoma de pequenas células do esôfago: estudo clínico patológico de dois casos Small cell carcinoma of the esophagus: clinical pathologic study of two cases

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    Maria Aparecida Coelho de Arruda Henry

    2008-03-01

    . CASES REPORT: Patient 1- a 55-year-old man presenting progressive dysphagia for 6 months, weight loss, and previous smoking and alcohol abuse history. Endoscopy showed a polypoid lesion, located 30 to 40 cm from the superior arcade. Anatomopathological analysis revealed undifferentiated small-cell carcinoma and positive immunohistochemical staining for neuroendocrine markers, including chromogranin and synaptophysin. The patient presented dysphagia remission after two cycles of chemotherapy (cisplatin and etoposide and radiotherapy. Patient 2 - a 55-year-old man complaining pirosis, dysphagia, and hoarseness for 6 months, associated to a 10 kg weight loss. Endoscopy showed an obstructive polypoid lesion located 30 cm from the superior dental arcade. Anatomopathological study revealed small-cell carcinoma and positive immunohistochemical staining for neuroendocrine tumor. Computed tomography showed liver metastases. Considering the advanced stage of the tumor, gastrostomy was performed. The patient developed pneumonia and died within two months. CONCLUSION: The evolution of patients presenting small-cell carcinoma of the esophagus depends on the tumor staging. Despite of its aggressiveness, the respective tumor responds positively to combined chemo-radiotherapy.

  20. A clinicopathological analysis of papillary endolymphatic sac tumor in inner ear

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    LIN Yu-jing

    2013-05-01

    Full Text Available Background Endolymphatic sac tumor (ELST is a rare tumor originating fromendolymphatic epithelium of inner ear. This tumor exhibits low-grade malignancy with benign histopathological appearance and clinically destructive behavior which occurs in the skull base and frequently invades the posterior petrous bone, the mastoid, semicircular canal, cerebellopontine angle structures and cranial nerve. The presence of intracranial ELST always makes the diagnosis challenge for clinicians and pathologists. Herein we describe a case of ELST in skull base. The clinicopathology of this tumor and its differential diagnosis are discussed. Methods The clinical manifestation of a patient with primary ELST occurring in right cerebellopontine angle was presented retrospectively. Resected mass was routinely paraffin-embedded and stained with hematoxylin and eosin. Dako EnVision immunohistochemical staining system was used to detect the tumor antigen expressions, including cytokeratin (CK, vimentin (Vim, epithelial membrane antigen (EMA, carcinoembryonic antigen (CEA, synaptophysin (Syn, chromogranin A (CgA, S-100 protein (S-100, glial fibrillary acidic protein (GFAP, thyroglobulin (TG, thyroid transcription factor-1 (TTF-1 and Ki-67. Results A 32-year-old male patient presented with 20-year history of progressive hearing loss. MRI scan revealed an expansile lytic lesion of the mastoid process of the right petrous bone, measuring 4.20 cm × 3.30 cm × 2.00 cm, occupied the right cerebellopontine angle with infiltration of surrounding dura mater. But the lesion did not break the dura mater and invade the brain parenchyma. Craniotomy was performed and the tumor was removed totally. Histological examination revealed a papillary, cystic or glandular architecture in mass. The papillary and glandular structures were lined by a single layer of flattened cuboidal-to-columnar cells. The stroma of the papillary fronds was richly vascularized and chronically inflamed. There

  1. Histologic and Immunohistochemical classification of 41 bovine adrenal gland neoplasms

    DEFF Research Database (Denmark)

    Grossi, Anette Blak; Leifsson, Páll S.; Jensen, Henrik Elvang

    2013-01-01

    . An immunohistochemistry panel consisting of antibodies against melan A, synaptophysin, and CNPase was considered most useful to classify bovine adrenal tumors. However, the distinction between benign and malignant adrenocortical tumors was based on histologic features as in human medicine....

  2. Multiple endocrine neoplasia similar to human subtype 2A in a dog ...

    African Journals Online (AJOL)

    Primary hyperparathyroidism was diagnosed by biochemical testing. Histopathology report was consistent with diagnosis of bilateral pheochromocytoma and parathyroid adenoma. Immunohistochemical staining was positive for calcitonin and synaptophysin, and negative for thyroglobulin, which confirmed medullary thyroid ...

  3. Identification of streptococcal proteins reacting with sera from Behçet's disease and rheumatic disorders.

    Science.gov (United States)

    Cho, Sung Bin; Lee, Ju Hee; Ahn, Keun Jae; Cho, Suhyun; Park, Yong-Beom; Lee, Soo-Kon; Bang, Dongsik; Lee, Kwang Hoon

    2010-01-01

    We evaluated the reactivity of sera from Behçet's disease (BD), systemic lupus erythematosus (SLE), dermatomyositis (DM), rheumatoid arthritis (RA), and Takayasu's arteritis (TA) patients against human α-enolase and streptococcal α-enolase, and identified additional streptococcal antigens. Enzyme-linked immunosorbent assay (ELISA) and immunoblotting were performed using sera from patients with BD, SLE, DM, RA, and TA and healthy volunteers (control) against human α-enolase and streptococcal α-enolase. Immunoblot analysis and matrix-assisted laser desorption ionisation-time-of-flight mass spectrometry were used to identify and recombine other streptococcal antigens. Specific positive signals against recombinant human α-enolase were detected by IgM ELISA of serum samples from 50% of BD, 14.3% of SLE, 57.1% of DM, 42.9% of RA, and 57.1% of TA patients. Specific positive signals against streptococcal α-enolase were detected from 42.9% of BD, 14.3% of DM, and 14.3% of TA patients. No SLE and RA sera reacted against streptococcal α-enolase antigen. Streptococcal proteins reacting with sera were identified as hypothetical protein (HP) for SLE and DM patients, acid phosphatase (AP) for RA patients, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) for TA patients. We observed that RA patients did not present serum reactivity against either HP or GAPDH though BD, SLE, DM, and TA patients did. Also, AP reacted with sera from BD, SLE, DM, RA, and TA patients.

  4. Origin of Androgen-Insensitive Poorly Differentiated Tumors in the Transgenic Adenocarcinoma of Mouse Prostate Model

    Directory of Open Access Journals (Sweden)

    Wendy J. Huss

    2007-11-01

    Full Text Available Following castration, the transgenic adenocarcinoma of mouse prostate (TRAMP model demonstrates rapid development of SV40-Tag-driven poorly differentiated tumors that express neuroendocrine cell markers. The cell population dynamics within the prostates of castrated TRAMP mice were characterized by analyzing the incorporation of 5-bromodeoxyuridine (BrdUrd and the expression of SV40-Tag, synaptophysin, and androgen receptor (AR. Fourteen days postcastration, the remaining epithelial cells and adenocarcinoma cells were nonproliferative and lacked detectable SV40-Tag or synaptophysin expression. In contrast, morphologically distinct intraglandular foci were identified which expressed SV40-Tag, synaptophysin, and Ki67, but that lacked AR expression. These proliferative SV40-Tag and synaptophysin-expressing intraglandular foci were associated with the rare BrdUrd-retaining cells. These foci expanded rapidly in the postcastration prostate environment, in contrast to the AR- and SV40-Tag-expressing adenocarcinoma cells that lost SV40-Tag expression and underwent apoptosis after castration. Intraglandular foci of synaptophysin-expressing cells were also observed in the prostates of intact TRAMP mice at a comparable frequency; however, they did not progress to rapidly expanding tumors until much later in the life of the mice. This suggests that the foci of neuroendocrine-like cells that express SV40-Tag and synaptophysin, but lack AR, arise independent of androgen-deprivation and represent the source of the poorly differentiated tumors that are the lethal phenotype in the TRAMP model.

  5. Clinicopathological characteristics of papillary tumor of the pineal region

    Directory of Open Access Journals (Sweden)

    Guang-yu JIANG

    2014-07-01

    Full Text Available Background Papillary tumor of the pineal region (PTPR is a newly recognized distinct entity in the 2007 WHO nomenclature. This tumor is characterized by epithelial-appearing areas with papillary features and more densely cellular areas that often display ependymal-like differentiation, which is likely to originate from the specialized ependymocytes of subcommissural organ near the Sylvian cerebral aqueduct. Due to its rarity and non-specific appearance in radiological exanimation, it is a diagnostic challenge for radiologists and histopathologists to differentiate PTPR from other primary or metastatic lesions located in the pineal region because of their similarities in radiological and histological findings. The aim of this study is to summarize the clinicopathological features of PTPR and discuss the differential diagnosis of histologically similar papillary tumors in pineal region.  Methods The clinical manifestations of a patient with PTPR occurring in supratentorial pineal region were presented retrospectively. Resected mass was routinely paraffin-embedded and stained with hematoxylin and eosin. Dako EnVision immunohistochemical staining system was used to detect the tumor antigen expressions, including vimentin (Vim, glial fibrillary acidic protein (GFAP, S-100 protein (S-100, pan cytokeratin (PCK, cytokeratin 7 (CK7, CK20, epithelial membrane antigen (EMA, neuronal nuclear antigen (NeuN, synaptophysin (Syn, neuron-specific enolase (NSE, and Ki-67 labeling index (MIB-1.  Results A 57-year-old male patient presented with 6-month history of mild headache, and became severe in last one month. MRI revealed a solid well-circumscribed lesion in supratentorial midline near the pineal region and the posterior third ventricle with mild heterogeneous enhancement. Craniotomy was performed and the tumor was removed totally. Histological examination revealed that the lesion contained papillary areas lined by columnar epithelioid tumor cells with

  6. Global species delimitation and phylogeography of the circumtropical ‘sexy shrimp’ Thor amboinensis reveals a cryptic species complex and secondary contact in the Indo-West Pacific

    KAUST Repository

    Titus, Benjamin M.; Daly, Marymegan; Hamilton, Natalie; Berumen, Michael L.; Baeza, J. Antonio

    2018-01-01

    Specimens of Thor amboinensis were obtained through field collection and museum holdings. We used one mitochondrial (COI) and two nuclear (NaK, enolase) gene fragments for global species delimitation and phylogenetic analyses (n = 83 individuals

  7. Simultaneous overexpression of enzymes of the lower part of glycolysis can enhance the fermentative capacity of Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Smits, H. P.; Hauf, J.; Muller, S.

    2000-01-01

    Recombinant S. cerevisiae strains, with elevated levels of the enzymes of lower glycolysis (glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate mutase, phosphoglycerate kinase, enolase, pyruvate kinase, pyruvate decarboxylase and alcohol dehydrogenase) were physiologically characterized...

  8. Detection of Dichlorvos Adducts in a Hepatocyte Cell Line

    Science.gov (United States)

    2014-06-30

    5453543 aldo -keto reductase family 1 member C1 aldo -keto reductase TRUE 3 156523970 alpha-2-HS-glycoprotein preproprotein 5 4503571 alpha-enolase...enolase, (YISPDQLADLYK), three variants were identified with adducts on the first, second, or both tyrosines (Figure 2), and for one peptide in aldo -keto...suggesting the possibility that DDVP adducts could alter biological activities. The modifications of aldo -keto reductase family 1 members at three

  9. Research Resource

    DEFF Research Database (Denmark)

    Engelstoft, Maja S; Lund, Mari L; Grunddal, Kaare V

    2015-01-01

    Chromogranin A (ChgA) is an acidic protein found in large dense-core secretory vesicles and generally considered to be expressed in all enteroendocrine cells of the gastrointestinal (GI) tract. Here, we characterize a novel reporter mouse for ChgA, ChgA-humanized Renilla reniformis (hr)GFP. The h...

  10. Plasma Levels of Soluble HLA-E and HLA-F at Diagnosis May Predict Overall Survival of Neuroblastoma Patients

    Directory of Open Access Journals (Sweden)

    Fabio Morandi

    2013-01-01

    Full Text Available The purpose of this study was to identify the plasma/serum biomarkers that are able to predict overall survival (OS of neuroblastoma (NB patients. Concentration of soluble (s biomarkers was evaluated in plasma (sHLA-E, sHLA-F, chromogranin, and B7H3 or serum (calprotectin samples from NB patients or healthy children. The levels of biomarkers that were significantly higher in NB patients were then analyzed considering localized or metastatic subsets. Finally, biomarkers that were significantly different in these two subsets were correlated with patient’s outcome. With the exception of B7H3, levels of all molecules were significantly higher in NB patients than those in controls. However, only chromogranin, sHLA-E, and sHLA-F levels were different between patients with metastatic and localized tumors. sHLA-E and -F levels correlated with each other but not chromogranin. Chromogranin levels correlated with different event-free survival (EFS, whereas sHLA-E and -F levels also correlated with different OS. Association with OS was also detected considering only patients with metastatic disease. In conclusion, low levels of sHLA-E and -F significantly associated with worse EFS/OS in the whole cohort of NB patients and in patients with metastatic NB. Thus, these molecules deserve to be tested in prospective studies to evaluate their predictive power for high-risk NB patients.

  11. Development of an Aquatic Bioassay using the Medaka (Oryzias latipes) to Assess Human Health Risk: Tumor Immunodiagnosis.

    Science.gov (United States)

    1995-01-10

    tumors, melanoma Actin Skeletal muscle Chromogranin Neuroendocrine cells Myelin associated protein Neurons ULEX europaeus agglutinin I Endothelial...Actin BioGenex + Ulex europaeus agglutinin I Vector Endothelial cell antigen BioGenex ND Lysozyme BioGenex ND S-100 protein BioGenex + MAP-2

  12. Plasma chromograninx

    DEFF Research Database (Denmark)

    Goetze, Jens P; Hilsted, Linda M; Rehfeld, Jens F

    2014-01-01

    Cardiovascular risk assessment remains difficult in elderly patients. We examined whether chromogranin A (CgA) measurement in plasma may be valuable in assessing risk of death in elderly patients with symptoms of heart failure in a primary care setting. A total of 470 patients (mean age 73 years...

  13. Case report

    African Journals Online (AJOL)

    abp

    2016-03-15

    Mar 15, 2016 ... color, soft and cystic with hemorrhagic area measuring 11cm x 6 cm. Cut section revealed solid homogenous grayish tumor with multiple small cystic areas and area of hemorrhage. Microscopic finding, showed small ... LCA, CD99 and Chromogranin can help in diagnosing and differentiating these tumors.

  14. Intestinal endocrine cells in radiation enteritis

    NARCIS (Netherlands)

    Pietroletti, R.; Blaauwgeers, J. L.; Taat, C. W.; Simi, M.; Brummelkamp, W. H.; Becker, A. E.

    1989-01-01

    In this study, the intestinal endocrine cells were investigated in 13 surgical specimens affected by radiation enteritis. Endocrine cells were studied by means of Grimelius' silver staining and immunostaining for chromogranin, a general marker of endocrine cells. Positively stained cells were

  15. The long-acting somatostatin analogue octreotide alleviates symptoms by reducing posttranslational conversion of prepro-glucagon to glucagon in a patient with malignant glucagonoma, but does not prevent tumor growth

    NARCIS (Netherlands)

    F. Jockenhövel (F.); S. Lederbogen (S.); T. Olbricht (T.); H. Schmidt-Gayk (H.); E.P. Krenning (Eric); S.W.J. Lamberts (Steven); D. Reinwein (D.)

    1994-01-01

    textabstractA 52-year-old female with metastatic glucagonoma secreting glucagon and chromogranin A was treated with the somatostatin analogue octreotide for 2 years without any additional tumor-reducing interventions. Before therapy plasma glucagon was above 8 μg/l (normal <0.2) and within 2 days 3

  16. Subcellular localization of SV2 and other secretory vesicle components in PC12 cells by an efficient method of preembedding EM immunocytochemistry for cell cultures

    DEFF Research Database (Denmark)

    Tanner, V A; Ploug, Thorkil; Tao-Cheng, J H

    1996-01-01

    substantially improved the efficiency of the preembedding EM ICC procedures for cell cultures. The advantages and related caveats of this method are discussed. SV2 was distinctly localized on dusters of synaptic vesicles and large dense-cored vesicles (LDCV). The distribution of SV2 on these two types...... of secretory vesicles was compared quantitatively to that of another secretory vesicle-associated transmembrane protein, synaptophysin. In cultures under similar experimental conditions, the ratio of SV2 vs synaptophysin ICC staining on synaptic vesicle dusters was about 1:1, whereas it was about 9:1 on LDCV...

  17. Evaluating the protective efficacy of antigen combinations against Photobacterium damselae ssp. piscicida infections in cobia, Rachycentron canadum L.

    Science.gov (United States)

    Ho, L-P; Chang, C-J; Liu, H-C; Yang, H-L; Lin, J H-Y

    2014-01-01

    Cobia, Rachycentron canadum L., is a very important aquatic fish that faces the risk of infection with the bacterial pathogen Photobacterium damselae ssp. piscicida, and there are few protective approaches available that use multiple antigens. In the present study, potent bivalent antigens from P. damselae ssp. piscicida showed more efficient protection than did single antigens used in isolation. In preparations of three antigens that included recombinant heat shock protein 60 (rHSP60), recombinant α-enolase (rENOLASE) and recombinant glyceraldehyde-3-phosphate dehydrogenase (rGAPDH), we analysed the doses that elicited the best immune responses and found that this occurred at a total of 30 μg of antigen per fish. Subsequently, vaccination of fish with rHSP60, rENOLASE and rGAPDH achieved 46.9, 52 and 25% relative per cent survival (RPS), respectively. In addition, bivalent subunit vaccines--combination I (rHSP60 + rENOLASE), combination II (rENOLASE + rGAPDH) and combination III (rHSP60 + rGAPDH)--were administered and the RPS in these groups (65.6, 64.0 and 48.4%, respectively), was higher than that achieved with single-antigen administration. Finally, in combination IV, the trivalent vaccine rHSP60 + rENOLASE + rGAPDH, the RPS was 1.6%. Taken together, our results suggest that combinations of two antigens may achieve a better efficiency than monovalent or trivalent antigens, and this may provide new insights into pathogen prevention strategies. © 2013 John Wiley & Sons Ltd.

  18. Salivary Hormones Response to Preparation and Pre-competitive Training of World-class Level Athletes

    Science.gov (United States)

    Guilhem, Gaël; Hanon, Christine; Gendreau, Nicolas; Bonneau, Dominique; Guével, Arnaud; Chennaoui, Mounir

    2015-01-01

    This study aimed to compare the response of salivary hormones of track and field athletes induced by preparation and pre-competitive training periods in an attempt to comment on the physiological effects consistent with the responses of each of the proteins measured. Salivary testosterone, cortisol, alpha-amylase, immunoglobulin A (IgA), chromogranin A, blood creatine kinase activity, and profile of mood state were assessed at rest in 24 world-class level athletes during preparation (3 times in 3 months) and pre-competitive (5 times in 5 weeks) training periods. Total mood disturbance and fatigue perception were reduced, while IgA (+61%) and creatine kinase activity (+43%) increased, and chromogranin A decreased (−27%) during pre-competitive compared to preparation period. A significant increase in salivary testosterone (+9 to +15%) and a decrease in testosterone/cortisol ratio were associated with a progressive reduction in training load during pre-competitive period (P athletics training. PMID:26635619

  19. Renal albumin excretion: twin studies identify influences of heredity, environment, and adrenergic pathway polymorphism

    DEFF Research Database (Denmark)

    Rao, Fangwen; Wessel, Jennifer; Wen, Gen

    2007-01-01

    biosynthesis (tyrosine hydroxylase), catabolism (monoamine oxidase A), storage/release (chromogranin A), receptor target (dopamine D1 receptor), and postreceptor signal transduction (sorting nexin 13 and rho kinase). Epistasis (gene-by-gene interaction) occurred between alleles at rho kinase, tyrosine...... hydroxylase, chromogranin A, and sorting nexin 13. Dopamine D1 receptor polymorphism showed pleiotropic effects on both albumin and dopamine excretion. These studies establish new roles for heredity and environment in albumin excretion. Urinary excretions of albumin and catecholamines are highly heritable......, and their parallel suggests adrenergic mediation of early glomerular permeability alterations. Albumin excretion is influenced by multiple adrenergic pathway genes and is, thus, polygenic. Such functional links between adrenergic activity and glomerular injury suggest novel approaches to its prediction, prevention...

  20. An incidentally found inflamed uterine myoma Causing low abdominal pain, using TC-99m-tektrotyd single photon emission computed tomography-CT hybrid imaging

    Energy Technology Data Exchange (ETDEWEB)

    Zandieh, Shahin; Schuetz, Matthias; Bernt, Reinhard; Zwerina, Jochen; Haller, Joerg [Hanusch-Hospital, Teaching Hospital of Medical University of Vienna, Vienna (Australia)

    2013-10-15

    We report the case of a 50-year-old woman presented with a history of right hemicolectomy due to an ileocecal neuroendocrine tumor and left breast metastasis. Owing to a slightly elevated chromogranin A-level and lower abdominal pain, single photon emission computed tomography-computer tomography (SPECT-CT) was performed. There were no signs of recurrence on the SPECT-CT scan, but the patient was incidentally found to have an inflamed intramural myoma. We believe that the slightly elevated chromogranin A-level was caused by the hypertension that the patient presented. In the clinical context, this is a report of an inflamed uterine myoma seen as a false positive result detected by TC-99m-Tc-EDDA/HYNIC-Tyr3-Octreotide (Tektrotyd) SPECT-CT hybrid imaging.

  1. Dicty_cDB: VFO725 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available phosphopyruvate hydratase (EC 4.2.1.11) - liver f... 264 1e-69 AM279157_1( AM279157 |pid:none) Echinostoma capron...i mRNA for enola... 254 9e-67 DQ869009_1( DQ869009 |pid:none) Echinostoma caproni enolase mRNA, ... 25

  2. Neuronal damage biomarkers in the identification of patients at risk of long-term postoperative cognitive dysfunction after cardiac surgery

    NARCIS (Netherlands)

    Kok, W F; Koerts, Janneke; Tucha, O; Scheeren, T W L; Absalom, A R

    Biomarkers of neurological injury can potentially predict postoperative cognitive dysfunction. We aimed to identify whether classical neuronal damage-specific biomarkers, including brain fatty acid-binding protein, neuron-specific enolase and S100 calcium-binding protein β, as well as plasma-free

  3. Efficient transduction of neurons using Ross River glycoprotein-pseudotyped lentiviral vectors

    DEFF Research Database (Denmark)

    Jakobsson, J; Nielsen, T Tolstrup; Staflin, K

    2006-01-01

    , including the possibility to establish stable producer cell lines. After injection of RRV-LV expressing green fluorescent protein into different structures in the rat brain we found efficient transduction of both neurons and glial cells. By using two cell-type-specific promoters, neuron-specific enolase...

  4. Effect of prolonged exposure to sublethal concentrations of DDT and DDE on protein expression in human pancreatic beta cells

    Czech Academy of Sciences Publication Activity Database

    Pavlíková, N.; Smetana, P.; Halada, Petr; Kovář, J.

    2015-01-01

    Roč. 142, OCT 2015 (2015), s. 257-263 ISSN 0013-9351 Grant - others:OPPK(CZ) CZ.2.16/3.1.00/24023 Source of funding: O - operačné programy Keywords : Diabetes * DDT/E * Alpha-enolase Subject RIV: CE - Biochemistry Impact factor: 3.088, year: 2015

  5. Dicty_cDB: Contig-U00903-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available ame: Full=Gamma-enolase; EC=4.2.1.11; AltN... 37 0.17 EU080354_1( EU080354 |pid:none) Phytophthora cuyabensi...1( EU080519 |pid:none) Phytophthora psychrophila isolate ... 37 0.17 EU080374_1( EU080374 |pid:none) Phytophthora cuy

  6. Neonatal acute megakaryoblastic leukemia mimicking congenital neuroblastoma

    OpenAIRE

    Kawasaki, Yukako; Makimoto, Masami; Nomura, Keiko; Hoshino, Akihiro; Hamashima, Takeru; Hiwatari, Mitsuteru; Nakazawa, Atsuko; Takita, Junko; Yoshida, Taketoshi; Kanegane, Hirokazu

    2014-01-01

    Key Clinical Message We describe a neonate with abdominal distension, massive hepatomegaly, and high serum neuron-specific enolase level suggestive of congenital neuroblastoma. The patient died of pulmonary hemorrhage after therapy. Autopsy revealed that the tumor cells in the liver indicated acute megakaryocytic leukemia with the RBM15-MKL1 fusion gene.

  7. Markers of cerebral damage during delirium in elderly patients with hip fracture

    NARCIS (Netherlands)

    van Munster, Barbara C.; Korse, Catharina M.; de Rooij, Sophia E.; Bonfrer, Johannes M.; Zwinderman, Aeilko H.; Korevaar, Johanna C.

    2009-01-01

    ABSTRACT: BACKGROUND: S100B protein and Neuron Specific Enolase (NSE) can increase due to brain cell damage and/or increased permeability of the blood-brain-barrier. Elevation of these proteins has been shown after various neurological diseases with cognitive dysfunction. Delirium is characterized

  8. Plasmodium ookinetes coopt mammalian plasminogen to invade the mosquito midgut

    DEFF Research Database (Denmark)

    Ghosh, Anil K; Coppens, Isabelle; Gårdsvoll, Henrik

    2011-01-01

    Ookinete invasion of the mosquito midgut is an essential step for the development of the malaria parasite in the mosquito. Invasion involves recognition between a presumed mosquito midgut receptor and an ookinete ligand. Here, we show that enolase lines the ookinete surface. An antienolase antibody...

  9. Protein S100 as outcome predictor after out-of-hospital cardiac arrest and targeted temperature management at 33 °C and 36 °C

    DEFF Research Database (Denmark)

    Stammet, Pascal; Dankiewicz, Josef; Nielsen, Niklas

    2017-01-01

    -specific enolase (NSE) did not further improve the AUC. CONCLUSIONS: The allocated target temperature did not affect S100 to a clinically relevant degree. High S100 values are predictive of poor outcome but do not add value to present prognostication models with or without NSE. S100 measured at 24 h and afterward...

  10. MicroRNA-22 and promoter motif polymorphisms at the Chga locus in genetic hypertension: functional and therapeutic implications for gene expression and the pathogenesis of hypertension

    Czech Academy of Sciences Publication Activity Database

    Friese, R. S.; Altshuler, A. E.; Zhang, K.; Miramontes-Gonzales, J. P.; Hightower, C. M.; Jirout, M. L.; Salem, R. M.; Gayen, J. R.; Mahapatra, N. R.; Biswas, N.; Cale, M.; Vaingankar, S. M.; Kim, H.-S.; Courel, M.; Taupenot, L.; Ziegler, M. G.; Schork, N. J.; Pravenec, Michal; Mahata, S. K.; Schmid-Schönbein, G. W.; O´Connor, D. T.

    2013-01-01

    Roč. 22, č. 18 (2013), s. 3624-3640 ISSN 0964-6906 R&D Projects: GA ČR(CZ) GAP301/10/0290; GA ČR(CZ) GAP301/12/0696 Institutional support: RVO:67985823 Keywords : Chromogranin A * spontaneously hypertensive rat * mir-22 * blood pressure * catecholamines Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.677, year: 2013

  11. Evidence of chromaffin oxygen sensing in neuroblastoma.

    Science.gov (United States)

    Hedborg, F; Franklin, G; Norrman, J; Grimelius, L; Wassberg, E; Hero, B; Schilling, F; Berthold, F; Harms, D; Sandstedt, B

    2001-01-01

    With the aid of IGF2 and VEGF in situ hybridization; tyrosine hydroxylase, chromogranin A, and Ki67 immunohistochemistry; and TUNEL staining applied to a large series of clinical neuroblastomas and to an animal model, we show here that stroma-poor neuroblastomas show evidence of chromaffin differentiation similar to that of type 1 small intensely fluorescent (SIF) cells and that this occurs in a vascular-dependent fashion, indicating a role for local tumor hypoxia in the differentiation process.

  12. Paragangliomas of the head and neck: clinical, morphological and immunohistochemical aspects

    Directory of Open Access Journals (Sweden)

    Pedro de Alcântara de Andrade Filho

    2001-05-01

    Full Text Available CONTEXT: Protein marker positivity can assist in the definition of the therapeutic approach towards head and neck paragangliomas. The establishment of the therapeutic approach should incorporate the results of such an investigation. OBJECTIVE: To establish criteria for benignancy and malignancy of vagal and jugular-tympanic paragangliomas, via the study of the relationships of sex, age, tumor size, duration of complaints, site, family history, presence of metastases, treatment, histological architecture and cell type with the immunohistochemical reactions to S100 protein, chromogranin and AgKi67. DESIGN: A retrospective study of histological and clinical records. SETTING: The Heliópolis and Oswaldo Cruz tertiary general hospitals, São Paulo. SAMPLE: 8 cases of head and neck paragangliomas. MAIN MEASUREMENTS: Determination of degree of positivity to paragangliomas via immunohistochemical reactions. RESULTS: 1. The protein markers for the principal cells (AgKi67 and chromogranin were sensitive in 100% of the tumors when used together. 2. S100 protein was well identified in the cytoplasm and nucleus of sustentacular cells and underwent reduction in the neoplasias. CONCLUSIONS: Chromogranin was proven to be a generic marker for neuroendocrine tumors; S100 protein was positive in all 8 cases and the AgKi67 had low positivity in all cases.

  13. Secretion of pancreastatins from the porcine digestive tract

    International Nuclear Information System (INIS)

    Boerglum Jensen, T.D.; Holst, J.J.; Fahrenkrug, J.

    1994-01-01

    Pancreastatin, a 49-amino acid peptide with a COOH-terminal glycine amide, was originally isolated from porcine pancreas, but pancreastatin immunoreactivity has been found in several neuroendocrine tissues. There are strong indications that pancreastatin is derived from chromogranin A, since the amino acid sequence 240-288 in porcine chromogranin A corresponds to pancreastatin flanked by typical signals for proteolytic processing. The authors studied the effect of electric stimulation of the nervous supply to perfused porcine pancreas, antrum, nonantral stomach, and small intestine on the release of immunoreactive pancreastatin, and they have characterized the molecular nature of the secreted immunoreactivity by using a radioimmunoassay specific for the COOH-terminal glycine amide of porcine pancreastatin in combination with chromatography. In all tissues nerve stimulation significantly increased the release of immunoreactive pancreastatin. The secreted immunoreactive pancreastatin was heterogeneous, consisting of pancreastatin itself, a COOH-terminal pancreastatin fragment, and NH 2 -terminally extended pancreastatin forms. Pancreastatin predominated in the perfusate from pancreas and antrum, whereas mainly NH 2 -terminally extended molecular forms were secreted from the antrectomized stomach and small intestine. The different molecular forms of pancreastatin were secreted from the perfused organs in the same molar ratio as they occur in extracts of the corresponding tissues. Thus, pancreastatin and other chromogranin A-derived peptides in organ-specific proportions regularly accompany the secretion of the peptide hormones from the gastrointestinal tissues on appropriate stimulation. 40 refs., 5 figs

  14. Morphogenetic and neuronal characterization of human neuroblastoma multicellular spheroids cultured under undifferentiated and all-trans-retinoic acid-differentiated conditions

    Directory of Open Access Journals (Sweden)

    Gwon-Soo Jung

    2013-05-01

    Full Text Available In this study, we aimed to compare the morphogenetic andneuronal characteristics between monolayer cells andspheroids. For this purpose, we established spheroid formationby growing SH-SY5Y cells on the hydrophobic surfaces ofthermally-collapsed elastin-like polypeptide. After 4 days ofculture, the relative proliferation of the cells within spheroidswas approximately 92% of the values for monolayer cultures.As measured by quantitative assays for mRNA and proteinexpressions, the production of synaptophysin and neuronspecificenolase (NSE as well as the contents of cell adhesionmolecules (CAMs and extracellular matrix (ECM proteins aremuch higher in spheroids than in monolayer cells. Under theall-trans-retinoic acid (RA-induced differentiation condition,spheroids extended neurites and further up-regulated theexpression of synaptophysin, NSE, CAMs, and ECM proteins.Our data indicate that RA-differentiated SH-SY5Y neurospheroidsare functionally matured neuronal architectures. [BMBReports 2013; 46(5: 276-281

  15. Expression of neuronal antigens and related ventral and dorsal proteins in the normal spinal cord and a surgically induced open neural tube defect of the spine in chick embryos: an immunohistochemical study.

    Science.gov (United States)

    Lee, Do-Hun; Phi, Ji Hoon; Chung, You-Nam; Lee, Yun-Jin; Kim, Seung-Ki; Cho, Byung-Kyu; Kim, Dong Won; Park, Moon-Sik; Wang, Kyu-Chang

    2010-05-01

    The aims of this study were to elucidate the processes of neuronal differentiation and ventrodorsal patterning in the spinal cord of the chick embryo from embryonic day (E) 3 to E17 and to study the effect of a prenatal spinal open neural tube defect (ONTD) on these processes. Expression patterns of neuronal antigens (neuronal nuclear antigen, neurofilament-associated protein (NAP), and synaptophysin) and related ventral markers [sonic hedgehog, paired box gene (PAX)6, and islet-1], and dorsal markers (bone morphogenetic protein, Notch homolog 1, and PAX7) were investigated in the normal spinal cord and in a surgically induced spinal ONTD in chick embryos. Four normal and ONTD chick embryos were used for each antigen group. There were no differences in the expression of neuronal and ventrodorsal markers between the control and ONTD groups. NAP and synaptophysin were useful for identifying dorsal structures in the distorted anatomy of the ONTD chicks.

  16. Caffeine and modafinil given during 48 h sleep deprivation modulate object recognition memory and synaptic proteins in the hippocampus of the rat.

    Science.gov (United States)

    Wadhwa, M; Sahu, S; Kumari, P; Kauser, H; Ray, K; Panjwani, U

    2015-11-01

    We aimed to evaluate the effect of caffeine/modafinil on sleep deprivation (SD) induced alterations in recognition memory and synaptic proteins. The data revealed a beneficial effect of caffeine/modafinil against deficit in the familiar object retrieval performance and object exploration ratio after 48 h SD. Caffeine treatment prevented the SD induced down-regulation of synaptophysin and synapsin I proteins with no change in PSD-95 protein in hippocampus. However, modafinil administration improved the down-regulation of synaptophysin, synapsin I and PSD-95 proteins in hippocampus. Hence, caffeine/modafinil can serve as counter measures in amelioration of SD induced consequences at behavioural and protein levels. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. The Role of NFIB in Prostate Cancer Progression

    Science.gov (United States)

    2015-09-01

    DHT ) and anti-androgens (bicalutamide [Bic] and enzalutamide [Enz]) in cell lines generated in Aim 1b. Cell lines used: LNCaP, 22RV1, PC-3, and DU145...prevent NED (loss of AR, gain of synaptophysin), alter the response to DHT and sensitivity to bicalutamide, an anti-androgen. Similarly, 22RV1 cells...sufficient to prevent the expression of genes associated with NED. NFIB modulates AR and AR-target gene expression in response to DHT Transient

  18. Growth and Progression of TRAMP Prostate Tumors in Relationship to Diet and Obesity

    Directory of Open Access Journals (Sweden)

    Melissa J. L. Bonorden

    2012-01-01

    Full Text Available To clarify effects of diet and body weight on prostate cancer development, three studies were undertaken using the TRAMP mouse model of this disease. In the first experiment, obesity was induced by injection of gold thioglucose (GTG. Age of prostate tumor detection (~33 wk and death (~43 wk was not significantly different among the groups. In the second study, TRAMP-C2 cells were injected into syngeneic C57BL6 mice and tumor progression was evaluated in mice fed either high-fat or low-fat diets. The high fat fed mice had larger tumors than did the low-fat fed mice. In the third study, tumor development was followed in TRAMP mice fed a high fat diet from 6 weeks of age. There were no significant effects of body weight status or diet on tumor development among the groups. When the tumors were examined for the neuroendocrine marker synaptophysin, there was no correlation with either body weight or diet. However, there was a significant correlation of the expression of synaptophysin with earlier age to tumor detection and death. In summary, TRAMP-C2 cells grew faster when the mice were fed a high-fat diet. Further synaptophysin may be a marker of poor prognosis independent of weight and diet.

  19. Ovarian hormones modify anxiety behavior and glucocorticoid receptors after chronic social isolation stress.

    Science.gov (United States)

    Ramos-Ortolaza, Dinah L; Doreste-Mendez, Raura J; Alvarado-Torres, John K; Torres-Reveron, Annelyn

    2017-06-15

    Chronic social isolation could lead to a disruption in the Hypothalamic-Pituitary-Adrenal (HPA) axis, resulting in anxiety and depressive-like behaviors but cycling estrogens could modify these behaviors. The aim of this study was to determine if changes in ovarian hormones during the normal cycle could interact with social isolation to alter anxiety and depressive-like behaviors. In parallel, we examined the expression of glucocorticoid receptor (GR) and synaptic vesicle protein synaptophysin in the hippocampus and hypothalamus of Sprague Dawley normal cycling female rats. We assigned rats to either isolated or paired housing for 8 weeks. To assess anxiety and depressive-like behaviors, we used the open field test and forced swim test, respectively. Female rats were tested at either diestrus, estrus, or proestrus stage of the estrous cycle. After behaviors, rats were perfused and brains collected. Brain sections containing hippocampus and hypothalamus were analyzed using immunohistochemistry for synaptophysin and glucocorticoid receptor (GR) levels. We found an increase in depressive-like behaviors for isolated animals compared to paired housed rats, regardless of the estrous cycle stage. Interestingly, we found a decrease in anxiety behaviors in females in the estrus stage accompanied by a decrease in GR expression in hippocampal DG and CA3. However, no changes in synaptophysin were observed in any of the areas of studied. Our results support the beneficial effects of circulating ovarian hormones in anxiety, possibly by decreasing GR expression. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Brain signaling and behavioral responses induced by exposure to (56)Fe-particle radiation

    Science.gov (United States)

    Denisova, N. A.; Shukitt-Hale, B.; Rabin, B. M.; Joseph, J. A.

    2002-01-01

    Previous experiments have demonstrated that exposure to 56Fe-particle irradiation (1.5 Gy, 1 GeV) produced aging-like accelerations in neuronal and behavioral deficits. Astronauts on long-term space flights will be exposed to similar heavy-particle radiations that might have similar deleterious effects on neuronal signaling and cognitive behavior. Therefore, the present study evaluated whether radiation-induced spatial learning and memory behavioral deficits are associated with region-specific brain signaling deficits by measuring signaling molecules previously found to be essential for behavior [pre-synaptic vesicle proteins, synaptobrevin and synaptophysin, and protein kinases, calcium-dependent PRKCs (also known as PKCs) and PRKA (PRKA RIIbeta)]. The results demonstrated a significant radiation-induced increase in reference memory errors. The increases in reference memory errors were significantly negatively correlated with striatal synaptobrevin and frontal cortical synaptophysin expression. Both synaptophysin and synaptobrevin are synaptic vesicle proteins that are important in cognition. Striatal PRKA, a memory signaling molecule, was also significantly negatively correlated with reference memory errors. Overall, our findings suggest that radiation-induced pre-synaptic facilitation may contribute to some previously reported radiation-induced decrease in striatal dopamine release and for the disruption of the central dopaminergic system integrity and dopamine-mediated behavior.

  1. Facial nerve ganglioneuroblastoma in a feline leukemia virus-positive cat

    Directory of Open Access Journals (Sweden)

    Paula Reis Pereira

    Full Text Available ABSTRACT: Neuroblastic tumors can originate from the central neuraxis, olfactory epithelium, adrenal medullary region or autonomous system. Ganglioneuroblastoma are a type of neuroblastic tumor, with very few case descriptions in animals. Diagnosis of facial nerve ganglioneuroblastoma was made in a feline leukemia virus-positive 11-month-old cat. The cat had hyporexia, left head tilt, depressed mental state, horizontal nystagmus, inability to retract the pinched left lip, anisocoria, ptosis, and absence of the menace reflex. Gross necropsy showed a mass at the left facial nerve root region. Histological examination of this mass showed neoplastic proliferation of neuroblasts arranged in a cohesive pattern and mature ganglion cells. Ganglion cells were positive for neurofilament, neuron-specific enolase, S100, and glial fibrillary acidic protein by immunohistochemistry, while neuroblasts were positive for vimentin, S100, neuron-specific enolase and feline leukemia virus.

  2. Proteomics analysis of ram sperm by heavy ion radiation

    International Nuclear Information System (INIS)

    He Yuxuan; Li Hongyan; Zhang Hong

    2013-01-01

    The objective of this study was to investigate the proteome changes induced by heavy ion radiation using irradiated ram sperm by a two-dimensional electrophoresis (2-DE) analysis. The 2D gels were stained with Coomassie Brilliant Blue. Differentially expressed proteins were detected by PDQuest 8.0 software and subjected to ion trap mass spectrometer equipped with a surveyor HPLC system, and differential protein spots were identified. Results showed there are five differential protein spots in irradiated sperm gels, four up-regulated protein spots and one spot missed. The differentially expressed protein spots were identified to be two up-regulated proteins including enolase, and enolase 1. It was concluded there was proteome changes induced by heavy ion radiation in ram sperm, which may be useful to clarify the physiology state of ram sperm in heavy ion radiation and provide a theoretical basis for radiation ram breeding. (authors)

  3. Brain injury markers (S100B and NSE) in chronic cocaine dependents

    OpenAIRE

    Kessler, Felix Henrique Paim; Woody, George; Portela, Luis Valmor Cruz; Tort, Adriano Bretanha Lopes; De Boni, Raquel Brandini; Peuker, Ana Carolina Wolf Baldino; Genro, Vanessa Krebs; Diemen, Lisia von; Souza, Diogo Onofre Gomes de; Pechansky, Flavio

    2007-01-01

    Objetivo: Estudos têm demonstrado sinais de lesão cerebral causadas por diferentes mecanismos em usuários de cocaína. A enolase sérica neurônio-específica e a proteína S100B são consideradas marcadores bioquímicos específicos de lesão neuronal e glial. Este estudo objetivou comparar os níveis sangüíneos de S100B e enolase sérica neurônio-específica em usuários crônicos de cocaína e em voluntários que não usam cocaína ou outras drogas ilícitas. Método: Vinte sujeitos dependentes de cocaína, ma...

  4. Neuroprotective Effects of the Glucagon-Like Peptide-1 Analog Exenatide After Out-of-Hospital Cardiac Arrest

    DEFF Research Database (Denmark)

    Wiberg, Sebastian; Hassager, Christian; Schmidt, Henrik

    2016-01-01

    points were feasibility, defined as initiation of the study drug in >90% patients within 240 minutes of return of spontaneous circulation, and efficacy, defined as the geometric area under the neuron-specific enolase curve from 24 to 72 hours after admission. The main secondary end points included...... a composite end point of death and poor neurological function, defined as a Cerebral Performance Category score of 3 to 5 assessed at 30 and 180 days. RESULTS: The study drug was initiated within 240 minutes of return of spontaneous circulation in 96% patients. The median blood glucose 8 hours after admission...... in patients receiving exenatide was lower than that in patients receiving placebo (5.8 [5.2-6.7] mmol/L versus 7.3 [6.2-8.7] mmol/L, Pneuron-specific enolase curve, or a composite end point of death and poor neurological function...

  5. Sub-lethal Ocular Trauma (SLOT): Establishing a Standardized Blast Threshold to Facilitate Diagnostic, Early Treatment, and Recovery Studies for Blast Injuries to the Eye and Optic Nerve

    Science.gov (United States)

    2014-09-01

    NSE (neuron specific enolase) PARK5/UCHL1 ( Parkinson Disease Protein 5) PARK7/DJ-1 ( Parkinson Disease Protein 7) 2. Human TH17 Magnetic Bead...for discovery of trauma-related biomarkers. 42 Figure 29. The average protein mass spectrum (abundance vs m/z). The color boxes indicate the...spectrum obtained from the tissue section shown in Figure 30. Color boxes indicate m/z ratios of corresponding protein spatial distributions in Figure 30

  6. Quantitative proteomics of the tonoplast reveals a role for glycolytic enzymes in salt tolerance.

    Science.gov (United States)

    Barkla, Bronwyn J; Vera-Estrella, Rosario; Hernández-Coronado, Marcela; Pantoja, Omar

    2009-12-01

    To examine the role of the tonoplast in plant salt tolerance and identify proteins involved in the regulation of transporters for vacuolar Na(+) sequestration, we exploited a targeted quantitative proteomics approach. Two-dimensional differential in-gel electrophoresis analysis of free flow zonal electrophoresis separated tonoplast fractions from control, and salt-treated Mesembryanthemum crystallinum plants revealed the membrane association of glycolytic enzymes aldolase and enolase, along with subunits of the vacuolar H(+)-ATPase V-ATPase. Protein blot analysis confirmed coordinated salt regulation of these proteins, and chaotrope treatment indicated a strong tonoplast association. Reciprocal coimmunoprecipitation studies revealed that the glycolytic enzymes interacted with the V-ATPase subunit B VHA-B, and aldolase was shown to stimulate V-ATPase activity in vitro by increasing the affinity for ATP. To investigate a physiological role for this association, the Arabidopsis thaliana cytoplasmic enolase mutant, los2, was characterized. These plants were salt sensitive, and there was a specific reduction in enolase abundance in the tonoplast from salt-treated plants. Moreover, tonoplast isolated from mutant plants showed an impaired ability for aldolase stimulation of V-ATPase hydrolytic activity. The association of glycolytic proteins with the tonoplast may not only channel ATP to the V-ATPase, but also directly upregulate H(+)-pump activity.

  7. Quantitative Proteomics of the Tonoplast Reveals a Role for Glycolytic Enzymes in Salt Tolerance[C][W

    Science.gov (United States)

    Barkla, Bronwyn J.; Vera-Estrella, Rosario; Hernández-Coronado, Marcela; Pantoja, Omar

    2009-01-01

    To examine the role of the tonoplast in plant salt tolerance and identify proteins involved in the regulation of transporters for vacuolar Na+ sequestration, we exploited a targeted quantitative proteomics approach. Two-dimensional differential in-gel electrophoresis analysis of free flow zonal electrophoresis separated tonoplast fractions from control, and salt-treated Mesembryanthemum crystallinum plants revealed the membrane association of glycolytic enzymes aldolase and enolase, along with subunits of the vacuolar H+-ATPase V-ATPase. Protein blot analysis confirmed coordinated salt regulation of these proteins, and chaotrope treatment indicated a strong tonoplast association. Reciprocal coimmunoprecipitation studies revealed that the glycolytic enzymes interacted with the V-ATPase subunit B VHA-B, and aldolase was shown to stimulate V-ATPase activity in vitro by increasing the affinity for ATP. To investigate a physiological role for this association, the Arabidopsis thaliana cytoplasmic enolase mutant, los2, was characterized. These plants were salt sensitive, and there was a specific reduction in enolase abundance in the tonoplast from salt-treated plants. Moreover, tonoplast isolated from mutant plants showed an impaired ability for aldolase stimulation of V-ATPase hydrolytic activity. The association of glycolytic proteins with the tonoplast may not only channel ATP to the V-ATPase, but also directly upregulate H+-pump activity. PMID:20028841

  8. (99m)Tc HYNIC-TOC imaging and 177Lu DOTA-octreotate treatment in non-iodine-concentrating dedifferentiated thyroid carcinoma metastases: an unusual alternative diagnosis.

    Science.gov (United States)

    Basu, Sandip; Joshi, Amit

    2014-07-01

    The value of Tc HYNIC-TOC scintigraphy clarifying skeletal and hepatic-predominant metastatic disease in a 55-year-old woman (diagnosed earlier to have papillary carcinoma thyroid and had undergone total thyroidectomy and radioiodine ablation) is illustrated. The whole-body radioiodine scan and battery of serum tumor markers were normal. Multiple metastatic foci in the liver and skeleton were Tc HYNIC-TOC avid. Serum chromogranin A level was substantially elevated (1771.60 ng/mL). This represents an unusual alternative diagnosis signified by a highly positive scan in the setting of apparent non-iodine-concentrating metastatic disease in a patient of differentiated thyroid carcinoma.

  9. Von Hippel-Lindau disease (vHL)

    DEFF Research Database (Denmark)

    Binderup, Marie Louise Mølgaard; Bisgaard, Søs Marie Luise; Harbud, Vibeke

    2013-01-01

    for vHL which is comprised of Danish doctors and specialists interested in vHL. The recommendations are based on longstanding clinical experience, Danish original research, and extensive review of the international literature. vHL is a hereditary multi-tumour disease caused by germline mutations....../MRI of the abdomen, e) annual plasma-metanephrine, plasma-normetanephrine, and plasma-chromogranin A tests, and f) annual hearing examination at a department of audiology. It is advised that one doctor takes on the responsibility of coordination of and referral to the many examinations, and the communication...

  10. Functioning adrenal myelolipoma: A rare cause of hypertension

    Directory of Open Access Journals (Sweden)

    Nagendar Jakka

    2013-01-01

    Full Text Available Co-occurrence of adrenal incidentaloma with hypertension calls for evaluation of endocrine causes including pheochromocytoma, Cushing′s disease, and primary aldosteronism. We are reporting 40-years-old man who presented with hypertension and adrenal mass. He had elevated metanephrines, histology of resected adrenal mass revealed adrenal myelolipoma, and immuno-histochemistry was positive for chromogranin A. Both his blood pressure and urinary metanephrines returned to normal after surgery. The association of hypertension and adrenal myelolipoma may not be entirely coincidental, as it may be associated with secreting catecholamine. Literature on such an uncommon association is reviewed briefly as well.

  11. PROGNOSTIC SIGNIFICANCE OF CLINICAL, HISTOPATHOLOGICAL, AND MOLECULAR CHARACTERISTICS OF MEDULLOBLASTOMAS IN THE PROSPECTIVE HIT2000 MULTICENTER CLINICAL TRIAL COHORT

    Science.gov (United States)

    Pietsch, Torsten; Schmidt, Rene; Remke, Marc; Korshunov, Andrey; Hovestadt, Volker; Jones, David TW; Felsberg, Jörg; Kaulich, Kerstin; Goschzik, Tobias; Kool, Marcel; Northcott, Paul A.; von Hoff, Katja; von Bueren, André O.; Friedrich, Carsten; Skladny, Heyko; Fleischhack, Gudrun; Taylor, Michael D.; Cremer, Friedrich; Lichter, Peter; Faldum, Andreas; Reifenberger, Guido; Rutkowski, Stefan; Pfister, Stefan M.

    2014-01-01

    BACKGROUND: This study aimed to prospectively evaluate clinical, histopathological and molecular variables for outcome prediction in medulloblastoma patients. METHODS: Patients from the HIT2000 cooperative clinical trial were prospectively enrolled based on the availability of sufficient tumor material and complete clinical information. This revealed a cohort of 184 patients (median age 7.6 years), which was randomly split at a 2:1 ratio into a training (n = 127), and a validation (n = 57) dataset. All samples were subjected to thorough histopathological investigation, CTNNB1 mutation analysis, quantitative PCR, MLPA and FISH analyses for cytogenetic variables, and methylome analysis. RESULTS: By univariable analysis, clinical factors (M-stage), histopathological variables (large cell component, endothelial proliferation, synaptophysin pattern), and molecular features (chromosome 6q status, MYC amplification, TOP2A copy-number, subgrouping) were found to be prognostic. Molecular consensus subgrouping (WNT, SHH, Group 3, Group 4) was validated as an independent feature to stratify patients into different risk groups. When comparing methods for the identification of WNT-driven medulloblastoma, this study identified CTNNB1 sequencing and methylation profiling to most reliably identify these patients. After removing patients with particularly favorable (CTNNB1 mutation, extensive nodularity) or unfavorable (MYC amplification) markers, a risk score for the remaining “intermediate molecular risk” population dependent on age, M-stage, pattern of synaptophysin expression, and MYCN copy-number status was identified and validated, with speckled synaptophysin expression indicating worse outcome. CONCLUSIONS: Methylation subgrouping and CTNNB1 mutation status represent robust tools for the risk-stratification of medulloblastoma. A simple clinico-pathological risk score for “intermediate molecular risk” patients was identified, which deserves further validation

  12. Modification of hippocampal markers of synaptic plasticity by memantine in animal models of acute and repeated restraint stress: implications for memory and behavior.

    Science.gov (United States)

    Amin, Shaimaa Nasr; El-Aidi, Ahmed Amro; Ali, Mohamed Mostafa; Attia, Yasser Mahmoud; Rashed, Laila Ahmed

    2015-06-01

    Stress is any condition that impairs the balance of the organism physiologically or psychologically. The response to stress involves several neurohormonal consequences. Glutamate is the primary excitatory neurotransmitter in the central nervous system, and its release is increased by stress that predisposes to excitotoxicity in the brain. Memantine is an uncompetitive N-methyl D-aspartate glutamatergic receptors antagonist and has shown beneficial effect on cognitive function especially in Alzheimer's disease. The aim of the work was to investigate memantine effect on memory and behavior in animal models of acute and repeated restraint stress with the evaluation of serum markers of stress and the expression of hippocampal markers of synaptic plasticity. Forty-two male rats were divided into seven groups (six rats/group): control, acute restraint stress, acute restraint stress with Memantine, repeated restraint stress, repeated restraint stress with Memantine and Memantine groups (two subgroups as positive control). Spatial working memory and behavior were assessed by performance in Y-maze. We evaluated serum cortisol, tumor necrotic factor, interleukin-6 and hippocampal expression of brain-derived neurotrophic factor, synaptophysin and calcium-/calmodulin-dependent protein kinase II. Our results revealed that Memantine improved spatial working memory in repeated stress, decreased serum level of stress markers and modified the hippocampal synaptic plasticity markers in both patterns of stress exposure; in ARS, Memantine upregulated the expression of synaptophysin and brain-derived neurotrophic factor and downregulated the expression of calcium-/calmodulin-dependent protein kinase II, and in repeated restraint stress, it upregulated the expression of synaptophysin and downregulated calcium-/calmodulin-dependent protein kinase II expression.

  13. Intestinal endocrine cells in radiation enteritis

    International Nuclear Information System (INIS)

    Pietroletti, R.; Blaauwgeers, J.L.; Taat, C.W.; Simi, M.; Brummelkamp, W.H.; Becker, A.E.

    1989-01-01

    In this study, the intestinal endocrine cells were investigated in 13 surgical specimens affected by radiation enteritis. Endocrine cells were studied by means of Grimelius' silver staining and immunostaining for chromogranin, a general marker of endocrine cells. Positively stained cells were quantified by counting their number per unit length of muscularis mucosa. Results in radiation enteritis were compared with matched control specimens by using Student's t test. Chromogranin immunostaining showed a statistically significant increase of endocrine cells in radiation enteritis specimens compared with controls both in small and large intestine (ileum, 67.5 +/- 23.5 cells per unit length of muscularis mucosa in radiation enteritis versus 17.0 +/- 6.1 in controls; colon, 40.9 +/- 13.7 cells per unit length of muscularis mucosa in radiation enteritis versus 9.5 +/- 4.1 in controls--p less than 0.005 in both instances). Increase of endocrine cells was demonstrated also by Grimelius' staining; however, without reaching statistical significance. It is not clear whether or not the increase of endocrine cells in radiation enteritis reported in this study is caused by a hyperplastic response or by a sparing phenomenon. We should consider that increased endocrine cells, when abnormally secreting their products, may be involved in some of the clinical features of radiation enteropathy. In addition, as intestinal endocrine cells produce trophic substances to the intestine, their increase could be responsible for the raised risk of developing carcinoma of the intestine in long standing radiation enteritis

  14. The neuropeptide catestatin promotes vascular smooth muscle cell proliferation through the Ca{sup 2+}-calcineurin-NFAT signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Xiaoxia [Department of Cardiology, People' s Hospital, Peking University, No. 11 South Avenue, Xi Zhi Men Xicheng District, Beijing 100044 (China); Zhou, Chunyan, E-mail: chunyanzhou@bjmu.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191 (China); Sun, Ningling, E-mail: nlsun@263.net [Department of Cardiology, People' s Hospital, Peking University, No. 11 South Avenue, Xi Zhi Men Xicheng District, Beijing 100044 (China)

    2011-04-22

    Highlights: {yields} Catestatin stimulates proliferation of vascular smooth muscle cells in a dose-dependent manner. {yields} Catestatin provokes sustained increase in intracellular Ca{sup 2+}. {yields} Catestatin produces increased activation of calcineurin and promotes NFATc1 translocation into the nucleus. -- Abstract: The Chromogranin A-derived neuropeptide catestatin is an endogenous nicotinic cholinergic antagonist that acts as a pleiotropic hormone. Since catestatin shares several functions with other members derived from the chromogranin/secretogranin protein family and other neuropeptides which exert proliferative effects on vascular smooth muscle cells (VSMCs), we therefore hypothesized that catestatin would regulate VSMC proliferation. The present study demonstrates that catestatin caused a dose-dependent induction of proliferation in rat aortic smooth muscle cells and furthermore evoked a sustained increase in intracellular calcium. This subsequently leaded to enhanced activation of the Ca{sup 2+}/calmodulin-dependent phosphatase, calcineurin and resulted in an activation of the Ca{sup 2+}-dependent transcription factor, nuclear factor of activated T cells (NFAT), initiating transcription of proliferative genes. In addition, cyclosporin A (CsA), a potent inhibitor of calcineurin, abrogated catestatin-mediated effect on VSMCs, indicating that the calcineurin-NFAT signaling is strongly required for catestatin-induced growth of VSMCs. The present study establishes catestatin as a novel proliferative cytokine on vascular smooth muscle cells and this effect is mediated by the Ca{sup 2+}-calcineurin-NFAT signaling pathway.

  15. TFH-derived dopamine accelerates productive synapses in germinal centres.

    Science.gov (United States)

    Papa, Ilenia; Saliba, David; Ponzoni, Maurilio; Bustamante, Sonia; Canete, Pablo F; Gonzalez-Figueroa, Paula; McNamara, Hayley A; Valvo, Salvatore; Grimbaldeston, Michele; Sweet, Rebecca A; Vohra, Harpreet; Cockburn, Ian A; Meyer-Hermann, Michael; Dustin, Michael L; Doglioni, Claudio; Vinuesa, Carola G

    2017-07-20

    Protective high-affinity antibody responses depend on competitive selection of B cells carrying somatically mutated B-cell receptors by follicular helper T (T FH ) cells in germinal centres. The rapid T-B-cell interactions that occur during this process are reminiscent of neural synaptic transmission pathways. Here we show that a proportion of human T FH cells contain dense-core granules marked by chromogranin B, which are normally found in neuronal presynaptic terminals storing catecholamines such as dopamine. T FH cells produce high amounts of dopamine and release it upon cognate interaction with B cells. Dopamine causes rapid translocation of intracellular ICOSL (inducible T-cell co-stimulator ligand, also known as ICOSLG) to the B-cell surface, which enhances accumulation of CD40L and chromogranin B granules at the human T FH cell synapse and increases the synapse area. Mathematical modelling suggests that faster dopamine-induced T-B-cell interactions increase total germinal centre output and accelerate it by days. Delivery of neurotransmitters across the T-B-cell synapse may be advantageous in the face of infection.

  16. INSL5 may be a unique marker of colorectal endocrine cells and neuroendocrine tumors

    Energy Technology Data Exchange (ETDEWEB)

    Mashima, Hirosato, E-mail: hmashima1-tky@umin.ac.jp [Department of Gastroenterology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543 (Japan); Ohno, Hideki [Division of Advanced Medical Science, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Yamada, Yumi; Sakai, Toshitaka; Ohnishi, Hirohide [Department of Gastroenterology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543 (Japan)

    2013-03-22

    Highlights: ► INSL5 is expressed in enteroendocrine cells along the colorectum. ► INSL5 is expressed increasingly from proximal colon to rectum. ► INSL5 co-localizes rarely with chromogranin A. ► All rectal neuroendocrine tumors examined expressed INSL5. -- Abstract: Insulin-like peptide 5 (INSL5) is a member of the insulin superfamily, and is a potent agonist for RXFP4. We have shown that INSL5 is expressed in enteroendocrine cells (EECs) along the colorectum with a gradient increase toward the rectum. RXFP4 is ubiquitously expressed along the digestive tract. INSL5-positive EECs have little immunoreactivity to chromogranin A (CgA) and might be a unique marker of colorectal EECs. CgA-positive EECs were distributed normally along the colorectum in INSL5 null mice, suggesting that INSL5 is not required for the development of CgA-positive EECs. Exogenous INSL5 did not affect the proliferation of human colon cancer cell lines, and chemically-induced colitis in INSL5 null mice did not show any significant changes in inflammation or mucosal healing compared to wild-type mice. In contrast, all of the rectal neuroendocrine tumors examined co-expressed INSL5 and RXFP4. INSL5 may be a unique marker of colorectal EECs, and INSL5–RXFP4 signaling might play a role in an autocrine/paracrine fashion in the colorectal epithelium and rectal neuroendocrine tumors.

  17. INSL5 may be a unique marker of colorectal endocrine cells and neuroendocrine tumors

    International Nuclear Information System (INIS)

    Mashima, Hirosato; Ohno, Hideki; Yamada, Yumi; Sakai, Toshitaka; Ohnishi, Hirohide

    2013-01-01

    Highlights: ► INSL5 is expressed in enteroendocrine cells along the colorectum. ► INSL5 is expressed increasingly from proximal colon to rectum. ► INSL5 co-localizes rarely with chromogranin A. ► All rectal neuroendocrine tumors examined expressed INSL5. -- Abstract: Insulin-like peptide 5 (INSL5) is a member of the insulin superfamily, and is a potent agonist for RXFP4. We have shown that INSL5 is expressed in enteroendocrine cells (EECs) along the colorectum with a gradient increase toward the rectum. RXFP4 is ubiquitously expressed along the digestive tract. INSL5-positive EECs have little immunoreactivity to chromogranin A (CgA) and might be a unique marker of colorectal EECs. CgA-positive EECs were distributed normally along the colorectum in INSL5 null mice, suggesting that INSL5 is not required for the development of CgA-positive EECs. Exogenous INSL5 did not affect the proliferation of human colon cancer cell lines, and chemically-induced colitis in INSL5 null mice did not show any significant changes in inflammation or mucosal healing compared to wild-type mice. In contrast, all of the rectal neuroendocrine tumors examined co-expressed INSL5 and RXFP4. INSL5 may be a unique marker of colorectal EECs, and INSL5–RXFP4 signaling might play a role in an autocrine/paracrine fashion in the colorectal epithelium and rectal neuroendocrine tumors

  18. Human CNS cultures exposed to HIV-1 gp120 reproduce dendritic injuries of HIV-1-associated dementia

    Directory of Open Access Journals (Sweden)

    Hammond Robert R

    2004-05-01

    Full Text Available Abstract HIV-1-associated dementia remains a common subacute to chronic central nervous system degeneration in adult and pediatric HIV-1 infected populations. A number of viral and host factors have been implicated including the HIV-1 120 kDa envelope glycoprotein (gp120. In human post-mortem studies using confocal scanning laser microscopy for microtubule-associated protein 2 and synaptophysin, neuronal dendritic pathology correlated with dementia. In the present study, primary human CNS cultures exposed to HIV-1 gp120 at 4 weeks in vitro suffered gliosis and dendritic damage analogous to that described in association with HIV-1-associated dementia.

  19. Dicty_cDB: [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available VF (Link to library) VFC171 (Link to dictyBase) - - - Contig-U16478-1 VFC171P (Link... to Original site) VFC171F 482 VFC171Z 633 VFC171P 1115 - - Show VFC171 Library VF (Link to library) Clone ID VFC171 (Link to dict...yBase) Atlas ID - NBRP ID - dictyBase ID - Link to Contig Contig-U16478-1 Original site URL http://dict...ptttrlptt trlstttrlptttrlptttrlptttrlptttrlsttrlxtttrlstswctswctswictr ygswissrllcwynhs*l*t*c*sfkksnerywyk*i...ologous to C-terminal repeat sequence of rhodopsin and synaptophysin. 88 1e-15 3 X54062 |X54062.1 Dictyostel

  20. Progressive dyspnea due to pulmonary carcinoid tumorlets

    Directory of Open Access Journals (Sweden)

    Anastasios Kallianos

    2017-01-01

    Full Text Available This is a case description of a female patient, 77 years-old, who presented with progressive dyspnea and cough. She had a mild hypoxemia in the arterial blood gases (PaO2 72 mmHg and normal spirometry. The chest computer tomography revealed diffuse “ground glass” opacities, segmental alveolitis, bronchiectasis, fibrotic lesions and numerous micronodules. A thoracoscopy was performed and the obtained biopsy showed carcinoid tumorlets, with positive CK8/18, CD56, TTF-1 and synaptophysin immunohistochemical markers. Pulmonary carcinoid tumorlets are rare, benign lesions and individuals with tumorlets are typically asymptomatic. Our report presents a symptomatic clinical case of carcinoid tumorlet.

  1. The dual effects of nitrite on hemoglobin-dependent redox reactions.

    Science.gov (United States)

    Lu, Naihao; Chen, Chao; He, Yingjie; Tian, Rong; Xiao, Qiang; Peng, Yi-Yuan

    2014-08-31

    Evidence to support the role of heme proteins-dependent reactions as major inducers of oxidative damage is increasingly present. Nitrite (NO2(-)) is one of the major end products of NO metabolism, and from the daily consumption. Although the biological significance of heme proteins/NO2(-)-mediated protein tyrosine nitration is a subject of great interest, the important roles of NO2(-) on heme proteins-dependent redox reactions have been greatly underestimated. In this study, we investigated the influence of NO2(-) on met-hemoglobin (Hb)-dependent oxidative and nitrative stress. It was found that NO2(-) effectively reduced cytotoxic ferryl intermediate back to ferric Hb in a biphasic kinetic reaction. However, the presence of NO2(-) surprisingly exerted pro-oxidant effect on Hb-H2O2-induced protein (bovine serum albumin, enolase) oxidation at low concentrations and enhanced the loss of HepG2 cell viability. In the reduction of ferryl Hb to ferric state, NO2(-) was decreased and oxidized to a nitrating agent NO2, Tyr12 and Tyr191 in enolase were subsequently nitrated. In contrast to the frequently inhibitive effect of nitrotyrosine, NO2(-)-triggered tyrosine nitration might play an important role in enolase activation. These data provided novel evidence that the dietary intake and potential therapeutic application of NO2(-) would possess anti- and pro-oxidant activities through interfering in hemoglobin-dependent redox reactions. Besides the classic role in protein tyrosine nitration, the dual effects on hemoglobin-triggered oxidative stress may provide new insights into the physiological and toxicological implications of NO2(-) with heme proteins. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Potential protein biomarkers for burning mouth syndrome discovered by quantitative proteomics.

    Science.gov (United States)

    Ji, Eoon Hye; Diep, Cynthia; Liu, Tong; Li, Hong; Merrill, Robert; Messadi, Diana; Hu, Shen

    2017-01-01

    Burning mouth syndrome (BMS) is a chronic pain disorder characterized by severe burning sensation in normal looking oral mucosa. Diagnosis of BMS remains to be a challenge to oral healthcare professionals because the method for definite diagnosis is still uncertain. In this study, a quantitative saliva proteomic analysis was performed in order to identify target proteins in BMS patients' saliva that may be used as biomarkers for simple, non-invasive detection of the disease. By using isobaric tags for relative and absolute quantitation labeling and liquid chromatography-tandem mass spectrometry to quantify 1130 saliva proteins between BMS patients and healthy control subjects, we found that 50 proteins were significantly changed in the BMS patients when compared to the healthy control subjects ( p ≤ 0.05, 39 up-regulated and 11 down-regulated). Four candidates, alpha-enolase, interleukin-18 (IL-18), kallikrein-13 (KLK13), and cathepsin G, were selected for further validation. Based on enzyme-linked immunosorbent assay measurements, three potential biomarkers, alpha-enolase, IL-18, and KLK13, were successfully validated. The fold changes for alpha-enolase, IL-18, and KLK13 were determined as 3.6, 2.9, and 2.2 (burning mouth syndrome vs. control), and corresponding receiver operating characteristic values were determined as 0.78, 0.83, and 0.68, respectively. Our findings indicate that testing of the identified protein biomarkers in saliva might be a valuable clinical tool for BMS detection. Further validation studies of the identified biomarkers or additional candidate biomarkers are needed to achieve a multi-marker prediction model for improved detection of BMS with high sensitivity and specificity.

  3. Cross-reactivity to fish and chicken meat - a new clinical syndrome.

    Science.gov (United States)

    Kuehn, A; Codreanu-Morel, F; Lehners-Weber, C; Doyen, V; Gomez-André, S-A; Bienvenu, F; Fischer, J; Ballardini, N; van Hage, M; Perotin, J-M; Silcret-Grieu, S; Chabane, H; Hentges, F; Ollert, M; Hilger, C; Morisset, M

    2016-12-01

    Fish is one of the most allergenic foods. While clinical cross-reactivity among different fishes is a widely accepted feature of fish allergy, associations with other food allergies are not well understood. This study aims at analyzing the relevance of clinical cross-reactivity between fish and chicken meat in patients with allergy to chicken meat without sensitization to hen's eggs. Patients with food allergy to fish and chicken meat (n = 29) or chicken meat only (n = 7) were recruited. IgE-reactive chicken proteins were identified (Edman, MS analysis) and quantified (ELISA). Allergens were used in IgE ELISA and skin testing. Chicken parvalbumin and two new allergens, aldolase and enolase, were identified at 12, 40, and 50 kDa, respectively. They were recognized by sIgE of 61%, 75%, and 83% of all patient sera which were in the majority of the cases positive for the fish homologues as well. Fish and chicken meat allergens were highly cross-reactive while high inhibition rates with fish or chicken allergens correlated with the patients' primary sensitization to fish or chicken. In cooked or roasted foods, enolase and aldolase were detectable in chicken breast while parvalbumin was detectable in chicken legs and wings. Fish and chicken meat are cross-reactive foods; both fish-allergic and chicken meat-allergic patients might be at risk of developing a food allergy to chicken meat or to fish, respectively. This clinical phenomenon is proposed to be termed 'fish-chicken syndrome' with cross-reactive allergens involved being parvalbumins, enolases, and aldolases. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Detection of anti-streptococcal, antienolase, and anti-neural antibodies in subjects with early-onset psychiatric disorders.

    Science.gov (United States)

    Nicolini, Humberto; López, Yaumara; Genis-Mendoza, Alma D; Manrique, Viana; Lopez-Canovas, Lilia; Niubo, Esperanza; Hernández, Lázaro; Bobes, María A; Riverón, Ana M; López-Casamichana, Mavil; Flores, Julio; Lanzagorta, Nuria; De la Fuente-Sandoval, Camilo; Santana, Daniel

    2015-01-01

    Infection with group A Streptococcus (StrepA) can cause post-infectious sequelae, including a spectrum of childhood-onset obsessive-compulsive (OCD) and tic disorders with autoimmune origin (PANDAS, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections). Until now, no single immunological test has been designed that unequivocally diagnoses these disorders. In this study, we assessed the detection of serum antibodies against human brain enolase (AE), neural tissue (AN) and Streptococcus (AS) as a laboratory tool for the diagnosis of early-onset psychiatric disorders. Serum antibodies against human brain enolase, total brain proteins, and total proteins from StrepA were detected by ELISA in 37 patients with a presumptive diagnosis of PANDAS and in 12 healthy subjects from Mexico and Cuba. The antibody titers against human brain enolase (AE) and Streptococcal proteins (AS) were higher in patients than in control subjects (t-student, tAE=-2.17, P=0.035; tAS=-2.68, P=0.01, n=12 and 37/group, df=47, significance level 0.05), while the neural antibody titers did not differ between the two groups (P(t)=0.05). The number of subjects (titers> meancontrol + CI95) with simultaneous seropositivity to all three antibodies was higher in the patient group (51.4%) than in the control group (8.3%) group (X2=5.27, P=0.022, df=1, n=49). The simultaneous detection of all three of these antibodies could provide valuable information for the etiologic diagnosis of individuals with early-onset obsessive-compulsive disorders associated with streptococcal infection and, consequently, for prescribing suitable therapy.

  5. September 2013 Arizona thoracic society notes

    Directory of Open Access Journals (Sweden)

    Robbins RA

    2013-09-01

    Full Text Available No abstract available. Article truncated at 150 words. The September Arizona Thoracic Society meeting was held on Wednesday, 9/25/2013 at Shea Hospital beginning at 6:30 PM. There were 13 in attendance representing the pulmonary, critical care, sleep, and pathology communities. After a brief discussion, Gerry Swartzberg was selected as Arizona’s 2014 nominee for Clinician of the Year. There was 1 case presented: Dr. Thomas Colby, pulmonary pathologist from Mayo Clinic Arizona, presented the case of a 67 year old woman with multiple pulmonary nodules. The largest was 1.2 cm CT scan. She had a fine needle aspiration of one of the nodules. The pathology revealed spindle-shaped cells which were synaptophysin + (also known as the major synaptic vesicle protein p38. Synaptophysin marks neuroendocrine tissue and on this basis the patient was diagnosed with multiple carcinoid tumors. Aguayo et al. (1 described six patients with diffuse hyperplasia and dysplasia of pulmonary neuroendocrine cells, multiple carcinoid tumorlets, and peribronchiolar fibrosis …

  6. The impairment of learning and memory and synaptic loss in mouse after chronic nitrite exposure.

    Science.gov (United States)

    Chen, Yongfang; Cui, Zhanjun; Wang, Lai; Liu, Hongliang; Fan, Wenjuan; Deng, Jinbo; Deng, Jiexin

    2016-12-01

    The objective of this study is to understand the impairment of learning and memory in mouse after chronic nitrite exposure. The animal model of nitrite exposure in mouse was created with the daily intubation of nitrite in adult healthy male mice for 3 months. Furthermore, the mouse's learning and memory abilities were tested with Morris water maze, and the expression of Synaptophysin and γ-Synuclein was visualized with immunocytochemistry and Western blot. Our results showed that nitrite exposure significantly prolonged the escape latency period (ELP) and decreased the values of the frequency across platform (FAP) as well as the accumulative time in target quadrant (ATITQ) compared to control, in dose-dependent manner. In addition, after nitrite exposure, synaptophysin (SYN) positive buttons in the visual cortex was reduced, in contrast the increase of γ-synuclein positive cells. The results above were supported by Western blot as well. We conclude that nitrite exposure could lead to a decline in mice's learning and memory. The overexpression of γ-synuclein contributed to the synaptic loss, which is most likely the cause of learning and memory impairment. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1720-1730, 2016. © 2015 Wiley Periodicals, Inc.

  7. Supplementation with complex milk lipids during brain development promotes neuroplasticity without altering myelination or vascular density

    Directory of Open Access Journals (Sweden)

    Rosamond B. Guillermo

    2015-03-01

    Full Text Available Background: Supplementation with complex milk lipids (CML during postnatal brain development has been shown to improve spatial reference learning in rats. Objective: The current study examined histo-biological changes in the brain following CML supplementation and their relationship to the observed improvements in memory. Design: The study used the brain tissues from the rats (male Wistar, 80 days of age after supplementing with either CML or vehicle during postnatal day 10–80. Immunohistochemical staining of synaptophysin, glutamate receptor-1, myelin basic protein, isolectin B-4, and glial fibrillary acidic protein was performed. The average area and the density of the staining and the numbers of astrocytes and capillaries were assessed and analysed. Results: Compared with control rats, CML supplementation increased the average area of synaptophysin staining and the number of GFAP astrocytes in the CA3 sub-region of the hippocampus (p<0.01, but not in the CA4 sub-region. The supplementation also led to an increase in dopamine output in the striatum that was related to nigral dopamine expression (p<0.05, but did not alter glutamate receptors, myelination or vascular density. Conclusion: CML supplementation may enhance neuroplasticity in the CA3 sub-regions of the hippocampus. The brain regions-specific increase of astrocyte may indicate a supporting role for GFAP in synaptic plasticity. CML supplementation did not associate with postnatal white matter development or vascular remodelling.

  8. Myosins and DYNLL1/LC8 in the honey bee (Apis mellifera L.) brain.

    Science.gov (United States)

    Calábria, Luciana Karen; Peixoto, Pablo Marco Veras; Passos Lima, Andreia Barcelos; Peixoto, Leonardo Gomes; de Moraes, Viviane Rodrigues Alves; Teixeira, Renata Roland; Dos Santos, Claudia Tavares; E Silva, Letícia Oliveira; da Silva, Maria de Fátima Rodrigues; dos Santos, Ana Alice Diniz; Garcia-Cairasco, Norberto; Martins, Antônio Roberto; Espreafico, Enilza Maria; Espindola, Foued Salmen

    2011-09-01

    Honey bees have brain structures with specialized and developed systems of communication that account for memory, learning capacity and behavioral organization with a set of genes homologous to vertebrate genes. Many microtubule- and actin-based molecular motors are involved in axonal/dendritic transport. Myosin-Va is present in the honey bee Apis mellifera nervous system of the larvae and adult castes and subcastes. DYNLL1/LC8 and myosin-IIb, -VI and -IXb have also been detected in the adult brain. SNARE proteins, such as CaMKII, clathrin, syntaxin, SNAP25, munc18, synaptophysin and synaptotagmin, are also expressed in the honey bee brain. Honey bee myosin-Va displayed ATP-dependent solubility and was associated with DYNLL1/LC8 and SNARE proteins in the membrane vesicle-enriched fraction. Myosin-Va expression was also decreased after the intracerebral injection of melittin and NMDA. The immunolocalization of myosin-Va and -IV, DYNLL1/LC8, and synaptophysin in mushroom bodies, and optical and antennal lobes was compared with the brain morphology based on Neo-Timm histochemistry and revealed a distinct and punctate distribution. This result suggested that the pattern of localization is associated with neuron function. Therefore, our data indicated that the roles of myosins, DYNLL1/LC8, and SNARE proteins in the nervous and visual systems of honey bees should be further studied under different developmental, caste and behavioral conditions. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. CNS development under altered gravity: cerebellar glial and neuronal protein expression in rat neonates exposed to hypergravity

    Science.gov (United States)

    Nguon, K.; Li, G.-H.; Sajdel-Sulkowska, E. M.

    2004-01-01

    The future of space exploration depends on a solid understanding of the developmental process under microgravity, specifically in relation to the central nervous system (CNS). We have previously employed a hypergravity paradigm to assess the impact of altered gravity on the developing rat cerebellum [Exp. Biol. Med. 226 (2000) 790]. The present study addresses the molecular mechanisms involved in the cerebellar response to hypergravity. Specifically, the study focuses on the expression of selected glial and neuronal cerebellar proteins in rat neonates exposed to hypergravity (1.5 G) from embryonic day (E)11 to postnatal day (P)6 or P9 (the time of maximal cerebellar changes) comparing them against their expression in rat neonates developing under normal gravity. Proteins were analyzed by quantitative Western blots of cerebellar homogenates; RNA analysis was performed in the same samples using quantitative PCR. Densitometric analysis of Western blots suggested a reduction in glial (glial acidic protein, GFAP) and neuronal (neuronal cell adhesion moiecule, NCAM-L1, synaptophysin) proteins, but the changes in individual cerebellar proteins in hypergravity-exposed neonates appeared both age- and gender-specific. RNA analysis suggested a reduction in GFAP and synaptophysin mRNAs on P6. These data suggest that exposure to hypergravity may interfere with the expression of selected cerebellar proteins. These changes in protein expression may be involved in mediating the effect of hypergravity on the developing rat cerebellum.

  10. Synaptic changes in the thalamocortical system of cathepsin D-deficient mice: a model of human congenital neuronal ceroid-lipofuscinosis.

    Science.gov (United States)

    Partanen, Sanna; Haapanen, Aleksi; Kielar, Catherine; Pontikis, Charles; Alexander, Noreen; Inkinen, Teija; Saftig, Paul; Gillingwater, Thomas H; Cooper, Jonathan D; Tyynelä, Jaana

    2008-01-01

    Cathepsin D (CTSD; EC 3.4.23.5) is a lysosomal aspartic protease, the deficiency of which causes early-onset and particularly aggressive forms of neuronal ceroid-lipofuscinosis in infants, sheep, and mice. Cathepsin D deficiencies are characterized by severe neurodegeneration, but the molecular mechanisms behind the neuronal death remain poorly understood. In this study, we have systematically mapped the distribution of neuropathologic changes in CTSD-deficient mouse brains by stereologic, immunologic, and electron microscopic methods. We report highly accentuated neuropathologic changes within the ventral posterior nucleus (ventral posteromedial [VPM]/ventral posterolateral [VPL]) of thalamus and in neuronal laminae IV and VI of the somatosensory cortex (S1BF), which receive and send information to the thalamic VPM/VPL. These changes included pronounced astrocytosis and microglial activation that begin in the VPM/VPL thalamic nucleus of CTSD-deficient mice and are associated with reduced neuronal number and redistribution of presynaptic markers. In addition, loss of synapses, axonal pathology, and aggregation of synaptophysin and synaptobrevin were observed in the VPM/VPL. These synaptic alterations are accompanied by changes in the amount of synaptophysin/synaptobrevin heterodimer, which regulates formation of the SNARE complex at the synapse. Taken together, these data reveal the somatosensory thalamocortical circuitry as a particular focus of pathologic changes and provide the first evidence for synaptic alterations at the molecular and ultrastructural levels in CTSD deficiency.

  11. Synaptic contacts impaired by styrene-7,8-oxide toxicity

    International Nuclear Information System (INIS)

    Corsi, P.; D'Aprile, A.; Nico, B.; Costa, G.L.; Assennato, G.

    2007-01-01

    Styrene-7,8-oxide (SO), a chemical compound widely used in industrial applications, is a potential hazard for humans, particularly in occupational settings. Neurobehavioral changes are consistently observed in occupationally exposed individuals and alterations of neurotransmitters associated with neuronal loss have been reported in animal models. Although the toxic effects of styrene have been extensively documented, the molecular mechanisms responsible for SO-induced neurotoxicity are still unclear. A possible dopamine-mediated effect of styrene neurotoxicity has been previously demonstrated, since styrene oxide alters dopamine neurotransmission in the brain. Thus, the present study hypothesizes that styrene neurotoxicity may involve synaptic contacts. Primary striatal neurons were exposed to styrene oxide at different concentrations (0.1-1 mM) for different time periods (8, 16, and 24 h) to evaluate the dose able to induce synaptic impairments. The expression of proteins crucial for synaptic transmission such as Synapsin, Synaptophysin, and RAC-1 were considered. The levels of Synaptophysin and RAC-1 decreased in a dose-dependent manner. Accordingly, morphological alterations, observed at the ultrastructural level, primarily involved the pre-synaptic compartment. In SO-exposed cultures, the biochemical cascade of caspases was activated affecting the cytoskeleton components as their target. Thus the impairments in synaptic contacts observed in SO-exposed cultures might reflect a primarily morphological alteration of neuronal cytoskeleton. In addition, our data support the hypothesis developed by previous authors of reactive oxygen species (ROS) initiating events of SO cytotoxicity

  12. Propofol Exposure in Pregnant Rats Induces Neurotoxicity and Persistent Learning Deficit in the Offspring

    Directory of Open Access Journals (Sweden)

    Ming Xiong

    2014-05-01

    Full Text Available Propofol is a general anesthetic widely used in surgical procedures, including those in pregnant women. Preclinical studies suggest that propofol may cause neuronal injury to the offspring of primates if it is administered during pregnancy. However, it is unknown whether those neuronal changes would lead to long-term behavioral deficits in the offspring. In this study, propofol (0.4 mg/kg/min, IV, 2 h, saline, or intralipid solution was administered to pregnant rats on gestational day 18. We detected increased levels of cleaved caspase-3 in fetal brain at 6 h after propofol exposure. The neuronal density of the hippocampus of offspring was reduced significantly on postnatal day 10 (P10 and P28. Synaptophysin levels were also significantly reduced on P28. Furthermore, exploratory and learning behaviors of offspring rats (started at P28 were assessed in open-field trial and eight-arm radial maze. The offspring from propofol-treated dams showed significantly less exploratory activity in the open-field test and less spatial learning in the eight-arm radial maze. Thus, this study suggested that propofol exposure during pregnancy in rat increased cleaved caspsase-3 levels in fetal brain, deletion of neurons, reduced synaptophysin levels in the hippocampal region, and persistent learning deficits in the offspring.

  13. Optical Dissection of Experience-Dependent Pre- and Postsynaptic Plasticity in the Drosophila Brain

    Directory of Open Access Journals (Sweden)

    Ulrike Pech

    2015-03-01

    Full Text Available Drosophila represents a key model organism for dissecting neuronal circuits that underlie innate and adaptive behavior. However, this task is limited by a lack of tools to monitor physiological parameters of spatially distributed, central synapses in identified neurons. We generated transgenic fly strains that express functional fluorescent reporters targeted to either pre- or postsynaptic compartments. Presynaptic Ca2+ dynamics are monitored using synaptophysin-coupled GCaMP3, synaptic transmission is monitored using red fluorescent synaptophysin-pHTomato, and postsynaptic Ca2+ dynamics are visualized using GCaMP3 fused with the postsynaptic matrix protein, dHomer. Using two-photon in vivo imaging of olfactory projection neurons, odor-evoked activity across populations of synapses is visualized in the antennal lobe and the mushroom body calyx. Prolonged odor exposure causes odor-specific and differential experience-dependent changes in pre- and postsynaptic activity at both levels of olfactory processing. The approach advances the physiological analysis of synaptic connections across defined groups of neurons in intact Drosophila.

  14. Neuronal apoptosis and synaptic density in the dentate gyrus of ischemic rats' response to chronic mild stress and the effects of Notch signaling.

    Directory of Open Access Journals (Sweden)

    Shaohua Wang

    Full Text Available Our previous research highlighted an inconsistency with Notch1 signaling-related compensatory neurogenesis after chronic mild stress (CMS in rodents suffering from cerebral ischemia, which continue to display post-stroke depressive symptoms. Here, we hypothesize that CMS aggrandized ischemia-related apoptosis injury and worsened synaptic integrity via gamma secretase-meditated Notch1 signaling. Adult rats were exposed to a CMS paradigm after left middle cerebral artery occlusion (MCAO. Open-field and sucrose consumption testing were employed to assess depression-like behavior. Gene expression of pro-apoptotic Bax, anti-apoptotic Bcl-2, and synaptic density-related synaptophysin were measured by western blotting and real-time PCR on Day 28 after MCAO surgery. CMS induced depressive behaviors in ischemic rats, which was accompanied by an elevation in Bax/bcl-2 ratio, TUNEL staining in neurons and reduced synaptophysin expression in the dentate gyrus. These collective effects were reversed by the gamma-secretase inhibitor DAPT (N-[N-(3,5-difluorophenacetyl-L-alanyl]-S-phenyl-glycine t-butyl ester. We found that post-stroke stressors made neurons in the dentate gyrus vulnerable to apoptosis, which supports a putative role for Notch signaling in neural integrity, potentially in newborn cells' synaptic deficit with regard to preexisting cells. These findings suggest that post-stroke depression therapeutically benefits from blocking gamma secretase mediated Notch signaling, and whether this signaling pathway could be a therapeutic target needs to be further investigated.

  15. Robot-Applied Resistance Augments the Effects of Body Weight-Supported Treadmill Training on Stepping and Synaptic Plasticity in a Rodent Model of Spinal Cord Injury.

    Science.gov (United States)

    Hinahon, Erika; Estrada, Christina; Tong, Lin; Won, Deborah S; de Leon, Ray D

    2017-08-01

    The application of resistive forces has been used during body weight-supported treadmill training (BWSTT) to improve walking function after spinal cord injury (SCI). Whether this form of training actually augments the effects of BWSTT is not yet known. To determine if robotic-applied resistance augments the effects of BWSTT using a controlled experimental design in a rodent model of SCI. Spinally contused rats were treadmill trained using robotic resistance against horizontal (n = 9) or vertical (n = 8) hind limb movements. Hind limb stepping was tested before and after 6 weeks of training. Two control groups, one receiving standard training (ie, without resistance; n = 9) and one untrained (n = 8), were also tested. At the terminal experiment, the spinal cords were prepared for immunohistochemical analysis of synaptophysin. Six weeks of training with horizontal resistance increased step length, whereas training with vertical resistance enhanced step height and movement velocity. None of these changes occurred in the group that received standard (ie, no resistance) training or in the untrained group. Only standard training increased the number of step cycles and shortened cycle period toward normal values. Synaptophysin expression in the ventral horn was highest in rats trained with horizontal resistance and in untrained rats and was positively correlated with step length. Adding robotic-applied resistance to BWSTT produced gains in locomotor function over BWSTT alone. The impact of resistive forces on spinal connections may depend on the nature of the resistive forces and the synaptic milieu that is present after SCI.

  16. Comparative analysis of inflamed and non-inflamed colon biopsies reveals strong proteomic inflammation profile in patients with ulcerative colitis

    DEFF Research Database (Denmark)

    Poulsen, Nina Aagaard; Andersen, Vibeke; Moller, Jens Christian

    2012-01-01

    colonic biopsies were characterized using 2D-gel electrophoresis, and peptide mass fingerprinting using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was applied for identification of differently expressed protein spots. Results: A total of 597 spots were...... mucosa with acute UC is strong. Totally, 43 individual protein spots were identified, including proteins involved in energy metabolism (triosephosphate isomerase, glycerol-3-phosphate-dehydrogenase, alpha enolase and L-lactate dehydrogenase B-chain) and in oxidative stress (superoxide dismutase...

  17. Fat and Sugar Metabolism During Exercise in Patients With Metabolic Myopathy

    Science.gov (United States)

    2017-08-31

    Metabolism, Inborn Errors; Lipid Metabolism, Inborn Errors; Carbohydrate Metabolism, Inborn Errors; Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency; Glycogenin-1 Deficiency (Glycogen Storage Disease Type XV); Carnitine Palmitoyl Transferase 2 Deficiency; VLCAD Deficiency; Medium-chain Acyl-CoA Dehydrogenase Deficiency; Multiple Acyl-CoA Dehydrogenase Deficiency; Carnitine Transporter Deficiency; Neutral Lipid Storage Disease; Glycogen Storage Disease Type II; Glycogen Storage Disease Type III; Glycogen Storage Disease Type IV; Glycogen Storage Disease Type V; Muscle Phosphofructokinase Deficiency; Phosphoglucomutase 1 Deficiency; Phosphoglycerate Mutase Deficiency; Phosphoglycerate Kinase Deficiency; Phosphorylase Kinase Deficiency; Beta Enolase Deficiency; Lactate Dehydrogenase Deficiency; Glycogen Synthase Deficiency

  18. Cerebral formation of free radicals during hypoxia does not cause structural damage and is associated with a reduction in mitochondrial PO2; evidence of O2-sensing in humans?

    DEFF Research Database (Denmark)

    Bailey, Damian M; Taudorf, Sarah; Berg, Ronan M G

    2011-01-01

    Cellular hypoxia triggers a homeostatic increase in mitochondrial free radical signaling. In this study, blood was obtained from the radial artery and jugular venous bulb in 10 men during normoxia and 9¿ hours hypoxia (12.9% O(2)). Mitochondrial oxygen tension (p(O(2))(mit)) was derived from...... cerebral blood flow and blood gases. The ascorbate radical (A(•-)) was detected by electron paramagnetic resonance spectroscopy and neuron-specific enolase (NSE), a biomarker of neuronal injury, by enzyme-linked immunosorbent assay. Hypoxia increased the cerebral output of A(•-) in proportion...

  19. Cerebral formation of free radicals during hypoxia does not cause structural damage and is associated with a reduction in mitochondrial PO2; evidence of O2-sensing in humans?

    DEFF Research Database (Denmark)

    Bailey, Damian M; Taudorf, Sarah; Berg, Ronan M G

    2011-01-01

    Cellular hypoxia triggers a homeostatic increase in mitochondrial free radical signaling. In this study, blood was obtained from the radial artery and jugular venous bulb in 10 men during normoxia and 9  hours hypoxia (12.9% O(2)). Mitochondrial oxygen tension (p(O(2))(mit)) was derived from...... cerebral blood flow and blood gases. The ascorbate radical (A(•-)) was detected by electron paramagnetic resonance spectroscopy and neuron-specific enolase (NSE), a biomarker of neuronal injury, by enzyme-linked immunosorbent assay. Hypoxia increased the cerebral output of A(•-) in proportion...

  20. [Nasal glial heterotopia: Clinical and morphological characteristics].

    Science.gov (United States)

    Bykova, V P; Bakhtin, A A; Polyakov, D P; Yunusov, A S; Daikhes, N A

    The paper describes a case of nasal glial heterotopia in a 10-month-old girl with a mixed (intranasal and subcutaneous) localization, which is accompanied by the divergence of the nasal bones. Histological examination supplemented by immunohistochemical reactions with antibodies to vimentin, S100 protein, neuron-specific enolase, as well as Ki-67 and smooth muscle actin confirmed the neural nature of the tumor. Fields of mature astrocytic glia including individual cells with neuronal differentiation were found among the fibrous and fibrovascular tissues. The paper provides a brief overview of the discussed pathology.

  1. Cross-reactivity to fish and chicken meat - a new clinical syndrome

    DEFF Research Database (Denmark)

    Kuehn, A; Codreanu-Morel, F; Lehners-Weber, C

    2016-01-01

    fish and chicken meat in patients with allergy to chicken meat without sensitization to hen's eggs. METHODS: Patients with food allergy to fish and chicken meat (n = 29) or chicken meat only (n = 7) were recruited. IgE-reactive chicken proteins were identified (Edman, MS analysis) and quantified (ELISA...... for the fish homologues as well. Fish and chicken meat allergens were highly cross-reactive while high inhibition rates with fish or chicken allergens correlated with the patients' primary sensitization to fish or chicken. In cooked or roasted foods, enolase and aldolase were detectable in chicken breast while...

  2. Brain injury markers (S100B and NSE in chronic cocaine dependents Marcadores de lesão cerebral (S100B e NSE em dependentes crônicos de cocaína

    Directory of Open Access Journals (Sweden)

    Felix Henrique Paim Kessler

    2007-06-01

    Full Text Available OBJECTIVE: Studies have shown signs of brain damage caused by different mechanisms in cocaine users. The serum neuron specific enolase and S100B protein are considered specific biochemical markers of neuronal and glial cell injury. This study aimed at comparing blood levels of S100B and NSE in chronic cocaine users and in volunteers who did not use cocaine or other illicit drugs. METHOD: Twenty subjects dependent on cocaine but not on alcohol or marijuana, and 20 non-substance using controls were recruited. Subjects were selected by consecutive and non-probabilistic sampling. Neuron specific enolase and S100B levels were determined by luminescence assay. RESULTS: Cocaine users had significantly higher scores than controls in all psychiatric dimensions of the SCL-90 and had cognitive deficits in the subtest cubes of WAIS and the word span. Mean serum S100B level was 0.09 ± 0.04 µg/l among cocaine users and 0.08 ± 0.04 µg/l among controls. Mean serum neuron specific enolase level was 9.7 ± 3.5 ng/l among cocaine users and 8.3 ± 2.6 ng/l among controls. CONCLUSIONS: In this first study using these specific brain damage markers in cocaine users, serum levels of S100B and neuron specific enolase were not statistically different between cocaine dependent subjects and controls.OBJETIVO: Estudos têm demonstrado sinais de lesão cerebral causadas por diferentes mecanismos em usuários de cocaína. A enolase sérica neurônio-específica e a proteína S100B são consideradas marcadores bioquímicos específicos de lesão neuronal e glial. Este estudo objetivou comparar os níveis sangüíneos de S100B e enolase sérica neurônio-específica em usuários crônicos de cocaína e em voluntários que não usam cocaína ou outras drogas ilícitas. MÉTODO: Vinte sujeitos dependentes de cocaína, mas não dependentes de álcool, maconha ou outra droga, e 20 sujeitos controles não usuários de drogas foram recrutados. Os sujeitos foram selecionados por

  3. Brain injury markers (S100B and NSE) in chronic cocaine dependents

    OpenAIRE

    Kessler, Felix Henrique Paim; Woody, George; Portela, Luís Valmor Cruz; Tort, Adriano Bretanha Lopes; De Boni, Raquel; Peuker, Ana Carolina Wolf Baldino; Genro, Vanessa; Diemen, Lísia von; Souza, Diogo Onofre Gomes de; Pechansky, Flavio

    2007-01-01

    OBJECTIVE: Studies have shown signs of brain damage caused by different mechanisms in cocaine users. The serum neuron specific enolase and S100B protein are considered specific biochemical markers of neuronal and glial cell injury. This study aimed at comparing blood levels of S100B and NSE in chronic cocaine users and in volunteers who did not use cocaine or other illicit drugs. METHOD: Twenty subjects dependent on cocaine but not on alcohol or marijuana, and 20 non-substance using controls ...

  4. Brain injury markers (S100B and NSE) in chronic cocaine dependents Marcadores de lesão cerebral (S100B e NSE) em dependentes crônicos de cocaína

    OpenAIRE

    Felix Henrique Paim Kessler; George Woody; Luís Valmor Cruz Portela; Adriano Bretanha Lopes Tort; Raquel De Boni; Ana Carolina Wolf Baldino Peuker; Vanessa Genro; Lísia von Diemen; Diogo Onofre Gomes de Souza; Flavio Pechansky

    2007-01-01

    OBJECTIVE: Studies have shown signs of brain damage caused by different mechanisms in cocaine users. The serum neuron specific enolase and S100B protein are considered specific biochemical markers of neuronal and glial cell injury. This study aimed at comparing blood levels of S100B and NSE in chronic cocaine users and in volunteers who did not use cocaine or other illicit drugs. METHOD: Twenty subjects dependent on cocaine but not on alcohol or marijuana, and 20 non-substance using controls ...

  5. Primary primitive neuroectodermal tumor of the cervix

    Science.gov (United States)

    Li, Bo; Ouyang, Ling; Han, Xue; Zhou, Yang; Tong, Xin; Zhang, Shulang; Zhang, Qingfu

    2013-01-01

    Primary primitive neuroectodermal tumors (PNETs) are rare and high-grade malignant tumors that mostly occur in children and young adults. The most common sites are the trunk, limbs, and retroperitoneum. Herein, we present a case of a PNET involving the cervix uteri in a 27-year-old woman. The lesion showed characteristic histologic features of a PNET and was positive for the immunohistochemical markers cluster of differentiation (CD) 99, vimentin, neuron-specific enolase, neural cell adhesion molecule 1 (CD56), and CD117 (c-kit), further defining the tumor while helping to confirm PNET. The clinical Stage IIIB tumor was treated with chemotherapy and radiotherapy. PMID:23836982

  6. The diagnostic efficiency of biomarkers in sporadic Creutzfeldt-Jakob disease compared to Alzheimer's disease

    DEFF Research Database (Denmark)

    Bahl, Justyna Maria Czarna; Heegaard, Niels Henrik Helweg; Falkenhorst, Gerhard

    2009-01-01

    ) together with the prion protein gene genotype to discriminate patients with sCJD (n=21) from neurological controls (n=164) and Alzheimer's disease (AD) patients (n=49). Low p-tau/t-tau ratio was the best single marker for sCJD with 90% specificity against neurological controls at 86% sensitivity whilst NSE......Laboratory markers have a prominent place among the diagnostic criteria for sporadic Creutzfeldt-Jakob disease (sCJD). Here we investigate the capability of protein 14-3-3, total-tau (t-tau), threonin-181-phosphorylated tau (p-tau), and neuron-specific enolase (NSE) in cerebrospinal fluid (CSF...

  7. Identification and validation of novel cerebrospinal fluid biomarkers for staging early Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Richard J Perrin

    Full Text Available Ideally, disease modifying therapies for Alzheimer disease (AD will be applied during the 'preclinical' stage (pathology present with cognition intact before severe neuronal damage occurs, or upon recognizing very mild cognitive impairment. Developing and judiciously administering such therapies will require biomarker panels to identify early AD pathology, classify disease stage, monitor pathological progression, and predict cognitive decline. To discover such biomarkers, we measured AD-associated changes in the cerebrospinal fluid (CSF proteome.CSF samples from individuals with mild AD (Clinical Dementia Rating [CDR] 1 (n = 24 and cognitively normal controls (CDR 0 (n = 24 were subjected to two-dimensional difference-in-gel electrophoresis. Within 119 differentially-abundant gel features, mass spectrometry (LC-MS/MS identified 47 proteins. For validation, eleven proteins were re-evaluated by enzyme-linked immunosorbent assays (ELISA. Six of these assays (NrCAM, YKL-40, chromogranin A, carnosinase I, transthyretin, cystatin C distinguished CDR 1 and CDR 0 groups and were subsequently applied (with tau, p-tau181 and Aβ42 ELISAs to a larger independent cohort (n = 292 that included individuals with very mild dementia (CDR 0.5. Receiver-operating characteristic curve analyses using stepwise logistic regression yielded optimal biomarker combinations to distinguish CDR 0 from CDR>0 (tau, YKL-40, NrCAM and CDR 1 from CDR<1 (tau, chromogranin A, carnosinase I with areas under the curve of 0.90 (0.85-0.94 95% confidence interval [CI] and 0.88 (0.81-0.94 CI, respectively.Four novel CSF biomarkers for AD (NrCAM, YKL-40, chromogranin A, carnosinase I can improve the diagnostic accuracy of Aβ42 and tau. Together, these six markers describe six clinicopathological stages from cognitive normalcy to mild dementia, including stages defined by increased risk of cognitive decline. Such a panel might improve clinical trial efficiency by guiding

  8. Morphofunctional characteristic of gastric adipocytes in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Ashot Musaelovich Mkrtumyan

    2009-06-01

    Full Text Available Aim. To measure gastrointestinal hormones in plasma, evaluate morphofunctional state of G- and beta-cells in patients with gastric pathology and concomitanttype 2 diabetes mellitus (DM2. Materials and methods. A total of 84 patients with gastric ulcer (GU and chronic gastritis (CG were available for observation including 46 with DM2.Semi-quantitative evaluation of stomach infection by H.pylori. was performed by a histological method. Stained G- and beta-cells were counted under 400xmagnification in 10 fields of vision for each medicinal preparation used in the study. Chromogranin A, somatostatin, and gastrin were detected by immunohistochemicalmethods, gastrin-17 and somatostatin-14 by the respective immunoassays. Control group comprised 10 practically healthy volunteers. Results. Patients with combined GU (or CG and DM2 pathology had smaller density of G- and beta-cells, lower plasma gastrin and somatostatin levelsthan those without DM2 (p

  9. Immunohistochemical findings in rectal duplication mimicking rectal prolapse.

    Science.gov (United States)

    Cortese, M G; Pucci, A; Macchieraldo, R; Sacco Casamassima, M G; Canavese, F

    2008-08-01

    Alimentary tract duplications represent rare anomalies, with only 5 % occurring in the rectum. The variety in clinical presentation may lead to a delay in diagnosis or to incorrect and multiple surgical procedures. We report the clinical, histological and immunohistochemical characteristics of a rectal duplication occurring in a 3-month-old male with an unusual clinical presentation. Using routine histology and immunohistochemistry, the rectal duplication showed the diffuse presence of gastric mucosa with a characteristic immunophenotype (i.e., diffuse cytokeratin 7 positivity and scattered chromogranin immunoreactivity). As far as we know, this is the first report showing an immunohistochemical differentiation pattern of gastric lining in a rectal duplication. Our results, showing the presence of gastric mucosa, are suggestive of a possible origin from the embryonic foregut.

  10. Primary hepatic neuroendocrine tumor after 4 years tumor-free follow-up.

    Science.gov (United States)

    Lambrescu, Ioana Maria; Martin, Sorina; Cima, Luminita; Herlea, Vlad; Badiu, Corin; Fica, Simona

    2015-06-01

    A primary hepatic neuroendocrine tumour (PHNET) is a very rare disease. The liver represents the preferential site for neuroendocrine tumors' metastases. A 45-year old Caucasian female who presented with nausea, vomiting, diarrhea, accompanied by diffuse abdominal pain was found to have on contrast-enhanced computer tomography an encapsulated, partially cystic liver mass. The patient underwent an uneventful left atypical hepatic resection. Histopatological and immunohistochemical examination revealed a slowly growing (G1) hepatic neuroendocrine tumour. Post surgery, the specific neuroendocrine markers (serum Chromogranin A and 24h urinary 5 hydroxy-indolacetic acid) were within normal range. Further functional imaging investigations were performed. No other lesions were found making probable the diagnosis of PHNET. The patient is presently after 4 years of follow-up with no local recurrence or distant metastases. The diagnosis of PHNET is a medical challenge that requires a thorough long term follow-up in order to exclude an occult primary neuroendocrine tumour.

  11. GLP1 and glucagon co-secreting pancreatic neuroendocrine tumor presenting as hypoglycemia after gastric bypass

    DEFF Research Database (Denmark)

    Guimarães, Marta; Rodrigues, Pedro; Pereira, Sofia S

    2015-01-01

    for the treatment of severe obesity, a 54-year-old female with previous type 2 diabetes, developed post-prandial sweating, fainting and hypoglycemic episodes, which eventually led to the finding by ultrasound of a 1.8-cm solid mass in the pancreatic head. The 72-h fast test and the plasma chromogranin A levels were...... (471 pmol/g), insulin (139 pmol/g) and somatostatin (23 pmol/g). This is the first report of a GLP1 and glucagon co-secreting pNET presenting as hypoglycemia after gastric bypass surgery. Although pNET are rare, they should be considered in the differential diagnosis of the clinical approach...

  12. Ectopic cervical thymoma mimicking as papillary thyroid carcinoma: A diagnostic dilemma

    Directory of Open Access Journals (Sweden)

    Thakur Abhijit

    2010-04-01

    Full Text Available Ectopic cervical thymomas are often confused with thyroid or parathyroid swellings due to their anatomical positioning. Predominant epithelial thymoma can be misdiagnosed as papillary thyroid carcinoma on fine needle aspiration and lymph node metastasis of epithelial tumor on frozen section. Predominantly lymphocytic thymomas have often been misinterpreted as Hashimoto′s thyroiditis or malignant lymphoma, either by fine needle aspiration or on frozen section analysis. If cytology is doubtful and is not correlating with clinical, anatomical and surgical findings; immunohistochemistry is a very important tool in such cases to give final answer. Thyroid cell specific proteins such as thyroglobulin, thyroid transcription factor-1, thyroperoxidase and dipeptidyl aminopeptidase-4, neuroendocrine markers chromogranin, calcitonin and parathyroid hormone could be used to rule out thyroid or parathyroid origin. We present such rare case of ectopic cervical thymoma mimicking as papillary thyroid carcinoma.

  13. Preoperative Embolization Reduces the Risk of Cathecolamines Release at the Time of Surgical Excision of Large Pelvic Extra-Adrenal Sympathetic Paraganglioma

    Directory of Open Access Journals (Sweden)

    Nicola Di Daniele

    2012-01-01

    Full Text Available A 30-year-old woman with severe hypertension was admitted to the hospital with a history of headache, palpitations, and diaphoresis following sexual intercourse. Twenty-four hour urinary excretion of free catecholamines and metabolites was markedly increased as was serum chromogranin A. Computed tomography scan revealed a large mass in the left adnex site and magnetic resonance imaging confirmed the computer tomography finding, suggesting the presence of extra-adrenal sympathetic paraganglioma. I-metaiodobenzyl guanidine scintigram revealed an increased uptake in the same area. Transcatheter arterial embolization of the mass resulted in marked decreases in blood pressure and urinary excretion of free catecholamines and metabolites. Surgical excision of the mass was then accomplished without complication. Preoperative embolization is a useful and safe procedure which may reduce the risk of catecholamines release at the time of surgical excision in large pelvic extra-adrenal sympathetic paraganglioma.

  14. Proteomic evaluation of myofibrillar carbonylation in chilled fish mince and its inhibition by catechin.

    Science.gov (United States)

    Pazos, Manuel; Maestre, Rodrigo; Gallardo, José M; Medina, Isabel

    2013-01-01

    The present study investigates the susceptibility of individual myofibrillar proteins from mackerel (Scomber scombrus) mince to undergo carbonylation reactions during chilled storage, and the antioxidant capacity of (+)-catechin to prevent oxidative processes of proteins. The carbonylation of each particular protein was quantified by combining the labelling of protein carbonyls by fluorescein-5-thiosemicarbazide (FTSC) with 1-D or 2-D gel electrophoresis. Alpha skeletal actin, glycogen phosphorylase, unnamed protein product (UNP) similar to enolase, pyruvate kinase, isoforms of creatine kinase, aldolase A and an isoform of glyceraldehyde 3-phosphate dehydrogenase (G3PDH) showed elevated oxidation in chilled non-supplemented mince. Myosin heavy chain (MHC) was not carbonylated in chilled muscle, but an extensive MHC degradation was observed in those samples. The supplementation of catechin reduced protein oxidation and lipid oxidation in a concentration-dependent manner: control>25>100≈200ppm. Therefore, the highest catechin concentrations (100 and 200ppm) exhibited the strongest antioxidant activity. Catechin (200ppm) reduced significantly carbonylation of protein spots identified as glycogen phosphorylase, pyruvate kinase muscle isozyme, isoforms of creatine kinase. Conversely, catechin was ineffective to inhibit the oxidation of actin and UNP similar to enolase. These results draw attention to the inefficiency of catechin to prevent actin oxidation, in contrast to the extremely high efficiency of catechin in inhibiting oxidation of lipids and other proteins. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Proteomic analysis of Taenia ovis metacestodes by high performance liquid chromatography-coupled tandem mass spectrometry.

    Science.gov (United States)

    Zheng, Yadong

    2017-03-15

    Taenia ovis metacestodes reside in the muscle of sheep and goats, and may cause great economic loss due to condemnation of carcasses if not effectively controlled. Although advances have been made in the control of T. ovis infection, our knowledge of T. ovis biology is limited. Herein the protein profiling of T. ovis metacestodes was determined by liquid chromatography-linked tandem mass spectrometry. A total of 966 proteins were identified and 25.1% (188/748) were annotated to be associated with metabolic pathways. Consistently, GO analysis returned a metabolic process (16.27%) as one of two main biological process terms. Moreover, it was found that 24 proteins, including very low-density lipoprotein receptor, enolase, paramyosin and endophilin B1, were abundant in T. ovis metacestodes. These proteins may be associated with motility, metabolism, signaling, stress, drug resistance and immune responses. Furthermore, comparative analysis of 5 cestodes revealed the presence of Taenia-specific enolases. These data provide clues for better understanding of T. ovis biology, which is informative for effective control of infection. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. MicroRNA-9 promotes the neuronal differentiation of rat bone marrow mesenchymal stem cells by activating autophagy

    Directory of Open Access Journals (Sweden)

    Guang-yu Zhang

    2015-01-01

    Full Text Available MicroRNA-9 (miR-9 has been shown to promote the differentiation of bone marrow mesenchymal stem cells into neuronal cells, but the precise mechanism is unclear. Our previous study confirmed that increased autophagic activity improved the efficiency of neuronal differentiation in bone marrow mesenchymal stem cells. Accumulating evidence reveals that miRNAs adjust the autophagic pathways. This study used miR-9-1 lentiviral vector and miR-9-1 inhibitor to modulate the expression level of miR-9. Autophagic activity and neuronal differentiation were measured by the number of light chain-3 (LC3-positive dots, the ratio of LC3-II/LC3, and the expression levels of the neuronal markers enolase and microtubule-associated protein 2. Results showed that LC3-positive dots, the ratio of LC3-II/LC3, and expression of neuron specific enolase and microtubule-associated protein 2 increased in the miR-9 + group. The above results suggest that autophagic activity increased and bone marrow mesenchymal stem cells were prone to differentiate into neuronal cells when miR-9 was overexpressed, demonstrating that miR-9 can promote neuronal differentiation by increasing autophagic activity.

  17. Level of action of cathodal DC polarisation induced inhibition of the human motor cortex.

    Science.gov (United States)

    Nitsche, Michael A; Nitsche, Maren S; Klein, Cornelia C; Tergau, Frithjof; Rothwell, John C; Paulus, Walter

    2003-04-01

    To induce prolonged motor cortical excitability reductions by transcranial direct current stimulation in the human. Cathodal direct current stimulation was applied transcranially to the hand area of the human primary motor cortex from 5 to 9 min in separate sessions in twelve healthy subjects. Cortico-spinal excitability was tested by single pulse transcranial magnetic stimulation. Transcranial electrical stimulation and H-reflexes were used to learn about the origin of the excitability changes. Neurone specific enolase was measured before and after the stimulation to prove the safety of the stimulation protocol. Five and 7 min direct current stimulation resulted in motor cortical excitability reductions, which lasted for minutes after the end of stimulation, 9 min stimulation induced after-effects for up to an hour after the end of stimulation, as revealed by transcranial magnetic stimulation. Muscle evoked potentials elicited by transcranial electric stimulation and H-reflexes did not change. Neurone specific enolase concentrations remained stable throughout the experiments. Cathodal transcranial direct current stimulation is capable of inducing prolonged excitability reductions in the human motor cortex non-invasively. These changes are most probably localised intracortically.

  18. Distribution and phylogenies of enzymes of the Embden-Meyerhof-Parnas pathway from archaea and hyperthermophilic bacteria support a gluconeogenic origin of metabolism

    Directory of Open Access Journals (Sweden)

    Ron S. Ronimus

    2003-01-01

    Full Text Available Enzymes of the gluconeogenic/glycolytic pathway (the Embden-Meyerhof-Parnas (EMP pathway, the reductive tricarboxylic acid cycle, the reductive pentose phosphate cycle and the Entner-Doudoroff pathway are widely distributed and are often considered to be central to the origins of metabolism. In particular, several enzymes of the lower portion of the EMP pathway (the so-called trunk pathway, including triosephosphate isomerase (TPI; EC 5.3.1.1, glyceraldehyde-3-phosphate dehydrogenase (GAPDH; EC 1.2.1.12/13, phosphoglycerate kinase (PGK; EC 2.7.2.3 and enolase (EC 4.2.1.11, are extremely well conserved and universally distributed among the three domains of life. In this paper, the distribution of enzymes of gluconeogenesis/glycolysis in hyperthermophiles—microorganisms that many believe represent the least evolved organisms on the planet—is reviewed. In addition, the phylogenies of the trunk pathway enzymes (TPIs, GAPDHs, PGKs and enolases are examined. The enzymes catalyzing each of the six-carbon transformations in the upper portion of the EMP pathway, with the possible exception of aldolase, are all derived from multiple gene sequence families. In contrast, single sequence families can account for the archaeal and hyperthermophilic bacterial enzyme activities of the lower portion of the EMP pathway. The universal distribution of the trunk pathway enzymes, in combination with their phylogenies, supports the notion that the EMP pathway evolved in the direction of gluconeogenesis, i.e., from the bottom up.

  19. Enterobacterial envelope proteins and their participation in pathogenicity and antibacterial immunity

    Directory of Open Access Journals (Sweden)

    Danuta Witkowska

    2009-04-01

    Full Text Available The problems concerning the pathogenicity and virulence of some bacteria of the [i]Enterobacteriaceae[/i] family are described. The structure and functional variety of the outer membrane proteins on the cell surface are presented as potent immunogens based on the structure of the cell envelope. These proteins participate in stabilization of the membrane structure and adhesion to other cells, are receptors for bacteriophages, and play a key role in signal transduction, intracellular transport, and energy transformation processes ensuring proper cell functioning. Moreover, these proteins have a protective function against immune reactions of the infected organism. Referring to current literature data, the authors’ own results are reviewed on the methodology of isolating outer membrane proteins and their participation in pathogenicity with regard to molecular mimicry. The isolated and characterized 45-kDa enolase-like protein expressing similarity to human enolase should not be a component of vaccine, although it is considered a diagnostic marker of tissue damage. Presented are also results of studies on the role of the outer membrane protein OMP38, recognized by the human immune system as an important factor in antibacterial immunity. OMP38 is considered an antigen and carrier in conjugate vaccines, but also a specific diagnostic marker of immune deficiencies useful in monitoring the level of immunity against bacteria of the [i]Enterobacteriaceae[/i] family.

  20. HUPO BPP pilot study: a proteomics analysis of the mouse brain of different developmental stages.

    Science.gov (United States)

    Wang, Jing; Gu, Yong; Wang, Lihong; Hang, Xingyi; Gao, Yan; Wang, Hangyan; Zhang, Chenggang

    2007-11-01

    This study is a part of the HUPO Brain Proteome Project (BPP) pilot study, which aims at obtaining a reliable database of mouse brain proteome, at the comparison of techniques, laboratories, and approaches as well as at preparing subsequent proteome studies of neurologic diseases. The C57/Bl6 mouse brains of three developmental stages at embryonic day 16 (E16), postnatal day 7 (P7), and 8 wk (P56) (n = 5 in each group) were provided by the HUPO BPP executive committee. The whole brain proteins of each animal were individually prepared using 2-DE coupled with PDQuest software analysis. The protein spots representing developmentally related or stably expressed proteins were then prepared with in-gel digestion followed with MALDI-TOF/TOF MS/MS and analyzed using the MASCOT search engines to search the Swiss-Prot or NCBInr database. The 2-DE gel maps of the mouse brains of all of the developmental stages were obtained and submitted to the Data Collection Centre (DCC). The proteins alpha-enolase, stathmin, actin, C14orf166 homolog, 28,000 kDa heat- and acid-stable phosphoprotein, 3-mercaptopyruvate sulfurtransferase and 40 S ribosomal protein S3a were successfully identified. A further Western blotting analysis demonstrated that enolase is a protein up-regulated in the mouse brain from embryonic stage to adult stage. These data are helpful for understanding the proteome changes in the development of the mouse brain.

  1. Impact of Autoantibodies against Glycolytic Enzymes on Pathogenicity of Autoimmune Retinopathy and Other Autoimmune Disorders

    Directory of Open Access Journals (Sweden)

    Grazyna Adamus

    2017-04-01

    Full Text Available Autoantibodies (AAbs against glycolytic enzymes: aldolase, α-enolase, glyceraldehyde-3-phosphate dehydrogenase, and pyruvate kinase are prevalent in sera of patients with blinding retinal diseases, such as paraneoplastic [cancer-associated retinopathy (CAR] and non-paraneoplastic autoimmune retinopathies, as well as in many other autoimmune diseases. CAR is a degenerative disease of the retina characterized by sudden vision loss in patients with cancer and serum anti-retinal AAbs. In this review, we discuss the widespread serum presence of anti-glycolytic enzyme AAbs and their significance in autoimmune diseases. There are multiple mechanisms responsible for antibody generation, including the innate anti-microbial response, anti-tumor response, or autoimmune response against released self-antigens from damaged, inflamed tissue. AAbs against enolase, GADPH, and aldolase exist in a single patient in elevated titers, suggesting their participation in pathogenicity. The lack of restriction of AAbs to one disease may be related to an increased expression of glycolytic enzymes in various metabolically active tissues that triggers an autoimmune response and generation of AAbs with the same specificity in several chronic and autoimmune conditions. In CAR, the importance of serum anti-glycolytic enzyme AAbs had been previously dismissed, but the retina may be without pathological consequence until a failure of the blood–retinal barrier function, which would then allow pathogenic AAbs access to their retinal targets, ultimately leading to damaging effects.

  2. A proteomic analysis of the functional effects of fatty acids in NIH 3T3 fibroblasts

    LENUS (Irish Health Repository)

    Magdalon, Juliana

    2011-11-24

    Abstract Previous studies have demonstrated that long chain fatty acids influence fibroblast function at sub-lethal concentrations. This study is the first to assess the effects of oleic, linoleic or palmitic acids on protein expression of fibroblasts, as determined by standard proteomic techniques. The fatty acids were not cytotoxic at the concentration used in this work as assessed by membrane integrity, DNA fragmentation and the MTT assay but significantly increased cell proliferation. Subsequently, a proteomic analysis was performed using two dimensional difference gel electrophoresis (2D-DIGE) and MS based identification. Cells treated with 50 μM oleic, linoleic or palmitic acid for 24 h were associated with 24, 22, 16 spots differentially expressed, respectively. Among the identified proteins, α-enolase and far upstream element binding protein 1 (FBP-1) are of importance due to their function in fibroblast-associated diseases. However, modulation of α-enolase and FBP-1 expression by fatty acids was not validated by the Western blot technique.

  3. Downregulation of bone morphogenetic protein receptor 2 promotes the development of neuroblastoma

    International Nuclear Information System (INIS)

    Cui, Ximao; Yang, Yili; Jia, Deshui; Jing, Ying; Zhang, Shouhua; Zheng, Shan; Cui, Long; Dong, Rui; Dong, Kuiran

    2017-01-01

    Neuroblastoma (NB) is the most common extracranial solid tumor of childhood. In this study, we examined the expression of bone morphogenetic protein receptor 2 (BMPR2) in primary NB and adjacent non-tumor samples (adrenal gland). BMPR2 expression was significantly downregulated in NB tissues, particularly in high-grade NB, and was inversely related to the expression of the NB differentiation markers ferritin and enolase. The significance of the downregulation was further explored in cultured NB cells. While enforced expression of BMPR2 decreased cell proliferation and colony-forming activity, shRNA-mediated knockdown of BMPR2 led to increased cell growth and clonogenicity. In mice, NB cells harboring BMPR2 shRNA showed significantly increased tumorigenicity compared with control cells. We also performed a retrospective analysis of NB patients and identified a significant positive correlation between tumor BMPR2 expression and overall survival. These findings suggest that BMPR2 may play an important role in the development of NB. - Highlights: • BMPR2 expression was downregulated in primary NB and was more signifcant in high grade NB. • BMPR2 expression was accompanied by the decrease of NB markers ferritin and enolase. • Enforced expression of BMPR2 decreased proliferation and colony formation ability of cultured NB cells. • Knockdown of BMPR2 led to increased cell growth, clonality and tumorigenicity in mice. • Patients with NB expressing higher level of BMPR2 had significant better overall survival than those with low level.

  4. Proteomic analysis of docetaxel resistance in human nasopharyngeal carcinoma cells using the two-dimensional gel electrophoresis method.

    Science.gov (United States)

    Peng, Xingchen; Gong, Fengming M; Ren, Min; Ai, Ping; Wu, ShaoYong; Tang, Jie; Hu, XiaoLin

    2016-09-01

    Docetaxel-based chemotherapy has been recommended for advanced nasopharyngeal carcinoma (NPC). However, treatment failure often occurs because of acquired drug resistance. In this study, a docetaxel-resistant NPC cell line CNE-2R was established with increasing doses of docetaxel for more than 6 months. Two-dimensional gel electrophoresis and ESI-Q-TOF-MS were used to compare the differential expression of docetaxel-resistance-associated proteins between human NPC CNE-2 cells and docetaxel-resistant CNE-2R cells. As a result, 24 differentially expressed proteins were identified, including 11 proteins with increased expression and 13 proteins with decreased expression. These proteins function in diverse biological processes such as metabolism, signal transduction, calcium ion binding, immune response, proteolysis, and so on. Among these, α-enolase (ENO1), significantly upregulated in CNE-2R, was selected for detailed analysis. Inhibition of ENO1 by shRNA restored CNE-2R cells' sensitivity to docetaxel. Moreover, overexpression of ENO1 could facilitate the development of acquired resistance of docetaxel in CNE-2 cells. Western blot and reverse-transcription PCR data of clinical samples confirmed that α-enolase was upregulated in docetaxel-resistant human NPC tissues. Finding such proteins might improve interpretation of the molecular mechanisms leading to the acquisition of docetaxel chemoresistance.

  5. Neutrophil Extracellular DNA Traps Induce Autoantigen Production by Airway Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Youngwoo Choi

    2017-01-01

    Full Text Available The hypothesis of autoimmune involvement in asthma has received much recent interest. Autoantibodies, such as anti-cytokeratin (CK 18, anti-CK19, and anti-α-enolase antibodies, react with self-antigens and are found at high levels in the sera of patients with severe asthma (SA. However, the mechanisms underlying autoantibody production in SA have not been fully determined. The present study was conducted to demonstrate that neutrophil extracellular DNA traps (NETs, cytotoxic molecules released from neutrophils, are a key player in the stimulation of airway epithelial cells (AECs to produce autoantigens. This study showed that NETs significantly increased the intracellular expression of tissue transglutaminase (tTG but did not affect that of CK18 in AECs. NETs induced the extracellular release of both tTG and CK18 in a concentration-dependent manner. Moreover, NETs directly degraded intracellular α-enolase into small fragments. However, antibodies against neutrophil elastase (NE or myeloperoxidase (MPO attenuated the effects of NETs on AECs. Furthermore, each NET isolated from healthy controls (HC, nonsevere asthma (NSA, and SA had different characteristics. Taken together, these findings suggest that AECs exposed to NETs may exhibit higher autoantigen production, especially in SA. Therefore, targeting of NETs may represent a new therapy for neutrophilic asthma with a high level of autoantigens.

  6. Psychophysiological responses of junior orienteers under competitive pressure.

    Directory of Open Access Journals (Sweden)

    Claudio Robazza

    Full Text Available The purpose of the study was to examine psychobiosocial states, cognitive functions, endocrine responses (i.e., salivary cortisol and chromogranin A, and performance under competitive pressure in orienteering athletes. The study was grounded in the individual zones of optimal functioning (IZOF and biopsychosocial models. Fourteen junior orienteering athletes (7 girls and 7 boys, ranging in age from 15 to 20 years (M = 16.93, SD = 1.77 took part in a two-day competitive event. To enhance competitive pressure, emphasis was placed on the importance of the competition and race outcome. Psychophysiological and performance data were collected at several points before, during, and after the races. Results showed that an increase in cortisol levels was associated with competitive pressure and reflected in higher perceived exertion (day 1, r = .32; day 2, r = .46, higher intensity of dysfunctional states (day 1, r = .59; day 2, r = .55, lower intensity of functional states (day 1, r = -.36; day 2, r = -.33, and decay in memory (day 1, r = -.27; day 2, r = -.35, visual attention (day 1, r = -.56; day 2, r = -.35, and attention/mental flexibility (day 1, r = .16; day 2, r = .26 tasks. The second day we observed better performance times, lower intensity of dysfunctional states, lower cortisol levels, improved visual attention and attention/mental flexibility (p < .050. Across the two competition days, chromogranin A levels were higher (p < .050 on the most difficult loops of the race in terms of both physical and psychological demands. Findings suggest emotional, cognitive, psychophysiological, and performance variables to be related and to jointly change across different levels of cognitive and physical load. Overall results are discussed in light of the IZOF and biopsychosocial models. The procedure adopted in the study also supports the feasibility of including additional cognitive load for possible practical applications.

  7. The early effects of radiation on in vitro explants of mouse pancreas. A morphological and immunocytochemical study

    International Nuclear Information System (INIS)

    Kosanlavit, R.

    2001-01-01

    Prodromal radiation sickness involving the digestive system may occur less than an hour following whole-body or abdominal irradiation, and may be of such severity as to prevent cancer patients from completing their course of radiotherapy. The contribution of radiation-induced pancreatic damage to radiation sickness is poorly understood. This study seeks to demonstrate the early effects of X-rays (0.5-10 Gy) on mouse pancreas in vitro. The response of exocrine acinar cells, and endocrine cells from the islets of Langerhans was examined using immunocytochemistry, light and transmission electron microscopy, and morphometric analysis. There was an approximate 50% decrease in the mean number of zymogen granules in acinar cells following 10 Gy irradiation at 1 hour, which may have been due to the acceleration of enzyme secretion or the interruption of enzyme synthesis or a combination of both. The frequency distributions of zymogen granules diameter showed minor change. The gross structure of acinar cells appeared not to be affected by irradiation at the doses and times used. Following 5 and 10 Gy irradiation a few pancreatic endocrine cells within each islet lost their chromogranin A-immunoreactivity whereas other islet cells showed more intense immunostaining for chromogranin A. A dose of 10 Gy significantly decreased the volume density of glucagon-containing cells at 1 hour. Doses of 5 and 10 Gy slightly decreased the volume density of somatostatin-containing cells from 30 minutes to 3 hours. Such changes in the expression of endocrine products from these cells are likely to have profound physiological effects. Radiation induced no changes in the volume density of insulin and PP-containing cells. The results of the present study suggest that X-irradiation induce changes to exocrine and endocrine pancreatic cells, and that this may contribute to some of the symptoms of radiation sickness. (author)

  8. Psychophysiological responses of junior orienteers under competitive pressure.

    Science.gov (United States)

    Robazza, Claudio; Izzicupo, Pascal; D'Amico, Maria Angela; Ghinassi, Barbara; Crippa, Maria Chiara; Di Cecco, Vincenzo; Ruiz, Montse C; Bortoli, Laura; Di Baldassarre, Angela

    2018-01-01

    The purpose of the study was to examine psychobiosocial states, cognitive functions, endocrine responses (i.e., salivary cortisol and chromogranin A), and performance under competitive pressure in orienteering athletes. The study was grounded in the individual zones of optimal functioning (IZOF) and biopsychosocial models. Fourteen junior orienteering athletes (7 girls and 7 boys), ranging in age from 15 to 20 years (M = 16.93, SD = 1.77) took part in a two-day competitive event. To enhance competitive pressure, emphasis was placed on the importance of the competition and race outcome. Psychophysiological and performance data were collected at several points before, during, and after the races. Results showed that an increase in cortisol levels was associated with competitive pressure and reflected in higher perceived exertion (day 1, r = .32; day 2, r = .46), higher intensity of dysfunctional states (day 1, r = .59; day 2, r = .55), lower intensity of functional states (day 1, r = -.36; day 2, r = -.33), and decay in memory (day 1, r = -.27; day 2, r = -.35), visual attention (day 1, r = -.56; day 2, r = -.35), and attention/mental flexibility (day 1, r = .16; day 2, r = .26) tasks. The second day we observed better performance times, lower intensity of dysfunctional states, lower cortisol levels, improved visual attention and attention/mental flexibility (p competition days, chromogranin A levels were higher (p < .050) on the most difficult loops of the race in terms of both physical and psychological demands. Findings suggest emotional, cognitive, psychophysiological, and performance variables to be related and to jointly change across different levels of cognitive and physical load. Overall results are discussed in light of the IZOF and biopsychosocial models. The procedure adopted in the study also supports the feasibility of including additional cognitive load for possible practical applications.

  9. Splenosis Mimicking Relapse of a Neuroendocrine Tumor at Gallium-68-DOTATOC PET/CT

    International Nuclear Information System (INIS)

    Treglia, Giorgio; Luca, Giovanella; Barbara, Muoio; Carmelo, Caldarella

    2014-01-01

    A 48-year-old female patient underwent splenopancreasectomy for a 4-cm pancreatic neuroendocrine tumor (pNET), grade G2, located in the pancreatic tail. One year after surgery, the patient presented an increased serum level of the tumor marker chromogranin A (value: 160 U/l). Therefore, she underwent somatostatin receptor PET/CT using gallium-68-DOTATOC for restaging. This imaging method showed a focal area of increased radiopharmaceutical uptake corresponding to a 2.5-cm nodule located in the left superior abdomen near a clip from the previous surgery, suggesting a possible relapse of pNET. Based on this PET/CT finding, the patient underwent ultrasonography-guided core biopsy of this nodule. Histology did not reveal findings suggestive of pNET but identified spleen tissue most likely caused by splenosis accidentally seeded at the previous operation. It is likely that the increased serum level of the tumor marker chromogranin A was due to the chronic proton-pump inhibitors use. Somatostatin receptor PET/CT is an accurate imaging method for staging and restaging pNET, presenting high sensitivity and specificity in this setting. Nevertheless, possible sources of false-negative and -positive findings with this method should be taken into account. Inflammatory lesions represent the most frequent causes of false-positive findings for pNET at somatostatin receptor imaging because inflammatory cellsmay overexpress somatostatin receptors on their cell surface. In our case, we showed that splenosis may represent a possible cause of false-positive findings for pNET relapse due to the physiological uptake of somatostatin analogs by the spleen tissue

  10. Total {sup 18}F-dopa PET tumour uptake reflects metabolic endocrine tumour activity in patients with a carcinoid tumour

    Energy Technology Data Exchange (ETDEWEB)

    Fiebrich, Helle-Brit; Walenkamp, Annemiek M.; Vries, Elisabeth G.E. de [University Medical Centre Groningen, Department of Medical Oncology, Groningen (Netherlands); Jong, Johan R. de; Koopmans, Klaas Pieter; Dierckx, Rudi A.J.O.; Brouwers, Adrienne H. [University Medical Centre Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); Kema, Ido P. [University Medical Centre Groningen, Department of Laboratory Medicine, Groningen (Netherlands); Sluiter, Wim; Links, Thera P. [University Medical Centre Groningen, Department of Endocrinology, Groningen (Netherlands)

    2011-10-15

    Positron emission tomography (PET) using 6-[{sup 18}F]fluoro-L-dihydroxyphenylalanine ({sup 18}F-dopa) has an excellent sensitivity to detect carcinoid tumour lesions. {sup 18}F-dopa tumour uptake and the levels of biochemical tumour markers are mediated by tumour endocrine metabolic activity. We evaluated whether total {sup 18}F-dopa tumour uptake on PET, defined as whole-body metabolic tumour burden (WBMTB), reflects tumour load per patient, as measured with tumour markers. Seventy-seven consecutive carcinoid patients who underwent an {sup 18}F-dopa PET scan in two previously published studies were analysed. For all tumour lesions mean standardised uptake values (SUVs) at 40% of the maximal SUV and tumour volume on {sup 18}F-dopa PET were determined and multiplied to calculate a metabolic burden per lesion. WBMTB was the sum of the metabolic burden of all individual lesions per patient. The 24-h urinary serotonin, urine and plasma 5-hydroxindoleacetic acid (5-HIAA), catecholamines (nor)epinephrine, dopamine and their metabolites, measured in urine and plasma, and serum chromogranin A served as tumour markers. All but 1 were evaluable for WBMTB; 74 patients had metastatic disease. {sup 18}F-dopa PET detected 979 lesions. SUV{sub max} on {sup 18}F-dopa PET varied up to 29-fold between individual lesions within the same patients. WBMTB correlated with urinary serotonin (r = 0.51) and urinary and plasma 5-HIAA (r = 0.78 and 0.66). WBMTB also correlated with urinary norepinephrine, epinephrine, dopamine and plasma dopamine, but not with serum chromogranin A. Tumour load per patient measured with {sup 18}F-dopa PET correlates with tumour markers of the serotonin and catecholamine pathway in urine and plasma in carcinoid patients, reflecting metabolic tumour activity. (orig.)

  11. Regional thalamic neuropathology in patients with hippocampal sclerosis and epilepsy: A postmortem study

    Science.gov (United States)

    Sinjab, Barah; Martinian, Lillian; Sisodiya, Sanjay M; Thom, Maria

    2013-01-01

    Purpose Clinical, experimental, and neuroimaging data all indicate that the thalamus is involved in the network of changes associated with temporal lobe epilepsy (TLE), particularly in association with hippocampal sclerosis (HS), with potential roles in seizure initiation and propagation. Pathologic changes in the thalamus may be a result of an initial insult, ongoing seizures, or retrograde degeneration through reciprocal connections between thalamic and limbic regions. Our aim was to carry out a neuropathologic analysis of the thalamus in a postmortem (PM) epilepsy series, to assess the distribution, severity, and nature of pathologic changes and its association with HS. Methods Twenty-four epilepsy PM cases (age range 25–87 years) and eight controls (age range 38–85 years) were studied. HS was classified as unilateral (UHS, 11 cases), bilateral (BHS, 4 cases) or absent (No-HS, 9 cases). Samples from the left and right sides of the thalamus were stained with cresyl violet (CV), and for glial firbillary acidic protein (GFAP) and synaptophysin. Using image analysis, neuronal densities (NDs) or field fraction staining values (GFAP, synaptophysin) were measured in four thalamic nuclei: anteroventral nucleus (AV), lateral dorsal nucleus (LD), mediodorsal nucleus (MD), and ventrolateral nucleus (VL). The results were compared within and between cases. Key Findings The severity, nature, and distribution of thalamic pathology varied between cases. A pattern that emerged was a preferential involvement of the MD in UHS cases with a reduction in mean ND ipsilateral to the side of HS (p = 0.05). In UHS cases, greater field fraction values for GFAP and lower values for synaptophysin and ND were seen in the majority of cases in the MD ipsilateral to the side of sclerosis compared to other thalamic nuclei. In addition, differences in the mean ND between classical HS, atypical HS, and No-HS cases were noted in the ipsilateral MD (p < 0.05), with lower values observed in

  12. Propofol exposure during late stages of pregnancy impairs learning and memory in rat offspring via the BDNF-TrkB signalling pathway.

    Science.gov (United States)

    Zhong, Liang; Luo, Foquan; Zhao, Weilu; Feng, Yunlin; Wu, Liuqin; Lin, Jiamei; Liu, Tianyin; Wang, Shengqiang; You, Xuexue; Zhang, Wei

    2016-10-01

    The brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB) (BDNF-TrkB) signalling pathway plays a crucial role in regulating learning and memory. Synaptophysin provides the structural basis for synaptic plasticity and depends on BDNF processing and subsequent TrkB signalling. Our previous studies demonstrated that maternal exposure to propofol during late stages of pregnancy impaired learning and memory in rat offspring. The purpose of this study is to investigate whether the BDNF-TrkB signalling pathway is involved in propofol-induced learning and memory impairments. Propofol was intravenously infused into pregnant rats for 4 hrs on gestational day 18 (E18). Thirty days after birth, learning and memory of offspring was assessed by the Morris water maze (MWM) test. After the MWM test, BDNF and TrkB transcript and protein levels were measured in rat offspring hippocampus tissues using real-time PCR (RT-PCR) and immunohistochemistry (IHC), respectively. The levels of phosphorylated-TrkB (phospho-TrkB) and synaptophysin were measured by western blot. It was discovered that maternal exposure to propofol on day E18 impaired spatial learning and memory of rat offspring, decreased mRNA and protein levels of BDNF and TrkB, and decreased the levels of both phospho-TrkB and synaptophysin in the hippocampus. Furthermore, the TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) reversed all of the observed changes. Treatment with 7,8-DHF had no significant effects on the offspring that were not exposed to propofol. The results herein indicate that maternal exposure to propofol during the late stages of pregnancy impairs spatial learning and memory of offspring by disturbing the BDNF-TrkB signalling pathway. The TrkB agonist 7,8-DHF might be a potential therapy for learning and memory impairments induced by maternal propofol exposure. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular

  13. Upregulation of TREM2 Ameliorates Neuroinflammatory Responses and Improves Cognitive Deficits Triggered by Surgical Trauma in Appswe/PS1dE9 Mice

    Directory of Open Access Journals (Sweden)

    Yanhua Jiang

    2018-04-01

    Full Text Available Background/Aims: TREM2 plays a crucial role in modulating microglial function through interaction with DAP12, the adapter for TREM2. Emerging evidence has demonstrated that TREM2 could suppress neuroinflammatory responses by repression of microglia-mediated cytokine production. This study investigated the potential role of TREM2 in surgery-induced cognitive deficits and neuroinflammatory responses in wild-type (WT and APPswe/PS1dE9 mice. Methods: Adult APPswe/PS1dE9 transgenic male mice (a classic transgenic model of Alzheimer’s disease, 3 months old and their age-matched WT mice received intracerebral lentiviral particles encoding the mouse TREM2 gene and then were subjected to partial hepatectomy at 1 month after the lentiviral particle injection. The behavioral changes were evaluated with an open-field test and Morris water maze test on postoperative days 3, 7, and 14. Hippocampal TREM2, DAP12, and interleukin (IL-1β were measured at each time point. Ionized calcium-binding adapter molecule 1 (Iba-1, microglial M2 phenotype marker Arg1, synaptophysin, tau hyperphosphorylation (T396, and glycogen synthase kinase-3β (GSK-3β were also examined in the hippocampus. Results: Surgical trauma induced an exacerbated cognitive impairment and enhanced hippocampal IL-1β expression in the transgenic mice on postoperative days 3 and 7. A corresponding decline in the levels of TREM2 was also found on postoperative days 3, 7, and 14. Overexpression of TREM2 downregulated the levels of IL-1β, ameliorated T396 expression, inhibited the activity of GSK-3β, and improved sickness behavior. Increased Arg1 expression and a high level of synaptophysin were also observed in the transgenic mice following TREM2 overexpression. Conclusion: The downregulation of TREM2 exacerbated surgery-induced cognitive deficits and exaggerated neuroinflammatory responses in this rodent model. Overexpression of TREM2 potentially attenuated these effects by decreasing the

  14. Mixed Capillary Venous Retroperitoneal Hemangioma

    Directory of Open Access Journals (Sweden)

    Mohit Godar

    2013-01-01

    Full Text Available We report a case of mixed capillary venous hemangioma of the retroperitoneum in a 61-year-old man. Abdominal ultrasonography showed a mass to be hypoechoic with increased flow in color Doppler imaging. Dynamic contrast-enhanced computed tomography revealed a centripetal filling-in of the mass, located anterior to the left psoas muscle at the level of sacroiliac joint. On the basis of imaging features, preoperative diagnosis of hemangioma was considered and the mass was excised by laparoscopic method. Immunohistochemical studies were strongly positive for CD31 and CD34, and negative for calretinin, EMA, WT1, HMB45, Ki67, synaptophysin, and lymphatic endothelial cell marker D2–40. Histologically, the neoplasm was diagnosed as mixed capillary venous hemangioma.

  15. Subchronic, Low-Level Intraperitoneal Injections of Manganese (IV) Oxide and Manganese (II) Chloride Affect Rat Brain Neurochemistry

    DEFF Research Database (Denmark)

    Nielsen, Brian S.; Larsen, Erik Huusfeldt; Ladefoged, Ole

    2017-01-01

    Manganese (Mn) is neurotoxic and can induce manganism, a Parkinson-like disease categorized as being a serious central nervous system irreversible neurodegenerative disease. An increased risk of developing symptoms of Parkinson disease has been linked to work-related exposure, for example......Cl2)/kg bw/day for 7 d/wk for 8 or 12 weeks. This dosing regimen adds relevant new knowledge about Mn neurotoxicity as a consequence of low-dose subchronic Mn dosing. Manganese concentrations increased in the striatum, the rest of the brain, and in plasma, and regional brain neurotransmitter...... with MnCl2. Plasma prolactin concentration was not significantly affected due to a potentially reduced dopaminergic inhibition of the prolactin release from the anterior hypophysis. No effects on the striatal α-synuclein and synaptophysin protein levels were detected....

  16. Antihypertensive drug Valsartan promotes dendritic spine density by altering AMPA receptor trafficking

    Science.gov (United States)

    Sohn, Young In; Lee, Nathanael J.; Chung, Andrew; Saavedra, Juan M.; Turner, R. Scott; Pak, Daniel T. S.; Hoe, Hyang-Sook

    2013-01-01

    Recent studies demonstrated that the antihypertensive drug Valsartan improved spatial and episodic memory in mouse models of Alzheimer’s Disease (AD) and human subjects with hypertension. However, the molecular mechanism by which Valsartan can regulate cognitive function is still unknown. Here, we investigated the effect of Valsartan on dendritic spine formation in primary hippocampal neurons, which is correlated with learning and memory. Interestingly, we found that Valsartan promotes spinogenesis in developing and mature neurons. In addition, we found that Valsartan increases the puncta number of PSD-95 and trends toward an increase in the puncta number of synaptophysin. Moreover, Valsartan increased the cell surface levels of AMPA receptors and selectively altered the levels of spinogenesis-related proteins, including CaMKIIα and phospho-CDK5. These data suggest that Valsartan may promote spinogenesis by enhancing AMPA receptor trafficking and synaptic plasticity signaling. PMID:24012668

  17. Rosette-forming glioneuronal tumor of the fourth ventricle.

    Science.gov (United States)

    Preusser, Matthias; Dietrich, Wolfgang; Czech, Thomas; Prayer, Daniela; Budka, Herbert; Hainfellner, Johannes A

    2003-11-01

    Rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle has been reported recently as a novel type of primary CNS neoplasm. We present the case of a 35-year-old male patient with RGNT of the fourth ventricle. The tumor was found incidentally; the patient did not suffer from any neurological symptoms. The tumor mass involved the caudal cerebellar vermis, filled the fourth ventricle and protruded into the caudal part of the mesencephalic aquaeduct. Smaller tumor nodules were visible in the adjacent right cerebellar hemisphere. Histologically, prominent neurocytic rosettes with synaptophysin expression were embedded in a glial tumor component resembling pilocytic astrocytoma. Clinicopathological features of our case closely resemble those reported in the original description. Thus, our case confirms RGNT as a new distinct type of primary CNS neoplasm. Due to its distinct features, adoption of RGNT as a new entity into the WHO classification of tumors should be considered.

  18. Oridonin Attenuates Synaptic Loss and Cognitive Deficits in an Aβ1-42-Induced Mouse Model of Alzheimer's Disease.

    Directory of Open Access Journals (Sweden)

    Sulei Wang

    Full Text Available Synaptic loss induced by beta-amyloid (Aβ plays a critical role in the pathophysiology of Alzheimer's disease (AD, but the mechanisms underlying this process remain unknown. In this study, we found that oridonin (Ori rescued synaptic loss induced by Aβ1-42 in vivo and in vitro and attenuated the alterations in dendritic structure and spine density observed in the hippocampus of AD mice. In addition, Ori increased the expression of PSD-95 and synaptophysin and promoted mitochondrial activity in the synaptosomes of AD mice. Ori also activated the BDNF/TrkB/CREB signaling pathway in the hippocampus of AD mice. Furthermore, in the Morris water maze test, Ori reduced latency and searching distance and increased the number of platform crosses in AD mice. These data suggest that Ori might prevent synaptic loss and improve behavioral symptoms in Aβ1-42-induced AD mice.

  19. Adult type granulosa cell tumor in adult testis: report of a case and review of the literature

    Directory of Open Access Journals (Sweden)

    Zhanyong Bing

    2011-10-01

    Full Text Available Granulosa cell tumors can be classified into juvenile and adult types and more commonly occur in ovaries. Adult testicular granulosa cell tumors are extremely rare and only 29 cases of adult type have previously been reported. We report here a 28-year-old Caucasian man with a left testicular adult type granulosa cell tumor. The tumor measured 2.6 x 2.6 x 2.5 cm and was mitotically active (10/10 HPF. Immunohistochemical stains showed the tumor diffusely positive for inhibin and vimentin, and negative for epithelial membrane antigen, cytokeratins, synaptophysin, HMB-45, OCT-4, placental-like alkaline phosphatase and lymphoid markers . The reported granulosa cell tumors in adult testis were briefly reviewed.

  20. Spinal Cord Glioneuronal Tumor with Rosetted Neuropil-Like Islands in Pediatric Age Group

    Directory of Open Access Journals (Sweden)

    Nil Comunoglu

    2014-01-01

    Full Text Available Glioneuronal neoplasms are rare tumors. Recently, an unusual glioneuronal tumor histologically showing neuropil-like islands has been described. Here, we present such a tumor originating from spinal cord of a 14-year-old girl, who has scoliosis and urinary incontinence. Microscopically, the glial component was chiefly fibrillary astrocytic, punctuated by neuropil-like islands. Immunohistochemically, glial tissue was GFAP positive, and neuropil-like areas and big neurons were synaptophysin reactive. For astrocytic component Ki-67 proliferation index was 1% and p53 was immunonegative. This case is unique in that in the literature it is the second reported case in pediatric age group that is located at spinal cord.

  1. Cortical compression rapidly trimmed transcallosal projections and altered axonal anterograde transport machinery.

    Science.gov (United States)

    Chen, Li-Jin; Wang, Yueh-Jan; Tseng, Guo-Fang

    2017-10-24

    Trauma and tumor compressing the brain distort underlying cortical neurons. Compressed cortical neurons remodel their dendrites instantly. The effects on axons however remain unclear. Using a rat epidural bead implantation model, we studied the effects of unilateral somatosensory cortical compression on its transcallosal projection and the reversibility of the changes following decompression. Compression reduced the density, branching profuseness and boutons of the projection axons in the contralateral homotopic cortex 1week and 1month post-compression. Projection fiber density was higher 1-month than 1-week post-compression, suggesting adaptive temporal changes. Compression reduced contralateral cortical synaptophysin, vesicular glutamate transporter 1 (VGLUT1) and postsynaptic density protein-95 (PSD95) expressions in a week and the first two marker proteins further by 1month. βIII-tubulin and kinesin light chain (KLC) expressions in the corpus callosum (CC) where transcallosal axons traveled were also decreased. Kinesin heavy chain (KHC) level in CC was temporarily increased 1week after compression. Decompression increased transcallosal axon density and branching profuseness to higher than sham while bouton density returned to sham levels. This was accompanied by restoration of synaptophysin, VGLUT1 and PSD95 expressions in the contralateral cortex of the 1-week, but not the 1-month, compression rats. Decompression restored βIII-tubulin, but not KLC and KHC expressions in CC. However, KLC and KHC expressions in the cell bodies of the layer II/III pyramidal neurons partially recovered. Our results show cerebral compression compromised cortical axonal outputs and reduced transcallosal projection. Some of these changes did not recover in long-term decompression. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Retrograde influences of SCG axotomy on uninjured preganglionic neurons.

    Science.gov (United States)

    Gannon, Sean M; Hawk, Kiel; Walsh, Brian F; Coulibaly, Aminata; Isaacson, Lori G

    2018-04-18

    There is evidence that neuronal injury can affect uninjured neurons in the same neural circuit. The overall goal of this study was to understand the effects of peripheral nerve injury on uninjured neurons located in the central nervous system (CNS). As a model, we examined whether axotomy (transection of postganglionic axons) of the superior cervical ganglion (SCG) affected the uninjured, preganglionic neurons that innervate the SCG. At 7 days post-injury a reduction in choline acetyltransferase (ChAT) and synaptophysin immunoreactivity in the SCG, both markers for preganglionic axons, was observed, and this reduction persisted at 8 and 12 weeks post-injury. No changes were observed in the number or size of the parent cell bodies in the intermediolateral cell column (IML) of the spinal cord, yet synaptic input to the IML neurons was decreased at both 8 and 12 weeks post-injury. In order to understand the mechanisms underlying these changes, protein levels of brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB) were examined and reductions were observed at 7 days post-injury in both the SCG and spinal cord. Taken together these results suggest that axotomy of the SCG led to reduced BDNF in the SCG and spinal cord, which in turn influenced ChAT and synaptophysin expression in the SCG and also contributed to the altered synaptic input to the IML neurons. More generally these findings provide evidence that the effects of peripheral injury can cascade into the CNS and affect uninjured neurons. Copyright © 2018. Published by Elsevier B.V.

  3. Influence of catch up growth on spatial learning and memory in a mouse model of intrauterine growth restriction.

    Directory of Open Access Journals (Sweden)

    Cristina Duran Fernandez-Feijoo

    Full Text Available Intrauterine growth restriction (IUGR and rapid postnatal weight gain or catch up growth (CUG increase the susceptibility to metabolic syndrome during adult life. Longitudinal studies have also revealed a high incidence of learning difficulties in children with IUGR. The aim of the present study was to investigate the effect of nutrition and CUG on learning memory in an IUGR animal model. We hypothesized that synaptic protein expression and transcription, an essential mechanism for memory consolidation, might be affected by intrauterine undernutrition.IUGR was induced by 50% maternal caloric undernutrition throughout late gestation. During the suckling period, dams were either fed ad libitum or food restricted. The pups were divided into: Normal prenatal diet-Normal postnatal diet (NN, Restricted prenatal diet- Normal postnatal diet + catch up growth (RN+, Normal prenatal diet-Restricted postnatal diet (NR and Restricted prenatal diet-Restricted postnatal diet (RR. At 4 weeks of age, memory was assessed via a water maze test. To evaluate synaptic function, 2 specific synaptic proteins (postsynaptic density-95 [PSD95], synaptophysin as well as insulin receptors (IR were tested by Western Blot and quantitative polymerase chain reaction (qPCR. Brain-derived neurotrophic factor and serum insulin levels were also studied.The RN+ group presented a learning curve similar to the NN animals. The RR animals without CUG showed learning disabilities. PSD95 was lower in the RR group than in the NN and RN+ mice. In contrast, synaptophysin was similar in all groups. IR showed an inverse expression pattern to that of the PSD95. In conclusion, perinatal nutrition plays an important role in learning. CUG after a period of prenatal malnutrition seems to improve learning skills. The functional alterations observed might be related to lower PSD95 activity and a possible dysfunction in the hormone regulation of synaptic plasticity.

  4. Antagonism of brain insulin-like growth factor-1 receptors blocks estradiol effects on memory and levels of hippocampal synaptic proteins in ovariectomized rats

    Science.gov (United States)

    Nelson, Britta S.; Springer, Rachel C.; Daniel, Jill M.

    2013-01-01

    Rationale Treatment with estradiol, the primary estrogen produced by the ovaries, enhances hippocampus-dependent spatial memory and increases levels of hippocampal synaptic proteins in ovariectomized rats. Increasing evidence indicates that the ability of estradiol to impact the brain and behavior is dependent upon its interaction with insulin-like growth factor-1 (IGF-1). Objectives The goal of the current experiment was to test the hypothesis that the ability of estradiol to impact hippocampus-dependent memory and levels of hippocampal synaptic proteins is dependent on its interaction with IGF-1. Methods Adult rats were ovariectomized and implanted with estradiol or control capsules and trained on a radial-maze spatial memory task. After training, rats were implanted with intracerebroventricular cannulae attached to osmotic minipumps (flow rate 0.15 μl/hr). Half of each hormone treatment group received continuous delivery of JB1 (300 μg/ml), an IGF-1 receptor antagonist, and half received delivery of aCSF vehicle. Rats were tested on trials in the radial-arm maze during which delays were imposed between the 4th and 5th arm choices. Hippocampal levels of synaptic proteins were measured by western blotting. Results Estradiol treatment resulted in significantly enhanced memory. JB1 blocked that enhancement. Estradiol treatment resulted in significantly increased hippocampal levels of postsynaptic density protein 95 (PSD-95), spinophilin, and synaptophysin. JB1 blocked the estradiol-induced increase of PSD-95 and spinophilin and attenuated the increase of synaptophysin. Conclusions Results support a role for IGF-1 receptor activity in estradiol-induced enhancement of spatial memory that may be dependent on changes in synapse structure in the hippocampus brought upon by estradiol/IGF-1 interactions. PMID:24146138

  5. Low-frequency transcranial magnetic stimulation is beneficial for enhancing synaptic plasticity in the aging brain

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    Zhan-chi Zhang

    2015-01-01

    Full Text Available In the aging brain, cognitive function gradually declines and causes a progressive reduction in the structural and functional plasticity of the hippocampus. Transcranial magnetic stimulation is an emerging and novel neurological and psychiatric tool used to investigate the neurobiology of cognitive function. Recent studies have demonstrated that low-frequency transcranial magnetic stimulation (≤1 Hz ameliorates synaptic plasticity and spatial cognitive deficits in learning-impaired mice. However, the mechanisms by which this treatment improves these deficits during normal aging are still unknown. Therefore, the current study investigated the effects of transcranial magnetic stimulation on the brain-derived neurotrophic factor signal pathway, synaptic protein markers, and spatial memory behavior in the hippocampus of normal aged mice. The study also investigated the downstream regulator, Fyn kinase, and the downstream effectors, synaptophysin and growth-associated protein 43 (both synaptic markers, to determine the possible mechanisms by which transcranial magnetic stimulation regulates cognitive capacity. Transcranial magnetic stimulation with low intensity (110% average resting motor threshold intensity, 1 Hz increased mRNA and protein levels of brain-derived neurotrophic factor, tropomyosin receptor kinase B, and Fyn in the hippocampus of aged mice. The treatment also upregulated the mRNA and protein expression of synaptophysin and growth-associated protein 43 in the hippocampus of these mice. In conclusion, brain-derived neurotrophic factor signaling may play an important role in sustaining and regulating structural synaptic plasticity induced by transcranial magnetic stimulation in the hippocampus of aging mice, and Fyn may be critical during this regulation. These responses may change the structural plasticity of the aging hippocampus, thereby improving cognitive function.

  6. Medulloblastoma: histopathologic and molecular markers of anaplasia and biologic behavior.

    Science.gov (United States)

    Min, Hye Sook; Lee, You Jeong; Park, Kyeongmee; Cho, Byung-Kyu; Park, Sung-Hye

    2006-07-01

    Large cell/anaplastic (LC/A) medulloblastoma (MB) is a recently recognized variant of medulloblastoma known to be associated with an advanced stage and a poor prognosis. Although Eberhart et al. suggested histopathologic grading of medulloblastoma in 2002, no consensus has been reached in terms of determining the criteria of an LC/A variant, and its biological behavior continues to be the subject of debate. We retrospectively analyzed 74 cases (range 0.25-15 years) of MB clinicopathologically using the criteria established by Eberhart et al. The LC/A variant was identified in 16 cases (22% of MB cases), five of which showed a poor outcome. Most LC/A variant cases revealed synaptophysin immunoexpression (75%), but no epidermal growth factor receptor (EGFR) expression. Expression of synaptophysin, NeuN, GFAP, p53, c-erbB2, and EGFR did not differ in LC/A and non-LC/A variants. Seven of the 74 cases of medulloblastoma showed erbB2 amplification by FISH, four of which were LC/A variants. N-myc amplification was observed in only one LC/A variant, but no c-myc amplification was found. In patients younger than 10 years, the LC/A variant showed a significantly poorer outcome than the non-LC/A variant (P = 0.02), while no difference was found in older patients. Multivariate analysis revealed only metastasis on MRI and p53 expression, but not anaplasia as unfavorable prognostic factors. Our study suggests that prognostic implications of anaplasia in medulloblastoma are uncertain, and that the reproducibility of the histopathologic criteria of the LC/A variant should be reassessed before they can be applied in practical use.

  7. Low-frequency transcranial magnetic stimulation is beneficial for enhancing synaptic plasticity in the aging brain.

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    Zhang, Zhan-Chi; Luan, Feng; Xie, Chun-Yan; Geng, Dan-Dan; Wang, Yan-Yong; Ma, Jun

    2015-06-01

    In the aging brain, cognitive function gradually declines and causes a progressive reduction in the structural and functional plasticity of the hippocampus. Transcranial magnetic stimulation is an emerging and novel neurological and psychiatric tool used to investigate the neurobiology of cognitive function. Recent studies have demonstrated that low-frequency transcranial magnetic stimulation (≤1 Hz) ameliorates synaptic plasticity and spatial cognitive deficits in learning-impaired mice. However, the mechanisms by which this treatment improves these deficits during normal aging are still unknown. Therefore, the current study investigated the effects of transcranial magnetic stimulation on the brain-derived neurotrophic factor signal pathway, synaptic protein markers, and spatial memory behavior in the hippocampus of normal aged mice. The study also investigated the downstream regulator, Fyn kinase, and the downstream effectors, synaptophysin and growth-associated protein 43 (both synaptic markers), to determine the possible mechanisms by which transcranial magnetic stimulation regulates cognitive capacity. Transcranial magnetic stimulation with low intensity (110% average resting motor threshold intensity, 1 Hz) increased mRNA and protein levels of brain-derived neurotrophic factor, tropomyosin receptor kinase B, and Fyn in the hippocampus of aged mice. The treatment also upregulated the mRNA and protein expression of synaptophysin and growth-associated protein 43 in the hippocampus of these mice. In conclusion, brain-derived neurotrophic factor signaling may play an important role in sustaining and regulating structural synaptic plasticity induced by transcranial magnetic stimulation in the hippocampus of aging mice, and Fyn may be critical during this regulation. These responses may change the structural plasticity of the aging hippocampus, thereby improving cognitive function.

  8. Sex-dependent alterations in motor and anxiety-like behavior of aged bacterial peptidoglycan sensing molecule 2 knockout mice.

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    Arentsen, Tim; Khalid, Roksana; Qian, Yu; Diaz Heijtz, Rochellys

    2018-01-01

    Peptidoglycan recognition proteins (PGRPs) are key sensing-molecules of the innate immune system that specifically detect bacterial peptidoglycan (PGN) and its derivates. PGRPs have recently emerged as potential key regulators of normal brain development and behavior. To test the hypothesis that PGRPs play a role in motor control and anxiety-like behavior in later life, we used 15-month old male and female peptidoglycan recognition protein 2 (Pglyrp2) knockout (KO) mice. Pglyrp2 is an N-acetylmuramyl-l-alanine amidase that hydrolyzes PGN between the sugar backbone and the peptide chain (which is unique among the mammalian PGRPs). Using a battery of behavioral tests, we demonstrate that Pglyrp2 KO male mice display decreased levels of anxiety-like behavior compared with wild type (WT) males. In contrast, Pglyrp2 KO female mice show reduced rearing activity and increased anxiety-like behavior compared to WT females. In the accelerated rotarod test, however, Pglyrp2 KO female mice performed better compared to WT females (i.e., they had longer latency to fall off the rotarod). Further, Pglyrp2 KO male mice exhibited decreased expression levels of synaptophysin, gephyrin, and brain-derived neurotrophic factor in the frontal cortex, but not in the amygdala. Pglyrp2 KO female mice exhibited increased expression levels of spinophilin and alpha-synuclein in the frontal cortex, while exhibiting decreased expression levels of synaptophysin, gephyrin and spinophilin in the amygdala. Our findings suggest a novel role for Pglyrp2asa key regulator of motor and anxiety-like behavior in late life. Copyright © 2017. Published by Elsevier Inc.

  9. Exposure of Neonatal Mice to Tobacco Smoke Disturbs Synaptic Proteins and Spatial Learning and Memory from Late Infancy to Early Adulthood.

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    Larissa Helena Torres

    Full Text Available Exposure to environmental tobacco smoke (ETS in the early postnatal period has been associated with several diseases; however, little is known about the brain effects of ETS exposure during this critical developmental period or the long-term consequences of this exposure. This study investigated the effects of the early postnatal ETS exposure on both reference and working memory, synaptic proteins and BDNF from late infancy to early adulthood (P3-P73. BALB/c mice were exposed to ETS generated from 3R4F reference research cigarettes (0.73 mg of nicotine/cigarette from P3 to P14. Spatial reference and working memory were evaluated in the Morris water maze during infancy (P20-P29, adolescence (P37-P42 and adulthood (P67-P72. Synapsin, synaptophysin, PSD95 and brain-derived neurotrophic factor (BDNF were assessed at P15, P35 and P65 by immunohistochemistry and immunoblotting. Mice that were exposed to ETS during the early postnatal period showed poorer performance in the spatial reference memory task. Specifically, the ETS-exposed mice exhibited a significantly reduced time and distance traveled in the target quadrant and in the platform location area than the controls at all ages evaluated. In the spatial working memory task, ETS disrupted the maintenance but not the acquisition of the critical spatial information in both infancy and adolescence. ETS also induced changes in synaptic components, including decreases in synapsin, synaptophysin, PSD95 and BDNF levels in the hippocampus. Exposure to ETS in the early postnatal period disrupts both spatial reference and working memory; these results may be related to changes in synaptogenesis in the hippocampus. Importantly, most of these effects were not reversed even after a long exposure-free period.

  10. Stress-altered synaptic plasticity and DAMP signaling in the hippocampus-PFC axis; elucidating the significance of IGF-1/IGF-1R/CaMKIIα expression in neural changes associated with a prolonged exposure therapy.

    Science.gov (United States)

    Ogundele, Olalekan M; Ebenezer, Philip J; Lee, Charles C; Francis, Joseph

    2017-06-14

    Traumatic stress patients showed significant improvement in behavior after a prolonged exposure to an unrelated stimulus. This treatment method attempts to promote extinction of the fear memory associated with the initial traumatic experience. However, the subsequent prolonged exposure to such stimulus creates an additional layer of neural stress. Although the mechanism remains unclear, prolonged exposure therapy (PET) likely involves changes in synaptic plasticity, neurotransmitter function and inflammation; especially in parts of the brain concerned with the formation and retrieval of fear memory (Hippocampus and Prefrontal Cortex: PFC). Since certain synaptic proteins are also involved in danger-associated molecular pattern signaling (DAMP), we identified the significance of IGF-1/IGF-1R/CaMKIIα expression as a potential link between the concurrent progression of synaptic and inflammatory changes in stress. Thus, a comparison between IGF-1/IGF-1R/CaMKIIα, synaptic and DAMP proteins in stress and PET may highlight the significance of PET on synaptic morphology and neuronal inflammatory response. In behaviorally characterized Sprague-Dawley rats, there was a significant decline in neural IGF-1 (pIGF-1R expression. These animals showed a significant loss of presynaptic markers (synaptophysin; pIGF-1 (pIGF-1R was recorded in the Stress-PET group (pIGF-1/IGF-1R, an increase in activated hippocampal and cortical microglia was seen in stress (pIGF1/IGF-1R/CaMKIIα. Firstly, we showed a direct relationship between IGF-1/IGF-1R expression, presynaptic function (synaptophysin) and neurotransmitter activity in stress and PET. Secondly, we identified the possible role of CaMKIIα in post-synaptic function and regulation of small ion conductance channels. Lastly, we highlighted some of the possible links between IGF1/IGF-1R/CaMKIIα, the expression of DAMP proteins, Microglia activation, and its implication on synaptic plasticity during stress and PET. Copyright © 2017

  11. Tropomyosin Receptor Kinase A Expression on Merkel Cell Carcinoma Cells.

    Science.gov (United States)

    Wehkamp, Ulrike; Stern, Sophie; Krüger, Sandra; Hauschild, Axel; Röcken, Christoph; Egberts, Friederike

    2017-11-01

    Merkel cell carcinoma (MCC) is a malignant neuroendocrine skin tumor frequently associated with the Merkel cell polyomavirus. Immune checkpoint therapy showed remarkable results, although not all patients are responsive to this therapy. Anti-tropomyosin receptor kinase A (TrkA)-targeted treatment has shown promising results in several tumor entities. To determine TrkA expression in MCC as a rationale for potential targeted therapy. This case series study investigated the MCC specimens of 55 patients treated at the Department of Dermatology, University Hospital of Schleswig-Holstein, Kiel, Germany, from January 1, 2005, through December 31, 2015. Thirty-nine of the 55 samples were suitable for further histopathologic examination. Expression of TrkA was explored by immunohistochemical analysis. Diagnosis of MCC was confirmed by staining positive for cytokeratin 20 (CK20) and synaptophysin. Expression of TrkA on the tumor cells. Specimens of 39 patients (21 women and 18 men; mean [SD] age, 75.0 [7.8] years) underwent immunohistochemical investigation. Thirty-eight of 38 specimens expressed CK20 and synaptophysin on the MCC tumor cells (100% expression). Merkel cell polyomavirus was detected in 32 of 38 specimens (84%). Tropomyosin receptor kinase A was found in all 36 evaluable specimens on the tumor cells; 34 (94%) showed a weak and 2 (6%) showed a strong cytoplasmic expression. In addition, strongly positive perinuclear dots were observed in 30 of 36 specimens (83%). Tropomyosin receptor kinase A was expressed on MCC tumor cells in 100% of evaluable specimens. This result may lead to the exploration of new targeted treatment options in MCC, especially for patients who do not respond to anti-programmed cell death protein 1 treatment.

  12. Learning and memory disabilities in IUGR babies: Functional and molecular analysis in a rat model.

    Science.gov (United States)

    Camprubí Camprubí, Marta; Balada Caballé, Rafel; Ortega Cano, Juan A; Ortega de la Torre, Maria de Los Angeles; Duran Fernández-Feijoo, Cristina; Girabent-Farrés, Montserrat; Figueras-Aloy, Josep; Krauel, Xavier; Alcántara, Soledad

    2017-03-01

    1Intrauterine growth restriction (IUGR) is the failure of the fetus to achieve its inherent growth potential, and it has frequently been associated with neurodevelopmental problems in childhood. Neurological disorders are mostly associated with IUGR babies with an abnormally high cephalization index (CI) and a brain sparing effect. However, a similar correlation has never been demonstrated in an animal model. The aim of this study was to determine the correlations between CI, functional deficits in learning and memory and alterations in synaptic proteins in a rat model of IUGR. 2Utero-placental insufficiency was induced by meso-ovarian vessel cauterization (CMO) in pregnant rats at embryonic day 17 (E17). Learning performance in an aquatic learning test was evaluated 25 days after birth and during 10 days. Some synaptic proteins were analyzed (PSD95, Synaptophysin) by Western blot and immunohistochemistry. 3Placental insufficiency in CMO pups was associated with spatial memory deficits, which are correlated with a CI above the normal range. CMO pups presented altered levels of synaptic proteins PSD95 and synaptophysin in the hippocampus. 4The results of this study suggest that learning disabilities may be associated with altered development of excitatory neurotransmission and synaptic plasticity. Although interspecific differences in fetal response to placental insufficiency should be taken into account, the translation of these data to humans suggest that both IUGR babies and babies with a normal birth weight but with intrauterine Doppler alterations and abnormal CI should be closely followed to detect neurodevelopmental alterations during the postnatal period.

  13. In vitro differentiation of neural cells from human adipose tissue derived stromal cells.

    Science.gov (United States)

    Dave, Shruti D; Patel, Chetan N; Vanikar, Aruna V; Trivedi, Hargovind L

    2018-01-01

    Stem cells, including neural stem cells (NSCs), are endowed with self-renewal capability and hence hold great opportunity for the institution of replacement/protective therapy. We propose a method for in vitro generation of stromal cells from human adipose tissue and their differentiation into neural cells. Ten grams of donor adipose tissue was surgically resected from the abdominal wall of the human donor after the participants' informed consents. The resected adipose tissue was minced and incubated for 1 hour in the presence of an enzyme (collagenase-type I) at 37 0 C followed by its centrifugation. After centrifugation, the supernatant and pellets were separated and cultured in a medium for proliferation at 37 0 C with 5% CO2 for 9-10 days in separate tissue culture dishes for generation of mesenchymal stromal cells (MSC). At the end of the culture, MSC were harvested and analyzed. The harvested MSC were subjected for further culture for their differentiation into neural cells for 5-7 days using differentiation medium mainly comprising of neurobasal medium. At the end of the procedure, culture cells were isolated and studied for expression of transcriptional factor proteins: orthodenticle homolog-2 (OTX-2), beta-III-tubulin (β3-Tubulin), glial-fibrillary acid protein (GFAP) and synaptophysin-β2. In total, 50 neural cells-lines were generated. In vitro generated MSC differentiated neural cells' mean quantum was 5.4 ± 6.9 ml with the mean cell count being, 5.27 ± 2.65 × 10 3/ μl. All of them showed the presence of OTX-2, β3-Tubulin, GFAP, synaptophysin-β2. Neural cells can be differentiated in vitro from MSC safely and effectively. In vitro generated neural cells represent a potential therapy for recovery from spinal cord injuries and neurodegenerative disease.

  14. Citalopram Ameliorates Synaptic Plasticity Deficits in Different Cognition-Associated Brain Regions Induced by Social Isolation in Middle-Aged Rats.

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    Gong, Wei-Gang; Wang, Yan-Juan; Zhou, Hong; Li, Xiao-Li; Bai, Feng; Ren, Qing-Guo; Zhang, Zhi-Jun

    2017-04-01

    Our previous experiments demonstrated that social isolation (SI) caused AD-like tau hyperphosphorylation and spatial memory deficits in middle-aged rats. However, the underlying mechanisms of SI-induced spatial memory deficits remain elusive. Middle-aged rats (10 months) were group or isolation reared for 8 weeks. Following the initial 4-week period of rearing, citalopram (10 mg/kg i.p.) was administered for 28 days. Then, pathophysiological changes were assessed by performing behavioral, biochemical, and pathological analyses. We found that SI could cause cognitive dysfunction and decrease synaptic protein (synaptophysin or PSD93) expression in different brain regions associated with cognition, such as the prefrontal cortex, dorsal hippocampus, ventral hippocampus, amygdala, and caudal putamen, but not in the entorhinal cortex or posterior cingulate. Citalopram could significantly improve learning and memory and partially restore synaptophysin or PSD93 expression in the prefrontal cortex, hippocampus, and amygdala in SI rats. Moreover, SI decreased the number of dendritic spines in the prefrontal cortex, dorsal hippocampus, and ventral hippocampus, which could be reversed by citalopram. Furthermore, SI reduced the levels of BDNF, serine-473-phosphorylated Akt (active form), and serine-9-phosphorylated GSK-3β (inactive form) with no significant changes in the levels of total GSK-3β and Akt in the dorsal hippocampus, but not in the posterior cingulate. Our results suggest that decreased synaptic plasticity in cognition-associated regions might contribute to SI-induced cognitive deficits, and citalopram could ameliorate these deficits by promoting synaptic plasticity mainly in the prefrontal cortex, dorsal hippocampus, and ventral hippocampus. The BDNF/Akt/GSK-3β pathway plays an important role in regulating synaptic plasticity in SI rats.

  15. Perinatal fluoxetine effects on social play, the HPA system, and hippocampal plasticity in pre-adolescent male and female rats: Interactions with pre-gestational maternal stress.

    Science.gov (United States)

    Gemmel, Mary; Hazlett, Mariah; Bögi, Eszter; De Lacalle, Sonsoles; Hill, Lesley A; Kokras, Nikolaos; Hammond, Geoffrey L; Dalla, Christina; Charlier, Thierry D; Pawluski, Jodi L

    2017-10-01

    Selective serotonin reuptake inhibitor medications (SSRIs) are the first lines of treatment for maternal affective disorders, and are prescribed to up to 10% of pregnant women. Concern has been raised about how perinatal exposure to these medications affect offspring neurobehavioral outcomes, particularly those related to social interactions, as recent research has reported conflicting results related to autism spectrum disorder (ASD) risk in children prenatally exposed to SSRIs. Therefore, the aim of this work was to investigate the effects of perinatal exposure to the SSRI fluoxetine on social play behaviors and the hypothalamic pituitary adrenal system, using a model of pre-gestational maternal stress. We also investigated synaptic proteins in the CA2, CA3, and dentate gyrus of the hippocampus, as well as number of immature neurons in the granule cell layer, as both measures of plasticity in the hippocampus have been linked to social behaviors. In pre-adolescent male and female Sprague-Dawley rat offspring, main findings show that perinatal fluoxetine prevents the negative effect of maternal stress on sibling play behavior. However, perinatal fluoxetine increased social aggressive play with a novel conspecific in both sexes and decreased time grooming a novel conspecific in males only. Perinatal fluoxetine also increased serum corticosteroid binding globulin levels, 5-HT levels in the hippocampus, and pre-synaptic density assessed via synaptophysin in the dentate gyrus. Social interaction was significantly correlated with changes in plasticity in the CA2 region of the hippocampus. Pre-gestational maternal stress exposure resulted in significantly decreased rates of hippocampal neurogenesis and synaptophysin density in the dentate gyrus of pre-adolescent males, but not females. Together, these results further characterize the role of perinatal SSRIs, maternal stress prior to conception, and sex/gender on developing social behaviors and related plasticity in the

  16. Bacterial variations on the methionine salvage pathway

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    Haas Dieter

    2004-03-01

    Full Text Available Abstract Background The thiomethyl group of S-adenosylmethionine is often recycled as methionine from methylthioadenosine. The corresponding pathway has been unravelled in Bacillus subtilis. However methylthioadenosine is subjected to alternative degradative pathways depending on the organism. Results This work uses genome in silico analysis to propose methionine salvage pathways for Klebsiella pneumoniae, Leptospira interrogans, Thermoanaerobacter tengcongensis and Xylella fastidiosa. Experiments performed with mutants of B. subtilis and Pseudomonas aeruginosa substantiate the hypotheses proposed. The enzymes that catalyze the reactions are recruited from a variety of origins. The first, ubiquitous, enzyme of the pathway, MtnA (methylthioribose-1-phosphate isomerase, belongs to a family of proteins related to eukaryotic intiation factor 2B alpha. mtnB codes for a methylthioribulose-1-phosphate dehydratase. Two reactions follow, that of an enolase and that of a phosphatase. While in B. subtilis this is performed by two distinct polypeptides, in the other organisms analyzed here an enolase-phosphatase yields 1,2-dihydroxy-3-keto-5-methylthiopentene. In the presence of dioxygen an aci-reductone dioxygenase yields the immediate precursor of methionine, ketomethylthiobutyrate. Under some conditions this enzyme produces carbon monoxide in B. subtilis, suggesting a route for a new gaseous mediator in bacteria. Ketomethylthiobutyrate is finally transaminated by an aminotransferase that exists usually as a broad specificity enzyme (often able to transaminate aromatic aminoacid keto-acid precursors or histidinol-phosphate. Conclusion A functional methionine salvage pathway was experimentally demonstrated, for the first time, in P. aeruginosa. Apparently, methionine salvage pathways are frequent in Bacteria (and in Eukarya, with recruitment of different polypeptides to perform the needed reactions (an ancestor of a translation initiation factor and Ru

  17. Burn encephalopathy and syndrome of hypermetabolism-hypercatabolism: is there an interrelation?

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    Олена Юріївна Сорокіна

    2015-11-01

    Full Text Available Aim: To define an influence of hypermetabolism-hypercatabolism syndrome on the burn encephalopathy development on the base of study of metabolic changes on the background of an acute period of burn disease.  Materials and methods: there were examined 104 patients separated in 2 groups depending on heaviness of injury. There were defined the levels of cortisol, neurospecific enolase (NSE, glucose and blood protein. There were assessed memory, thinking and psychological state of patients.Results: At admission to hospital the cortisol level in patients of 1 and 2 groups was 270,5±29,2 ng/ml and 330,3±17,4 ng/ml, glucose level - 6,0±0,4 mmol/l and 7,7±0,5 mmol/l in 1 and 2 groups respectively. The protein level of blood maximally decreased at 3 day and was 53,6±1,1 g/l in patients of the 1 group and 48,9±1,1 g/l in patients of the 2 group. An increase of cortisol level depended on heaviness of thermal trauma.  There was defined correlation between the levels of cortisol and neuron specific enolase in patients of the 1 group at 3 day (R=0.638, p=0.006, in patients of the 2 group at 7 day (R=0.488, p=0.002. In patients of the 1 group sleep disorder and delirium development did not depended on the level of metabolic changes. At the 7 day there was defined correlative connection between cortisol level and memory (R=-0,681, p=0,071 and thinking (R=-0,520, p=0,038. In patients of the 2 group cortisol level at 1 day determined the memory and thinking disorders to the septic-toxemia stage.  Sleep disorder correlated with expressed hypoproteinomia at 3 day (R=-0,483, p=0,001. The delirium development was caused with an increase of blood serum cortisol at 1 day after thermal trauma (R=0,467, p=0,058.Conclusion: The one of mechanisms of nerve tissue injury was the development of metabolic changes caused by stress on the background of heavy thermal trauma. The dynamics of cortisol level to the burn shock stage corresponded with the changes of

  18. Serdemetan antagonizes the Mdm2-HIF1α axis leading to decreased levels of glycolytic enzymes.

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    Jason A Lehman

    Full Text Available Serdemetan (JNJ-26854165, an antagonist to Mdm2, was anticipated to promote the activation of p53. While regulation of p53 by Mdm2 is important, Mdm2 also regulates numerous proteins involved in diverse cellular functions. We investigated if Serdemetan would alter the Mdm2-HIF1α axis and affect cell survival in human glioblastoma cells independently of p53. Treatment of cells with Serdemetan under hypoxia resulted in a decrease in HIF1α levels. HIF1α downstream targets, VEGF and the glycolytic enzymes (enolase, phosphoglycerate kinase1/2, and glucose transporter 1, were all decreased in response to Serdemetan. The involvement of Mdm2 in regulating gene expression of glycolytic enzymes raises the possibility of side effects associated with therapeutically targeting Mdm2.

  19. An oral vaccine against candidiasis generated by a yeast molecular display system.

    Science.gov (United States)

    Shibasaki, Seiji; Aoki, Wataru; Nomura, Takashi; Miyoshi, Ayuko; Tafuku, Senji; Sewaki, Tomomitsu; Ueda, Mitsuyoshi

    2013-12-01

    Enolase 1 (Eno1p) of Candida albicans is an immunodominant antigen. However, conventional technologies for preparing an injectable vaccine require purification of the antigenic protein and preparation of an adjuvant. To develop a novel type of oral vaccine against candidiasis, we generated Saccharomyces cerevisiae cells that display the Eno1p antigen on their surfaces. Oral delivery of the engineered S. cerevisiae cells prolonged survival rate of mice that were subsequently challenged with C. albicans. Given that a vaccine produced using molecular display technology avoids the need for protein purification, this oral vaccine offers a promising alternative to the use of conventional and injectable vaccines for preventing a range of infectious diseases. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  20. The Effect of Electroporation of a Lyotroic Liquid Crystal Genistein-Based Formulation in the Recovery of Murine Melanoma Lesions.

    Science.gov (United States)

    Danciu, Corina; Berkó, Szilvia; Varju, Gábor; Balázs, Boglárka; Kemény, Lajos; Németh, István Balázs; Cioca, Andreea; Petruș, Alexandra; Dehelean, Cristina; Cosmin, Citu Ioan; Amaricai, Elena; Toma, Claudia Crina

    2015-07-08

    A lamellar lyotropic liquid crystal genistein-based formulation (LLC-Gen) was prepared in order to increase the aqueous solubility of the lipophilic phytocompound genistein. The formulation was applied locally, in a murine model of melanoma, with or without electroporation. The results demonstrated that, when the formulation was applied by electroporation, the tumors appeared later. During the 21 days of the experiment, the LLC-Gen formulation decreased the tumor volume, the amount of melanin and the degree of erythema, but when electroporation was applied, all these parameters indicated a better prognosis even (lower tumor volume, amount of melanin and degree of erythema). Although hematoxylin-eosin (HE) staining confirmed the above events, application of the LLC-Gen formulation by electroporation did not lead to a significant effect in terms of the serum concentrations of the protein S100B and serum neuron specific enolase (NSE), or the tissue expression of the platelet-derived growth factor receptor β (PDGFRβ) antibody.

  1. Fluorescence-based thermal shift data on multidrug regulator AcrR from Salmonella enterica subsp. entrica serovar Typhimurium str. LT2

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    Babu A. Manjasetty

    2016-06-01

    Full Text Available The fluorescence-based thermal shift (FTS data presented here include Table S1 and Fig. S1, and are supplemental to our original research article describing detailed structural, FTS, and fluorescence polarization analyses of the Salmonella enterica subsp. entrica serovar Typhimurium str. LT2 multidrug transcriptional regulator AcrR (StAcrR (doi:10.1016/j.jsb.2016.01.008 (Manjasetty et al., 2015 [1]. Table S1 contains chemical formulas, a Chemical Abstracts Service (CAS Registry Number (CAS no., FTS rank (a ligand with the highest rank has the largest difference in the melting temperature (ΔTm, and uses as drug molecules against various pathological conditions of sixteen small-molecule ligands that increase thermal stability of StAcrR. Thermal stability of human enolase 1, a negative control protein, was not affected in the presence of various concentrations of the top six StAcrR binders (Fig. S1.

  2. Fluorescence-based thermal shift data on multidrug regulator AcrR from Salmonella enterica subsp. entrica serovar Typhimurium str. LT2.

    Science.gov (United States)

    Manjasetty, Babu A; Halavaty, Andrei S; Luan, Chi-Hao; Osipiuk, Jerzy; Mulligan, Rory; Kwon, Keehwan; Anderson, Wayne F; Joachimiak, Andrzej

    2016-06-01

    The fluorescence-based thermal shift (FTS) data presented here include Table S1 and Fig. S1, and are supplemental to our original research article describing detailed structural, FTS, and fluorescence polarization analyses of the Salmonella enterica subsp. entrica serovar Typhimurium str. LT2 multidrug transcriptional regulator AcrR (StAcrR) (doi:10.1016/j.jsb.2016.01.008) (Manjasetty et al., 2015 [1]). Table S1 contains chemical formulas, a Chemical Abstracts Service (CAS) Registry Number (CAS no.), FTS rank (a ligand with the highest rank) has the largest difference in the melting temperature (ΔT m), and uses as drug molecules against various pathological conditions of sixteen small-molecule ligands that increase thermal stability of StAcrR. Thermal stability of human enolase 1, a negative control protein, was not affected in the presence of various concentrations of the top six StAcrR binders (Fig. S1).

  3. DeltaFosB induces osteosclerosis and decreases adipogenesis by two independent cell-autonomous mechanisms

    DEFF Research Database (Denmark)

    Kveiborg, Marie; Sabatakos, George; Chiusaroli, Riccardo

    2004-01-01

    establishes that the skeletal phenotype is cell autonomous to the osteoblast lineage and independent of adipocyte formation. It also strongly suggests that the decreased fat phenotype of NSE-DeltaFosB mice is independent of the changes in the osteoblast lineage. In vitro, overexpression of Delta......Osteoblasts and adipocytes may develop from common bone marrow mesenchymal precursors. Transgenic mice overexpressing DeltaFosB, an AP-1 transcription factor, under the control of the neuron-specific enolase (NSE) promoter show both markedly increased bone formation and decreased adipogenesis...... of DeltaFosB on adipocyte differentiation appears to occur at early stages of stem cell commitment, affecting C/EBPbeta functions. It is concluded that the changes in osteoblast and adipocyte differentiation in DeltaFosB transgenic mice result from independent cell-autonomous mechanisms....

  4. Electrochemical Detecting Lung Cancer-Associated Antigen Based on Graphene-Gold Nanocomposite

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    Zheng Wei

    2017-03-01

    Full Text Available Using a Au nanoparticle/reduced graphene oxide composite (AuNP-RGO, a signal-enhanced electrochemical immunosensor without label was created to detect neuron-specific enolase (NSE. Furthermore, an environmentally-friendly method was developed to prepare AuNP-RGO by employing chitosan (CS, which served as reducing and stabilizing agent. We showed that the sensitivity of the immunosensor designed in this report was remarkably enhanced because of the numerous active sites in the sensor provided by the AuNP-RGO nanostructure. For the quantification of NSE, the immunosensor exhibited a positive linear relationship with the concentration in the range of 0.1 to 2000 ng/mL, where the limit of the detection was 0.05 ng/mL.

  5. Increased cerebral output of free radicals during hypoxia: implications for acute mountain sickness?

    DEFF Research Database (Denmark)

    Bailey, Damian M; Taudorf, Sarah; Berg, Ronan M G

    2009-01-01

    This study examined whether hypoxia causes free radical-mediated disruption of the blood-brain barrier (BBB) and impaired cerebral oxidative metabolism and whether this has any bearing on neurological symptoms ascribed to acute mountain sickness (AMS). Ten men provided internal jugular vein...... paramagnetic resonance spectroscopy and ozone-based chemiluminescence were employed for direct detection of spin-trapped free radicals and nitric oxide metabolites. Neuron-specific enolase (NSE), S100beta, and 3-nitrotyrosine (3-NT) were determined by ELISA. Hypoxia increased the arterio-jugular venous...... concentration difference (a-v(D)) and net cerebral output of lipid-derived alkoxyl-alkyl free radicals and lipid hydroperoxides (P

  6. Identification of proteins of altered abundance in oil palm infected with Ganoderma boninense.

    Science.gov (United States)

    Al-Obaidi, Jameel R; Mohd-Yusuf, Yusmin; Razali, Nurhanani; Jayapalan, Jaime Jacqueline; Tey, Chin-Chong; Md-Noh, Normahnani; Junit, Sarni Mat; Othman, Rofina Yasmin; Hashim, Onn Haji

    2014-03-24

    Basal stem rot is a common disease that affects oil palm, causing loss of yield and finally killing the trees. The disease, caused by fungus Ganoderma boninense, devastates thousands of hectares of oil palm plantings in Southeast Asia every year. In the present study, root proteins of healthy oil palm seedlings, and those infected with G. boninense, were analyzed by 2-dimensional gel electrophoresis (2-DE). When the 2-DE profiles were analyzed for proteins, which exhibit consistent significant change of abundance upon infection with G. boninense, 21 passed our screening criteria. Subsequent analyses by mass spectrometry and database search identified caffeoyl-CoA O-methyltransferase, caffeic acid O-methyltransferase, enolase, fructokinase, cysteine synthase, malate dehydrogenase, and ATP synthase as among proteins of which abundances were markedly altered.

  7. Fish allergy and fish allergens

    DEFF Research Database (Denmark)

    Kuehn, A; Hilger, Christiane; Ollert, Markus

    2016-01-01

    Fish is one of the main elicitors for food allergies. For a long time, the clinical picture of fish allergy was reduced to the following features. First, fish-allergic patients suffer from a high IgE cross-reactivity among fishes so that they have to avoid all species. Second, clinically relevant...... symptoms are linked to the presence of IgE-antibodies recognizing parvalbumin, the fish panallergen. This view was challenged by results from recent studies as follows. 1. Allergic reactions which are limited to single or several fish species (mono-or oligosensitisations) apply not only to single cases...... but patients with this phenotype constitute an important sub-group among fish-allergic individuals. 2. Newly identified fish allergens, enolases, aldolases, and fish gelatin, are of high relevance as the majority of the fish-allergic individuals seem to develop specific IgE against these proteins. The present...

  8. Skin mucus proteins of lumpsucker (Cyclopterus lumpus

    Directory of Open Access Journals (Sweden)

    Deepti Manjari Patel

    2017-03-01

    Full Text Available Fish skin mucus serves as a first line of defense against pathogens and external stressors. In this study the proteomic profile of lumpsucker skin mucus was characterized using 2D gels coupled with tandem mass spectrometry. Mucosal proteins were identified by homology searches across the databases SwissProt, NCBInr and vertebrate EST. The identified proteins were clustered into ten groups based on their gene ontology biological process in PANTHER (www.patherdb.org. Calmodulin, cystatin-B, histone H2B, peroxiredoxin1, apolipoprotein A1, natterin-2, 14-3-3 protein, alfa enolase, pentraxin, warm temperature acclimation 65 kDa (WAP65kDa and heat shock proteins were identified. Several of the proteins are known to be involved in immune and/or stress responses. Proteomic profile established in this study could be a benchmark for differential proteomics studies.

  9. Study on effect of Nimodepine on the changes of serum NSE levels in patients with acute cerebral hemorrhage

    International Nuclear Information System (INIS)

    Zhang Chunying; Li Zuoxiao; Gan Xilun; Li Xiaohong; Tan Hua

    2006-01-01

    Objective: To investigate the changes of serum NSE levels in patients with acute cerebral hemorrhage and the effect of nimodepine treatment. Methods: Serum neuron specific enolase (NSE) levels were measured with CLIA in 60 patients with cerebral hemorrhage both before and after treatment as well as in 30 controls. Half of the patients (n=30) were treated with nimodepine and the their half were not. Results: In all the 60 patients, serum NSE levels were significantly higher than those in Controls (P<0.01). After treatment, the NSE levels dropped markedly in all the patients. However, the decrease in the patient group treated with nimodepine was significantly higher than that in the patient group treated without nimodepine (P<0.01). Conclusion: Nimodepine treatment is efficient for reducing the serum NSE levels, which may be related to the residual hematoma size. (authors)

  10. Creutzfeldt-Jakob Disease with a prion protein gene codon 180 mutation presenting asymmetric cortical high-intensity on magnetic resonance imaging.

    Science.gov (United States)

    Amano, Yuko; Kimura, Noriyuki; Hanaoka, Takuya; Aso, Yasuhiro; Hirano, Teruyuki; Murai, Hiroyuki; Satoh, Katsuya; Matsubara, Etsuro

    2015-01-01

    Here we report a genetically confirmed case of Creutzfeldt-Jakob disease with a prion protein gene codon 180 mutation presenting atypical magnetic resonance imaging findings. The present case exhibited an acute onset and lateralized neurologic signs, and progressive cognitive impairment. No myoclonus or periodic synchronous discharges on electroencephalography were observed. Diffusion-weighted images revealed areas of high signal intensity in the right frontal and temporal cortices at onset that extended to the whole cortex and basal ganglia of the right cerebral hemisphere at 3 months. Although the cerebrospinal fluid (CSF) was initially negative for neuron specific enolase, tau protein, 14-3-3 protein, and abnormal prion protein, the CSF was positive for these brain-derived proteins at 3 months after onset.

  11. Shenfu injection provides protection for perinatal asphyxia in neonates

    Directory of Open Access Journals (Sweden)

    Yu Jiang

    2016-03-01

    Full Text Available This study aimed to investigate the efficacy of shenfu injection for the protection of neonates with asphyxia. Eighty neonates with asphyxia were randomly divided into two groups, treatment group and control group (n=40. Both groups received interventions such as ventilation, oxygen, and circulation support. Treatment group was administrated with shenfu injection additionally. Serum levels of creatine kinase, alanine aminotransferase, aspartate aminotransferase, creatinine, and neuron-specific enolase were significantly lower but the oxygenation index was significantly higher in treatment group on day 7 and day 14. The neurobehavioral score was significantly higher in treatment group than in control group. On the 14th day, the survival rate of treatment group (77.5% was higher than that of control group (55%. Shenfu injection could protect the function of the brain, heart, lung, liver and kidney by attenuating ischemia reperfusion after severe asphyxia resuscitation, improve neurobehavioral ability and increase the survival of neonates.

  12. Identification of Proteins of Altered Abundance in Oil Palm Infected with Ganoderma boninense

    Science.gov (United States)

    Al-Obaidi, Jameel R.; Mohd-Yusuf, Yusmin; Razali, Nurhanani; Jayapalan, Jaime Jacqueline; Tey, Chin-Chong; Md-Noh, Normahnani; Junit, Sarni Mat; Othman, Rofina Yasmin; Hashim, Onn Haji

    2014-01-01

    Basal stem rot is a common disease that affects oil palm, causing loss of yield and finally killing the trees. The disease, caused by fungus Ganoderma boninense, devastates thousands of hectares of oil palm plantings in Southeast Asia every year. In the present study, root proteins of healthy oil palm seedlings, and those infected with G. boninense, were analyzed by 2-dimensional gel electrophoresis (2-DE). When the 2-DE profiles were analyzed for proteins, which exhibit consistent significant change of abundance upon infection with G. boninense, 21 passed our screening criteria. Subsequent analyses by mass spectrometry and database search identified caffeoyl-CoA O-methyltransferase, caffeic acid O-methyltransferase, enolase, fructokinase, cysteine synthase, malate dehydrogenase, and ATP synthase as among proteins of which abundances were markedly altered. PMID:24663087

  13. Identification of Proteins of Altered Abundance in Oil Palm Infected with Ganoderma boninense

    Directory of Open Access Journals (Sweden)

    Jameel R. Al-Obaidi

    2014-03-01

    Full Text Available Basal stem rot is a common disease that affects oil palm, causing loss of yield and finally killing the trees. The disease, caused by fungus Ganoderma boninense, devastates thousands of hectares of oil palm plantings in Southeast Asia every year. In the present study, root proteins of healthy oil palm seedlings, and those infected with G. boninense, were analyzed by 2-dimensional gel electrophoresis (2-DE. When the 2-DE profiles were analyzed for proteins, which exhibit consistent significant change of abundance upon infection with G. boninense, 21 passed our screening criteria. Subsequent analyses by mass spectrometry and database search identified caffeoyl-CoA O-methyltransferase, caffeic acid O-methyltransferase, enolase, fructokinase, cysteine synthase, malate dehydrogenase, and ATP synthase as among proteins of which abundances were markedly altered.

  14. Inflammation and oxidative stress biomarkers in neonatal brain hypoxia and prediction of adverse neurological outcome: a review

    Directory of Open Access Journals (Sweden)

    Marianna Varsami

    2013-06-01

    Full Text Available Despite advances in perinatal care, the outcome of newborns with hypoxic-ischemic encephalopathy is poor and the issue still remains challenging in neonatology. The use of an easily approachable and practical biomarker not only could identify neonates with severe brain damage and subsequent adverse outcome, but could also target the group of infants that would benefit from a neuroprotective intervention. Recent studies have suggested interleukin-1b, interleukin-6, tumour necrosis alpha (TNF-a and neuron specific enolase (NSE to be potential biomarkers of brain damage in asphyxiated newborns. S100B, lactate dehydrogenase, nitrated albumin-nitrotyrosine, adrenomedullin, activin-A, non protein bound iron, isoprostanes, vascular endothelial growth factor and metalloproteinases have also been proposed by single-centre studies to play a similar role in the field. With this review we aim to provide an overview of existing data in the literature regarding biomarkers for neonatal brain damage.

  15. Paravertebral Burkitt's Lymphoma in a Child: An Unusual Presentation

    Directory of Open Access Journals (Sweden)

    C. Hoyoux

    2012-01-01

    Full Text Available Paravertebral malignant tumors constitute 4.8% of cancer cases in pediatric oncology and are mostly composed of neuroblastoma (46.4% and soft tissue sarcomas (35.7%. We describe the case of a Caucasian 6-year-old boy who was admitted for middle back pain radiated to limbs and progressively increasing weakness of the legs, suggesting a spinal cord disease. The exploration revealed two paravertebral masses extending through the neural foraminae into the epidural space. The association with elevated serum neuron specific enolase suggested at first the diagnosis of neuroblastoma, but the pathological examination revealed a Burkitt's lymphoma. This is a rare location of sporadic Burkitt's lymphoma with neurologic syndrome as first symptoms.

  16. Primary pleomorphic sarcoma of the ovary with rhabdomyosarcomatous differentiation

    Directory of Open Access Journals (Sweden)

    Mukherjee Sumana

    2009-04-01

    Full Text Available A 49-year-old patient presented with a right ovarian mass, which, on microscopy, showed to consist of haphazardly oriented large pleomorphic cells with abundant cytoplasm. Periodic acid Schiff stain was positive but negative with diastase digestion. Immunohistochemical staining with Desmin showed intense cytoplasmic positivity in almost all the cells. Cytokeratin, epithelial membrane antigen, smooth muscle actin, HMB-45, S-100 and neurone-specific enolase were negative. Immunohistochemical staining with Myogenin showed intense nuclear positivity. There was no other primary tumor on extensive search. A diagnosis of primary sarcoma of the ovary with rhabdomyosarcomatous differentiation was made. The incidence of similar tumors of the ovary are low and therefore little data are available on this uniformly lethal tumor. Thus, such cases need to be reported to pool experience so that the tumor can be diagnosed early.

  17. Inhibition of cellular oxidation by fluoride

    Energy Technology Data Exchange (ETDEWEB)

    Borei, H

    1945-01-01

    An attempt has been made to investigate the inhibition by fluoride of the oxidative processes which occur in the cell by way of the cytochrome oxidase-cytochrome system. Some chemical and physical properties of the fluoride ion are discussed, together with certain quantitative methods for the determination of fluoride. An exhaustive review of the literature concerning the effect of fluoride on enzymic processes has been compiled. The experiments have shown that the point of the attack by fluoride is to be found among the cytochromes. The inhibitory mechanism appears to be such that the haemoprotein is prevented from taking part in the preceding and succeeding links in the reaction chain. The blocking action leaves the prosthetic group of the haemoprotein completely unchanged. The experimental results indicate the formation of a fluorophosphoprotein complex, analogous to that found in the case of enolase. Magnesium may possibly play a part in this process.

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

    Science.gov (United States)

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

    2015-01-14

    The nonspecific and variable presentation of traumatic brain injury (TBI) has motivated an intense search for blood-based biomarkers that can objectively predict the severity of injury. However, it is not known how cytosolic proteins released from traumatized brain tissue reach the peripheral blood. Here we show in a murine TBI model that CSF movement through the recently characterized glymphatic pathway transports biomarkers to blood via the cervical lymphatics. Clinically relevant manipulation of glymphatic activity, including sleep deprivation and cisternotomy, suppressed or eliminated TBI-induced increases in serum S100β, GFAP, and neuron specific enolase. We conclude that routine TBI patient management may limit the clinical utility of blood-based biomarkers because their brain-to-blood transport depends on glymphatic activity. Copyright © 2015 the authors 0270-6474/15/350518-09$15.00/0.

  19. An unusual case of intestinal leiomyositis in a Bernese mountain dog.

    Science.gov (United States)

    Gianella, P; Tecilla, M; Bellino, C; Buracco, R; Martano, M; Zanatta, R; Cagnasso, A; D'angelo, A

    2015-10-01

    A 1-year-old, female Bernese mountain dog was presented to the Veterinary Teaching Hospital of Turin University with a 3-month history of weight loss, intermittent anorexia, vomiting, constipation, and abdominal distension. Full-thickness biopsies from the stomach, duodenum, jejunum and ileum were collected for histological and immunohistochemical examination. Microscopic lesions displayed severe diffuse degeneration and loss of leiomyocytes, with lymphocytic leiomyositis, fibroplasia, angiogenesis, severe diffuse neuronal atrophy, and ganglioneuritis in the myenteric (Auerbach's) plexus. A diagnosis of chronic idiopatic intestinal pseudo-obstruction was made. Response to immunosuppressive therapy was poor and the dog was humanely euthanized. Unique findings were mononuclear infiltration composed predominantly of B-cell, angiogenesis and weak immunoreactivity for neuron-specific enolase.

  20. Identification of novel direct protein-protein interactions by irradiating living cells with femtosecond UV laser pulses.

    Science.gov (United States)

    Itri, Francesco; Monti, Daria Maria; Chino, Marco; Vinciguerra, Roberto; Altucci, Carlo; Lombardi, Angela; Piccoli, Renata; Birolo, Leila; Arciello, Angela

    2017-10-07

    The identification of protein-protein interaction networks in living cells is becoming increasingly fundamental to elucidate main biological processes and to understand disease molecular bases on a system-wide level. We recently described a method (LUCK, Laser UV Cross-linKing) to cross-link interacting protein surfaces in living cells by UV laser irradiation. By using this innovative methodology, that does not require any protein modification or cell engineering, here we demonstrate that, upon UV laser irradiation of HeLa cells, a direct interaction between GAPDH and alpha-enolase was "frozen" by a cross-linking event. We validated the occurrence of this direct interaction by co-immunoprecipitation and Immuno-FRET analyses. This represents a proof of principle of the LUCK capability to reveal direct protein interactions in their physiological environment. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Histomorphologic and Immunohistochemical Characterization of a Cardiac Purkinjeoma in a Bearded Seal (Erignathus barbatus

    Directory of Open Access Journals (Sweden)

    G. Krafsur

    2014-01-01

    Full Text Available The most common cardiac tumors of heart muscle are rhabdomyomas, solitary or multiple benign tumors of striated muscle origin. While cardiac rhabdomyomas are well described in human medical literature, limited information depicting the occurrence of cardiac rhabdomyomas in veterinary species exists. A case of multiple firm white nonencapsulated nodules in the heart of a bearded seal is described. Microscopic findings included cytoplasmic vacuolization with formation of spider cells, glycogen vacuoles, and striated myofibrils. These cells expressed immunoreactivity for neuron-specific enolase and protein gene product 9.5, a marker for neuronal tissue and Purkinje fiber cells. Immunoreactivity for protein gene product 9.5 along with other microscopic findings substantiates Purkinje fiber cell origin of the cardiac rhabdomyoma in the bearded seal and use of the term purkinjeoma to describe this lesion.

  2. Stress-induced rise in serum anti-brain autoantibody levels in the rat.

    Science.gov (United States)

    Andrejević, S; Bukilica, M; Dimitrijević, M; Laban, O; Radulovic, J; Kovacevic-Jovanovic, V; Stanojevic, S; Vasiljevic, T; Marković, B M

    1997-02-01

    Sera from Wistar rats subjected to different stress procedures were tested by ELISA for the presence of autoantibodies with specificity for neuron-specific enolase (NSE) and S100 protein that are preferentially localized in neurons and glia, respectively. Autoantibodies were present in sera of animals before exposure to stress, and raised with age. Anti-NSE and anti-S100 autoantibody levels were increased one day after termination of restraint (2 hours daily, 10 days) and electric tail shock (80 shocks daily, 19 days), and in fifth and tenth week of overcrowding stress. Differences between stressed and control animals were not present one month following restraint and electric tail shock and in twentieth week of overcrowding.

  3. Effects of High-Pressure Treatment on the Muscle Proteome of Hake by Bottom-Up Proteomics.

    Science.gov (United States)

    Carrera, Mónica; Fidalgo, Liliana G; Saraiva, Jorge A; Aubourg, Santiago P

    2018-05-02

    A bottom-up proteomics approach was applied for the study of the effects of high-pressure (HP) treatment on the muscle proteome of fish. The performance of the approach was established for a previous HP treatment (150-450 MPa for 2 min) on frozen (up to 5 months at -10 °C) European hake ( Merluccius merluccius). Concerning possible protein biomarkers of quality changes, a significant degradation after applying a pressure ≥430 MPa could be observed for phosphoglycerate mutase-1, enolase, creatine kinase, fructose bisphosphate aldolase, triosephosphate isomerase, and nucleoside diphosphate kinase; contrary, electrophoretic bands assigned to tropomyosin, glyceraldehyde-3-phosphate dehydrogenase, and beta parvalbumin increased their intensity after applying a pressure ≥430 MPa. This repository of potential protein biomarkers may be very useful for further HP investigations related to fish quality.

  4. Calcium carbonate-gold nanocluster hybrid spheres: synthesis and versatile application in immunoassays.

    Science.gov (United States)

    Peng, Juan; Feng, Li-Na; Zhang, Kui; Li, Xing-Hua; Jiang, Li-Ping; Zhu, Jun-Jie

    2012-04-23

    Fluorescent gold nanoclusters (AuNCs) were incorporated into porous calcium carbonate spheres through electrostatic interaction. The resulting CaCO(3)/AuNCs hybrid material exhibited interesting properties, such as porous structure, excellent biocompatibility, good water solubility, and degradability. These properties make the CaCO(3)/AuNCs hybrid material a promising template to assemble horseradish peroxidase/antibody conjugates (HRP-Ab(2)). By using CaCO(3)/AuNCs/HRP-Ab(2) bioconjugates as probes, a versatile immunosensor was developed for fluorescent and electrochemical detection of the cancer biomarker neuron-specific enolase (NSE). The detection limits of the sensor were 2.0 and 0.1 pg mL(-1) for fluorescent and electrochemical detection, respectively. The immunosensor shows high sensitivity and offers an alternative strategy for the detection of other proteins and DNA. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Clinical usefulness of determination of NSE contents in drainage fluid of patients with chronic subdural hematoma

    International Nuclear Information System (INIS)

    Che Ruchang; Wu Jianyuan; Tao Zhiqiang

    2008-01-01

    Objective: To investigate the relationship between the neuron-specific enolase (NSE) contents of serum and drainage fluid in patients with chronic subdural hematoma (CSDH). Methods: Serum and drainage fluid NSE contents were determined with RIA right after and 24, 48, 72, 96, 120 hours after trephining in 28 patients with CSDH as well as 28 controls (once and serum only). Results: The serum contents of NSE in the patients were significantly higher than those in the controls (P<0.01). The drainage fluid contents of NSE were correlated with the patients concurrent own serum NSE contents (r=0.917) and were higher than the respective serum NSE value (P<0.01). All the NSE contents dropped continuously throughout the observation period. Conclusion: Changes of drainage fluid NSE contents might reflect progress of the degree of nervous tissue injury in patients with chronic subdural hematoma. (authors)

  6. The role of immunohistochemistry, electron microscopy, and ultrastructural cytochemistry in the diagnosis of mixed carcinoma-neuroendocrine neoplasms.

    Science.gov (United States)

    Graham, A R; Payne, C M; Nagle, R B; Angel, E

    1987-02-01

    We studied four mixed carcinoma-neuroendocrine neoplasms from gastrointestinal tract and pancreas by routine light microscopy (LM), immunohistochemistry (IH), electron microscopy (EM), and ultrastructural cytochemistry (UC). By LM, the individual tumors showed fairly pure neuroendocrine (carcinoid) or epithelial (papillary) patterns, mixed neuroendocrine-carcinoma features and poorly-differentiated tumor in sheets and nests which did not lend itself to morphologic characterization. IH demonstrated mixed expression, within different areas of the same neoplasm, of epithelial antigens (keratins and carcinoembryonic antigen [CEA]) and neuroendocrine markers (neuron-specific enolase [NSE], bombesin and neurohormonal peptides). By EM, each tumor showed ultrastructural features of epithelial and neuroendocrine differentiation which varied substantially in terms of number of cells involved and their distribution; two of the neoplasms showed biphasic differentiation within single cells. The nature of the neurosecretory granules was verified with the uranaffin reaction (UR). This study illustrates the value of combining LM, IH, EM and UC for the identification of mixed carcinoma-neuroendocrine lesions.

  7. Robust Trypsin Coating on Electrospun Polymer Nanofibers in Rigorous Conditions and Its Uses for Protein Digestion

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Hye-Kyung; Kim, Byoung Chan; Jun, Seung-Hyun; Chang, Mun Seock; Lopez-Ferrer, Daniel; Smith, Richard D.; Gu, Man Bock; Lee, Sang-Won; Kim, Beom S.; Kim, Jungbae

    2010-12-15

    An efficient protein digestion in proteomic analysis requires the stabilization of proteases such as trypsin. In the present work, trypsin was stabilized in the form of enzyme coating on electrospun polymer nanofibers (EC-TR), which crosslinks additional trypsin molecules onto covalently-attached trypsin (CA-TR). EC-TR showed better stability than CA-TR in rigorous conditions, such as at high temperatures of 40 °C and 50 °C, in the presence of organic co-solvents, and at various pH's. For example, the half-lives of CA-TR and EC-TR were 0.24 and 163.20 hours at 40 ºC, respectively. The improved stability of EC-TR can be explained by covalent-linkages on the surface of trypsin molecules, which effectively inhibits the denaturation, autolysis, and leaching of trypsin. The protein digestion was performed at 40 °C by using both CA-TR and EC-TR in digesting a model protein, enolase. EC-TR showed better performance and stability than CA-TR by maintaining good performance of enolase digestion under recycled uses for a period of one week. In the same condition, CA-TR showed poor performance from the beginning, and could not be used for digestion at all after a few usages. The enzyme coating approach is anticipated to be successfully employed not only for protein digestion in proteomic analysis, but also for various other fields where the poor enzyme stability presently hampers the practical applications of enzymes.

  8. Tc-99m-bicisate (ECD)-brain-SPECT in rapidly progressive dementia; Hirn-SPECT mit Tc-99m-Bicisat (ECD) bei rasch progredientem dementiellen Syndrom

    Energy Technology Data Exchange (ETDEWEB)

    Marienhagen, J.; Eilles, C. [Regensburg Univ. (Germany). Abt. fuer Nuklearmedizin; Weingaertner, U.; Blaha, L. [Bezirkskrankenhaus Mainkofen (Germany). Psychiatrische Klinik; Zerr, I.; Poser, S. [Goettingen Univ. (Germany). Klinik und Poliklinik fuer Neurologie

    1999-07-01

    We present a 61-year-old male patient with progressive dementia. A brain SPECT with Tc-99m-bicisate was performed for confirmation of clinically suspected Alzheimer-dementia. At the time of the SPECT-investigation marked apraxia and aphasia besides severe dementia were present. Electrophysiological as well as anatomical neuroimaging findings showed non-diagnostic alterations. SPECT revealed distinct perfusion defects, which made Alzheimer Dementia unlikely. The further course of the patient was determined by rapidly progressive deterioration with development of akinetic mutism. Thereafter, increased levels of neuron-specific enolase as well as 14-3-3 proteins were found in the cerebro-spinal fluid (CSF). The patient finally died with signs of cerebral decortication. Due to the clinical course and the CSF-findings the patient's final diagnosis was Creutzfeld-Jakob-disease, nevertheless no autopsy was performed. The presented case report underscores the clinical utility of perfusion brain SPECT in the differential diagnosis of dementias. (orig.) [German] Wir berichten ueber einen 61jaehrigen Patienten mit progredientem dementiellen Syndrom, der unter der Verdachtsdiagnose einer Demenz vom Alzheimer-Typ (DAT) zur Hirn-SPECT-Untersuchung mit TC-99m-Bicisat (ECD) vorgestellt wurde. Zum Untersuchungszeitpunkt bestanden neben dem Vollbild einer Demenz eine ausgepraegte Apraxie und Aphasie bei unspezifischen Veraenderungen im EEG sowie der neuroradiologischen Bildgebung. In der Hirn-SPECT-Untersuchung fanden sich fuer eine DAT untypische ausgedehnte, vorwiegend rechtshemisphaerische Perfusionsstoerungen. Im weiteren Verlauf rasche Progredienz des Krankheitsbildes mit Entwicklung eines akinetischen Mutismus sowie Nachweis erhoehter Werte der neuronspezifischen Enolase und des 14-3-3-Proteins im Liquor. Der Patient verstarb schliesslich unter dem Bild einer Decortication. Aufgrund des klinischen Verlaufs sowie der Liquorbefunde wurde, da eine autoptische Befundsicherung

  9. Proteomic analysis of plasma membrane proteins in wheat roots exposed to phenanthrene.

    Science.gov (United States)

    Shen, Yu; Du, Jiangxue; Yue, Le; Zhan, Xinhua

    2016-06-01

    Polycyclic aromatic hydrocarbons (PAHs) are potentially carcinogenic and toxic to humans through ingestion of contaminated food crops. PAHs can enter crop roots through proton/PAH symporters; however, to date, the symporter remains unclear. Here we reveal, for the first time, the plasma membrane proteome of Triticum aestivum seedling roots in response to phenanthrene (a model PAH) exposure. Two-dimensional gel electrophoresis (2-DE) coupled with MALDI-TOF/TOF-MS and protein database search engines were employed to analyze and identify phenanthrene-responsive proteins. Over 192 protein spots are reproducibly detected in each gel, while 8 spots are differentially expressed under phenanthrene treatment. Phenanthrene induces five up-regulated proteins distinguished as 5-methyltetrahydropteroyltriglutamate-homocysteine methyltransferase 2, enolase, heat shock protein 80-2, probable mediator of RNA polymerase II transcription subunit 37e (heat shock 70-kDa protein 1), and lactoylglutathione lyase. Three proteins identified as adenosine kinase 2, 4-hydroxy-7-methoxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl glucoside beta-D-glucosidase 1c, and glyceraldehyde-3-phosphate dehydrogenase 3 are down-regulated under exposure to phenanthrene. The up-regulated proteins are related to plant defense response, antioxidant system, and glycolysis. The down-regulated proteins involve the metabolism of high-energy compounds and plant growth. Magnesium, which is able to bind to enolase, can enhance the transport of phenanthrene into wheat roots. Therefore, it is concluded that phenanthrene can induce differential expression of proteins in relation to carbohydrate metabolism, self-defense, and plant growth on wheat root plasma membrane. This study not only provides novel insights into PAH uptake by plant roots and PAH stress responses, but is also a good starting point for further determination and analyses of their functions using genetic and other approaches.

  10. A cell wall protein-based vaccine candidate induce protective immune response against Sporothrix schenckii infection.

    Science.gov (United States)

    Portuondo, Deivys Leandro; Batista-Duharte, Alexander; Ferreira, Lucas Souza; Martínez, Damiana Téllez; Polesi, Marisa Campos; Duarte, Roberta Aparecida; de Paula E Silva, Ana Carolina Alves; Marcos, Caroline Maria; Almeida, Ana Marisa Fusco de; Carlos, Iracilda Zeppone

    2016-02-01

    Sporotrichosis is a subcutaneous mycosis caused by several closely related thermo-dimorphic fungi of the Sporothrix schenckii species complex, affecting humans and other mammals. In the last few years, new strategies have been proposed for controlling sporotrichosis owning to concerns about its growing incidence in humans, cats, and dogs in Brazil, as well as the toxicity and limited efficacy of conventional antifungal drugs. In this study, we assessed the immunogenicity and protective properties of two aluminum hydroxide (AH)-adsorbed S. schenckii cell wall protein (ssCWP)-based vaccine formulations in a mouse model of systemic S. schenckii infection. Fractioning by SDS-PAGE revealed nine protein bands, two of which were functionally characterized: a 44kDa peptide hydrolase and a 47kDa enolase, which was predicted to be an adhesin. Sera from immunized mice recognized the 47kDa enolase and another unidentified 71kDa protein, whereas serum from S. schenckii-infected mice recognized both these proteins plus another unidentified 9.4kDa protein. Furthermore, opsonization with the anti-ssCWP sera led to markedly increased phagocytosis and was able to strongly inhibit the fungus' adhesion to fibroblasts. Immunization with the higher-dose AH-adjuvanted formulation led to increased ex vivo release of IL-12, IFN-γ, IL-4, and IL-17, whereas only IL-12 and IFN-γ were induced by the higher-dose non-adjuvanted formulation. Lastly, passive transference of the higher-dose AH-adjuvanted formulation's anti-ssCWP serum was able to afford in vivo protection in a subsequent challenge with S. schenckii, becoming a viable vaccine candidate for further testing. Copyright © 2015 Elsevier GmbH. All rights reserved.

  11. Proteomic profiling and post-translational modifications in human keratinocytes treated with Mucuna pruriens leaf extract.

    Science.gov (United States)

    Cortelazzo, Alessio; Lampariello, Raffaella L; Sticozzi, Claudia; Guerranti, Roberto; Mirasole, Cristiana; Zolla, Lello; Sacchetti, Gianni; Hajek, Joussef; Valacchi, Giuseppe

    2014-02-03

    Mucuna pruriens (Mp) is a plant belonging to the Fabaceae family, with several medicinal properties among which its potential to treat diseases where reactive oxygen species (ROS) play an important role in the pathogeneses. The aim was to investigate the effects of Mp leaf methanolic extract (MPME) on human keratinocytes protein expression and its role in preventing proteins oxidation after oxidative stress (OS) exposure. The effects of MPME on HaCaT cells protein expression were evaluated treating cells with different concentrations of MPME, with glucose oxidase (GO, source of OS) and with MPME subsequently treated with GO. The protein patterns of treated HaCaT cells are analyzed by two-dimensional gel electrophoresis (2-DE) and compared with that of untreated HaCaT. Immunoblotting was then used to evaluate the role of MPME in preventing the 4-hydroxynonenal protein adducts (4-HNE PAs) formation (marker of OS). Eighteen proteins, identified by mass spectrometry (LC-ESI-CID-MS/MS), were modulated distinctly by MPME in HaCaT. Overall, MPME counteract GO effect, reducing the GO-induced overexpression of several proteins involved in stress response (T-complex protein 1, Protein disulfide-isomerase A3, Protein DJ-1, and Stress-induced-phosphoprotein 1), in cell energy methabolism (Inorganic pyrophosphatase, Triosephosphate isomerase isoform 1, 2-phosphopyruvate-hydratase alpha-enolase, and Fructose-bisphosphate aldolase A isoform 1), in cytoskeletal organization (Cytokeratins 18, 9, 2, Cofilin-1, Annexin A2 and F-actin-capping protein subunit beta isoform 1) and in cell cycle progression (Eukaryotic translation initiation factor 5A-1 isoform B). In addition, MPME decreased the 4-HNE PAs levels, in particular on 2-phosphopyruvate-hydratase alpha-enolase and Cytokeratin 9. Our findings show that MPME might be helpful in the treatment of OS-related skin diseases by preventing protein post-translational modifications (4-HNE PAs). © 2013 Published by Elsevier Ireland Ltd.

  12. Early prediction of coma recovery after cardiac arrest with blinded pupillometry.

    Science.gov (United States)

    Solari, Daria; Rossetti, Andrea O; Carteron, Laurent; Miroz, John-Paul; Novy, Jan; Eckert, Philippe; Oddo, Mauro

    2017-06-01

    Prognostication studies on comatose cardiac arrest (CA) patients are limited by lack of blinding, potentially causing overestimation of outcome predictors and self-fulfilling prophecy. Using a blinded approach, we analyzed the value of quantitative automated pupillometry to predict neurological recovery after CA. We examined a prospective cohort of 103 comatose adult patients who were unconscious 48 hours after CA and underwent repeated measurements of quantitative pupillary light reflex (PLR) using the Neurolight-Algiscan device. Clinical examination, electroencephalography (EEG), somatosensory evoked potentials (SSEP), and serum neuron-specific enolase were performed in parallel, as part of standard multimodal assessment. Automated pupillometry results were blinded to clinicians involved in patient care. Cerebral Performance Categories (CPC) at 1 year was the outcome endpoint. Survivors (n = 50 patients; 32 CPC 1, 16 CPC 2, 2 CPC 3) had higher quantitative PLR (median = 20 [range = 13-41] vs 11 [0-55] %, p < 0.0001) and constriction velocity (1.46 [0.85-4.63] vs 0.94 [0.16-4.97] mm/s, p < 0.0001) than nonsurvivors. At 48 hours, a quantitative PLR < 13% had 100% specificity and positive predictive value to predict poor recovery (0% false-positive rate), and provided equal performance to that of EEG and SSEP. Reduced quantitative PLR correlated with higher serum neuron-specific enolase (Spearman r = -0.52, p < 0.0001). Reduced quantitative PLR correlates with postanoxic brain injury and, when compared to standard multimodal assessment, is highly accurate in predicting long-term prognosis after CA. This is the first prognostication study to show the value of automated pupillometry using a blinded approach to minimize self-fulfilling prophecy. Ann Neurol 2017;81:804-810. © 2017 American Neurological Association.

  13. Comparative Genomics of Mycoplasma bovis Strains Reveals That Decreased Virulence with Increasing Passages Might Correlate with Potential Virulence-Related Factors

    Directory of Open Access Journals (Sweden)

    Muhammad A. Rasheed

    2017-05-01

    Full Text Available Mycoplasma bovis is an important cause of bovine respiratory disease worldwide. To understand its virulence mechanisms, we sequenced three attenuated M. bovis strains, P115, P150,